bluuebunny/crossref_metadata_2025_split huggingface dataset:
Orbitofrontal-striatal structural alterations linked to negative symptoms at different stages of the schizophrenia spectrum
Authors: Kirschner Matthias , Schmidt André , Hodzic-Santor Benazir , Burrer Achim , Manoliu Andrei , Zeighami Yashar , Yau Yvonne , Abbasi Nooshin , Maatz Anke , Habermeyer Benedikt , Abivardi Aslan , Avram Mihai , Brandl Felix , Sorg Christian , Homan Philipp , Riecher-Rössler Anita , Borgwardt Stefan , Seifritz Erich , Dagher Alain , Kaiser Stefan 
Published: April 2020

AbstractAmong the most debilitating manifestations of schizophrenia are negative symptoms such as anhedonia and apathy. Imaging studies have linked these symptoms to morphometric abnormalities in two brain regions implicated in reward and motivation: the orbitofrontal cortex (OFC) and ventral striatum. Negative symptoms generally are associated with reduced OFC thickness, while apathy specifically maps to reduced striatal volume. However, it remains unclear whether these tissue losses are a consequence of chronic illness and its treatment, or an underlying phenotypic trait. Here we use multicentre MRI data to investigate orbitofrontal-striatal abnormalities across the schizophrenia-spectrum from healthy populations with schizotypy, to unmedicated and medicated first-episode psychosis patients, and patients with chronic schizophrenia. Striatal volumes and OFC thickness were estimated from T1-weighted images acquired in all three diagnostic groups and controls from four sites (n=337). Results were first established in one test cohort (“Zurich sample”) and replicated in three independent samples. There was a correlation between apathy and striatal volume only in healthy individuals with schizotypy; however, medicated patients exhibited larger striatal volumes, which appears to be a consequence of antipsychotic medications. The association between reduced OFC thickness and negative symptoms generally also appeared to vary along the disease course, being significant only in first-episode psychosis patients. In schizotypy there was increased OFC relative to controls. Our findings suggest that negative symptoms associate with a temporal continuum of orbitofrontal-striatal abnormalities that may predate the occurrence of schizophrenia. Thicker OFC in schizotypy may represent either compensatory or pathological mechanisms prior to disease-onset.
The role of procalcitonin in early differential diagnosis of suspected children with COVID-19
Authors: Peng Denggao , Zhang Jing , Xu Yingqi , Liu Zhichao , Wu Pengyao 
Published: April 2020

AbstractBackgroundWe aimed to identify clinical features of coronavirus disease 2019 (COVID-19) in children and evaluate the role of procalcitonin in early differential diagnosis.MethodsA retrospective analysis was performed on all suspected pediatric cases.Results39 (50.6%) of 77 suspected cases were comfirmed, 4 (5.2%) of them had viral coinfection. Compared with non-COVID-19 group (n=33), COVID-19 confirmed group (n=39) had fewer fever(OR[95% CI]0.467[0.314-0.694]; P=.000) and symptoms of acute respiratory infection (0.533[0.36–0.788]; P=.001), more asymptomatic (13.568[1.895-96.729]; P=.000), and more family cluster infections (5.077[2.224-11.591]; P=.000), while computed tomography had more positive findings of viral pneumonia (1.822[1.143-2.906]; P=.008). Age (6.9[3.6-10.5] vs 5[2.1-7.6]; P=. 088) and gender were statistically insignificant. Procalcitonin (0.05[0.029-0.076] vs 0.103[0.053-0.21]; P= 000) of COVID-19 alone group (n=35) was significantly reduced. While compared with coinfection group (n=4), procalcitonin (0.05[0.029-0.076] vs 0.144[0.109-2.26]; P=.010) was also reduced. The area under curve of model is 0.834 ([95% CI][0.741-0.926]; P=.000). Procalcitonin as a differential indicator of COVID-19 alone, its area under curve is 0.809 ([0.710-0.909]; P=.000). The optimal cut-off value is 0.1 ng/mL, the sensitivity, specificity, positive and negative predictive value of differentiating are 65.9%, 78.6%, 82.9%, and 59.2%, respectively.ConclusionsAsymptoms or mild symptoms, positive computed tomography findings and family cluster infection are the main clinical features of COVID-19 in children. With good performance, procalcitonin can provide an important basis for differentiating COVID-19 alone and other viral infection or viral coinfection.
Body stoichiometry of heterotrophs: assessing drivers of interspecific variations in elemental composition
Authors: Andrieux Benjamin , Signor Juliette , Guillou Vincent , Danger Michael , Jabot Franck 
Published: April 2020

ABSTRACTAimTo document how body stoichiometry of heterotrophs varies globally and to assess phylogenetic, trophic, habitat and body mass drivers of this interspecific variation in elemental composition, focusing on carbon (C), nitrogen (N) and phosphorus (P).LocationWorldwide.Time period1930 – 2018.Major taxa studiedAmphibians, fishes (Euteleosteomorpha and Otomorpha), invertebrates, mammals, microbes and sauropsids (birds and reptiles).MethodsWe compiled from the scientific literature a global database of body elemental composition of heterotrophs in marine, freshwater and terrestrial realms. We used model selection and ANCOVA analyses to investigate the proportion of variance in elemental composition explained by taxonomic groups, diet, habitat and body mass. We assessed the phylogenetic signal in body stoichiometry using Blomberg’s K and Pagel’s λ statistics. We assessed the phylogenetic structure of interspecific variation in body stoichiometry using mixed models with nested taxonomic levels as random factors. We finally assessed the co-variation in elemental composition using linear models.ResultsOur database currently gathers 17848 independent observations on 1491 species. Body elemental composition was found to be widely variable among species with the four assessed drivers significantly contributing to this variation. Taxonomic group is the strongest contributor to interspecific variance for the stoichiometric traits studied, followed by habitat, diet and body mass. More precisely, stoichiometric traits are generally variable at the three taxonomic levels studied (class, order and family), resulting in a significant but relatively modest phylogenetic signal. Finally, we found significant co-variation among the three body elemental contents, resulting in taxonomic group-specific C:N:P spectrums.Main conclusionsOur global synthesis of body stoichiometry of heterotrophs reveals a strong interspecific variability that is only modestly explained by the species attributes investigated: body mass, habitat and diet. It further reveals that this taxonomically structured residual variation in body stoichiometry seems to be constrained along taxonomic group-specific elemental spectrums.
Humans sacrifice decision-making for action execution when a demanding control of movement is required
Authors: Reynaud Amélie J. , Saleri Lunazzi Clara , Thura David 
Published: April 2020

ABSTRACTA growing body of evidence suggests that decision-making and action execution are governed by partly overlapping operating principles. Especially, previous work proposed that a shared decision urgency/movement vigor signal, possibly computed in the basal ganglia, coordinates both deliberation and movement durations in a way that maximizes the reward rate. Recent data support one aspect of this hypothesis, indicating that the urgency level at which a decision is made influences the vigor of the movement produced to express this choice. Here we investigated whether conversely, the motor context in which a movement is executed determines decision speed and accuracy. Twenty human subjects performed a probabilistic decision task in which perceptual choices were expressed by reaching movements toward targets whose size and distance from a starting position varied in distinct blocks of trials. We found strong evidence for an influence of the motor context on most of the subjects’ decision policy but contrary to the predictions of the “shared regulation” hypothesis, we observed that slow movements executed in the most demanding motor blocks in terms of accuracy were often preceded by faster and less accurate decisions compared to blocks of trials in which big targets allowed expression of choices with fast and inaccurate movements. These results suggest that decision-making and motor control are not regulated by one unique “invigoration” signal determining both decision urgency and action vigor, but more likely by independent, yet interacting, decision urgency and movement vigor signals.NEW & NOTEWORTHYRecent hypotheses propose that choices and movements share optimization principles derived from economy, possibly implemented by one unique context-dependent regulation signal determining both processes speed. In the present behavioral study conducted on human subjects, we demonstrate that action properties indeed influence perceptual decision-making, but that decision duration and action vigor are actually independently set depending on the difficulty of the movement executed to report a choice.
Visual function restoration in genetically blind mice via endogenous cellular reprogramming
Authors: Fu Xin , Zhu Jie , Duan Yaou , Li Gen , Cai Huimin , Zheng Lianghong , Qian Hao , Zhang Changjun , Jin Zibing , Fu Xiang-Dong , Zhang Kang 
Published: April 2020

AbstractIn this study, we developed an in-situ cellular reprogramming strategy for potent restoration of vision in advanced/end-stage retinitis pigmentosa (RP). Via repressing PTB, an RNA binding protein critical for converting non-neuronal cells to the neuronal lineage, we successfully reprogramed Müller glia to a retinal neuronal fate, and then to cones. We demonstrated that this cellular reprogramming approach was able to rescue retinal photoreceptor degeneration and restore visual functions in two RP mouse models with total blindness, suggesting a novel universal strategy for treating end-stage degenerative diseases.
Natural variation identifies aPxygene controlling root vascular organization and formation of nodules and lateral roots inLotus japonicus
Authors: Kawaharada Yasuyuki , Sandal Niels , Gupta Vikas , Jin Haojie , Kawaharada Maya , Schneeberger Korbinian , Stougaard Jens , Andersen Stig U. 
Published: April 2020

AbstractForward and reverse genetics using the model legumesLotus japonicusandMedicago truncatulahave been instrumental for identifying the essential genes governing legume-rhizobial symbiosis. However, little is known about the effects of intraspecific variation on symbiotic signaling. TheLotusaccessions Gifu and MG20 show differentiated phenotypic responses to theMesorhizobium loti exoUmutant that produces truncated exopolysaccharides. Using Quantitative Trait Locus sequencing (QTL-seq), we identify thePxygene as a component of this differentialexoUresponse.Lotus Pxyencodes a leucine-rich-repeat kinase similar toArabidopsisPXY, which regulates stem vascular development. We show thatLotus pxyinsertion mutants display defects in root vascular organization, as well as lateral root and nodule formation. Our work linksPxytode novoorganogenesis in the root, highlights the genetic overlap between regulation of lateral root and nodule formation, and demonstrates that specific natural variants ofPxydifferentially affect nodulation signaling.
Spontaneous liver disease in wild-type C57BL/6JOlaHsd mice fed semisynthetic diet
Authors: Ronda Onne A.H.O. , van de Heijning Bert J. M. , de Bruin Alain , Thomas Rachel E. , Martini Ingrid , Koehorst Martijn , Gerding Albert , Koster Mirjam H. , Bloks Vincent W. , Jurdzinski Angelika , Mulder Niels L. , Havinga Rick , van der Beek Eline M. , Reijngoud Dirk-Jan , Kuipers Folkert , Verkade Henkjan J. 
Published: April 2020

AbstractMouse models are frequently used to study mechanisms of human diseases. Recently, we observed a spontaneous bimodal variation in liver weight in C57BL/6JOlaHsd mice fed a semisynthetic diet. We now characterized the spontaneous variation in liver weight and its relationship with parameters of hepatic lipid and bile acid (BA) metabolism. In male C57BL/6JOlaHsd mice fed AIN-93G from birth to postnatal day (PN)70, we measured plasma BA, lipids, Very low-density lipoprotein (VLDL)-triglyceride (TG) secretion, and hepatic mRNA expression patterns. Mice were sacrificed at PN21, PN42, PN63 and PN70. Liver weight distribution was bimodal at PN70. Mice could be subdivided into two nonoverlapping groups based on liver weight: 0.6 SD 0.1 g (approximately one-third of mice, small liver; SL), and 1.0 SD 0.1 g (normal liver; NL; p<0.05). Liver histology showed a higher steatosis grade, inflammation score, more mitotic figures and more fibrosis in the SLversusthe NL group. Plasma BA concentration was 14-fold higher in SL (p<0.001). VLDL-TG secretion rate was lower in SL mice, both absolutely (−66%, p<0.001) and upon correction for liver weight (−44%, p<0.001). Mice that would later have the SL-phenotype showed lower food efficiency ratios during PN21-28, suggesting the cause of the SL phenotype is present at weaning (PN21). Our data show that approximately one-third of C57BL/6JOlaHsd mice fed semisynthetic diet develop spontaneous liver disease with aberrant histology and parameters of hepatic lipid, bile acid and lipoprotein metabolism. Study designs involving this mouse strain on semisynthetic diets need to take the SL phenotype into account. Plasma lipids may serve as markers for the identification of the SL phenotype.
CytoPy: an autonomous cytometry analysis framework
Authors: Burton Ross J. , Ahmed Raya , Cuff Simone M. , Baker Sarah , Artemiou Andreas , Eberl Matthias 
Published: April 2020

AbstractCytometry analysis has seen a considerable expansion in recent years in the maximum number of parameters that can be acquired in a single experiment. In response to this technological advance there has been an increased effort to develop new computational methodologies for handling high-dimensional single cell data acquired by flow or mass cytometry. Despite the success of numerous algorithms and published packages to replicate and outperform traditional manual analysis, widespread adoption of these techniques has yet to be realised in the field of immunology. Here we present CytoPy, a Python framework for automated analysis of cytometry data that integrates a document-based database for a data-centric and iterative analytical environment. In addition, our algorithm agnostic design provides a platform for open-source cytometry bioinformatics in the Python ecosystem. We demonstrate the ability of CytoPy to phenotype T cell subsets in whole blood samples even in the presence of significant batch effects due to technical and user variation. The complete analytical pipeline was then used to immunophenotype the local inflammatory infiltrate in individuals with and without acute bacterial infection. CytoPy is open-source and licensed under the MIT license. CytoPy is open source and available athttps://github.com/burtonrj/CytoPy, with notebooks accompanying this manuscript (https://github.com/burtonrj/CytoPyManuscript) and software documentation athttps://cytopy.readthedocs.io/.
Mistranslating tRNA identifies a deleterious S213P mutation in theSaccharomyces cerevisiae eco1-1allele
Authors: Zhu Yanrui , Berg Matthew D. , Yang Phoebe , Loll-Krippleber Raphaël , Brown Grant W. , Brandl Christopher J. 
Published: April 2020

ABSTRACTMistranslation occurs when an amino acid not specified by the standard genetic code is incorporated during translation. Since the ribosome does not read the amino acid, tRNA variants aminoacylated with a non-cognate amino acid or containing a non-cognate anticodon dramatically increase the frequency of mistranslation. In a systematic genetic analysis, we identified a suppression interaction between tRNASerUGG, G26A, which mistranslates proline codons by inserting serine, andeco1-1,a temperature sensitive allele of the gene encoding an acetyltransferase required for sister chromatid cohesion. The suppression was partial with a tRNA that inserts alanine at proline codons and not apparent for a tRNA that inserts serine at arginine codons. Sequencing of theeco1-1allele revealed a mutation that would convert the highly conserved serine 213 within β7 of the GCN5-related N-acetyltransferase core to proline. Mutation of P213 ineco1-1back to the wild-type serine restored function of the enzyme at elevated temperature. Our results indicate the utility of mistranslating tRNA variants to identify functionally relevant mutations and identifyeco1as a reporter for mistranslation. We propose that mistranslation could be used as a tool to treat genetic disease.
An in vitro model to study the naïve human peripheral blood mononuclear cell response toCryptococcus neoformansinfection
Authors: Pline Katherine , Johnston Simon A. 
Published: April 2020

AbstractCryptococcus neoformansis a facultative intracellular pathogenic yeast which causes cryptococcal meningitis. Infection most commonly occurs via the lungs in humans and is cleared without clinical signs in the immunocompetent, but may cause life-threatening infection in immunocompromised.C. neoformanscan be phagocytosed by host phagocytes, but may manipulate the intracellular niche of phagocytes for replication and dissemination. The interaction of macrophages with cryptococcal cells has been studied in detail but little is known about the interaction between human peripheral blood mononuclear cells (PBMC) andC. neoformans. PBMCs are rapidly recruited to the site of initial infection in the lung, peripheral tissues, and also respond to cryptococci that disseminate via the bloodstream. Therefore, deciphering the interactions between PBMCs and cryptococci is an important but neglected aspect of our understanding of the immune response during cryptococcal infection. Here, using time lapse imaging of primary human PBMCsin vitro, we are able to measure the PBMC response to cryptococci. Using this approach we find that naïve, undifferentiated human monocytes phagocytose cryptococcal cells, and that aggregates (swarms) of monocytes and T cells often form in response to engulfment of cryptococci. Interestingly, we find a correlation between the size of the PBMC aggregates and proliferative ability of the cryptococci within. While these aggregates slow intracellular cryptococcal growth, cryptococci are able to replicate within this niche and escape from PBMCs to replicate extracellularly. These results provide evidence for PBMC control of cryptococcal infection and provide a model for thein vitrostudy of cryptococcal granuloma biology.
A cranio-incudo joint as the solution to early birth in marsupials and monotremes
Authors: Anthwal Neal , Fenelon Jane , Johnston Stephen D. , Renfree Marilyn B , Tucker Abigail S 
Published: April 2020

AbstractMammals articulate their jaws using a novel joint between the dentary and squamosal bones. In eutherian mammals, this joint forms in the embryo, supporting feeding and vocalisation from birth. In contrast, marsupials and monotremes exhibit extreme altriciality and are born before the bones of the novel mammalian jaw joint form. These mammals need to rely on other mechanisms to allow them to feed. Here we show that this vital function is carried out by the earlier developing, cartilaginous incus of the middle ear, abutting the cranial base to form a cranio-mandibular articulation. The nature of this articulation varies between monotremes and marsupials, with monotremes retaining a double articulation, similar to that described in the fossil mammaliaform,Morganucodon, while marsupials use a versican rich matrix to stabilise the jaw against the cranial base. These findings provide novel insight into the evolution of mammals and the relationship between the jaw and ear.
User-friendly, scalable tools and workflows for single-cell analysis
Authors: Moreno P. , Huang N. , Manning J.R. , Mohammed S. , Solovyev A. , Polanski K. , Chazarra R. , Talavera-Lopez C. , Doyle M. , Marnier G. , Grüning B. , Rasche H. , Bacon W. , Perez-Riverol Y. , Haeussler M. , Meyer K.B. , Teichmann S. , Papatheodorou I. 
Published: April 2020

AbstractSingle-cell RNA-Seq (scRNA-Seq) data analysis requires expertise in command-line tools, programming languages and scaling on compute infrastructure. As scRNA-Seq becomes widespread, computational pipelines need to be more accessible, simpler and scalable. We introduce an interactive analysis environment for scRNA-Seq, based on Galaxy, with ~70 functions from major single-cell analysis tools, which can be run on compute clusters, cloud providers or single machines, to bring compute to the data in scRNA-Seq.
Bet hedging buffers budding yeast against environmental instability
Authors: Bagamery Laura E. , Justman Quincey A. , Garner Ethan C. , Murray Andrew W. 
Published: April 2020

ABSTRACTTo grow and divide, cells must extract resources from dynamic and unpredictable environments. Organisms thus possess redundant metabolic pathways for distinct contexts. In budding yeast, ATP can be produced from carbon by mechanisms that prioritize either speed (fermentation) or yield (respiration). We find that in the absence of predictive cues, cells vary in their intrinsic ability to switch metabolic strategies from fermentation to respiration. We observe subpopulations of yeast cells which either rapidly adapt or enter a shock state characterized by deformation of many cellular structures, including mitochondria. This capacity to adapt is a bimodal and heritable state. We demonstrate that metabolic preparedness confers a fitness advantage during an environmental shift but is costly in a constant, high-glucose environment, and we observe natural variation in the frequency of prepared cells across wild yeast strains. These experiments suggest that bet-hedging has evolved in budding yeast.
Engineered lactobacilli display anti-biofilm and growth suppressing activities againstPseudomonas aeruginosa
Authors: Chappell Todd C. , Nair Nikhil U. 
Published: April 2020

AbstractBiofilms are an emerging target for new therapeutics in the effort to address the continued increase in resistance and tolerance to traditional antimicrobials. In particular, the distinct nature of the biofilm growth state often means that traditional antimicrobials, developed to combat planktonic cells, are ineffective. Biofilm treatments are designed to both reduce pathogen load at an infection site and decrease the development of resistance by rendering the embedded organisms more susceptible to treatment at lower antimicrobial concentrations. In this work, we developed a new antimicrobial treatment modality by characterizing the natural capacity of two lactobacilli,L. plantarumandL. rhamnosus, to inhibitP. aeruginosagrowth, biofilm formation, and biofilm viability. We further engineered these lactic acid bacteria (LAB) to secrete enzymes known to degradeP. aeruginosabiofilms and show that our best performing engineered LAB, secreting a pathogen-derived enzyme (PelAhyd), degrades up to 85 % ofP. aeruginosabiofilm.