The alleged misconduct took place on a April 13 flight from Florida to California This is Prudie Phones a Friend, a new feature where Jenée Desmond-Harris calls a few experts for their advice to a letter writer. Submit questions to Prudence here “Brandon,” has been testing my patience lately it’s become clear that he has a need for control and validation Brandon recently confessed that he’s been deliberately leading on a man—flirting with him and then pulling back whenever the man tries to take things further admitted that he does it because he loves the ego boost it gives him Nothing turns me on more than making someone want me who can never have me Brandon wasn’t just confessing; he was bragging He seemed proud of the way he was toying with this man’s emotions and hearing Brandon talk about him in this way felt personal It wasn’t just about Brandon’s toxic behavior; it was about the way he reduced this man to a pawn in his little power game I wanted to call him out right then and there I tried to explore why he feels the need to dominate others but he just laughed it off and told me that it wasn’t that deep—he just found this guy fun to mess with Every session with him leaves me drained and angry and I’m starting to wonder if I’m the right person to help him Maybe Brandon doesn’t really want to change But then I wonder if perhaps I’m the one with the problem It is not my job to only help clients I like I have an ethical duty to help clients even if I wouldn’t associate with them in the real world Maybe this is a learning experience for me that will make me a better therapist Should I do the easy thing and drop Brandon as a client Or should I take this as a challenge to put my personal feelings aside and help someone who clearly needs it I think it’s a good sign that you’re paying attention to this I imagine some less thoughtful people in your position might either say to Brandon and is probably what Brandon needs to hear from a good friend but wouldn’t solve the underlying problem) or tell him that due to a scheduling conflict they wouldn’t be able to fit him in anymore and that means you’re heading in the right direction You need some instructions on how to move forward You presented your options as A) working with Brandon despite taking his behavior and personality personally and feeling drained and angry after your sessions I felt a little stuck answering your letter because I did not think either of those choices would leave you feeling great I can tell that you feel a sense of responsibility to be there for your clients But it seems unsustainable —and not ultimately helpful to Brandon—for you to continue to meet with him while suppressing your negative feelings and working hard to keep your composure I wasn’t sure if therapists had a framework for thinking about situations like the one you’re in and didn’t want to advise you in a way that would go against professional norms So I reached out to Pamela LiVecchi, a clinical psychologist, professor, and the author of the book, Ethics for Counselors: Integrating Counseling and Psychology Standards After noting that she appreciated your self-awareness and candor “We’re all human and having reactions to one another is expected,” she told me that situations like yours in which a therapist is bothered by their negative reactions to a client’s behavior or simply doesn’t like a client there are a few actions to take before you decide to end the relationship evaluate (and improve) the current state of your work situation like when therapists have too many clients or lack support it can be harder to feel empathetic,” LiVecchi said I wonder if that kind of workplace sounds familiar Is there anything you could do to slightly decrease your workload or streamline your days so you feel less frazzled The perspective you bring to your sessions with Brandon might differ depending on whether you’ve had a chance to eat lunch or are breathlessly rushing from one client to another But you might have more capacity to hear about his antics and practice patience if you can decrease the stress in your workday overall You should also consult with a trusted colleague about what you’re dealing with and how you’re feeling “Therapists often consult when they’re struggling with their feelings about a client,” LiVecchi said “We aren’t ethically obligated to help everyone but we are obligated to behave ethically with everyone who we choose to work with we’re determining if we have the necessary training and skills to be helpful and if we’re going to be able to have a healthy professional relationship.” You don’t have to figure this out alone Is there anyone in a similar role to yours whom you’d feel comfortable bouncing this issue off of (while still keeping patient confidentiality Their perspective might help you clarify things talking things through with a colleague isn’t enough you might seek out professional supervision “Feeling drained and angry after every session may be unhealthy for you and your client,” LiVecchi said “Professional supervision can support deeper reflection on our emotional responses it could help you better understand your reactions to your client’s behavior.” So consider turning to a more experienced therapist for guidance Maybe you’ll even learn that they’ve been here before you’ll need to evaluate whether therapy can be helpful to Brandon and whether you’re comfortable with your reactions to him But if you conclude that Brandon isn’t open to much self-reflection or you are still having a strong negative reaction to him another therapist with a fresh perspective may be best you will be tasked with referring him to someone who can meet his needs—not just ghosting him it won’t be an agonizing decision because you’ll know you’ve left no stone unturned when it comes to trying to make the relationship work LiVecchi encouraged me to remind readers that if you’re wondering how your therapist feels about you “This can lead to healthy and productive conversations that serve to strengthen the relationship and create a safe atmosphere,” she said So maybe also have a quick answer ready just in case Brandon surprises you one day by asking – The Irondequoit Town Police are looking for 62-year-old Gunther Powers who they say is a vulnerable adult with dementia who might need medical attention Police say Powers was last seen on foot along Brower Road in Irondequoit on Saturday at around 9:30 a.m Police describe Powers as a bald man who weighs 200Ibs and is 5 feet 10 inches tall They say he was last seen in a black hooded sweatshirt call 911 or the Irondequoit Police Department at (585) 336-6000 Any person with disabilities who needs help accessing the content of the FCC Public file should contact Richard Reingold at rreingold@whec.com or 585-546-1701 There may not be obvious successors to the likes of Martin Amis and Salman Rushdie among today’s hotshot young writers But is a new publisher dedicated to ‘overlooked’ male voices necessary Who are this generation’s hotshot young male novelists the modern incarnations of the Amis/McEwan/Rushdie crew of the 80s The question flared again this week as writer Jude Cook launched a new press Cook says the publishing landscape has changed “dramatically” over the last 15 years as a reaction to the “toxic male-dominated” scene of the 80s excitement in publishing circles centres on a “new breed of young female authors While this is “only right as a timely corrective” the side-effect is that male authors are “often overlooked” Some metrics certainly say so: of all the writers to appear on the weekly Sunday Times bestseller lists for fiction hardbacks so far this year In nonfiction the picture is clearer: men make up 63% of authors to feature on the Sunday Times nonfiction hardback bestseller lists so far this year and 70% of those on the nonfiction paperback charts with titles such as Atomic Habits by James Clear continuing to sell well years after publication Writers and publishing insiders disagree over the extent of the gender imbalance in fiction and the extent to which that imbalance is a concern “There is no doubt male voices talking about male experiences – in middle age especially – are not getting much traction among agencies and publishers at the moment,” said one male agent, who asked to remain anonymous. However, men are “hardly underrepresented in the entertainment industry, and they need to earn their place as much as anyone else”. Men “should make the work and let everyone decide if it’s worth anyone’s time, rather than pretend they are a minority in the arts”, says Sheena Patel, author of I’m a Fan. “I feel like men are doing just fine.” Free weekly newsletterDiscover new books and learn more about your favourite authors with our expert reviews, interviews and news stories. Literary delights delivered direct to you who runs the leading literary agency of the same name “There was certainly a time when we needed more female novelists particularly in the areas of crime and suspense so I’m thrilled that female-led psychological suspense is still so popular but the pendulum ultimately needs to land somewhere in the middle,” she said While Milburn is “excited” about Conduit Books, she believes “we also need more male editors acquiring fiction in the areas men want to read”. The latest Publishers Association workforce survey suggests that 68% of publishing staff are women Another female agent said that class may be a “bigger issue than gender when it comes to what’s being published” Lacking racial representation also continues to be a problem: just one person of colour appeared on each of the Top 10 fiction and nonfiction hardback bestseller lists last week Chimamanda Ngozi Adichie for fiction and Roxie Nafousi for nonfiction said he knows “so many working-class men from my generation who got into reading fiction through Irvine Welsh because it spoke to a world they recognised” Welsh himself says that “men need to start reading before they start writing My take is that men are becoming stupider because they over-rely on the internet and women are becoming smarter because they read more books.” some suggest the decline of male novelists being commissioned is due to low demand from men 37% of fiction purchases in the UK were made by men having made 58% of all book purchases last year men buy more nonfiction (55% v 45% bought by women) “Men need to read women and I think women should read men,” says Brown “It’s one of the great ways we can come to understand each other better” Cook’s new venture met with some criticism online Mukherjee said that the project comes from a position that is “the opposite of Farage-ist grievance or misogyny-driven rabble-rousing.” “No doubt there will be a lot of hand-wringing about this “But writing and publishing are not zero-sum games.” The state of Maine continues to defy President Donald Trump's executive order that bans males whether they "identify" as girls and women or not males continue to win girls' competitions.  On Friday, Soren Stark-Chessa won both the 800-meter and the 1,600-meter races at an event in Hiram, Maine, finishing the latter nearly 20 seconds ahead of the next-closest competitor with Lilah Connor falling short of her male competitor by one-and-a-half seconds Connor is seen shaking her head after coming in second place to a male athlete racing against girls.  Had Stark-Chessa competed in the boys' category which would be the correct category since Stark-Chessa is male the athlete would have finished in 12th place in the 1600-meter race and eighth in the 800-meter.  As OutKick's Amber Harding previously reported this is not the first time Stark-Chessa has won girls' events the male athlete is a Maine state champion.  "The runner won the 800-meter at the Maine Principals’ Association (MPA) Class C Girls’ Outdoor Track and Field State Championship as a sophomore in June Stark-Chessa competed on the boys' teams," Harding wrote.  Last month, the United States federal government filed a civil lawsuit against the state of Maine for continuing to allow males to compete in women's sports but that doesn't seem to have dissuaded the state from stopping it.  won two track and field events in Maine on Saturday with the state currently being sued by the federal government It appears that Maine, and its governor, are not interested in protecting fairness in girls' and women's sports on their own, and unfortunately, the only option left is to allow the legal system to do it for them.  Written by Dan began his sports media career at ESPN He is secure enough in his masculinity to admit he is a cat-enthusiast with three cats one of which is named "Brady" because his wife wishes she were married to Tom instead of him You are agreeing to OutKick's Terms of Use and Privacy Policy DISCLAIMER: This site is 100% for entertainment purposes only and does not involve real money betting. Gambling related content is not intended for anyone under the age of 21. If you or someone you know has a gambling problem and wants help, call 1-800-GAMBLER (WHP) — A deceased male has been found by police after an extensive search detail in Lancaster County according to the Lancaster County Coroner's Office Officials state that a deceased male was found near a rail trail at the intersection of Landisville Road and Spooky Nook Road in East Hempfield Township The coroner states that it appears that the man died by suicide East Hempfield Police is the primary police agency on scene The search detail was initiated around 4:00p.m More » More » More » More » More » More » as well as later life health conditions that occur in adults who were born after a complicated pregnancy Researchers analyzed male and female placental samples from a larger study for differences in their methylation patterns and found differences in gene activity between male and female placentas that may play a role in birthweight and adult diseases The study identified 2,497 previously unreported DNA sites that had different methylation patterns for males and females Of these and more than 2,500 sites that had also been identified by previous studies 66.9% of large increases in methylation occurred in DNA from male placentas and 33.1% from female placentas Increases in methylation in male placentas was linked with greater neonatal size whereas those in females was linked with greater placental size Some increases in methylation found in male placentas were located near the CCDC6 gene Lower activation of CCDC6 has been linked with preterm birth in previous studies inflamed skin) and higher risk for breast cancer later in life The study was conducted by Fasil Tekola-Ayele of the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and colleagues at other institutions Tekola-Ayele F, et al. Sex-differentiated placental methylation and gene expression regulation has implications for neonatal traits and adult diseases Nature Communications. DOI: https://doi.org/10.1038/s41467-025-58128-3 (2025) About the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): NICHD leads research and training to understand human development, improve reproductive health, enhance the lives of children and adolescents, and optimize abilities for all. For more information, visit https://www.nichd.nih.gov National Institutes of Health (NIH) NIH…Turning Discovery Into Health® U.S. Department of Health and Human Services The week of April 27-May 3 was filled with some outstanding individual performances from Des Moines metro-area high school male athletes Boys track and field athletes had a productive week between the Drake Relays and state qualifying meets 1 West Des Moines Valley won a 1-0 battle over 3A No Area boys golfers and tennis players also stepped up their game with the postseason just around the corner Here are the Des Moines Register's male Athlete of the Week candidates from the Des Moines metro area for the week of April 27-May 3 DesMoinesRegister.com readers vote to determine the winners who will be announced at the end of the week ValleyMendez scored the winning goal for the 4A No 1 Valley boys soccer team during its 1-0 victory over 3A No Mendez put the ball in the net off a feed from Eric Foust during the second half to give the Tigers the victory Curtis led a balanced attack for the 4A No 2 Des Moines Roosevelt boys soccer team during its 10-0 victory over Waterloo East on April 29 at Waterloo Curtis converted his only shot on goal into a score during the game He also dished out one assists to help the Roughriders improve to 9-1-1 on the season JohnstonKumaresan helped the Johnston boys tennis team prevail in both the No 1 singles and doubles matches during the Dragons' 9-2 victory at Dowling Catholic on April 29 Kumaresan defeated Dowling's Brady Frye in straight sets 1 doubles match he teamed with Aadil Patel to sweep past Frye and Rob Beecher with a pair of 6-3 victories Haisman took medalist by four strokes for the North Polk boys golf team during the Winterset Invitational on May 2 at the Lakeview Country Club in Winterset Haisman carded a 2-under-par round of 68 to defeat Perry's Daxon Weeks' score of 72 for the top individual score Haisman also helped the Comets win the team title with a 302 to Winterset's 309 Des Moines EastParker helped the Des Moines East boys track and field team win the boys sprint medley relay at the Valley Relays on May 2 in West Des Moines Parker anchored East to a winning time of one minute The Scarlets finished comfortably ahead of Dowling Catholic's runner-up time of 1:34.80 Joe Randleman covers high school sports for the Ames Tribune. Contact him at jrandleman@gannett.com. Follow him on Twitter at @JoeRandleman How would you feel if your coworker found your dating app profile and decided to treat you like you were desperate for trying to find love that’s the situation this young woman is now in She works in an industry that is mainly male but she says that she adores her job and it’s her favorite one she’s ever held so far One of her male coworkers recently came across her profile on a dating app but he did mention his brother was the one who found it first and guessed what company she was at based on her location and industry “I wasn’t working the day he made this discovery he made it a point to let everyone know I was,” she explained I then realized it was in a ‘…she’s desperate’ fashion Not only is the workplace and field in general male-dominated but I am more than 20 years younger than the majority of my coworkers with the exception of the guy who spread the info and a couple of others.” He and a few others bring it up in a mocking or teasing way quite regularly It really wasn’t funny the first time There’s no way her coworker is trying to be funny with how he’s going on about her dating app profile; he’s clearly doing this in a way intended to demean her This is hardly the only nasty thing this man does as he loves to give her advice she doesn’t ask for on her appearance She’s wondering how on earth she can handle this quietly as she does not want to go to HR and blow this up into a bigger mess than it already is Sign up for Chip Chick’s newsletter and get stories like this delivered to your inbox. Her plan is to change jobs in the middle of next year so she wants to lay low until then and try to make the best of her time at her current company “What should I say next time he or another coworker brings it up More About: ARIZONA NEWS 11:00 AM | Updated: 11:29 am BY KTAR.COM PHOENIX — A Phoenix high school teacher who was arrested in April for sex crimes against male students was indicted the Maricopa County Attorney’s Office (MCAO) announced on Monday Chapman’s arrest was prompted by a tip the Phoenix Police Department received from a social media provider via the National Center for Missing and Exploited Children The tip said he had been enticing an account that had self-identified as a minor Chapman, who is from Surprise, taught at Cortez High School, which is near 31st and Dunlap avenues, ABC15 reported Court documents accused Chapman of filming himself sexually abusing a 16-year-old student in an alley near the boy’s home a week before his arrest Chapman also allegedly sexually assaulted a 17-year-old victim on campus Investigators found that Chapman also filmed himself having sex with a former student inside his current classroom Chapman began sexually abusing him while he was a minor Investigators also found Chapman saved various files depicting children being sexually abused He allegedly claimed to prefer boys around 7 and 8 years old Follow @KTAR923 Have a story idea or tip? Pass it along to the KTAR News team here Sponsored Content by Bright Wealth Management Vote now for the Chillicothe Gazette high school male athlete of the weekChillicothe GazetteThis week's poll has athletes from baseball A reminder to coaches/parents: If we do not have stats from games/matches we can't put the athlete up for athlete of the week Stats for any games/matches can be sent to cgosport@nncogannett.com after each event please send complete stats to cgosport@nncogannett.com no later than 5 p.m More: Glory Days: Chip Maxwell and the 1970 Zane Trace Pioneers Last week's winner was Piketon's Wadye Fout The week of April 27-May 3 was another eventful stretch of competition for Ames-area high school male athletes competing in spring sports 3 Ames boys soccer team defeated Des Moines Lincoln (4-0) and Des Moines Hoover (2-1) scored a pair of 3-0 victories over Bondurant-Farrar and top rival Nevada The Ames boys tennis team earned an 8-3 victory over Mason City on April 29 in Ames and the Ballard boys golf team defeated Adel-Desoto-Minburn in a nine-hole dual at the Ballard Golf and Country Club in Huxley on April 29 golf and soccer teams also had a productive week Area boys track and field teams continued to keep busy in the week between the Drake Relays and the state qualifying meets Here are the Ames Tribune male Athlete of the Week nominees for the week of April 27-May 3. AmesTrib.com readers vote to determine the winner 3 Ames boys soccer team to a 4-0 victory over No Sigurdsson put two goals on the board to help the Little Cyclones improve to 8-2-1 on the season and he did an excellent job helping the Class 2A No 3 Gilbert boys soccer team dominate possession of the ball during a 3-0 victory over rival Nevada on May 1 at Gilbert Mattson's goal came on a 25-yard direct kick with 21 seconds left in the first half BallardColvin had a strong nine-hole round for the Ballard boys golf team during a 143-159 dual victory over Adel-Desoto-Minburn on April 29 at the Ballard Golf and Country Club in Huxley Colvin was the individual medalist at the meet He shot a 2-under-par round of 34 to win medalist by one stroke over teammates Mason Gatchel and Alex Weeks Lucchesi gave the Roland-Story boys track and field team a win in the 3,200-meter run during the Norsemen Relays boys track and field meet on May 1 at Story City Lucchesi won the 3,200 with a time of 10 minutes Wierson won both the 100 and 200 dash events for the Collins-Maxwell boys track and field team at the South Hardin Invitational in Eldora on May 2 Wierson clocked in at 11.22 seconds in the 100 and 23.52 in the 200 MANSFIELD — It's time to make your vote count Voting for the Mansfield News Journal Male Athlete of the Week is now open CHANGES COMING: Everything is on the table: OHSAA looking at potential changes to football playoff format Mansfield Senior's Will Fortner was voted the Mansfield News Journal Male Athlete of the Week last week with 3,406 votes Fairfax, Va. – Diverse: Issues in Higher Education magazine named UMBC senior track and field student-athlete Jayo Adegboyo (Columbia Diverse: Issues In Higher Education sponsors the Arthur Ashe Jr Sports Scholar Awards to honor students of color who have excelled in the classroom and on the athletic field Jr.'s commitment to education and love for the game of tennis colleges and universities are invited to participate in this annual awards program by nominating their outstanding sports scholars In addition to their athletic ability and academic performance Sports Scholars demonstrate a commitment to community service and student leadership Thanks for visiting The use of software that blocks ads hinders our ability to serve you the content you came here to enjoy We ask that you consider turning off your ad blocker so we can deliver you the best experience possible while you are here This week's winner will be recognized in the May 18 edition of The Advocate Metrics details The anterior cingulate cortex (ACC) is essential for social behavior and its dysfunction is implicated in social interaction deficits in autism Pyramidal neuron activity in the ACC is modulated by parvalbumin (PV) and somatostatin (SST) interneurons though their specific roles in social interactions remain unclear we demonstrate that PV and SST interneurons differentially contribute to the regulation of social interactions is reduced in both PV and SST interneurons Knocking out Kcnh7 in either interneuron subtype leads to social interaction deficits projections from the lateral posterior thalamic nucleus (mediorostral part LPMR) to PV interneurons and from the ventral hippocampus (vHPC) to SST interneurons differentially modulate social interactions These findings provide new insights into the distinct roles of PV and SST interneurons in social processes and their contributions to autism-related pathophysiology the precise mechanisms of ACC in regulating social interaction remain relatively understudied complicating both the diagnosis and treatment of ASD patients If PV and SST interneurons indeed selectively modulate ACC-related social processes it is worth investigating whether they contribute to the heterogeneity of social deficits and exploring the underlying mechanisms Using a Cre-dependent CRISPR-Cas9 viral approach to knockout Kcnh7 in PV or SST interneurons in the ACC we found that PV interneurons primarily regulate sociability whereas SST interneurons influence both sociability and social preference The distinct contributions of PV and SST interneurons are partially due to their differential inputs These findings provide direct evidence for the specific roles of ACC PV and SST interneurons in social interaction and offer insights into the potential mechanisms underlying social dysfunction in individuals with ASD a Schematic diagram of AAV-FLEX-GCaMP7s injection (The 3D brain image was created with CEBSIT/ION Digital Brain https://www.digital-brain.cn/) b Example image showing fiber placement in the ACC (left) and GCaMP7s expression (right) d Cartoon depicting the social recognition behavior in the home cage test e Ca2+ signals associated with social recognition in (d) Right: the peri-event plot of the average Ca2+ transients: thick lines indicate the mean shaded areas represent the SEM (n = 11 mice) g Schematic diagram of the three-chamber sociability test n = 11 mice) mice in social preference test m Comparison of AUC (area under curve) (left) and the correlation index between social duration and neuronal activity in the PV-Cre and SST-Cre groups (right) (n = 11 mice per group n Same as (m) but for sociability (n = 9 PV-Cre mice o Same as (m) but for social preference (n = 9 PV-Cre mice Source data are provided as a Source Data File PV and SST interneuron activity was suppressed during social interaction with PV interneuron activity changes being more prominent during sociability and SST interneuron changes being more pronounced during social preference a Schematic diagram of virus injection (The 3D brain image was created with CEBSIT/ION Digital Brain https://www.digital-brain.cn/) c Representative immunofluorescence images d Number of PV+ cells (left) and Pvalb mRNA levels (right) (left: n = 6 slices from 2 mice per group e Same as (d) but for SST-Cre mice (left: n = 6 slices from 2 mice per group two-tailed unpaired separate variance estimation t test P < 0.0001; right: n = 10 mice for the control and n = 15 mice for taCasp3 f Traces of PV-Cre mice before (left) and after (right) viral intervention in the sociability test g Quantification of time spent in the social zone and empty zone before and after viral intervention for PV-Cre mice (n = 8 mice per group; two-tailed paired t test P = 0.0097 for Pre; Two-sided Wilcoxon signed-rank test h Discrimination score for PV-Cre mice in (g) (n = 8 mice i Quantification of time spent in the stranger zone and original zone before and after viral intervention for PV-Cre mice (n = 8 mice j Discrimination score for PV-Cre mice in (i) (n = 8 mice k Same as (g) but for SST-Cre mice (n = 8 mice; two-tailed paired t test m Traces of SST-Cre mice before (left) and after (right) viral intervention in the social preference test n Same as (i) but for SST-Cre mice (n = 8 mice; two-tailed paired t test o Same as (j) but for SST-Cre mice (n = 8 mice a Schematic diagram of AAV- DIO-ChR2 injection into the ACC of PV-Cre mice and SST-Cre mice (left, the 3D brain image was created with CEBSIT/ION Digital Brain https://www.digital-brain.cn/) and diagram of the home cage test with laser delivery strategy (right panel is designed by us) b Optogenetic stimulation of PV interneurons modulates social behaviors in the home cage test Left: The raster plot of different types of social behavior in the home cage test; B body contact Right: Statistical analysis of total social interaction time (n = 10 mice c Same as (b) but for SST-Cre mice (n = 9 mice d Comparison of slope coefficient in the PV-Cre SST-Cre and Cre negative groups: X-axis: STON (social time when laser ON) -STOFF1 (social time during OFF1)/TT (total time of test); Y-axis: STOFF2 (social time during OFF2)- STON (social time when laser ON)/TT (total time of test) (n = 10 mice e Comparison of the social inhibition index between the PV-Cre and SST-Cre groups (n = 10 PV-Cre mice f Summary data of the time spent with toys for PV-Cre group in the OFF1 ON and OFF2 stages in the home cage (n = 10 mice g Same as (f) but for SST-Cre group (n = 9 mice The results indicate that both PV and SST interneurons modulate sociability in the home cage test with PV interneuron activation exerting a stronger inhibitory effect on social behavior compared to SST interneuron activation a Traces of PV-Cre mice in the sociability test c Social interaction time (b) and discrimination score (c) from the sociability test (n = 9 mice P = 0.008 for OFF1; two-tailed paired t test P = 0.036 for ON; two-tailed paired t test P = 0.161 for OFF2; two-tailed paired t test d Traces of PV-Cre mice in the social preference test c) but in the social preference test (n = 9 mice P = 0.028 for ON; two-tailed paired t test m Delay time when the first social behavior stopped during the sociability test (n = 9 PV-Cre mice n = 8 SST-Cre mice; two-tailed unpaired t test n Comparison of normalized discrimination scores in the sociability test (n = 9 PV-Cre mice o Delay time when the first social behavior stopped in the stranger zone (n = 9 PV-Cre mice q Time spent in the center zone for PV-Cre (p) and SST-Cre (q) in the social preference test (n = 9 mice r Same as (n) but in the social preference test (n = 9 PV-Cre mice n = 10 SST-Cre mice; two-tailed unpaired t test These findings suggest that PV interneurons primarily regulate sociability whereas SST interneurons have a more prominent influence on social preference in the three-chamber test these results indicated that while both PV and SST interneurons contribute to sociability SST interneurons play a more prominent role in regulating social preference a RNAscope showing Kcnh7 (gray) and Pvalb (red) expression in WT (left) and Shank3 KO mice (middle) with the quantification of Kcnh7+/Pvalb+ ratio (right b Normalized fluorescence intensity of Kcnh7 (left) and normalized number of Kcnh7+ puncta (right) in Pvalb+ neurons (n = 13 cells in WT and n = 12 cells in KO from 3 mice per group; Mann‒Whitney U test P = 0.003 for intensity; two-tailed unpaired t test c Action potential trace at 200 pA in PV-tdTomato mice d Input‒output curve (left) and spike frequency at 380 pA (right) (Stim int.: stimulus intensity; n = 9 cells in WT and n = 10 cells in KO from 3 mice per group Pwithin group < 0.0001 for input‒output; two-tailed unpaired t test e Representative traces of the Kv11.3 current (left) and quantification (right) (n = 4 cells for the WT and n = 3 cells for the KO group from 2 mice per group; two-tailed unpaired t test f Same as (a) but for Sst+ interneurons (right g Same as (b) but for Sst+ interneurons (n = 11 cells for the WT and n = 12 cells for the KO from 3 mice per group h Same as (c) but for SST-Cre::Ai9 neurons i Same as (d) but for SST-Cre::Ai9 neurons (n = 9 cells in WT and n = 8 cells in KO from 3 mice per group j Same as (e) but for SST-Cre::Ai9 neurons (n = 3 cells in WT and n = 4 cells in KO from 2 mice per group a Time spent in the social zone and empty zone before and after viral intervention in PV-Cre mice during the sociability test (n = 9 mice P = 0.008 for Pre; two-tailed paired t test b Comparison of discrimination score for PV-Cre mice in the sociability test (n = 9 mice c Time spent in the stranger zone and original zone before and after viral intervention in PV-Cre mice during the social preference test (n = 9 mice P = 0.011 for Pre; two-tailed paired t test d Comparison of discrimination score for PV-Cre mice in the social preference test (n = 9 mice e Time spent in the social zone and empty zone before and after viral intervention in SST-Cre mice during the sociability test (n = 8 mice f Comparison of discrimination score for SST-Cre mice in the sociability test (n = 8 mice g Time spent in the stranger zone and original zone before and after viral intervention in SST-Cre mice during the social preference test (n = 8 mice P = 0.012 for Pre; two-tailed paired t test h Comparison of discrimination score for SST-Cre mice in the social preference test (n = 8 mice a Schematic of experimental design (The 3D brain image was created with CEBSIT/ION Digital Brain https://www.digital-brain.cn/ and the right panel is designed by us) b Representative images showing the starter neurons in ACC from a PV-Cre and a SST-Cre mice c Representative images showing starter neurons in the ACC co-expressing AAV-helper (His-EGFP and PV or SST (gray) (n = 6 slices from 3 mice per group) d PV interneurons in the ACC receive direct inputs from the LPMR (top) while SST interneurons in the ACC receive direct inputs from the vHPC (bottom) Images are from representative animals of each group e Quantification of principal starter neurons (expressing His-EGFP and RV-dsRed) in the ACC and PFC (n = 6 mice per group) The value 1.00 indicates all detected starter neurons f Analysis of RV-dsRed-positive cell density in upstream brain region (n = 5 mice per group) Cl/DEn claustrum/dorsal endopiriform nucleus HDB/VDB nucleus of the horizontal/vertical limb of the diagonal band VL/AM ventrolateral thalamic nucleus/anteromedial thalamic nucleus This study focused on two primary interneuron subtypes We found that both types of interneurons significantly influence social behavior through distinct and nuanced mechanisms we observed a reduced expression of the Kcnh7 gene specifically in PV and SST interneurons within the ACC Deletion of Kcnh7 in either PV or SST interneurons contributed to altered social interactions highlighting the involvement of these interneuron subtypes in ASD-related behavioral variability our pathway-specific analyses revealed that the LPMR-PV(ACC) and vHPC-SST(ACC) projections underline the roles of PV and SST interneurons in regulating social behavior The LPMR-PV(ACC) pathway exerted a stronger influence on sociability whereas the vHPC-SST(ACC) pathway predominantly affected social preference our findings demonstrate that PV and SST interneurons in the ACC play a critical role in regulating social interactions through distinct synaptic inputs and downstream circuit mechanisms the four strategies used to manipulate SST interneurons produced consistent effect on social preference while their impact on sociability was more variable These results suggest that SST neurons may be more actively involved in social preference This conclusion is further supported by comparing the effects of PV and SST interneuron modulation PV and SST interneurons showed reduced responses to both novel objects and conspecifics but their suppression was stronger during interactions with novel mice enabling differential regulation of pyramidal neuron responses to excitatory inputs These distinctions allow PV and SST interneurons to fine-tune ACC activity during social information processing contributing to the precise regulation of social behavior While our study emphasizes specific projections to PV and SST interneurons further research is needed to explore how upstream regions regulate other interneurons Abnormal activation of PV or SST interneurons in the ACC could contribute to the aberrant social behavior indicating that dysregulated upstream projections targeting these interneurons could be a critical factor contributing to such abnormalities normal ACC activity during social recognition likely depends on the interaction between upstream projections and local circuits Quantifying these contributions and developing mathematical models to describe the regulation of pyramidal neurons by PV and SST interneurons could elucidate their roles in social interaction and related behaviors these findings highlight the complex interplay between molecular factors (such as Shank3 and Kcnh7) cellular processes involving PV and SST interneurons projection neurons and behavioral outcomes This deeper understanding of how these elements interact offers valuable insights into the neurobiological basis of social dysfunction and its related disorders the present research provides strong evidence that PV and SST interneurons in the ACC play differential roles in social interaction These nuanced roles likely contribute to the various manifestations of social interaction deficits This insight not only enhances our understanding of social behavior but also opens new avenues for addressing related disorders By targeting the specific functions of PV and SST interneurons within the ACC complex network novel therapeutic approaches may be developed underlying the new mechanisms of social dysfunction 017688) and C57BL6 mice were used in this study The animals were housed under a 12 h:12 h light:dark cycle (lights on at 8 AM) and no mice were excluded unless they exhibited weight loss exceeding 10% during subsequent experiments or if viral injections were performed inaccurately as confirmed by post hoc analysis of viral targeting The researchers were blinded to the experimental groups All mice were euthanized using a humane method in accordance with the Principles of Medical Laboratory Animal Care Six-to-eight-week-old mice were used for stereotaxic injections The mice were anesthetized with 1% pentobarbital sodium and placed in a stereotaxic instrument (RWD) Eye ointment and a piece of silver paper were applied to prevent corneal drying A thermostatic heating pad (RWD) was used to keep the mouse body temperature constant during surgery A small craniotomy hole was made using a dental drill (RWD) and injections were carried out using a microsyringe pump (KD Scientific) at a flow rate of 40 nL/min to minimize brain tissue damage Fiber photometry was used to record calcium signals via a commercialized fiber photometry system 240 nL/injection) was injected unilaterally into the ACC of PV-Cre or SST-Cre mice (AP: +0.73 mm; ML: −0.28 mm; DV: −1.75 mm) optical fibers (2.5 mm optical density (O.D.) 2.5 mm length) were implanted ipsilaterally We used dental acrylic resin (Super Bond) to support the ceramic ferrule The mice were housed individually and allowed to recover for at least one week before subsequent experiments AAV2/9-DIO-ChR2-EYFP was injected unilaterally into the ACC of PV-Cre or SST-Cre mice (virus titer: 3.2E + 12 vg/mL 240 nL/injection; AP: +0.73 mm; ML: −0.28 mm; DV: −1.75 mm) 2.0 mm length) were implanted ipsilaterally A mixture of AAV2/9-CaMKII-GCaMP6s (5.36E + 12 vg/mL) and AAV2/9-hSyn-DIO-ChrimsonR-mCherry (2.50E + 12 vg/mL) at 1:8 ratio (200 nl total volume) was injected unilaterally into the ACC of PV-Cre or SST-Cre mice at the same coordinates as the previous site (AP: +0.73 mm; ML: −0.28 mm; DV: −1.75 mm) The density of upstream neurons was analyzed with reference to the Mouse Brain in Stereotaxic Coordinates (Second Edition) To trace synaptic connections from the LPMR to PV interneurons and from the vHPC to SST interneurons in the ACC and to confirm the functional role of these projections a mixture of AAVRetro-ChR2 (5.08E + 12 vg/mL) and AAV2/9-CAG-FLEX-GCaMP7s (2.21E + 12 vg/mL) was injected into the ACC of PV-Cre and SST-Cre mice (240 nL/injection) Optical fibers (3.0 mm length or 4.0 mm length) were implanted in the ipsilateral LPMR (AP: −1.95 mm; ML: −1.64 mm; DV: −2.52 mm) or vHPC (AP: −3.2 mm; ML: −3.81 mm; DV: −1.57 mm) at a 15° angle optical fiber (2.5 mm length) was implanted ipsilaterally in the ACC To confirm the function of these two projections in vitro AAV2/9-hSyn-ChR2-mCherry (3.84 E + 12 vg/mL 240 nL/injection) was injected into the LPMR or vHPC of PV-tdTomato or SST-Cre::Ai9 mice The optical fibers were implanted in ACC ipsilaterally For specific regulation of MD → PV interneurons MD → SST interneurons and Cl/DEn→SST interneurons in the ACC AAV1-Flp-EGFP was injected into the MD (AP: −1.0 mm; ML: −0.75 mm; DV: −3.4 mm) Po (AP: −1.95 mm; ML: −1.25 mm; DV: −3.5 mm) and Cl/Den (AP: +1.5 mm; ML: −0.85 mm; DV: −3.0 mm) To suppress the activity of PV or SST interneurons and observe the impact on social behavior in mice 240 nL/injection) was bilaterally injected into the ACC To specifically knockout Kcnh7 on PV and SST neurons a mixture of AAV-MECP2-DIO-Cas9 (4.79E + 13 vg/mL) and AAV-kcnh7-gRNA-hSyn-GFP (1.55E + 13 vg/mL) was injected bilaterally into the ACC of PV-Cre and SST-Cre mice we did not define separate zero-points for each event the zero-point was defined as the moment when the subject mouse approached the cage within a distance shorter than its head length and signals were analyzed over a 5 s window following this point The total observation time for both the home cage and three-chamber tests was 10 min Changes in fluorescence intensity (ΔF/F0) were calculated as ΔF/F0  =  (Fsignal–F0)/F0–Foffset where F0 was defined as the baseline fluorescence signal averaged over a 2 s-long control time window and Foffset was the system bias data recorded in the dark Fsignal represented the peak value of the fluorescence signal Data analysis was performed using MATLAB-based software provided by Thinker Tech For optical stimulation during behavioral tests, the device connection followed a previously described protocol7 which was linked to a fiber-optic rotary joint The other end of the fiber was then connected to the ferrule mounted on the mouse’s head Following a brief recovery period from handling In the excitatory photogenetic experiments the test was divided into three phases: laser stimulation off Photostimulation of PV interneurons or SST interneurons in the ACC was induced by 40 Hz light trains with 5 ms pulses generated by a 473 nm laser (IOS-465 The laser power was adjusted to approximately 5.0 mW at the tip of the fiber-optic cable Each phase (OFF1-ON-OFF2) lasted 3 min during both the home cage and three-chamber tests divided by the total time of the test (TT); the Y-axis represented the social time after the laser was on (SToff2) minus the social time when the laser was on (STon) divided by the total time of the test (TT) Social inhibition index: the time spent with a social object when the laser was OFF1 minus when the laser was ON divided by the total time spent with a social object when the laser was OFF1 and ON To observe the effect of PV or SST neuron activation on the activity of pyramidal neurons in vivo 5 mW) was used to stimulate ChrimsonR-expressing interneurons The stimulation protocol consisted of 10 cycles of 30 s ON followed by 1 min OFF during the home cage test This experiment was performed as previously described7 The apparatus consisted of three identical chambers (30 cm × 45 cm × 20 cm) made of black perspex acrylic sheets Two cylindrical grid cages were placed in the corners of the outer chambers and auditory interaction between the test mouse and the caged mouse the test animal was placed in the chamber for 10 min to habituate and then was isolated in the middle chamber to wait for the experiment to begin a novel juvenile male mouse was placed in a wire cage in one chamber and another empty wire cage was placed in the opposite chamber The subject mouse was then allowed to explore all three chambers freely the second stranger juvenile male mouse was put into the other empty cage and the experimental subject mouse was allowed to explore freely in three-chambers again The data was analyzed via SMART v.3.0 software The discrimination score in the sociability test was calculated as the time spent in the social zone minus the time spent in the empty zone divided by the total time spent in both zones The discrimination score in the social preference test was calculated as the time spent in the stranger zone minus the time spent in the original zone The latency of the first social behavior stop was defined as the time from the start of the social interaction to the cessation of the behavior When the subject mouse approached within a distance shorter than a mouse’s head length from the cage of the object mouse time recording and optical stimulation were initiated manually Laser activation was defined as the zero-point and the end of the interaction was recorded when the subject mouse turned its body away from the cage or stepped back to initiate another behavior Each trial included only one scenario in which the subject mouse entered a social zone The experiment was conducted in an open field arena Fresh urine was collected on the day of the experiment Ten three-week-old male mice were placed in a cage lined with clean filter paper the urine-stained portions of the filter paper were excised Collected filter paper segments were placed into one dish which was then covered with cling film punctured with a fine array of small holes the filter paper was saturated with saline The petri dishes with urine filter paper and saline filter paper were placed on opposite sides of the open field arena The movement of the mice was recorded under two conditions: with the laser off and with the laser on The time spent in each corner was analyzed using SMART v.3.0 software a new round of social interaction experiments was conducted The total observation time for each session was 10 min The videos were analyzed via SMART v.3.0 software Social promotion index: (social interaction time after viral intervention minus social interaction time before viral intervention) divided by (social interaction time after viral intervention plus social interaction time before viral intervention) All animals were anesthetized with 1% pentobarbital sodium and perfused intracardially with 0.9% saline followed by 4% paraformaldehyde The whole brain was then removed and placed in 30% sucrose solution for 3 days 40 μm-thick brain tissue sections containing the ACC were placed in blocking solution for 1 h before incubation with primary antibodies against PV (rabbit brains were collected one hour after the behavior test and tissue sections were processed as described above These sections were stained with anti-Fos antibody (rabbit The sections were incubated with the secondary antibody at a dilution of 1:800 for 4 h at room temperature all the sections were incubated with Hoechst 33342 (Sigma) rinsed in 0.01 M PBS Each section was mounted a microscope slide and a cover glass was sealed on it with a mixture of 50% (v/v) glycerol in 0.01 M PBS and were then imaged with confocal (FV31S-SW For the RV retrograde tracing of PV or SST interneuron monosynaptic inputs 7 days after RV-EnvA-ΔG-dsRed viral injection the preparation of 40 μm-thick brain tissue sections was the same as described above All the sections were incubated with Hoechst 33342 (Sigma) Each section was mounted on a microscope slide and covered with a cover glass using a mixture of 50% (v/v) glycerol in 0.01 M PBS The slides were then scanned using a VS200 Slide Scanner (Olympus) The number of positive cells was analyzed via ImageJ software and the area of the upstream brain region was measured via OlyVIA (Olympus) The density of cells was calculated as the number of positive cells/the area of the upstream brain region the mice were deeply anesthetized with isoflurane and sacrificed Fresh ACC tissues were isolated from the corresponding coronal sections under a stereomicroscope Total RNA was extracted with TRIzol reagent and PrimeScriptTM RT Master Mix (Takara) was used to reverse transcribe the total RNA (500 ng) into complementary DNA Real-time PCR was carried out via a StepOnePlusTM Real-Time PCR instrument (Thermo) with 2× Universal SYBR Green Fast qPCR Mix (ABclonal) The sequences of the primers used were as follows: mice were deeply anesthetized with isoflurane and transcardially perfused with ice-cold carbogenated (95% O2 5% CO2) cutting solution containing 115 mM choline chloride Coronal sections (300 µm thick) containing the ACC were cut using a vibratome (7000SMZ the brain slices were incubated with carbogenated cutting solution (95% O2 the slices were incubated for 1 h at room temperature in artificial cerebral spinal fluid (ACSF; 119 mM NaCl the slices were placed in the recording chamber and continuously perfused with ACSF Recordings were obtained using an Axon Multiclamp 700B amplifier (Molecular Devices) filtered at 5 kHz and sampled at 20 kHz with a Digidata 1550B Clampex 10.6 and Clampfit 10.7 were used for acquisition and analysis Data were excluded if the resting membrane potential of neurons were more positive than −60 mV or the series resistance changed by >20% To record light-induced spikes with a current clamp in PV-positive and SST-positive neurons in the ACC patch pipettes were filled with a solution containing the following: 128 mM potassium gluconate In the current clamp mode of the whole-cell patch 5 ms pulse width and 40 Hz 473 nm light stimulus (IOS-465 RWD) was delivered to evoke spikes during each stimulus The Event Detection function in the Clampfit software was used to quantify the number and amplitude of the spikes Patch pipettes were filled with a solution containing 103 mM CsCl The membrane potential of pyramidal neurons was held at −65 mV during laser-evoked IPSCs and PPR recordings PV or SST interneurons were stimulated with a 5 ms pulse of 473 nm light (IOS-465 100 μM) was added to verify the properties of the IPSCs To evaluate the intrinsic membrane properties of PV interneurons and SST interneurons in the ACC whole-cell recordings were performed in current-clamp mode and spikes were elicited by incrementally increasing the current injection in 20 pA steps Patch pipettes were filled with an internal solution containing the following 120 mM CsMeSO3 The laser intensity was adjusted to achieve a maximal response without overstimulation and 0.5 ms pulses of blue light was applied with the cells clamped at −65 mV An additional 1 μM tetrodotoxin (TTX) and 100 μM 4-AP were added to determine whether the light-evoked PSCs were excitatory or inhibitory To investigate the role of the Kv11.3 channel in action potentials 1-[2-(6-methyl-2-pyridyl)ethyl]-4-(4-methylsulfonylaminobenzoyl) piperidine (E-4031 Stock solutions of E-4031 (100 µM) were prepared in DMSO and diluted in ACSF ensuring that the final DMSO concentration did not exceed 0.1% which had no detectable effect on the membrane potential or membrane currents To record Kv11 currents from PV or SST-positive neurons in the ACC 50 μM D-AP5 and 10 μM bicuculline were added to high-K+ intracellular solutions (10 mM KCl and no Ca2+) The use of high-K+ extracellular and low-K+ intracellular solutions allowed the K+ currents to be recorded as large The signals were filtered at 3 kHz and digitized at 10 kHz in experiments for Kv11 current measurements The activation curve of the Kv11 channels was extracted by dividing the peak amplitudes of the E-4031-sensitive tail current traces at 0.5 ms after the voltage was stepped to −100 mV ACC tissues were rapidly dissected from the cortices of Shank3 KO and WT mice using freshly frozen mouse brain samples and sequencing were performed by Gene Denovo Biotechnology Co China) following the 10× Genomics (USA) guidelines the tissues were homogenized in ice-cold homogenization buffer (0.25 M sucrose The homogenates were sequentially filtered through a 70 µm cell strainer to isolate the nuclear fraction The nuclear fraction was mixed with an equal volume of 50% iodixanol and carefully layered onto a discontinuous gradient of 30–33% iodixanol This mixture was centrifuged at 10,000 × g for 20 min at 4 °C After removing the myelin layer from the top of the gradient nuclei were harvested from the interface between the 30% and 33% iodixanol layers The isolated nuclei were resuspended in nuclei wash and resuspension buffer (0.04% bovine serum albumin and 0.1 mM PMSF protease inhibitor in phosphate-buffered saline) and pelleted by centrifugation at 500 × g for 5 min at 4 °C To remove cell debris and large aggregates the nuclei suspension was further filtered through a 40 µm cell strainer The nuclei concentration was quantified using trypan blue exclusion staining and a hemocytometer and adjusted to 800–1200 nuclei/µL and library preparation were performed according to the 10× Genomics protocol Cellular suspensions were loaded onto a 10× Genomics GemCode single-cell instrument which generated single-cell Gel Bead-in-EMulsion (GEMs) Libraries were generated and sequenced from the cDNA using Chromium Next GEM Single Cell 3′ Reagent Kits v3.1 The cell-by-gene matrices were produced via UMI counting and cell barcodes calling The resulting matrices were individually imported into Seurat (version 3.1.1) for downstream analysis The expression levels of each gene in a given cluster were compared against those in the remaining cells using the Wilcoxon rank sum test60 The mice were deeply anesthetized with isoflurane and transcardially perfused with 0.01 M PBS (pH: 7.4) followed by 4% paraformaldehyde in 0.01 M PB Brains were removed and fixed in 4% paraformaldehyde for 2 h and then sequentially incubated in 10% The tissues were frozen and cut into 10 μm thick coronal sections using a cryostat (Leica) RNAscope in situ hybridization was performed using the RNAscope™ Multiplex Fluorescent Reagent Kit v2 (ACD) for fixed-frozen tissue following the manufacturer’s instructions the sections were dehydrated in sequential incubations with different concentrations of ethanol followed by 30 min of Protease III treatment and washing in ddH2O with each target incubated with a specific dye Hoechst counterstaining and mounting were performed with antifade mounting medium The fluorescence intensity was analyzed via ImageJ software The total number of puncta was used to normalize mRNA expression Single PV-positive or SST-positive neurons in the ACC with red fluorescence signals were aspirated using a patch clamp Each single cell was ejected into a tube with 5 µL of 0.01 M D-PBS Total RNA and cDNA from single neurons were isolated using a REPLI-g® WTA single-cell kit (Qiagen) according to the manufacturer’s instructions qRT‒PCR was performed with SYBR® Premix Ex Taq (ABclonal) in a CFX96 Touch Real-time PCR Detection System (Bio-Rad) The mean expression value of the control group was calculated The data of the experimental group and control group were divided by this mean and the resulting values were used for statistical analysis An AAV CRISPR/Cas9 approach was used to conduct the in vivo Kcnh7 knockdown experiments Single guide RNAs (sgRNAs) with high specificity and high efficiency were computationally identified in sgRNA libraries for genome-wide CRISPR knockout screening Three U6-sgRNA (FE) gene fragments with the F + E tracrRNA backbone were synthesized by Integrated DNA Technologies (sequences are provided below These fragments were subsequently cloned and inserted into the pX552-EGFP plasmid via In-Fusion Snap assembly master mix (Takara resulting in the construct pX552-3xsgRNA(FE)-EGFP The AAV vectors were serotyped with PHP.eB coat plasmid #112867) and pUCmini-iCAP-PHP.eB (Addgene plasmid #103005) were cotransfected into HEK293T cells using polyethylenimine (Cat the cells were harvested by centrifugation at 5000 × g for 10 min at 4 °C The AAV vectors in the media were precipitated with 8% PEG8000 (89510-1KG-F The cell pellets and vectors precipitated from the media were resuspended in digestion buffer containing 500 mM NaCl Novoprotein) was added to the digestion buffer and the mixture was incubated at 37 °C for 1 h the mixture was centrifuged at 2000 × g for 10 min and the supernatant was added to a 39 mL ultracentrifuge tube with discontinuous gradients of 15% Ultracentrifugation was performed at 350,000 × g for 2.5 h at 18 °C Fractions (5 ml) from the 40% layer and 40–60% interface were collected and desalted using a 100 kDa cutoff ultrafiltration tube (15 ml The buffer was exchanged four times with 1× PBS containing 0.001% Pluronic F-68 AAV titers were determined via qRT‒PCR using the primers for ITR Forward primer: 5′-GGAACCCCTAGTGATGGAGTT-3′; Reverse primer: 5′-CGGCCTCAGTGAGCGA -3′ gagggcctatttcccatgattccttcatatttgcatatacgatacaaggctgttagagagataattggaattaatttgactgtaaacacaaagatattagtacaaaatacgtgacgtagaaagtaataatttcttgggtagtttgcagttttaaaattatgttttaaaatggactatcatatgcttaccgtaacttgaaagtatttcgatttcttggctttatatatcttgtggaaaggacgaaacaccgCTGGGCAATATCATGCCTCTgtttaagagctatgctggaaacagcatagcaagtttaaataaggctagtccgttatcaacttgaaaaagtggcaccgagtcggtgct AaggtcgggcaggaagagggcctatttcccatgattccttcatatttgcatatacgatacaaggctgttagagagataattagaattaatttgactgtaaacacaaagatattagtacaaaatacgtgacgtagaaagtaataatttcttgggtagtttgcagttttaaaattatgttttaaaatggactatcatatgcttaccgtaacttgaaagtatttcgatttcttggctttatatatcttgtggaaaggacgaaacaccGAATATCGGGTTGACCCTCTCgtttaagagctatgctggaaacagcatagcaagtttaaataaggctagtccgttatcaacttgaaaaagtggcaccgagtcggtgct AaggtcgggcaggaagagggcctatttcccatgattccttcatatttgcatatacgatacaaggctgttagagagataattagaattaatttgactgtaaacacaaagatattagtacaaaatacgtgacgtagaaagtaataatttcttgggtagtttgcagttttaaaattatgttttaaaatggactatcatatgcttaccgtaacttgaaagtatttcgatttcttggctttatatatcttgtggaaaggacgaaacaccgATGCCCTCCGTATGCTACAGgttttagagctagaaatagcaagttaaaataaggctagtccgttatcaacttgaaaaagtggcaccgagtcggtgc Statistical significance was considered when p < 0.05 Further information on research design is available in the  Nature Portfolio Reporting Summary linked to this article Neural circuit mechanisms of social behavior Sociability and preference for social novelty in five inbred strains: an approach to assess autistic-like behavior in mice Impact of the circadian nuclear receptor REV-ERBα in dorsal raphe 5-HT neurons on social interaction behavior Modeling SHANK3-associated autism spectrum disorder in Beagle dogs via CRISPR/Cas9 gene editing Pharmacological (ethanol) and mutation (sam2 KO) induced impairment of novelty preference in zebrafish quantified using a new three-chamber social choice task Beyond the three-chamber test: toward a multimodal and objective assessment of social behavior in rodents Anterior cingulate cortex dysfunction underlies social deficits in Shank3 mutant mice Shank3 mutant mice display autistic-like behaviours and striatal dysfunction A role for the macaque anterior cingulate gyrus in social valuation Neural mechanisms of social cognition in primates Abnormal functional connectivity of default mode sub-networks in autism spectrum disorder patients Decreased cortical thickness in the anterior cingulate cortex in adults with autism Cell-type-specific effects of somatostatin on synaptic transmission in the anterior cingulate cortex Dynamics of a disinhibitory prefrontal microcircuit in controlling social competition Morphine coordinates SST and PV interneurons in the prelimbic cortex to disinhibit pyramidal neurons and enhance reward Interneuron-specific plasticity at parvalbumin and somatostatin inhibitory synapses onto CA1 pyramidal neurons shapes hippocampal output rate and bursts of hippocampal place cells by dendritic and somatic inhibition GABAergic interneurons in the neocortex: from cellular properties to circuits Research review: constraining heterogeneity: the social brain and its development in autism spectrum disorder Targeted massively parallel sequencing of autism spectrum disorder-associated genes in a case control cohort reveals rare loss-of-function risk variants ERG channels regulate excitability in stellate and bushy cells of mice ventral cochlear nucleus A disinhibitory microcircuit mediates conditioned social fear in the prefrontal cortex A molecularly defined amygdala-independent tetra-synaptic forebrain-to-hindbrain pathway for odor-driven innate fear and anxiety Gamma frequency entrainment attenuates amyloid load and modifies microglia SHANK proteins: roles at the synapse and in autism spectrum disorder Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3 Autism-associated insertion mutation (InsG) of Shank3 Exon 21 causes impaired synaptic transmission and behavioral deficits Altered striatal synaptic function and abnormal behaviour in Shank3 Exon4-9 deletion mouse model of autism Adult restoration of Shank3 expression rescues selective autistic-like phenotypes Altered mGluR5-Homer scaffolds and corticostriatal connectivity in a Shank3 complete knockout model of autism Mice with Shank3 mutations associated with ASD and Schizophrenia display both shared and distinct defects Integrating single-cell transcriptomic data across different conditions Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage Monosynaptic circuit tracing with glycoprotein-deleted rabies viruses Interneuron cell types are fit to function Oxytocin administration in neonates shapes hippocampal circuitry and restores social behavior in a mouse model of autism Neural correlates of novel object and novel location recognition behavior in the mouse anterior cingulate cortex A systematic review of the development and application of home cage monitoring in laboratory mice and rats Neuronal diversity and temporal dynamics: the unity of hippocampal circuit operations Sleep and movement differentiates actions of two types of somatostatin-expressing GABAergic interneuron in rat hippocampus Topography in the projections of lateral posterior thalamus with cingulate and medial agranular cortex in relation to circuitry for directed attention and neglect A translational study on looming-evoked defensive response and the underlying subcortical pathway in autism Reduced modulation of thalamocortical connectivity during exposure to sensory stimuli in ASD Long-range inhibitory intersection of a retrosplenial thalamocortical circuit by apical tuft-targeting CA1 neurons Long-range inhibition from prelimbic to cingulate areas of the medial prefrontal cortex enhances network activity and response execution Brain-wide mapping of inputs to the mouse lateral posterior (LP/Pulvinar) thalamus-anterior cingulate cortex network eIF2α controls memory consolidation via excitatory and somatostatin neurons Loss of MeCP2 in parvalbumin-and somatostatin-expressing neurons in mice leads to distinct rett syndrome-like phenotypes Dysfunction of cortical GABAergic neurons leads to sensory hyper-reactivity in a Shank3 mouse model of ASD A whole-brain atlas of monosynaptic input targeting four different cell types in the medial prefrontal cortex of the mouse ExBoX - a simple Boolean exclusion strategy to drive expression in neurons Excitatory and inhibitory synaptic imbalance caused by brain-derived neurotrophic factor deficits during development in a valproic acid mouse model of autism Kv11 (ether-à-go-go-related gene) voltage-dependent K(+) channels promote resonance and oscillation of subthreshold membrane potentials EmptyDrops: distinguishing cells from empty droplets in droplet-based single-cell RNA sequencing data Multilineage communication regulates human liver bud development from pluripotency Download references Guoping Feng (Massachusetts Institute of Technology) for his suggestions and conversation This study was supported by the Natural Science Foundation of China (32394032 to S.W.) the Science and Technology Innovation 2030 Project of China (2021ZD0201005 to S.W.) the Natural Science Foundation of China (82221001 to S.W. the Shaanxi Provincial Key Research and Development Program (2020ZDLSF01–09 to S.W.) the Shaanxi Provincial Innovation Chain Project of Key Industries (2023-ZDLSF-47 to W.W.) the Shaanxi Province Key Research and Development Plan (2024SF-YBXM-033 the Joint Founding Project of Innovation Research Institute the Shanghai Pujiang Program (22PJ1415500 to Q.C.) the Zhongshan Municipal Bureau of Science and Technology Grant (CXTD2022013 to Q.C.) Guangdong Province High-level Innovative Research Institute project (2021B0909050003 and Innovation Team Accredited by Shaanxi Science and Technology (2022TD-49 to W.W.) We thank Analysis & Testing Laboratory for Life Sciences and Medicine of Fourth Military Medical University for their assistance with behavioral test We thank American Journal Experts for language editing (Certificate NO: 9183-20FC-2A00-204D-DD6P) These authors contributed equally: Chuchu Qi performed the experiments and analyzed the data The authors declare no competing interests Nature Communications thanks the anonymous reviewers for their contribution to the peer review of this work Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Download citation DOI: https://doi.org/10.1038/s41467-025-59473-z Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article Sign up for the Nature Briefing newsletter — what matters in science England’s governing body for professional and amateur soccer will no longer allow transgender-identifying males to compete in women’s soccer starting next month The English Football Association (EFA) said the change will take effect on June 1 It comes in response to a United Kingdom Supreme Court ruling last month that the definition of woman under the Equality Act of 2010 is based on anatomical sex “As the governing body of the national sport, our role is to make football accessible to as many people as possible, operating within the law and international football policy defined by UEFA and FIFA,” EFA said in a statement.  which allows transgender women to participate in the women’s game was based on this principle and supported by expert legal advice.”  EFA expressed empathy for transgender-identifying people and said it hopes to keep them involved with the sport.  and our position has always been that if there was a material change in law or the operation of the policy in grassroots football then we would review it and change it if necessary,” EFA said.   “We understand that this will be difficult for people who simply want to play the game they love in the gender by which they identify and we are contacting the registered transgender women currently playing to explain the changes and how they can continue to stay involved in the game.”  EFA isn’t the only sporting body in the United Kingdom to change its transgender athlete policy since last month’s ruling. The Scottish Football Association did the same last week and the U.K.’s Ultimate Pool changed its policy the week prior.  “We respect that some people within the pool community may find the changes challenging,” Ultimate Pool posted on X last month we are committed to being empathetic to all members of our community and we expect all members of our community to reflect this.”  Ultimate Pool made the change after Harriet Haynes and Lucy Smith competed against each other in the championship round of its Women’s Pro Series event last month Haynes defeated Smith and got the British equivalent of $2,300 in prize money.   Protesters at the event held signs saying, “Save women’s sport” and “He’s a man,” as The Lion reported.  A February 2025 YouGov poll found 74% of Britons oppose letting transgender-identifying male athletes compete in women’s sports A school sports coach is seeking advice after being invited to a pool party by his team While he believes that the get-together is inappropriate and uncomfortable the teachers and parents do not see the issue he is wondering how he should politely decline the invitation without making it into a big deal or is he right to feel uncomfortable about attending Sharing his predicament to the subreddit r/Teachers the coach admitted that he found it bizarre that none of the parents or teachers believed that extending the invite to him would be inappropriate he feared that sharing his concerns would land him in further trouble “My main problem is I feel even saying that it may be inappropriate for me to come to the party would make the parents think 'Why is it inappropriate?’ Which then makes me look like I have a perverted mind.” He explained that last year’s get-together was not an issue given that the team invited him bowling and no one was in a bathing suit RELATED: Male Teacher Is Uncomfortable With School’s New Rule To Close & Lock The Classroom Door At All Times — Even If There's One Female Student In The Classroom With Him but they should know in today's age how this would be inappropriate.” The coach also feared that if he attended the pool party word would spread among other school parents who might complain He asked others what the best approach to the situation would be “I am a male and I coached 7th and 8th grade girls' volleyball for 7 years. I would thank them for the offer and kindly decline You don't need to give a reason,” one Redditor suggested We understand and will follow suit,” another wrote “I’m a male coach of a high school girls team I got invited to a grad party last year that was a pool party and got there right when it started when no one was in the pool let alone in bathing suits yet Had a great time and left,” another user shared While no one would argue that the coach's presence is no different than if he were at a public pool or at a beach, but it's important to remember that even though he is not technically working during the party, he is still there in a professional capacity. That means he needs to put his coach hat on and keep his workplace boundaries in place Kevin Chapman, Ph.D., clinical psychologist and founder of The Kentucky Center for Anxiety and Related Disorders, told True Sport we have unrealistic expectations for coaches people expect coaches to parent their kids Coaches are responsible for enhancing the development of the student athlete by teaching them discipline which are those skills that they won’t learn necessarily in other settings And that’s why being an athlete is so incredibly rewarding: If you have the right coaches None of those expectations for coaches include attending a pool party that makes their relationship seem more familiar than it should RELATED: Mom Expresses Concern After Her 7-Year-Old Daughter Drove To School Alone In A Car With A Male Teacher She’s Never Met While extending the invitation to the coach was a kind gesture a pool party is not exactly the right setting He needs to do what he feels is right for him as a professional coach and as a man If his team wants to thank him for a great season, it would be better to organize a casual team dinner where his boundaries and comfort would not be in jeopardy it is a good thing that the coach recognized the bizarre nature of the setting for a team gathering Not only does he have integrity that makes him a good person but it most likely makes him one great coach that his team — and their parents — can trust RELATED: Male Substitute Teacher Is Fired After A Student Hugs Him Megan Quinn is a staff writer with a bachelor's degree in English and a minor in Creative Writing She covers news and lifestyle topics that focus on justice in the workplace © 2025 by Tango Publishing Corporation All Rights Reserved Class of 2026 catcher prospect Francisco Rivero was recently selected the 5A Sonoran Player of the Year after powering Canyon del Oro to an impressive 10-game winning streak to end April Rivero went an incredible 18 for 29 (.621) with five home runs and 23 RBIs in that 10-game stretch that was key to the Dorados’ current 24-5 record and being in the second round of the 5A state playoffs in a 10-6 win over Catalina Foothills on April 22 Rivero is the Jet Sports Training Male Athlete of the Month The former Sunnyside Little League standout who was part of the team that came a win away from the Little League World Series in 2019 spent his first two years of high school in the Dominican Republic training with the hope of being selected in the international draft The family chose to have him finish his high school experience in Tucson and potentially either play in college or go to a major-league organization after graduating from CDO next year Rivero is batting .513 overall with seven home runs and 36 RBIs FOLLOW @JAVIERJMORALES ON TWITTER He became an educator five years ago and is presently a special education teacher at Gallego Fine Arts Intermediate in the Sunnyside Unified School District A unique website covering youth and high school sports and Pima Community College and University of Arizona athletics combining in-depth analysis and professional reporting from award-winning journalists This website is using a security service to protect itself from online attacks The action you just performed triggered the security solution There are several actions that could trigger this block including submitting a certain word or phrase You can email the site owner to let them know you were blocked Please include what you were doing when this page came up and the Cloudflare Ray ID found at the bottom of this page Georgia Gov. Brian Kemp on Monday signed into law a bill that prohibits males who claim to be females from participating in women’s and girl’s sports. The measure passed the Republican-controlled state House and Senate largely along party lines with a total of just five Democrats supporting the bill The new law bars males from participating on any K-12 or collegiate level female-only sports teams Girls are also prohibited from participating on male teams unless a corresponding female team does not exist private schools that participate in competitions and higher education institutions are required to separate multiple occupancy restrooms and facilities by sex Dig deeper: Read Christina Grube’s report about the U.S House of Representatives sending a subpoena to fencing officials in regards to athletes who call themselves transgender If you enjoyed this article and would like to support WORLD's brand of Biblically sound journalism, click here Lauren Canterberry is a reporter for WORLD She graduated from the World Journalism Institute and the University of Georgia with a degree in journalism She worked as a local reporter in Texas and now lives in Georgia with her husband An actual newsletter worth subscribing to instead of just a collection of links Please wait while we load the latest comments.. Please register, subscribe, or log in to comment on this article Boyd McWhorter Male Scholar-Athlete of the Year4/30/2025 | Baseball Please press and hold the button until it turns completely green If you believe this is an error, please contact our support team. 147.45.197.102 : f6390134-57be-4f56-b9e6-6e102ea6 I wouldn’t be the best at beard maintenance I cut a few hairs that refuse to do anything but stand horizontally or vertically out from my face Sometimes I look like I’ve been receiving mild electric shocks while I was asleep In the bathroom I have a little beard brush yoke and a dust buster which I bought to get rid of the detritus and to keep my marriage stable: hairs are a contentious issue the beard will take on an odd shape and I’ll start to look like that cliched image of a crazy old fellah who has been trapped alone on a desert island for years It always strikes me as somewhat miraculous that a barber can transform the unruly mess on my chin into something neat and pretty presentable; and do it while having shouted conversations with some of the other people there I tend not to engage in this talk because, obviously, I have to keep my chin still, but also because – in my experience – the conversations are almost exclusively about football about which I have an almost total ignorance an entry method for serious discussions or gentle joshing it also seems to be a way of comforting the clients Because the clients are vulnerable: sitting powerless while another man deploys razor-sharp implements around them The clients also have to reveal thoughts about their own appearance: how they want their hair or beard talking about this kind of thing might make some men uncomfortable They might not seem to be obviously connected but barber shops make me think of record shops I don’t mean the big high-street multiples flogging T-shirts games and over-priced vinyl reissues of Dark Side of the Moon and Rumours where at least half the stock is second-hand and it’s taken on trust that these records will be in playable condition These kinds of places are all over country and it’s become a habit for me to visit the good ones in various towns and cities the owners of these shops may well object to that depiction: they’ll argue that their clientele consists of all ages and genders But I would guess that their core cohort of customers is made up of men of a certain age The proprietors of these shops – in my experience – are all men like me But that’s not a bad thing. I go in and have a bit of a dig around. Sometimes, the owner is having a conversation with a customer. It’s usually, though not exclusively, about music the owner may well have a short chat with me as well [ ‘That’s a Tesla,’ my daughter said. ‘We don’t like them’Opens in new window ] And I always find the experience comforting. The phrase “male space” can come with all sorts of negative connotations, and for all sorts of justifiable reasons. Yet that’s not always the case. Young men are starved of role models. And the few who wish to promote themselves as exemplars all too often want to define “maleness” as something that is purely oppositional: being a man means being angry at the shape of the world. But there are alternatives. Go for a haircut, buy a few records. You could do a lot worse. Facebook pageTwitter feed© 2025 The Irish Times DAC Thank you!We have emailed you a PDF version of the article you requested You can also addnewsletters@iflscience.comto your safe senders list to ensure you never miss a message from us IFLScience HomeSperm-Blocking Male Contraceptive Could Hit The Market "As Soon As 2028" After Promising 2-Year Trial ResultsComplete the form below to listen to the audio version of this article IFLScience needs the contact information you provide to us to contact you about our products and services You may unsubscribe from these communications at any time For information on how to unsubscribe, as well as our privacy practices and commitment to protecting your privacy, check out ourPrivacy Policy IFLScience HomeJoin for Exclusive emailLaura is an editor and staff writer at IFLScience. She obtained her Master's in Experimental Neuroscience from Imperial College London. emailEditedbyKaty EvansKaty Evans FacebookemailKaty is Managing Editor at IFLScience where she oversees editorial content from News articles to Features the developers say it blocks sperm transit without affecting ejaculation or sensation The makers of a non-hormonal male contraceptive just announced a key milestone during their first human clinical trials with the treatment demonstrating safety and efficacy at the two-year mark believe their product could come to market before the end of the decade The treatment is called ADAM™ and it works by temporarily blocking the transit of sperm through the vas deferens the long muscular tube that connects the testes and urethra.  The injectable hydrogel, administered within a 30-minute appointment prevents sperm movement without blocking ejaculation or affecting sexual sensation the gel will harmlessly liquefy and sperm flow will be restored as Contraline CEO Kevin Eisenfrats told IFLScience “No other method can provide long-lasting (two years) I believe we're now closer than ever to figuring out the science piece for those in possession of a male reproductive system There are even other approaches similar to ADAM™ These approaches are appealing for the same reasons as the female contraceptive implant or IUD – once it’s in place you theoretically don’t have to think about it again for months or even years There’s no remembering to take a pill every day Eisenfrats believes that even within this field “Other vas-occlusive methods are designed to be permanent and require a second procedure to remove the implant the harder it becomes to successfully reverse Vas-occlusion is nice in that it is 'set and forget' and the mechanism of action is to block sperm right at the source without affecting anything else in the body,” he told IFLScience Ultimately, the goal would be for male and female contraceptives to be available in a similar range of choices “We understand that not every guy may want to get a procedure “We need to offer men a bunch of options.” Contraline’s latest announcement is an update on the first-in-human trials of ADAM™ now that some patients have reached the two-year milestone Two patients have been shown to have azoospermia – an absence of viable sperm in their semen – 24 months after the administration of the hydrogel Other patients who were recruited later are still in the trial with successful contraceptive efficacy being shown at 12 No participants have experienced serious adverse effects from the treatment meaning the study team is confident in progressing to Phase 2 trials Eisenfrats told us they hope to recruit 30 people at a minimum “We believe ADAM™ will be available by the end of this decade and potentially as soon as 2028,” he said.  Recruitment is unlikely to be a major barrier if the interest in Contraline’s products is any indication “[We] have a waiting list of 15,000+ men (without any advertising/marketing) and what we have found is that a large percentage of men want a quick and minimally invasive procedure like ADAM™ that offers years of non-hormonal birth control,” Eisenfrats told IFLScience If ADAM™ were to progress successfully through all the stages of a clinical trial “Researchers have been working on male contraception for 60+ years but there has never been a method that has shown full safety and reversibility beyond Phase 2 trials,” said Eisenfrats “With recent advancements in drug development and medicinal chemistry I believe we're now closer than ever to figuring out the science piece.” maybe now is the right time – perhaps ADAM™ will be the treatment that finally breaks the deadlock and sets us on the path to a greater range of male contraceptive options “[I] also do believe men are more ready for new male contraceptives now than they were 20 There's no question that there is demand from consumers.” medicineRFK Jr Calls For Placebo Trials For All New Vaccines. Experts Say You Can’t – And Shouldn’t – Do That1 hour agolink to article healthMaking Art For 45 Minutes A Day Can Lower Stress Levels, Even If It’s Rubbish23 hours ago130link to article Biofluorescence vs Bioluminescencelink to article T. Rex Leather, Glow-In-The-Dark Gas Clouds, And Musical Sea Lionslink to article © 2025 IFLScience. All Rights Reserved. RSS but revolutionary test has been developed to help unravel the mystery of infertility among men who display normal semen parameters Infertility affects an estimated one in every six couples worldwide with male factor prevalent in about half of those cases For many of those men who have seemingly otherwise healthy sperm the anguish of their condition is deepened by the perplexity of an underlying reproductive dysfunction called CatSper-related male infertility there are defects in the chemosensory CatSper channels of sperm that allows them to move in a whip-like fashion essential to penetrate the coating of a female egg There are many case histories in fertility treatment of couples where conventional IVF and intrauterine insemination (IUI) has failed but where single sperm injection of an egg – known as intracytoplasmic sperm injection The 2025 Congress of the Asia Pacific Initiative on Reproduction (ASPIRE) in Singapore today heard of a breakthrough diagnostic test for CatSper-related male infertility that has delivered remarkable validation results a pathfinding researcher in the Centre of Reproductive Medicine and Andrology at the University Hospital Münster in Germany said a desire to better understand the role of CatSper in male fertility led to the development of the test as a novel diagnostic tool "Sperm generate a powerful swimming behaviour known as hyperactivation a specific calcium channel found exclusively in the tail of sperm sperm cannot hyperactivate and the egg remains unfertilised "The CatSper test is a simple procedure with a standard semen analysis It quickly and reliably determines whether a CatSper defect is present enabling evidence-based therapy choices for couples with unexplained infertility "We used it to screen 2,386 patients as a proof-of-concept study It showed exceptional sensitivity and specificity of the test with precise assessment of CatSper function "It has transformed the CatSper test from a scientific possibility into a diagnostic device for everyday clinical practice "For the first time it allows diagnosis of CatSper defect in male infertility potentially preventing couples from embarking on unsuccessful medically assisted reproduction attempts such as IUI and IVF "This has the potential to save patient expense and possible adverse effects of hormonal stimulation in IVF for the female partners "The time factor of going through cycles of IVF is also an important consideration for couples striving to conceive especially when almost every day counts among women in their thirties and forties when fertility is in decline "The CatSper test can guide clinicians toward more personalised The ASPIRE Congress in Singapore has attracted around 2,000 scientists nurses and counsellors in fertility health to address latest global advances in assisted reproduction ★ Poor ★ ★ Promising ★★★ Good ★★★★ Very good ★★★★★ Exceptional Vietnam Investment Review under the Ministry of Finance Advertisement  | Contact us CHARLOTTESVILLE, VA – The Charlottesville Police Department is asking for assistance in locating Joshua Allen Fitzgerald, who was last seen on April 29th, 2025, at approximately 1100 in the area of the 100 block of Burnet Street.adButlerLazyLoad("1677532145205220530",100,["688449","688449","688449"],"177030"); Joshua Allen Fitzgerald, born October 3, 1989, is a white male who stands approximately 5’5”, weighs approximately 315 lbs., with brown eyes, and balding red hair. It has been reported that Joshua has recently shaved his beard. Anyone with information regarding the whereabouts of Joshua Fitzgerald is asked to contact Detective J. Houchens at (434) 970-3676. Dori Zook is a reporter at NewsRadio WINA and CvilleRightNow.com. She can be reached at dzook@charlottesvilleradiogroup.com or by phone at 434-977-6397. UVA Alert Monday morning from self-inflicted gunshot incident The Nelson County Sheriff and The AWARE Foundation of Virginia asking help finding a missing Nelson County teen. On Friday, Governor Youngkin took final actions to complete the legislative session for 2025 in the General Assembly. Charlottesville Police Chief Kochis presented to City Council last night a plea to implement a one-year program that would combine department program data, asking Council for a $150,000 appropriation. Virginia’s standing as one of the top states in the nation for patient safety in hospital settings has again been affirmed in the Leapfrog Group Hospital Safety Grade rankings. Your GPS did not respond. Be sure you have your GPS enabled and try again. The Hidden Social Lives of Male African Elephants male African elephants turn out to have surprisingly rich social lives By Caitlin O'Connell edited by Kate Wong Young male elephant (right) greets an older male (left) I woke up in the research tower to a soft exhale and then a trickle of water at the waterhole below The full moon hung low and dim in the west I wondered which of my elephant study subjects had come to drink at this hour and they typically don’t show up here at the Mushara waterhole in Namibia’s Etosha National Park until at least 11 A.M But the full moon does funny things to elephant movements I rolled over in my sleeping bag to look out at the visitors Two bulls stood at the source of the spring and the younger one had his back toward me Focusing my binoculars on the edges of their ears I could see a telltale tab on the left ear of the older one and two sharp cuts on the right ear of the younger one My team and I had been following the older bull Abe hadn’t visited Mushara for the entire 2024 field season his tusks having grown out nicely after breaking a few years ago not only because I enjoyed observing his endearing patience with younger males but also because he was one of my most important study subjects If you're enjoying this article, consider supporting our award-winning journalism by subscribing By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today Abe was an integral member of a social group whose behavior I had been focused on documenting for years African elephants have matriarchal societies in which elder females lead families made up of their female relatives and young to water Most of what we know about elephant social behavior has come from studies of these female-led family groups leave their family group as they reach adolescence and go off to live as bachelors little research was conducted on the social dynamics of adult male elephants because they were thought to be largely solitary It seemed safe to assume their social lives were simple with none of the complex rules and rituals seen in the family groups When young male elephants visit the waterhole with their families they get to interact with bachelor males and learn who they can trust when the time comes to set out on their own But research that I and other scientists have been carrying out is finally starting to fill this gap in our understanding of elephant behavior Our long-term observations of Abe and the other males who have visited Mushara over the past two decades reveal that male elephant societies have incredibly intricate rules are sensitive social animals that crave companionship and need emotional support Their experiences of growing up parallel those of human males who undergo similar social changes and pressures as they enter the adult world—from backslapping in the bar to defending another’s honor by taking on a bully Having a social network of other trusted males may be important for navigating the transition to adulthood These findings indicate that this highly intelligent species is even more socially complex than we previously understood it to be—and could inform vital efforts to manage and protect these animals in the wild and in captivity One of our most exciting discoveries concerns vocal communication Researchers have long known that female African elephants use vocalizations to coordinate group behavior In family groups gathered at a water source align herself toward the direction she wants to leave in and then rumble a call to action—“Let’s go!” It’s understandable why families would engage in this behavior Coordinating a group of 20 to 40 or more elephants isn’t a simple task Using a vocal tool to call the group into line is well documented in other species one ape’s grunt triggers another to grunt until consensus is reached and all leave the area together who sneeze to reach consensus about departure engaged in similar vocal coordination was unclear I suspected based on a handful of observations that the male elephants were indeed communicating in this way but I needed a larger sample to prove the pattern was real The male elephants that congregate at Mushara tend to be most vocal at night which also happens to be when conditions are best for recording their sounds And so I found myself working the late shift during our field seasons timing my observation sessions to when the bachelors were chattiest Recently my collaborators and I published a paper containing the fruits of this labor We were able to show that when a group of male associates leaves the waterhole one of the core members of the group flaps his ears gently while emitting a long low rumble—the “let’s go” signal the others respond with their own rumble while following the instigator away from the water each waiting for another to finish their call before contributing their own say in the matter The paper marks the first time such coordination has been documented in male elephants as well as the first time vocalizations have been shown to trigger action within male groups When I first witnessed groups of bonded males engaging in this kind of vocal ritual Why would these males want to leave together in which the dominant females who determine the group’s movements are acting in the interests of their close relatives male elephants have traditionally dispersed far from their natal group This arrangement meant that they were often not related to the other males with whom they associated Bonded males arrive at the waterhole together using vocal coordination (top) Such groups also coordinate their departure this way After a socially connected male initiates the "let's go" rumble the rest of the group members take turns rumbling their assent as they walk away together (bottom) Leaving together implies they’ll be sharing resources at their next destination I had seen powerful older males shake full-grown acacia trees to make the seed pods—a favorite food of elephants—shower down to the ground On some of these occasions a younger bull or two came in to sample the spoils Usually established group members would shove chancers away from the prized pods but they tolerated ones who had arrived at the invitation of the older male There had to be some advantage to older males inviting younger males to join them in their travels Why would older males want to share with younger associates when they didn’t have to What advantage was there in staying together Could these males want the companionship even if it meant sharing Did male elephants form even tighter-knit groups than previously thought Our observations of vocal coordination among the Mushara males sparked many such questions Studies of other aspects of their behavior have led to some answers the most obvious ritual exchange between male associates is what we call the greeting A younger individual often initiates the greeting placing the tip of his trunk either within or just at the entrance to the mouth of a buddy or an older male The greeting is typically reciprocated—unless the recipient is very high-ranking the gesture is more like a salute of one or more individuals to a general or a kiss of a royal’s ring the behind-the-scenes decorum in male engagement is so fine-tuned it’s like the list of steps for having tea with the queen We can look at the ritual of play for another example play is important for building trust and developing skills needed to compete for mates later in life Our data show that individuals of all ages within a bonded group of male elephants solicit play with other individuals in equal amounts younger elephants must wait until the older one initiates the play bout Such conventions are hallmarks of a very sophisticated society Each ritual helps to reinforce the rules of engagement within the group This is all very much in keeping with what we already know about elephant intelligence empathy and sense of self based on studies of the female-led family groups What’s new and surprising here is that we’re documenting these group dynamics in males who were long thought to be mostly solitary And not only do we see rituals in these male groups but the groups also engage in behaviors indicative of a hierarchical social structure In our study of vocal coordination triggering group action a case of active leadership in male elephants An active leader is one who solicits others to follow him and exerts social influence through means of dominance ranks passive leadership might occur when an older individual is followed by an uninvited youngster the older individual often signals his displeasure by turning around and shaking his head This response usually deters unwanted companions but it depends on how determined the younger one is My colleagues and I got our first inkling of male leadership in the Mushara social club back in 2004 A dominant bull we named Greg seemed to call the shots Long conga lines of males of all ages and sizes followed Greg in and out of the waterhole He was beloved by his underlings and either feared or revered by many of his contemporaries and elders He led with a carrot-and-stick style—forgiving of the transgressions of youngsters but hard on his contemporaries Bachelor males of all ages benefit from socializing with other males Such interactions can lead to lifelong companionship When Greg decided it was time to depart Mushara turn in the direction he planned to go and invite the others to leave with a “let’s go” rumble ritualized rumbles from the rest of the group On occasion Greg would give some of the youngest ones a gentle shove to expedite any deliberations The simple act of inviting others to leave with him showed that Greg and males like him actually make an effort to keep the group together This behavior is news because leadership in male social groups is not a given in mammals A dominant male baboon has seemingly no interest in leading his underlings His primary interest is in securing the best resources for himself It’s the female baboons who do the leading as I observed Greg and the other males at the Mushara I thought about why male elephants might come together in these groups and coordinate their actions Forming coalitions could be one explanation Ritualized vocal coordination could solidify and reinforce bonds the elephants needed to work together to intimidate or push off rival males An unwanted individual could suddenly find himself facing a wall of imposing elephant ears It would be a lot easier to gain access to the best resources as a group than for an individual to defend them on his own And considering that the Mushara waterhole was one of only three water points in the region I couldn’t help wondering whether there were other factors in play Perhaps there was a reproductive advantage for older males who adopted the emotionally needy underlings when elephants were free to roam in an environment unobstructed by fences built by humans male elephants left their natal families during their coming-of-age testosterone spikes and were thought to settle far from their genetic line This dispersal pattern maintained the diversity of the elephant gene pool and it implied that males found socializing together were not related But the realities of modern Africa are such that elephant movements are often impeded by human activity and young males can’t move as far away from their families as they might have in the past Older male Abe (front) and younger male (back) listen for the arrival of their companions This ecological shift increases the odds that a bachelor will encounter his male relatives on the landscape after dispersing from his natal group If males within bonded groups were in fact related to one another their genetic line would have a better chance of getting passed along if older males could help ensure that their relatives survive and reproduce can smell related individuals and hence avoid inbreeding It occurred to me that male elephants might have a similarly innate ability to recognize relatives a father elephant might be able to identify his offspring through olfactory cues and choose his companions accordingly another recent study by my team indicates that male elephants track one another over space and time in a way that could be achieved only through olfaction and possibly vocalizations We found evidence that males remotely monitor one another’s locations and move toward or away from other elephants depending on their social relationships adult males find mates by listening for the distinctive calls of estrus females and smelling olfactory cues in their urine.) We are still studying the relatedness of individuals in these bachelor groups Future findings may shift our understanding of whether males are acting to maximize their ability to reproduce and pass their genes to the next generation There may be additional factors to consider as well Another advantage of keeping a group together is companionship who are still struggling to adjust socially to life outside a huge family certainly benefit from older males who can model good behavior Older males may gain from this association In another recent study we conducted on male elephant character we showed that adult males profit psychologically from the companionship of younger males We collected behavioral data from 34 individually known males at Mushara over a five-year period and found that the presence of young males in a group reduces aggression and increases affiliative Male elephants of all ages need socialization just like any other social animal They seek interaction and bonding from youngsters contemporaries and elders they can look up to Given how important bonded groups are to elephants I never would have expected that the structure of male elephant society was vulnerable to collapse But after our 2011 fieldwork season at Mushara Instead we witnessed a complete destabilization of the social club Greg’s absence ushered in an era of small factions; no one took up his leadership torch Abe just didn’t seem to have the titanium stomach required to rule Being at the top is a lot of work—always having to posture appeasing the youngsters while signaling dominance to one’s ever-watchful upwardly mobile contemporaries facing the threat of being toppled by a potentially mortal blow at any moment Yet somehow Greg was able to do it with surprisingly little stress which we assessed by collecting and analyzing his feces over the years now displays signs of active leadership and may one day become the leader of the social club at Mushara Some 14 years after Greg’s disappearance Young adults Kelly and Shaka have shown signs of wanting to mentor the next generation They have allowed younger males to explore their faces and tusks place tentative trunks in their mouths and hang a trunk on their tusk They have even permitted two youngsters to hang their trunks on their tusks I’d give anything to know what these young males are thinking in these moments of exploration and seeming admiration of the grown-ups Puberty is a traumatic period of uncertainty for these youngsters For a male that has grown up within a tight-knit elephant family it’s a big social adjustment to live outside the family I suspect that any ritual of connection would give a young male a sense of belonging—whether it be a secret handshake or tolerance from an elder Acceptance goes a long way toward easing the transition to adulthood It takes a certain kind of male character to have patience with these youngsters—and to take up the mantle of leadership the right stuff seems to be a combination of self-confidence and a sense of decorum that gains the confidence of the group Leaders tend to be the most socially integrated members of the group After an older male allows young males to explore his face and body with their inquisitive trunks the next sign that he has an interest in mentorship is the act of inviting these younger males to join him as he departs the waterhole I can tell from the perky posture of the young males who receive such an invitation that they understand exactly what it means—that they have been accepted into the most important social club of their lives I eagerly await these moments of active leadership The more we understand about the complexities of male elephant society the better we will be able to protect and manage this species All our recent findings and the findings of others further speak to the social nature of male elephants people who manage captive elephants might be able to improve their welfare by putting the males in mixed-age groups and organizing these groups around older males who have demonstrated leadership potential efforts to manage elephant populations in the wild ought to factor in the importance of postreproductive bulls to coming-of-age males Not only does their presence keep younger males but they also contribute to the younger males’ sense of belonging Now every time I hear a male “let’s go” rumble exchange I jump out of my sleeping bag and turn on the sound recorder and the night vision scope I quickly document who is involved in the exchange—who initiated and who responded and when These observations give me hope for a return to the good old days at Mushara All too soon after Abe and Andries finally showed up at the waterhole last year and Earth’s largest land animal emitted the lowest-frequency vocalization on the planet It was the “let’s go” rumble—the invitation to accompany him It was the call that Abe had so often enjoyed responding to but rarely initiated himself Andries answered the call to action with an equally long and low response I rolled over and tucked myself back into my sleeping bag for just a little while longer In an hour the camp would be a buzz of activity to pack up and leave and I was grateful for Abe’s appearance even if only in the final hours of my stay It gave me peace of mind to know he was still out there offering new coming-of-age males safe harbor The sound of the “let’s go” duet faded I imagined Abe and Andries saying to each other I’ll go high!” as they harmonized and disappeared into the bush bound for their next destination in good company Why Animals Play. Caitlin O'Connell; August 2021. ScientificAmerican.com/archive Caitlin O'Connell is a behavioral ecologist at Stanford University's Center for Conservation Biology and Harvard University's Center for the Environment Her research focuses on elephant behavior and communication O'Connell's latest book is Wild Rituals: 10 Lessons Animals Can Teach Us about Connection Subscribe to Scientific American to learn and share the most exciting discoveries innovations and ideas shaping our world today Scientific American is part of Springer Nature which owns or has commercial relations with thousands of scientific publications (many of them can be found at www.springernature.com/us) Scientific American maintains a strict policy of editorial independence in reporting developments in science to our readers and they typically don’t show up here at the Mushara waterhole in Namibia’s Etosha National Park until at least 11 A.M After a socially connected male initiates the \\"let's go\\" rumble Caitlin O'Connell is a behavioral ecologist at Stanford University's Center for Conservation Biology and Harvard University's Center for the Environment Why Animals Play. Caitlin O'Connell; August 2021. ScientificAmerican.com/archive Whether you are part of our community or are interested in joining us we welcome you to Washington University School of Medicine Mouse study may lead to new approaches for contraception by Mark Reynolds•May 2 a BJC Investigator and professor of cell biology and physiology has shown in mice that sperm have a temperature-controlled switch that changes their movements and is key to male fertility have evolved to keep male reproductive organs cooler than their core body temperature In mammals — including us humans — sperm are surprisingly picky about temperature thriving best in conditions a few degrees cooler than normal body temperature given that the female reproductive tract is warmer than normal body temperature how do these heat-sensitive swimmers manage to fertilize an egg in such a toasty environment Research from Washington University School of Medicine in St Louis has an answer: warmer temperatures — such as those of the female reproductive tract — trigger a specific signal that activates sperm changing their behavior from the relatively smooth motions used for navigation to the thrashing and twisting motions needed to enter the egg for fertilization The discovery of that trigger provides a possible target for male contraceptives and treatments for male infertility the researchers showed that a specific protein common to all mammals triggers a hyperactive state in sperm when the surrounding temperature matches that of the female reproductive tract published in Nature Communications April 17 also help explain the evolution of mammalian anatomy “That hyperactive state in sperm is key for successful fertilization, and no one knew exactly how temperature triggers it,” said Polina Lishko, PhD a BJC Investigator and professor of cell biology and physiology at WashU Medicine “Our work has identified a temperature-controlled switch in sperm that triggers these increased movements precisely when they are needed during fertilization.” All mammals share a particular protein embedded in the surface of sperm called CatSper It controls the entry of particles needed to power the hyperactive movements in the tail-like flagella that propel the sperm forward Temperature activation of CatSper was not known however it had been believed to be activated by a combination of the pH level in the female reproductive channel and because most mammalian sperm do not respond to progesterone so there had to be another controlling factor to flip the CatSper switch Mammalian evolution has developed ingenious ways to keep male reproductive organs at or below 34 degrees Celsius (93.2 degrees Fahrenheit) lower the temperature of blood destined for their internal testes by first passing it through their dorsal fin; elephants use a similar system that cools blood through their ears create and store sperm in testicles outside of their body Animals without these cooling adaptations for their male reproductive organs Using micron-scaled tools and techniques originally developed to study brain cells Lishko’s team observed the pattern of electric charges distinctive to CatSper’s activation in individual sperm cells measuring clear spikes when the temperature surrounding the cell surpassed 38 degrees Celsius (100.4 degrees Fahrenheit) the sperm’s behavior switched from the relatively smooth motions they use for navigation to the hyperactive movements needed for them to enter the egg for fertilization Lishko said that understanding temperature’s role in fertility may help to improve male contraception and treatments for infertility targeting it would not affect other bodily functions There have been attempts to develop contraceptives that deactivate the channel but Lishko said those have not been very effective so far The insights from this discovery might point to new approaches it might be possible to activate CatSper with temperature thus prematurely switching on this channel to drain the sperm of energy so that by the time the sperm cell is ready to do its job and enter the egg cell Swain DK, Vergara C, Castro-Arnau J, Lishko PV. The essential calcium channel of sperm CatSper is temperature-gated. Nature Communications. April 17, 2025. DOI: 10.1038/s41467-025-58824-0 This work was supported by the BJC Investigator fund About Washington University School of Medicine WashU Medicine has a storied history in MD/PhD training recently dedicated $100 million to scholarships and curriculum renewal for its medical students and is home to top-notch training programs in every medical subspecialty as well as physical therapy j.church@wustl.edu Mark Reynolds r.mark@wustl.edu and both occupational and physical therapy specializing in science and medicine with publications in CNRS International He is a former editor of McGill University’s Headway/En Tête research magazine and has won awards from the Canada Council for the Advancement of Education including for best science writing He has a bachelor’s degree from Dalhousie University in Halifax Could help determine which patients are likely to benefit from new Alzheimer’s drugs GLP-1 medications tied to decreased risk of dementia At WashU Medicine, we transform lives and shape the future of healthcare through pioneering research, world-class education, and unparalleled patient care. As one of the nation's largest academic clinical practices, we bring the full power of WashU Medicine to every patient, advancing treatment and training the medical leaders of tomorrow at Barnes-Jewish and St. Louis Children's hospitals and more than 130 clinics across Missouri and Illinois Consistently recognized among the nation's top institutions for research we are driven to challenge convention and elevate care for all “Is this creepy given I don’t know this person or is it just me?” the woman asked on a community forum Metrics details Agonists and antagonists of the glucose-dependent insulinotropic polypeptide receptor (GIPR) enhance body weight loss induced by glucagon-like peptide-1 receptor (GLP-1R) agonism while GIPR agonism decreases body weight and food intake in a GLP-1R-independent manner via GABAergic GIPR+ neurons it remains unclear whether GIPR antagonism affects energy metabolism via a similar mechanism Here we show that the body weight and food intake effects of GIPR antagonism are eliminated in mice with global loss of either Gipr or Glp-1r but are preserved in mice with loss of Gipr in either GABAergic neurons of the central nervous system or peripherin-expressing neurons of the peripheral nervous system Single-nucleus RNA-sequencing shows opposing effects of GIPR agonism and antagonism in the dorsal vagal complex GIPR antagonism and GLP-1R agonism both regulate genes implicated in synaptic plasticity we show that GIPR agonism and antagonism decrease body weight via different mechanisms these findings support the notion that both GIPR agonism and antagonism hold therapeutic value to accelerate GLP-1-induced weight loss we find that the body weight and food intake inhibitory effects of GIPR antagonism are absent in global Glp-1r-deficient mice suggesting dependency on GLP-1R-mediated signalling single-nuclei RNA-sequencing (snRNA-seq) revealed that GIPR agonism and antagonism have opposing effects in the brain with GIPR antagonism but not agonism mimicking the transcriptional responses of GLP-1R agonism in the dorsal vagal complex of the hindbrain (DVC) and with GIPR antagonism and GLP-1R agonism both modulating DVC gene programmes implicated in synapse formation and neuronal plasticity we show that while GIPR agonism and antagonism have similar effects on body weight and food intake they do so via different neuronal mechanisms depending on GLP-1R signalling to affect energy metabolism Source data. Source data. Source data. Body weight in grams (a) and percent (b) and food intake (c) of HFD-fed 14–16-week-old male C57BL6/J WT mice treated s.c with a single dose (30 mg kg−1) of either a control mAb (vehicle; n = 5) or an anti-GIPR antagonist (ant.) antibody (n = 6) Body weight in grams (d) and percent (e) and food intake (f) of HFD-fed 14–16-week-old male C57BL6/J global Gipr KO mice treated s.c with a single dose (30 mg kg−1) of either a control mAb (vehicle) or an anti-GIPR antagonist antibody (n = 6 each group) Body weight in grams (g) and percent (h) and food intake (i) of HFD-fed 14–16-week-old male C57BL6/J global Glp-1r KO mice treated s.c with a single dose (30 mg kg−1) of either a control mAb (vehicle) or an anti-GIPR antibody (n = 6 each group) Data in a–i were analysed by a two-way ANOVA with Bonferroni’s post hoc test for comparison of individual timepoints Source data. A schematic of the experimental design (a) and the body weight (b) of 36-week-old male C57BL/6J WT mice fed either a standard chow diet (cntrl.) or a HFD and treated s.c with a single dose of either vehicle (vhcl) an acylated peptide GIPR antagonist (1,500 nmol kg−1) or the GIPR:GLP-1R co-agonist MAR709 (50 nmol kg−1) (n = 6 each group) UMAP representations of gene expression coloured by C12-level cell type in the DVC (c) and C25-level cell type in hypothalamus (d) as well as by experimental group in the DVC (e) and hypothalamus (f) A bar graph showing mean expression of Glp-1r and Gipr in the DVC and hypothalamus The number of nuclei isolated from each brain region The colours correspond to log-normalized expression values scaled to the maximum of each gene Source data. A comparison of log fold-change differences in gene expression in DVC neurons between male DIO C57BL/6J WT mice (DIO cntrl.) treated with acyl-GIP or the GIPR antagonist (ant.) (a) GIPR antagonist versus MAR709 (e) or acyl-GLP-1 versus acyl-GIP (f) (n = 6 mice per group from which n = 3 mice were pooled to receive n = 2 independent biological replicates per group) UMAP representation of gene expression of DVC neurons coloured by neuron type (g) and with expression of Glp-1r (h) and Gipr (i) Heat maps showing mean gene expression of Glp-1r and Gipr in DVC neuronal populations (j) and experimental group (k) and with the colour corresponding to log-normalized expression values scaled to the maximum of each gene Source data. Bar plots and UMAP representations of gene expression in DVC neurons of male DIO mice treated with a GIPR antagonist (ant.) (a) acyl-GIP (c) or MAR709 (d) (n = 6 mice per group The bar plots and UMAPs are coloured by Augur score representing cell type-specific changes in gene expression of the treatment group relative to DIO vehicle controls Volcano plots (log2 fold change (FC) versus adjusted P values from a two-sided Wilcoxon rank-sum test corrected for multiple comparison) of differentially expressed genes (DEGs) following treatment with either the GIPR antagonist or acyl-GLP-1 in the top GIPR antagonist affected neuronal clusters Glut10 (e) Venn diagrams show the overlap of significant DEGs (adjusted P < 0.05) from GIPR antagonist and acyl-GLP-1 groups P values of DEGs were obtained by Wilcoxon rank-sum tests and were adjusted for multiple comparisons using the Benjamini–Hochberg method Source data. these data not only show that GIPR antagonism and GLP-1R agonism act on the same neuronal populations in the DVC but also that they similarly downregulate gene programmes implicated in synaptic plasticity and synapse formation UMAP representation of hypothalamic neuronal gene expression coloured by expression of Glp-1r (a) experimental group (c) or C66-level neuron type (d) Heat maps showing Glp-1r and Gipr mean gene expression in hypothalamic neuronal types Bar plots and UMAP representations of gene expression in DVC neurons of DIO mice treated with a GIPR antagonist (f) or acyl-GLP-1 (g) and UMAPs and bar plots are coloured by Augur score representing cell-specific change in gene expression of the experimental group versus vehicle DIO controls (f and g) The top ten most likely cell–cell communication events between DVC GABA4 or Glut 10 neurons and hypothalamic C66-19: Pomc.GLU-4; C66-46: Agrp.GABA-4 or all other hypothalamic neurons in DIO mice treated with vehicle Cellphone P values are permutation-based P values Source data. these data suggest that GLP-1R agonism and GIPR antagonism may exert their effects on energy balance by downregulating signalling from DVC C35 GABA4 and C35 Glut10 neurons to hypothalamic feeding circuits our snRNA-seq analysis revealed that GIPR antagonism DVC neuronal gene expression changes correlate negatively in mice after treatment with GIPR agonism versus antagonism but positively in mice treated with GIPR antagonism versus GLP-1R agonism We observed the greatest transcriptional changes induced by GIPR antagonism in the C35 GABA4 which were also among the highest affected neuronal populations targeted by GLP-1R agonism GIPR antagonism and GLP-1R agonism are separated from GIPR agonism in that they both similarly downregulate gene programmes indicative of neuronal plasticity and synapse formation These findings further support the notion that GIPR antagonism and GLP-1R agonism are functionally related and act similarly on DVC neurons and in a clearly distinct manner from GIPR agonism we show here that GIPR agonism and antagonism affect body weight and food intake via different with GIPR antagonism affecting body weight and food intake via modulation of GLP-1R signalling The observation that gene expression changes induced by GIPR agonism versus its antagonism correlate negatively further argues that our GIPR agonist is not a functional antagonist it seems plausible to hypothesize that weight loss induced by GIPR signal modification may involve modulation of the hypothalamic and/or hindbrain serotonergic system Body composition was analysed using a magnetic resonance whole-body composition analyser (EchoMRI) Plasma levels of glucose and insulin were measured after 6 h fasting insulin (Humalog; Eli Lilly) was injected i.p HbA1c was assessed from fresh blood using the DCA Vantage Analyzer (Siemens) For assessment of glucose-induced insulin secretion glucose was given orally at a dose of 4 g kg−1 in 6 h fasted mice followed by blood sampling at timepoints 0 15 and 30 min after glucose administration Commercially available enzyme-linked immunosorbent assays (ELISAs) were used according to the manufacturer’s instruction to measure insulin (Crystal Chem Zaandam ab65336) or total cholesterol (Thermo Fisher Scientific Brains were then fixed for 24 h at 4 °C in 4% PFA and then transferred to 15% sucrose for 24 h tissues were extracted and fixed for 1–2 h in 4% PFA and transferred to 30% sucrose overnight at 4 °C All tissues were frozen in Tissue-Tek O.C.T (Sakura Finetek cut in 12–14 µm sections and placed on microscopic slides (Thermo Fisher Scientific The slides were heated for 30 min at 60 °C followed by antigen retrieval using a steamer then processed by the RNAscope Multiplex Fluorescent Reagent kit v2 (Advanced Cell Diagnostics 323270) according to the manufacturer’s instructions a custom-made probe was designed to bind to the deleted exons of mouse Gipr (Advanced Cell Diagnostics 1138821-C1) and Vgat (Advanced Cell Diagnostics amplifiers and dyes were added for visualization of GIPR and Vgat The slides were incubated with rabbit anti-peripherin antibody (Thermo Fisher Scientific PA316723; 1:200) for 1 h at room temperature followed by 30 min incubation with goat anti-rabbit-HRP (Thermo Fisher Scientific TSA vivid dyes 650 and 520 (Advanced Cell Diagnostics both 1:500 dilution) were added to detect GIPR peripherin or vesicular GABA transporter (VGAT) Slides were counterstained with 4,6-diamidino-2-phenylindole (DAPI) (Advanced Cell Diagnostics 320858) and imaged using Leica SP8 Laser Confocal Microscope using LAS X (version 3.5.7.23225) followed immediately by clamping of the bile duct and perfusion with collagenase P (Roche Diagnostics Tissues were incubated in a 15 ml Falcon tube with 1 ml of collagenase P solution for 15 min at 37 °C followed by the addition of 12 ml of cold G-solution (Sigma-Aldrich) and centrifugation at 586g at room temperature The pellet was subsequently washed with 10 ml of G-solution (500 ml HBSS (Life Technologies 126615-25 ml) and 1% penicillin–streptomycin (Life Technologies 15140122)) and resuspended in 5.5 ml of gradient solution comprising 15% Optiprep (5 ml 10% RPMI (Life Technologies 11875093) + 3 ml of 40% Optiprep that was diluted from 60% Optiprep with G-solution (Sigma-Aldrich and placed on top of 2.5 ml of the gradient solution 6 ml of the G-solution was added on the top Samples were then incubated for 10 min at room temperature and centrifuged at 630g The interphase was then collected and filtered through a 70 μm nylon filter (BD Falcon Islets were handpicked by a micropipette under the microscope and cultured in RPMI 1640 medium (Life Technologies Culture medium was removed and islet microtissues were equilibrated for 1 h with Krebs Ringer HEPES buffer (131 mM NaCl 1.2 mM MgSO4 and 2% BSA) containing 2.8 mM glucose The supernatant was collected as a sample under the low glucose condition for 45 min incubation and islets were incubated for another 45 min at 37 °C with Krebs Ringer HEPES buffer containing 16.7 mM glucose and supplements as above The supernatant was collected as a sample under the high glucose condition and stored at −20 °C native mouse GIP or GLP-1 (provided by Novo Nordisk) were diluted in 1× KRK buffer with 20 mM glucose to reach a concentration of 50 nM Cells were subsequently treated with either mouse GIP or GLP-1 for 45 min Insulin concentrations were determined using a Mouse Insulin ELISA (Crystal Chem The hypothalamus and DVC were collected 8 h after drug administration and stored in liquid nitrogen Mice were euthanized followed by immediate decapitation and then the skull was removed An earlier alignment of the brain was determined using a brain matrix and the entire hypothalamus (includes all the nuclei) was collected by microdissection The hindbrain DVC was microdissected in an area postrema-centric manner after removal of cerebellar cortex Tissue samples were flash frozen into liquid nitrogen and frozen tissues were stored in liquid nitrogen vapour phase for further processing to single-nuclei isolation Nuclei were isolated using the 10X Genomics Chromium Nuclei Isolation kit including RNase Inhibitor (10X Genomics and using the 10X Genomics protocol for Single Cell Multiome ATAC + Gene Expression (10X Genomics Nuclei concentration was determined using a Luna-II Automated Cell Counter (Logos biosystems L40002) and adjusted to 6,250 nuclei per microlitre after pooling of n = 3 mice per sample Nuclei were then processed using the 10X Genomics Chromium Next GEM Single Cell Multiome ATAC + Gene Expression (Rev E) according to the manufacturer’s instructions Pooled samples were loaded into two lanes per group for a total of 24 lanes across three 10X Chromium chips Equal numbers of cells per sample were loaded on a 10X Genomics Chromium controller instrument to generate single-cell gel beads in emulsion at the Helmholtz Munich Genomics Core Facility Single-nucleus multimodal libraries were sequenced using the Illumina NovaSeq 6000 FASTQ files were generated from base calls with bcl2fastq software v2.20 (Illumina) Reads were mapped to the pre-built mm10 mouse reference (University of California Santa Cruz mm10 reference genome) using Cell Ranger ARC (v2.0.2 The resulting cell-by-peak and cell-by-gene matrices (ATAC and gene expression assays respectively) from the 24 samples were integrated using Cellranger aggr (10X Genomics) Then the expression of marker genes from the HypoMap was evaluated in each Leiden cluster and then was manually annotated informed by marker gene expression and the majority cell type from scArches label transfer The HypoMap hierarchical cell-type annotation framework was then used to map C25 as there is no comparable atlas and annotation framework to the hypomap for the DVC each Leiden cluster was manually annotated into 35 fine-grained cell types (C35 cell type) and were then mapped to the coarser-grained C12 and C2 levels of cell type based on the expression of marker genes DVC neurons were further subdivided into individual clusters labelled by major neurotransmitter expression drugs were aliquoted by a lead scientist in number-coded vials and most handling investigators were blinded to the treatment condition Analyses of glucose and insulin tolerance were performed by experienced research assistants who did not know prior treatment conditions Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: the SURMOUNT-4 randomized clinical trial Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind Tirzepatide once weekly for the treatment of obesity Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial Effect of subcutaneous tirzepatide vs placebo added to titrated insulin glargine on glycemic control in patients with type 2 diabetes: the SURPASS-5 randomized clinical Trial Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised Tirzepatide vs insulin lispro added to basal insulin in type 2 diabetes: the SURPASS-6 randomized clinical trial Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind Glucose-dependent insulinotropic polypeptide (gastric inhibitory polypeptide; GIP) Therapeutic potential for GIP receptor agonists and antagonists Loss of GIPR in LEPR cells impairs glucose control by GIP and GIP:GLP-1 co-agonism without affecting body weight and food intake in mice Glucose-dependent insulinotropic polypeptide regulates body weight and food intake via GABAergic neurons in mice The glucose-dependent insulinotropic polypeptide (GIP) regulates body weight and food intake via CNS–GIPR signaling a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: from discovery to clinical proof of concept Unimolecular dual incretins maximize metabolic benefits in rodents Optimized GIP analogs promote body weight lowering in mice through GIPR agonism not antagonism Specific loss of GIPR signaling in GABAergic neurons enhances GLP-1R agonist-induced body weight loss Hypothalamic and brainstem glucose-dependent insulinotropic polypeptide receptor neurons employ distinct mechanisms to affect feeding Glucose-dependent insulinotropic polypeptide receptor-expressing cells in the hypothalamus regulate food intake Discovery of a potent GIPR peptide antagonist that is effective in rodent and human systems Anti-obesity effects of GIPR antagonists alone and in combination with GLP-1R agonists in preclinical models Chronic glucose-dependent insulinotropic polypeptide receptor (GIPR) agonism desensitizes adipocyte GIPR activity mimicking functional GIPR antagonism GIPR antagonist antibodies conjugated to GLP-1 peptide are bispecific molecules that decrease weight in obese mice and monkeys A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings Gut-derived GIP activates central Rap1 to impair neural leptin sensitivity during overnutrition leads to enhanced weight loss and metabolic improvements in cynomolgus monkeys GIP as a therapeutic target in diabetes and obesity: insight from incretin co-agonists Sensory and motor physiological functions are impaired in gastric inhibitory polypeptide receptor-deficient mice Glucose-dependent insulinotropic polypeptide (GIP) and its receptor (GIPR): cellular localization Relevance of sympathetic nervous system activation in obesity and metabolic syndrome GIP-induced vasodilation in human adipose tissue involves capillary recruitment The gluco- and liporegulatory and vasodilatory effects of glucose-dependent insulinotropic polypeptide (GIP) are abolished by an antagonist of the human GIP receptor TCF1 links GIPR signaling to the control of beta cell function and survival Inactivation of the glucose-dependent insulinotropic polypeptide receptor improves outcomes following experimental myocardial infarction Murine peripherin gene sequences direct Cre recombinase expression to peripheral neurons in transgenic mice A new neuronal intermediate filament protein NF-L and peripherin immunoreactivities define distinct classes of rat sensory ganglion cells Neuronal GLP1R mediates liraglutide’s anorectic but not glucose-lowering effect Spatiotemporal GLP-1 and GIP receptor signaling and trafficking/recycling dynamics induced by selected receptor mono- and dual-agonists Cell type prioritization in single-cell data Neuregulin-ERBB signaling in the nervous system and neuropsychiatric diseases NGL-2 regulates input-specific synapse development in CA1 pyramidal neurons NGL-1/LRRC4C deletion moderately suppresses hippocampal excitatory synapse development and function in an input-independent manner The synaptic and neuronal functions of the X-linked intellectual disability protein interleukin-1 receptor accessory protein like 1 (IL1RAPL1) HypoMap-a unified single-cell gene expression atlas of the murine hypothalamus LIANA+ provides an all-in-one framework for cell–cell communication inference CellPhoneDB: inferring cell–cell communication from combined expression of multi-subunit ligand-receptor complexes Inferring neuron–neuron communications from single-cell transcriptomics through NeuronChat Tanycytes control hypothalamic liraglutide uptake and its anti-obesity actions Hes, C. et al. 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Pertpy: an end-to-end framework for perturbation analysis. Preprint at bioRxiv https://doi.org/10.1101/2024.08.04.606516 (2024) Download references This work was funded by the European Union within the scope of the European Research Council ERC-CoG Trusted no The views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Council Neither the European Union nor the awarding authority can be held responsible for them further received funding from the German Research Foundation (grant nos SFB1123 and GRK 2816/1) and the German Center for Diabetes Research (DZD e.V.) The skilful technical support of the Core Facility Genomics at Helmholtz Munich is highly acknowledged De la Rosa Velazquez for their help with the snRNA-seq Open access funding provided by Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) These authors contributed equally: Robert M Arkadiusz Liskiewicz & Daniela Liskiewicz Institute of Experimental and Clinical Pharmacology and Pharmacogenomics Obesity and Complications Therapeutic Area Walther-Straub Institute for Pharmacology and Toxicology designed and performed experiments and analysed and interpreted data participated in the molecular design and interpretation of data analysis of data and interpretation of results supervised experiments and analysed and interpreted data is a member of the scientific advisory board of ERX Pharmaceuticals He was a member of the Research Cluster Advisory Panel (ReCAP) of the Novo Nordisk Foundation between 2017 and 2019 He attended a scientific advisory board meeting of the Novo Nordisk Foundation Center for Basic Metabolic Research He received funding for his research projects by Novo Nordisk (2016–2020) and Sanofi-Aventis (2012–2019) He was a consultant for Bionorica SE (2013–2017) As former Director of the Helmholtz Diabetes Center and the Institute for Diabetes and Obesity at Helmholtz Zentrum München (2011–2018) he has been responsible for collaborations with a multitude of companies and institutions he discussed potential projects with and has signed/signs contracts for his institute(s) and for the staff for research funding and/or collaborations with industry and academia including but not limited to pharmaceutical corporations like Boehringer Ingelheim he was/is further responsible for commercial technology transfer activities of his institute(s) including diabetes related patent portfolios of Helmholtz Zentrum München as none of the above funding sources were involved in the preparation of this paper receives research funding by Novo Nordisk and has received speaking fees from Novo Nordisk is a co-inventor on intellectual property owned by Indiana University and licensed to Novo Nordisk The other authors declare no competing interests Nature Metabolism thanks Alice Adriaenssens reviewer(s) for their contribution to the peer review of this work Primary Handling Editor: Christoph Schmitt in collaboration with the Nature Metabolism editorial team RNAscope validation of GIPR deletion in 20 week-old male chow-fed Vgat cre+ Giprwt/wt (WT) and Vgat cre+ Giprflx/flx (KO) mice (pictures are representative examples of n = 3 mice per group) (a,b) Absolute values of body weight development (c–e) and total change in body weight (f) of 33-wk old male C57BL/6 J wildtype (WT) or Vgat-Gipr knockout (KO) mice treated daily over 24 days with either vehicle or the combination of acyl-GLP-1 (10 nmol/kg) and a GIPR antagonist (1,500 nmol/kg) (n = 8 each group) Absolute changes of body composition of 36-wk old male C57BL/6 J wildtype and Vgat-Gipr KO mice treated either with Vehicle (n = 8 WT and n = 8 KO) or the co-therapy of acyl-GLP-1 and the GIPR antagonist (n = 8 WT and n = 7 KO) (g,h) Data in panel d and e were analyzed by repeated measures 2-way ANOVA with Bonferroni’s post-hoc test for comparison of individual time points Data in panel f-h were analyzed using 1-way ANOVA Data represent mean ± SEM; asterisks indicate * p < 0.05; ** p < 0.01 and *** p < 0.001 Individual p-values are shown in the Data Source file Source data Expression of peripherin corrected by the housekeeping gene peptidylprolyl isomerase A (Ppia) in hippocampus (n = 6) dorsal root ganglion (n = 5) and iWAT (n = 4) of 15-week old male chow-fed Per-Cre+Giprwt/wt mice and in pancreas (n = 7) of 45-week old male chow-fed Per-Cre+Giprwt/wt mice (a) Expression of peripherin corrected by the housekeeping gene Ppia in the cerebellum (n = 8) colon (n = 8) and trigeminal ganglion (n = 7) of 12-week old male chow-fed WT mice (b) Expression of Gipr in dorsal root ganglion (n = 9 WT eWAT (n = 12 each group) (g) and pancreas (n = 12 each group) (h) of 45-week old male mice Chow-fed Per-Cre+Giprwt/wt (WT) and Per-Cre+Giprflx/flx (KO) mice Expression of Gipr in the cerebellum (n = 8 each group) (i) n = 8 KO) (o) and colon (n = 8 each group) (p) of 12-week old male mice Chow-fed WT and KO mice RNAscope validation of Gipr deletion in trigeminal ganglion of 44-week old male chow-fed WT and KO mice (q) and of the DRG of 51-week old male chow-fed WT and KO mice (r) Data in panels q and r are representative examples of n = 3 mice each group Data in panel c-f and h-p were analyzed using two-sided data in panel g were analyzed two-sided by Mann-Whitney test Source data Body weight development of female C57BL6/J Per-Cre+Giprwt/wt (WT) and Per-Cre+Giprflx/flx (KO) mice fed with a HFD (n = 8 each group) (a) Fat and lean tissue mass of 35-week old female WT and KO mice (n = 8 each group) (b,c) Cumulative food intake of 52-week old female WT (n = 6) and KO mice (n = 7) (d) locomotor activity (f) and respiratory exchange ratio (RER) (g) of 52-week old female WT (n = 6) and KO mice (n = 7) Glucose tolerance (h) and corresponding area under curve (AUC) (i) after i.p dosing with 2 g/kg glucose in 48-week old female WT and KO mice (n = 7 each group) Glucose-induced insulin secretion (j) and corresponding AUC (k) after oral glucose bolus administration of 4 g/kg glucose in 54-week old female WT and KO mice (n = 6 each group) dosing with 0.75U/kg insulin (Humalog) in 50-week old female WT (n = 6) and KO mice (n = 8) Fasting levels of blood glucose (n = 8 each group) (m) and insulin (n = 6 WT n = 7 KO) (n) in 54-week old female WT and KO mice as well as fasting plasma levels of triglycerides (n = 6 WT n = 7 KO) (p) in 55-week old female WT and KO mice Data in panel a,c,f and g were analyzed by repeated measures 2-way ANOVA with Bonferroni’s post-hoc test for comparison of individual time points Data in panel a,d,e,h,j and l were analyzed using 2-way ANOVA and with Bonferroni post-hoc comparison of individual time points Data in panel e was analyzed using ANCOVA with body weight as covariate Data in panel b,c,i,k,m-p were analyzed using Student’s two-tailed Source data Body weight development of 47-week old male C57BL/6 J wildtype (WT) and Per-Gipr knockout (KO) mice treated daily with either vehicle or the combination of acyl-GLP-1 (10 nmol/kg) and a GIPR antagonist (1,500 nmol/kg) (n = 8 each group) (a) Body composition (n = 8 each group) 47-wk old male C57BL/6 J DIO wildtype and Per-Gipr KO mice after 25 days of treatment (b,c) Data in panel a was analyzed by 2-way ANOVA with Bonferroni’s post-hoc test for comparison of individual time points Data in panel b,c were were analyzed using 1-way ANOVA Source data Comparison of Log fold change differences in gene expression between male DIO C57BL/6 J wildtype mice treated with acyl-GIP or the GIPR antagonist (a) the GIPR antagonist (f) (n = 6 mice per group Bar plots are ranked Augur score in mice treated with either acyl-GIP (g) or MAR709 (h) representing cell-specific change in gene expression of the respective groups relative to Vehicle-treated DIO controls The top 10 most likely cell-cell communication events between DVC GABA4 or Glut 10 neurons and hypothalamic C66-19: Pomc.GLU-4 or all other hypothalamic neurons in mice treated with MAR709 (i) Cellphone p-values are permutation-based p-values Lr means are mean ligand-receptor expression Source data UMAP representations of gene expression of DVC non-neuronal cells colored by experimental group (a) or expression of either Glp-1r (c) or Gipr (d) Bar plots with Augur scores of DVC non-neuronal cells from mice treated with either the GIPR antagonist (e) Bar plots are ranked and colored by Augur score representing cell-specific change in gene expression of the respective group relative to vehicle-treated DIO controls Source data UMAP representations of gene expression of hypothalamus non-neuronal cells colored by experimental group (a) (e) Heatmap showing Glp-1r and Gipr mean gene expression in hypothalamic non-neuronal cell types Color corresponds to log-normalized expression values scaled to the maximum of each gene Bar plots showing Augur scores of hypothalamic non-neuronal cells from mice treated with the GIPR antagonist (f) Source data and by the experimental group from each study (e) Source data Pairwise heatmap showing the proportion of cells labeled by Hes et al predicted to belong to each DVC cell-type from this study (x-axis) using scHPL Source data Pairwise heatmap showing the proportion of cells labeled by Ludwig et al Source data RNAscope analysis of GIPR in the nodose ganglion of 59-week-old male chow-fed WT and Per-GIPR KO mice Data are representative examples of n = 3 mice each group Statistical source data for Extended Data Fig Download citation DOI: https://doi.org/10.1038/s42255-025-01294-x After finishing the indoor season as a second team all-american Lewis looked to continue his success into the outdoor season The 2024 OVC Male Field Athlete of the Year would have no problem picking up right where he left off securing a first place finish in shot put and two second place finishes in hammer throw and discus at the Georgia Tech Invitational Coach Crumpecker spoke on Lewis and his transition from indoor to outdoor season “He's coming off of a tremendous indoor season and he's continuing that into the outdoor season and I expect that you'll continue to see bigger and bigger things as we get closer to the end of this (season).” Crumpecker said Lewis was honored to be rewarded for his hard work and looks to continue his success “It feels good to be recognized by the OVC especially for the hard work I put in over the fall and this whole season.” Lewis said or at least one more before the end of the season.” While Lewis has shown exceptional strength throughout his tenure at SEMO (Southeast Missouri State University) his teammates say it’s his technique that has allowed him to thrive Sophomore first year thrower Jachys Brown spoke on what puts Lewis ahead of the competition he warms up the way he’s supposed to and he just studies everything…I feel like that’s what separates him.” Brown said “I really expect him to get to Nationals and do great I feel like he could be a good contender at Nationals I really do.” Lewis along with the rest of the Redhawks will look to have another good outing as they will be back in action at the Memphis Tiger Invitational on May 2 SPLC and Florida Decides Healthcare File Lawsuit Challenging DeSantis’ Attack on Direct Democracy — Read More Far-right extremists celebrated President Donald Trump’s 2024 election as an opportunity to further entrench a male supremacist culture that is permissive to violence against women Through his appointments of white men dogged by allegations of sexual harassment Trump has publicly affirmed his hostility for feminism to his male supporters and fed the male supremacist belief that white men are victims threatened by a changing social order whose privilege must be restored and protected There are serious consequences to selecting male supremacists and potential perpetrators of violence against women to top government positions both for the women working in these agencies and for the rest of the country His actions will strengthen hierarchies of both gender and race As the election results came in last year on Nov. 5, white nationalist Nick Fuentes tweeted: “Your body, my choice. Forever.” The tweet was viewed over 100 million times and became a popular refrain to harass girls in school a social media influencer who faces allegations of rape and human trafficking “You no longer have rights.” A Texas Proud Boys chapter shared a meme depicting The Handmaid’s Tale dystopia see Trump’s victory as a rebuke of feminism and progressive politics He symbolizes the forceful rollback of women’s rights Trump’s new administration has welcomed many personnel with histories of sexual misconduct. In the first few weeks after he was reelected to the presidency, Fortune reported nearly one-third of his Cabinet nominees and other key members of his administration had allegations of sexual misconduct a self-identified “raging misogynist” who was also accused of domestic violence and subject to a temporary restraining order in 2022 which was dismissed days later as part of an agreement as general counsel for the Office of Personnel Management white men — as the ultimate victims of a changing social order In their article for the Council on Foreign Relations Jacob Ware and Noël James wrote that by nominating candidates “who have been accused or found guilty of sexual harassment for consideration for top positions leading the government a message is sent to the public that renders these crimes as insignificant in regards to service in the government alongside broader approval that legitimizes crimes related to violence against women.” who has been accused of sexually harassing and groping his former babysitter now leads the Department of Health and Human Services — an agency where he has a great deal of power over policies that impact women’s health and the health of women living in poverty and women of color On a podcast in November 2024, Hegseth said “I’m straight up just saying we should not have women in combat roles.” In his 2024 book The War on Warriors: Behind the Betrayal of the Men Who Keep Us Free “Women cannot physically meet the same standards as men.” In another comment in this book But not in the military.” Hegseth’s actions as secretary of defense will have a disproportionate impact on Black women who make up 29% of active-duty enlisted women Male supremacists celebrated these views and what they indicated about women’s position in society which the Southern Poverty Law Center defines as a hate group “Will Donald Trump’s 2nd Term Turn The US Into A More Patriarchal Society?” The user specifically noted Hegseth’s views on women and his hope this would help diminish the influence of feminism Despite some support for Trump and Hegseth in the thread arguing that his views and policies are not extreme enough for their tastes Title IX is part of federal civil rights legislation that bans sex discrimination at educational institutions that receive federal funding This includes gender- and sex-based harassment MRAs are ideologically opposed to these Title IX protections which they believe unfairly privileges women at the expense of maligning men and contributing to what they consider to be “an epidemic of false rape allegations.” Reporting from Democracy Forward revealed an extensive relationship between DeVos’ Department of Education and these organizations who were directly involved in drafting new Title IX regulations which weakened federal guidance on reporting investigating and responding to sexual assault and harassment allegations at K-12 schools and universities while offering new protections to accused perpetrators The new Trump administration’s decision to reaffirm this guidance leaves survivors vulnerable and unsupported human trafficking and forming an organized crime group Romanian authorities identified at least 35 known victims of their sex-trafficking operation the Tate brothers continued this abusive operation even while under house arrest and its recommendations threaten the privacy rights of patients who receive abortion care These restrictions will have a disparate impact on women of color and those who live in poverty, in addition to further exacerbating the gap in maternal mortality between white and Black women Despite trying to distance himself from Project 2025 during his campaign Trump has since selected several of its authors to fill key positions within his administration and has taken steps to force this deeply unpopular policy agenda on the American people The ideology of the Trump administration seems to be inching closer to that of organized far-right extremists “You got to protect women from themselves … they’re indecisive This is the version of protection the Trump administration is advocating for: “protecting” women by restoring traditional restrictive gender roles and enforcing a social hierarchy dominated by cisgender men and permissive of violence against women President Trump symbolizes the forceful rollback of women’s rights The SPLC and American University’s Polarization & Extremism Research & Innovation Lab have published Not Just a Joke: Understanding & Preventing Gender- & Sexuality-Based Bigotry The guide helps readers identify warning signs that a young person has become susceptible to these ideologies best practices for responding and ways to build resilience against manipulation It also provides guidance on how to support and care for those who have been harmed by people who have been influenced by or hold bigoted beliefs Comments or suggestions? Send them to [email protected]. Have tips about the far right? Please email: [email protected]. Have documents you want to share? Submit here tax-exempt 501(c)(3) organization (EIN: 63-0598743) The Southern Poverty Law Center400 Washington AvenueMontgomery They were likely on your mind since April 25 was World Penguin Day This document may not be reprinted without the express written permission of Northwest Arkansas Newspapers LLC El material de Associated Press es Copyright © 2025 derechos reservados Associated Press y no puede ser publicado audio y/o video de Associated Press no será publicado reescrito para su transmisión o publicación ni redistribuido directa o indirectamente en ningún medio Ni estos materiales de AP ni ninguna parte de los mismos pueden almacenarse en una computadora errores u omisiones de los mismos o de la transmisión o entrega de la totalidad o parte de los mismos o de cualquier daño que surja de cualquiera de los anteriores A progressive Maine law firm that represents several school districts throughout the state issued a memo alongside the Maine School Board Association on Friday arguing that Maine school districts are required to continue forcing female athletes to compete against male athletes who claim they are transgender The email, dated May 2 with the subject line “Title IX FAQ,” was sent to Maine school board chairs and members from MSBA President Faye Anderson, Executive Director Steven Bailey and Drummond Woodsum attorney Melissa Hewey “This memo was developed in response to questions submitted to the Maine School Superintendents Association following an April 17th meeting with the Maine Department of Education,” the email reads “The attached FAQs address concerns related to Title IX and compliance with both state and federal law,” it reads is to provide all Maine public school board members with “clarity and guidance as you navigate these important legal obligations.” “We think it is especially important that all public school board members receive this memo,” the email reads followed by a statement that Drummond Woodsum attorney Melissa Hewey made “major contributions” to the development of the FAQ document Federal Funding and Maine Schools,” answers four questions regarding the legal precedence between federal and state law and whether Maine schools must allow transgender athletes to participate in girls’ athletic events The Maine School Board Association (MSBA) and the Maine School Superintendents Association (MSSA) are two nonprofit organizations that collectively form the Maine School Management Association (MSMA) a taxpayer-funded quasi-governmental organization that promotes left-wing education policies The memo comes amid an ongoing legal battle between the Trump administration and the State of Maine for Maine’s refusal to comply with Donald Trump’s executive order “Keeping Men out of Women’s Sports.” The order established the current administration’s interpretation of Title IX anti-discrimination laws that considers it a violation for males to be allowed in women’s sports It is argued in the Drummond Woodsum FAQ memo that “State and federal law take precedence over executive orders,” and that the Maine Human Rights Act which prohibits discrimination based on gender identity is “not preempted by Title IX,” and that Maine schools must comply with both laws “The Maine Human Rights Act is currently consistent with Title IX,” it is claimed in the memo The memo goes on to state that while Title IX does prohibit discrimination in education on the basis of sex it “has nothing to do with athletics.” In response to the question “Must Maine schools allow transgender girls to participate in girls’ athletic events?” the memo answers “The Maine Human Rights Act requires this as do the rules of the Maine Principals’ Association and Title IX does not prohibit it,” the memo reads “If state law is amended as has been proposed The Maine Principals’ Association (MPA) is a private nonprofit corporation that regulates interscholastic high school athletics statewide Last year, the MPA adopted a new “Gender Identity Participation Policy” to make it easier for transgender or non-binary students to participate on high school sports teams in accordance with their “gender identity.” The final question addressed in the FAQ memo is whether Maine school administrative units (SAUs) that choose to align with President Trump’s executive order and keep males out of girls’ athletics events will receive federal funding even if that funding is withheld from the state This question appears to be in reference to Hodgdon school district (MSAD 70), whose board voted unanimously last month to adopt the federal government’s interpretation of Title IX becoming the first school board in the state to do so It was indicated by Attorney General Pam Bondi at a press conference last month announcing the Department of Justice’s lawsuit against Maine for their noncompliance with Title IX that MSAD 70 would not be losing out on federal funding withheld from Maine by the Trump administration it is argued in the Drummond Woodsum memo that school districts who do decide to align with the Trump administration will indeed be affected by federal funds being withheld from the state at large “The State of Maine is the grantee for virtually all federal funds flowing to schools in the state so if one or more federal agencies decides to stop funding to the state that decision will affect all SAUs regardless of their position on transgender participation in athletics,” the memo states “There is no provision in the law for the federal government to provide funds directly to SAUs.” The full MSBA/Drummond Woodsum memo to Maine school board members can be read below: a school board member in Piscataquis county was one of the Maine school board members who received the FAQ memo via email on Friday “Today I received this email and attachment from the Maine School Boards Association with Title IX guidance for public schools Namely: 1) state and federal law take precedence over executive orders; 2) the Maine Human Rights Act is not preempted by Title IX therefore schools must comply with both laws; and 3) Maine schools must allow transgender girls to participate in girls’ athletic events because the MHRA requires it and Title IX does not prohibit it,” Perkins wrote in an email to the Maine Wire on Friday Perkins pointed to Drummond Woodsum Attorney Hewey’s biography on the law firm’s website indicates that she has given past presentations entitled “Student Rights: Zooming in on the Rights of Transgender and Gender Expansive Students,” “The New Era of Title IX” and “Supporting Transgender Students in Maine Schools.” “Knowing Melissa Hewey gave ‘major contributions’ to the document leads me to believe that public school board members in Maine are receiving slanted advice and direction,” Perkins said Friday’s memo is not the first time Drummond Woodsum has issued a memo to Maine public school officials related to obstructing the policies of the Trump administration In January, the law firm sent out a memo advising public school officials on how they can effectively resist potential immigration enforcement actions that may involve the families of minors who attend government-run schools including by destroying evidence of potential immigration crimes Regarding information on noncitizen students in public schools Drummond Woodsum advised their public school administrator clients “[T]his information should not be stored as part of a students education record and should be destroyed as soon as it is no longer needed.” Drummond Woodsum is the law firm representing the Great Salt Bay Community School in a lawsuit funded by Damariscotta area taxpayers The lawsuit was initiated by a parent who uncovered that a conditionally licensed social worker at the school was covertly trying to persuade her 13-year-old daughter to embrace a gender transition Edward Tomic is a reporter for The Maine Wire based in Southern Maine Massachusetts and is a graduate of Boston University He can be reached at tomic@themainewire.com Δdocument.getElementById( "ak_js_1" ).setAttribute( "value" Δdocument.getElementById( "ak_js_2" ).setAttribute( "value" Time to either say no or just go with it same with you parents Your schools and politicians are against you are being held hostage by a corrupt law firm Drummond Woodsum is a scourge on this state and need to be fired from every school district they represent Once again Maine “legislators” ignoring what 80% of us don’t want Rather than treat mentally ill boys we subject our daughters to this gender bending nonsense If you are female student athlete in maine you have no rights Time for Maine voters/legislators to do the right thing and get this changed School boards should request a second legal opinion To say the federal government won’t be giving federal funds to individual schools implying it is because that’s not how it works Individual districts can apply for grants from the federal government so they are not being truthful If they are a district who can demonstrate that they are in compliance with the federal title IX Get a second legal opinion for crying out loud MSMA and D W are not much more than a clanging symbol in an echo chamber what if they want to organize their own private invitation only ‘girls only’ event I’d be willing to bet there would be plenty of moral and financial support Maine needs to address a huge mental health issue Buckle up everyone gonna be interesting for the parents at these games We need to direct our anger in force towards legislatures Boys stay away from our girls or face domestic abuse charges for hitting a female Maybe the girls need to join boys teams and hang out in their locker room How pissed would parents and their girlfriends be REFUSE TO PLAY…girls need to be a team and protest en masse no facilities… it’s in the girls’ court Fly those Maine Flags upside down and you girls need to boycott this bull$hit en masse don’t accept your diploma when graduation comes around Your refusal to engage in this madness is more powerful than all the money they make from it They will graduate and move on never to have this experience again We need to start the process to stop those in power creating this fiasco Our babies deserve a positive life experience Mills and Bellows disgust me.when do we stand up for our children… this is a conviction with meaning After three generations of boys getting screwed How about boys play against other boys and girls play other girls and trans play against other trans in sports That’s neither what domestic abuse is and the fact that someone would claim this shows how much of an anti-male crusade the VAWA actually is They already are — it used to be called the Boy Scouts I don’t see why boys can’t play field hockey Maine did the right thing and stood up for fairness and inclusion defied the Trump anti-trans bandwagon–and won I hope this is an indication of a new trend So Drummond Woodsum is in charge of Maine state athletics now a far left progressive law firm advocating for mentally ill boys to compete against girls So now we have a left wing “law firm” and a “non profit” (yeah right) running Maine sports Perhaps the Maine Wire could check on the % of administrative fees the MPA is taking in for salaries Or what the sponsors on thier website think about thier position on boys competing with girls….Hammond Lumber I bet they’ll run for the hills if you ask So let me understand this….if 2 high school girls are sitting on a park bench and some 18 year old guy comes and pulls his junk out in front of them he gets arrested But that same guy can claim he’s a girl and the same 2 girls have to share a bathroom and Locker room with him where he is free to pull out his junk in front of them….yeah makes total sense The “New Maine” where Women are Women and Men want to be Women too Disgraceful State all because of a Lunatic in the Governor’s seat We are funding this attack on our children This and the teacher in Waterville are a showcase of what fools the body politic and public education system have made of the electorate the fact it is still going on tells u we r getting played cant justify why other than for thier own selfish reasons its now up to the student athletes to stand for what is right maybe they wont be getting played if they dont play the game maybe if the top 1% didnt have all the money a local rich guy would put up 100 mill and make a non profit privite sports leauge… The Maine Wire story on the Bonney Eagle alleged rape may be something to consider before turning their daughters over to this utter nonsense “to participate on high school sports teams in accordance with their “gender identity.” Gender delusion is the term for stating how you wish to be identified as opposed to how you are identified in reality and scientific terms Gender identity is not something you can make one choice on weekdays wake up each day and choose what gender you will be for that day It is like we in a Hunger Games state of mind Me and Janet (see you in court) Mills love watching when a guy beats the living tar out of women in athletic endeavors This crap would never have happened under a LePage administration I have absolutely no respect for anyone who believes XY belongs in female sports so now we have boys sports and misc sports the women rights activists are no where to be found they are the clowns allowing men to put set you back I just started 3 weeks ago this web income system that my friend recommended to me and I’ve gotten 2 checks for a total of $9,200… this is the best decision I made in a long time This extra cash n4550 has changed my life in so many ways Here is I started_______ Tinyurl.com/homestar2?/n4550 For the record seventy two percent of high school graduates can not identify where girls pee from So maybe it’s time to stop crying over genitalia I mean clearly y’all missed the biology class that covers that but did you skip health class too So here we are with a ton of 40+ men and women pouting because some sissy dude did indeed place better than a girl on a high school track team?!? Every single kid in Maine who is homeschooled gets screwed out of the opportunity to even try playing sports You know if you aren’t willing or can’t vaccinate 4-21 year old children in accordance with cdc recommendations then they are completely denied a right to public or private education/sports etc in Maine?!? these fairy boys would have been delt with is there any part of the RICO Statutes that apply to child abuse &/or endangerment in the public education system For those with the bright idea of pulling another Charlie Howard, see: https://www.legislature.maine.gov/lawlibrary/what-is-maines-law-on-hate-crimes/9469 Eyewitness News is The Bahamas #1 trusted source for local news By signing up, I agree to our TOS and Privacy Policy Conduit Books will not ‘seek an adversarial stance … but the emphasis at first will be on ambitious political and cerebral fiction by men that is being passed by’ A writer and critic has launched a new independent press that will focus on publishing books by male writers. Conduit Books, founded by Jude Cook, will publish literary fiction and memoir, “focusing initially on male authors”. Cook said the publishing landscape has changed “dramatically” over the past 15 years as a reaction to the “prevailing toxic male-dominated literary scene of the 80s, 90s and noughties”. Now, “excitement and energy around new and adventurous fiction is around female authors – and this is only right as a timely corrective”. “This new breed of young female authors, spearheaded by Sally Rooney et al, ushered in a renaissance for literary fiction by women, giving rise to a situation where stories by new male authors are often overlooked, with a perception that the male voice is problematic,” he said. These “overlooked narratives” might address fatherhood, masculinity, working class male experiences, sex, relationships, and “negotiating the 21st century as a man” – “precisely the narratives” that Conduit hopes to publish. Cook said conversations about toxic masculinity after the second election of Donald Trump and the popular Netflix series Adolescence means that the “subject of what young men read has become critically important”. whose book The Borrowed Hills was shortlisted for this year’s Sunday Times young writers’ award what with the next generation of them simmering with rage online but it’s a question I’ve been hearing for a long time can sometimes be dismissed as unserious or unevolved A book press willing to tackle that is a good start but the hard part will be cobbling together an audience out of readers who have become neglected.” The press is actively looking for a book to launch with “preferably a debut novel by a male UK novelist under 35” with submissions open throughout the month of May short story collections or memoirs a year beginning in spring 2026 It “can’t be over-stressed” that Conduit Books “doesn’t seek an adversarial stance” “Nor is the press looking to exclude writers of colour Men have not suddenly stopped reading and writing literary fiction, said Cook – rather, they are simply “not being commissioned”. He pointed to 2020 data suggesting that 78% of those in editorial roles in the publishing industry are women Free weekly newsletterDiscover new books and learn more about your favourite authors with our expert reviews “Whenever I send out a novel to editors, the list [of names] is nearly all female,” a male agent told Johanna Thomas-Corr for an Observer piece in 2021 “But it’s not the gender makeup that bothers him it’s the prevailing groupthink – the lack of interest in male novelists and the widespread idea that the male voice is problematic,” wrote Thomas-Corr The declining prominence of young male writers has been a topic of debate in the publishing industry for several years, in part sparked online by a Times piece by James Marriott titled “Booker prize 2020 longlist: where are the new male hotshot novelists?” There has “never been an independent publisher that champions literary fiction by men,” said Cook “Which is not to say we won’t publish fiction by women in the future – but the emphasis at first will be on male authors political and cerebral fiction by men that is being passed by.” Cook is the author of the books Byron Easy and Jacob’s Advice He regularly reviews books for outlets including the Guardian and TLS and teaches creative writing at Westminster University He said that since announcing the new press the response “has been overwhelmingly positive especially from female authors and women who work in publishing” All 5 Releases The number of cases involving male victims of stalking and harassment rose nearly 11 percent last year while the number of incidents involving female perpetrators jumped 14.5 percent data released yesterday by the Ministry of the Interior showed Police agencies handled 2,806 stalking and harassment cases last year The number of cases involving female victims fell approximately 3.7 percent to 2,427 while incidents involving male victims were up 10.8 percent to 379 Photo courtesy of the Ministry of the Interior About 32 percent of the victims were aged 21 to 30 27.7 percent were aged 31 to 40 and 20.5 percent were aged 41 to 50 403 were female and in 123 cases the gender was not known the number of cases involving male suspects fell 4.4 percent while that of those involving female suspects rose 14.5 percent About 25 percent of the suspected perpetrators were aged 31 to 40 20.5 percent were aged 21 to 30 and 19.9 percent were aged 41 to 50 64.1 percent were categorized as general stalking and harassment cases while 35.9 percent were categorized as involving domestic violence About 79 percent of the suspected perpetrators in the general cases were male while the number of female suspects increased 8.5 percent Eighty-five percent of the suspected perpetrators in domestic violence-related stalking and harassment were male while the number of cases involving female suspects increased 26.5 percent About 85 percent of the victims in domestic violence-triggered stalking and harassment cases were female while cases involving male victims surged 39.6 percent police agencies issued 1,867 written warnings for stalking and harassment No warnings were issued in 939 cases because the allegations did not constitute stalking and harassment or no perpetrators were located Judicial Yuan data showed that courts issued restraining orders in 105 cases representing 67.3 percent of all petitions filed by victims Police agencies handled 143 cases in which a suspect violated a restraining order Among the 27 petitions to remand suspects in custody Sheridan County YMCA Executive Director Liz Cassiday told Sheridan Media the Sheridan County YMCA was short on female camp counselors before the beginning of the camp season Cassiday reached out and Sheridan County answered the call the Y is searching for a few more male camp counselors to join the team.  Camp counselors are more than just chaperons watching over campers as they enjoy their summer season mentors and make long lasting positive impacts on the lives of children.  The job of camp counselor also guarantees a summer job that is anything but routine The position provides plenty of time outside and the chance to mentor children while they learn safe and time tested techniques on taking full advantage of living in the Bighorn Mountains being a camp counselor offers numerous advantages and a chance to positively impact children’s lives It’s a rewarding experience that fosters leadership all while enjoying the great outdoors and making lasting memories To learn more and to contact the Sheridan County YMCA, click here.  and website in this browser for the next time I comment