bluuebunny/crossref_metadata_2025_split huggingface dataset:
Label-free optical detection of bioelectric potentials using electrochromic thin films
Authors: Alfonso Felix S. , Zhou Yuecheng , Liu Erica , McGuire Allister F. , Yang Yang , Kantarci Husniye , Li Dong , Copenhaver Eric , Zuchero J. Bradley , Müller Holger , Cui Bianxiao 
Published: May 2020

AbstractUnderstanding how a network of interconnected neurons receives, stores, and processes information in the human brain is one of the outstanding scientific challenges of our time. The ability to reliably detect neuroelectric activities is essential to addressing this challenge. Optical recording using voltage-sensitive fluorescent probes has provided unprecedented flexibility for choosing regions of interest in recording neuronal activities. However, when recording at a high frame rate such as 500-1000 Hz, fluorescence-based voltage sensors often suffer from photobleaching and phototoxicity, which limit the recording duration. Here, we report a new approach, Electro-Chromic Optical REcording (ECORE), that achieves label-free optical recording of spontaneous neuroelectrical activities. ECORE utilizes the electrochromism of PEDOT:PSS thin films, whose optical absorption can be modulated by an applied voltage. Being based on optical reflection instead of fluorescence, ECORE offers the flexibility of an optical probe without suffering from photobleaching or phototoxicity. Using ECORE, we optically recorded spontaneous action potentials in cardiomyocytes, cultured hippocampal and dorsal root ganglion neurons, and brain slices. With minimal perturbation to cells, ECORE allows long-term optical recording over multiple days.
Non-thalamic origin of zebrafish sensory relay nucleus: convergent evolution of visual pathways in amniotes and teleosts
Authors: Bloch Solal , Hagio Hanako , Thomas Manon , Heuzé Aurélie , Hermel Jean-Michel , Lasserre Elodie , Colin Ingrid , Saka Kimiko , Affaticati Pierre , Jenett Arnim , Kawakami Koichi , Yamamoto Naoyuki , Yamamoto Kei 
Published: May 2020

AbstractAscending visual projections similar to the mammalian thalamocortical pathway are found in a wide range of vertebrate species, but their homologous relationship is debated. To get better insights into their evolutionary origin, we examined the developmental origin of a visual relay nucleus in zebrafish (a teleost fish). Similarly to the tectofugal visual thalamic nuclei in amniotes, the lateral part of the preglomerular complex (PG) in teleosts receives tectal information and projects to the pallium. However, our cell lineage study reveals that the majority of PG cells are derived from the midbrain, not from the forebrain. We also demonstrate that the PG projection neurons develop gradually until juvenile stage, unlike the thalamic projection neurons. Our data suggest that teleost PG is not homologous to the amniote thalamus and that thalamocortical-like projections can evolve from a non-forebrain cell population. Thus, sensory pathways in vertebrate brains exhibit a surprising degree of variation.
Unraveling molecular interactions in a phase-separating protein by atomistic simulations
Authors: Paloni Matteo , Bailly Rémy , Ciandrini Luca , Barducci Alessandro 
Published: May 2020

AbstractMembraneless organelles are dynamical cellular condensates formed by the liquid-liquid phase separation of proteins and RNA molecules. Multiple evidence suggests that disordered proteins are structural scaffolds that drive the condensation by forming a dynamic network of inter- and intra-molecular contacts. Despite the blooming research activity in this field, the structural characterization of these condensates is very limited and we still do not understand how the phase behaviour is encoded in the amino-acid sequences of the scaffolding proteins. Here we exploited explicit-solvent atomistic simulations to disentangle the molecular interactions governing the phase behaviour of the N-terminal disordered region of DEAD-box helicase 4 (NDDX4), which is a well-established model for phase separationin vitroandin vivo. Single-molecule simulations clarified the interplay between the intramolecular interactions that shape NDDX4 conformational ensemble and the known determinants of its phase behaviour, such as the attraction between oppositely-charged regions and the presence of arginine and phenylalanine. We then investigated intermolecular interactions associated with phase separation via a divide-and-conquer strategy based on the simulations of various NDDX4 fragments at high concentration. Our approach allowed us to probe conditions mimicking real condensates and revealed, in agreement with mutagenesis results, how these interactions arise from the complex interplay of diverse molecular mechanisms. Particularly, we characterized the transient formation of clusters of arginine and aromatic residues, which may stabilize the assembly of several MLOs. Overall, our results reveal the potential of atomistic simulations in the investigation of biomolecular phase separation paving the way for future studies.
The effect of boundaries on grid cell patterns
Authors: Monsalve-Mercado Mauro M. , Leibold Christian 
Published: May 2020

Mammalian grid cells represent spatial locations in the brain via triangular firing patterns that tessellate the environment. They are regarded as the biological substrate for path integration thereby generating an efficient code for space. However, grid cell patterns are strongly influenced by environmental manipulations, in particular exhibiting local geometrical deformations and defects tied to the shape of the recording enclosure, challenging the view that grid cells constitute a universal code for space. We show that the observed responses to environmental manipulations arise as a natural result under the general framework of feedforward models with spatially unstructured feedback inhibition, which puts the development of triangular patterns in the context of a Turing pattern formation process over physical space. The model produces coherent neuronal populations with equal grid spacing, field size, and orientation.PACS numbers87.19.lv,87.10.Ed,02.30.Jr
A comprehensive germline variant and expression analyses ofACE2,TMPRSS2and SARS-CoV-2 activatorFURINgenes from the Middle East: Combating SARS-CoV-2 with precision medicine
Authors: Al-Mulla Fahd , Mohammad Anwar , Al Madhoun Ashraf , Haddad Dania , Ali Hamad , Eaaswarkhanth Muthukrishnan , John Sumi Elsa , Nizam Rasheeba , Channanath Arshad , Abu-Farha Mohamed , Ahmad Rasheed , Abubaker Jehad , Thanaraj Thangavel Alphonse 
Published: May 2020

AbstractThe severity of the new COVID-19 pandemic caused by the SARS-CoV-2 virus is strikingly variable in different global populations. SARS-CoV-2 usesACE2as a cell receptor,TMPRSS2protease, andFURINpeptidase to invade human cells. Here, we investigated 1,378 whole-exome sequences of individuals from the Middle Eastern populations (Kuwait, Qatar, and Iran) to explore natural variations in theACE2,TMPRSS2,andFURINgenes. We identified two activating variants (K26R and N720D) in theACE2gene that are more common in Europeans than in the Middle Eastern, East Asian, and African populations. We postulate that K26R can activateACE2and facilitate binding to S-protein RBD while N720D enhancesTMPRSS2cutting and, ultimately, viral entry. We also detected deleterious variants inFURINthat are frequent in the Middle Eastern but not in the European populations. This study highlights specific genetic variations in theACE2andFURINgenes that may explain SARS-CoV-2 clinical disparity. We showed structural evidence of the functionality of these activating variants that increase the SARS-CoV-2 aggressiveness. Finally, our data illustrate a significant correlation betweenACE2variants identified in people from Middle Eastern origins that can be further explored to explain the variation in COVID-19 infection and mortality rates globally.
The Mystery of a Marine Monster: Morphological and Performance Modifications in the World’s only Marine Lizard, the Galápagos Marine Iguana
Authors: Berry Kate A. , Muñoz-Pérez Juan Pablo , Vintimilla-Palacios Cristina P. , Clemente Christofer J. 
Published: May 2020

AbstractReptiles have repeatedly invaded and thrived in aquatic environments throughout history, however fewer than 8% of the 6000 extant species are primarily aquatic. The Galápagos Marine Iguana (Amblyrhynchus cristatus), the world’s only marine lizard, may have had one of the most unique and challenging transitions to aquatic life. Curiously, previous studies have identified relatively few physiological adaptations in Marine Iguanas, however, little is known about the extent of morphological specialisation and performance trade-offs associated with the marine environment. By examining the morphology and locomotory performance of the Marine Iguana in comparison to their closely related mainland ancestors, the Black Spiny-tailed iguana (Ctenosaura similis) and Green Iguana (Iguana iguana), we found variation reflected specialisation to ecological niches. However, variation was more pronounced among subspecies of Marine Iguana, suggesting that little morphological or performance modification is required for iguanids to successfully invade aquatic environments, thus raising the question why there are so few extant aquatic reptilian lineages. We found that specialisation for the marine environment resulted in a trade-off in sprint speed in a terrestrial environment, similar to that seen in extant crocodilians. Reduced performance in a terrestrial environment likely poses little risk to large-bodied apex predators, whereas in iguanids, a performance trade-off would likely incur increased predation. As such, we suggest that this may explain why iguanids and other ancestral lineages have not undergone transitions to aquatic life. Additionally, we found that the magnitude of morphological and performance variation was more pronounced between subspecies of Marine Iguana than between iguanid species.Summary StatementThe Marine Iguana has undergone a unique evolutionary transition to aquatic behaviour, we explore the extent of morphological and performance specialisation required and why there are so few extant marine reptiles.
MutantHuntWGS: A Pipeline for IdentifyingSaccharomyces cerevisiaeMutations
Authors: Ellison Mitchell A. , Walker Jennifer L. , Ropp Patrick J. , Durrant Jacob D. , Arndt Karen M. 
Published: May 2020

ABSTRACTMutantHuntWGS is a user-friendly pipeline for analyzingSaccharomyces cerevisiaewhole-genome sequencing data. It uses available open-source programs to: (1) perform sequence alignments for paired and single-end reads, (2) call variants, and (3) predict variant effect and severity. MutantHuntWGS outputs a shortlist of variants while also enabling access to all intermediate files. To demonstrate its utility, we use MutantHuntWGS to assess multiple published datasets; in all cases, it detects the same causal variants reported in the literature. To encourage broad adoption and promote reproducibility, we distribute a containerized version of the MutantHuntWGS pipeline that allows users to install and analyze data with only two commands. The MutantHuntWGS software and documentation can be downloaded free of charge fromhttps://github.com/mae92/MutantHuntWGS.
Chromatin folding variability across single-cells results from state degeneracy in phase-separation
Authors: Conte Mattia , Fiorillo Luca , Bianco Simona , Chiariello Andrea M. , Esposito Andrea , Nicodemi Mario 
Published: May 2020

AbstractChromosome spatial organization controls functional interactions between genes and regulators, yet the molecular and physical mechanisms underlying folding at the single DNA molecule level remain to be understood. Here we employ models of polymer physics to investigate the conformations of two 2Mb-wide DNA loci in human HCT116 and IMR90 wild-type and cohesin depleted cells. Model predictions on the 3D structure of single-molecules are consistently validated against super-resolution single-cell imaging data, providing evidence that the architecture of the studied loci is controlled by a thermodynamics mechanism ofpolymer phase separationwhereby chromatin self-assembles in segregated globules. The process is driven by interactions between distinct types of cognate binding sites, correlating each with a different combination of chromatin factors, including CTCF, cohesin and histone marks. The intrinsic thermodynamics degeneracy of conformations results in a broad structural and time variability of single-molecules, reflected in their varying TAD-like contact patterns. Globules breathe in time, inducing stochastic unspecific interactions, yet they produce stable, compact environments where specific contacts become highly favored between regions enriched for cognate binding sites, albeit characterized by weak biochemical affinities. Cohesin depletion tends to reverse globule phase separation into a coil, randomly folded state, resulting in much more variable contacts across single-molecules, hence erasing population-averaged patterns. Overall, globule phase separation appears to be a robust, reversible mechanism of chromatin organization, where stochasticity and specificity coexist.
Cell-Derived Vesicles as TRPC1 Channel Delivery Systems for the Recovery of Cellular Respiratory and Proliferative Capacities
Authors: Kurth Felix , Tai Yee Kit , Parate Dinesh , van Oostrum Marc , Schmid Yannick R. F. , Toh Shi Jie , Yee Yap Jasmine Lye , Wollscheid Bernd , Othman Alaa , Dittrich Petra S. , Franco-Obregón Alfredo 
Published: May 2020

AbstractPulsed electromagnetic fields (PEMFs) are capable of specifically activating a TRPC1-mitochondrial axis underlying cell expansion and mitohormetic survival adaptations. This study characterizes cell-derived vesicles (CDVs) generated from C2C12 murine myoblasts and shows that they are equipped with the sufficient molecular machinery to confer mitochondrial respiratory capacity and associated proliferative responses upon their fusion with recipient cells. CDVs derived from wild type C2C12 myoblasts include the cation-permeable transient receptor potential (TRP) channels, TRPC1 and TRPA1, and directly respond to PEMF exposure with TRPC1-mediated calcium entry. By contrast, CDVs derived from C2C12 muscle cells in which TRPC1 had been genetically knocked-down using CRISPR/Cas9 genome editing, do not. Wild type C2C12-derived CDVs are also capable of restoring PEMF-induced proliferative and mitochondrial activation in two C2C12-derived TRPC1 knockdown clonal cell lines in accordance to their endogenous degree of TRPC1 suppression. C2C12 wild type CDVs respond to menthol with calcium entry and accumulation, likewise verifying TRPA1 functional gating and further corroborating compartmental integrity. Proteomic and lipidomic analyses confirm the surface membrane origin of the CDVs providing an initial indication of the minimal cellular machinery required to recover mitochondrial function. CDVs hence possess the potential of restoring respiratory and proliferative capacities to senescent cells and tissues.
CATA: a comprehensive chromatin accessibility database for cancer
Authors: Zhou Jianyuan , Li Xuecang , Chen Jiaxin , Li Taisong , Zhan Weijie , Zhao Jianmei , Li Meng , Yu Zhengmin , Yu Rui , Zou Haiying , Fang Wangkai , Wang Qiuyu , Xie Jianjun 
Published: May 2020

AbstractChromatin accessibility is a crucial epigenetic concept that plays a biological role in oncology. As humans become more involved in cancer research, a comprehensive database is required to identify and annotate tumor chromatin accessible regions (CARs). Here, CATA was developed to provide cancer-related CAR annotation. Currently, CATA possesses 2,991,163 CARs, relevant clinical data, and transcription factor binding predictions for cancer CARs from 410 tumor samples of 24 cancer types. Furthermore, CARs were annotated by SNPs, risk SNPs, eQTLs, linkage disequilibrium SNPs, transcription factors, CNV, SNV, enhancer, and 450K methylation sites in our database. By combining all these resources, we believe that CATA will provide better service for researchers on oncology. Our database is accessible athttp://bio.licpathway.net/cata/
Higher prevalence ofBacteroides fragilisin Crohn’s disease exacerbations and strain-dependent increase of epithelial resistance
Authors: Becker Heike E. F. , Jamin Casper , Bervoets Liene , Xu Pan , Pierik Marie J. , Stassen Frank R. M. , Savelkoul Paul H. M. , Penders John , Jonkers Daisy M. A. E. 
Published: May 2020

AbstractBacteroides fragilishas previously been linked to Crohn’s disease (CD) exacerbations, but results are inconsistent and underlying mechanisms unknown. This study investigates the epidemiology ofB. fragilisand its virulence factorsbft (enterotoxin) andubiquitinamong 181 CD patients and the impact on the intestinal epithelial barrierin vitro.The prevalence ofB. fragiliswas significantly higher in active (n=69/88, 78.4%) as compared to remissive (n=58/93, 62.4%, p=0.018) CD patients. Moreover,B. fragiliswas associated with intestinal strictures. Interestingly, the intestinal barrier function, as examined by transepithelial electrical resistance (TEER) measurements of Caco-2 monolayers, improved when exposed to secretomes ofbft-positive (increased TEER ∼160%,p<0.001) but not when exposed tobft-negative strains. Whole metagenome sequencing and metabolomics, respectively, identified 19 coding sequences and two metabolites that discriminated TEER-increasing from non-TEER-increasing strains.This study revealed a higherB. fragilisprevalence during exacerbation. Surprisingly,bft-positive secretomes improved epithelial resistance.
Multifocal imaging for precise, label-free tracking of fast biological processes in 3D
Authors: Hansen Jan N. , Gong An , Wachten Dagmar , Pascal René , Turpin Alex , Jikeli Jan F. , Kaupp U. Benjamin , Alvarez Luis 
Published: May 2020

AbstractMany biological processes happen on a nano-to millimeter scale and within milliseconds. Established methods such as confocal microscopy are suitable for precise 3D recordings but lack the temporal or spatial resolution to resolve fast 3D processes and require labeled samples. Multifocal imaging (MFI) allows high-speed 3D imaging but is limited by the compromise between high spatial resolution and large field-of-view (FOV), and the requirement for bright fluorescent labels. Here, we provide a new open-source 3D reconstruction algorithm for multifocal images that allows using MFI for fast, precise, label-free tracking spherical and filamentous structures in a large FOV and across a high depth. We characterize fluid flow and flagellar beating of human and sea urchin sperm with a high z-precision of 0.15 μm, in a large volume of 240 x 260 x 21 μm, and at high speed (500 Hz). The large sampling volume allowed to follow sperm trajectories while simultaneously recording their flagellar beat. Our MFI concept is cost-effective, can be easily implemented, and does not rely on object labeling, which renders it broadly applicable.
CRYPTOCHROME suppresses the circadian proteome and promotes protein homeostasis
Authors: Wong David C.S. , Seinkmane Estere , Stangherlin Alessandra , Zeng Aiwei , Rzechorzek Nina M. , Beale Andrew D. , Day Jason , Reed Martin , Chew Sew Peak , Styles Christine T. , Edgar Rachel S. , Putker Marrit , O’Neill John S. 
Published: May 2020

AbstractThe daily organisation of most mammalian cellular functions is attributed to circadian regulation of clock-controlled protein expression, driven by daily cycles of CRYPTOCHROME-dependent transcriptional feedback repression. To test this, we compared the circadian proteome and phosphoproteome of wild type and CRY-deficient fibroblast cells. Strikingly, CRY-deficient cells showed a two-fold increase in circadian-regulated proteins, phosphopeptides, and K+transport. This was accompanied by extensive remodelling of the cellular proteome overall, including reduced phosphatase and proteasome subunit expression. These adaptations rendered CRY-deficient cells more sensitive to stress, which may account for their reduced circadian robustness and contribute to the wide-ranging phenotypes of CRY-deficient mice. We suggest that CRY ultimately functions to suppress, rather than generate, daily rhythms in cellular protein abundance, thereby maintaining protein and osmotic homeostasis.
The structural variation landscape in 492 Atlantic salmon genomes
Authors: Bertolotti Alicia C. , Layer Ryan M. , Gundappa Manu Kumar , Gallagher Michael D. , Pehlivanoglu Ege , Nome Torfinn , Robledo Diego , Kent Matthew P. , Røsæg Line L. , Holen Matilde M. , Mulugeta Teshome D. , Ashton Thomas J. , Hindar Kjetil , Sægrov Harald , Florø-Larsen Bjørn , Erkinaro Jaakko , Primmer Craig R. , Bernatchez Louis , Martin Samuel A.M. , Johnston Ian A. , Sandve Simen R. , Lien Sigbjørn , Macqueen Daniel J. 
Published: May 2020

AbstractStructural variants (SVs) are a major source of genetic and phenotypic variation, but remain challenging to accurately type and are hence poorly characterized in most species. We present an approach for reliable SV discovery in non-model species using whole genome sequencing and report 15,483 high-confidence SVs in 492 Atlantic salmon (Salmo salar L.) sampled from a broad phylogeographic distribution. These SVs recover population genetic structure with high resolution, include an active DNA transposon, widely affect functional features, and overlap more duplicated genes retained from an ancestral salmonid autotetraploidization event than expected. Changes in SV allele frequency between wild and farmed fish indicate polygenic selection on behavioural traits during domestication, targeting brain-expressed synaptic networks linked to neurological disorders in humans. This study offers novel insights into the role of SVs in genome evolution and the genetic architecture of domestication traits, along with resources supporting reliable SV discovery in non-model species.
Identification of deleterious single nucleotide polymorphism (SNP)s on the humanTBX5gene & prediction of their structural & functional consequences: Anin silicoapproach
Authors: Mahfuz A M U B , Khan Md. Arif 
Published: May 2020

AbstractT-box transcription factor 5 (TBX5) gene encodes the transcription factor TBX5, which plays a crucial role in developing the heart and upper limbs. Damaging single nucleotide variants in this gene alters the protein structure, disturbs the functions of TBX5, and ultimately causes Holt-Oram Syndrome (HOS). By analyzing available single nucleotide polymorphism information in the dbSNP database, this study was designed to identify the most deleteriousTBX5SNPs throughsilicoapproaches and predict their structural and functional consequences.Fifty-eight missense substitutions were found damaging by sequences homology-based tools like SIFT and PROVEAN and structure homology-based tools like PolyPhen-2. These SNPs were further scrutinized by various disease association meta-predictor tools. Additionally, the conservation profile of amino acid residues, their surface accessibility, stability, and structural integrity of the native protein upon mutations was assessed. From these analyses, finally 5 SNPs were detected as the most damaging ones [rs1565941579 (P85S), rs1269970792 (W121R), rs772248871 (V153D), rs769113870 (E208D), and rs1318021626 (I222N)]. Analyses of stop-loss, nonsense, UTR, and splice site SNPs were also conducted.Through integrative bioinformatics analyses, this study has identified SNPs that are deleterious to the TBX5 protein structure and have the potential to cause HOS. Further wet-lab experiments can validate these findings.