Z went to a Duke recruiting weekend where accepted kids can get a feel for the university. He hung out with some kids who decided to go to Harvard and Stanford, and a bunch of kids who decided on Duke. What was similar about all of them? They talked openly about having autism. At lunch […]

The post What explains the outsized success of autistic applicants to college appeared first on Penelope Trunk Careers.

Three-time Oscar nominee Torill Kove, who won the Academy Award for her short 'The Danish Poet,' is back in the Oscars race this year with a new film about her memories of growing up in Kenya.

As the country’s civil war decimated elephant populations, the proportion of tuskless females rose dramatically. A new study explains why the tuskless trend continued in peacetime.

Over Sukkot, over 150 young Russian-speaking immigrants gathered to celebrate the opening of the center, SSY stated. 

By Mariane Angela Democratic New York City Mayor Eric Adams’ office announced Thursday that New York City will stop providing food vouchers to migrants, CBS News New York reported. NYC will phase out out a program that gave prepaid debit cards to migrant families in city-funded hotels to purchase their own meals and essentials, according to […]

The post NYC Mayor Eric Adams Announces End To NYC Food Vouchers For Illegal Immigrants appeared first on Liberty Unyielding.

A court challenge means the government will look again at the cap on the Disabled Facilities Grant.

Trump's win has been welcomed by Israel but the change he brings may not be to its liking, writes Lucy Williamson.

McLaren’s Lando Norris explains why he wants to win the British Grand Prix more than any other race in Formula 1.

1. 'There's a guy in Indian team whose Test average is 63...': Tim Paine wants Rohit and Gambhir to open their eyes  Hindustan Times
2. EXCLUSIVE | Dhruv Jurel can be the X-factor India are looking for in Australia, says Suresh Raina  The Times of India
3. Former Australia captain tips India youngster to shine Down Under  ICC Cricket
4. Not Rishabh Pant or Yashasvi Jaiswal; Ex- Australian captain backs this Indian young player to impress everyone in Border-Gavaskar Trophy, says 'class above all his teammates on this tour'  SportsTak
5. Why India should play Jurel as a specialist batsman at Perth  The Indian Express

Côte d'Ivoire is sub Sahara Africa's biggest importer of wine, says the US department of agriculture, and it is time American companies take advantage of the market.

The quirky folks at Fodor’s let me share some of the world’s weirdest plants, fungi, and microorganisms to inspire your #plantnerd bucket list (I’ve seen 5 out of 10 of these weirdos out in the wild!) 10 Plants From Around the World That Will Upset and Delight | Fodor’s Travel

The article EIT Elsewhere | Sharing the World’s Weirdest Plants on Fodor’s Travel originated at EverInTransit.com

New York Judge Juan Merchan — who is overseeing President-elect Donald Trump’s business records case — agreed to freeze the case until Nov. 19. There was to be a hearing […]

The post Judge Juan Merchan Grants Request from Trump's Legal Team and DA in NY Hush Money Case appeared first on The Western Journal.

HIV Type 1 (HIV-1) and simian immunodeficiency virus (SIV) display differential replication kinetics in macrophages. This is because high expression levels of the active host deoxynucleotide triphosphohydrolase sterile α motif domain and histidine-aspartate domain–containing protein 1 (SAMHD1) deplete intracellular dNTPs, which restrict HIV-1 reverse transcription, and result in a restrictive infection in this myeloid cell type. Some SIVs overcome SAMHD1 restriction using viral protein X (Vpx), a viral accessory protein that induces proteasomal degradation of SAMHD1, increasing cellular dNTP concentrations and enabling efficient proviral DNA synthesis. We previously reported that SAMHD1-noncounteracting lentiviruses may have evolved to harbor RT proteins that efficiently polymerize DNA, even at low dNTP concentrations, to circumvent SAMHD1 restriction. Here we investigated whether RTs from SIVmac239 virus lacking a Vpx protein evolve during in vivo infection to more efficiently synthesize DNA at the low dNTP concentrations found in macrophages. Sequence analysis of RTs cloned from Vpx (+) and Vpx (−) SIVmac239–infected animals revealed that Vpx (−) RTs contained more extensive mutations than Vpx (+) RTs. Although the amino acid substitutions were dispersed indiscriminately across the protein, steady-state and pre-steady-state analysis demonstrated that selected SIVmac239 Vpx (−) RTs are characterized by higher catalytic efficiency and incorporation efficiency values than RTs cloned from SIVmac239 Vpx (+) infections. Overall, this study supports the possibility that the loss of Vpx may generate in vivo SIVmac239 RT variants that can counteract the limited availability of dNTP substrate in macrophages.

Expert

E. A. Rakhmanov and S. P. Suetin
Trans. Moscow Math. Soc. 83 (), 269-290.
Abstract, references and article information

Daniel López Neumann
Trans. Amer. Math. Soc. 377 (), 5361-5387.
Abstract, references and article information

Forty-six mathematical scientists have been named recipients of AMS-Simons Research Enhancement Grants for Primarily Undergraduate Institution (PUI) Faculty. Each awardee will receive $3,000 per year for three years. 

The grants foster and support research collaboration by full-time mid-career mathematicians at US institutions that do not offer a mathematics doctoral degree.

This year’s grant recipients hail from 42 institutions across 21 US states. The grants will support their research in several different areas, from number theory to applied mathematics.

This is the grant program’s second cohort, said Sarah Bryant, associate vice president of programs. “Over the first two years, we’ve worked with faculty from 75 different institutions, including 19 minority-serving institutions, which shows just how much this program is expanding and making an impact,” Bryant said. She noted that “in the first year, the grants supported 87 trips, helped produce 70 publications and preprints, and gave awardees the resources needed to collaborate and advance their work.”

The grant allows for any activities that will further the awardee’s research program. Expenses include but are not limited to conference participation, institute visits, collaboration travel (awardee or collaborator), computer equipment or software, family-care expenses, and teaching assistants.

Administration of the award by the grantee’s institution is required; annual discretionary funds for a grantee’s department and administrative funds for a grantee's institution will be available at the end of each grant year.

The grants are made possible through funding from the Simons Foundation and the American Mathematical Society (AMS), as well as Eve, Kirsten, Lenore, and Ada of the Menger family.

Applications for the next cohort are anticipated to open on MathPrograms.org on January 9, 2025. Visit the AMS website to view an informational PowerPoint or sign up to receive email updates about the program. Faculty who applied for but did not receive the 2023 or 2024 awards are encouraged to reapply if they are still eligible for the grant. 

Broad-specificity glycoside hydrolases (GHs) contribute to plant biomass hydrolysis by degrading a diverse range of polysaccharides, making them useful catalysts for renewable energy and biocommodity production. Discovery of new GHs with improved kinetic parameters or more tolerant substrate-binding sites could increase the efficiency of renewable bioenergy production even further. GH5 has over 50 subfamilies exhibiting selectivities for reaction with β-(1,4)–linked oligo- and polysaccharides. Among these, subfamily 4 (GH5_4) contains numerous broad-selectivity endoglucanases that hydrolyze cellulose, xyloglucan, and mixed-linkage glucans. We previously surveyed the whole subfamily and found over 100 new broad-specificity endoglucanases, although the structural origins of broad specificity remained unclear. A mechanistic understanding of GH5_4 substrate specificity would help inform the best protein design strategies and the most appropriate industrial application of broad-specificity endoglucanases. Here we report structures of 10 new GH5_4 enzymes from cellulolytic microbes and characterize their substrate selectivity using normalized reducing sugar assays and MS. We found that GH5_4 enzymes have the highest catalytic efficiency for hydrolysis of xyloglucan, glucomannan, and soluble β-glucans, with opportunistic secondary reactions on cellulose, mannan, and xylan. The positions of key aromatic residues determine the overall reaction rate and breadth of substrate tolerance, and they contribute to differences in oligosaccharide cleavage patterns. Our new composite model identifies several critical structural features that confer broad specificity and may be readily engineered into existing industrial enzymes. We demonstrate that GH5_4 endoglucanases can have broad specificity without sacrificing high activity, making them a valuable addition to the biomass deconstruction toolset.

Replication protein A (RPA) is a eukaryotic ssDNA-binding protein and contains three subunits: RPA70, RPA32, and RPA14. Phosphorylation of the N-terminal region of the RPA32 subunit plays an essential role in DNA metabolism in processes such as replication and damage response. Phosphorylated RPA32 (pRPA32) binds to RPA70 and possibly regulates the transient RPA70-Bloom syndrome helicase (BLM) interaction to inhibit DNA resection. However, the structural details and determinants of the phosphorylated RPA32–RPA70 interaction are still unknown. In this study, we provide molecular details of the interaction between RPA70 and a mimic of phosphorylated RPA32 (pmRPA32) using fluorescence polarization and NMR analysis. We show that the N-terminal domain of RPA70 (RPA70N) specifically participates in pmRPA32 binding, whereas the unphosphorylated RPA32 does not bind to RPA70N. Our NMR data revealed that RPA70N binds pmRPA32 using a basic cleft region. We also show that at least 6 negatively charged residues of pmRPA32 are required for RPA70N binding. By introducing alanine mutations into hydrophobic positions of pmRPA32, we found potential points of contact between RPA70N and the N-terminal half of pmRPA32. We used this information to guide docking simulations that suggest the orientation of pmRPA32 in complex with RPA70N. Our study demonstrates detailed features of the domain-domain interaction between RPA70 and RPA32 upon phosphorylation. This result provides insight into how phosphorylation tunes transient bindings between RPA and its partners in DNA resection.

Oktawia Nilsson
Nov 17, 2020; 0:jlr.RA120000920v1-jlr.RA120000920
Research Articles

Apolipoprotein A-I (ApoA-I) of high-density lipoprotein (HDL) is essential for the transportation of cholesterol between peripheral tissues and the liver. However, specific mutations in Apolipoprotein A-I (ApoA-I) of high-density lipoprotein (HDL) are responsible for a late-onset systemic amyloidosis, the pathological accumulation of protein fibrils in tissues and organs. Carriers of these mutations do not exhibit increased cardiovascular disease risk despite displaying reduced levels of ApoA-I/ HDL-cholesterol. To explain this paradox, we show that the HDL particle profile of patients carrying either L75P or L174S ApoA-I amyloidogenic variants a higher relative abundance of the 8.4 nm vs 9.6 nm particles, and that serum from patients, as well as reconstituted 8.4 and 9.6 nm HDL particles (rHDL), possess increased capacity to catalyze cholesterol efflux from macrophages. Synchrotron radiation circular dichroism and hydrogen-deuterium exchange revealed that the variants in 8.4 nm rHDL have altered secondary structure composition and display a more flexible binding to lipids compared to their native counterpart. The reduced HDL-cholesterol levels of patients carrying ApoA-I amyloidogenic variants are thus balanced by higher proportion of small, dense HDL particles and better cholesterol efflux due to altered, region-specific protein structure dynamics.

Influenza A virus (IAV) mutates rapidly, resulting in antigenic drift and poor year-to-year vaccine effectiveness. One challenge in designing effective vaccines is that genetic mutations frequently cause amino acid variations in IAV envelope protein hemagglutinin (HA) that create new N-glycosylation sequons; resulting N-glycans cause antigenic shielding, allowing viral escape from adaptive immune responses. Vaccine candidate strain selection currently involves correlating antigenicity with HA protein sequence among circulating strains, but quantitative comparison of site-specific glycosylation information may likely improve the ability to design vaccines with broader effectiveness against evolving strains. However, there is poor understanding of the influence of glycosylation on immunodominance, antigenicity, and immunogenicity of HA, and there are no well-tested methods for comparing glycosylation similarity among virus samples. Here, we present a method for statistically rigorous quantification of similarity between two related virus strains that considers the presence and abundance of glycopeptide glycoforms. We demonstrate the strength of our approach by determining that there was a quantifiable difference in glycosylation at the protein level between WT IAV HA from A/Switzerland/9715293/2013 (SWZ13) and a mutant strain of SWZ13, even though no N-glycosylation sequons were changed. We determined site-specifically that WT and mutant HA have varying similarity at the glycosylation sites of the head domain, reflecting competing pressures to evade host immune response while retaining viral fitness. To our knowledge, our results are the first to quantify changes in glycosylation state that occur in related proteins of considerable glycan heterogeneity. Our results provide a method for understanding how changes in glycosylation state are correlated with variations in protein sequence, which is necessary for improving IAV vaccine strain selection. Understanding glycosylation will be especially important as we find new expression vectors for vaccine production, as glycosylation state depends greatly on the host species.

The therapy helps the brain work more efficiently and lifts depression.

How do you reach people trapped in a reality shaped by propaganda? Exploring the dark psychology of disinformation, author and academic Peter Pomerantsev draws on lessons from a forgotten World War II operation to suggest strategies for cutting through misinformation and rebuilding trust in facts today.

The new U.S. Department of Education guidance creates a federal process for individuals and organizations to file complaints under the federal Religious Freedom Restoration Act.

Academic achievement at Ohio schools eligible for School Improvement Grants during the Obama administration increased for a few years, a new study says, but SIG's legacy remains complicated.

A California organization is tasked with giving out $9.4 million in grants to local programs across the state to solve shortages.

Georgia wants to allow districts to use a series of "formative assessments" instead of one big test at the end of the year.

The state's board voted not to open the Common Core to revision, but its commissioner still plans to review them informally, with an eye to future changes.

It's pretty obvious by now that many Democrats are growing increasingly uncomfortable supporting charter schools. But New Hampshire lawmakers have taken the unusual step of rejecting federal charter school grant money.

Teachers across the state are outraged over a new rule that requires 15 hours of workforce-related professional development.

A new study from Smithsonian scientists analyzes ant and fungus species, and uncovers the origins of their close partnership

Our host, Eric Schulze, has the answer

Kennedy Center president Deborah Rutter interviews the co-founder of MIT’s Little Devices Lab about democratizing health technology

Historically feared by humans, brown bears were once aggressively hunted in the contiguous U.S. Because of this, 95% of these majestic creatures live in Alaska.

In this one-minute video, our Ask Smithsonian Host, Eric Schulze, weighs in on whether or not elephants can jump.

Smithsonian magazine commissioned Drew Gardner for a project that connects Black Americans today to their lost ancestry. Read about Gardner’s project and process, as well as more details about the subjects of this incredible series here: https://www.smithsonianmag.com/history/descendants-black-civil-war-heroes-wear-heritage-pride-180983397/ Video produced by Sierra Theobald. Special thanks to Drew Gardner Additional credits: Emma MacBeath, WikiTree US Black Heritage project; Ottawa Goodman, research and coordinator; Sam Dole, Penumbra Foundation; Elizabeth Zuck, set design; Calvin Osbourne, props and costume; Angela Huff, hair and make up; Diego Huerta, Lexia Krebs, behind-the-scenes filming; background prints by Fujifilm USA

In Panama, researchers recorded army ants crafting living bridges to take the most efficient route along the forest floor. (Christopher R. Reid, Matthew J. Lutz, Simon Garnier, and the New Jersey Institute of Technology)

Read more about elephants at http://www.smithsonianmag.com/science-nature/How-Male-Elephants-Bond.html Keepers and pachyderms alike are enjoying the new Asian elephant exhibit, Elephant Trails, at the National Zoo.