bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Gene Expression Profiles to study Malaria Vaccine Dose Efficacy & Immune Response Modulation
Authors: Dey Supantha , Kaur Harpreet , Mazumder Mohit , Brodsky Elia 
Published: August 2021

AbstractMalaria is a life-threatening disease, and the Africa is still one of the most affected endemic regions despite years of policy to limit infection and transmission rates. Further, studies into the variable efficacy of the vaccine are needed to provide a better understanding of protective immunity. Thus, the current study is designed to delineate the effect of the different vaccination doses on the transcriptional profiles of subjects to determine its efficacy and understand the molecular mechanisms underlying the protection this vaccine provides. Here, we used gene expression profiles of pre and post-vaccination patients after various doses of RTS,S based on 275 and 583 samples collected from the GEO datasets. At first, exploratory data analysis based Principal component analysis (PCA) shown the distinct pattern of different doses. Subsequently, differential gene expression analysis using edgeR revealed the significantly (FDR <0.005) 158 down-regulated and 61 upregulated genes between control vs. Controlled Human Malaria Infection (CHMI) samples. Further, enrichment analysis of significant genes using Annotation and GAGE tools delineate the involvement of CCL8, CXCL10, CXCL11, XCR1, CSF3, IFNB1, IFNE, IL12B, IL22, IL6, IL27, etc.,genes which found to be upregulated after earlier doses but downregulated after the 3rd dose in cytokine-chemokine pathways. Notably, we identified 13 cytokine genes whose expression significantly varied during three doses. Eventually, these findings give insight to the dual role of cytokine responses in malaria pathogenesis and variations in their expression patterns after various doses of vaccination involved in protection.
On the edge: Evolution of polarity protein BASL and the capacity for stomatal lineage asymmetric divisions
Authors: Nir Ido , Amador Gabriel O. , Gong Yan , Smoot Nicole K. , Cai Le , Shohat Hagai , Bergmann Dominique C. 
Published: August 2021

ABSTRACTAsymmetric and oriented stem cell divisions enable the continued production of patterned tissues. The molecules that guide these divisions include several “polarity proteins” that are localized to discrete plasma membrane domains, are differentially inherited during asymmetric divisions, and whose scaffolding activities can guide division plane orientation and subsequent cell fates. In the stomatal lineages on the surfaces of plant leaves, asymmetric and oriented divisions create distinct cell types in physiologically optimized patterns. The polarity protein BASL is a major regulator of stomatal lineage division and cell fate asymmetries in Arabidopsis, but its role in the stomatal lineages of other plants is unclear. Here, using phylogenetic and functional assays, we demonstrate that BASL is a eudicot-specific polarity protein. Among dicots, divergence in BASL’s roles may reflect some intrinsic protein differences, but more likely reflects previously unappreciated differences in how asymmetric cell divisions are employed for pattern formation in different species. This multi-species analysis therefore provides insight into the evolution of a unique polarity regulator and into the developmental choices available to cells as they build and pattern tissues.HIGHLIGHTSBASL is a eudicot-specific regulator of stomatal lineage asymmetric cell divisionsBASL protein evolution includes stepwise addition of polarity domains to an ancestral MAPK-binding chassisCellular quiescence and BASL-guided polarity generate proper stomatal spacing in tomatoCell size and fate asymmetries are uncoupled in the tomato stomatal lineage
DBpred: A deep learning method for the prediction of DNA interacting residues in protein sequences
Authors: Patiyal Sumeet , Dhall Anjali , Raghava Gajendra P. S. 
Published: August 2021

AbstractDNA-protein interaction is one of the most crucial interactions in the biological system, which decide the fate of many processes such as transcription, regulation of gene expression, splicing, and many more. Though many computational approaches exist that can predict the DNA interacting residues from the protein sequences, there is still a significant opportunity for improvement in terms of performance and accessibility. In this study, we have downloaded the benchmark dataset from method hybridNAP and recently published method ProNA2020, for training and validation purposes, that comprise 864 and 308 proteins, respectively. We have implemented CD-HIT software to handle the redundancy with 30% identity, and left with 646 proteins for training and 46 proteins for validation purposes, in which the validation dataset do not share more than 30% of sequence identity with the training dataset. We have generated amino acid binary profiles, physicochemical-properties based binary profiles, PSSM profiles, and a combination of all profiles described as hybrid feature. 1D-CNN based model performed best as compared to other models for each set of features. The model developed using amino acid binary profile achieved AUROC of 0.83 and 0.74 for training and validation dataset. Using physicochemical properties based binary profile, model attained AUROC of 0.86 and 0.73 for training and validation dataset. Model generated using PSSM profile resulted in the better performance with AUROC 0.91 and 0.74 for training and validation dataset. And, model developed using hybrid of all features performed best with AUROC of 0.91, and 0.79 for training and validation dataset, respectively. We have compared our method’s performance with the current approach and shown improvements. We have included the best-performing models in the standalone and web server accessible athttps://webs.iiitd.edu.in/raghava/dbpred. DBPred is an effective approach to predict the DNA interacting residues in the protein using its primary structure.
Adaptation of the autosomal part of the genome on the presence of dioecy
Authors: Žlůvová Jitka , Hobza Roman , Janoušek Bohuslav 
Published: August 2021

AbstractWe have attempted to answer the question of whether the presence of sex chromosomes in the genome can affect the evolution of the autosomal part of the genome. As a model, we used dioecious plants from the section Otites of the genus Silene. We have observed a rise in adaptive evolution in the autosomal and pseudoautosomal parts of the genome, which are associated with the evolution of dioecy. This rise is caused neither by the accumulation of sexually antagonistic genes in the pseudoautosomal region nor by the co-evolution of genes acting in mitochondria (in spite of the fact that the dioecy evolved in this case most likely from cytoplasmic male sterility). Thus, this rise in the amount of positively selected codons is most likely caused by the adaptive evolution of genes involved in the specialization of the autosomal part of the genome on the dioecy as described in sex-allocation theory.
Interleukin-33 coordinates a microglial phagocytic response and limits corticothalamic excitability and seizure susceptibility
Authors: Han Rafael T. , Vainchtein Ilia D. , Schlachetzki Johannes C. M. , Cho Frances S. , Dorman Leah C. , Johung Tessa , Ahn Eunji , Barron Jerika T. , Nakao-Inoue Hiromi , Joshi Akshaj , Molofsky Ari. B , Glass Christopher K. , Paz Jeanne T. , Molofsky Anna V. 
Published: August 2021

SummaryMicroglia are key remodelers of neuronal synapses during brain development, but the mechanisms that regulate this process and its ultimate impact on neural circuit function are not well defined. We previously identified the IL-1 family cytokine Interleukin-33 (IL-33) as a novel mediator of microglial synapse remodeling. Here we define the phagocytic program induced in microglia in response to IL-33. We find that IL-33 markedly alters the microglial enhancer landscape and exposes AP-1 transcription factor sites that promote target gene expression. We identify the scavenger receptor MARCO and the pattern recognition receptor TLR2 as downstream mediators of IL-33 dependent synapse engulfment. Conditional deletion of IL-33 in the CNS or its receptor on microglia results in increased numbers of excitatory synapses in the corticothalamic circuit and spontaneous epileptiform activity as well as increased seizure susceptibility by early adulthood. These findings define novel mechanisms through which IL-33 coordinates experience-dependent synaptic refinement to restrict hyperexcitability in the developing brain.
Presenting the Compendium Isotoporum Medii Aevi (CIMA) and Bayesian Case Studies
Authors: Cocozza Carlo , Cirelli Enrico , Groß Marcus , Teegen Wolf-Rüdiger , Fernandes Ricardo 
Published: August 2021

AbstractThe Compendium Isotoporum Medii Aevi (CIMA) gathers more than 50 000 isotopic measurements for bioarchaeological samples located within Europe and its margins dating between AD 500–1500. This volume of isotopic data, together with collected supporting information, offers multiple research opportunities. This is illustrated here using novel Bayesian modelling methods on selected case studies to reconstruct medieval human lifeways (i.e. human subsistence, spatial mobility), animal management practices, and paleo-environmental conditions. We also discuss how the integration of isotopic data with other types of archaeological and historical data can improve our knowledge of historical developments throughout medieval Europe.
Voltage imaging in Drosophila using a hybrid chemical-genetic rhodamine voltage reporter
Authors: Kirk Molly J. , Benlian Brittany R. , Han Yifu , Gold Arya , Ravi Ashvin , Deal Parker E. , Molina Rosana S. , Drobizhev Mikhail , Dickman Dion , Scott Kristin , Miller Evan W. 
Published: August 2021

AbstractWe combine a chemically-synthesized, voltage-sensitive fluorophore with a genetically encoded, self-labeling enzyme to enable voltage imaging in Drosophila melanogaster. Previously, we showed that a rhodamine voltage reporter (RhoVR) combined with the HaloTag self-labeling enzyme could be used to monitor membrane potential changes from mammalian neurons in culture and brain slice. Here, we apply this hybrid RhoVR-Halo approach in vivo to achieve selective neuron labeling in intact fly brains. We generate a Drosophila UAS-HaloTag reporter line in which the HaloTag enzyme is expressed on the surface of cells. We validate the voltage sensitivity of this new construct in cell culture before driving expression of HaloTag in specific brain neurons in flies. We show that selective labeling of synapses, cells, and brain regions can be achieved with RhoVR-Halo in either larval neuromuscular junction (NMJ) or in whole adult brains. Finally, we validate the voltage sensitivity of RhoVR-Halo in fly tissue via dual-electrode/imaging at the NMJ, show the efficacy of this approach for measuring synaptic excitatory post-synaptic potentials (EPSPs) in muscle cells, and perform voltage imaging of carbachol-evoked depolarization and osmolarity-evoked hyperpolarization in projection neurons and in interoceptive subesophageal zone neurons in fly brain explants following in vivo labeling. We envision the turn-on response to depolarizations, fast response kinetics, and two-photon compatibility of chemical indicators, coupled with the cellular and synaptic specificity of genetically-encoded enzymes, will make RhoVR-Halo a powerful complement to neurobiological imaging in Drosophila.Significance StatementVoltage imaging is a powerful method for interrogating neurobiology. Chemical indicators possess fast response kinetics, turn-on responses to membrane depolarization, and can be compatible with two-photon excitation. However, selective cell labeling in intact tissues and in vivo remains a challenge for completely synthetic fluorophores. Here, we show that a chemical – genetic hybrid approach in Drosophila enables cell-specific staining in vivo and voltage imaging in whole-brain explants and at neuromuscular junction synapses.
A population of descending neurons that regulate the flight motor of Drosophila
Authors: Namiki Shigehiro , Ros Ivo G. , Morrow Carmen , Rowell William J. , Card Gwyneth M. , Korff Wyatt , Dickinson Michael H. 
Published: August 2021

SummaryLike many insect species, Drosophila melanogaster are capable of maintaining a stable flight trajectory for periods lasting up to several hours(1, 2). Because aerodynamic torque is roughly proportional to the fifth power of wing length(3), even small asymmetries in wing size require the maintenance of subtle bilateral differences in flapping motion to maintain a stable path. Flies can even fly straight after losing half of a wing, a feat they accomplish via very large, sustained kinematic changes to the both damaged and intact wings(4). Thus, the neural network responsible for stable flight must be capable of sustaining fine-scaled control over wing motion across a large dynamic range. In this paper, we describe an unusual type of descending neurons (DNg02) that project directly from visual output regions of the brain to the dorsal flight neuropil of the ventral nerve cord. Unlike most descending neurons, which exist as single bilateral pairs with unique morphology, there is a population of at least 15 DNg02 cell pairs with nearly identical shape. By optogenetically activating different numbers of DNg02 cells, we demonstrate that these neurons regulate wingbeat amplitude over a wide dynamic range via a population code. Using 2-photon functional imaging, we show that DNg02 cells are responsive to visual motion during flight in a manner that would make them well suited to continuously regulate bilateral changes in wing kinematics. Collectively, we have identified a critical set of DNs that provide the sensitivity and dynamic range required for flight control.
Vinculin recruitment to α-catenin halts the differentiation and maturation of enterocyte progenitors to maintain homeostasis of the Drosophila intestine
Authors: Bohère Jérôme , Eldridge-Thomas Buffy L. , Kolahgar Golnar 
Published: August 2021

AbstractMechanisms communicating changes in tissue stiffness and size are particularly relevant in the intestine, because it is subject to constant mechanical stresses caused by peristalsis of its variable content. Using the Drosophila intestinal epithelium, we investigate the role of vinculin, one of the best characterised mechanoeffectors, which functions in both cadherin and integrin adhesion complexes. We discovered that vinculin regulates cell fate decisions, by preventing precocious activation and differentiation of intestinal progenitors into absorptive cells. It achieves this in concert with α-catenin at sites of cadherin adhesion, rather than as part of integrin function. Following asymmetric division of the stem cell into a stem cell and an enteroblast, the two cells initially remain connected by adherens junctions, where vinculin is required, only on the enteroblast side, to maintain the enteroblast in a quiescent state and inhibit further divisions of the stem cell. Removing vinculin increases enteroblast differentiation and numbers, resulting in an enlarged gut with improved ability to recover after starvation. Thus, mechanical regulation at the contact between stem cells and their progeny is used to control tissue cell number.
Impaired dynamics of brain precapillary sphincters and pericytes at first order capillaries explains reduced neurovascular functions in aging
Authors: Cai Changsi , Zambach Stefan Andreas , Grubb Søren , Thomsen Kirsten Joan , Lind Barbara Lykke , Hald Bjørn Olav , Lønstrup Micael , Nielsen Reena Murmu , Lauritzen Martin Johannes 
Published: August 2021

ABSTRACTThe microvascular inflow tract (MIT), comprising the penetrating arterioles, precapillary sphincters, and first order capillaries, is the bottleneck for brain blood flow and energy supply. However, the exact structural and functional alterations of the MIT during aging remain elusive. In vivo 4-dimensional two-photon imaging showed an age-dependent decrease in vaso-responsivity, with reduced sensitivity of the MIT to pinacidil and papaverine, vasoconstrictor endothelin-1, and nitric oxide synthase inhibitor L-NAME. This was accompanied by an age-dependent decrease in capillary density close to the arterioles and loss of pericyte processes, though the number of pericyte somas and pericyte αSMA density were preserved. The age-related reduction in vascular reactivity was most pronounced at precapillary sphincters, highlighting their crucial role in capillary blood flow regulation. Mathematical modeling revealed dysregulated but preserved pressure and flow in aged mice during vasoconstriction. Preventing reduced responsivity of the MIT may ameliorate the blood flow decrease associated with aging-related brain frailty.
Transitions in the proteome and phospho-proteome duringXenopus laevisdevelopment
Authors: Van Itallie Elizabeth , Sonnett Matthew , Kalocsay Marian , Wühr Martin , Peshkin Leonid , Kirschner Marc W. 
Published: August 2021

ABSTRACTVertebrate development from an egg to a complex multi-cell organism is accompanied by multiple phases of genome-scale changes in the repertoire of proteins and their post-translational modifications. While much has been learned at the RNA level, we know less about changes at the protein level. In this paper, we present a deep analysis of changes of ∼15,000 proteins and ∼11,500 phospho-sites at 11 developmental time points inXenopus laevisembryos ranging from the stage VI oocyte to juvenile tadpole. We find that the most dramatic changes to the proteome occur during the transition to functional organ systems, which occurs as the embryo becomes a tadpole. At that time, the absolute amount of non-yolk protein increases two-fold, and there is a shift in the balance of expression from proteins regulating gene expression to receptors, ligands, and proteins involved in cell-cell and cell-environment interactions. Between the early and late tadpole, the median increase for membrane and secreted proteins is substantially higher than that of nuclear proteins. To begin to appreciate changes at the post-translational level, we have measured quantitative phospho-proteomic data across the same developmental stages. In contrast to the significant protein changes that are concentrated at the end of the time series, the most significant phosphorylation changes are concentrated in the very early stages of development. A clear exception are phosphorylations of proteins involved in gene expression: these increase just after fertilization, with patterns that are highly correlated with the underlying protein changes. To facilitate the interpretation of this unique phospho-protoeme data set, we created a pipeline for identifying homologous human phosphorylations from the measured Xenopus phospho-proteome. Overall, we detected many profound temporal transitions, that suggest concerted changes in developmental strategies in the embryo, which are particularly pronounced once early patterning and specification are complete.
A general deep learning model for bird detection in high resolution airborne imagery
Authors: Weinstein Ben G. , Garner Lindsey , Saccomanno Vienna R. , Steinkraus Ashley , Ortega Andrew , Brush Kristen , Yenni Glenda , McKellar Ann E. , Converse Rowan , Lippitt Christopher D. , Wegmann Alex , Holmes Nick D. , Edney Alice J. , Hart Tom , Jessopp Mark J. , Clarke Rohan H , Marchowski Dominik , Senyondo Henry , Dotson Ryan , White Ethan P. , Frederick Peter , Ernest S.K. Morgan 
Published: August 2021

AbstractAdvances in artificial intelligence for computer vision hold great promise for increasing the scales at which ecological systems can be studied. The distribution and behavior of individuals is central to ecology, and computer vision using deep neural networks can learn to detect individual objects in imagery. However, developing supervised models for ecological monitoring is challenging because it needs large amounts of human-labeled training data, requires advanced technical expertise and computational infrastructure, and is prone to overfitting. This limits application across space and time. One solution is developing generalized models that can be applied across species and ecosystems. Using over 250,000 annotations from 13 projects from around the world, we develop a general bird detection model that achieves over 65% recall and 50% precision on novel aerial data without any local training despite differences in species, habitat, and imaging methodology. Fine-tuning this model with only 1000 local annotations increase these values to an average of 84% recall and 69% precision by building on the general features learned from other data sources. Retraining from the general model improves local predictions even when moderately large annotation sets are available and makes model training faster and more stable. Our results demonstrate that general models for detecting broad classes of organisms using airborne imagery are achievable. These models can reduce the effort, expertise, and computational resources necessary for automating the detection of individual organisms across large scales, helping to transform the scale of data collection in ecology and the questions that can be addressed.
Peptidergic modulation of fear responses by the Edinger-Westphal nucleus
Authors: Priest Michael F. , Freda Sara N. , Badong Deanna , Dumrongprechachan Vasin , Kozorovitskiy Yevgenia 
Published: August 2021

AbstractMany neuronal populations that release fast-acting excitatory and inhibitory neurotransmitters in the brain also contain slower acting neuropeptides. These facultative peptidergic cell types are common, but it remains uncertain whether obligate peptidergic neurons exist. Our fluorescence in situ hybridization, genetically-targeted electron microscopy, and electrophysiological characterization data strongly suggest that neurons of the non-cholinergic, centrally-projecting Edinger-Westphal nucleus in mice are fundamentally obligately peptidergic. We further show, using fiber photometry, monosynaptic retrograde tracing, anterograde projection mapping, and a battery of behavioral assays, that this peptidergic population both promotes fear responses and analgesia and activates in response to loss of motor control and pain. Together, these findings elucidate an integrative, ethologically relevant function for the Edinger-Westphal nucleus and functionally align the nucleus with the periaqueductal gray, where it resides. This work advances our understanding of the peptidergic modulation of fear and provides a framework for future investigations of putative obligate peptidergic systems.