bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Virtual-Reality, 360-Degree Fly-Through of an Arteriovenous Malformation Resection: 2-Dimensional Operative Video
Authors: Steinberger Jeremy , Nistal Dominic , Schlachter Leslie , Costa Anthony , Oemke Holly , Bederson Joshua B 
Published: April 2019

Abstract
The application of navigation integrated virtual reality (VR) in neurosurgery is an emerging paradigm that may offer improved situational awareness for the surgeon. Here, we present a case of a complex arteriovenous malformation (AVM) with complex venous drainage and observe how VR impacted structural delineation during approach, resection, and overall strategic planning. The patient was a 30-yr-old female with no past medical history who presented with headaches and a generalized tonic clonic seizure. Workup included computed tomography, computed tomography angiography, magnetic resonance imaging, magnetic resonance angiography, and magnetic resonance venography; a high flow right frontal AVM was found. The AVM was safely resected using navigation integrated with VR; careful arterial devascularization preceded resection of the draining veins and then the AVM nidus. Postoperative scans confirmed complete resection of the AVM. This case outlines the application of a current state-of-the-art VR platform to assist the craniotomy for resection of an AVM.
Successful classification of macrophage-mannose receptor CD206 in severity of anti-MDA5 antibody positive dermatomyositis associated ILD
Authors: Horiike Yasuoki , Suzuki Yuzo , Fujisawa Tomoyuki , Yasui Hideki , Karayama Masato , Hozumi Hironao , Furuhashi Kazuki , Enomoto Noriyuki , Nakamura Yutaro , Inui Naoki , Ogawa Noriyoshi , Suda Takafumi 
Published: April 2019

Abstract

Objectives
Macrophage-mannose receptor, CD206, is a marker of alternatively activated macrophages. Activated macrophages play key roles in DM. Interstitial lung disease (ILD) is a leading cause of mortality in patients with DM/clinically amyopathic DM (CADM). In particular, patients with the anti-melanoma differential gene 5 antibody (MDA5) frequently develop fatal rapid progressive ILD. This study aimed to evaluate the clinical implications of alternatively activated macrophages in patients with CADM/DM-ILD with anti-MDA5 antibody (MDA5-CADM/DM-ILD).

Methods
We measured serum concentrations of soluble CD206 (sCD206) in 33 patients with MDA5-CADM/DM-ILD and 36 age- and sex-matched control subjects. Expression levels of CD206 in the lungs from MDA5-CADM/DM-ILD were also examined.

Results
Patients with MDA5-CADM/DM-ILD had higher levels of sCD206 than those in controls (P < 0.0001). Of the 33 patients, 10 MDA5-CADM/DM-ILD patients developed fatal respiratory failure. Concentrations of sCD206 in patients with fatal ILD cases were significantly higher than those in the survivors, and increased sCD206 levels were associated with a higher mortality rate (Log-rank test, P = 0.0009). Age- and gender-adjusted logistic regression analyses showed that sCD206 was an independent prognostic factor for MDA5-CADM/DM-ILD. Importantly, assessment by sCD206 together with PaO2 successfully divided into three groups by their prognosis (P < 0.005, respectively). Pathological analyses showed accumulations of CD206-positive macrophages in lungs from the fatal case rather than those in the non-fatal cases.

Conclusions
Levels of serum sCD206 are increased in MDA5-CADM/DM-ILD and associated with poor prognosis. sCD206 is a potential biomarker to predict the severity of MDA5-CADM/DM-ILD.
No Evidence for Widespread Positive Selection Signatures in Common Risk Alleles Associated with Schizophrenia
Authors: Yao Yao , Yang Jia , Xie Yimin , Liao Hai , Yang Baoying , Xu Qi , Rao Shuquan 
Published: April 2019

Abstract
Schizophrenia poses an evolutionary-genetic paradox as it exhibits strongly negative fitness effects (early mortality and decreased fecundity), yet it persists at a prevalence of approximately 1% worldwide. Evidence from several studies have suggested that schizophrenia is evolved and maintained in part as a maladaptive byproduct of recent positive selection and adaptive evolution in human beings. However, inconsistent results have been also proposed, challenging the recent positive selection theory to explain the high population frequency of schizophrenia-associated alleles. Here, we used public domain data to locate signatures of positive selection based on genetic diversity, derived allele frequency, differentiation between populations, and long haplotypes at schizophrenia-associated single nucleotide polymorphisms (SNPs) and randomly selected SNPs (as negative controls). We found evidence for positive selection at 10 out of the 105 schizophrenia-associated SNPs, while 5 of these SNPs involved positive selection for the protective allele. Taken together, the absence of widespread positive selection signals at the schizophrenia-associated SNPs, along with the fact that half of the positive selection favored the protective allele, provide little evidence supporting the positive selection theory in schizophrenia.
Identification of circular RNAs in porcine sperm and their relation to sperm motility
Authors: Gòdia Marta , Castelló Anna , Rocco Martina , Cabrera Betlem , Rodríguez-Gil Joan E. , Sánchez Armand , Clop Alex 
Published: April 2019

AbstractCircular RNAs (circRNAs) are emerging as a novel class of noncoding RNAs which potential role as gene regulators is quickly gaining interest. Although circRNAs have been studied in several tissues and cell types across several animal species, the characterization of the circRNAome in ejaculated sperm remains unexplored. In this study, we profiled the sperm circRNA catalogue in 40 boar samples. A complex population of 1,598 circRNAs was shared in at least 30 samples. The predicted circRNAs presented in general low abundances and were highly tissue-specific. Circa 80% of the circRNAs identified in the boar sperm were reported as novel. We also constructed a circRNA-miRNA interaction network based on experimental and predictive microRNA (miRNA) binding sites. Moreover, we found significant correlation between the abundance of some circRNAs and sperm motility parameters and confirmed two of these correlations by RT-qPCR in 36 samples with extreme sperm quality. Our study provides a thorough characterization of a novel cell type for the circRNA encyclopedia collection and suggests that circRNAs are potential noninvasive biomarkers for male sperm quality and thus, might also hold potential to predict male fertility.
Body mass index, earnings and partnership: genetic instrumental variable analysis in two nationally representative UK samples
Authors: Hughes Amanda , Bao Yanchun , Smart Melissa , Kumari Meena 
Published: April 2019

AbstractIn high-income countries there is an established link between high body mass index (BMI) and low income, but the direction of this association is unclear. Recent analyses in a large UK population using genetically-instrumented BMI supported a causal influence of BMI on household income, educational attainment and job class. Since analyses were based on an age-restricted and relatively wealthy population, it is unclear whether results are generalizable, and limited income data precluded decomposition of household income effects into own-income and partnership effects. Investigation is therefore warranted in more representative UK populations where associations may differ, and where individual and partner-based mechanisms can be studied separately.Data came from two nationally-representative samples, the UK Household Longitudinal Survey (UKHLS) and the English Longitudinal Study of Ageing (ELSA). Analysis was conducted in each sample, with results then pooled by meta-analysis. We used externally-weighted polygenic scores based on the latest genome-wide association study for BMI to examine the influence of genetically-instrumented BMI on earnings, probability of employment, job class conditional on working, likelihood of partnership, and partner’s earnings.A one-unit (kg/m2) increase in genetically-instrumented BMI was associated with a roughly 9% decrease in own monthly earnings (pooled coefficient: 0.91, CI:0.86, 0.97) and lower probability of employment (OR: 0.89, CI:0.83, 0.96) or having a university degree (OR: 0.95, CI:0.90, 0.99). Employed individuals with higher genetically-instrumented BMI were less likely to have professional or managerial occupations (OR: 0.91, CI:0.86, 0.96). No associations were seen with partnership. A one-unit increase in BMI was associated with a 5% decrease in partners’ earnings, but estimates were imprecise (pooled coefficient: 0.95, CI:0.88,1.01).Results are consistent with a negative influence of body mass index on a range of labour market and educational outcomes for both men and women.Key MessagesHigher genetically-instrumented BMI was associated with lower earnings and odds of workingAlso with lower odds of holding a managerial/professional occupation or a degreeNo associations were seen with probability of cohabiting partnership
A 3D molecular atlas of the chick embryonic heart
Authors: Anderson Claire , Hill Bill , Lu Hui-Chun , Moverley Adam , Yang Youwen , Oliveira Nidia M.M. , Baldock Richard A. , Stern Claudio D. 
Published: April 2019

AbstractWe present a detailed analysis of gene expression in the 2-day (HH12) embryonic chick heart. RNA-seq of 13 micro-dissected regions reveals regionalised expression of 15,570 genes. Of these, 132 were studied byin situhybridisation and a subset (38 genes) was mapped by Optical Projection Tomography or serial sectioning to build a detailed 3-dimensional atlas of expression. We display this with a novel interactive 3-D viewer and as stacks of sections, revealing the boundaries of expression domains and regions of overlap. Analysis of the expression domains also defines some sub-regions distinct from those normally recognised by anatomical criteria at this stage of development, such as a previously undescribed subdivision of the atria into two orthogonal sets of domains (dorsoventral and left-right). We also include a detailed comparison of expression in the chick with the mouse and other species.
Methods for the generation of heritable germline mutations in the disease vector Culex quinquefasciatus using CRISPR/Cas9
Authors: Li Ming , Li Ting , Liu Nannan , Raban Robyn , Wang Xuegui , Akbari Omar S. 
Published: April 2019

AbstractCulex quinquefasciatus is vector of many diseases that adversely impact human and animal health; however, compared to other mosquito vectors limited genome engineering technologies have been characterized for this vector. CRISPR-Cas9 based technologies are a powerful tool for genome engineering and functional genomics and consequently have transformed genomics studies in many organisms. Our objective was to improve upon the limited technologies available for genome editing in Cx. quinquefasciatus to create a reproducible and straightforward method for CRISPR-Cas9-targeted mutagenesis in this vector. Here we describe methods to both improve embryo survival rates as well as mutagenesis rates by optimizing injection supplies and equipment, embryo injection procedures, embryo handling and gRNA target design. Through these efforts, we achieved embryo survival rates and germline mutagenesis rates that greatly exceed any previously reported rates in this vector. This work was also the first characterize the white gene marker, which is a valuable phenotypic marker for future transgenesis or mutagenesis of this vector. In the end, these tools provide the framework for future functional genomic studies in this important disease vector and may support the development of future gene drive and genetic technologies that can be used to control this vector.
RNA-seq analysis of transcriptomes for assessing stress tolerance of S. cerevisiae strain, NCIM3186
Authors: Goud Burragoni Sravanthi , Ulaganathan Kandasamy 
Published: April 2019

AbstractWe have previously sequenced the draft genome of high ethanol producing S. cerevisiae strain, NCIM3186. Towards assessing the stress tolerance by this strain transcriptomes from control and in response to glucose, ethanol and furfural stress were sequenced. Comparative RNA-seq analysis of these transcriptomes identified 573 differentially expressed genes of which thiamine biosynthesis genes under furfural stress, TDH1, heat shock proteins and hexose transporter gene under ethanol stress were observed to be highly differentially expressed. Apart from thiamine biosynthesis genes and TDH1, 2 other proteins of unknown function were highly differentially expressed under glucose stress. Most importantly, TAR1 gene was highly down-regulated under all the stress conditions compared to control. Among 93 fermentome genes, 7 (TPS1, TPS2, SIN3, PTK2, SSQ1, ZAP1, DOA4) out of 9 stuck genes are found to be differentially expressed. Several stress-related genes like PHO4, SOD2, STR3, GRE2, GLR1, MEP1,3, MLH3, SNF1, MSN2, ATG1, GLC7 were differentially expressed.
Lineage specific core-regulatory circuits determine gene essentiality in cancer cells
Authors: Rauscher Benedikt , Henkel Luisa , Heigwer Florian , Boutros Michael 
Published: April 2019

ABSTRACTCancer cells rely on dysregulated gene expression programs to maintain their malignant phenotype. A cell’s transcriptional state is controlled by a small set of interconnected transcription factors that form its core-regulatory circuit (CRC). Previous work in pediatric cancers has shown, that disruption of the CRC by genetic alterations causes tumor cells to become highly dependent on its components creating new opportunities for therapeutic intervention. However, the role of CRCs and the mechanisms by which they are controlled remain largely unknown for most tumor types. Here, we developed a method that infers lineage dependency scores to systematically predict functional CRCs and associated biological processes from context-dependent essentiality data sets. Analysis of genome-scale CRISPR-Cas9 screens in 558 cancer cell lines showed that most tumor types specifically depend on a small number of transcription factors for proliferation. We found that these transcription factors compose the CRCs in these tumor types. Moreover, they are frequently altered in patient tumor samples indicating their oncogenic potential. Finally, we show that biological processes associated with each CRC are revealed by analyzing codependency between lineage-specific essential genes. Our results demonstrate that genetic addiction to lineage-specific core transcriptional mechanisms occurs across a broad range of tumor types. We exploit this phenomenon to systematically infer CRCs from lineage specific gene essentiality. Furthermore, our findings shed light on the selective genetic vulnerabilities that arise as the consequence of transcriptional dysregulation in different tumor types and show how the plasticity of regulatory circuits might influence drug resistance and metastatic potential.
Caenorhabditis eleganssensory neurons modulate pathogen specific responses via HLH-30/TFEB transcription factor and FSHR-1 GPCR axes of immunity
Authors: Gupta Anjali , Varma Manoj , Singh Varsha 
Published: April 2019

ABSTRACTPattern recognition receptors allow animals to sense microbe associated molecular patterns and mount effective immune responses. It is not clear howCaenorhabditis elegansrecognizes pathogenic microbes in absence of classical pattern recognition pathways. Here, we asked if sensory neurons ofC. elegansallow it to distinguish between pathogens. Exposure ofC. elegansto a Gram positive bacteriumEnterococcus faecalisor to a Gram negative bacteriumPseudomonas aeruginosashowed predominantly pathogen-specific signatures. Using nematodes defective in sensory perception, we show that neuronal sensing is essential to mount pathogen specific immune response. OSM-6 expressing, ciliated neurons exert non-cell autonomous control of immune effector production via an OSM-6-FSHR-1 GPCR axis as well as an OSM-6-HLH-30/TFEB transcription factor axis duringE. faecalisinfection. OSM-6-FSHR-1 axis also controls immune response toP. aeruginosa. In all, this study delineates essential role of sensory perception in the regulation of pathogen-specific immunity inC. elegans.
Relationship between Dynamic Instability of Individual Microtubules and Flux of Subunits into and out of Polymer
Authors: Mauro Ava J. , Jonasson Erin M. , Goodson Holly V. 
Published: April 2019

ABSTRACTBehaviors of dynamic polymers such as microtubules and actin are frequently assessed at one or both of two scales: (i) net assembly or disassembly of bulk polymer, (ii) growth and shortening of individual filaments. Previous work has derived various forms of an equation to relate the rate of change in bulk polymer mass (i.e., flux of subunits into and out of polymer, often abbreviated as “J”) to individual filament behaviors. However, these versions of this “Jequation” differ in the variables used to quantify individual filament behavior, which correspond to different experimental approaches. For example, some variants of theJequation use dynamic instability parameters, obtained by following particular individuals for long periods of time. Another form of the equation uses measurements from many individuals followed over short time steps. We use a combination of derivations and computer simulations that mimic experiments to (i) relate the various forms of theJequation to each other; (ii) determine conditions under which theseJequation forms are and are not equivalent; and (iii) identify aspects of the measurements that can affect the accuracy of each form of theJequation. Improved understanding of theJequation and its connections to experimentally measurable quantities will contribute to efforts to build a multi-scale understanding of steady-state polymer behavior.
Rapid characterisation of hERG channel kinetics II: temperature dependence
Authors: Lei Chon Lok , Clerx Michael , Beattie Kylie A. , Melgari Dario , Hancox Jules C. , Gavaghan David J. , Polonchuk Liudmila , Wang Ken , Mirams Gary R. 
Published: April 2019

ABSTRACTIon channel behaviour can depend strongly on temperature, with faster kinetics at physiological temperatures leading to considerable changes in currents relative to room temperature. These temperature-dependent changes in voltage-dependent ion channel kinetics (rates of opening, closing and inactivating) are commonly represented with Q10coefficients or an Eyring relationship. In this paper we assess the validity of these representations by characterising channel kinetics at multiple temperatures. We focus on the hERG channel, which is important in drug safety assessment and commonly screened at room temperature, so that results require extrapolation to physiological temperature. In Part I of this study we established a reliable method for high-throughput characterisation of hERG1a (Kv11.1) kinetics, using a 15 second information-rich optimised protocol. In this Part II, we use this protocol to study the temperature dependence of hERG kinetics using CHO cells over-expressing hERG1a on the Nanion SyncroPatch 384PE, a 384-well automated patch clamp platform, with temperature control. We characterise the temperature dependence of hERG gating by fitting the parameters of a mathematical model of hERG kinetics to data obtained at five distinct temperatures between 25 and 37 °C, and validate the models using different protocols. Our models reveal that activation is far more temperature sensitive than inactivation, and we observe that the temperature dependency of the kinetic parameters is not represented well by Q10coefficients: it broadly follows a generalised, but not the standardly-used, Eyring relationship. We also demonstrate that experimental estimations of Q10coefficients are protocol-dependent. Our results show that a direct fit using our 15 second protocol best represents hERG kinetics at any given temperature, and suggests that predictions from the Generalised Eyring theory may be preferentially used if no experimentally-derived data are available.Statement of SignificanceIon channel currents are highly sensitive to temperature changes. Yet because many experiments are performed more easily at room temperature, it is common to extrapolate findings to physiological temperatures through the use of Q10coefficients or Eyring rate theory. By applying short, information-rich protocols that we developed in Part I of this study we identify how kinetic parameters change over temperature. We find that the commonly-used Q10and Eyring formulations are incapable of describing the parameters’ temperature dependence, a more Generalised Eyring relationship works well, but remeasuring kinetics and refitting a model is optimal. The findings have implications for the accuracy of the many applications of Q10coefficients in electrophysiology, and suggest that care is needed to avoid misleading extrapolations in their many scientific and industrial pharmaceutical applications.
Longevity Relatives Count score identifies heritable longevity carriers and suggests case improvement in genetic studies
Authors: van den Berg Niels , Rodríguez-Girondo Mar , Mandemakers Kees , Janssens Angelique A.P.O. , Beekman Marian , Slagboom P. Eline 
Published: April 2019

AbstractLongevity loci represent key mechanisms of a life-long decreased mortality and decreased/compressed morbidity. However, identifying such loci is challenging. One of the most plausible reasons is the uncertainty in defining long-lived cases with the heritable longevity trait amongst long-living phenocopies. To avoid phenocopies, family selection scores have been constructed but these have not yet been adopted as state of the art in longevity research. Here we aim to identify individuals with the heritable longevity trait by using current insights and a novel family score based on these insights. We use a unique dataset connecting living study participants to their deceased ancestors covering 37,825 persons from 1,326 five-generational families, living between 1788 and 2019. Our main finding suggests that longevity is transmitted for at least 2 subsequent generations only when at least 20% of all relatives are long-lived. This proves the importance of family data to avoid phenocopies in genetic studies.
Brown adipocyte NOSEMPE promotes nonmitochondrial thermogenesis and improves systemic metabolism through ATF4 activation
Authors: Paulo Esther , Zhang Yun , Masand Ruchi , Huynh Tony L. , Seo Youngho , Swaney Danielle L. , Soucheray Margaret , Jimenez-Morales David , Krogan Nevan J. , Wang Biao 
Published: April 2019

AbstractMitochondrial transcription factor A (Tfam)-mediated mtDNA maintenance and transcription, as well as leucine-rich PPR motif-containing protein (Lrpprc)-mediated mtRNA maturation and translation are essential steps of mtDNA-encoded electron transport chain (ETC) protein expression. ETC is essential for mitochondrial thermogenesis, the process of oxygen-dependent heat production inside the mitochondria in brown adipocytes. Here we describe that Tfam or Lrpprc deficiency in brown adipocytes cause non-synchronized ETC mRNA and protein expression (NOSEMPE) and mitochondrial ETC imbalance, ultimately abolish mitochondrial thermogenesis. However, mice with NOSEMPE in brown adipocytes are cold resistant upon an acute 4°C cold challenge, because of augmented nonmitochondrial thermogenesis driven by the “NOSEMPE→ATF4→proteome turnover” pathway. Importantly, mice with either NOSEMPE or ATF4 overexpression in brown adipocytes are protected against high-fat-diet-induced metabolic abnormalities, indicating a positive association between nonmitochondrial thermogenesis in brown adipocytes and metabolic fitness. Thus, although brown adipocytes are defined by their unique ability to produce heat through mitochondrial respiration, our study demonstrates a novel cytosolic nonmitochondrial thermogenesis in brown adipocytes. Targeting this ATF4-dependent nonmitochondrial thermogenesis in brown adipocytes may represent a new therapeutic strategy for combating metabolic disorders.