bluuebunny/crossref_metadata_2025_split huggingface dataset:
GetOrganelle: a fast and versatile toolkit for accurate de novo assembly of organelle genomes
Authors: Jin Jian-Jun , Yu Wen-Bin , Yang Jun-Bo , Song Yu , dePamphilis Claude W. , Yi Ting-Shuang , Li De-Zhu 
Published: March 2018

AbstractGetOrganelle is a state-of-the-art toolkit to assemble accurate organelle genomes from NGS data. This toolkit recruit organelle-associated reads using a modified “baiting and iterative mapping” approach, conducts de novo assembly, filters and disentangles assembly graph, and produces all possible configurations of circular organelle genomes. For 50 published samples, we reassembled the circular plastome in 47 samples using GetOrganelle, but only in 12 samples using NOVOPlasty. In comparison with published/NOVOPlasty plastomes, we demonstrated that GetOrganelle assemblies are more accurate. Moreover, we assembled complete mitogenomes of fungi and animals using GetOrganelle. GetOrganelle is freely released under a GPL-3 license (https://github.com/Kinggerm/GetOrganelle).
An important class of intron retention events in human erythroblasts is regulated by cryptic exons proposed to function as splicing decoys
Authors: Parra Marilyn , Booth Ben W. , Weiszmann Richard , Yee Brian , Yeo Gene W. , Brown James B. , Celniker Susan E. , Conboy John G. 
Published: March 2018

AbstractDuring terminal erythropoiesis, the splicing machinery in differentiating erythroblasts executes a robust intron retention (IR) program that impacts expression of hundreds of genes. We studied IR mechanisms in the SF3B1 splicing factor gene, which expresses ~50% of its transcripts in late erythroblasts as a nuclear isoform that retains intron 4. RNA-seq analysis of nonsense-mediated decay (NMD)-inhibited cells revealed previously undescribed splice junctions, rare or not detected in normal cells, that connect constitutive exons 4 and 5 to highly conserved cryptic cassette exons within the intron. Minigene splicing reporter assays showed that these cassettes promote IR. Genome-wide analysis of splice junction reads demonstrated that cryptic noncoding cassettes are much more common in large (>1kb) retained introns than they are in small retained introns or in non-retained introns. Functional assays showed that heterologous cassettes can promote retention of intron 4 in the SF3B1 splicing reporter. Although many of these cryptic exons were spliced inefficiently, they exhibited substantial binding of U2AF1 and U2AF2 adjacent to their splice acceptor sites. We propose that these exons function as decoys that engage the intron-terminal splice sites, blocking cross-intron interactions required for excision. Developmental regulation of decoy function underlies a major component of the erythroblast IR program.
Neural coding of leg proprioception inDrosophila
Authors: Mamiya Akira , Gurung Pralaksha , Tuthill John 
Published: March 2018

SummaryAnimals rely on an internal sense of body position and movement to effectively control motor behavior. This sense of proprioception relies on diverse populations of mechanosensory neurons distributed throughout the body. However, little is known about how proprioceptor neurons collectively encode sensory stimuli. Here, we investigate neural coding of leg proprioception inDrosophila, usingin vivotwo-photon calcium imaging of proprioceptors during controlled movements of the fly tibia. We found that the axons of leg proprioceptors are organized into distinct functional projections that contain topographic representations of specific kinematic features. Using subtype-specific genetic driver lines, we show that one group of axons encodes tibia position (flexion/extension), another encodes movement direction, and a third encodes bidirectional movement and vibration frequency. Thus, proprioceptive sensing of a single leg joint is mediated by multiple subtypes of specialized sensory neurons. This architecture may help to maximize information transmission, processing speed, and robustness, which are critical for feedback control of the limbs during locomotion.
A strategy to study intrinsically mixed folded proteins: The structure in solution of ataxin-3
Authors: Sicorello A. , Kelly G. , Oregioni A. , Nováček J. , Sklenář V. , Pastore A. 
Published: March 2018

AbstractIt has increasingly become clear over the last two decades that proteins can contain both globular domains and intrinsically unfolded regions which both can contribute to function. While equally interesting, the disordered regions are difficult to study because they usually do not crystallize unless bound to partners and are not easily amenable to cryo-electron microscopy studies. Nuclear magnetic resonance spectroscopy remains the best technique to capture the structural features of intrinsically mixed folded proteins and describe their dynamics. These studies rely on the successful assignment of the spectrum, task not easy per se given the limited spread of the resonances of the disordered residues. Here, we describe assignment of the spectrum of ataxin-3, the protein responsible for the neurodegenerative Machado-Joseph disease. We used a 42 kDa construct containing a globular N-terminal josephin domain and a C-terminal tail which comprises thirteen polyglutamine repeats within a low-complexity region. We developed a strategy which allowed us to achieve 87% assignment of the spectrum. We show that the C-terminal tail is flexible with extended helical regions and interacts only marginally with the rest of the protein. We could also, for the first time, deduce the structure of the polyglutamine repeats within the context of the full-length protein and show that it has a strong helical propensity stabilized by the preceding region.
Lipid droplet phase transition in freezing cat embryos and oocytes probed by Raman spectroscopy
Authors: Okotrub K.A. , Mokrousova V.I. , Amstislavsky S.Y. , Surovtsev N.V. 
Published: March 2018

ABSTRACTEmbryo and oocyte cryopreservation is a widely used technology for cryopreservation of genetic resources. One challenging limitation of this technology is the cell damage during freezing associated with the intracellular lipid droplets. We exploit a Raman spectroscopy to investigate the freezing of cumulus-oocyte complexes, mature oocytes and early embryos of a domestic cat. All these cells are rich in lipids. The degree of lipid unsaturation, lipid phase transition from liquid-like disordered to solid-like ordered state (main transition) and triglyceride polymorphic state are studied. For all cells examined, the average degree of lipid unsaturation is estimated about 1.3 (with ±20 % deviation) double bonds per acyl chain. The onset of the main lipid phase transition occurs in a temperature range from −10 to +4 °C and does not depend significantly on the cell type. It is found that lipid droplets in cumulus-oocyte complexes undergo an abrupt lipid crystallization, which not completely correlate with the ordering of lipid molecule acyl chains. In the case of mature oocytes and early embryos obtainedin vitrofrom cumulus-oocyte complexes, the lipid phase transition is broadened. In frozen state lipid droplets inside the cumulus-oocyte complexes have higher content of triglyceride polymorphic β and β′ phases (∼66%) than it is estimated for the mature oocytes and the early embryos (∼50%). For the first time, to our knowledge, temperature evolution of lipid droplets phase state is examined. Raman spectroscopy is proved as a prospective tool forin situmonitoring of lipid phase state in single embryo/oocyte during freezing.
Interaction of diabetes and smoking on stroke: A population-based cross-sectional survey in China
Authors: Lou Heqing , Dong Zongmei , Zhang Pan , Shao Xiaoping , Li Ting , Zhao Chunyan , Zhang Xunbao , Lou Peian 
Published: March 2018

AbstractObjectivesDiabetes and smoking are known independent risk factors for stroke; however, their interaction concerning stroke is less clear. We aimed to explore such interaction and its influence on stroke in Chinese adults.DesignCross-sectional study.SettingCommunity-based investigation in Xuzhou, China.ParticipantsA total of 39,887 Chinese adults who fulfilled the inclusion criteria were included.MethodsParticipants were selected using a multi-stage stratified cluster method, and completed self-reported questionnaires on stroke and smoking. Type 2 diabetes mellitus (DM2) was assessed by fasting blood glucose or use of antidiabetic medication. Interaction, relative excess risk owing to interaction (RERI), attributable proportion (AP), and synergy index (S) were evaluated using a logistic regression model.ResultsAfter adjustment for age, sex, marital status, educational level, occupation, physical activity, body mass index, hypertension, family history of stroke, alcohol use, and blood lipids, the relationships between DM2 and stroke, and between smoking and stroke, were still significant: odds ratios were 2.75 (95% confidence interval [CI]: 2.03–3.73) and 1.70 (95% CI: 1.38–2.10), respectively. In subjects with DM2 who smoked, the RERI, AP, and S values (and 95% CIs) were 1.80 (1.24–3.83), 0.52 (0.37–0.73), and 1.50 (1.18–1.84), respectively.ConclusionsThe results suggest there are additive interactions between DM2 and smoking and that these affect stroke in Chinese adults.Article Summary: Strengths and limitations of this studyThe strengths of this study were that a large sample population was randomly selected from the general population of Xuzhou and many confounding risk factors were adjusted for.Owing to the cross-sectional design, we could not determine a causal combined relationship among diabetes, smoking and stroke.We were not able to control for some important and well-known risk factors of diabetes, such as heart rate and cardiovascular causes.We did not measure fresh fruit consumption, which is causally related to stroke.
An epigenetic score for BMI based on DNA methylation correlates with poor physical health and major disease in the Lothian Birth Cohort 1936
Authors: Hamilton Olivia KL , Zhang Qian , McRae Allan F , Walker Rosie M , Morris Stewart W , Redmond Paul , Campbell Archie , Murray Alison D , Porteous David J , Evans Kathryn L , McIntosh Andrew M , Deary Ian J , Marioni Riccardo E 
Published: March 2018

ABSTRACTBackgroundThe relationship between obesity and adverse health is well established, but little is known about the contribution of DNA methylation to obesity-related health outcomes. Additionally, it is of interest whether such contributions are independent of those attributed by the most widely used clinical measure of body mass – the Body Mass Index (BMI).MethodWe tested whether an epigenetic BMI score accounts for inter-individual variation in health-related, cognitive, psychosocial and lifestyle outcomes in the Lothian Birth Cohort 1936 (n=903). Weights for the epigenetic BMI score were derived using penalised regression on methylation data from unrelated Generation Scotland participants (n=2566).ResultsThe Epigenetic BMI score was associated with variables related to poor physical health (R2 ranges from 0.02-0.10), metabolic syndrome (R2 ranges from 0.01-0.09), lower crystallised intelligence (R2=0.01), lower health-related quality of life (R2=0.02), physical inactivity (R2=0.02), and social deprivation (R2=0.02). The epigenetic BMI score (per SD) was also associated with self-reported type 2 diabetes (OR 2.25, 95 % CI 1.74, 2.94), cardiovascular disease (OR 1.44, 95 % CI 1.23, 1.69) and high blood pressure (OR 1.21, 95% CI 1.13, 1.48; all at p<0.0011 after Bonferroni correction).ConclusionsOur results show that regression models with epigenetic and phenotypic BMI scores as predictors account for a greater proportion of all outcome variables than either predictor alone, demonstrating independent and additive effects of epigenetic and phenotypic BMI scores.
Big data approaches to decomposing heterogeneity across the autism spectrum
Authors: Lombardo Michael V. , Lai Meng-Chuan , Baron-Cohen Simon 
Published: March 2018

AbstractAutism is a diagnostic label based on behavior. While the diagnostic criteria attempts to maximize clinical consensus, it also masks a wide degree of heterogeneity between and within individuals at multiple levels of analysis. Understanding this multi-level heterogeneity is of high clinical and translational importance. Here we present organizing principles to frame the work examining multi-level heterogeneity in autism. Theoretical concepts such as ‘spectrum’ or ‘autisms’ reflect non-mutually exclusive explanations regarding continuous/dimensional or categorical/qualitative variation between and within individuals. However, common practices of small sample size studies and case-control models are suboptimal for tackling heterogeneity. Big data is an important ingredient for furthering our understanding heterogeneity in autism. In addition to being ‘feature-rich’, big data should be both ‘broad’ (i.e. large sample size) and ‘deep’ (i.e. multiple levels of data collected on the same individuals). These characteristics help ensure the results from a population are more generalizable and facilitate evaluation of the utility of different models of heterogeneity. A model’s utility can be shown by its ability to explain clinically or mechanistically important phenomena, but also by explaining how variability manifests across different levels of analysis. The directionality for explaining variability across levels can be bottom-up or top-down, and should include the importance of development for characterizing change within individuals. While progress can be made with ‘supervised’ models built upon a priori or theoretically predicted distinctions or dimensions of importance, it will become increasingly important to complement such work with unsupervised data-driven discoveries that leverage unknown and multivariate distinctions within big data. Without a better understanding of how to model heterogeneity between autistic people, progress towards the goal of precision medicine may be limited.
25 Years of Molecular Biology Databases: A Study of Proliferation, Impact, and Maintenance
Authors: Imker Heidi J. 
Published: March 2018

ABSTRACTOnline resources enable unfettered access to and analysis of scientific data and are considered crucial for the advancement of modern science. Despite the clear power of online data resources, including web-available databases, proliferation can be problematic due to challenges in sustainability and long-term persistence. As areas of research become increasingly dependent on access to collections of data, an understanding of the scientific community’s capacity to develop and maintain such resources is needed.The advent of the Internet coincided with expanding adoption of database technologies in the early 1990s, and the molecular biology community was at the forefront of using online databases to broadly disseminate data. The journalNucleic Acids Researchhas long published articles dedicated to the description of online databases, as either debut or update articles. Snapshots throughout the entire history of online databases can be found in the pages ofNucleic Acids Research‘s “Database Issue.” Given the prominence of the Database Issue in the molecular biology and bioinformatics communities and the relative rarity of consistent historical documentation, database articles published in Database Issues provide a particularly unique opportunity for longitudinal analysis.To take advantage of this opportunity, the study presented here first identifies each unique database described in 3055Nucleic Acids ResearchDatabase Issue articles published between 1991-2016 to gather a rich dataset of databases debuted during this time frame, regardless of current availability. In total, 1727 unique databases were identified and associated descriptive statistics were gathered for each, including year debuted in a Database Issue and the number of all associated Database Issue publications and accompanying citation counts. Additionally, each database identified was assessed for current availability through testing of all associated URLs published. Finally, to assess maintenance, database websites were inspected to determine the last recorded update. The resulting work allows for an examination of the overall historical trends, such as the rate of database proliferation and attrition as well as an evaluation of citation metrics and on-going database maintenance.
Zebrafish as a model to investigate the effects of exercise in cancer
Authors: Yin Alexandra , Campbell Nathaniel R. , Jones Lee W. , White Richard M. 
Published: March 2018

AbstractEmerging data indicates that exercise may regulate cancer pathogenesis, but the mechanisms underpinning how it regulates the tumor as well as surrounding microenvironment are poorly understood. Dissecting this complex, highly integrated physiology requires model systems which accurately recapitulate key aspects of human response to exercise, yet permit rapid and unbiased genetic interrogation of relevant pathways. The zebrafish has emerged as a new model for cancer due to its high resolution in vivo imaging and capacity for large-scale, unbiased screening approaches. Here, we have developed a set of tools to study the effects of exercise in a zebrafish model of melanoma. Using a flow chamber, we studied the effects of endurance exercise bouts (3-6 hour/d, 5d/wk for 1 to 3 wks) in both larval and adult zebrafish. The regimen was well tolerated, with no unexpected toxicities or changes in survival. When the zebrafish were transplanted with ZMEL1-GFP melanoma cells, we found that endurance exercise over a 2-week period led to a significant decrease in cancer growth in the larval zebrafish. As zebrafish cancer models show strong conservation in human disease, our findings have direct application to understanding the human exercise/cancer relationship.
Dystroglycan proteolysis is conformationally-regulated and disrupted by disease-associated mutations
Authors: Hayward Amanda N. , Gordon Wendy R. 
Published: March 2018

AbstractThe adhesion receptor dystroglycan provides a critical mechanical link between the extracellular matrix (ECM) and the actin cytoskeleton to help muscle cells withstand contraction and neural cells maintain the blood brain barrier. Disrupting the link is associated with diseases such as cancer and muscular dystrophy. Proteolysis of dystroglycan by Matrix Metalloproteases (MMPs) also breaks the mechanical anchor and is amplified in several pathogenic states. We use a combination of biochemical and cell-based assays to show that dystroglycan proteolysis is conformationally regulated by an extracellular, juxtamembrane “proteolysis domain”, comprised of tandem Ig-like and SEA-like domains. The intact proteolysis domain is resistant to MMP cleavage, but structurally-disruptive muscular dystrophy-related mutations sensitize dystroglycan to proteolysis. Moreover, increased dystroglycan proteolysis correlates with faster cell migration, linking proteolysis to a disease-relevant cellular phenotype. Intriguingly, previously uncharacterized cancer-associated mutations that map to the proteolysis domain similarly lead to increases in proteolysis and rates of cell migration, potentially revealing a new pathogenic mechanism in cancer.
Effect of tributyltin chloride (TBT-Cl) exposure on expression ofHSP90β1in the river pufferfish (Takifugu obscurus): evidences for its immunologic function involving in exploring process
Authors: Dong-po Xu , Di-an Fang , Chang-sheng Zhao , Shu-lun Jiang , Hao-yuan Hu 
Published: March 2018

AbstractHSP90β1(known as GP96) is a vital endoplasmic reticulum depended chaperonin among the HSPs family. It plays important roles in regulating the growth, development, differentiation, and apoptosis of cells. Furthermore, it always processes and presents antigen of the tumor and keeps balance for the intracellular environment. In the present study, we explored the effect of tributyltin chloride (TBT-Cl) exposure onHSP90β1expression in river pufferfish,Takifugu obscurus. The full length ofTo-HSP90β1was gained with 2775 bp in length, an ORF obtained with 2412 bp encoding an 803 aa polypeptide. The phylogenetic tree was constructed and showed the close relationship to other fish species. TheHSP90β1mRNA transcript was expressed in all tissues investigated. After the acute and chronic exposure of TBT-Cl, the mRNA level ofTo-HSP90β1significantly up-regulated in tissues of liver and gill. Moreover, the histochemistry study indicated the injury degree of TBT-Cl on liver and gill. Immunohistochemistry (IHC) staining results implied the cytoplasm reorganization after TBT-Cl stress and the function of immunoregulation forTo-HSP90β1. All the results indicated thatHSP90β1may involve in the resistance to the invasion of TBT-Cl for keeping autoimmune homeostasis.
Contribution of structural variation to genome structure: TAD fusion discovery and ranking
Authors: Huynh Linh , Hormozdiari Fereydoun 
Published: March 2018

AbstractThe significant contribution of structural variants to function, disease, and evolution is widely reported. However, in many cases, the mechanism by which these variants contribute to the phenotype is not well understood. Recent studies reported structural variants that disrupted the three-dimensional genome structure by fusing two topologically associating domains (TADs), such that enhancers from one TAD interacted with genes from the other TAD, and could cause severe developmental disorders. However, no computational method exists for directly scoring and ranking structural variations based on their effect on the three-dimensional structure such as the TAD disruption to guide further studies of their biological function. In this paper, we formally define TAD fusion and provide a combinatorial approach for assigning a score to quantify the level of TAD fusion for each deletion denoted as TAD fusion score. We also show that our method outperforms the approaches which use predicted TADs and overlay the deletion on them to predict TAD fusion. Furthermore, we show that deletions that cause TAD fusion are rare and under negative selection in general population. Finally, we show that our method correctly gives higher scores to deletions reported to cause various disorders (developmental disorder and cancer) in comparison to the deletions reported in the 1000 genomes project.