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Found 37443 matches. Displaying 41-50
Paez S, Mapholi NO, Nesengani LT, Lamont SJ, Aggrey SE, Hanotte O, Bottema CD...
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Supporting social justice through equity-based actions for a sustainable futu...

ANIMAL GENETICS 2025 FEB; 56(1):? Article e13506
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.
Hong SJ, Resnick SJ, Iketani S, Cha JW, Albert BA, Fazekas CT, Chang CW, Liu ...
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A multiplex method for rapidly identifying viral protease inhibitors

MOLECULAR SYSTEMS BIOLOGY 2025 FEB 3; 21(2):158-172
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.
Gong R, Reynolds MJ, Sun XY, Alushin GM
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Afadin mediates cadherin-catenin complex clustering on F-actin linked to coop...

SCIENCE ADVANCES 2025 FEB 14; 11(7):? Article eadu0989
The E-cadherin-beta-catenin-alpha E-catenin (cadherin-catenin) complex couples the cytoskeletons of neighboring cells at adherens junctions (AJs) to mediate force transmission across epithelia. Mechanical force and auxiliary binding partners converge to stabilize the cadherin-catenin complex's inherently weak binding to actin filaments (F-actin) through unclear mechanisms. Here, we show that afadin's coiled-coil (CC) domain and vinculin synergistically enhance the cadherin-catenin complex's F-actin engagement. The cryo-electron microscopy (cryo-EM) structure of an E-cadherin-beta-catenin-alpha E-catenin-vinculin-afadin-CC supra-complex bound to F-actin reveals that afadin-CC bridges adjacent alpha E-catenin actin-binding domains along the filament, stabilizing flexible alpha E-catenin segments implicated in mechanical regulation. These cooperative binding contacts promote the formation of supra-complex clusters along F-actin. Additionally, cryo-EM variability analysis links supra-complex binding along individual F-actin strands to nanoscale filament curvature, a deformation mode associated with cytoskeletal forces. Collectively, this work elucidates a mechanistic framework by which vinculin and afadin tune cadherin-catenin complex-cytoskeleton coupling to support AJ function across varying mechanical regimes.
Smith MH, Bai ZL, Lakhanpal A, Ramirez D, Dicarlo E, Donlin L, Orange D, Good...
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Characterizing molecular targets in difficult-to-treat rheumatoid arthritis

SEMINARS IN ARTHRITIS AND RHEUMATISM 2025 FEB; 70(?):? Article 152588
O'May JB, Vanes L, de Boer LL, Lewis DA, Hartweger H, Kunzelmann S, Hayward D...
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WNK1-dependent water influx is required for CD4+ T cell activation...

NATURE COMMUNICATIONS 2025 FEB 21; 16(1):? Article 1857
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.
Short B
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FAT3 provides a flicker of light

JOURNAL OF GENERAL PHYSIOLOGY 2025 FEB 11; 157(2):? Article e202513772
Gleicher N, Barad DH
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New insights into the effects of endometriosis on IVF

REPRODUCTIVE BIOMEDICINE ONLINE 2025 FEB; 50(2):? Article 104482
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.
Koyano KW, Taubert J, Robison W, Waidmann EN, Leopold DA
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Face pareidolia minimally engages macaque face selective neurons

PROGRESS IN NEUROBIOLOGY 2025 FEB; 245(?):? Article 102709
The macaque cerebral cortex contains concentrations of neurons that prefer faces over inanimate objects. Although these so-called face patches are thought to be specialized for the analysis of facial signals, their exact tuning properties remain unclear. For example, what happens when an object by chance resembles a face? Everyday objects can sometimes, through the accidental positioning of their internal components, appear as faces. This phenomenon is known as face pareidolia. Behavioral experiments have suggested that macaques, like humans, perceive illusory faces in such objects. However, it is an open question whether such stimuli would naturally stimulate neurons residing in cortical face patches. To address this question, we recorded single unit activity from four fMRI-defined face-selective regions: the anterior medial (AM), anterior fundus (AF), prefrontal orbital (PO), and perirhinal cortex (PRh) face patches. We compared neural responses elicited by images of real macaque faces, pareidolia-evoking objects, and matched control objects. Contrary to expectations, we found no evidence of a general preference for pareidolia-evoking objects over control objects. Although a subset of neurons exhibited stronger responses to pareidolia-evoking objects, the population responses to both categories of objects were similar, and collectively much less than to real macaque faces. These results suggest that neural responses in the four regions we tested are principally concerned with the analysis of realistic facial characteristics, whereas the special attention afforded to face-like pareidolia stimuli is supported by activity elsewhere in the brain.
da Conceicao PJP, Ayusso GM, Carvalho T, Lima MLD, Marinho MD, Moraes FR, Gal...
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In Vitro Evaluation of the Antiviral Activity of Polyphenol (-)-Epigallocatec...

VIRUSES-BASEL 2025 FEB; 17(2):? Article 258
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.
Mclean TC, Balaguer-Pérez F, Chandanani J, Thomas CM, Aicart-Ramos C, Burick ...
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KorB switching from DNA-sliding clamp to repressor mediates long-range gene s...

NATURE MICROBIOLOGY 2025 FEB; 10(2):?
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.