bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unbalanced Sample Size Introduces Spurious Correlations to Genome-wide Heterozygosity Analyses
Authors: Liu Li , Caselli Richard J 
Published: February 2020

AbstractExcess of heterozygosity (H) is a widely used measure of genetic diversity of a population. As high-throughput sequencing and genotyping data become readily available, it has been applied to investigating the associations of genome-wide genetic diversity with human diseases and traits. However, these studies often report contradictory results. In this paper, we present a meta-analysis of five whole-exome studies to examine the association of H scores with Alzheimer’s disease. We show that the mean H score of a group is not associated with the disease status, but is associated with the sample size. Across all five studies, the group with more samples has a significantly lower H score than the group with fewer samples. To remove potential confounders in empirical data sets, we perform computer simulations to create artificial genomes controlled for the number of polymorphic loci, the sample size and the allele frequency. Analyses of these simulated data confirm the negative correlation between the sample size and the H score. Furthermore, we find that genomes with a large number of rare variants also have inflated H scores. These biases altogether can lead to spurious associations between genetic diversity and the phenotype of interest. Based on these findings, we advocate that studies shall balance the sample sizes when using genome-wide H scores to assess genetic diversities of different populations, which helps improve the reproducibility of future research.
DoesDrosophila sechelliaescape parasitoid attack by feeding on a toxic resource?
Authors: Salazar-Jaramillo Laura , Wertheim Bregje 
Published: February 2020

ABSTRACTHost shifts can drastically change the selective pressures that animals experience from their environment.Drosophila sechelliais a species restricted to the Seychelles islands, where it specialized on the fruitMorinda citrifolia(noni). This fruit is known to be toxic to closely relatedDrosophilaspecies, includingD. melanogasterandD. simulans, releasingD. sechelliafrom interspecific competition when breeding on this substrate. Previously, we showed thatD. sechelliais unable to mount an effective immunological response against wasp attack, while the closely-related species can defend themselves from parasitoid attack by melanotic encapsulation. We hypothesized that this inability constitutes a trait loss due to a reduced risk of parasitoid attack in noni. Here we present a field study aimed to test the hypothesis that specialization on noni has releasedD. sechelliafrom the antagonistic interaction with its larval parasitoids. Our results from the field survey indicate thatD. sechelliawas found in ripe noni, whereas anotherDrosophilaspecies,D. malerkotliana, was present in unripe and rotting stages. Parasitic wasps of the speciesLeptopilina boulardiemerged from rotten noni, whereD. malerkotlianawas the most abundant host. These results indicate that the specialization ofD. sechelliaon noni has indeed drastically altered its ecological interactions, leading to a relaxation in the selection pressure to maintain parasitoid resistance.
Transcranial Photobiomodulation with Near-Infrared Light from Childhood to Elderliness: Simulation of Dosimetry
Authors: Yuan Yaoshen , Cassano Paolo , Pias Matthew , Fang Qianqian 
Published: February 2020

AbstractSignificanceMajor depressive disorder (MDD) affects over 40 million US adults in their lifetimes. Transcranial photobiomodulation (t-PBM) has been shown to be effective in treating MDD, but the current treatment dosage does not account for anatomical head and brain changes due to aging.AimWe study effective t-PBM dosage and its variations across age groups using state-of-the-art Monte Caxrlo (MC) simulations and age-dependent brain atlases ranging between 5 to 85 years of age.ApproachAge-dependent brain models are derived from 18 MRI brain atlases. Two extracranial source positions, F3-F4 and Fp1-Fpz-Fp2 in the EEG 10-20 system, are simulated at five selected wavelengths and energy depositions at two MDD-relevant cortical regions – dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC) – are quantified.ResultsAn overall decrease of energy deposition was found with increasing age. A strong negative correlation between the thickness of extra-cerebral tissues (ECT) and energy deposition, suggesting that increasing ECT thickness over age is primarily responsible for reduced energy delivery. The F3-F4 position appears to be more efficient in reaching dlPFC compared to treating vmPFC via the Fp1-Fpz-Fp2 position.ConclusionQuantitative simulations revealed age-dependent light delivery across the lifespan of human brains, suggesting the needs for personalized and age-adaptive t-PBM treatment planning.
Abstract sequential task control is facilitated by practice and embedded motor sequences
Authors: Trach Juliana E. , McKim Theresa H. , Desrochers Theresa M. 
Published: February 2020

AbstractEveryday task sequences, such as cooking, contain overarching goals (completing the meal), sub-goals (prepare vegetables), and motor actions (chopping). Such tasks generally are considered hierarchical because superordinate levels (e.g., goals) affect performance at subordinate levels (e.g., sub-goals and motor actions). However, there is debate as to whether this hierarchy is “strict” with unidirectional, top-down influences, and it is unknown if and how practice affects performance at the superordinate levels. To investigate these questions, we manipulated practice with sequences at the goal and motor action levels using an abstract, or non-motor, task sequence paradigm (Desrochers et al., 2015; Schneider & Logan, 2006). In three experiments, participants performed memorized abstract task sequences composed of simple tasks (e.g., color/shape judgements), where some contained embedded motor response sequences. We found that practice facilitated performance and reduced control costs for abstract task sequences and subordinate tasks. The interrelation was different between the hierarchical levels, demonstrating a strict relationship between abstract task sequence goals and sub-goals and a non-strict relationship between sub-goal and motor response levels. Under some conditions, the motor response level influenced the abstract task sequence level in a non-strict manner. Further, manipulating the presence or absence of a motor sequence after learning indicated that these effects were not the result of an integrated representation produced by practice. These experiments provide evidence for a mixed hierarchical model of task sequences and insight into the distinct roles of practice and motor processing in efficiently executing task sequences in daily life.
Development of a Murine Model of Pyogenic Flexor Tenosynovitis
Authors: Qiu Bowen , Cobb Justin , Loiselle Alayna , Ketonis Constantinos 
Published: February 2020

ABSTRACTBackgroundTo demonstrate the plausibility of a murine model of pyogenic flexor tenosynovitis.Methods2μL of sterile PBS or bioluminescent Xen29Staphylococcus aureuswas administered to the tendon sheath of 36 male C57BL/6J mice. The infectious course was monitored by bioluminescence (BLI) signal via IVIS imaging and recording of weight change. The infected hind paws were harvested at four time points: 24 hours, 72 hours, 1 week and 2 weeks for histopathology using Alcian Blue hematoxylin staining. Two-way ANOVA with Sidak’s multiple comparison test was used for statistical analysis.ResultsThe infected cohort displayed significantly elevated bioluminescent values, reductions in weight, and exhibited swelling of the infected digit throughout the course of infection. By day 7 most infected mice saw a substantial decrease in BLI signal intensity, however two infected mice exhibited persistent BLI intensity through day 14. Histopathology of the infected cohort showed tissue disorganization and the presence of a cellular infiltrate in and around the flexor tendon sheath.ConclusionsA murine model of pyogenic flexor tenosynovitis is possible. Further optimization of the model offers an experimental platform for investigation of the pathophysiology of pyogenic flexor tenosynovitis.Clinical RelevanceThis animal model can be utilized in order to elucidate the basic molecular/cellular mechanisms of pyogenic flexor tenosynovitis while simultaneously evaluating novel therapeutic strategies.
STRIDER: Steric hindrance estimator
Authors: Prasad Patro L Ponoop , Rathinavelan Thenmalarchelvi 
Published: February 2020

AbstractIn silicomodeling plays a vital role in thede novodesigning and docking of biomacromolecules as well as in exploring their conformational dynamics. Additionally, it has a major role in acquiring the structural insights from the parameters derived from the experimental techniques such as cryo-electron microscopy. Steric hindrance is one of the important measures to validate the accuracy of the constructed model. A web user interface (WUI) namely, STRIDER (steric hindranceestimator) (www.iith.ac.in/strider/) can estimate and report pairwise inter- and intra- molecular steric hindrances using the van der Waals radius of 117 elements through a user interactive interface. STRIDER also identifies and reports the coordination number of 64 metals along with their interacting pattern in an interactive mode. STRIDER can analyze an ensemble of conformers, wherein, multiple conformers are used to circumvent sampling issue in flexible docking, understand protein folding and facilitate structure based virtual screening. Further, it generates a pymol session file that can be used for offline analysis. As STRIDER simply requires the Cartesian coordinates of the given molecule in protein data bank format, any chemical structure can be an input.AvailabilityIt can be freely accessible through:www.iith.ac.in/strider/without any registration.Theme Of the Concept
Spatial inter-centromeric interactions facilitated the emergence of evolutionary new centromeres
Authors: Guin Krishnendu , Chen Yao , Mishra Radha , Muzaki Siti Rawaidah B. M. , Thimmappa Bhagya C. , O’Brien Caoimhe E. , Butler Geraldine , Sanyal Amartya , Sanyal Kaustuv 
Published: February 2020

AbstractCentromeres ofCandida albicansform on unique and different DNA sequences but a closely related species,Candida tropicalis, possesses homogenized inverted repeat (HIR)-associated centromeres. To investigate the mechanism of centromere-type transition, we improved the fragmented genome assembly and constructed a chromosome-level genome assembly ofC. tropicalisby employing PacBio sequencing, chromosome conformation capture sequencing (3C-seq), chromoblot, and genetic analysis of engineered aneuploid strains. Further, we analyzed the 3D genome organization using 3C-seq data, which revealed spatial proximity among the centromeres as well as telomeres of seven chromosomes inC. tropicalis. Intriguingly, we observed evidence of inter-centromeric translocations in the common ancestor ofC. albicansandC. tropicalis. Identification of putative centromeres in closely relatedCandida sojae, Candida viswanathiiandCandida parapsilosisindicates loss of ancestral HIR-associated centromeres and establishment of evolutionary new centromeres (ENCs) inC. albicans. We propose that spatial proximity of the homologous centromere DNA sequences facilitated karyotype rearrangements and centromere type transitions in human pathogenic yeasts of the CUG-Ser1 clade.
Augmenting Vascular Disease Diagnosis by Vasculature-aware Unsupervised Learning
Authors: Wang Yong , Ji Mengqi , Jiang Shengwei , Wang Xukang , Wu Jiamin , Duan Feng , Fan Jingtao , Huang Laiqiang , Ma Shaohua , Fang Lu , Dai Qionghai 
Published: February 2020

AbstractVascular diseases are among the leading causes of death and threaten human health worldwide. Imaging examination of vascular pathology with reduced invasiveness is challenging due to the intrinsic vasculature complexity and the non-uniform scattering from bio-tissues. Here, we report VasNet, a vasculature-aware unsupervised learning algorithm that augments pathovascular recognition from small sets of unlabeled fluorescence and digital subtraction angiography (DSA) images. The VasNet adopts the multi-scale fusion strategy with a domain adversarial neural network (DANN) loss function that induces biased pattern reconstruction, by strengthening the features relevant to the retinal vasculature reference while weakening the irrelevant features. VasNet delivers outputs of “Structure + X”, where X refers to multi-dimensional features such as blood flows, the distinguishment of blood dilation and its suspicious counterparts, and the dependence of new pattern emergence on a disease progression, which may assist the discovery of novel diagnostics. Therefore, explainable imaging output from VasNet and other algorithm extensions hold the promise to revolutionize the practice of medical diagnosis, as it improves performance while reduces the cost on human expertise, equipment exquisite and time consumption.
Sparse latent factor regression models for genome-wide and epigenome-wide association studies
Authors: Jumentier Basile , Caye Kevin , Heude Barbara , Lepeule Johanna , François Olivier 
Published: February 2020

AbstractAssociation of phenotypes or exposures with genomic and epigenomic data faces important statistical challenges. One of these challenges is to account for variation due to unobserved confounding factors, such as individual ancestry or cell-type composition in tissues. This issue can be addressed with penalized latent factor regression models, where penalties are introduced to cope with high dimension in the data. If a relatively small proportion of genomic or epigenomic markers correlate with the variable of interest, sparsity penalties may help to capture the relevant associations, but the improvement over non-sparse approaches has not been fully evaluated yet. Here, we present least-squares algorithms that jointly estimate effect sizes and confounding factors in sparse latent factor regression models. In simulated data, sparse latent factor regression models generally achieved higher statistical performance than other sparse methods, including the least absolute shrinkage and selection operator (LASSO) and a Bayesian sparse linear mixed model (BSLMM). In generative model simulations, statistical performance was slightly lower (while being comparable) to non-sparse methods, but in simulations based on empirical data, sparse latent factor regression models were more robust to departure from the model than the non-sparse approaches. We applied sparse latent factor regression models to a genome-wide association study of a flowering trait for the plantArabidopsis thalianaand to an epigenome-wide association study of smoking status in pregnant women. For both applications, sparse latent factor regression models facilitated the estimation of non-null effect sizes while overcoming multiple testing issues. The results were not only consistent with previous discoveries, but they also pinpointed new genes with functional annotations relevant to each application.
Snow Microbiome Functional Analyses Reveal Novel Microbial Metabolism of Complex Organic Compounds
Authors: Zhu Chengsheng , Miller Maximilian , Lusskin Nicholas , Bergk Pinto Benoît , Maccario Lorrie , Haggblom Max , Vogel Timothy , Larose Catherine , Bromberg Yana 
Published: February 2020

AbstractMicrobes active in extremely cold environments are not as well explored as those of other extreme environments. Studies have revealed a substantial microbial diversity and identified cold-specific microbiome molecular functions. We analyzed the metagenomes and metatranscriptomes of twenty snow samples collected during early and late spring in Svalbard, Norway using our computational read-based microbiome function annotation tool, mi-faser. Our results revealed a more diverse microbiome functional capacity and activity in the early compared to in the late spring samples. The dissimilarity between the metagenomes and metatranscriptomes of the same samples was also significantly higher in the early spring. These findings suggest that early spring samples may contain a larger fraction of DNA of dormant organisms, while late spring samples reflect a new community that is metabolically active. We additionally showed that the abundance of the sequencing reads mapping to the fatty acid synthesis-related microbial pathways was significantly positively correlated with organic acid levels, in both our late spring metagenomes and metatranscriptomes. Moreover, the geraniol degradation pathway and the styrene degradation pathway read abundances correlated and inversely correlated, respectively, with the organic acid levels. These results suggest a possible nutrient switch. Our study thus highlights the activity of microbial degradation pathways of complex organic compounds previously unreported at low temperatures.
SCRINSHOT, a spatial method for single-cell resolution mapping of cell states in tissue sections
Authors: Sountoulidis Alexandros , Liontos Andreas , Nguyen Hong Phuong , Firsova Alexandra B. , Fysikopoulos Athanasios , Qian Xiaoyan , Seeger Werner , Sundström Erik , Nilsson Mats , Samakovlis Christos 
Published: February 2020

AbstractChanges in cell identities and positions underlie tissue development and disease progression. Although, single-cell mRNA sequencing (scRNA-Seq) methods rapidly generate extensive lists of cell-states, spatially resolved single-cell mapping presents a challenging task. We developed SCRINSHOT (SingleCellResolutionINSituHybridizationOnTissues), a sensitive, multiplex RNA mapping approach. Direct hybridization of padlock probes on mRNA is followed by circularization with SplintR ligase and rolling circle amplification (RCA) of the hybridized padlock probes. Sequential detection of RCA-products using fluorophore-labeled oligonucleotides profiles thousands of cells in tissue sections. We evaluated SCRINSHOT specificity and sensitivity on murine and human organs. SCRINSHOT quantification of marker gene expression shows high correlation with published scRNA-Seq data over a broad range of gene expression levels. We demonstrate the utility of SCRISHOT by mapping the locations of abundant and rare cell types along the murine airways. The amenability, multiplexity and quantitative qualities of SCRINSHOT facilitate single cell mRNA profiling of cell-state alterations in tissues under a variety of native and experimental conditions.
Familial primary ovarian insufficiency associated with aSYCE1point mutation: Defective meiosis elucidated in humanized mice
Authors: Hernández-López Diego , Geisinger Adriana , Trovero María Fernanda , Santiñaque Federico F. , Brauer Mónica , Folle Gustavo A. , Benavente Ricardo , Rodríguez-Casuriaga Rosana 
Published: February 2020

AbstractObjectiveTo investigate if nonsense mutationSYCE1c.613C˃T-found in women with familial primary ovarian insufficiency (POI)- is actually responsible for infertility, and to elucidate the involved molecular mechanisms.DesignAs most fundamental mammalian oogenesis events occur during the embryonic phase, thus hindering the study of POI’s etiology/pathogeny in infertile women, we have used CRISPR/Cas9 technology to generate a mouse model line with an equivalent genome alteration (humanized mice).SettingAcademic research laboratories.InterventionsWe present the characterization of the biallelic mutant mice phenotype, compared to wild type and monoallelic littermates.AnimalsStudies were conducted employing the generated humanized mice. All studies were performed for both genders, except otherwise stated.Main outcome measuresreproductive capability by fertility tests; gonadal histological analysis; evaluation of chromosome synapsis and synaptonemal complex (SC) assembly by immunolocalizations; protein studies by Western blotting; transcript quantification by RT-qPCR.ResultsThe studied mutation proved to be the actual cause of the infertile phenotype, both in female and male mice homozygous for the change, confirming infertility of genetic origin with a recessive mode of inheritance. The mechanisms that lead to infertility are related to chromosome synapsis defects; no putative truncated SYCE1 protein was observed, andSyce1transcript was hardly detected in biallelic mutants.ConclusionsWe present for the first time the generation of humanized mice to study the actual consequences of a SC component mutation found in women with familial POI. By this approach we could confirm the suspected etiology, and shed light on the underlying molecular mechanism.
Large extracellular vesicles can be characterised by multiplex labelling using imaging flow cytometry
Authors: Johnson Suzanne M , Banyard Antonia , Smith Christopher , Mironov Aleksandr , McCabe Martin G 
Published: February 2020

ABSTRACTExtracellular vesicles (EVs) are heterogeneous in size (30nm-10µm), content (lipid, RNA, DNA, protein) and potential function(s). Many isolation techniques routinely discard the large EVs at the early stages of small EV or exosome isolation protocols. We describe here a standardised method to isolate large EVs and examine EV marker expression and diameter using imaging flow cytometry.MethodsWe describe step-wise isolation and characterisation of a subset of large EVs from the medulloblastoma cell line UW228-2 assessed by fluorescent light microscopy, transmission electron microscopy (TEM) and TRPS. Viability of parent cells was assessed by Annexin V exposure by flow cytometry. Imaging flow cytometry (Imagestream Mark II) identified EVs by direct fluorescent membrane labelling with Cell Mask Orange (CMO) in conjunction with EV markers. A stringent gating algorithm based on side scatter and fluorescence intensity was applied and expression of EV markers CD63, CD9 and LAMP 1 assessed.ResultsUW228-2 cells prolifically release EVs of up to 6 µm. We show that the Imagestream Mark II imaging flow cytometer allows robust and reproducible analysis of large EVs, including assessment of diameter. We also demonstrate a correlation between increasing EV size and co-expression of markers screened.ConclusionsWe have developed a labelling and stringent gating strategy which is able to explore EV marker expression (CD63, CD9 and LAMP1) on individual EVs within a widely heterogeneous population. Taken together data presented here strongly support the value of exploring large EVs in clinical samples for potential biomarkers, useful in diagnostic screening and disease monitoring.
In Vitro Assessment of Antioxidant activity, Antimicrobial, and cytotoxicity of ultrasound-assisted acetone extracts of Plectranthus amboinicus
Authors: Ye Xian-wen , Deng Ya-ling , Xia Lan-ting , Ren Hong-min , Zhang Jin-lian 
Published: February 2020

Disclaimer statementThe authors have withdrawn their manuscript whilst they perform additional experiments to test some of their conclusions further. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.