bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dissecting the initiation of female meiosis in the mouse at single-cell resolution
Authors: Ge Wei , Wang Jun-Jie , Zhang Rui-Qian , Tan Shao-Jing , Zhang Fa-Li , Liu Wen-Xiang , Li Lan , Sun Xiao-Feng , Cheng Shun-Feng , Dyce Paul W. , De Felici Massimo , Shen Wei 
Published: October 2019

ABSTRACTGerm cell meiosis is one of the most finely orchestrated events during gametogenesis with distinct developmental patterns in males and females. However, in mammals, the molecular mechanisms involved in this process remain not well known. Here, we report detailed transcriptome analyses of cell populations present in the mouse female gonadal ridges (E11.5) and the embryonic ovaries from E12.5 to E14.5 using single cell RNA sequencing (scRNA seq). These periods correspond with the initiation and progression of meiosis throughout the first stage of prophase I. We identified 13 transcriptionally distinct cell populations and 7 transcriptionally distinct germ cell subclusters that correspond to mitotic (3 clusters) and meiotic (4 clusters) germ cells. By comparing the signature gene expression pattern of 4 meiotic germ cell clusters, we found that the 4 cell clusters correspond to different cell status en route to meiosis progression, and therefore, our research here characterized detailed transcriptome dynamics during meiotic prophase I. Reconstructing the progression of meiosis along pseudotime, we identified several new genes and molecular pathways with potential critical roles in the mitosis/meiosis transition and early meiotic progression. Last, the heterogeneity within somatic cell populations was also discussed and different cellular states were identified. Our scRNA seq analysis here represents a new important resource for deciphering the molecular pathways driving meiosis initiation and progression in female germ cells and ovarian somatic cells.
Orientation to polarized light in tethered flying honeybees
Authors: Kobayashi Norihiro , Okada Ryuichi , Sakura Midori 
Published: October 2019

ABSTRACTBehavioral responses of honeybees to a zenithal polarized light stimulus were observed using a tethered animal in a flight simulator. Flight direction of the bee was recorded by monitoring the horizontal movement of its abdomen, which was strongly anti-correlated with its torque. When the e-vector orientation of the polarized light was rotated clockwise or counterclockwise, the bee responded with periodic right-and-left abdominal movements; however, the bee did not show any clear periodic movement under the static e-vector or depolarized stimulus. The steering frequency of the bee was well coordinated with the e-vector rotation frequency of the stimulus, indicating that the flying bee oriented itself to a certain e-vector orientation, i.e., exhibited polarotaxis. The percentage of bees exhibiting clear polarotaxis was much smaller under the fast stimulus (3.6 ° s-1) compared with that of the slow stimulus (0.9 or 1.8 ° s-1). The bee did not demonstrate any polarotactic behavior after the dorsal rim region of its eyes, which mediates insect polarization vision in general, was bilaterally covered with black paint. The bees demonstrated a high preference for e-vector orientations between 120 to 180°. Each bee exhibited similar e-vector preferences under clockwise and counterclockwise stimuli, indicating that each bee has its own e-vector preference, which probably depends on the bee’s previous foraging experience. Our results strongly suggest that the flying honeybees utilize the e-vector information from the skylight to deduce their heading orientation for navigation.Summary statementTethered flying bees exhibited polarotaxis under a zenithal rotating e-vector stimulus, in which their right-and-left abdominal movements were coincident with the rotation of the stimulus.
Argonaute-mediated system for supersensitive and multiplexed detection of rare mutations
Authors: Liu Qian , Guo Xiang , Xun Guanhua , Li Zhonglei , Chong Yuesheng , Yang Litao , Wang Hongxia , Zhang Fengchun , Luo Shukun , Deng Zixin , Li Kai , Feng Yan 
Published: October 2019

AbstractThe ability to detect rare mutations has revolutionized diagnosis and monitoring of tumors, but is limited by the shortage of sensitive, cost-effective and high coverage methods for identification of extremely low abundant mutations. Here, we establish a single-tube multiplex PCR system by employing thermophilic Argonaute-derived DNA-guided nuclease for highly efficient rare mutation detection, referred to as A-Star (Argonaute-directed specific target enrichment and detection), that combines the selective cleavage of the wild type DNA in the DNA denaturation step and the followed amplification of mutant DNA during PCR. A-Star enables easy detection and quantitation of rare mutations originally as low as 0.01% in allele frequency with a ⩾ 5500-fold efficiency. We also demonstrate the feasibility of A-Star for detecting oncogenic mutations in complex biological systems such as solid tumors tissues and blood samples. Remarkably, A-Star could achieve the detection of multiple oncogenic genes simultaneously through a simple single-tube reaction. Taken together, our work illustrates a supersensitive and rapid nucleic acid detection system, thereby extending the utility for both research and therapeutic applications.
Balance Control Mechanisms Do Not Benefit From Successive Stimulation Of Different Sensory Systems
Authors: Cyr Jean-Philippe , Anctil Noémie , Simoneau Martin 
Published: October 2019

ABSTRACTIn humans, to reduce deviations from a perfect upright position, information from various sensory cues is combined and continuously weighted based on its reliability. Combining noisy sensory information to produce a coherent and accurate estimate of body sway is a central problem in human balance control. In this study, we first compared the ability of the sensorimotor control mechanisms to deal with altered ankle proprioception or vestibular information (i.e., the single sensory condition). Then, we evaluated whether successive stimulation of difference sensory systems (e.g., Achilles tendon vibration followed by electrical vestibular stimulation, or vice versa) produced a greater alteration of balance control (i.e., the mix sensory condition). Electrical vestibular stimulation (head turned ∼90°) and Achilles tendon vibration induced backward body sways. We calculated the root mean square value of the scalar distance between the center of pressure and the center of gravity as well as the time needed to regain balance (i.e., stabilization time). Furthermore, the peak ground reaction force along the anteroposterior axis, immediately following stimulation offset, was determined to compare the balance destabilization across the different conditions. In single conditions, during vestibular or Achilles tendon vibration, no difference in balance control was observed. When sensory information returned to normal, balance control was worse following Achilles tendon vibration. Compared to that of the single sensory condition, successive stimulation of different sensory systems (i.e., mix conditions) increased stabilization time. Overall, the present results reveal that single and successive sensory stimulation challenges the sensorimotor control mechanisms differently.
GABA-ergic dynamics in human frontotemporal networks confirmed by pharmaco-magnetoencephalography
Authors: Adams Natalie E. , Hughes Laura E. , Phillips Holly N. , Shaw Alexander D. , Murley Alexander G. , Cope Thomas E. , Bevan-Jones W. Richard , Passamonti Luca , Rowe James B. 
Published: October 2019

AbstractTo bridge the gap between preclinical cellular models of disease and in vivo imaging of human cognitive network dynamics, there is a pressing need for informative biophysical models. Here we assess dynamic causal models (DCM) of cortical network responses, inverted to magnetoencephalographic observations during an auditory oddball roving paradigm in healthy adults. This paradigm induces robust perturbations that permeate frontotemporal networks, including an evoked ‘mismatch negativity’ response and transiently induced oscillations. Here, we probe GABAergic influences of the networks using double-blind placebo-controlled randomised-crossover administration of the GABA re-uptake inhibitor, tiagabine (oral, 10mg) in healthy older adults. We demonstrate the facility of conductance-based neural mass mean-field models, incorporating local synaptic connectivity, to investigate laminar-specific and GABAergic mechanisms of the auditory response. The neuronal model accurately recapitulated the observed magnetoencephalographic data. Using parametric empirical Bayes for optimal model inversion across both sessions, we identify the effect of tiagabine on GABAergic modulation of deep pyramidal and interneuronal cell populations. Moreover, in keeping with the hierarchical coding of beliefs and sensory evidence, we found a transition of the main GABAergic drug effects from auditory cortex in standard trials to prefrontal cortex in deviant trials. The successful integration of pharmaco-magnetoencephalography with dynamic causal models of frontotemporal networks provides a potential platform on which to evaluate the effects of disease and pharmacological interventions.Significance StatementUnderstanding human brain function and developing new treatments require good models of brain function. We tested a detailed generative model of cortical microcircuits that accurately reproduced human magnetoencephalography, to quantify network dynamics and connectivity in frontotemporal cortex. This approach correctly identified the effect of a test drug (tiagabine) on neuronal function (GABA-ergic dynamics), opening the way for psychopharmacological studies in health and disease with the mechanistic precision afforded by generative models of the brain.
Antifungal susceptibility testing ofAspergillus nigeron silicon microwells by intensity-based reflectometric interference spectroscopy
Authors: Heuer Christopher , Leonard Heidi , Nitzan Nadav , Lavy-Alperovitch Ariella , Massad-Ivanir Naama , Segal Ester 
Published: October 2019

AbstractThe increasing number of invasive fungal infections among immunocompromised patients and the emergence of antifungal resistant pathogens has resulted in the need for rapid and reliable antifungal susceptibility testing (AFST). Accelerating antifungal susceptibility testing allows for advanced treatment decisions and the reduction in future instances of antifungal resistance. In this work, we demonstrate the application of a silicon phase grating as sensor for the detection of growth ofAspergillus niger(A. niger) by intensity-based reflectometric interference spectroscopy and its use as an antifungal susceptibility test. The silicon gratings provide a solid-liquid interface to capture micron-sizedAspergillusconidia within microwell arrays. Fungal growth is optically tracked and detected by the reduction in the intensity of reflected light from the silicon grating. The growth ofA. nigerin the presence of various concentrations of the antifungal agents voriconazole and amphotericin B is investigated by intensity-based reflectometric interference spectroscopy and used for the determination of the minimal inhibitory concentrations (MIC), which are compared to standard broth microdilution testing. This assay allows for expedited detection of fungal growth and provides a label-free alternative to standard antifungal susceptibility testing methods, such as broth microdilution and agar diffusion methods.
Genetic regulators of mineral amount in Nelore cattle muscle predicted by a new co-expression and regulatory impact factor approach
Authors: Afonso Juliana , Fortes Marina Rufino Salinas , Reverter Antonio , da Silva Diniz Wellison Jarles , Cesar Aline Silva Mello , de Lima Andressa Oliveira , Petrini Juliana , de Souza Marcela M. , Coutinho Luiz Lehmann , Mourão Gerson Barreto , Zerlotini Adhemar , Gromboni Caio Fernando , Nogueira Ana Rita Araújo , de Almeida Regitano Luciana Correia 
Published: October 2019

AbstractMineral amount in bovine muscle affect meat quality, growth, health and reproductive traits in beef cattle. To better understand the genetic basis of this phenotype, we implemented new applications of use for two complementary algorithms: the partial correlation and information theory (PCIT) and the regulatory impact factor (RIF), by including GEBVs as part of the input. We used PCIT to determine putative regulatory relationships based on significant associations between gene expression and mineral amount. Then, RIF was used to determine the regulatory impact of genes and miRNA expression over mineral amount. We also investigated over-represented pathways, as well as evidences from previous studies carried in the same population, to determine regulatory genes for mineral amounte.g. NOX1, whose expression was positively correlated to Zn and was described as regulated by this mineral in humans. With this methodology, we were able to identify genes, miRNAs and pathways not yet described as important for mineral amount. The results support the hypothesis that extracellular matrix interactions are the core regulator of mineral amount in muscle cells. Putative regulators described here add information to this hypothesis, expanding the molecular relationships between gene expression and minerals.
XTRACT - Standardised protocols for automated tractography in the human and macaque brain
Authors: Warrington S , Bryant KL , Khrapitchev AA , Sallet J , Charquero-Ballester M , Douaud G , Jbabdi S , Mars RB , Sotiropoulos SN 
Published: October 2019

AbstractWe present a new software package with a library of standardised tractography protocols devised for the robust automated extraction of white matter tracts both in the human and the macaque brain. Using in vivo data from the Human Connectome Project (HCP) and the UK Biobank and ex vivo data for the macaque brain datasets, we obtain white matter atlases, as well as atlases for tract endpoints on the white-grey matter boundary, for both species. We illustrate that our protocols are robust against data quality, generalisable across two species and reflect the known anatomy. We further demonstrate that they capture inter-subject variability by preserving tract lateralisation in humans and tract similarities stemming from twinship in the HCP cohort. Our results demonstrate that the presented toolbox will be useful for generating imaging-derived features in large cohorts, and in facilitating comparative neuroanatomy studies. The software, tractography protocols, and atlases are publicly released through FSL, allowing users to define their own tractography protocols in a standardised manner, further contributing to open science.
Same same but different: a web-based deep learning application for the histopathologic distinction of cortical malformations
Authors: Kubach J. , Muehlebner-Farngruber A. , Soylemezoglu F. , Miyata H. , Niehusmann P. , Honavar M. , Rogerio F. , Kim S-H. , Aronica E. , Garbelli R. , Vilz S. , Popp A. , Walcher S. , Neuner C. , Scholz M. , Kuerten S. , Schropp V. , Roeder S. , Eichhorn P. , Eckstein M. , Brehmer A. , Kobow K. , Coras R. , Bluemcke I. , Jabari S. 
Published: October 2019

AbstractWe trained a convolutional neural network (CNN) to classify H.E. stained microscopic images of focal cortical dysplasia type IIb (FCD IIb) and cortical tuber of tuberous sclerosis complex (TSC). Both entities are distinct subtypes of human malformations of cortical development that share histopathological features consisting of neuronal dyslamination with dysmorphic neurons and balloon cells. The microscopic review of routine stainings of such surgical specimens remains challenging. A digital processing pipeline was developed for a series of 56 FCD IIb and TSC cases to obtain 4000 regions of interest and 200.000 sub-samples with different zoom and rotation angles to train a CNN. Our best performing network achieved 91% accuracy and 0.88 AUCROC (area under the receiver operating characteristic curve) on a hold-out test-set. Guided gradient-weighted class activation maps visualized morphological features used by the CNN to distinguish both entities. We then developed a web application, which combined the visualization of whole slide images (WSI) with the possibility for classification between FCD IIb and TSC on demand by our pretrained and build-in CNN classifier. This approach might help to introduce deep learning applications for the histopathologic diagnosis of rare and difficult-to-classify brain lesions.
In silicoidentification of potential inhibitors against human 2’-5’-oligoadenylate synthetase (OAS) proteins
Authors: Gonzalez Karen J. , Moncada-Giraldo Diego , Gutierrez Juan B. 
Published: October 2019

AbstractAs part of the type I IFN signaling, the 2’-5’- oligoadenylate synthetase (OAS) proteins have been involved in the progression of several non-viral diseases. Notably, OAS has been correlated with immune-modulatory functions that promote chronic inflammatory conditions, autoimmune disorders, cancer, and infectious diseases. In spite of this, OAS enzymes have been ignored as drug targets, and to date, there are no reports of compounds that can inhibit their activity. In this study, we have used homology modeling and virtual high-throughput screening to identify potential inhibitors of the human proteins OAS1, OAS2, and OAS3. Altogether, we have found 37 molecules that could exert a competitive inhibition in the ATP binding sites of OAS proteins, independently of the activation state of the enzyme. This latter characteristic, which might be crucial for a versatile inhibitor, was observed in compounds interacting with the residues Asp75, Asp77, Gln229, and Tyr230 in OAS1, and their equivalents in OAS2 and OAS3. Although there was little correlation between specific chemical fragments and particular interactions, intermolecular contacts with OAS catalytic triad and other critical amino acids were mainly promoted by heterocycles with π electrons and hydrogen bond acceptors. In conclusion, this study provides a potential set of OAS inhibitors as well as valuable information for their design, development, and optimization.
Estimating relative CWD susceptibility and disease progression in farmed whitetail deer with rare PRNP alleles
Authors: Haley NJ , Merrett K , Buros Stein A , Simpson D , Carlton A , Mitchell G , Staskevicius A , Nichols T , Lehmkuhl AD , Thomsen BV 
Published: October 2019

AbstractChronic wasting disease is a prion disease affecting both free-ranging and farmed cervids in North America and Scandinavia. A range of cervid species have been found to be susceptible, each with variations in the gene for the normal prion protein, PRNP, reportedly influencing both disease susceptibility and progression in the respective hosts. Despite the finding of several different PRNP alleles in whitetail deer, the majority of past research has focused on two of the more common alleles identified – the 96G and 96S alleles. In the present study, we evaluate both infection status and disease stage in nearly 2100 farmed deer depopulated in the United States and Canada, including 714 CWD-positive deer and correlate our findings with PRNP genotype, including the more rare 95H, 116G, and 226K alleles. We found significant differences in either likelihood of being found infected or disease stage (and in many cases both) at the time of depopulation in all genotypes present, relative to the most common 96GG genotype. Despite high prevalence in many of the herds examined, infection was not found in several of the reported genotypes. These findings suggest that additional research is necessary to more properly define the role that these genotypes may play in managing CWD in both farmed and free-ranging whitetail deer, with consideration for factors including relative fitness levels, incubation periods, and the kinetics of shedding in animals with these rare genotypes.
Cryo-EM structure of the potassium-chloride cotransporter KCC4 in lipid nanodiscs
Authors: Reid Michelle S. , Kern David M. , Brohawn Stephen G. 
Published: October 2019

AbstractCation-chloride-cotransporters (CCCs) catalyze transport of Cl− with K+ and/or Na+ across cellular membranes. CCCs play roles in volume regulation, neural development and function, audition, blood pressure regulation, and renal function. CCCs are targets of drugs including loop diuretics and their disruption is implicated in pathophysiologies including epilepsy, hearing loss, and the genetic disorders Andermann, Gitelman, and Bartter syndromes. Here we present the cryo-EM structure of a CCC, the Mus musculus K+-Cl− cotransporter KCC4, in lipid nanodiscs. The structure, captured in an inside-open conformation, reveals the architecture of KCCs including an extracellular domain poised to regulate transport activity through an outer gate. We further identify substrate K+ and Cl− binding sites and provide a structural explanation for differences in substrate specificity and transport ratio between CCCs. These results provide mechanistic insight into the function and regulation of a physiologically important transporter family.
pydca v1.0: a comprehensive software for Direct Coupling Analysis of RNA and Protein Sequences
Authors: Zerihun Mehari B. , Pucci Fabrizio , Peter Emanuel Karl , Schug Alexander 
Published: October 2019

AbstractThe ongoing advances in sequencing technologies have provided a massive increase in the availability of sequence data. This made it possible to study the patterns of correlated substitution between residues in families of homologous proteins or RNAs and to retrieve structural and stability information. Direct coupling Analysis (DCA) infers coevolutionary couplings between pairs of residues indicating their spatial proximity, making such information a valuable input for subsequent structure prediction. Here we present pydca, a standalone Python-based software package for the DCA of protein- and RNA-homologous families. It is based on two popular inverse statistical approaches, namely, the mean-field and the pseudo-likelihood maximization and is equipped with a series of functionalities that range from multiple sequence alignment trimming to contact map visualization. Thanks to its efficient implementation, features and user-friendly command line interface, pydca is a modular and easy-to-use tool that can be used by researchers with a wide range of backgrounds.Availabilityhttps://github.com/KIT-MBS/pydca