bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal changes in the gut microbiota in farmed Atlantic cod (Gadus morhua) outweigh the response to diet supplementation with macroalgae
Authors: Keating C. , Bolton-Warberg M. , Hinchcliffe J. , Davies R. , Whelan S. , Wan A.H.L. , Fitzgerald R. D. , Davies S. J. , Ijaz U. Z. , Smith C. J. 
Published: August 2020

AbstractBackgroundAquaculture successfully meets global food demands for many fish species. However, aquaculture production of Atlantic cod (Gadus morhua) is modest in comparison to market demand. For cod farming to be a viable economic venture specific challenges on how to increase growth, health and farming productivity need to be addressed. Feed ingredients play a key role here. Macroalgae (seaweeds) have been suggested as a functional feed supplement with both health and economic benefits for terrestrial farmed animals and fish. The impact of such dietary supplements to cod gut integrity and microbiota, which contribute to overall fish robustness is unknown. The objective of this study was to supplement the diet of juvenile Atlantic cod with macroalgae and determine the impacts on fish condition and growth, gut morphology and hindgut microbiota composition (16S rRNA amplicon sequencing). Fish were fed one of three diets: control (no macroalgal inclusion), 10% inclusion of either egg wrack (Ascophyllum nodosum) or sea lettuce (Ulva rigida) macroalgae in a 12-week trial.ResultsThe results demonstrated there was no significant difference in fish condition, gut morphology or hindgut microbiota between theU. rigidasupplemented fish group and the control group at any time-point. This contrasts with theA. nodosumtreatment. Fish within this group were further categorised as either ‘Normal’ or ‘Lower Growth’. ‘Lower Growth’ individuals found the diet unpalatable resulting in reduced weight and condition factor combined with an altered gut morphology and microbiome relative to the other treatments. Excluding this group, our results show that the hindgut microbiota was largely driven by temporal pressures with the microbial communities becoming more similar over time irrespective of dietary treatment. The core microbiome at the final time-point consisted of the ordersVibrionales(VibrioandPhotobacterium),Bacteroidales(BacteroidetesandMacellibacteroides) andClostridiales(Lachnoclostridium).ConclusionsOur study indicates thatU. rigidamacroalgae can be supplemented at 10% inclusion levels in the diet of juvenile farmed Atlantic cod without any impact on fish condition or hindgut microbial community structure. We also conclude that 10% dietary inclusion ofA. nodosumis not a suitable feed supplement in a farmed cod diet.
Heat-treated virus inactivation rate depends strongly on treatment procedure: illustration with SARS-CoV-2
Authors: Gamble Amandine , Fischer Robert J. , Morris Dylan H. , Yinda Kwe Claude , Munster Vincent J. , Lloyd-Smith James O. 
Published: August 2020

AbstractDecontamination helps limit environmental transmission of infectious agents. It is required for the safe re-use of contaminated medical, laboratory and personal protective equipment, and for the safe handling of biological samples. Heat treatment is a common decontamination method, notably used for viruses. We show that for liquid specimens (here, solution of SARS-CoV-2 in cell culture medium), virus inactivation rate under heat treatment at 70°C can vary by almost two orders of magnitude depending on the treatment procedure, from a half-life of 0.86 min (95% credible interval: [0.09, 1.77]) in closed vials in a heat block to 37.00 min ([12.65, 869.82]) in uncovered plates in a dry oven. These findings suggest a critical role of evaporation in virus inactivation via dry heat. Placing samples in open or uncovered containers may dramatically reduce the speed and efficacy of heat treatment for virus inactivation. Given these findings, we reviewed the literature temperature-dependent coronavirus stability and found that specimen containers, and whether they are closed, covered, or uncovered, are rarely reported in the scientific literature. Heat-treatment procedures must be fully specified when reporting experimental studies to facilitate result interpretation and reproducibility, and must be carefully considered when developing decontamination guidelines.ImportanceHeat is a powerful weapon against most infectious agents. It is widely used for decontamination of medical, laboratory and personal protective equipment, and for biological samples. There are many methods of heat treatment, and methodological details can affect speed and efficacy of decontamination. We applied four different heat-treatment procedures to liquid specimens containing SARS-CoV-2. Our results show that the container used to store specimens during decontamination can substantially affect inactivation rate: for a given initial level of contamination, decontamination time can vary from a few minutes in closed vials to several hours in uncovered plates. Reviewing the literature, we found that container choices and heat treatment methods are only rarely reported explicitly in methods sections. Our study shows that careful consideration of heat-treatment procedure — in particular the choice of specimen container, and whether it is covered — can make results more consistent across studies, improve decontamination practice, and provide insight into the mechanisms of virus inactivation.
Arabidopsis thalianaZn2+-efflux ATPases HMA2 and HMA4 are required for resistance to the necrotrophic fungusPlectosphaerella cucumerinaBMM
Authors: Escudero Viviana , Castro-León Álvaro , Sánchez Darío Ferreira , Abreu Isidro , Bernal María , Krämer Ute , Grolimund Daniel , González-Guerrero Manuel , Jordá Lucía 
Published: August 2020

SUMMARYZinc is an essential nutrient at low concentrations, but toxic at slightly higher ones. This could be used by plants to fight pathogens colonization.Elemental distribution inArabidopsis thalianaleaves inoculated with the necrotrophic fungusPlectosphaerella cucumerinaBMM (PcBMM) was determined and compared to mock-inoculated ones. Infection assays were carried out in wild type and long-distance zinc trafficking double mutanthma2hma4, defective in root-to-shoot zinc partitioning. Expression levels of genes involved in zinc homeostasis or in defence phytohormone-mediated pathways were determined.Zinc and manganese levels increased at the infection site. Zinc accumulation was absent inhma2hma4. HMA2 and HMA4transcription levels were upregulated uponPcBMMinoculation. Consistent with a role of these genes in plant immunity,hma2hma4mutants were more susceptible toPcBMMinfection, phenotype rescued upon zinc supplementation. Transcript levels of genes involved in the salicylic acid, ethylene and jasmonate pathways were constitutively upregulated inhma2hma4plants.These data are consistent with a role of zinc in plant immunity not only of hyperaccumulator plants, but also of plants containing ordinary levels of zinc. This new layer of immunity seems to run in parallel to the already characterized defence pathways, and its removal has a direct effect on pathogen resistance.
Dysregulation of the secretory pathway connects Alzheimer’s disease genetics to aggregate formation
Authors: Kuo Chih-Chung , Chiang Austin WT , Baghdassarian Hratch M. , Lewis Nathan E. 
Published: August 2020

AbstractA hallmark of amyloid disorders, such as Alzheimer’s disease, is aggregation of secreted proteins. However, it is largely unclear how the hundreds of secretory pathway proteins contribute to amyloid formation. We developed a systems biology framework that integrates expression data with protein-protein interaction networks to successfully estimate a tissue’s fitness for producing specific secreted proteins. Using this framework, we analyzed the fitness of the secretory pathway of various brain regions and cell types for synthesizing the Alzheimer’s disease-associated amyloid-precursor protein (APP). While none of the key amyloidogenic pathway components were differentially expressed in AD brain, we found the deposition of Aβ is associated with repressed expression of the secretory pathway components proximal to APP. Concurrently, we detected systemic up-regulation of the secretory pathway components proximal to β- and γ-secretases in AD brains. Our analyses suggest that perturbations from 3 high confidence AD risk genes cascade through the secretory machinery support network for APP and into the endocytosis pathway. Thus, we present a model where amyloidogenesis is associated with dysregulation of dozens of secretory pathway components supporting APP, which could yield novel therapeutic targets for the treatment of AD.
Comparative analyses of SARS-CoV-2 binding (IgG, IgM, IgA) and neutralizing antibodies from human serum samples
Authors: Mazzini Livia , Martinuzzi Donata , Hyseni Inesa , Lapini Giulia , Benincasa Linda , Piu Pietro , Trombetta Claudia Maria , Marchi Serena , Razzano Ilaria , Manenti Alessandro , Montomoli Emanuele 
Published: August 2020

ABSTRACTA newly identified coronavirus, named SARS-CoV-2, emerged in December 2019 in Hubei Province, China, and quickly spread throughout the world; so far, it has caused more than 18 million cases of disease and 700,000 deaths. The diagnosis of SARS-CoV-2 infection is currently based on the detection of viral RNA in nasopharyngeal swabs by means of molecular-based assays, such as real-time RT-PCR. Furthermore, serological assays aimed at detecting different classes of antibodies constitute the best surveillance strategy for gathering information on the humoral immune response to infection and the spread of the virus through the population, in order to evaluate the immunogenicity of novel future vaccines and medicines for the treatment and prevention of COVID-19 disease. The aim of this study was to determine SARS-CoV-2-specific antibodies in human serum samples by means of different commercial and in-house ELISA kits, in order to evaluate and compare their results first with one another and then with those yielded by functional assays using wild-type virus. It is important to know the level of SARS-CoV-2-specific IgM, IgG and IgA antibodies in order to predict population immunity and possible cross-reactivity with other coronaviruses and to identify potentially infectious subjects. In addition, in a small sub-group of samples, we performed a subtyping Immunoglobulin G ELISA. Our data showed an excellent statistical correlation between the neutralization titer and the IgG, IgM and IgA ELISA response against the receptor-binding domain of the spike protein, confirming that antibodies against this portion of the virus spike protein are highly neutralizing and that the ELISA Receptor-Binding Domain-based assay can be used as a valid surrogate for the neutralization assay in laboratories which do not have Biosecurity level-3 facilities.
Whole-Brain Longitudinal Profiling of Serotonergic Reuptake Inhibition
Authors: Ioanas Horea-Ioan , Saab Bechara John , Rudin Markus 
Published: August 2020

AbstractThe serotonergic system is widely implicated in affect regulation, and a common target for psychopharmacological interventions. Selective Serotonin Reuptake Inhibitors (SSRIs) are the foremost drug class for treating depression, as well as anxiety, phobia and other affective disorders. However, the functional mechanisms determining SSRI efficacy remain elusive, hindering the targeted further development of serotonergic system interventions. Assays for longitudinal whole-brain interrogation of the serotonergic system are unavailable, yet such techniques are essential for identifying differential intervention effects across projection areas. We present a novel longitudinal opto-fMRI assay suitable for imaging longitudinal drug treatment effects on the mouse serotonergic system — within-subject and with sub-millimetre spatial resolution. We apply this assay to a longitudinal fluoxetine treatment, and document reliable segmentation of brain-wide treatment effects, including identification of a brainstem cluster with a highly significant longitudinal trajectory, constituting a novel neurophenotype for psychopharmacological interventions. We differentiate serotonergic neuron activation from projection area activation, and offer brain-wide fMRI evidence for the prominent autoinhibition down-regulation theory of SSRI effects. Further, we show that given the sensitivity of the assay, SSRI treatment produces no persistent effects after treatment cessation in healthy subjects.
Ap2s1mutation in mice causes familial hypocalciuric hypercalcemia type 3
Authors: Hannan Fadil M. , Stevenson Mark , Bayliss Asha L. , Stokes Victoria J. , Stewart Michelle , Kooblall Kreepa G. , Gorvin Caroline M. , Codner Gemma , Teboul Lydia , Wells Sara , Thakker Rajesh V. 
Published: August 2020

AbstractMutations of the adaptor protein-2 sigma subunit (AP2S1) gene which encodes AP2σ2, a component of the ubiquitous AP2 heterotetrameric complex involved in endosomal trafficking of the calcium-sensing receptor (CaSR), cause familial hypocalciuric hypercalcemia type 3 (FHH3). FHH3 patients have heterozygousAP2S1missense Arg15 mutations (p.Arg15Cys, p.Arg15His or p.Arg15Leu) with marked hypercalcemia and occasional hypophosphatemia and osteomalacia. To further characterise the phenotypic spectrum and calcitropic pathophysiology of FHH3, we used CRISPR/Cas9 genome editing to generate mice harboring theAP2S1p.Arg15Leu mutation, which causes the most severe FHH3 phenotype. Heterozygous (Ap2s1+/L15) mice were viable, and had marked hypercalcemia, hypermagnesemia, hypophosphatemia, and increased plasma concentrations of parathyroid hormone, fibroblast growth factor 23 and alkaline phosphatase activity, but normal pro-collagen type 1 N-terminal pro-peptide and 1,25 dihydroxyvitamin D. Homozygous (Ap2s1L15/L15) mice invariably died perinatally. TheAP2S1p.Arg15Leu mutation impaired protein-protein interactions between AP2σ2 and the other AP2 subunits, and the CaSR. Cinacalcet, a CaSR allosteric activator, ameliorated the hypercalcemia and elevated PTH concentrations, but not the diminished AP2σ2-CaSR interaction. Thus, our studies have established a mouse model with a germline loss-of-functionAP2S1mutation that is representative for FHH3 in humans, and demonstrated that cinacalcet corrects the abnormalities of plasma calcium and PTH.
Rhizosphere Microbiomes in a Historical Maize/Soybean Rotation System respond to Host Species and Nitrogen Fertilization at Genus and Sub-genus Levels
Authors: Meier Michael A. , Lopez-Guerrero Martha G. , Guo Ming , Schmer Marty R. , Herr Joshua R. , Schnable James C. , Alfano James R. , Yang Jinliang 
Published: August 2020

AbstractRoot associated microbes are key players in plant health, disease resistance, and nitrogen (N) use efficiency. It remains largely unclear how the interplay of biological and environmental factors affects rhizobiome dynamics in agricultural systems. Here, we quantified the composition of rhizosphere and bulk soil microbial communities associated with maize (Zea mays L.) and soybean (Glycine max L.) in a long-term crop rotation study under conventional fertilization and low N regimes. Over two growing seasons, we evaluated the effects of environmental conditions and several treatment factors on the abundance of rhizosphere and soil colonizing microbial taxa. Time of sampling, host plant species and N fertilization had major effects on microbiomes, while no effect of crop rotation was observed. Using variance partitioning as well as 16S sequence information, we further defined a set of 82 microbial genera and sub-genus groups that show distinct responses to treatment factors. We identified taxa that are highly specific to either maize or soybean rhizospheres, as well as taxa that are sensitive to N fertilization in plant rhizospheres and bulk soil. This study provides insights to harness the full potential of soil microbes in maize and soybean agricultural systems through plant breeding and field management.
Distributed harmonic patterns of structure-function dependence orchestrate human consciousness
Authors: Luppi Andrea I. , Vohryzek Jakub , Kringelbach Morten L. , Mediano Pedro A.M. , Craig Michael M. , Adapa Ram , Carhart-Harris Robin L. , Roseman Leor , Pappas Ioannis , Peattie Alexander R.D. , Manktelow Anne E. , Sahakian Barbara J. , Finoia Paola , Williams Guy B. , Allanson Judith , Pickard John D. , Menon David K. , Atasoy Selen , Stamatakis Emmanuel A. 
Published: August 2020

AbstractA central question in neuroscience is how consciousness arises from the dynamic interplay of brain structure and function. Departing from the predominant location- centric view in neuroimaging, here we provide an alternative perspective on the neural signatures of human consciousness: one that is intrinsically centered on how the distributed network architecture of the human structural connectome shapes functional activation across scales. We decompose cortical dynamics of resting-state functional MRI into fundamental distributed patterns of structure- function association: the harmonic modes of the human structural connectome. We contrast wakefulness with a wide spectrum of states of consciousness, spanning chronic disorders of consciousness but also pharmacological perturbations of consciousness induced with the anaesthetic propofol and the psychoactive drugs ketamine and LSD. Decomposing this wide spectrum of states of consciousness in terms of “connectome harmonics” reveals a generalisable structure-function signature of loss of consciousness, whether due to anaesthesia or brain injury. A mirror-reverse of this harmonic signature characterises the altered state induced by LSD or ketamine, reflecting psychedelic-induced decoupling of brain function from structure. The topology and neuroanatomy of the human connectome are crucial for shaping the repertoire of connectome harmonics into a fine-tuned indicator of consciousness, correlating with physiological and subjective scores across datasets and capable of discriminating between behaviourally indistinguishable sub-categories of brain-injured patients, tracking the presence of covert consciousness. Overall, connectome harmonic decomposition identifies meaningful relationships between neurobiology, brain function, and conscious experience.
Biodiversity genomics of small metazoans: high qualityde novogenomes from single specimens of field-collected and ethanol-preserved springtails
Authors: Schneider Clément , Woehle Christian , Greve Carola , D’Haese Cyrille A. , Wolf Magnus , Janke Axel , Bálint Miklós , Hüttel Bruno 
Published: August 2020

ABSTRACTGenome sequencing of all known eukaryotes on Earth promises unprecedented advances in evolutionary sciences, ecology, systematics and in biodiversity-related applied fields such as environmental management and natural product research. Advances in DNA sequencing technologies make genome sequencing feasible for many non-genetic model species. However, genome sequencing today relies on large quantities of high quality, high molecular weight (HMW) DNA which is mostly obtained from fresh tissues. This is problematic for biodiversity genomics of Metazoa as most species are small and yield minute amounts of DNA. Furthermore, briging living specimens to the lab bench not realistic for the majority of species.Here we overcome those difficulties by sequencing two species of springtails (Collembola) from single specimens preserved in ethanol. We used a newly developed, genome-wide amplification-based protocol to generate PacBio libraries for HiFi long-read sequencing.The assembled genomes were highly continuous. They can be considered complete as we recovered over 95% of BUSCOs. Genome-wide amplification does not seem to bias genome recovery. Presence of almost complete copies of the mitochondrial genome in the nuclear genome were pitfalls for automatic assemblers. The genomes fit well into an existing phylogeny of springtails. A neotype is designated for one of the species, blending genome sequencing and creation of taxonomic references.Our study shows that it is possible to obtain high quality genomes from small, field-preserved sub-millimeter metazoans, thus making their vast diversity accessible to the fields of genomics.
Different mutant RUNX1 oncoproteins program alternate haematopoietic differentiation trajectories
Authors: Kellaway Sophie G , Keane Peter , Edginton-White Benjamin , Kakkad Regha , Kennett Ella , Bonifer Constanze 
Published: August 2020

AbstractMutations of the hematopoietic master regulator RUNX1 cause acute myeloid leukaemia, familial platelet disorder and other haematological malignancies whose phenotypes and prognoses depend upon the class of RUNX1 mutation. The biochemical behaviour of these oncoproteins and their ability to cause unique diseases has been well studied, but the genomic basis of their differential action is unknown. To address this question we compared integrated phenotypic, transcriptomic and genomic data from cells expressing four types of RUNX1 oncoproteins in an inducible fashion during blood development from embryonic stem cells. We show that each class of mutated RUNX1 deregulates endogenous RUNX1 function by a different mechanism, leading to specific alterations in developmentally controlled transcription factor binding and chromatin programming. The result is distinct perturbations in the trajectories of gene regulatory network changes underlying blood cell development that are consistent with the nature of the final disease phenotype. The development of novel treatments for RUNX1-driven diseases will therefore require individual consideration.
Somatic mosaicism in the mature brain reveals clonal cellular distributions during cortical development
Authors: Breuss Martin W. , Yang Xiaoxu , Antaki Danny , Schlachetzki Johannes C. M. , Lana Addison J. , Xu Xin , Chai Guoliang , Stanley Valentina , Song Qiong , Newmeyer Traci Fang , Nguyen An , Cao Beibei , Nott Alexi , McEvoy-Venneri Jennifer , Pasillas Martina P. , Nahas Shareef , Van Der Kraan Lucitia , Ding Yan ,   NIMH Brain Somatic Mosaicism Network, Glass Christopher K. , Gleeson Joseph G. 
Published: August 2020

AbstractThe structure of the human neocortex underlies species-specific features and is a reflection of intricate developmental programs. Here we analyzed neocortical cellular lineages through a comprehensive assessment of brain somatic mosaicism—which acts as a neutral recorder of lineage history. We employed deep whole genome and variant sequencing in a singlepostmortemneurotypical human brain across 25 anatomic regions and three distinct modalities: bulk geographies, sorted cell types, and single nuclei. We identified 259 mosaic variants, revealing remarkable differences in localization, clonal abundance, cell type specificity, and clade distribution. We identified a set of hierarchical cellular diffusion barriers, whereby the left-right axis separation of the neocortex occurs prior to anterior-posterior and dorsal-ventral axis separation. We also found that stochastic distribution is a driver of clonal dispersion, and that rules regarding cellular lineages and anatomical boundaries are often ignored. Our data provides a comprehensive analysis of brain somatic mosaicism across the human cerebral cortex, deconvolving clonal distributions and migration patterns in the human embryo.One Sentence SummaryComprehensive evaluation of brain somatic mosaicism in the adult human identifies rules governing cellular distribution during embryogenesis.