bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromosomal rearrangements and loss of subtelomeric adhesins linked to clade-specific phenotypes in Candida auris
Authors: Muñoz José F. , Welsh Rory M. , Shea Terrance , Batra Dhwani , Gade Lalitha , Litvintseva Anastasia P. , Cuomo Christina A. 
Published: September 2019

ABSTRACTCandida auris is an emerging fungal pathogen of rising concern due to its increasing incidence, its ability to cause healthcare-associated outbreaks and antifungal resistance. Genomic analysis revealed that early cases of C. auris that were detected contemporaneously were geographically stratified into four major clades. Clade II, also termed East Asian clade, consists of the initial isolates described from cases of ear infection, is less frequently resistant to antifungal drugs and to date, the isolates from this group have not been associated with outbreaks. Here, we generate nearly complete genomes (“telomere-to-telomere”) of an isolate of this clade and of the more widespread Clade IV. By comparing these to genome assemblies of the other two clades, we find that the Clade II genome appears highly rearranged, with 2 inversions and 9 translocations resulting in a substantially different karyotype. In addition, large subtelomeric regions have been lost from 10 of 14 chromosome ends in the Clade II genomes. We find that shorter telomeres and genome instability might be a consequence of a naturally occurring loss-of-function mutation in DCC1 exclusively found in Clade II isolates, resulting in a hypermutator phenotype. We also determine that deleted subtelomeric regions might be linked to clade-specific adaptation as these regions are enriched in Hyr/Iff-like cell surface proteins, novel candidate cell surface proteins, and an ALS-like adhesin. The presence of these cell surface proteins in the clades responsible for global outbreaks causing invasive infections suggests an explanation for the different phenotypes observed between clades.IMPORTANCECandida auris was unknown prior to 2009 and since then it has quickly spread around the world, causing outbreaks in healthcare facilities and representing a high fraction of candidemia cases in some regions. The emergence of C. auris is a major concern, since it is often multidrug-resistant, easily spread between patients, and causes invasive infections. While isolates from three global clades cause invasive infections, isolates from Clade II primarily cause ear infections and have not been implicated in outbreaks, though cases of Clade II infections have been reported on different continents. Here, we describe genetic differences between Clade II and Clades I, III and IV, including a loss-of-function mutation in a gene associated with telomere length maintenance and genome stability, and the loss of cell wall proteins involved in adhesion and biofilm formation, that may suggest an explanation for the lower virulence and potential for transmission of Clade II isolates.
A collection of genetic mouse lines and related tools for inducible and reversible intersectional misexpression
Authors: Ahmadzadeh Elham , Bayin N. Sumru , Qu Xinli , Singh Aditi , Madisen Linda , Stephen Daniel , Zeng Hongkui , Joyner Alexandra L. , Rosello-Diez Alberto 
Published: September 2019

AbstractThanks to many advances in genetic manipulation, mouse models have become very powerful in their ability to interrogate biological processes. In order to precisely target expression of a gene of interest to particular cell types, intersectional genetic approaches utilizing two promoter/enhancers unique to a cell type are ideal. Within these methodologies, variants that add temporal control of gene expression are the most powerful. We describe the development, validation and application of an intersectional approach that involves three transgenes, requiring the intersection of two promoter/enhancers to target gene expression to precise cell types. Furthermore, the approach utilizes available lines expressing tTA/rTA to control timing of gene expression based on whether doxycycline is absent or present, respectively. We also show that the approach can be extended to other animal models, using chicken embryos. We generated three mouse lines targeted at the Tigre (Igs7) locus with TRE-loxP-tdTomato-loxP upstream of three genes (p21, DTA and Ctgf) and combined them with Cre and tTA/rtTA lines that target expression to the cerebellum and limbs. Our tools will facilitate unraveling biological questions in multiple fields and organisms.Summary statementAhmadzadeh et al. present a collection of four mouse lines and genetic tools for misexpression-mediated manipulation of cellular activity with high spatiotemporal control, in a reversible manner.
Gaze stabilisation behaviour is anisotropic across visual field locations in zebrafish
Authors: Dehmelt Florian A. , Meier Rebecca , Hinz Julian , Yoshimatsu Takeshi , Simacek Clara A. , Wang Kun , Baden Tom , Arrenberg Aristides B. 
Published: September 2019

AbstractMany animals have large visual fields, and sensory circuits may sample those regions of visual space most relevant to behaviours such as gaze stabilisation and hunting. Despite this, relatively small displays are often used in vision neuroscience. To sample stimulus locations across most of the visual field, we built a spherical stimulus arena with 14,848 independently controllable LEDs, measured the optokinetic response gain of immobilised zebrafish larvae, and related behaviour to previously published retinal photoreceptor densities. We measured tuning to steradian stimulus size and spatial frequency, and show it to be independent of visual field position. However, zebrafish react most strongly and consistently to lateral, nearly equatorial stimuli, consistent with previously reported higher spatial densities in the central retina of red, green and blue photoreceptors. Upside-down experiments suggest further extra-retinal processing. Our results demonstrate that motion vision circuits in zebrafish are anisotropic, and preferentially monitor areas with putative behavioural relevance.Author summaryThe visual system of larval zebrafish mirrors many features present in the visual system of other vertebrates, including its ability to mediate optomotor and optokinetic behaviour. Although the presence of such behaviours and some of the underlying neural correlates have been firmly established, previous experiments did not consider the large visual field of zebrafish, which covers more than 160° for each eye. Given that different parts of the visual field likely carry unequal amount of behaviourally relevant information for the animal, this raises the question whether optic flow is integrated across the entire visual field or just parts of it, and how this shapes behaviour such as the optokinetic response. We constructed a spherical LED arena to present visual stimuli almost anywhere across their visual field, while tracking horizontal eye movements. By displaying moving gratings on this LED arena, we demonstrate that the optokinetic response, one of the most prominent visually induced behaviours of zebrafish, indeed strongly depends on stimulus location and stimulus size, as well as on other parameters such as the spatial and temporal frequency of the gratings. This location dependence is consistent with areas of high retinal photoreceptor densities, though evidence suggests further extraretinal processing.
Similar somatotopy for active and passive digit representation in primary somatosensory cortex
Authors: Sanders Zeena-Britt , Wesselink Daan B , Dempsey-Jones Harriet , Makin Tamar R 
Published: September 2019

AbstractScientists traditionally use passive stimulation to examine organisational properties of the primary somatosensory cortex (SI). Recent research has, however, emphasised the close and bidirectional relationship between somatosensory and motor systems. This suggests active contributions (e.g., direct inputs from the motor system to SI) should also be considered when studying SI representations. Under such a framework, discrepant results are possible when different tasks are used to study the same underlying somatosensory representation. Here we examined whether SI hand representation is consistent when compared between active and passive tasks. Moreover, we ask whether this holds when task demands and stimulus properties are not directly matched. Using 7T fMRI, we examined three key digit representation features – spatial location, activity gradient profiles and multivariate representational structure. We show that although activity was increased overall in the active task, all key features of digit somatotopy were consistent over tasks, using both traditional univariate (activity-level) and multivariate (pattern structure) measurements. Despite overall comparability, when investigating fine-grained features of somatotopy using multivariate analysis, the active task was superior for individuating the representation across digits. We suggest that the information produced by an active task is more aligned with typical, ecologically relevant patterns of hand sensory input, resulting in more optimal SI activity patterns. Our findings validate the utilisation of active tasks for studying SI somatotopy.
Genome-wide association analyses of multiple traits in Duroc pigs using low-coverage whole-genome sequencing strategy
Authors: Yang Ruifei , Guo Xiaoli , Zhu Di , Bian Cheng , Zhao Yiqiang , Tan Cheng , Wu Zhenfang , Wang Yuzhe , Hu Xiaoxiang , Li Ning 
Published: September 2019

AbstractHigh-density markers discovered in large size samples are essential for mapping complex traits at the gene-level resolution for agricultural livestock and crops. However, the unavailability of large reference panels and array designs for a target population of agricultural species limits the improvement of array-based genotype imputation. Recent studies showed very low coverage sequencing (LCS) of a large number of individuals is a cost-effective approach to discover variations in much greater detail in association studies. Here, we performed cohort-wide whole-genome sequencing at an average depth of 0.73× and identified more than 11.3 M SNPs. We also evaluated the data set and performed genome-wide association analysis (GWAS) in 2885 Duroc boars. We compared two different pipelines and selected a proper method (BaseVar/STITCH) for LCS analyses and determined that sequencing of 1000 individuals with 0.2× depth is enough for identifying SNPs with high accuracy in this population. Of the seven association signals derived from the genome-wide association analysis of the LCS variants, which were associated with four economic traits, we found two QTLs with narrow intervals were possibly responsible for the teat number and back fat thickness traits and identified 7 missense variants in a single sequencing step. This strategy (BaseVar/STITCH) is generally applicable to any populations and any species which have no suitable reference panels. These findings show that the LCS strategy is a proper approach for the construction of new genetic resources to facilitate genome-wide association studies, fine mapping of QTLs, and genomic selection, and implicate that it can be widely used for agricultural animal breeding in the future.
An insight to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) pathogenesis; evidence from high-throughput data integration and meta-analysis
Authors: Mozhgani Sayed-Hamidreza , Piran Mehran , Zarei-Ghobadi Mohadeseh , Jafari Mohieddin , Mokhtari-Azad Talat , Jazayeri Seyed-Mohammad , Teymoori-Rad Majid , Valizadeh Narges , Farajifard Hamid , Mirzaie Mehdi , Khamseh Azam , Rafatpanah Houshang , Rezaee Seyed-Abdolrahim , Norouzi Mehdi 
Published: September 2019

AbstractHuman T-lymphotropic virus 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive disease of the central nervous system that affected significantly spinal cord, nevertheless, the pathogenesis pathway. This study aimed to employ high throughput meta-analysis to find major genes involved in the pathogenesis of HAM/TSP. High-throughput statistical analyses identified 385, 49, and 22 differentially expressed genes for normal vs. ACs, normal vs. HAM/TSP and ACs vs. HAM/TSP groups, respectively. STRING and further network analyses highlighted 32, 29, and 13 hub genes for normal vs. ACs, normal vs. HAM/TSP, and ACs vs. HAM/TSP groups, respectively. Biological network analyses indicated the involvement of hub genes in the HAM/TSP group in many vital pathways like apoptosis and immune pathways. Moreover, the meta-analysis results disclosed three major genes including STAT1, TAP1, and PSMB8 which have function role in HAM/TSP progression. Real-time PCR revealed the meaningful down-regulation of STAT1 in HAM/TSP samples than AC and normal samples (P=0.01 and P=0.02, respectively), up-regulation of PSMB8 in HAM/TSP samples than AC and normal samples (P=0.04 and P=0.01, respectively), and down-regulation of TAP1 in HAM/TSP samples than those in AC and normal samples (P=0.008 and P=0.02, respectively). No significant difference was found among three groups in terms of percentage of T helper and cytotoxic T lymphocytes (P= 0.55 and P=0.12). Our results confirm that STAT1, TAP1, and PSMB8 are three important genes which their expressions levels were changed in three different groups. These proteins in association with other proteins can involve in the immune and apoptosis pathways.
Nested tandem duplications of the geneMelanoma antigen recognized by T-cells(Mlana) underlie the sexual dimorphism locus in domestic pigeons
Authors: Krishnan Shreyas 
Published: September 2019

AbstractBirds have classic examples of exaggerated sexually dimorphic traits, including colors. Sexes among the wild rock dove and its derived domestic breeds, however, are quite indistinguishable and sex can only be ascertained through genotyping or egg laying and successful hatching of eggs. Yet, the pigeon fancy has discovered sexually dimorphic traits and harnessed some of these traits in some auto-sexing breeds. Early genetics pioneers characterized the sex-linkedStipperlocus and showed it to be linked to the pigeon Z linkedB-locus(Tyrp1). The alleles of theStipperlocus have variable dominance relative to wild-type (more severe alleles are incompletely dominant, less severe alleles are reportedly fully dominant), characterized by a continuum of lightening in homozygotes and increased variegation in heterozygotes corresponding with severity. We leveraged this positional information and population structure among breeds in a candidate gene approach to identify the genetic mechanism of de novo pigeon sex dichromatism. A large tandem duplication (77 kb) centered on the geneMelanoma antigen recognized by T cells(Mlana) is completely associated with alleles of theStipperlocus. Copy number of the 77 kb genetic lesion was not correlated with allele severity suggesting that other mechanisms, including epigenetic regulation could underlie both allele severity and degree of variegation.
A kinematic analysis ofMicruruscoral snakes reveals unexpected variation in stereotyped anti-predator displays within a mimicry system
Authors: Moore Talia Y. , Danforth Shannon M. , Larson Joanna G. , Davis Rabosky Alison R. 
Published: September 2019

AbstractWarning signals in chemically defended organisms are critical components of predator-prey interactions, often requiring multiple coordinated display components for a signal to be effective. When threatened by a predator, venomous coral snakes (genusMicrurus) display a vigorous, non-locomotory thrashing behaviour that has been only qualitatively described. Given the high-contrast and often colourful banding patterns of these snakes, this thrashing display is hypothesized to be a key component of a complex aposematic signal under strong stabilizing selection across species in a mimicry system.By experimentally testing snake response across simulated predator cues, we analysed variation in the presence and expression of a thrashing display across five species of South American coral snakes.Although the major features of the thrash display were conserved across species, we found significant variation in the propensity to perform a display at all, the duration of thrashing, and the curvature of snake bodies that was mediated by predator cue type, snake body size, and species identity. We also found an interaction between curve magnitude and body location that clearly shows which parts of the display vary most across individuals and species.Our results suggest that contrary to the assumption in the literature that all species and individuals perform the same display, a high degree of variation persists in thrashing behaviour exhibited byMicruruscoral snakes despite presumably strong selection to converge on a common signal. This quantitative behavioural characterization presents a new framework for analysing the non-locomotory motions displayed by snakes in a broader ecological context, especially for signalling systems with complex interaction across multiple modalities.
Mental Workload Estimation Using Wireless EEG Signals
Authors: Adewale Quadri , Panoutsos George 
Published: September 2019

AbstractPrevious studies have shown that electroencephalogram (EEG) can be used in estimating mental workload. However, developing fast and reliable models for cross-task, cross-subject and cross-session classifications of workload remains a challenge. In this study, a wireless Emotiv EPOC headset was used to evaluate workload in two different mental tasks: n-back task and mental arithmetic task. 0-back task and 2-back task were employed as low and high workload in the n-back task while 1-digit and 3-digit addition were used as the two different workload levels in the arithmetic task. Using power spectral density as features, a fast signal processing and feature extraction framework was developed to facilitate real-time estimation of workload. Within-session accuracies of 98.5% and 95.5% were achieved in the n-back and arithmetic tasks respectively. Adaptive subspace feature matching (ASFM) was applied for cross-session, cross-task and cross-subject classifications. The feature adaptation provided average cross-session accuracies of 80.5% and 74.4% in the n-back and the arithmetic tasks respectively. An average cross-task accuracy of 68.6% was achieved while cross-subject accuracies were 74.4% and 64.1% in the n-back and arithmetic tasks respectively. The framework generalised well across subjects and tasks, and it provided a promising approach towards developing subject and task-independent models. This study also shows that a consumer-level wireless EEG headset can be applied in cognitive monitoring for real-time estimation of workload in practice.
Statistical significance in DTI group analyses: How the choice of the estimator can inflate effect sizes
Authors: David Szabolcs , Mesri Hamed Y. , Viergever Max A. , Leemans Alexander 
Published: September 2019

AbstractDiffusion magnetic resonance imaging (dMRI) is one of the most prevalent methods to investigate the micro- and macrostructure of the human brain in vivo. Prior to any group analysis, dMRI data are generally processed to alleviate adverse effects of known artefacts such as signal drift, data noise and outliers, subject motion, and geometric distortions. These dMRI data processing steps are often combined in automated pipelines, such as the one of the Human Connectome Project (HCP). While improving the performance of processing tools has clearly shown its benefits at each individual step along the pipeline, it remains unclear whether – and to what degree – choices for specific user-defined parameter settings can affect the final outcome of group analyses. In this work, we demonstrate how making such a choice for a particular processing step of the pipeline drives the final outcome of a group study. More specifically, we performed a dMRI group analysis on gender using HCP data sets and compared the results obtained with two diffusion tensor imaging estimation methods: the widely used ordinary linear least squares (OLLS) and the more reliable iterative weighted linear least squares (IWLLS). Our results show that the effect sizes for group analyses are significantly smaller with IWLLS than with OLLS. While previous literature has demonstrated higher estimation reliability with IWLLS than with OLLS using simulations, this work now also shows how OLLS can produce a larger number of false positives than IWLLS in a typical group study. We therefore highly recommend using the IWLLS method. By raising awareness of how the choice of estimator can artificially inflate effect size and thus alter the final outcome, this work may contribute to improvement of the reliability and validity of dMRI group studies.
Interacting with volatile environments stabilizes hidden-state inference and its brain signatures
Authors: Weiss Aurélien , Chambon Valérian , Lee Junseok K. , Drugowitsch Jan , Wyart Valentin 
Published: September 2019

AbstractMaking accurate decisions in uncertain environments requires identifying the generative cause of sensory cues, but also the expected outcomes of possible actions. Although both cognitive processes can be formalized as Bayesian inference, they are commonly studied using different experimental frameworks, making their formal comparison difficult. Here, by framing a reversal learning task either as cue-based or outcome-based inference, we found that humans perceive the same volatile environment as more stable when inferring its hidden state by interaction with uncertain outcomes than by observation of equally uncertain cues. Multivariate patterns of magnetoencephalo-graphic (MEG) activity reflected this behavioral difference in the neural interaction between inferred beliefs and incoming evidence, an effect originating from associative regions in the temporal lobe. Together, these findings indicate that the degree of control over the sampling of volatile environments shapes human learning and decision-making under uncertainty.
Isolates from ancient permafrost help to elucidate species boundaries in Acanthamoeba castellanii complex (Amoebozoa: Discosea)
Authors: Malavin Stas , Shmakova Lyubov 
Published: September 2019

AbstractAcanthamoeba castellanii species complex (genotype T4) comprises of more than ten species with unclear synonymy. Its molecular phylogeny has several conflicts with published morphological data. In this paper, we analyze morphometric traits and temperature preferences in six new strains belonging to A. castellanii complex isolated from Arctic permafrost in the framework of molecular phylogeny. This integrative approach allows us to cross-link genotypic and phenotypic variability and identify species-level boundaries inside the complex. We also analyze previously known and newly found discrepancies between the nuclear and mitochondrial gene-based phylogenies. We hypothesize that one reason for these discrepancies may be the intragenomic polymorphism of ribosomal RNA genes.