Solar Power World By Billy Ludt | May 5 Solargik an international solar tracker manufacturer its next-generation intelligent monitoring and control platform SOMA Pro is a tracker-native software system that fully integrates monitoring diagnostics and performance control in one service is built into the core of the company’s own tracker hardware Its integrated design breaks down silos common to third-party SCADA systems or bolt-on controls and provides operators with real-time visibility and full remote control over tracker positioning Optimized for complex terrains and light conditions SOMA Pro includes management options for remotely stowing the site or fine-tuning behavior at the single tracker level SOMA Pro continuously optimizes tracker positioning based on dynamic elements of the solar plant operators gain full command of tracker tilt stow modes (manual or automatic) and production status we’ve redefined how solar installations can be managed – especially in environments where traditional systems fall short,” said Gil Kroyzer “By combining our lightweight tracker technology with an intelligent control system designed in-house insight and flexibility that helps operators extract more value from every site.” Billy Ludt is senior editor of Solar Power World and currently covers topics on mounting Δdocument.getElementById( "ak_js_1" ).setAttribute( "value" Copyright © 2025 WTWH Media LLC. All Rights Reserved. The material on this site may not be reproduced, distributed, transmitted, cached or otherwise used, except with the prior written permission of WTWH Media Privacy Policy | RSS Learn how to describe the purpose of the image (opens in a new tab) Leave empty if the image is purely decorative We're working on a visual shortcode editor until then please follow these instructions Email us to support@plugin.builders for any problems two-tower multifamily community in downtown Bellevue has sold for $192.85 million to a California company as well as two- and four-bedroom penthouse suites Soma Towers, a 273-unit multifamily community in downtown Bellevue, sold for $192.85 million, according to a news release from CBRE Bellevue-based Su Development sold the property to The Sobrato Organization whose purchase marks its first acquisition in Bellevue noting that Sobrato owns other multifamily assets in the Puget Sound region Other Sobrato properties in the area include the Bella Vista apartments and townhomes in Renton LionsGate North townhomes and apartments in Redmond and Axis and Dexter Lake Union apartments in Seattle according to the website for Mountain View and Mark Washington represented the seller Located at 258 and 288 106th Ave. NE in Bellevue, at Northeast 2nd Street, Soma Towers has two towers Community amenities include a heated lap pool The towers also have 29,964 square feet of commercial space across two floors that is 90% leased to restaurants The first tower was built in 2014 and the second in 2016, county records show. Su Development in 2019 won the Bellevue Downtown Association’s Placemaking Award for its Soma Towers an award that recognizes outstanding contributions to the city and its skyline BDA that year cited Soma Towers as an iconic project and noted Su Development’s “above and beyond” commitment to the city’s cultural vitality over the previous 30 years The Sobrato Organization has been developing commercial real estate for high-growth companies investing in entrepreneurial enterprises and giving back to the communities in which we live and conduct business,” Chad Froman “Soma Towers is directly aligned with our objective of making a positive impact by providing a high-quality living experience and a place that engages the broader community through its retail lifestyle offerings.” the company owns more than 75 commercial properties in Silicon Valley and hundreds of acres of land throughout Santa Clara and Alameda counties in California; has developed more than 15 million square feet of office and R&D properties; owns 7.2 million square feet of commercial space — mostly Class A midrise office buildings; and has developed or purchased more than 10,000 units since its founding and now owns 28 apartment communities totaling approximately 6,450 units along the West Coast “Our valued client had a tight timing window to make this deal happen going from launch to non-refundable within 60 days The property garnered significant interest from buyers because of the exceptional quality of the asset Email notifications are only sent once a day Your browser is out of date and potentially vulnerable to security risks.We recommend switching to one of the following browsers: Memorial services will be held at 10:00 AM on Tuesday Visitation will be held from 2:00 PM – 4:00 PM on Monday and will continue one hour prior to services at the church on Tuesday memorials may be directed to Trinity Lutheran Church More Weather Details Δdocument.getElementById( "ak_js_1" ).setAttribute( "value" A pedestrian and their pet were struck and killed in the area of Howard and Seventh streets in San Francisco's South of Market neighborhood Thursday afternoon The incident happened around 2 pm Thursday. SFPD officers responded to the scene on Howard Street at Seventh, and found an elderly pedestrian who had been struck by a vehicle, as the Chronicle reports An earlier version of the story indicated that the victim was a man in his 80s but those details don't appear anywhere as of Friday morning A photo from the scene posted to Reddit shows what appears to be a straw hat and a shoe lying in the street near a crosswalk The victim was transported to an area hospital and later pronounced dead from injuries sustained in the collision A deceased dog was also found at the scene The driver of the vehicle involved reportedly remained on the scene and cooperated with police The SFPD is seeking witnesses of the crash and if you have information you are asked to call the tip line at 415-575-4444 This appears to be San Francisco's fourth pedestrian death of the year to date, and the victims in these incidents are all too often elderly. In mid-March, a 77-year-old was killed by a driver in the area of 39th Avenue and Geary Boulevard Also this week, as Bay Area News Group reports a woman in her 70s was killed in a hit-and-run in Palo Alto while she was trying to cross the street 52-year-old East Palo Alto resident Ignacio Estrada was arrested for the crime Maybe not coincidentally on Thursday Waymo released new data showing that its robocars are better than humans at avoiding hitting pedestrians and bicycles. CA's largest reservoir has hit capacity for the third year in a row; Santa Rosa police engaged in an intense standoff with a residential burglar; and Trump wants to rename Veterans Day. Get the latest posts delivered right to your inbox Jay C. Barmann is a fiction writer and web editor who's lived in San Francisco for 20+ years. Stay up to date! Get all the latest & greatest posts delivered straight to your inbox "With SOMA Pro, we’ve redefined how solar installations can be managed - especially in environments where traditional systems fall short," said Gil Kroyzer, Solargik's CEO. "By combining our lightweight tracker technology with an intelligent control system designed in-house, we offer a level of adaptability, insight, and flexibility that helps operators extract more value from every site." Integrated architecture for unmatched reliability SOMA Pro is Solargik’s own proprietary SCADA platform that seamlessly integrates production monitoring, tracker configuration, and component diagnostics. This unified architecture reduces operational complexity, improves site stability, and eliminates the data blind spots that plague third-party monitoring tools. AI-driven optimization: Proprietary loss attribution with actionable results At the heart of SOMA Pro is Solargik’s in-house AI performance model, capable of identifying and quantifying energy loss down to specific rows or components. Leveraging advanced machine learning algorithms, the platform achieves detection accuracy exceeding 95%, enabling operators to recover up to 6% in lost energy. Its predictive analytics support targeted maintenance and strengthen EPC contractor collaboration - protecting long-term asset value. Real-time operational intelligence, not just monitoring Learning from real site conditions, SOMA Pro continuously optimizes tracker positioning based on dynamic elements of the solar plant, such as irradiance, cloudiness, wind speed and topography. Through a cloud-based interface, operators gain full command of tracker tilt, stow modes (manual or automatic), and production status - from the entire site down to an individual tracker or inverter - enabling faster response to changing conditions and improved energy yield. Solargik will officially debut SOMA Pro at Intersolar 2025. Journalists and analysts can schedule executive briefings and live demonstrations by contacting the Solargik media relations team or requesting a meeting here. Copyright © 2025 FactSet Research Systems Inc.© 2025 TradingView Please enable JS and disable any ad blocker 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 It looked like the end of an era for Ken Fulk's loft-like office and event space on Seventh Street in SoMa when he put it on the market three years ago and Fulk now says he's going to get back to throwing parties there Designer Ken Fulk has put his stamp on a number of Bay Area restaurants, wealthy socialites' mansions, and even the ultra-VIP section of Outside Lands. But as the Robb Report noted when it first hit the market in the fall of 2022 his 'Magic Factory' live-work space at 310 Seventh Street "has always been his calling card." "It’s an epic place to throw a party,” Fulk told the publication “Much of the building’s legendary status has been forged through the parties and people it’s hosted.” Fulk also told the Robb Report that he and his design and event-planning firm had "simply outgrown" the building and he was listing it for sale at $8.9 million It was then re-listed last spring at a slightly lower price, $7.7 million, and the asking price was lowered again in September to $7 million But, after failing to find a buyer, Fulk tells the SF Business Times this week that he's been inspired to start using the space again "That building has become such a part of my identity and has so many memories and I was trying to find the right steward and had the epiphany that maybe I am the right steward," Fulk tells the paper "I feel like our city is buzzing and always looking for the best version of itself and I feel it's time for this place to be ap art of this new conversation too." The 14,000-square-foot brick-and-timber building which has living quarters and entertaining space on the upper level and office space below was the former workshop and showroom of Mr which relocated to its current space at 385 8th Street in the 90s And Fulk says the space therefore "always sort of had this wink toward San Francisco's slightly naughty side combined with the highbrow work that we do." And the main living and entertaining area is anchored Fulk lives with his husband in Clarendon Heights and Fulk has a design studio in New York as well his work has taken him to Los Angeles for the first time where he's working on a full-scale renovation of the Beverly Hills Hotel He also bought the Paramour Estate in the Silver Lake neighborhood and restored that into a nine-room He now says his focus is shifting back to San Francisco, and he recently threw a 200-person party with Architectural Digest at the old Magic Factory. (Fulk is an AD100 designer, and was profiled by the magazine in 2023.) As he tells the Business Times, "We are going to have cool events and programing and welcoming people back into the space that I think has a vibration — it's like that building has a soul." He adds, "I think there is an inclination for us in 2025... people want to be together and we live in such a hyperdigital world ... I think as a counterbalance to that we want to be truly connected." So, be on the lookout for your party invite I guess. Far fewer tourists from other countries are visiting California since Donald Trump took office again, and visits from Canada and Mexico are down particularly sharply, amidst immigration anxiety and tariff resentment. South San Francisco police shot and killed a man Monday evening in what's been described as a shootout. AMSC ASA (under liquidation) (AMSC) currently holds 91,422,601 shares in Solstad Maritime ASA (SOMA), equalling approximately 19.6% of the shares in the company. SOMA has today published its 2025 first quarter results, which can be found on https://newsweb.oslobors.no/message/645222. On 24 April 2025, the annual general meeting of AMSC resolved to distribute the company's shares in SOMA as dividend-in-kind to its shareholders in connection with the contemplated listing of SOMA on Euronext Oslo Børs, and also resolved that AMSC shall be liquidated. The dividend-in-kind is conditional upon necessary approvals by Euronext Oslo Børs related to the listing of SOMA on Euronext Oslo Børs. As announced on 1 April 2025, subject to such approval AMSC expects that the last day of trading of the AMSC share including the rights to receive 1.272 SOMA shares per share held in AMSC (rounded down to the nearest whole number of shares) is on 6 May 2025, and that the shares of AMSC will be traded ex such dividend from and including 7 May 2025. Furthermore, due to the ongoing liquidation process, AMSC will not publish quarterly results for the first quarter ended 31 March 2025. This information is subject to the disclosure requirements pursuant to section 5 -12 of the Norwegian Securities Trading Act. https://news.cision.com/amsc-asa/r/amsc-asa--under-liquidation----solstad-maritime-asa-first-quarter-results--update-on-dividend-and-fi%2Cc4144873 By: Andrew Nelson 5:30 am on April 24 FORMA is looking to replace its own offices with 132 apartments inside a 26-story pencil-thin tower The 240-foot-tall infill is expected to yield around 114,070 square feet and 600 square feet for ground-level retail Parking will be included for 20 cars inside the two-level basement garage Unit types will vary with 72 studios/junior one-bedrooms and 60 three-bedrooms 20 will be designated as affordable housing The design by FORMA appears similar to 777 Sutter Street with a mix of ceramic panels and floor-to-ceiling glass The project team emphasizes that the design is consistent with the building scale and design of Central SoMa with window and facade articulation that accentuates the structure’s verticality The rooftop will be partially opened with an amenity terrace providing residents with a panoramic vantage point 896 Folsom Street street elevation overlooking 5th Street The project utilizes Assembly Bill 1287 to achieve an increased state density bonus and AB 2011 to streamline the approval process to add housing to a commercial lot The latest filing shows a minor increase in residential capacity from plans filed for 125 units last December The roughly 0.1-acre property is located by the corner of Folsom Street and 5th Street Future residents will be a four-minute walk away from the Yerba Buena/Moscone underground light rail station City records show the property last sold in 2008 for $2.05 million The team’s own offices are located inside the two-story commercial building at 896 Folsom Street The estimated cost and timeline for construction have yet to be shared Subscribe to YIMBY’s daily e-mail Follow YIMBYgram for real-time photo updates Like YIMBY on Facebook Follow YIMBY’s Twitter for the latest in YIMBYnews Hopefully there are some interesting details so we don’t have tall blank walls for 50+ years like we do with much of the back of the St Concern with facades (quality materials vs garish cheapo panels) the pedestrian experience and the overall character of the structure are imperative to building attractive This entire section of the city is filled with blank walls and garage doors (some of the worst versions built in the last 30 years) which have destroyed the sense of safety walkability and arguably compromised the cleanliness as well This 50ft slice of street front might not matter on it’s own but when you fill large portions of a neighborhood with bad design you get a bad neighborhood (home values dip Just walk a few blocks of SOMA in this area and you’ll see what bad design does It reminds me that something might be built adjacent to it in the future I’d assume we’re talking about streelevel… if not and we’re talking about 75ft in the air …and this addition is not helping to improve the situation even San Jose has better looking recent high rise projects than this And how many of those SJ towers have been built most properties with ‘plans’ are still vacant lots There are at most like 5 cities in the US that look anything like that at all There are Victorian townhomes in every single city in America I can’t tell if you’re being simple intentionally or arguing in good faith Do you not want to avoid overtly cheap boring design packed in between all the spaces Nothing screams progress than the hundreds of garden sheds stuffed under highways being used as shelters for those unable to afford a decent home I would take affordable housing any day over the humanitarian disaster that has been the Tenderloin for years and what has recently become of 16th and Mission (Both not directly the effect of piss poor urban planning but certainly an influence of the mess.) Once we can eliminate the need for students and blue-collar workers to sleep in cars then we can start being snobbish about our skyscrapers Except that your for-profit housing market doesn’t work like that If you want housing for anyone apart from wealthy tech bros the government has either got to subsidize it or build it or New York City was built while the majority of the population was living in squalor but the only thing worse than an ugly building is a beautiful building that never gets built And anything is better than a housing shortage that leaves people living under bridges Let’s build a couple hundred buildings like this in SoMa replace a lot of derelict/underutilized buildings Do you think these architects could learn how to build something other than drab boxes A great city like San Francisco deserves better than another round of this kind of crap architecture I don’t care about the details except the risk of downsizing this is like a really nice looking building in a neighborhood that needs a lot more housing and has the transit to support it and everyone thinks its too ugly Get out of here with your armchair architecture perfectionism and get a life ga('send', 'event', ‘Robert ‘Becker, 'Impression', 'https://sfyimby.com/wp-content/uploads/2024/11/desktop-ad.jpg', { nonInteraction: true }); ADVERTISEMENT ga('send', 'event', 'SF YIMBY', 'Impression', 'https://sfyimby.com/wp-content/uploads/2020/10/sfyimbyadnews.jpg', { nonInteraction: true }); ga('send', 'event', 'SF YIMBY', 'Impression', 'https://sfyimby.com/wp-content/uploads/2021/02/sf-yimby-dot-com-graphic.jpg', { nonInteraction: true }); Follow on Instagram © COPYRIGHT New York YIMBY LLC The heart of Wilkes-Barre’s SOMA Arts District pulsed with color and energy during the one-of-a-kind SOMA Night Lights event. Hosted by Diamond City Partnership and Sordoni Art Gallery family-friendly night brought creativity to a whole new level in the city From video-mapped projections that transformed buildings into vibrant, living art to mesmerizing creations from Keystone College‘s mobile glass blowing studio The Rusty Iris stole the show — a double-decker bus turned rolling sculpture thumping with music and setting the night ablaze with fire performances that lit up the street It was a night to remember and proof that Wilkes-Barre is putting free entertainment on the map Mostly cloudy this evening with thunderstorms developing after midnight Come summer, coffee will be brewing inside a downtown Bloomington building that once housed fiery kilns that dried wood made into furniture at Bloomington’s historic Showers factory who owns three other Soma Coffee House and Juice Bars in Bloomington said the fourth location will offer a large outdoor seating area fruit smoothies and food offerings will be available at this fourth location on the north edge of downtown which for $50,000 purchased the structure that once contained five large ovens that dried lumber before it was manufactured into furniture The group pledged to invest $2 million in the project with a goal of providing renovated office and restaurant space The Kiln Collective: Former Showers kiln building to become new business space The rustic interior brick walls from the old kiln rooms remain. The installation of large thick-paned windows brought in light and transformed the building, which already has several offices open for business. Earlier this month, Costello was among business owners sweeping up shattered glass after vandals broke out the windows at his future coffee house’s location. The damage delayed his plans, but he was hopeful to open on schedule. The three other Somas are at 322 E. Kirkwood Ave, 1400 E. Third St. and 581 E. Hillside Drive. Contact H-T reporter Laura Lane at llane@heraldt.com or 812-318-5967. Julia Chen, Lani Conway, Ricky Rodriguez & Patrick Wong CA 94103">.css-56eu0z{width:1em;height:1em;display:inline-block;line-height:1em;-webkit-flex-shrink:0;-ms-flex-negative:0;flex-shrink:0;color:var(--chakra-colors-gray100);vertical-align:middle;fill:currentColor;}355 11th St San Francisco This Mexican fine dining restaurant is where we send people looking to blow hundreds of dollars on a single dinner that will solidify into a core memory That’s because the 16 courses of dishes are nothing short of thrilling and grilled bananas are served in savory dulce de leche and crowned with caviar While dinner doesn’t come cheap ($325 a head) the cavernous all-black space and phenomenal food make this meal a production you won’t want to end 9.1Niku Steakhouse433 Clay St San Francisco Japanese Design District This place revolves entirely around Japanese A5 wagyu, which is just another way of saying: save this fancy steakhouse for special occasions or when you’re dining with a coworker who really cares about wagyu beef marble scores and whether a cow ate organic grass or was massaged before it died The massive binchotan grill is the centerpiece of the room and chefs barely take their eyes off filet mignons and Jurassic-looking tomahawks cooking over the flame Expensive cuts of raw meat are paraded around the space on a platter for diners to inspect before they order And you even get to pick your own personal steak knife for the evening dinner here is an immersive beef-centric experience that’s unlike anything else in town Access exclusive reservations with your sapphire reserve card 8.7HK Lounge BistroDim Sum Soma officially reopened in SoMa under a new name The Cantonese classics are still worth following this place across town for where you’ll find meaty and flawless siu mai and xiao long bao that are delicate soup bombs And don’t skip the fried sesame balls for dessert—they’re the ideal crispy finisher 8.5Square Pie GuysPizza But Square Pie Guys and their Detroit-style pizzas rise above thanks to their thick-but-light crust and cheddar baked edge that gives a cheesy crunch to every bite The precise presentation of pepperoni cups and toppings like garlic ricotta cream and hot honey is also a work of art which is why you’ll also find knockout chicken wings You’ll spend at least five minutes wondering how the golden-brown chicken thigh is crackly and juicy at the same time and marvel at how your fingers sink into the slices of milk bread as if it were a Tempur-Pedic mattress If you’re somehow not in the mood for a sandwich the spicy tuna bowls and curry plates are also worth getting into PlayUnmute8.5MoyaEthiopian We’ve never ordered something we didn’t love at Moya. The snug Ethiopian spot with the big windows on the corner of Minna and 8th Streets does both vegetarian and meat dishes equally well and everything is perfect for casual dinners and in-and-out lunches What makes this counter-service spot stand out are the depth of spices and layers of flavor We love the buttery kitfo with the tangy housemade cheese And you’ll never go wrong with the onion-packed doro tibs 8.4Deli BoardSandwiches It’s not that hard to make a good sandwich. But making a great one that’s worthy of planning an entire day around? That’s a feat in itself—and no place does it like Deli Board. This spot on Folsom between 6th and 7th Streets cranks out tank-sized sandwiches that are well-stuffed with everything from corned beef to tuna salad and falafel Whatever you order off of their usual menu or eponymous board of daily-changing specials will be fantastic Sushi Wabi-Sabi is a tiny sushi spot with a lot going on Chefs work just steps away from your plate assembling pristine nigiri while waitstaff field takeout orders and phone calls but the $49 moriawase—a rotating 11-piece set that’s often upgraded with a bonus bite or two—is one of the best sushi deals in SF Grab a bar seat and hope for salmon with lemon zest or a shiso and amberjack combo 8.3The Bird115 New Montgomery St San Francisco A meal at The Bird is all about fried chicken, which is why you’ll see it in salad, biscuit, and sandwich form and even “naked” (aka just a fried thigh with slaw on the side) and prepare to get messy—we’re pretty sure this place single handedly keeps the world’s napkin suppliers in business bright red juices you’ll lick off your hand and refreshing apple slaw spills out from the squishy bun When you’re done making your way through the handheld behemoth get some just-sweet-enough apple fritters for dessert PlayUnmute8.2RoohIndian This high-end restaurant located several blocks from Oracle Park is reimagining traditional Indian cuisine and mixing in ingredients and cooking styles from around the world with the precision of a lauded scientist Rich mawa-stuffed black morel mushrooms are slathered in decadent yakhni sauce The spiced chickpeas topped with potato mousse and crispy salli shreds are hearty enough to double as the world’s best campfire meal And the avocado-filled puri puffs topped with chilled yogurt mousse crack in your mouth in a satisfying way when you bite into them The best part is you'll eat it in the presence of a fancy ayurvedic-inspired cocktail 8.2MontesacroBini’s KitchenNepali PlayUnmute8.1Que Viet570 4th St San Francisco Vietnamese When you’re looking for a last-minute spot for a group, it’s tough to find a spot that hits the golden trifecta of easy-to-get-in, affordable, and delicious. Enter Quê Việt. The long menu of Vietnamese dishes has a lot of range, with everything from phở to bánh hỏi to a simple but fantastic charred chicken thigh rice plate 8.1TaksimTurkish It’s easy to love Taksim. The upscale Turkish restaurant near Brannan and 4th Streets from the Lokma people has a large dining space centered around a wood-fired oven and is pretty enough for an easy weeknight dinner or meals with coworkers when snacks at the bar just won’t do The biggest reason to come here is the food and large plates—just about everything is what you want to eat over convivial conversation about water signs The golden branzino is balanced with salty sea beans the lamb and beef kabob is perfectly cooked and the plump king shrimp wrapped in finely shredded kadaif are a dream over sweet pomegranate molasses And the interesting cocktails infuse Mediterranean ingredients like carob molasses and urfa pepper 8.0Burma Love8 Mint Plaza San Francisco Burmese and second level that looks like a VIP lounge this place feels like a nightclub—so it’s definitely an above-average casual dinner spot PlayUnmute7.8Tú Lan RestaurantVietnamese spot has run a straightforward operation for almost 50 years the casual place is bustling with workers grabbing lunch to-go and folks stopping in for a quick meal at a table in the back Everyone is there for one thing: the imperial rolls The umami-packed pork filling and bubbly exterior make these worthy of a last meal in the city And the best part about this place is that the portions are huge and you can get in and out (with leftovers) for less than $20 7.7Ebiko100 1st St San Francisco it’s one of the best fresh fish deals you can get in SF PlayUnmute7.5Yank SingJapanese House510 Mission St San Francisco Japanese House is a prime sit-down spot for nearby office workers looking to escape their desks Get the bento box special that comes with two mini-entrees Just make sure to arrive before noon to snag a table or take advantage of the speedy takeout if you're short on time Village Tea HouseChinese A guide to the most restaurant-filled neighborhood in San Francisco 18 great spots to go before or after a Warriors game or concert Julia is a Bay Area native who has been eating and writing with Infatuation since 2020 Her quest to find SF's best dumplings is ongoing Ricky Rodriguez is searching San Francisco far and wide for the best burgers and hottest salsas in his neverending hunt for food that'll make him gasp Patrick is a content marketer and journalist who lives (and eats a lot) in San Francisco His previous beats include tech and finance Supervisor Matt Dorsey: “It’s a well-sequenced strategy that’s focused on the right priorities — getting people better reclaiming the public realm and reversing years of perverse incentives.” The Central SoMa Plan sets zoning rules and development requirements for a portion of San Francisco's downtown that seemed ripe for redevelopment prior to the pandemic which supporters say could clear way for more housing San Francisco city leaders are changing the development plan for a portion of the SoMa neighborhood by removing requirements that favored the creation of new office space The Board of Supervisors on Tuesday unanimously approved revisions to the Central SoMa Plan which governs how the area can be redeveloped Supporters say the changes will help unlock more housing growth and spur downtown activity after years of economic upheavals Tuesday’s vote marked a “much-needed reimagination of our downtown,” said Supervisor Matt Dorsey who joined with Mayor Daniel Lurie to co-sponsor the legislation behind the changes The City first adopted the Central SoMa development plan in 2018 a time when a tech-fueled economic boom had sent demand for downtown offices through the roof But following the outbreak of the COVID-19 pandemic, San Francisco’s commercial real-estate market collapsed earlier hopes have faded that the plan might lead to rapid development growth — including new office towers parks and infrastructure envisioned by planners — in the 230-acre portion of SoMa The 2018 plan — the product of eight years of rezoning work — sets zoning rules and community-benefit requirements for the portion of SoMa that lies between 2nd and 6th streets and is bisected by Highway 80 the plan increased the limit on new commercial space that could be built in the area by millions of square feet making room for approximately 32,000 new jobs As one means of prodding developers to focus on new office space the zoning rules included requirements that meant that most of the square footage constructed in large developments had to be commercial rather than residential Supervisors on Tuesday approved a revision that essentially eliminates those requirements supervisors also got rid of similar requirements for a neighboring planning area that surrounds the Transbay Transit Center Dorsey said he hopes that by granting developers more flexibility the change will help rejuvenate a number of development projects that seemed promising six years ago but have since stalled out He said the legislation is also intended to l unleash more housing development which has become “a much more pressing need today than the office space we once contemplated meeting at the time the Central SoMa Plan was originally enacted.” San Francisco planners confronted a vastly different economic reality is struggling to keep its services going after two of its grants were cancelled Those rescued from brink say it helped keep them housed Supervisors launched a process that could end with added protections for dozens of neighborhood domiciles “When we first approved it we had such a shortage of available office space we were down at a 3% vacancy rate,” said Anne Taupier director of development for The City’s Office of Economic and Workforce Development The area that planners are calling Central SoMa — which for decades had been zoned largely for light industrial use — seemed like a good candidate for new office construction given that it included a number of large parcels that seemed ripe for development planners also looked forward to the introduction of the Central Subway line which runs through the area and opened in 2022 Following the outbreak of COVID-19 and the sudden shift to online work While downtown office activity has recovered somewhat vacancy rates still stood at 34% at the close of last year according to a report from the San Francisco Office of the Controller and the Office of Economic Analysis the development of new office buildings is currently not financially viable and likely won’t be for some time supporters of Tuesday’s zoning change have argued the requirement for commercial space has weighed down projects that might otherwise be economically sound Now, the reformed plan, “gives us an opportunity to course correct on how much housing we can provide,” Taupier said. It could also give developers who have already entitled projects the chance to revamp construction plans shifting them away from office space and towards housing The economic report included a forecast that predicted that removing the commercial-space requirements could lead to the construction of approximately 325 new homes over the next 20 years the economic headwinds for downtown real estate remain daunting “What we can't control is the cost of construction … which everyone is keeping a very close eye on,” Taupier said kmenconi@sfexaminer.com Account processing issue - the email address may already exist Ben Pimentel’s new weekly newsletter covering the biggest technology stories in San Francisco Receive our newspaper electronically with the e-edition email Receive occasional local offers from our website and its advertisers Sneak peek of the Examiner real estate section We'll send breaking news and news alerts to you as they happen Invalid password or account does not exist Submitting this form below will send a message to your email with a link to change your password An email message containing instructions on how to reset your password has been sent to the email address listed on your account and retailers on Folsom Street between 7th and 10th streets are having a multi-block party Thursday night It's called SOMA Nights and it's going to be a semi-monthly activation along three to four blocks of Folsom Street every second and fourth Thursday There was a soft-launch of the event two weeks ago which is meant to help support this group of businesses as Folsom undergoes its second year of street-improvement construction "Many of these businesses are queer owned and operated, and with all of the construction, things have been a little rough," says Honey Mahogany in an Instagram post. "Let’s support our local community businesses and have some fun while we do it - check out what West SOMA has to offer!" SOMA Nights kicks off with a performance by Mahogany at 6pm, and DJs starting at 6:15 pm on Langton Street, the small alley between 7th and 8th streets, next to the new Stud. There will be arts and crafts vendors on the next alley over, Hallam Street, and various bars and restaurants will have specials — with buy-one-get-one drinks at Powerhouse, oyster and beer specials at Thai Basil, and taquito and margarita specials at Azucar Lounge, to name a few. View this post on Instagram A post shared by Honey Mahogany (@honeymahogany) The Stud will be having cabaret performances and nearby Akari sushi will have specials too The event is co-sponsored by the SOMA West Community Benefit District See more info here. For updates on future SOMA Nights, follow them on Instagram Penny Wong has been Chinatown royalty ever since 1948 when she won the first-ever Miss Chinatown Pageant and now she’s gearing up to celebrate her 100th birthday It’s the first time in more than 100 years that a police officer in the Yuba County city of Marysville was killed in the line of duty as a Wednesday morning raid led to a shootout that killed an officer and suspected drug dealer Barmann is a fiction writer and web editor who's lived in San Francisco for 20+ years Get all the latest & greatest posts delivered straight to your inbox Metrics details The versatility of somatosensation arises from heterogeneous dorsal root ganglion (DRG) neurons soma transcriptomes of individual human (h)DRG neurons—critical information to decipher their functions—are lacking due to technical difficulties we isolated somata from individual hDRG neurons and conducted deep RNA sequencing (RNA-seq) to detect These results were corroborated and validated by spatial transcriptomics and RNAscope in situ hybridization Cross-species analyses revealed divergence among potential pain-sensing neurons and the likely existence of human-specific neuronal types Molecular-profile-informed microneurography recordings revealed temperature-sensing properties across human sensory afferent types by employing single-soma deep RNA-seq and spatial transcriptomics which provides insights into human somatosensory physiology and serves as a foundation for translational work underscoring the need to elucidate the molecular profiles and cell types of hDRG neurons features associated with different strategies for single-cell RNA-seq of hDRG neurons example of the laser dissection of an hDRG neuron soma UMAP plot showing the clusters of 1,066 hDRG neurons Violin plots showing total number of detected genes (c) and the expression of neuronal marker SLC17A6 (d) The grouping clusters based on the top 50% soma diameter and the expression of INA UMAPs showing some canonical marker gene expression in each cluster The color gradient represents the log-normalized expression levels of each gene across cells the lower and upper bounds of the box correspond to the first quartile (Q1 A gray dot within the box represents the median value (Q2 The lower end of the whiskers indicates the minimal value within 1.5 times the interquartile range (IQR) from the first quartile (Q1 The upper end of the whiskers indicates the maximal value within 1.5 times the IQR from the third quartile (Q3 Source data We sequenced 1,066 hDRG neurons with minimum satellite glial cell contamination from six lower thoracic and lumbar DRGs of three donors detecting an average of approximately 9,000 unique genes per neuron and identifying 16 molecularly distinct neuron types Cross-species analyses revealed similarities as well as considerable differences among human We also uncovered a set of marker genes that distinguished the different sensory neuron types 10x Xenium spatial transcriptomics confirmed the 16 populations of hDRG neurons and revealed previously unidentified spatial clustering patterns we predicted temperature and chemical response properties of various human skin afferents which were confirmed using human microneurography recordings Our results reveal a close relationship between the molecular profiles and functional properties of human sensory afferents TRPM8 and non-peptidergic (NP) neurons except NP3); and (3) human peptidergic neuron types were designated as hPEP (marker gene) implying that they might be previously unsegregated subtypes The lower and upper bounds of the box correspond to the first quartile (Q1 Summary of correspondence of DRG neuron clusters among three species and dashed lines represent partial similarity Heatmap visualization of cross-species-conserved and species-specific TF-associated gene patterns across mouse The color gradient bar depicts the distances of gene patterns from close (red) to distant (dark blue) in arbitrary units Species are color coded in the right column We observed evolutionarily conserved TF-GRNs defining C-fiber nociceptors hNP2 and hSST) and C-LTMRs (yellow boxes) as well as species-specific networks The color scale represents the average expression level (log-normalized counts) of each gene in the clusters The black boxes highlight the corresponding cell types based on the label transfer and neural network scoring analysis Overall workflow of 10x Xenium spatial transcriptomics and data analysis orange)/FABP7 (green) and H&E staining used for manual segmentation (the experiment was repeated independently four times with similar results) UMAP plot showing the cluster annotation of 1,340 hDRG neurons from 10x Xenium spatial transcriptomics Four DRG sections from two donors (section 1 Dot plot showing the top marker genes expressed in each hDRG neuron cell type from single-soma sequencing (blue) and Xenium (red) The color scale represents the normalized average expression level (from 0 to 1) of each gene in the clusters Example images showing expression of marker genes expressed in each cell type (scale bar 50 μm) (the experiment was repeated independently four times with similar results) Percentage of each cell type in the 10x Xenium dataset Spatial distribution of different types of DRG neurons in one example hDRG section (scale bar Clustering probability of each neuron within a given type Pearson’s chi-squared test with degree of freedom of 1 was used and no adjustments for multiple comparisons were made for the data analysis and y axis is the frequency (percentage of cell count) Different colors indicate data from different hDRG sections (section 1 Low P value (P < 0.05) indicates significant cell clustering and the MRGPRA3 gene does not have a human orthologue hNP1 and hNP2 populations likely have conserved functions in mediating itch sensation but involve different key molecular receptors suggesting that this population might innervate deep tissues hPEP.PIEZOh neurons might function in sensing mechanical forces from blood vessels and internal organs Given that there is no clear mouse DRG PEP+ population with high PIEZO2 expression we speculate that hPEP.PIEZOh neurons are human/primate specific or greatly expanded in humans/primates The hPEP.KIT cluster had specific expression of KIT and medium-to-low expression of PIEZO2 (Fig. 4e), while in mouse DRG neurons, Kit is more broadly expressed and found in four peptidergic clusters (Fig. 3b) Cross-species analysis suggested that this cluster mainly corresponds to the PEP3 population in mouse and macaque which are A-fiber high-threshold mechanoreceptors (HTMRs) the hPEP.KIT cluster likely functions as fast-conducting mechano-nociceptors it is possible that hPEP.CHRNA7 may contain muscle-innervating A-fiber nociceptive sensory afferents ATF3 is a TF associated with sensory afferent injury Because there were no medical records indicating obvious nerve injuries in our human donors we speculate that these neurons might represent a cluster that has undergone low levels of afferent insult although we cannot exclude the possibility that it represents a population of normal DRG neurons Because opioid receptors are inhibitory GPCRs these results suggest that activation of OPRM1 could directly inhibit human nociceptive afferents whereas OPRD1 could be a molecular target for inhibiting itch transmission suggesting that OPRK1 agonists may relieve itch through indirect or other mechanisms we were able to identify cutaneous hSST and hPEP.KIT afferents demonstrating that our dataset is useful for selecting specific molecular markers to label different types of somatosensory afferents Superimposed spike activity of an hA.LTMR field unit in response to repeated sensory stimulation of the receptive field The receptive field location is indicated by the blue dot Individual and mean (± s.e.m.) responses of hA.LTMR field units to soft brushing (f) The A-LTMR units responded robustly to soft brush stroking (n = 16 units none of them responded to heating (n = 6 units Each data point for heating and cooling (zero responses) represents at least two trials from an individual unit a, Mechanical and temperature sensitivity of hA.HTMR sensory fibers predicted based on gene expression obtained from single-soma deep RNA-seq (the same violin plot parameters as in Fig. 1) Superimposed spike activity of an A-HTMR Cool+ Heat− unit (putatively a hPEP.KIT neuron) in response to repeated sensory stimulation of the receptive field Individual and mean (± s.e.m.) responses of A-HTMR Cool+ Heat− units to brushing (c) The A-HTMR Cool+ Heat− units predictably showed no response to soft brushing but all responded to coarse brushing (n = 5 units they did not respond to heating but displayed responses to cooling during both the dynamic (4 °C per s) and sustained phases Each data point for heating and cooling represents the mean of triplicate responses from an individual unit (n = 5 units) An increased response was observed during sustained cooling compared to dynamic cooling (two-tailed paired t-test: t(4) = 4.889 Superimposed spike activity of an A-HTMR Cool− Heat− unit in response to mechanical stimulation of the receptive field The receptive field location is indicated by the red dot Individual and mean (± s.e.m.) responses of A-HTMR Cool− Heat− units to soft and coarse brushing (g) All A-HTMR Cool− Heat− units responded to coarse brushing whereas none responded to soft brushing (n = 5 units Each data point for heating and cooling represents a mean of triplicate responses from an individual unit (n = 5 units each) a, Temperature sensitivity of hC-HTMRs and hC-LTMRs predicted based on gene expression from single-soma deep RNA-seq (the same violin plot parameters as in Fig. 1) Number of C-HTMRs responding to heating (MH) Individual and mean (± s.e.m.) responses of C-HTMRs to brushing (c,d) MH and MHC units showed no response to soft brushing but responded to coarse brushing (n = 7 units total Temperature data are shown as the mean of triplicate responses for each unit with increased responses during sustained heating for MH and MHC units compared to dynamic heating (n = 7 units; two-tailed paired t-test: t(6) = 9.667 A similar pattern was observed for sustained cooling in MC and MHC units (n = 3 units total) Superimposed spike activity of an hC.LTMR in response to repeated sensory stimulation of the receptive field (marked by the green dot) Individual and mean (± s.e.m.) responses of hC.LTMRs to soft brushing (f) C-LTMRs responded robustly to soft brushing (n = 17 units Each data point represents the mean of triplicate responses with increased responses during dynamic heating in heat-responsive C-LTMRs compared to sustained heating (n = 7 units; two-tailed paired t-test: t(6) = 6.591 with increased responses during dynamic cooling compared to sustained cooling (two-way ANOVA: F1,24 = 144.6 P < 0.0001; Tukey’s test: P < 0.0001) No significant differences (P > 0.05) were observed in cooling (h) between heat-responsive and non-heat-responsive C-LTMRs (two-way ANOVA: F1,24 = 0.2860 C-LTMRs and C-HTMRs in response to cooling (i) or heating (j) stimuli Each data point represents the mean (± s.e.m.) responses of five A-HTMR Cool+ three C-HTMR MC/MHC and seven C-HTMR MH/MHC units conduction delays were adjusted based on the latency of electrically triggered spiking These findings demonstrate that human C-LTMRs have polymodal response properties In comparing heating and cooling responses (Fig. 8i,j) A-HTMR Cool+ fibers responded to both dynamic and sustained cooling whereas the responses of C-LTMRs and C-HTMRs tapered off during sustained thermal stimulation whereas C-LTMRs preferred innocuous temperatures This suggests that C-LTMRs may be a polymodal channel for innocuous or pleasurable touch have generated pioneering datasets of human DRG neurons single-soma transcripts are preferable for cell type clustering and functional interpretation we combined LCM of individual hDRG neuronal soma with Smart-seq2 deep sequencing and employed 10x Xenium spatial transcriptomics Our dataset overlaps with previous ones to some extent but also exhibits notable differences Given the high sequencing depth of transcripts from the neuronal soma and the soma size information of dissected hDRG neurons our dataset is useful for discovering functional molecules expressed at a low level and for accurate cell type clustering This LCM approach is readily applicable to other human neurons with large soma sizes such as other neurons of the peripheral nervous system and motor neurons although broad functional groups of DRG sensory afferents are generally conserved across species there are noticeable molecular differences The greatest divergence between mouse and human DRG neurons was observed among C-fiber and A-fiber nociceptors Mice contain four C-fiber nociceptors (PEP1): two (PEP1.1 and PEP1.2) express TRPV1 but not TRPA1 or PIEZO2 whereas the other two (PEP1.3 and PEP1.4) express all three channels this diversity appears to be conflated into two types We identified five types of A-fiber nociceptors in hDRG neurons Two populations have conserved features: hPEP.CHRNA7 is similar to mouse and macaque PEP2/CGRP-zeta and hPEP.KIT is similar to mouse and macaque PEP3/CGRP-eta hPEP.PIEZOh and hPEP.0—display greater divergence The hPEP.PIEZOh cluster is particularly interesting because these neurons express very high levels of PIEZO2 and likely mediate mechanical sensations in blood vessels and internal organs Our results suggest that fast pain and interoception are evolutionarily privileged in humans which are A mechano-nociceptors expressing TRPM8 are potential candidates for this function We also identified that human C-LTMRs were activated by innocuous cooling and warming The similar mechanical sensitivity of A-LTMRs (field receptors) and C-LTMRs suggests that the cooling response of C-LTMRs is unlikely to be due to cold-induced tissue deformation It is unclear why C-LTMRs respond to innocuous warmth Comparing molecular and cellular changes between donors at the baseline condition (as in this study) and those with chronic itch or pain could increase understanding of the pathological mechanisms and help in identifying molecular targets for effective treatments This study complies with all relevant ethical regulations and the revised Declaration of Helsinki The protocols of collecting skin biopsies from consent human donors were approved by the College of Medicine University of Florida institutional review board (IRB) committee (IRB201500232 and IRB202300291) The protocol of performing microneurographic recordings with consent human subjects was approved by the Swedish Ethical Review Authority (dnr 2020-04426) The protocol of collecting DRG tissues from consent patients was approved by the University of Pennsylvania IRB committee (IRB834222) The National Disease Research Interchange (NDRI supported by National Institutes of Health (NIH) grant U42OD11158) has an IRB protocol (IRB704541) for procuring human tissues from postmortem donors approved by the University of Pennsylvania IRB committee The Luo laboratory research application was approved by the NDRI Feasibility Committee (RLUW1 01) as determined by the University of Pennsylvania IRB committee the Luo laboratory experiments using human DRG samples from de-identified consent postmortem donors were exempted from the human subject requirements the Luo laboratory received two DRGs from consent patients for the initial pilot experiments through collaboration with the Department of Neurosurgery Patients were unpaid for donating their surgically extracted tissues (otherwise discarded) for research The human skin biopsies were extracted from three healthy unpaid volunteer donors at the College of Medicine, University of Florida. Information regarding human skin biopsies and de-identified donors is summarized in Supplementary Table 3 These three donors are members of one family and have no noticeable abnormal somatosensation or peripheral neuropathy All participants were provided written informed consent and signed the document In vivo recordings of peripheral sensory afferents of healthy human subjects were performed at Linköping University in Sweden These subjects were recruited through social media and were compensated for their time at a rate of 200 SEK per hour All participants provided written informed consent before the start of the experiment The hDRGs imbedded in OCT were cryosectioned (Leica CM1950 Cryostat) into 20-μm sections and mounted onto Arcturus PEN Membrane Frame Slides (Applied Biosystems One of every five consecutive sections was collected for LCM to avoid repeated dissection of the soma from the same neuron in different sections The slides were stored at −80 °C until further use There were three quality control steps before the sequencing (1) Use housekeeping gene GAPDH (see primer sequences in the supplementary Yu_Material_Reagents file) and neuronal marker PGP9.5 (see primer sequences in the supplementary Yu_Material_Reagents file) to do the RT–PCR after reverse transcription and pre-amplification The selection standard was the sample with clear and specific GAPDH and PGP9.5 bands (2) Measure the concentration of the sample after the first purification The selection standard was the sample with concentration greater than 0.2 ng μl−1 The success rate in this step was more than 99% (3) Measure the concentration of the final library The selection standard was the sample with concentration greater than 1 nM The success rate in this step was more than 98% The libraries passing through all quality controls were selected for the final sequencing STAR quantMode GeneCounts was used to quantify unique mapped reads to gene counts Anchors were first defined using FindIntegrationAnchors (scale = T and the data were then integrated (IntegrateData (normalization.method = LogNormalize followed by principal component analysis (PCA) (RunPCA the final parameters were as follows: RunUMAP Highly similar clusters without clearly distinguishable markers were merged to produce the final 16 clusters For Conos22 analysis single-soma hDRG data were integrated using CCA space $buildGraph (k = 8 For human single-soma and human single-nucleus dataset co-integration was performed as $buildGraph (k = 8 mouse (Sharms) dataset was downsampled to maximum 300 cells per cluster and co-integration was performed as $buildGraph (k = 8 SmartSeq2 dataset) was used for interspecies analysis macaque/human graph was built as $buildGraph (k = 4 For all uniform manifold approximation and projection (UMAP) plots in Conos graph embedding was performed as: $embedGraph (method = UMAP Label propagation ($propagateLabels) was run using the ‘diffusion’ method These three methods have different strengths and weaknesses Conos finds shared principal components between integrated datasets but some species-specific features may be lost and can lead to impaired statistical sufficiency during integration and can be affected by the number of principal components and nearest neighbor distance Machine learning is based on gene expression and is not supervised by shared latent space (that is Each single reference dataset is used to train the machine learning module and is then tested by the other dataset probability calculations are not affected by principal components or nearest distance because it emphasizes the features of each cell type the learning accuracy and reliability depend on the robustness of the reference or training dataset machine-learning-based hierarchical clustering we extracted the weight of cell-type-specific features to construct the latent space covering all cell types across species we tried to obtain sufficient latent space by training and predicting every dataset independently parameterization was used to find the most robust hierarchical clustering The assessment of cell type purity, the probabilistic similarity and cell type integration across species were performed using packages in a machine-learning-based single-cell analysis toolkit, scCAMEL, released separately at https://sccamel.readthedocs.io/ The calculation of cell type probabilistic score is described in the SWAPLINE package52 a vanilla neural network model was built for cell type classification we removed the cell-cycle-related genes and then computed the most variable features we ranked the marker genes for each cell type by two heuristics for the cell type specificity of both fold change and enrichment score change the ranked marker genes and the most variable genes were merged log transformed and scaled by minimum–maximum normalization for learning models The frame of the neural network model and the parameters are described in the SWAPLINE package The learning accuracy of the neural network classifier was inspected against epoch numbers and was estimated by k-fold cross-validation (k = 3) The learning rate and learning epochs were selected according to the maximum point of the learning curve reaching the accuracy plateaus The probabilistic scores from mouse and macaque species against human reference were visualized in a violin plot we applied interpretable neural network learning We trained a neural network classifier by learning the transcriptional features of each cell type in this dataset and then calculated the probabilistic scores against all cell types we used all other datasets as query datasets and calculated the probabilistic score of every cell in each query dataset using the trained classifier we took another dataset from the dataset pool and repeated the training and prediction We repeated the training and prediction until every dataset had been used as a training reference for the predictions we considered that the probabilistic score of each cell reflected the weighted gene patterns representing each trained cell type we merged the probabilistic scores of all cells from all trained and predicted datasets for the PCA The most significant principal components were determined by the elbow method and subsequently used as the latent space for further downstream analysis The tree plot was constructed with the parameter of 11 principal components 90 nearest neighbors and correlation metric The trained cell type similarity was calculated with the correlation distance and the average/UPGMA linkage and visualized in the hierarchical heatmap The result was visualized as a hierarchical heatmap The expression datasets from previously published studies were downloaded and randomly downsampled to match the sample size of our study The compared two datasets were integrated by FindTransferAnchors (reference The assignment possibility of each neuron in the query datasets to the reference cluster was calculated by TransferData (anchorset The correlation heatmap was generated based on the mean value of prediction in each cluster of the query dataset to each cluster of the reference dataset The heatmap was plotted by the R package ‘heatmap’ Spatial transcriptomics was performed using the Xenium Analyzer (10x Genomics) following the manufacturer’s instructions (https://cdn.10xgenomics.com/image/upload/v1710785024/CG000584_Xenium_Analyzer_UserGuide_RevE.pdf) 10-μm-thick tissue cryosections were mounted on Xenium slides and mRNAs were targeted using a custom gene panel consisting of 100 genes including 87 neuronal marker genes and 13 non-neuronal marker genes (see the list below) Post-Xenium H&E staining was subsequently performed Cell segmentation was performed manually based on the clustering expression of pan-neuronal marker gene PGP9.5 satellite glia cell marker FABP7 and the corresponding H&E staining Each transcript was mapped back to the new segmentation for downstream analysis 87 neuronal marker genes were used for clustering using Seurat (version 4.0.5) The final parameters were as follows: RunUMAP Neurons with bad or unclear neuronal soma morphology from H&E staining were excluded for further analysis Cell type annotation for each cluster was based on the marker gene expression The area \(A\) of the hDRG section containing neurons was calculated using ImageJ software For each neuron cell type with \(N\) cells The centroid for each cell was identified based on its cell boundary We were interested in examining if cells from the same cell type tended to be spatially near each other we define its neighborhood by drawing a circle centered around the cell centroid with radius \(r\) If there is no spatial enrichment of cells from the same cell type in the neighborhood we expect to get \({n}_{\exp }=\pi \times {r}^{2}/a\) cells from the same cell type within the circle The number of observed cells of the same cell type in the neighborhood was counted by including cells whose Euclidian distance with the center cell was less than \(r\) To test if there was an enrichment of cells of the same cell type in the given cell’s neighborhood we calculated the chi-squared statistic as \({({n}_{{obs}}-{n}_{\exp })}^{2}/{n}_{\exp }\) and the corresponding P value was calculated using function \({\rm{pchisq}}()\) in the R ‘stats’ package with degree of freedom set to 1 Repeating this analysis for every cell in a given cell type we obtained the P value distribution for each cell type The P value distribution was visualized using \({\rm{geom\_histogram}}()\) function in the R ‘ggplot2’ package To determine if the P value distribution was enriched toward 0 We first generated a group of random numbers of length \(N\) from uniform distribution between 0 and 1 and then we performed two-sample one-sided t-tests to compare the observed P values with these randomly generated numbers in −log10 scale using the t.test() function in the R ‘stats’ package We repeated this one-sided t-test 1,000 times and calculated the mean P value for each cell type Our results indicated that the mean P values were less than 0.05 for all 12 considered cell types after multiple testing correction indicating that cells from the same cell type were spatially near each other OCT-embedded freshly dissected human lumbar or thoracic DRG tissues were cryosectioned at 20-µm thickness and mounted on glass slides The slides were stored at −80 °C to preserve RNA integrity RNAscope Fluorescent Multiplex Reagent Kit and RNAscope probes for the targeted genes (Advanced Cell Diagnostics) were used for multiplex FISH RNAscope in situ hybridization was performed in accordance with the manufacturer’s instructions The sections were then hybridized with the respective target probe for 2 h at 40 °C followed by 2–3 rounds of signal amplification The sections were then mounted under coverslips sealed with nail polish and stored in the dark at 4 °C until imaged A Leica SP5 confocal microscope was used to capture images The criteria for defining a cell as positive for a particular channel/gene were as follows The real RNAscope signals should be composed of small fluorescent dots (>10) in a cell area as opposed to the surrounding areas or in other negative cells and they should not completely overlap with signals from all other channels accumulation of lipofuscin in part of cells caused strong autofluorescence visible in all channels These signals were considered as non-specific background and were excluded for analysis The percentage of each cluster over all DRG neurons could be somewhat overestimated due to the following two reasons: (1) some marker genes or marker gene combinations were not specific and may also label a small subset of other cell types; and (2) an underestimation in quantification of total neuronal numbers because some cells had neither multiple FISH signals nor DAPI nucleus staining signals In brief, 1 cc of lidocaine was injected subdermally at each biopsy location (Supplementary Table 3) A total of six 3-mm dermal skin punch biopsies were performed on each of the three subjects Excised skin was immediately placed in 1.5-ml Eppendorf tubes containing 4 °C 4% paraformaldehyde (PFA) solution that was freshly prepared on the same day of the skin biopsy procedure Biopsy tissue was fixed in 4% PFA (dissolved in PBS) for exactly 4 h at 4 °C followed by 2 × 30-min washes in PBS solution and then cryoprotected using 1× PBS and 30% sucrose at 4 °C 30% sucrose were overnight shipped to the laboratory of Integrated Tissue Dynamics The skin biopsies were mounted in OCT and cryosectioned into 14-μm sections Adjacent sections were collected by continuous slides Immunofluorescence was performed using combinations of mouse monoclonal anti-human PGP9.5 (Protein Gene Product mouse monoclonal anti-human NEFH (Sigma-Aldrich Slides were pre-incubated in 1% BSA and 0.3% Triton X-100 in PBS (PBS-TB) for 30 min and then incubated with primary antibodies diluted in PBS-TB overnight in a humid atmosphere at 4 °C Slides were then rinsed in excess PBS for 30 min and incubated for 2 h at room temperature with the appropriate secondary antibodies diluted in PBS-TB (Jackson ImmunoResearch 1:250 and Alexa Fluor 488 donkey anti-sheep IgG the sections were rinsed for 30 min in PBS and coverslipped under 90% glycerol in PBS Images were collected using a ×20 objective on an Olympus BX51-WI microscope equipped with conventional fluorescence filters (Cy3:528–553 nm excitation 590–650 nm emission; Cy2/Alexa Fluor 488: 460–500 nm excitation a linear focus encoder and a three-axis motorized stage system interfaced with Neurolucida software (MBF Bioscience) Single-unit axonal recordings (microneurography) were performed from the right posterior antebrachial cutaneous radial or superficial peroneal nerve of 62 healthy participants (29 males and 33 females Participants were comfortably seated in an adjustable chair with legs and arms stretched out (and hand pronated) supported by vacuum pillows and covered in a blanket if they reported feeling cold Neural activity was sampled at 20 kHz and recorded using the ADInstruments data acquisition system (LabChart software version 8.1.24 and PowerLab 16/35 hardware PL3516/P) and then exported to Spike2 (version 10.13 Single action potentials were identified semiautomatically with visual verification on an expanded timescale Threshold crossing was used to distinguish action potentials from noise with a signal-to-noise ratio of at least 2:1 and spike morphology was confirmed by template matching Recordings were discarded if multiple units were present (for example non-physiological spike intervals/firing rates) or if spike amplitudes were not distinct from the noise preventing secure action potential identification The neural response was always spatially locked—that is evoked (or modulated) only when the specific area of skin (the receptive field) was stimulated repeat trials for each stimulus were conducted to ensure reproducibility Under real-time ultrasound guidance (LOGIQ P9 the target nerve was impaled with an insulated tungsten recording electrode (FHC an uninsulated reference electrode was inserted just under the skin A high-impedance pre-amplifier (MLT185 Headstage ADInstruments) was attached to the skin near the recording electrode and used together with a low-noise Once the electrode tip was intrafascicular single LTMRs were searched for by soft brush stroking and single HTMRs were searched for by coarse brush stroking pinching and hair tugging in the fascicular innervation zone while making minute electrode adjustments Mechanical threshold and receptive field size were determined using Semmes–Weinstein monofilaments (nylon fiber; Aesthesio Mechanical threshold was defined as the weakest monofilament to which the unit responded in at least 50% of trials The conduction velocity of the recorded afferent was estimated from latency responses to surface electrical stimulation (FE180 Stimulus Isolator ADInstruments) or rapid mechanical tapping using an electronic filament (Physiology Section Electrically and mechanically evoked spikes were compared on an expanded timescale to confirm that they originated from the same unit Thermal responsiveness was tested by placing a Peltier probe (T09 and T10 After recording baseline activity for at least 30 s (with the thermode in contact with the receptive field) at a neutral temperature of 30 °C a series of cooling (down to 0 °C at 4 °C s−1) and warming (up to 50 °C at 4 °C s−1) stimuli were delivered at 30-s intervals the thermode was mounted on a stand for better stability The gauze pad was covered with an adhesive film to prevent evaporation of ethanol and the emergence of any spontaneous spiking activity from the recorded afferent was monitored All data shown in column and line graphs represent mean ± s.e.m. Significance levels are indicated as *P < 0.05; **P < 0.01; ***P < 0.001; and ****P < 0.0001 statistical methods and repeatability are mentioned in respective figure legends Data collection and analysis were not performed blinded to the conditions of the experiments Data distribution was tested to inform the choice between parametric or non-parametric tests with the specific test mentioned alongside the statistical results in the figure legends Figures were generated in PowerPoint (Microsoft Office) and GraphPad Prism (versions 8 and 9, GraphPad Software). Some cartoons were made partially in BioRender (BioRender, 2022, RRID: SCR_018361) Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE165569 http://loom.linnarssonlab.org/clone/Mousebrain.org.level6/L6_Peripheral_sensory_neurons.loom https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE139088 Human (Tavares-Ferreira) DRG data are available at https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001158.v2.p1 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE168243 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE201654 GRCh38 GENCODE database (genome sequence alignment reference) is available at http://hgdownload.cse.ucsc.edu/goldenPath/hg38/bigZips/hg38.fa.gz GTF database (human genome annotation reference) is available at https://ftp.ensembl.org/pub/release-104/gtf/homo_sapiens/. Source data are provided with this paper Custom code has been deposited to GitHub (https://github.com/taimeimiaole/NN_hDRG-neuron-sequencing). Previously published codes and software used for this study are cited in the Methods Animal models of chronic pain: advances and challenges for clinical translation NK1 (substance P) receptor antagonists—why are they not analgesic in humans Studying human nociceptors: from fundamentals to clinic mRNA-Seq whole-transcriptome analysis of a single cell Single-cell RNA sequencing technologies and bioinformatics pipelines Unbiased classification of sensory neuron types by large-scale single-cell RNA sequencing The emergence of transcriptional identity in somatosensory neurons Single cell transcriptomics of primate sensory neurons identifies cell types associated with chronic pain Single-cell transcriptomic analysis of somatosensory neurons uncovers temporal development of neuropathic pain Enzymatic dissociation induces transcriptional and proteotype bias in brain cell populations Single-nucleus transcriptomic analysis of human dorsal root ganglion neurons Spatial transcriptomics of dorsal root ganglia identifies molecular signatures of human nociceptors Cross-species transcriptomic atlas of dorsal root ganglia reveals species-specific programs for sensory function Bhuiyan, S. A. et al. Harmonized cross-species cell atlases of trigeminal and dorsal root ganglia. Sci. Adv. https://doi.org/10.1126/sciadv.adj9173 (2024) Systematic comparison of single-cell and single-nucleus RNA-sequencing methods Full-length RNA-seq from single cells using Smart-seq2 Integrated analysis of multimodal single-cell data Principles of Neurobiology 265–267 (Garland Science Transcriptional regulator PRDM12 is essential for human pain perception Joint analysis of heterogeneous single-cell RNA-seq dataset collections Molecular architecture of the mouse nervous system A developmental switch in the response of DRG neurons to ETS transcription factor signaling The role of the Mrgpr receptor family in itch Human cutaneous C fibres activated by cooling The capsaicin receptor: a heat-activated ion channel in the pain pathway Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin Pathologic alterations of cutaneous innervation and vasculature in affected limbs from patients with complex regional pain syndrome GPR68 senses flow and is essential for vascular physiology Biological functions of angiotensin and its receptors Genetic control of the segregation of pain-related sensory neurons innervating the cutaneous versus deep tissues PIEZO2 in sensory neurons and urothelial cells coordinates urination An ultrafast system for signaling mechanical pain in human skin Discriminative and affective touch: sensing and feeling Receptive field characteristics of tactile units with myelinated afferents in hairy skin of human subjects Specialized mechanosensory nociceptors mediating rapid responses to hair pull Low‐threshold mechanoreceptive and nociceptive units with unmyelinated (C) fibres in the human supraorbital nerve Nav1.7 is required for normal C-low threshold mechanoreceptor function in humans and mice The functional organization of cutaneous low-threshold mechanosensory neurons A topographical and physiological exploration of C-tactile afferents and their response to menthol and histamine Human and mouse trigeminal ganglia cell atlas implicates multiple cell types in migraine Emergence of the sensory nervous system as defined by Foxs1 expression A 4-year follow-up of non-freezing cold injury with cold allodynia and neuropathy in 26 naval soldiers Identification of gene expression profile of dorsal root ganglion in the rat peripheral axotomy model of neuropathic pain Electrophysiological and transcriptomic correlates of neuropathic pain in human dorsal root ganglion neurons Cutadapt removes adapter sequences from high-throughput sequencing reads Comprehensive integration of single-cell data Neural network learning defines glioblastoma features to be of neural crest perivascular or radial glia lineages Inferring regulatory networks from expression data using tree-based methods SCENIC: single-cell regulatory network inference and clustering Unmyelinated afferents constitute a second system coding tactile stimuli of the human hairy skin Topical menthol—a human model for cold pain by activation and sensitization of C nociceptors Coding of pleasant touch by unmyelinated afferents in humans Xu, S. et al. Mechanoreceptive Aβ primary afferents discriminate naturalistic social touch inputs at a functionally relevant time scale. In IEEE Transactions on Affective Computing 1–15 https://doi.org/10.1109/TAFFC.2024.3435060 (IEEE Download references We thank all tissue donors and their families for the generous donations The new knowledge pieces generated from this study would not be possible without their precious gifts We thank the National Disease Research Interchange for helping with hDRG procurement; I Unger and other members of the University of Pennsylvania (UPenn) Department of Neurosurgery for helping with patient DRG procurement and method optimization; the UPenn Skin Biology and Disease Resource-based Center for helping with laser capture microdissection; and the Children’s Hospital of Philadelphia Center for Applied Genomics for helping with sequencing Li for his encouragement in starting this new research direction and all members of the Luo and Ma laboratories for their help in conducting this project Ng for his assistance in some of the microneurography data collection and M Mercado for neuronal segmentation of 10x Xenium analysis This project is supported by internal funding from UPenn to W.L are co-recipients of a National Institutes of Health (NIH) HEAL U19 grant (U19-NS-135528) is also supported by NIH grants R01-NS-131209 is supported by the Swedish Research Council (2019-00761) the Knut and Alice Wallenberg Foundation and a European Research Council advanced grant (PainCells 740491) is supported by the Swedish Research Council (2023-01874) the Knut and Alice Wallenberg Foundation (grants KAW 2019.0047 and KAW 2019.0487) and ALF Grants is supported by the Swedish Research Council (2021-03054) and the Swedish Medical Society The computations and data handling were enabled by resources in projects NAISS 2023/23-464 and -944 provided by the National Academic Infrastructure for Supercomputing in Sweden at UPPMAX funded by the Swedish Research Council through grant agreement number 2022-06725 These authors contributed equally: Huasheng Yu Department of Biomedical and Clinical Sciences Department of Medical Biochemistry and Biophysics Department of Biostatistics in Biostatistics and Epidemiology Department of Biochemistry and Molecular Biology Institute of Life Course and Medical Sciences performed experiments and collected data; H performed or supervised the data analysis; S.P contributed to developing the LCM-based single-soma collection method; J.W Gautam reviewed and edited the manuscript; W.L. acquired funding to support this study; W.L. The authors declare no competing interests reviewer(s) 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 (a-c) Size distribution of all DRG neurons (a) and dissected neuronal soma (b) (c) Cumulative curve of size distribution of all DRG neurons in (a) and dissected neuronal somata in (b) and statistic comparison by two-sided Kolmogorov–Smirnov test (d-f) Violin plots showing total number of detected genes in different batches (d) (g-i) UMAP plots showing the contribution of individual batches (g) donors (h) and DRG levels (i) to each cluster The insets in each panel show a zoomed-in view of hTRPM8 and hC.LTMR clusters (j-k) Violin plots showing the expression of pan-neuronal markers SYP and UCHL1 (l-m) A representative image of human DRG neurons stained by HistoGeneTM dye (l) and quantification of the percentage of neurons with or without the nucleus in 20-μm human DRG tissue sections (m (n) The distribution of soma diameters of dissected neurons in each cluster A grey dot within the box represents the median value (Q2 50%) The lower end of the whiskers indicates the minimal value within 1.5 times the interquartile range (IQR) from the first quartile (Q1 (o) UMAPs showing expression pattern of additional canonical marker genes in each cluster The color scale represents the log-normalized expression levels of each gene across cells Source data (b) The accuracy of neural-network classifier in learning hDRG neurons was visualized as learning curve and the X-axis represents the training epoch numbers the maximum accuracy plateaus of this learning curve reaching ~88% the consistency of assigned hDRG neurons by the neural-network scoring module Blue and red sections of the bars indicate ratio of cells within each type with and without (d) hierarchical heatmap visualization of the probabilistic similarity across cell types The color gradient depicts similarity score from high (yellow (e) Percentage of each cell type in single-soma RNA-seq dataset (a-f) Heatmaps comparing the similarities of human DRG neuron cell types between different datasets analyzed by Seurat Integration Mapping and Annotating Query Datasets module The color gradient represents cell type similarity Single-soma indicates the dataset of this study single-nucleus dataset 1 indicates the Nguyen et al single-nucleus dataset 2 indicates the Jung et al and spatial indicates the Tavares-Ferreira et al dataset (e) Radial hierarchical dendrogram showing the similarity between cell types in humans (h Branch lengths indicate the degree of similarity The scale bar from center to the terminus represents 100% similarity “Single-soma” is the dataset from this study “Spatial” refers to the dataset from the Tavares-Ferreira et al and “Single-nucleus” refers to the dataset from the Nguyen et al The circles represent the number of detected genes in these gene families across the three datasets The heatmaps display the expression levels of the top genes from each of the three datasets The color scale represents the expression level normalized to the maximum gene expression in each dataset (b-c) Expression of putative itch receptors in hDRG neurons shown by dot plots while some receptors are barely detected (c) in human itch populations and other genes enriched in human itch populations shown by dot plot the size of the dot represents the percentage of cells within a cluster and the color corresponds to the average expression (scaled data) across all cells within a cluster for each gene shown (a-d) Heatmap showing the expression of top 50 GPCRs (a) chemokine receptors (c) and neuropeptides (d) in hDRG neurons Genes were ranked by average expression level in all DRG neurons Color scale represents the average gene expression level normalized to the maximum average gene expression within each clusters (a-f) Double immunostaining of human skin sections showing SST+ sensory fibers are a subset of CGRP+ sensory fibers in the dermis and entering the epidermis (a-c) and near the hair follicle (d-f) The white dashed line indicates the dermis-epidermis junction Yellow arrows indicate SST + /CGRP+ sensory afferents green arrows indicate CGRP+ only sensory afferents (g-o) Double immunostaining of KIT with PGP9.5 (g-i) NEFH (j-l) and CGRP (m-o) in human hairy skin showing KIT+ sensory afferents are a subset of CGRP + /NEFH+ sensory afferents around the hair follicles Inserts in large white rectangles are 2X enlargements of areas in the small white rectangles Yellow dashed lines outline hair follicles Yellow arrows indicate double positive sensory afferents green arrows indicate PGP9.5+ only or CGRP+ only or NEFH+ only sensory afferents white arrows indicate macrophages that were previously known to be KIT +  Given that the macrophage KIT immunolabeling is far more intense than that on the innervation the macrophages are overexposed and blurred at the exposure setting needed to capture the labeling of the innervation The experiment was repeated independently three times with similar results (a) Validation of TRPM8, PIEZO2, CGRP, CASQ2 and TRPV1 expression in the hPEP.KIT and hC.LTMR populations by multiplex FISH (The experiment was repeated independently two times with similar results, the same violin plot parameters as the Fig. 1) (b) Receptive field locations of A-HTMR Cool+ and Cool- units (c-e) Comparisons between A-HTMR subtypes showed no significant differences in monofilament thresholds (median ± IQR coarse-brush responses (mean of triplicate responses per unit n = 5 units each; Two-tailed unpaired t-test: t(8) = 0.2692 Cool+ units: n = 3; Two-tailed independent Mann Whitney test: U = 6 (f) Superimposed spike activity of a C-HTMR Heat+ (MH) unit in response to repeated sensory stimulations of the receptive field (g-l) Responses of a C-HTMR (MH) to soft-brushing (g) (l) Response of a TRPM8 (mechano-unresponsive C cold) unit to menthol (m) Individual and mean ( ± SEM) responses of C-LTMR Heat+ and C-HTMR Heat+ units to capsaicin Capsaicin to the receptive field evoked spontaneous activity in both C-HTMRs (n = 3 units) and C-LTMRs (n = 5 units) P < 0.0001) and longer-lasting (F (2.695 P < 0.0001) in C-HTMRs compared to C-LTMRs (2-way RM-ANOVA) Multiple comparisons were performed using Uncorrected Fisher’s LSD test The duration of spontaneous activity in C-HTMRs is truncated to 120 s (post-capsaicin removal) aligning with the disappearance of spontaneous activity in C-LTMRs (n) Example trace of a heat-unresponsive C-LTMR (o) Soft-brush responses were not different between heat-responsive and non-heat-responsive C-LTMRs (mean of at least two responses per unit n = 7 units each; Two-tailed unpaired t-test: t(12) = 0.6649 (p) Example trace showing no response to menthol in a hC.LTMR Statistical source data for Extended Data Figs Download citation DOI: https://doi.org/10.1038/s41593-024-01794-1 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 Metrics details The abilities of an organism to cope with extrinsic stresses and activate cellular stress responses decline during aging The signals that modulate stress responses in aged animals remain to be elucidated we discover that feeding Caenorhabditis elegans (C elegans) embryo lysates to adult worms enabled the animals to activate the mitochondrial unfolded protein response (UPRmt) upon mitochondrial perturbations This discovery led to subsequent investigations that unveil a hedgehog-like signal that is transmitted from the germline to the soma in adults to inhibit UPRmt in somatic tissues we find that the levels of germline-expressed piRNAs in adult animals markedly decreased This reduction in piRNA levels coincides with the production and secretion of a hedgehog-like signal and suppression of the UPRmt in somatic cells our study further elucidates the intricate mechanisms of germline-to-soma signaling and its role in modulating the trade-offs between reproduction and somatic maintenance within the context of organismal aging These phenomena correlate with the observations that mitochondrial disorders occur during aging and mitochondria play essential roles in age-related diseases such as neurodegenerations we identify a potential piRNA-regulated germline-to-soma Hedgehog signaling pathway that enables the germline to communicate with key metabolic and stress response tissues prioritizing resource allocation for reproduction over somatic maintenance a Schematic depicting the experimental procedure to treat day 7 hsp-6p::gfp adult worms with antimycin and lysates from embryos or day 6 adult worms Embryo were harvested from day 1 adult worms b Representative fluorescence images of hsp-6p::gfp worms with the indicated treatments Antimycin and embryo/day 6 worm lysates were administered to day 7 adult worms for 24 h prior to visualization c Quantification of GFP fluorescence intensity in panel (b) d Survival rate of day 9 N2 adults after 72 h exposure to antimycin and embryo/worm lysates e qRT-PCR analysis of the indicated UPRmt genes in day 7 wild-type (N2) worms with the indicated treatments g Quantification of GFP fluorescence intensity in hsp-6p::gfp worms with the indicated treatments Antimycin and embryo/worm lysates were provided to day 7 adult worms for 24 h h Survival rate of day 9 N2 adults after 72 h exposure to antimycin and embryo lysates (from N2 Quantification of GFP fluorescence intensity in hsp-6p::gfp worms with the indicated treatments Antimycin and embryo lysates were provided to day 7 adult worms for 24 h e) and (h) represents the number of independent experiments; for panels (c p values were assessed using a two-tailed t test RNAi treatment started at the L1 stage across all figure panels Source data are provided as a Source data file a–f Survival curves of wild-type (N2) worms (a-c) or atfs-1 mutants (d-f) treated with embryo lysates or day 6 worm lysates Lifespan data from 3 biological replicates are shown g Median lifespan extension of wild-type (N2) worms and atfs-1 mutant worms treated with embryo lysates or day 6 worm lysates l Gene Ontology analysis of embryo lysate feeding-dependent upregulated (h) or downregulated (l) genes in day 7 wild-type worms m Heat map plots illustrate the differentially expressed genes that depend on embryo lysate feeding n Representative fluorescence images of adult day 7 N2 worms treated with Nile Red and/or lysates for 24 h o Quantification of Nile Red intensity in panel (n) n represents the number of independent experiments for panel (g) p values were assessed using the Log-rank (Mantel–Cox) test for panels (a–f) a hypergeometric distribution test is used to assess enrichment of differentially expressed genes Detailed methods are in the methods section a two-tailed t test is used to evaluate differential gene expression Source data are provided as a Source Data file a Representative fluorescence images of hsp-6p::gfp worms with the indicated treatments Antimycin treatment occurred on day 3 of adulthood for 24 h b Immunoblotting of GFP and tubulin in lysates collected from day 3 hsp-6p::gfp worms with the treatments described in panel (a) c qRT-PCR analysis of the indicated UPRmt genes in day 3 N2 worms subjected to the indicated treatments d Schematic depicting the experimental procedure in panels (e e qRT-PCR analysis of genes related to hedgehog signaling in day 7 N2 worms with the indicated treatments f Survival rate of Day 7 N2 worms treated with embryo or worm lysates followed by exposure to antimycin and the specified combinations of RNAi for 72 h RNAi of individual genes started on day 7 of adulthood n represents the number of independent experiments for panels (c This indicates that the increased animal survival caused by embryo lysates ingestion was primarily through suppression of the function of the hedgehog-like signaling proteins WRT-5 and WRT-6 a-d Interactions of PTR-8 and PTR-16 with WRT-5 and WRT-6 HEK293T cells transfected with the indicated cDNAs and followed by the indicated immunoprecipitations e qRT-PCR analysis of genes related to hedgehog signali ng in glp-4 worms at the indicated developmental stage Worms were raised at the specified temperatures f Quantification of GFP fluorescence intensity in hsp-6p::gfp worms treated with antimycin Antimycin treatment started at indicated stage for 24 h g Survival rate of N2 worms after 48 h of exposure to antimycin started at the indicated developmental stage n represents the number of independent experiments for panels (e These results suggest that the activation of wrt-5 and wrt-6 is associated with the initiation of reproduction highlighting a potential role for hedgehog-like signaling in early aging processes Antimycin treatment occurred on day 3 of adulthood for 24 h b Quantification of GFP fluorescence intensity in panel (a) c Heatmap showing the expression levels of piRNAs targeting wrt-5 and the control gene wrt-1 in lysates from different stages d Quantification of GFP fluorescence intensity in hsp-6p::gfp worms with the indicated treatments prg-1 embryo lysates and piRNAs were administered to day 7 worms for 24 h e Survival rate of day 9 N2 worms after 72 h exposure to antimycin n represents the number of independent experiments for panel (e) and the number of worms for panels (b) and (d) b Survival rate of day 9 wild-type (N2) worms treated with indicated RNAi and exposed to antimycin RNAi treatment was applied either “whole-life” (starting at L1) or “adult-only” (starting on day 1 of adulthood) c qRT-PCR analysis of UPRmt genes in day 9 N2 adults treated with RNAi and exposed to antimycin e Survival rate of day 5 N2 adults treated with RNAi and exposed to PA14 f Representative fluorescence images of day 5 irg-1p::gfp adults with the indicated treatments Pathogen infections were done on day 5 of adulthood for 48 h unless otherwise noted g qRT-PCR analysis of innate immune response genes in day 5 N2 animals exposed to PA14 h Representative fluorescence images of day 5 N2 worms treated with PAO1(GFP) i Quantification of PAO1 or PA14 CFU in day 5 N2 worms k Survival rates of day 9 and day 5 hsp-6p::gfp adults overexpressing piRNAs targeting wrt-5 with antimycin treatment on day 9 and PA14 on day 5 l Brood size of N2 worms treated with RNAi from L1 stage (“whole life”) or day 1 adulthood (“adult-only”) m Brood size of hsp-6p::gfp worms overexpressing piRNAs targeting wrt-5 n Representative fluorescence images of day 5 vit-2::gfp worms treated with RNAi o qRT-PCR analysis of the vit family genes in day 1 N2 adults treated with RNAi p values were assessed using a two-tailed t test for panels (c and using the Log-rank (Mantel–Cox) test for panels (a These data indicate that suppressing the hedgehog-like signal inhibits fertility and post-embryonic development a–f Survival curves of control AMJ345 worms (a–c) or atfs-1-deficient AMJ345 worms (d–f) upon feeding with RNAi E coli targeting a hedgehog pathway-related gene g-i Quantification of relative TMRE fluorescence in adult day 3 (g) j Comparison of fumarase activity in different subcellular fractions in adult day 5 N2 worms Fumarase activity was normalized to the quantity of protein used in the assay n represents the number of independent experiments for panel j p values were assessed using a two-tailed t test for panels (g–j) and the Log-rank (Mantel–Cox) test for panels (a–f) demonstrating that UPRmt is not essential for this reduction These findings confirm that hedgehog-like signaling regulates innate immunity and developmental processes through ATFS-1-dependent and independent mechanisms a Heat map showing the effect of tissue-specific knockdown of hedgehog pathway-related genes on the indicated phenotypes f qRT-PCR analysis of hsp-6 mRNA levels in the day 3 germline- (b) and intestine-specific (f) RNAi strain treated with the indicated RNAi and antimycin g Brood size of the germline- (c) and intestine-specific (g) RNAi strain treated with the indicated RNAi h Survival rate of the day 9 germline- (d) and intestine-specific (h) RNAi strain treated with the indicated RNAi and exposed to antimycin Survival rate of the day 5 germline- (e) and intestine-specific (i) RNAi strain treated with the indicated RNAi and exposed to PA14 j A germline-to-soma hedgehog-like signal initiates resource reinvestment to promote reproduction while inhibiting somatic maintenance in adult worms n represents the number of independent experiments for panels (b p values were assessed using a two-tailed t test for panels (b and the Log-rank (Mantel–Cox) test for panels (d b Representative fluorescence images of hsp-6p::gfp worms with germline-specific wrt-5/6 or intestine-specific ptr-8/16 overexpression Antimycin treatment occurred on L4 (a) or day 1 (b) of adulthood for 24 h d Quantification of GFP fluorescence intensity in panels (a e–g qRT-PCR analysis of the indicated UPRmt genes in day 3 hsp-6p::gfp worms with the indicated treatments i Survival rate of the day 9 (h) and day 5 (i) hsp-6p::gfp worms with the indicated treatments j Brood size of hsp-6p::gfp worms with germline-specific wrt-5/6 or intestine-specific ptr-8/16 overexpression n represents the number of independent experiments for panels (e–g) p values were assessed using a two-tailed t test for panels (c–g and the Log-rank (Mantel–Cox) test for panels (h and Smo mRNA levels in seven-month-old C57BL/6J male (a) and female (b) mice treated with DMSO or itraconazole d qRT-PCR analysis of Chop and Asns mRNA levels in seven-month-old C57BL/6J male (c) and female (d) mice treated with DMSO or oligomycin f Weight loss in seven-month-old C57BL/6J male (e) and female (f) mice during oligomycin treatment g Litter size of seven-month-old C57BL/6J females treated with DMSO or itraconazole mated with males of the same treatment group i Serum AMH (h) or testosterone (i) levels assessed by ELISA in mice treated with DMSO or itraconazole Blue indicates a positive correlation and white indicates a negative correlation The intensity of the colors corresponds to the correlation coefficient and human milk mRNA levels in human breast tissues These findings indicate that the hedgehog signaling pathway may play a conserved role in regulating UPRmt and fertility across species The ability to cope with different cellular stresses declines during animal aging suppressed the mitochondrial stress response in the intestine in adult animals this study uncovers the biological meaning of the age-related decline of mitochondrial stress response from an evolutionary point of view The current findings support the “antagonistic pleiotropy” and the “disposable soma” theories The genes related to hedgehog signaling are beneficial at the larval stages when they promote development and reproduction but are detrimental in later life when they suppress the mitochondrial stress response the generation and transmission of the hedgehog-like signal from the germline to the soma suppresses the mitochondrial stress response in the somatic tissues allowing the worms to invest more resources in reproduction rather than somatic maintenance The initiation of this project was stemming from an artificial experiment where we fed adult C elegans with embryo lysates and noted the induction of UPRmt This approach was instrumental in identifying potential factors capable of modulating UPRmt in adults Subsequent investigations revealed that germline-expressed piRNAs played a significant role with their levels markedly decreasing in young adults This reduction may facilitate the production and secretion of a Hedgehog-like signal that suppresses somatic UPRmt While the initial experiment with embryo lysates was artificial it paved the way for discovering a naturally occurring germline-to-soma communication mechanism Our findings demonstrate that the signal is primarily transmitted from the germline suggesting the absence of other essential components in day 6 lysates that are pivotal for UPRmt induction These insights collectively highlight the complex interplay between piRNAs and other molecular constituents in modulating the mitochondrial stress response suggesting a broader regulatory landscape that extends beyond piRNA action alone Whether UPRER is regulated in a similar manner requires further exploration The selective regulatory mechanisms by which germline signals influence specific somatic stress responses are yet to be fully understood Delving into the mechanisms through which germline signals selectively modulate distinct somatic stress pathways could offer profound insights into how organismal stress responses are coordinated and the intricate dynamics between reproductive status and somatic health Worms were grown and maintained at 20 °C and fed with E. coli OP50 on Nematode Growth Medium (NGM) (0.25% Bacto peptone, 0.3% sodium chloride, 1.7% agar, 5 μg/mL cholesterol, 25 mM potassium phosphate pH 6.0, 1 mM magnesium sulfate, 1 mM calcium chloride) unless otherwise indicated. Strains used in this study are detailed in Supplementary Data 3 Bacterial strains used in this study were Escherichia coli strains OP50 and HT115 OP50 was cultured with LB medium at 37 °C unless otherwise indicated PAO1 and PAO1(GFP) were cultured with LB medium containing ampicillin (50 mg/ml) at 37 °C unless otherwise indicated For induction of UPRmt in worms by treatment with mitochondrial inhibitor synchronized L1 worms were raised on NGM plates at 20 °C Adult worms were transferred every day to new plates Worms were transferred to NGM plates containing mitochondrial inhibitor (1 μg/ml antimycin 0.5 mM paraquat) at the indicated time stage For induction of UPRmt by feeding worms with PA14 Adult worms were transferred every day to new plates starting at day 3 of adulthood Worms were transferred to PA14 slow-killing NGM plates For the induction of UPRmt in worms by RNAi synchronized L1 worms were cultured on NGM plates at 20 °C Adult worms were transferred to new plates daily starting on day 3 of adulthood The worms were synchronized and raised on NGM plates containing atp-2 Synchronized L1 worms were raised on NGM plates at 20 °C Worms were transferred to NGM plates containing tunicamycin (4 μg/ml) at the indicated stage Worms were transferred to pre-heated NGM plates at the indicated stage cultured at 33 °C for 2 h and then transferred to 20 °C worms were transferred to PA14 slow killing plates Wild-type worms were collected for RNA extraction after 48 h Pseudomonas aeruginosa (PA) was cultured in LB containing 50 mg/ml ampicillin at 37 °C for 16 h Concentrated PA were seeded onto air-dried slow killing plates then incubated at 37 °C for 24 h and subsequently at room temperature for another 24 h 50-100 worms were transferred to slow killing plates at the indicated stage Living worms were counted every day until all worms were dead Animals that crawled off the plate or died due to vulva bursting were excluded worms were transferred to new plates containing drug at the appropriate time if viable offspring were produced The selection of Days 5 and 9 for the antimycin and PA14 survival experiments was aimed at identifying the most suitable time points for plotting survival curves This choice helps avoid scenarios where median survival times are either too long or too short The worms were transferred to pre-heated NGM plates at the indicated stage cultured at 37 °C for 4 h and then transferred to 20 °C worms were transferred daily to new plates they were moved daily to fresh lysate-treated NGM plates and then every other day to fresh NGM plates from Day 7 onwards synchronized L1 worms were fed either control RNAi E worms were transferred daily to fresh RNAi plates and then every other day from Day 7 onwards living worms were counted daily until all had died Animals that crawled off the plates or died due to vulva bursting were censored No 5-fluoro-2′-deoxyuridine (FUDR) was added to the plates Day 1 hermaphrodites were collected from plates and washed 3 times in M9 buffer (42.3 mM Na2HPO4 The worms were then bleached to release the embryos at mixed developmental stages Day 6 hermaphrodites were collected from plates and washed 3 times in M9 buffer The embryo or worm pellet were washed and resuspended with PBS Dounce tissue grinders were used to homogenize embryos or worms A dissection microscope was used to monitor the level of homogenization to ensure no visible intact worms or embryos in the lysates The homogenizing process was carried out on ice Each lysate within an experiment was normalized to the starting volume of embryos/worm pellet lysates were cleared by centrifugation at 3000 g at 4 °C for 1 min For treatment of the lysates with different enzymes Proteinase K (0.1 mg per lysate sample derived from 2 million embryos) RNase AT1 (0.1 mg per lysate sample derived from 2 million embryos) or DNase I (0.1 mg per lysate sample derived from 2 million embryos) were added to the lysates The lysates were then incubated at 37 °C and gently rotated at 500 rpm for 1 h 300 µl of embryo lysate (derived from 2 million embryos) or 300 ul of worm lysate (derived from 100,000 worms) was immediately spread onto 3.5 cm NGM OP50 plates Synchronized worms at the indicated stage were then transferred to the lysate-treated plates synchronized worms were placed in M9 buffer containing 2 mM levamisole worms were decapitated with a single scissoring motion allowing one arm of the gonad to be fully released from the body cavity contrasts with the clear gonad which has a distal tapered tip the germlines were placed into tubes containing 500 µl of TransZol Up reagent (TransGen Biotech Approximately 50 germlines were collected for each biological replicate For germline piRNA overexpression, the piRTarBase (http://cosbi6.ee.ncku.edu.tw/piRTarBase/) was utilized to predict piRNAs related to wrt-5 and wrt-6. The piRNA-mediated interference system (‘piRNAi’) was employed to overexpress endogenous piRNAs. Scaffold information for the piRNA expression cluster E was obtained from https://www.wormbuilder.org/piRNAi/ Overexpression clusters targeting wrt-5 and wrt-6 as well as a control piRNA overexpression cluster Transgenic animals harboring piRNAi transgenes were created by Suny Biotech following standard protocols The injection mix for creating transgenes included 10 ng/µl of synthetic dsDNA for piRNA overexpression cluster and 10 ng/µl of a co-injection marker (myo-2p::mCherry) The sequences of the piRNA overexpression clusters used in this study are listed below: piRNA overexpression cluster targeting wrt-5 (uppercase: piRNAs) piRNA overexpression cluster targeting wrt-6 (uppercase: piRNAs) piRNA overexpression cluster control (uppercase: piRNAs) and a control gene wrt-1 were synthesized by Xianghong Biotech 60 µg of total piRNAs (10 µg per single piRNA) were combined with prg-1 embryo or worm lysates and then applied directly to OP50-seeded NGM plates Synchronized worms at the indicated stage were subsequently transferred to these lysate-seeded plates The piRNA oligos were 5′-monophosphorylated and 2′-O-methylation at their 3′ termini Nile Red was added into OP50-seeded NGM plates to achieve a final concentration of 0.05 µg/ml in the agar Synchronized worms were cultured on OP50-seeded NGM plates starting from the L1 stage the worms were transferred to OP50-seeded NGM plates containing Nile Red the worms were imaged using a Zeiss Imager M2 microscope and the images were analyzed with ImageJ software For the tetramethylrhodamine ethyl ester (TMRE) staining assay TMRE was added to OP50-seeded NGM plates at a final concentration of 0.1 µM Synchronized worms were cultured on RNAi plates starting from the L1 stage the worms were transferred to RNAi plates that contained TMRE the worms were imaged using a Zeiss Imager M2 microscope and the images were analyzed using ImageJ software Synchronized worms were harvested from the plates and washed at least three times with M9 buffer The worms were then homogenized using Dounce tissue grinders Cytosolic and mitochondrial fractions were separated via differential centrifugation using a Fumarate Hydratase Assay Kit (Grace Biotech Protein concentrations in each fraction were quantified using a BCA assay (Thermo Scientific Fumarase activity in these fractions was measured with the Fumarate Hydratase Assay Kit Synchronized worms were randomly picked into 2 mM levamisole droplets on 2% agarose pads and imaged by a Zeiss Imager M2 microscope Exposure time was the same in each experiment At least three biologically independent experiments were performed and similar results were obtained Synchronized worms were collected from plates washed at least three times with M9 buffer and then resuspended with SDS loading buffer (100 mM Tris-HCl pH 6.8 0.004% bromophenol blue) and boiled at 100 °C for 15 min Lysates containing the same amount of protein were loaded into an SDS-PAGE gel 5% non-fat milk was used to block PVDF membranes The membranes were then incubated with the designated primary and secondary antibodies the following primary antibodies were used: anti-GFP (Sungene #KM8009 The membranes were developed with the enhanced chemiluminescence method (Thermo) and visualized by a Tanon 5200 chemical luminescence imaging system Some RNAi clones were obtained from the Ahringer library; other RNAi clones were generated by PCR amplification of worm cDNA or gDNA and ligated into L4440 vector. Supplementary Data 5 summarizes the information about all RNAi clones RNAi plasmids were transformed into HT115 competent cells (ZOMANBIO HT115 clones were cultured in LB containing 50 mg/ml ampicillin at 37 °C for 12 h IPTG was then added to the final concentration of 1 mM coli was concentrated and then seeded onto a plate containing 1.2 mg/ml IPTG The plates were air-dried and incubated at 37 °C overnight Worms were transferred onto the plates when the plate temperature dropped to 20 °C the concentrated RNAi clones were mixed at a 1:1 ratio and seeded on the plates All RNAi treatments were started upon hatching and proceeded throughout post-embryonic development and adulthood Control RNAi experiments were carried out using an empty vector plasmid L4440 RNAi screening was performed by feeding worms with Escherichia coli HT115 RNAi clones were taken from the Ahringer library Embryos from hsp-6p::gfp worms were collected by bleach synchronization then 80-100 synchronized L1 worms were added to each well of 12-well plates containing RNAi bacteria Adult worms were transferred every day to new wells containing RNAi bacteria Larval L4 or adult day 3 worms were transferred to RNAi NGM plates containing mitochondrial inhibitor (1 µg/ml antimycin) Scores were recorded from ns (no induction of GFP expression) to +++ (strong induction of GFP expression) Synchronized worms at the indicated stage were exposed to PAO1(GFP) or PA14 worms were washed at least three times with M9 buffer then transferred to M9 buffer containing 1 mg/ml kanamycin and rotated for 20 min Washing and kanamycin treatment were repeated for at least four times to kill external bacteria on the surface of worms Worms were then spread on an empty plate and air-dried 20 worms were randomly picked into 100 μl M9 buffer and ground with a motorized pestle triplicates of 10 μl suspension were dropped onto LB plates containing 50 mg/ml of ampicillin Synchronized L4 worms were transferred to RNAi plates (one worm per plate) Worms were transferred to new RNAi plates every day until day 3 of adulthood and then transferred to new RNAi plates every two days Offspring were allowed to grow at 20 °C for 24-48 h and then counted Offspring from 10–20 individual worms were counted for each condition To quantify developmental delay caused by knocking down hedgehog-related genes synchronized L1 wild-type worms were fed with control RNAi E.coli or RNAi E.coli targeting hedgehog-related genes To quantify developmental delays caused by knocking out hedgehog-related genes wild-type worms and hedgehog-related mutants were fed with OP50 starting at the L1 stage The developmental stages of worms were analyzed Larval stages were visually determined based on vulval development To quantify the exploded (ruptured vulva) phenotype resulting from the knockdown of hedgehog-related genes synchronized L1 wild-type worms were fed with control RNAi E To assess the exploded phenotype upon knockout of hedgehog-related genes wild-type worms and hedgehog-related gene mutants were fed with OP50 starting at the L1 stage Data on the exploded phenotype were collected from day 1 to day 5 of adulthood data on the exploded phenotype were collected throughout all life stages PAO1(GFP) was cultured in LB containing 50 mg/ml ampicillin at 37 °C for 16 h Concentrated PAO1(GFP) were seeded onto slow-killing plates air-dried and incubated at 37 °C for 24 h and then at room temperature for another 24 h Synchronized L1 worms were raised on control or hedgehog-related gene RNAi plates at 20 °C worms were transferred to PAO1(GFP) plates worms were washed at least three times with M9 buffer and imaged vit-2::gfp images were taken at day 5 of adulthood Fluorescence intensity was quantified using ImageJ 100 day 1 N2 worms were picked into M9 buffer and washed at least three times with M9 buffer 100 µL of 2x Laemmli sample buffer (Sigma) was added and then loaded onto Criterion XT precast gels (4%–12% Bis-Tris Bio-Rad) using XT MOPS (Bio-Rad) as the running buffer Gels were stained and destained following standard Coomassie blue dye protocols and YP88) were identified based on published data and normalized to myosin approximately 500 synchronized day 7 N2 worms were treated with either untreated or treated with embryo lysates for 24 h and resuspended in TransZol Up reagent (TransGen Biotech Total RNA was then isolated using chloroform extraction followed by isopropanol precipitation with sequencing quality evaluation performed using FastQC (version 0.11.9) prior to mapping The reads were aligned to the Caenorhabditis elegans genome (Ensembl WBcel235/ce11 assembly) using HISAT2 (version 2.2.1) with default parameters, retaining only uniquely mapped reads for further analysis. Gene annotations for WBcel235/ce11 in GTF format were sourced from Ensembl (ftp://ftp.ensembl.org/pub/release-110/gtf/caenorhabditis_elegans/) Gene count matrices were generated using HTSeq-count from HTSeq (version 0.12.4) a two-tailed t test is used to assess whether a gene is differentially expressed HEK293T cells were cultured in Dulbecco’s Modified Eagle’s Medium (DMEM) containing 4.5 g/L glucose supplemented with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin Cultures were maintained in a humidified incubator at 37 °C with 5% CO2 Approximately 1×106 cells were seeded in each 6 cm dish and immediately transfected with 1 ng of p3.3-wrt-2/5/6-Flag combined with 1 ng of p3.3-ptr-8/16-HA plasmids using a PEIMax (Polysciences cells were lysed by adding 1 mL of Triton X-100 Lysis Buffer supplemented with protease and phosphatase inhibitors to each dish The cell lysates were then collected and cleared by centrifugation at 20,000 g for 10 min at 4 °C supernatants were mixed with 4× Laemmli sample buffer (Bio-Rad) and boiled for 5 min at 95 °C For samples destined for immunoprecipitations (IP) supernatants were incubated with pre-washed Flag or agarose beads for 3 h at 4 °C with gentle rotation The beads were subsequently washed three times with IP lysis buffer containing 500 mM NaCl Samples were then resolved by SDS-PAGE and analyzed by immunoblotting 13778-150) transfection reagent to transfect siRNAs into cells the culture medium was replaced with fresh DMEM In experiments involving transfection of both siRNAs and cDNAs cDNAs were first transfected into the cells Cells were harvested 48 h after siRNA transfection siptr-8-antisense-1: AUGAGGAAUGGUUGGAGGGTT siptr-8-antisense-2: UAUCCAUGAAUAUAGCCGCTT siptr-8-antisense-3: AAUGGAAUGCGACAUGAGCTT siptr-16-antisense-1: AAGCACAAACGGGUCUUCCTT siptr-16-antisense-2: AUAGACAUUAAUGUGGUGCTT siptr-16-antisense-3: AUUGAGGUUGAGUUCUUGCTT Experiments were conducted with prior approval from the Institutional Animal Care and Use Committee (IACUC) at Peking University Seven-month-old wild-type (WT) female and male C57BL/6 J mice were obtained from Biocytogen Pharmaceuticals (Beijing All mice were maintained on a 12-h light/dark cycle at 25 ± 2 °C and relative humidity (50%) Seven-month-old C57BL/6 J female and male mice were randomly assigned to experimental groups mice received daily intraperitoneal injections of Itraconazole (MedChemExpress R51211) at a concentration of 10 mg/kg; control mice were administered a vehicle solution consisting of 0.1% DMSO in Sulfobutylether-β-Cyclodextrin (MedChemExpress all mice were injected intraperitoneally with oligomycin (MedChemExpress HY-N6782) at a concentration of 0.5 mg/kg once a day the weight of each mouse was recorded every 7 days blood samples were drawn via the retro-orbital sinus using a serum separator tube (SST) Samples were allowed to clot for 2 h at room temperature before being centrifuged for 15 min at 1000 g The serum was then stored at −80 °C until analysis Serum AMH levels were measured using an enzyme-linked immunosorbent assay (ELISA) kit (CUSABIO 100 mg of testis tissue was rinsed with PBS The supernatants were aliquoted and stored at −80 °C Tissue testosterone levels were measured using an ELISA kit (CUSABIO Seven-month-old C57BL/6J female and male mice were randomly assigned to experimental groups mice were injected intraperitoneally once a day with Itraconazole (MedChemExpress R51211) at a concentration of 10 mg/kg; control mice received a vehicle of 0.1% DMSO in Sulfobutylether-β-Cyclodextrin (MedChemExpress One week after beginning the Itraconazole injections one Itraconazole-injected female mouse was placed in a cage with one Itraconazole-injected male for one week one control female mouse was paired with one control male for one week the number of offspring per female was counted Seven-month-old C57BL/6J female and male mice were treated as indicated Total RNA was isolated from the livers of these mice using TransZol Up reagent (TransGen Biotech The isolated RNA was then converted into cDNA using the EasyScript® One-Step gDNA Removal and cDNA Synthesis SuperMix (TransGen Biotech This cDNA was used to detect the expression of hedgehog pathway-related genes For genetic correlation analyses, GeneNetwork (http://www.genenetwork.org) was used to download and analyze datasets Pearson’s r was employed to measure the correlations All statistical analyses were performed with GraphPad Prism 9.0 All survival curves were estimated with the log-rank (Mantel–Cox) test the two-tailed t test was used to determine statistical significance quantitative data were obtained from at least three biologically independent experiments All images shown in the figures are representative of at least three biologically independent experiments All western blots were repeated at least twice with different samples Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article The RNA-seq data generated in this study have been deposited in the GEO under accession code GSE265886. All data supporting the findings of this study are available within this paper and its Supplementary Information files. Source data are provided with this paper Distinct temporal actions of different types of unfolded protein responses during aging Collapse of proteostasis represents an early molecular event in Caenorhabditis elegans aging Age-related alterations in the activation of heat shock transcription factor 1 in rat hepatocytes Concomitant decline in heat-induced hyperthermia and HSP70 mRNA expression in aged rats Age-related changes of heat shock protein gene transcription in human peripheral blood mononuclear cells Human aging alters the first phase of the molecular response to stress in T-cells Ubiquitin-like protein 5 positively regulates chaperone gene expression in the mitochondrial unfolded protein response Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR activation The cell-non-autonomous nature of electron transport chain-mediated longevity Aging augments mitochondrial susceptibility to heat stress Caenorhabditis elegans pathways that surveil and defend mitochondria Rejuvenation of aged progenitor cells by exposure to a young systemic environment Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy Maternal age generates phenotypic variation in Caenorhabditis elegans The influences of PRG-1 on the expression of small RNAs and mRNAs Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C A role for the RNase III enzyme DCR-1 in RNA interference and germ line development in Caenorhabditis elegans Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C PRDE-1 is a nuclear factor essential for the biogenesis of Ruby motif-dependent piRNAs in C and evolution of Caenorhabditis elegans piRNAs Distinct argonaute-mediated 22G-RNA pathways direct genome surveillance in the C The Argonaute CSR-1 and its 22G-RNA cofactors are required for holocentric chromosome segregation piRNAs can trigger a multigenerational epigenetic memory in the germline of C A nuclear Argonaute promotes multigenerational epigenetic inheritance and germline immortality P granules protect RNA interference genes from silencing by piRNAs GLH/VASA helicases promote germ granule formation to ensure the fidelity of piRNA-mediated transcriptome surveillance Biogenesis and germline functions of piRNAs Characterization of a germ-line proliferation mutation in C a gene required for cell communication during development in Caenorhabditis elegans a germ-line-specific sex determination gene required for hermaphrodite spermatogenesis in Caenorhabditis elegans elegans: analysis of tra-3 suppressors and characterization of fem genes Vitamin K2 enhances fat degradation to improve the survival of C Insulin-like signalling to the maternal germline controls progeny response to osmotic stress piRNAs regulate a Hedgehog germline-to-soma pro-aging signal Systemic regulation of mitochondria by germline proteostasis prevents protein aggregation in the soma of C Prostaglandin signals from adult germ stem cells delay somatic aging of Caenorhabditis elegans The role of the Cer1 transposon in horizontal transfer of transgenerational memory DNA damage in germ cells induces an innate immune response that triggers systemic stress resistance Small-RNA-mediated transgenerational silencing of histone genes impairs fertility in piRNA mutants piRTarBase: a database of piRNA targeting sites and their roles in gene regulation Reprogramming the piRNA pathway for multiplexed and transgenerational gene silencing in C Vitellogenins-Yolk gene function and regulation in Caenorhabditis elegans elegans eats its own intestine to make yolk leading to multiple senescent pathologies Age-associated vulval integrity is an important marker of nematode healthspan Extracellular RNA is transported from one generation to the next in Caenorhabditis elegans The UPRmt preserves mitochondrial import to extend lifespan Optogenetic rejuvenation of mitochondrial membrane potential extends C Mitochondrial UPR-regulated innate immunity provides resistance to pathogen infection Soo, S. K. & Van Raamsdonk, J. M. High confidence ATFS-1 target genes for quantifying activation of the mitochondrial unfolded protein response. MicroPubl. Biol 2021, https://doi.org/10.17912/micropub.biology.000484 (2021) Insulin/FOXO signaling regulates ovarian prostaglandins critical for reproduction Oocyte signals derived from polyunsaturated fatty acids control sperm recruitment in vivo elegans rrf-1 mutations maintain RNAi efficiency in the soma in addition to the germline a commonly used antifungal that inhibits Hedgehog pathway activity and cancer growth Cellular and molecular mechanisms of Hedgehog signalling A review of why and how we age: a defense of multifactorial aging Mitochondrial genome content is regulated during nematode development The germline coordinates mitokine signaling Repression of the heat shock response is a programmed event at the onset of reproduction Germline stem cell arrest inhibits the collapse of somatic proteostasis early in Caenorhabditis elegans adulthood Download references The authors thank the Caenorhabditis Genetics Center (CGC) and the National BioResource Project (NBRP) for worm strains Di Chen and Qinghua Zhou for generously providing worm strains Ying Liu was supported by grants from the National Natural Science Foundation of China (grants no and the Ministry of Science and Technology of China (National Key Research and Development Program of China Ying Liu acknowledges support from the Tencent Foundation through the New Cornerstone Investigator Program Academy for Advanced Interdisciplinary Studies conceived the study and designed the experiments analyzed the data and wrote the manuscript Nature Communications thanks David Vilchez and the other Download citation DOI: https://doi.org/10.1038/s41467-024-53064-0 By: Andrew Nelson 5:00 am on January 29 Updated permits have been filed for the now-foreclosed project at 342-360 5th Street in SoMa, San Francisco. The parcel has been a stalled pit in the ground since LEAP Development excavated the site in 2019. Paul Thompson of Novato-based Thompson Builders is now responsible for the application Trammell Crow Company secured entitlements in 2017 for an eight-story mixed-use infill with 127 apartments and 8,000 square feet of light industrial use City records show LEAP Development purchased the site in mid-2018 for nearly $3.3 million and secured site permits for construction in late 2018 Construction started in 2019 but was suspended in mid-March of 2020 360 5th Street stoops along Shipley Street water-filled hole in the ground ever since LEAP Development defaulted on a $10 million loan related to the project in May of last year and faced a lawsuit from the city by September The new developer is requesting that the city treat this application as a pipeline project so that the plans can benefit from a local ordinance that “temporarily reduces the Inclusionary Affordable Housing requirements and development impact fees in an effort to improve the feasibility of residential development.” Several changes have been made to the latest iteration of 360 5th Street with slightly fewer units and no more commercial space The plans now seek to build 115 for-sale condominiums across 97,400 square feet and a 63-car garage Additional space will be provided for parking 123 bicycles Handel Architects has taken over design from KTGY the plan sets retain many of the design elements first drafted by the original architects and the hole in the ground is a breeding ground for mosquitos One night I woke up with mosquito bites all over my head after leaving my window open Rats can climb you sides of buildings & enter into an open window (I have vid of one climbing on our building 25’ up…) It’s been an eye source for too long This should be at least double the height that is proposed YIMBY’s want double everything except the % of BMR units YIMBY’s want enough housing options so that we don’t need to create lotteries for the lucky few that qualify I understand the ROI on commercial space is iffy at the moment but would love if — in these situations — the ground levels were flex spaces or live/work units in order to activate street and adapt to the neighborhood as it changes Obv not every part of the city needs retail activation but SOMA could use more feet-on-the-street and less blank walls with garage doors and utility access panels (let alone water-filled holes in the ground) I’d love to see the updated design/plan I wish this was a larger project but a massive improvement over the current soma lake Shoji comes from superstar chefs Ingi “Shota” Son of the Shota and Intu-on Kornnawong of Jo’s Modern Thai the cafe offers ultra-thoughtful coffee drinks with a hushed But a pleasant surprise has emerged for ardent fans of the Bay’s food scene, though. Chef Intu-on Kornnawong, formerly of Jo’s Modern Thai Guests can expect the addition of those nighttime hours by mid-March Kornnawong says the offerings will skew Japanese in origin sort of like skinnier V60s for precise pour-overs And there are highly detailed notes are presented by staff with each beverage; there are specialty drinks including the warm sake-inspired cold brew cocktail Tosō and a matcha einspänner The cafe team is high-end, which makes sense: Son and Kornnawong are no-joke chefs. His bonafides include Shota, Sushi Hashiri, and Omakase. Pop-up bakery Tiny Croissanterie handles the pastry side for that cafe arm initially selling strawberry-filled white chocolate bow-tie croissants Shoji (140 New Montgomery Street) is open 7 a.m This article was corrected to clarify the chefs’ roles at Shoji Midtown Village in Wilkes-Barre is shown during one of SOMA’s pop up events in 2022 The Diamond City Partnership and Sordoni Art Gallery at Wilkes University announced SOMA Night Lights which will temporarily transform part of the city into a colorful canvas for the visual and performing arts named for downtown Wilkes-Barre’s newly branded South Main Arts District (SOMA) is set for 6 to 11 p.m on the 100 block of South Main Street in Downtown Wilkes-Barre SOMA Night Lights will feature several video-mapped projections on buildings throughout the district including one compiled from community submissions The video-mapping technique aligns video artwork to three-dimensional forms using surfaces beyond flat screens to create immersive visuals the event will include a pop-up “Kid’s Courtyard” offering free crafts for children and open houses at participating SOMA galleries Demonstrations for this event include the Rusty Iris led by Bad Hat Fire and a community “graffiti bomb” led by Wilkes University alumna Paige Edwards The Rusty Iris is a school bus transformed into a double-decker describe themselves as “an eclectic group of hard-working hard-playing people who share the love of fire and movement.” Located in the Sordoni Art Gallery parking lot (141 S there will be three fire performances at the Rusty Iris beginning at 7:30 p.m. The Keystone College Mobile Glass Studio will offer live glass blowing demonstrations from 6 to 9 p.m is complete with its own glass furnace and all the component parts of a working glass studio The Studio provides high school students with a unique opportunity to experience glass making In addition to the artistic and aesthetic aspect of the process students learn some of the chemistry and physics principles behind the heating and molding of raw materials used to make glass objects Paige Edwards is a NEPA-based artist specializing in illustration she has created several murals in the region including “At Wilkes Wilkes-Barre) and “The Grand Canyon” (342 Wyoming Ave. She will be leading a community “graffiti bomb” where participants will be invited to spray paint a car that will be temporarily installed on the Wilkes University campus after the event Building on the success of 2021’s “Light the Way Forward,” SOMA Night Lights demonstrates the continued partnership between the Sordoni Art Gallery and Diamond City Partnership to engage both Downtown and campus communities “Light the Way Forward” transformed the University’s Weckesser Hall and showcased video-mapped projections by artist Jeff Debrow and music by Aboriginal artists The dynamic display was synchronized with electronic music by Electric Fields creating an immersive experience celebrating the inauguration of the University’s seventh president To more about the SOMA Night Lights event, visit wilkes.edu/snl the building will have 1320 units of which 330 will be offered at a percentage of area median income March 19, 2025 • Real Estate across 1.1 million square feet of interior space — it’s the largest conversion in the country Residents have been living there for the past month and a half “SoMA offers 100,000 square feet of unmatched amenities — indoors and out every space invites you to enrich your daily life,” the website says Plus the entire brick façade was replaced along with the addition of more expansive windows and of course a gut reno inside The units will be available to individuals and families earning between 40 and 90 percent of “area median income” or AMI which you can see on this chart at the city’s Housing Preservation & Development site 40 percent of AMI is $43,480; 90 percent is $97,830 The building was designed by the architecture firm CetraRuddy The affordable units come out of the city’s 467-M tax exemption program Tribeca Citizen on Instagram By: Michael Young 8:00 am on February 1 New renderings have been revealed for SoMA, the largest office-to-residential conversion in the Unites States at 25 Water Street in Lower Manhattan’s Financial District Designed by CetraRuddy and developed by GFP Real Estate the project involves the replacement of the building’s brick façade with a modern fenestration featuring more expansive windows a gut renovation of its 1.1 million square feet of interiors and the construction of ten new stories above its former parapet making it the largest conversion in the country by unit count surpassing the 566-unit redevelopment of One Wall Street a few streets to the north The building will also feature approximately 100,000 square feet of amenities Pavarini McGovern is the general contractor for the property which is bound by Water Street to the north the New York Vietnam Veterans Memorial to the east The name SoMA pays homage to the building’s location in South Manhattan sitting at the southernmost tip of Manhattan at the nexus of Fidi The exterior renderings above and below depict the final appearance of the vertically expanded tower the revamped landscaping street level along Water Street and the new steel-framed pavilion structure featuring setbacks that make room for outdoor terraces with seating Residential amenities will include concierge services by LIVunLtd and a landscaped roof terrace with grilling stations and views of the New York Harbor and Lower Manhattan The bulk of the indoor amenities are part of the 18,000-square-foot SoMA Athletic Club There is also a 75-foot-long swimming pool plus an additional outdoor pool on the 25th floor Entertainment options include a bowling alley called Bowling Green the SoMA Lounge featuring a karaoke room and poker room coworking space called The Nook with private meeting rooms and a conference room Homes at SoMA will feature lofty ceiling heights custom Italian kitchens outfitted with paneled appliances Compass Development Marketing Group is in charge of leasing and marketing SoMA is the first office-to-residential conversion project to use the 467-m housing tax incentive which is a key policy of the mayor’s housing goal to produce 500,000 units over ten years The program was proposed in partnership between the Mayor and Governor Hochul and authorized in April 2024 by the state legislature The 467-m housing tax incentive is expected to produce more than 20,000 new homes across New York City 25 Water Street’s anticipated completion date is slated for November 2025 Subscribe to YIMBY’s daily e-mail Follow YIMBYgram for real-time photo updates Like YIMBY on Facebook Follow YIMBY’s Twitter for the latest in YIMBYnews The most logical thing would be from offices to residential Resi to office conversion would almost never happen Office requires too many and resi floorplates are too small youd eat up the whole thing in no time with lifts I actually liked the original Brutalistic brown brick facade a fortress-like construction with small windows this would not meet fenestration requirements for residential buildings and change was necessary So wondering how they made such deep floor plates work with residential Checked the website and they are all listed as studios/one bedrooms with multiple “home offices” Conveniently there are no listed floor plans They carved two courtyards through the center of the building and took the removed square footage and added it to the top of the building If you google: “site:somanyc.com filetype:pdf” you can find their floorplans An “office” and even a “den” is still a habitable space that requires light and air After looking at this we need to reintroduce old tenement laws These laws are 125 years old and this moronic conversion defies the whole concept of an antiquated law We are talking about people’s health and well-being nhe rooms are cramped and often lack windows and a living/dining room with one small window I wish I could say people wont pay $3k for some of these apartments but at that price point they would be competing with and beating LES tenements especially since they also offer access to amenities I really hope these large office conversions suck some of the energy out of the nearby LES rental market because the rents there have been insane let’s provide our dediiated drone workforce with enhanced cubicles to use as residences – no doubt inspired by the caged spaces our factory-farmed animal are force to endure Perhaps they’ll even provide freeChicken McNoggets in the lobby for the lucky cave dwellers Does anyone know what SoMA is an abbreviation for Probably just South Manhattan or something stupid like that Renderings have the feel of a human beehive..overwhelming This adaptive reuse project has two interior courts carved out of the large floor plates to provide the required Zoning Building Code and Multiple Dwelling Law required “light and ventilation (“air”)” required for all Habitable Spaces The FA lost for the Inner Courts was used for the new vertical enlargement It was the world’s first mainframe operation for worldwide banking for Chase Manhattan Bank Floors with small windows were floors with the IBM 360 mainframes the flrs with larger windows were office floors “Originally known as 4 New York Plaza the building began construction in 1967 and was completed in 1969 It was built in a Brutalist style and was designed by the architecture firm Carson You apparently don’t understand what the brutality architecture is “Brutalist” refers to exposed concrete facades and was the most attractive of the post war buildings downtown This present design is just bland and boring While Brutalism often uses exposed concrete The Breuer museum building on Madison is clad in granite I would agree that many examples of this style are not lovable “Brutalist architecture is an architectural style that emerged during the 1950s in the United Kingdom among the reconstruction projects of the post-war era Brutalist buildings are characterised by minimalist constructions that showcase the bare building materials and structural elements over decorative design angular geometric shapes and a predominantly monochrome colour palette; other materials ga('send', 'event', 'beautyofblock', 'Impression', 'https://newyorkyimby.com/wp-content/uploads/2025/04/Standard_336x280-100-2.jpg', { nonInteraction: true }); ga('send', 'event', 'PCRichards Builders Division', 'Impression', 'https://newyorkyimby.com/wp-content/uploads/2025/05/PCR_Beko_Compact_YIMB_336x280.jpg', { nonInteraction: true }); ga('send', 'event', 'yimby+', 'Impression', 'https://newyorkyimby.com/wp-content/uploads/2024/01/image.png', { nonInteraction: true }); Follow on Instagram var sb_instagram_js_options = {"font_method":"svg","placeholder":"https:\/\/newyorkyimby.com\/wp-content\/plugins\/instagram-feed\/img\/placeholder.png","resized_url":"https:\/\/newyorkyimby.com\/wp-content\/uploads\/sb-instagram-feed-images\/","ajax_url":"https:\/\/newyorkyimby.com\/wp-admin\/admin-ajax.php"}; © COPYRIGHT New York YIMBY® LLC YIMBY IS A REGISTERED TRADEMARK OF NIKOLAI FEDAK / NEW YORK YIMBY LLC Metrics details To investigate the developmental trajectory of PNS microglia-like cells created a time-resolved scRNA-seq dataset encompassing the human CNS and PNS tissues from CS10 (Carnegie Stage 10) to 24 PCW (postconceptional weeks) and performed trajectory analysis to infer the development of PNS microglia-like cells These results suggest that PNS microglia-like cells are likely derived from YS macrophage progenitors and differentiate in parallel with CNS microglia Prices may be subject to local taxes which are calculated during checkout Microglia Biology: One Century of Evolving Concepts Tissue-Resident Macrophage Ontogeny and Homeostasis Macrophages at CNS interfaces: ontogeny and function in health and disease Microglia and Central Nervous System–Associated Macrophages—From Origin to Disease Modulation Wu Z, Wang Y, Chen WW, Sun H, Chen X, Li X, et al. Peripheral nervous system microglia-like cells regulate neuronal soma size throughout evolution. Cell 2025. https://doi.org/10.1016/j.cell.2025.02.007 (In Press) Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages A Lineage of Myeloid Cells Independent of Myb and Hematopoietic Stem Cells Emerging importance of satellite glia in nervous system function and dysfunction Colony-Stimulating Factor 1 Receptor Signaling Is Necessary for Microglia Viability Unmasking a Microglia Progenitor Cell in the Adult Brain An immune cell atlas reveals the dynamics of human macrophage specification during prenatal development Download references Download citation DOI: https://doi.org/10.1038/s41423-025-01276-9 a global hospitality group that owns and operates over 560 hotels in 58 countries in Asia Pacific announces that it has entered into a Memorandum of Understanding with Soma Bay Hotel Company SAE to develop a hotel under its luxury Anantara brand in Egypt The first project under this partnership is expected to be announced later this year a coastal resort destination on the Red Sea in Egypt 2,500-acre community is just 45 km south of Hurghada International Airport Soma Bay offers a wide range of leisure activities The emerging resort destination also features one of the largest naturally occurring spas and thalassotherapy offerings in the region where guests can experience a range of seawater-based treatments designed to promote relaxation and wellness using the healing properties of the Red Sea's mineral-rich waters Anantara is set to bring its signature luxury experience to Soma Bay with a new resort and branded residence complex authentic travel experiences that connect guests to the unique culture Anantara's hotels and resorts are in vibrant cities Thai-rooted hospitality and creating unforgettable memories for every traveller operates in the hospitality sector and owns several luxury properties along the Red Sea Hotel website Brand OwnerMinor Hotels