bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Minimal Biophysical Model of Neocortical Pyramidal Cells: Implications for Frontal Cortex Microcircuitry and Field Potential Generation
Authors: Herrera Beatriz , Sajad Amirsaman , Woodman Geoffrey F. , Schall Jeffrey D. , Riera Jorge J. 
Published: January 2020

AbstractCa2+spikes initiated in the apical dendrites of layer-5 pyramidal cells (PC) underlie nonlinear dynamic changes in the gain of cellular response, which is critical for top-down cognitive control. Detailed models with several compartments and dozens of ionic channels have been proposed to account for this Ca2+spike-dependent gain with its associated critical frequency. However, current models do not account for all known Ca2+-dependent features. Previous attempts to include more features have required increasing complexity, limiting their interpretability and utility for studying large population dynamics. We present a minimal 2-compartment biophysical model, overcoming these limitations. In our model, a basal-dendritic/somatic compartment included typical Na+and K+conductances, while an apical-dendritic/trunk compartment included persistent Na+, hyperpolarization-activated cation (Ih), slow inactivation K+, muscarinic K+, and Ca2+L-type. The model replicated the Ca2+spike morphology and its critical frequency plus three other defining features of layer-5 PC synaptic integration: linear frequency-current relationships, backpropagation-activated Ca2+spike firing, and a shift in the critical frequency by blocking Ih. Simulating 1,000 synchronized layer-5 PCs, we reproduced the current source density patterns evoked by Ca2+-spikes both with and without Ihcurrent. Thus, a 2-compartment model with five non-classic ionic currents in the apical-dendrites reproduces all features of these neurons. We discuss the utility of this minimal model to study the microcircuitry of agranular areas of the frontal lobe involved in cognitive control and responsible for event-related potentials such as the error-related negativity.Significance StatementA tractable model of layer-5 pyramidal cells replicates all known features crucial for distal synaptic integration in these neurons. This minimal model enables new multi-scale investigations of microcircuit functions with associated current flows measured by intracranial local field potentials. It thus establishes a foundation for the future computational evaluation of scalp electroencephalogram signatures imprinted by Ca2+spikes in pyramidal cells, a phenomenon underlying many brain cognitive processes.
microRNA-seq of cartilage reveals an over-abundance of miR-140-3p which contains functional isomiRs
Authors: Woods Steven , Charlton Sarah , Cheung Kat , Hao Yao , Soul Jamie , Reynard Louise N , Crowe Natalie , Swingler Tracey E. , Skelton Andrew J. , Piróg Katarzyna A. , Miles Colin G. , Tsompani Dimitra , Jackson Robert M. , Dalmay Tamas , Clark Ian M. , Barter Matt J. , Young David A. 
Published: January 2020

ABSTRACTMiR-140 is selectively expressed in cartilage. Deletion of the entire miR-140 locus in mice results in growth retardation and early-onset osteoarthritis-like pathology, however the relative contribution of miR-140-5p or miR-140-3p to the phenotype remains to be determined. An unbiased small RNA sequencing approach identified miR-140-3p as significantly more abundant (>10-fold) than miR-140-5p in human cartilage. Analysis of these data identified multiple miR-140-3p isomiRs differing from the miRBase annotation at both the 5’ and 3’ end, with >99% having one of two seed sequences (5 ‘ bases 2-8). Canonical (miR-140-3p.2) and shifted (miR-140-3p.1) seed isomiRs were overexpressed in chondrocytes and transcriptomics performed to identify targets. miR-140-3p.1 and miR-140-3p.2 significantly down-regulated 694 and 238 genes respectively, of which only 162 genes were commonly down-regulated. IsomiR targets were validated using 3 ‘UTR luciferase assays. miR-140-3p.1 targets were enriched within up-regulated genes in rib chondrocytes ofMir140-null mice and within down-regulated genes during human chondrogenesis. Finally, through imputing the expression of miR-140 from the expression of the host geneWWP2in 124 previously published datasets, an inverse correlation with miR-140-3p.1 predicted targets was identified. Together these data suggest the novel seed containing isomiR miR-140-3p.1 is more functional than original consensus miR-140-3p seed containing isomiR.
Pervasive phenotypic impact of a large non-recombining introgressed region in yeast
Authors: Brion Christian , Caradec Claudia , Pflieger David , Friedrich Anne , Schacherer Joseph 
Published: January 2020

AbstractTo explore the origin of the diversity observed in natural populations, many studies have investigated the relationship between genotype and phenotype. In yeast species, especially inSaccharomyces cerevisiae, these studies are mainly conducted using recombinant offspring derived from two genetically diverse isolates, allowing to define the phenotypic effect of genetic variants. However, large genomic variants such as interspecies introgressions are usually overlooked even if they are known to modify the genotype-phenotype relationship. To have a better insight into the overall phenotypic impact of introgressions, we took advantage of the presence of a 1-Mb introgressed region, which lacks recombination and contains the mating-type determinant in theLachancea kluyveribudding yeast. By performing linkage mapping analyses in this species, we identified a total of 89 loci affecting growth fitness in a large number of conditions and 2,187 loci affecting gene expression mostly grouped into two major hotspots, one being the introgressed region carrying the mating-type locus. Because of the absence of recombination, our results highlight the presence of a sexual dimorphism in a budding yeast for the first time. Overall, by describing the phenotype-genotype relationship in theL. kluyverispecies, we expanded our knowledge on how genetic characteristics of large introgression events can affect the phenotypic landscape.
Molecular mechanism of light-driven sodium pumping
Authors: Kovalev K. , Astashkin R. , Gushchin I. , Orekhov P. , Volkov D. , Zinovev E. , Marin E. , Rulev M. , Alekseev A. , Royant A. , Carpentier P. , Vaganova S. , Baeken C. , Sergeev I. , Zabelskii D. , Balandin T. , Bourenkov G. , Borshchevskiy V. , Büldt G. , Bamberg E. , Gordeliy V. 
Published: January 2020

ABSTRACTMicrobial rhodopsins appeared to be the most abundant light-harvesting proteins on the Earth and are the major contributes to the solar energy captured in the sea. They possess highly diverse biological functions. Explosion of research on microbial rhodopsins led to breakthroughs in their applications, in particular, in neuroscience.An unexpected new discovery was a Na+-pumping KR2 rhodopsin fromKrokinobacter eikastus, the first light-driven non-proton cation pump. A fundamental difference between proton and other cation pumps is that non-proton pumps cannot use tunneling or Grotthuss mechanism for the ion translocation and, therefore, Na+pumping cannot be understood in the framework of classical proton pump, like bacteriorhodopsin. Extensive studies on the molecular mechanism of KR2 failed to reveal mechanism of pumping. The existing high-resolution structures relate only to the ground state of the protein and revealed no Na+inside the protein, which is unusual for active ion transporters.KR2 is only known non proton cation transporter with demonstrated remarkable potential for optogenetic applications and, therefore, elucidation of the mechanism of cation transport is important. To understand conception of cation pumping we solved crystal structures of the functionally key O-intermediate state of physiologically relevant pentameric form of KR2 and its D116N and H30A key mutants at high resolution and performed additional functional studies.The structure of the O-state reveals a sodium ion near the retinal Schiff base coordinated by N112 and D116 residues of the characteristic (for the whole family) NDQ triad. The structural and functional data show that cation uptake and release are driven by a switching mechanism. Surprisely, Na+pathway in KR2 is lined with the chain of polar pores/cavities, similarly to the channelrhodopsin-2. Using Parinello fast molecular dynamics approach we obtained a molecular movie of a probable ion release.Our data provides insight into the mechanism of a non-proton cation light-driven pumping, strongly suggest close relation of sodium pumps to channel rhodopsins and, we believe, expand the present knowledge of rhodopsin world. Certainly they might be used for engineering of cation pumps and ion channels for optogenetics.
Coupling of Ca2+and voltage activation in BK channels through the αB helix/voltage sensor interface
Authors: Geng Yanyan , Deng Zengqin , Zhang Guohui , Budelli Gonzalo , Butler Alice , Yuan Peng , Cui Jianmin , Salkoff Lawrence , Magleby Karl L. 
Published: January 2020

AbstractLarge conductance Ca2+and voltage activated K+(BK) channels control membrane excitability in many cell types. BK channels are tetrameric. Each subunit is comprised of a voltage sensor domain (VSD), a central pore gate domain, and a large cytoplasmic domain (CTD) that contains the Ca2+sensors. While it is known that BK channels are activated by voltage and Ca2+, and that voltage and Ca2+activations interact, less is known about the mechanisms involved. We now explore mechanism by examining the gating contribution of an interface formed between the VSDs and the αB helices located at the top of the CTDs. Proline mutations in the αB helix greatly decreased voltage activation while having negligible effects on gating currents. Analysis with the HCA model indicated a decreased coupling between voltage sensors and pore gate. Proline mutations decreased Ca2+activation for both Ca2+bowl and RCK1 Ca2+sites, suggesting that both high affinity Ca2+sites transduce their effect, at least in part, through the αB helix. Mg2+activation was also decreased. The crystal structure of the CTD with proline mutation L390P showed a flattening of the first helical turn in the αB helix compared to WT, without other notable differences in the CTD, indicating structural change from the mutation was confined to the αB helix. These findings indicate that an intact αB helix/VSD interface is required for effective coupling of Ca2+binding and voltage depolarization to pore opening, and that shared Ca2+and voltage transduction pathways involving the αB helix may be involved.SignificanceLarge conductance BK (Slo1) K+channels are activated by voltage, Ca2+, and Mg2+to modulate membrane excitability in neurons, muscle, and other cells. BK channels are of modular design, with pore-gate and voltage sensors as transmembrane domains and a large cytoplasmic domain CTD containing the Ca2+sensors. Previous observations suggest that voltage and Ca2+sensors interact, but less is known about this interaction and its involvement in the gating process. We show that a previously identified structural interface between the CTD and voltage sensors is required for effective activation by both voltage and Ca2+, suggesting that these processes may share common allosteric activation pathways. Such knowledge should help explain disease processes associated with BK channel dysfunction.
Cell polarisation in a bulk-surface model can be driven by both classic and non-classic Turing instability
Authors: Borgqvist Johannes , Malik Adam , Lundholm Carl , Logg Anders , Gerlee Philip , Cvijovic Marija 
Published: January 2020

AbstractThe GTPase Cdc42 is the master regulator of eukaryotic cell polarisation. During this process the active form of Cdc42 is accumulated at a particular site on the cell membrane called thepole. It is believed that the accumulation of the active Cdc42 resulting in a pole is driven by a combination of activation-inactivation reactions and diffusion. It has been proposed using mathematical modelling that this is the result of diffusion-driven instability, originally proposed by Alan Turing. In this study we developed, analysed and validated a 3D bulk-surface model of the dynamics of Cdc42. We show that the model can undergo both classic and non-classic Turing instability by deriving necessary conditions for which this occurs and conclude that the non-classic case can be viewed as a limit case of the classic case of diffusion driven instability. We thoroughly investigate the parameter space. Using three-dimensional spatio-temporal simulation we predicted pole size and time to polarisation, suggesting that cell polarisation is mainly driven by the reaction strength parameter and that the size of the pole is determined by the relative diffusion.
The impediment to replication at tRNA genes inS. cerevisiaedoes not require tRNA transcription, and is facilitated by topoisomerases and Rad18-dependent repair pathways
Authors: Yeung Rani , Smith Duncan J. 
Published: January 2020

ABSTRACTtRNA genes are widely studied sites of replication-fork pausing and genome instability in the budding yeastSaccharomyces cerevisiae. tRNAs are extremely highly transcribed and serve as constitutive condensin binding sites. tRNA transcription by RNA polymerase III has previously been identified as stimulating replication-fork pausing at tRNA genes, but the nature of the block to replication has not been incontrovertibly demonstrated. Here, we describe a systematic, genome-wide analysis of the contributions of candidates to replication-fork progression at tDNAs in yeast: transcription factor binding, transcription, topoisomerase activity, condensin-mediated clustering, and Rad18-dependent DNA repair. We show that an asymmetric block to replication is maintained even when tRNA transcription is abolished by depletion of one or more subunits of RNA polymerase III. By contrast, analogous depletion of the essential transcription factor TFIIIB removes the obstacle to replication. Therefore, our data suggest that the RNA polymerase III transcription complex itself represents an asymmetric obstacle to replication even in the absence of RNA synthesis. We additionally demonstrate that replication-fork progression past tRNA genes is unaffected by the global depletion of condensin from the nucleus, and can be stimulated by the removal of topoisomerases or Rad18-dependent DNA repair pathways.
Analysis of metagenome-assembled genomes from the mouse gut microbiota reveals distinctive strain-level characteristics
Authors: Li Shenghui , Zhang Siyi , Li Bo , Sha Shanshan , Kang Jian , Li Peng , Zhang Aiqin , Ji Qianru , Lv Qingbo , Zhang Xiao-Xuan , Ni Hongbo , Han Xiuyan , Xu Miao , Wang Guangyang , Zhang Wenzhe , Sun Yuanyuan , Xu Roujia , Xin Yi , Yan Qiulong , Ma Yufang 
Published: January 2020

AbstractThe laboratorial mouse harbors a unique gut microbiota with potential value for human microbiota-associated studies. Mouse gut microbiota has been explored at the genus and species levels, but features rarely been showed at the strain level. The identification of 833,051 and 658,438 nonredundant genes of faeces and gut content samples from the laboratorial C57/BL mice showed over half of these genes were newly found compared to the previous mouse gut microbial gene catalogue. Metagenome-assembled genomes (MAGs) was used to reconstruct 46 nonredundant MAGs belonging to uncultured specieses. These MAGs included members across all phyla in mouse gut (i.e. Firmicutes, Bacteroidetes, Proteobacteria, Deferribacteres, Verrucomicrobia, and Tenericutes) and allowed a strain-level delineating of the mouse gut microbiota. Comparison of MAGs with human gut colonies revealed distinctive genomic and functional characteristics of mouse’s Bacteroidetes and Firmicutes strains. Genomic characteristics of rare phyla in mouse gut microbiota were demonstrated by MAG approach, including strains ofMucispirillum schaedleri, Parasutterella excrementihominis, Helicobacter typhlonius, andAkkermansia muciniphila.ImportanceThe identification of nonredundant genes suggested the existence of unknown microbes in the mouse gut samples. The metagenome-assembled genomes (MAGs) instantiated the specificity of mouse gut species and revealed an intestinal microbial correlation between mouse and human. The cultivation of faeces and gut contents sample validated the existence of MAGs and estimate their accuracy. Full-length 16S ribosomal RNA gene sequencing enabled taxonomic characterization. This study highlighted a unique ecosystem in the gut of laboratorial mice that obviously differed with the human gut flora at the strain level. The outcomes may be beneficial to researches based on laboratorial mouse models.
Degrees of compositional shift in tree communities vary along a gradient of temperature change rates over one decade: Application of an individual-based temporal beta-diversity concept
Authors: Nakadai Ryosuke 
Published: January 2020

AbstractTemporal patterns in communities have gained widespread attention recently, to the extent that temporal changes in community composition are now termed “temporal beta-diversity”. Previous studies of beta-diversity have made use of two classes of dissimilarity indices: incidence-based (e.g., Sørensen and Jaccard dissimilarity) and abundance-based (e.g., Bray–Curtis and Ružička dissimilarity). However, in the context of temporal beta-diversity, the persistence of identical individuals and turnover among other individuals within the same species over time have not been considered, despite the fact that both will affect compositional changes in communities. To address this issue, I propose new index concepts for beta-diversity and the relative speed of compositional shifts in relation to individual turnover based on individual identity information. Individual-based beta-diversity indices are novel dissimilarity indices that consider individual identity information to quantitatively evaluate temporal change in individual turnover and community composition. I applied these new indices to individually tracked tree monitoring data in deciduous and evergreen broad-leaved forests across the Japanese archipelago with the objective of quantifying the effect of climate change trends (i.e., rates of change of both annual mean temperature and annual precipitation) on individual turnover and compositional shifts at each site. A new index explored the relative contributions of mortality and recruitment processes to temporal changes in community composition. Clear patterns emerged showing that an increase in the temperature change rate facilitated the relative contribution of mortality components. The relative speed of compositional shift increased with increasing temperature change rates in deciduous forests but decreased with increasing warming rates in evergreen forests. These new concepts provide a way to identify novel and high-resolution temporal patterns in communities.
Population genomic structure in Goodman’s mouse lemur reveals long-standing separation of Madagascar’s Central Highlands and eastern rainforests
Authors: Tiley George P. , Blanco Marina B. , Ralison José M. , Rasoloarison Rodin M. , Stahlke Amanda R. , Hohenlohe Paul A. , Yoder Anne D. 
Published: January 2020

AbstractThe Central Highland Plateau of Madagascar is largely composed of grassland savanna, interspersed with patches of closed-canopy forest. Conventional wisdom has it that these grasslands are anthropogenic in nature, having been created very recently via human agricultural practices. Yet, the ancient origins of the endemic grasses suggest that the extensive savannas are natural biomes, similar to others found around the globe. We use a phylogeographic approach to compare these two competing scenarios. By sampling multiple populations of Goodman’s mouse lemur (Microcebus lehilahytsara), a small-bodied nocturnal primate, we reconstruct the phylogeographic and demographic history of these “environmental metronomes” to estimate the time at which their populations diverged, and thus proximally, when their habitats would have become fragmented. We applied coalescent methods to RADseq data to infer phylogenetic relationships, population structure, and migration corridors among sampling sites. These analyses indicate that forest fragmentation occurred rapidly during a period of decreased precipitation near the last glacial maximum and would have affected both the Central Highlands and eastern forests. Though there is clear genomic structure separating the populations of the Central Highland from those of the eastern rainforests, there is also evidence of historical migration between them. Findings support the hypothesis that the Central Highland savanna predates human arrival, indicating that it is a natural landscape that has long impacted the population dynamics of Goodman’s mouse lemur, and by extension, other forest-dwelling organisms in Madagascar.
metaVaR: introducing metavariant species models for reference-free metagenomic-based population genomics
Authors: Laso-Jadart Romuald , Ambroise Christophe , Peterlongo Pierre , Madoui Mohammed-Amin 
Published: January 2020

AbstractMotivationThe availability of large metagenomic data offers great opportunities for the population genomic analysis of uncultured organisms, especially for small eukaryotes that represent an important part of the unexplored biosphere while playing a key ecological role. However, the majority of these species lacks reference genome or transcriptome which constitutes a technical barrier for classical population genomic analyses.ResultsWe introduce the metavariant species (MVS) model, a representation of the species only by intra-species nucleotide polymorphism. We designed a method combining reference-free variant calling, multiple density-based clustering and maximum weighted independent set algorithms to cluster intra-species variant into MVS directly from multisample metagenomic raw reads without reference genome or reads assembly. The frequencies of the MVS variants are then used to compute population genomic statistics such asFSTin order to estimate genomic differentiation between populations and to identify loci under natural selection. The MVSs construction was tested on simulated and real metagenomic data. MVs showed the required quality for robust population genomics and allowed an accurate estimation of genomic differentiation (ΔFST<0.0001 and < 0.03 on simulated and real data respectively). Loci predicted under natural selection on real data were all found by MVSs. MVSs represent a new paradigm that may simplify and enhance holistic approaches for population genomics and evolution of microorganisms.AvailabilityThe method was implemented in a R package,metaVaR.https://github.com/madoui/MetaVaRContactamadoui@genoscope.cns.fr