bluuebunny/crossref_metadata_2025_split huggingface dataset:
Older adults demonstrate interlimb transfer of reactive gait adaptations to repeated unpredictable gait perturbations
Authors: McCrum Christopher , Karamanidis Kiros , Grevendonk Lotte , Zijlstra Wiebren , Meijer Kenneth 
Published: June 2019

AbstractThe ability to rapidly adjust gait to cope with unexpected mechanical perturbations declines with ageing. Previous studies however, have not ensured that pre-perturbation gait stability was equivalent, meaning that differences in unperturbed gait stability may have influenced the outcomes, which this study addresses. We also examine if interlimb transfer of gait adaptations are observed in healthy older adults, potentially driven by the increased motor error experienced due to their reduced ability to cope with the perturbations. 30 young and 28 older healthy adults experienced ten unpredictable treadmill belt accelerations (the first and last applied to the right leg, the others to the left) during walking at their stability-normalised walking speeds (young: 1.32±0.07m/s; older: 1.31±0.13m/s). Using kinematic data, we assessed the margins of stability during unperturbed walking and the first eight post-perturbation recovery steps. Older adults required three more steps to recover during the first perturbation to each leg than the young adults. Yet, after repeated perturbations of the left leg, older adults required only one more step to recover. Interestingly, for the untrained right leg, we found an improvement of three steps in the recovery of the older adults, indicating interlimb transfer of the improvements. Age differences in reactive gait stability remain even when participants’ walk with equivalent stability. Furthermore, we show that healthy older adults can transfer improvements in balance recovery made during repeated perturbations to one limb to their recovery following a perturbation to the untrained limb.
Meaningful patterns of information in the brain revealed through analysis of errors
Authors: Woolgar Alexandra , Dermody Nadene , Afshar Soheil , Williams Mark A. , Rich Anina N. 
Published: June 2019

SummaryGreat excitement has surrounded our ability to decode task information from human brain activity patterns, reinforcing the dominant view of the brain as an information processor. We tested a fundamental but overlooked assumption: that such decodable information is actually used by the brain to generate cognition and behaviour. Participants performed a challenging stimulus-response task during fMRI. Our novel analyses trained a pattern classifier on data from correct trials, and used it to examine stimulus and rule coding on error trials. There was a striking interaction in which frontoparietal cortex systematically representedincorrectrule but correct stimulus information when participants used the wrong rule, andincorrectstimulus but correct rule information on other types of errors. Visual cortex, by contrast, did not code correct or incorrect information on error. Thus behaviour was tightly linked to coding in frontoparietal cortex and only weakly linked to coding in visual cortex. Human behaviour may indeed result from information-like patterns of activity in the brain, but this relationship is stronger in some brain regions than in others. Testing for information coding on error can help establish which patterns constitute behaviourally-meaningful information.
Somatic aging pathways regulate reproductive plasticity inCaenorhabditis elegans
Authors: Ow Maria C. , Nichitean Alexandra M. , Hall Sarah E. 
Published: June 2019

SummaryEarly life stress of an animal often results in changes in gene expression that correspond with changes in their adult phenotype. In the nematodeC. elegans, starvation during early larval stages promotes entry into a non-feeding, stress-resistant stage named dauer until environmental conditions improve. Here we show that the endocrine signaling attributed to the somatic aging pathways inC. elegansadults lacking a functional germline also regulate the reproductive phenotypes of adults that have experienced dauer as a result of early life starvation. Postdauer adults modulate their fatty acid metabolism in order to re-allocate fat reserves in a manner benefitting their progeny at the expense of the parental somatic fat reservoir. Our results also show that the metabolic plasticity in postdauer animals and the inheritance of ancestral starvation memory in the progeny are a result of crosstalk between somatic and reproductive tissues mediated by the HRDE-1 nuclear RNAi Argonaute.
Mechanoreceptor-mediated circuit regulates cold tolerance in Caenorhabditis elegans
Authors: Takagaki Natsune , Ohta Akane , Ohnishi Kohei , Minakuchi Yohei , Toyoda Atsushi , Fujiwara Yuichiro , Kuhara Atsushi 
Published: June 2019

AbstractC. elegans mechanoreceptors located in the ASG sensoryneuron have been found to sense temperature — a key trait for animal survival. Experimental loss of xanthine dehydrogenase (XDH-1) function in the AIN and AVJ interneurons resulted in reduced cold tolerance and atypical neuronal response to changes in temperature. These interneurons are synapse with upstream neurons such as the mechanoreceptor-expressing ASG. Ca2+ imaging revealed that ASG responsiveness to temperature change via mechanoreceptor DEG-1, a Degenerin/Epithelial Sodium Channel (DEG/ENaC), affects downstream AIN and AVJ circuits. Ectopic expression of DEG-1 in the ASE gustatory neuron resulted in acquisition of thermosensitivity, while electrophysiological analysis revealed that DEG-1 was involved in temperature sensation. Together, these results suggest that cold tolerance is regulated by mechanoreceptor-mediated circuit calculation.
Leveraging eQTLs to identify individual-level tissue of interest for a complex trait
Authors: Majumdar Arunabha , Giambartolomei Claudia , Cai Na , Haldar Tanushree , Schwarz Tommer , Gandal Michael J. , Flint Jonathan , Pasaniuc Bogdan 
Published: June 2019

AbstractGenetic predisposition for complex traits often acts through multiple tissues at different time points during development. As a simple example, the genetic predisposition for obesity could be manifested either through inherited variants that control metabolism through regulation of genes expressed in the brain, or that control fat storage through dysregulation of genes expressed in adipose tissue, or both. Here we describe a statistical approach that leverages tissue-specific expression quantitative trait loci (eQTLs) corresponding to tissue-specific genes to prioritize a relevant tissue underlying the genetic predisposition of a given individual for a complex trait. Unlike existing approaches that prioritize relevant tissues for the trait in the population, our approach probabilistically quantifies the tissue-wise genetic contribution to the trait for a given individual. We hypothesize that for a subgroup of individuals the genetic contribution to the trait can be mediated primarily through a specific tissue. Through simulations using the UK Biobank, we show that our approach can predict the relevant tissue accurately and can cluster individuals according to their tissue-specific genetic architecture. We analyze body mass index (BMI) and waist to hip ratio adjusted for BMI (WHRadjBMI) in the UK Biobank to identify subgroups of individuals whose genetic predisposition act primarily through brain versus adipose tissue, and adipose versus muscle tissue, respectively. Notably, we find that these individuals have specific phenotypic features beyond BMI and WHRadjBMI that distinguish them from random individuals in the data, suggesting biological effects of tissue-specific genetic contribution for these traits.
Altered dorsal CA1 neuronal population coding in the APP/PS1 mouse model of Alzheimer’s disease
Authors: Chockanathan Udaysankar , Warner Emily , Turpin Loel , O’Banion M. Kerry , Padmanabhan Krishnan 
Published: June 2019

AbstractWhile the link between amyloid β (Aβ) accumulation and synaptic degradation in Alzheimer’s disease (AD) is known, the consequences of this pathology on coding remain unknown. We found that the entropy across neural ensembles was lower in the CA1 region in the APP/PS1 mouse model of Aβ, thereby reducing the population’s coding capacity. Our results reveal a network level signature of the deficits Aβ accumulation causes to the computations performed by neural circuits.
ForageGrassBase: Molecular resource for the forage grass Festuca pratensis Huds
Authors: Antony Samy Jeevan Karloss , Rognli Odd Arne , Kovi Mallikarjuna Rao 
Published: June 2019

AbstractBackgroundMeadow fescue (Festuca pratensis Huds.) is one of the most important forage grasses in temperate regions. F. pratensis is a diploid (2n =14) outbreeding species that belongs to the genus Festuca. Together with Lolium, they are the most important genera of forage grasses in temperate regions. F. pratensis has good winter survival, with high quality dry matter yields and persistency, and is suitable both for frequent-cutting conservation regimes and for grazing. It is a significant component of species-rich permanent pastures in the temperate regions, ensuring high forage yield under harsh climatic conditions where other productive forage grass species are unable to grow. However, genomic resources for F. Pratensis is not available so far.ResultsThe draft genome sequences of two F. pratensis genotypes “HF7/2” and “B14/16” are reported in this study. Here, using the draft genome, functional annotation datasets of two F. pratensis cultivars, we have constructed the F. pratensis genome database http://foragegrass.org/, the first open-access platform to provide comprehensive genomic resources related to this forage grass species. The current version of this database provides the most up-to-date draft genome sequence along with structural and functional annotations for genes using Genome Browser (GBrowse). In addition, we have integrated comparative genomic tracks for F. pratensis genomes by mapping F.pratensis genome to the barley, rice, Brachypodium and maize genomes. We have integrated homologus search tool BLAST also for the users to analyze their data. Combined, GBrowse, BLAST and downloadble data gives an user friendly access to F. pratensis genomic resouces. All data in the database were manually curated.ConclusionTo our knowledge, ForageGrassBase is the first genome database dedicated to forage grasses. It provides valuable resources for a range of research fields related to F. pratensis and other forage crop species, as well as for plant research communities in general. The genome database can be accessed at http://foragegrass.org. In the near future, we will expand the ForageGrassBase by adding genomic tools for other forage grass species, as soon as their genomes become available.
Genome-Wide Association Study of Over 427,000 Individuals Establishes Executive Functioning as a Neurocognitive Basis of Psychiatric Disorders Influenced by GABAergic Processes
Authors: Hatoum Alexander S. , Morrison Claire L. , Mitchell Evann C. , Lam Max , Benca-Bachman Chelsie E. , Reineberg Andrew E. , Palmer Rohan H. C. , Evans Luke M. , Keller Matthew C. , Friedman Naomi P. 
Published: June 2019

AbstractDeficits in executive functions (EFs), cognitive processes that control goal-directed behaviors, are associated with psychopathology and neurological disorders. Little is known about the molecular bases of EF individual differences; existing EF genome-wide association studies (GWAS) used small sample sizes and/or focused on individual tasks that are imprecise measures of EF. We conducted a GWAS of a Common EF (cEF) factor based on multiple tasks in the UK Biobank (N=427,037 European-descent individuals), finding 129 independent genome-wide significant lead variants in 112 distinct loci. cEF was associated with fast synaptic transmission processes (synaptic, potassium channel, and GABA pathways) in gene-based analyses. cEF was genetically correlated with measures of intelligence (IQ) and cognitive processing speed, but cEF and IQ showed differential genetic associations with psychiatric disorders and educational attainment. Results suggest that cEF is a genetically distinct cognitive construct that is particularly relevant to understanding the genetic variance in psychiatric disorders.
Serotonin Neurons in the Dorsal and Medial Raphe Nuclei: from Single-Cell Transcriptomes to Whole-Brain Projections
Authors: Ren Jing , Isakova Alina , Friedmann Drew , Zeng Jiawei , Grutzner Sophie , Pun Albert , Zhao Grace Q. , Kolluru Sai Saroja , Wang Ruiyu , Lin Rui , Li Pengcheng , Li Anan , Raymond Jennifer L. , Luo Qingming , Luo Minmin , Quake Stephen R. , Luo Liqun 
Published: June 2019

AbstractSerotonin neurons of the dorsal and medial raphe nuclei (DR and MR) collectively innervate the entire forebrain and midbrain, modulating diverse physiology and behavior. To gain a fundamental understanding of their molecular heterogeneity, we used plate-based single-cell RNA-sequencing to generate a comprehensive dataset comprising eleven transcriptomically distinct serotonin neuron clusters. Systematic in situ hybridization mapped specific clusters to the principal DR, caudal DR, or MR. These transcriptomic clusters differentially express a rich repertoire of neuropeptides, receptors, ion channels, and transcription factors. We generated novel intersectional viral-genetic tools to access specific subpopulations. Whole-brain axonal projection mapping revealed that DR serotonin neurons co-expressing vesicular glutamate transporter-3 preferentially innervate the cortex, whereas those co-expressing thyrotropin-releasing hormone innervate subcortical regions in particular the hypothalamus. Reconstruction of 50 individual DR serotonin neurons revealed segregated axonal projection patterns at the single-cell level. Together, these results provide a molecular foundation of the heterogenous serotonin neuronal phenotypes.
Revisiting Parameter Estimation in Biological Networks: Influence of Symmetries
Authors: Sreedharan Jithin K. , Turowski Krzysztof , Szpankowski Wojciech 
Published: June 2019

AbstractGraph models often give us a deeper understanding of real-world networks. In the case of biological networks they help in predicting the evolution and history of biomolecule interactions, provided we map properly real networks into the corresponding graph models. In this paper, we show that for biological graph models many of the existing parameter estimation techniques overlook the critical property of graph symmetry (also known formally as graph automorphisms), thus the estimated parameters give statistically insignificant results concerning the observed network. To demonstrate it and to develop accurate estimation procedures, we focus on the biologically inspired duplication-divergence model, and the up-to-date data of protein-protein interactions of seven species including human and yeast. Using exact recurrence relations of some prominent graph statistics, we devise a parameter estimation technique that provides the right order of symmetries and uses phylogenetically old proteins as the choice of seed graph nodes. We also find that our results are consistent with the ones obtained from maximum likelihood estimation (MLE). However, the MLE approach is significantly slower than our methods in practice.
Biofilm inhibitor taurolithocholic acid alters colony morphology, specialized metabolism, and virulence ofPseudomonas aeruginosa
Authors: Condren Alanna R. , Kahl Lisa Juliane , Kritikos George , Banzhaf Manuel , Dietrich Lars E. P. , Sanchez Laura M. 
Published: June 2019

AbstractBiofilm inhibition by exogenous molecules has been an attractive strategy for the development of novel therapeutics. We investigated the biofilm inhibitor taurolithocholic acid (TLCA) and its effects on the specialized metabolism, virulence and biofilm formation of the clinically relevant bacteriumPseudomonas aeruginosastrain PA14. Our study shows that TLCA alters specialized metabolism, thereby affectingP. aeruginosacolony biofilm physiology. We observed an upregulation of metabolites correlated to virulence such as the siderophore pyochelin. A wax moth virulence assay confirmed that treatment with TLCA increases virulence ofP. aeruginosa. Based on our results, we believe that future endeavors to identify biofilm inhibitors must consider how a putative lead is altering the specialized metabolism of a bacterial community to prevent pathogens from entering a highly virulent state.
COMPASS: a COMprehensive Platform for smAll RNA-Seq data analySis
Authors: Li Jiang , Kho Alvin T. , Chase Robert P. , Pantano-Rubino Lorena , Farnam Leanna , Amr Sami S. , Tantisira Kelan G. 
Published: June 2019

AbstractBackgroundCirculating RNAs are potential disease biomarkers and their function is being actively investigated. Next generation sequencing (NGS) is a common means to interrogate the small RNA’ome or the full spectrum of small RNAs (<200 nucleotide length) of a biological system. A pivotal problem in NGS based small RNA analysis is identifying and quantifying the small RNA’ome constituent components. Most existing NGS data analysis tools focus on the microRNA component and a few other small RNA types like piRNA, snRNA and snoRNA. A comprehensive platform is needed to interrogate the full small RNA’ome, a prerequisite for down-stream data analysis.ResultsWe present COMPASS, a comprehensive modular stand-alone platform for identifying and quantifying small RNAs from small RNA sequencing data. COMPASS contains prebuilt customizable standard RNA databases and sequence processing tools to enable turnkey basic small RNA analysis. We evaluated COMPASS against comparable existing tools on small RNA sequencing data set from serum samples of 12 healthy human controls, and COMPASS identified a greater diversity and abundance of small RNA molecules.ConclusionCOMPASS is modular, stand-alone and integrates multiple customizable RNA databases and sequence processing tool and is distributed under the GNU General Public License free to non-commercial registered users at https://regepi.bwh.harvard.edu/circurna/ and the source code is available at https://github.com/cougarlj/COMPASS.
Spatial analysis of gut microbiome reveals a distinct ecological niche associated with the mucus layer
Authors: Duncan Kellyanne , Carey-Ewend Kelly , Vaishnava Shipra 
Published: June 2019

AbstractMucus associated bacterial communities are critical for determining disease pathology and promoting colonization resistance. Yet the key ecological properties of mucus resident communities remain poorly defined. Using an approach that combines in situ hybridization, laser microdissection and 16s rRNA sequencing of spatially distinct regions of the mouse gut lumen, we discovered that a dense microbial community resembling a biofilm is embedded in the mucus layer. The mucus associated biofilm-like community excluded bacteria belonging to phylum Proteobacteria. Additionally, it was significantly more diverse and consisted of bacterial species that were unique to it. By employing germ-free mice deficient in T and B lymphocytes we found that formation of biofilm-like structure was independent of adaptive immunity. Instead the integrity of biofilm-like community depended on Gram-positive commensals such as Clostridia. Additionally, biofilm-like community in the mucus lost fewer Clostridia and showed smaller bloom of Proteobacteria compared to the lumen upon antibiotic treatment. When subjected to time restricted feeding biofilm like structure significantly enhanced in size and showed enrichment of Clostridia. Taken together our work discloses that mucus associated biofilm-like community represent a specialized community that is structurally and compositionally distinct that excludes aerobic bacteria while enriching for anaerobic bacteria such as Clostridia, exhibits enhanced stability to antibiotic treatment and that can be modulated by dietary changes.
Symmetry breaking transition towards directional locomotion in Physarum microplasmodia
Authors: Zhang Shun , Lasheras Juan C. , del Álamo Juan C. 
Published: June 2019

AbstractTrue slime mold Physarum polycephalum has been widely used as a model organism to study flow-driven amoeboid locomotion as well as the dynamics of its complex mechanochemical self-oscillations. The aim of this work is to quantify the mechanical aspects of symmetry breaking and its transition into directional flow-driven amoeboid locomotion in small (<∼ 200 µm) fragments of Physarum polycephalum. To this end, we combined measurements of traction stresses, fragment morphology, and ectoplasmic microrheology with experimental manipulations of cell-substrate adhesion, cortical strength and microplasmodium size. These measurements show that initiation of locomotion is accompanied by the symmetry breaking of traction stresses and the polarization of ectoplasmic mechanical properties, with the rear part of the microplasmodium becoming significantly stiffer after the onset of locomotion. Our experimental data suggests that the initiation of locomotion in Physarum could be analogous to an interfacial instability process and that microplasmodial size is a critical parameter governing the instability. Specifically, our results indicate that the instability driving the onset of locomotion is strengthened by substrate adhesiveness and weakened by cortical stiffness. Furthermore, the Fourier spectral analysis of morphology revealed lobe number n = 2 as the consistent dominant mode number across various experimental manipulations, suggesting that the instability mechanism driving the onset of Physarum locomotion is robust with respect to changes in environmental conditions and microplasmodial properties.
A neuronal signature for monogamous reunion
Authors: Scribner Jennifer L. , Vance Eric , Protter David S.W. , Sheeran William M. , Saslow Elliott , Cameron Ryan , Klein Eric , Jimenez Jessica C. , Kheirbek Mazen A. , Donaldson Zoe R. 
Published: June 2019

AbstractPair bond formation depends vitally on neuromodulatory signaling within the nucleus accumbens, but the neuronal dynamics underlying this behavior remain unclear. Using in vivo Ca2+ imaging in monogamous prairie voles, we found that pair bonding does not elicit differences in overall nucleus accumbens Ca2+ activity. Instead, we identified distinct neuronal ensembles in this region recruited during approach to either a partner or novel vole. The partner-approach neuronal ensemble increased in size following bond formation and differences in the size of approach ensembles for partner and novel voles predicts bond strength. In contrast, neurons comprising departure ensembles do not change over time and are not correlated with bond strength indicating that ensemble plasticity is specific to partner approach. Further, the neurons comprising partner and novel approach ensembles are non-overlapping while departure ensembles are more overlapping than chance, which may reflect another key feature of approach ensembles. We posit that the features of the partner approach ensemble and its expansion upon bond formation make it a potential key substrate underlying bond formation and maturation.HighlightsWe performed in vivo Ca2+ in the nucleus accumbens of pair bonded prairie volesOverall nucleus accumbens activity did not differ during partner versus stranger interactionDistinct approach neurons exist for the partner and for the strangerPartner-approach ensemble increases as partner preference emergesWe identify a putative neuronal substrate underlying bond formation and maturation