bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clustering of home delivery in Bangladesh and its predictors: evidence from the linked household and health facility level survey data
Authors: Fatima Kaniz , Khanam Shimlin Jahan , Rahman Md Mostafizur , Kabir Md Iqbal , Khan Md Nuruzzaman 
Published: October 2023

AbstractBackgroundAround half of births in Bangladesh occur at home without skilled birth personnel. This study aims to identify the geographical hot spots and cold spots of home delivery in Bangladesh and associated factors.MethodsWe analyzed data from the 2017/2018 Bangladesh Demographic and Health Survey and the 2017 Bangladesh Health Facility Survey. The outcome variable was home delivery without skilled personnel supervision (yes, no). Explanatory variables included individual, household, community, and healthcare facility factors. Moran’s I was used to determine hot spots and cold spots of home delivery. Geographically weighted regression models were used to identify cluster-specific predictors of home delivery.ResultsThe prevalence of non-supervised and unskilled supervised home delivery was 53.18%. Hot spots of non-supervised and unskilled supervised home delivery were primarily in Dhaka, Khulna, Rajshahi, and Rangpur divisions. Cold spots of home delivery were mainly in Mymensingh and Sylhet divisions. Predictors of higher home births in hot spot areas included women’s illiteracy, lack of formal job engagement, higher number of children ever born, partner’s agriculture occupation, higher community-level illiteracy, and greater distance to the nearest healthcare facility from women’s homes.ConclusionsUnskilled supervised home delivery is prevalent in Bangladesh, and the distance between women’s homes and healthcare facilities plays a significant role. Awareness-building programs should emphasize the importance of skilled and supervised hospital deliveries, particularly among the poor and disadvantaged groups.
Associations of arterial thickness, stiffness and blood pressure with brain morphology in early adolescence: A prospective population-based study
Authors: Defina Serena , Silva Carolina C.V. , Cecil Charlotte A.M. , Tiemeier Henning , Felix Janine F. , Mutzel Ryan L. , Jaddoe Vincent W.V. 
Published: October 2023

AbstractBackgroundArterial wall thickness and stiffness and high blood pressure have been repeatedly associated with poorer brain health. However, previous studies largely focused on mid- or late-life stages. It is unknown whether any arterial health-related brain changes may be observable already in adolescence.MethodsWe examined whether(i)carotid intima-media thickness,(ii)carotid distensibility and(iii)systolic and diastolic blood pressure, measured at age 10, were associated with brain volumes and/or white matter microstructure (i.e., fractional anisotropy and mean diffusivity) at age 14. In addition to cross-sectional analyses, we explored associations with longitudinal change in each brain outcome from 10 to 14 years. Analyses were based on 5341 children from the Generation R Study.ResultsHigher diastolic blood pressure was associated with lower total brain (β[95%CI] = -0.04 [- 0.07;-0.01]) and grey matter volumes (β[95%CI] = -0.04 [-0.07;-0.01]) at age 14 years, with stronger associations in higher diastolic blood pressure ranges. Similar associations emerged between systolic blood pressure and brain volumes but these were no longer significant after adjusting for birthweight. No associations were observed between blood pressure and white matter microstructure, nor between carotid intima-media thickness or distensibility and brain morphology.ConclusionsArterial blood pressure, but not intima-media thickness and distensibility, is associated with structural neuroimaging markers in early adolescence. Volumetric measures may be more sensitive to these early arterial health differences compared to microstructural properties of the white matter, but further studies are needed to confirm these results and assess potential causal mechanisms.Graphic Abstract
VIPERA: Viral Intra-Patient Evolution Reporting and Analysis
Authors: Álvarez-Herrera Miguel , Sevilla Jordi , Ruiz-Rodriguez Paula , Vergara Andrea , Vila Jordi , Cano-Jiménez Pablo , González-Candelas Fernando , Comas Iñaki , Coscollá Mireia 
Published: October 2023

AbstractViral mutations within patients nurture the adaptive potential of SARS-CoV-2 during chronic infections, which are a potential source of variants of concern. However, there is no integrated framework for the evolutionary analysis of intra-patient SARS-CoV-2 serial samples. Herein we describe VIPERA (Viral Intra-Patient Evolution Reporting and Analysis), a new software that integrates the evaluation of the intra-patient ancestry of SARS-CoV-2 sequences with the analysis of evolutionary trajectories of serial sequences from the same viral infection. We have validated it using positive and negative control datasets and have successfully applied it to a new case, thus enabling an easy and automatic analysis of intra-patient SARS-CoV-2 sequences.
Stage-Specific Modulation of Multinucleation, Fusion and Resorption by the Long Non-coding RNA DLEU1 and miR-16 in Human Primary Osteoclasts
Authors: Moura Sara Reis , Sousa Ana Beatriz , Olesen Jacob Bastholm , Barbosa Mário Adolfo , Søe Kent , Almeida Maria Inês 
Published: October 2023

AbstractOsteoclasts are multinucleated cells formed through fusion of mononucleated precursors of the myeloid lineage and are the only cells that can resorb all the constituents of the bone matrix. Our goal was to investigate the role of long non-coding RNADLEU1and miR-16-5p in the fusion of human primary osteoclasts and their resorptive capacity. We foundDLEU1to be markedly upregulated, whereas miR-16 was significantly suppressed, during osteoclast differentiation, suggesting a potential involvement in the multinucleation process. The knockdown ofDLEU1or the overexpression of miR-16 in human primary pre-osteoclasts from male human donors (50 years or older) impaired fusion at both early and late time-points, each in distinct ways, without affecting cell viability. Time-lapse recordings confirmed the impairment of the fusion process and showed an abrogation of the phagocytic cup fusion modality, as well as a reduction of the fusion between mononucleated precursors and multinucleated osteoclasts duringDLEU1silencing. Furthermore, mass spectrometry-based quantitative proteomics revealed that the effects ofDLEU1and miR-16 on osteoclast fusion were mediated by distinct proteins and processes. Thus, bothDLEU1inhibition and/or miR-16 overexpression hinder osteoclast fusion through modulation of different mechanisms. Moreover, decreased levels ofDLEU1specifically affected the resorption speed of pit-making osteoclasts, while increased levels of miR-16 promoted bone resorption mainly through pit-formation, impairing the resorption speed of the osteoclasts making trenches and affecting their resorbed area. Taken together, these findings identifyDLEU1and miR-16 as mediators of osteoclast fusion and activity, offering potential new therapeutic targets to ameliorate bone destruction in skeletal diseases with accentuated bone deterioration.
Representing context and priority in working memory
Authors: Wan Quan , Ardalan Adel , Fulvio Jacqueline M. , Postle Bradley R. 
Published: October 2023

AbstractThe ability to prioritize among contents in working memory (WM) is critical for successful control of thought and behavior. Recent work has demonstrated that prioritization in WM can be implemented by representing different states of priority in different representational formats. Here, we explored the mechanisms underlying WM prioritization by simulating the double serial retrocuing (DSR) task with recurrent neural networks (RNNs). Visualization of stimulus representational dynamics using principal component analysis (PCA) revealed that the network represented trial context (order of presentation) and priority via different mechanisms. Ordinal context, a stable property lasting the duration of the trial, was accomplished bysegregatingrepresentations into orthogonal subspaces. Priority, which changed multiple times during a trial, was accomplished byseparatingrepresentations into different manifolds within each subspace. We assessed the generality of these mechanism by applying dimensionality reduction and multiclass decoding to fMRI and EEG datasets and found that priority and context are represented differently along the dorsal visual stream, and that behavioral performance is sensitive to trial-by-trial efficacy of priority coding, but not context coding.
An ancient subcortical circuit decides when to orient to threat in humans
Authors: Trier Hailey A , Khalighinejad Nima , Hamilton Sorcha , Harbison Caroline , Priestley Luke , Laubach Mark , Scholl Jacqueline , Rushworth Matthew FS 
Published: October 2023

AbstractMany psychiatric symptoms have been linked to threat-related perception and learning processes. In addition, however, there may also be mechanisms for balancing effectively between threat- and reward-related behaviors and these may also vary between individuals. We investigated neural activity associated with spontaneous switching between foraging for rewards and vigilance for threats with 7T fMRI. In a virtual naturalistic environment, participants freely switched between the two modes of behavior. Switching was driven by estimates of likelihood of threat and reward. Both tracking of threat and switching to vigilance were associated with specific but distributed patterns of activity spanning habenula, dorsal raphe nucleus (DRN), anterior cingulate cortex, and anterior insula cortex. Distinct distributed patterns heralded returns to reward-oriented behavior. Individual variation in DRN activity reflected individual variation in vigilance. All activity patterns were replicated in an initially held-out portion of data.
Inducible degradation-coupled phosphoproteomics identifies PP2ARts1as a novel eisosome regulator
Authors: DeMarco Andrew G. , Dibble Marcella G. , Hall Mark C. 
Published: October 2023

ABSTRACTReversible protein phosphorylation is an abundant post-translational modification dynamically regulated by opposing kinases and phosphatases. Protein phosphorylation has been extensively studied in cell division, where waves of cyclin-dependent kinase activity, peaking in mitosis, drive the sequential stages of the cell cycle. Here we developed and employed a strategy to specifically probe kinase or phosphatase substrates at desired times or experimental conditions in the model organismSaccharomyces cerevisiae.We combined auxin- inducible degradation (AID) with mass spectrometry-based phosphoproteomics, which allowed us to arrest physiologically normal cultures in mitosis prior to rapid phosphatase degradation and phosphoproteome analysis. Our results revealed that protein phosphatase 2A coupled with its B56 regulatory subunit, Rts1 (PP2ARts1), is involved in dephosphorylation of numerous proteins in mitosis, highlighting the need for phosphatases to selectively maintain certain proteins in a hypophosphorylated state in the face of high mitotic kinase activity. Unexpectedly, we observed elevated phosphorylation at many sites on several subunits of the fungal eisosome complex following rapid Rts1 degradation. Eisosomes are dynamic polymeric assemblies that create furrows in the plasma membrane important in regulating nutrient import, lipid metabolism, and stress responses, among other things. We found that PP2ARts1-mediated dephosphorylation of eisosomes promotes their plasma membrane association and we provide evidence that this regulation impacts eisosome roles in metabolic homeostasis. The combination of rapid, inducible protein degradation with proteomic profiling offers several advantages over common protein disruption methods for characterizing substrates of regulatory enzymes involved in dynamic biological processes.
Structure and regulation of GSDMD pores at the plasma membrane of pyroptotic cells
Authors: Kappelhoff Shirin , Holtmannspötter Michael , Schaefer Stefan L. , Margheritis Eleonora G. , Veit Hannah , Danial John S.H. , Strauss Sebastian , Franzkoch Rico , Psathaki Olympia Ekaterini , Jungmann Ralf , Kurre Rainer , Hummer Gerhard , Piehler Jacob , Cosentino Katia 
Published: October 2023

ABSTRACTGasdermin D (GSDMD) executes inflammatory cell death pyroptosis by permeabilizing the plasma membrane (PM). We introduce polymer-supported PM (PSPM) to gain access to the cytoplasmic side of the PM with imaging techniques while preserving the native PM complexity and lipid microenvironment. By combining PSPM with DNA-PAINT super-resolution microscopy we visualized, for the first time, GSDMD nanostructures directly at the PM of pyroptotic cells. We resolved diverse macromolecular architectures with ring-and arc-shaped GSDMD oligomers that enable PM permeabilization. The pyroptotically-inactive mutant GSDMD-C192A (human C191A) still interacts with the PM however fails to form pores. GSDMD expression levels affect pore density but not permeabilization ability. Finally, we identified the local PI(3,4,5)P3concentration as a key regulatory element of PM permeabilization. Increase in PI(3,4,5)P3levels in the PM during pyroptosis facilitates growth into large ring-shaped pores. Using molecular dynamics (MD) simulations, we identified the mechanism by which PI(3,4,5)P3stabilizes the GSDMD assembly.
Fast-track adaptive laboratory evolution ofCupriavidus necatorH16 with divalent metal cations
Authors: Sitompul Sepwin Nosten , Price Joseph , Tee Kang Lan , Wong Tuck Seng 
Published: October 2023

AbstractMicrobial strain improvement through adaptive laboratory evolution (ALE) has been a key strategy in biotechnology for enhancing desired phenotypic traits. Here, we present an accelerated ALE (aALE) workflow and its successful implementation in evolvingC. necatorH16 for enhanced tolerance towards elevated glycerol concentrations. The method involves the deliberate induction of genetic diversity through controlled exposure to divalent metal cations, enabling the rapid identification of improved variants. Through this approach, we observed the emergence of robust variants capable of growing in high glycerol concentration environments, demonstrating the efficacy of our aALE workflow. Our method offers several advantages over traditional ALE approaches, including its independence from genetically modified strains, specialized genetic tools, and potentially hazardous DNA-modifying agents. By utilizing divalent metal cations as mutagens, we offer a safer, more efficient, and cost-effective alternative for expansion of genetic diversity. With its ability to foster rapid microbial evolution, aALE serves as a valuable addition to the ALE toolbox, holding significant promise for the advancement of microbial strain engineering and bioprocess optimization.
Metataxonomic analysis of halophilic archaea community in two geothermal springs sources in southern Tunisian Sahara
Authors: Najjari Afef , Elmnasri Khaled , Cherif Hanene , Guesmi Amel , Mahjoubi Mouna , Linares-Pastén Javier A. , Cherif Ameur , Ouzari Hadda-Imene 
Published: October 2023

AbstractIn this study, we assess the phylogenetic diversity of the halophilic archaeal community of biotechnological interest that inhabit in geothermal water in southern Tunisia. These waters are usually used for farming purposes, particularly for irrigation of the oases and greenhouses, due to the limited availability of surface freshwater resources and the arid climate. The samples processed from two separated geothermal sources in southern Tunisia based on the Illumina Miseq sequencing approach. Three samples including water, sediment, and halite-soil crust, were collected from downstream of two geothermal springs of Ksar Ghilane (KGH) and Zaouet Al Aness (ZAN) oases. Results showed that several haloarchaea-related members were identified in geothermal springs. The average taxonomic composition showed that 20 genera out of 33 were shared between the two geothermal sources with uneven distribution, where theHalogranumgenus is the most represented genus with an abundance of 18.9% and 11.58% for ZAW and KGH, respectively. Several unique site-specific genera were also observed; the case ofHalonotius, Halopelagius, Natronorubrum, andHaloarculain ZAN, andHaloprofundus, Halomarina, Halovivax, Haloplanus, Natrinema, Halobium, Natronoarchaeum, Haloterrigenadetected in KGH pool. We noticed that the majority of genus members are usually found in low-salinity ecosystems. The finding of this study suggests that haloarchaea-related members could survive in downstream geothermal sources, which may have resulted from the leaching of salts and minerals through drilling waters creating chemically complex saline systems.
Structure of the yeast ceramide synthase
Authors: Schäfer Jan-Hannes , Clausmeyer Lena , Körner Carolin , Esch Bianca M. , Wolf Verena N. , Walter Stefan , Januliene Dovile , Moeller Arne , Fröhlich Florian 
Published: October 2023

AbstractCeramides play a pivotal role as essential lipids, serving as foundational components for complex sphingolipids and potent signaling molecules. Ceramides are the products of the N-acylation of a sphingoid base and a CoA-activated fatty acid. This reaction is catalyzed by the enzymes of the evolutionarily conserved ceramide synthase (CerS) family. Yet, the precise structural details and catalytic mechanisms of CerSs have remained elusive. Here, we employed cryo-EM single particle analysis to unravel the structure of the yeast ceramide synthase complex in both an active and a fumonisin B1 inhibited state. Our findings shed light on the complex’s architecture, revealing a dimer of Lip1 subunits bound to the two catalytic subunits, Lag1 and Lac1. Each catalytic subunit forms a hydrophobic crevice that is accessible from both the cytosolic site as well as from the intermembrane space of the endoplasmic reticulum (ER). Within this cavity, we identify amino acids forming the active center and a sphingoid base, one of the substrates of the complex. Together, this suggests a pre-loaded state of the CerS. Additionally, the fumonisin B1 bound structure reveals the inhibitory mechanism by blocking the cytosolic acyl-CoA binding site.
The signal sequence of yeast killer toxin K2 confers producer self-protection and allows conversion into a modular toxin-antitoxin system
Authors: Prins Rianne C. , Billerbeck Sonja 
Published: October 2023

AbstractSome antimicrobial proteins secreted by yeast, known as yeast killer toxins, also target the producer species itself, necessitating a means of self-protection. Intriguingly, the M2 dsRNA killer virus inSaccharomyces cerevisiaecontains a single open reading frame (ORF) that encodes both the pore-forming killer toxin K2 as well as a cognate immunity factor. Here, a systematic deletion screen reveals that expression of a 49-amino acid N-terminal peptide from this ORF is both necessary and sufficient for immunity and that the K2 toxin and this 49-residue immunity peptide can be functionally split into a modular toxin-antitoxin system. Further, the immunity peptide exhibits characteristics of a signal peptide and we thus propose that the K2 signal peptide serves a dual function: 1) Toxin targeting into the secretory pathway, and 2) establishing self-protective immunity. This case further implies that (signal) peptides form a potential source for antimicrobial resistance.
Regulator of G protein signaling 6 (RGS6) in ventral tegmental area (VTA) dopamine neurons promotes EtOH seeking, behavioral reward and susceptibility to relapse
Authors: Spicer Mackenzie M. , Weber Matthew A. , Luo Zili , Yang Jianqi , Narayanan Nandakumar S. , Fisher Rory A. 
Published: October 2023

AbstractMesolimbic dopamine (DA) transmission is believed to play a critical role in mediating reward responses to drugs of abuse, including alcohol (EtOH). EtOH is the most abused substance worldwide with chronic consumption often leading to the development of dependence and abuse. Unfortunately, the neurobiological mechanisms underlying EtOH-seeking behavior and dependence are not fully understood, and abstinence remains the only effective way to prevent alcohol use disorders (AUDs). Here, we developed novel RGS6fl/fl; DAT-iCreER mice to determine the role of RGS6 in VTA DA neurons on EtOH consumption and reward behaviors. We found that RGS6 is expressed in DA neurons in both human and mouse VTA, and that RGS6 loss in mice upregulates DA transporter (DAT) expression in VTA DA neuron synaptic terminals. Remarkably, loss of RGS6 in VTA DA neurons significantly reduced EtOH consumption, preference, and reward in a manner indistinguishable from that seen in RGS6−/−mice. Strikingly, RGS6 loss from VTA DA neurons before or after EtOH behavioral reward is established significantly reduced (∼50%) re-instatement of reward following extinguishment, demonstrating distinct roles of RGS6 in promoting reward and relapse susceptibility to EtOH. These studies illuminate a critical role of RGS6 in the mesolimbic circuit in promoting EtOH seeking, reward, and reinstatement. We propose that RGS6 functions to promote DA transmission through its function as a negative modulator of GPCR-Gαi/o-DAT signaling in VTA DA neurons. These studies identify RGS6 as a potential therapeutic target for behavioral reward and relapse to EtOH.
Spatially resolved DNP-assisted NMR illuminates the conformational ensemble of α-synuclein in intact viable cells
Authors: Kragelj Jaka , Ghosh Rupam , Xiao Yiling , Dumarieh Rania , Lagasca Dominique , Krishna Sakshi , Frederick Kendra K. 
Published: October 2023

ABSTRACTThe protein α-syn adopts a wide variety of conformations including an intrinsically disordered monomeric form and an α-helical rich membrane-associated form that is thought to play an important role in cellular membrane processes. However, despite the high affinity of α-syn for membranes, evidence that the α-helical form is adopted inside cells has been indirect. DNP-assisted solid state NMR on frozen cellular samples can report on protein conformations inside cells. Moreover, by controlling the distribution of the DNP polarization agent throughout the cellular biomass, such experiments can provide quantitative information upon the entire structural ensemble or provide information about spatially resolved sub-populations. Using DNP-assisted magic angle spinning (MAS) NMR we establish that purified α-syn in the membrane-associated and intrinsically disordered forms have distinguishable spectra. We then introduced isotopically labeled monomeric α-syn into cells. When the DNP polarization agent is dispersed homogenously throughout the cell, we found that a minority of the α-syn inside cells adopted a highly α-helical rich conformation. When the DNP polarization agent is peripherally localized, we found that the α-helical rich conformation predominates. Thus, we provide direct evidence that α-helix rich conformations of α-syn are adopted near the cellular periphery inside cells under physiological conditions. Moreover, we demonstrate how selectively altering the spatial distribution of the DNP polarization agent can be a powerful tool to observe spatially distinct structural ensembles. This approach paves the way for more nuanced investigations into the conformations that proteins adopt in different areas of the cell.