bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large-scale monitoring of resistance to coumaphos, amitraz and pyrethroids inVarroa destructor
Authors: Hernández-Rodríguez Carmen Sara , Marín Óscar , Calatayud Fernando , Mahiques María José , Mompó Ana , Segura Inmaculada , Simó Enrique , González-Cabrera Joel 
Published: November 2020

ABSTRACTVarroa destructoris an ectoparasitic mite causing devastating damages to honey bee colonies around the world. Its impact is considered a major factor contributing to the significant seasonal losses of colonies recorded every year. Beekeepers are usually relying on a reduced set of acaricides to manage the parasite, usually the pyrethroids tau-fluvalinate or flumethrin, the organophosphate coumaphos and the formamidine amitraz. However, the evolution of resistance in the populations is leading to an unsustainable scenario with almost no alternatives to reach an adequate control of the mite.Here we present the results from the first, large-scale and extensive monitoring of the susceptibility to acaricides in the Comunitat Valenciana, one of the most prominent apicultural regions in Spain. Our ultimate goal was to provide beekeepers with timely information to help them decide what would be the best alternative for a long-term control of the mites in their apiaries. Our data show that there is a significant variation in the expected efficacy of coumaphos and pyrethroids across the region, indicating the presence of a different ratio of resistant individuals to these acaricides in each population. On the other hand, the expected efficacy of amitraz was more consistent, although slightly below the expected efficacy according to the label.HIGHLIGHTSVarroa destructoris causing severe damages to honey bee colonies worldwide.There are very few acaricides available to manage the parasite.The evolution of resistance is limiting our capacity to control the mite.We estimated the expected efficacy of the main acaricides in many Spanish apiaries.The information was shared with beekeepers for them to decide the best treatment to control the mite.
Rapid Anthropocene realignment of allometric scaling rules
Authors: Santini Luca , Isaac Nick J.B. 
Published: November 2020

AbstractThe negative relationship between body size and population density (SDR) in mammals is often interpreted as resulting from energetic constraints. In a global change scenario, however, this relationship might be expected to change, given the size-dependent nature of anthropogenic pressures and vulnerability to extinction. Here we test whether the SDR in mammals has changed over the last 50 years. We show that the relationship has shifted down and became shallower, corresponding to a decline in population density of 32-72%, for the largest and smallest mammals, respectively. However, the SDRs become steeper in some groups (e.g. carnivores) and shallower in others (e.g. herbivores). The Anthropocene reorganization of biotic systems is apparent in macroecological relationships that were previously believed to be immutable, reinforcing the notion that biodiversity pattens are contingent upon conditions at the time of investigation. We call for an increased attention on the role of global change on macroecological inferences.
Genome-wide association studies reveal the complex genetic architecture of DMI fungicide resistance inCercospora beticola
Authors: Spanner Rebecca , Taliadoros Demetris , Richards Jonathan , Rivera-Varas Viviana , Neubauer Jonathan , Natwick Mari , Hamilton Olivia , Vaghefi Niloofar , Pethybridge Sarah , Secor Gary A. , Friesen Timothy L. , Stukenbrock Eva H. , Bolton Melvin D. 
Published: November 2020

AbstractCercospora leaf spot is the most important disease of sugar beet worldwide. The disease is caused by the fungusCercospora beticolaand is managed principally by timely application of fungicides including those of the sterol demethylation inhibitor (DMI) class. However, reliance on DMIs has caused an increase in resistance to this class of fungicides in multipleC. beticolapopulations. To better understand the genetic and evolutionary basis for resistance inC. beticola, a genome-wide association study (GWAS) and selective sweep analysis were conducted for the first time in this fungal plant pathogen. We performed whole genome resequencing of 190C. beticolaisolates predominantly from North Dakota and Minnesota that were phenotyped for sensitivity to tetraconazole, the most widely used DMI fungicide in this region. GWAS identified mutations in genes associated with DMI fungicide resistance including a Regulator of G-protein Signaling (RGS) protein, an ATP-binding cassette (ABC) pleiotropic drug resistance transporter, a dual-specificity tyrosine phosphorylation-regulated kinase (DYRK), and a gene annotated as a hypothetical protein. A SNP upstream ofCbCYP51, the gene encoding the target of DMI fungicides, was also identified via GWAS. Haplotype analysis of CbCYP51 identified a synonymous mutation (E170) in high linkage disequilibrium with the upstream SNP, and multiple non-synonymous mutations (L144F, I387M and Y464S) associated with DMI resistance. Additionally, a putative codon bias effect for the L144F substitution was identified that generated different resistance potentials. We also identified a CbCYP51 paralog inC. beticola, CbCYP51-like, with high protein homology to CYP51C found uniquely inFusariumspecies butCbCYP51-likedoes not appear to influence DMI sensitivity. Genome-wide scans of selection showed that several of the GWAS mutations for fungicide resistance resided in regions that have recently undergone a selective sweep. Using radial plate growth on selected media as a fitness proxy, we did not find a trade-off associated with DMI fungicide resistance suggesting that resistance mutations can persist inC. beticolapopulations. Taken together, we show that population genomic data from a crop pathogen can allow the identification of mutations conferring fungicide resistance and inform about their origins in the pathogen population.
Sex-specific Alterations in Hepatic Cholesterol Metabolism in Young Uteroplacental Insufficiency-induced Low Birth Weight Adult Guinea Pig Offspring
Authors: Sarr Ousseynou , Mathers Katherine E. , Vanderboor Christina , Devgan Aditya , Hardy Daniel B. , Zhao Lin , Regnault Timothy R.H. 
Published: November 2020

AbstractBackgroundIntrauterine growth restriction (IUGR) and low birth weight (LBW) have been widely reported as an independent risk factor for hypercholesterolemia and increased hepatic cholesterol underlying liver dysfunction in adulthood. However, the specific impact of uteroplacental insufficiency (UPI), a leading cause of LBW in developed world, on hepatic cholesterol metabolism in later life, is ill defined and is clinically relevant in understanding later life liver metabolic health trajectories.MethodsHepatic cholesterol metabolism pathways were studied in uterine artery ablation-induced LBW and normal birth weight (NBW) male and female guinea pig offspring at postnatal day 150.ResultsHepatic free and total cholesterol were increased in LBWversusNBW males. Transcriptome analysis of LBWversusNBW livers revealed that “Cholesterol metabolism” was an enriched pathway in LBW males but not females. Microsomal triglyceride transfer protein and cytochrome P450 7A1 protein, involved in hepatic cholesterol efflux and catabolism, respectively, and catalase activity were decreased in LBW male livers. Superoxide dismutase activity was reduced in LBW males but increased in LBW females.ConclusionsUPI environment is associated with a later life programed hepatic cholesterol accumulation via impaired cholesterol elimination, in a sex-specific manner. These programmed alterations could underlie later life cholesterol-induced hepatic lipotoxicity in LBW male offspring.Impact StatementLow birth weight (LBW) is a risk factor for adult hypercholesterolemia and increased hepatic cholesterol.Uteroplacental insufficiency (UPI) resulting in LBW increased hepatic cholesterol content, altered hepatic expression of cholesterol metabolism-related genes in young adult guinea pigs.UPI-induced LBW was also associated with markers of a compromised hepatic cholesterol elimination process and failing antioxidant system in young adult guinea pigs.These changes, at the current age studied, were sex-specific, only being observed in LBW males and not LBW females.These programmed alterations could lead to further hepatic damage and greater predisposition to liver diseases in UPI-induced LBW male offspring as they age.
ABLE: Attention Based Learning for Enzyme Classification
Authors: Mohan Vamsi Nallapareddy , Dwivedula Rohit 
Published: November 2020

AbstractClassifying proteins into their respective enzyme class is an interesting question for researchers for a variety of reasons. The open source Protein Data Bank (PDB) contains more than 1,60,000 structures, with more being added everyday. This paper proposes an attention-based bidirectional-LSTM model (ABLE) trained on oversampled data generated by SMOTE to analyse and classify a protein into one of the six enzyme classes or a negative class using only the primary structure of the protein described as a string by the FASTA sequence as an input. We achieve the highest F1-score of 0.834 using our proposed model on a dataset of proteins from the PDB. We baseline our model against seventeen other machine learning and deep learning models, including CNN, LSTM, BILSTM and GRU. We perform extensive experimentation and statistical testing to corroborate our results.
Pseudoreplication in genomics-scale datasets
Authors: Waples Robin S. , Waples Ryan K. , Ward Eric J. 
Published: November 2020

AbstractIn genomics-scale datasets, loci are closely packed within chromosomes and hence provide correlated information. Averaging across loci as if they were independent creates pseudoreplication, which reduces the effective degrees of freedom (df’) compared to the nominal degrees of freedom,df. This issue has been known for some time, but consequences have not been systematically quantified across the entire genome. Here we measured pseudoreplication (quantified by the ratiodf’/df) for a common metric of genetic differentiation (FST) and a common measure of linkage disequilibrium between pairs of loci (r2). Based on data simulated using models (SLiMandmsprime) that allow efficient forward-in-time and coalescent simulations while precisely controlling population pedigrees, we estimateddf’anddf’/dfby measuring the rate of decline in the variance of meanFSTand meanr2as more loci were used. For both indices,df’increases withNeand genome size, as expected. However, even for largeNeand large genomes,df’for meanr2plateaus after a few thousand loci, and a variance components analysis indicates that the limiting factor is uncertainty associated with sampling individuals rather than genes. Pseudoreplication is less extreme forFST, butdf’/df≤0.01 can occur in datasets using tens of thousands of loci. Commonly-used block-jackknife methods consistently overestimated var(FST), producing very conservative confidence intervals. Predictingdf’based on our modeling results as a function ofNe,L,S, and genome size provides a robust way to quantify precision associated with genomics-scale datasets.
Defining the ultrastructure of the hematopoietic stem cell niche by correlative light and electron microscopy
Authors: Agarwala Sobhika , Kim Keun-Young , Phan Sebastien , Ju Saeyeon , Kong Ye Eun , Castillon Guillaume A. , Bushong Eric A. , Ellisman Mark H. , Tamplin Owen J. 
Published: November 2020

AbstractThe blood system is supported by hematopoietic stem and progenitor cells (HSPCs) found in a specialized microenvironment called the niche. Many different niche cell types support HSPCs, however how they interact and their ultrastructure has been difficult to define. Here we show that single endogenous HSPCs can be tracked by light microscopy, then identified by serial block-face scanning electron microscopy (SBEM) at multiscale levels. Using the zebrafish larval kidney marrow (KM) niche as a model, we followed single fluorescently-labeled HSPCs by light sheet microscopy, then confirmed their exact location in a 3D SBEM dataset. Our approach allowed us to identify dopamine beta-hydroxylase (dbh) positive ganglia cells as a previously uncharacterized functional cell type in the HSPC niche. By integrating multiple imaging modalities, we could resolve the ultrastructure of single rare cells deep in live tissue and define all contacts between an HSPC and its surrounding niche cell types.
Bayesian modeling of skewed X inactivation in genetically diverse mice identifies a novelXceallele associated with copy number changes
Authors: Sun Kathie Y , Oreper Daniel , Schoenrock Sarah A , McMullan Rachel , Giusti-Rodríguez Paola , Zhabotynsky Vasyl , Miller Darla R , Tarantino Lisa M , Villena Fernando Pardo-Manuel de , Valdar William 
Published: November 2020

ABSTRACTFemale mammals are functional mosaics of their parental X-linked gene expression due to X chromosome inactivation (XCI). This process inactivates one copy of the X chromosome in each cell during embryogenesis and that state is maintained clonally through mitosis. In mice, the choice of which parental X chromosome remains active is determined by the X chromosome controlling element (Xce), which has been mapped to a 176 kb candidate interval. A series of functionalXcealleles has been characterized or inferred for classical inbred strains based on biased, or skewed, inactivation of the parental X chromosomes in crosses between strains. To further explore the function-structure basis and location of theXce, we measured allele-specific expression of X-linked genes in a large population of F1 females generated from Collaborative Cross strains. Using published sequence data and applying a Bayesian “Pólya urn” model of XCI skew, we report two major findings. First, inter-individual variability in XCI suggests mouse epiblasts contain on average 20-30 cells contributing to brain. Second, NOD/ShiLtJ has a novel and unique functional allele,Xcef, that is the weakest in theXceallelic series. Despite phylogenetic analysis confirming that NOD/ShiLtJ carries a haplotype almost identical to the well-characterized C57BL/6J (Xceb), we observed unexpected patterns of XCI skewing in females carrying the NOD/ShiLtJ haplotype within theXce. Copy number variation is common at theXcelocus and we conclude that the observed allelic series is a product of independent and recurring duplications shared between weakXcealleles.
Contemplative mental training reduces hair glucocorticoid levels in a randomized clinical trial
Authors: Puhlmann Lara M.C. , Vrtička Pascal , Linz Roman , Stalder Tobias , Kirschbaum Clemens , Engert Veronika , Singer Tania 
Published: November 2020

AbstractObjectiveThis study had the objective to investigate the effect of regular contemplative mental training on endocrine indices of long-term stress.MethodsAn open-label efficacy trial comprising three distinct 3-month modules targeting attention and interoception, socio-affective or socio-cognitive abilities through dyadic exercises and secularised meditation practices was designed and carried out in 332 healthy meditation-naive adults. Participants underwent the training for up to 9 months or were assigned to a retest control cohort. Chronic stress indices were assayed at four timepoints, i.e., pre-training and following each module. The main outcome measures were cortisol and cortisone concentration in hair and self-reported chronic stressResultsN=362 initial individuals were randomized, of whom n=30 dropped out before study initiation, n=4 before first sampling and n=2 were excluded. N=99 participants did not provide hair samples. Data from three separate training cohorts revealed consistent decreases in hair cortisol and cortisone levels over the training period. This effect increased with practice frequency, was independent of training content and not associated with change in self-reported chronic stress.ConclusionsOur results point to the reduction of long-term cortisol exposure as a mechanism via which contemplative mental training may exert positive effects on practitioners’ health.Trial registrationClinicalTrials.gov identifier:NCT01833104
Brief Report: The Virucidal Efficacy of Oral Rinse Components Against SARS-CoV-2 In Vitro
Authors: Statkute Evelina , Rubina Anzelika , O’Donnell Valerie B , Thomas David W. , Stanton Richard J. 
Published: November 2020

AbstractThe ability of widely-available mouthwashes to inactivate SARS-CoV-2 in vitro was tested using a protocol capable of detecting a 5-log10 reduction in infectivity, under conditions mimicking the naso/oropharynx. During a 30 second exposure, two rinses containing cetylpyridinium-chloride and a third with ethanol/ethyl lauroyl arginate eliminated live virus to EN14476 standards (>4-log10 reduction), while others with ethanol/essential oils and povidone-iodine (PVP-I) eliminated virus by 2-3-log10. Chlorhexidine or ethanol alone displayed little or no ability to inactivate virus. Studies are warranted to determine whether these formulations can inactivate virus in the human oropharynxin vivo, and whether this might impact transmission risk.
In VitroActivity of Itraconazole Against SARS-CoV-2
Authors: Van Damme Ellen , De Meyer Sandra , Bojkova Denisa , Ciesek Sandra , Cinatl Jindrich , De Jonghe Steven , Jochmans Dirk , Leyssen Pieter , Buyck Christophe , Neyts Johan , Van Loock Marnix 
Published: November 2020

AbstractBackgroundAs long as there is no vaccine available, having access to inhibitors of SARS-CoV-2 will be of utmost importance. Antivirals against coronaviruses do not exist, hence global drug re-purposing efforts have been carried out to identify agents that may provide clinical benefit to patients with COVID-19. Itraconazole, an antifungal agent, has been reported to have potential activity against animal coronaviruses.MethodsUsing cell-based phenotypic assays, thein vitroantiviral activity of itraconazole and 17-OH itraconazole was assessed against clinical isolates from a German and Belgian patient infected with SARS-CoV-2.ResultsItraconazole demonstrated antiviral activity in human Caco-2 cells (EC50= 2.3 μM; MTT assay). Similarly, its primary metabolite, 17-OH itraconazole, showed inhibition of SARS-CoV-2 activity (EC50= 3.6 μM). Remdesivir inhibited viral replication with an EC50= 0.4 μM. Itraconazole and 17-OH itraconazole resulted in a viral yield reductionin vitroof approximately 2-log10and approximately 1-log10, as measured in both Caco-2 cells and VeroE6-eGFP cells, respectively. The viral yield reduction brought about by remdesivir or GS-441524 (parent nucleoside of the antiviral prodrug remdesivir; positive control) was more pronounced, with an approximately 3 log10drop and >4 log10drop in Caco-2 cells and VeroE6-eGFP cells, respectively.DiscussionItraconazole and 17-OH itraconazole exertin vitrolow micromolar activity against SARS-CoV-2. Despite thein vitroantiviral activity, itraconazole did not result in a beneficial effect in hospitalized COVID-19 patients in a clinical study (EudraCT Number: 2020-001243-15).HighlightsItraconazole exertedin vitrolow micromolar activity against SARS-CoV-2 (EC50= 2.3 μM)Remdesivir demonstrated potent antiviral activity, confirming validity of the assayItraconazole has since shown no efficacy in a clinical study in hospitalized COVID-19 patients
Conserved prolines in the coiled coil-OB domain linkers of proteasomal ATPases facilitate eukaryotic proteasome base assembly
Authors: Cheng Chin Leng , Wong Michael K , Li Yanjie , Hochstrasser Mark 
Published: November 2020

AbstractThe proteasome is a large protease complex that degrades both misfolded and regulatory proteins. In eukaryotes, the 26S proteasome contains six different AAA+ ATPase subunits, Rpt1-Rpt6, which form a hexameric ring as part of the base subcomplex that drives unfolding and translocation of substrates into the proteasome core. Archaeal proteasomes contain only a single type of ATPase subunit, the proteasome-activating nucleotidase (PAN), which forms a trimer-of-dimers and is homologous to the eukaryotic Rpt subunits. A key PAN proline residue (P91) formscisandtranspeptide bonds in successive subunits around the ring, allowing efficient dimerization through upstream coiled coils. The importance of the equivalent Rpt prolines in eukaryotic proteasome assembly was unknown. We show an equivalent proline is strictly conserved in Rpt3 (inS. cerevisiae, P93) and Rpt5 (P76), well conserved in Rpt2 (P103), and loosely conserved in Rpt1 (P96) in deeply divergent eukaryotes, but in no case is its mutation strongly deleterious to yeast growth. However, therpt2-P103A,rpt3-P93A, andrpt5-P76Amutations all cause synthetic defects with specific base assembly chaperone deletions. The Rpt5-P76A mutation decreases the levels of the protein and induces a mild proteasome assembly defect. The yeastrpt2-P103A rpt5-P76Adouble mutant has strong growth defects attributable to defects in proteasome base formation. Several Rpt subunits in this mutant form aggregates that are cleared, at least in part, by the Hsp42-mediated protein quality control (PQC) machinery. We propose that the conserved Rpt linker prolines promote efficient 26S proteasome base assembly by facilitating specific ATPase heterodimerization.
Keeping weight off: Mindfulness-Based Stress Reduction alters amygdala functional connectivity during weight loss maintenance in a randomized control trial
Authors: Chumachenko Serhiy Y. , Cali Ryan , Rosal Milagros C. , Allison Jeroan , Person Sharina , Ziedonis Douglas , Nephew Benjamin C. , Moore Constance M. , Zhang Nanyin , King Jean A. , Fulwiler Carl 
Published: November 2020

AbstractObesity is associated with significant comorbidities and financial costs. While behavioral interventions produce clinically meaningful weight loss, weight loss maintenance is challenging. The objective was to improve understanding of the neural and psychological mechanisms modified by mindfulness that may predict clinical outcomes.Individuals who intentionally recently lost weight were randomized to Mindfulness-Based Stress Reduction (MBSR) or a control healthy living course. Anthropometric and psychological factors were measured at baseline, 8 weeks and 6 months. Functional connectivity (FC) analysis was performed at baseline and 8 weeks to examine FC changes between regions of interest selected a priori, and independent components identified by independent component analysis. The association of pre-post FC changes with 6-month weight and psychometric outcomes was then analyzed.Significant group x time interaction was found for FC between the amygdala and ventromedial prefrontal cortex, such that FC increased in the MBSR group and decreased in controls. Non-significant changes in weight were observed at 6 months, where the mindfulness group maintained their weight while the controls showed a weight increase of 3.4% in BMI. Change in FC at 8-weeks between ventromedial prefrontal cortex and several ROIs was associated with change in depression symptoms but not weight at 6 months. This pilot study provides preliminary evidence of neural mechanisms that may be involved in MBSR’s impact on weight loss maintenance that may be useful for designing future clinical trials and mechanistic studies.