bluuebunny/crossref_metadata_2025_split huggingface dataset:
Information Confusion Reveals an Innate Limit of the Information Processing by Neurons
Authors: Tian Yang , Gardner Justin L. , Li Guoqi , Sun Pei 
Published: October 2020

AbstractInformation experiences complex transformation processes in the brain, involving various errors. A daunting and critical challenge in neuroscience is to understand the origin of these errors and their effects on neural information processing. While previous efforts have made substantial progresses in studying the information errors in bounded, unreliable and noisy transformation cases, it still remains elusive whether the neural system is inherently error-free under an ideal and noise-free condition. This work brings the controversy to an end with a negative answer. We propose a novel neural information confusion theory, indicating the widespread presence of information confusion phenomenon after the end of transmission process, which originates from innate neuron characteristics rather than external noises. Then, we reformulate the definition of zero-error capacity under the context of neuroscience, presenting an optimal upper bound of the zero-error transformation rates determined by the tuning properties of neurons. By applying this theory to neural coding analysis, we unveil the multi-dimensional impacts of information confusion on neural coding. Although it reduces the variability of neural responses and limits mutual information, it controls the stimulus-irrelevant neural activities and improves the interpretability of neural responses based on stimuli. Together, the present study discovers an inherent and ubiquitous precision limitation of neural information transformation, which shapes the coding process by neural ensembles. These discoveries reveal that the neural system is intrinsically error-prone in information processing even in the most ideal cases.Author summaryOne of the most central challenges in neuroscience is to understand the information processing capacity of the neural system. Decades of efforts have identified various errors in nonideal neural information processing cases, indicating that the neural system is not optimal in information processing because of the widespread presences of external noises and limitations. These incredible progresses, however, can not address the problem about whether the neural system is essentially error-free and optimal under ideal information processing conditions, leading to extensive controversies in neuroscience. Our work brings this well-known controversy to an end with a negative answer. We demonstrate that the neural system is intrinsically error-prone in information processing even in the most ideal cases, challenging the conventional ideas about the superior neural information processing capacity. We further indicate that the neural coding process is shaped by this innate limit, revealing how the characteristics of neural information functions and further cognitive functions are determined by the inherent limitation of the neural system.
Evaluation of CRISPR gene-editing tools in zebrafish
Authors: Uribe-Salazar José M. , Kaya Gulhan , Sekar Aadithya , Weyenberg KaeChandra , Ingamells Cole , Dennis Megan Y. 
Published: October 2020

ABSTRACTBackgroundZebrafish have practical features that make them a useful model for higher-throughput tests of gene function using CRISPR/Cas9 editing to create ‘knockout’ models. In particular, the use of G0mosaic mutants has potential to increase throughput of functional studies significantly but may suffer from transient effects of introducing Cas9 via microinjection. Further, a large number of computational and empirical tools exist to design CRISPR assays but often produce varied predictions across methods leaving uncertainty in choosing an optimal approach for zebrafish studies.MethodsTo systematically assess accuracy of tool predictions of on- and off-target gene editing, we subjected zebrafish embryos to CRISPR/Cas9 with 50 different guide RNAs (gRNAs) targeting 14 genes. We also investigate potential confounders of G0-based CRISPR screens by screening control embryos for spurious mutations and altered gene expression.ResultsWe compared our experimentalin vivoediting efficiencies in mosaic G0embryos with those predicted by eight commonly used gRNA design tools and found large discrepancies between methods. Assessing off-target mutations (predictedin silicoandin vitro) found that the majority of tested loci had lowin vivofrequencies (<1%). To characterize if commonly used ‘mock’ CRISPR controls (larvae injected with Cas9 enzyme or mRNA with no gRNA) exhibited spurious molecular features that might exacerbate studies of G0mosaic CRISPR knockout fish, we generated an RNA-seq dataset of various control larvae at 5 days post fertilization. While we found no evidence of spontaneous somatic mutations of injected larvae, we did identify several hundred differentially-expressed genes with high variability between injection types. Network analyses of shared differentially-expressed genes in the ‘mock’ injected larvae implicated a number of key regulators of common metabolic pathways, and gene-ontology analysis revealed connections with response to wounding and cytoskeleton organization, highlighting a potentially lasting effect from the microinjection process that requires further investigation.ConclusionOverall, our results provide a valuable resource for the zebrafish community for the design and execution of CRISPR/Cas9 experiments.
Internalization of the host alkaline pH signal in a fungal pathogen
Authors: Brown Hannah E. , Pianalto Kaila M. , Fernandes Caroline M. , Mueller Katherine D. , Del Poeta Maurizio , Alspaugh J. Andrew 
Published: October 2020

AbstractThe ability for cells to internalize extracellular cues allows them to adapt to novel and stressful environments. This adaptability is especially important for microbial pathogens that must sense and respond to drastic changes when encountering the human host.Cryptococcus neoformansis an environmental fungus and opportunistic pathogen that naturally lives in slightly acidic reservoirs, but must adapt to the relative increase in alkalinity in the human host in order to effectively cause disease. The fungal-specific Rim alkaline response signaling pathway effectively converts this extracellular signal into an adaptive cellular response allowing the pathogen to survive in its new environment. The newly identified Rra1 protein, the most upstream component of theC. neoformansRim pathway, is an essential component of this alkaline response. Previous work connected Rra1-mediated signaling to the dynamics of the plasma membrane. Here we identify the specific mechanisms of Rim pathway signaling through detailed studies of the activation of the Rra1 protein. Specifically, we observe that the Rra1 protein is internalized and recycled in a pH-dependent manner, and that this dynamic pattern of localization further depends on specific residues in its C-terminal tail, clathrin-mediated endocytosis, and the integrity of the plasma membrane. The data presented here continue to unravel the complex and intricate processes of pH-sensing in a relevant human fungal pathogen. These studies will further elucidate general mechanisms by which cells respond to and internalize extracellular stress signals.Author SummaryThe work described here explores the genetics and mechanics of a cellular signaling pathway in a relevant human fungal pathogen,Cryptococcus neoformans. The findings presented in this manuscript untangle the complex interactions involved in the activation of a fungal-specific alkaline response pathway, the Rim pathway. Specifically, we find thatC. neoformansis able to sense an increase in pH within the human host, internalize a membrane-bound pH-sensor, and activate a downstream signaling pathway enabling this pathogen to adapt to a novel host environment and effectively cause disease. Revealing the mechanisms of Rim pathway activation within the larger context of the fungal cell allows us to understand how and when this microorganism interprets relevant host signals. Furthermore, understanding how this pathogenic organism converts extracellular stress signals into an adaptive cellular response will elucidate more general mechanisms of microbial environmental sensing and stress response.
Consensus clustering applied to multi-omic disease subtyping
Authors: Brière Galadriel , Darbo Élodie , Thébault Patricia , Uricaru Raluca 
Published: October 2020

AbstractBackgroundFacing the diversity of omic data and the difficulty of selecting one result over all those produced by several methods, consensus strategies have the potential to reconcile multiple inputs and to produce robust results.ResultsHere, we introduce ClustOmics, a generic consensus clustering tool that we use in the context of cancer subtyping. ClustOmics relies on a non-relational graph database, which allows for the simultaneous integration of both multiple omic data and results from various clustering methods. This new tool conciliates input clusterings, regardless of their origin, their number, their size or their shape. ClustOmics implements an intuitive and flexible strategy, based upon the idea ofevidence accumulation clustering. It computes co-occurrences of pairs of samples in input clusters and uses this score as a similarity measure to reorganise data into consensus clusters.ConclusionWe applied ClustOmics to multi-omic disease subtyping on real TCGA cancer data from ten different cancer types. We showed that ClustOmics is robust to heterogeneous qualities of input partitions, smoothing and reconciling preliminary predictions into high quality consensus clusters, both from a computational and a biological point of view. The comparison to a state-of-the-art consensus based integration tool, COCA, further corroborated this statement. However, the main interest of ClustOmics is not to compete with other tools, but rather to make profit from their various predictions when no gold-standard metric is available to assess their significance.AvailabilityClustOmics’ source code, released under MIT licence, as well as the results obtained on TCGA cancer data are available on Github:https://github.com/galadrielbriere/ClustOmics.
Juvenile corals inherit mutations acquired during the parent’s lifespan
Authors: Kuntz Kate L. Vasquez , Kitchen Sheila A. , Conn Trinity L. , Vohsen Samuel A. , Chan Andrea N. , Vermeij Mark J. A. , Page Christopher , Marhaver Kristen L. , Baums Iliana B. 
Published: October 2020

Abstract128 years ago, August Weismann proposed that the only source of inherited genetic variation in animals is the germline1. Julian Huxley reasoned that if this were true, it would falsify Jean-Baptiste Lamarck’s theory that acquired characteristics are heritable2. Since then, scientists have discovered that not all animals segregate germline cells from somatic cells permanently and early in development3. In fact, throughout their lives, Cnidaria4–6and Porifera7maintain primordial stem cells that continuously give rise to both germline and somatic cells. The fate of mutations generated in this primordial stem cell line during adulthood remains an open question. It was unknown whether post-embryonic mutations could be heritable in animals8–10—until now. Here we use two independent genetic marker analyses to show that post-embryonic mutations are inherited in the coralAcropora palmata(Cnidaria, Anthozoa). This discovery upends the long-held supposition that post-embryonic genetic mutations acquired over an animal’s lifetime in non-germline tissues are not heritable2. Over the centuries-long lifespan of a coral, the inheritance of post-embryonic mutations may not only change allele frequencies in the local larval pool but may also spread novel alleles across great distances via larval dispersal. Thus, corals may have the potential to adapt to changing environments via heritable somatic mutations10. This mechanism challenges our understanding of animal adaptation and prompts a deeper examination of both the process of germline determination in Cnidaria and the role of post-embryonic genetic mutations in adaptation and epigenetics of modular animals. Understanding the role of post-embryonic mutations in animal adaptation will be crucial as ecological change accelerates in the Anthropocene.
Lentiviral vectors transduce lung stem cells without disrupting plasticity
Authors: Cooney Ashley L. , Thurman Andrew L. , McCray Paul B. , Pezzulo Alejandro A. , Sinn Patrick L. 
Published: October 2020

AbstractLife-long expression of a gene therapy agent likely requires targeting stem cells. Here we ask the question: does viral vector transduction or ectopic expression of a therapeutic transgene preclude airway stem cell function? We used a lentiviral vector containing a GFP or cystic fibrosis transmembrane conductance regulator (CFTR) transgene to transduce primary airway basal cells from human cystic fibrosis (CF) or non-CF lung donors and monitored expression and function after differentiation. Ussing chamber measurements confirmed CFTR-dependent chloride channel activity in CF donor cells. Immunostaining, quantitative real-time PCR, and single-cell sequencing analysis of cell-type markers indicated that vector transduction or CFTR expression does not alter the formation of pseudostratified, fully-differentiated epithelial cell cultures or cell type distribution. These results have important implications for use of gene addition or gene editing strategies as life-long curative approaches for lung genetic diseases.
Diversity and genomic determinants of the microbiomes associated with COVID-19 and non-COVID respiratory diseases
Authors: Hoque M. Nazmul , Rahman M. Shaminur , Ahmed Rasel , Hossain Md. Sabbir , Islam Md. Shahidul , Crandall Keith A , Islam Md Tofazzal , Hossain M. Anwar , Siddiki AMAM Zonaed 
Published: October 2020

AbstractThe novel coronavirus disease 2019 (COVID-19) is a rapidly emerging and highly transmissible disease caused by the Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2). Understanding the microbiomes associated with the upper respiratory tract infection (URTI), chronic obstructive pulmonary disease (COPD) and COVID-19 diseases has clinical interest. We hypothesized that the diversity of microbiome compositions and their genomic features are associated with different pathological conditions of these human respiratory tract diseases (COVID-19 and non-COVID; URTI and COPD). To test this hypothesis, we analyzed 21 whole metagenome sequences (WMS) including eleven COVID-19 (BD = 6 and China = 5), six COPD (UK = 6) and four URTI (USA = 4) samples to unravel the diversity of microbiomes, their genomic features and relevant metabolic functions. The WMS data mapped to 534 bacterial, 60 archaeal and 61 viral genomes with distinct variation in the microbiome composition across the samples (COVID-19>COPD>URTI). Notably, 94.57%, 80.0% and 24.59% bacterial, archaeal and viral genera shared between the COVID-19 and non-COVID samples, respectively, however, the COVID-19 related samples had sole association with 16 viral genera other than SARS-CoV-2. Strain-level virome profiling revealed 660 and 729 strains in COVID-19 and non-COVID sequence data, respectively and of them 34.50% strains shared between the conditions. Functional annotation of metagenomics sequences of thevCOVID-19 and non-COVID groups identified the association of several biochemical pathways related to basic metabolism (amino acid and energy), ABC transporters, membrane transport, replication and repair, clustering-based subsystems, virulence, disease and defense, adhesion, regulation of virulence, programmed cell death, and primary immunodeficiency. We also detected 30 functional gene groups/classes associated with resistance to antibiotics and toxic compounds (RATC) in both COVID-19 and non-COVID microbiomes. Furthermore, a predominant higher abundance of cobalt-zinc-cadmium resistance (CZCR) and multidrug resistance to efflux pumps (MREP) genes were detected in COVID-19 metagenome. The profiles of microbiome diversity and associated microbial genomic features found in both COVID-19 and non-COVID (COPD and URTI) samples might be helpful for developing the microbiome-based diagnostics and therapeutics for COVID-19 and non-COVID respiratory diseases. However, future studies might be carried out to explore the microbiome dynamics and the cross-talk between host and microbiomes employing larger volume of samples from different ethnic groups and geoclimatic conditions.
Stem bending generates electrical response in poplar
Authors: Tinturier Erwan , Badel Éric , Leblanc-Fournier Nathalie , Julien Jean-Louis 
Published: October 2020

AbstractUnder natural conditions, plants experience external mechanical stresses such as wind and touch that impact their growth. A remarkable feature of this mechanically induced growth response is that it may occur at distance from the stimulation site, suggesting the existence of a signal propagating through the plant. In this study, we investigated the electrical response of poplar trees to a transient controlled bending stimulation of the stem that mimics the mechanical effect of wind. Stem bending was found to cause an electrical response that we called ‘gradual’ potential, similar in shape to an action potential. However, this signal distinguished from the well-known plant action potential by its propagation up to 20 cm along the stem and its strong dumping in velocity and amplitude. Two hypotheses regarding the mode of propagation of the ‘gradual’ potential are discussed.One sentence summaryPoplar stem bending induces an electrical response with high speed and strong decrement.
APOE4 Lowers Energy Expenditure and Impairs Glucose Oxidation by Increasing Flux through Aerobic Glycolysis
Authors: Farmer Brandon C. , Williams Holden C. , Devanney Nicholas , Piron Margaret A. , Nation Grant K. , Carter David J. , Walsh Adeline E. , Khanal Rebika , Young Lyndsay E. A. , Kluemper Jude C. , Hernandez Gabriela , Allenger Elizabeth J. , Mooney Rachel , Brandon J. Anthony , Gupta Vedant A. , Kern Philip A. , Gentry Matthew S. , Morganti Josh M. , Sun Ramon C. , Johnson Lance A. 
Published: October 2020

AbstractCerebral glucose hypometabolism is consistently observed in individuals with Alzheimer’s disease (AD), as well as in young cognitively normal carriers of the E4 allele of Apolipoprotein E (APOE), the strongest genetic predictor of late-onset AD. While this clinical feature has been described for over two decades, the mechanism underlying these changes in cerebral glucose metabolism remains a critical knowledge gap in the field. Here, we undertook a multi-omic approach by combining single-cell RNA sequencing (scRNAseq) and stable isotope resolved metabolomics (SIRM) to define a metabolic rewiring across astrocytes, brain tissue, mice, and human subjects expressing APOE4. Single-cell analysis of brain tissue from mice expressing human APOE revealed E4-associated decreases in genes related to oxidative phosphorylation, particularly in astrocytes. This shift was confirmed on a metabolic level with isotopic tracing of13C-glucose in E4 mice and astrocytes, which showed decreased pyruvate entry into the TCA cycle and increases in lactate synthesis. Metabolic phenotyping of E4 astrocytes showed elevated glycolytic activity, decreased oxygen consumption, blunted oxidative flexibility, and a lower rate of glucose oxidation in the presence of lactate. Together, these cellular findings suggested an E4 associated increase in aerobic glycolysis (i.e. the Warburg effect). To test whether this phenomenon translated to APOE4 humans, we analyzed the plasma metabolome of young and middle-aged human participants with and without the E4 allele, and used indirect calorimetry to measure whole body oxygen consumption and energy expenditure. In line with data from E4-expressing mice, young female E4 carriers showed a striking decrease in energy expenditure compared to non-carriers. This decrease in energy expenditure was primarily driven by a lower rate of oxygen consumption, and was exaggerated following a dietary glucose challenge. Further, the stunted oxygen consumption was accompanied by markedly increased lactate in the plasma of E4 carriers, and a pathway analysis of the plasma metabolome suggested an increase in aerobic glycolysis. Together, these results suggest astrocyte, brain and system-level metabolic reprogramming in the presence of APOE4, a ‘Warburg like’ endophenotype that is observable in young humans decades prior to clinically manifest AD.
Investigation of biochemical changes in barley inoculated withTrichoderma harzianumT-22 under salt stress
Authors: Gupta Sneha , Smith Penelope M. C. , Boughton Berin A. , Rupasinghe Thusitha W. T. , Natera Siria H.A. , Roessner Ute 
Published: October 2020

AbstractIncreases in soil salinity impacts growth and yield of agricultural plants by inhibiting plant functions. Soil salinization is increasing because of the pressure of a growing population on food supply. Genetically modified crops and plant breeding techniques are being used to produce plants tolerant to salt stress. However, interactions of fungal endophytes with crop plants can also improve tolerance and is a less expensive approach. Here, the role ofTrichoderma harzianumT-22 in alleviating NaCl-induced stress in two barley genotypes (cv. Vlamingh and cv. Gairdner) has been investigated. Metabolomics using GC-MS for polar metabolites and LC-MS for lipids was employed to provide insights into the biochemical changes in barley roots inoculated with fungus during the early stages of interaction.T. harzianumincreased the root length of both genotypes under controlled and saline conditions. The fungus reduced the relative concentration of sugars in both genotypes and caused no change in organic acids under saline conditions. Amino acids decreased only in cv. Gairdner in fungus-inoculated roots under saline conditions. Lipid analyses suggest that salt stress causes large changes in the lipid profile of roots but that inoculation with fungus greatly reduces the extent of these changes. By studying a tolerant and a sensitive genotype and their responses to salt and inoculation we have been able to develop hypotheses about what lipid species and metabolites may be involved in the tolerant genotype for its tolerance to salt and how fungal inoculation changes the response of the sensitive genotype to improve its tolerance.