bluuebunny/crossref_metadata_2025_split huggingface dataset:
OligoPVP: Phenotype-driven analysis of individual genomic information to prioritize oligogenic disease variants
Authors: Boudellioua Imane , Kulmanov Maxat , Schofield Paul N , Gkoutos Georgios V , Hoehndorf Robert 
Published: May 2018

ABSTRACTPurposeAn increasing number of Mendelian disorders have been identified for which two or more variants in one or more genes are required to cause the disease, or significantly modify its severity or phenotype. It is difficult to discover such interactions using existing approaches. The purpose of our work is to develop and evaluate a system that can identify combinations of variants underlying oligogenic diseases in individual whole exome or whole genome sequences.MethodsInformation that links patient phenotypes to databases of gene–phenotype associations observed in clinical research can provide useful information and improve variant prioritization for Mendelian diseases. Additionally, background knowledge about interactions between genes can be utilized to guide and restrict the selection of candidate disease modules.ResultsWe developed OligoPVP, an algorithm that can be used to identify variants in oligogenic diseases and their interactions, using whole exome or whole genome sequences together with patient phenotypes as input. We demonstrate that OligoPVP has significantly improved performance when compared to state of the art pathogenicity detection methods.ConclusionsOur results show that OligoPVP can efficiently detect oligogenic interactions using a phenotype-driven approach and identify etiologically important variants in whole genomes.
Ghrelin enhances food odor conditioning in healthy humans: an fMRI study
Authors: Han Jung Eun , Frasnelli Johannes , Zeighami Yashar , Larcher Kevin , Boyle Julie , McConnell Ted , Malik Saima , Jones-Gotman Marilyn , Dagher Alain 
Published: May 2018

SummaryVulnerability to obesity includes eating in response to food cues, which acquire incentive value through conditioning. The conditioning process is largely subserved by dopamine, theorized to encode the discrepancy between expected and actual rewards, known as the reward prediction error (RPE). Ghrelin is a gut-derived homeostatic hormone that triggers hunger and eating. Despite extensive evidence that ghrelin stimulates dopamine, it remains unknown in humans if ghrelin modulates food cue learning. Here we show using functional magnetic resonance imaging that intravenously administered ghrelin increased RPE-related activity in dopamine-responsive areas during food odor conditioning in healthy volunteers. Participants responded faster to food odor-associated cues and perceived them to be more pleasant following ghrelin injection. Ghrelin also increased functional connectivity between hippocampus and ventral striatum. Our work demonstrates that ghrelin promotes the ability of cues to acquire incentive salience, and has implications for the development of vulnerability to obesity.
Characterization of a human-specific tandem repeat associated with bipolar disorder and schizophrenia
Authors: Song Janet , Lowe Craig B. , Kingsley David M. 
Published: May 2018

AbstractBipolar disorder (BD) and schizophrenia (SCZ) are highly heritable diseases that affect over 3% of individuals worldwide. Genomewide association studies have strongly and repeatedly linked risk for both of these neuropsychiatric diseases to a 100 kb interval in the third intron of the human calcium channel gene CACNA1C. However, the causative mutation is not yet known. We have identified a novel human-specific tandem repeat in this region that is composed of 30 bp units, often repeated hundreds of times. This large tandem repeat is unstable using standard polymerase chain reaction and bacterial cloning techniques, which may have resulted in its incorrect size in the human reference genome. The large 30-mer repeat region is polymorphic in both size and sequence in human populations. Particular sequence variants of the 30-mer are associated with risk status at several flanking single nucleotide polymorphisms in the third intron of CACNA1C that have previously been linked to BD and SCZ. The tandem repeat arrays function as enhancers that increase reporter gene expression in a human neural progenitor cell line. Different human arrays vary in the magnitude of enhancer activity, and the 30-mer arrays associated with increased psychiatric disease risk status have decreased enhancer activity. Changes in the structure and sequence of these arrays likely contribute to changes in CACNA1C function during human evolution, and may modulate neuropsychiatric disease risk in modern human populations.
Recurrent Loss of APOBEC3H Activity during Primate Evolution
Authors: Garcia Erin I. , Emerman Michael 
Published: May 2018

AbstractGenes in the APOBEC3 family encode cytidine deaminases that provide a barrier against viral infection and retrotransposition. Of all APOBEC3 genes in humans, APOBEC3H (A3H) is the most polymorphic: some haplotypes encode stable and active A3H proteins, while others are unstable and inactive. Such variation in human A3H affects interactions with the lentiviral antagonist Vif, which counteracts A3H via proteasomal degradation. In order to broaden our understanding of A3H-Vif interactions as well as its evolution in Old World monkeys, we characterized A3H variation within four African green monkey (AGM) subspecies. We found that A3H is highly polymorphic in AGMs and has lost antiviral activity in multiple Old World monkeys. This loss of function was partially related to protein expression levels but was also influenced by amino acid mutations in the N-terminus. Moreover, we demonstrate that the evolution of A3H in the primate lineages leading to AGMs was not driven by Vif. Our work suggests that activity of A3H is evolutionarily dynamic and may have a negative effect on host fitness, resulting in its recurrent loss in primates.ImportanceAdaptation of viruses to their hosts is critical for transmission of viruses between different species. Previous studies had identified changes in a protein from the APOBEC3 family that influenced species-specificity of simian immunodeficiency viruses (SIVs) in African green monkeys. We studied the evolution of a related protein in the same system, APOBEC3H, which has experienced a loss of function in humans. This evolutionary approach revealed that recurrent loss of APOBEC3H activity has taken place during primate evolution suggesting that APOBEC3H places a fitness cost on hosts. The variability of APOBEC3H activity between different primates highlights the differential selective pressures on the APOBEC3 gene family.
Further expansion of methane metabolism in the Archaea
Authors: Wang Yulin , Hua Zheng-Shuang , Goh Kian Mau , Evans Paul N. , Liu Lei , Mao Yanping , Hugenholtz Philip , Tyson Gene W. , Li Wen-Jun , Zhang Tong 
Published: May 2018

AbstractThe recent discovery of key methane-metabolizing genes in the genomes from the archaeal phyla Bathyarchaeota and Verstraetearchaeota has expanded our understanding of the distribution of methane metabolism outside of the phylum Euryarchaeota. Here, we recovered two near-complete crenarchaeotal metagenome-assembled genomes (MAGs) from circumneutral hot springs that contain genes for methanogenesis, including the genes that encode for the key methyl-coenzyme M reductase (MCR) complex. These newly recovered archaea phylogenetically cluster with Geoarchaeota (deep lineage of archaeal order Thermoproteales), and the MCR-encoding genes clustered with the recently reported methanogens within the Verstraetearchaeota. In addition, genes encoding hydroxybutyryl-CoA dehydratase were identified in the newly recovered methanogens, indicating they might carry out the β-oxidation process. Together, our findings further expanded the methane metabolism outside the phylum Euryarchaeota.
Dynamic gait transition in theScolopendromorpha scolopocryptops rubiginosus L. Kochcentipede
Authors: Kuroda Shigeru , Uchida Nariya , Nakagaki Toshiyuki 
Published: May 2018

ABSTRACTCrawling using locomotory waves is a common method of locomotion for limbless and many-legged invertebrates. It is generally believed that the direction of locomotory waves is fixed for a given species. However, by recording and performing detailed analyses of the gait patterns of aScolopendromorpha scolopocryptops rubiginosus L. Kochcentipede in various conditions, we found that it dynamically generated its gait to allow for locomotory waves that varied in direction. By introducing thewave-indexorder parameter to characterise locomotory waves, we showed that gait patterns were associated with control of stride rather than rotation frequency.
A high-throughput method for unbiased quantitation and categorisation of nuclear morphology
Authors: Skinner Benjamin Matthew , Rathje Claudia Cattoni , Bacon Joanne , Johnson Emma Elizabeth Philippa , Larson Erica Lee , Kopania Emily Emiko Konishi , Good Jeffrey Martin , Yousafzai Gullalaii , Affara Nabeel Ahmed , Ellis Peter James Ivor 
Published: May 2018

AbstractThe physical arrangement of chromatin in the nucleus is cell type and species specific. This is particularly evident in sperm, in which most of the cytoplasm has been lost; the shape of the nucleus reflects the shape of the cell. Mice have distinctive falciform (‘hook shaped’) sperm heads and nuclei. Quantification of the differences in shape variation between mouse species and lines often relies on manual measurement and classification that leads to subjective results, making comparisons within and between samples difficult.We have developed an analysis program for assessing the morphology of asymmetric nuclei, and characterised the sperm of mice from a range of inbred, outbred and wild-derived mouse lines. We find that laboratory lines have elevated sperm shape variability both within and between samples in comparison to wild-derived inbred lines, and that sperm shape in the F1 offspring of CBA and C57Bl6J lines is subtly affected by the direction of the cross.Hierarchical clustering can distinguish distinct sperm shapes with greater efficiency and reproducibility than even experienced manual assessors. We quantified the range of morphological defects in the inbred BALB/c line, demonstrating we can identify different morphological subgroups. This approach has applications for studies of sperm development, infertility and toxicology.
Diagnostic Use of PCR in Carbapenamase-producing Enterobacteriaceae (CPE): An Improved Method to Overcome the presence of inhibitors for DNA Extraction from Blood Cultures
Authors: Salmuna Zeti Norfidiyati , Hassan Murnihayati 
Published: May 2018

AbstractBackgroundCarpanenamase-producingEnterobacteriaceae(CPE) has emerged as a threat to hospitalized patients. Phenotypic test such as Modified hodge test was less sensitive and specific especially to detectblaNDM-1 which is the most predominant genotype in this region. Nucleic acid amplification technology offers improved specificity and sensitivity. However, there is limitation in this method which is failed amplification due to the presence of inhibitors. In this study, we try to use previous method described by Villumseen et al with some modification using another DNA extraction kit.Methodology/Principle findingsThree confirmed isolates ofblaNDM-1 carbapenamase-producingKlebsiella pneumoniaewas spiked with 10 mls sterile whole blood in an aerobic Bactec Plus until the growth was detected. The blood specimen was taken and was subjected to DNA extraction method using two commercialized kits followed with multiplex PCR. All the three isolates revealedblaNDM-1 genotypes. Internal control was amplified in all three isolates.Conclusion/significanceThis study proved that we can get a specific and early diagnosis of CPE by using nucleic acid amplification technique directly from blood culture bottle and eliminate the effect of inhibitors.
Diverse homeostatic responses to visual deprivation by uncovering recurrent subnetworks
Authors: Sweeney Yann , Barnes Samuel J. , Clopath Claudia 
Published: May 2018

ABSTRACTMultiple homeostatic plasticity mechanisms are thought to be critical for the prevention of excessively high or aberrantly low neural activity in the adult cortex. In L2/3 of adult mouse visual cortex the interplay between disinhibition and local functional interactions may support homeostatic recovery following visual deprivation. Despite blanket disinhibition only a subset of L2/3 excitatory neurons are observed to exhibit homeostatic recovery. Recovering neurons tend to be correlated with each other, forming functional networks prior to deprivation. How homeostatic recovery occurs in this way is therefore unclear, particularly in conditions of global disinhibition.Here, we employ a computational modelling approach to investigate the origin of diverse homeostatic responses in the cortex. This model finds network size to be a critical determinant of the diverse homeostatic activity profiles observed following visual deprivation, as neurons which belong to larger networks exhibit a stronger homeostatic response. Our simulations provide mechanistic insights into the emergence of diverse homeostatic responses, and predict that neurons with a high proportion of enduring functional associations will exhibit the strongest homeostatic recovery. We test and confirm these predictions experimentally.
MECP2 duplication and mutations impair NSCs differentiation via miR-197 regulated ADAM10
Authors: Wang Yu-Meng , Zheng Yu-Fang , Yang Si-Yu , Yang Zhang-Min , Zhang Lin-Na , He Yan-Qin , Gong Xiao-Hong , Liu Dong , Finnell Richard H. , Qiu Zi-Long , Du Ya-Song , Wang Hong-Yan 
Published: May 2018

AbstractHow MECP2 (Methyl-CpG-binding protein 2) duplication affects cortex development remains elusive. We found that elevated MeCP2 expression promotes neurogenesis during cortex development in Tg(MECP2) mouse brain. Ectopic expression of MeCP2 in NPCs inhibits ADAM10 and hence compromises the NOTCH pathway during NPC differentiation. MeCP2 up-regulates miR-197 to down-regulate ADAM10. The enhanced NPC differentiation/migration in Tg(MECP2) embryonic brain can be repressed by overexpression of ADAM10 or a miR-197 inhibitor.Consistently, the reduced neurogenesis induced by three rare MeCP2 missense mutations (H371R, E394K, G428S) identified in a Han Chinese autism spectrum disorders (ASD) cohort, can be reversed by miR-197 both in vitro and in vivo. Our results revealed that a regulatory axis involving MeCP2, miR-197, ADAM10, and NOTCH signaling is critical for neurogenesis, which is affected by both MeCP2 duplication and mutation.
DNA Gap Repair-Mediated Site-Directed Mutagenesis is Different from Mandecki and Recombineering Approaches
Authors: Lyozin George T. , Brunelli Luca 
Published: May 2018

AbstractSite-directed mutagenesis allows the generation of mutant DNA sequences for downstream functional analysis of genetic variants involved in human health and disease. Understanding the mechanisms of different mutagenesis methods can help select the best approach for specific needs. We compared three different approaches for in vivo site-directed DNA mutagenesis that utilize a mutant single-stranded DNA oligonucleotide (ssODN) to target a wild type DNA sequence in the host Escherichia coli (E. coli). The first method, Mandecki, uses restriction nucleases to introduce a double stranded break (DSB) into a DNA sequence which needs to be denatured prior to co-transformation. The second method, recombineering (recombination-mediated genetic engineering), requires lambda red gene products and a mutant ssODN with homology arms of at least 20 nucleotides. In a third method described here for the first time, DNA gap repair, a mutant ssODN targets a DNA sequence containing a gap introduced by PCR. Unlike recombineering, both DNA gap repair and Mandecki can utilize homology arms as short as 10 nucleotides. DNA gap repair requires neither red gene products as recombineering nor DNA denaturation or nucleases as Mandecki, and unlike other methods is background-free. We conclude that Mandecki, recombineering, and DNA gap repair have at least partly different mechanisms, and that DNA gap repair provides a new, straightforward approach for effective site-directed mutagenesis.
Cortical spike multiplexing using gamma frequency latencies
Authors: Ballard Dana H. , Zhang Ruohan 
Published: May 2018

AbstractOne of the fundamental problems in understanding the brain, in particular the cerebral cortex, is that we only have a partial understanding of the basic communication protocols that underlie signal transmission. This makes it difficult to interpret the significance of particular phenomena such as basic firing patterns and oscillations at different frequencies. There are, of course, useful models. Motivated by single-cell recording technology, Poisson statistics of cortical action potentials have long been a basic component in models of signal representation in the cortex. However, it is increasingly difficult to integrate Poisson spiking with spike timing signals in the gamma frequency spectrum. A potential way forward is being sparked by new technologies that allow the exploration of very low-level communication strategies. Specifically, the voltage potential of a cell’s soma now can be recorded with very high fidelity in vivo, allowing correlation of its fine structure to be correlated with behaviors. To interpret this data, we have developed a unified model (gamma spike multiplexing, or GSM) wherein a cell’s somatic gamma frequencies can modulate the generation of action potentials. Such spikes can be seen as the basis for a general-purpose method of modulating fast communication in cortical networks. In particular, the model has several important advantages over traditional formalisms: 1) It allows multiple, independent processes to run in parallel, greatly increasing the processing capability of the cortex 2) Its processing speed is 102 to 103 times faster than population coding methods 3) Its processes are not bound to specific locations, but migrate across cortical cells as a function of time, facilitating the maintenance of cortical cell calibration.
Generation of white-eyedDaphnia magnamutants lackingscarletfunction
Authors: Binti Ismail Nur Izzatur , Kato Yasuhiko , Matsuura Tomoaki , Watanabe Hajime 
Published: May 2018

ABSTRACTThe crustaceanDaphnia magnais an important model in multi-disciplinary scientific fields such as genetics, evolutionary developmental biology, toxicology, and ecology. Recently, draft genome sequence and transcriptome data became publicly available for this species. Genetic transformation by introduction of plasmid DNA into a genome has been achieved. To further advanceD. magnafunctional genomics, identification of a screenable marker gene and generation of its mutant are indispensable. BecauseDaphniais more closely related to insects among crustaceans, we hypothesized that eye color-related genes can function as a marker gene as used inDrosophilagenetics. We searched orthologs ofDrosophilaeye pigment transporters White, Scarlet, and Brown in the genome ofD. magna. Amino acid sequence alignment and phylogenetic analysis suggested thatD. magnahas sixwhiteand onescarletorthologs, but lacks thebrownortholog. Due to a multiplicity ofwhiteorthologs, we analyzed function of thescarletortholog,DapmaSt, using RNA interference.DapmaStRNAi embryos showed disappearance of black pigments both in the compound eye and in the ocellus, suggesting thatDapmaStis necessary for black pigmentation inDaphniaeyes. To disruptDapmaStby using the Crispr/Cas9 system, we co-injectedDapmaSt-targeting gRNAs with Cas9 mRNAs into eggs and established white-eyedDapmaStmutant lines that lack eye pigments throughout their lifespan. Our results suggest thatDapmaStcan be used as a transformation marker inD. magng+aand theDapmaStmutants would be an important resource for genetic transformation of this species in the future.
Oscillation phenomenon and its mechanism of an energy-saving and emission-reduction system
Authors: Yin Jiuli , Bian Lishuang , Fan Qin , Fan Xinghua , Ai Huaqiang , Tian Lixin 
Published: May 2018

PurposeThis paper aims to study the oscillation phenomenon before chaos as well as its mechanism of occurrence in the energy-saving and emission-reduction system.Design/methodology/approachThe system dynamics analysis, phase portrait analyses, equilibrium point analysis and bifurcation curve were applied to this paper.FindingsFirst, the authors find an oscillation phenomenon previous to chaos. Second, on the one hand, the existence of two unstable saddles is the reason for the occurrence of oscillation phenomenon. On the other hand, the increasing of carbon emissions can arouse oscillation phenomenon.Originality/valueThis paper finds an oscillation phenomenon previous to chaos in the energy-saving and emission-reduction system. The mechanism of occurrence of oscillation phenomenon is studied. The existence of two unstable saddles is the reason for the occurrence of such oscillation phenomenon. The oscillation is related with fold bifurcation. The study also provides a theoretical basis for the further study of chaos control.
An intelligent algorithm for optimizing emergency department job and patient satisfaction
Authors: Azadeh Ali , Yazdanparast Reza , Abdolhossein Zadeh Saeed , Keramati Abbas 
Published: May 2018

PurposeResilience engineering, job satisfaction and patient satisfaction were evaluated and analyzed in one Tehran emergency department (ED) to determine ED strengths, weaknesses and opportunities to improve safety, performance, staff and patient satisfaction. The paper aims to discuss these issues.Design/methodology/approachThe algorithm included data envelopment analysis (DEA), two artificial neural networks: multilayer perceptron and radial basis function. Data were based on integrated resilience engineering (IRE) and satisfaction indicators. IRE indicators are considered inputs and job and patient satisfaction indicators are considered output variables. Methods were based on mean absolute percentage error analysis. Subsequently, the algorithm was employed for measuring staff and patient satisfaction separately. Each indicator is also identified through sensitivity analysis.FindingsThe results showed that salary, wage, patient admission and discharge are the crucial factors influencing job and patient satisfaction. The results obtained by the algorithm were validated by comparing them with DEA.Practical implicationsThe approach is a decision-making tool that helps health managers to assess and improve performance and take corrective action.Originality/valueThis study presents an IRE and intelligent algorithm for analyzing ED job and patient satisfaction – the first study to present an integrated IRE, neural network and mathematical programming approach for optimizing job and patient satisfaction, which simultaneously optimizes job and patient satisfaction, and IRE. The results are validated by DEA through statistical methods.