Understanding the evolution of chromatin conformation among species is fundamental to elucidate the architecture and plasticity of genomes. Nonrandom interactions of linearly distant loci regulate gene function in species-specific patterns, affecting genome function, evolution, and, ultimately, speciation. Yet, data from nonmodel organisms are scarce. To capture the macroevolutionary diversity of vertebrate chromatin conformation, here we generate de novo genome assemblies for two cryptodiran (hidden-neck) turtles via Illumina sequencing, chromosome conformation capture, and RNA-seq: Apalone spinifera (ZZ/ZW, 2n = 66) and Staurotypus triporcatus (XX/XY, 2n = 54). We detected differences in the three-dimensional (3D) chromatin structure in turtles compared to other amniotes beyond the fusion/fission events detected in the linear genomes. Namely, whole-genome comparisons revealed distinct trends of chromosome rearrangements in turtles: (1) a low rate of genome reshuffling in Apalone (Trionychidae) whose karyotype is highly conserved when compared to chicken (likely ancestral for turtles), and (2) a moderate rate of fusions/fissions in Staurotypus (Kinosternidae) and Trachemys scripta (Emydidae). Furthermore, we identified a chromosome folding pattern that enables "centromere–telomere interactions" previously undetected in turtles. The combined turtle pattern of "centromere–telomere interactions" (discovered here) plus "centromere clustering" (previously reported in sauropsids) is novel for amniotes and it counters previous hypotheses about amniote 3D chromatin structure. We hypothesize that the divergent pattern found in turtles originated from an amniote ancestral state defined by a nuclear configuration with extensive associations among microchromosomes that were preserved upon the reshuffling of the linear genome.

The development of transforming growth factor βreceptor inhibitors (TGFβRi) as new medicines has been affected by cardiac valvulopathy and arteriopathy toxicity findings in nonclinical toxicology studies. PF-06952229 (MDV6058) selected using rational drug design is a potent and selective TGFβRI inhibitor with a relatively clean off-target selectivity profile and good pharmacokinetic properties across species. PF-06952229 inhibited clinically translatable phospho-SMAD2 biomarker (≥60%) in human and cynomolgus monkey peripheral blood mononuclear cells, as well as in mouse and rat splenocytes. Using an optimized, intermittent dosing schedule (7-day on/7-day off/cycle; 5 cycles), PF-06952229 demonstrated efficacy in a 63-day syngeneic MC38 colon carcinoma mouse model. In the pivotal repeat-dose toxicity studies (rat and cynomolgus monkey), PF-06952229 on an intermittent dosing schedule (5-day on/5-day off cycle; 5 cycles, 28 doses) showed no cardiac-related adverse findings. However, new toxicity findings related to PF-06952229 included reversible hepatocellular (hepatocyte necrosis with corresponding clinically monitorable transaminase increases) and lung (hemorrhage with mixed cell inflammation) findings at ≥ targeted projected clinical efficacious exposures. Furthermore, partially reversible cartilage hypertrophy (trachea and femur in rat; femur in monkey) and partially to fully reversible, clinically monitorable decreases in serum phosphorus and urinary phosphate at ≥ projected clinically efficacious exposures were observed. Given the integral role of TGFβ in endochondral bone formation, cartilage findings in toxicity studies have been observed with other TGFβRi classes of compounds. The favorable cumulative profile of PF-06952229 in biochemical, pharmacodynamic, pharmacokinetic, and nonclinical studies allowed for its evaluation in cancer patients using the intermittent dosing schedule (7-day on/7-day off) and careful protocol-defined monitoring.

A nudibranch from the midnight zone has fingers on its tail, collects food with a hood, and glows.

Astronomer Jo Dunkley is planning to use the Simons Observatory to snare evidence for inflation, the theory that the universe expanded at incredible speed after its birth

Jacob Hando discusses why 'Harry Potter and the Goblet of Fire' has such an impactful front cover.

A new species of Jurassic dinosaur related to Tyrannosaurus rex has been discovered by paleontologists in Kyrgyzstan in Central Asia.

The sun blasted a coronal mass at Earth earlier this week, and after back-to-back major hurricanes, some are concerned it could impact the power grid.

Archaeologists have discovered a "remarkable" section of one of Britain's most important Roman roads in southeast London.

A new genus and species of early-diverging oviraptorosaurian dinosaur has been identified from two specimens found in Inner Mongolia, China.

The post New Oviraptorosaur Species Discovered in China appeared first on Sci.News: Breaking Science News.

A new genus and species of ankylosaur has been identified from an articulated and partial skeleton found in 1986 in southern China.

The post Paleontologists Discover New Species of Ankylosaurid Dinosaur appeared first on Sci.News: Breaking Science News.

The first ever piece of the Antarctic amber was found in a sediment core from the mid-shelf section of Pine Island trough in Antarctica.

The post Amber Discovered in Antarctica for the First Time appeared first on Sci.News: Breaking Science News.

Marine biologists at Queensland Museum Kurilpa have described a new species of hermit crab, Strigopagurus fragarchela (common name is the strawberry-clawed hermit), from the continental shelf off south‑east Queensland, Australia.

The post New Species of Hermit Crab Discovered in Australia appeared first on Sci.News: Breaking Science News.

Jay-yi Nah is an underwater archaeological site dating to the Early Classic Maya period (250-600 CE) that focused on salt production for local use or perhaps local production for down-the-line trading.

The post Earliest-Known Maya Salt Works Discovered in Belize appeared first on Sci.News: Breaking Science News.

The 2024 Nobel prize in physiology or medicine has gone to Victor Ambros and Gary Ruvkun for their discovery that tiny pieces of RNA called microRNAs play a key role in controlling genes

Scientists continue to learn new things about the planet, its sweeping rings and its many moons

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Here's how the aerial acrobats are able to survive on a nearly all-sugar diet, fly higher than many helicopters can and migrate over the open ocean

Though technically not a planet, it has as rich geology as any of its planetary siblings in the solar system

Despite the lack of a dedicated mission to the planet, scientists have learned plenty through ground observations and space telescopes

Imagine walking into your yard with a coffee in one hand, no lawn mower in sight, and the kind of lush greenery that looks effortlessly perfect. No frantic trimming or sweating under the summer sun. Sounds too good to be true? It’s possible when you pick the right low-maintenance grass. Let’s walk through some game-changing […]

The post Looking for Low-Maintenance Grasses? Discover the Best Choices for Busy Gardeners appeared first on Chart Attack.

A police officer from the Mexican border state of Tamaulipas faces a murder charge for his role in the killing of an underage teenager he allegedly mistook for a gunman. He and five other officers are also charged with planting evidence to cover up the incident.

The post Mexican Cops Accused of Killing Innocent Teen, Cover Up appeared first on Breitbart.

For a lot of folks who have been following Capcom’s fighting games over the years, the Marvel vs Capcom Fighting …

Continue reading "Marvel vs Capcom Fighting Collection: Arcade Classics Review – Switch, Steam Deck, and PS5 Covered"

The addition of Discover to LabX’s portfolio strengthens its position as a leading voice in science and research media, bringing one of the most recognized science publications into its family.

Scientists have discovered the oldest-known fossil of a tadpole, which lived among the Jurassic dinosaurs 160 million years ago.

CBC has announced it's investing more in local and regional news. The coverage includes up to 25 journalists in more than a dozen communities and four new daily local podcasts.

The Indian pharmaceutical industry is advocating for enhanced fire safety measures and improved insurance coverage for employees working in pharmaceutical facilities.

Peytant has announced that the U.S. Food and Drug Administration (FDA) granted marketing authorisation (clearance to market in the United States as a Class II device) for the AMStent Tracheobronchial Covered Stent System, a therapy platform.

As radiopharmaceuticals enter a new phase, industry leaders must rethink external services and internal capabilities to master the complexities of delivering advanced therapies.

The post Unlocking the Future of Radioligand Therapy: From Discovery to Delivering at Scale appeared first on MedCity News.

Between 1999 and 2014, opioid use disorder (OUD) among pregnant women more than quadrupled, risking the health of the women—before and after giving birth—and their infants. As states grapple with COVID-19’s exacerbation of the opioid crisis, several are taking innovative steps to address the needs of high-risk groups, including low-income, postpartum patients with OUD.

Jan 10, 2023

The aim of the report is to focus specifically on the critical role of private sector investment in Ukraine’s economic reconstruction, and how the private sector, both within Ukraine and internationally, can enable Ukraine to win the peace. It provides a short overview of the economic challenges facing Ukraine, including governance, the sectors that will be critical to Ukraine's reconstruction, the roles and responsibilities for the G7, EU, IFIs, and DFIs, and then recommendations for how Ukraine and its partners can best attract private sector investment.

Be Prepared! Protect your home from sudden heating repairs with a home warranty from AHS this winter. Home warranties help homeowners control repair or replacement costs during a break down.

Campen Auktioner A/S - Specialbilauktion #482 Palmes�ndag

1981 Ferrari Recovered After Theft 29 Years Ago

Conoce a la familia Méndez, pionera en la transformación extrema de camiones. Texas Trocas, nueva serie de Discovery en Español. Estreno 15 de septiembre a las 10PM E/P.

Conoce al legendario restaurador y mecánico Martín Vaca quien construye autos fuera de serie desde hace más de 50 años. MEXICÁNICOS, estreno el 2 de marzo a las 10PM

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Institut Marqu�s

A landmark study helps to explain the genetic roots of cancer risk in children and how this may ultimately change patient care in the future.

Good morning everyone. I'm so pleased to direct you to BookPage, which has my cover revealed today for Winterkeep! Also for the new covers of Graceling, Fire, and Bitterblue. Not to mention a Q&A about Winterkeep, and an excerpt. Thank you, BookPage, for helping me share all this. Enjoy, everyone!

Click through for the Winterkeep cover reveal.

Hello, lovely people.

I have another craft post planned for sometime soon… I'm hoping to write about The Housekeeper and the Professor, by Yoko Ogawa, if I can just figure out how to articulate what I want to say. It's such a beautiful book! One of those rare books I got out of the library, read, then decided I needed to own.

Until then, I wanted to share a little bit of blather about Winterkeep (January 19, 2021), plus display all eight new covers — the new USA and UK covers for Graceling, Fire, Bitterblue, and Winterkeep — altogether in one place. If you don't care about the blather and just want to see pretty pictures, scroll down.

So. The first few drafts of Winterkeep were written in many, many points of view. It was early days, and I was trying to figure out how to tell the story I wanted to tell. I pretty much allowed anyone a point of view, sort of as an experiment, to see how each character felt, and figure out whose feelings were most important. Then gradually, across revisions, I whittled those POVs down. In its final form, Winterkeep is told from five points of view — and only three of them are human! 

One is Queen Bitterblue, whose POV will be familiar to those who've read my book Bitterblue. Bitterblue is a little bit older now, twenty-three. She's always working, always doing the best with the problems facing a young queen, and at the moment, she's worried about two of her advisers who died mysteriously in a shipwreck in Winterkeep. She's also worried about a friend, a Keepish man she's sort-of-maybe romantically involved with, named Katu Cavenda. Everyone says Katu is traveling… so why does it seem like he's actually disappeared? These questions, among others, bring Bitterblue to Winterkeep, to figure things out for herself.

Another point of view is Giddon, a character who'll be familiar to readers of Graceling and Bitterblue. Remember what a jerk Giddon was in Graceling? He actually told Katsa once that he was confident she'd want babies someday, because after all, she wasn't "an unnatural woman." YUCK! 

Then, when I started to write Bitterblue, I discovered that Giddon had evolved. I was touched by the friendship he began to develop with Bitterblue, which surprised me while I was writing. I realized that over the course of the last few years of his life, he'd taken responsibility for his behavior and grown up a bit. After all, he was only eighteen years old in Graceling, and he hadn't encountered much pushback against his viewpoints yet. I like to think that Giddon paid attention to the good influences around him and rethought a few things. Anyway, now he's back, and he's had a few more years to grow up even more.

Another point of view is a Keepish girl named Lovisa Cavenda, age 16, who's depicted on the USA cover (below). Lovisa's a sneak and a secret keeper; she's a manipulator and a survivor. Katu Cavenda's niece and a student of politics and government at the Winterkeep Academy, she lives in the dorms but sneaks home frequently, spying on her own parents, who are important political figures in Winterkeep. If I had to choose one character at the very heart of this book, it would be Lovisa Cavenda. Through no fault of her own, she finds herself in an impossible situation… Will she find a way out?

Another point of view is a telepathic blue fox, who has a special, exclusive mental bond with Lovisa Cavenda's mother, Ferla Cavenda. And trust me, though Ferla has a warm hearth and a warm coat with a fuzzy hood it's cozy to ride inside, Ferla's mind is not always a comfortable place! The rules of foxkind are fairly strict. What happens to a fox who can't decide whether to follow the rules?

Finally, my last point of view is a gigantic sea creature with thirteen legs and twenty-three eyes who lives at the bottom of the ocean, protecting her treasures (sunken anchors, sunken human corpses, sunken ships). All she wants is to be left alone… but the machinations of humans and the interests of her undersea world keep interrupting her peace.

Those are my five points of view! Together, they tell the story of Winterkeep, which is, above all, a story of relationships. I hope you'll enjoy watching these five characters come together.

And now for my shiny new covers. 

First up are the USA covers. In the USA and Canada, Graceling is published by Houghton Mifflin Harcourt and Fire, Bitterblue, and Winterkeep are published by Penguin Books. These covers were illustrated by Kuri Huang (@kuri_huang) and designed by Theresa Evangelista and Jessica Jenkins. Shown below in series order.

One of my absolute favorite things about this reboot is that both my USA and my UK publishers are updating the series, and both went with a beautiful, rich, textured look — but they're so different from each other. Below are my new UK covers. In the UK, Australia, and New Zealand, my books are published by Gollancz. The covers were illustrated by Micaela Alcaino (@micaelaalcaino) and designed by Tomás Almeida.

And that's my update for today. Hope you're all hanging in there. More soon. ????

The AAAR, Tamil Nadu in the case of M/s Faiveley Transport Rail Technologies India (P.) Ltd., In Re [A.R. Appeal No. 03/2024 AAAR dated July 10, 2024] upheld the ruling passed by AAR Tamil Nadu wherein it was ruled that GST would be applicable on Car facility extended to employees when the amount of

Fewer lakes are freezing over each winter compared with past years, posing environmental and economic consequences around the world

Welcome back to Cover Snark! From Rachael: I have so many questions: Does she not want him to save her from what looks to be an alligator? Is that alligator okay? His hips seem off. Should his gun be that close to the water? Why are they casually having a moment in this clearly dangerous water??!! Did they keep their shoes on? Sarah: She’s a shifter. So is the gator. That’s her brother and she … Continue reading Cover Snark: Reptiles are an Unintentional Theme →