bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying characteristics and clinical conditions associated with hand grip strength in adults: the Baseline Health Study
Authors: Taylor Kenneth A. , Carroll Megan K. , Short Sarah , Goode Adam P. 
Published: February 2023

AbstractBackgroundLow hand grip strength (HGS) predicts several conditions, but its value outside of the older adult population is unclear. We sought to identify the most salient factors associated with HGS using a rich list of candidate variables while stratifying by age and sex.MethodsWe used data from the initial visit from the Project Baseline Health Study (N=2502) which captured detailed demographic, occupational, social, lifestyle, and clinical data. We applied MI-LASSO using group methods to determine variables most associated with HGS out of 175 candidate variables. We performed analyses separately for sex and age (<65 vs. ≥65).ResultsRace was associated with HGS to varying degrees across groups. Osteoporosis and osteopenia were negatively associated with HGS in female study participants. Immune cell counts were negatively associated with HGS for male participants ≥65 (neutrophils) and female participants (≥65, monocytes; <65, lymphocytes). Most findings were age and/or sex group-specific; few were common across all groups.ConclusionsSeveral of the variables associated with HGS in each group were novel, while others corroborate previous research. Our results support HGS as a useful indicator of a variety of clinical characteristics; however, its utility varies by age and sex.
TopNEXt: Automatic DDA Exclusion Framework for Multi-Sample Mass Spectrometry Experiments
Authors: McBride Ross , Wandy Joe , Weidt Stefan , Rogers Simon , Davies Vinny , Daly Rónán , Bryson Kevin 
Published: February 2023

AbstractMotivationLiquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) experiments aim to produce high quality fragmentation spectra which can be used to identify metabolites. However, current Data-Dependent Acquisition (DDA) approaches may fail to collect spectra of sufficient quality and quantity for experimental outcomes, and extend poorly across multiple samples by failing to share information across samples or by requiring manual expert input.ResultsWe present TopNEXt, a real-time scan prioritisation framework that improves data acquisition in multi-sample LC-MS/MS metabolomics experiments. TopNEXt extends traditional DDA exclusion methods across multiple samples by using a Region of Interest (RoI) and intensity-based scoring system. Through both simulated and lab experiments we show that methods incorporating these novel concepts acquire fragmentation spectra for an additional 10% of our set of target peaks and with an additional 20% of acquisition intensity. By increasing the quality and quantity of fragmentation spectra, TopNEXt can help improve metabolite identification with a potential impact across a variety of experimental contexts.AvailabilityTopNEXt is implemented as part of the ViMMS framework and the latest version can be found athttps://github.com/glasgowcompbio/vimms. A stable version used to produce our results can be found at10.5281/zenodo.7468914. Data can be found at10.5525/gla.researchdata.1382.Contactr.mcbride.1@research.gla.ac.ukorvinny.davies@glasgow.ac.ukSupplementary informationSupplementary data are available atBioarxivonline.
The histone chaperone activity of SPT2 controls chromatin structure and function in Metazoa
Authors: Saredi Giulia , Carelli Francesco N. , Furlan Giulia , Rolland Stephane , Piquet Sandra , Appert Alex , Sanchez-Pulido Luis , Price Jonathan L. , Alcon Pablo , Lampersberger Lisa , Déclais Anne-Cécile , Ramakrishna Navin B. , Toth Rachel , Ponting Chris P. , Polo Sophie E. , Miska Eric A. , Ahringer Julie , Gartner Anton , Rouse John 
Published: February 2023

AbstractHistone chaperones control nucleosome density and chromatin structure. In yeast, the H3-H4 chaperone Spt2 controls histone deposition at active genes but its roles in metazoan chromatin structure and organismal physiology are not known. Here we identify theCaenorhabditis elegansorthologue of SPT2 (CeSPT-2) and show that its ability to bind histones H3-H4 is important for germline development and transgenerational epigenetic gene silencing, and thatspt-2mutants display signatures of a global stress response. Genome-wide profiling showed that CeSPT-2 binds to a range of highly expressed genes, and we find thatspt-2 mutants have increased chromatin accessibility at these loci. We also show that human SPT2 controls the incorporation of new H3.3 into chromatin. Our work reveals roles for SPT2 in controlling chromatin structure and function in Metazoa.
3D Microcapsules for Human Bone Marrow Derived Mesenchymal Stem Cell Biomanufacturing in a Vertical-Wheel Bioreactor
Authors: Teryek Matthew , Jadhav Pankaj , Bento Raphaela , Parekkadan Biju 
Published: February 2023

AbstractMicroencapsulation of human mesenchymal stromal cells (MSCs) via electrospraying has been well documented in tissue engineering and regenerative medicine. Herein, we report the use of microencapsulation, via electrospraying, for MSC expansion using a commercially available hydrogel that is durable, optimized to MSC culture, and enzymatically degradable for cell recovery. Critical parameters of the electrospraying encapsulation process such as seeding density, correlation of microcapsule output with hydrogel volume, and applied voltage were characterized to consistently fabricate cell-laden microcapsules of uniform size. Upon encapsulation, we then verified ∼ 10x expansion of encapsulated MSCs within a vertical-wheel bioreactor and the preservation of critical quality attributes such as immunophenotype and multipotency after expansion and cell recovery. Finally, we highlight the genetic manipulation of encapsulated MSCs as an example of incorporating bioactive agents in the capsule material to create new compositions of MSCs with altered phenotypes.
Genetic manipulation of betta fish
Authors: Palmiotti Alec , Lichak Madison R , Shih Pei-Yin , Bendesky Andres 
Published: February 2023

AbstractBetta splendens, also known as Siamese fighting fish or ‘betta’, are renowned for their astonishing morphological diversity and extreme aggressive behavior. Despite recent advances in our understanding of the genetics and neurobiology of betta, the lack of tools to manipulate their genome has hindered progress at functional and mechanistic levels. In this study, we outline the use of three genetic manipulation technologies, which we have optimized for use in betta: CRISPR/Cas9-mediated knockout, CRISPR/Cas9-mediated knockin, and Tol2-mediated transgenesis. We knocked out three genes:alkal2l, bco1l, andmitfa, and analyzed their effects on viability and pigmentation. Furthermore, we successfully knocked in a fluorescent protein into themitfalocus, a proof-of-principle experiment of this powerful technology in betta. Finally, we used Tol2-mediated transgenesis to create fish with ubiquitous expression of GFP, and then developed a bicistronic plasmid with heart-specific expression of a red fluorescent protein to serve as a visible marker of successful transgenesis. Our work highlights the potential for the genetic manipulation of betta, providing valuable resources for the effective use of genetic tools in this animal model.
Proteomic analyses of the Arabidopsis cap-binding complex define core set and TOR-dependent protein components
Authors: Matthes Annemarie , Ouibrahim Laurence , Lecampion Cécile , Caranta Carole , Davanture Marlène , Lebrun Régine , Couté Yohann , Baudet Mathieu , Meyer Christian , Robaglia Christophe 
Published: February 2023

AbstractThe eukaryotic cap-binding complex (CBC) is a hub for regulations affecting mRNA behaviour including translation, degradation and storage. Beside the core eukaryotic translation initiation factors, other proteins, many of which are yet unknown, are thought to interact stably or transiently with the CBC depending on cell status. The prototype of these regulators is the animal eIF4E binding protein (4E-BP), a direct target of the TOR (Target of Rapamycin) kinase that competes with the cap-binding protein eIF4E, thus repressing translation. In plants, no functional homologs of 4E-BP have so far been characterized. In this work we performed several deep proteomic analyses of the Arabidopsis CBC after cap-affinity purification from wild-type plants. We also investigated the CBC in eIF4E mutant plants, Arabidopsis lines with lower TOR activity, or during infection with eIF4E-dependent potyviruses, conditions which are all affecting translation at the initiation level. These analyses allowed us to define a limited core set of CBC components, which were detected in all samples. Interestingly, we identified proteins, like AGO1 or VCS, which were always detected in conditions where either TOR or mRNA translation were reduced. Meta-analysis of these data revealed several new plant interactors of the CBC, potentially defining pathways related to mRNA stability and degradation, metabolism and viral life cycle. A search for eIF4E binding motifs identified several new potential 4E-BP relatives in plants.
Endothelial Cells are Heterogeneous in Different Brain Regions and are Dramatically Altered in Alzheimer’s Disease
Authors: Bryant Annie , Li Zhaozhi , Jayakumar Rojashree , Serrano-Pozo Alberto , Woost Benjamin , Hu Miwei , Woodbury Maya E. , Wachter Astrid , Lin Gen , Kwon Taekyung , Talanian Robert V. , Biber Knut , Karran Eric H. , Hyman Bradley T. , Das Sudeshna , Bennett Rachel 
Published: February 2023

AbstractVascular endothelial cells play an important role in maintaining brain health, but their contribution to Alzheimer’s disease (AD) is obscured by limited understanding of the cellular heterogeneity in normal aged brain and in disease. To address this, we performed single nucleus RNAseq on tissue from 32 AD and non-AD donors each with five cortical regions: entorhinal cortex, inferior temporal gyrus, prefrontal cortex, visual association cortex and primary visual cortex. Analysis of 51,586 endothelial cells revealed unique gene expression patterns across the five regions in non-AD donors. Alzheimer’s brain endothelial cells were characterized by upregulated protein folding genes and distinct transcriptomic differences in response to amyloid beta plaques and cerebral amyloid angiopathy (CAA). This dataset demonstrates previously unrecognized regional heterogeneity in the endothelial cell transcriptome in both aged non-AD and AD brain.Significance StatementIn this work, we show that vascular endothelial cells collected from five different brain regions display surprising variability in gene expression. In the presence of Alzheimer’s disease pathology, endothelial cell gene expression is dramatically altered with clear differences in regional and temporal changes. These findings help explain why certain brain regions appear to differ in susceptibility to disease-related vascular remodeling events that may impact blood flow.
The pseudokinase Trib1 regulates the transition of exhausted T cells to a KLR+CD8+effector state and its deletion improves checkpoint blockade
Authors: McClory Susan E. , Bardhan Oishi , Rome Kelly S. , Giles Josephine R. , Baxter Amy E. , Xu Lanwei , Gimotty Phyllis A. , Faryabi Robert B. , Wherry E. John , Pear Warren S. , Jordan Martha S. 
Published: February 2023

AbstractT cell exhaustion (TEX) impairs the ability of T cells to clear chronic infection or cancer. While exhausted T cells are hypofunctional, some exhausted T cells retain effector gene signatures, a feature that is associated with expression of KLRs (killer lectin-like receptors). Although KLR+T cells may improve control of chronic antigen, the signaling molecules regulating this population are poorly understood. Using scRNA-seq, flow cytometry, RNA velocity, and scTCR-seq, we demonstrate that deleting the pseudokinase Trib1 shifts TEXtowards CX3CR1+intermediates (TINT) with robust enrichment of KLR+CD8+T cells (TKLR) via clonal T cell expansion. These changes are associated with globally increased KLR gene expression throughout the exhaustion program. Further, Trib1 loss augments anti-PD-L1 blockade to improve viral clearance by expanding the TKLRpopulation. Together, these data identify Trib1 as an important regulator of T cell exhaustion whose targeting enhances the KLR+effector state and improves the response to checkpoint inhibitor therapy.
Enhanced simulations of whole-brain dynamics using hybrid resting-state structural connectomes
Authors: Manos Thanos , Diaz-Pier Sandra , Fortel Igor , Driscoll Ira , Zhan Liang , Leow Alex 
Published: February 2023

AbstractThe human brain, composed of billions of neurons and synaptic connections, is an intricate network coordinating a sophisticated balance of excitatory and inhibitory activity between brain regions. The dynamical balance between excitation and inhibition is vital for adjusting neural input/output relationships in cortical networks and regulating the dynamic range of their responses to stimuli. To infer this balance using connectomics, we recently introduced a computational framework based on the Ising model, first developed to explain phase transitions in ferromagnets, and proposed a novel hybrid resting-state structural connectome (rsSC). Here, we show that a generative model based on the Kuramoto phase oscillator can be used to simulate static and dynamic functional connectomes (FC) with rsSC as the coupling weight coefficients, such that the simulated FC well aligns with the observed FC when compared to that simulated with traditional structural connectome. Simulations were performed using the open source framework The Virtual Brain on High Performance Computing infrastructure.
Exploring the Optimization of Autoencoder Design for Imputing Single-Cell RNA Sequencing Data
Authors: Xi Nan Miles , Li Jingyi Jessica 
Published: February 2023

AbstractAutoencoders are the backbones of many imputation methods that aim to relieve the sparsity issue in single-cell RNA sequencing (scRNA-seq) data. The imputation performance of an autoencoder relies on both the neural network architecture and the hyperparameter choice. So far, literature in the single-cell field lacks a formal discussion on how to design the neural network and choose the hyperparameters. Here, we conducted an empirical study to answer this question. Our study used many real and simulated scRNA-seq datasets to examine the impacts of the neural network architecture, the activation function, and the regularization strategy on imputation accuracy and downstream analyses. Our results show that (i) deeper and narrower autoencoders generally lead to better imputation performance; (ii) the sigmoid and tanh activation functions consistently outperform other commonly used functions including ReLU; (iii) regularization improves the accuracy of imputation and downstream cell clustering and DE gene analyses. Notably, our results differ from common practices in the computer vision field regarding the activation function and the regularization strategy. Overall, our study offers practical guidance on how to optimize the autoencoder design for scRNA-seq data imputation.
Regulated assembly and neurosteroid modulation constrain GABAAreceptor pharmacologyin vivo
Authors: Sun Chang , Zhu Hongtao , Clark Sarah , Gouaux Eric 
Published: February 2023

SummaryType A GABA receptors (GABAARs) are the principal inhibitory receptors in the brain and the target of a wide range of clinical agents, including anesthetics, sedatives, hypnotics, and antidepressants. However, our understanding of GABAAR pharmacology has been hindered by the vast number of pentameric assemblies that can be derived from a total 19 different subunits and the lack of structural knowledge of clinically relevant receptors. Here, we isolate native murine GABAAR assemblies containing the widely expressed α1subunit, and elucidate their structures in complex with drugs used to treat insomnia (zolpidem and flurazepam) and postpartum depression (the neurosteroid allopregnanolone). Using cryo-EM analysis and single-molecule photobleaching experiments, we uncover only three structural populations in the brain: the canonical α1β2γ2receptor containing two α1subunits and two unanticipated assemblies containing one α1and either an α2, α3or α5subunit. Both of the noncanonical assemblies feature a more compact arrangement between the transmembrane and extracellular domains. Interestingly, allopregnanolone is bound at the transmembrane α/β subunit interface, even when not added to the sample, revealing an important role for endogenous neurosteroids in modulating native GABAARs. Together with structurally engaged lipids, neurosteroids produce global conformational changes throughout the receptor that modify both the pore diameter and binding environments for GABA and insomnia medications. Together, our data reveal that GABAAR assembly is a strictly regulated process that yields a small number of structurally distinct complexes, defining a structural landscape from which subtype-specific drugs can be developed.
Nine-residue low-complexity disordered peptide as a model system, an NMR/CD study
Authors: Vugmeyster Liliya , Rodgers Aryana , Gwin Kirsten , Ostrovsky Dmitry , Smirnov Serge L. 
Published: February 2023

AbstractDisordered proteins and protein segments can be crucial for biological function. In this work we present a detailed biophysical characterization of the low-complexity nine-residue peptide with the sequence GGKGMGFGL. Based on proton solution NMR chemical shifts, circular dichroism measurements, as well as the analysis of concentration dependence of NMR linewidth, proton longitudinal relaxation times, hydrogen-deuterium exchange measurements, and15N rotating frame NMR relaxation measurements, we conclude that the peptide is fully disordered and monomeric in solution. The peptide will serve as a model system for future structural and dynamics studies of biologically relevant disordered peptides in solution and solid states.
Mechanistic insights into the UFM1 E3 ligase complex in ufmylation and ribosome-associated protein quality control
Authors: Ishimura Ryosuke , Ito Sota , Mao Gaoxin , Komatsu-Hirota Satoko , Inada Toshifumi , Noda Nobuo N , Komatsu Masaaki 
Published: February 2023

SummaryUbiquitin-fold modifier 1 (UFM1) is a ubiquitin-like protein covalently conjugated with intracellular proteins through ufmylation, similar to ubiquitylation. Ufmylation is involved in processes such as endoplasmic reticulum (ER)-associated protein degradation, ribosome-associated protein quality control (RQC) at the ER (ER-RQC), and ER-phagy. However, it remains unclear how ufmylation regulates such distinct ER-related functions. Herein, we provide insights into the mechanism of the UFM1 E3 complex in not only ufmylation but also ER-RQC. The E3 complex consisting of UFL1 and UFBP1 interacted with UFC1, UFM1 E2, and subsequently CDK5RAP3, the last of which is an adaptor for ufmylating ribosomal subunit RPL26. When CDK5RAP3 was absent from the E3 complex, UFBP1 ufmylation occurred, a process thought to drive ER-phagy. Further, upon treatment with anisomycin, an inducer of disome formation, the UFM1 E3 complex associated with ufmylated RPL26 on the 60S ribosomal subunit through the UFM1-interacting region of UFBP1. Loss of E3 components or disruption of the interaction between UFBP1 and ufmylated RPL26 attenuated ER-RQC. These results clarify the molecular mechanism of the UFM1 system and provide new insights into the role of ufmylation.
Generation of human cerebral organoids with a structured outer subventricular zone
Authors: Walsh Ryan , Giacomelli Elisa , Ciceri Gabriele , Rittenhouse Chelsea , Galimberti Maura , Wu Youjun , Muller James , Vezzoli Elena , Jungverdorben Johannes , Zhou Ting , Barker Roger A , Cattaneo Elena , Studer Lorenz , Baggiolini Arianna 
Published: February 2023

SummaryMammalian outer radial glia (oRG) emerge as cortical progenitor cells that directly support the development of an enlarged outer subventricular zone (oSVZ) and, in turn, the expansion of the neocortex. Thein vitrogeneration of oRG is essential to model and investigate the underlying mechanisms of human neocortical development and expansion. By activating the STAT3 pathway using LIF, which is not produced in guided cortical organoids, we developed a cerebral organoid differentiation method from human pluripotent stem cells (hPSCs) that recapitulates the expansion of a progenitor pool into the oSVZ. The structured oSVZ is composed of progenitor cells expressing specific oRG markers such asGFAP, LIFR, HOPX, which closely matches human oRGin vivo. In this microenvironment, cortical neurons showed faster maturation with enhanced metabolic and functional activity. Incorporation of hPSC-derived brain vascular LIF- producing pericytes in cerebral organoids mimicked the effects of LIF treatment. These data indicate that the cellular complexity of the cortical microenvironment, including cell-types of the brain vasculature, favors the appearance of oRG and provides a platform to routinely study oRG in hPSC-derived brain organoids.
‘Brave men’ and ‘pampered children’: Male bodies, labour and coming of age in Belgian Congo
Authors: Henriet Benoît 
Published: February 2023

AbstractThis article sheds light on male identities in interwar Belgian Congo by using the colony's largest palm oil concession as a case study. Based on colonial archives and oral testimonies, it shows how vernacular and colonial understandings of masculinity interplayed and keep on influencing ways to ‘be a man’ in the present. This article is divided into four parts. First, it highlights how vigorous male bodies supposedly constituted entry points in the colonial ‘civilizing mission’. Second, it addresses the convergences between coming‐of‐age rituals and of palm oil labour as markers of adulthood. Third, it nuances the association of dominant masculinity with brute force by showing how the ‘strongest’ palm oil workers were suspected to use witchcraft. Fourth, it addresses the apparent contradiction between recollection of colonial labour as an experience of hardships and paternalist ‘pampering’.
FRINGE FINANCIAL ECOLOGIES AND PLACE‐BASED EXCLUSION: A Tale of Two Cities
Authors: Dunham Ian , Foster Alec 
Published: February 2023

AbstractAccess to safe and affordable financial services is essential to the economic well‐being of individual households and entire urban neighborhoods. However, prior research raises concerns about spatial inequities in the distribution of brick‐and‐mortar financial services offerings—either mainstream financial institutions or alternative ‘fringe’ financial service providers—and the resulting implications for financial inclusion and social justice. This study uses a novel method to identify fringe financial ecologies that captures the recent tandem processes of abandonment by mainstream financial institutions and the proliferation of alternative financial service providers. We explore how fringe financial ecologies potentially overlap existing inequalities of race, class and subprime mortgage lending in two US metropolitan areas, Los Angeles, California, and Miami, Florida. Our results raise concerns that communities of color, low‐income neighborhoods and otherwise vulnerable segments of the population are disproportionately at risk of both financial exclusion and predatory targeting. We find that fringe financial ecologies are associated with a high prevalence of subprime mortgage lending. The results advance an understanding of financial ecologies that raises awareness about place‐based financial exclusion as a form of systemic racism in the broader context of the national reckoning with racial justice in the US.