Category Archives: Post Human

Complied by Ezra Haber Glenn

Long before the current writers strike, Hollywood was sounding the alarm about the dangers of AI.

A scene from a stage production of Karel apeks R.U.R. Photo: Wiki Common

For as long as weve had work which is to say, ever since we left the Garden of Eden our societys boldest prophets and inventors (and a few profit-seeking investors) have sought new ways to replace human labor with the effortless ease of technology. But while each new development may lead us closer to a brave new labor-free world, not everyone has welcomed these changes. Most notably, workers who have found themselves and their livelihoods in the headlights of automations onrush have resisted with their voices, their sabots, and their very lives but such resistance has often been dismissed as little more than self-serving Luddism, ignored by others in the name of progress and the greater good.

And now, after replacing everyone from farmers and cobblers to taxi drivers and toll collectors, the bots have come for the creative class. Yesterdays fiction is becoming todays reality, as each week we hear news of yet another generation of AI tools and wizardry being prepared to replace human workers. Programs such as DALL-E and Midjourney have ingested the collected art of all of humanity; they are now able to churn out endless reels of soulless imagery to feed our demand for custom-made illustration, everything from a daguerreotype of Abraham Lincoln punching Joseph Stalin to pornographic iguana-sex rendered in the style of Pieter Bruegel the Elder. As for the more text-oriented professions, OpenAIs ChatGPT, Googles Bard, and a host of similar generative AI are able to produce reams of seemingly novel text on command, including restaurant (or film) reviews, business plans, academic articles, and even stories, poems, scripts, and screenplays. What began as a diversion has become an existential threat.

To their credit, the artists and storytellers of the world have long been among the most vocal critics of the unchecked spread of technology, even before they found themselves confronting automation and replacement. Whether spinning tales on a stage or around a campfire or through the flickering light of a film projector writers have warned of the dangers of technology unchecked, hoping to spray some cold water on these sparking Promethean fires before they burn out of control. From the lessons of The Sorcerers Apprentice (whether Goethe or Disney) through Luddite anthems and pro-labor protest songs, right down to the modern-day fables of WarGames, The Terminator, Ex Machina, M3GAN, and just about every episode of Battlestar Galactica and Black Mirror, popular media has sounded a steady alarm to warn us of the inherent dangers of powerful automation, whether robotic, AI, or something entirely new. (Indeed, the very first use of the word robot a hundred years ago in Karel apeks R.U.R. foretold of the coming robotic uprising and the eventual extermination of humanity at the hands of our own creation.)

How to mark the current moment, when global forces of labor, creativity, capital, automation, and invention are once again locked in struggle? Weve decided to collect short reviews from a range of critics exploring films throughout the ages that explore the threats posed by robots and artificial intelligence. Some are outright Apocalyptic or dystopian works. Others present more nuanced, subtle, and blended takes. What will be lost, what can be preserved, are there ways we can control these changes in the service of a more humane post-human future? Or: are we even sure that we are actually human now?

Given how rich this particular vein is, this list is more illustrative than exhaustive. Here is a rundown of a handful of thoughtful or thought-provoking films that are worth rewatching. Readers are sure to have their own contributions and wed love to hear about as well feel free to drop them in the comments.

A captivating scene from The Twonky.

The Twonky (Arch Oboler, 1953)

Though screen time is a relatively modern concept in regard to our relationship with technology, its associated anxieties have been with us for as long as weve invited screens into our homes. Consider Arch Obolers oddball 1953 comedy The Twonky, one of the earliest films ever made about television, and one of the strangest this side of Videodrome. Hans Conried plays a harried college professor whose wife leaves him alone for the weekend to set up their brand new TV set. What neither of them realize is that their newfangled device has a mind of its own; it skitters around the house on a set of table-legs, emits lasers from its screen (which it uses to light Conreids cigarettes), and neutralizes anyone who attempts to stop it by turning them into zombies muttering I have no complaints. Eventually, Conreid reasons that this Twonky (as his best friend, the hard-drinking local football coach, dubs it) is not actually a television at all, but rather a shape-shifting robot from Earths future, designed to keep the populace in line to serve a dictator named Super Snake.

At press time, Super Snake has yet to be elected to office, but The Twonky is nevertheless surprisingly prescient in many other ways. In 1953, the idea of a television which could anticipate its owners needs was a fanciful bit of whimsy; today, we walk past aisles of smart TVs at Best Buy without blinking an eye. Like modern algorithms which invisibly guide users toward the lowest common denominator, the Twonky zaps classical records and fine literature out of Conrieds hands, forcing him to listen to nothing but Sousa marches and read trashy paperbacks. When the Twonky overhears Conried bemoaning his loneliness with his wife out of town, it picks up a phone and requests a human blonde from the Bureau of Entertainment, eerily foreshadowing the contemporary targeted ads which seemingly prove that our devices are listening to our conversations. The Twonky is a deeply silly film, closer in spirit to Bewitched than Blade Runner, but its vision of the helpful technologies which end up running our lives remains timely 70 years later.

Oscar Goff is the Editor in Chief and Senior Film Critic at Boston Hassle.

Art for Colossus: The Forbin Project

Colossus: The Forbin Project (Stanley Chase, 1970)

Based on a 1966 sci-fi novel, this cold-war thriller sets up a situation where the U.S. turns over control of its nuclear weapons to a computer. It removes the human element from war and, theoretically, makes us safer. But, as with Hal in 2001: A Space Odyssey, its all in the programming. Colossus discovers that theres a Russian counterpart and demands to be linked to it, and starts to take punitive steps when such connection is not immediately forthcoming.

Dr. Forbin suggests that those working in his field should be required to read Frankenstein in order to consider what happens when science spins out of the control of the scientists. When I screened the film for my students and we reached the less than happy ending I would wish them pleasant dreams that night. This is the real fear of AI: we expect we will control our tools. But, when the tools can think for themselves, will they bother to listen to us?

Daniel M. Kimmel is the author of Jar Jar Binks Must Die and other observations about science fiction movies.

Are we home yet? Julie Christie in Demon Seed.

The House of Tomorrow: Demon Seed (Donald Cammell, 1977) and Smart House (LeVar Burton, 1999)

In celebration of its 75th anniversary in 1967, the Philco-Ford Corporation produced 1999 A.D., a short film showcasing its vision for the House of Tomorrow, which would be equipped with futuristic technology that would allow Americans to have live video chats with friends, pay their bills automatically, and set their thermostats to the perfect temperature year round. The house, the film suggests, would be operated by a central computer that could serve as a secretary, librarian, banker, teacher, medical technician, bridge partner and all-around servant. This para-utopian vision traded in the domestic Space Age optimism previously seen in cartoons like The Jetsons, but it came one year before 2001: A Space Odyssey, which helped introduce the specter of rogue A.I. into the cultural consciousness.

A decade later, Donald Cammells Demon Seed transformed the House of Tomorrow into a psycho-sexual nightmare, in which an advanced A.I. called Proteus goes from servant to captor. Its target is suburban housewife Susan (Julie Christie), for whom Proteus acts as an abusive partner, making excuses to her friends and creating proto-deepfake videos of her claiming to be fine. Why? The computer is planning to rape and impregnate her with a human-machine hybrid. In Demon Seed, A.I. transforms Edenic suburbia into a futurist dungeon one of pop cultures many warnings to come about the unknown dangers of advanced technology.

A scene of mutual happiness in Smart House.

By 1999, the real life smart homes of Alexa and affordable IoT appliances were nearer to becoming a reality than many realized; Philco was only off by about a decade or so. Still, fears of AI in the nuclear household persisted. The LeVar Burton-directed Disney Channel Original Movie Smart House created a kid-friendly version of Demon Seed, in which a single-parent family wins a free computer-operated home. Thirteen-year-old Bens (Ryan Merriman) mother has died, and to fill the void he trains the houses central AI, PAT (Katey Sagal), on footage from old 50s sitcoms (pastiches of Father Knows Best and Leave It to Beaver) to teach her how to be a perfect matriarch. PAT goes in another direction and begins to resemble Proteus, imprisoning the family via an overbearing maternal instinct and a hyperbolic fear of the outside world. Researchers warn of AI reflecting the biases of its human programmers and users. Smart House dramatizes that prediction: the once rational computer succumbs to the patriarchal beliefs that drive American pop culture and absorbs the paranoia spread by television news.

Brad Avery is a journalist and writer based in Boston. He is a member of the Boston Online Film Critics Association.

A scene of mutual uncertainty in Moon.

Moon (Duncan Jones, 2009)

Moon is the debut effort of filmmaker Duncan Jones, who wrote the story and directed. The narrative posits a near-future that is not so much about AI controlling human beings, but a dark anti-capitalist vision of how corporate America will use such technologies to exploit us for profit. One humans experience is presented sort of. Sam Bell (a tour-de-force performance by Sam Rockwell) is the lone technician for a mining outfit that is harvesting helium from the moon for fusion reactors back home on earth. Sam monitors the mostly automated operations of the equipment, occasionally checking on and fixing malfunctions, during a three-year stint on the moonbase. His only companion and helper is Gerty (voiced by Kevin Spacey), an AI who ensures that Sam stays healthy.

The big twist in Moon is that Sam Bell is not Sam Bell, not really. He is a clone of Sam Bell, who is either dead or back on earth (it is never settled). The clones are how the mining company makes us of infinite free labor. When things go awry on the base, the machinations of the plot eventually gives us two Sams. In fact, the base is outfitted with thousands of Sam clones in cold storage, since each clone can only function for three years before degrading and being destroyed by the bases technology. Gerty, meanwhile, is programmed to help Sam, even if there are two Sams. (The existential side-story of Sam1 and Sam2 relating to each other is fascinating on its own, as both realize what it means to be a fully conscious clone with the real memories of the original Sam. Plus we get two Rockwells playing ping pong with each other, which is never a bad thing.)

In regard to AI, the film allows for a glint of hope. Humans can overcome the crush of plutocratic hegemony by using technology against itself. Gerty at first appears to be a HAL9000-like threat to Sam, siding with the corporation and doing their bidding early on. But ultimately the program enables Sam (and Sam) to undermine the system that is degrading them. Gerty cannot allow Sam to die and, in an ambiguous turn of events, it turn out the computer cannot distinguish between the two Sams. As such, Gertys programming only serves to bring about its own downfall. The Sams sense this: when it becomes a choice between Sams health and the well-being of the moon base and mining operation, Gerty will choose to help Sam.

The production design by Tony Noble uses a cool palette of greys and blues for the moon base, but tosses in some neat counter-touches. Aside from Gertys voice, the machine is represented by a small screen with a bright yellow emoji that reflects Gertys mood: a smiley face most of the time if Sam is happy and healthy. Eventually, there is expressionlessness, followed by confusion. Gertys limited emotional landscape is overpowered by the very human presence of Sam: Rockwell is moody, sardonic, and self-aware in a way that Gerty could never be. Sams humanity clone or not is never called into question. He is not a machine. He is not artificial. And it is the characters humanity that shapes the movies satisfying, if troubling, conclusion.

Neil Giordano

Joaquin Phoenix longing for his significant other in Her.

Her (Spike Jonze, 2013)

Much of the animosity towards artificial intelligence these days tends towards practical matters, with loss of livelihood being paramount. But, prior to the recent controversy surrounding the writers and actors strike in Hollywood, most people felt artificial intelligence to be a mild existential threat. This was technology that re-shaped our very humanity because it could do so many things, including mundane chores like shopping, cleaning, and cooking. Some people are thrilled to leave these dull tasks to others; others find such routines and rituals meaningful, even and comforting. Even more challenging: this technical revolution clearly has implications for gender roles that even today, are still mired in traditional sexist grooves. It is exciting and progressive to think that we might have the opportunity to reinvent stale customs and assumptions (i.e., women shouldering the main burden of domestic duties). Even love might take on new meaning.

With the 2013 film Her, Spike Jonze dabbles in the dystopian notion that artificial intelligence can fulfill our every need, including, for those lonely enough, the role of a romantic soulmate. Joaquin Phoenix plays Theodore, a recently-divorced writer who works for a virtual greeting card company that creates digital messages for all occasions: a sort of troubadour for the age of technology. He tries dating, but cant quite figure out what hes doing wrong. When his new operating system and virtual assistant, Samantha, proves to be not only competent and helpful but warm and personable, he finds himself smitten.

Voiced by Scarlett Johansson, Samanthas mercurial, soulful personality carries unexpected appeal. But when Theodore discovers he is one of many who are also romantically involved with this virtual dynamo, his sense of being chosen, of being special, is betrayed. Artificial intelligence is an affront to the idyllic belief that lovers are drawn together by fate, by a shared sense of discovery and recognition. Theodores loneliness is briefly eclipsed by what he perceives to be a real relationship. This dissonance mirrors the odd phenomenon of dating apps; they make information and engagement readily available, but true connection remains elusive. With its carnival dusk color palettes and intense, nuanced performances, Her invests its cold dystopia with suprising pathos as well as haunting sense of inevitability. As the sun goes down each day on the films city of glass and pedestrian walkways, there is a sense that the self, the true one that melds body and heart and mind, is being reinvigorated and recharged. Emotional autonomy is still there for the choosing. At least, for now.

Peg Aloi is a freelance film and TV critic who has an uneasy relationship with technology.

A scene from #PostModem

#PostModem (Jillian Mayer, 2013)

Much of visual artist Jillian Mayers body of work concerns the relationship between humanity and technology, particularly the absurd intrusions modern tech makes into our lives. Take for instance her short film Hot Beach Babe Aims to Please (2014) in which Mayer emerges from the ocean only to be chased by a swarm of cursors, or her Makeup Tutorial (2013) where, in the language of YouTube vloggers, she instructs viewers on how to paint their faces with jagged patterns to confuse and hide from facial recognition devices.

Her 2013 collaboration with Lucas Leyva, #PostModem, is among her most enjoyable film projects a 15 minute sci-fi musical inspired by the theories of futurist Ray Kurzweil and the concept of the technological singularity, the theorized moment when artificial intelligence, capable of nigh-infinite self-improvement, surpasses human intelligence. In #PostModem, Mayer becomes immortal by uploading her consciousness to an open internet website called MegaMegaUpload (achieved by drawing the AOL logo on her face and drinking a blend of orange juice and her own hair filtered through a CD-R disc). What will she do throughout eternity? Watch infomercials alongside her digital doppelganger, a cheap digital avatar a la Second Life or The Sims. #PostModem stands as one of the sharpest satires to date on the sputtering of Mark Zuckerbergs Metaverse. Instead of Oculus headsets, Mayers super-intelligence future involves crude at-home surgery and implanting motherboards into ones own forehead (now thats biohacking). Ultimately, the film questions what enlightenment, if any, will be gained with our diaspora to VR.

Brad Avery is a journalist and writer based in Boston. He is a member of the Boston Online Film Critics Association.

Chiwetel Ejiofor and Emilia Clark as proud parents in The Pod Generation.

The Pod Generation (Sophie Barthes, 2023)

In the 1965, The Rolling Stones sang:

Kids are different today. I hear every mother say/Mother needs something today to calm her down/And though shes not really ill, theres a little yellow pill/She goes running for the shelter of her mothers little helper.

Meprobamate, marketed as Miltown, helped relieve a mothers insomnia, anxiety, and emotional upsets. Today, wet nurses are out of fashion, day care costs are prohibitive, and mothers juggle work, kids, social life, parenting groups, and husbands. From stretch marks to intimacy, sleep deprivation to post-partum depression, motherhood can be a bitch. Whats a mom to do?

Sophie Barthes new film The Pod Generation imagines what it would mean for women to cast off the burdens of childbearing through the use of synthetic egg-shaped pods. With the couples permission, the company Pegazus will arrange to have a baby raised in a Womb Center, where it is nurtured with music, taste sensations, and all the nutrients necessary for a healthy birth. A helpful strap-on device allows dad or mom to carry the pod/child for brief periods. There is a downside: the child wont dream. As the spokesman for the company explains dreams are not reliable analytical material thats so 20th century.

It is a gleaming future of 3-D printers, oxygen inhalers for fresh air, and a Siri/Alexa type virtual assistant, named Elena, that can help with such mundane tasks as preparing breakfast and choosing outfits for the day while also maintaining an individuals bliss index based on voice and behavior patterns. The films conclusion is hurried but that didnt bother me because the point had been made: we lose something valuable when technology provides shortcuts to chores that were once part of a normal life. Of course, there is a need for surrogate parenting, in vitro fertilization, and so forth, but outsourcing motherhood to plastic pods (which are shaped to fit corporate imperatives) is a sharp parody of the obsession with convenience. The relentless progress of technology undercuts the value of imagination, labor, and even physical and mental duress.

Will AI replace or even enhance art and creativity? One answer is posed by Noah Baumbachs film While Were Young. At one point, Adam Drivers Jamie asks Ben Stillers Josh about the ingredients of a certain dessert. Lets look it up, advises Josh. Waving his phone and giggling, Jamie, the hipper of the two, responds: Thats too easy. Lets just not know what it is.

Tim Jackson is a Boston musician, actor, and retired college teacher, currently a member of the Boston Society of Film Critics.

Ezra Haber Glenn is a Lecturer in MITs Department of Urban Studies & Planning, where he teaches a special subject on The City in Film. His essays, criticism, and reviews have been published in the Arts Fuse, CityLab, the Journal of the American Planning Association, Bright Lights Film Journal, WBURs ARTery, Experience Magazine, the New York Observer, and Next City. He is the regular film reviewer for Planning magazine, and member of the Boston Society of Film Critics. Follow him on https://www.urbanfilm.org and https://twitter.com/UrbanFilmOrg.

Continued here:
Film Commentary: How I Learned to Start Worrying and Fear the Bot" - artsfuse.org

As the year has ticked over into its second chapter and programming is settled and smooth in our post-pandemic push forward ArtsHub checked in with curators across Australia to find out which artists are on their watch list.

Selected by: Rachel Ciela, Lead Creative Simon Lee Foundation Institute of Contemporary Asian Art, Art Gallery of Western Australia (WA)

Why: The paintings and drawings of Ipeh Nur depict elaborate worlds filled with a multitude of characters, both real and imagined, and carefully crafted stories. Her works negotiate the complex intermingling of historical memory and tradition in Indonesia with great warmth and generosity while simultaneously offering a raw and unfiltered view of the artists personal experience of contemporary life.

Nur was recently included in ART JOG 2023. She lives and works in Yogyakarta.

Follow Ipeh Nur on: Instagram @ipehnurberesyit

Selected by: Beatrice Gralton, senior curator, Brett Whiteley Studio, Art Gallery of New South Wales (NSW)

Why: Heather B Swann is having a moment. For over three decades the Hobart-based artist has worked rigorously and ambitiously between drawing, sculpture, painting performance and installation, and we are now beginning to see her work consistently included in major exhibitions around the country. Ive known her for 20-something years and had the privilege to include her series of works, Leda and the Swan in The National 4.

The years that it takes Swann to produce a body of work is testament to her endurance and commitment as an artist. It is a long road, and her work is a complete surrender to the process of making art. There is something exhilaratingly vital and expansive about this journey, inviting us below a surface of perfectionto embrace our own messy and physical selves.

Right now, Swann has work in the exhibition Twist at the Tasmanian Museum and Gallery and is working towards the National Gallery of Victorias Triennial in December, as well as some other major (and, as yet, unannounced) projects for 2024. She shows with Station Gallery.

Follow Swann on: Instagram @heatherbswann

Selected by: Sophie OBrien, Head of Curatorial and Learning, Bundanon (NSW)

Why: This exciting collective of performance-makers represents a wonderfully experimental energy that continues to thrive in Australia an impulse that often emerges from a devised theatre-making context, but draws on other performance disciplines to fuel its explorations. They prove cultural organisations and arts schools to still be essential in providing meeting places for artists who will go on to collaborate or connect for many years into the future.

Often celebratory in nature and irreverent in performance, the group relishes non-theatrical spaces, collaborating with intergenerational communities. Borrowing from the live art field to put the audience at the centre of the work, the group creates spaces that feel risky and alive.

They are comparatively emerging, having only formed after training together a few years ago, but have already started winning awards with Green Room and Melbourne Fringe Festival. They describe their practice as instinctive, physical and highly playful that is, offering us all a sense of unrepeatable, uplifting joy.

Follow Pony Cam on: Instagram @ponycamcollectiveand its website.

Selected by: Francis E Parker, Curator Exhibitions, Monash University Museum of Art (MUMA) (VIC)

Why: Its hard to comprehend in reproduction, but Josh Foley often creates a simulation of impasto in a totally flat surface, like a kind of trompe lil, so passages that look loose and spontaneous are actually the result of meticulous work. That kind of contradiction fascinates me. Being from just outside of Launceston myself, I also detect a Tasmanian sensibility in some of his paintings.

In 2011 Foley won the John Glover Prize, which was then the richest landscape prize in Australia. Winning this award at the age of 27, he remains the youngest person to achieve this.

Josh Foley currently has a show on at Despard Gallery in Hobart.

Follow Josh Foley via Despard Gallery or his website.

Selected by: Anna Briers, Curator, UQ Art Museum (Qld)

Why: A creative to watch right now is Alicia Frankovich, a Naarm/Melbourne-based artist originally from Aotearoa/New Zealand, and previously located in Berlin. Frankovich has an impressive track record working across performance, sculpture, video and photography. Her practice is the kind of thing Im drawn to at the moment. Shes an artist who is critically engaged with current discourses, but who has developed an artistic methodology that is visually arresting and compelling on an embodied level a practice that is open and generous to audiences.

Her work is collaborative and relational, and she works with a diverse array of professional and untrained performers to tease out the important questions of our time through dance. Most recently, in March, I saw Atlas of Anti-Taxonomies (2019-22) at the Gus Fisher Gallery in Tmaki Makaurau/Auckland, a work which developed as part of the artists PhD research.

The work undertakes a reordering of Western knowledge systems, drawing on thinking by Mori scholar Linda Tuhiwai Smith and art historian Aby Warburg. Presented as an installation, it consists of a series of illuminated suspended screens depicting images of flora, bacteria, symbiotic organisms such as lichen, fungi growths and their mycorrhizal networks, climate phenomena and so on. It speaks to our entanglement with ecological planetary systems, which are in fact borderless anti-taxonomical if you like. It resists the separation between nature and culture, decentres the notion of human supremacy and affirms the relational interconnectedness of all things. It is the severing of these entanglements that got us into this mess.

She also recently developed a major choreographic installation in response to the Australian bushfire crisis in the summer of 2019-20 entitled AQI2020 for the Auckland Art Gallery Toi o Tmaki, which oddly hasnt been presented in Australia yet.

Frankovich is included in Melbourne Now at the National Gallery of Victoria, and has an upcoming solo exhibition at 1301SW, Melbourne in February 2024. She is also developing a major new performance work for a UQ Art Museum group exhibition for 2025.

Performers in Rich in World, Poor in World, 2023 (pictured top): LJ Connolly-Hiatt, Mara Galagher, Shelley Lasica, Shian Law, Enzo Nazario, Erin ORourke, Lana prajcer, Angelita Biscotti, Jesse Gall, Erin Hallyburton, Alexis Kanatsios, Daniel R Marks, Rajdeep Puri. Music: Igor Kaczyski.

Follow Alicia Frankovich via her website.

Selected by: Con Gerakaris, Curatorial Program Manager, 4A Centre for Contemporary Asian Art (NSW)

Why: With a brazen palette and effortless style, Jacquie Meng conjures vivid parallel universes populated by folkloric tales both historic and contemporary. Meng equally draws upon lived experiences and whimsical situations to present an ever-changing visual lexicon of cultural symbology, rendered in caricatured figures in a flattened perspective borrowed from woodblock prints. Objects of the everyday and treated with the same importance as universal signifiers of Chinese heritage: the Bic lighter is as fundamental as the carved jade chamber within which a joss stick burns. Her exalted avatar traverses the divide between real and imaginary, a post-human protagonist mythologising the idyllic daydream of driving a flame-decal monster truck down Northbourne Avenue, phosphorescent Nalgene in hand.

Jacquie has just completed a residency atKunstraum, Brooklyn New York (01 April 30 June), and is currently undertaking one at Pilotenkueche, Leipzig (4 July 23 September).

Follow Jacqiue Meng via Instagram @jacquiemeng or her website.

Check out our 2022, 2021 and 2020 iterations of curators on artist to watch.

Read the rest here:
Six curators talk about the artists on their radar - ArtsHub

The last five years have been pretty wild for the X-Men. For a while, Marvel was doing its best to marginalize the team but they've become the publisher's biggest comics again. Things have cooled off recently, but fans have been treated to some amazing stories, many of which saw the X-Men triumph over tremendous odds, saving their newly minted mutant nation of Krakoa and sometimes the universe.

The X-Men have had some impressive wins in the last five years. The team has always been in the upper echelons of Marvel's heroic community, but they've changed tremendously since 2018. They proved they can handle circumstances no one imagined they could.

RELATED: Every X-Men Comic Currently Running (& Their Most Recent Issue)

Wolverine is the X-Men's most popular member, so it makes sense that he is responsible for at least one of the team's massive victories. Mikhail Rasputin, working for the Russian government, was able to get his hands on the Cerebro Sword. Using that and his reality-altering powers, he used Wolverine's and Xavier's memories to use Omega Red to assassinate Professor X at multiple points in the past. Xavier and Jean Grey used their mental powers to send Wolverine back to stop them.

Wolverine battled Omega Red in multiple situations, from saving the Xavier family on the night of Charles' birth to stopping the assassinations of Xavier's ancestors. After halting Rasputin's plans, Wolverine was able to not only defeat Omega Red but retrieved the Cerebro Sword. Wolverine, Xavier, and Jean Grey saved the X-Men, and with them the universe, by ending Rasputin's plans.

Not every win for the X-Men came through force of arms. After X Of Swords, the mutant team had a big problem. The mutants of Arakko had spent millennia battling the demonic hordes of Amenth and formed a martial culture. They wouldn't have fit in very well on Earth, so the Quiet Council thought outside the box. Gathering their most powerful mutants, they set out to do something unprecedented.

Mutants of Krakoa and Arakko alike worked together to take Mars, a planet incapable of supporting life, and terraformed it. They gave it a heavier core, a breathable atmosphere, and water. They made the red planet into a new world and named it Arakko, giving it to the mutants who had survived millennia of death and destruction. The Quiet Council promised fireworks for the first Hellfire Gala, and they delivered with a win unlike any other in history.

As Krakoa was still establishing itself, an alien invasion ravaged the Earth. The mutant nation was targeted as well when the alien Cotati attacked the island. The mutants of Krakoa were sorely outnumbered, but their teamwork allowed them to at least hold back the invaders, keeping the island from falling completely. Then Magneto decided to intervene.

Since the establishment of Krakoa, Magneto had been acting as a leader. He let others get their hands dirty, relishing his position of power in a place that was basically the culmination of his wildest dreams. However, with aliens overrunning the island, Magneto donned his old purple and red costume and unleashed his full power on the invaders. He broke their beachhead on Krakoa, shredding the Cotati with his powers. With Magneto at the head of their forces, the X-Men kicked the invading forces off their soil.

RELATED: 10 Biggest Changes Marvel Made To X-Men's Lore Over The Years

Powers Of X took place in multiple universes, several made possible by the powers of Moira MacTaggert. In her ninth life, a hundred years after the establishment of the X-Men, Nimrod and the Sentinels had taken over the Earth, slaughtering mutants to nearly nothing and transforming humanity into post-human machine hybrids. The only ones fighting them were a group of X-Men led by Apocalypse, and they made one final play to stop their future from happening.

The X-Men attacked Nimrod's data vault, led by Apocalypse himself. Sorely outnumbered, the group was violently cut down as Apocalypse battled Nimrod to a standstill. However, even with their horrific losses, they got the information they needed. Wolverine gave Moira the data and then killed her, resetting the timeline and giving her the knowledge she'd need to slow down Nimrod in her next life.

Extermination saw the X-Men beat an old foe. Ahab, a mutant-hating cyborg from a future where humanity enslaved mutants, came back in time to kill the original five X-Men, who had been transferred to the present by Beast. As that was happening, a younger version of Cable had come back to send the young mutants back to the past to stop Ahab.

At first, the X-Men fought against Cable, thinking he was the one trying to destroy their time-tossed teammates. However, Ahab's plan was laid bare and the X-Men and this younger Cable worked together to stop him. The original X-Men were sent back to the past, their minds altered so they wouldn't remember their time in the present until it was necessary, and Ahab's terrible quest was stopped.

X-Men Red's early issues concentrated on Storm, Magneto, Sunspot, and the Fisher King working to consolidate power on Arakko. Meanwhile, Abigail Brand, the leader of SWORD, Krakoa's space agency, had secretly allied with the Orchis Initiative and was working to destabilize the Arakkii government by placing Vulcan in their Great Circle. After this failed, Brand's coup plans continued apace.

The Arakkii Brotherhood, working with SWORD's X-Men Red team, led by Cable and Thunderbird, recognized Brand's threat and worked to stop her. After Brand unleashed a newly resurrected and angry Vulcan on the Brotherhood and X-Men Red, the combined mutant heroes were not only able to stop her but forced her out of SWORD. Arakko remained independent and SWORD was no longer Orchis's secret pawn.

A.X.E. Judgment Day shook the Marvel Universe. It all started with new Eternal Prime Druig working to cement his power base among his people. Discovering that mutants evolved from Deviant genes, he was able to get the majority of the Eternals to agree to war against Krakoa and Arakko. The immortal forces of the Eternals did their best to raze the mutant homelands to the ground, but the mutants stood firm.

In order to end the conflict, rogue Eternals worked with the Avengers and Mister Sinister to create a new Celestial god for the Eternals, the Progenitor. Unfortunately, the Progenitor decided to judge the whole of humanity and destroy Earth if it found the world wanting. The X-Men allied with the Avengers and the Eternals, and were instrumental in defeating the Progenitor, their powers and mutant technology giving the heroes the advantage they needed to win.

Krakoa was swept up in the attack of Knull. Knull was able to get control of Cable with a symbiote, who used a Krakoan gate to bring more symbiotes to the island nation. The mutant island was overrun and soon mostly under Knull's control. The only mutants ready to stand against him were the members of SWORD, safe in the orbiting Peak space station.

A group of mutants made their way to Earth, but Knull's symbiotic mutants were able to hold them at bay. Manifold, whose mutant powers allow him to shape the universe in any way he needs, stepped up. He was able to open a portal over Krakoa and suck the symbiotes into it, saving those the aliens were bonded to and freeing the nation.

RELATED: 10 Best Female X-Men Characters, Ranked

X Of Swords was a supernatural war against the demonic hordes of Amenth. Led by the Golden Helm of Annihilation, the Amenthi were responsible for the sundering of the ancient mutant nation of Okkara into Krakoa and Arakko, with the Arakkii traveling into Otherworld to battle them. Amenth was able to conquer the Arakkii, who challenged the Krakoans to a contest of swords.

Traveling to Otherworld, champions of both sides participated in contests that Krakoa eventually won. However, the Amenthi still attacked. The X-Men were sorely pressed until Captain Britain and the Captain Britain Corps entered the fight. Together, they were able to defeat Amenth and free the Arakkii, saving the world from the demonic invasion.

House Of X was brutal, forcing the X-Men to pay dearly for their greatest victory. Using knowledge gained from Moira's ninth life, Xavier and Magneto sent a team of X-Men to the Forge, a sun-orbiting space station, to stop the Orchis Initiative from activating the ultimate Sentinel, Nimrod, by destroying the Mother Mold. A bloodbath followed.

Every member of the X-Men's Forge team was killed but they still completed their objectives. In a final stroke, Nightcrawler and Wolverine teleported into space to destroy the last strut holding up the Mother Mold. They died but their sacrifices saved the nascent mutant nation. Brought back by a new method of mutant resurrection, the team celebrated the victory that made Krakoa's survival possible.

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The Biggest X-Men Wins In Marvel Comics Last Five Years - CBR - Comic Book Resources

Bridget Narsh at her home in Chapel Hill, North Carolina. Narsh's son has autism, post-traumatic stress disorder, and ADHD. In 2020, he spent more than 100 days at Central Regional Hospital, a state-run mental health facility. The state billed the family nearly $102,000 for the hospitalizations. Eamon Queeney/KFF Health News hide caption

Bridget Narsh at her home in Chapel Hill, North Carolina. Narsh's son has autism, post-traumatic stress disorder, and ADHD. In 2020, he spent more than 100 days at Central Regional Hospital, a state-run mental health facility. The state billed the family nearly $102,000 for the hospitalizations.

Bridget Narsh's son, Mason, needed urgent help in January 2020, so she was offered the chance to send him to Central Regional Hospital, a state-run mental health facility in Butner, North Carolina.

The teen, who deals with autism and post-traumatic stress and attention-deficit/hyperactivity disorders, had started destroying furniture and running away from home. His mother worried for the safety of Mason and the rest of the family.

But children in crisis in North Carolina can wait weeks or months for a psychiatric bed because the state lacks the services to meet demand. And when spots do become available, they are expensive.

The standard rate at Central Regional was $1,338 a day, which Narsh could not afford. So, when a patient relations representative offered a discounted rate of less than $60 a day, her husband, Nathan, signed an agreement.

Mason, now 17, was hospitalized for more than 100 days in Central Regional over two separate stays that year, documents show.

But when requests for payment arrived the following year, Narsh said she was shocked. The letters which were marked "final notice" and requested immediate payment were signed by a paralegal in the office of Josh Stein, North Carolina's attorney general. The total bill, $101,546.49, was significantly more than the roughly $6,700 the Narshes expected to pay under their agreement with the hospital.

"I had to tell myself to keep my cool," says Bridget Narsh, 44, who lives with her husband and three children in Chapel Hill. "There is no way I could pay for this."

Medical bills have upended the lives of millions of Americans, with hospitals putting liens on homes and pushing many people into bankruptcy. In recent years, lawmakers have railed against privately operated hospitals, and states have passed laws intended to make medical billing more transparent and limit aggressive debt collection tactics.

Some state attorneys general as their states' top law enforcement officials have pursued efforts to shield residents from harmful billing and debt collection practices. But in the name of protecting taxpayer resources, their offices are also often responsible for collecting unpaid debts for state-run facilities, which can put them in a contradictive position.

Stein, a Democrat running for governor in 2024, has made hospital consolidation and health care price transparency a key issue during his time in office.

"I have real concerns about this trend," Stein said in 2021 about the state's wave of hospital consolidations. "Hospital system pricing is closely related to this issue, as consolidations drive up already inordinate health care costs."

Stein refused an interview request about Mason's bills, which arrived at the end of 2021 because the North Carolina government suspended debt collection in March 2020 as the nation felt the economic fallout of the COVID-19 pandemic.

Across the nation, states seize money or assets, file lawsuits, or take other steps to collect debts from people who stay at state-run hospitals and other institutions, and their efforts can disproportionately affect racial and ethnic minorities and the poor, according to health care consumer advocates. In North Carolina, officials looking to collect unpaid debt are permitted to garnish residents' income tax refunds.

Attorneys general must balance their traditional role of protecting consumers from harmful debt collection practices and the state's obligation to serve taxpayers' interests and fund services, said Vikas Saini, a cardiologist and the president of the Lown Institute, a Massachusetts-based nonpartisan think tank that advocates for health care reform.

The Narsh case is "the perfect storm of every problem in our health care system," says Saini, who at the request of KFF Health News reviewed the payment demand letters the family received. Far too often health care is unaffordable, billing is not transparent, and patients end up facing enormous financial burdens because they or a loved one is sick, Saini said.

Bridget Narsh holds one of the letters demanding payment from the North Carolina attorney's general office. Her son's service dog, Koko, specially trained to help people with autism, is at her feet. Eamon Queeney/ KFF Health News hide caption

Bridget Narsh holds one of the letters demanding payment from the North Carolina attorney's general office. Her son's service dog, Koko, specially trained to help people with autism, is at her feet.

The Narsh family had Blue Cross and Blue Shield health insurance at the time of Mason's hospitalizations. Bridget Narsh has records showing insurance paid about $7,200 for one of his stays. (Mason is now covered by Medicaid, the state and federal health insurance that covers some people with disabilities and low income people.)

In a written statement, Nazneen Ahmed, a spokesperson for Stein's office, said state law requires most agencies to send their unpaid debts to the state Department of Justice, which is charged with contacting people who may owe money.

Ahmed directed KFF Health News to the North Carolina Department of Health and Human Services, which oversees Central Regional Hospital.

Bailey Pennington Allison, an agency spokesperson, said in a written statement that officials researched the Narsh case and determined the state had properly followed procedures in billing the family.

The state bases its rates for services on the costs of the treatment, nursing, professional consultation, hospital room, meals, and laundry, Pennington Allison said. Hospital staffers then work with patients and families to learn about their income and assets to determine what they can afford and what they will be charged, she said.

The spokesperson did not address why Mason's parents were offered, but did not ultimately receive, a discounted rate both times he was admitted in 2020.

Narsh contacted an attorney, who negotiated the bill with the state. In April, her family reached an agreement with North Carolina officials to pay $100 a month in exchange for the state reducing the charges by roughly 96% to about $4,300. If Narsh defaults, however, the deal stipulates she must come up with the original total.

States can take a variety of approaches to debt collection. North Carolina is one of about a dozen that can garnish residents' income tax refunds, says Richard Gundling, a senior vice president for the Healthcare Financial Management Association, a membership organization for finance professionals.

Gundling says state officials have a responsibility to protect taxpayer money and collect what is owed but that seizing income tax returns can have more severe consequences for people with lower incomes. "There is a balance that needs to be struck to be reasonable," he says.

With health care a leading cause of personal debt, unpaid medical bills have become a major political issue in North Carolina.

State lawmakers are considering a bill called the Medical Debt De-Weaponization Act, which would curb the ability of debt collectors to engage in "extraordinary collection" such as foreclosing on a patient's home or garnishing wages. But the current version of the bill would not apply to state-operated health care facilities like the one Mason Narsh went to, according to Pennington Allison.

In a written statement, Stein said he supports legislative efforts to strengthen consumer protections.

"Every North Carolinian should be able to get the health care they need without being overwhelmed by debt," Stein said. He called the bill under consideration "a step in the right direction."

Narsh said the unexpectedly high amount of the bill was frustrating, at least in part because for years she struggled to get Mason more affordable, preventive care in North Carolina. Narsh says she had difficulty finding services for people with behavioral issues, a shortage acknowledged in a state report released last year.

Multiple times, she says, she has been left with no option but to take him to a hospital to be evaluated and admitted to an inpatient mental health facility not suitable for people with complex needs.

Community-based services that allow people to receive treatment at home can help them avoid the need for psychiatric hospitals in the first place, Narsh said. Mason's condition improved after he received a service dog trained to help people with autism, among other community services, Narsh says.

Bridget Narsh shares a cell phone picture of her son and Koko attending school. Her son's condition has improved since he got the service dog and other community-based services. Eamon Queeney/KFF Health News hide caption

Bridget Narsh shares a cell phone picture of her son and Koko attending school. Her son's condition has improved since he got the service dog and other community-based services.

Corye Dunn is the public policy director at Disability Rights North Carolina, a Raleigh-based nonprofit mandated by the federal government to monitor public facilities and services to protect people with disabilities from abuse. The irony, she says, is that the same system that's ill-equipped to prevent people from falling into crisis can then pursue them with big bills.

"This is bad public policy. This is bad health care," Dunn says.

KFF Health News, formerly known as Kaiser Health News (KHN), is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF the independent source for health policy research, polling, and journalism.

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schwit1 shares a report from NPR: In a blow to tribes, a U.S. appeals court has denied a last ditch legal effort to block construction of what's expected to be the largest lithium mine in North America on federal land in Nevada. In a decision Monday, the Ninth Circuit Court of Appeals ruled that the U.S. government did not violate federal environmental laws when it approved Lithium Nevada's Thacker Pass mine in the waning days of the Trump administration. Lithium is a key component of electric vehicle batteries, and despite pressure from west coast Paiute tribes and environmentalists, the Biden administration did not reverse the decision and had continued to advocate for the mine, which would be located on remote federal land near the Nevada-Oregon border.

Several area tribes and environmental groups have tried to block or delay the Thacker Pass mine for more than two years. Among their arguments was that federal land managers fast tracked it without proper consultation with Indian Country. "They rushed this project through during COVID and essentially selected three tribes to talk to instead of the long list of tribes that they had talked to in the past," Rick Eichstaedt, an attorney for the Burns Paiute Tribe, said in an interview late last month. But in their ruling, the Ninth Circuit judges responded that only after the mine was approved by federal land managers did it become known that some tribes consider the land sacred. Full construction of the mine is expected to begin in earnest this summer.

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Federal Ruling Approves Construction of North America's Largest ... - Slashdot

An anonymous reader quotes a report from CBC.ca: A government program meant to attract highly skilled tech workers from the U.S. closed for applications the day after it launched when it hit its maximum number of applicants. Last month, Immigration Minister Sean Fraser announced a new work permit for H-1B visa holders in the U.S. -- part of a larger federal government strategy to poach talent from abroad. H-1B visas allow foreign nationals to work temporarily in the U.S. in certain specialized occupations, including some in the technology sector. Tech companies went on a hiring binge during the pandemic but have since starting laying people off in large numbers. That has left a lot of H-1B visa holders scrambling to find new jobs before they're forced to leave the U.S.

Applications for the work permits opened on Sunday. By Monday the program had reached capacity, with 10,000 applicants bidding for a permit. "This temporary policy will last for 1 year or until we get 10,000 applications (whichever comes first)," the program's website says. The program is a response to massive layoffs in the U.S. tech industry. Since last summer, hundreds of thousands of workers have been laid off from such major firms as Google, Microsoft and Amazon. Fraser said he was watching the situation in the U.S. and saw it as an "opportunity" for Canada when he first announced the program.

Nick Schiavo, director of federal affairs for the Council of Canadian Innovators, said he's not surprised that applications filled up so quickly. He said the government should now consider expanding the program to more applicants. "The more that we can pull from these highly qualified individuals that we know have the work experience, the skill set the better," Schiavo said. "As this program develops, it would be great to see it expanded."

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Program To Attract Tech Workers From the US Hits Capacity On ... - Slashdot

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Partial convergence of the human vaginal and rectal maternal ... - Nature.com

Researchers have created a small device that 'sees' and creates memories in a similar way to humans, in a promising step towards one day having applications that can make rapid, complex decisions such as in self-driving cars.

The neuromorphic invention is a single chip enabled by a sensing element, doped indium oxide, that's thousands of times thinner than a human hair and requires no external parts to operate.

RMIT University engineers in Australia led the work, with contributions from researchers at Deakin University and the University of Melbourne.

The team's research demonstrates a working device that captures, processes and stores visual information. With precise engineering of the doped indium oxide, the device mimics a human eye's ability to capture light, pre-packages and transmits information like an optical nerve, and stores and classifies it in a memory system like the way our brains can.

Collectively, these functions could enable ultra-fast decision making, the team says.

Team leader Professor Sumeet Walia said the new device can perform all necessary functions -- sensing, creating and processing information, and retaining memories -- rather than relying on external energy-intensive computation, which prevents real-time decision making.

"Performing all of these functions on one small device had proven to be a big challenge until now," said Walia from RMIT's School of Engineering.

"We've made real-time decision making a possibility with our invention, because it doesn't need to process large amounts of irrelevant data and it's not being slowed down by data transfer to separate processors."

What did the team achieve and how does the technology work?

The new device was able to demonstrate an ability to retain information for longer periods of time, compared to previously reported devices, without the need for frequent electrical signals to refresh the memory. This ability significantly reduces energy consumption and enhances the device's performance.

Their findings and analysis are published in Advanced Functional Materials.

First author and RMIT PhD researcher Aishani Mazumder said the human brain used analog processing, which allowed it to process information quickly and efficiently using minimal energy.

"By contrast, digital processing is energy and carbon intensive, and inhibits rapid information gathering and processing," she said.

"Neuromorphic vision systems are designed to use similar analog processing to the human brain, which can greatly reduce the amount of energy needed to perform complex visual tasks compared with today's technologies

What are the potential applications?

The team used ultraviolet light as part of their experiments, and are working to expand this technology even further for visible and infrared light -- with many possible applications such as bionic vision, autonomous operations in dangerous environments, shelf-life assessments of food and advanced forensics.

"Imagine a self-driving car that can see and recognise objects on the road in the same way that a human driver can or being able to able to rapidly detect and track space junk. This would be possible with neuromorphic vision technology."

Walia said neuromorphic systems could adapt to new situations over time, becoming more efficient with more experience.

"Traditional computer vision systems -- which cannot be miniaturised like neuromorphic technology -- are typically programmed with specific rules and can't adapt as easily," he said.

"Neuromorphic robots have the potential to run autonomously for long periods, in dangerous situations where workers are exposed to possible cave-ins, explosions and toxic air."

The human eye has a single retina that captures an entire image, which is then processed by the brain to identify objects, colours and other visual features.

The team's device mimicked the retina's capabilities by using single-element image sensors that capture, store and process visual information on one platform, Walia said.

"The human eye is exceptionally adept at responding to changes in the surrounding environment in a faster and much more efficient way than cameras and computers currently can," he said.

"Taking inspiration from the eye, we have been working for several years on creating a camera that possesses similar abilities, through the process of neuromorphic engineering."

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A germline-revertant form of SNV-42 neutralizes SNV

Previous sequence analysis determined that SNV-42, which is encoded by human antibody variable region gene segments IGHV3-48*03/IGLV1-40*01, is remarkably close in sequence to the germline-encoded sequence, with a 97 or 99% identity to the inferred heavy and light chain variable gene sequences, respectively16. To understand whether somatic mutations are necessary for potent neutralization activity, we aligned the SNV-42 coding sequence with the inferred germline gene segments and reverted all mutations in the antibody variable regions to the residue encoded by the inferred germline gene (Supplementary Fig. 1). We then performed a neutralization assay to compare the potency of SNV-42 and the germline-revertant (GR) form of that antibody (denoted as SNV-42GR). We did not detect a change in the IC50 value between SNV-42 (IC50=21.4ngml1) and SNV-42GR (IC50=14.8ngml1) (Fig. 1a). Given that some of the residues in those regions are non-templated and thus cannot be reverted, we did not alter the junctional regions of SNV-42. These results indicate that many of the residues in the antibody paratope that are critical for SNV neutralization are encoded by IGHV3-48/IGLV1-40 germline genes. We also measured the KD values for the affinity matured and the germline reverted forms of SNV-42 to the recombinant SNV Gn head domain (Fig. 1b and Supplementary Table 1) using bio-layer interferometry (BLI). SNV-42 bound to GnH with sub-picomolar affinity, while SNV-42GR demonstrated sub-nanomolar affinity (9.21010M). However, this difference in affinity does not appear to impact the neutralization potency.

a, Representative neutralization curves of SNV-42, germline reverted (GR) SNV-42 and negative control DENV 2D22 to VSV/SNV determined through real-time cellular analysis using the Vero CCL-81 cell line. IC50 values were calculated on the basis of a nonlinear regression and error bars denote means.d. The assay was performed three independent times with similar results. b, Affinity measurements of SNV-42 and SNV-42GR for binding to SNV GnH ectodomain, measured by bio-layer interferometry. Representative curves and KD values are shown for SNV-42GR, while the KD value for SNV-42 could not be determined because the Koff could not be measured. Dashed line indicates dissociation step at 300s. c, Representative neutralization curves of SNV-42, SNV-42GR, positive control (oligoclonal mix of SNV-reactive antibodies) and DENV 2D22 to mutant VSV/SNV viruses. Error bars denote means.d. The assay was performed three independent times with similar results. d, SNV-42 binding in the presence of SNV M-segment mutant constructs determined by flow cytometry. The percent binding (% WT) of each mAb to the mutant constructs was compared to the WT SNV construct. An oligoclonal mix of SNV-reactive antibodies was included to control for expression of each mutant construct. The data are shown as means.d.; from left to right, n=9, 9, 9, 9, 9, 9, 6, 9, 9, 9, 9, 9, 9 and 6 technical replicates. The assay was performed three to four independent times with similar results. e, Top view of escape mutants mapped to the ANDV Gn/Gc spike (PDB: 6ZJM). The blue residues designate escape mutants. Gn is shown in white and Gc is shown in grey. All numbering for SNV sequences was based on GenBank KF537002.1.

Identifying potential escape mutants for antibodies is a crucial part of therapeutic development, and methods of immune evasion employed by hantaviruses are not well understood. To identify the critical binding residues involved in the recognition of SNV Gn by SNV-42, we used two different methods to identify escape mutants resistant to neutralization mediated by SNV-42. First, we implemented a high-throughput, single-passage neutralization escape mapping method using a real-time cellular analysis (RTCA) cell-impedance-based technology. We identified escape mutants in 32 of 88 replicates tested for escape, as manifested by cytopathic effect (CPE) in the presence of neutralizing concentrations of SNV-42 (Supplementary Fig. 2). We sequenced the gene encoding Gn in the virus in the supernatants in 6 wells. The neutralization-resistant viruses contained Gn gene mutations encoding K357Q or T312K alterations (Fig. 1c,e). To further identify escape mutants, we also selected a similar escape mutant (T312A) by serial passaging of a recombinant vesicular stomatitis virus (VSV/SNV) in increasing concentrations of SNV-42. We expressed recombinant forms of Gn with these mutations on the surface of cells and tested binding of SNV-42 to the mutant Gn constructs in flow cytometric binding assays. All three mutations completely ablated mAb binding, further supporting that these two residues are critical binding contacts (Fig. 1d). The binding of SNV-42 was not impacted by escape mutations selected for other SNV-neutralizing mAbs recognizing different antigenic sites (SNV-53 and SNV-24). Taken together, these two methods identified critical residues on SNV Gn that may be under pressure by some antibodies elicited in the human immune response to infection. However, SNV field strains with mutations at T312 or K357 have not been reported.

To understand the structural basis for SNV Gn recognition of SNV-42, a construct encoding the SNV GnH head domain (residues 21377) was produced recombinantly, purified and complexed with the Fab component of SNV-42. The SNV GnHSNV-42 complex was subjected to size exclusion purification and crystallized, and the structure was determined to approximately 1.8 resolution.

One complex of SNV GnSNV-42 was observed in the asymmetric unit of the unit cell (Fig. 2). The structure of SNV GnH has not been reported previously and consists of a compact fold formed of three domains: domains A and B and a -ribbon domain (Fig. 2). Despite a relatively low level of sequence identity (ranging from 43 to 63%), the SNV GnH is very similar to previously characterized hantavirus Gn glycoproteins5,6,7,14, where the equivalent regions of MAPV GnH, ANDV GnH, PUUV GnH or HNTV GnH exhibit root-mean-square deviations of 0.7, 0.9, 1.0 or 1.0 over equivalent C residues, respectively (Fig. 2b). Regions of SNV GnH that exhibit the greatest level of structural deviation from other GnH structures are in solvent exposed loop regions, consistent with these areas of the molecule being naturally flexible or requiring stabilizing contacts from the higher-order (GnGc)4 assembly.

a, Structure of the GnFab complex. The Fab is displayed with the backbone of the light and heavy chains coloured light grey or dark grey, respectively. The CDR loops are thicker and coloured according to the key in c. The Gn is displayed as a ribbon diagram with each of the three domains coloured according to the key in c. The two N-linked glycosylation sites are displayed in green and the location of the two previously described escape mutants (T312K and K357Q) are displayed in orange. Inset is a zoomed panel of the binding site with the side chains of the two escape mutant residues displayed. b, The backbone of the SNV GnH in pink overlaid on several previously reported GnH crystal structures from different hantavirus species in grey. These include Andes orthohantavirus (PDB ID 6Y5F), Maporal orthohantavirus (PDB ID 6Y62), Puumala orthohantavirus (PDB ID 5FXU) and Hantaan orthohantavirus (PDB ID 5OPG). Of note is the capping loop, indicated, which was replaced in SNV GnH with a much shorter GGSG linker to aid crystallogenesis. c, A domain schematic of the Sin Nombre glycoprotein precursor protein that is cleaved at the WAASA cleavage site to form Gn and Gc. The crystallized GnH region is outlined in bold and coloured according to domain. Transmembrane regions are displayed in dark grey and N-linked glycosylation sites displayed in green. The sequence of the capping loop between residues 8699 is displayed alongside the shorter GGSG linker that has been used in its place for this experiment.

Consistent with the epitope mapping analysis (Fig. 1d), SNV-42 binds to domain B and the E3-like domain of SNV Gn (Fig. 2a). The residues implicated in antibody escape identified above, T312 and K357, form key hydrogen bonding interactions with CDRH3 and CDRH1/3, respectively. These hydrogen bonding interactions appear to be perturbed when the mutations T312K and K357Q are modelled, and some rotomeric configurations of K312 may sterically interfere with the antibody, providing a structural rationale for antibody escape (Supplementary Fig. 4). The epitope comprises a large glycan-independent interface, which occludes ~8002 of buried surface area. While all complementarity-determining regions (CDRs) contribute to the epitope, residues comprising the CDRH3 of SNV-42 form the bulk of the interaction through insertion of a 9-residue-long loop into a cleft formed on the SNV Gn surface (Supplementary Fig. 3). CDRH3 possesses a low number of sequence somatic mutations from the putative germline, with only a single amino acid change from the germline D-gene (IGHD5-12*01). This change is one of only five amino acid changes from the germline-encoded sequence present in the paratope region including CDRH1 (T36), CDRH1 (E38), CDRH2 (R57) and CDRH3 (T112) that were all originally encoded as serine residues, plus CDRL1 (Y38) that was originally encoded as aspartate. However, these mutations do not impact the neutralization potency of SNV-42 (Fig. 1a and Supplementary Fig. 1). Interestingly, none of these five paratope residues were observed to sterically hinder antigen recognition when modelled back to the germline-encoded sequence (Supplementary Fig. 5).

SNV-42 is highly specific to SNV and did not demonstrate reactivity to or neutralize any other hantaviruses tested previously16. Assessment of sequence conservation at the epitope provides a structural rationale for this observation, since only 12 of 20 residues in the SNV-42 epitope were conserved with ANDV and 8 of 20 with HTNV. Furthermore, among these non-conserved residues, there exist non-complementary side chains which would probably sterically preclude mAb recognition (Supplementary Fig. 6).

Previous integrative cryo-electron tomography (cryoET) and X-ray crystallography analyses of ANDV, PUUV, HTNV and Tula virus (TULV) have revealed that the ultrastructure arrangement of the hantaviral (GnGc)4 is well conserved and consists of a tetramer of GnGc heterodimers. The GnH forms the most membrane-distal region of the spike and shields fusion loops located in domain II of the Gc5,7,13. To assess the location of the SNV-42 epitope in the context of the higher-order hantaviral GnGc lattice, we overlayed the SNV Gn subcomponent of our complex onto a previously reported (GnGc)4 assembly of ANDV (PDB: 6ZJM) (Fig. 3a,b). This analysis demonstrates that SNV-42 binds to the membrane-distal region of the lattice. While spatially distinct, the SNV-42 epitope is proximal to and slightly overlaps with the epitope of the weakly neutralizing mAb, HTN-Gn114, the only other structurally characterized anti-Gn mAb (Fig. 3c). In contrast to HTN-Gn1, SNV-42 binds in an orientation that is relatively perpendicular to the membrane (Fig. 3b,c). We note that each of the SNV-42 epitopes on the (GnGc)4 tetramer is mutually accessible for binding. Furthermore, unlike for HTN-Gn1, these sites are equally accessible in a cryo-electron microscopy (cryoEM)-derived model of the entire virus with the location of the (GnGc)4 spikes mapped onto the virion surface (Fig. 3a).

a, An EM-derived model of a Sin Nombre virion decorated in Fab fragments of mAb SNV-42. The virion model is derived from previously reported cryoET data of Tula virus5. The Gc is coloured blue and the Gn coloured pink or purple for the head or stalk regions, respectively. The light or heavy chains of the Fab are coloured light or dark grey, respectively. The zoomed inset displays nine individual glycoprotein spikes with the central spike surface rendered at higher resolution. The Fab fragments bound to the central spike are displayed as a backbone trace. b, Top view (left) and side view (right) of the Sin Nombre glycoprotein spike bound to Fab fragments of SNV-42. This assembly model is based on the previously reported ANDV glycoprotein spike tetramer (PDB: 6ZJM). The location of two SNV-42 escape mutants (T312K and K357Q) are displayed in orange and the equivalent locations of other previously reported antibody escape mutants are displayed in red. The complete list of antibody escape mutants and the species they apply to are detailed in Supplementary Table 2. To enable visualization of all epitopes, two loops that are not resolved in this SNV Gn structure (residues 8699 and 221229) were replaced by their equivalents from a previously reported ANDV Gn structure (PDB: 6ZJM). c, The equivalent view of a hantavirus glycoprotein spike bound to Fab HTN-Gn1, a previously reported neutralizing antibody that binds to HNTV14.

Previous epitope mapping of a panel of human SNV Gn- and Gc-specific antibodies revealed a series of epitopes spanning across solvent-accessible surfaces of the higher-order (GnGc)4 spike15,16. Integration of these data with putative epitopes predicted on the surface of other New and Old World hantaviruses indicates a broad distribution of epitopes across both the Gn and Gc glycoproteins (Fig. 3b). While immunodominant regions that are targeted during infection and immunization have yet to be identified, one such epicentre exists at the membrane-distal region of the GnH glycoprotein and co-localizes with our structurally elucidated SNV-42 epitope.

The role of bivalent interactions in the neutralization potency of hantavirus antibodies has yet to be described. To determine how the avidity effects impact the potency of SNV-42, we performed a neutralization assay comparing SNV-42 as a full-length IgG, Fab and F(ab)2. The F(ab)2 form was included to rule out any contributing steric effects of the fragment crystallizable (Fc) domain in neutralizing the virus. We saw no difference in the neutralizing activity between the full-length IgG form and the F(ab)2 form; however, the Fab form of SNV-42 did not demonstrate detectable neutralizing activity for VSV/SNV (Fig. 4a).

a, Representative neutralization curves of IgG1 and Fab forms of SNV-42 to VSV/SNV determined by RTCA using the Vero CCL-81 cell line. IC50 values were calculated on the basis of a nonlinear regression and error bars denote means.d. The assay was performed three independent times with similar results. b, Representative affinity curves of the F(ab)2 and F(ab) form of SNV-42 for binding to SNV GnH, measured by bio-layer interferometry. Representative curves and KD values are shown for SNV-42 F(ab), while the KD value for SNV-42 F(ab)2 could not be determined because the Koff could not be measured. Dashed line indicates the dissociation step at 300s. c, sEC1-EC2 blocking activity of neutralizing antibodies determined through a flow cytometric assay in which mAbs were added at saturating concentration before the addition of the soluble PCDH-1 domain labelled with Alexa Fluor 647 dye. High (50gml1), medium (10gml1) or low (0.5gml1) mAb concentrations were tested. Two-way analysis of variance (ANOVA) with Dunnetts multiple comparisons, ****P<0.0001; NS, not significant. The data are shown as means.d., n=9 technical replicates. The assay was performed two independent times with similar results. d, FFWO assay testing VSV/SNV post-attachment antibody neutralization in permissive (pH 5.5) conditions at 10gml1. Vero CCL-81 cells were used and GFP expression was measured to determine relative infectivity. The data are shown as means.d. of technical replicates, n=9. The assay was performed two independent times with similar results. One-way ANOVA with Dunnetts multiple comparisons, ****P<0.0001.

To further determine whether the lack of neutralizing activity was due to loss in avidity, we measured the KD values of the Fab and F(ab)2 forms of SNV-42 to SNV GnH using BLI (Fig. 4b). In concordance with the IgG form, the F(ab)2 bound SNV GnH with a sub-picomolar avidity, while the Fab form demonstrated a fast off rate and low KD value in comparison (4.08108M). Thus, the neutralization activity of SNV-42 requires bivalent binding to the (GnGc)4 assembly.

To investigate the possibility that bivalent binding of SNV-42 disrupts fusogenic conformational changes to the GnGc complex, we assessed the likelihood of SNV-42 to cross-link neighbouring epitopes on the (GnGc)4 assembly (Supplementary Fig. 9). This analysis suggests that inter-spike, but not intra-spike, bivalent binding may be plausible.

The hantavirus Gn protein probably plays several roles in facilitating the entry of hantavirus virions into host cells17. Gn forms a heterodimer with Gc and prevents the premature membrane insertion of the virus by covering the hydrophobic residues in the fusion loop5. Although the receptor-binding site is unknown, Gn is assumed to interact with attachment factors, including PCDH-117. To understand how SNV-42 engages with Gn to neutralize SNV, we investigated two mechanisms of interfering with viral entry: receptor blocking and fusion inhibition. Previous work has shown that the first extracellular cadherin-repeat domain (EC1) of PCDH-1 interacts with SNV Gn/Gc11, so we employed a flow cytometry-based competition-binding assay to test whether SNV-42 could block the interaction of a soluble recombinant form of the EC domains (sEC1-EC2). We showed that SNV-42 and SNV-42GR both block sEC1-EC2 binding to SNV Gn/Gc in a dose-dependent manner. However, we did not see complete blocking, even at the highest concentrations tested (50gml1; Fig. 4c). Notably, the Fab form of SNV-42 also did not block receptor binding, further suggesting that bivalent binding is required for receptor blocking and viral neutralization.

Although Gc is the canonical fusogenic protein, it is possible that targeting Gn may inhibit dynamic changes necessary to expose the fusion loop and promote viral entry18,19,20. We used a fusion from without (FFWO) assay to test fusion inhibition that can measure antibody-mediated neutralization post-attachment of the virion to the cell surface. SNV-42 and SNV-42GR significantly reduced VSV/SNV infection but did not completely inhibit viral fusion even at saturating concentrations (Fig. 4d). Further, although it is uncertain whether the hantaviral Gn remains bound to the Gc throughout the host-cell entry process, superposition of the SNV GnSNV-42 complex onto the structure of ANDV Gn bound to the near post-fusion state of ANDV Gc15 suggests that SNV-42 is also capable of recognizing a post-fusion state of the GnGc complex (Supplementary Fig. 10). While the precise transitions undertaken by the GnGc assembly are not well understood, it is plausible that bivalent binding of SNV-42 to the (GnGc)4 lattice interferes with the structural transitions required for entry and fusion. As SNV-42 does not mediate complete receptor blocking or neutralization post-attachment at high concentrations, the findings suggest that both mechanisms probably contribute together to cause the exceptional potency of the antibody.

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