The post Wonderful Colors of the Caspian Sea appeared first on English Russia.

The hepatitis E virus protein ORF1 contains a region that scientists have struggled to characterize, making the structure and function of this region the subject of much debate. Now, Princeton scientists show that this region of the protein does not behave as a protease, as has been previously suggested, but instead serves as a molecular scaffold to stabilize the rest of the ORF1 protein.

National survey highlights vibrancy and growth of campus research

Amichai Feit had known Seema Jayachandran as a Twitter-famous development economist.  She became Feit’s senior thesis advisor for a policy-analysis project that included economic field research in India.

This is the second round of Princeton Alliance for Collaborative Research (PACRI) projects partnering HBCU and Princeton researchers.

New paper from Princeton team challenges the conventional wisdom of superconducting quantum transitions.

An international team of researchers and gamers, led by Princeton’s Mala Murthy and Sebastian Seung, mapped every neuron and every synaptic connection in an adult fruit fly's brain, building a comprehensive “connectome” that represents a massive step toward understanding the human brain.

Craig B. Arnold has been named Princeton’s first University Innovation Officer and heads the new office.

The program, now in its fifth year, recognizes and supports outstanding scholars primed to make important contributions in their fields. The 2024 cohort includes disciplines spanning the humanities, engineering, the sciences and the social sciences.

In the Class of 2028, 71.5% of students qualify for financial aid and 21.7% of the class are lower-income students eligible for federal Pell grants.

Princeton engineers and industry leaders have squelched a threat that had lurked for years in the internet’s encryption system.

Last November an odd, rather hard, bump suddenly appeared in the palm of my right hand. A few weeks later, in a routine physical exam, I asked my Dr. what the lump might be. She thought it was a harmless, ganglion cyst. In January, suddenly two more lumps appeared in the same area of my palm, about 1.5 inches below my little and ring fingers. Feeling some concern about this, I made an appointment with a hand specialist, a surgeon, who told me with absolute certainty that I had Dupuytren’s Disease.

You can skip this paragraph if you are not so interested in the disease in general. In the following paragraphs, I’ll tell you about my personal experience with it so far... Some other names for Dupuytren’s Disease are: claw hand, Viking disease, palmar fascia contracture, and flexion contracture. Because it often causes one or more fingers to curl inward toward the palm, it is sometimes confused with trigger finger, an entirely different affliction. It is linked to heredity, Northern European descent, diabetes and other auto-immune diseases. Men are more likely to have it than women, and its incidence increases in older (over 50) folks for both men and women. Often it is dormant until there is injury or trauma to the hand(s). There are currently four categories of treatment: radiation therapy (successful only in the very early developmental stage of the disease), needle aponeurotomy (generally considered for stage 1 or 2 of the disease with 6 to 90 degrees of deformation), collagenase injection (also stage 1 or 2), and surgery (advanced stages).

Register for our "Writing Seminar Research Clinic" to be held in the Firestone Library Tea Room on Sunday November 17 between 2:00 p.m. and 8:00 p.m. Consult with Writing Center Fellows and Librarians to move your Research Paper to the next level while munching on movie theater style popcorn, cookies, and sipping caffeinated beverages! Please register for a time slot here: 2:00pm-2:30pm 2:30pm-3:00pm 3:00pm-3:30pm 3:30pm-4:00pm 4:00pm-4:30pm 4:30pm-5:00pm 5:00pm-5:30pm 5:30pm-6:00pm 6:00pm-6:30pm 6:30pm-7:00pm 7:00pm-7:30pm 7:30pm-8:00pm If you need research help and none of these time slots work for you, feel free to sign up for a consultation with your seminar librarian.

In this Oscar-qualified short, a group of friends go on a roadtrip as their car – and their country – falls apart.

Power fans are anxiously waiting for season 7, and we are here to answer the speculations and rumours. Power is an American crime drama first released on June 7th, 2014, and the latest episode came out in February 2020. Power gained positive reviews when it was released and had one of the highest Starz ratings. ... Read more

The post Power Season 7: Will There Be A New Season? appeared first on Star Two.

The release of a third season, although not confirmed, is highly anticipated by the fans. To know everything about the upcoming season, make sure you read till the end. A Peek Into The Story The plot of the story is centered on three friends, Dylan, Luke, and Evie inhabiting a common house in Glasgow. The ... Read more

The post Lovesick Season 4 – Review and Release Date 2024 appeared first on Star Two.

Now in Feeds Box you can change feeds title, add tags to your feeds, and, most remarkable, you can edit feeds' settings. We have also fine-tuned feeds search in your Feeds Box.

The post Feeds Editing And Better Search appeared first on RSSground.com.

During a recent study, a group of magpies removed their GPS trackers, astounding their observers. But were the birds actually trying to help each other?

Here is how oil and heat can form a durable coating.

Patterns of lines and dots associated with specific animal species in cave art may point to an early writing system.

The comic can pick up on the "micro bad mood" of whoever she's talking to. She writes about pregnancy, childbirth and motherhood in a new book of essays, Lifeform. Originally broadcast March 12, 2024.

In this tutorial, I'll show you exactly how to install the SEALTEAM 6 Kodi Addon on your Android TV box or Amazon Firestick, plus unique features.

Cameras started rolling for The White Lotus cast on the Thai islands in February

Hurricanes Helene and Milton have bookended a particularly stormy period. What's behind it?

It was 200 times bigger than the one that wiped out the dinosaurs nearly three billion years later.

Climate change and sea ice loss leaves polar bears exposed to more diseases, research suggests.

Gabriel Bortoleto, 20, will make his Formula One debut for the Audi-owned Sauber next season.

Properly seasoned firewood is the key to efficient and enjoyable fires during the cold months. But how long should you let firewood season after splitting it? This critical step in firewood preparation ensures that the wood burns cleanly and produces maximum heat. In this article, we will delve into the factors that influence the seasoning […]

The post How Long To Season Firewood After Splitting? appeared first on Patriot Outdoor News.

Vinay Menon knew nothing about football when he went for a meeting at a west London mansion in 2009. A few weeks later he was in the heart of the Chelsea dressing room.

Arsenal boss Mikel Arteta praises his side's performance against Chelsea in the Premier League, but says that getting results is "what is missing" at the moment.

A fair number of Mac users have discovered that Spotlight Search is not working well in MacOS Sequoia, either missing files, apps, and sometimes not working at all to find any local file. For some users the issues with Spotlight happens right after they update to MacOS Seqouia, and for others it may happen later ... Read More

Teachers can assess young students’ literacy skills and knowledge by encouraging them to produce books based on animal facts.

A nuclear-powered aircraft carrier, like American carriers, would be a major jump for China, giving its navy a global reach.

If Trump's proposed 60% tariff against China is enacted and the country responds aggressively, it could pressure some of America's largest companies.

A tech recruiting firm left a database unsecured that exposed emails, passport numbers and partial SSNs of job seekers, a security researcher says.

Ghana's main opposition leader John Dramani Mahama looks set to win December's presidential election, an opinion poll showed on Monday.

This article describes the current findings on phonics and phonological awareness instruction. It uses a question & answer format to explore 10 common questions that teachers ask about teaching phonics and phonemic awareness. Here are a few key questions addressed in the article: What are phonics and phonemic awareness? Should phonemic awareness be paired with print and taught together? Should phonological awareness be coordinated with phonics instruction? What is the best sequence for teaching phonics?

  We have been working on this idea over the summer and have now launched the next stage of the AI labs in London Here are some more details. Think of AI labs – as a club for AI research AI labs addresses three problems a)  Today, even if you are working on Machine Learning [...]

Google DeepMind’s AlphaFold 3 is available to access by researchers around the world via open-source. Google DeepMind, the tech giant’s… Continue reading Google DeepMind opens AlphaFold 3 up to researchers worldwide

The post Google DeepMind opens AlphaFold 3 up to researchers worldwide appeared first on ReadWrite.

The University of KwaZulu-Natal will share R2 million in research funding from the UK government to improve 3D-printing techniques for rocket engine components.

An underwater rover deployed by the Minderoo-UWA Deep-Sea Research Centre captured remarkable footage 3,300-meters down at the bottom of the Tonga Trench. It shows a rarely-seen bigfin squid (Magnapinna) "taking a walk" on its 13-foot tentacles. Watch below.

There have only been around 20 documented sightings of this beautifully bizarre creature in two decades. — Read the rest

The post Deep sea video of weird sea creature walking around on its 13-foot "legs" appeared first on Boing Boing.

This morning we awoke to one story dominating the tech news landscape: OpenAI is “expanding into search,” launching SearchGPT, a prototype that appears to be a direct competitor to Google (and Bing and Perplexity, not that they really matter). But despite the voluminous coverage, my initial take is that once the hype cycle passes – … Continue reading "What’s SearchGPT Really About? Moving Past the Training Data Dilemma."

The human cardiovascular system has adapted to function optimally in Earth's 1G gravity, and microgravity conditions cause myocardial abnormalities, including atrophy and dysfunction. However, the underlying mechanisms linking microgravity and cardiac anomalies are incompletely understood. In this study, we investigated whether and how calpain activation promotes myocardial abnormalities under simulated microgravity conditions. Simulated microgravity was induced by tail suspension in mice with cardiomyocyte-specific deletion of Capns1, which disrupts activity and stability of calpain-1 and calpain-2, and their WT littermates. Tail suspension time-dependently reduced cardiomyocyte size, heart weight, and myocardial function in WT mice, and these changes were accompanied by calpain activation, NADPH oxidase activation, and oxidative stress in heart tissues. The effects of tail suspension were attenuated by deletion of Capns1. Notably, the protective effects of Capns1 deletion were associated with the prevention of phosphorylation of Ser-345 on p47phox and attenuation of ERK1/2 and p38 activation in hearts of tail-suspended mice. Using a rotary cell culture system, we simulated microgravity in cultured neonatal mouse cardiomyocytes and observed decreased total protein/DNA ratio and induced calpain activation, phosphorylation of Ser-345 on p47phox, and activation of ERK1/2 and p38, all of which were prevented by calpain inhibitor-III. Furthermore, inhibition of ERK1/2 or p38 attenuated phosphorylation of Ser-345 on p47phox in cardiomyocytes under simulated microgravity. This study demonstrates for the first time that calpain promotes NADPH oxidase activation and myocardial abnormalities under microgravity by facilitating p47phox phosphorylation via ERK1/2 and p38 pathways. Thus, calpain inhibition may be an effective therapeutic approach to reduce microgravity-induced myocardial abnormalities.

Dilated cardiomyopathy (DCM) is associated with mutations in cardiomyocyte sarcomeric proteins, including α-tropomyosin. In conjunction with troponin, tropomyosin shifts to regulate actomyosin interactions. Tropomyosin molecules overlap via tropomyosin–tropomyosin head-to-tail associations, forming a continuous strand along the thin filament. These associations are critical for propagation of tropomyosin's reconfiguration along the thin filament and key for the cooperative switching between heart muscle contraction and relaxation. Here, we tested perturbations in tropomyosin structure, biochemistry, and function caused by the DCM-linked mutation, M8R, which is located at the overlap junction. Localized and nonlocalized structural effects of the mutation were found in tropomyosin that ultimately perturb its thin filament regulatory function. Comparison of mutant and WT α-tropomyosin was carried out using in vitro motility assays, CD, actin co-sedimentation, and molecular dynamics simulations. Regulated thin filament velocity measurements showed that the presence of M8R tropomyosin decreased calcium sensitivity and thin filament cooperativity. The co-sedimentation of actin and tropomyosin showed weakening of actin-mutant tropomyosin binding. The binding of troponin T's N terminus to the actin-mutant tropomyosin complex was also weakened. CD and molecular dynamics indicate that the M8R mutation disrupts the four-helix bundle at the head-to-tail junction, leading to weaker tropomyosin–tropomyosin binding and weaker tropomyosin–actin binding. Molecular dynamics revealed that altered end-to-end bond formation has effects extending toward the central region of the tropomyosin molecule, which alter the azimuthal position of tropomyosin, likely disrupting the mutant thin filament response to calcium. These results demonstrate that mutation-induced alterations in tropomyosin–thin filament interactions underlie the altered regulatory phenotype and ultimately the pathogenesis of DCM.

The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has emerged to a pandemic and caused global public health crisis. Human angiotensin-converting enzyme 2(ACE2) was identified as the entry receptor for SARS-CoV-2. As a carboxypeptidase, ACE2 cleaves many biological substrates besides angiotensin II to control vasodilatation and vascular permeability. Given the nanomolar high affinity between ACE2 and SARS-CoV-2 spike protein, we investigated how this interaction would affect the enzymatic activity of ACE2. Surprisingly, SARS-CoV-2 trimeric spike protein increased ACE2 proteolytic activity ∼3-10 fold against model peptide substrates, such as caspase-1 substrate and Bradykinin-analog. The enhancement in ACE2 enzymatic function was mediated by the binding of SARS-CoV-2 spike RBD domain. These results highlighted the potential for SARS-CoV-2 infection to enhance ACE2 activity, which may be relevant to the cardiovascular symptoms associated with COVID-19.

Heterotrimeric G-proteins are signaling switches broadly divided into four families based on the sequence and functional similarity of their Gα subunits: Gs, Gi/o, Gq/11, and G12/13. Artificial mutations that activate Gα subunits of each of these families have long been known to induce oncogenic transformation in experimental systems. With the advent of next-generation sequencing, activating hotspot mutations in Gs, Gi/o, or Gq/11 proteins have also been identified in patient tumor samples. In contrast, patient tumor-associated G12/13 mutations characterized to date lead to inactivation rather than activation. By using bioinformatic pathway analysis and signaling assays, here we identified cancer-associated hotspot mutations in Arg-200 of Gα13 (encoded by GNA13) as potent activators of oncogenic signaling. First, we found that components of a G12/13-dependent signaling cascade that culminates in activation of the Hippo pathway effectors YAP and TAZ is frequently altered in bladder cancer. Up-regulation of this signaling cascade correlates with increased YAP/TAZ activation transcriptional signatures in this cancer type. Among the G12/13 pathway alterations were mutations in Arg-200 of Gα13, which we validated to promote YAP/TAZ-dependent (TEAD) and MRTF-A/B-dependent (SRE.L) transcriptional activity. We further showed that this mechanism relies on the same RhoGEF-RhoGTPase cascade components that are up-regulated in bladder cancers. Moreover, Gα13 Arg-200 mutants induced oncogenic transformation in vitro as determined by focus formation assays. In summary, our findings on Gα13 mutants establish that naturally occurring hotspot mutations in Gα subunits of any of the four families of heterotrimeric G-proteins are putative cancer drivers.

The inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), which form tetrameric channels, play pivotal roles in regulating the spatiotemporal patterns of intracellular calcium signals. Mutations in IP3Rs have been increasingly associated with many debilitating human diseases such as ataxia, Gillespie syndrome, and generalized anhidrosis. However, how these mutations affect IP3R function, and how the perturbation of as-sociated calcium signals contribute to the pathogenesis and severity of these diseases remains largely uncharacterized. Moreover, many of these diseases occur as the result of autosomal dominant inheritance, suggesting that WT and mutant subunits associate in heterotetrameric channels. How the in-corporation of different numbers of mutant subunits within the tetrameric channels affects its activities and results in different disease phenotypes is also unclear. In this report, we investigated representative disease-associated missense mutations to determine their effects on IP3R channel activity. Additionally, we designed concatenated IP3R constructs to create tetrameric channels with a predefined subunit composition to explore the functionality of heteromeric channels. Using calcium imaging techniques to assess IP3R channel function, we observed that all the mutations studied resulted in severely attenuated Ca2+ release when expressed as homotetramers. However, some heterotetramers retained varied degrees of function dependent on the composition of the tetramer. Our findings suggest that the effect of mutations depends on the location of the mutation in the IP3R structure, as well as on the stoichiometry of mutant subunits assembled within the tetrameric channel. These studies provide insight into the pathogenesis and penetrance of these devastating human diseases.

Ignat V. Shilov
Sep 1, 2007; 6:1638-1655
Technology

Leukocidin ED (LukED) is a pore-forming toxin produced by Staphylococcus aureus, which lyses host cells and promotes virulence of the bacteria. LukED enables S. aureus to acquire iron by lysing erythrocytes, which depends on targeting the host receptor Duffy antigen receptor for chemokines (DARC). The toxin also targets DARC on the endothelium, contributing to the lethality observed during bloodstream infection in mice. LukED is comprised of two monomers: LukE and LukD. LukE binds to DARC and facilitates hemolysis, but the closely related Panton–Valentine leukocidin S (LukS-PV) does not bind to DARC and is not hemolytic. The interaction of LukE with DARC and the role this plays in hemolysis are incompletely characterized. To determine the domain(s) of LukE that are critical for DARC binding, we studied the hemolytic function of LukE–LukS-PV chimeras, in which areas of sequence divergence (divergence regions, or DRs) were swapped between the toxins. We found that two regions of LukE's rim domain contribute to hemolysis, namely residues 57–75 (DR1) and residues 182–196 (DR4). Interestingly, LukE DR1 is sufficient to render LukS-PV capable of DARC binding and hemolysis. Further, LukE, by binding DARC through DR1, promotes the recruitment of LukD to erythrocytes, likely by facilitating LukED oligomer formation. Finally, we show that LukE targets murine Darc through DR1 in vivo to cause host lethality. These findings expand our biochemical understanding of the LukE–DARC interaction and the role that this toxin-receptor pair plays in S. aureus pathophysiology.