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Category Archives: Transhuman News

Immortality a possibility? This jellyfish could have the answer – Ohmymag

Posted: September 17, 2022 at 11:34 pm

Published on September 16, 2022 at 11:32 AM by Jaysi Sharma

A jellyfish is currently being studied by scientists to explain its immortality. What will this mean for humans?

Everyone has dreamed of immortality and eternal youth. While humans are still far from having found the fountain of youth, one type of jellyfish has managed to avoid dying of old age, as reported by Le Parisien on Saturday 10 September 2022. The aptly named immortal jellyfish, or its scientific name Turritopsis dohrnii, which has been multiplying around the world for years, has managed to return to its youthful form, called a polyp, by attaching itself to the walls.

No, we are not talking about the stinging, dangerous jellyfish. A team of Spanish researchers, led by biologist Maria Pascual-Torner from the University of Oviedo, has set out to study an immortal jellyfish. In an article published at the end of August 2022 in the journal Proceedings of the National Academy of Sciences (PNAS), the researchers explained that they had compared the immortal jellyfish with a related English species called the crimson jellyfish.

They found that the Turritopsis dohrnii jellyfish had twice as many copies of genes that promote DNA repair and protection. Certain mutations also allow it to slow down cell division and cell ageing. The scientists showed that when the jellyfish is weakened by a change in environment or an injury, it becomes a polyp again, and its cells become young again. They also discovered that the crimson jellyfish has these genes, but cannot rejuvenate as often.

Studies are still underway to try to understand how the special functioning of this jellyfish could help human medicine. According to the researchers, the genes identified could be useful in providing information about age-related diseases in humans, such as cancers or neurodegeneration.

There is no word yet on whether the secret of eternal youth has been unlocked, but the discoveries made thanks to this jellyfish could help to treat many diseases. A similar study was carried out on an immortal worm, which could fight bacteria.

This article was translated from Gentside FR.

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Early Puberty Resulting From Excessive Smartphone Screen Time? Here’s What This Study Found – Forbes

Posted: at 11:34 pm

A new study presented at the 60th Annual European Society for Paediatric Endocrinology Meeting ... [+] further highlighted the possible dangers of excessive smartphone use. (Photo: Getty)

If you are wondering whether blue light exposure may result in early puberty, you may not want to check your smartphone too often for the answer. More and more studies have been shedding increasing light on the potential risks of using such blue light-emitting mobile devices. And a study presented on September 16 at the 60th Annual European Society for Paediatric Endocrinology Meeting found exposure to blue light to be associated with decreased levels of melatonin, increased levels of two major reproductive hormones (estradiol and luteinizing hormone), and changes in ovarian tissue that may be indicative of early onset of puberty in females. In fact, changes occurred even after just six hours of exposure to blue light, which is really not that long. Its the amount of time that it would take to watch the Baby Shark Dance video on YouTube only about 159 times, depending on how many ads that have to click through along the way.

Now, if you had said rats to this study, youd have been right. The subjects of this study were not humans but instead rats, female rats. As described by the study abstract, team from the Gazi University Faculty of Medicine in Ankara, Turkey, (Aylin Kln Uurlu, Aysun Bideci, Aye Mride Demirel, Glnur Take Kaplanolu, Duygu Dayanr, zlem Glbahar, Tuba Saadet Deveci Bulut, Esra Der, and M. Orhun amurdan) divided 18 immature female Sprague Dawley rats into three groups of six rats apiece. In this case, immature didnt mean that they said whatever way too often. It meant that they were 21-days-old and hadnt undergone puberty yet. Six of the rats were in the control group under standard 12 hour light and 12 hour cycles typical of natural conditions. Another six rats underwent six hours of exposure to blue light (450-470 nm/irradiance level 0.03 uW/cm2). The third group of six rats had even longer (12 hours) of exposure to the blue light.

While the female rat in the control group entered puberty on the 38th day on average, those in the six-hour blue light exposure group entered puberty significantly earlier, on average the 32nd day. Those in the 12-hour blue light exposure group began puberty even earlier, on the 30th day on average. Longer durations of blue light exposure were associated with earlier puberty in the rats. The researchers also found significantly higher levels of luteinizing hormone and estradiol levels among those rats with at least six hours of blue light exposure compared to the control group. Additionally, longer blue light exposure correlated with lower melatonin levels. Finding signs of inflammation, such as dilation of blood vessels and the accumulation of fluid, in the ovaries provided further evidence that the rats had indeed entered puberty. In fact, the research team found polycystic ovary-like (PCO-like) changes in those female rats who had undergone blue light exposure.

The study was done in rats, who may not be exactly the same as humans. But there are similarities. ... [+] (Photo: Getty)

Of course, humans are not rats, at least not in the physical sense, no matter what you may think about your school and work colleagues. Rats are different from humans in various ways such as body size, the number of days before puberty onset, life expectancy, and the propensity to wear mullets. It would be rather alarming for a human infant to begin puberty after only 38 days. So, not all rat studies necessarily apply to you or your children, assuming that you dont have whiskers and a tail. Plus, its not as if the study gave rats little smartphones and Instagram (or perhaps Instacheese) accounts. Although the researchers tried to mimic the blue light exposure from smartphones to some degree, the study wasnt able to replicate the exact conditions associated with human smartphone use.

Additionally, the threshold for presenting a study at a scientific meeting is much, much, much lower than the threshold for publishing it in a respectable peer-reviewed scientific journal. Whats presented at scientific meetings can be a mixed bag of very good studies, good studies, OK studies, not so good studies, and that-is-never-going-to-make-it-into-a-real-respectable-scientific-journal studies.

That being said, this latest study does offer a good squeak at what could be a growing problem. Before you say that rats going through puberty is not the same because they dont listen to Taylor Swift or Nirvana, keep in mind that rats typically do progress through similar pre-puberty and puberty hormonal and ovulatory changes as humans do. And adjusting for differences in life expectancy, rats do actually begin puberty at similar stages in life as humans do.

Plus, consider this yet another piece of evidence that too much blue light exposure could be messing with your and your kids bodies in various ways. This certainly isnt the first study to raise concerns about how blue light exposure may be affecting human hormone levels. For example, previous studies have found associations between blue light exposure and changes in melatonin and cortisol levels. This video from Hamilton Health Sciences in Hamilton, Ontario, Canada, showed how blue light can affect your pineal glands release of melatonin:

Studies have found use of blue-light emitting mobile devices to be correlated with disruptions in sleep patterns potentially due at least in part to changes in melatonin levels. And your melatonin levels on average tend to be higher right before you enter puberty. Melatonin in some ways behave like Wilson Phillips and say hold on to your body to prevent the early onset of puberty.

Then theres all that earlier earlier evidence out there. Over the past decade or so, as covered by Jessa Gamble for Nature, researchers have been noting how girls on average have been entering puberty at earlier and earlier ages. There have been reports of girls developing breasts as early as six years of age. The concern is this may be the result of the increasing amount of artificial bleep around us such as more and more chemicals in the environment, more and more things being added to food, and more and more blue light.

Remember, its not clear how many tech companies said, gee, I wonder how all of this is going to affect everyones health before rolling out all of the smartphones, apps, and social media stuff that now pervade our society. Just because everyone seems to be using something doesnt necessarily mean that the thing is 100% safe. So you really dont know what using smartphones and similar devices all the time may be doing to you. More studies are needed to shed more light on the subject and ways to protect yourself. In the meantime, you may want to do your best to limit your and your kids exposure to blue light.

Recall the immortal words of Eiffel 65, who first said in 1998, over two decades ago, Yo, listen up. Here's a story about a little guy that lives in a blue world. And all day and all night. And everything he sees is just blue like him inside and outside. That song may not have been talking about blue light exposure at the time. But things these days may be looking a bit too blue in more ways than one.

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Godard’s assisted suicide – not an option everywhere – SWI swissinfo.ch – SWI swissinfo.ch in English

Posted: at 11:34 pm

Legendary Franco-Swiss film director Jean-Luc Godard was a pioneer in his lifetime -and in his death, by assisted suicide in Switzerland. Four people a day opt for assisted suicide in Switzerland, but in other countries the issue is still controversial.

After some years in the regional print and broadcast media in French Switzerland, in 2000 I joined Radio Swiss International, which then became swissinfo.ch. Since then I have been writing (and producing short videos) on a variety of subjects, from politics to business, and including culture and science.

with Keystone-SDA and RTS

The news of the iconic filmmakers assisted suicidewas confirmed on September 13. Godard's legal advisor Patrick Jeanneret later told the AFP news agency that the 91-year-old "had recourse to legal assistance in Switzerland for a voluntary departure as he was stricken with 'multiple invalidating illnesses', according to the medical report".

Swiss law tolerates assisted suicide when patients commit the act themselves and helpers have no vested interest in their death.

Exit, the country's leading assisted suicide organisation, accompanied almost 1,400 in 2021. Exit only offers its services to Swiss residents and Swiss nationals living abroad. Other organisations will assist people from abroad, where the practice is forbidden.

In May 2022, the Swiss Medical Association tightened its conditions for assisted suicide. Doctors must now conduct at least two interviews, at least two weeks apart, with the person who wishes to end their life. The patient must prove that his or her suffering is unbearable.

Death was a topic that frequently featured in Godards works. I want to be immortal and then die, says the writer played by Jean-Pierre Melville in the film A Bout de Souffle (Breathless). And in Pierrot le Fou (Pierrot the madman), Jean-Paul Belmondo ties sticks of dynamite to his head.

Godard himself spoke about his own death in 1995 in his documentary film JLG/JLG Self-Portrait in December, a monument of a film in which mournful weeping willows suffer in a romantic landscape that celebrates the unshakeable force of nature. Trees and a lake reflect the image of the final season, winter, as theLe MondeExternal linknewspaper described it. In 2004, Godard told the Libration newspaper that he had attempted suicide after 1968, "in a rather fraudulent mannerso that people would pay attention to me". He also told Les Inrockuptibles magazine that he had thought of killing himself several times and had hesitated, "out of fear".

>> From the archives: watch Jean-Luc Godard talking about assisted suicide ontheSwiss public television RTS programme Pardonnez-moi on May 25, 2014

In France, the issue of assisted suicide is a big topic of debate. On the day that Godards assisted suicide was confirmed, French President Emmanuel Macron announced a national debate on end-of-life options that will include exploring the possibility of legalising assisted suicide. This would include regional debates and consultations with the medical profession and parliamentarians.

A 2016 French law provides that doctors can keep terminally ill patients sedated before death but stops short of allowing assisted suicide. Recently, the country'sNational Consultative Ethics Committeeruled that"active assistance in dying" could be applied in France "under certain strict conditions".

The French president is said to be considering a referendum for the law change, which would be the first since he came to office in 2017.

Assisted suicide, which involves patients self-administering a lethal dose of drugs, is allowed in ten countries, including Switzerland.

Euthanasia, a process in which a medical professional directly gives the drugs, is currently legal in the Netherlands, Belgium, Luxembourg and Spain, Canada and Colombia under certain conditions.

However, people who wish to end their own lives face many obstacles. Most countries that allow assisted suicide limit this option to adults with an incurable disease. Only the Netherlands and Belgium allow for the "right to die", also for people under 18 years of age.

In most countries, especially in Asia and the Middle East, assisted suicide and direct active euthanasia remain taboo, mainly for religious or cultural reasons.

Adapted from French by Isobel Leybold-Johnson/sb

In compliance with the JTI standards

More: SWI swissinfo.ch certified by the Journalism Trust Initiative

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Akudaaya: Tinubu, Abacha and Shettima’s Theory of Ruthless Leadership -By Festus Adedayo – Opinion Nigeria

Posted: at 11:34 pm

In what seems to affirm that he wears controversies like apparel, Vice Presidential candidate of the All Progressives Party, (APC) Kashim Shettima,leapt into yet another at the twilight of last week. On Thursday, at the 96th anniversary celebration of the Yoruba Tennis Club in Ikoyi, Lagos State, Shettima was quoted to have said that Nigeria needed the hospitality of General Sani Abacha, Nigerias despotic military ruler, Nigerias own contribution to the list of infamous rulers who ruled the world with infernal ruthlessness. As the controversy over what he actually said raged, Shettima came out with a clarification: He actually said that in 2023, Nigeria needed a president who possessed a dose of ruthlessness and taciturnity. Nigerians have since been engaged with dissecting what lay atop the mind of a man who could be the countrys vice president.

We need a leader with a dose of ruthlessness and taciturnity of General Sani Abacha Nice men do not make leaders There is no one, with all due respect, that fits this better than Asiwaju Bola Ahmed Tinubu, he said.

In a subsequent clarification made on his Twitter handle, Shettima claimed that the report that he attributed hospitality to Abacha didnt only quote him out of context, it was the continuation of an obsession with distorting ones views to settle partisan scores. What he actually meant, maintained the former Borno State governor, was that Nigeria needed a ruthless president in the mould of Abacha so as to address the insecurity menace it faces. I never attributed hospitality to Abacha in my speech. I did a rundown of our past Presidents and played up the taciturnity and a dose of ruthlessness of a Sani Abacha to show we need strongmen to deal with the non state actors whove turned Nigeria into a vast killing-field he continued.

Shettimas pontification and equivocation about Sani Abacha remind me of this subsisting theory about the intrusion of the dead into lives of the living and how the dead, whose lives were terminated abruptly, can, through transmigration of souls, continue to fulfill their abrogated destinies in another form. At a point when necromantic pundits submitted that President Muhammadu Buhari had but few hours to live and could not return alive from his UK infirmary where he had gone to receive treatment, his return spurned the major theory that he had in fact died in the United Kingdom. Continued the theory, a lookalike Jibril, or Jubril of Sudan was procured as his placeholder. Of all his sins against the State, Nnamdi Kanus most unpardonable against Buhari will seem to be that he took this necromantic pontification to a soberingly believable height.

A couple of weeks ago, unknown to him, I presume, medical practitioner and activist, Mahdi Shehu, also provoked the concept of death, or what the Yoruba callakudaaya.I will explain it presently. On anArise TVinterview programme, Shehu had flogged what was, in the opinion of the APC and its 2023 presidential campaign team, a dead horse, by raising a couple of critical questions that border on the educational and health history of Bola Tinubu, the partys presidential candidate.On the TV interview, Shehu submitted that Nigerians are in search of the identity of the true Tinubu. Some fundamental questions, he said, were in urgent need of answers.

We have searched the secret file of Bola Tinubu and we are asking, Bola Tinubu, please tell Nigerians, what is the name of the primary school you attended? Who were your classmates, dead or alive? If you cant remember them at least you can remember the name of your own headmaster. If you cant remember them, tell us in which town, maybe the school has been overrun by reconstructions of Lagos State or Ibadan or Oyo, Ondo. Who were your mates in secondary school? What is the name of the secondary school you attended? Who was your mathematics teacher, you said you were a good mathematics student? Shehu had asked on and on.

Was Shehu suggesting that the APC presidential candidate was anakudaaya? Or put differently, will a suggestion that Bola Tinubu is probably anakudaayaanswer to the hovering spirit of his APC-irritating questions? A few weeks ago, Dele Alake defended this same Shehu allegations with outright lies and spewed disingenuous concoctions in laundry of this Lagos contraption in a glib intervention on aChannelsTV programme. Rather than that laborious journey of untruth, couldnt he have maneuvered out of the bundle of lies by simply embracing theakudaayaphenomenon and stating simply that Tinubu died after those primary and secondary school years and just transmigrated into a new soul? As I will state underleaf, there are people who live today and who are presumed to beakudaayas. Theakudaayaphenomenon lacks empiricism, though supported by long-held beliefs and assumptions. Alake would have been more believable if he entered the world of nil empiricism to support his drudgery than manipulating Nigerians knowledge of an issue that is raging in the public domain.

So let me quickly dwell on the phenomenon of life after death, a subject that has engaged philosophy and religion over the centuries. Curiosity about what happens when man dies is a universal phenomenon. To man, sudden cessation of life and living is absurd. Man thus wants to know what transpires after consciousness ceases. Man is baffled that maggots, decay and smell take over an otherwise admirable body. Greek philosophers, Plato and Socrates tried to offer an explanation. Plato, for instance, gave a clear demarcation between the body and the soul, submitting that there is immortality of the soul. His argument is that, because the soul is immortal, it survives deaths lieutenants rigor mortis and decay who feast on the body after cessation of breath and collapse of the functions of all organs of the body. Pythagoras and Empedocles submit that people are reborn in accordance with the merits of the lives they live, whether as humans, animals and can be reborn as vegetables. This belief was rampant in Rome and Africa, giving birth to the concept of apotheosis. In apotheosis, human beings are deified after their death and given god-like status. In ancient Greece, some founders of cities like Romulus were elevated to the level of god at death. This led to the deification of Roman Emperors Julius and Augustus Caesar. In Africas Oyo Empire, King Sango became a deity at death and is today held as an ancestor.

Christian and Islamic theologians will hear none of those. After death comes judgment, they say. To them, the process of living and dying is a singular, mono occurrence. African epistemology took that fear and curiosity of death to another plane. In Yoruba theory of knowledge, for instance, a few concepts were designed to answer this curiosity about afterlife. The prominent ones among them are the theories of transmigration of souls calledakudaayaand reincarnation after life. Whileakudaayais a doctrine which holds that at death, the soul moves into another body, human or animal, afterlife holds that at death, benevolent leaders, called ancestors, continue to live, superintending over the welfare of their offspring.Akudaayais he who enters the town midday no one knows his last place of habitat, nor the bird that laid his last egg.Akudaayahas no family, no foe and is sired by nobody. Reincarnation on its own believes that after death, the Plato immortal soul leaves the body and begins another life in another physical body.

Of all these, the theory ofakudaayahas been held to be the most controversial. It is a phenomenon whichdescribes how the dead return to life, appear to man to carry out unfinished assignments and most times, sojourn in another territory. Religionists are vehemently engaged in disputations about the existence ofakudaayabecause it nullifies the main foundation of their belief. To them, deathis not only irreversible, it is the cessation of life. However,akudaayaaffirms the continuation of life after death and a linkage between unfulfilled destiny and death by seeking to resolve the conflict between them.

There have been several stories of people having encounters with certified dead persons and who have been affirmed not to be hallucinating carrying out the usual physical interactions with them. At the point of discovery that they had once lived and died, the dead disappear into thin air. A journalist once undertook to go to a place that is the town of the dead and interviewed people there. They confirmed that the dead live their normal lives in the town. Nollywood movies escalate this ancient Yoruba belief by churning out films which affirm that the mysterious phenomenon is an everyday life narrative among the Yoruba.

Most often, theakudaayais said to be dead persons whose lives were cut short prematurely and who seek a fulfillment of their destinies somewhere else. The belief is also that theori destiny of the dead person, while alive, got terminated abruptly by an individual or circumstance and so as to fulfill the corpus of that destiny, he relocates at death to another locale to fulfill that destiny. They thus reincarnate in another body but with similar physical features as they bore pre-death.

So even though the narratives are engaging, sometimes very logical and even temptingly believable, the afterlife phenomenon is still in the realm of conjecture. For science and its verifiable principles,akudaayafails woefully. Science dwells on seven essential principles of verifiability and they are theprinciple of universal open access, principle of open licensing, principle of rigorous and ongoing peer review, principle of supporting metadata, principle of access by future generations, principle of respecting various publication traditions and principle of grasping opportunities.Akudaayacannot fulfill even one of those. It is however supported by age-long beliefs, tradition and norms.

Shettima will seem to believe, in his nostalgia for Sani Abachas ruthlessness and taciturnity, that though he died in 1998 in unexplained circumstance, the late despot can continue to live in our hearts and our polity as anakudaaya. It is curious that though Abacha is a pariah in the hearts of the world, judging by his unexampled notoriety and thirst for blood, till today, he is a besotted jewel in many parts of the north. Recall that even Buhari frowned at labeling of Abacha as looter of the Nigerian economy. He has been too lip-tied to apologize for his blind, nepotistic northernism when Abacha began to cough out his loots in death. Shettima, the man who could be Nigerias vice presidents nostalgia for Abachas kind of iron fist rule is benumbing.

While APC apologists have trumpeted Shettimas so-called brilliance, he appears to me as a loose cannon and a man whose mind is a bomb waiting to explode. That is if he is not a bomb thrower at heart. If you conduct a mind analysis on him, especially through his bombasts and off-the-cuff remarks, you will discover that he is just a whiff off Abubakar Shekaus bloodthirsty notoriety. Same Shettima it was who, in June of this year said that the president Nigeria needs is not one who possesses intellect, is cerebral or is nice.Osinbajo is a good man; hes a nice man. But nice men do not make good leaders, because nice men tend to be nasty.Nice men should be selling popcorn, ice cream.But hes a very decent person, he had said, to the consternation of his audience.

By repeating this same nonsensical argument again last Thursday at the Yoruba Tennis Club in Lagos, Nigeria must begin to take a more than passing interest in the constitution of Shettimas mind. Do not forget the hovering allegation, leveled by no less a person than an ex-president of Nigeria, Goodluck Jonathan, that Shettima has a dialogical relationship with terrorism. Allegations are also flying in high places that Shettimas alleged kidnap of Chibok girls while he was governor was to remove the rug off the feet of the PDP government of Jonathan and that the girls were subsequently re-kidnapped by some Boko Haram elements. That was why, in an earlier comment, I asked that, rather than make his religion an issue, Christendom should be bothered about the propensity of having as Nigerias vice president a professed romancer and believer in Boko Harams maniacal insurgency ideology.

But what exactly does Shettima mean by Nigeria not needing a nice person as president? Nigeria is in the turmoil it is today because its successive leaders have never been empathetic to, nor sympathetic to the peoples travails. If they did, they would be concerned about their plights. Muhammadu Buharis is worse because he seems to have breakfast, lunch and dinner with a single delicacy of the head of a tortoise. His queer taciturnity draws a thick blanket on his mind and people cannot sniff the odious sewage that emanates therefrom.

Yoruba say that anyone who is as unfeeling, soul-dead and without empathy as to be able to eat the meat-less, bony, scraggy-looking head of a tortoise must have had their souls seared with hot iron. That is replicated in virtually all Nigerian leaders. Surveying the Nigerian presidential aspiration landscape, what I can see is its virtual takeover by ruthless leaders. You can only possess a ruthless mind if you stole your country blind as the allegation of looting the Nigerian till that hangs on the aspirants necks like necklaces seem to be. There is actually no dividing line between Sani Abacha and Muhammadu Buhari. They are/were both taciturn but ruthless. Only a ruthless leader will drag a country to the precipice as Buhari has done and go to Imo State on a visit as he did last week asking that he be deified for having changed the destiny of Nigeria for good.

Going back to Shehu Mahdi, it will appear that the character he constructed in that interview on Arise TV could only have been anakudaaya. No real human being could assume such benumbing notoriety other than one who passed on at a particular stage of his life, transmigrated into another body with a different name and continues to live his past in the present. The questions Mahdi then asked about primary school attended, Mathematics teacher, classmates and all that would be irrelevant for anakudaaya. When Dele Alake embarked on that esophagus defence by submitting that Tinubu sat at home to acquire the certificates he swore to on oath that he possessed in 1999, he forgot that critical cannon, the Number One rule that liars must not run foul of: A liar must have a very good memory. All the mountainous lies about their principal being daily spun would have been needless if travelers on this mendacious boat had gone back to the ancient corpus of traditional Africa to say, simply that Tinubu is anakudaaya.

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Akudaaya: Tinubu, Abacha and Shettima's Theory of Ruthless Leadership -By Festus Adedayo - Opinion Nigeria

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On The Lord Of The Rings: The Rings Of Power, a hard rains a-gonna fall – The A.V. Club

Posted: at 11:34 pm

Cynthia Addai-Robinson (Queen Regent Mriel), Morfydd Clark (Galadriel)Photo: Matt Grace (Prime Video)

Trees dont just bear fruit and provide shade in Lord Of The Rings; theyre living, breathing, as we saw in episode one, moving things. J.R.R. Tolkien held trees in such regard that he took issue with the immortal bards shabby approach to walking trees in Macbeth. As a young man, he felt bitter disappointment and disgust that Birnam wood didnt explicitly march upon Dunsinane. Soldiers camouflaged by leaves and twigs wont cut it.

Since trees have such significance to its prime architect, its unsurprising that Lord Of The Rings would make them the centerpiece of conflict. Last week, Arondir considered sacrificing an old tree for the lives of his friends, and now, the show presents a classic Tolkienian image, white leaves falling from an ancient tree. Tolkiens trees are the Earths thermometer, taking its temperature and reporting its general health. If leaves are falling and trees are cut down, it will require some strong medicine and fast.

Ismael Cruz Cordova

Arondir

Markella Kavenagh

Elanor 'Nori' Brandyfoot

Sara Zwangobani

Marigold Brandyfoot

Megan Richards

Poppy Proudfellow

The Great Wave isnt as fleet-footed as previous entries and relies on a few too many surprises and occasionally forced cliffhangers to keep the action moving. Every scene doesnt need to end with a catastrophe to hold our attention. Yet, they do provide crucial leadership moments that will escort Galadriel into the final half of the season. Even still, it presents its hope with a tinge of the inevitable. We might quell the symptoms, but the sickness lingers.

Director Wayne Che Yip doesnt wait long to deliver the episodes titular star. Within moments, Queen Mriel, who is busy christening newborn Nmenreans in her chambers, witnesses a shower of white leaves from the pale tree in the kings courtyard. Moments later, a tsunami crashes on the island, and she awakens from the nightmare.

Things are changing in Nmenor. An Elf and a mysterious man landed on its shores and the star fall from weeks prior are bad omens. Distraught and frustrated, the men Halband bodied last week complained in city squares about Elves coming to their shores and taking their jobs. Aside from the ridiculous notion that Elves would spend their eternal lives working in Nmenrean bars and ports is laughable, but their fears shouldnt come as a surprise to those living in a world with humans on it.

Chancellor Pharazn (Trystan Gravelle) isnt having it, though. Adept in statecraft, Pharazn maintains things on a street level, shaking hands with shopkeepers and providing drinks and merriment for the island of men, cooling the hottest coals, as Disa would say. He knows everyone in Nmenor, and his affable charms have won him their trust.

Cynthia Addai-Robinson (Queen Regent Mriel)Photo: Prime Video

Mriel and Pharazn work in perfect tandem, even if their personal life is opaque, offering a revealing juxtaposition to Elrond and Galadriel. Galadriel, who tries and fails to convince the Queen Regent to join the Elves and fight Sauron, finds herself jailed for sedition. The Elf might be a skilled warrior and rider, but shes an awful diplomat, as Halbrand, her cellmate, points out. There is a tempest in me, Galadriel says as negotiations collapse. It swept me to this island for a reason, and it will not be quelled by you, Regent. Hard to believe that that didnt get her a meeting with the exiled Tar-Palantir (Ken Blackburn). Galadriel could really use a skilled diplomat like Elrond right about now. After all, politics requires strength and finesse.

Still, Galadriel will have it her way. After scaling Palantirs tower in a breezy dress and sandals, she finds Mriel waiting for her. Unfortunately, things are not what they seem. The people ousted Palantir and installed his daughter Mriel because of the kings hardline belief that Nmenor had defied the gods. As he grew older and more righteous in his beliefs, he repented by pledging fealty to the Elves, an unpopular opinion, leading to revolution and the installation of his daughter as queen. However, his decline was also a mental one. He now remains out of sight, bedridden, and unable to rule.

Palantir, meaning far sighted in an ancient form of Elvish, shares his name with the seeing stones. Thats no coincidence. Tar-Palantir is known as a clairvoyant, having prophesied the downfall of Nmenor, beginning with the death of the great tree and ending with a greater flood. Appropriately enough, Tar-Palantir has one of the seven seeing stones, and Mriel invites Galadriel to take a gander. From there, she sees the queens nightmare: The white leaves, the flood, and the citys destruction.

OrcsPhoto: Ben Rothstein (Prime Video)

Ancient, secret treasures like the palantir play a prominent role in The Great Wave. After taking last week off, Elrond is back with the Dwarves, checking in with his friend Durin, who has inexplicably been a little cagey about what hes up to in the old mines. The Dwarves have made significant progress on Celebrimbors tower, but something feels off between Durin and Elrond, a secret wedged between them. So our resident gumshoe, Elrond, is on the case.

Thankfully, we also get another few scenes with Disa, who protects her husbands secret. Hes discovered a new oar, mithril, a powerful, lightweight metal that could be used for weapons, defense, and other non-combat-based uses, in the old mine. Disa and Durins conversation on the bridge of Khazad-dm is beautifully shot, particularly the final profile close-up of Durin, with the beams of light framing his head, nose, and beard with a white, glowing border. Unfortunately, creepazoid Elrond saw the whole thing, including the lovely bit of flirting the couple does.

Elrond wants to know more. He confronts Durin, who makes him swear on the mountain not to tell another soul about the mithril. Holding it in his hands, Elrond reacts to the stone like he is gazing upon the Ring. Hes entranced by the stone, with its light coming from inside. But he offers it back, showing Durin that their friendship means more to him than a bit of rock. Robert Aramayo and Owain Arthur sell this connection hard, and its totally effective. (Wed like a bottle episode with these two yesterday, please and thank you.) Nevertheless, one of the deus ex machina moments happens when the mine collapses moments after their conversation. He and the remaining miners are fine, but to Durins dismay, his father, King Durin III (Peter Mullan) shuts down the operation. Dads.

Robert Aramayo (Elrond), Owain Arthur (Prince Durin IV)Photo: Ben Rothstein (Prime Video)

After a stirring piece of writing from Stephany Folsom, J.D. Payne, and Patrick McKay, Durin realizes these personal connections are more important than wealth, silver, or even mithril. My father single handily sailed to Valinor, Elrond tells him. Would he be proud of what I accomplished with his legacy or disappointed by the countless ways I failed to live up to it? Then one night, it struck me that I would only be too happy to hear any judgment, so long as it the opportunity to have one more conversation with my father. Do not waste what time you have left with yours. Elrond comforts like none other.

The Dwarves pursuit of mithril ended without tragedy, but theyre not the only ones hunting for treasure. Theo heads to town for food, and the Orcs head to town for that hilt of his. When hes discovered, Theo stabs the jagged pummel of the hilt into the back of his forearm. The blade flames on and begins to reforge. Thankfully, help is on the way. After being freed by Adar, who appears to be a fallen Elf with a real simmering vulnerability and terrifying calm, Arondir makes a sudden rescue. Arondir has a message for the town: Bow to Adar, or hes bringing the fight to them.

The end comes with a truce between Mriel and Galadriel. After the tree starts shedding for real, the Queen announces that she will escort the Elf to Middle-earth, and the connection between Elves and Men will reforge. But there is the feeling that all of this is too late. The wheels are in motion, and the stars are strange. Something is coming, and these factions can let their differences doom them or unite against the shadow.

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On The Lord Of The Rings: The Rings Of Power, a hard rains a-gonna fall - The A.V. Club

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The longevity diet: Lots of beans and periodic fasts slow ageing – The New Daily

Posted: at 11:34 pm

Live

Valter Longo grew up in a village in Calabria called Molochio, famous for being a so-called blue zone an area where the locals were known to live exceptionally long lives and to suffer lower rates of chronic disease.

In recent years, the towns abundance of centenarians has become a curiosity for the likes National Geographic and what has emerged is a story of people who eating mainly beans and fruit, and no red meat.

And, in frequent harder times, they barely ate at all.

Perhaps it was all those ancient people that freaked young Valter Longo out. As a teenager he fled to the US, where he lived with extended family and planned on being a rock star.

But he eventually abandoned his guitar and took up studying those old home-town people and asking why they have managed to live longer and healthier lives than most and along the way hes become a rock star in the somewhat controversial field of slowing down ageing.

A paper he wrote in 1994 that detailed the ageing pathway of yeast was rejected and even mocked for seven years. It was eventually published in 2001.

As an enthusiastic 2017 profile in Stat News reported, the paper has since been cited hundreds of times.

If someone said, What are you working on? we would say oxidative chemistry, Dr Longo told Stat. You couldnt say ageing. That was viewed as a joke.

Some theorists, such as the British molecular biologist Aubrey de Grey, believe ageing is a disease that can be cured. Once thats achieved we could live to 1000 years, is de Greys contentious claim.

Dr Longo professor of gerontology and the biological sciences at the USC Davis School of Gerontology and director of the USC Longevity Institute is more modest in his ambitions. Hes has become convinced that diet is the key to living vigorously to the age of 110.

By way of contrast, he pointed out in his 2016 Ted Talk that if we could completely cure cancer, the gains in longevity would be relatively modest, maybe an extra four or five years on average.

Where Aubrey de Grey is something of a superstar in the immortality sphere, his ideas have been written off by many serious scientists.

Professor Longo, on the other hand, has convinced many of his colleagues that hes truly on to something. Even sceptics have suggested his ideas are plausible, but want to see larger studies in humans.

In April, Professor Longo having been in the pursuit of longevity for 30 years co-authored a widely reported article with Dr Rozalyn Anderson, director of the metabolism of ageing program at the University of Wisconsin school of medicine and public health.

The researchers reviewed hundreds of studies on nutrition, diseases and longevity in laboratory animals and humans and combined them with their own studies on nutrients and ageing.

The net result was a clearer picture of the best diet for a longer, healthier life.

We explored the link between nutrients, fasting, genes and longevity in short-lived species, and connected these links to clinical and epidemiological studies in primates and humans including centenarians, Professor Longo said.

By adopting an approach based on over a century of research, we can begin to define a longevity diet that represents a solid foundation for nutritional recommendations and for future research.

The short version: Lots of legumes, whole grains, and vegetables; some fish; no red meat or processed meat and very low white meat; low sugar and refined grains; good levels of nuts and olive oil, and some dark chocolate.

In fact, this is essentially the diet that Professor Longo previously published in book form but now the science is catching up.

On the face of it, it doesnt appear to be that ground-breaking.

But the innovation isnt in the foods you consume most of the time under the plan, the life-extending potential is in whats called a fasting-mimicking diet.

Its a rather neat trick, where the body goes into fasting mode for five days which prompts stem cells to regenerate the immune system while you actually continue to eat a modest number of calories.

The Longo plan includes eating 1100 plant-based calories made up of nuts, vegetables, soups, olive and teas on the first day and then around 800 for the next four days.

In 2017, Professor Longo and colleagues published a randomised Phase II clinical trial involving 71 healthy people aged 20 to 70.

On and off, for three months, the participants followed a periodic, five-day fasting diet designed by Longo.

The diet reduced cardiovascular risk factors including blood pressure, signs of inflammation (measured by C-reactive protein levels), as well as fasting glucose and reduced levels of IGF-1, a hormone that affects metabolism.

It also shrank waistlines and resulted in weight loss, both in total body fat and trunk fat, but not in muscle mass.

Overall, the diet reduced the study participants risks for cancer, diabetes, heart disease and other age-related diseases.

These positive results were found to be sustained three months after the trial.

What happens next? A large, FDA phase III clinical trial to test the fast-mimicking diet on patients diagnosed with age-related diseases or at high risk for them.

Professor Longo might be a very old man by the time he fully cracks the code for the longevity. By then, hell be walking proof of his own theories. Or not.

For more on Professor Longo and fast-mimicking might slow ageing, see here.

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The longevity diet: Lots of beans and periodic fasts slow ageing - The New Daily

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Revealing the Hidden Genome: Unknown DNA Sequences Identified That May Be Critical to Human Health – SciTechDaily

Posted: at 11:25 pm

Scientists have developed a new technique to reveal the hidden human genome.

Numerous short RNA sequences that code for microproteins and peptides have been identified, providing new opportunities for the study of diseases and the development of drugs.

Researchers from Duke-NUS Medical School and their collaborators have discovered thousands of previously unknown DNA sequences in the human genome that code for microproteins and peptides that could be critical for human health and disease.

Much of what we understand about the known two per cent of the genome that codes for proteins comes from looking for long strands of protein-coding nucleotide sequences, or long open reading frames, explained computational biologist Dr Sonia Chothani, a research fellow with Duke-NUS Cardiovascular and Metabolic Disorders (CVMD) Programme and first author of the study. Recently, however, scientists have discovered small open reading frames (smORFs) that can also be translated from RNA into small peptides, which have roles in DNA repair, muscle formation and genetic regulation.

Scientists have been seeking to identify smORFs and the tiny peptides they code for since smORF disruption can cause disease. However, the currently available techniques are quite limited.

Much of the current datasets do not provide information that is detailed enough to identify smORFs in RNA, added Dr Chothani. The majority also comes from analyses of immortalised human cells that are propagatedsometimes for decadesto study cell physiology, function and disease. However, these cell lines arent always accurate representations of human physiology.

Chothani and her colleagues from Singapore, Germany, the United Kingdom, and Australia present an approach they created to address these challenges in a recentstudy published in Molecular Cell. They scoured existing ribosome profiling datasets for short strands of RNA with periodic three-base sections that covered more than 60% of the RNAs length. They then performed their own RNA sequencing and Ribosome profiling to establish a combined data set of six kinds of cells and five types of tissue derived from hundreds of patients.

Analyses of these data identified nearly 8,000 smORFs. Interestingly, they were highly specific to the tissues that they were found in, meaning that these smORFs may perform a function specific to their environment. The team also identified 603 microproteins coded by some of these smORFs.

The genome is littered with smORFs, said Assistant Professor Owen Rackham, senior author of the study from the CVMD Programme. Our comprehensive and spatially resolved map of human smORFs highlights overlooked functional components of the genome, pinpoints new players in health and disease and provides a resource for the scientific community as a platform to accelerate discoveries.

Professor Patrick Casey, Senior Vice-Dean of Research at Duke-NUS, said, With the healthcare system evolving to not only treat diseases but also prevent them, identifying potential new targets for disease research and drug development could open avenues to new solutions. This research by Dr Chothani and her team, published as a resource for the scientific community, brings important insights to the field.

Reference: A high-resolution map of human RNA translation by Sonia P. Chothani, Eleonora Adami, Anissa A. Widjaja, Sarah R. Langley, Sivakumar Viswanathan, Chee Jian Pua, Nevin Tham Zhihao, Nathan Harmston, Giuseppe DAgostino, Nicola Whiffin, Wang Mao, John F. Ouyang, Wei Wen Lim, Shiqi Lim, Cheryl Q.E. Lee, Alexandra Grubman, Joseph Chen, J.P. Kovalik, Karl Tryggvason, Jose M. Polo, Lena Ho, Stuart A. Cook, Owen J.L. Rackham and Sebastian Schafer, 15 July 2022, Molecular Cell.DOI: 10.1016/j.molcel.2022.06.023

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Uncovering the genetic basis of mental illness requires data and tools that aren’t just based on white people this international team is collecting…

Posted: at 11:25 pm

Mental illness is a growing public health problem. In 2019, an estimated 1 in 8 people around the world were affected by mental disorders like depression, schizophrenia or bipolar disorder. While scientists have long known that many of these disorders run in families, their genetic basis isnt entirely clear. One reason why is that the majority of existing genetic data used in research is overwhelmingly from white people.

In 2003, the Human Genome Project generated the first reference genome of human DNA from a combination of samples donated by upstate New Yorkers, all of whom were of European ancestry. Researchers across many biomedical fields still use this reference genome in their work. But it doesnt provide a complete picture of human genetics. Someone with a different genetic ancestry will have a number of variations in their DNA that arent captured by the reference sequence.

When most of the worlds ancestries are not represented in genomic data sets, studies wont be able to provide a true representation of how diseases manifest across all of humanity. Despite this, ancestral diversity in genetic analyses hasnt improved in the two decades since the Human Genome Project announced its first results. As of June 2021, over 80% of genetic studies have been conducted on people of European descent. Less than 2% have included people of African descent, even though these individuals have the most genetic variation of all human populations.

To uncover the genetic factors driving mental illness, I, Sinad Chapman and our colleagues at the Broad Institute of MIT and Harvard have partnered with collaborators around the world to launch Stanley Global, an initiative that seeks to collect a more diverse range of genetic samples from beyond the U.S. and Northern Europe, and train the next generation of researchers around the world. Not only does the genetic data lack diversity, but so do the tools and techniques scientists use to sequence and analyze human genomes. So we are implementing a new sequencing technology that addresses the inadequacies of previous approaches that dont account for the genetic diversity of global populations.

To study the genetics of psychiatric conditions, researchers use data from genome-wide association studies that compare the genetic variations between people with and without a particular disease. However, these data sets are mostly based on people of European ancestry, largely because research infrastructure and funding for large-scale genetics studies, and the scientists conducting these studies, have historically been concentrated in Europe and the United States.

One way to close this gap is to sequence genetic data from diverse populations. My colleagues and I are working in close partnership with geneticists, statisticians and epidemiologists in 14 countries across four continents to study the DNA of tens of thousands of people of African, Asian and Latino ancestries who are affected by mental illness. We work together to recruit participants and collect DNA samples that are sequenced at the Broad Institute in Massachusetts and shared with all partners for analysis.

Prioritizing the voices and priorities of local communities and scientists is foundational to our work. All partners have joint ownership of the project, including decision-making and sample and data ownership and control. To do this, we build relationships and trust with the local communities we are studying and the local university leaders and scientists with whom we are partnering. We work to understand local cultures and practices, and adapt our collection methods to ensure study participants are comfortable. For example, because there are different cultural sensitivities around providing saliva and blood samples, we have adapted our practices by location to ensure study participants are comfortable.

We also freely share knowledge and materials with our partners. There is a two-way exchange of information between the Broad Institute and local teams on study progress and results, enabling continual learning, teaching and unity between teams. We strive to meet each other where we are by exchanging practices and training scientists to support the development of locally grown and locally led research programs.

Our collaboration with African research groups provides a prime example of our model. For example, our African research colleagues are co-leaders on the grants that fund the lab equipment, scientists and other staff for projects based at their study sites. And we help to support the next generation of African geneticists and bioinformaticians through a dedicated training program.

Collecting samples from more diverse populations is only half of the challenge.

Existing genomic sequencing and analysis technologies do not adequately capture genetic variation across populations from around the world. Thats because these technologies were designed to detect genetic variations based on reference DNA from people of European ancestry, and they reduce accuracy when analyzing sequences that arent derived from the reference genome. When these tools are applied to genetic data from other populations, they fail to detect much of the rich variation in their genomes. This can lead researchers to miss out on important biomedical discoveries.

To address this issue, we developed an approach to genome sequencing that can detect more genetic variation from populations around the world. It works by sequencing the exome the less than 2% of the genome that codes for proteins in high detail, as well as sequencing the 98% of the genome that does not code for proteins in less detail.

This combined approach reduces the trade-offs geneticists often have to make in sequencing projects. High-depth whole genome sequencing, which reads through the entire genome multiple times to get detailed data, is too costly to do on a large number of DNA samples. While low-coverage sequencing reduces costs by reading smaller segments of the genome, it may miss some important genetic variation. With our new technology, geneticists can get the best of both worlds: sequencing the exome in depth maximizes the likelihood of pinpointing specific genes that play a role in mental illness, while sequencing the whole genome less in depth allows researchers to process large numbers of whole genomes more cost-effectively.

Our hope is that this new technology will allow researchers to sequence large sample sizes from a diverse range of ancestries to capture the full breadth of genetic variation. With a better understanding of the genetics of mental illness, clinicians and researchers will be better equipped to develop new treatments that work for everyone.

Genomic sequencing opened a new era of personalized medicine, which promises to deliver treatments tailored to each individual person. This can be done only if the genetic variations of all ancestries are represented in the data sets that researchers use to make new discoveries about disease and develop treatments.

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Uncovering the genetic basis of mental illness requires data and tools that aren't just based on white people this international team is collecting...

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Explainer: The Basics of DNA and Genetic Systems – Visual Capitalist

Posted: at 11:25 pm

A Newfound Link Between Cancer and Aging?

A new study in 2022 reveals a thought-provoking relationship between how long animals live and how quickly their genetic codes mutate.

Cancer is a product of time and mutations, and so researchers investigated its onset and impact within 16 unique mammals. A new perspective on DNA mutation broadens our understanding of aging and cancer developmentand how we might be able to control it.

Cancer is the uncontrolled growth of cells. It is not a pathogen that infects the body, but a normal body process gone wrong.

Cells divide and multiply in our bodies all the time. Sometimes, during DNA replication, tiny mistakes (called mutations) appear randomly within the genetic code. Our bodies have mechanisms to correct these errors, and for much of our youth we remain strong and healthy as a result of these corrective measures.

However, these protections weaken as we age. Developing cancer becomes more likely as mutations slip past our defenses and continue to multiply. The longer we live, the more mutations we carry, and the likelihood of them manifesting into cancer increases.

Since mutations can occur randomly, biologists expect larger lifeforms (those with more cells) to have greater chances of developing cancer than smaller lifeforms.

Strangely, no association exists.

It is one of biologys biggest mysteries as to why massive creatures like whales or elephants rarely seem to experience cancer. This is called Petos Paradox. Even stranger: some smaller creatures, like the naked mole rat, are completely resistant to cancer.

This phenomenon motivates researchers to look into the genetics of naked mole rats and whales. And while weve discovered that special genetic bonuses (like extra tumor-suppressing genes) benefit these creatures, a pattern for cancer rates across all other species is still poorly understood.

Researchers at the Wellcome Sanger Institute report the first study to look at how mutation rates compare with animal lifespans.

Mutation rates are simply the speed at which species beget mutations. Mammals with shorter lifespans have average mutation rates that are very fast. A mouse undergoes nearly 800 mutations in each of its four short years on Earth. Mammals with longer lifespans have average mutation rates that are much slower. In humans (average lifespan of roughly 84 years), it comes to fewer than 50 mutations per year.

The study also compares the number of mutations at time of death with other traits, like body mass and lifespan. For example, a giraffe has roughly 40,000 times more cells than a mouse. Or a human lives 90 times longer than a mouse. What surprised researchers was that the number of mutations at time of death differed only by a factor of three.

Such small differentiation suggests there may be a total number of mutations a species can collect before it dies. Since the mammals reached this number at different speeds, finding ways to control the rate of mutations may help stall cancer development, set back aging, and prolong life.

The findings in this study ignite new questions for understanding cancer.

Confirming that mutation rate and lifespan are strongly correlated needs comparison to lifeforms beyond mammals, like fishes, birds, and even plants.

It will also be necessary to understand what factors control mutation rates. The answer to this likely lies within the complexities of DNA. Geneticists and oncologists are continuing to investigate genetic curiosities like tumor-suppressing genes and how they might impact mutation rates.

Aging is likely to be a confluence of many issues, like epigenetic changes or telomere shortening, but if mutations are involved then there may be hopes of slowing genetic damageor even reversing it.

While just a first step, linking mutation rates to lifespan is a reframing of our understanding of cancer development, and it may open doors to new strategies and therapies for treating cancer or taming the number of health-related concerns that come with aging.

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Explainer: The Basics of DNA and Genetic Systems - Visual Capitalist

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Intellia Therapeutics Announces Positive Interim Clinical Data for its Second Systemically Delivered Investigational CRISPR Candidate, NTLA-2002 for…

Posted: at 11:25 pm

DetailsCategory: DNA RNA and CellsPublished on Saturday, 17 September 2022 10:29Hits: 269

CAMBRIDGE, MA, USA I September 16, 2022 I Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage genome editing company focused on developing potentially curative therapeutics leveraging CRISPR-based technologies, today announced positive interim results from an ongoing Phase 1/2 clinical study of NTLA-2002, its second in vivo genome editing candidate. NTLA-2002 is a systemically administered CRISPR candidate being developed for hereditary angioedema (HAE) and is designed to knock out the KLKB1 gene in liver cells, thereby reducing the production of kallikrein protein. Uncontrolled activity of kallikrein is responsible for the overproduction of bradykinin, which leads to the recurring, debilitating and potentially fatal swelling attacks that occur in people living with HAE. The interim data were shared today in an oral presentation at the 2022 Bradykinin Symposium held in Berlin, Germany.

The data presented are from the initial six adult patients with HAE in the ongoing dose-escalation study with a data cut-off date of July 27, 2022. Single doses of 25 mg (n=3) and 75 mg (n=3) of NTLA-2002 were administered via intravenous infusion, and changes from baseline values of plasma kallikrein protein were measured for each patient. Administration of NTLA-2002 led to dose-dependent reductions in plasma kallikrein and achieved maximal reductions by week eight, with mean reductions of 65% and 92% in the 25 mg and 75 mg dose cohorts, respectively. Furthermore, these reductions were sustained through at least 16 weeks in the 25 mg cohort and eight weeks in the 75 mg cohort for which complete cohort biomarker data were available.

In addition to plasma kallikrein levels, HAE attack rates are also being measured in the study, with the first analysis occurring at the end of the pre-specified 16-week primary observation period. To date, all three patients in the 25 mg dose cohort have reached the end of this initial observation period. Patients in this group had a baseline HAE attack rate ranging from 1.1 to 7.2 attacks per month, as confirmed by the investigator. Treatment with a single dose of 25 mg of NTLA-2002 resulted in a mean reduction in HAE attacks of 91% throughout the 16-week observation period. Additionally, two of the three patients have not had a single HAE attack since treatment, and all three patients have been attack free since week 10 (follow-up through weeks 24 - 32). Patients in the 75 mg cohort have not completed the primary 16-week observation period. Attack-rate data for this cohort will be presented at the American College of Allergy, Asthma & Immunology (ACAAI) Annual Scientific Meeting, November 10 14 in Louisville, Kentucky.

Prophylaxis medications are permitted in the Phase 1 part of the study. Two of the three patients in the 25 mg cohort were actively receiving prophylaxis therapy prior to administration of NTLA-2002. For these two patients, the study protocol permitted investigators to withdraw the patients prophylaxis therapy after completion of the 16-week primary observation period. This treatment approach was implemented for the two applicable patients in this cohort, and neither patient has had an HAE attack since discontinuing their prophylaxis therapy through the latest follow-up.

These initial data represent a significant milestone for both Intellia and people around the world suffering from genetic diseases, such as HAE, said Intellia President and Chief Executive Officer John Leonard, M.D. We are strongly encouraged by the greater than 90% reduction in HAE attacks observed in the 25 mg dose cohort, as these interim results support our belief that a single dose of NTLA-2002 has the potential to permanently prevent the debilitating swelling attacks associated with HAE. Additionally, todays announcement continues to validate our genome editing approach and the modular platform we have built. This is now the second time in history clinical data have been generated suggesting we can precisely edit target cells within the human body to potentially treat genetic diseases with a single, systemic administration of a CRISPR-based therapy. We plan to move as quickly and judiciously as possible on behalf of people living with HAE and a number of additional genetic diseases in the months and years ahead.

At both dose levels, NTLA-2002 was generally well-tolerated, and the majority of adverse events were mild in severity. The most frequent adverse events were infusion-related reactions, which were mostly Grade 1 and resolved within one day. There have been no dose-limiting toxicities, no serious adverse events and no adverse events of Grade 3 or higher observed to date. No clinically significant laboratory abnormalities were observed, including any significant elevation in liver enzymes.

Many people living with HAE continue to experience breakthrough attacks despite currently available treatments and often find the burden of untreated attacks, frequent infusions or injections to be tremendously disruptive to their lives, said Hilary Longhurst, M.D., Ph.D., Faculty of Medical and Health Sciences, University of Auckland, New Zealand, and the trials principal investigator in New Zealand. These early data support NTLA-2002 as a potential one-time treatment capable of producing profound reductions in HAE attacks. While the clinical data are still emerging, I am highly optimistic that NTLA-2002 could become a new treatment option for the HAE community.

Based on the interim data presented today, Intellia selected a third dose of 50 mg to be evaluated in the ongoing dose-escalation portion of the Phase 1/2 study. Dosing at this level has recently completed, and Intellia expects to select up to two doses to further evaluate in the Phase 2, placebo-controlled, dose-expansion portion of the study, which is expected to begin in the first half of 2023. Intellia anticipates expanding country and site participation, including U.S. clinical sites, as part of the Phase 2 study.

Intellia Therapeutics Investor Event and Webcast Information Intellia will host a live webcast today, Friday, September 16, 2022, at 8:00 a.m. ET, to provide a clinical update from its in vivo portfolio, during which the company will review the presented clinical data at the 2022 Bradykinin Symposium alongside interim results from NTLA-2001. To join the webcast, please visit this link, or the Events and Presentations page of the Investors & Media section of the companys website at http://www.intelliatx.com. A replay of the webcast will be available on Intellias website for at least 30 days following the call.

About the NTLA-2002 Clinical ProgramIntellias multi-national Phase 1/2 study is evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of NTLA-2002 in adults with Type I or Type II hereditary angioedema (HAE). This includes the measurement of plasma kallikrein protein levels and activity as determined by HAE attack rate measures. The Phase 1 portion of the study is an open-label, single-ascending dose design used to identify up to two dose levels of NTLA-2002 that will be further evaluated in the randomized, placebo-controlled Phase 2 portion of the study. This Phase 1/2 study will identify the dose of NTLA-2002 for use in future studies.Visit clinicaltrials.gov (NCT05120830) for more details.

About NTLA-2002

Based on Nobel Prize-winning CRISPR/Cas9 technology, NTLA-2002 is the first single-dose investigational treatment being explored in clinical trials for the potential to continuously reduce kallikrein activity and prevent attacks in people living with hereditary angioedema (HAE). NTLA-2002 is a wholly owned investigational CRISPR therapeutic candidate designed to inactivate thekallikrein B1 (KLKB1) gene, which encodes for prekallikrein, the kallikrein precursor protein. NTLA-2002 is Intelliassecond investigational CRISPR therapeutic candidate to be administered systemically, by intravenous infusion, to edit disease-causing genes inside the human body with a single dose of treatment. Intellias proprietary non-viral platform deploys lipid nanoparticles to deliver to the liver a two-partgenome editingsystem: guide RNAspecific to the disease-causing gene and messenger RNAthat encodes the Cas9 enzyme, which together carry out the precision editing.

About Hereditary Angioedema

Hereditary angioedema (HAE) is a rare, genetic disorder characterized by severe, recurring and unpredictable inflammatory attacks in various organs and tissues of the body, which can be painful, debilitating and life-threatening. It is estimated that one in 50,000 people are affected by HAE, and current treatment options often include life-long therapies, which may require chronic intravenous (IV) or subcutaneous (SC) administration as often as twice per week, or daily oral administration to ensure constant pathway suppression for disease control. Despite chronic administration, breakthrough attacks still occur. Kallikrein inhibition is a clinically validated strategy for the preventive treatment of HAE attacks.

About Intellia TherapeuticsIntellia Therapeutics, a leading clinical-stage genome editing company, is developing novel, potentially curative therapeutics leveraging CRISPR-based technologies. To fully realize the transformative potential of CRISPR-based technologies, Intellia is pursuing two primary approaches. The companys in vivo programs use intravenously administered CRISPR as the therapy, in which proprietary delivery technology enables highly precise editing of disease-causing genes directly within specific target tissues. Intellias ex vivo programs use CRISPR to create the therapy by using engineered human cells to treat cancer and autoimmune diseases. Intellias deep scientific, technical and clinical development experience, along with its robust intellectual property portfolio, have enabled the company to take a leadership role in harnessing the full potential of genome editing to create new classes of genetic medicine. Learn more at intelliatx.com. Follow us on Twitter@intelliatx.

SOURCE: Intellia Therapeutics

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