bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic and intrinsic functions of ATRX in glial cell fate and CNS myelination
Authors: Rowland Megan E. , Jiang Yan , Shafiq Sarfraz , Ghahramani Alireza , Pena-Ortiz Miguel A. , Dumeaux Vanessa , Bérubé Nathalie G. 
Published: September 2022

SummaryNeurodevelopmental disorders are often characterized by abnormal production of myelin, an extension of the oligodendrocyte plasma membrane wrapped around axons to facilitate nerve conduction. However, the molecular mechanisms that control myelination during brain development are incompletely resolved. Here, we provide evidence that loss of ATRX, encoded by the gene mutated in the ATR-X intellectual disability syndrome, leads to myelin deficits in the mouse CNS. While postnatal systemic thyroxine administration can improve myelination, the rescue is incomplete, pointing to additional roles of ATRX in this process. We show that targeted inactivation of ATRX in postnatal oligodendrocyte progenitor cells (OPCs), but not in neurons, also leads to myelination deficits, demonstrating cell-intrinsic effects of ATRX deficiency. A subset of ATRX-null OPCs express lower levels of oligodendrocyte specification and differentiation markers, including the basic helix-loop-helix Olig2 transcription factor. Mechanistically, we provide evidence that ATRX occupies genomic sites in OPCs marked by H3K27Ac, CHD7 and CHD8 and demonstrate that reduced Olig2 expression is associated with decreased H3K27Ac. Finally, our data suggest that ATRX-null OPCs acquire a more plastic state and can exhibit astrocyte-like features in vitro and in vivo, supporting a model in which ATRX regulates the onset of myelination by promoting OPC identity and suppressing astrogliogenesis. These previously unrecognized functions of ATRX might explain white matter pathogenesis in ATR-X syndrome patients.
Exploring problematic internet use and gaming in young adults with autism spectrum disorder
Authors: Normand Claude L. , Fisher Marisa H. , Fecteau Stéphanie-M. , Tremblay Kelly , Roy Evelyne , Poulin Marie-Hélène 
Published: September 2022

AbstractCharacteristics of autism spectrum disorder (ASD) could lead individuals with ASD to spend large amounts of time on internet and potentially becoming addicted. Sixty-five individuals with ASD (mean age = 23.77, SD = 4.3) completed an online survey measuring compulsive internet use and gaming disorder. Six participants (9.3%) had problematic internet use, while only two (3%) scored above cut-off for gaming disorder. Exploratory analyses found no differences according to gender, age, employment or co-occurring diagnoses of anxiety, ADHD or depression. Our data suggest that problematic internet could be more frequent than gaming disorder in Canadian young adults with autism and that these issues should be investigated further.
Re-exploiting multiple RNA-seq data to identify transcript variations in Podospora anserina
Authors: Lelandais Gaëlle , Remy Damien , Malagnac Fabienne , Pierre Grognet 
Published: September 2022

ABSTRACTBackgroundPublicly available RNA-seq datasets are often underused although being helpful to improve functional annotation of eukaryotic genomes. This is especially true for filamentous fungi genomes which structure differs from most well annotated yeast genomes. Podospora anserina is a filamentous fungal model, which genome has been sequenced and annotated in 2008. Still, the current annotation lacks information about cis-regulatory elements, including promoters, transcription starting sites and terminators, which are instrumental to integrate epigenomic features into global gene regulation strategies.ResultsHere we took advantage of 37 RNA-seq experiments that were obtained in contrasted developmental and physiological conditions, to complete the functional annotation of P. anserina genome. Out of the 10,800 previously annotated genes, 5’UTR and 3’UTR were defined for 7,554, among which, 3,328 showed differential transcriptional signal starts and/or transcriptional end sites. In addition, alternative splicing events were detected for 2350 genes, mostly due alternative 3’splice site and 1,958 novel transcriptionally active regions (nTARs) in unannotated regions were identified.ConclusionsOur study provides a comprehensive genome-wide functional annotation release of P. anserina genome, including chromatin features, cis-acting elements such as UTRs, alternative splicing events and transcription of non-coding regions. These new findings will likely improve our understanding of gene regulation strategies in compact genomes, such as those of filamentous fungi. Characterization of alternative transcripts and nTARs paves the way to the discovery of putative new genes, alternative peptides or regulatory non-coding RNAs.
IRescue: uncertainty-aware quantification of transposable elements expression at single cell level
Authors: Benedetto Polimeni , Federica Marasca , Valeria Ranzani , Beatrice Bodega 
Published: September 2022

AbstractTransposable elements (TEs) are mobile DNA repeats that contribute to the evolution of eukaryotic genomes. In complex organisms, TE expression is tissue specific. However, their contribution to cellular heterogeneity is still unknown and challenging to investigate in single-cell RNA sequencing (scRNA-seq), due to the ubiquity and homology of TEs in the genome. We introduce IRescue (Interspersed Repeats single-cell quantifier), the first software that accurately estimates the expression of TE subfamilies at single-cell level, implementing a UMI deduplication algorithm to allocate reads ambiguously mapped on TEs, while correcting for UMI sequencing errors. Applying IRescue on simulated datasets and real scRNA-seq of colorectal cancers, we could precisely estimate TE subfamilies expression. We show that IRescue improves the definition of cellular heterogeneity, detecting TE expression signatures and specific TE-containing splicing isoforms.
Change in functional trait diversity mediates the effects of nutrient addition on grassland stability
Authors: Chen Qingqing , Wang Shaopeng , Seabloom Eric W. , Isbell Forest , Borer Elizabeth T. , Bakker Jonathan D. , Bharath Siddharth , Roscher Christiane , Peri Pablo Luis , Power Sally A. , Donohue Ian , Stevens Carly , Ebeling Anne , Nogueira Carla , Caldeira Maria C , MacDougall Andrew S. , Moore Joslin L. , Bagchi Sumanta , Jentsch Anke , Tedder Michelle , Kirkman Kevin , Alberti Juan , Hautier Yann 
Published: September 2022

AbstractNutrient enrichment impacts grassland plant diversity such as species richness, functional trait composition and diversity, but whether and how these changes affect ecosystem stability in the face of increasing climate extremes remains largely unknown.We quantified the direct and diversity-mediated effects of nutrient addition (by nitrogen, phosphorus, and potassium) on the stability of aboveground biomass production in 10 long-term grassland experimental sites. We measured five facets of stability as the temporal invariability, resistance during and recovery after extreme dry and wet growing seasons.Leaf traits (leaf carbon, nitrogen, phosphorus, potassium, and specific leaf area) were measured under ambient and nutrient addition conditions in the field and were used to construct the leaf economic spectrum (LES). We calculated functional trait composition and diversity of LES and of single leaf traits. We quantified the contribution of intraspecific trait shifts and species replacement to change in functional trait composition as responses to nutrient addition and its implications for ecosystem stability.Nutrient addition decreased functional trait diversity and drove grassland communities to the faster end of the LES primarily through intraspecific trait shifts, suggesting that intraspecific trait shifts should be included for accurately predicting ecosystem stability. Moreover, the change in functional trait diversity of the LES in turn influenced different facets of stability. That said, these diversity-mediated effects were overall weak and/or overwhelmed by the direct effects of nutrient addition on stability. As a result, nutrient addition did not strongly impact any of the stability facets. These results were generally consistent using individual leaf traits but the dominant pathways differed. Importantly, major influencing pathways differed using average trait values extracted from global trait databases (e.g. TRY).Synthesis. Investigating changes in multiple facets of plant diversity and their impacts on multidimensional stability under global changes such as nutrient enrichment can improve our understanding of the processes and mechanisms maintaining ecosystem stability.
Age and micronutrient effects on the microbiome in a mouse model of zinc depletion and supplementation
Authors: Davis Edward W. , Wong Carmen P. , Arnold Holly K. , Kasschau Kristin , Gaulke Christopher A. , Sharpton Thomas J. , Ho Emily 
Published: September 2022

AbstractOlder adult populations are at risk for elevated zinc deficiency, which may predispose them to immune dysfunction and age-related chronic inflammation that drives myriad diseases and disorders. Recent work also implicates the gut microbiome in the onset and severity of age-related inflammation, indicating that dietary zinc status and the gut microbiome may interact to impact age-related host immunity. We hypothesize that age-related alterations in the gut microbiome contribute to the demonstrated zinc deficits in host zinc levels and increased inflammation. We tested this hypothesis with a multifactor two-part study design in a C57BL/6 mouse model. The two studies included young (2 month old) and aged (24 month old) mice fed either (1) a zinc adequate or zinc supplemented diet, or (2) a zinc adequate or marginal zinc deficient diet, respectively. Overall microbiome composition did not significantly change with zinc status; beta diversity was driven almost exclusively by age effects. Microbiome differences due to age are evident at all taxonomic levels, with more than half of all taxonomic units significantly different at each. Furthermore, we found 150 out of 186 genera were significantly different between the two age groups, with Bacteriodes and Parabacteroides being the primary components of young and old mice, respectively. These data suggest that modulating individual micronutrient concentrations does not lead to comprehensive microbiome shifts, but rather affects specific components of the gut microbiome. However, a phylogenetic agglomeration technique (ClaaTU) revealed phylogenetic clades of microbiota that respond to modulation of dietary zinc status in an age-dependent manner. Collectively, these results suggest that there exists a complex interplay between host age, gut microbiome composition, and dietary zinc status.
Compressed Data Structures for Population-Scale Positional Burrows–Wheeler Transforms
Authors: Bonizzoni Paola , Boucher Christina , Cozzi Davide , Gagie Travis , Kashgouli Sana , Köppl Dominik , Rossi Massimiliano 
Published: September 2022

AbstractThe positional Burrows–Wheeler Transform (PBWT) was presented in 2014 by Durbin as a means to find all maximal haplotype matches inhsequences containingwvariation sites in 𝒪(hw)-time. This time complexity of finding maximal haplotype matches using the PBWT is a significant improvement over the naïve pattern-matching algorithm that requires 𝒪(h2w)-time. Compared to the more famous Burrows-Wheeler Transform (BWT), however, a relatively little amount of attention has been paid to the PBWT. This has resulted in less space-efficient data structures for building and storing the PBWT. Given the increasing size of available haplotype datasets, and the applicability of the PBWT to pangenomics, the time is ripe for identifying efficient data structures that can be constructed for large datasets. Here, we present a comprehensive study of the memory footprint of data structures supporting maximal haplotype matching in conjunction with the PBWT. In particular, we present several data structure components that act as building blocks for constructing six different data structures that store the PBWT in a manner that supports efficiently finding the maximal haplotype matches. We estimate the memory usage of the data structures by bounding the space usage with respect to the input size. In light of this experimental analysis, we implement the solutions that are deemed to be superior with respect to the memory usage and show the performance on haplotype datasets taken from the 1000 Genomes Project data.
Using pressure-driven flow systems to evaluate laser speckle contrast imaging
Authors: Sullender Colin T. , Santorelli Adam , Richards Lisa M. , Mannava Pawan K. , Smith Christopher , Dunn Andrew K. 
Published: September 2022

AbstractSignificanceMicrofluidic flow phantom studies are commonly used for characterizing the performance of laser speckle contrast imaging (LSCI) instruments. The selection of the flow control system is critical for the reliable generation of flow during testing. The majority of recent LSCI studies using microfluidics used syringe pumps for flow control.AimWe quantified the uncertainty in flow generation for a syringe pump and a pressure-regulated flow system. We then assessed the performance of both LSCI and multi-exposure speckle imaging (MESI) using the pressure-regulated flow system across a range of flow speeds.ApproachThe syringe pump and pressure-regulated flow systems were evaluated during stepped flow profile experiments in a microfluidic device using an inline flow sensor. The uncertainty associated with each flow system was calculated and used to determine the reliability for instrument testing. The pressure-regulated flow system was then used to characterize the relative performance of LSCI and MESI during stepped flow profile experiments while using the inline flow sensor as reference.ResultsThe pressure-regulated flow system produced much more stable and reproducible flow outputs compared to the syringe pump. The expanded uncertainty for the syringe pump was 8–20× higher than that of the pressure-regulated flow system across the tested flow speeds. Using the pressure-regulated flow system, MESI outperformed single-exposure LSCI at all flow speeds and closely mirrored the flow sensor measurements, with average errors of 4.6 ± 2.6% and 15.7 ± 4.6%, respectively.ConclusionsPressure-regulated flow systems should be used instead of syringe pumps when assessing the performance of flow measurement techniques with microfluidic studies. MESI offers more accurate relative flow measurements than traditional LSCI across a wide range of flow speeds.
The balance N1 and the ERN correlate in amplitude across individuals in small samples of younger and older adults
Authors: Payne Aiden M. , Ting Lena H. , Hajcak Greg 
Published: September 2022

AbstractThe error-related negativity (ERN) is a neural correlate of error monitoring often used to investigate individual differences in developmental, mental health, and adaptive contexts. However, limited experimental control over errors presents several confounds to its measurement. An experimentally controlled disturbance to standing balance evokes the balance N1, which we previously suggested may share underlying mechanisms with the ERN based on a number of shared features and factors. We now measure whether the balance N1 and ERN are correlated across individuals within two small groups (N=21 young adults and N=20 older adults). ERNs were measured in arrow flanker tasks using hand and foot response modalities (ERN-hand and ERN-foot). The balance N1 was evoked by sudden slip-like movements of the floor while standing. The ERNs and the balance N1 showed good and excellent internal consistency, respectively, and were correlated in amplitude in both groups. One principal component strongly loaded on all three evoked potentials, suggesting that the majority of individual differences are shared across the three ERPs. However, there remains a significant component of variance shared between the ERN-hand and ERN-foot beyond what they share with the balance N1. It is unclear whether this component of variance is specific to the arrow flanker task, or something fundamentally related to error processing that is not evoked by a sudden balance disturbance. If the balance N1 were to reflect error processing mechanisms indexed by the ERN, balance paradigms offer several advantages in terms of experimental control over errors.
Historical biogeography of Cannabis in the Iberian Peninsula: palynological evidence
Authors: Rull V. , Burjachs F. , Carrión J.S. , Ejarque A. , Fernández S. , López-Sáez J.A. , Luelmo-Lautenschlaeger R. , Ochando J. , Pérez-Díaz S. , Revelles J. , Riera S. , Rodríguez S. 
Published: September 2022

AbstractThe tempo and mode of colonization of the Iberian Peninsula (IP) by Cannabis sativa, its further internal spreading and the potential cultural and environmental factors involved remain unknown. The available continental-wide European meta-analyses using pollen and archaeological evidence account for only a few IP sites, insufficient for a sound assessment. This paper presents a nearly comprehensive database of almost 60 IP sites with palynological evidence of Cannabis and analyzes the corresponding spatiotemporal patterns. The first scattered records of this pollen type, likely corresponding to wild Cannabis, date from the Middle and Upper Paleolithic (150 to 12 ky BP) and would have entered the IP by maritime Mediterranean or terrestrial continental pathways, or both. A first burst of introductions, probably in a cultivated form, would have occurred during the Neolithic (7-5 ky BP) using similar paths. Human participation in this Neolithic acceleration remains unclear but cannot be dismissed. A period of reduced Cannabis arrivals (mostly via MP) occurred between the Chalcolithic and the Roman Epoch (4.5-2 ky BP), when the innermost parts of the IP were colonized (Late Bronze). A second, likely anthropogenic, introduction acceleration took place in the Middle Ages (1.5 ky BP onward) using the MP and CP. Maximum cultivation and hemp retting activity was recorded during the Modern Ages (16th-19th centuries), coinciding with the increased demand of hemp fiber to supply the Spanish royal navy for imperial expansion and commerce. A potential link between Cannabis colonization/introduction bursts and climatic warmings has been observed that should be tested with future studies. Regional moisture variations seem to be less influential. Further efforts to enhance and improve the database used in this study are encouraged. The results of this paper should be compared with archaeological and historical evidence to clarify the role of human migrations and cultural changes in the historical biogeography of Cannabis in the IP.
Microbial interactions impact the growth response ofClostridioides difficileto antibiotics
Authors: Hromada Susan , Venturelli Ophelia 
Published: September 2022

ABSTRACTIn the human gut, the growth ofClostridioides difficileis impacted by a complex web of inter-species interactions with members of human gut microbiota. We investigate the contribution of inter-species interactions on the antibiotic response ofC. difficileto clinically relevant antibiotics using bottom-up assembly of human gut communities. We discover two classes of microbial interactions that alterC.difficile’s antibiotic susceptibility: infrequent increases in tolerance at high antibiotic concentrations and frequent growth enhancements at low antibiotic concentrations. Based on genome-wide transcriptional profiling data, we demonstrate that metal sequestration due to hydrogen sulfide production by the prevalent gut speciesDesulfovibrio pigerincreases metronidazole tolerance ofC. difficile. Competition with species that display higher sensitivity to the antibiotic thanC. difficileleads to enhanced growth ofC. difficileat low antibiotic concentrations. A dynamic computational model identifies the ecological design principles driving this effect. Our results provide a deeper understanding of ecological and molecular principles shapingC. difficile’s response to antibiotics, which could inform therapeutic interventions.
A Computational Model of Learning Flexible Navigation in a Maze by Layout-Conforming Replay of Place Cells
Authors: Gao Yuanxiang 
Published: September 2022

ABSTRACTRecent experimental observations have shown that the reactivation of hippocampal place cells (PC) during sleep or immobility depicts trajectories that can go around barriers and can flexibly adapt to a changing maze layout. Such layout-conforming replay sheds a light on how the activity of place cells supports the learning of flexible navigation in a dynamically changing maze. However, existing computational models of replay fall short of generating layout-conforming replay, restricting their usage to simple environments, like linear tracks or open fields. In this paper, we propose a computational model that generates layout-conforming replay and explains how such replay drives the learning of flexible navigation in a maze. First, we propose a Hebbian-like rule to learn the inter-PC synaptic strength during exploring a maze. Then we use a continuous attractor network (CAN) with feedback inhibition to model the interaction among place cells and hippocampal interneurons. The activity bump of place cells drifts along a path in the maze, which models layout-conforming replay. During replay in rest, the synaptic strengths from place cells to striatal medium spiny neurons (MSN) are learned by a novel dopamine-modulated three-factor rule to store place-reward associations. During goal-directed navigation, the CAN periodically generates replay trajectories from the animal’s location for path planning, and the trajectory leading to a maximal MSN activity is followed by the animal. We have implemented our model into a high-fidelity virtual rat in the MuJoCo physics simulator. Extensive experiments have demonstrated that its superior flexibility during navigation in a maze is due to a continuous re-learning of inter-PC and PC-MSN synaptic strength.
Impact of airline travel network on the global importation risk of monkeypox, 2022
Authors: Kinoshita Ryo , Sassa Miho , Otake Shogo , Yoshimatsu Fumi , Shi Shoi , Ueno Ryo , Suzuki Motoi , Yoneoka Daisuke 
Published: September 2022

AbstractBackgroundAs of 4 September 2020, a total of 53,996 monkeypox cases were confirmed globally. Currently, most monkeypox cases are concentrated in Europe and the Americas, while many countries outside these regions are also continuously observing imported cases. We aimed to estimate the potential global risk of monkeypox importation and consider hypothetical scenarios of travel restrictions by varying passenger volumes via airline travel network.MethodPassenger volume data for the airline network, and the time of first confirmed monkeypox case for a total of 1680 airports in 176 countries (and territories) were extracted from publicly available data sources. A survival analysis technique in which the hazard function was a function of effective distance was utilized to estimate the importation risk. Scenarios which selectively reduced the passenger volume from/to countries with detected monkeypox cases and increased/decreased the global passenger volume to the level of 2019 (high volume) or 2021 (low volume) regardless of monkeypox detection were considered for travel restrictions.ResultsThe arrival time ranged from 9 to 48 days since the first case was identified in the UK on 6 May 2022. The estimated risk of importation showed that regardless of the geographic region, most locations will have an intensified importation risk by 31 December 2022. Travel restrictions had a minor impact on the global airline importation risk against monkeypox.ConclusionsInstead of preventing the importation of monkeypox cases via airline networks, high risk countries should enhance local capacities for the identification of monkeypox and prepare to carry out contact tracing and isolation.