bluuebunny/crossref_metadata_2025_split huggingface dataset:
Green tea infusion aggravates nutritional status of the juvenile untreated STZ-induced type 1 diabetic rat
Authors: Ladeira Luiz Carlos Maia , dos Santos Eliziária Cardoso , Mendes Bruno Ferreira , Gutierrez Eliana Alviarez , Santos Cynthia Fernandes Ferreira , de Souza Fernanda Batista , Machado-Neves Mariana , Maldonado Izabel Regina dos Santos Costa 
Published: January 2020

SummaryWe have described for the first time the potential harmful effects of green tea on the metabolism and body composition of untreated juvenile experimental type 1 diabetic rats. The treatment containing 19.38% of epigallocatechin-3-gallate, its main catechin, increased blood glucose and water intake. It also increased oxygen consumption, enhanced energy expenditure and led to a lipid oxidation tendency in diabetic animals, which worsened the development of body fat in a way significantly more aggravated than diabetes alone. Taken together, our findings indicate that green tea treatment, when provided to juvenile diabetics, increases glycaemia, changes the body composition by reducing fat content and increases oxygen consumption, besides affecting energy expenditure. Therefore, the nutritional status of the juvenile type 1 diabetic rat is aggravated.
Molecular Choreography of Acute Exercise
Authors: Contrepois Kévin , Wu Si , Moneghetti Kegan J , Hornburg Daniel , Ahadi Sara , Tsai Ming-Shian , Metwally Ahmed A , Wei Eric , Lee-McMullen Brittany , Quijada Jeniffer V , Chen Songjie , Christle Jeffrey W , Ellenberger Mathew , Balliu Brunilda , Taylor Shalina , Durrant Matthew , Knowles David A , Choudhry Hany , Ashland Melanie , Bahmani Amir , Enslen Brooke , Amsallem Myriam , Kobayashi Yukari , Avina Monika , Perelman Dalia , Rose Sophia Miryam Schüssler-Fiorenza , Zhou Wenyu , Ashley Euan A , Montgomery Stephen B , Chaib Hassan , Haddad Francois , Snyder Michael P. 
Published: January 2020

AbstractExercise testing is routinely used in clinical practice to assess fitness - a strong predictor of survival - as well as causes of exercise limitations. While these studies often focus on cardiopulmonary response and selected molecular pathways, the dynamic system-wide molecular response to exercise has not been fully characterized. We performed a longitudinal multi-omic profiling of plasma and peripheral blood mononuclear cells including transcriptome, immunome, proteome, metabolome and lipidome in 36 well-characterized volunteers before and after a controlled bout of acute exercise (2, 15, 30 min and 1 hour in recovery). Integrative analysis revealed an orchestrated choreography of biological processes across key tissues. Most of these processes were dampened in insulin resistant participants. Finally, we discovered biological pathways involved in exercise capacity and developed prediction models revealing potential resting blood-based biomarkers of fitness.
A multi-phase flux balance model reveals flexibility of guard cell central carbon metabolism
Authors: Tan Joshua XL , Cheung C. Y. Maurice 
Published: January 2020

SummaryExperimental research in guard cell metabolism has revealed the roles of the accumulation of various metabolites in guard cell function, but a comprehensive understanding of their metabolism over the diel cycle is still incomplete, given the limitations of current experimental methods. In this study, we constructed a four-phase flux balance model of guard cell metabolism to investigate the changes in guard cell metabolism over the diel cycle, including the day and night and stomata opening and closing. Our model demonstrated the metabolic flexibility in guard cells, showing that multiple metabolic processes can contribute to the synthesis and metabolism of malate and sucrose as osmolytes during stomatal opening and closing. We showed that guard cells can adapt to varying light availability and sucrose uptake from the apoplast during the day by operating in a mixotrophic mode with a switch between sucrose synthesis via the Calvin-Benson cycle and sucrose degradation via the oxidative pentose phosphate pathway. During stomatal opening, our model predicted an alternative flux mode of the Calvin-Benson cycle with all dephosphorylating steps diverted to diphosphate—fructose-6-phosphate 1-phosphotransferase to produce PPi, which is used to pump protons across the tonoplast for the accumulation of osmolytes. An analysis of the energetics of the use of different osmolytes in guard cells showed that malate and Cl-are similarly efficient as the counterion of K+during stomatal opening.Significance statementThis work presents the first four-phase metabolic model for predicting guard cell metabolism over the diel cycle, which predicted an alternative flux model of the Calvin-Benson cycle that maximises the production of PPiduring stomatal opening. While multiple metabolic processes were shown be important in synthesising and metabolising osmolytes in guard cells of different experimental systems, our model demonstrated that these processes can operate simultaneously and at different rates depending on conditions.
Taking extreme measures: A quantitative study of multiple stress interactions at the limits of life
Authors: Cane Rosie , Cockell Charles 
Published: January 2020

AbstractEnvironments exposed to simultaneously occurring extremes are prevalent in the natural world, yet analysis of such settings tends to focus on the effect of single environmental stresses. In this study, quantitative multiplicative and minimising models previously used to study nutrient limitation were applied to the growth of the hydrothermal vent-dwelling organismHalomonas hydrothermaliswhen subjected to combined nutrient limitation and NaCl-salt stress. Results showed an interactive effect from both salt and nutrient stresses under optimal conditions. However, the fit became more non-interactive as salinity is increased; at which point NaCl-salt had a more dominating effect on growth than inorganic phosphate (Pi). We discuss biochemical hypotheses to explain these data. This work shows that models developed to understand nutrient limitation can be used to quantify and separate the contributions of stresses under other physical and chemical extremes, such as extreme salinity, and facilitate the development of biochemical hypotheses of how extremes may be influencing cell physiology.ImportanceVery few environments in the natural world are exposed to just one extreme or stress at a time. To understand life’s ability to survive in multiple-extreme environments, we must be able to quantify how different extremes interact. Using methods developed for the study of multiple nutrient limitation, this study uses kinetic growth models to investigate at the effect of extreme environments on bacterial growth. Results show that closer to the extremes of life, individual stresses dominate growth; whereas under optimal conditions there is a multiplicative effect from both salt and nutrient stresses. This approach offers a new way to quantify and potentially understand and develop hypotheses for how life operates under multiple extremes.
Adaptive repulsion of long-term memory representations is triggered by event similarity
Authors: Chanales Avi J. H. , Tremblay-McGaw Alexandra G. , Kuhl Brice A. 
Published: January 2020

ABSTRACTWe tested whether similarity between events triggers an adaptive repulsion of long-term memories. Subjects completed an associative learning task in which objects were paired with faces. Critically, the objects consisted of pairs that were identical except for their color values, which were parametrically varied in order to manipulate interference. Performance on associative memory tests confirmed that color similarity robustly influenced interference. Separate tests of color memory showed that high similarity triggered a repulsion of long-term memories, wherein remembered colors were biased away from colors of competing objects. This repulsion effect was replicated across three experiments. In a fourth experiment, the repulsion effect was fully eliminated when task demands promoted integration, instead of discrimination, of similar memories. Finally, we show that repulsion of color memory was highly adaptive: greater repulsion was associated with less memory interference. These findings reveal that similarity between events triggers adaptive distortions in how events are remembered.SUPPLEMENTARY INFORMATIONThree supplementary figures are included.
Myofiber stretch induces tensile and shear deformation of muscle stem cells in their native niche
Authors: Haroon Mohammad , Klein-Nulend Jenneke , Bakker Astrid D. , Jin Jianfeng , Offringa Carla , Grand Fabien Le , Giordani Lorenzo , Liu Karen J. , Knight Robert D. , Jaspers Richard T. 
Published: January 2020

ABSTRACTBackgroundMuscle stem cells (MuSCs) are requisite for skeletal muscle regeneration and homeostasis. Proper functioning of MuSCs, including activation, proliferation, and fate decision, is determined by an orchestrated series of events and communication between MuSCs and their niche consisting of the host myofiber and neighbouring cells. A multitude of biochemical stimuli are known to regulate fate and function of MuSCs. However, in addition to biochemical factors, it is conceivable that MuSCs residing between basal lamina and sarcolemma of myofibers are subjected to mechanical forces during muscle stretch-shortening cycles due to myofascial connections between MuSCs and myofibers. MuSCs have been shown to respond to mechanical forcesin vitrobut it remains to be proven whether physical forces are also exerted on MuSCs in their native niche and whether they contribute to the functioning and fate of MuSCs.MethodsMuSCs deformation in their native niche resulting from mechanical loading ofex vivomyofiber bundles were visualized utilizingmT/mGdouble-fluorescent Cre-reporter mouse and multiphoton microscopy. MuSCs were subjected to 1 hour pulsating fluid shear stress with a peak shear stress rate of 8.8 Pa/s. After treatment, nitric oxide and mRNA expression levels of genes involved in regulation of MuSC proliferation and differentiation were determined.ResultsEx vivostretching of extensor digitorum longus and soleus myofiber bundles caused compression as well as tensile and shear deformation of MuSCs in their niche. MuSCs responded to pulsating fluid shear stressin vitrowith increased nitric oxide production and an upward trend iniNOSmRNA levels, whilenNOSexpression was unaltered. Pulsating fluid shear stress enhanced gene expression ofc-Fos, Cdk4, andIL-6, while expression ofWnt1, MyoD, Myog, Wnt5a, COX2, Rspo1, Vangl2, Wnt10b, andMGFremained unchanged.ConclusionsWe conclude that MuSCs in their native niche are subjected to force-induced deformations due to myofiber stretch-shortening. Moreover, MuSCs are mechanoresponsive as evident by pulsating fluid shear stress-mediated expression of factors by MuSCs known to promote proliferation.
Condensin I subunit Cap-G is essential for proper gene expression during the maturation of post-mitotic neurons
Authors: Hassan Amira , Rodriguez Pablo Araguas , Heidmann Stefan K. , Walmsley Emma L. , Aughey Gabriel N. , Southall Tony D. 
Published: January 2020

AbstractThe condensin complex is essential for mitotic chromosome assembly and segregation during cell divisions, however, little is known about its function in post-mitotic, differentiated cells. Here we report a novel role for the condensin I subunit Cap-G inDrosophilaneurons. We show that, despite not requiring condensin for mitotic chromosome compaction, post-mitotic neurons express Cap-G and that knockdown of Cap-G specifically in neurons (from their birth onwards) results in developmental arrest, behavioural defects, and dramatic gene expression changes. These include reduced expression of a subset of neuronal genes and aberrant expression of genes that are not normally expressed in the developing brain. Knockdown of Cap-G in more mature neurons also results in similar phenotypes but to a lesser degree. Furthermore, we see dynamic binding of Cap-G to chromatin at distinct loci in neural stem cells and differentiated neurons. Therefore, Cap-G is essential for proper gene expression in neurons and plays an important role during the early stages of neuronal development.
NLRP3 inflammasome priming and activation are regulated by a novel phosphatidylinositol-dependent mechanism
Authors: Hamilton Claire , Olona Antoni , Leishman Stuart , MacDonald-Ramsahai Kelly , Cockcroft Shamshad , Larrouy-Maumus Gerald , Anand Paras K. 
Published: January 2020

SummaryImbalance in lipid homeostasis is associated with discrepancies in immune signalling and is tightly linked to metabolic disorders. The diverse ways in which lipids impact immune signalling, however, remain ambiguous. The phospholipid phosphatidylinositol (PI), which is implicated in numerous immune disorders, is chiefly defined by its phosphorylation status. By contrast, the significance of the two fatty acid chains attached to the PI remains unknown. Here, by employing a mass-spectrometry-based assay, we demonstrate a role for PI acyl group chains in regulating both the priming and activation steps of the NLRP3 inflammasome in mouse macrophages. In response to NLRP3 stimuli, cells deficient in ABC transporter ABCB1, which effluxes lipid derivatives, revealed defective inflammasome activation. Mechanistically,Abcb1-deficiency shifted the total PI configuration exhibiting a reduced ratio of short-chain to long-chain PI-acyl lipids. Consequently,Abcb1-deficiency resulted in rapid degradation of TIRAP, the TLR adaptor protein which binds PI(4,5)-phosphate. Moreover, this accompanied increased NLRP3 phosphorylation at the Ser293 position and blunted inflammasome activation. Exogenously supplementing WT cells with linoleic acid, but not arachidonic acid, reconfigured PI acyl chains. Accordingly, linoleic acid supplementation increased TIRAP degradation, elevated NLRP3 phosphorylation, and abrogated inflammasome activation. Altogether, our study reveals a novel metabolic-inflammatory circuit which contributes to calibrating immune responses.
Predicting transcription factor binding in single cells through deep learning
Authors: Fu Laiyi , Zhang Lihua , Dollinger Emmanuel , Peng Qinke , Nie Qing , Xie Xiaohui 
Published: January 2020

AbstractCharacterizing genome-wide binding profiles of transcription factor (TF) is essential for understanding many biological processes. Although techniques have been developed to assess binding profiles within a population of cells, determining binding profiles at a single cell level remains elusive. Here we report scFAN (Single Cell Factor Analysis Network), a deep learning model that predicts genome-wide TF binding profiles in individual cells. scFAN is pre-trained on genome-wide bulk ATAC-seq, DNA sequence and ChIP-seq data, and utilizes single-cell ATAC-seq to predict TF binding in individual cells. We demonstrate the efficacy of scFAN by studying sequence motifs enriched within predicted binding peaks and investigating the effectiveness of predicted TF peaks for discovering cell types. We develop a new metric “TF activity score” to characterize each cell, and show that the activity scores can reliably capture cell identities. The method allows us to discover and study cellular identities and heterogeneity based on chromatin accessibility profiles.
Correlative Fluorescence- and Electron Microscopy of Whole Breast Cancer Cells Reveals Different Distribution of ErbB2 Dependent on Underlying Actin
Authors: Dahmke Indra Navina , Trampert Patrick , Weinberg Florian , Mostajeran Zahra , Lautenschläger Franziska , de Jonge Niels 
Published: January 2020

AbstractEpidermal growth factor receptor 2 (ErbB2) is found overexpressed in several cancers, such as gastric, and breast cancer, and is, therefore, an important therapeutic target. ErbB2 plays a central role in cancer cell invasiveness, and is associated with cytoskeletal reorganization. In order to study the spatial correlation of single ErbB2 proteins and actin filaments, we applied correlative fluorescence microscopy, and scanning transmission electron microscopy (STEM) to image specifically labeled SKBR3 breast cancer cells. The breast cancer cells were grown on microchips, transformed to express an actin-green fluorescent protein (GFP) fusion protein, and labeled with quantum dot (QD) nanoparticles attached to specific anti-ErbB2 Affibodies. Fluorescence microscopy was performed to identify cellular regions with spatially correlated actin and ErbB2 expression. For STEM of the intact plasma membrane of whole cells, the cells were fixed and covered with graphene. Spatial distribution patterns of ErbB2 in the actin rich ruffled membrane regions were examined, and compared to adjacent actin-low regions of the same cell, revealing an association of putative signaling active ErbB2 homodimers with actin-rich regions. ErbB2 homodimers were found absent from actin-low membrane regions, as well as after treatment of cells with Cytochalasin D, which breaks up larger actin filaments. In both latter data sets, a significant inter-label distance of 36 nm was identified, possibly indicating an indirect attachment to helical actin filaments via the formation of heterodimers of ErbB2 with epidermal growth factor receptor (EGFR). The possible attachment to actin filaments was further explored by identifying linear QD-chains in actin-rich regions, which also showed an inter-label distance of 36 nm.
Development of humanized mouse and rat models with full-thickness human skin and autologous immune cells
Authors: Agarwal Yash , Beatty Cole , Ho Sara , Thurlow Lance , Das Antu , Kelly Samantha , Castronova Isabella , Salunke Rajeev , Biradar Shivkumar , Yeshi Tseten , Richardson Anthony , Bility Moses 
Published: January 2020

AbstractThe human skin is a major barrier for host defense against many human pathogens, with several pathogens directly targeting the skin for replication and disease. The skin is also the primary route of infection for a myriad of vector-borne diseases; thus cutaneous immune cells play a major role in modulating transmission for such infectious diseases. Several human pathogens that target the skin as a major route of infection are unable to infect traditional rodent models or recapitulate the pathogenesis in humans. It is well established that differences exist in human skin and immune cell biology compared to rodent models. Therefore, rodent (mouse and rat) models that incorporate human skin and immune cells would addressed the above discussed technical gap, and enablein vivomechanistic studies of human host-skin pathogen interactions, and support the development of novel therapeutics. Here, we introduce the novel human Skin and Immune System (hSIS)-humanized NOD-scidIL2Rgnull(NSG) mouse and Sprague-Dawley-Rag2tm2heraIl2rgtm1hera(SRG) rat models, co-engrafted with full-thickness human fetal skin, autologous fetal lymphoid tissues, and fetal liver-derived hematopoietic stem cells. hSIS-humanized rodents support the development of adult-like, full-thickness human skin and human lymphoid tissues, and support human immune cell development. Furthermore, the engrafted human skin supports Methicillin-resistantStaphylococcus aureusinfection, demonstrating the utility of these humanized rodent models in studying human disease.
Simultaneous Determination of Contents of Flavonol Glycosides and Terpene Lactones in Ginkgo Biloba Tablets by Ultra High Performance Liquid Chromatography Tandem Single Quadrupole Mass Spectrometry Detector
Authors: Ma Lin , Zhang Jie , Jin Wei-rong , Wang Siwang 
Published: January 2020

AbstractGinkgo biloba leaf tablets is an effective ingredient in the treatment of cardiovascular and cerebrovascular diseases. In the process of drug production, the quality of ginkgo preparations is often controlled by measuring the content of seven ingredients in ginkgo leaves. To establish UPLC-MS multicomponent analysis method for ginkgo biloba tablets and to simultaneously determine the contents of quercetin (QUE), isorhamnetin(ISO), kaempferol(KAE) and GinkgolideA (GA),ginkgolideB(GB),ginkgolideC(GC) and bilobalide (BB) in ginkgo tablets. Waters Xbridge C18(4.6×150mm,3.5um) column was used, mobile phase A was acetonitrile and mobile phase B was water (containing 0.10% formic acid). The injection volume was 10μL.Negative ion mode monitoring was conducted with ESI. Scanning range:m/z100∼1400.The detection ions of the seven tested components includem/z301.0(QUE),m/z284.9(KAE),m/z315.1(ISO),m/z453.1(GA),m/z423.1(G B),m/z439.0(GC)and m/z325.0(BB), respectively. Within a space of 10min, flavonoids and terpene lactones in ginkgo biloba tablets were completely separated. The peak area exhibited an excellent linear relationship with the concentration. The sample recovery rate ranged from 91.74% to 109.77%.Precision RSDs of within-day and between-day were lower than 2.879% and 3.928% respectively. The method for determination of seven components in ginkgo biloba tablets displays good repeatability, recovery rate and precision, for which it can be applied to quality control of ginkgo biloba tablets.
Analysis of gene expression and connectivity on hippocampus of Alzheimer’s disease by a new comprehensive approach
Authors: Jiang Shan 
Published: January 2020

AbstractGene expression and gene connectivity describe two different functional aspects of a gene. These two different measures reveal different information about the involvement of genes in disorders. Previous case-control gene expression studies have often focused on expression level of individual genes. Correlated expression relationships among genes, measured as gene connectivity, have obtained limited attention. We developed a comprehensive method, TRIple Differentiation (TRID), to assess these two measures, both separately and jointly. We applied TRID to gene expression data in hippocampus tissue samples from three Alzheimer’s disease (AD) microarray datasets. Following TRID, comparisons among the three datasets showed poor consistency for disease-associated individual genes but reproducible changes of disease-associated biological pathways annotated for functional protein-protein interaction (PPI) modules identified from network analysis. Our results suggest that changes of gene expression in hippocampus of AD patients are highly heterogeneous at the individual gene level, while biological pathways annotated for PPI modules identified based on TRID weights demonstrate consistency among the three datasets. The R package TRID can be accessed from GitHub (https://github.com/shannjiang/TRID).
Dendritic normalisation improves learning in sparsely connected artificial neural networks
Authors: Bird Alex D , Cuntz Hermann 
Published: January 2020

AbstractInspired by the physiology of neuronal systems in the brain, artificial neural networks have become an invaluable tool for machine learning applications. However, their biological realism and theoretical tractability are limited, resulting in poorly understood parameters. We have recently shown that biological neuronal firing rates in response to distributed inputs are largely independent of size, meaning that neurons are typically responsive to the proportion, not the absolute number, of their inputs that are active. Here we introduce such a normalisation, where the strength of a neuron’s afferents is divided by their number, to various sparsely-connected artificial networks. The learning performance is dramatically increased, providing an improvement over other widely-used normalisations in sparse networks. The resulting machine learning tools are universally applicable and biologically inspired, rendering them better understood and more stable in our tests.