bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling the impact of urban and hospital wastewaters eco-exposomes on the antibiotic-resistance dynamics
Authors: Henriot Paul , Buelow Elena , Petit Fabienne , Ploy Marie-Cécile , Dagot Christophe , Opatowski Lulla 
Published: December 2021

AbstractAntibiotic-resistance emergence and selection have become major public health issues globally. The presence of antibiotic resistant bacteria (ARB) in natural and anthroposophical environments threatens to compromise the sustainability of care in human and animal populations. This study was undertaken to develop a simple model formalizing the selective impact of antibiotics and pollutants on the dynamics of bacterial resistance in water and use the model to analyze longitudinal spatiotemporal data collected in hospital and urban wastewaters. Longitudinal-sampling data were collected between 2012 and 2015 in four different locations in Haute-Savoie, France: hospital and urban wastewaters, before and after water-treatment plants. Concentration in three different types of compounds: 1) heavy metals 2) antibiotics and 3) surfactants; and abundance of 88 individual genes and mobile genetic elements, mostly conferring resistance to antibiotics, were simultaneously collected. A simple hypothesis-driven model describing the weekly ARB dynamics was proposed to fit available data by assuming normalized gene abundance to be proportional to ARB populations in water. Compounds impacts on the dynamics of 17 genes found in multiple sites were estimated. We found that while mercury and vancomycin had relevant effects on ARB dynamics, respectively positively affecting the dynamics of 10 and 12 identified genes, surfactants antagonistically affected genes dynamics (identified for three genes). This simple model enables analyzing the relationship between resistance-gene persistence in aquatic environments and specific compounds inherent to human activities. Applying our model to longitudinal data, we identified compounds that act as co-selectors for antibiotic resistance.HighlightsWe analyzed longitudinal wastewater resistance genes and environmental dataWe developed a simple hypothesis-driven model to assess resistance selectionMercury and vancomycin were key drivers of antibiotic resistance in wastewater
Functional connectivity and information pathways in the human entorhinal-hippocampal circuitry
Authors: Grande Xenia , Sauvage Magdalena , Becke Andreas , Düzel Emrah , Berron David 
Published: December 2021

AbstractCortical processing streams for item and contextual information come together in the entorhinal-hippocampal circuitry. Various evidence suggest that information-specific pathways organize the cortical – entorhinal interaction and the circuitry’s inner communication along the transversal axis. Here, we leveraged ultra-high field functional imaging and advance Maass, Berron et al. (2015) who report two functional routes segregating the entorhinal cortex (EC) and subiculum. Our data show specific scene processing in the functionally connected posterior-medial EC and distal subiculum. The regions of another route, that connects the anterior-lateral EC and a newly identified retrosplenial-based anterior-medial EC subregion with the CA1/subiculum border, process object and scene information similarly. Our results support topographical information flow in human entorhinal-hippocampal subregions with organized convergence of cortical processing streams and a unique route for contextual information. They characterize the functional organization of the circuitry and underpin its central role in memory function and pathological decline.
Integration of public DNA methylation and expression networks via eQTMs improves prediction of functional gene–gene associations
Authors: Li Shuang , Qi Cancan , Deelen Patrick , Boulogne Floranne , de Klein Niek ,   BIOS Consortium, Koppelman Gerard H. , van der Velde K. Joeri , Franke Lude , Swertz Morris A. , Westra Harm-Jan 
Published: December 2021

AbstractGene co-expression networks can be used to infer functional relationships between genes, but they do not work well for all genes. We investigated whether DNA methylation can provide complementary information for such genes. We first carried out an eQTM meta-analysis of 3,574 gene expression and methylation samples from blood, brain and nasal epithelial brushed cells to identify links between methylated CpG sites and genes. This revealed 6,067 significant eQTM genes, and we observed that histone modification information is predictive of both eQTM direction and presence, enabling us to link many CpG sites to genes. We then generated a co-methylation network – MethylationNetwork – using 27,720 publicly available methylation profiles and integrated it with a public RNA-seq co-expression dataset of 31,499 samples. Here, we observed that MethylationNetwork can identify experimentally validated interacting pairs of genes that could not be identified in the RNA-seq datasets. We then developed a novel integration pipeline based on CCA and used the integrated methylation and gene networks to predict gene pairs reported in the STRING database. The integrated network showed significantly improved prediction performance compared to using a DNA co-methylation or a gene co-expression network alone. This is the first study to integrate data from two -omics layers from unmatched public samples across different tissues and diseases, and our results highlight the issues and potential of integrating public datasets from multiple molecular phenotypes. The eQTMs we identified can be used as an annotation resource for epigenome-wide association, and we believe that our integration pipeline can be used as a framework for future -omics integration analyses of public datasets.We provide supporting materials and results, including the harmonized DNA methylation data from multiple tissues and diseases in https://data.harmjanwestra.nl/comethylation/, the discovered and predicted eQTMs, the corresponding CCA components and the trained prediction models in a Zenodo repository (https://zenodo.org/record/4666994). We provide notebooks to facilitate use of the proposed pipeline in a GitHub repository (https://github.com/molgenis/methylationnetwork).
Planning the potential future during multi-item visual working memory
Authors: Nasrawi Rose , van Ede Freek 
Published: December 2021

AbstractWorking memory allows us to retain visual information to guide upcoming future behavior. In line with this future-oriented purpose of working memory, recent studies have shown that action planning occurs during encoding and retention of a single visual item, for which the upcoming action is certain. We asked whether and how this extends to multi-item visual working memory, when visual representations serve the potential future. Human participants performed a visual working memory task with a memory-load manipulation (one/two/four items), and a delayed orientation-reproduction report (of one item). We measured EEG to track 15-25 Hz beta activity in electrodes contralateral to the required response hand – a canonical marker of action planning. We show an attenuation of beta activity, not only in load one (with one certain future action), but also in load two (with two potential future actions), compared to load four (with low prospective-action certainty). Moreover, in load two, potential action planning occurs regardless whether both visual items afford similar or dissimilar manual responses; and it predicts the speed of ensuing memory-guided behavior. This shows that potential action planning occurs during multi-item visual working memory, and brings the perspective that working memory helps us prepare for the potential future.
Single cell mRNA signals reveal a distinct developmental state of KMT2A-rearranged infant B-cell acute lymphoblastic leukemia
Authors: Khabirova Eleonora , Jardine Laura , Coorens Tim H. H. , Webb Simone , Treger Taryn D. , Englebert Justin , Porter Tarryn , Prigmore Elena , Collord Grace , Piapi Alice , Teichmann Sarah , Inglott Sarah , Williams Owen , Heidenreich Olaf , Young Matthew D. , Straathof Karin , Bomken Simon , Bartram Jack , Haniffa Muzlifah , Behjati Sam 
Published: December 2021

AbstractInfant B-cell acute lymphoblastic leukemia (B-ALL) has not followed the increasing trend towards cure seen in other childhood B-ALLs. The prognosis for infants with KMT2A gene fusions is especially poor, and the origins of this aggressive leukemia remain unknown. Here, we investigated the developmental state of KMT2A-rearranged infant B-ALL within hematopoietic hierarchies of human fetal bone marrow, using bulk mRNA meta-analysis of childhood leukemia and examination of single lymphoblast transcriptomes. KMT2A-rearranged infant B-ALL was uniquely dominated by an early lymphocyte precursor (ELP) state. Direct comparison of infant lymphoblasts with ELP cells distilled the core oncogenic transcriptome of cancer cells which harboured potentially targetable hybrid myeloid-lymphoid features. Overall our quantitative molecular analyses demonstrate a distinct developmental state of KMT2A-rearranged infant B-ALL.
Capturing the start point of the virus-cell interaction with high-speed 3D single-particle tracking
Authors: Johnson Courtney , Exell Jack , Lin Yuxin , Aguilar Jonathan , Welsher Kevin D. 
Published: December 2021

AbstractThe early stages of the virus-cell interaction have long evaded observation by existing microscopy methods due to the rapid diffusion of virions in the extracellular space and the large 3D cellular structures involved. Here we present an active-feedback single-particle tracking method with simultaneous volumetric imaging of the live cell environment to address this knowledge gap to present unprecedented detail to the extracellular phase of the infectious cycle. We report previously unobserved phenomena in the early stages of the virus-cell interaction, including skimming contact events at the millisecond timescale, orders of magnitude change in diffusion coefficient upon binding, and cylindrical and linear diffusion modes along cellular protrusions. Finally, we demonstrate how this new method can move single-particle tracking from simple monolayer culture towards more tissue-like conditions by tracking single virions in tightly packed epithelial cells. This multi-resolution method presents new opportunities for capturing fast, 3D processes in biological systems.One-Sentence SummaryActive-feedback 3D single-particle tracking enables an unprecedented look at the early stages of virus-cell interactions.
Differential regulation of SHH signaling and the developmental control of species-specific jaw size through neural crest-mediated Gas1 expression
Authors: Vavrušová Zuzana , Chu Daniel B. , Nguyen An , Fish Jennifer L. , Schneider Richard A. 
Published: December 2021

AbstractDevelopmental control of jaw size is crucial to prevent disease and facilitate evolution. We have shown that species-specific differences in jaw size are established by neural crest mesenchyme (NCM), which are the jaw progenitors that migrate into the mandibular primordia. NCM relies on multiple signaling molecules including Sonic Hedgehog (SHH) to mediate interactions with mandibular epithelium that facilitate outgrowth of the jaws. SHH signaling is known to promote outgrowth and so we tested if differential regulation of the SHH pathway can account for species-specific variation in mandibular primordia size. We analyze gene expression of SHH pathway members in duck, chick, and quail, and find higher transcriptional activation in the larger mandibular primordia of duck relative to those of chick and quail. We generate quail-duck chimeras and demonstrate that such activation is NCM-mediated. Gain- and loss-of-function experiments reveal a species-specific response to SHH signaling, with the targetGas1being most sensitive to manipulations.Gas1overexpression and knockdown in NCM alters cell number and/or mandibular primordia size. Our work suggests that NCM-mediated changes in SHH signaling may modulate jaw size during development, disease, and evolution.Summary StatementWe have determined thatGas1, which is a component of the SHH signaling pathway, plays a key role in the development and evolution of jaw size.
Geographic Disparities and Determinants of COVID-19 Incidence Risk in the Greater St. Louis Area, Missouri
Authors: Das Praachi , Igoe Morganne , Lenhart Suzanne , Luong Lan , Lanzas Cristina , Lloyd Alun L. , Odoi Agricola 
Published: December 2021

AbstractBackgroundEvidence suggests that the risk of Coronavirus Disease 2019 (COVID-19) varies geographically due to differences in population characteristics. Therefore, the objectives of this study were to identify: (a) geographic disparities of COVID-19 risk in the Greater St. Louis area of Missouri, USA; (b) predictors of the identified disparities.MethodsData on COVID-19 incidence and chronic disease hospitalizations were obtained from the Departments of Health and Missouri Hospital Association, respectively. Socioeconomic and demographic data were obtained from the 2018 American Community Survey while population mobility data were obtained from the SafeGraph website. Choropleth maps were used to identify geographic disparities of COVID-19 risk and its predictors at the ZIP Code Tabulation Area (ZCTA) spatial scale. Global negative binomial and local geographically weighted negative binomial models were used to identify predictors of ZCTA-level geographic disparities of COVID-19 risk.ResultsThere were geographic disparities in COVID-19 risk. Risks tended to be higher in ZCTAs with high percentages of the population with a bachelor’s degree (p<0.0001) and obesity hospitalizations (p<0.0001). Conversely, risks tended to be lower in ZCTAs with high percentages of the population working in agriculture (p<0.0001). However, the association between agricultural occupation and COVID-19 risk was modified by per capita between ZCTA visits. Areas that had both high per capita between ZCTA visits and high percentages of the population employed in agriculture had high COVID-19 risks. The strength of association between agricultural occupation and COVID-19 risk varied by geographic location.ConclusionsGeographic Information Systems, global and local models are useful for identifying geographic disparities and predictors of COVID-19 risk. Geographic disparities of COVID-19 risk exist in the St. Louis area and are explained by differences in sociodemographic factors, population movements, and obesity hospitalization risks. The latter is particularly concerning due to the growing prevalence of obesity and the known immunological impairments among obese individuals. Therefore, future studies need to focus on improving our understanding of the relationships between COVID-19 vaccination efficacy, obesity and waning of immunity among obese individuals so as to better guide vaccination regimens, reduce disparities and improve population health for all.
Adaptive tail-length evolution in deer mice is associated with differential Hoxd13 expression in early development
Authors: Kingsley Evan P. , Hager Emily R. , Lassance Jean-Marc , Turner Kyle M. , Harringmeyer Olivia S. , Kirby Christopher , Neugeboren Beverly I. , Hoekstra Hopi E. 
Published: December 2021

SUMMARYVariation in the size and number of axial segments underlies much of the diversity in animal body plans. Here, we investigate the evolutionary, genetic, and developmental mechanisms driving tail-length differences between forest and prairie ecotypes of deer mice (Peromyscus maniculatus). We first show that long-tailed forest mice perform better in an arboreal locomotion assay, consistent with tails being important for balance during climbing. The long tails of these forest mice consist of both longer and more caudal vertebrae than prairie mice. Using quantitative genetics, we identify six genomic regions that contribute to differences in total tail length, three of which associate with vertebra length and the other three with vertebra number. For all six loci, the forest allele increases tail length, consistent with the cumulative effect of natural selection. Two of the genomic regions associated with variation in vertebra number contain Hox gene clusters. Of those, we find an allele-specific decrease in Hoxd13 expression in the embryonic tail bud of long-tailed forest mice, consistent with its role in axial elongation. Additionally, we find that forest embryos have more presomitic mesoderm than prairie embryos, and that this correlates with an increase in the number of neuromesodermal progenitors (NMPs), which are modulated by Hox13 paralogs. Together, these results suggest a role for Hoxd13 in the development of natural variation in adaptive morphology on a microevolutionary timescale.HIGHLIGHTSIn deer mice, the long-tailed forest ecotype outperforms the short-tailed prairie ecotype in climbing, consistent with the tail’s role in balance.Long tails are due to mutations on distinct chromosomes that affect either length or number of caudal vertebrae.QTL mapping identifies Hox clusters, one gene of which – Hoxd13 – shows low allele-specific expression in the embryonic tail bud of forest mice.Forest mouse embryos have a larger presomitic mesoderm (PSM), likely mediated by a larger progenitor population (NMPs) and lower Hoxd13 levels.
Determination of Slow-binding HDAC Inhibitor Potency and Subclass Selectivity
Authors: Moreno-Yruela Carlos , Olsen Christian A. 
Published: December 2021

ABSTRACTHistone deacetylases (HDACs) 1–3 regulate chromatin structure and gene expression. These three enzymes are targets for cancer chemotherapy and are studied for the treatment of immune disorders and neurodegeneration, but there is a lack of selective pharmacological tool compounds to unravel their individual roles. Potent inhibitors of HDACs 1–3 often display slow-binding kinetics, which causes a delay in inhibitor–enzyme equilibration and may affect assay readout. Here, we compare the potency and selectivity of slow-binding inhibitors measured by discontinuous and continuous assays. We find that entinostat, a clinical candidate, inhibits HDACs 1–3 by a two-step, slow-binding mechanism with lower potencies than previously reported. In addition, we show that RGFP966, commercialized as HDAC3-selective probe, is a slow-binding inhibitor with inhibitor constants of 57 nM, 31 nM, and 13 nM against HDACs 1–3, respectively. These data highlight a need for thorough kinetic investigation in the development of selective HDAC probes.Table of Contents artwork
Reversable deformation of artificial cell colony for muscle behavior mimicry triggered by actin polymerization
Authors: Li Chao , Zhang Xiangxiang , Yang Boyu , Wei Feng , Ren Yongshuo , Mu Wei , Han Xiaojun 
Published: December 2021

AbstractThe mimicry of living tissues from artificial cells is beneficial to understanding the interaction mechanism among cells, as well as holding great potentials in the tissue engineering field. Self-powered artificial cells capable of reversible deformation are developed by encapsulating living mitochondria, actin proteins, and methylcellulose. Upon the addition of pyruvate molecules, the mitochondria produce ATP molecules as energy sources to trigger the polymerization of actin. ATP molecules were produced by mitochondria (2.76×1010/ml) with the concentrations of 35.8±3.2 µM, 158.2±19.3 µM and 200.7±20.1 μM by adding pyruvate molecules with the concentration of 3 μM, 12 μM and 21 μM, respectively. The reversible deformation of artificial cells is experienced with spindle shape resulting from the polymerization of actins to form filaments adjacent to the lipid bilayer, subsequently back to spherical shape resulting from the depolymerization of actin filaments upon laser irradiations. The linear colonies composed of these artificial cells exhibit collective contraction and relaxation behavior to mimic muscle tissues. At the stage of maximum contraction, the long axis of each GUV is in parallel to each other. All colonies are synchronized in the contraction phase. The deformation of each GUV in the colonies is influenced by its adjacent GUVs. The muscle-like artificial cell colonies paved the path to develop sustainably self-powered artificial tissues in the field of tissue engineering.
All-optical imaging and patterned stimulation with a one-photon endoscope
Authors: Zhang Jinyong , Hughes Ryan N. , Kim Namsoo , Fallon Isabella P. , Bakhurin Konstantin , Kim Jiwon , Ulloa Severino Francesco Paolo , Yin Henry H. 
Published: December 2021

AbstractWhile in vivo calcium imaging makes it possible to record activity in defined neuronal populations with cellular resolution, optogenetics allows selective manipulation of neural activity. Recently, these two tools have been combined to stimulate and record neural activity at the same time, but current approaches often rely on two-photon microscopes that are difficult to use in freely moving animals, or one-photon fiberscopes with benchtop-based digital micromirror devices that limit system portability. To address these limitations, we have developed a new integrated system combining a one-photon endoscope and a digital micromirror device for simultaneous calcium imaging and precise optogenetic photo-stimulation (Miniscope with All-optical Patterned Stimulation and Imaging, MAPSI). Using this system, we were able to successfully image striatal neurons from either the direct pathway or the indirect pathway while simultaneously activating any neuron of choice within the field of view or synthesizing arbitrary spatio-temporal patterns of photo-stimulation in freely moving mice. We could also select neurons based on their relationship with behavior and recreate the behavior by mimicking the natural neural activity with photo-stimulation. MAPSI thus provides a powerful tool for in vivo interrogation of neural circuit function.