bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diversity of excitatory release sites
Authors: Karlocai Maria Rita , Heredi Judit , Benedek Tünde , Holderith Noemi , Lorincz Andrea , Nusser Zoltan 
Published: February 2021

AbstractThe molecular mechanisms underlying the diversity of cortical glutamatergic synapses is still only partially understood. Here, we tested the hypothesis that presynaptic active zones (AZs) are constructed from molecularly uniform, independent release sites (RSs), the number of which scales linearly with the AZ size. Paired recordings between hippocampal CA1 pyramidal cells and fast-spiking interneurons followed by quantal analysis demonstrate large variability in the number of RSs (N) at these connections. High resolution molecular analysis of functionally characterized synapses reveals highly variable Munc13-1 content of AZs that possess the sameN. Replica immunolabeling also shows a 3-fold variability in the Munc13-1 content of AZs of identical size. Munc13-1 is clustered within the AZs; cluster size and density are also variable. Our results provide evidence for quantitative molecular heterogeneity of RSs and support a model in which the AZ is built up from variable numbers of molecularly heterogeneous, but independent RSs.
Neurovascular unit alterations in the growth restricted newborn are improved following ibuprofen treatment
Authors: Chand Kirat K. , Miller Stephanie M. , Cowin Gary J. , Mohanty Lipsa , Pienaar Jany , Colditz Paul B. , Bjorkman Stella Tracey , Wixey Julie A. 
Published: February 2021

AbstractFetal brain development is particularly vulnerable to the effects of fetal growth restriction (FGR) and abnormal neurodevelopment is common in the FGR infant. Adverse outcomes range from behavioural and learning disorders through to cerebral palsy. Unfortunately, no treatment exists to protect the FGR newborn brain. Recent evidence suggests inflammation may play a key role in the mechanism responsible for the progression of brain impairment in the FGR newborn, including disruption to the neurovascular unit (NVU). We explored whether ibuprofen, a non-steroidal anti-inflammatory drug, could reduce NVU disruption and brain impairment in the FGR newborn. We used a preclinical piglet model of growth restriction in which FGR occurs spontaneously. Newborn FGR (birthweight <10thcentile) and normally grown piglets were collected on day of birth and oral ibuprofen was administered daily for 3 days (20mg/kg/day, day 1 and 10mg/kg/day days 2 and 3). FGR brains demonstrated an inflammatory state, with changes to glial morphology (astrocytes and microglia), and blood brain barrier disruption, assessed by IgG and albumin leakage into the brain parenchyma and a decrease in blood vessel density. Loss of interaction between astrocytic end-feet and blood vessels was evident in the microvasculature where leakage was present, suggestive of structural deficits to the NVU. Ibuprofen treatment reduced the pro-inflammatory response in FGR piglets, reducing levels of pro-inflammatory cytokines and number of activated microglia and astrocytes associated with blood vessels. Ibuprofen treatment also attenuated albumin and IgG leakage. There were no alterations to angiogenesis, or blood vessel proliferation in treated-FGR piglets. These findings suggest postnatal administration of ibuprofen on day of birth modulates the inflammatory state, allowing for stronger interaction between vasculature and astrocytic end-feet to restore NVU integrity. These changes to the FGR brain microenvironment may be key to neuroprotection.
Change of information by positive frequency-dependent selection in two very different models (laser-like and chirality of shell-coiling in the snailPartula suturalis)
Authors: Tiefenbrunner W. A. 
Published: February 2021

AbstractAlthough according to the second law of thermodynamics the world tends toward maximum disorder, over millions of years evolution has given rise to an enormous variety of complex organisms. To explain this, one must assume that natural selection is a process of information acquisition. Since some years an information theory of selection exists that can quantify this change and thus helps to understand the apparent contradiction between the existence of biological complexity and the tendency toward disorder that generally prevails in nature. Here I apply this theory to examples of frequency-dependent selection (this means: in which phenotype frequency determines its fitness).The snailPartula suturalisgave an evolutionary and ecologically unique and hence very valuable example of this type of selection before it became extinct about thirty years ago on its native island. Spatially separated populations with left- and right-coiled shells occurred on Moorea, but also hybridization zones. Since both types of shells were the same except for chirality, the question is whether selection happened at all. The inheritance of this character is monogenic and in this respect simple, but is complicated by the fact that it is the maternal genotype, not the own, that determines the phenotype. This causes that for the calculation of the information change by selection not the genotype or phenotype frequencies are sufficient, but one must consider their combination. The simulation shows that frequency-dependent selection inP. suturalisindeed increased information.It has already been shown that selection can also be important outside animate nature, for example in the generation of laser light, which has extraordinary properties: it is monochromatic, monoaxial and monophasic. Phase selection is frequency(=density)-dependent and therefore of interest here. In selection theory the mean fitness ω is of special significance. In a laser-like model, in modeling phase selection, we find that ω=1+A2, where A2is the the light intensity or the square of the amplitude, respectively. During selection, ω increases and, in parallel, since selection is a process of information acquisition, so does the information. Because of the connection between ω and A2this also means for the laser-like model that – assuming a constant number of photons – a larger amplitude always means more information (less entropy).
Seasonal Dynamics in the Number and Composition of Coliform Bacteria in Drinking Water Reservoirs
Authors: Reitter Carolin , Petzoldt Heike , Korth Andreas , Schwab Felix , Stange Claudia , Hambsch Beate , Tiehm Andreas , Lagkouvardos Ilias , Gescher Johannes , Hügler Michael 
Published: February 2021

AbstractWorldwide, surface waters like lakes and reservoirs are one of the major sources for drinking water production, especially in regions with water scarcity. In the last decades, they have undergone significant changes due to climate change. This includes not only an increase of the water temperature but also microbiological changes. In recent years, increased numbers of coliform bacteria have been observed in these surface waters. In our monitoring study we analyzed two drinking water reservoirs (Klingenberg and Kleine Kinzig Reservoir) over a two-year period in 2018 and 2019. We detected high numbers of coliform bacteria up to 2.4 x 104bacteria per 100 ml during summer months, representing an increase of four orders of magnitude compared to winter. Diversity decreased to one or two species that dominated the entire water body, namelyEnterobacter asburiaeandLelliottiaspp., depending on the reservoir. Interestingly, the same, very closely related strains have been found in several reservoirs from different regions. Fecal indicator bacteriaEscherichia coliand enterococci could only be detected in low concentrations. Furthermore, fecal marker genes were not detected in the reservoir, indicating that high concentrations of coliform bacteria were not due to fecal contamination. Microbial community revealedFrankialesandBurkholderialesas dominant orders.Enterobacterales,however, only had a frequency of 0.04% within the microbial community, which is not significantly affected by the extreme change in coliform bacteria number. Redundancy analysis revealed water temperature, oxygen as well as nutrients and metals (phosphate, manganese) as factors affecting the dominant species. We conclude that this sudden increase of coliform bacteria is an autochthonic process that can be considered as a mass proliferation or “coliform bloom” within the reservoir. It is correlated to higher water temperatures in summer and is therefore expected to occur more frequently in the near future, challenging drinking water production.HighlightsColiform bacteria proliferate in drinking water reservoirsto values above104per 100 mlThe generaLelliottiaandEnterobacter can form these “coliform blooms”Mass proliferation is an autochthonic process, not related to fecal contaminationsIt is related to water temperature and appears mainly in summerIt is expected to occur more often in future due to climate changeGraphical abstract
A chicken IgY can efficiently inhibit the entry and replication of SARS-CoV-2 by targeting the ACE2 binding domain in vitro
Authors: Wei Jingchen , Lu Yunfei , Rui Ying , Zhu Xuanyu , He Songqing , Wu Shuwen , Xu Qing 
Published: February 2021

AbstractCOVID-19 pneumonia has now spread widely in the world. Currently, no specific antiviral drugs are available. The vaccine is the most effective way to control the epidemic. Passive immune antibodies are also an effective method to prevent and cure COVID-19 pneumonia. We used the SARS-CoV-2 S receptor-binding domain (RBD) as an antigen to immunize layers in order to extract, separate, and purify SARS-CoV-2-IgY from egg yolk. SARS-CoV-2-IgY (S-IgY)can block the entry of SARS-CoV-2 into the Cells and reduce the viral load in cells. The Half effective concentration (EC50) of W3-IgY (S-IgY in the third week after immunization) is 1.35 ± 0.15nM. The EC50of W9-IgY (S-IgY in the ninth week after immunization) is 2.76 ± 1.54 nM. When the dose of S-IgY is 55 nM, the fluorescence representing intracellular viral protein is obviously weakened in Immunofluorescence microscopy.Results of Sars-CoV-2 /Vero E6 cell experiment confirmed that S-IgY has a strong antiviral effect on SARS-CoV-2, and its (EC50) is 27.78 ±1.54 nMvs3,259 ± 159.62 nM of Redesivir (differ > 106 timesP<0.001).S-IgY can inhibit the entry and replication of SARS-CoV-2, which is related to its targeting the ACE2 binding domain.S-IgY is safe, efficient, stable, and easy to obtain. This antibody can be an effective tool for preventing and treating COVID-19 pneumonia.Abstract FigureFig. 1.Graphical AbstractThe figure briefly illustrates that the preparation and extraction of S-IgY and its anti-S-CoV-2 mechanism is to inhibit the entry and replication of SARS-CoV-2 by targeting the ACE2.
scGAE: topology-preserving dimensionality reduction for single-cell RNA-seq data using graph autoencoder
Authors: Luo Zixiang , Xu Chenyu , Zhang Zhen , Jin Wenfei 
Published: February 2021

ABSTRACTDimensionality reduction is crucial for the visualization and interpretation of the high-dimensional single-cell RNA sequencing (scRNA-seq) data. However, preserving topological structure among cells to low dimensional space remains a challenge. Here, we present the single-cell graph autoencoder (scGAE), a dimensionality reduction method that preserves topological structure in scRNA-seq data. scGAE builds a cell graph and uses a multitask-oriented graph autoencoder to preserve topological structure information and feature information in scRNA-seq data simultaneously. We further extended scGAE for scRNA-seq data visualization, clustering, and trajectory inference. Analyses of simulated data showed that scGAE accurately reconstructs developmental trajectory and separates discrete cell clusters under different scenarios, outperforming recently developed deep learning methods. Furthermore, implementation of scGAE on empirical data showed scGAE provided novel insights into cell developmental lineages and preserved inter-cluster distances.
Simulating homeostatic, allostatic and goal-directed forms of interoceptive control using Active Inference
Authors: Tschantz Alexander , Barca Laura , Maisto Domenico , Buckley Christopher L. , Seth Anil K. , Pezzulo Giovanni 
Published: February 2021

AbstractThe adaptive regulation of bodily and interoceptive parameters, such as body temperature, thirst and hunger is a central problem for any biological organism. Here, we present a series of simulations using the framework of Active Inference to formally characterize interoceptive control and some of its dysfunctions. We start from the premise that the goal of interoceptive control is to minimize a discrepancy between expected and actual interoceptive sensations (i.e., a prediction error or free energy). Importantly, living organisms can achieve this goal by using various forms of interoceptive control: homeostatic, allostatic and goal-directed. We provide a computationally-guided analysis of these different forms of interoceptive control, by showing that they correspond to distinct generative models within Active Inference. Furthermore, we illustrate how these generative models may support empirical research, by predicting physiological and brain signals that may accompany both adaptive and maladaptive interoceptive control.HighlightsWe use Active Inference to provide formal models of interoceptive controlWe model homeostatic, allostatic and goal-directed forms of interoceptive controlOur simulations illustrate both adaptive interoceptive control and its dysfunctionsWe discuss how the models can aid empirical research on interoception
Decoupling alignment strategy from feature quantification using a standard alignment incidence data structure
Authors: Choi Kwangbom , Vincent Matthew J. , Churchill Gary A. 
Published: February 2021

AbstractSummaryThe abundance of genomic feature such as gene expression is often estimated from observed total number of alignment incidences in the targeted genome regions. We introduce a generic data structure and associated file format for alignment incidence data so that method developers can create novel pipelines comprising models, each optimal for read alignment, post-alignment QC, and quantification across multiple sequencing modalities.Availability and Implementationalntoolssoftware is freely available athttps://github.com/churchill-lab/alntoolsunder MIT license.Contactkb.choi@jax.orgorgary.churchill@jax.org
Positive selection in multiple salivary gland proteins of Anophelinae reveals potential targets for vector control
Authors: Freitas Lucas , Nery Mariana F. 
Published: February 2021

AbstractAnophelesis a genus belonging to the Culicidae family, which has great medical importance due to its role as a vector ofPlasmodium, the parasite responsible for malaria. FromAnopheles’functional genomics, great focus has been given to the salivary gland proteins (SGPs) group. This class of proteins is essential to blood-feeding behavior as they have attributes such as vasodilators and anti-clotting properties. Recently, a comprehensive review onAnophelesSGPs was performed, however the authors did not deeply explore the adaptive molecular evolution of these genes. In this context, this work aimed to perform a more detailed analysis of the adaptive molecular evolution of SGPs inAnopheles, carrying out positive selection and gene families evolution analysis on 824 SGPs. Our results show that most SGPs have positively selected sites that can be used as targets in the development of new strategies for vector control. Notably, we were not able to find any evidence of an accelerated shift in the copy-number variation of SGPs compared with other proteins, as suggested in previous works.Significance StatementSalivary gland proteins (SGPs) are essential to blood-feeding behavior inAnophelesand they are the most studied class of proteins in blood-feeding insects. However a proper molecular evolution analysis on SGPs inAnophelesis missing. In our analyses we observed that most SGPs have positively selected sites and we were not able to find any evidence of an accelerated shift in the copy-number of SGPs compared with other proteins, as stated in the literature. Our results can open new venues in the development of new strategies for vector control.
Higher-order visual areas broaden stimulus responsiveness in mouse primary visual cortex
Authors: oude Lohuis Matthijs N. , Cantón Alexis Cerván , Pennartz Cyriel M. A. , Olcese Umberto 
Published: February 2021

SummaryOver the past few years, the various areas that surround the primary visual cortex in the mouse have been associated with many functions, ranging from higher-order visual processing to decision making. Recently, some studies have shown that higher-order visual areas influence the activity of the primary visual cortex, refining its processing capabilities. Here we studied howin vivooptogenetic inactivation of two higher-order visual areas with different functional properties affects responses evoked by moving bars in the primary visual cortex. In contrast with the prevailing view, our results demonstrate that distinct higher-order visual areas similarly modulate early visual processing. In particular, these areas broaden stimulus responsiveness in the primary visual cortex, by amplifying sensory-evoked responses for stimuli not moving along the orientation preferred by individual neurons. Thus, feedback from higher-order visual areas amplifies V1 responses to non-preferred stimuli, which may aid their detection.
Corticotropin-releasing factor distribution in the brain of the brown anole lizard
Authors: Kabelik David 
Published: February 2021

AbstractCorticotropin-releasing factor (CRF) is best known for its involvement in peripheral glucocorticoid release across vertebrate species. However, CRF is also produced and released throughout various brain regions to regulate central aspects of the stress response. While these various CRF populations have been described extensively in mammals, less is known about their distributions in other amniotes, and only a handful of studies have ever examined CRF distributions in reptiles. Out study is the first to map CRF cell and fiber distributions in the brain of a lizard, the brown anole (Anolis sagrei). Our results indicate that brown anole CRF distributions are highly similar to those in snakes and turtles. However, unlike in these other reptile species, we find immunofluorescent CRF neurons in a few additional brown anole locations, most notably the supraoptic nucleus. The CRF distribution in the present study is also similar to published CRF descriptions in mammals and birds, although our findings, as well as the other published reports in reptiles, collectively suggest that reptiles possess a slightly more restricted distribution of CRF cell populations than do mammals and birds.
Supervised Semantic Similarity
Authors: Sousa Rita T. , Silva Sara , Pesquita Catia 
Published: February 2021

AbstractBackgroundSemantic similarity between concepts in knowledge graphs is essential for several bioinformatics applications, including the prediction of protein-protein interactions and the discovery of associations between diseases and genes. Although knowledge graphs describe entities in terms of several perspectives (or semantic aspects), state-of-the-art semantic similarity measures are general-purpose. This can represent a challenge since different use cases for the application of semantic similarity may need different similarity perspectives and ultimately depend on expert knowledge for manual fine-tuning.ResultsWe present a new approach that uses supervised machine learning to tailor aspect-oriented semantic similarity measures to fit a particular view on biological similarity or relatedness. We implement and evaluate it using different combinations of representative semantic similarity measures and machine learning methods with four biological similarity views: protein-protein interaction, protein function similarity, protein sequence similarity and phenotype-based gene similarity.ConclusionsThe results demonstrate that our approach outperforms non-supervised methods, producing semantic similarity models that fit different biological perspectives significantly better than the commonly used manual combinations of semantic aspects.
From GWAS Variant to Function: a Study of ~148,000 Variants for Blood Cell Traits
Authors: Sun Quan , Crowley Cheynna A. , Huang Le , Wen Jia , Chen Jiawen , Bao Erik L. , Auer Paul L. , Lettre Guillaume , Reiner Alexander P. , Sankaran Vijay G. , Raffield Laura M. , Li Yun 
Published: February 2021

AbstractGenome-wide association studies (GWAS) have identified hundreds of thousands of genetic variants associated with complex diseases and traits. However, most variants are noncoding and not clearly linked to genes, making it challenging to interpret these GWAS signals. We present a systematic variant-to-function study, prioritizing the most likely functional elements of the genome for experimental follow-up, for >148,000 variants identified for hematological traits. Specifically, we developed VAMPIRE: Variant Annotation Method Pointing to Interesting Regulatory Effects, an interactive web application implemented in R Shiny (http://shiny.bios.unc.edu/vampire/). This tool efficiently integrates and displays information from multiple complementary sources, including epigenomic signatures from blood cell relevant tissues or cells, functional and conservation summary scores, variant impact on protein and gene expression, chromatin conformation information, as well as publicly available GWAS and phenome-wide association study (PheWAS) results. Leveraging data generated from independently performed functional validation experiments, we demonstrate that our prioritized variants, genes, or variant-gene links are significantly more likely to be experimentally validated. This study not only has important implications for systematic and efficient revelation of functional mechanisms underlying GWAS variants for hematological traits, but also provides a prototype that can be adapted to many other complex traits, paving the path for efficient variant to function (V2F) analyses.
Development of chemosynthetic microbial communities in organic falls deployed in the deep Southwest Atlantic Ocean
Authors: Amendola Augusto M. , Peres Francielli V. , Moreira Julio C. F. , Sumida Paulo Y. G. , Paula Fabiana S. , Pellizari Vivian H. 
Published: February 2021

ABSTRACTThe assembly and successional processes of microbial communities inhabiting deep-sea whale and wood falls are highly complex and vastly unknown, as a myriad of factors may affect the development of a chemosynthetic-based ecosystem on these organic islands. The chemoautotrophy supported by organic substrates is the basis of long-lasting ecosystems, considered biodiversity hotspots in the oligotrophic deep sea. Understanding how these microbial communities develop and the factors affecting them could shed light on processes related to the maintenance of biodiversity in this environment. We performed a whale- and wood-fall experiment in the southwest Atlantic on the Brazilian continental margin and investigated biofilm-forming bacterial and archaeal communities colonising these substrates, deployed at 1500 and 3300 m depth. The composition of the prokaryotic communities shared some similarities with previously reported organic falls in the north Pacific and the Mediterranean Sea, mainly regarding sulphur oxidising chemolithotrophic taxa from the phyla Campylobacterota and Proteobacteria. Communities were found to be highly different between the organic substrates, as whale fall associated biofilms presented a higher dominance of sulphur oxidising chemolithotrophs. We also observed a significant difference between the two sites, with the whale associated communities at the 1500 isobath presenting a faster establishment of the chemosynthetic taxa.