bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of high-resolution atmospheric and oceanic simulations of the California Current System
Authors: Renault Lionel , McWilliams James C. , Kessouri Faycal , Jousse Alexandre , Frenzel Hartmut , Chen Ru , Deutsch Curtis 
Published: February 2020

AbstractThis paper is the first of two that present a 16-year hindcast solution from a coupled physical and biogeochemical model of the California Current System (CCS) along the U. S. West Coast and validate the physical solution with respect to mean, seasonal, interannual, and sub-seasonal fields and, to a lesser degree, eddy variability. Its companion paper is Deutsch et al. (2021a). The intent is to construct and demonstrate a modeling tool that will be used for mechanistic explanations, attributive causal assessments, and forecasts of future evolution for circulation and biogeochemistry, with particular attention to the increasing oceanic stratification, deoxygenation, and acidification. A well-resolved mesoscale (dx= 4 km) simulation of the CCS circulation is made with the Regional Oceanic Modeling System over a hindcast period of 16 years from 1995 to 2010. The oceanic solution is forced by a high-resolution (dx= 6 km) regional configuration of the Weather and Research Forecast (WRF) atmospheric model. Both of these high-resolution regional oceanic and atmospheric simulations are forced by lateral open boundary conditions taken from larger-domain, coarser-resolution parent simulations that themselves have boundary conditions from the Mercator and Climate Forecast System reanalyses, respectively. We show good agreement between the simulated atmospheric forcing of the oceanic and satellite measurements for the spatial patterns and temporal variability for the surface fluxes of momentum, heat, and freshwater. The simulated oceanic physical fields are then evaluated with satellite andin situmeasurements. The simulation reproduces the main structure of the climatological upwelling front and cross-shore isopycnal slopes, the mean current patterns (including the California Undercurrent), and the seasonal, interannual, and subseasonal variability. It also shows agreement between the mesoscale eddy activity and the windwork energy exchange between the ocean and atmosphere modulated by influences of surface current on surface stress. Finally, the impact of using a high frequency wind forcing is assessed for the importance of synoptic wind variability to realistically represent oceanic mesoscale activity and ageostrophic inertial currents.
Ultra-low DNA input into whole genome methylation assays and detection of oncogenic methylation & copy number variants in circulating tumour DNA
Authors: Whalley Celina , Payne Karl , Domingo Enric , Blake Andrew , Richman Susan , Brooks Jill , Batis Nikolaos , Spruce Rachel ,   S-CORT Consortium, Mehanna Hisham , Nankivell Paul , Beggs Andrew D 
Published: February 2020

AbstractBackgroundCpG methylation in cancer is ubiquitous and generally detected in tumour specimens using a variety of techniques at a resolution encompassing single CpG loci to genome wide. Analysis of samples with very low DNA inputs, such as formalin fixed (FFPE) biopsy specimens from clinical trials or circulating tumour DNA has been challenging and has only been typically at single CpG sites. Analysis of genome wide methylation in these specimens has been limited because of the relative expense of techniques need to carry this out. We present the results of low input experiments into the Illumina Infinium HD methylation assay on FFPE specimens and ctDNA samples.MethodsFor all experiments, the Infinium HD assay for Methylation was used. In total, forty-eight FFPE specimens were used at varying concentrations (lowest input 50ng), eighteen blood derived specimens (lowest input 10ng) and six matched ctDNA input (lowest input 10ng) / fresh tumour specimens (lowest input 250ng) were processed. Downstream analysis was performed in R/Bioconductor for QC metrics and differential methylation analysis as well as copy number calls.ResultsCorrelation coefficients for CpG methylation at the probe level averaged R2=0.99 for blood derived samples and R2>0.96 for the FFPE samples. When matched ctDNA/fresh tumour samples were compared R2>0.91. Results of differential methylation analysis did not vary significantly by DNA input in either the blood or FFPE groups. There were differences seen in the ctDNA group as compared to their paired tumour sample, possibly because of enrichment for tumour material without contaminating normal. Copy number variants observed in the tumour were generally also seen in the paired ctDNA sample.ConclusionsThe Illumina Infinium HD methylation assay can robustly detect methylation across a range of sample types, including ctDNA, down to a input of 10ng. It can also reliably detect oncogenic methylation changes and copy number variants in ctDNA.
Epidemiological and Clinical Characteristics of 17 Hospitalized Patients with 2019 Novel Coronavirus Infections Outside Wuhan, China
Authors: Li Jie , Li Shilin , Cai Yurui , Liu Qin , Li Xue , Zeng Zhaoping , Chu Yanpeng , Zhu Fangcheng , Zeng Fanxin 
Published: February 2020

SUMMARYAn increasing number of cases of novel coronavirus pneumonia (NCP) infected with 2019-nCoV have been identified in Wuhan and other cities in China, since December 2019. We analyzed data on the 17 confirmed cases in Dazhou to provide the epidemiologic characteristics of NCP outside Wuhan. Among them, 12 patients were still quarantined in the hospital, 5 patients were discharged NCP patients according to the national standards. Compared with non-discharged NCP patients, the discharged NCP patients had younger ages. Moreover, discharged NCP patients had higher heart rate, lymphocytes levels and monocytes levels than non-discharged NCP patients on admission to the hospital. Notably, all of 17 patients had abnormal increased C-reactive protein levels, and 16 patients had abnormal computed tomography images. This study provided some information that younger age, higher lymphocytes levels and monocytes levels at the diagnoses of 2019-nCoV may contributed to faster recovery and better therapeutic outcome.
Untangling biological factors influencing trajectory inference from single cell data
Authors: Charrout Mohammed , Reinders Marcel J.T. , Mahfouz Ahmed 
Published: February 2020

Advances in single-cell RNA sequencing over the past decade has shifted the discussion of cell identity towards the transcriptional state of the cell. While the incredible resolution provided by single-cell RNA sequencing has led to great advances in unravelling tissue heterogeneity and inferring cell differentiation dynamics, it raises the question of which sources of variation are important for determining cellular identity. Here we show that confounding biological sources of variation, most notably the cell cycle, can distort the inference of differentiation trajectories. We show that by factorizing single cell data into distinct sources of variation, we can select a relevant set of factors that constitute the core regulators for trajetory inference, while filtering out confounding sources of variation (e.g. cell cycle) which can perturb the inferred trajectory. Script are available publicly onhttps://github.com/mochar/cell_variation.Significance StatementPseudotime inference is a bioinformatics tool used to characterize and understand the role and activity of genes involved in cell differentiation. To achieve this, the level of expression of thousands of genes are simultaneously used to order cells along a developmental axis. However, this may result in distorted trajectories as many genes are not necessary involved in cell differentiation, and might even provide the pseudotime inference tool with conflicting (confounding) information. Here we present a methodology for improving inference of the differentiation trajectories by restricting it to a small set of genes assumed to regulate cell differentiation.
Paladin is a PI(4,5)P2phosphoinositide phosphatase that regulates endosomal signaling and angiogenesis
Authors: Nitzsche Anja , Pietilä Riikka , Testini Chiara , Ninchoji Takeshi , Smith Ross O. , Ekvärn Elisabet , Larsson Jimmy , Roche Francis P. , Egaña Isabel , Jauhiainen Suvi , Berger Philipp , Claesson-Welsh Lena , Hellström Mats 
Published: February 2020

ABSTRACTCell signaling governs cellular behavior and is therefore subject to tight spatiotemporal regulation. Signaling output is regulated by specialized cell membranes and vesicles which contain unique combinations of lipids and proteins. The phospholipid phosphatidylinositol 4,5-bisphosphate, (PI(4,5)P2), an important component of the plasma membrane as well as other subcellular membranes, is involved in multiple processes, including signaling. However, which enzymes drive the formation and degradation of non-plasma membrane PI(4,5)P2, and their impact on cell signaling and function at the organismal level are unknown. Here we show in a mouse model that Paladin is a vascular PI(4,5)P2phosphatase that regulates endosomal signaling and angiogenesis. Paladin was localized to the endosomal and Golgi compartments, and interacted with vascular endothelial growth factor receptor 2 (VEGFR2)in vitroandin vivo. Loss of Paladin resulted in increased internalization of the receptor, over-activation of extracellular regulated kinase, and hypersprouting of endothelial cells in the developing retina of mice. These findings suggest that inhibition of Paladin, or other endosomal PI(4,5)P2phosphatases, could be exploited to modulate VEGFR2 signaling and angiogenesis, when direct and full inhibition of the receptor is not desirable.
mAML: an automated machine learning pipeline with a microbiome repository for human disease classification
Authors: Yang Fenglong , Zou Quan 
Published: February 2020

AbstractDue to the concerted efforts to utilize the microbial features to improve disease prediction capabilities, automated machine learning (AutoML) systems designed to get rid of the tediousness in manually performing ML tasks are in great demand. Here we developed mAML, an ML model-building pipeline, which can automatically and rapidly generate optimized and interpretable models for personalized microbial classification tasks in a reproducible way. The pipeline is deployed on a web-based platform and the server is user-friendly, flexible, and has been designed to be scalable according to the specific requirements. This pipeline exhibits high performance for 13 benchmark datasets including both binary and multi-class classification tasks. In addition, to facilitate the application of mAML and expand the human disease-related microbiome learning repository, we developed GMrepo ML repository (GMrepo Microbiome Learning repository) from the GMrepo database. The repository involves 120 microbial classification tasks for 85 human-disease phenotypes referring to 12,429 metagenomic samples and 38,643 amplicon samples. The mAML pipeline and the GMrepo ML repository are expected to be important resources for researches in microbiology and algorithm developments.Database URLhttp://39.100.246.211:8050/Home
Homophilic and heterophilic cadherin bond rupture forces in homo- or hetero-cellular systems measured by AFM based SCFS
Authors: Viji Babu Prem Kumar , Mirastschijski Ursula , Belge Gazanfer , Radmacher Manfred 
Published: February 2020

AbstractCadherins enable intercellular adherens junctions to withstand tensile forces in tissues, e.g. generated by intracellular actomyosin contraction. Single molecule force spectroscopy experiments inin-vitroexperiments can reveal the cadherin-cadherin extracellular region binding dynamics such as bond formation and strength. However, characterization of cadherin homophilic and heterophilic binding in their native conformational and functional state in living cells has rarely been done. Here, we used Atomic Force Microscopy (AFM) based Single cell force Spectroscopy (SCFS) to measure rupture forces of homophilic and heterophilic bond formation of N-, OB- and E-cadherins in living fibroblast and epithelial cells in homo- and hetero-cellular arrangements, i.e. between same type of cells and between cells of different type. In addition, we used indirect immunofluorescence labelling to study and correlate the expression of these cadherins in intercellular adherens junctions. We showed that N/N and E/E cadherin homophilic bindings are stronger than N/OB, E/N and E/OB heterophilic bindings. Disassembly of intracellular actin filaments reduces the cadherin bond rupture forces suggesting a contribution of actin filaments in cadherin extracellular binding. Inactivation of myosin did not affect the cadherin rupture force in both homo- and hetero-cellular arrangements. Whereas, myosin inactivation particularly strengthened the N/OB heterophilic bond and reinforced the other cadherins homophilic bonds.
Niche theory for mutualism: A graphical approach to plant-pollinator network dynamics
Authors: Valdovinos Fernanda S. , Marsland Robert 
Published: February 2020

AbstractContemporary Niche Theory is a useful framework for understanding how organisms interact with each other and with their shared environment. Its graphical representation, popularized by Tilman’s Resource Ratio Hypothesis, facilitates the analysis of the equilibrium structure of complex dynamical models including species coexistence. This theory has been applied primarily to resource competition since its early beginnings. Here, we integrate mutualism into niche theory by expanding Tilman’s graphical representation to the analysis of consumer-resource dynamics of plant-pollinator networks. We graphically explain the qualitative phenomena previously found by numerical simulations, including the effects on community dynamics of nestedness, adaptive foraging, and pollinator invasions. Our graphical approach promotes the unification of niche and network theories, and deepens the synthesis of different types of interactions within a consumer-resource framework.Secondary AbstractTeoría de Nicho para Mutualismos: Una aproximación gráfica a la dinámica de redes planta-polinizadorLa Teoría Contemporánea de Nicho es un marco útil para entender cómo los organismos interactúan entre ellos y con su ambiente compartido. Su representatión gráfica, popularizada por la Hipótesis de Razón de Recursos de Tilman, facilita el análisis de la estructura de equilibrio de modelos dinámicos complejos, incluyendo la coexistencia de especies. Esta teoría ha sido aplicada primariamente a competencia por recursos desde sus inicios. Aquí, integramos el mutualismo dentro de la teoría de nicho al expandir la representatión gráfica de Tilman al análisis de la dinámica consumidor-recurso de las redes planta-polinizador. Explicamos gráficamente fenómenos cualitativos encontrados previamente mediante simulaciones numéricas, incluyendo los efectos sobre la dinámica comunitaria del anidamiento, forrajeo adaptativo y de las invasiones por polinizadores. Nuestra aproximación gráfica promueve la unificatión de las teorías de nicho y de redes, y profundiza la síntesis de diferentes tipos de interacciones dentro de un marco de consumidor-recurso.
Identifying states of collateral sensitivity during the evolution of therapeutic resistance in Ewing’s sarcoma
Authors: Scarborough Jessica A. , McClure Erin , Anderson Peter , Dhawan Andrew , Durmaz Arda , Lessnick Stephen L. , Hitomi Masahiro , Scott Jacob G. 
Published: February 2020

SummaryAdvances in the treatment of Ewing’s sarcoma (EWS) are desperately needed, particularly in the case of metastatic disease. A deeper understanding of collateral sensitivity, where the evolution of therapeutic resistance to one drug aligns with sensitivity to another drug, may improve our ability to effectively target this disease. For the first time in a solid tumor, we produced a temporal collateral sensitivity map that demonstrates the evolution of collateral sensitivity and resistance in EWS. We found that the evolution of collateral resistance was predictable with some drugs, but had significant variation in response to other drugs. Using this map of temporal collateral sensitivity in EWS, we can see that the path towards collateral sensitivity is not always repeatable, nor is there always a clear trajectory towards resistance or sensitivity. Identifying transcriptomic changes that accompany these states of transient collateral sensitivity could improve treatment planning for EWS patients.
Presynaptic inhibition rapidly stabilises recurrent excitation in the face of plasticity
Authors: Naumann Laura Bella , Sprekeler Henning 
Published: February 2020

AbstractHebbian plasticity, a mechanism believed to be the substrate of learning and memory, detects and further enhances correlated neural activity. Because this constitutes an unstable positive feedback loop, it requires additional homeostatic control.Computational work suggests that in recurrent networks, the homeostatic mechanisms observed in experiments are too slow to compensate instabilities arising from Hebbian plasticity and need to be complemented by rapid compensatory processes. We suggest presynaptic inhibition as a candidate that rapidly provides stability by compensating recurrent excitation induced by Hebbian changes. Presynaptic inhibition is mediated by presynaptic GABA receptors that effectively and reversibly attenuate transmitter release. Activation of these receptors can be triggered by excess network activity, hence providing a stabilising negative feedback loop that weakens recurrent interactions on sub-second timescales. We study the stabilising effect of presynaptic inhibition in a recurrent networks, in which presynaptic inhibition is implemented as a multiplicative reduction of recurrent synaptic weights in response to increasing inhibitory activity. We show that networks with presynaptic inhibition display a gradual increase of firing rates with growing excitatory weights, in contrast to traditional excitatory-inhibitory networks. This alleviates the positive feedback loop between Hebbian plasticity and network activity and thereby allows homeostasis to act on timescales similar to those observed in experiments. Our results generalise to spiking networks with a biophysically more detailed implementation of the presynaptic inhibition mechanism. In conclusion, presynaptic inhibition provides a powerful compensatory mechanism that rapidly reduces effective recurrent interactions and thereby stabilises Hebbian learning.
Bile acid composition regulates the manganese transporter Slc30a10 in intestine
Authors: Ahmad Tiara R. , Higuchi Sei , Bertaggia Enrico , Hung Allison , Shanmugarajah Niroshan , Guilz Nicole C. , Gamarra Jennifer R. , Haeusler Rebecca A. 
Published: February 2020

ABSTRACTBile acids (BAs) comprise heterogenous amphipathic cholesterol-derived molecules that carry out physicochemical and signaling functions. A major site of BA action is the terminal ileum, where enterocytes actively reuptake BAs and express high levels of BA-sensitive nuclear receptors. BA pool size and composition are affected by changes in metabolic health, and vice versa. One of several factors that differentiate BAs is the presence of a hydroxyl group on C12 of the steroid ring. 12a-hydroxylated BAs (12HBAs) are altered in multiple disease settings, but the consequences of 12HBA abundance are incompletely understood. We employed mouse primary ileum organoids to investigate the transcriptional effects of varying 12HBA abundance in BA pools. We identifiedSlc30a10as one of the top genes differentially induced by BA pools with varying 12HBA abundance. SLC30A10 is a manganese (Mn) efflux transporter critical for whole-body manganese excretion. We found that BA pools, especially those low in 12HBAs, induce cellular manganese efflux, and thatSlc30a10induction by BA pools is driven primarily by lithocholic acid signaling via the vitamin D receptor. Administration of lithocholic acid or a vitamin D receptor agonist resulted in increasedSlc30a10expression in mouse ileum epithelia. These data demonstrate a previously unknown role for BAs in intestinal control of Mn homeostasis.
Characterizing the tumor microenvironment of metastatic ovarian cancer by single cell transcriptomics
Authors: Olalekan Susan , Xie Bingqing , Back Rebecca , Eckart Heather , Basu Anindita 
Published: February 2020

AbstractEpithelial ovarian cancer is a highly heterogenous, metastatic and lethal disease. The presence of CD8+T cells within ovarian tumors is positively associated with overall patient survival. Determining if a patient has T cells that respond to immunotherapies, their characteristics and how they can be manipulated to target cancer cells is an area of intense investigation in cancer therapy. This study determines the cellular composition and the transcriptional state of immune cells in metastatic ovarian cancer samples from patients using single cell RNA sequencing (scRNA-seq). Hierarchical clustering stratified our patient cohort into 2 main groups: 1) a high T cell infiltration (high Tinf) group and 2) a low T cell infiltration (low Tinf) group. To assess the immune response in these patient samples, we performed an unsupervised clustering of the T cell population in each group. The T cell population clustered into 4 and 3 subpopulations in the high TinfT cell and low Tinfrespectively. A granulysin expressing T cell cluster was identified and unique to the High Tinfgroup. Interestingly, although both groups had resident memory CD8+T (CD8+Trm) cells, only the CD8+Trm cells in the high Tinfgroup expressed TOX, a recently described transcription factor. TOX confers longevity to T cells within immunosuppressive environment such as cancer. Interestingly, along with TOX+T cells, we found a unique plasmablast cluster and an IRF8+macrophage cluster unique to the high Tinfgroup. Our comprehensive scRNA-seq study provides important insights in elucidating the immune response in ovarian cancer patients.
Molecular control of interfacial protein structure on graphene-based substrates steers cell fate
Authors: Kumar Sachin , Parekh Sapun H. 
Published: February 2020

AbstractThe use of graphene-based materials (GBMs) for tissue-engineering applications is growing exponentially due to the seemingly endless multi-functional and tunable physicochemical properties of graphene, which can be exploited to influence cellular behaviours. Despite many demonstrations wherein cell physiology can be modulated on GBMs, a clear mechanism connecting the different physicochemical properties of different GBMs to cell fate has remained elusive. In this work, we demonstrate how different GBMs can be used to cell fate in a multi-scale study – starting from serum protein (Fibronectin) adsorption to molecular scale morphology, structure and bioactivity, and finally ending with stem cell response. By changing the surface chemistry of graphene substrates with only heating, we show that molecular conformation and morphology of surface adsorbed fibronectin controls epitope presentation, integrin binding, and stem cell attachment. Moreover, this subtle change in protein structure is found to drive increased bone differentiation of cells, suggesting that physicochemical properties of graphene substrates exert cell control by influencing adsorbed protein structure.