the San Timoteo Nature Sanctuary is an exemplar of land management that serves the public increases access to nature in urban environments and supports wildlife via restoration of native species. We came together as a band of strangers and left connected to the land and energized to protect the environment.  The outing offered me a chance to reflect on the last time I was in San Bernardino County approximately 6 years ago with my daughter – which happened to be the first day we met upon my return from a deployment to the Middle East Everything about the day reminded me why our sacrifices as servicemembers are worth it how nature is the best place to find community It reminded me of my commitment to ensuring the planet will continue to be protected for people just like me Our day started with a tour by longtime volunteer land manager, Martin Lemon, who introduced us to the diverse flora and fauna of the land in addition to sharing the story of how the Redlands Conservancy filled a need via private philanthropy to protect the land and maintain the sanctuary resulting in an accessible green space open to all Our newly minted scientists then had the opportunity to explore two different ecosystems on either side of the Cocomaricopa Trail – hilly chaparral to the northeast and riparian wetland to the southeast along San Timoteo Creek.  “Volunteer-collected data is crucial for documenting species present in all of the more than 200 ecoregions of California. Through community efforts, we’re providing scientists access to data that would otherwise be too difficult or expensive to collect on their own,” said Alison Ormsby, Associate Director of Design at Adventure Scientists. California is one of 36 global biodiversity hotspots: places that are rich in biodiversity The soil samples will be analyzed by a lab at the University of California Santa Cruz to find and document organisms in the soil co-hosted by the Military Outdoors campaign was to coordinate efforts between national and local partners to uplift conservation initiatives in California and encourage more members of the military community – which is quite large in the region – to take action to protect the biodiversity in their backyards We know that southern California is the epicenter of U.S Military operations as the home to ~159,000 active duty service members across all branches of service We also know that 41% of all servicemembers are of ranks “E4” and under which means that they’re likely 19-25 years old and living away from home for the first time.  Uplifting projects like these to that demographic will be crucial in our efforts to cultivate champions for conservation and uplift veteran voices for the environment and special outreach to the military community is crucial to the health of our veterans and servicemembers and look forward to uplifting this success as a prototype The results of this Earth Day field day definitely showed that people of all ages will turn out for purpose-based projects with enthusiasm.  it is essential for us to lean into the strength of our community and work together to advance our shared vision of a sustainable and healthy planet,” said Andrea Iniguez a Sierra Club field organizer with the Angeles Chapter Andrea and other members of the Angeles and San Gorgonio Chapters participated in the event as well.  In the short term we served the immediate needs of an ecosystem undergoing restoration the California Biodiversity Project of Adventure Scientists and transferred a love for the outdoors across generations in a manner that will ensure a passion for conservation lives on during challenging times for our plant Together under the sun we generated hope and reaffirmed that nature is worth fighting for As the effects of climate change, wildfires, and other factors transform existing ecosystems, it is crucial to have records of plants, fungi, and animals to inform conservation priorities and actions across the state. Adventure Scientists’ California Biodiversity project runs through August 2025 so there’s still time to get involved. Check out the project page for more information on how to join.  We are facing monumental threats to our planet’s future We are fighting back with every tool at our disposal – but to face these challenges *Providing your email OR phone number allows us to follow up at a later time to ask for your help in preserving our precious wildlife With this action you affirm you want to receive Sierra Club communications and may vote on policy designated by the Sierra Club Board Msg & Data Rates May Apply.Text STOP to opt out. No purchase necessary. You'll also receive Sierra Club mobile action alerts (expect 4 msgs/mo). Terms and Conditions Sierra Club® and "Explore, enjoy and protect the planet"® are registered trademarks of the Sierra Club. © Sierra Club 2025.The Sierra Club Seal is a registered copyright We have the address for the funeral home & the family on file If you're not happy with your card we'll send a replacement or refund your money Timoteo H. Deluna, loving father, brother, and grandfather embraced God on January 14, 2025, in San Antonio, Texas, at the age of 81. He was born on September 11, 1943. He is preceded in death by brothers Fred Deluna and Moses Deluna; sisters... View Obituary & Service Information Deluna created this Life Tributes page to make it easy to share your memories © 2025 Mission Park Funeral Chapels & Cemeteries Made with love by funeralOne A Friday evening crash on Morgan Road just outside the Ceres city limits took the life of a 32-year-old Ceres man The crash occurred at approximately 5:30 p.m Timoteo Alvarez Torres was driving southbound on Morgan Road in a blue Mustang when for some unknown reason he crossed into the northbound lane where he collided with a semi tractor-trailer rig Alvarez Torres had to be cut from the wreckage by Modesto Fire Department firefighters The married father was loaded into an ambulance but was declared dead at a Modesto hospital The driver of the big-rig sustained only minor injuries Anyone who may have witnessed the crash is encouraged to call Modesto Police Officer Cody Chesney at chesneyc@modestopd.com A GoFundMe account has been established for the victim’s family to assist with burial and other expenses It may be found at https://www.gofundme.com/f/assist-timoteos-family-with-funeral-expenses Your access to this service has been limited If you think you have been blocked in error contact the owner of this site for assistance If you are a WordPress user with administrative privileges on this site please enter your email address in the box below and click "Send" You will then receive an email that helps you regain access Wordfence is a security plugin installed on over 5 million WordPress sites The owner of this site is using Wordfence to manage access to their site You can also read the documentation to learn about Wordfence's blocking tools or visit wordfence.com to learn more about Wordfence Click here to learn more: Documentation 6 May 2025 2:52:03 GMT.Your computer's time: document.write(new Date().toUTCString()); was arrested Monday in connection with aggravated assault Ron Wood has been a professional journalist in Arkansas for about 40 years He has covered state and federal courts in Northwest Arkansas since 1995 Over the course of his award-winning career he has covered a wide range of beats including city and county governments This document may not be reprinted without the express written permission of Arkansas Democrat-Gazette Material from the Associated Press is Copyright © 2025 audio and/or video material shall not be published rewritten for broadcast or publication or redistributed directly or indirectly in any medium Neither these AP materials nor any portion thereof may be stored in a computer except for personal and noncommercial use The AP will not be held liable for any delays errors or omissions therefrom or in the transmission or delivery of all or any part thereof or for any damages arising from any of the foregoing Playwright and performer Farren Timoteo takes audiences to 1970s Jasper where an Italian teenager dreams of making his mark caught between two cultures and driven by the heart of Rocky Balboa and the swagger of John Travolta The show has been celebrated for its vibrant storytelling and Betty Mitchell Award (Calgary) for Outstanding Lead Performance in a Comedy along with the Calgary Theatre Critics’ Award for Outstanding Performance in a One-Person Show Deputies arrested a man who they say shot at another man and a 6-year-old boy during an argument inside an Apple Valley grocery store on Thursday afternoon The gunfire took place shortly before 1:50 p.m according to the San Bernardino County Sheriff's Department "The investigation revealed the suspect, William Timoteo Moller, and the 37-year-old victim were arguing inside the store when the suspect pulled out a handgun and fired one round," sheriff's officials said in a written statement no one was hit by gunfire and there were no physical injuries." Responding deputies detained Timoteo without a struggle and recovered the gun beleived to have been used in the shooting He was described as a 37-year-old Apple Valley man Timoteo was booked on suspicion of attempted murder Bail was set at $2 million pending an initial court appearance scheduled Monday in San Bernardino County Superior Court More: DUI arrest in Hesperia leads to discovery of 44 pounds of methamphetamine Any witnesses, or anyone with information, was urged to contact the Apple Valley Police Department at (760) 240-7400, or Sheriff's Dispatch at (760) 956-5001. Information may also be submitted anonymously to the We-Tip hotline at (800) 782-7463 Metrics details Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease due to gradual motoneurons (MN) degeneration Among the processes associated to ALS pathogenesis there is the formation of cytoplasmic inclusions produced by aggregation of mutant proteins in neuronal cells and in iPSC-derived MN expressing mutant FUS such inclusions are significantly reduced in number and dissolve faster when the RNA m6A content is diminished stress granules formed in ALS conditions showed a distinctive transcriptome with respect to control cells which reverted to similar to control after m6A downregulation cells expressing mutant FUS were characterized by higher m6A levels suggesting a possible link between m6A homeostasis and pathological aggregates we show that FUS inclusions are reduced also in patient-derived fibroblasts treated with STM-2457 paving the way for its possible use for counteracting aggregate formation in ALS we investigated the interplay between SG and m6A in the context of ALS demonstrating that while m6A plays a limited role in SG physiology in control conditions it has a strong impact in ALS genetic contexts such as those where the FUS protein is mutated in domains that confer to it a cytoplasmic relocation we found that SG formed in the presence of mutant FUS differs from those of control cells not only in the number of condensates and in the rate of recovery from stress but also in RNA composition We found that cells expressing mutant FUS were characterized by higher m6A levels and that METTL3 downregulation re-established its amount similar to control the recovery of normal m6A levels produced the rescue of altered SG dynamics and reverted the transcriptome composition towards the one of control cells either the overexpression of METTL3 or the downregulation of the m6A eraser ALKBH5 worsened SG properties both in control and ALS cells inhibition of METTL3 activity through the inhibitor STM-2457 led to an effective reduction of FUS-containing SG formation both in neuronal cell lines as well as in fibroblasts derived from ALS patients we observed reduced FUS confinement within condensates when m6A levels were lowered these data indicate the overall importance of m6A modification in the conversion of physiological SG into pathological ones and might foresee a potential therapeutic approach in those cases where protein aggregates formation has pathological implications a Schematic representation of the experimental flow used for comparing stress granule transcriptomes b–d Scatter plot depicting RNA differential enrichment in SG in FUSWT vs FUSWT METTL3-KD (b) or FUSP525L vs FUSP525L METTL3-KD (c) or FUSWT vs FUSP525L METTL3-KD (d) conditions Axes describe log2FC of SG RNA enrichment in the indicated conditions Black dots indicate commonly enriched RNAs e Pie charts displaying the percentage of meRIP-Seq enriched RNAs among invariant and relocated defined in the comparison between FUSP525L vs FUSP525L METTL3-KD Source data are provided as a Source Data file In order to identify transcripts possibly altered in their association with SG upon m6A reduction RNA-seq data were analyzed through “Differential Enrichment Analysis” (DEA) comparing transcripts enrichment in SG in the presence of METTL3 and upon its downregulation We distinguished four groups of transcripts: (1) RNAs significantly enriched in SG both in control and METTL3 knock-down conditions defined as “commonly enriched”; (2) transcripts enriched only upon METTL3 depletion named “ΔMETTL3-enriched”; (3) transcripts not enriched upon METTL3 depletion defined as “ΔMETTL3-depleted”; (4) RNAs not enriched or showing no significant difference in SG enrichment these data indicate that while FUSWT and FUSP525L SG transcriptomes are markedly different they revert similarly under conditions of m6A downregulation the downregulation of METTL3 allowed the relocation in mutant SG of a considerable fraction of RNAs restoring the wild type SG RNA composition indicated that FUSP525L SG tend to enrich less m6A-containing transcripts thus suggesting a link between m6A modification and altered SG composition in ALS indicating that m6A target regions per se are not preferred sites for FUS binding These data are in agreement with the observation that methylated species are less recruited in FUSP525L SG (loss species) and only reimported upon METTL3 downregulation (relocated species) these results allowed us to conclude that in ALS conditions m6A-enriched species are present at a lower percentage in SG and are not preferential targets of mutant FUS In order to investigate if the downregulation of METTL3 could impact not only on the RNA content of FUSP525L SG, but also on their number and size, we combined immunostaining for FUS and G3BP1 (Fig. 2a). a Representative images of the indicated stressed SK-N-BE cells G3BP1 antibody staining is depicted in green (n = 3 biologically independent replicates.) b Representative single focal planes captions of mFISH for CLSTN1 transcript (red) immunofluorescence for stress granule marker G3BP1 (green) and DAPI (blue) in the indicated SK-N-BE cells (top) the digital magnification of G3BP1 granules is highlighted by dashed squares Bar plot showing representing the percentage of CLSTN1 smFISH signals colocalizing with stress granules as mean of replicates with standard deviation The ratio of each sample versus its control was tested by a two-tailed Student’s t-test d Box plots illustrating the number of stress granules per cell in the indicated SK-N-BE cell lines (n = 3 biologically independent replicates.) or iPS-derived MN (n = 4 biologically independent replicates) and maximum (See Source Data file for values) The red dot indicates the average number of granules in each sample after 1 h stress Each black dot represents the number of granules in a single field Seven fields were acquired for each biological replicate e Box plots illustrating the number of stress granules per cell in SK-N-BE cells either overexpressing METTL3 (“oeMETTL3”) or downregulated for ALKBH5 (“ALKBH5 KD”) with respect to a control condition (“Ctrl”) combined with immunofluorescence for G3BP1 the CLSTN1 mRNA showed a clear re-localization in SG upon METTL3 downregulation while the other controls behave as expected CALM1 as unchanged in all conditions and HUWE1 always enriched in SG indicating that such group is not differentially affected by METTL3 downregulation although METTL3 decrease did not affect SG number and size in a physiological context where wild type FUS is expressed it reduced the number of SG to levels similar to the control in the FUS-associated ALS models tested these data indicate that the effect of m6A on SG dynamics is the same in cells expressing either the endogenous or the overexpressed mutant FUS both FUSP525L and FUSWT cells displayed an increased number of SG in these conditions we did not observe FUSWT delocalization in the cytoplasm alongside the observation that m6A decreases rescues FUSP525L SG number and transcriptome towards control conditions a Representative images of the indicated SK-N-BE cells after 1 h stress followed by 4 h recovery (n = 4 biologically independent replicates) b Box plots showing the percentage of unrecovered indicated SK-N-BE cells after 1 h stress followed by 4 h recovery The red dot indicates the average percentage in each sample Each black dot represents the percentage in a single field The ratio of each sample versus its experimental control was tested by a two-tailed Student’s t-test c Box plots showing the percentage of unrecovered SK-N-BE cells either overexpressing METTL3 or downregulated for ALKBH5 after 1 h stress followed by 4 h recovery These observations suggest the hypothesis that SG containing both G3BP1 and FUSP525L are formed G3BP1 is released free into the cytoplasm while FUSP525L persists in an aggregate form FUS aggregation is relieved if the levels of m6A are reduced Consistently with the hypothesis that RNA hypermethylation can alter granules dynamics, either the overexpression of the writer METTL3 or the downregulation of the eraser ALKBH5 lowered the recovery ability both in FUSP525L and FUSWT cells (Fig. 3c) Given the availability of a small molecule, STM-2457, which has been previously validated as an effective and specific inhibitor of METTL330 it was worth it to verify whether it could reproduce some of the phenotypes observed in ALS cellular models a Representative images of the indicated stressed patients-derived fibroblasts G3BP1 antibody staining is depicted in green and FUS in red (n = 3 biologically independent replicates.) b c Box plots illustrating the number of stress granules per cell in stressed iPS-derived MN expressing FUSP525L or patient-derived fibroblasts treated either with DMSO or STM-2457 The red dot indicates the average number of granules in each sample d Box plots showing the percentage of unrecovered patients-derived fibroblasts treated either with DMSO or STM-2457 f Box plots illustrating the diffusion coefficients (D) of FUSP525L in living SK-N-BE cells treated with either DMSO or STM-2457 in stress or recovery conditions The red dot indicates the average diffusion coefficient value single measurements were carried out for each condition in line with the finding that while G3BP1 is released from granules in the cytoplasm FUSP525L increases its diffusion coefficient and decreases its confinement into SG when METTL3 is inhibited further confirming the finding that reduction of m6A levels relieves FUS aggregation we demonstrate a new approach to reduce the formation of mutant FUS-containing SG and to facilitate their dissolution consisting in reducing the levels of m6A deposition on RNA reduction of FUS-containing SG condensates was obtained in cell lines and in patient-derived fibroblasts also with the small molecule STM-2457 a known fully validated inhibitor of the methyltransferase activity of the METTL3-METTL14 complex The deepening of this phenomenon indicated a possible molecular link between mutant FUS and m6A in aberrant SG formation: we found that in FUSP525L cells the m6A levels are higher than in control cells and lowering them rescued both the RNA content and SG dynamics to normal conditions targeting this modification can indeed revert not only the morphology but also the RNA composition of these condensates we also show that FUS is a poor direct interactor of m6A-containing RNAs These data are in agreement with the observation that a lower percentage of m6A-containing transcripts is recruited in FUSP525L SG (18%) in comparison to FUSWT (26%) and that these RNAs are relocated upon METTL3 downregulation for the inhibition of protein aggregates in FUS-associated ALS cases Our research complies with all relevant ethical regulations and was conducted in accordance with the criteria set by the Declaration of Helsinki Human primary fibroblasts were obtained from a patient carrying the p.R518I in FUS gene after written informed consent and approval of the Ethic Committee (Protocol nr SK-N-BE cells were cultured in RPMI (Sigma-Aldrich USA) supplemented with 10% FBS (Sigma-Aldrich GlutaMAX supplement 1X (Thermo Fisher Scientific sodium-pyruvate 1 mM (Thermo Fisher Scientific #11360070) and Pen/Strep 1X (Sigma-Aldrich For the inducible expression of FUSWT or FUSP525L SK-N-BE cells were exposed to 50 ng/mL Doxycycline (Sigma-Aldrich #D9891) for 24 h before the sodium arsenite treatment (Sigma-Aldrich SK-N-BE cells were dissociated with Trypsin 1X (Sigma-Aldrich #T4549) and 20,000–30,000 cells/well were plated on glass coverslips in 24-well plates cells were dissociated with Accutase (Thermo Fisher Scientific #00-4555-56) and 200,000 cells/well were plated on geltrex-coated glass coverslips in 24-well plates After an additional 6 days of differentiation the iPSC-derived motoneurons were treated with sodium arsenite As regards for METTL3-inhibition experiments while control MN were treated with the same volumes of DMSO All cell lines used in were grown at 37 °C All cell lines were tested for mycoplasma contamination and primary fibroblasts were exposed to 0.5 mM sodium arsenite for 1 h Rescue experiments were performed by restoring normal growth medium for 4 or 2 h after acute arsenite treatment in SK-N-BE cells or fibroblasts For METTL3 overexpression and ALKBH5 downregulation experiments SK-N-BE cells were plated on a 35 mm plate and transfected with lipofectamine 2000 transfection reagent (Thermo Fisher Scientific with either 1 μg of a vector expressing METTL3 or with the combination of 500 ng of sh1 and 500 ng of sh2 against ALKBH5 (TRCN0000291769 and TRCN0000291838) Transfection with 1 μg of a vector expressing scramble shRNA was used as a control (SHC202 TRC2) Eight hours after transfection 30,000 cells of each condition were trypsinized and transferred on glass coverslips in 24-well plates FUS expression was induced with 50 ng/mL doxycycline for 24 h and acute oxidative stress or recovery conditions were obtained as described below STM-2457 has been prepared according to published procedures30 Oligonucleotides and smFISH probes used in this study are listed in Supplementary Data 4 Cells were fixed for 20 min at RT with cold 4% paraformaldehyde (Electron Microscopy Sciences #15710) diluted to in complete PBS (Sigma-Aldrich rinsed 3 times with complete PBS and stored in PBS at 4 °C Cells were permeabilized with 0.3% Triton X-100 (Sigma-Aldrich #648466) diluted in complete PBS for 10 min and blocked for 30 min at RT with 5% goat and/or donkey serum depending on the host species of the secondary antibody used Samples were then incubated overnight at 4 °C with the primary antibody diluted in blocking solution (5% goat and/or donkey serum in PBS Cells were washed with complete PBS three times for 5 min at RT and then incubated with the following secondary antibodies for 1 h at RT diluted in blocking solution and were incubated for 1 h at RT Nuclei were stained with 1 μg/ml DAPI (#D9542 Sigma-Aldrich) diluted in complete PBS for 5 min and coverslips were mounted applying ProLong™ Glass Antifade Mountant (Thermo Fischer Scientific #P36980) leaving the slides overnight on the bench Confocal images were acquired with an inverted Olympus iX73 equipped with an X-Light V3 spinning disc head (Crest Optics) a Prime BSI Scientific CMOS (sCMOS) camera (Photometrics) and MetaMorph software (Molecular Devices) as Z-stacks (0.3-um step size) with a 60× oil-immersion objective The following antibodies were used for immunohistochemistry in this study: anti-FUS mouse antibody (Santa Cruz Biotechnology anti-METTL3 rabbit monoclonal antibody (Abcam anti-Beta III Tubulin (TUJ1) chicken antibody (1:400 donkey anti-mouse Alexa Fluor Plus 647 (1:300 donkey anti-rabbit Alexa Fluor Plus 647 (1:300 The analysis of immunofluorescence images was performed through the ImageJ software48 The ImageJ tool “3D Object Counter” was used for the quantification of SGs number and volumes For the estimation of cells forming SGs in the recovery experiments cells were scored as SG-positive when they presented at least one G3BP1 spotted cytoplasmic signal a nuclear mask was generated using the DAPI signal to specifically select nuclear regions; this mask was then used to measure the METTL3 fluorescence intensity mean of each nucleus with the ImageJ tool “Measure” For the signal colocalization analysis the ImageJ plugin “Jacop” was used to calculate the Manders coefficient of FUS signal colocalizing with the G3BP1 signal In order to consider only the cytoplasmatic signal of FUS a nuclear mask was created for each image and removed from both the FUS and G3BP1 images prior to proceed with the analysis For the signal profile analysis random granules were selected and sectioned with a 20-pixel length straight line and the ImageJ tool “Signal Profile” was used to quantify the signal intensity For the quantification of “FUS-only” granules in recovery experiments the G3BP1 signal was used to create a mask and then removed from the FUS signal before the quantification of the number and volumes of FUS-only granules using the ImageJ tool “3D Object Counter” Protein analyses were carried out as described in ref. 51 The following antibodies were used in western blots for protein analyses: Anti-FUS mouse antibody (Santa Cruz Biotechnology Anti-METTL3 rabbit monoclonal antibody (Abcam Anti-METTL3 [EPR18810] monoclonal antibody (Abcam Anti-Flag M2-Peroxidase (HRP) (Sigma-Aldrich Anti-ACTB-Peroxidase (AC-15) monoclonal antibody (Sigma-Aldrich Anti-GAPDH (6C5) monoclonal antibody (Santa Cruz Biotechnology Anti-Rabbit IgG (H + L) Secondary Antibody Anti-Actinin monoclonal antibody (Santa Cruz Biotechnology Anti-HPRT (HRP) antibody (Santa Cruz Biotechnology Anti-ALKBH5 monoclonal antibody (Proteintech After polyA+ RNA selection through Poly(A)Purist-MAG kit (Invitrogen m6A level quantification was performed thanks to the EpiQuik m6A RNA Methylation Quantification Kit (EPIGENTEK # P-9005) according to manufacturer’s instructions using 50–200 ng of RNA per well In order to normalize the immunoprecipitation efficiency we used the invariant transcript CALM1 as an endogenous control in the comparison of different SG isolation experiments In case of genes with multiple isoforms a representative isoform was selected (the longest isoform with the same biotype of the gene was selected as representative; the longest isoform for non-coding RNAs) In order to overcome the high variability related to immunoprecipitation-based experiments we performed an Enrichment convergence analysis we first ranked the expressed RNAs by their SG enrichment (log2FC) and then we selected a fixed number of enriched RNAs for each dataset and compared these three equally sized RNA sets We repeated this analysis selecting different fixed numbers of enriched RNAs gradually reducing the inclusion of the noise from the background transcriptome (fixed numbers of top enriched RNAs: 5000 Reads coverage for the forward and reverse strand were generated using deepTools bamCoverage software (v3.5.1; https://deeptools.readthedocs.io/en/develop/content/tools/bamCoverage.html) Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article The data supporting the findings of this study are available from the corresponding authors upon request. The high throughput sequencing data generated in this study have been deposited in the GEO database under accession code GSE242771 or tools used for this work are referred to in the methods section or in the figure legends Additional dedicated scripts developed for this work are available upon request Stress granule dysregulation in amyotrophic lateral sclerosis Mammalian stress granules and P bodies at a glance RNA granules and diseases: a case study of stress granules in ALS and FTLD Differences between acute and chronic stress granules and how these differences may impact function in human disease Zaccara, S., Ries, R. J. & Jaffrey, S. R. Reading, writing and erasing mRNA methylation. Nat. Rev. Mol. Cell Biol. https://doi.org/10.1038/s41580-019-0168-5 (2019) m6A-binding YTHDF proteins promote stress granule formation m6A governs length-dependent enrichment of mRNAs in stress granules Limited effects of m6A modification on mRNA partitioning into stress granules FUS stimulates microRNA biogenesis by facilitating co-transcriptional Drosha recruitment ALS mutant FUS disrupts nuclear localization and sequesters wild-type FUS within cytoplasmic stress granules METTL3-mediated m6A RNA methylation promotes the anti-tumour immunity of natural killer cells METTL3 depletion contributes to tumour progression and drug resistance via N6 methyladenosine-dependent mechanism in HR+HER2-breast cancer invasion and immunity in esophageal squamous cell carcinoma Isolation of mammalian stress granule cores for RNA-Seq analysis Mariani, D. et al. ALS-associated FUS mutation reshapes the RNA and protein composition and dynamic of stress granules. Preprint at bioRxiv https://doi.org/10.1101/2023.09.11.557245 (2024) The stress granule transcriptome reveals principles of mRNA accumulation in stress granules Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons m6A modified short RNA fragments inhibit cytoplasmic TLS/FUS aggregation induced by hyperosmotic stress Long noncoding RNA pncRNA-D reduces cyclin D1 gene expression and arrests cell cycle through RNA m6A modification Rapid protein depletion in human cells by auxin-inducible degron tagging with short homology donors A METTL3–METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation ALS mutant FUS proteins are recruited into stress granules in induced pluripotent stem cell-derived motoneurons Conversion of human induced pluripotent stem cells (iPSCs) into functional spinal and cranial motor neurons using piggyBac vectors Stress granules as crucibles of ALS pathogenesis Genetic convergence brings clarity to the enigmatic red line in ALS Aberrant deposition of stress granule-resident proteins linked to C9orf72-associated TDP-43 proteinopathy Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia Confocal-based fluorescence fluctuation spectroscopy with a SPAD array detector Single-photon microscopy to study biomolecular condensates ALS/FTD mutation-induced phase transition of FUS liquid droplets and reversible hydrogels into irreversible hydrogels impairs RNP granule function Context-dependent and disease-specific diversity in protein interactions within stress granules Protein aggregation in amyotrophic lateral sclerosis TDP-43 binds and transports G-quadruplex-containing mRNAs into neurites for local translation Age-dependent neurodegeneration and organelle transport deficiencies in mutant TDP43 patient-derived neurons are independent of TDP43 aggregation Widespread mislocalization of FUS is associated with mitochondrial abnormalities in skeletal muscle in amyotrophic lateral sclerosis with FUS mutations Spinal muscular atrophy: the role of SMN in axonal mRNA regulation Compromised autophagy and neurodegenerative diseases HspB8 prevents aberrant phase transitions of FUS by chaperoning its folded RNA binding domain Antisense oligonucleotide silencing of FUS expression as a therapeutic approach in amyotrophic lateral sclerosis RNA methylation influences TDP43 binding and disease pathogenesis in models of amyotrophic lateral sclerosis and frontotemporal dementia Gain and loss of function of ALS-related mutations of TARDBP (TDP-43) cause motor deficits in vivo ALS-related FUS mutations alter axon growth in motoneurons and affect HuD/ELAVL4 and FMRP activity ALS-linked SOD1 mutants enhance neurite outgrowth and branching in adult motor neurons NIH Image to ImageJ: 25 years of image analysis Enzymatic production of single-molecule FISH and RNA capture probes CircVAMP3: A circRNA with a role in alveolar rhabdomyosarcoma cell cycle progression The m6A reader YTHDC1 and the RNA helicase DDX5 control the production of rhabdomyosarcoma-enriched circRNAs Spot variation fluorescence correlation spectroscopy allows for superresolution chronoscopy of confinement times in membranes Quantifying membrane binding and diffusion with fluorescence correlation spectroscopy diffusion laws Fast calculation of fluorescence correlation data with asynchronous time-correlated single-photon counting Trimmomatic: a flexible trimmer for Illumina sequence data Cutadapt removes adapter sequences from high-throughput sequencing reads HTSeq-A Python framework to work with high-throughput sequencing data From reads to genes to pathways: differential expression analysis of RNA-Seq experiments using Rsubread and the edgeR quasi-likelihood pipeline Mapping identifiers for the integration of genomic datasets with the R/Bioconductor package biomaRt Transcriptome-wide mapping of N6-methyladenosine by m6A-seq based on immunocapturing and massively parallel sequencing Genome-wide location analyses of N6-methyladenosine modifications (m6A-Seq) BamTools: a C++ API and toolkit for analyzing and managing BAM files The sequence alignment/Map format and SAMtools RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome RNAmod: an integrated system for the annotation of mRNA modifications Konig, J. et al. ICLIP - transcriptome-wide mapping of protein-RNA interactions with individual nucleotide resolution. J. Vis. Exp. https://doi.org/10.3791/2638 (2011) OmniCLIP: probabilistic identification of protein-RNA interactions from CLIP-seq data WebGestalt 2019: gene set analysis toolkit with revamped UIs and APIs Download references Colantoni for useful discussions and suggestions This work is dedicated to the memory of Dr whose legacy of dedication to science and teaching will forever remain a great example This work was partially supported by grants from ERC-2019-SyG 855923-ASTRA and PRIN 2017 2017P352Z4 to I.B.; “National Center for Gene Therapy and Drug based on RNA Technology” (CN00000041) and NextGenerationEU PNRR MUR to I.B and G.V.; ERC-2018-CoG 818669-BrightEyes to G.V.; “Sapienza” Ateneo Project 2021 n RM12117A61C811CE and Regione Lazio PROGETTI DI GRUPPI DI RICERCA 2020 - A0375-2020-36597 NextGenerationEU through the Italian Ministry of University and Research under PNRR - M4C2-I1.3 Project PE_00000019 “HEAL ITALIA” CUP (B53C22004000006) to D.R.; Sapienza departmental projects 2023 (RD12318A998C70B8) to G.D.T These authors contributed equally: Gaia Di Timoteo Department of Biology and Biotechnology Charles Darwin Center for Life Nano- & Neuro-Science@Sapienza Fondazione Istituto Italiano di Tecnologia (IIT) Center for Human Technologies@Istituto Italiano di Tecnologia (IIT) Department of Life Sciences and Public Health Department of Drug Chemistry and Technologies The experiments were performed and analyzed by G.D.T. Bioinformatics data analysis was performed by A.S The original draft of the manuscript was written by I.B. Giuliani with suggestions from all the other authors Fondazione Istituto Italiano di Tecnologia (IIT) are currently in the process of a patent application Patent applicant: Sapienza University of Rome Fondazione Istituto Italiano di Tecnologia (IIT) name of inventors: Irene Bozzoni Adriano Setti application number: IT102023000022302 status of application: pending specific aspect of manuscript covered in patent application: use of METTL3 inhibitors in the treatment of protein aggregation diseases The remaining authors declared 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 Reprints and permissions Download citation DOI: https://doi.org/10.1038/s41467-024-49416-5 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: Translational Research newsletter — top stories in biotechnology Timoteo L’Esperance’s search for the best law school ultimately came down to a single practical criterion: good employment outcomes “I started out looking at highly ranked schools in cities where my fiancée and I would enjoy spending three years my priority became more focused on choosing a school where I could graduate with a job at a Big Law firm.” A visit to Nashville helped confirm Timoteo’s decision to choose Vanderbilt “My fiancée received a good job offer here so we spent a weekend exploring Nashville and had fun watching the Predators [Nashville’s professional hockey team] in the playoffs and talking to people I was confident that I would land a good job if I went to Vanderbilt and its relatively small size reassured me that I could make friends here,” he said Before he arrived for Orientation Week as an entering 1L Timoteo was invited to join the first cohort of OneElevate a leadership mentoring program that connects first-generation law students with upper-level student and alumni mentors “It felt nice to have a sense of community as soon as I arrived on campus and I met a bunch of students I don’t think I would have met otherwise since we didn’t end up having many classes together,” he said He also joined the Vanderbilt student chapter of the American Constitution Society as a 1L which helped him connect with other students and with lawyers nationwide and he served as the organization’s vice president as a 2L “We were able to bring in a ton of interesting speakers who included judges and lawyers from ACS and other organizations and they often gave great advice on the practice of law that you don’t necessarily get in the classroom,” he said Timoteo majored in political science in undergraduate but plans to focus on corporate and finance law. He particularly enjoyed his class in Corporations and Business Entities with Professor Amanda Rose and her courses in Corporations and Securities Regulation have done a really good job in preparing me to practice,” he said and I found myself enjoying corporate transactional work.” To increase his understanding of finance, Timoteo applied to Vanderbilt’s JD/MSF program a dual-degree program that allows current J.D and a Master of Science in Finance at Vanderbilt’s Owen Graduate School of Management Students in the JD/MSF program take law electives throughout their 2L year and then spend the first semester of their 3L year as full-time finance students at Owen which is directly adjacent to the law school Students divide the final semester of school between finance and law electives “The JD/MSF gave me a great opportunity to gain a better understanding my future clients and their needs and priorities,” he said He found his finance courses an interesting contrast to law classes “Business students work on projects in teams while you’re working individually in most law classes,” he said Timoteo and his fiancée wanted to return to a large legal market near their home state of New Mexico He worked at Gibson Dunn & Crutcher in Denver as a summer associate in 2022 and 2023 and plans to join the firm’s Denver office permanently after graduation In addition to the availability of the JD/MSF program Timoteo found the strong community a major advantage of attending Vanderbilt and I like being surrounded by hardworking individuals who push me to do my best and making lifelong friends all contributed to my success in finding a career I am excited about after graduation,” he said He advises incoming 1Ls not to worry about ‘imposter syndrome.’ “Realize that everyone else is in the same position as you Keep up on your readings and try to prioritize understanding the big concepts from the cases over the small details so remember that whatever you’re working on is probably better than you think!” Vanderbilt University’s Online Privacy Notice CA — Forensic work is underway at the San Bernadino County Sheriff's Department after skeletal human remains were discovered over the weekend on a Loma Linda property At 11:29 a.m. Sunday, the sheriff's department was called to the property in the 11400 block of San Timoteo Canyon Road for a report of "found skeletal remains," according to the law enforcement agency but it's not clear how or where exactly they were found The area is dotted with some businesses and homes will undergo examination and autopsy to determine the identity of the deceased as well as the cause of death," the sheriff's department reported "Additional information on this case will be released as it becomes available." The department did not publicly speculate about the victim's age or gender or about any missing persons cases in its files Anyone with information about the investigation is asked to contact Detective Michael Roth, Specialized Investigations Division at 909-890-4904. Callers can remain anonymous and contact We-Tip at 800-78CRIME or www.wetip.com Get more local news delivered straight to your inbox. Sign up for free Patch newsletters and alerts. Mose Timoteo will take over as head coach of the American Raptors for the remainder of the 2024 Super Rugby Americas season Rugby Foundation Hall of Fame inductee returns to the Raptors after most recently serving as the backs and attack coach from 2021 to 2023 Timoteo put together an impressive career as a player in both the sevens and fifteens game Timoteo appeared in 100 games for the United States Eagles and competed in the 2001 and 2005 Rugby World Cup Sevens He also totaled 28 appearances in iRB Sevens Series tournaments for the Eagles notching 14 tries and 12 conversions on the circuit Timoteo earned 32 fifteens caps as a scrumhalf which included an appearance at the 2003 Rugby World Cup in Australia He moved to the United States to join the United States Army and continued his rugby career for Fort Drum RFC Timoteo has built an impressive trophy case of accomplishments at the highest levels of rugby in the country These include championship titles in the Super League Timoteo was also the first-ever American Samoan to be capped for the USA Eagles Timoteo has served as a coach in various capacities for several different high school and adult men’s and women’s teams across the country He earned his Level 300 Coaching certificate in 2019 through the Premiership Rugby Scholarship program in England Timoteo will now set his sights on pushing the Raptors in a positive direction for the remainder of the 2024 Super Rugby Americas season “We as a team need to stay on course and really focus on things that we can control and improve in some areas that we need to improve on We must be competitive in all aspects of the game.” Timoteo said ahead of the remainder of the season City of Glendale American Raptors Super Rugby Americas RugbyTown USA Privacy Policy | Privacy Settings | Terms Of Service | Cookie Policy presented research on cannabis cultivation practices and optimizing terpene content In the Cultivation Track at the Cannabis Science Conference research assistant at the University of Maryland Eastern Shore “Maximizing Terpene Yields with Precise Harvest Timing in Cannabis sativa L.” discussed the effect of harvest times on terpene content the testing of terpene content during different stages of flowering (mid-flowering the different terpenoid content in plant generations He also noted the effect of inbreeding on terpenoid content concluded his presentation with advice for cultivators: “It depends on the genotype—each cultivar will behave different—but my recommendation is if you are working with cannabis and you want to increase the content of your terpene you need to study the cultivars you're working with because you need to know when those compounds increases and when they decrease in order to optimize and read the transcript below for more insights into the effect of harvest time on terpene content How did you become involved in cannabis research I'm a PhD researcher at the University of Maryland Eastern Shore because that was about the time when I finished my master's I was stuck for a couple months and then all of a sudden I got this PhD in food and agriculture science I start understanding the beneficial effects of cannabinoids and terpenoids and the plant as a whole and it just brought in me that interests in the plant I started researching and working and today we are here I think I was made for the plant and the plant for me What are takeaways from your presentation titled Timoteo Jr.: The objective of this of this presentation the lab being as the scientists and the table being like the consumer which need our help in order to maximize the quantity and quality of these compounds what I was presenting was basically to understand the dynamic of the terpenes so we can know when to harvest to maximize its concentration so that we can meet commercial demands I established my research over the course of a year is to know that at certain flowering stage development the concentration of terpenes are high and in others are low I have successfully identified that and today I can provide the guidance to farmers; I believe I have laid the foundation and they can proceed from there What do you most look forward to at the Cannabis Science Conference I think this is a thriving industry and the more we work together We have people like us who are pretty much doing the research in cultivation people who are working in analysis of the compounds people that are in regulations and industry when it comes to dispensary and formulations The goal here is to bridge the gap so everybody can work together so at the end of the day we can definitely improve even more this industry So I do believe it's coming together and that's what this conference is all about I mean for some reason you are the first and the pioneer and the biggest one in the country so I've been in more than three events back-to-back Almost all the good friends that I have I got them from here so those events definitely have shaped the future for cannabis for all of us Best of the Week: April 25 – May 1, 2025 we bring you our top five recent articles covering our newest publication and supplement Result Manipulation: From THC Inflation to Aspergillus High Cannabis Use May Be Connected to Increased Mortality Seen in Colon Cancer Patients A recent study found that high cannabis usage in colon cancer patients may experience increased mortality Impact of Water Activity on the Chemical Composition and Smoking Quality of Cannabis Flower: The Science of Smokability Phase I Results Smoking remains the most common method of cannabis consumption particularly for patients seeking rapid relief little is known about what defines a high-quality smokable product This study investigated how varying water activity levels (0.45 aW 0.85 aW) affect cannabis flower’s chemistry and perceived smoke quality Chemical analyses showed that 0.65 aW yielded the highest terpene content and comparable cannabinoid delivery to 0.45 aW while 0.85 aW significantly reduced cannabinoid levels Sensory panelists noted minimal differences between 0.45 and 0.65 aW samples Higher water activity increased moisture and product weight—suggesting economic benefits for producers These findings offer insights into optimizing water activity to balance chemical and financial factors in cannabis production 2024 Market Report of New York’s First Two Years of Legal Cannabis Sales Released by OCM New York’s OCM releases 2024 Market Report of the state’s first two years of legal cannabis sales THC Beverages Study Looking to Explore Wellness Alternative Possibility to Alcohol An upcoming study is seeking to investigate THC beverages as a wellness alternative to alcohol 609-716-7777 Ahimsa Timoteo Bodhrán is a multimedia artist and terrestrial techniques to produce work across 22 nations in the Americas Bodhrán is the author of Antes y después del Bronx: Lenapehoking and South Bronx Breathing Lessons both forthcoming; editor of the international queer Indigenous issue of Yellow Medicine Review: A Journal of Indigenous Literature and Thought; and co-editor of the Native dance and performance issue of Movement Research Performance Journal Bodhrán has received scholarships/fellowships from the Voices of Our Nations Arts Foundation an entwined poetry and prose multigenre book one component of a larger interdisciplinary multimedia project comprised of visual and interpersonal research and collaborative travel throughout New York and California and in and across the Americas and Atlantic and Pacific Oceans Employing transcompositional techniques to produce innovative I am utilizing a range of tools and equipment to develop my pan-artistic both a National Endowment for the Arts Fellowship and a Tulsa Artist Fellowship means I can finally have a safe secure base from which to work expansively and help others bring about their own healing and transformation in their own lives Experiencing the dynamism of receiving both awards at this pivotal stage of my career as I increasingly embrace more collaborative and multimedia modes of inquiry means I will be able to more fully manifest and materialize the complete range of my artistic vision and Pacific—our concentric worlds—so I can reimagine these territories I seek to collaborate and build in ways that center and support our communities and the special gifts they bring this world View Transcript Saturday & Sunday: 1:30PMNo performances Wednesday 2 hours 10 minutes (including intermission) For assistance in booking special access seats or for information about our Accessibility Services For Group savings on 10-29 tickets, book online or call 1.800.461.3333 for assistance A Marquis Entertainment Production in association with the Citadel Theatre