Key residues in the VDAC2-BAK complex can be targeted to modulate apoptosis
by Zheng Yuan, Mark F. van Delft, Mark Xiang Li, Fransisca Sumardy, Brian J. Smith, David C. S. Huang, Guillaume Lessene, Yelena Khakam, Ruitao Jin, Sitong He, Nicholas A. Smith, Richard W. Birkinshaw, Peter E. Czabotar, Grant Dewson BAK and BAX execute intrinsic apoptosis by permeabilising the mitochondrial outer membrane. Their activity is regulated through interactions with pro-survival BCL-2 family proteins and with non-BCL-2 proteins including the mitochondrial porin VDAC2. VDAC2 is important for bringing both BAK and BAX to mitochondria where they execute their apoptotic function. Despite this important function in ...
Source: PLoS Biology: Archived Table of Contents - May 2, 2024 Category: Biology Authors: Zheng Yuan Source Type: research

A network-based modeling framework reveals the core signal transduction network underlying high carbon dioxide-induced stomatal closure in guard cells
by Xiao Gan, Palanivelu Sengottaiyan, Kyu Hyong Park, Sarah M. Assmann, R éka Albert Stomata are pores on plant aerial surfaces, each bordered by a pair of guard cells. They control gas exchange vital for plant survival. Understanding how guard cells respond to environmental signals such as atmospheric carbon dioxide (CO2) levels is not only insightful to fundamental biology but also relevant to real-world issues of crop productivity under global climate change. In the past decade, multiple important signaling elements for stomatal closure induced by elevated CO2 have been identified. Yet, there is no comprehensive under...
Source: PLoS Biology: Archived Table of Contents - May 1, 2024 Category: Biology Authors: Xiao Gan Source Type: research

The human AAA-ATPase VPS4A isoform and its co-factor VTA1 have a unique function in regulating mammalian cytokinesis abscission
by Inbar Dvilansky, Yarin Altaras, Nikita Kamenetsky, Dikla Nachmias, Natalie Elia Mutations in the human AAA-ATPase VPS4 isoform, VPS4A, cause severe neurodevelopmental defects and congenital dyserythropoietic anemia (CDA). VPS4 is a crucial component of the endosomal sorting complex required for transport (ESCRT) system, which drives membrane remodeling in numerous cellular processes, including receptor degradation, cell division, and neural pruning. Notably, while most organisms encode for a single VPS4 gene, human cells have 2 VPS4 paralogs, namely VPS4A and VPS4B, but the functional differences between these paralogs...
Source: PLoS Biology: Archived Table of Contents - April 30, 2024 Category: Biology Authors: Inbar Dvilansky Source Type: research

Blik is an extensible 3D visualisation tool for the annotation and analysis of cryo-electron tomography data
by Lorenzo Gaifas, Moritz A. Kirchner, Joanna Timmins, Irina Gutsche Powerful, workflow-agnostic and interactive visualisation is essential for the ad hoc, human-in-the-loop workflows typical of cryo-electron tomography (cryo-ET). While several tools exist for visualisation and annotation of cryo-ET data, they are often integrated as part of monolithic processing pipelines, or focused on a specific task and offering limited reusability and extensibility. With each software suite presenting its own pros and cons and tools tailored to address specific challenges, seamless integration between available pipelines is often a d...
Source: PLoS Biology: Archived Table of Contents - April 30, 2024 Category: Biology Authors: Lorenzo Gaifas Source Type: research

Multiple checkpoints ensure ribosomes have the correct end
by Jacob Gordon, Robin E. Stanley The 3 ′ end of the 18S ribosomal RNA is formed by the endoribonuclease Nob1. How cells ensure the accuracy of the 3′ end has remained a mystery. A new study in PLOS Biology revealed that there are multiple checkpoints to ensure that only ribosomes containing the correct 3′ end participate in transla tion. The 3’ end of 18S ribosomal RNA is formed by the endoribonuclease Nob1, but how cells ensure the accuracy of the 3’ end has been a mystery. A new study in PLOS Biology has revealed multiple checkpoints that ensure only ribosomes containing the correct 3’ end participate in t...
Source: PLoS Biology: Archived Table of Contents - April 30, 2024 Category: Biology Authors: Jacob Gordon Source Type: research

Single-cell RNA-seq of < i > Drosophila miranda < /i > testis reveals the evolution and trajectory of germline sex chromosome regulation
by Kevin H-C. Wei, Kamalakar Chatla, Doris Bachtrog Although sex chromosomes have evolved from autosomes, they often have unusual regulatory regimes that are sex- and cell-type-specific such as dosage compensation (DC) and meiotic sex chromosome inactivation (MSCI). The molecular mechanisms and evolutionary forces driving these unique transcriptional programs are critical for genome evolution but have been, in the case of MSCI inDrosophila, subject to continuous debate. Here, we take advantage of the younger sex chromosomes inD.miranda (XR and the neo-X) to infer how former autosomes acquire sex-chromosome-specific regula...
Source: PLoS Biology: Archived Table of Contents - April 30, 2024 Category: Biology Authors: Kevin H-C. Wei Source Type: research

Brain high-throughput multi-omics data reveal molecular heterogeneity in Alzheimer ’s disease
by Abdallah M. Eteleeb, Brenna C. Novotny, Carolina Soriano Tarraga, Christopher Sohn, Eliza Dhungel, Logan Brase, Aasritha Nallapu, Jared Buss, Fabiana Farias, Kristy Bergmann, Joseph Bradley, Joanne Norton, Jen Gentsch, Fengxian Wang, Albert A. Davis, John C. Morris, Celeste M. Karch, Richard J. Perrin, Bruno A. Benitez, Oscar Harari Unbiased data-driven omic approaches are revealing the molecular heterogeneity of Alzheimer disease. Here, we used machine learning approaches to integrate high-throughput transcriptomic, proteomic, metabolomic, and lipidomic profiles with clinical and neuropathological data from multiple h...
Source: PLoS Biology: Archived Table of Contents - April 30, 2024 Category: Biology Authors: Abdallah M. Eteleeb Source Type: research

Neural populations within macaque early vestibular pathways are adapted to encode natural self-motion
by Mohammad Mohammadi, Jerome Carriot, Isabelle Mackrous, Kathleen E. Cullen, Maurice J. Chacron How the activities of large neural populations are integrated in the brain to ensure accurate perception and behavior remains a central problem in systems neuroscience. Here, we investigated population coding of naturalistic self-motion by neurons within early vestibular pathways in rhesus macaques (Macacca mulatta). While vestibular neurons displayed similar dynamic tuning to self-motion, inspection of their spike trains revealed significant heterogeneity. Further analysis revealed that, during natural but not artificial stim...
Source: PLoS Biology: Archived Table of Contents - April 30, 2024 Category: Biology Authors: Mohammad Mohammadi Source Type: research

A host-directed oxadiazole compound potentiates antituberculosis treatment via zinc poisoning in human macrophages and in a mouse model of infection
by Alexandra Maure, Emeline Lawar ée, Francesco Fiorentino, Alexandre Pawlik, Saideep Gona, Alexandre Giraud-Gatineau, Matthew J. G. Eldridge, Anne Danckaert, David Hardy, Wafa Frigui, Camille Keck, Claude Gutierrez, Olivier Neyrolles, Nathalie Aulner, Antonello Mai, Mélanie Hamon, Luis B. Barreiro, Priscille Brodin, Roland Brosch , Dante Rotili, Ludovic Tailleux Antituberculosis drugs, mostly developed over 60 years ago, combined with a poorly effective vaccine, have failed to eradicate tuberculosis. More worryingly, multiresistant strains ofMycobacterium tuberculosis (MTB) are constantly emerging. Innovative strategie...
Source: PLoS Biology: Archived Table of Contents - April 29, 2024 Category: Biology Authors: Alexandra Maure Source Type: research

Bruno 1/CELF regulates splicing and cytoskeleton dynamics to ensure correct sarcomere assembly < i > Drosophila < /i > flight muscles
by Elena Nikonova, Jenna DeCata, Marc Canela, Christiane Barz, Alexandra Esser, Jessica Bouterwek, Akanksha Roy, Heidemarie Gensler, Martin He ß, Tobias Straub, Ignasi Forne, Maria L. Spletter Muscles undergo developmental transitions in gene expression and alternative splicing that are necessary to refine sarcomere structure and contractility. CUG-BP and ETR-3-like (CELF) family RNA-binding proteins are important regulators of RNA processing during myogenesis that are misregulated in diseases such as Myotonic Dystrophy Type I (DM1). Here, we report a conserved function for Bruno 1 (Bru1, Arrest), a CELF1/2 family homolo...
Source: PLoS Biology: Archived Table of Contents - April 29, 2024 Category: Biology Authors: Elena Nikonova Source Type: research

The C-terminus of the prototypical M2 muscarinic receptor localizes to the mitochondria and regulates cell respiration under stress conditions
by Irene Fasciani, Francesco Petragnano, Ziming Wang, Ruairidh Edwards, Narasimha Telugu, Ilaria Pietrantoni, Ulrike Zabel, Henrik Zauber, Marlies Grieben, Maria E. Terzenidou, Jacopo Di Gregorio, Cristina Pellegrini, Silvano Santini Jr, Anna R. Taddei, B ärbel Pohl, Stefano Aringhieri, Marco Carli, Gabriella Aloisi, Francesco Marampon, Eve Charlesworth, Alexandra Roman, Sebastian Diecke, Vincenzo Flati, Franco Giorgi, Fernanda Amicarelli, Andrew B. Tobin, Marco Scarselli, Kostas Tokatlidis, Mario Rossi, Martin J. Lohse, Paolo Annibale, Roberto Magg io Muscarinic acetylcholine receptors are prototypical G protein-coupled...
Source: PLoS Biology: Archived Table of Contents - April 29, 2024 Category: Biology Authors: Irene Fasciani Source Type: research

Developmental fine-tuning of medial superior olive neurons mitigates their predisposition to contralateral sound sources
by Martijn C. Sierksma, J. Gerard G. Borst Having 2 ears enables us to localize sound sources by exploiting interaural time differences (ITDs) in sound arrival. Principal neurons of the medial superior olive (MSO) are sensitive to ITD, and each MSO neuron responds optimally to a best ITD (bITD). In many cells, especially those tuned to low sound frequencies, these bITDs correspond to ITDs for which the contralateral ear leads, and are often larger than the ecologically relevant range, defined by the ratio of the interaural distance and the speed of sound. Using in vivo recordings in gerbils, we found that shortly after he...
Source: PLoS Biology: Archived Table of Contents - April 29, 2024 Category: Biology Authors: Martijn C. Sierksma Source Type: research

< i > Bacillus subtilis < /i > uses the SigM signaling pathway to prioritize the use of its lipid carrier for cell wall synthesis
by Ian J. Roney, David Z. Rudner Peptidoglycan (PG) and most surface glycopolymers and their modifications are built in the cytoplasm on the lipid carrier undecaprenyl phosphate (UndP). These lipid-linked precursors are then flipped across the membrane and polymerized or directly transferred to surface polymers, lipids, or proteins. Despite its essential role in envelope biogenesis, UndP is maintained at low levels in the cytoplasmic membrane. The mechanisms by which bacteria distribute this limited resource among competing pathways is currently unknown. Here, we report that theBacillus subtilis transcription factor SigM ...
Source: PLoS Biology: Archived Table of Contents - April 29, 2024 Category: Biology Authors: Ian J. Roney Source Type: research

The development of brain pericytes requires expression of the transcription factor < i > nkx3 < /i > . < i > 1 < /i > in intermediate precursors
by Suchit Ahuja, Cynthia Adjekukor, Qing Li, Katrinka M. Kocha, Nicole Rosin, Elodie Labit, Sarthak Sinha, Ankita Narang, Quan Long, Jeff Biernaskie, Peng Huang, Sarah J. Childs Brain pericytes are one of the critical cell types that regulate endothelial barrier function and activity, thus ensuring adequate blood flow to the brain. The genetic pathways guiding undifferentiated cells into mature pericytes are not well understood. We show here that pericyte precursor populations from both neural crest and head mesoderm of zebrafish express the transcription factornkx3.1 develop into brain pericytes. We identify the gene sig...
Source: PLoS Biology: Archived Table of Contents - April 29, 2024 Category: Biology Authors: Suchit Ahuja Source Type: research

Direct < i > Salmonella < /i > injection into enteroid cells allows the study of host –pathogen interactions in the cytosol with high spatiotemporal resolution
by Chantal Ernst, Patrick R. Andreassen, Gabriel H. Giger, Bidong D. Nguyen, Christoph G. G äbelein, Orane Guillaume-Gentil, Stefan A. Fattinger, Mikael E. Sellin, Wolf-Dietrich Hardt, Julia A. Vorholt Intestinal epithelial cells (IECs) play pivotal roles in nutrient uptake and in the protection against gut microorganisms. However, certain enteric pathogens, such asSalmonella enterica serovar Typhimurium (S. Tm), can invade IECs by employing flagella and type III secretion systems (T3SSs) with cognate effector proteins and exploit IECs as a replicative niche. Detection of flagella or T3SS proteins by IECs results in rapi...
Source: PLoS Biology: Archived Table of Contents - April 29, 2024 Category: Biology Authors: Chantal Ernst Source Type: research