bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single cell RNA-seq analysis reveals compartment-specific heterogeneity and plasticity of microglia
Authors: Zheng Junying , Ru Wenjuan , Adolacion Jay R , Spurgat Michael S , Liu Xin , Yuan Subo , Liang Rommel X , Dong Jianli , Potter Andrew S , Potter S Steven , Varadarajan Navin , Tang Shao-Jun 
Published: March 2020

AbstractMicroglia are heterogeneous and ubiquitous CNS-resident macrophages that maintain homeostasis of neural tissues and protect them from pathogen attacks. Yet, their differentiation in different compartments remains elusive. We performed single cell RNA-seq (scRNA-seq) analysis to compare the transcriptomes of microglia in adult mouse (C57/Bl) brains and spinal cords to identify microglial subtypes in these CNS compartments. Cortical microglia from 2-month mice consisted of a predominant population of the homeostatic subtype (HOM-M) and a small population (4%) of the inflammatory subtype (IFLAM-M), while spinal microglia consisted of 55% HOM-M and 45% IFLAM-M subtype. Comparison of cortical and spinal microglia at 2, 4 and 8 months revealed consistently a higher composition of the IFLAM-M subtype in the spinal cord. At 8-month, cortical microglia differentiated a small new subtype with interferon response phenotypes (INF-M), while spinal microglia polarized toward a proinflammatory phenotype, as indicated by the increase of microglia expressing IL-1β. To further characterize the differential plasticity of cortical and spinal microglial heterogeneity, we determined the microglial transcriptomes from HIV-1 gp 120 transgenic (Tg) mice, a model of HIV-associated neurological disorders. Compared with wild-type (Wt) cortical microglia, the gp120Tg cortical microglia had three new subtypes, with signatures of interferon I response (INF-M), cell proliferation (PLF-M), and myelination or demyelination (MYE-M) respectively; while INF-M and PLF-M subtypes presented at all ages, the MYE-M only at 4-month. In contrast, only the INF-M subtype was observed in the spinal microglia from 2- and 4-month gp120tg mice. Bioinformatic analysis of regulated molecular pathways of individual microglial subtypes indicated that gp120 more severely impaired the biological function of microglia in cortices than in the spinal cord. The results collectively reveal differential heterogeneity and plasticity of cortical and spinal microglia, and suggest functional differentiation of microglia in different CNS compartments.
VarStack: a Web Tool for Data Retrieval to Interpret Somatic Variants in Cancer
Authors: Howard Morgan , Kane Bruce , Lepry Mary , Stey Paul , Ragavendran Ashok , Gamsiz Uzun Ece D. 
Published: March 2020

AbstractBackground and objectiveAdvances in tumor genome sequencing created an urgent need for bioinformatics tools to support the interpretation of the clinical significance of the variants detected. VarStack is a web tool which is a base to retrieve somatic variant data in cancer from existing databases.MethodsVarStack incorporates data from several publicly available databases and presents them with an easy-to-navigate user-interface. It currently supports data from the Catalogue of Somatic Mutations in Cancer (COSMIC), gnomAD, cBioPortal, ClinVar, OncoKB and UCSC Genome browser. It retrieves the data from these databases and returns back to the user in a fraction of the time it would take to manually navigate each site independently.ResultsUsers submit a variant with gene symbol, peptide change, and coding sequence change. They may select a variety of tumor specific studies in cBioportal to search through in addition to their original query. The results from the databases are presented in tabs. Users can export the results as a CSV file. VarStack also has the batch search feature in which user submits a list of variants and download a CSV file with the data from the databases. With the batch search and data download options users can easily incorporate VarStack into their workflow or tools. VarStack saves time by providing variant data to the user from multiple databases in an easy-to-export and interpretable format.AvailabilityVarStack is freely available underhttps://varstack.brown.edu.
LED Zappelin’: An open source LED controller for arbitrary spectrum visual stimulation and optogenetics during 2-photon imaging
Authors: Zimmermann M.J.Y. , Chagas A.M. , Bartel P. , Pop S. , Godino L.L. Prieto , Baden T. 
Published: March 2020

AbstractTwo-photon (2P) microscopy is a cornerstone technique in neuroscience research. However, combining 2P imaging with spectrally arbitrary light stimulation can be challenging due to crosstalk between stimulation light and fluorescence detection. To overcome this limitation, we present a simple and low-cost electronic solution based on an ESP32 microcontroller and a TLC5947 LED driver to rapidly time-interleave stimulation and detection epochs during scans. Implemented for less than $100, our design can independently drive up to 24 arbitrary spectrum LEDs to meet user requirements. We demonstrate the utility of our stimulator for colour vision experiments on thein vivotetrachromatic zebrafish retina and for optogenetic circuit mapping inDrosophila.https://github.com/BadenLab/LED-Zappelin
RainbowSTORM: An open-source ImageJ plugin for spectroscopic single-molecule localization microscopy (sSMLM) data analysis and image reconstruction
Authors: Davis Janel L. , Soetikno Brian , Song Ki-Hee , Zhang Yang , Sun Cheng , Zhang Hao F. 
Published: March 2020

AbstractSummarySpectroscopic single-molecule localization microscopy (sSMLM) simultaneously captures the spatial locations and full spectra of stochastically emitting fluorescent single molecules. It provides an optical platform to develop new multi-molecular and functional imaging capabilities. While several open-source software suites provide sub-diffraction localization of fluorescent molecules, software suites for spectroscopic analysis of sSMLM data remain unavailable. RainbowSTORM is an open-source, user-friendly ImageJ/FIJI plugin for end-to-end spectroscopic analysis and visualization for sSMLM images. RainbowSTORM allows users to calibrate, preview, and quantitatively analyze emission spectra acquired using different reported sSMLM system designs and fluorescent labels.AvailabilityRainbowSTORM is a java plugin for ImageJ (https://imagej.net)/FIJI (http://fiji.sc) freely available through:https://github.com/FOIL-NU/RainbowSTORM. RainbowSTORM has been tested with Windows and Mac operating systems and ImageJ/FIJI version 1.52.Supplementary informationSupplementary data are available online.
SUMOylation of rice DELLA SLR1 modulates transcriptional responses and improves yield under salt stress
Authors: Gonçalves Nuno M. , Fernandes Telma , Nunes Cátia , Rosa Margarida T. G. , Matiolli Cleverson C. , Rodrigues Mafalda A. A. , Barros Pedro M. , Oliveira M. Margarida , Abreu Isabel A. 
Published: March 2020

ABSTRACTDELLA proteins modulate GA signalling and are major regulators of plant plasticity to endure stress. DELLAs are mostly regulated at the post-translational level, and their activity relies on the interaction with upstream regulators and transcription factors (TFs). SUMOylation is a post-translational modification (PTM) capable of changing protein interaction and found to influence DELLA activity in Arabidopsis. We determined that SUMOylation of the single rice DELLA SLENDER RICE1 (SLR1) occurs in a lysine residue different from the one previously identified in Arabidopsis REPRESSOR OF GA (RGA). Remarkably, artificially increasing SUMOylated SLR1 (SUMO1SLR1) levels attenuated the penalty of salt stress on plant yield. Gene expression analysis revealed that the overexpression of SUMOylated SLR1 regulates key dioxygenases that modulate active GA levels, namelyGA20ox2andGA2ox3, which could partially explain the sustained productivity upon salt stress imposition. Besides, SLR1 SUMOylation blocked the interaction with the growth regulator YAB4, which may fine-tuneGA20ox2expression. Mechanistically, we propose that SLR1 SUMOylation disrupts the interaction with members of several transcription factor families to modulate gene expression. We found that SLR1 SUMOylation represents a novel mechanism modulating DELLA activity, which attenuates the impact of stress on plant performance.One sentence summaryRice plants show increased yield under salt stress when its gibberellin transcriptional regulator DELLA protein is artificially SUMOylated.
Distinguish between Duplication of Essential Genes and Duplication of Dispensable Genes
Authors: Gu Xun 
Published: March 2020

AbstractWhen a dispensable gene is duplicated (ancestral dispensability), genetic buffering and duplicate compensation together maintain the gene dispensability, whereas duplicate compensation is the only mechanism when an essential gene is duplicated (ancestral essentiality). To explore the distinct pattern of genetic robustness between these evolutionary scenarios, we formulated a probabilistic model with some biologically reasonable assumptions for analyzing a set of duplicate pairs with three possible states: double-dispensable (DD), semi-dispensable (one dispensable one essential, DE) or double-essential (EE). A computational pipeline is then developed to predict the distribution of three states (DD, DE and EE) conditional of ancestral dispensability or essentiality, respectively. This model was applied to yeast duplicate pairs from a whole-genome duplication, revealing that the process of essentiality of those duplicated from essential genes could be significantly higher than that of those duplicated from dispensable genes. We thus proposed a hypothesis that the process of sub-functionalization may be faster than neo-functionalization. Our analysis may provide some new insights about the role of duplicate compensation on genetic robustness.
Graphical-Model Framework for Automated Annotation of Cell Identities in Dense Cellular Images
Authors: Chaudhary Shivesh , Lee Sol Ah , Li Yueyi , Patel Dhaval S. , Lu Hang 
Published: March 2020

AbstractAlthough identifying cell names in dense image stacks is critical in analyzing functional whole-brain data enabling comparison across experiments, unbiased identification is very difficult, and relies heavily on researchers’ experiences. Here we present a probabilistic-graphical-model framework, CRF_ID, based on Conditional Random Fields, for unbiased and automated cell identification. CRF_ID focuses on maximizing intrinsic similarity between shapes. Compared to existing methods, CRF_ID achieves higher accuracy on simulated and ground-truth experimental datasets, and better robustness against challenging noise conditions common in experimental data. CRF_ID can further boost accuracy by building atlases from annotated data in highly computationally efficient manner, and by easily adding new features (e.g. from new strains). We demonstrate cell annotation in C. elegans images across strains, animal orientations, and tasks including gene-expression localization, multi-cellular and whole-brain functional imaging experiments. Together, these successes demonstrate that unbiased cell annotation can facilitate biological discovery, and this approach may be valuable to annotation tasks for other systems.
Selection of forage oat genotypes through GGE Biplot and BLUP
Authors: Santos Franklin , Marza y Félix 
Published: March 2020

AbstractIn Bolivia, there is a low predominance of forage oat productivity. Therefore, it was proposed to select more productive and stable genotypes through statistical methods of GGE Biplot and BLUP. The research was conducted in three environments in Bolivia and six commercial varieties of forage oats were evaluated; three of them correspond to INIA Peru and the rest of Bolivia. Data were analyzed through GGE Biplot and BLUP (Best Linear Unbiased Prediction) and an average yield of 10.29 ±3.51 t ha−1of dry matter was obtained. BLUP accumulated greater variance than GGE Biplot in the first two components. In terms of productivity and stability values, both models have the same selection trend. Thus, Tayco and Texas were selected for their outstanding characteristic in dry matter yield and phenotypic stability.
A surface metric and software toolbox for EEG electrode grids in the macaque
Authors: Li Fan , Teichert Tobias 
Published: March 2020

AbstractBackgroundThe past years have seen increased appreciation of non-invasive extracranial electroencephalographic (EEG) recordings in non-human primates (NHP) as a tool for translational research. In humans, the international 10-20 system or extensions thereof provide standardized electrode positions that enable easy comparison of data between subjects and laboratories. In the NHP, no such generally accepted, standardized placement system is available.New MethodHere we introduce a surface metric and software package (NHP1020) that automates the planning of large, approximately evenly spaced electrode grids on the NHP skull.ResultsThe system is based on one CT and one MRI image and requires the user to specify two intracranial markers. Based on this, the software defines electrode positions on the brain surface using a surface-based spherical metric similar to the one used by the international 10-20 system. The electrode positions are then projected to the surface of the skull. Standardized electrode grids can be shared, imported or defined with few high-level commands.Existing MethodsNHP EEG electrodes are often placed on an individual basis relative to extracranial markers, or relative to underlying neural structures. Both approaches are time-consuming and require manual intervention. Furthermore, the use of extracranial markers in this species may be more problematic than in humans, because cranial muscles and ridges are larger and keep maturing long into adulthood thus potentially affecting electrode positions.ConclusionThe key advantage of the current approach is the automated and objective identification of corresponding electrode positions in different animals. Automation was made possible by the use of a two-dimensional metric on the brain surface which has a simpler, i.e., more convex and sphere-like anatomy than the skull. This enables fast and efficient planning, optimization and calculation of large electrode grids.
Molecular mechanism of the pH-dependent calcium affinity in langerin
Authors: Joswig Jan-O. , Anders Jennifer , Zhang Hengxi , Rademacher Christoph , Keller Bettina G. 
Published: March 2020

AbstractThe C-type lectin receptor langerin plays a vital role in the mammalian defense against invading pathogens. Its function hinges on the affinity to its co-factor Ca2+which in turn is regulated by the pH. We studied the structural consequences of protonating the allosteric pH-sensor histidine H294 by molecular dynamics simulations (total simulation time: about 120 µs) and Markov models. We discovered a mechanism in which the signal that the pH has dropped is transferred to the Ca2+-binding site without transferring the initial proton. Instead, protonation of H294 unlocks a conformation in which a protonated lysine side-chain forms a hydrogen bond with a Ca2+-coordinating aspartic acid. This destabilizes Ca2+in the binding pocket, which we probed by steered molecular dynamics. After Ca2+-release, the proton is likely transferred to the aspartic acid and stabilized by a dyad with a nearby glutamic acid, triggering a conformational transition and thus preventing Ca2+-rebinding.
Cerebellar Purkinje cells can differentially modulate coherence between sensory and motor cortex depending on region and behavior
Authors: Lindeman Sander , Kros Lieke , Hong Sungho , Mejias Jorge F. , Romano Vincenzo , Negrello Mario , Bosman Laurens W.J. , De Zeeuw Chris I. 
Published: March 2020

AbstractCoherence among sensory and motor cortices is indicative of binding of critical functions in perception, motor planning, action and sleep. Evidence is emerging that the cerebellum can impose coherence between cortical areas, but how and when it does so is unclear. Here, we studied coherence between primary somatosensory (S1) and motor (M1) cortices during sensory stimulation of the whiskers in the presence and absence of optogenetic stimulation of cerebellar Purkinje cells in awake mice. Purkinje cell activation enhanced and reduced sensory-induced S1-M1 coherence in the theta and gamma bands, respectively. This impact only occurred when Purkinje cell stimulation was given simultaneously with sensory stimulation; a 20 ms delay was sufficient to alleviate its impact, suggesting the existence of a fast, cerebellar sensory pathway to S1 and M1. The suppression of gamma band coherence upon Purkinje cell stimulation was significantly stronger during trials with relatively large whisker movements, whereas the theta band changes did not show this correlation. In line with the anatomical distribution of the simple spike and complex spike responses to whisker stimulation, this suppression also occurred following focal stimulation of medial crus 2, but not of lateral crus 1. Granger causality analyses and computational modeling of the involved networks suggest that Purkinje cells control S1-M1 coherence most prominently via the ventrolateral thalamus and M1. Our results indicate that coherences between sensory and motor cortices in different frequency ranges can be dynamically modulated by cerebellar input, and that the modulation depends on the behavioral context and is site-specific.Significance StatementCoherent activity between sensory and motor areas is essential in sensorimotor integration. We show here that the cerebellum can differentially affect cortical theta and gamma band coherences evoked by whisker stimulation via a fast ascending and predictive pathway. In line with the functional heterogeneity of its modular organization, the impact of the cerebellum is region-specific and tuned to ongoing motor responses. These data highlight site-specific and context-dependent interactions between the cerebellum and the cerebral cortex that can come into play during a plethora of sensorimotor functions.
Multiple midfrontal thetas revealed by source separation of simultaneous MEG and EEG
Authors: Zuure Marrit B. , Hinkley Leighton B.N. , Tiesinga Paul H.E. , Nagarajan Srikantan S. , Cohen Michael X 
Published: March 2020

AbstractTheta-band (∼6 Hz) rhythmic activity within and over the medial prefrontal cortex (“midfrontal theta”) has been identified as a distinctive signature of “response conflict,” the competition between multiple actions when only one action is goal-relevant. Midfrontal theta is traditionally conceptualized and analyzed under the assumption that it is a unitary signature of conflict that can be uniquely identified at one electrode (typically FCz). Here we recorded simultaneous MEG and EEG (total of 328 sensors) in nine human subjects (7 female) and applied a feature-guided multivariate source-separation decomposition to determine whether conflict-related midfrontal theta is a unitary or multidimensional feature of the data. For each subject, a generalized eigendecomposition (GED) yielded spatial filters (components) that maximized the ratio between theta and broadband activity. Components were retained based on significance thresholding and midfrontal EEG topography. All of the subjects individually exhibited multiple (mean 5.89, SD 2.47) midfrontal components that contributed to sensor-level midfrontal theta power during the task. Component signals were temporally uncorrelated and asynchronous, suggesting that each midfrontal theta component was unique. Our findings call into question the dominant notion that midfrontal theta represents a unitary process. Instead, we suggest that midfrontal theta spans a multidimensional space, indicating multiple origins, but can manifest as a single feature at the sensor level due to signal mixing.Significance statement“Midfrontal theta” is a rhythmic electrophysiological signature of the competition between multiple response options. Midfrontal theta is traditionally considered to reflect a single process. However, this assumption could be erroneous due to “mixing” (multiple sources contributing to the activity recorded at a single electrode). We investigated the dimensionality of midfrontal theta by applying advanced multivariate analysis methods to a multimodal M/EEG dataset. We identified multiple topographically overlapping neural sources that drove response conflict-related midfrontal theta. Midfrontal theta thus reflects multiple uncorrelated signals that manifest with similar EEG scalp projections. In addition to contributing to the cognitive control literature, we demonstrate both the feasibility and the necessity of signal de-mixing to understand the neural dynamics underlying cognitive processes.
Conditional repeatability and the variance explained by reaction norm variation in random slope models
Authors: Schielzeth Holger , Nakagawa Shinichi 
Published: March 2020

AbstractIndividuals differ in average phenotypes and in sensitivity to environmental variation. Such context-sensitivity can be modelled as random-slope variation. Random-slope variation implies that the proportion of between-individual variation varies across the range of a covariate (environment/context/time/age) and has thus been called ‘conditional’ repeatability. We propose to put conditional repeatabilities in perspective of the total phenotypic variance and suggest a way of standardization using the random-slope coefficient of determination. Furthermore, we illustrate that the marginalized repeatabilityRmaraveraged across an environmental gradient offers a biologically relevant description of between-individual variation. We provide simple equations for calculating key descriptors of conditional repeatabilities, clarify the difference between random-intercept variation and average between-individual variation and make recommendations for comprehensive reporting. While we introduce the concept with individual variation in mind, the framework is equally applicable to other type of between-group/cluster variation that varies across some (environmental) gradient.
Super-enhancer switching drives a burst in germline gene expression at the mitosis-to-meiosis transition
Authors: Maezawa So , Yukawa Masashi , Chen Xiaoting , Sakashita Akihiko , Alavattam Kris G. , Weirauch Matthew T. , Barski Artem , Namekawa Satoshi H. 
Published: March 2020

AbstractThe testis has the most diverse and complex transcriptome of all organs due to bursts in expression of thousands of germline-specific genes. Much of this unique gene expression takes place when mitotic germ cells differentiate and enter into meiotic prophase. Here, we demonstrate that the genome-wide reorganization of super-enhancers (SEs) drives bursts of germline genes after the mitosis-to-meiosis transition. At the mitosis-to-meiosis transition, mitotic SEs dissolve while meiotic SEs are established. Meiotic SEs are associated with the activation of key germline genes, defining the cellular identity of germ cells. This SE switching is regulated by the establishment of meiotic SEs via A-MYB (MYBL1), a key transcription factor for germline genes, and by the resolution of mitotic SEs via SCML2, a germline-specific Polycomb protein required for spermatogenesis-specific gene expression. Prior to the entry into meiosis, meiotic SEs are preprogrammed in mitotic spermatogonia, serving to direct the unidirectional differentiation of spermatogenesis. We identify key regulatory factors for both mitotic and meiotic enhancers, revealing a molecular logic for the concurrent activation of mitotic enhancers and suppression of meiotic enhancers in the somatic and/or mitotically proliferating phase.