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The 39th International Society for Animal Genetics conference (ISAG) was held for the first time in Africa under the theme 'Animal genetics for a sustainable future' in 2023. The conference convened scientists, policy makers, industry professionals, and students from interdisciplinary fields to share and discuss the latest developments in the space of animal genetics. Since its inception as a society, ISAG has sought to provide a platform advocating for a just and equitable future in animal genetics. At the 39th ISAG conference, this commitment towards furthering inclusion in animal genetic science was progressed with two new offerings to attendees. The first session guided discussions on the political, ethical, legal, socioeconomic, and cultural dynamics that present barriers to participating in and benefitting from the genomic and genetic science fraternity. This session also included principles of social justice, specifically equity, diversity, and inclusion, towards enacting fairness in an unfair world, and focused on constraints related to sustainability in animal genetics. The second session used the important tradition of storytelling to transfer knowledge and wisdom from experienced scientists to upcoming researchers. Experienced scientists shared lived experiences on educational and career paths, challenges, and opportunities, providing networking and opportunities for further mentoring. Here, we report on these equity-based actions and their relevance to address the urgent continent-specific and global disparities in animal genetics to move towards a sustainable future.

With current treatments addressing only a fraction of pathogens and new viral threats constantly evolving, there is a critical need to expand our existing therapeutic arsenal. To speed the rate of discovery and better prepare against future threats, we establish a high-throughput platform capable of screening compounds against 40 diverse viral proteases simultaneously. This multiplex approach is enabled by using cellular biosensors of viral protease activity combined with DNA-barcoding technology, as well as several design innovations that increase assay sensitivity and correct for plate-to-plate variation. Among >100,000 compound-target interactions explored within our initial screen, a series of broad-acting inhibitors against coronavirus proteases were uncovered and validated through orthogonal assays. A medicinal chemistry campaign was performed to improve one of the inhibitor's potency while maintaining its broad activity. This work highlights the power of multiplex screening to efficiently explore chemical space at a fraction of the time and costs of previous approaches.

Editor's note: This is the 25th article in a series on clinical research by nurses coordinated by the Heilbrunn Family Center for Research Nursing at Rockefeller University. The series is designed to be used as a resource for nurses to understand the concepts and principles essential to research. Each column will present the concepts that underpin evidence-based practice-from research design to data interpretation. To see all the articles in the series, go to https://links.lww.com/AJN/A204.

Solute carrier (SLC) proteins play critical roles in maintaining cellular and organismal homeostasis by transporting small molecules and ions. Despite a growing body of research over the past decade, physiological substrates and functions of many SLCs remain elusive. This perspective outlines key challenges in studying SLC biology and proposes an evidence-based framework for defining SLC substrates. To accelerate the deorphanization process, we explore systematic technologies, including human genetics, biochemistry, and computational and structural approaches. Finally, we suggest directions to better understand SLC functions beyond substrate identification in physiology and disease.

This Letter presents the first measurements of the groomed jet radius R-g and the jet girth g in events with an isolated photon recoiling against a jet in lead-lead (PbPb) and proton-proton (pp) collisions at the LHC at a nucleon-nucleon center-of-mass energy of 5.02 TeV. The observables R-g and g provide a quantitative measure of how narrow or broad a jet is. The analysis uses PbPb and pp data samples with integrated luminosities of 1.7 nb(-1) and 301 pb(-1), respectively, collected with the CMS experiment in 2018 and 2017. Events are required to have a photon with transverse momentum p(T)(gamma) > 100 GeV and at least one jet back-to-back in azimuth with respect to the photon and with transverse momentum p(T)(jet) such that p(T)(jet)/p(T)(gamma) > 0.4. The measured R-g and g distributions are unfolded to the particle level, which facilitates the comparison between the PbPb and pp results and with theoretical predictions. It is found that jets with p(T)(jet)/p(T)(gamma) > 0.8, i.e., those that closely balance the photon p(T)(gamma), are narrower in PbPb than in pp collisions. Relaxing the selection to include jets with p(T)(jet)/p(T)(gamma) > 0.4 reduces the narrowing of the angular structure of jets in PbPb relative to the pp reference. This shows that selection bias effects associated with jet energy loss play an important role in the interpretation of jet substructure measurements.

The phylogenetic inference package GCtree uses abundance of sampled sequences to improve the performance of parsimony-based inference, using a branching process model. Our previous work showed that GCtree performs competitively on B-cell receptor data, compared with other similar tools. In this article, we describe recent enhancements to GCtree, including an efficient tree storage data structure that discovers additional diversity of parsimonious trees with negligible additional computational cost. We also describe a suite of new objective functions that can be used to rank these trees, including a Poisson context likelihood function that models sequence evolution in a context-sensitive way. We validate these additions to GCtree with simulated B-cell receptor data, and benchmark performance against other phylogenetic inference tools.This article is part of the theme issue '"A mathematical theory of evolution": phylogenetic models dating back 100 years'.

It is not uncommon that a published paper offers unintended insights, unnoticed by its authors. This was to a substantial degree the case with a recent publication addressing the effects of endometriosis on IVF. Using donor-recipient cycles as the study population to isolate recipient effects, the well-executed study demonstrated only mildly adverse outcome effects of endometriosis on IVF cycle outcomes, to a substantial degree laying to rest this still controversial issue. In the process, however, the study also raised some very interesting - but left undiscussed - insights into a host of other issues with considerable relevance to endometriosis and IVF practice in the USA and UK. These are the subject of this communication.

Examples of long-range gene regulation in bacteria are rare and generally thought to involve DNA looping. Here, using a combination of biophysical approaches including X-ray crystallography and single-molecule analysis for the KorB-KorA system in Escherichia coli, we show that long-range gene silencing on the plasmid RK2, a source of multi-drug resistance across diverse Gram-negative bacteria, is achieved cooperatively by a DNA-sliding clamp, KorB, and a clamp-locking protein, KorA. We show that KorB is a CTPase clamp that can entrap and slide along DNA to reach distal target promoters up to 1.5 kb away. We resolved the tripartite crystal structure of a KorB-KorA-DNA co-complex, revealing that KorA latches KorB into a closed clamp state. DNA-bound KorA thus stimulates repression by stalling KorB sliding at target promoters to occlude RNA polymerase holoenzymes. Together, our findings explain the mechanistic basis for KorB role switching from a DNA-sliding clamp to a co-repressor and provide an alternative mechanism for long-range regulation of gene expression in bacteria.

Signaling from the T cell antigen receptor (TCR) on CD4+ T cells plays a critical role in adaptive immune responses by inducing T cell activation, proliferation, and differentiation. Here we demonstrate that WNK1, a kinase implicated in osmoregulation in the kidney, is required in T cells to support T-dependent antibody responses. We show that the canonical WNK1-OXSR1-STK39 kinase signaling pathway is required for TCR signaling in CD4+ T cells, their subsequent entry into the cell cycle, and suppression of the ATR-mediated G2/M cell cycle checkpoint. We show that the WNK1 pathway regulates ion influx leading to water influx, potentially through AQP3, and that water influx is required for TCR-induced signaling and cell cycle entry. Thus, TCR signaling via WNK1, OXSR1, STK39 and AQP3 leads to water entry that is essential for CD4+ T cell proliferation and hence T cell-dependent antibody responses.

The Mayaro virus (MAYV), Togaviridae family, genus Alphavirus, has caused several sporadic outbreaks, affecting countries in the Americas. Currently, there are no licensed drugs against MAYV, requiring the search for effective antiviral compounds. Thus, this study aimed to evaluate the antiviral potential of polyphenol (-)-epigallocatechin-3-gallate (EGCG) against MAYV infection, in vitro. Antiviral assays against MAYV were performed in BHK-21 and Vero E6 cells. In addition, molecular docking was performed with EGCG and the MAYV non-structural and structural proteins. EGCG showed a significant protective effect against MAYV infection in both cell lines. The virucidal assay showed an effect on extracellular viral particles at the entry stage into BHK-21 cells. Finally, it also showed significant inhibition in the post-entry stages of the MAYV replication cycle, acting on the replication of the genetic material and late stages, such as assembly and release. In addition, the MAYV proteins E1 and nsP1 were significantly inhibited by the EGCG treatment in BHK-21 cells. Molecular docking analysis also showed that EGCG could interact with MAYV Capsid and Envelope proteins (E1 and E2). Therefore, this study shows the potential of EGCG as a promising antiviral against MAYV, as it acts on different stages of the MAYV replication cycle.