bluuebunny/crossref_metadata_2025_split huggingface dataset:
The human visual system preserves the hierarchy of 2-dimensional pattern regularity
Authors: Kohler Peter J. , Clarke Alasdair D. F. 
Published: February 2021

AbstractSymmetries are present at many scales in images of natural scenes. A large body of literature has demonstrated contributions of symmetry to numerous domains of visual perception. The four fundamental symmetries, reflection, rotation, translation and glide reflection, can be combined in exactly 17 distinct ways. Thesewallpaper groupsrepresent the complete set of symmetries in 2D images and have recently found use in the vision science community as an ideal stimulus set for studying the perception of symmetries in textures. The goal of the current study is to provide a more comprehensive description of responses to symmetry in the human visual system, by collecting both brain imaging (Steady-State Visual Evoked Potentials measured using high-density EEG) and behavioral (symmetry detection thresholds) data using the entire set of wallpaper groups. This allows us to probe the hierarchy of complexity among wallpaper groups, in which simpler groups are subgroups of more complex ones. We find that this hierarchy is preserved almost perfectly in both behavior and brain activity: A multi-level Bayesian GLM indicates that for most of the 63 subgroup relationships, subgroups produce lower amplitude responses in visual cortex (posterior probability: > 0.95 for 56 of 63) and require longer presentation durations to be reliably detected (posterior probability: > 0.95 for 49 of 63). This systematic pattern is seen only in visual cortex and only in components of the brain response known to be symmetric-specific. Our results show that representations of symmetries in the human brain are precise and rich in detail, and that this precision is reflected in behavior. These findings expand our understanding of symmetry perception, and open up new avenues for research on how fine-grained representations of regular textures contribute to natural vision.
epitopepredict: A tool for integrated MHC binding prediction
Authors: Farrell Damien 
Published: February 2021

AbstractA key step in the cellular adaptive immune response is the presentation of antigen to T cells. During this process short peptides processed from self or foreign proteins may be presented on the surface bound to MHC molecules for binding to T cell receptors. Those that bind and activate an immune response are called epitopes. Computational prediction of T cell epitopes has many applications in vaccine design and immuno-diagnostics. This is the basis of immunoinformatics which allows in silico screening of peptides before experiments are performed. The most effective approach is to estimate the binding affinity of a given peptide fragment to MHC class I or II molecules. With the availability of whole genomes for many microbial species it is now feasible to computationally screen whole proteomes for candidate peptides. epitopepredict is a programmatic framework and command line tool designed to aid this process. It provides access to multiple binding prediction algorithms under a single interface and scales for whole genomes using multiple target MHC alleles. A web interface is provided to assist visualization and filtering of the results. The software is freely available under an open source license fromhttps://github.com/dmnfarrell/epitopepredict
Exercise Attenuates Sickness Behavior And Protects Against Dopaminergic Impairment Induced By Neuroinflammation
Authors: de Bem Alves Ana Cristina , Pires Ananda Christina Staats , Speck Ana Elisa , Lopes Samantha Cristiane , Scheffer Débora da Luz , Melo Hiago Murilo , Prediger Rui Daniel , de Paula Martins Roberta , Latini Alexandra , Aguiar Aderbal S 
Published: February 2021

ABSTRACTNeuroinflammation affects dopamine metabolism and produces a set of symptoms known as sickness behavior, including fever, anhedonia, anorexia, weight loss, decreased sociability and mobility, and cognitive impairment. Motor and cognitive impairments related to sickness behavior are associated with dopamine (DA) metabolism imbalance in the prefrontal cortex. Lipopolysaccharide (LPS) administration induces neuroinflammation and causes sickness behavior in mice, while physical exercise has anti-inflammatory properties and may attenuate sickness behavior and DA impairment. We investigated the effect of exercise on DA levels and sickness behavior induced by LPS in mice. Adult Swiss male mice (8–10 weeks, 47.1 ± 0.7 g, n=495) performed six weeks of voluntary exercise in free-running wheels (RW group) or had the blocked wheel in their cages (sedentary, SED group). After six weeks of exercise, both groups received an intraperitoneal injection (i.p.) of either saline (SAL) or LPS (0.33 mg/kg, i.p.). All animals were submitted to behavioral tests for sickness behavior assessment (fatigue, locomotion, anhedonia, and social interaction). Neuroinflammation markers and DA metabolism were assessed in the prefrontal cortex. LPS administration provoked anorexia, body weight loss, impaired motor function, social withdrawal, and anhedonia. This sickness behavior was accompanied by reduced cortical DA metabolism and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC). Neuroinflammation was confirmed through increased levels of the proinflammatory cytokines IL-1β and IL-6. Inflammation was also confirmed in the blood by an increased content of IL-1β. Physical exercise intervention prevented animals from neurochemical, biochemical, and behavioral alterations. These findings provide new evidence of physical exercise’s potential as an environmental approach to treating neuroinflammatory conditions.
Differentiable molecular simulation can learn all the parameters in a coarse-grained force field for proteins
Authors: Greener Joe G , Jones David T 
Published: February 2021

AbstractFinding optimal parameters for force fields used in molecular simulation is a challenging and time-consuming task, partly due to the difficulty of tuning multiple parameters at once. Automatic differentiation presents a general solution: run a simulation, obtain gradients of a loss function with respect to all the parameters, and use these to improve the force field. This approach takes advantage of the deep learning revolution whilst retaining the interpretability and efficiency of existing force fields. We demonstrate that this is possible by parameterising a simple coarse-grained force field for proteins, based on training simulations of up to 2,000 steps learning to keep the native structure stable. The learned potential matches chemical knowledge and PDB data, can fold and reproduce the dynamics of small proteins, and shows ability in protein design and model scoring applications. Problems in applying differentiable molecular simulation to all-atom models of proteins are discussed along with possible solutions. The learned potential, simulation scripts and training code are made available athttps://github.com/psipred/cgdms.
Cardiac and behavioural responses to hypoxia and warming in free-swimming gilthead seabreamSparus aurata
Authors: Mignucci Alexandre , Bourjea Jérôme , Forget Fabien , Allal Hossein , Dutto Gilbert , Gasset Eric , McKenzie David J. 
Published: February 2021

ABSTRACTCardiac and behavioural responses to hypoxia and warming were investigated in free-swimming gilthead seabreamSparus aurataequipped with biologging tags in the peritoneal cavity. After suitable recovery in a holding tank, heart rate (fH) and the variance of tri-axial body acceleration (VARm) were logged during exposure to stepwise progressive hypoxia or warming, comparing when either swimming in a tank or confined to individual respirometer chambers. When undisturbed under control conditions (normoxia, 21 °C), meanfHwas significantly lower in tank than respirometers. In progressive hypoxia (100 - 15% oxygen saturation), meanfHin the tank was significantly lower than respirometers at oxygen levels until 40%, with significant bradycardia in both holding conditions below this. Mean VARmwas low and invariant in hypoxia. Warming (21 to 31 °C) caused progressive tachycardia with no differences infHbetween holding conditions. Mean VARmwas, however, significantly higher in the tank during warming, with a positive relationship between VARmandfHacross all temperatures. Therefore, spontaneous activity contributed to raisingfHof fish in the tank during warming. MeanfHin respirometers had a highly significant linear relationship with mean rates of oxygen uptake, considering data from hypoxia and warming together. The highfHof confinedS. aurataindicates that static respirometry techniques may bias estimates of metabolic traits in some fish species. Biologging on free-swimming fish revealed novel information about cardiac responses to environmental stressors, which may be closer to responses exhibited by fish in their natural environment.SUMMARY STATEMENTImplantable biologgers were used to provide the first measurements of cardiac responses to hypoxia and warming in a free-swimming fish, revealing that confinement in respirometer chambers raises heart rate, with consequences for estimates of metabolic rates.
Memory destabilization during reconsolidation – A consequence of homeostatic plasticity?
Authors: Amorim F.E. , Chapot R.L. , Moulin T.C. , Lee J.L.C. , Amaral O.B. 
Published: February 2021

ABSTRACTRemembering is not a static process: when retrieved, a memory can be destabilized and become prone to modifications. This phenomenon has been demonstrated in a number of brain regions, but the neuronal mechanisms that rule memory destabilization and its boundary conditions remain elusive. Using two distinct computational models that combine Hebbian plasticity and synaptic downscaling, we show that homeostatic plasticity can function as a destabilization mechanism, accounting for behavioral results of protein synthesis inhibition upon reactivation with different reexposure times. Furthermore, by performing systematic reviews, we identify a series of overlapping molecular mechanisms between memory destabilization and synaptic downscaling, although direct experimental links between both phenomena remain scarce. In light of these results, we propose a theoretical framework where memory destabilization can emerge as an epiphenomenon of homeostatic adaptations prompted by memory retrieval.
Differential optogenetic excitation of the auditory midbrain in freely moving behaving mice
Authors: Rogalla Meike M. , Seibert Adina , Hildebrandt K Jannis 
Published: February 2021

AbstractIn patients with severe sensory impairment due to compromised peripheral function, partial restoration can be achieved by implantation of sensory prostheses for the electrical stimulation of the central nervous system. However, these state of the art approaches suffer from the drawback of limited spectral resolution. Electrical field spread depends on the impedance of the surrounding medium, impeding spatially focused electrical stimulation in neural tissue. To overcome these technical limitations, optogenetic excitation could be applied in such prostheses to achieve enhanced resolution through precise and differential stimulation of nearby neuronal ensembles within the central sensory pathway. Previous experiments have provided a first proof for behavioral detectability of optogenetic excitation in the rodent auditory system. However, little is known about the generation of complex and behaviorally relevant sensory patterns involving differential excitation. In this study, we developed an optogenetic implant to excite two spatially separated points along the tonotopy of the murine central inferior colliculus (ICc). Using a newly-devised reward-based operant Go/No-Go paradigm for the evaluation of optogenetic excitation of the auditory midbrain in freely moving, behaving mice, we demonstrate that differential optogenetic excitation of a sub-cortical sensory pathway is possible and efficient. Here we demonstrate how animals which were previously trained in a frequency discrimination paradigm a) rapidly generalize between sound and optogenetic excitation, b) generally detect optogenetic excitation at two different neuronal ensembles, and c) discriminate between them. Our results demonstrate for the first time that optogenetic excitation at different points of the ICc tonotopy elicits a stable response behavior over time periods of several months. With this study, we provide the first proof of principle for sub-cortical differential stimulation of sensory systems using complex artificial cues in freely moving animals.
Modulating the left inferior frontal cortex by task domain, cognitive challenge and tDCS
Authors: Nardo Davide , Pappa Katerina , Duncan John , Zeidman Peter , Callaghan Martina F. , Leff Alexander , Crinion Jennifer 
Published: February 2021

ABSTRACTThe left inferior frontal cortex (LIFC) is a key region for spoken language processing, but its neurocognitive architecture remains controversial. Here we assess the domain-generality vs. domain-specificity of the LIFC from behavioural, functional neuroimaging and neuromodulation data. Using concurrent fMRI and transcranial direct current stimulation (tDCS) delivered to the LIFC, we investigated how brain activity and behavioural performance are modulated by task domain (naming vs. non-naming), cognitive challenge (low vs. high), and tDCS (anodal vs. sham). The data revealed: (1) co-existence of neural signatures both common and distinct across tasks within the LIFC; (2) domain-preferential effects of task (naming); (3) significant tDCS modulations of activity in a LIFC sub-region selectively during high-challenge naming. The presence of both domain-specific and domain-general signals, and the existence of a gradient of activation where naming relied more on sub-regions within the LIFC, may help reconcile both perspectives on spoken language processing.
Neuronal modulation in the mouse superior colliculus during covert visual selective attention
Authors: Wang Lupeng , Herman James P. , Krauzlis Richard J. 
Published: February 2021

AbstractCovert visual attention is accomplished by a cascade of mechanisms distributed across multiple brain regions. Recent studies in primates suggest a parcellation in which visual cortex is associated with enhanced representations of relevant stimuli, whereas subcortical circuits are associated with selection of visual targets and suppression of distractors. Here we identified how neuronal activity in the superior colliculus (SC) of head-fixed mice is modulated during covert visual attention. We found that spatial cues modulated both firing rate and spike-count correlations, and that the cue-related modulation in firing rate was due to enhancement of activity at the cued spatial location rather than suppression at the uncued location. This modulation improved the neuronal discriminability of visual-change-evoked activity between contralateral and ipsilateral SC neurons. Together, our findings indicate that neurons in the mouse SC contribute to covert visual selective attention by biasing processing in favor of locations expected to contain relevant information.
Analysis of independent cohorts of outbred CFW mice reveals novel loci for behavioral and physiological traits and identifies factors determining reproducibility
Authors: Zou Jennifer , Gopalakrishnan Shyam , Parker Clarissa C. , Nicod Jerome , Mott Richard , Cai Na , Lionikas Arimantas , Davies Robert W , Palmer Abraham A. , Flint Jonathan 
Published: February 2021

ABSTRACTCombining samples for genetic association is standard practice in human genetic analysis of complex traits, but is rarely undertaken in rodent genetics. Here, using 23 phenotypes and genotypes from two independent laboratories, we obtained a sample size of 3,076 commercially available outbred mice and identified 70 loci, more than double the number of loci identified in the component studies. Fine-mapping in the combined sample reduced the number of likely causal variants, with a median reduction in set size of 51%, and indicated novel gene associations, including Pnpo, Ttll6 and GM11545 with bone mineral density, and Psmb9 with weight. However replication at a nominal threshold of 0.05 between the two component studies was surprisingly low, with less than a third of loci identified in one study replicated in the second. In addition to overestimates in the effect size in the discovery sample (Winner’s Curse), we also found that heterogeneity between studies explained the poor replication, but the contribution of these two factors varied among traits. Available methods to control Winner’s Curse were contingent on the power of the discovery sample, and depending on the method used, both overestimated and underestimated the true effect. Leveraging these observations we integrated information about replication rates, confounding, and Winner’s Curse corrected estimates of power to assign variants to one of four confidence levels. Our approach addresses concerns about reproducibility, and demonstrates how to obtain robust results from mapping complex traits in any genome-wide association study.
Chronic COVID-19 Syndrome and Chronic Fatigue Syndrome (ME/CFS) following the first pandemic wave in Germany – a first analysis of a prospective observational study
Authors: Kedor C , Freitag H , Meyer-Arndt L , Wittke K , Zoller T , Steinbeis F , Haffke M , Rudolf G , Heidecker B , Volk HD , Skurk C , Paul F , Bellmann-Strobl J , Scheibenbogen C 
Published: February 2021

AbstractObjectiveCharacterization of the clinical features of patients with persistent symptoms after mild to moderate COVID-19 infection and exploration of factors associated with the development of Chronic COVID-19 Syndrome (CCS).MethodsSetting: Charité Fatigue Center with clinical immunologists and rheumatologist, neurologists and cardiologists at Charité University hospital.Participants: 42 patients who presented with persistent moderate to severe fatigue six months following a mostly mild SARS-CoV-2 infection at the Charité Fatigue Center from July to November 2020.Main outcome measures: The primary outcomes were clinical and paraclinical data and meeting diagnostic criteria for Chronic Fatigue Syndrome (ME/CFS). Relevant neurological and cardiopulmonary morbidity was excluded.ResultsThe median age was 36.5, range 22–62, 29 patients were female and 13 male. At six months post acute COVID-19 all patients had fatigue (Chalder Fatigue Score median 25 of 33, range 14–32), the most frequent other symptoms were post exertional malaise (n=41), cognitive symptoms (n=40), headache (n=38), and muscle pain (n=35). Most patients were moderately to severely impaired in daily live with a median Bell disability score of 50 (range 15–90) of 100 (healthy) and Short Form 36 (SF-36) physical function score of 63 (range 15-80) of 100. 19 of 42 patients fulfilled the 2003 Canadian Consensus Criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). These patients reported more fatigue in the Chalder Fatigue Score (p=0.006), more stress intolerance (p=0.042) and more frequent and longer post exertional malaise (PEM) (p=0.003), and hypersensitivity to noise (p=0.029), light (p=0.0143) and temperature (p=0.024) compared to patients not meeting ME/CFS criteria. Handgrip force was diminished in most patients compared to healthy control values, and lower in CCS/CFS compared to non-CFS CCS (Fmax1 p=0.085, Fmax2, p=0.050, Fmean1 p=0.043, Fmean2 p=0.034, mean of 10 repeat handgrips, 29 female patients). Mannose-binding lectin (MBL) deficiency was observed frequently (22% of all patients) and elevated IL-8 levels were found in 43% of patients.ConclusionsChronic COVID-19 Syndrome at months 6 is a multisymptomatic frequently debilitating disease fulfilling diagnostic criteria of ME/CFS in about half of the patients in our study. Research in mechanisms and clinical trials are urgently needed.
Grey and white matter micro-structure is associated with polygenic risk for schizophrenia
Authors: Stauffer Eva-Maria , Bethlehem Richard A.I. , Warrier Varun , Murray Graham K. , Romero-Garcia Rafael , Seidlitz Jakob , Bullmore Edward T. 
Published: February 2021

ABSTRACTBackgroundRecent discovery of approximately 270 common genetic variants associated with schizophrenia has enabled polygenic risk scores (PRS) to be measured in the population. We hypothesized that normal variation in PRS would be associated with magnetic resonance imaging (MRI) phenotypes of brain morphometry and tissue composition.MethodsWe used the largest extant genome-wide association dataset (N = 69,369 cases and N = 236,642 healthy controls) to measure PRS for schizophrenia in a large sample of adults from the UK Biobank (Nmax = 29,878) who had multiple micro- and macro-structural MRI metrics measured at each of 180 cortical areas, seven subcortical structures, and 15 major white matter tracts. Linear mixed effect models were used to investigate associations between PRS and brain structure at global and regional scales, controlled for multiple comparisons.ResultsPolygenic risk was significantly associated with reduced neurite density index (NDI) at global brain scale, at 149 cortical regions, five subcortical structures and 14 white matter tracts. Other micro-structural parameters, e.g., fractional anisotropy, that were correlated with NDI were also significantly associated with PRS. Genetic effects on multiple MRI phenotypes were co-located in temporal, cingulate and prefrontal cortical areas, insula, and hippocampus. Post-hoc bidirectional Mendelian randomization analyses provided preliminary evidence in support of a causal relationship between (reduced) thalamic NDI and (increased) risk of schizophrenia.ConclusionsRisk-related reduction in NDI is plausibly indicative of reduced density of myelinated axons and dendritic arborization in large-scale cortico-subcortical networks. Cortical, subcortical and white matter micro-structure may be linked to the genetic mechanisms of schizophrenia.
COVID-19 increases age- and sex-controlled 21-day fatality rates for patients with melanoma, hematologic malignancies, uterine cancer, or kidney cancer
Authors: Li Haiquan , Baldwin Edwin , Zhang Xiang , Kenost Colleen , Luo Wenting , Calhoun Elizabeth A. , An Lingling , Bennett Charles L. , Lussier Yves A. 
Published: February 2021

AbstractIntroductionPrior research has reported an increased risk of fatality for cancer patients, but most studies investigated the risk by comparing cancer patients to non-cancer patients among COVID-19 infections. Only a few studies have compared the impact of a COVID-19 infection to non-infection with matched cancer patients and types.Methods & MaterialsWe conducted survival analyses of 4,606 cancer patients with COVID-19 test results from March 16 to October 11, 2020 in UK Biobank and estimated the overall hazard ratio of fatality with and without COVID-19 infection. We also examined the hazard ratios of thirteen specific cancer types with at least 100 patients.ResultsCOVID-19 resulted in an overall hazard ratio of 7.76 (95% CI: [5.78, 10.40], p<10−10) by studying the survival rate of 4,606 cancer patients for 21-days after the tests. The hazard ratio was shown to vary among cancer type, with over a 10-fold increase in fatality rate (false discovery rate≤0.02) for melanoma, hematologic malignancies, uterine cancer, and kidney cancer using a stratified analysis on each of the cancer types. Although COVID-19 imposed a higher risk for localized cancers compared to distant metastasis ones, those of distant metastasis yielded higher fatality rates due to their multiplicative effects.ConclusionThe results highlight the importance of timely care for localized and hematological cancer patients and the necessity to vaccinate uninfected patients as soon as possible, particularly for the cancer types influenced most by COVID-19.