bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stable machine-learning parameterization of subgrid processes for climate modeling at a range of resolutions
Authors: Yuval Janni , O’Gorman Paul A. 
Published: July 2020

AbstractGlobal climate models represent small-scale processes such as convection using subgrid models known as parameterizations, and these parameterizations contribute substantially to uncertainty in climate projections. Machine learning of new parameterizations from high-resolution model output is a promising approach, but such parameterizations have been prone to issues of instability and climate drift, and their performance for different grid spacings has not yet been investigated. Here we use a random forest to learn a parameterization from coarse-grained output of a three-dimensional high-resolution idealized atmospheric model. The parameterization leads to stable simulations at coarse resolution that replicate the climate of the high-resolution simulation. Retraining for different coarse-graining factors shows the parameterization performs best at smaller horizontal grid spacings. Our results yield insights into parameterization performance across length scales, and they also demonstrate the potential for learning parameterizations from global high-resolution simulations that are now emerging.
The ataxin-1 interactome reveals direct connection with multiple disrupted nuclear transport pathways
Authors: Zhang Sunyuan , Williamson Nicholas A. , Duvick Lisa , Lee Alexander , Orr Harry T. , Korlin-Downs Austin , Yang Praseuth , Mok Yee-Foong , Jans David A. , Bogoyevitch Marie A. 
Published: July 2020

AbstractThe expanded polyglutamine (polyQ) tract form of ataxin-1 drives disease progression in spinocerebellar ataxia type 1 (SCA1). Although known to form distinctive intranuclear bodies, the cellular pathways and processes that polyQ-ataxin-1 influences remain poorly understood. Here we identify the direct and proximal partners constituting the interactome of ataxin-1[85Q] in Neuro-2a cells, pathways analyses indicating a significant enrichment of essential nuclear transporters, pointing to disruptions in nuclear transport processes in the presence of elevated levels of ataxin-1. Our direct assessments of nuclear transporters and their cargoes confirm these observations, revealing disrupted trafficking often with relocalisation of transporters and/or cargoes to ataxin-1[85Q] nuclear bodies. Analogous changes in importin-β1, nucleoporin 98 and nucleoporin 62 nuclear rim staining are observed in Purkinje cells of ATXN1[82Q] mice. The results highlight a disruption of multiple essential nuclear protein trafficking pathways by polyQ-ataxin-1, a key contribution to furthering understanding of pathogenic mechanisms initiated by polyQ tract proteins.
Oculomotor freezing reflects tactile temporal expectation and aids tactile perception
Authors: Badde Stephanie , Myers Caroline F. , Yuval-Greenberg Shlomit , Carrasco Marisa 
Published: July 2020

AbstractThe oculomotor system keeps the eyes steady in expectation of visual events. Here, recording microsaccades while people performed a tactile, frequency discrimination task enabled us to test whether the oculomotor system shows an analogous preparatory response for unrelated tactile events. We manipulated the temporal predictability of tactile targets using tactile cues, which preceded the target by either constant (high predictability) or variable (low predictability) time intervals. We find that microsaccades are inhibited prior to tactile targets and more so for constant than variable intervals, revealing a tight crossmodal link between tactile temporal expectation and oculomotor action. These findings portray oculomotor freezing as a marker of crossmodal temporal expectation. Moreover, microsaccades occurring around the tactile target presentation are associated with reduced task performance, suggesting that oculomotor freezing mitigates potential detrimental, concomitant effects of microsaccades and revealing a crossmodal coupling between tactile perception and oculomotor action.
Progressive nitrogen limitation across the Tibetan alpine permafrost region
Authors: Kou Dan , Yang Guibiao , Li Fei , Feng Xuehui , Zhang Dianye , Mao Chao , Zhang Qiwen , Peng Yunfeng , Ji Chengjun , Zhu Qiuan , Fang Yunting , Liu Xueyan , Xu-Ri  , Li Siqi , Deng Jia , Zheng Xunhua , Fang Jingyun , Yang Yuanhe 
Published: July 2020

AbstractThe ecosystem carbon (C) balance in permafrost regions, which has a global significance in understanding the terrestrial C-climate feedback, is significantly regulated by nitrogen (N) dynamics. However, our knowledge on temporal changes in vegetation N limitation (i.e., the supply of N relative to plant N demand) in permafrost ecosystems is still limited. Based on the combination of isotopic observations derived from a re-sampling campaign along a ~3000 km transect and simulations obtained from a process-based biogeochemical model, here we detect changes in ecosystem N cycle across the Tibetan alpine permafrost region over the past decade. We find that vegetation N limitation becomes stronger despite the increased available N production. The enhanced N limitation on vegetation growth is driven by the joint effects of elevated plant N demand and gaseous N loss. These findings suggest that N would constrain the future trajectory of ecosystem C cycle in this alpine permafrost region.
An ecological framework to understand the efficacy of fecal microbiota transplantation
Authors: Xiao Yandong , Angulo Marco Tulio , Lao Songyang , Weiss Scott T. , Liu Yang-Yu 
Published: July 2020

AbstractHuman gut microbiota plays critical roles in physiology and disease. Our understanding of ecological principles that govern the dynamics and resilience of this highly complex ecosystem remains rudimentary. This knowledge gap becomes more problematic as new approaches to modifying this ecosystem, such as fecal microbiota transplantation (FMT), are being developed as therapeutic interventions. Here we present an ecological framework to understand the efficacy of FMT in treating conditions associated with a disrupted gut microbiota, using the recurrent Clostridioides difficile infection as a prototype disease. This framework predicts several key factors that determine the efficacy of FMT. Moreover, it offers an efficient algorithm for the rational design of personalized probiotic cocktails to decolonize pathogens. We analyze data from both preclinical mouse experiments and a clinical trial of FMT to validate our theoretical framework. The presented results significantly improve our understanding of the ecological principles of FMT and have a positive translational impact on the rational design of general microbiota-based therapeutics.
Megaevolutionary dynamics and the timing of evolutionary innovation in reptiles
Authors: Simões Tiago R. , Vernygora Oksana , Caldwell Michael W. , Pierce Stephanie E. 
Published: July 2020

AbstractThe origin of phenotypic diversity among higher clades is one of the most fundamental topics in evolutionary biology. However, due to methodological challenges, few studies have assessed rates of evolution and phenotypic disparity across broad scales of time to understand the evolutionary dynamics behind the origin and early evolution of new clades. Here, we provide a total-evidence dating approach to this problem in diapsid reptiles. We find major chronological gaps between periods of high evolutionary rates (phenotypic and molecular) and expansion in phenotypic disparity in reptile evolution. Importantly, many instances of accelerated phenotypic evolution are detected at the origin of major clades and body plans, but not concurrent with previously proposed periods of adaptive radiation. Furthermore, strongly heterogenic rates of evolution mark the acquisition of similarly adapted functional types, and the origin of snakes is marked by the highest rates of phenotypic evolution in diapsid history.
Wnt-controlled sphingolipids modulate Anthrax Toxin Receptor palmitoylation to regulate oriented mitosis in zebrafish
Authors: Castanon I. , Hannich J. T. , Abrami L. , Huber F. , Dubois M. , Müller M. , van der Goot F. G. , Gonzalez-Gaitan M. 
Published: July 2020

AbstractOriented cell division is a fundamental mechanism to control asymmetric stem cell division, neural tube elongation and body axis extension, among other processes. During zebrafish gastrulation, when the body axis extends, dorsal epiblast cells display divisions that are robustly oriented along the animal-vegetal embryonic axis. Here, we use a combination of lipidomics, metabolic tracer analysis and quantitative image analysis to show that sphingolipids mediate spindle positioning during oriented division of epiblast cells. We identify the Wnt signaling as a regulator of sphingolipid synthesis that mediates the activity of serine palmitoyltransferase (SPT), the first and rate-limiting enzyme in sphingolipid production. Sphingolipids determine the palmitoylation state of the Anthrax receptor, which then positions the mitotic spindle of dividing epiblast cells. Our data show how Wnt signaling mediates sphingolipid-dependent oriented division and how sphingolipids determine Anthrax receptor palmitoylation, which ultimately controls the activation of Diaphanous to mediate spindle rotation and oriented mitosis.
Personalised mapping of tumour development in synchronous colorectal cancer patients
Authors: Thomas Valentina , Cotter Maura B. , Tosetto Miriam , Khaw Yi Ling , Geraghty Robert , Winter Desmond C. , Ryan Elizabeth J. , Sheahan Kieran , Furney Simon J. 
Published: July 2020

AbstractSynchronous colorectal cancers (syCRCs) are two or more primary tumours identified simultaneously in a patient. Previous studies report high inter-tumour heterogeneity between syCRCs, suggesting independent origin and different treatment response, making their management particularly challenging, with no specific guidelines currently in place. Here, we performed in-depth bioinformatic analyses of genomic and transcriptomic data of a total of eleven syCRCs and one metachronous CRC collected from three patients. We found mixed microsatellite status between and within patients. Overlap of mutations between synchronous tumours was consistently low (<0.5%) and heterogeneity of driver events across syCRCs was high in all patients. Microbial analysis revealed the presence of Fusobacterium nucleatum species in patients with MSI tumours, while quantification of tumour immune infiltration showed varying immune responses between syCRCs. Our results suggest high heterogeneity of syCRCs within patients but find clinically actionable biomarkers that help predict responses to currently available targeted therapies. Our study highlights the importance of personalised genome and transcriptome sequencing of all synchronous lesions to aid therapy decision and improve management of syCRC patients.
Coronavirus disease 2019 (COVID-19) outbreak: some serious consequences with urban and rural water cycle
Authors: Bhowmick Gourav Dhar , Dhar Dhruba , Nath Dibyojyoty , Ghangrekar Makarand Madhao , Banerjee Rintu , Das Soumen , Chatterjee Jyotirmoy 
Published: July 2020

AbstractThe COVID-19 outbreak due to SARS-CoV-2 has raised several concerns for its high transmission rate and unavailability of any treatment to date. Although major routes of its transmission involve respiratory droplets and direct contact, the infection through faecal matter is also possible. Conventional sewage treatment methods with disinfection are expected to eradicate SARS-CoV-2. However, for densely populated countries like India with lower sewage treatment facilities, chances of contamination are extremely high; as SARS-CoVs can survive up to several days in untreated sewage; even for a much longer period in low-temperature regions. With around 1.8 billion people worldwide using faecal-contaminated source as drinking water, the risk of transmission of COVID-19 is expected to increase by several folds, if proper precautions are not being taken. Therefore, preventing water pollution at the collection/distribution/consumption point along with proper implementation of WHO recommendations for plumbing/ventilation systems in household is crucial for resisting COVID-19 eruption.
Increased Alcohol Consumption in Mice Lacking Sodium Bicarbonate Transporter NBCn1
Authors: Schank Jesse R. , Lee Soojung , Gonzalez-Islas Carlos E. , Nennig Sadie E. , Fulenwider Hannah D. , Chang Jianjun , Li Jun Ming , Kim Yejin , Jeffers Lauren A. , Chung Jaegwon , Lee Jae-Kyung , Jin Zhe , Aalkjaer Christian , Boedtkjer Ebbe , Choi Inyeong 
Published: July 2020

AbstractThe previous reports on an addiction vulnerability marker in the human SLC4A7 gene encoding the Na/HCO3 transporter NBCn1 suggest that this pH-regulating protein may affect alcohol-related behavior and response. Here, we examined alcohol consumption and sensitivity to the sedative effects of alcohol in male NBCn1 knockout mice. These mice displayed lower pH in neurons than wildtype controls, determined by intracellular pH in hippocampal neuronal cultures. Neurons from knockout mice had a higher action potential threshold and a more depolarized membrane potential, thus reducing membrane excitability. In a two-bottle free choice procedure, knockout mice consumed more alcohol than controls and consistently increased alcohol consumption after repeated alcohol deprivation periods. Quinine and sucrose preference was similar between genotypes. Knockout mice showed increased propensity for alcohol-induced conditioned place preference. In loss of righting reflex assessment, knockout mice revealed increased sensitivity to alcohol-induced sedation and developed tolerance to the sedation after repeated alcohol administrations. Furthermore, chronic alcohol consumption caused NBCn1 downregulation in the hippocampus and striatum of mice and humans. These results demonstrate an important role of NBCn1 in regulation of alcohol consumption and sensitivity to alcohol-induced sedation.
Laryngopharyngeal reflux image quantization and analysis of its severity
Authors: Kuo Chung-Feng Jeffrey , Kao Chih-Hsiang , Dlamini Sifundvolesihle , Liu Shao-Cheng 
Published: July 2020

AbstractLaryngopharyngeal reflux (LPR) is a prevalent disease affecting a high proportion of patients seeking laryngology consultation. Diagnosis is made subjectively based on history, symptoms, and endoscopic assessment. The results depend on the examiner's interpretation of endoscopic images. There are still no consistent objective diagnostic methods. The aim of this study is to use image processing techniques to quantize the laryngeal variation caused by LPR, to judge and analyze its severity. This study proposed methods of screening sharp images automatically from laryngeal endoscopic images and using throat eigen structure for automatic region segmentation. The proposed image compensation improved the illumination problems from the use of laryngoscope lens. Fisher linear discriminant was used to find out features and classification performance while support vector machine was used as the classifier for judging LPR. Evaluation results were 97.16% accuracy, 98.11% sensitivity, and 3.77% false positive rate. To evaluate the severity, quantized data of the laryngeal variation was used. LPR images were combined with reflux symptom index score chart, and severity was graded using a neural network. The results indicated 96.08% accuracy. The experiment indicated that laryngeal variation induced by LPR could be quantized by using image processing techniques to assist in diagnosing and treating LPR.
Multiplex profiling of serum proteins in solution using barcoded antibody fragments and next generation sequencing
Authors: Brofelth Mattias , Ekstrand Anna Isinger , Gour Shashank , Jansson Ronnie , Hedhammar My , Elleby Björn , Kvist Anders , Wingren Christer , Axelsson Ulrika , Borrebaeck Carl A. K. 
Published: July 2020

AbstractThe composition of serum proteins is reflecting the current health status and can, with the right tools, be used to detect early signs of disease, such as an emerging cancer. An earlier diagnosis of cancer would greatly increase the chance of an improved outcome for the patients. However, there is still an unmet need for proficient tools to decipher the information in the blood proteome, which calls for further technological development. Here, we present a proof-of-concept study that demonstrates an alternative approach for multiplexed protein profiling of serum samples in solution, using DNA barcoded scFv antibody fragments and next generation sequencing. The outcome shows high accuracy when discriminating samples derived from pancreatic cancer patients and healthy controls and represents a scalable alternative for serum analysis.
Zeb1 promotes corneal neovascularization by regulation of vascular endothelial cell proliferation
Authors: Jin Lei , Zhang Yingnan , Liang Wei , Lu Xiaoqin , Piri Niloofar , Wang Wei , Kaplan Henry J. , Dean Douglas C. , Zhang Lijun , Liu Yongqing 
Published: July 2020

AbstractAngiogenesis is required for tissue repair; but abnormal angiogenesis or neovascularization (NV) causes diseases in the eye. The avascular status in the cornea is a prerequisite for corneal clarity and thought to be maintained by the equilibrium between proangiogenic and antiangiogenic factors that controls proliferation and migration of vascular endothelial cells (ECs) sprouting from the pericorneal plexus. VEGF is the most important intrinsic factor for angiogenesis; anti-VEGF therapies are available for treating ocular NV. However, the effectiveness of the therapies is limited because of VEGF-independent mechanism(s). We show that Zeb1 is an important factor promoting vascular EC proliferation and corneal NV; and a couple of small molecule inhibitors can evict Ctbp from the Zeb1–Ctbp complex, thereby reducing EC Zeb1 expression, proliferation, and corneal NV. We conclude that Zeb1-regulation of angiogenesis is independent of Vegf and that the ZEB1–CtBP inhibitors can be of potential therapeutic significance in treating corneal NV.
Salmonella-based platform for efficient delivery of functional binding proteins to the cytosol
Authors: Chabloz Antoine , Schaefer Jonas V. , Kozieradzki Ivona , Cronin Shane J. F. , Strebinger Daniel , Macaluso Francesca , Wald Jiri , Rabbitts Terence H. , Plückthun Andreas , Marlovits Thomas C. , Penninger Josef M. 
Published: July 2020

AbstractProtein-based affinity reagents (like antibodies or alternative binding scaffolds) offer wide-ranging applications for basic research and therapeutic approaches. However, whereas small chemical molecules efficiently reach intracellular targets, the delivery of macromolecules into the cytosol of cells remains a major challenge; thus cytosolic applications of protein-based reagents are rather limited. Some pathogenic bacteria have evolved a conserved type III secretion system (T3SS) which allows the delivery of effector proteins into eukaryotic cells. Here, we enhance the T3SS of an avirulent strain of Salmonella typhimurium to reproducibly deliver multiple classes of recombinant proteins into eukaryotic cells. The efficacy of the system is probed with both DARPins and monobodies to functionally inhibit the paradigmatic and largely undruggable RAS signaling pathway. Thus, we develop a bacterial secretion system for potent cytosolic delivery of therapeutic macromolecules.
Task rule and choice are reflected by layer-specific processing in rodent auditory cortical microcircuits
Authors: Zempeltzi Marina M. , Kisse Martin , Brunk Michael G. K. , Glemser Claudia , Aksit Sümeyra , Deane Katrina E. , Maurya Shivam , Schneider Lina , Ohl Frank W. , Deliano Matthias , Happel Max F. K. 
Published: July 2020

AbstractThe primary auditory cortex (A1) is an essential, integrative node that encodes the behavioral relevance of acoustic stimuli, predictions, and auditory-guided decision-making. However, the realization of this integration with respect to the cortical microcircuitry is not well understood. Here, we characterize layer-specific, spatiotemporal synaptic population activity with chronic, laminar current source density analysis in Mongolian gerbils (Meriones unguiculatus) trained in an auditory decision-making Go/NoGo shuttle-box task. We demonstrate that not only sensory but also task- and choice-related information is represented in the mesoscopic neuronal population code of A1. Based on generalized linear-mixed effect models we found a layer-specific and multiplexed representation of the task rule, action selection, and the animal’s behavioral options as accumulating evidence in preparation of correct choices. The findings expand our understanding of how individual layers contribute to the integrative circuit in the sensory cortex in order to code task-relevant information and guide sensory-based decision-making.
Cell-to-cell expression dispersion of B-cell surface proteins is linked to genetic variants in humans
Authors: Triqueneaux Gérard , Burny Claire , Symmons Orsolya , Janczarski Stéphane , Gruffat Henri , Yvert Gaël 
Published: July 2020

AbstractVariability in gene expression across a population of homogeneous cells is known to influence various biological processes. In model organisms, natural genetic variants were found that modify expression dispersion (variability at a fixed mean) but very few studies have detected such effects in humans. Here, we analyzed single-cell expression of four proteins (CD23, CD55, CD63 and CD86) across cell lines derived from individuals of the Yoruba population. Using data from over 30 million cells, we found substantial inter-individual variation of dispersion. We demonstrate, via de novo cell line generation and subcloning experiments, that this variation exceeds the variation associated with cellular immortalization. We detected a genetic association between the expression dispersion of CD63 and thers971SNP. Our results show that human DNA variants can have inherently-probabilistic effects on gene expression. Such subtle genetic effects may participate to phenotypic variation and disease outcome.
Optical analogues to the equatorial Kerr–Newman black hole
Authors: Tinguely R. A. , Turner Andrew P. 
Published: July 2020

AbstractOptical analogues to black holes allow the investigation of general relativity in a laboratory setting. Previous works have considered analogues to Schwarzschild black holes in an isotropic coordinate system; the major drawback is that required material properties diverge at the horizon. We present the dielectric permittivity and permeability tensors that exactly reproduce the equatorial Kerr–Newman metric, as well as the gradient-index material that reproduces equatorial Kerr–Newman null geodesics. Importantly, the radial profile of the scalar refractive index is finite along all trajectories except at the point of rotation reversal for counter-rotating geodesics. Construction of these analogues is feasible with available ordinary materials. A finite-difference frequency-domain solver of Maxwell’s equations is used to simulate light trajectories around a variety of Kerr–Newman black holes. For reasonably sized experimental systems, ray tracing confirms that null geodesics can be well-approximated in the lab, even when allowing for imperfect construction and experimental error.