bluuebunny/crossref_metadata_2025_split huggingface dataset:
Astrocyte-like subpopulation of NG2 glia in the adult mouse cortex exhibits characteristics of neural progenitor cells and is capable of forming neuron-like cells after ischemic injury
Authors: Janeckova Lucie , Knotek Tomas , Kriska Jan , Hermanova Zuzana , Kirdajova Denisa , Kubovciak Jan , Berkova Linda , Tureckova Jana , Garcia Sara Camacho , Galuskova Katerina , Kolar Michal , Anderova Miroslava , Korinek Vladimir 
Published: February 2023

ABSTRACTGlia cells expressing neuron-glial antigen 2 (NG2) play a critical role as oligodendrocyte precursor cells (OPCs) in the healthy brain; however, their differentiation potential after ischemic injury remains an unresolved question. Here, we aimed to elucidate the heterogeneity and role of NG2 glia in the ischemic brain. We used transgenic mice to label NG2-expressing cells and their progeny with red fluorescent protein tdTomato in the healthy brains and those after focal cerebral ischemia (FCI). Based on single-cell RNA sequencing, the labeled glial cells were divided into five distinct subpopulations. The identity of these subpopulations was determined based on gene expression patterns. In addition, membrane properties were further analyzed using the patch-clamp technique. Three of the observed subpopulations represented OPCs, whereas the fourth group exhibited characteristics of cells destined for oligodendrocyte fate. The fifth subpopulation of NG2 glia carried astrocytic markers. Importantly, we detected features of neural progenitors in these cells. This subpopulation was present in both healthy and post-ischemic tissue; however, its gene expression changed after ischemia, with genes related to neurogenesis being more abundant. Neurogenic gene expression was monitored over time and complemented by immunohistochemical staining, which showed increased numbers of Purkinje cell protein 4-positive NG2 cells at the edge of the ischemic lesion 12 days after FCI, and NeuN-positive NG2 cells 28 days after injury, indicating the existence of neuron-like cells that develop from NG2 glia in the ischemic tissue. Our results provide further insight into the differentiation plasticity and neurogenic potential of NG2 glia after stroke.Main PointsDifferent subpopulations of NG2 glia in the healthy and ischemic adult cortex were identified based on their gene expression and membrane properties.Astrocyte-like NG2 glia exhibit neurogenic gene expression and are more abundant in post-ischemic tissue.Progeny of NG2-positive cells carrying neuronal marker NeuN was observed at the edge of the ischemic lesion.
A stochastic analysis of the interplay between antibiotic dose, mode of action, and bacterial competition in the evolution of antibiotic resistance
Authors: Czuppon Peter , Day Troy , Débarre Florence , Blanquart François 
Published: February 2023

AbstractThe use of an antibiotic may lead to the emergence and spread of bacterial strains resistant to this antibiotic. Experimental and theoretical studies have investigated the drug dose that minimizes the risk of resistance evolution over the course of treatment of an individual, showing that the optimal dose will either be the highest or the lowest drug concentration possible to administer; however, no analytical results exist that help decide between these two extremes. To address this gap, we develop a stochastic mathematical model of bacterial dynamics under antibiotic treatment. We explore various scenarios of density regulation (bacterial density affects cell birth or death rates), and antibiotic modes of action (biostatic or biocidal). We derive analytical results for the survival probability of the resistant subpopulation until the end of treatment, the size of the resistant subpopulation at the end of treatment, the carriage time of the resistant subpopulation until it is replaced by a sensitive one after treatment, and we verify these results with stochastic simulations. We find that the scenario of density regulation and the drug mode of action are important determinants of the survival of a resistant subpopulation. Resistant cells survive best when bacterial competition reduces cell birth and under biocidal antibiotics. Compared to an analogous deterministic model, the population size reached by the resistant type is larger and carriage time is slightly reduced by stochastic loss of resistant cells. Moreover, we obtain an analytical prediction of the antibiotic concentration that maximizes the survival of resistant cells, which may help to decide which drug dosage (not) to administer. Our results are amenable to experimental tests and help link the within and between host scales in epidemiological models.
Event-related modulation of alpha rhythm explains the auditory P300 evoked response in EEG
Authors: Studenova A.A. , Forster C. , Engemann D.A. , Hensch T. , Sander C. , Mauche N. , Hegerl U. , Loeffler M. , Villringer A. , Nikulin V.V. 
Published: February 2023

AbstractEvoked responses and oscillations represent two major electrophysiological phenomena in the human brain yet the link between them remains rather obscure. Here we show how most frequently studied EEG signals: the P300-evoked response and alpha oscillations (8–12 Hz) can be linked with the baseline-shift mechanism. This mechanism states that oscillations generate evoked responses if oscillations have a non-zero mean and their amplitude is modulated by the stimulus. Therefore, the following predictions should hold: 1) the temporal evolution of P300 and alpha amplitude is similar, 2) spatial localisations of the P300 and alpha amplitude modulation overlap, 3) oscillations are non-zero mean, 4) P300 and alpha amplitude correlate with cognitive scores in a similar fashion. To validate these predictions, we analysed the data set of elderly participants (N=2230, 60–82 years old), using a) resting-state EEG recordings to quantify the mean of oscillations, b) the event-related data, to extract parameters of P300 and alpha rhythm amplitude envelope. We showed that P300 is indeed linked to alpha rhythm, according to all four predictions. Our results provide an unifying view on the interdependency of evoked responses and neuronal oscillations and suggest that P300, at least partly, is generated by the modulation of alpha oscillations.
Rainbow trout neomales broodstocks are able to eat and use a high carbohydrate diet during a complete reproductive cycle
Authors: Nathan Favalier , Anne Surget , Vincent Véron , Patrick Maunas , Nicolas Turonnet , Frederic Terrier , Stéphane Panserat , Lucie Marandel 
Published: February 2023

AbstractThe main challenge of the aquaculture relies on the shift from fishmeal to more sustainable ingredients. Interest on carbohydrates has growing rapidly as they are considered as promising resources, providing energy and preserving proteins for growth. However, rainbow trout is considered as a poor user of carbohydrates displaying postprandial hyperglycaemia and impaired growth performances when fed with diets containing more than 20% of carbohydrates. Nonetheless, recent evidence points that broodstocks could be better user of high carbohydrate diet compared to juveniles. However, no study investigates how sex-reversed females – neomales – eat, grow and reproduce under a high carbohydrate diet. Our objective was thus to assess growth and reproductive performances of neomales fed with a high carbohydrate diet during an entire reproductive cycle. Our results demonstrate that neomales display specific metabolic and physiological changes when fed with a high carbohydrate diet compared to both females and males broodstocks as well as compared to juveniles. Altogether, our data demonstrate the critical relevance to formulate specific diets in accordance with specificities of each type of broodstocks (i.e. females, males and neomales).
Molecular Investigation of TSHR gene in Bangladeshi Congenital Hypothyroid patients
Authors: Begum Mst. Noorjahan , Mahtarin Rumana , Islam Md Tarikul , Ahmed Sinthyia , Konika Tasnia Kawsar , Mannoor Kaiissar , Akhteruzzaman Sharif , Qadri Firdausi 
Published: February 2023

AbstractThe disorder of thyroid gland development or thyroid dysgenesis (TH) accounts for 80-85% cases of congenital hypothyroidism (CH). Hence, the understanding of molecular etiology of TH is prerequisite. Mutations in TSHR gene is mostly associated with thyroid dysgenesis, prevent or disrupt normal development of the gland. The current study detects two nonsynonymous mutations (p.Ser508Leu, p.Asp727Glu) in transmembrane (TM)-region (Exon 10) of TSHR gene in 21 patients with dysgenesis by sequencing-based analysis. Later, transmembrane (TM)-region of TSHR protein is modelled by homology modeling. Transmembrane (TM)-region of TSHR protein is targeted by small molecules thyrogenic drugs, MS437 and MS438 to perceive the effect of mutations. The damaging effect in drug-protein complexes of mutants were envisaged by molecular docking and interactions. The binding affinity of wild type protein was much higher than the mutant cases for both of the ligands (MS437 and MS438). Molecular dynamics simulates dynamic behavior of wild type and mutant complexes. MS437-TSHR368-764MT2 and MS438-TSHR368-764MT1 show stable conformations in biological environments. Finally, PCA reveals structural and energy profile discrepancies. TSHR368-764MT1 exhibits much variations than TSHR368-764WT and TSHR368-764MT2, emphasizing more damaging pattern in TSHR368-764MT1. The study might be helpful to understand molecular etiology of thyroid dysgenesis (TH) exploring the mutational impact on TSHR protein to the interaction with agonists.
Gene expression plasticity followed by genetic change during colonization a high-elevation environment
Authors: She Huishang , Hao Yan , Song Gang , Luo Xu , Lei Fumin , Zhai Weiwei , Qu Yanhua 
Published: February 2023

AbstractPhenotypic 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) and colonized highland (colonized stage). Using a group of co-expressed genes from the cardiac and flight muscle, respectively, we demonstrate that gene expression plasticity to hypoxia tolerance is more often reversed than reinforced at the colonized stage. By correlating gene expression change with muscle phenotypes, we show that colonized tree sparrows reduce maladaptive plasticity that largely associates with decrease hypoxia tolerance. Conversely, adaptive plasticity that is congruent with increase hypoxia tolerance is often reinforced in the colonized tree sparrows. Genes displaying large levels of reinforcement or reversion plasticity (i.e., 200% of original level) show greater genetic divergence between ancestral and colonized populations. Overall, our work demonstrates that gene expression plasticity at the initial stage of high-elevation colonization can be reversed or reinforced through selection-driven adaptive modification.
Variability of the innate immune response is globally constrained by transcriptional bursting
Authors: Alachkar Nissrin , Norton Dale , Wolkensdorfer Zsofia , Muldoon Mark , Paszek Pawel 
Published: February 2023

AbstractTranscription of almost all mammalian genes occurs in stochastic bursts, however the fundamental control mechanisms that allow appropriate single-cell responses remain unresolved. Here we utilise single cell genomics data and stochastic models of transcription to perform global analysis of the toll-like receptor (TLR)-induced gene expression variability. Based on analysis of more than 2000 TLR-response genes across multiple experimental conditions we demonstrate that the single-cell, gene-by-gene expression variability can be empirically described by a linear function of the population mean. We show that response heterogeneity of individual genes can be characterised by the slope of the mean-variance line, which captures how cells respond to stimulus and provides insight into evolutionary differences between species. We further demonstrate that linear relationships theoretically determine the underlying transcriptional bursting kinetics, revealing different regulatory modes of TLR response heterogeneity. Stochastic modelling of temporal scRNA-seq count distributions demonstrates that increased response variability is associated with larger and more frequent transcriptional bursts, which emerge via increased complexity of transcriptional regulatory networks between genes and different species. Overall, we provide a methodology relying on inference of empirical mean-variance relationships from single cell data and new insights into control of innate immune response variability.
A Mechanistic Insight into Sources of Error of Visual Working Memory in Multiple Sclerosis
Authors: Motahharynia Ali , Pourmohammadi Ahmad , Adibi Armin , Shaygannejad Vahid , Ashtari Fereshteh , Adibi Iman , Sanayei Mehdi 
Published: February 2023

AbstractWorking memory (WM) is one of the most affected cognitive domains in multiple sclerosis (MS), which is mainly studied by the previously established binary model for information storage (slot model). However, recent observations based on the continuous reproduction paradigms have shown that assuming dynamic allocation of WM resources (resource model) instead of the binary hypothesis will give more accurate predictions in WM assessment. Moreover, continuous reproduction paradigms allow for assessing the distribution of error in recalling information, providing new insights into the organization of the WM system. Hence, by utilizing two continuous reproduction paradigms, memory-guided localization (MGL) and analog recall task with sequential presentation, we investigated WM dysfunction in MS. Our results demonstrated an overall increase in recall error and decreased recall precision in MS. Furthermore, computational modeling of the results from the sequential paradigm determined that imprecision in decoding information and swap error (mistakenly reporting the feature of other presented items) were responsible for WM dysfunction in MS. Overall, this study offered a sensitive measure for assessing WM deficit and provided new insight into the organization of the WM system in MS population.
Towards estimating the number of strains that make up a natural bacterial population
Authors: Viver Tomeu , Conrad Roth E. , Rodriguez-R Luis M. , Ramírez Ana S. , Venter Stephanus N. , Rocha-Cárdenas Jairo , Llabrés Mercè , Amann Rudolf , Konstantinidis Konstantinos T. , Rossello-Mora Ramon 
Published: February 2023

AbstractWhat a strain is and how many strains make up a natural bacterial population remain elusive concepts despite their apparent importance for assessing the role of intra-population diversity in disease emergence or response to environmental perturbations. To advance these concepts, we sequenced 138 randomly selectedSalinibacter ruberisolates from two solar salterns and assessed these genomes against companion short-read metagenomes from the same samples. The distribution of genome-aggregate average nucleotide identity (ANI) values among these isolates revealed a bimodal distribution, with significantly lower occurrence of values between 99.2% and 99.8% relative to ANI >99.8% or <99.2%, revealing a natural “gap” in the sequence space within species. Accordingly, we used this ANI gap to define genomovars and a higher ANI value of >99.99% and shared gene-content >99.0% to define strains. Using these thresholds and extrapolating from how many metagenomic reads each genomovar uniquely recruited, we estimated that –although our 138 isolates represented about 80% of theSal. ruberpopulation– the total population in one pond is composed of 5,500 to 11,000 genomovars, the great majority of which appear to be rarein situ. These data also revealed that the most frequently recovered isolate in lab media was often not the most abundant genomovarin situ, suggesting that cultivation biases are significant, even in cases that cultivation procedures are thought to be robust. Preliminary analyses of available genomes revealed that the thresholds used for defining strains and distinct intra-species units (genomovars) may be broadly applicable to additional bacterial species.Significance StatementStrains are the smallest distinguishable units within a microbial species. Strains that carry unique gene content often underly the emergence of disease outbreaks and the response of the species to environmental perturbations. Therefore, a major challenge in microbiome research across environmental and clinical settings is to evaluate how many strains of the same species coexist in nature and how dominant strains emerge from this diversity. Unfortunately, the available theoretical concept of strain is not directly applicable to culture-independent surveys. Here, we provide such a practical definition for strain and use it to show that that the number of strains making up a natural bacterial population may be large, in the order of a few thousands, but not infinite.
MYC-driven increases in mitochondrial DNA copy number occur early and persist throughout prostatic cancer progression
Authors: Chen Jiayu , Zheng Qizhi , Hicks Jessica L. , Trabzonlu Levent , Ozbek Busra , Jones Tracy , Vaghasia Ajay , Larman Tatianna C. , Wang Rulin , Markowski Mark C. , Denmeade Sam R. , Pienta Kenneth J. , Hruban Ralph H. , Antonarakis Emmanuel S. , Gupta Anuj , Dang Chi V , Yegnasubramanian Srinivasan , De Marzo Angelo M. 
Published: February 2023

AbstractIncreased mitochondrial function may render some cancers vulnerable to mitochondrial inhibitors. Since mitochondrial function is regulated partly by mitochondrial DNA copy number (mtDNAcn), accurate measurements of mtDNAcn could help reveal which cancers are driven by increased mitochondrial function and may be candidates for mitochondrial inhibition. However, prior studies have employed bulk macrodissections that fail to account for cell type-specific or tumor cell heterogeneity in mtDNAcn. These studies have often produced unclear results, particularly in prostate cancer. Herein, we developed a multiplexin situmethod to spatially quantify cell type specific mtDNAcn. We show that mtDNAcn is increased in luminal cells of high-grade prostatic intraepithelial neoplasia (HGPIN), is increased in prostatic adenocarcinomas (PCa), and is further elevated in metastatic castration-resistant prostate cancer. Increased PCa mtDNAcn was validated by two orthogonal methods and is accompanied by increases in mtRNAs and enzymatic activity. Mechanistically, MYC inhibition in prostate cancer cells decreases mtDNA replication and expression of several mtDNA replication genes, and MYC activation in the mouse prostate leads to increased mtDNA levels in the neoplastic prostate cells. Ourin situapproach also revealed elevated mtDNAcn in precancerous lesions of the pancreas and colon/rectum, demonstrating generalization across cancer types using clinical tissue samples.
A tRNA modification inMycobacterium tuberculosisfacilitates optimal intracellular growth
Authors: Tomasi Francesca G. , Kimura Satoshi , Rubin Eric J. , Waldor Matthew K. 
Published: February 2023

AbstractDiverse chemical modifications fine-tune the function and metabolism of tRNA. Although tRNA modification is universal in all kingdoms of life, profiles of modifications, their functions, and physiological roles have not been elucidated in most organisms including the human pathogen,Mycobacterium tuberculosis(Mtb), the causative agent of tuberculosis. To identify physiologically important modifications, we surveyed the tRNA ofMtb, using tRNA sequencing (tRNA-seq) and genome-mining. Homology searches identified 23 candidate tRNA modifying enzymes that are predicted to create 16 tRNA modifications across all tRNA species. Reverse transcription-derived error signatures in tRNA-seq predicted the sites and presence of 9 modifications. Several chemical treatments prior to tRNA-seq expanded the number of predictable modifications. Deletion ofMtbgenes encoding two modifying enzymes, TruB and MnmA, eliminated their respective tRNA modifications, validating the presence of modified sites in tRNA species. Furthermore, the absence ofmnmAattenuatedMtbgrowth in macrophages, suggesting that MnmA-dependent tRNA uridine sulfation contributes toMtbintracellular growth. Our results lay the foundation for unveiling the roles of tRNA modifications inMtbpathogenesis and developing new therapeutics against tuberculosis.
Non-decision time: the Higg’s boson of decision
Authors: Bompas A. , Sumner P. , Hedge C. 
Published: February 2023

AbstractGenerative models of decision now permeate all subfields of psychology, cognitive and clinical neuroscience. To successfully represent decision mechanisms, it is necessary to also assume the presence of delays for sensory and motor information to travel through the brain; but like the Higg’s boson in particle physics, directly observing this “non-decision time” from behaviour long appeared beyond reach. Here, we describe and apply a set of methods to empirically measure and characterise the properties of non-decision time in fast visually guided decisions (without requiring modelling assumptions). We gather 11 datasets from humans and monkeys from multiple labs and validate the method by showing that visual properties (brightness, colour, size) consistently affect empirically measured non-decision time, as predicted by neurophysiology. We then show that endogenous factors (pro-active slowing, attention) consistently do not affect non-decision time, in contrast to widespread reports based on model fits. Last, contrasting empirically observed non-decision time with estimates from the EZ, DDM and LBA models, we conclude that models cannot be generally trusted to provide valid estimates, either at a group level or for individual differences, and propose a hybrid approach that combines our empirical method with standard modelling.
It’s all about location: reliance on spatial rather than visual context when trying to remember
Authors: Taub Keren , Yuval-Greenberg Shlomit 
Published: February 2023

AbstractWhen people try to remember visual information, they often move their eyes similarly to encoding. The mechanism underlying this behavior has not yet been fully understood. Specifically, it is unclear whether the purpose of this behavior is to recreate the visual input produced during encoding, or the motor and spatial elements of encoding. In this experiment, participants (N=40) encoded pairs of greyscale objects, overlaying colored squares. During test, participants were asked about objects’ orientation, while presented with squares of the same colors, either at the same location (controlled trials) or switched in their locations (test trials) relative to encoding. Results show that during test trials, participants tended to gaze at the square appearing at the location where the remembered object was previously presented, rather than on the square of the same color. This indicates a superiority of motor and spatial elements of eye movements rather than near-peripheral visual cues.