bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rearing water microbiomes in white leg shrimp (Litopenaeus vannamei) larviculture assemble stochastically and are influenced by the microbiomes of live feed products
Authors: Heyse Jasmine , Props Ruben , Kongnuan Pantipa , De Schryver Peter , Rombaut Geert , Defoirdt Tom , Boon Nico 
Published: August 2020

SummaryThe development of effective management strategies to reduce the occurrence of diseases in aquaculture is hampered by the limited knowledge on the microbial ecology of these systems. In this study, the dynamics and dominant community assembly processes in the rearing water ofLitopenaeus vannameilarviculture tanks were determined. Additionally, the contribution of peripheral microbiomes, such as those of live and dry feeds, to the rearing water microbiome were quantified. The community assembly in the hatchery rearing water over time was dominated by stochasticity, which explains the observed heterogeneity between replicate cultivations. The community undergoes two shifts that match with the dynamics of the algal abundances in the rearing water. Source tracking analysis revealed that 37% of all bacteria in the hatchery rearing water were either introduced by the live or dry feeds, or during water exchanges. The contribution of the microbiome from the algae was the largest, followed by that of theArtemia, the exchange water and the dry feeds. Our findings provide fundamental knowledge on the assembly processes and dynamics of rearing water microbiomes and illustrate the crucial role of these peripheral microbiomes in maintaining health-promoting rearing water microbiomes.Originality-Significance StatementMost studies on rearing water microbiomes are characterized by sampling resolutions of multiple days and by few replicate cultivations. Through an 18-day sampling campaign in aLitopenaeus vannameihatchery where five replicate cultivations were studied at a sampling resolution of one day, we studied the microbiome dynamics in this system. We show that the community assembly is dominated by stochasticity, which explains the heterogeneity between replicate cultivations. The dynamics of the algal community in the rearing water induced shifts in community composition at two differerent timepoints. Finally, we quantified the contribution of live and dry feed microbiomes to the rearing water community for the first time. We found that the contribution of each source was dependent on its taxonomic composition, the bacterial load caused by the addition of this source and the timing of the introduction. These new insights will aid in the further development of effective microbiome management to reduce the frequency and magnitude of bacterial diseases.
Canonical EEG Microstate Dynamic Properties and Their Associations with fMRI Signals at Resting Brain
Authors: Zoubi Obada Al , Misaki Masaya , Tsuchiyagaito Aki , Mayeli Ahmad , Zotev Vadim ,   Tulsa 1000 Investigators, Refai Hazem , Paulus Martin , Bodurka Jerzy 
Published: August 2020

AbstractElectroencephalography microstates (EEG-ms) capture and reflect the spatio-temporal neural dynamics of the brain. A growing literature is employing EEG-ms-based analyses to study various mental illnesses and to evaluate brain mechanisms implicated in cognitive and emotional processing. The spatial and functional interpretation of the EEG-ms is still being investigated. Previous works studied the association of EEG-ms time courses with blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal and suggested an association between EEG-ms and resting-state networks (RSNs). However, the distinctive association between EEG-ms temporal dynamics and brain neuronal activities is still not clear, despite the assumption that EEG-ms are an electrophysiological representation of RSNs activity. Recent works suggest a role for brain spontaneous EEG rhythms in contributing to and modulating canonical EEG-ms topographies and determining their classes (coined A through D) and metrics. This work simultaneously utilized EEG and fMRI to understand the EEG-ms and their properties further. We adopted the canonical EEG-ms analysis to extract three types of regressors for EEG-informed fMRI analyses: EEG-ms direct time courses, temporal activity per microstate, and pairwise temporal transitions among microstates (the latter two coined activity regressors). After convolving EEG-ms regressors with a hemodynamic response function, a generalized linear model whole-brain voxel-wise analysis was conducted to associate EEG-ms regressors with fMRI signals. The direct time course regressors replicated prior findings of the association between the fMRI signal and EEG-ms time courses but to a smaller extent. Notably, EEG-ms activity regressors were mostly anticorrelated with fMRI, including brain regions in the somatomotor, visual, dorsal attention, and ventral attention fMRI networks with no significant overlap for default mode, limbic or frontoparietal networks. A similar pattern emerged in using the transition regressors among microstates but not in self-transitions. The relatively short duration of each EEG-ms and the significant association of EEG-ms activity regressors with fMRI signals suggest that EEG-ms manifests successive transition from one brain functional state to another rather than being associated with specific brain functional state or RSN networks.
Methylene Blue has a potent antiviral activity against SARS-CoV-2 in the absence of UV-activation in vitro
Authors: Cagno Valeria , Medaglia Chiara , Cerny Andreas , Cerny Thomas , Tapparel Caroline , Cerny Erich 
Published: August 2020

ABSTRACTMethylene blue is an FDA and EMA approved drug with an excellent safety profile. It displays broad-spectrum virucidal activity in the presence of UV light and has been shown to be effective in inactivating various viruses in blood products prior to transfusions. In addition, its use has been validated for methemoglobinemia and malaria treatment. Here we show the virucidal activity of methylene blue at low micromolar concentrations and in the absence of UV activation against SARS-CoV2.
Vitamin D status is heritable and under environment-dependent selection in the wild
Authors: Sparks Alexandra M. , Johnston Susan E. , Handel Ian , Pilkington Jill G. , Berry Jacqueline , Pemberton Josephine M. , Nussey Daniel H. , Mellanby Richard J. 
Published: August 2020

AbstractVitamin D has a well-established role in skeletal health and is increasingly linked to chronic disease and mortality in humans and companion animals. Despite the clear significance of vitamin D for health and obvious implications for fitness under natural conditions, no longitudinal study has tested whether the circulating concentration of vitamin D is under natural selection in the wild. Here, we show that concentrations of dietary-derived vitamin D2 and endogenously-produced vitamin D3 metabolites are heritable and largely polygenic in a wild population of Soay sheep (Ovis aries). Vitamin D2 status was positively associated with female adult survival, and vitamin D3 status predicted female fecundity in particular, good environment years. Our study provides evidence that vitamin D status has the potential to respond to selection, as well as new insights into how vitamin D metabolism is associated with fitness in the wild.
Life story of Tunisian durum wheat landraces revealed by their genetic and phenotypic diversity
Authors: Ben Krima Safa , Slim Amine , Gélisse Sandrine , Kouki Hajer , Nadaud Isabelle , Sourdille Pierre , Yahyaoui Amor , Ben M’barek Sarrah , Suffert Frédéric , Marcel Thierry C 
Published: August 2020

AbstractDurum wheat (Triticum turgidumL. subsp.durum) landraces represent a prominent genetic resource for Mediterranean farming systems and breeding programs. Fourteen landraces sampled in Tunisia were genotyped with 9 microsatellite markers and characterized with 15 morphological descriptors, including resistance to the fungal diseaseSeptoria triticiblotch (STB). The genetic diversity, nearly was as important within landraces populations (45%) than between populations (54%). It was structured in seven genetic groups and was only partly explained by the variety name or the locality of origin. Populations were also greatly diversified phenotypically (Shannon-Weaver H’=0.54) with traits related to spike and awn colours being the most diversified. Resistance to STB was either qualitative in two populations or with varying degrees of quantitative resistance in the others. A Pst-Fstcomparison indicate a local adaptation of the populations. Overall, the genetic structure of Tunisian durum wheat landraces revealed a complex selection trajectory and seed exchanges between farmers.
Humanization ofDrosophilaGαo to modelGNAO1paediatric encephalopathies
Authors: Savitsky Mikhail , Solis Gonzalo P. , Katanaev Vladimir L. 
Published: August 2020

AbstractSeveral hundred genes have been identified to contribute to epilepsy – the disease affecting 65 million people worldwide. One of these genes isGNAO1encoding Gαo, the major neuronal α-subunit of heterotrimeric G proteins. An avalanche of dominantde novomutations inGNAO1have been recently described in paediatric epileptic patients, suffering in addition to epilepsy from motor dysfunction and developmental delay. Although occurring in amino acids conserved from humans toDrosophila, these mutations and their functional consequences have only poorly been analysed at the biochemical or neuronal levels. Adequate animal models to study molecular aetiology ofGNAO1encephalopathies have also so far been lacking. As the first step towards modelling the disease inDrosophila, we here describe humanization of theGαolocus in the fruit fly. A two-step CRISPR/Cas9-mediated replacement was conducted, first substituting the coding exons 2-3 ofGαowith respective humanGNAO1sequences. At the next step, the remaining exons 4-7 were similarly replaced, keeping intact the geneCyp49a1embedded in-between, as well as the non-coding exon 1 and the surrounding regulatory sequences. The resulting flies, homozygous for the humanizedGNAO1loci, are viable and fertile without any visible phenotypes; their body weight and longevity are also normal. Human Gαo-specific antibodies confirm the endogenous-level expression of the humanized Gαo, which fully replaces theDrosophilafunctions. The genetic model we established will make it easy to incorporate encephalopathicGNAO1mutations and will permit intensive investigations into the molecular aetiology of the human disease through the powerful toolkit ofDrosophilagenetics.
A non-canonical DNA damage checkpoint response in a major fungal pathogen
Authors: Shor Erika , Garcia-Rubio Rocio , DeGregorio Lucius , Perlin David S. 
Published: August 2020

ABSTRACTTo protect genome integrity, eukaryotic cells respond to DNA damage by triggering highly conserved checkpoint mechanisms involving the phosphorylation of Rad53/CHK2 kinase. Budding yeastCandida glabrata, closely related to model eukaryoteSaccharomyces cerevisiae, is an opportunistic pathogen characterized by high genetic diversity and rapid emergence of drug resistant mutants. However, the mechanisms enabling this genetic variability are unclear. Here we show thatC. glabratacells exposed to DNA damage neither induce CgRad53 phosphorylation nor accumulate in S phase, and exhibit higher lethality thanS. cerevisiae. Furthermore, time-lapse microscopy showedC. glabratacells continuing to divide in the presence of DNA damage, resulting in mitotic errors and cell death. Finally, RNAseq analysis revealed transcriptional rewiring of the DNA damage response inC. glabrataand identified several key protectors of genome stability upregulated by DNA damage inS. cerevisiaebut downregulated inC. glabrata, including PCNA. Together, our results reveal a non-canonical fungal DNA damage response, which may contribute to rapidly generating genetic change and drug resistance.
The Multivariate Genome-wide Architecture of Interrelated Literacy, Language and Working Memory Skills Reveals Distinct Etiologies
Authors: Shapland Chin Yang , Verhoef Ellen , Smith George Davey , Fisher Simon E. , Verhulst Brad , Dale Philip S. , Pourcain Beate St 
Published: August 2020

AbstractThere is genetic overlap between many measures of literacy, language and phonological working memory (PWM) though our knowledge of multivariate genetic architectures is incomplete. Here, we directly modeled genetic trait interrelationships in unrelated UK youth (8-13 years, N=6,453), as captured by genome-wide relationship matrices, using novel structural equation modeling techniques. We identified, besides shared genetic factors across different domains (explaining 91-97% genetic variance in literacy-related measures such as passage reading fluency, spelling, phonemic awareness, 44% in oral language and 53% in PWM), evidence for distinct cognitive abilities; trait-specific genetic influences ranged between 47% for PWM to 56% for oral language. Among reading fluency measures (non-word, word and passage reading), single-word reading was genetically most diverse. Multivariate genetic and residual covariance patterns showed concordant effect directionality, except for near-zero residual correlations between oral language and literacy-related abilities. These findings suggest differences in etiological mechanisms and trait modifiability even among genetically highly correlated skills.
The FDA-approved drug Alectinib compromises SARS-CoV-2 nucleocapsid phosphorylation and inhibits viral infection in vitro
Authors: Yaron Tomer M. , Heaton Brook E. , Levy Tyler M. , Johnson Jared L. , Jordan Tristan X. , Cohen Benjamin M. , Kerelsky Alexander , Lin Ting-Yu , Liberatore Katarina M. , Bulaon Danielle K. , Kastenhuber Edward R. , Mercadante Marisa N. , Shobana-Ganesh Kripa , He Long , Schwartz Robert E. , Chen Shuibing , Weinstein Harel , Elemento Olivier , Piskounova Elena , Nilsson-Payant Benjamin E. , Lee Gina , Trimarco Joseph D. , Burke Kaitlyn N. , Hamele Cait E. , Chaparian Ryan R. , Harding Alfred T. , Tata Aleksandra , Zhu Xinyu , Tata Purushothama Rao , Smith Clare M. , Possemato Anthony P. , Tkachev Sasha L. , Hornbeck Peter V. , Beausoleil Sean A. , Anand Shankara K. , Aguet François , Getz Gad , Davidson Andrew D. , Heesom Kate , Kavanagh-Williamson Maia , Matthews David , tenOever Benjamin R. , Cantley Lewis C. , Blenis John , Heaton Nicholas S. 
Published: August 2020

ABSTRACTWhile vaccines are vital for preventing COVID-19 infections, it is critical to develop new therapies to treat patients who become infected. Pharmacological targeting of a host factor required for viral replication can suppress viral spread with a low probability of viral mutation leading to resistance. In particular, host kinases are highly druggable targets and a number of conserved coronavirus proteins, notably the nucleoprotein (N), require phosphorylation for full functionality. In order to understand how targeting kinases could be used to compromise viral replication, we used a combination of phosphoproteomics and bioinformatics as well as genetic and pharmacological kinase inhibition to define the enzymes important for SARS-CoV-2 N protein phosphorylation and viral replication. From these data, we propose a model whereby SRPK1/2 initiates phosphorylation of the N protein, which primes for further phosphorylation by GSK-3α/β and CK1 to achieve extensive phosphorylation of the N protein SR-rich domain. Importantly, we were able to leverage our data to identify an FDA-approved kinase inhibitor, Alectinib, that suppresses N phosphorylation by SRPK1/2 and limits SARS-CoV-2 replication. Together, these data suggest that repurposing or developing novel host-kinase directed therapies may be an efficacious strategy to prevent or treat COVID-19 and other coronavirus-mediated diseases.
Belowground competition favors character convergence but not character displacement in root traits
Authors: Colom Sara M , Baucom Regina S 
Published: August 2020

SummaryCharacter displacement can play a major role in species ecology and evolution, however, research testing whether character displacement can influence the evolution of root traits in plant systems remains scarce in the literature. Here we investigated the potential that character displacement may influence the evolution of root traits using two closely related morning glory species,Ipomoea purpureaandI. hederacea.We performed a field experiment where we grew the common morning glory,I. purpurea, in the presence and absence of competition fromI. hederaceaand examined the potential that the process of character displacement could influence the evolution of root traits.We found maternal line variation in root phenotypes and evidence that belowground competition acts as an agent of selection on these traits. Our test of character displacement, however, showed evidence of characterconvergence on our measure of root architecture rather thandisplacement. These results suggest that plants may be constrained by their local environments to express a phenotype that enhances fitness. Therefore, the conditions of the competitive environment experienced by a plant may influence the potential for character convergence or displacement to influence the evolution of root traits.
Rab7 mediates Wnt-dependent mesoderm patterning and gastrulation inXenopus
Authors: Kreis Jennifer , Wielath Fee M. , Vick Philipp 
Published: August 2020

AbstractEarly embryogenesis requires tightly controlled temporal and spatial activity of growth factors. Modulation is achieved at multiple levels, from cellular transcription to tissue-scale propagation, concerning activation, maintenance, or termination of signaling. Intracellularly, the endolysosomal system emerged as important factor for such regulations. Endocytosis and early endosomes mainly orchestrate activation and transduction of signals, while late endosomes are thought to mediate lysosome-based termination. Only few reports attributed activating roles to late endosomes, mainly for Wnt pathway activation. InXenopus, few is known about developmental roles of endosomal regulators, or their function for signaling, especially true for late endosomes. Therefore, we chose to analyze a hypothesized positive role of Rab7 in this context, a small GTPase mainly known for its role as a late endosomal regulator. We analyzed if Rab7 participates in early activation of growth factor signaling, focusing on Wnt signaling. We foundrab7expressed very localized throughout development, and inhibition resulted in strong gastrulation defects. Concomitantly, Rab7 was strictly required for both, exogenous activation and endogenous Wnt-mediated patterning of the mesoderm.Summary StatementThe late endosomal regulator Rab7 is required for gastrulation movements and axis elongation inXenopusby positively regulating Wnt signaling-mediated mesoderm patterning.
MethylSPWNet and MethylCapsNet: Biologically Motivated Organization of DNAm Neural Network, Inspired by Capsule Networks
Authors: Levy Joshua J. , Chen Youdinghuan , Azizgolshani Nasim , Petersen Curtis L. , Titus Alexander J. , Moen Erika L. , Vaickus Louis J. , Salas Lucas A. , Christensen Brock C. 
Published: August 2020

AbstractDNA methylation (DNAm) alterations have been heavily implicated in carcinogenesis and the pathophysiology of diseases through upstream regulation of gene expression. DNAm deep-learning approaches are able to capture features associated with aging, cell type, and disease progression, but lack incorporation of prior biological knowledge. Here, we present modular, user-friendly deep learning methodology and software,MethylCapsNetandMethylSPWNet, that group CpGs into biologically relevant capsules – such as gene promoter context, CpG island relationship, or user-defined groupings – and relate them to diagnostic and prognostic outcomes. We demonstrate these models’ utility on 3,897 individuals in the classification of central nervous system (CNS) tumors.MethylCapsNetandMethylSPWNetprovide an opportunity to increase DNAm deep learning analyses’ interpretability by enabling a flexible organization of DNAm data into biologically relevant capsules.
A chlorzoxazone-baclofen combination improves cerebellar impairment in spinocerebellar ataxia type 1
Authors: Bushart David D. , Huang Haoran , Man Luke J. , Morrison Logan M. , Shakkottai Vikram G. 
Published: August 2020

AbstractBackgroundA combination of central muscle relaxants, chlorzoxazone and baclofen (chlorzoxazone-baclofen), has been proposed for treatment of cerebellar symptoms in human spinocerebellar ataxia (SCA). However, central muscle relaxants can worsen balance. The optimal dose for target engagement without toxicity remains unknown.ObjectivesUsing the genetically preciseAtxn1154Q/2Qmodel of SCA1, we determine the role of cerebellar dysfunction in motor impairment. We also aim to identify appropriate concentrations of chlorzoxazone-baclofen needed for target engagement without toxicity to plan for human clinical trials.MethodsWe use patch clamp electrophysiology in acute cerebellar slices and immunostaining to identify the specific ion channels targeted by chlorzoxazone-baclofen. Behavioral assays for coordination and grip strength are used to determine specificity of chlorzoxazone-baclofen for improving cerebellar dysfunction without off-target effects inAtxn1154Q/2Qmice.ResultsWe identify irregular Purkinje neuron firing in association with reduced expression of the ion channelsKcnma1andCacna1ginAtxn1154Q/2Qmice. Usingin vitroelectrophysiology in brain slices, we identify concentrations of chlorzoxazone-baclofen that improve Purkinje neuron spike regularity without reducing firing frequency. At a disease stage inAtxn1154Q/2Qmice when motor impairment is due to cerebellar dysfunction, orally administered chlorzoxazone-baclofen improves motor performance without affecting muscle strength.ConclusionWe identify a tight relationship between baclofen-chlorzoxazone concentrations needed to engage target, and levels above which cerebellar function will be compromised. We propose to use this information for a novel clinical trial design, using sequential dose escalation within each subject, to identify dose levels that are likely to improve ataxia symptoms while minimizing toxicity.
CopR, a global regulator of transcription to maintain copper homeostasis inPyrococcus furiosus
Authors: Grünberger Felix , Reichelt Robert , Waege Ingrid , Ned Verena , Bronner Korbinian , Kaljanac Marcell , Weber Nina , El Ahmad Zubeir , Knauss Lena , Madej M. Gregor , Ziegler Christine , Grohmann Dina , Hausner Winfried 
Published: August 2020

AbstractAlthough copper is in many cases an essential micronutrient for cellular life, higher concentrations are toxic. Therefore, all living cells have developed strategies to maintain copper homeostasis. In this manuscript, we have analysed the transcriptome-wide response ofPyrococcus furiosusto increased copper concentrations and described the essential role of the putative copper-sensing metalloregulator CopR in the detoxification process.To this end, we employed biochemical and biophysical methods to characterise the role of CopR. Additionally, acopRknockout strain revealed an amplified sensitivity in comparison to the parental strain towards increased copper levels, which designates an essential role of CopR for copper homeostasis. To learn more about the CopR-regulated gene network, we performed differential gene expression and ChIP-seq analysis under normal and 20 μM copper-shock conditions. By integrating the transcriptome and genome-wide binding data, we found that CopR binds to the upstream regions of many copper-induced genes. Negative-stain transmission electron microscopy and 2D class averaging revealed an octameric assembly formed from a tetramer of dimers for CopR, similar to published crystal structures from the Lrp family. In conclusion, we propose a model for CopR-regulated transcription and highlight the complex regulatory network that enablesPyrococcusto respond to increased copper concentrations.