bluuebunny/crossref_metadata_2025_split huggingface dataset:
Target-enrichment sequencing yields valuable genomic data for difficult-to-culture bacteria of public health importance
Authors: Dennis Tristan P. W. , Mable Barbara K. , Brunelle Brian , Devault Alison , Carter Ryan , Ling Clare L. , Mmbaga Blandina T. , Halliday Jo E. B. , Oravcova Katarina , Forde Taya L. 
Published: February 2022

AbstractGenomic data contribute invaluable information to the epidemiological investigation of pathogens of public health importance. However, whole genome sequencing (WGS) of bacteria typically relies on culture, which represents a major hurdle for generating such data for a wide range of species for which culture is challenging. In this study, we assessed the use of culture-free target-enrichment sequencing as a method for generating genomic data for two bacterial species: 1) Bacillus anthracis, which causes anthrax in both people and animals and whose culture requires high level containment facilities; and 2) Mycoplasma amphoriforme, a fastidious emerging human respiratory pathogen. We obtained high quality genomic data for both species directly from clinical samples, with sufficient coverage (>15X) for confident variant calling over at least 80% of the baited genomes for over two thirds of the samples tested. Higher qPCR cycle threshold (Ct) values (indicative of lower pathogen concentrations in the samples), pooling libraries prior to capture, and lower captured library concentration were all statistically associated with lower capture efficiency. The Ct value had the highest predictive value, explaining 52% of the variation in capture efficiency. Samples with Ct values ≤ 30 were over 6 times more likely to achieve the threshold coverage than those with a Ct > 30. We conclude that target-enrichment sequencing provides a valuable alternative to standard WGS following bacterial culture and creates opportunities for an improved understanding of the epidemiology and evolution of many clinically important pathogens for which culture is challenging.Data summaryThe authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files. Scripts used in this study can be accessed on GitHub at https://github.com/tristanpwdennis/bactocap. All sequence data generated during this study have been deposited in the European Nucleotide Archive (ENA) Sequence Read Archive (SRA) under project accession numbers PRJEB46822 (B. anthracis) and PRJEB50216 (M. amphoriforme). Accession numbers for individual samples, along with metadata, laboratory parameters and sequence quality metrics, are available at the University of Glasgow’s data repository, Enlighten, at http://dx.doi.org/10.5525/gla.researchdata.1249.
Autism is associated with inter-individual variations of gray and white matter morphology
Authors: Mei Ting , Forde Natalie J. , Floris Dorothea L. , Dell’Acqua Flavio , Stones Richard , Ilioska Iva , Durston Sarah , Moessnang Carolin , Banaschewski Tobias , Holt Rosemary J. , Baron-Cohen Simon , Rausch Annika , Loth Eva , Oakley Bethany , Charman Tony , Ecker Christine , Murphy Declan G. M. ,   the EU-AIMS LEAP group, Beckmann Christian F. , Llera Alberto , Buitelaar Jan K. 
Published: February 2022

AbstractBackgroundAlthough many studies have explored atypicalities in gray and white matter (GM, WM) morphology of autism, most of them rely on unimodal analyses that do not benefit from the likelihood that different imaging modalities may reflect common neurobiology. We aimed to establish multimodal brain patterns that differentiate between autism and typically developing (TD) controls and explore associations between these brain patterns and clinical measures.MethodsWe studied 183 individuals with autism and 157 TD individuals (6-30 years) in a large deeply phenotyped autism dataset (EU-AIMS LEAP). Linked Independent Component Analysis was utilized to link all participants’ GM and WM images, and group comparisons of modality shared variances were examined. Subsequently, we performed a canonical correlation analysis to explore the aggregated effects between all multimodal GM-WM covariations and clinical profiles.ResultsOne multimodal pattern was significantly related to autism. This pattern was primarily associated with GM in bilateral insula, frontal, pre- and post-central, cingulate, and caudate areas, and co-occurred with altered WM features in the superior longitudinal fasciculus. The canonical analysis showed a significant multivariate correlation primarily between multimodal brain patterns that involved variation of corpus callosum, and symptoms of social affect in the autism group.ConclusionsOur findings demonstrate the assets of integrated analyses of GM and WM alterations to study the brain mechanisms that underpin autism, and show that the complex clinical autism phenotype can be interpreted by multimodal brain patterns that are spread across the brain involving both cortical and subcortical areas.
Xist expression impacts chromatin structure and YY1 mediated transcription of X-linked genes in hematopoietic progenitor cells
Authors: Yang Tianqi , Ou Jianhong , Yildirim Eda 
Published: February 2022

ABSTRACTX chromosome inactivation (XCI) is a dosage compensation phenomenon that occurs in females. Initiation of XCI depends on Xist RNA, which triggers silencing of one of the two X chromosomes, except for genes that escape XCI. This inactive state is propagated during cell divisions with continuous Xist expression. How Xist impacts XCI maintenance remains an open question. Here, we delete Xist in hematopoietic cells of mice and report increased fraction of cycling hematopoietic progenitors and differentiation defects during hematopoiesis. Xist loss results in upregulation of a subset of X-linked genes, several of which escape XCI and have functions in hematopoiesis and immunity. We find that the underlying mechanism of transcriptional upregulation involves reduced H3K27me3 occupancy and increased chromatin accessibility which accommodate binding of YY1 transcription factor (TF). We propose that XCI maintenance defects in Xist deficient mice rely on the landscape of open chromatin sites, TF availability, and cell cycle stress in specific cellular context during hematopoiesis.
Targeting the fronto-parietal network using multifocal personalized transcranial alternating current stimulation to enhance motor sequence learning in healthy older adults
Authors: Draaisma L.R. , Wessel M.J. , Moyne M. , Morishita T. , Hummel F.C. 
Published: February 2022

AbstractBackgroundHealthy older adults show a decrease in motor learning capacity as well as in working memory (WM) performance. WM has been suggested to be involved in motor learning processes, such as sequence learning. Correlational evidence has shown the involvement of the fronto-parietal network (FPN), a network underlying WM processes, in motor sequence learning. However, causal evidence is currently lacking. Non-invasive brain stimulation (NIBS) studies have focused so far predominantly on motor related areas to enhance motor sequence learning while areas associated with more cognitive aspects of motor learning have not yet been addressed.HypothesisIn this study, we aim to provide causal evidence for the involvement of WM processes and the underlying FPN in successful motor sequence learning by using a theta transcranial alternating current stimulation (tACS) paradigm targeting the FPN during motor sequence learning.MethodsIn a cohort of 20 healthy older adults, we applied bifocal tACS in the theta range to the FPN during a sequence learning task. With the use of a double-blind, cross-over design, we tested the efficacy of active compared with sham stimulation. Two versions of the motor task were used: one with high and one with low WM load, to explore the efficacy of stimulation on tasks differing in WM demand. Additionally, the effects of stimulation on WM performance were addressed using an N-back task. The tACS frequency was personalized by means of EEG measuring the individual theta peak frequency during the N-back task.ResultsThe application of personalized theta tACS to the FPN improved performance on the motor sequence learning task with high WM load (p <.001), but not with low WM load. Active stimulation significantly improved both speed (p <.001), and accuracy (p =.03) during the task with high WM load. In addition, the stimulation paradigm improved performance on the N-back task for the 2-back task (p = .013), but not for 1-back and 3-back.ConclusionMotor sequence learning can be enhanced with the use of personalized bifocal theta tACS to the FPN when WM load is high. This indicates that the efficacy of this stimulation paradigm is dependent on the cognitive demand during the learning task and provides further causal evidence for the critical involvement of WM processes and the FPN in motor sequence learning in healthy older adults. These findings open new exciting possibilities to counteract the age-related decline in motor learning capacity and WM performance.
Vps60 initiates formation of alternative membrane-bound ESCRT-III filaments
Authors: Pfitzner Anna-Katharina , Zivkovic Henry , Humbert Frédéric , Roux Aurélien 
Published: February 2022

AbstractEndosomal sorting complex required for transport-III (ESCRT-III)-driven membrane remodeling participates in many crucial cellular functions, from cell division to endosome maturation, and occurs on essentially all cellular organelles. In eukaryotes, ESCRT-III displays a remarkable molecular diversity in its subunits which may have been acquired through evolution to perform novel cellular functions. Here, we describe and characterize a novel ESCRT-III polymer initiated by the subunit Vps60. Membrane-bound Vps60 polymers recruit ESCRT-III subunits Vps2, Vps24, Did2 and Ist1, and undergo polymer turnover powered by the ATPase Vps4. Snf7- and Vps60 filaments can coexist on membranes without interacting. Their nucleation, polymerization and recruitment of downstream subunits remains unaffected by the presence of the respective other polymer. Taken together, our results suggest Vps60 and Snf7 form distinct ESCRT-III polymers, which overall, supports the notion of evolutionary diversification of ESCRT-III assemblies to perform specific cellular functions.
Comparisons of cell proliferation and cell death across life histories in the hemichordate Schizocardium californicum
Authors: Bump Paul , Khariton Margarita , Stubbert Clover , Moyen Nicole E. , Yan Jia , Wang Bo , Lowe Christopher J. 
Published: February 2022

AbstractBackgroundThere are a wide range of developmental strategies in animal phyla, but most insights into adult body plan formation come from direct-developing species. For indirect-developing species, there are distinct larval and adult body plans that are linked together by metamorphosis. Some outstanding questions in indirect-developing organisms include the extent to which larval tissue undergoes cell death during the process of metamorphosis and when the tissue that will give rise to the adult originates. Here we present patterns of cell proliferation and cell death during larval development, metamorphosis, and adult body plan formation, in the hemichordate Schizocardium californium to answer these questions.ResultsWe identified distinct patterns of cell proliferation between larval and adult body plan formation of S. californicum. We found that some adult tissues proliferate prior to the start of any morphological metamorphosis. Additionally, we describe a genetic signature of proliferative cells with an irradiation approach that revealed markers shared between the life history states and others that are unique to larvae or juveniles. Finally, we observed that cell death is minimal in larval stages but begins with the onset of metamorphosis.ConclusionsCell proliferation during the development of S. californicum has distinct patterns in the formation of larval and adult body plans. However, cell death is very limited in larvae and begins during the onset of metamorphosis and into early juvenile development in specific domains. The populations of cells that proliferate and give rise to the larva and juvenile have a genetic signature that is more suggestive of a heterogeneous pool of proliferative progenitors versus a population of pluripotent set-aside cells. Taken together, we propose that S. californicum has a transformative metamorphosis that may be more representative of the development strategies that characterize metamorphosis in many metazoan animals.
Hypoxic response is driven by the BAF form of SWI/SNF
Authors: Tran Kathleen Diep , Chakravarty Tomali , Garzon Jada Lauren , Saraf Anita , Florens Laurence , Washburn Michael P. , Dutta Arnob 
Published: February 2022

AbstractSWI/SNF has been shown to have important functions in hypoxia-mediated gene expression through roles of its catalytic and core subunits. Since SWI/SNF exists as three distinct assemblies, and usage of complex specific subunits of the complex can be expected to vary within a given cell under changing environmental conditions. It remains an open question as to the compositional makeup of SWI/SNF and the roles of individual complexes in gene expression and cell viability in a hypoxic environment. In our current study, we find that hypoxia regulates levels of unique subunits that define each complex. Protein levels of ARID2 and PBRM1, members of PBAF and BRD9, a member of ncBAF, are downregulated in hypoxic cells, while members of BAF complex are retained. Our studies further show that loss of ARID1A, ARID1B and DPF2, which are unique subunits of BAF, reduces induction of HIF target genes and ARID1A or DPF2 are important for cell survival during hypoxia. Collectively, our results provide evidence that levels of SWI/SNF forms are not static within cells, but can be dynamically altered as a response to environmental changes.
Synaptic basis of a sub-second representation of time
Authors: Barri A. , Wiechert M. T. , Jazayeri M. , DiGregorio D. A. 
Published: February 2022

AbstractTemporal sequences of neural activity are essential for driving well-timed behaviors, but the underlying cellular and circuit mechanisms remain elusive. We leveraged the well-defined architecture of the cerebellum, a brain region known to support temporally precise actions, to explore theoretically whether the experimentally observed diversity of short-term synaptic plasticity (STP) at the input layer could generate neural dynamics sufficient for subsecond temporal learning. Simulated synaptic input generated a diverse set of transient, firing patterns in granule cells (GCs) that provided a temporal basis set for learning precisely timed pauses of Purkinje cell activity associated with delayed eyelid conditioning and Bayesian interval estimation. The learning performance across time intervals was influenced by the temporal bandwidth of the GC basis, which was determined by the input layer synaptic properties. The ubiquity of STP throughout the brain positions it as a general, tunable cellular mechanism for sculpting neural dynamics and fine-tuning behavior.
A single 2’-O-methylation of ribosomal RNA gates assembly of a functional ribosome
Authors: Yelland James N. , Bravo Jack P.K. , Black Joshua J. , Taylor David W. , Johnson Arlen W. 
Published: February 2022

AbstractRNA modifications are widespread in biology, and particularly abundant in ribosomal RNA. However, the significance of these modifications is not well understood. We show that methylation of a single universally conserved nucleotide, in the catalytic center of the large subunit, gates ribosome assembly. Massively parallel mutational scanning of the essential nuclear GTPase Nog2 identified important interactions with ribosomal RNA helix 92, particularly with the methylated A-site base Gm2922. We found that 2’-O-methylation of G2922 is needed for efficient nuclear export of the large subunit. Critically, we identified single amino acid changes in Nog2 that completely bypass its dependence on G2922 methylation. By solving the cryo-EM structure of the unmodified nascent subunit, we reveal how methylation flips Gm2922 into the active site channel of Nog2. This work demonstrates that a single RNA modification is a critical checkpoint in ribosome biogenesis, and suggests that RNA modifications can play an important role in regulation and assembly of macromolecular machines.
Modeling exercise using optogenetically contractible Drosophila larvae
Authors: Ghosh Arpan C. , Liu Yifang , Tattikota Sudhir Gopal , Hu Yanhui , Perrimon Norbert 
Published: February 2022

AbstractThe pathophysiological effects of a number of metabolic and age-related disorders can be prevented to some extent by exercise and increased physical activity. However, the molecular mechanisms that contribute to the beneficial effects of muscle activity remain poorly explored. Availability of a fast, inexpensive, and genetically tractable model system for muscle activity and exercise will allow the rapid identification and characterization of molecular mechanisms that mediate the beneficial effects of exercise. Here, we report the development and characterization of an optogenetically-inducible muscle contraction (OMC) model in Drosophila larvae that we used to study acute exercise-like physiological responses. To characterize muscle-specific transcriptional responses to acute exercise, we performed bulk mRNA-sequencing, revealing striking similarities between acute exercise-induced genes in flies and those previously identified in humans. Our larval muscle contraction model opens a path for rapid identification and characterization of exercise-induced factors.
GSK3 inhibition improves skeletal muscle function and whole-body metabolism in the severe DBA/2Jmdxmouse model
Authors: Marcella Bianca M. , Hockey Briana L. , Braun Jessica L. , Whitley Kennedy C. , Geromella Mia S. , Baranowski Ryan W. , Watson Colton J.F. , Silvera Sebastian , Hamstra Sophie I. , Wasilewicz Luc J. , Crozier Robert W.E. , Marais Amelie , Vandenboom Rene , Roy Brian D. , MacNeil Adam J. , MacPherson Rebecca E.K. , Fajardo Val A. 
Published: February 2022

Introductory paragraphDuchenne muscular dystrophy (DMD) is a severe X-linked muscle wasting disorder that affects 1 in 5,000 males worldwide1. It is caused by the absence of functional dystrophin, which compromises muscle integrity, leading to progressive muscle wasting and weakness2. Glucocorticoids are the standard of care for patients with DMD as they delay the loss of ambulation by an average of 3 years3; however, they are also associated with adverse effects such as insulin resistance and increased risk of type 2 diabetes4. Thus, alternative therapeutic options should be explored. Here, we show that treating the DBA/2Jmdxmouse with the glycogen synthase kinase 3 (GSK3) inhibitor, tideglusib, improved skeletal muscle function and insulin sensitivity, while also attenuating the hypermetabolic phenotype previously observed in these mice5. Furthermore, treatingmdxmice with the GSK3 inhibitor, lithium, augmented the benefits of voluntary wheel running on insulin sensitivity and skeletal muscle function despite running half of the total distance compared to control-treatedmdxmice. This is important given that some patients with DMD may not be able to engage in adequate amounts of physical activity. Thus, GSK3 inhibition alone or in combination with exercise can enhance skeletal muscle function and insulin sensitivity inmdxmice.
Postnatal environmental enrichment enhances memory by shaping hippocampal-prefrontal theta and gamma rhythms in diploid and trisomic female mice
Authors: Alemany-González Maria , Vilademunt Marta , Gener Thomas , Nebot Pau , Puig M. Victoria 
Published: February 2022

ABSTRACTRich social, physical, and cognitively stimulating lifestyles have powerful effects on cognitive abilities, especially when they are experienced early in life. Cognitive therapies are widely used to attenuate cognitive impairment due to intellectual disability, but also aging and neurodegeneration, however the underlying neural mechanisms are poorly understood. Here we investigated the neural substrates of memory amelioration induced by postnatal environmental enrichment (EE) in diploid female mice and Ts65Dn female mice with partial trisomy of genes ortholog to human chromosome 21, a standard model of Down syndrome (DS, trisomy 21). We recorded neural activities in two brain structures key for cognitive function, the hippocampus and the prefrontal cortex, during rest, sleep and memory performance in mice reared in standard or enriched environments for 7 weeks post-weaning. We found that EE shaped hippocampal- prefrontal neural dynamics in diploid mice and rescued the same disrupted pathways in Ts65Dn mice. The neural activity changes detected in EE-reared wild-type mice combined task-independent adjustments (augmented hippocampal pyramidal activity and gamma synchrony across different brain states) and memory-dependent adjustments (enhanced theta-gamma coupling and ripples in the HPC). Therefore, both brain state adjustments and memory-associated adjustments are good candidates to underlie the beneficial effects of EE on cognition in diploid female mice. Concomitantly, EE attenuated hippocampal and prefrontal hypersynchrony in trisomic females, suggesting distinct neural mechanisms for the generation and rescue of healthy and pathological brain synchrony, respectively, by EE. These results put forward hippocampal hypersynchrony and hippocampal-prefrontal miscommunication as major neural mechanisms underlying the beneficial effects of EE for intellectual disability in DS.