bluuebunny/crossref_metadata_2025_split huggingface dataset:
No evidence of coronaviruses or other potentially zoonotic viruses in Sunda pangolins (Manis javanica) entering the wildlife trade via Malaysia
Authors: Lee Jimmy , Hughes Tom , Lee Mei-Ho , Field Hume , Rovie-Ryan Jeffrine Japning , Sitam Frankie Thomas , Sipangkui Symphorosa , Nathan Senthilvel K.S.S. , Ramirez Diana , Kumar Subbiah Vijay , Lasimbang Helen , Epstein Jonathan H. , Daszak Peter 
Published: June 2020

AbstractThe legal and illegal trade in wildlife for food, medicine and other products is a globally significant threat to biodiversity that is also responsible for the emergence of pathogens that threaten human and livestock health and our global economy. Trade in wildlife likely played a role in the origin of COVID-19, and viruses closely related to SARS-CoV-2 have been identified in bats and pangolins, both traded widely. To investigate the possible role of pangolins as a source of potential zoonoses, we collected throat and rectal swabs from 334 Sunda pangolins (Manis javanica) confiscated in Peninsular Malaysia and Sabah between August 2009 and March 2019. Total nucleic acid was extracted for viral molecular screening using conventional PCR protocols used to routinely identify known and novel viruses in extensive prior sampling (>50,000 mammals). No sample yielded a positive PCR result for any of the targeted viral families – Coronaviridae, Filoviridae, Flaviviridae, Orthomyxoviridae and Paramyxoviridae. In light of recent reports of coronaviruses including a SARS-CoV-2 related virus in Sunda pangolins in China, the lack of any coronavirus detection in our ‘upstream’ market chain samples suggests that these detections in ‘downstream’ animals more plausibly reflect exposure to infected humans, wildlife or other animals within the wildlife trade network. While confirmatory serologic studies are needed, it is likely that Sunda pangolins are incidental hosts of coronaviruses. Our findings further support the importance of ending the trade in wildlife globally.
Transcriptomic signatures associated with regional cortical thickness changes in Parkinson’s disease
Authors: Keo Arlin , Dzyubachyk Oleh , van der Grond Jeroen , van Hilten Jacobus J. , Reinders Marcel J. T. , Mahfouz Ahmed 
Published: June 2020

AbstractCortical atrophy is a common manifestation in Parkinson’s disease, particularly in later disease stages. Here, we investigated patterns of cortical thickness using T1-weighted anatomical MRI data of 149 Parkinson’s disease patients and 369 controls. To elucidate the molecular underpinnings of cortical thickness changes in Parkinson’s disease, we performed an integrated analysis of brain-wide healthy transcriptomic data from the Allen Human Brain Atlas and neuroimaging features. For this purpose, we used partial least squares regression to identify gene expression patterns correlated with cortical thickness changes. In addition, we identified gene expression patterns underlying the relationship between cortical thickness and clinical domains of Parkinson’s disease. Our results show that genes whose expression in the healthy brain is associated with cortical thickness changes in Parkinson’s disease are enriched in biological pathways related to sumoylation, regulation of mitotic cell cycle, mitochondrial translation, DNA damage responses, and ER-Golgi traffic. The associated pathways were highly related to each other and all belong to cellular maintenance mechanisms. The expression of genes within most pathways was negatively correlated with cortical thickness changes, showing higher expression in regions associated with decreased cortical thickness (atrophy). On the other hand, sumoylation pathways were positively correlated with cortical thickness changes, showing higher expression in regions with increased cortical thickness (hypertrophy). Our findings suggest that alterations in the balanced interplay of these mechanisms play a role in changes of cortical thickness in Parkinson’s disease and possibly influence motor and cognitive functions.
Shortlisting genes important in seed maturation by principal component analysis of gene expression data
Authors: Pathak Ashish K , Singla Ridhima , Juneja Mamta , Tuli Rakesh 
Published: June 2020

AbstractTranscriptome data are widely used for functional analysis of genes. De-novo assembly of transcriptome gives a large number of unigenes. A large proportion of them remain unannotated. Efficient computational methods are required for identifying genes and modeling those for regulatory and functional roles. Principal component analysis (PCA) was used in a novel approach to shortlist genes, independently of annotation in genome expression data, taking seed development inArabidopsis thalianaas a representative case. PCA was applied to published genome expression data from four lines of Arabidopsis, mutated in seed development. The PC separating all the developmental stages between a mutant and its respective wild type was selected for shortlisting genes as functionally more important. The shortlisted genes identified by PCA belong to a number of biological functions. The genes reported to give sensitivity to desiccation were identified in PCA analysis also in desiccation intolerant lines only. With respect to the network of 98 genes targeted by ABI3, a higher number of genes was identified as important in the mutants abi 3-5, fus 3-3 andlec 1-1 in comparison to abi 3-1. Ontological analysis and comparison with earlier studies suggest that PCA of genome expression data is useful for shortlisting functionally important genes.
Antiviral treatment of SARS-CoV-2-infected hamsters reveals a weak effect of favipiravir and a complete lack of effect for hydroxychloroquine
Authors: Kaptein Suzanne JF , Jacobs Sofie , Langendries Lana , Seldeslachts Laura , ter Horst Sebastiaan , Liesenborghs Laurens , Hens Bart , Vergote Valentijn , Heylen Elisabeth , Maas Elke , De Keyzer Carolien , Bervoets Lindsey , Rymenants Jasper , Van Buyten Tina , Thibaut Hendrik Jan , Dallmeier Kai , Boudewijns Robbert , Wouters Jens , Augustijns Patrick , Verougstraete Nick , Cawthorne Christopher , Weynand Birgit , Annaert Pieter , Spriet Isabel , Velde Greetje Vande , Neyts Johan , Rocha-Pereira Joana , Delang Leen 
Published: June 2020

AbstractSARS-CoV-2 rapidly spread around the globe after its emergence in Wuhan in December 2019. With no specific therapeutic and prophylactic options available, the virus was able to infect millions of people. To date, close to half a million patients succumbed to the viral disease, COVID-19. The high need for treatment options, together with the lack of small animal models of infection has led to clinical trials with repurposed drugs before any preclinicalin vivoevidence attesting their efficacy was available. We used Syrian hamsters to establish a model to evaluate antiviral activity of small molecules in both an infection and a transmission setting. Upon intranasal infection, the animals developed high titers of SARS-CoV-2 in the lungs and pathology similar to that observed in mild COVID-19 patients. Treatment of SARS-CoV-2-infected hamsters with favipiravir or hydroxychloroquine (with and without azithromycin) resulted in respectively a mild or no reduction in viral RNA and infectious virus. Micro-CT scan analysis of the lungs showed no improvement compared to non-treated animals, which was confirmed by histopathology. In addition, both compounds did not prevent virus transmission through direct contact and thus failed as prophylactic treatments. By modelling the PK profile of hydroxychloroquine based on the trough plasma concentrations, we show that the total lung exposure to the drug was not the limiting factor. In conclusion, we here characterized a hamster infection and transmission model to be a robust model for studyingin vivoefficacy of antiviral compounds. The information acquired using hydroxychloroquine and favipiravir in this model is of critical value to those designing (current and) future clinical trials. At this point, the data here presented on hydroxychloroquine either alone or combined with azithromycin (together with previously reportedin vivodata in macaques and ferrets) provide no scientific basis for further use of the drug in humans.
Genetic architecture and gene mapping of cyanide in cassava (Manihot esculenta Crantz.)
Authors: Ogbonna Alex C , de Andrade Luciano Rogerio Braatz , Rabbi Ismail Y. , Mueller Lukas A. , de Oliveira Eder Jorge , Bauchet Guillaume J. 
Published: June 2020

AbstractCassava is a root crop originating from South America and a major staple crop in the Tropics, including marginal environments. In this study, we focused on South American and African cassava germplasm and investigated the genetic architecture of Hydrogen Cyanide (HCN), a major component of tuber quality. HCN is a plant defense component against herbivory but also toxic for human consumption. We genotyped 3,354 landraces and modern breeding lines originating from 26 Brazilian states and 1,389 individuals were phenotypically characterized across multi-year trials for HCN. All plant material was subjected to high density genotyping using Genotyping-by-sequencing (GBS). We performed genome wide association mapping (GWAS) to characterize the genetic architecture and gene mapping of HCN. Field experiment revealed strong broad and narrow-sense trait heritability (0.82 and 0.41 respectively). Two major loci were identified, encoding for an ATPase and a MATE protein and contributing up to 7% and 30% of the cyanide concentration in roots, respectively. We developed diagnostic markers for breeding applications, validated trait architecture consistency in African germplasm and investigated further evidence for domestication of sweet and bitter cassava. Fine genomic loci characterization indicate; (i) a major role played by vacuolar transporter in regulating HCN content, (ii) co-domestication of sweet and bitter cassava major alleles to be geographical zone dependant, and (ii) major loci allele for high cyanide cassava inManihot esculenta Crantzseems to originate from its ancestor,M. esculentassp.flabellifolia.Taken together these findings expand insights on cyanide in cassava and its glycosylated derivatives in plants.One-sentence summaryIdentification of an intracellular transporter gene and its allelic variation allow to point out cultivars with up to 30 percent decrease in cassava root cyanide content, toxic for human consumption.
IGF2BP1 is a targetable SRC/MAPK-dependent driver of invasive growth in ovarian cancer
Authors: Bley Nadine , Schott Annekatrin , Müller Simon , Misiak Danny , Lederer Marcell , Fuchs Tommy , Aßmann Chris , Glaß Markus , Ihling Christian , Sinz Andrea , Pazaitis Nikolaos , Wickenhauser Claudia , Vetter Martina , Ungurs Olga , Strauss Hans-Georg , Thomssen Christoph , Hüttelmaier Stefan 
Published: June 2020

AbstractEpithelial-to-mesenchymal transition (EMT) is a hallmark of aggressive, mesenchymal-like high-grade serous ovarian carcinoma (HG-SOC). The SRC kinase is a key driver of cancer-associated EMT promoting adherens junction (AJ) disassembly by phosphorylation-driven internalization and degradation of AJ proteins. Here we show, that the IGF2 mRNA binding protein 1 (IGF2BP1) is up-regulated in mesenchymal-like HG-SOC and promotes SRC activation by a previously unknown protein-ligand-induced, but RNA-independent mechanism. IGF2BP1-driven invasive growth of ovarian cancer cells essentially relies on the SRC-dependent disassembly of AJs. Concomitantly, IGF2BP1 enhances ERK2 expression in a RNA-binding dependent manner. Together this reveals a post-transcriptional mechanism of interconnected stimulation of SRC/ERK signaling in ovarian cancer cells. The IGF2BP1-SRC/ERK2 axis is targetable by the SRC-inhibitor saracatinib and MEK-inhibitor selumetinib. However, due to IGF2BP1-directed stimulation only combinatorial treatment effectively overcomes the IGF2BP1-promoted invasive growth in 3D culture conditions as well as intraperitoneal mouse models. In conclusion, we reveal an unexpected role of IGF2BP1 in enhancing SRC/MAPK-driven invasive growth of ovarian cancer cells. This provides a rational for the therapeutic benefit of combinatorial SRC/MEK inhibition in mesenchymal-like HG-SOC.Graphical Abstract
Developmental Influences on Symptom Expression in Antipsychotic-Naïve First-Episode Psychosis
Authors: Bridgwater Miranda , Bachman Peter , Tervo-Clemmens Brenden , Haas Gretchen , Hayes Rebecca , Luna Beatriz , Salisbury Dean F. , Jalbrzikowski Maria 
Published: June 2020

AbstractIntroductionThe neurodevelopmental model of psychosis was established over 30 years ago; however, the developmental influence on psychotic symptom expression – how a person’s age affects clinical presentation in first-episode psychosis – has not been thoroughly investigated.MethodUsing generalized additive modeling, which allows for linear and non-linear functional forms of age-related change, we leveraged symptom data from a large sample of antipsychotic-naïve individuals experiencing a first episode of psychosis (N=340, 12-40 years, 1-12 visits), collected at the University of Pittsburgh from 1990-2017. We examined relationships between age and severity of perceptual and non-perceptual positive symptoms and negative symptoms. We also tested for age-associated effects onchangein positive or negative symptom severity following baseline assessment, and explored the time-varying relationship between perceptual and non-perceptual positive symptoms across adolescent development.ResultsIn the cross-sectional and longitudinal data, perceptual positive symptoms significantly decreased with increasing age (F=7.0, p=0.0007; q=0.003) while non-perceptual positive symptoms increased with increasing age (F=4.1,p=0.01,q=0.02). These relationships remained significant when SES, IQ, and illness duration were included as covariates. There were no developmental effects on change in positive or negative symptom severity (allp>0.25). Finally, an association between severity of non-perceptual and perceptual symptoms developed with increasing age, with a significant association starting at age 18.ConclusionThese findings suggest that as cognitive maturation proceeds, perceptual symptoms attenuate while non-perceptual symptoms are enhanced, reflecting influences of developmental processes on psychosis expression. Findings underscore how pathological brain-behavior relationships vary as a function of development.
The legacy of recurrent introgression during the radiation of hares
Authors: Ferreira Mafalda S. , Jones Matthew R. , Callahan Colin M. , Farelo Liliana , Tolesa Zelalem , Suchentrunk Franz , Boursot Pierre , Mills L. Scott , Alves Paulo C. , Good Jeffrey M. , Melo-Ferreira José 
Published: June 2020

AbstractHybridization may often be an important source of adaptive variation, but the extent and long-term impacts of introgression have seldom been evaluated in the phylogenetic context of a radiation. Hares (Lepus) represent a widespread mammalian radiation of 32 extant species characterized by striking ecological adaptations and recurrent admixture. To understand the relevance of introgressive hybridization during the diversification ofLepus, we analyzed whole exome sequences (61.7 Mb) from 15 species of hares (1- 4 individuals per species), spanning the global distribution of the genus, and two outgroups. We used a coalescent framework to infer species relationships and divergence times, despite extensive genealogical discordance. We found high levels of allele sharing among species and show that this reflects extensive incomplete lineage sorting and temporally layered hybridization. Our results revealed recurrent introgression at all stages along theLepusradiation, including recent gene flow between extant species since the last glacial maximum, but also pervasive ancient introgression occurring since near the origin of the hare lineages. We show that ancient hybridization between northern hemisphere species has resulted in shared variation of potential adaptive relevance to highly seasonal environments, including genes involved in circadian rhythm regulation, pigmentation, and thermoregulation. Our results illustrate how the genetic legacy of ancestral hybridization may persist across a radiation, leaving a long-lasting signature of shared genetic variation that may contribute to adaptation within and among species.
Rapid kinetics of lipid second messengers controlled by a cGMP signalling network coordinates apical complex functions inToxoplasmatachyzoites
Authors: Katris Nicholas J. , Yamaryo-Botte Yoshiki , Janouškovec Jan , Shunmugam Serena , Arnold Christophe-Sebastien , Yang Annie S. P. , Vardakis Alexandros , Stewart Rebecca J. , Sauerwein Robert , McFadden Geoffrey I. , Tonkin Christopher J. , Cesbron-Delauw Marie-France , Waller Ross. F. , Botte Cyrille Y. 
Published: June 2020

ABSTRACTHost cell invasion and subsequent egress byToxoplasmaparasites is regulated by a network of cGMP, cAMP, and calcium signalling proteins. Such eukaryotic signalling networks typically involve lipid second messengers including phosphatidylinositol phosphates (PIPs), diacylglycerol (DAG) and phosphatidic acid (PA). However, the lipid signalling network inToxoplasmais poorly defined. Here we present lipidomic analysis of a mutant of central flippase/guanylate cyclase TgGC inToxoplasma, which we show has disrupted turnover of signalling lipids impacting phospholipid metabolism and membrane stability. The turnover of signalling lipids is extremely rapid in extracellular parasites and we track changes in PA and DAG to within 5 seconds, which are variably defective upon disruption of TgGC and other signalling proteins. We then identify the position of each protein in the signal chain relative to the central cGMP signalling protein TgGC and map the lipid signal network coordinating conoid extrusion and microneme secretion for egress and invasion.
A Biodiversity Composition Map of California Derived from Environmental DNA Metabarcoding and Earth Observation
Authors: Lin Meixi , Simons Ariel Levi , Curd Emily E. , Harrigan Ryan J. , Schneider Fabian D. , Ruiz-Ramos Dannise V. , Gold Zack , Osborne Melisa G. , Shirazi Sabrina , Schweizer Teia M. , Moore Tiara N. , Fox Emma A. , Turba Rachel , Garcia-Vedrenne Ana E. , Helman Sarah K. , Rutledge Kelsi , Mejia Maura Palacios , Munguia Ramos Miroslava N. , Wetzer Regina , Pentcheff Dean , McTavish Emily Jane , Dawson Michael N. , Shapiro Beth , Wayne Robert K. , Meyer Rachel S. 
Published: June 2020

AbstractUnique ecosystems globally are under threat from ongoing anthropogenic environmental change. Effective conservation management requires more thorough biodiversity surveys that can reveal system-level patterns and that can be applied rapidly across space and time. We offer a way to use environmental DNA, community science and remote sensing together as methods to reduce the discrepancy between the magnitude of change and historical approaches to measure it. Taking advantages of modern ecological models, we integrate environmental DNA and Earth observations to evaluate regional biodiversity patterns for a snapshot of time, and provide critical community-level characterization. We collected 278 samples in Spring 2017 from coastal, shrub and lowland forest sites in California, a large-scale biodiversity hotspot. We applied gradient forest to model 915 family occurrences and community composition together with environmental variables and multi-scalar habitat classifications to produce a statewide biodiversity-based map. 16,118 taxonomic entries recovered were associated with environmental variables to test their predictive strength on alpha, beta, and zeta diversity. Local habitat classification was diagnostic of community composition, illuminating a characteristic of biodiversity hotspots. Using gradient forest models, environmental variables predicted 35% of the variance in eDNA patterns at the family level, with elevation, sand percentage, and greenness (NDVI32) as the top predictors. This predictive power was higher than we found in published literature at global scale. In addition to this indication of substantial environmental filtering, we also found a positive relationship between environmentally predicted families and their numbers of biotic interactions. In aggregate, these analyses showed that strong eDNA community-environment correlation is a general characteristic of temperate ecosystems, and may explain why communities easily destabilize under disturbances. Our study provides the first example of integrating citizen science based eDNA with biodiversity mapping across the tree of life, with promises to produce large scale, high resolution assessments that promote a more comprehensive and predictive understanding of the factors that influence biodiversity and enhance its maintenance.
Combined transient ablation and single cell RNA sequencing reveals the development of medullary thymic epithelial cells
Authors: Wells Kristen L. , Miller Corey N. , Gschwind Andreas R. , Wei Wu , Phipps Jonah D. , Anderson Mark S. , Steinmetz Lars M. 
Published: June 2020

AbstractMedullary thymic epithelial cells (mTECs) play a critical role in central immune tolerance by mediating negative selection of autoreactive T cells through the collective expression of the peripheral self-antigen compartment, including tissue-specific antigens (TSAs). Recent work has shown that gene expression patterns within the mTEC compartment are remarkably heterogenous and include multiple differentiated cell states. To further define mTEC development and medullary epithelial lineage relationships, we combined lineage tracing and recovery from transientin vivomTEC ablation with single cell RNA-sequencing. The combination of bioinformatic and experimental approaches revealed a non-stem transit-amplifying population of cycling mTECs that precededAireexpression. Based on our findings, we propose a branching model of mTEC development wherein a heterogeneous pool of transit-amplifying cells gives rise toAire- andCcl21a-expressing mTEC subsets. We further use experimental techniques to show that within theAire-expressing developmental branch, TSA expression peaked asAireexpression decreased, implyingAireexpression must be established before TSA expression can occur. Collectively, these data provide a higher order roadmap of mTEC development and demonstrate the power of combinatorial approaches leveraging bothin vivomodels and high-dimensional datasets.