bluuebunny/crossref_metadata_2025_split huggingface dataset:
Propagation and update of auditory perceptual priors through alpha and theta rhythms
Authors: Ho Hao Tam , Burr David C. , Alais David , Morrone Maria Concetta 
Published: August 2020

AbstractTo maintain a continuous and coherent percept over time, the brain makes use of past sensory information to anticipate forthcoming stimuli. We recently showed that auditory experience in the immediate past is propagated through ear-specific reverberations, manifested as rhythmic fluctuations of decision bias at alpha frequency. Here, we apply the same time-resolved behavioural method to investigate how perceptual performance changes over time under conditions of high stimulus expectation, and to examine the effect of unexpected events on behaviour. As in our previous study, participants were required to discriminate the ear-of-origin of a brief monaural pure tone embedded in uncorrelated dichotic white noise. We manipulated stimulus expectation by increasing the target probability in one ear to 80%. Consistent with our earlier findings, performance did not remain constant across trials, but varied rhythmically with delay from noise onset. Specifically, decision bias showed a similar oscillation at ~9 Hz that depended on ear congruency between successive targets. This suggests rhythmic communication of auditory perceptual history occurs early and is not readily influenced by top-down expectations. In addition, we report a novel observation specific to infrequent, unexpected stimuli that gave rise to oscillations in accuracy at ~7.6 Hz one trial after the target occurred in the non-anticipated ear. This new behavioural oscillation may reflect a mechanism for updating the sensory representation once a prediction error has been detected.
ERAP2 increases the abundance of a peptide submotif highly selective for the Birdshot Uveitis-associated HLA-A29
Authors: Venema W.J. , Hiddingh S. , de Boer J.H. , Claas F.H.J. , Mulder A , Den Hollander A.I. , Stratikos E. , Sarkizova S. , van der Veken L.T. , Janssen G.M.C. , van Veelen P.A. , Kuiper J.J.W. 
Published: August 2020

ABSTRACTBirdshot Uveitis (BU) is a blinding inflammatory eye condition that only affects HLA-A29-positive individuals. Genetic association studies linkedERAP2with BU, an aminopeptidase which trims peptides before their presentation by HLA class I at the cell surface, which suggests that ERAP2-dependent peptide presentation by HLA-A29 drives the pathogenesis of BU. However, it remains poorly understood whether the effects of ERAP2 on the HLA-A29 peptidome are distinct from its effect on other HLA allotypes. To address this, we focused on the effects of ERAP2 on the immunopeptidome in patient-derived antigen presenting cells. Using complementary HLA-A29-based and pan-class I immunopurifications, isotope-labelled naturally processed and presented HLA-bound peptides were sequenced by mass spectrometry. We show that the effects of ERAP2 on the N-terminus of ligands of HLA-A29 are shared across endogenous HLA allotypes, but discover and replicate that one peptide motif generated in the presence of ERAP2 is specifically bound by HLA-A29. This motif can be found in the amino acid sequence of putative autoantigens. We further show evidence for internal sequence specificity for ERAP2 imprinted in the immunopeptidome. These results reveal that ERAP2 can generate an HLA-A29-specific antigen repertoire, which supports that antigen presentation is a key disease pathway in BU.
DeepKhib: a deep-learning framework for lysine 2-hydroxyisobutyrylation sites prediction
Authors: Zhang Luna , Zou Yang , He Ningning , Chen Yu , Chen Zhen , Li Lei 
Published: August 2020

AbstractAs a novel type of post-translational modification, lysine 2-Hydroxyisobutyrylation (Khib) plays an important role in gene transcription and signal transduction. In order to understand its regulatory mechanism, the essential step is the recognition of Khibsites. Thousands of Khibsites have been experimentally verified across five different species. However, there are only a couple traditional machine-learning algorithms developed to predict Khib sites for limited species, lacking a general prediction algorithm. We constructed a deep-learning algorithm based on convolutional neural network with the one-hot encoding approach, dubbed CNNOH. It performs favorably to the traditional machine-learning models and other deep-learning models across different species, in terms of cross-validation and independent test. The area under the ROC curve (AUC) values for CNNOHranged from 0.82 to 0.87 for different organisms, which is superior to the currently-available Khibpredictors. Moreover, we developed the general model based on the integrated data from multiple species and it showed great universality and effectiveness with the AUC values in the range of 0.79 to 0.87. Accordingly, we constructed the on-line prediction tool dubbed DeepKhib for easily identifying Khibsites, which includes both species-specific and general models. DeepKhib is available athttp://www.bioinfogo.org/DeepKhib.
MRLocus: identifying causal genes mediating a trait through Bayesian estimation of allelic heterogeneity
Authors: Zhu Anqi , Matoba Nana , Wilson Emmaleigh , Tapia Amanda L. , Li Yun , Ibrahim Joseph G. , Stein Jason L. , Love Michael I. 
Published: August 2020

AbstractExpression quantitative trait loci (eQTL) studies are used to understand the regulatory function of non-coding genome-wide association study (GWAS) risk loci, but colocalization alone does not demonstrate a causal relationship of gene expression affecting a trait. Evidence for mediation, that perturbation of gene expression in a given tissue or developmental context will induce a change in the downstream GWAS trait, can be provided by two-sample Mendelian Randomization (MR). Here, we introduce a new statistical method, MRLocus, for Bayesian estimation of the gene-to-trait effect from eQTL and GWAS summary data for loci displaying allelic heterogeneity, that is, containing multiple LD-independent eQTLs. MRLocus makes use of a colocalization step applied to each eQTL, followed by an MR analysis step across eQTLs. Additionally, our method involves estimation of allelic heterogeneity through a dispersion parameter, indicating variable mediation effects from each individual eQTL on the downstream trait. Our method is evaluated against state-of-the-art methods for estimation of the gene-to-trait mediation effect, using an existing simulation framework. In simulation, MRLocus often has the highest accuracy among competing methods, and in each case provides more accurate estimation of uncertainty as assessed through interval coverage. MRLocus is then applied to five causal candidate genes for mediation of particular GWAS traits, where gene-to-trait effects are concordant with those previously reported. We find that MRLocus’ estimation of the causal effect across eQTLs within a locus provides useful information for determining how perturbation of gene expression or individual regulatory elements will affect downstream traits. The MRLocus method is implemented as an R package available athttps://mikelove.github.io/mrlocus.
Synaptic anchoring of the endoplasmic reticulum depends on myosin V and caldendrin activity
Authors: Konietzny Anja , Grendel Jasper , Hertrich Nathalie , Dekkers Dick H. W. , Demmers Jeroen A. A. , Mikhaylova Marina 
Published: August 2020

AbstractExcitatory synapses of principal hippocampal neurons are frequently located on dendritic spines. The dynamic strengthening or weakening of individual inputs results in a great structural and molecular diversity of dendritic spines. Active spines with large Ca2+transients are frequently invaded by a single protrusion from the endoplasmic reticulum (ER), which is dynamically transported into and out of spines by the actin-based motor myosin V. An increase in synaptic strength often correlates with stable anchoring of the ER, followed by the formation of the spine apparatus organelle. Here we show that synaptic ER stabilization depends on the interplay of two Ca2+-binding proteins: calmodulin serves as a light chain of myosin V and activates the motor function, whereas caldendrin acts as an inhibitor which transforms myosin into a stationary F-actin tether. Together, they provide a Ca2+-sensing module for fine-tuning myosin V activity and thereby regulate the formation of the spine apparatus in a subset of active dendritic spines.
Mapping the Human Visual Thalamus and its Cytoarchitectonic Subdivisions Using Quantitative MRI
Authors: Müller-Axt Christa , Eichner Cornelius , Rusch Henriette , Kauffmann Louise , Bazin Pierre-Louis , Anwander Alfred , Morawski Markus , von Kriegstein Katharina 
Published: August 2020

AbstractThe human lateral geniculate nucleus (LGN) of the visual thalamus is a key subcortical processing site for visual information analysis. A non-invasive assessment of the LGN and its functionally and microstructurally distinct magnocellular (M) and parvocellular (P) subdivisionsin-vivoin humans is challenging, because of its small size and location deep inside the brain. Here we tested whether recent advances in high-field structural quantitative MRI (qMRI) can enable MR-based mapping of human LGN subdivisions. We employed ultra-high resolution 7 Tesla qMRI of apost-mortemhuman LGN specimen and high-resolution 7 Teslain-vivoqMRI in a large participant sample. We found that a quantitative assessment of the LGN and a differentiation of its subdivisions was possible based on microstructure-informed MR-contrast alone. In both thepost-mortemandin-vivoqMRI data, we identified two components of shorter and longer longitudinal relaxation time (T1) within the LGN that coincided with the known anatomical locations of a dorsal P and a ventral M subdivision, respectively. Through a subsequent ground truth histological examination of the samepost-mortemLGN specimen, we showed that the observed T1contrast pertains to cyto- and myeloarchitectonic differences between LGN subdivisions. These differences were based on cell and myelin density, but not on iron content. Our qMRI-based mapping strategy overcomes shortcomings of previous fMRI-based mapping approaches. It paves the way for an in-depth understanding of the function and microstructure of the LGN in humans. It also enables investigations into the selective contributions of LGN subdivisions to human behavior in health and disease.Significance StatementThe lateral geniculate nucleus (LGN) is a key processing site for the analysis of visual information. Due to its small size and deep location within the brain, non-invasive mapping of the LGN and its microstructurally distinct subdivisions in humans is challenging. Using quantitative MRI methods that are sensitive to underlying microstructural tissue features, we show that a differentiation of the LGN and its microstructurally distinct subdivisions is feasible in humans non-invasively. These findings are important because they open up novel opportunities to assess the hitherto poorly understood complex role of the LGN in human perception and cognition, as well as the contribution of selective LGN subdivision impairments to various clinical conditions including developmental dyslexia, glaucoma and multiple sclerosis.
Discriminating Lineages ofBatrachochytrium dendrobatidisusing quantitative PCR
Authors: Ghosh Pria N , Verster Ruhan , Sewell Thomas , O’Hanlon Simon , Brookes Lola M , Rieux Adrien , Garner Trenton WJ , Weldon Ché , Fisher Matthew C 
Published: August 2020

AbstractThe ability to detect and monitor infectious disease in a phylogenetically informative manner is critical for their management. Phylogenetically informative diagnostic tests enable patterns of pathogen introduction or changes in the distribution of genotypes to be measured, enabling research into the ecology of the pathogen.Batrachochytrium dendrobatidis(Bd), a causative agent of chytridiomycosis in amphibian populations, emerged worldwide in the 21stcentury and is composed of six lineages which are display varying levels of virulence in their hosts.Research into the distribution, ecology and pathogenicity of these lineages has been hampered by an inability to type lineage efficiently. Here, we describe a lineage-specific TaqMan qPCR assay that differentiates the two lineages ofBdmost commonly associated with chytridiomycosis:BdGPL andBdCAPE. We demonstrate how this assay can be used for the surveillance of wild populations of amphibians in Southern Africa using skin swabs, tissue samples and cultured isolates.
Capturingin situVirus-Host Range and Interaction Dynamics through Gene Fusion with epicPCR
Authors: Sakowski Eric G. , Arora-Williams Keith , Tian Funing , Zayed Ahmed A , Zablocki Olivier , Sullivan Matthew B. , Preheim Sarah P. 
Published: August 2020

AbstractViruses impact microbial diversity, phenotype, and gene flow through virus-host interactions that in turn alter ecology and biogeochemistry. Though metagenomics surveys are rapidly cataloging viral diversity, capturing specific virus-host interactionsin situwould identify hosts for novel viruses and reveal influential ecological or environmental factors. We leveraged metagenomics and a high-throughput, cultivation-independent gene fusion technique (epicPCR) to investigate viral diversity and virus-host interactions over time in a critical estuarine environment, the Chesapeake Bay. EpicPCR capturedin situvirus-host interactions for viral clades with no closely related database representatives. Abundant freshwater Actinobacteria lineages were the most common hosts for these poorly characterized viruses, and observed viral interactions with one abundant Actinobacterial population (Rhodoluna) were correlated with environmental factors. Tracking virus-host interaction dynamics also revealed ecological differences between multi-host (generalist) and single-host (specialist) viruses. Generalist viruses had significantly longer periods with observed virus-host interactions but specialist viruses were observed interacting with hosts at lower minimum abundances, suggesting more efficient interactions. Together, these observations reveal ecological differences between generalist and specialist viruses that provide insight into evolutionary trade-offs. Capturingin situinteractions with epicPCR revealed environmental and ecological factors that shape virus-host interactions, highlighting epicPCR as a scalable new tool in viral ecology.
Probabilistic Thermodynamic Analysis of Metabolic Networks
Authors: Gollub Mattia G. , Kaltenbach Hans-Michael , Stelling Jörg 
Published: August 2020

AbstractRandom sampling of metabolic fluxes can provide an unbiased description of the capabilities of a metabolic network. However, current sampling approaches do not model thermodynamics explicitly, leading to inaccurate predictions of an organism’s potential or actual metabolic operations. We present a probabilistic framework combining thermodynamic quantities with steady-state flux constraints to analyze the properties of a metabolic network. It includes methods for probabilistic metabolic optimization and for joint sampling of thermodynamic and flux spaces. Applied to a model ofE. coli, we use the methods to reveal known and novel mechanisms of substrate channeling, and to accurately predict reaction directions and metabolite concentrations. Interestingly, predicted flux distributions are multimodal, leading to discrete hypotheses onE. coli‘s metabolic capabilities. C++ source code with MATLAB interface available athttps://gitlab.com/csb.ethz/pta.
Adolescent female rats undergo full systems consolidation of an aversive memory, while males of the same age fail to discriminate contexts
Authors: Crestani Ana P. , Lotz Fernanda N. , Casagrande Mirelle A. , Popik Bruno , Guerra Kétlyn T. K. , de Oliveira Alvares Lucas , Quillfeldt Jorge A. 
Published: August 2020

ABSTRACTGeneralization is an adaptive process that allows animals to deal with threatening circumstances similar to prior experiences. Systems consolidation is a time-dependent process in which memory loses it precision concomitantly with reorganizational changes in the brain structures that support memory retrieval. In this, memory becomes progressively independent from the hippocampus and more reliant on cortical structures. Generalization, however, may take place much faster in adult animals depending on the presence of sex hormones. Notwithstanding its relevance, there are few studies on sex differences in memory modulation. Here, a contextual fear discrimination task was used to investigate the onset of memory generalization and hippocampus-independence in adolescent male and female rats (P42-49). Subjects were tested 2, 7, 14, 21 or 28 days after training, with females showing memory generalization from day 21 on, whereas males surprisingly unable to discriminate contexts at any time. Ovariectomized females, however, displayed an early onset of generalization. Consistently, pre-test pharmacological blocking of dorsal hippocampus was able to impair memory retrieval in females, but not in males, which indicate that precise memory is dependent on the hippocampus. To our notice, this is the first report of a memory systems consolidation process – expressed in its two dimensions, neuroanatomical and qualitative – in adolescent female rats, and one that can also be accelerated by the reduction of sex hormones through ovariectomy. It is also unprecedented that despite adolescent male rats being able to remember fear learning, they did not discriminate contexts with any precision.
Common and distinct neural correlates of music and food-induced pleasure: a coordinate-based meta-analysis of neuroimaging studies
Authors: Mas-Herrero Ernest , Maini Larissa , Sescousse Guillaume , Zatorre Robert J. 
Published: August 2020

ABSTRACTNeuroimaging studies have shown that, despite the abstractness of music, it may mimic biologically rewarding stimuli (e.g. food) in its ability to engage the brain’s reward circuity. However, due to the lack of research comparing music and other types of reward, it is unclear to what extent the recruitment of reward-related structures overlaps among domains. To achieve this goal, we performed a coordinate-based meta-analysis of 38 neuroimaging studies (703 subjects) comparing the brain responses specifically to music and food-induced pleasure. Both engaged a common set of brain regions including the ventromedial prefrontal cortex, ventral striatum, and insula. Yet, comparative analyses indicated a partial dissociation in the engagement of the reward circuitry as a function of the type of reward, as well as additional reward type-specific activations in brain regions related to perception, sensory processing, and learning. These results support the idea that hedonic reactions rely on the engagement of a common reward network, yet through specific routes of access depending on the modality and nature of the reward.
High resolution visual information via a gap junction-mediated spike order code
Authors: Tong Rudi , Trenholm Stuart 
Published: August 2020

AbstractGap junctions promote correlated spiking between coupled neurons. Recording from pairs of coupled retinal ganglion cells, we find that differences in firing rate between coupled neurons dictates which cell leads correlated spike-pairs, and that the precise temporal order of spike activity between pairs of cells changes depending on the spatial position of a visual stimulus. We thus demonstrate a spike order spatial code for encoding sensory information.
Red light imaging for programmed cell death visualization and quantification in plant-pathogen interactions
Authors: Villanueva Sergio Landeo , Malvestiti Michele C. , Joosten Matthieu H.A.J. , van Ieperen Wim , van Kan Jan A.L. 
Published: August 2020

AbstractStudies on plant-pathogen interactions often involve monitoring disease symptoms or responses of the host plant to pathogen-derived immunogenic patterns, either visually or by staining the plant tissue. Both these methods have limitations with respect to resolution, reproducibility and the ability to quantify the results. In this study we show that red light detection in a multi-purpose fluorescence imaging system that is probably available in many labs can be used to visualize plant tissue undergoing cell death. Red light emission is the result of chlorophyll fluorescence upon thylakoid membrane disassembly during the development of a programmed cell death process. The activation of programmed cell death can occur either during a hypersensitive response to a biotrophic pathogen or an apoptotic cell death triggered by a necrotrophic pathogen. Quantifying the intensity of the red light signal enables to evaluate the magnitude of programmed cell death and provides a non-invasive readout of the plant immune response in a faster and safer manner as compared to chemical staining methodologies previously developed. This application can be implemented to screen for differences in symptom severity in plant-pathogen interactions, and to visualize and quantify in a sensitive and objective manner the intensity of a plant response upon perception of a given immunological pattern. We illustrate the utility and versatility of the method using diverse immunogenic patterns and pathogens.
Involvement of uterine natural killer cells in the natural selection of human embryos at implantation
Authors: Kong Chow-Seng , Ordoñez Alexandra Almansa , Turner Sarah , Tremaine Tina , Muter Joanne , Lucas Emma S. , Salisbury Emma , Vassena Rita , Fouladi-Nashta Ali A. , Tiscornia Gustavo , Hartshorne Geraldine , Brosens Jan J. , Brighton Paul J. 
Published: August 2020

AbstractDecidualizing endometrial stromal cells (EnSC) critically determine the maternal response to an implanting conceptus, triggering either menstruation-like disposal of low-fitness embryos or creating an environment that promotes further development. However, the mechanism that couples maternal recognition of low-quality embryos to tissue breakdown remains poorly understood. Recently, we demonstrated that successful transition of the cycling endometrium to a pregnancy state requires selective elimination of pro-inflammatory senescent decidual cells by activated uterine natural killer (uNK) cells. Here we report that uNK cells express CD44, the canonical hyaluronan (HA) receptor, and demonstrate that high-molecular weight HA (HMWHA) inhibits uNK cell-mediated killing of senescent decidual cells. By contrast, low-molecular weight HA (LMWHA) did not attenuate uNK cell activity in co-culture experiments. Killing of senescent decidual cells by uNK cells was also inhibited upon exposure to medium conditioned by IVF embryos that failed to implant, but not successful embryos. Embryo-mediated inhibition of uNK cell activity was reversed by recombinant hyaluronidase 2 (HYAL2), which hydrolyses HMWHA. We further report a correlation between the levels of HYAL2 secretion by human blastocysts, morphological scores, and implantation potential. Taken together, the data suggest a pivotal role for uNK cells in embryo biosensing and endometrial fate decisions at implantation.