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Transformer-based spatial–temporal detection of apoptotic cell death in live-cell imaging eLife (IF 7.7) Pub Date : 2024-03-18 Alain Pulfer, Diego Ulisse Pizzagalli, Paolo Armando Gagliardi, Lucien Hinderling, Paul Lopez, Romaniya Zayats, Pau Carrillo-Barberà, Paola Antonello, Miguel Palomino-Segura, Benjamin Grädel, Mariaclaudia Nicolai, Alessandro Giusti, Marcus Thelen, Luca Maria Gambardella, Thomas T Murooka, Olivier Pertz, Rolf Krause, Santiago Fernandez Gonzalez
Intravital microscopy has revolutionized live-cell imaging by allowing the study of spatial–temporal cell dynamics in living animals. However, the complexity of the data generated by this technology has limited the development of effective computational tools to identify and quantify cell processes. Amongst them, apoptosis is a crucial form of regulated cell death involved in tissue homeostasis and
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Single-cell RNA sequencing unveils the hidden powers of zebrafish kidney for generating both hematopoiesis and adaptive antiviral immunity eLife (IF 7.7) Pub Date : 2024-03-18 Chongbin Hu, Nan Zhang, Yun Hong, Ruxiu Tie, Dongdong Fan, Aifu Lin, Ye Chen, Li-xin Xiang, Jian-zhong Shao
The vertebrate kidneys play two evolutionary conserved roles in waste excretion and osmoregulation. Besides, the kidney of fish is considered as a functional ortholog of mammalian bone marrow that serves as a hematopoietic hub for generating blood cell lineages and immunological responses. However, knowledge about the properties of kidney hematopoietic cells, and the functionality of the kidney in
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Linking environmental factors and gene regulation eLife (IF 7.7) Pub Date : 2024-03-18 Signe Penner-Goeke, Elisabeth B Binder
A technique called mSTARR-seq sheds light on how DNA methylation may shape responses to external stimuli by altering the activity of sequences that control gene expression.
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Caspase-1 activates gasdermin A in non-mammals eLife (IF 7.7) Pub Date : 2024-03-18 Zachary Paul Billman, Stephen Bela Kovacs, Bo Wei, Kidong Kang, Ousmane H Cissé, Edward A Miao
Gasdermins oligomerize to form pores in the cell membrane, causing regulated lytic cell death called pyroptosis. Mammals encode five gasdermins that can trigger pyroptosis: GSDMA, B, C, D, and E. Caspase and granzyme proteases cleave the linker regions of and activate GSDMB, C, D, and E, but no endogenous activation pathways are yet known for GSDMA. Here, we perform a comprehensive evolutionary analysis
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Habitat loss weakens the positive relationship between grassland plant richness and above-ground biomass eLife (IF 7.7) Pub Date : 2024-03-18 Yongzhi Yan, Scott Jarvie, Qing Zhang
Habitat loss and fragmentation per se have been shown to be a major threat to global biodiversity and ecosystem function. However, little is known about how habitat loss and fragmentation per se alters the relationship between biodiversity and ecosystem function (BEF relationship) in the natural landscape context. Based on 130 landscapes identified by a stratified random sampling in the agro-pastoral
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Pleiotropic effects of trisomy and pharmacologic modulation on structural, functional, molecular, and genetic systems in a Down syndrome mouse model eLife (IF 7.7) Pub Date : 2024-03-18
Down syndrome (DS) is characterized by skeletal and brain structural malformations, cognitive impairment, altered hippocampal metabolite concentration and gene expression imbalance. These alterations were usually investigated separately, and the potential rescuing effects of green tea extracts enriched in epigallocatechin-3-gallate (GTE-EGCG) provided disparate results due to different experimental
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Dynamic 1D search and processive nucleosome translocations by RSC and ISW2 chromatin remodelers eLife (IF 7.7) Pub Date : 2024-03-18 Jee Min Kim, Claudia C Carcamo, Sina Jazani, Zepei Xie, Xinyu A Feng, Maryam Yamadi, Matthew Poyton, Katie L Holland, Jonathan B Grimm, Luke D Lavis, Taekjip Ha, Carl Wu
Eukaryotic gene expression is linked to chromatin structure and nucleosome positioning by ATP-dependent chromatin remodelers that establish and maintain nucleosome-depleted regions (NDRs) near transcription start sites. Conserved yeast RSC and ISW2 remodelers exert antagonistic effects on nucleosomes flanking NDRs, but the temporal dynamics of remodeler search, engagement, and directional nucleosome
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The molecular mechanism and evolutionary divergence of caspase 3/7-regulated gasdermin E activation eLife (IF 7.7) Pub Date : 2024-03-15 Hang Xu, Zihao Yuan, Kunpeng Qin, Shuai Jiang, Li Sun
Caspase (CASP) is a family of proteases involved in cleavage and activation of gasdermin, the executor of pyroptosis. In humans, CASP3 and CASP7 recognize the same consensus motif DxxD, which is present in gasdermin E (GSDME). However, human GSDME is cleaved by CASP3 but not by CASP7. The underlying mechanism of this observation is unclear. In this study, we identified a pyroptotic pufferfish GSDME
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Multiple objects evoke fluctuating responses in several regions of the visual pathway eLife (IF 7.7) Pub Date : 2024-03-15
How neural representations preserve information about multiple stimuli is mysterious. Because tuning of individual neurons is coarse (e.g., visual receptive field diameters can exceed perceptual resolution), the populations of neurons potentially responsive to each individual stimulus can overlap, raising the question of how information about each item might be segregated and preserved in the population
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Metabolic reprogramming of cancer cells by JMJD6-mediated pre-mRNA splicing associated with therapeutic response to splicing inhibitor eLife (IF 7.7) Pub Date : 2024-03-15 Carolyn M Jablonowski, Waise Quarni, Shivendra Singh, Haiyan Tan, Dhanushka Hewa Bostanthirige, Hongjian Jin, Jie Fang, Ti-Cheng Chang, David Finkelstein, Ji-Hoon Cho, Dongli Hu, Vishwajeeth Pagala, Sadie Miki Sakurada, Shondra M Pruett-Miller, Ruoning Wang, Andrew Murphy, Kevin Freeman, Junmin Peng, Andrew M Davidoff, Gang Wu, Jun Yang
Dysregulated pre-mRNA splicing and metabolism are two hallmarks of MYC-driven cancers. Pharmacological inhibition of both processes has been extensively investigated as potential therapeutic avenues in preclinical and clinical studies. However, how pre-mRNA splicing and metabolism are orchestrated in response to oncogenic stress and therapies is poorly understood. Here, we demonstrate that jumonji
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Gut microbiota-derived gamma-aminobutyric acid from metformin treatment reduces hepatic ischemia/reperfusion injury through inhibiting ferroptosis eLife (IF 7.7) Pub Date : 2024-03-15 Fangyan Wang, Xiujie Liu, Furong Huang, Yan Zhou, Xinyu Wang, Zhengyang Song, Sisi Wang, Xiaoting Wang, Dibang Shi, Gaoyi Ruan, Xiawei Ji, Eryao Zhang, Zenglin Tan, Yuqing Ye, Chuang Wang, Jesse Zhu, Wantie Wang
Hepatic ischemia/reperfusion injury (HIRI) is a common and inevitable factor leading to poor prognosis in various liver diseases, making the outcomes of current treatments in clinic unsatisfactory. Metformin has been demonstrated to be beneficial to alleviate HIRI in recent studies, however, the underpinning mechanism remains unclear. In this study, we found metformin mitigates HIRI-induced ferroptosis
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Sensitive remote homology search by local alignment of small positional embeddings from protein language models eLife (IF 7.7) Pub Date : 2024-03-15 Sean R Johnson, Meghana Peshwa, Zhiyi Sun
Accurately detecting distant evolutionary relationships between proteins remains an ongoing challenge in bioinformatics. Search methods based on primary sequence struggle to accurately detect homology between sequences with less than 20% amino acid identity. Profile- and structure-based strategies extend sensitive search capabilities into this twilight zone of sequence similarity but require slow pre-processing
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Comparative neuroimaging of sex differences in human and mouse brain anatomy eLife (IF 7.7) Pub Date : 2024-03-15 Elisa Guma, Antoine Beauchamp, Siyuan Liu, Elizabeth Levitis, Jacob Ellegood, Linh Pham, Rogier B Mars, Armin Raznahan, Jason P Lerch
In vivo neuroimaging studies have established several reproducible volumetric sex differences in the human brain, but the causes of such differences are hard to parse. While mouse models are useful for understanding the cellular and mechanistic bases of sex-specific brain development, there have been no attempts to formally compare human and mouse neuroanatomical sex differences to ascertain how well
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The pelvic organs receive no parasympathetic innervation eLife (IF 7.7) Pub Date : 2024-03-15 Margaux Sivori, Bowen Dempsey, Zoubida Chettouh, Franck Boismoreau, Maïlys Ayerdi, Annaliese Eymael, Sylvain Baulande, Sonia Lameiras, Fanny Coulpier, Olivier Delattre, Hermann Rohrer, Olivier Mirabeau, Jean-François Brunet
The pelvic organs (bladder, rectum, and sex organs) have been represented for a century as receiving autonomic innervation from two pathways – lumbar sympathetic and sacral parasympathetic – by way of a shared relay, the pelvic ganglion, conceived as an assemblage of sympathetic and parasympathetic neurons. Using single-cell RNA sequencing, we find that the mouse pelvic ganglion is made of four classes
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The voyage is as important as the harbor eLife (IF 7.7) Pub Date : 2024-03-15 Anton Sabantsev, Sebastian Deindl
To find nucleosomes, chromatin remodelers slide and hop along DNA, and their direction of approach affects the direction that nucleosomes slide in.
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Open-top Bessel beam two-photon light sheet microscopy for three-dimensional pathology eLife (IF 7.7) Pub Date : 2024-03-15
Nondestructive pathology based on three-dimensional (3D) optical microscopy holds promise as a complement to traditional destructive hematoxylin and eosin (H&E) stained slide-based pathology by providing cellular information in high throughput manner. However, conventional techniques provided superficial information only due to shallow imaging depths. Herein, we developed open-top two-photon light
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Mitochondrial genomes of Pleistocene megafauna retrieved from recent sediment layers of two Siberian lakes eLife (IF 7.7) Pub Date : 2024-03-15 Peter Andreas Seeber, Laura Batke, Yury Dvornikov, Alexandra Schmidt, Yi Wang, Kathleen Stoof-Leichsenring, Katie Moon, Samuel H Vohr, Beth Shapiro, Laura S Epp
Ancient environmental DNA (aeDNA) from lake sediments has yielded remarkable insights for the reconstruction of past ecosystems, including suggestions of late survival of extinct species. However, translocation and lateral inflow of DNA in sediments can potentially distort the stratigraphic signal of the DNA. Using three different approaches on two short lake sediment cores of the Yamal peninsula,
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Autistic and abroad eLife (IF 7.7) Pub Date : 2024-03-15 Andrew K Schulz
An AuDHD researcher recounts the highs and lows of relocating from the United States to Germany for his postdoc.
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WRNIP1 prevents transcription-associated genomic instability eLife (IF 7.7) Pub Date : 2024-03-15
R-loops are non-canonical DNA structures that form during transcription and play diverse roles in various physiological processes. Disruption of R-loop homeostasis can lead to genomic instability and replication impairment, contributing to several human diseases, including cancer. Although the molecular mechanisms that protect cells against such events are not fully understood, recent research has
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Causal role of the frontal eye field in attention-induced ocular dominance plasticity eLife (IF 7.7) Pub Date : 2024-03-13 Fangxing Song, Xue Dong, Jiaxu Zhao, Jue Wang, Xiaohui Sang, Xin He, Min Bao
Previous research has found that prolonged eye-based attention can bias ocular dominance. If one eye long-termly views a regular movie meanwhile the opposite eye views a backward movie of the same episode, perceptual ocular dominance will shift towards the eye previously viewing the backward movie. Yet it remains unclear whether the role of eye-based attention in this phenomenon is causal or not. To
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TLR2 regulates hair follicle cycle and regeneration via BMP signaling eLife (IF 7.7) Pub Date : 2024-03-14 Luyang Xiong, Irina Zhevlakova, Xiaoxia Z West, Detao Gao, Rakhilya Murtazina, Anthony Horak, J Mark Brown, Iuliia Molokotina, Eugene A Podrez, Tatiana V Byzova
The etiology of hair loss remains enigmatic, and current remedies remain inadequate. Transcriptome analysis of aging hair follicles uncovered changes in immune pathways, including Toll-like receptors (TLRs). Our findings demonstrate that the maintenance of hair follicle homeostasis and the regeneration capacity after damage depend on TLR2 in hair follicle stem cells (HFSCs). In healthy hair follicles
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A common cis-regulatory variant impacts normal-range and disease-associated human facial shape through regulation of PKDCC during chondrogenesis eLife (IF 7.7) Pub Date : 2024-03-14 Jaaved Mohammed, Neha Arora, Harold S Matthews, Karissa Hansen, Maram Bader, Susan Walsh, John R Shaffer, Seth M Weinberg, Tomek Swigut, Peter Claes, Licia Selleri, Joanna Wysocka
Genome-wide association studies (GWAS) identified thousands of genetic variants linked to phenotypic traits and disease risk. However, mechanistic understanding of how GWAS variants influence complex morphological traits and can, in certain cases, simultaneously confer normal-range phenotypic variation and disease predisposition, is still largely lacking. Here, we focus on rs6740960, a single nucleotide
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C9orf72 polyPR directly binds to various nuclear transport components eLife (IF 7.7) Pub Date : 2024-03-14 Hamidreza Jafarinia, Erik van der Giessen, Patrick R Onck
The disruption of nucleocytoplasmic transport (NCT) is an important mechanism in neurodegenerative diseases. In the case of C9orf72-ALS, trafficking of macromolecules through the nuclear pore complex (NPC) might get frustrated by the binding of C9orf72-translated arginine-containing dipeptide repeat proteins (R-DPRs) to the Kapβ family of nuclear transport receptors. Besides Kapβs, several other types
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Deciphering the genetic interactions between Pou4f3, Gfi1, and Rbm24 in maintaining mouse cochlear hair cell survival eLife (IF 7.7) Pub Date : 2024-03-14
Mammals harbor a limited number of sound-receptor hair cells (HCs) that cannot be regenerated after damage. Thus, investigating the underlying molecular mechanisms that maintain HC survival is crucial for preventing hearing impairment. Intriguingly, Pou4f3-/- or Gfi1-/- HCs form initially but then rapidly degenerate, whereas Rbm24-/- HCs degenerate considerably later. However, the transcriptional cascades
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Activity-dependent mitochondrial ROS signaling regulates recruitment of glutamate receptors to synapses eLife (IF 7.7) Pub Date : 2024-03-14 Rachel L Doser, Kaz M Knight, Ennis W Deihl, Frederic J Hoerndli
Our understanding of mitochondrial signaling in the nervous system has been limited by the technical challenge of analyzing mitochondrial function in vivo. In the transparent genetic model Caenorhabditis elegans, we were able to manipulate and measure mitochondrial ROS (reactive oxygen species) signaling of individual mitochondria as well as neuronal activity of single neurons in vivo. Using this approach
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Plasma extracellular vesicle synaptic proteins as biomarkers of clinical progression in patients with Parkinson’s disease eLife (IF 7.7) Pub Date : 2024-03-14
Synaptic dysfunction plays a key role in Parkinson’s disease (PD), and plasma extracellular vesicle (EV) synaptic proteins are emerging as biomarkers for neurodegenerative diseases. Assessment of plasma EV synaptic proteins for their efficacy as biomarkers in PD and their relationship with disease progression was conducted. In total, 144 participants were enrolled, including 101 people with PD (PwP)
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The catalytic mechanism of the RNA methyltransferase METTL3 eLife (IF 7.7) Pub Date : 2024-03-12 Ivan Corbeski, Pablo Andrés Vargas-Rosales, Rajiv Kumar Bedi, Jiahua Deng, Dylan Coelho, Emmanuelle Braud, Laura Iannazzo, Yaozong Li, Danzhi Huang, Mélanie Ethève-Quelquejeu, Qiang Cui, Amedeo Caflisch
The complex of methyltransferase-like proteins 3 and 14 (METTL3-14) is the major enzyme that deposits N6-methyladenosine (m6A) modifications on messenger RNA (mRNA) in humans. METTL3-14 plays key roles in various biological processes through its methyltransferase (MTase) activity. However, little is known about its substrate recognition and methyl transfer mechanism from its cofactor and methyl donor
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FBXO24 modulates mRNA alternative splicing and MIWI degradation and is required for normal sperm formation and male fertility eLife (IF 7.7) Pub Date : 2024-03-12
Spermiogenesis is a critical, post-meiotic phase of male gametogenesis, in which the proper gene expression is essential for sperm maturation. However, the underFlying molecular mechanism that controls mRNA expression in the round spermatids remains elusive. Here, we identify that FBXO24, an orphan F-box protein, is highly expressed in the testis of humans and mice and interacts with the splicing factors
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The push-pull intercrop Desmodium does not repel, but intercepts and kills pests eLife (IF 7.7) Pub Date : 2024-03-13 Anna L Erdei, Aneth B David, Eleni C Savvidou, Vaida Džemedžionaitė, Advaith Chakravarthy, Béla P Molnár, Teun Dekker
Over two decades ago, an intercropping strategy was developed that received critical acclaim for synergizing food security with ecosystem resilience in smallholder farming. The push-pull strategy reportedly suppresses lepidopteran pests in maize through a combination of a repellent intercrop (push), commonly Desmodium spp., and an attractive, border crop (pull). Key in the system is the intercrop's
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Structural constraints on the emergence of oscillations in multi-population neural networks eLife (IF 7.7) Pub Date : 2024-03-13 Jie Zang, Shenquan Liu, Pascal Helson, Arvind Kumar
Oscillations arise in many real-world systems and are associated with both functional and dysfunctional states. Whether a network can oscillate can be estimated if we know the strength of interaction between nodes. But in real-world networks (in particular in biological networks) it is usually not possible to know the exact connection weights. Therefore, it is important to determine the structural
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Maturation of cortical input to dorsal raphe nucleus increases behavioral persistence in mice eLife (IF 7.7) Pub Date : 2024-03-13 Nicolas Gutierrez-Castellanos, Dario Sarra, Beatriz S Godinho, Zachary F Mainen
The ability to persist towards a desired objective is a fundamental aspect of behavioral control whose impairment is implicated in several behavioral disorders. One of the prominent features of behavioral persistence is that its maturation occurs relatively late in development. This is presumed to echo the developmental time course of a corresponding circuit within late-maturing parts of the brain
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Mechanosensory neurons under pressure eLife (IF 7.7) Pub Date : 2024-03-13 Erin Cram
A build-up of eggs in the uterus of the nematode C. elegans triggers the release of large extracellular vesicles, called exophers, from neurons that are sensitive to mechanical forces.
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Noradrenaline release from the locus coeruleus shapes stress-induced hippocampal gene expression eLife (IF 7.7) Pub Date : 2024-03-13 Mattia Privitera, Lukas M von Ziegler, Amalia Floriou-Servou, Sian N Duss, Runzhong Zhang, Rebecca Waag, Sebastian Leimbacher, Oliver Sturman, Fabienne K Roessler, Annelies Heylen, Yannick Vermeiren, Debby Van Dam, Peter P De Deyn, Pierre-Luc Germain, Johannes Bohacek
Exposure to an acute stressor triggers a complex cascade of neurochemical events in the brain. However, deciphering their individual impact on stress-induced molecular changes remains a major challenge. Here, we combine RNA sequencing with selective pharmacological, chemogenetic, and optogenetic manipulations to isolate the contribution of the locus coeruleus-noradrenaline (LC-NA) system to the acute
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Sorting of secretory proteins at the trans-Golgi network by human TGN46 eLife (IF 7.7) Pub Date : 2024-03-11 Pablo Lujan, Carla Garcia-Cabau, Yuichi Wakana, Javier Vera Lillo, Carmen Rodilla-Ramírez, Hideaki Sugiura, Vivek Malhotra, Xavier Salvatella, Maria F Garcia-Parajo, Felix Campelo
Secretory proteins are sorted at the trans-Golgi network (TGN) for export into specific transport carriers. However, the molecular players involved in this fundamental process remain largely elusive. Here, we identified the human transmembrane protein TGN46 as a receptor for the export of secretory cargo protein PAUF in CARTS – a class of protein kinase D-dependent TGN-to-plasma membrane carriers.
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Articular cartilage corefucosylation regulates tissue resilience in osteoarthritis eLife (IF 7.7) Pub Date : 2024-03-11 Kentaro Homan, Tomohiro Onodera, Hisatoshi Hanamatsu, Jun-ichi Furukawa, Daisuke Momma, Masatake Matsuoka, Norimasa Iwasaki
This study aimed to investigate the glycan structural changes that occur before histological degeneration in osteoarthritis (OA) and to determine the mechanism by which these glycan conformational changes affect cartilage degeneration. An OA model was established in rabbits using mannosidase injection, which reduced high-mannose type N-glycans and led to cartilage degeneration. Further analysis of
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A novel imaging method (FIM-ID) reveals that myofibrillogenesis plays a major role in the mechanically induced growth of skeletal muscle eLife (IF 7.7) Pub Date : 2024-03-11 Kent W Jorgenson, Jamie E Hibbert, Ramy KA Sayed, Anthony N Lange, Joshua S Godwin, Paulo HC Mesquita, Bradley A Ruple, Mason C McIntosh, Andreas N Kavazis, Michael D Roberts, Troy A Hornberger
An increase in mechanical loading, such as that which occurs during resistance exercise, induces radial growth of muscle fibers (i.e. an increase in cross-sectional area). Muscle fibers are largely composed of myofibrils, but whether radial growth is mediated by an increase in the size of the myofibrils (i.e. myofibril hypertrophy) and/or the number of myofibrils (i.e. myofibrillogenesis) is not known
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Developmental conversion of thymocyte-attracting cells into self-antigen-displaying cells in embryonic thymus medulla epithelium eLife (IF 7.7) Pub Date : 2024-03-11 Izumi Ohigashi, Andrea J White, Mei-Ting Yang, Sayumi Fujimori, Yu Tanaka, Alison Jacques, Hiroshi Kiyonari, Yosuke Matsushita, Sevilay Turan, Michael C Kelly, Graham Anderson, Yousuke Takahama
Thymus medulla epithelium establishes immune self-tolerance and comprises diverse cellular subsets. Functionally relevant medullary thymic epithelial cells (mTECs) include a self-antigen-displaying subset that exhibits genome-wide promiscuous gene expression promoted by the nuclear protein Aire and that resembles a mosaic of extrathymic cells including mucosal tuft cells. An additional mTEC subset
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Coordinated head direction representations in mouse anterodorsal thalamic nucleus and retrosplenial cortex eLife (IF 7.7) Pub Date : 2024-03-12 Marie-Sophie H van der Goes, Jakob Voigts, Jonathan P Newman, Enrique HS Toloza, Norma J Brown, Pranav Murugan, Mark T Harnett
The sense of direction is critical for survival in changing environments and relies on flexibly integrating self-motion signals with external sensory cues. While the anatomical substrates involved in head direction (HD) coding are well known, the mechanisms by which visual information updates HD representations remain poorly understood. Retrosplenial cortex (RSC) plays a key role in forming coherent
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Random genetic drift sets an upper limit on mRNA splicing accuracy in metazoans eLife (IF 7.7) Pub Date : 2024-03-12 Florian Bénitière, Anamaria Necsulea, Laurent Duret
Most eukaryotic genes undergo alternative splicing (AS), but the overall functional significance of this process remains a controversial issue. It has been noticed that the complexity of organisms (assayed by the number of distinct cell types) correlates positively with their genome-wide AS rate. This has been interpreted as evidence that AS plays an important role in adaptive evolution by increasing
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Demystifying the ‘hidden curriculum’ for minoritized graduate students eLife (IF 7.7) Pub Date : 2024-03-12 Michael J Hopkins, Brittni N Moore, Jasmin L Jeffery, Andrea S Young
Graduate programs in the biomedical sciences dedicate considerable resources to recruiting students from underrepresented racial and ethnic groups. However, students from these minoritized groups have decreased access to the ‘hidden curriculum’ that must be navigated in order to be successful in graduate school. Here, we describe a student-led initiative at Johns Hopkins University, the Hidden Curriculum
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Perirenal adipose tissue contains a subpopulation of cold-inducible adipocytes derived from brown-to-white conversion eLife (IF 7.7) Pub Date : 2024-03-12 Houyu Zhang, Yan Li, Carlos F Ibáñez, Meng Xie
Perirenal adipose tissue (PRAT) is a unique visceral depot that contains a mixture of brown and white adipocytes. The origin and plasticity of such cellular heterogeneity remains unknown. Here, we combine single-nucleus RNA sequencing with genetic lineage tracing to reveal the existence of a distinct subpopulation of Ucp1-&Cidea+ adipocytes that arises from brown-to-white conversion during postnatal
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Neural criticality from effective latent variables eLife (IF 7.7) Pub Date : 2024-03-12 Mia C Morrell, Ilya Nemenman, Audrey Sederberg
Observations of power laws in neural activity data have raised the intriguing notion that brains may operate in a critical state. One example of this critical state is ‘avalanche criticality’, which has been observed in various systems, including cultured neurons, zebrafish, rodent cortex, and human EEG. More recently, power laws were also observed in neural populations in the mouse under an activity
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Combinatorial expression of γ-protocadherins regulates synaptic connectivity in the mouse neocortex eLife (IF 7.7) Pub Date : 2024-03-12 Yi-jun Zhu, Cai-yun Deng, Liu Fan, Ya-Qian Wang, Hui Zhou, Hua-tai Xu
In the process of synaptic formation, neurons must not only adhere to specific principles when selecting synaptic partners but also possess mechanisms to avoid undesirable connections. Yet, the strategies employed to prevent unwarranted associations have remained largely unknown. In our study, we have identified the pivotal role of combinatorial clustered protocadherin gamma (γ-PCDH) expression in
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Neural attentional filters and behavioural outcome follow independent individual trajectories over the adult lifespan eLife (IF 7.7) Pub Date : 2024-03-12 Sarah Tune, Jonas Obleser
Preserved communication abilities promote healthy ageing. To this end, the age-typical loss of sensory acuity might in part be compensated for by an individual’s preserved attentional neural filtering. Is such a compensatory brain–behaviour link longitudinally stable? Can it predict individual change in listening behaviour? We here show that individual listening behaviour and neural filtering ability
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Gene expression plasticity followed by genetic change during colonization in a high-elevation environment eLife (IF 7.7) Pub Date : 2024-03-12 Huishang She, Yan Hao, Gang Song, Xu Luo, Fumin Lei, Weiwei Zhai, Yanhua Qu
Phenotypic plasticity facilitates organismal invasion of novel environments, and the resultant phenotypic change may later be modified by genetic change, so called ‘plasticity first.’ Herein, we quantify gene expression plasticity and regulatory adaptation in a wild bird (Eurasian Tree Sparrow) from its original lowland (ancestral stage), experimentally implemented hypoxia acclimation (plastic stage)
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Imidacloprid disrupts larval molting regulation and nutrient energy metabolism, causing developmental delay in honey bee Apis mellifera eLife (IF 7.7) Pub Date : 2024-03-11 Zhi Li, Yuedi Wang, Qiqian Qin, Lanchun Chen, Xiaoqun Dang, Zhengang Ma, Zeyang Zhou
Imidacloprid is a global health threat that severely poisons the economically and ecologically important honeybee pollinator, Apis mellifera. However, its effects on developing bee larvae remain largely unexplored. Our pilot study showed that imidacloprid causes developmental delay in bee larvae, but the underlying toxicological mechanisms remain incompletely understood. In this study, we exposed bee
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A binding site for phosphoinositides described by multiscale simulations explains their modulation of voltage-gated sodium channels eLife (IF 7.7) Pub Date : 2024-03-11 Yiechang Lin, Elaine Tao, James P Champion, Ben Corry
Voltage-gated sodium channels (Naᵥ) are membrane proteins which open to facilitate the inward flux of sodium ions into excitable cells. In response to stimuli, Naᵥ channels transition from the resting, closed state to an open, conductive state, before rapidly inactivating. Dysregulation of this functional cycle due to mutations causes diseases including epilepsy, pain conditions, and cardiac disorders
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Oxygen isotopes in orangutan teeth reveal recent and ancient climate variation eLife (IF 7.7) Pub Date : 2024-03-08 Tanya M Smith, Manish Arora, Christine Austin, Janaína Nunes Ávila, Mathieu Duval, Tze Tshen Lim, Philip J Piper, Petra Vaiglova, John de Vos, Ian S Williams, Jian-xin Zhao, Daniel R Green
Studies of climate variation commonly rely on chemical and isotopic changes recorded in sequentially produced growth layers, such as in corals, shells, and tree rings, as well as in accretionary deposits—ice and sediment cores, and speleothems. Oxygen isotopic compositions (δ18O) of tooth enamel are a direct method of reconstructing environmental variation experienced by an individual animal. Here
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Interactions between circuit architecture and plasticity in a closed-loop cerebellar system eLife (IF 7.7) Pub Date : 2024-03-07 Hannah L Payne, Jennifer L Raymond, Mark S Goldman
Determining the sites and directions of plasticity underlying changes in neural activity and behavior is critical for understanding mechanisms of learning. Identifying such plasticity from neural recording data can be challenging due to feedback pathways that impede reasoning about cause and effect. We studied interactions between feedback, neural activity, and plasticity in the context of a closed-loop
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TEAD1 is crucial for developmental myelination, Remak bundles, and functional regeneration of peripheral nerves eLife (IF 7.7) Pub Date : 2024-03-08 Matthew Grove, Hyukmin Kim, Shuhuan Pang, Jose Paz Amaya, Guoqing Hu, Jiliang Zhou, Michel A Lemay, Young-Jin Son
Previously we showed that the hippo pathway transcriptional effectors, YAP and TAZ, are essential for Schwann cells (SCs) to develop, maintain and regenerate myelin (Grove et al., 2017; Grove, Lee, Zhao, & Son, 2020). Although TEAD1 has been implicated as a partner transcription factor, the mechanisms by which it mediates YAP/TAZ regulation of SC myelination are unclear. Here, using conditional and
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Structural basis for the phase separation of the chromosome passenger complex eLife (IF 7.7) Pub Date : 2024-03-08 Nikaela W Bryan, Aamir Ali, Ewa Niedzialkowska, Leland Mayne, P Todd Stukenberg, Ben E Black
The physical basis of phase separation is thought to consist of the same types of bonds that specify conventional macromolecular interactions yet is unsatisfyingly often referred to as 'fuzzy'. Gaining clarity on the biogenesis of membraneless cellular compartments is one of the most demanding challenges in biology. Here, we focus on the chromosome passenger complex (CPC), that forms a chromatin body
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How larvae feel the world around them eLife (IF 7.7) Pub Date : 2024-03-08
A complete map of the external sense organs shows how fruit fly larvae detect different aspects of their environment.
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Ex vivo expansion potential of murine hematopoietic stem cells is a rare property only partially predicted by phenotype eLife (IF 7.7) Pub Date : 2024-03-06
The scarcity of hematopoietic stem cells (HSCs) restricts their use in both clinical settings and experimental research. Here, we examined a recently developed method for expanding rigorously purified murine HSCs ex vivo. After 3 weeks of culture, only 0.1% of cells exhibited the input HSC phenotype, but these accounted for almost all functional long-term HSC activity. Input HSCs displayed varying
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The non-muscle actinopathy-associated mutation E334Q in cytoskeletal γ-actin perturbs interaction of actin filaments with myosin and ADF/cofilin family proteins eLife (IF 7.7) Pub Date : 2024-03-06 Johannes N Greve, Anja Marquardt, Robin Heiringhoff, Theresia Reindl, Claudia Thiel, Nataliya Di Donato, Manuel H Taft, Dietmar J Manstein
Various heterozygous cytoskeletal γ-actin mutations have been shown to cause Baraitser–Winter cerebrofrontofacial syndrome, non-syndromic hearing loss, or isolated eye coloboma. Here, we report the biochemical characterization of human cytoskeletal γ-actin carrying mutation E334Q, a mutation that leads to a hitherto unspecified non-muscle actinopathy. Following expression, purification, and removal
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Dorsolateral prefrontal activity supports a cognitive space organization of cognitive control eLife (IF 7.7) Pub Date : 2024-03-06 Guochun Yang, Haiyan Wu, Qi Li, Xun Liu, Zhongzheng Fu, Jiefeng Jiang
Cognitive control resolves conflicts between task-relevant and -irrelevant information to enable goal-directed behavior. As conflicts can arise from different sources (e.g., sensory input, internal representations), how a limited set of cognitive control processes can effectively address diverse conflicts remains a major challenge. Based on the cognitive space theory, different conflicts can be parameterized
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Establishment of transgenic fluorescent mice for labeling synapses and screening synaptogenic adhesion molecules eLife (IF 7.7) Pub Date : 2024-03-07 Lei Yang, Jingtao Zhang, Sen Liu, Yanning Zhang, Li Wang, Xiaotong Wang, Shanshan Wang, Ke Li, Mengping Wei, Chen Zhang
Synapse is the fundamental structure for neurons to transmit information between cells. The proper synapse formation is crucial for developing neural circuits and cognitive functions of the brain. The aberrant synapse formation has been proved to cause many neurological disorders, including autism spectrum disorders and intellectual disability. Synaptic cell adhesion molecules (CAMs) are thought to
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Disrupting abnormal neuronal oscillations with adaptive delayed feedback control eLife (IF 7.7) Pub Date : 2024-03-07 Domingos L Castro, Miguel Aroso, A Pedro Aguiar, David B Grayden, Paulo Aguiar
Closed-loop neuronal stimulation has a strong therapeutic potential for neurological disorders such as Parkinson's disease. However, at the moment, standard stimulation protocols rely on continuous open-loop stimulation and the design of adaptive controllers is an active field of research. Delayed Feedback Control (DFC), a popular method used to control chaotic systems, has been proposed as a closed-loop
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Exploring factors shaping antibiotic resistance patterns in Streptococcus pneumoniae during the 2020 COVID-19 pandemic eLife (IF 7.7) Pub Date : 2024-03-07 Aleksandra Kovacevic, David RM Smith, Eve Rahbé, Sophie Novelli, Paul Henriot, Emmanuelle Varon, Robert Cohen, Corinne Levy, Laura Temime, Lulla Opatowski
Non-pharmaceutical interventions implemented to block SARS-CoV-2 transmission in early 2020 led to global reductions in the incidence of invasive pneumococcal disease (IPD). By contrast, most European countries reported an increase in antibiotic resistance among invasive Streptococcus pneumoniae isolates from 2019 to 2020, while an increasing number of studies reported stable pneumococcal carriage
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Identification of fallopian tube microbiota and its association with ovarian cancer eLife (IF 7.7) Pub Date : 2024-03-07 Bo Yu, Congzhou Liu, Sean C Proll, Enna Manhardt, Shuying Liang, Sujatha Srinivasan, Elizabeth Swisher, David N Fredricks
Investigating the human fallopian tube (FT) microbiota has significant implications for understanding the pathogenesis of ovarian cancer (OC). In this large prospective study, we collected swabs intraoperatively from the FT and other surgical sites as controls to profile the microbiota in the FT and to assess its relationship with OC. Eighty-one OC and 106 non-cancer patients were enrolled and 1001
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Sequentially activated discrete modules appear as traveling waves in neuronal measurements with limited spatiotemporal sampling eLife (IF 7.7) Pub Date : 2024-03-07 Yuval Orsher, Ariel Rom, Rotem Perel, Yoav Lahini, Pablo Blinder, Mark Shein-Idelson
Numerous studies have identified traveling waves in the cortex and suggested they play important roles in brain processing. These waves are most often measured using macroscopic methods that are unable to assess the local spiking activity underlying wave dynamics. Here, we investigated the possibility that waves may not be traveling at the single neuron scale. We first show that sequentially activating