bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbial associations and spatial proximity predict North American moose (Alces alces) gastrointestinal community composition
Authors: Fountain-Jones Nicholas M. , Clark Nicholas J. , Kinsley Amy C. , Carstensen Michelle , Forester James , Johnson Timothy J. , Miller Elizabeth , Moore Seth , Wolf Tiffany M. , Craft Meggan E. 
Published: January 2019

AbstractMicrobial communities are increasingly recognised as crucial for animal health. However, our understanding of how microbial communities are structured across wildlife populations is poor. Mechanisms such as interspecific associations are important in structuring free-living communities, but we still lack an understanding of how important interspecific associations are in structuring gut microbial communities in comparison to other factors such as host characteristics or spatial proximity of hosts.Here we ask how gut microbial communities are structured in a population of North American moose (Alces alces). We identify key microbial interspecific associations within the moose gut and quantify how important they are relative to key host characteristics, such as body condition, for predicting microbial community composition.We sampled gut microbial communities from 55 moose in a population experiencing decline due to a myriad of factors, including pathogens and malnutrition. We examined microbial community dynamics in this population utilizing novel graphical network models that can explicitly incorporate spatial information.We found that interspecific associations were the most important mechanism structuring gut microbial communities in moose and detected both positive and negative associations. Models only accounting for associations between microbes had higher predictive value compared to models including moose sex, evidence of previous pathogen exposure, or body condition. Adding spatial information on moose location further strengthened our model and allowed us to predict microbe occurrences with ∼90% accuracy.Collectively, our results suggest that microbial interspecific associations coupled with host spatial proximity are vital in shaping infra communities in a large herbivore. In this case, previous pathogen exposure and moose body condition were not as important in predicting gut microbial community composition. The approach applied here can be used to quantify interspecific associations and gain a more nuanced understanding of the spatial and host factors shaping microbial communities in non-model hosts.
Dynamic coordination of the perirhinal cortical neurons supports coherent representations between task epochs
Authors: Ohnuki Tomoya , Osako Yuma , Manabe Hiroyuki , Sakurai Yoshio , Hirokawa Junya 
Published: January 2019

AbstractCortical neurons show distinct firing patterns across multiple task-epochs characterized by distinct computational aspects. Recent studies suggest that such distinct patterns underly dynamic population code achieving computational flexibility, whereas neurons in some cortical areas often show coherent firing patterns across epochs. To understand how such coherent single-neuron code contribute to dynamic population code, we analyzed neural responses in the perirhinal cortex (PRC) during cue and reward epochs of a two-alternative forced-choice task. We found that the PRC neurons often encoded the opposite choice-directions between those epochs. By using principal component analysis as population-level analysis, we identified neural subspaces associated with each epoch, which reflected coordinated patterns across the neurons. The cue and reward epochs shared neural dimensions where the choice directions were consistently discriminated. Interestingly, those dimensions were supported by dynamically changing contributions of individual neurons. These results indicated heterogeneity of coherent single-neuron responses in their contribution to population code.
Visual signal evolution along complementary color axes in four bird lineages
Authors: Krishnan Anand , Singh Avehi , Tamma Krishnapriya 
Published: January 2019

AbstractAnimal color patterns function in varied behavioral contexts including recognition, camouflage and even thermoregulation. The diversity of visual signals may be constrained by various factors, for example, dietary factors, and the composition of ambient environmental light (sensory drive). How have high-contrast and diverse signals evolved within these constraints? In four bird lineages, we present evidence that plumage colors cluster along a line in tetrachromatic color space. Additionally, we present evidence that this line represents complementary colors, which are defined as opposite sides of a line passing through the achromatic point (putatively for higher chromatic contrast). Finally, we present evidence that interspecific color variation over at least some regions of the body is not constrained by phylogenetic relatedness. Thus, we hypothesize that species-specific plumage patterns within these bird lineages evolve by swapping the distributions of a complementary color pair (or dark and light patches in one group, putatively representing an achromatic complementary axis). The relative role of chromatic and achromatic contrasts in discrimination may depend on the environment that each species inhabits.
The mGlu7 receptor provides protective effects against epileptogenesis and epileptic seizures
Authors: Girard Benoit , Tuduri Pola , Moreno Maria Paula , Sakkaki Sophie , Barboux Cedric , Bouschet Tristan , Varrault Annie , Vitre Jihane , McCort Isabelle , Dairou Julien , Acher Francine , Fagni Laurent , Marchi Nicola , Perroy Julie , Bertaso Federica 
Published: January 2019

ABSTRACTFinding new targets to control or reduce seizure activity is essential to improve the management of epileptic patients. We hypothesized that activation of the pre-synaptic and inhibitory metabotropic glutamate receptor type 7 (mGlu7) reduces spontaneous seizures.We tested LSP2-9166, a recently developed mGlu7/4 agonist with unprecedented potency on mGlu7 receptors, in two paradigms of epileptogenesis. In a model of chemically induced epileptogenesis (pentylenetetrazol systemic injection), LSP2-9166 induces an anti-epileptogenic effect rarely observed in preclinical studies. In particular, we found a bidirectional modulation of seizure progression by mGlu4 and mGlu7 receptors, the latter preventing kindling. In the intra-hippocampal injection of kainic acid mouse model that mimics the human mesial temporal lobe epilepsy, we found LSP2-9166 reduced seizure frequency and hippocampal sclerosis. LSP2-9166 also acts as an anti-epileptic drug on established seizures in both models tested.Specific modulation of the mGlu7 receptor could represent a novel approach to reduce pathological network remodeling.
Mosaic origin of the eukaryotic kinetochore
Authors: van Hooff Jolien J.E. , Tromer Eelco , Kops Geert J.P.L. , Snel Berend 
Published: January 2019

AbstractThe emergence of eukaryotes from ancient prokaryotic lineages was accompanied by a remarkable increase in cellular complexity. While prokaryotes use simple systems to connect DNA to the segregation machinery during cell division, eukaryotes use a highly complex protein assembly known as the kinetochore. Although conceptually similar, prokaryotic segregation systems and eukaryotic kinetochore proteins share no homology, raising the question of the origins of the latter. Using large-scale gene family reconstruction, sensitive profile-versus-profile homology detection and protein structural comparisons, we here reveal that the kinetochore of the last eukaryotic common ancestor (LECA) consisted of 52 proteins that share deep evolutionary histories with proteins involved in a few prokaryotic processes and a multitude of eukaryotic processes, including ubiquitination, chromatin regulation and flagellar as well as vesicular transport systems. We find that gene duplications played a major role in shaping the kinetochore: roughly half of LECA kinetochore proteins have other kinetochore proteins as closest homologs. Some of these (e.g. subunits of the Mis12 complex) have no detectable homology to any other eukaryotic protein, suggesting they arose as kinetochore-specific proteins de novo before LECA. We propose that the primordial kinetochore evolved from proteins involved in various (pre-)eukaryotic systems as well as novel proteins, after which a subset duplicated to give rise to the complex kinetochore of LECA.
Modeling Primary Fields of TMS Coils with the Fast Multipole Method
Authors: Makarov Sergey N. , de Lara Lucia Navarro , Noetscher Gregory M. , Nummenmaa Aapo 
Published: January 2019

Abstract:In this study, an accurate TMS-coil modeling approach based on conductor’s cross-section representation with many distributed current filaments coupled with an efficient fast multipole method (FMM) accelerator is developed and tested. Uniform (Litz wire) or skin-effect based current distributions are included into consideration. Speed and accuracy estimates as well as two application examples are given, which indicate that this approach is potentially capable of rapid and accurate evaluation of various detailed TMS coil designs and arrays of such coils.The MATLAB-based wire and CAD mesh generator for the coil geometry is interfaced with the FMM FORTAN program, which is also compiled within the MATLAB shell. No extra MATLAB toolboxes are necessary. The CAD model of the coil can be imported into any other computational software package in STL format. The algorithm is organized in the form of a MATLAB-based toolkit. First, a coil model is generated using a dedicated script. Then, we compute high-resolution 2D contour plots for any component of the electric and/or magnetic field in coronal, sagittal, and transverse planes via FMM. These two scripts may be further augmented with a parametric loop to enable rapid analysis.ObjectiveWe show how the fast multipole method can be applied to compute primary electric and magnetic fields for detailed TMS coil models
Allele-Specific Expression and High-Throughput Reporter Assay Reveal Functional Variants in Human Brains with Alcohol Use Disorders
Authors: Rao Xi , Thapa Kriti S. , Chen Andy B , Lin Hai , Gao Hongyu , Reiter Jill L , Hargreaves Katherine A. , Ipe Joseph , Lai Dongbing , Xuei Xiaoling , Gu Hongmei , Kapoor Manav , Farris Sean P. , Tischfield Jay , Foroud Tatiana , Goate Alison M. , Skaar Todd C , Mayfield R. Dayne , Edenberg Howard J. , Liu Yunlong 
Published: January 2019

AbstractTranscriptome studies can identify genes whose expression differs between alcoholics and controls. To test which variants associated with alcohol use disorder (AUDs) may cause expression differences, we integrated deep RNA-seq and genome-wide association studies (GWAS) data from four postmortem brain regions of 30 AUDs subjects and 30 controls (social/non-drinkers) and analyzed allele-specific expression (ASE). We identified 90 genes with differential ASE in subjects with AUDs compared to controls. Of these, 61 genes contained 437 single nucleotide polymorphisms (SNPs) in the 3’ untranslated regions (3’UTR) with at least one heterozygote among the subjects studied. Using a modified PASSPORT-seq (parallel assessment of polymorphisms in miRNA target-sites by sequencing) assay, we identified 25 SNPs that showed affected RNA levels in a consistent manner in two neuroblastoma cell lines, SH-SY5Y and SK-N-BE(2). Many of these are in binding sites of miRNAs and RNA binding proteins, indicating that these SNPs are likely causal variants of AUD-associated differential ASE.
Lower-limb rigidity is associated with frequent falls in Parkinson disease
Authors: McKay J. Lucas , Hackney Madeleine. E. , Factor Stewart A. , Ting Lena H. 
Published: January 2019

AbstractBACKGROUND AND OBJECTIVE:The role of muscle rigidity as an etiological factor of falls in Parkinson disease (PD) is poorly understood. Our objective was to determine whether lower leg rigidity was differentially associated with frequent falls in PD compared to upper limb, neck, and total rigidity measures. METHODS: We examined associations between UPDRS-III (motor) rigidity subscores and history of monthly or more frequent falls in N=216 individuals with PD (age, 66±10 y; 36% female, disease duration, 7±5 y) with logistic regression. RESULTS: N=35 individuals were frequent fallers. Significant associations were identified between lower limb rigidity and frequent falls (P=0.01) after controlling for age, sex, PD duration, total UPDRS-III score, and presence of FOG. No significant associations (P≥0.14) were identified for total, arm, or neck rigidity. CONCLUSION: Lower limb rigidity is related to frequent falls in people with PD. Further investigation may be warranted into how parkinsonian rigidity could cause falls.Financial Disclosures/Conflict of Interest concerning the research related to the manuscript: NoneFunding:NIH K25HD086276, R01HD046922, R21HD075612, UL1TR002378, UL1TR000454; Department of Veterans Affairs R&D Service Career Development Awards E7108M and N0870W, Consolidated Anti-Aging Foundation, and the Sartain Lanier Family Foundation.
Control of MYC-dependent apoptotic threshold by a co-amplified ubiquitin E3 ligase UBR5
Authors: Qiao Xi , Liu Ying , Prada Maria Llamazares , Gupta Abhishekh , Jaiswal Alok , Sharma Mukund , Haikala Heidi , Talvinen Kati , Yetukuri Laxman , Pylvänäinen Joanna W. , Klefström Juha , Kronqvist Pauliina , Meinander Annika , Aittokallio Tero , Hietakangas Ville , Eilers Martin , Westermarck Jukka 
Published: January 2019

AbstractMYC protein expression has to be tightly controlled to allow for maximal cell proliferation without inducing apoptosis. Here we discover UBR5 as a novel MYC ubiquitin ligase and demonstrate how it functions as a molecular rheostat to prevent excess accumulation of MYC protein. UBR5 effects on MYC protein stability are independent on N-terminal FBW7 degron of MYC. Endogenous UBR5 inhibition induces MYC protein expression and activates MYC target genes. Moreover, UBR5 governs MYC-dependent phenotypes in vivo in Drosophila. In cancer cells, UBR5-mediated MYC protein suppression diminishes cell killing activity of cancer therapeutics. Further, we demonstrate that UBR5 dominates MYC protein expression at the single-cell level in human basal-type breast cancer tissue. Myc and Ubr5 are co-amplified in MYC-driven human cancer types, and UBR5 controls MYC-mediated apoptotic threshold in co-amplified basal type breast cancer cells. In summary, UBR5 is a novel MYC ubiquitin ligase and an endogenous rheostat for MYC protein expression in vivo. Clinically, expression of UBR5 may be important for protection of breast cancer cells from drug-induced, and MYC-dependent, apoptosis.
Effects of enucleation on the direct reciprocal corticocortical connections between primary visual and somatosensory cortices of the mouse
Authors: Massé Ian Omer , Bronchti Gilles , Boire Denis 
Published: January 2019

AbstractMultisensory convergence is present in the cerebral cortex even at the initial stages of processing in the primary and low-level sensory cortices. Direct connections between primary sensory cortices are a particular feature of rodent cortical connectivity. Our previous studies have shown asymmetric projections between the primary visual and somatosensory cortices in mice. Binocular enucleation produces a relative reduction of the projections from the somatosensory cortex to the visual cortex in mice. The purpose of this study is to compare the direct reciprocal cross-modal connections between the primary visual (V1) and somatosensory (S1) cortices in intact and enucleated C57Bl/6 mice, and to determine quantitative differences in the proportion and laminar distribution of neurons and terminals in these projections. CTB labeled neurons were used to estimate the relative importance of projections between V1 and S1, and their laminar distribution used to classify them as feedback, feedforward or lateral projections. The size of axonal swellings was measured and frequency distribution determined for each cortical layer. Axon diameters were also sampled in these connections. Injections in V1 resulted in a reduced proportion of labeled cells in S1 of enucleated mice. There was a relative decrease of the projection from the somatosensory cortex to the visual cortex in enucleated mice due to a greater relative reduction of supragranular layers neurons. Enucleation otherwise had no effect on the connectivity of the somatosensory cortex with other motor and somatosensory cortices. In the projection from the visual to the somatosensory cortex in enucleated mice, the size of axonal swellings was reduced in all layers. Conversely, in the projection from the somatosensory cortex to the visual cortex, some larger swellings appeared in the supragranular layers. This shows pathway and laminar specific changes in cortical circuitry following loss of sensory afferent activity that results in changes in the relationship between visual and somatosensory cortices in the enucleated mice.
Complex pleiotropic genetic architecture of evolved heat stress and oxidative stress resistance in the nematodeCaenorhabditis remanei
Authors: O’Connor Christine H. , Sikkink Kristin L. , Nelson Thomas C. , Fierst Janna L. , Cresko William A. , Phillips Patrick C. 
Published: January 2019

ABSTRACTThe adaptation of complex organisms to changing environments has been a central question in evolutionary quantitative genetics since its inception. The structure of the genotype-phenotype maps is critical because pleiotropic effects can generate widespread correlated responses to selection and potentially restrict the extent of evolutionary change. In this study we use experimental evolution to dissect the genetic architecture of natural variation for acute heat stress and oxidative stress response in the nematodeCaenorhabiditis remanei. Previous work in the classic model nematodeC. eleganshas found that abiotic stress response is controlled by a handful of genes of major effect and that mutations in any one of these genes can have widespread pleiotropic effects on multiple stress response traits. Here, we find that acute heat stress response and acute oxidative response inC. remaneiare polygenic, complex traits, with hundreds of genomic regions responding to selection. In contrast to expectation from mutation studies, we find that evolved acute heat stress and acute oxidative stress response for the most part display independent genetic bases. This lack of correlation is reflected at the levels of phenotype, gene expression, and in the genomic response to selection. Thus, while these findings support the general view that rapid adaptation can be generated by changes at hundreds to thousands of sites in the genome, the architecture of segregating variation is likely to be strongly parcellated by the pleiotropic structure of the underlying genetic networks.
Differential gene expression in brain and liver tissue of Wistar rats after rapid eye movement sleep deprivation
Authors: Pandey Atul , Oliver Ryan , Kar Santosh K 
Published: January 2019

AbstractSleep is essential for the survival of most living beings. Numerous researchers have identified a series of genes that are thought to regulate “sleep-state” or the “deprived state”. As sleep has significant effect on physiology, we believe that lack of sleep or particularly REM sleep for a prolonged period would have a profound impact on various body tissues. Therefore, using microarray method, we sought to determine which genes and processes are affected in the brain and liver of rats following 9 days of REM sleep deprivation. Our findings showed that REM sleep deprivation affected a total of 652 genes in the brain and 426 genes in the liver. Only 23 genes were affected commonly, 10 oppositely and 13 similarly across brain and liver tissue. Our results suggest that 9-day REM sleep deprivation differentially affects genes and processes in the brain and liver of rats.Highlights of the study➢Gene expression profile of brain and liver tissues of rats was analyzed using microarray technique following 9 days of REM Sleep deprivation.➢Many of the genes involved in essential physiological processes, such as protein synthesis and neuronal metabolism are affected differently in the brain and liver tissue of rats after 9-day REM sleep deprivation.
Preoptic galanin neuron activation is specific to courtship reproductive tactic in fish with two male morphs
Authors: Tripp Joel A. , Salas-Allende Isabella , Makowski Andrea , Bass Andrew H. 
Published: January 2019

AbstractSpecies exhibiting alternative reproductive tactics (ARTs) provide ideal models for investigating neural mechanisms underlying robust and consistent differences in social behavioral phenotypes between individuals within a single sex. Using phospho-S6 protein (pS6), a neural activity marker, we investigate the activation of galanin-expressing neurons in the preoptic area-anterior hypothalamus (POA-AH) during ARTs in midshipman fish (Porichthys notatus) that have two adult male morphs: type I’s that reproduce using an acoustic-dependent courtship tactic or a cuckolding tactic, and type II’s that only cuckold. The proportion of pS6-labelled galanin neurons increases during mating by courting type I males, but not cuckolders of either male morph or females, and is not explained by vocalization, eggs in the nest, or cuckolders present during mating. These differences within the same behavioral context indicate a male phenotype-specific role for galanin neurons in mating interactions, providing the most direct evidence to date for the role of a specific neuronal population in the differential activation of one mating behavior over the other in species exhibiting ARTs. More broadly, together with their known role in mammalian mating, the results suggest a deep-rooted, phylogenetically shared function for POA-AH galanin neurons in reproductive behavior. As such, these findings also provide new insights into the evolutionary relationship between POA-AH populations involved in social behavior regulation in teleosts, the most species-rich vertebrate group, with those in the more highly differentiated POA-AH of mammals.Significance StatementGalanin-expressing neurons in the preoptic area-anterior hypothalamus (POA-AH) are associated with mating and parental care in mammals. Here, we show that POA-AH galanin neurons are also active in a teleost fish during mating in a social context specific to one of two male morphs of a species with alternative reproductive tactics (ARTs). Together, the results suggest a key role for galanin-expressing neurons in the performance of reproductive-related social behaviors that is shared between distantly related vertebrate lineages and for galanin neuron activation in the evolution of ARTs. The results also help to clarify the relationship between molecularly-defined populations in the teleost POA-AH with the more highly differentiated mammalian POA-AH.