bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expectations May Influence the Effects of Transcranial Direct Current Stimulation
Authors: Rabipour Sheida , Wu Allan D. , Davidson Patrick S. R. , Iacoboni Marco 
Published: March 2018

AbstractGrowing interest surrounds transcranial direct current stimulation (tDCS) as a safe and inexpensive method for improving cognitive functions and mood. Nevertheless, tDCS studies rarely examine psychological factors such as expectations of outcomes, which may influence tDCS responsiveness through placebo-like effects. Here we sought to evaluate the potential influence of expectations on tDCS intervention outcomes. We assessed expectations of tDCS outcomes in 88 healthy young adults on three occasions: i) at baseline; ii) after reading information implying either high or low effectiveness of stimulation; and iii) after a single-session of sham-controlled anodal tDCS applied to the left dorsolateral prefrontal cortex, during working memory (WM) training. Participants were largely uncertain about the effectiveness of stimulation in improving cognitive function at baseline. High or low expectation priming using simple positive or cautionary messages significantly increased or decreased expectation ratings, respectively, but ratings significantly decreased following stimulation in all groups. We found greater improvement in participants who received high compared to low expectation priming. Participants who received active stimulation and low expectation priming exhibited the lowest performance, suggesting that expectation priming and stimulation may have interacted. We did not find a significant effect of baseline expectations, belief of group assignment, or individual characteristics on measures of WM and verbal fluency. However, controlling for baseline expectations revealed greater post-intervention improvement on the executive function measures in participants who received high (compared to low) expectation priming. People randomly assigned to receive high expectation priming reported having a more pleasant experience overall, including greater satisfaction. Our findings suggest that expectations of outcomes should be taken into account in tDCS-based experimental studies and clinical trials.Highlights- Based on prior knowledge, healthy subjects are uncertain about NIBS effectiveness.- Expectations of NIBS can change after a single exposure to simple written messages.- Expectations of outcomes may influence cognitive performance.- High expectations may lead to a more positive experience and motivation to perform.- Low expectations may be counterproductive to NIBS.
Shared Polygenicity detection using Elastic Nets: SHARPEN
Authors: John Majnu , Lencz Todd 
Published: March 2018

AbstractCurrent research suggests that hundreds to thousands of single nucleotide polymorphisms (SNPs) with modest effect sizes contribute to the genetic basis of many disorders, a phenomenon labeled as polygenicity. Additionally, many such disorders demonstrate polygenic overlap, in which risk alleles are shared at associated genetic loci. However, there are currently no well-developed statistical methods that can be utilized to detect specific subsets of SNPs involved in the shared polygenicity of phenotypes. In this paper, we illustrate how elastic nets, with appropriate adaptation in selecting the penalty parameter, can be utilized for narrowing the range of SNPs involved in shared polygenicity. We first develop the method when individual-level data from genomewide association studies (GWASs) are available; we also extend the approach so that it can be used when only summary level data from GWASs are available. We illustrate and assess the performance of the proposed methods using extensive simulations, and by applying the methods to summary level data from a pair of related GWASs with fasting glucose level and BMI as the phenotypes.
BioFeatureFinder: Flexible, unbiased analysis of biological characteristics associated with genomic regions
Authors: Ciamponi Felipe E. , Lovci Michael T. , Cruz Pedro R. S. , Massirer Katlin B. 
Published: March 2018

AbstractBioFeatureFinder is a novel algorithm which allows analyses of many biological genomic landmarks (including alternatively spliced exons, DNA/RNA-binding protein binding sites, and gene/transcript functional elements, nucleotide content, conservation, k-mers, secondary structure) to identify distinguishing features. BFF uses a flexible underlying model that combines classical statistical tests with Big Data machine-learning strategies. The model is created using thousands of biological characteristics (features) that are used to build a feature map and interpret category labels in genomic ranges. Our results show that BFF is a reliable platform for analyzing large-scale datasets. We evaluated the RNA binding feature map of 110 eCLIP-seq datasets and were able to recover several well-known features from the literature for RNA-binding proteins; we were also able to uncover novel associations. BioFeatureFinder is available at https://github.com/kbmlab/BioFeatureFinder/.
Ancient genomes document multiple waves of migration in Southeast Asian prehistory
Authors: Lipson Mark , Cheronet Olivia , Mallick Swapan , Rohland Nadin , Oxenham Marc , Pietrusewsky Michael , Pryce Thomas Oliver , Willis Anna , Matsumura Hirofumi , Buckley Hallie , Domett Kate , Hai Nguyen Giang , Hiep Trinh Hoang , Kyaw Aung Aung , Win Tin Tin , Pradier Baptiste , Broomandkhoshbacht Nasreen , Candilio Francesca , Changmai Piya , Fernandes Daniel , Ferry Matthew , Gamarra Beatriz , Harney Eadaoin , Kampuansai Jatupol , Kutanan Wibhu , Michel Megan , Novak Mario , Oppenheimer Jonas , Sirak Kendra , Stewardson Kristin , Zhang Zhao , Flegontov Pavel , Pinhasi Ron , Reich David 
Published: March 2018

AbstractSoutheast Asia is home to rich human genetic and linguistic diversity, but the details of past population movements in the region are not well known. Here, we report genome-wide ancient DNA data from thirteen Southeast Asian individuals spanning from the Neolithic period through the Iron Age (4100–1700 years ago). Early agriculturalists from Man Bac in Vietnam possessed a mixture of East Asian (southern Chinese farmer) and deeply diverged eastern Eurasian (hunter-gatherer) ancestry characteristic of Austroasiatic speakers, with similar ancestry as far south as Indonesia providing evidence for an expansive initial spread of Austroasiatic languages. In a striking parallel with Europe, later sites from across the region show closer connections to present-day majority groups, reflecting a second major influx of migrants by the time of the Bronze Age.
Genome-scale fitness profile of Caulobacter crescentus grown in natural freshwater
Authors: Hentchel Kristy L. , Ruiz Leila M. Reyes , Curtis Patrick D. , Fiebig Aretha , Coleman Maureen L. , Crosson Sean 
Published: March 2018

ABSTRACTBacterial genomes evolve in complex ecosystems and are best understood in this natural context, but replicating such conditions in the lab is challenging. We used transposon sequencing to define the fitness consequences of gene disruption in the bacteriumCaulobacter crescentusgrown in natural freshwater, compared to axenic growth in common laboratory media. Gene disruptions in amino acid and nucleotide biosynthesis pathways and in metabolic substrate transport machinery impaired fitness in both lake water and defined minimal medium relative to complex peptone broth. Fitness in lake water was enhanced by insertions in genes required for flagellum biosynthesis and reduced by insertions in genes involved in biosynthesis of the holdfast surface adhesin. We further uncovered numerous hypothetical and uncharacterized genes for which disruption impaired fitness in lake water, defined minimal medium, or both. At the genome scale, the fitness profile of mutants cultivated in lake water was more similar to that in complex peptone broth than in defined minimal medium. Microfiltration of lake water did not significantly affect the terminal cell density or the fitness profile of the transposon mutant pool, suggesting thatCaulobacterdoes not strongly interact with other microbes in this ecosystem on the measured timescale. Fitness of select mutants with defects in cell surface biosynthesis and environmental sensing were significantly more variable in lake water than in defined medium, presumably owing to day-to-day heterogeneity in the lake environment. This study reveals genetic interactions betweenCaulobacterand a natural freshwater environment, and provides a new avenue to study gene function in complex ecosystems.
Serotonin signaling in hippocampus during initial cocaine abstinence drives persistent drug seeking
Authors: Kohtz Amy S. , Aston-Jones Gary 
Published: March 2018

AbstractBackgroundThe initiation of abstinence (extinction day 1, ED1) represents a stressful event involving abstinence from drug. We showed previously that ED1 cocaine-seeking behavior is reduced by blocking 5-HT signaling in dorsal hippocampus in both male and female rats. We hypothesized that the experience of ED1 can substantially influence later relapse behavior, and that dorsal raphe serotonin (DR 5-HT) signaling to dorsal hippocampus (DH) may be involved.MethodsWe used pharmacological inhibition of dorsal hippocampus 5-HT1A/1B receptors (via WAY100,635 plus GR127935), and chemogenetic inhibition of dorsal raphe-dHPC signaling to test the roles of these pathways on cocaine-seeking 2 weeks after ED1. We also tested specific effects of 5-HT1A or 5-HT1B receptor antagonism on conditioned place preference for cocaine.ResultsInhibition of DR-DH signaling via DREADDs or 5-HT1A/1B antagonists decreased ED1 drug-seeking with persistent effects on cocaine-seeking 2 weeks later, confirming the involvement of 5-HT signaling to dorsal hippocampus in driving drug-seeking persistence. Administration of a 5-HT1B antagonist alone on ED1 transiently decreased drug-associated memory performance in CPP, whereas administration of a 5-HT1A antagonist had no effect on memory but blocked CPP on a subsequent test 24h later.ConclusionsWe conclude that blockade of DR inputs or 5HT1 signaling in DH on ED1 prevents recall of the drug-associated context and reduces drug seeking via antagonism of 5-HT1B receptors, and consolidates the memory of the newly non-drug context via antagonism of 5-HT1A receptors. Thus, treatments that modulate 5-HT-dependent memory mechanisms during initial abstinence may facilitate later maintenance of abstinence.
The X chromosome of the German cockroach, Blattella germanica, is homologous to a fly X chromosome despite 400 million years divergence
Authors: Meisel Richard P , Delclos Pablo J , Wexler Judith R 
Published: March 2018

AbstractBackgroundSex chromosome evolution is a dynamic process that can proceed at varying rates across lineages. For example, different chromosomes can be sex-linked between closely related species, whereas other sex chromosomes have been conserved for>100 million years. Cases of long-term sex chromosome conservation could be informative of factors that constrain sex chromosome evolution. Cytological similarities between the X chromosomes of the German cockroach (Blattella germanica) and most flies suggest that they may be homologous—possibly representing an extreme case of long-term conservation.ResultsTo test the hypothesis that the cockroach and fly X chromosomes are homologous, we analyzed whole genome sequence data from cockroach. We found evidence in both sequencing coverage and heterozygosity that a significant excess of the same genes are on both the cockroach and fly X chromosomes. We also present evidence that the candidate X-linked cockroach genes may be dosage compensated in hemizygous males. Consistent with this hypothesis, three regulators of transcription and chromatin on the fly X chromosome are conserved in the cockroach genome.ConclusionsOur results support our hypothesis that the German cockroach shares the same X chromosome as most flies. This may represent convergent evolution of the X chromosome in the lineages leading to cockroaches and flies. Alternatively, the common ancestor of most insects may have had an X chromosome that resembled the extant cockroach and fly X. Cockroaches and flies diverged ∼400 million years ago, which would be the longest documented conservation of a sex chromosome. Cockroaches and flies have different mechanisms of sex determination, raising the possibility that the X chromosome was conserved despite evolution of the sex determination pathway.
Assessment of the petroleum hydrocarbon biodegradation potential of the sediment microbial community from an urban fringing tidal marsh of Northern New England
Authors: Ní Chadhain Sinéad M. , Miller Jarett L. , Dustin John P. , Trethewey Jeff P. , Jones Stephen H. , Launen Loren A. 
Published: March 2018

AbstractWe assessed the impact of dodecane,n-hexane and gasoline on the microbial diversity of chronically polluted fringing tidal marsh sediment from the Great Bay Estuary of New Hampshire. Dilution cultures containing saturated alkane concentrations were sampled at zero, one and 10 days, andalkBandcyp153A1alkane hydroxylase gene libraries and 16S rRNA sequences were analyzed. The initial sediment had the most diverse alkane hydroxylase sequences and phylogenetic composition whereas treated sediments became less functionally and phylogenetically diverse with alkane substrates apparently enriching a few dominant taxa. All 1-and 10-day samples were dominated byPseudomonas-type alkane hydroxylase sequences except in dodecane treatments where primarilyRhodococcus--type alkane hydroxylases were detected. 16S rRNA profiling revealed that the Gammaproteobacteria, particularlyPseudomonas, dominated all one day samples, especially then-hexane and gasoline treatments (63.2 and 47.2% respectively) and the 10-dayn-hexane treatment (which contained 60.8%Pseudomonasand 18.6%Marinobacter).In contrast, the 10 days of dodecane treatment enriched for Actinobacteria (26.2%Rhodococcusand 32.4%Mycobacterium)and gasoline treatment enriched for Firmicutes (29.7%; mainlyBacillus, LysinibacillusandRumelibacillus).Our data indicate that fringing tidal marshes contain microbial communities with alkane-degrading abilities similar to larger meadow marshes, and support the hypothesis that alkane exposure reduces the functional and phylogenetic diversity of microbial communities in an alkane-specific manner. Further research to evaluate the ability of such fringing marsh communities to rebound to pre-pollutant diversity levels should be conducted to better assess the threat of petroleum to these habitats.
Compendium of Synovial Signatures Identifies Pathologic Characteristics for Predicting Treatment Response in Rheumatoid Arthritis
Authors: Kim Ki-Jo , Kim Minseung , Tagkopoulos Ilias 
Published: March 2018

ABSTRACTTreatment of patients with rheumatoid arthritis (RA) is challenging due to clinical heterogeneity and variability. Integration of RA synovial genome-scale transcriptomic profiling of different patient cohorts can provide insights on the causal basis of drug responses. A normalized compendium was built that consists of 256 RA synovial samples that cover an intersection of 11,769 genes from 11 datasets. Differentially expression genes (DEGs) that were identified in three independent methods were fed into functional network analysis, with subsequent grouping of the samples based on a non-negative matrix factorization method. Finally, we built a predictive model for treatment response by using RA-relevant pathway activation scores and four machine learning classification techniques. We identified 876 up-regulated DEGs including 24 known genetic risk factors and 8 drug targets. DEG-based subgrouping revealed 3 distinct RA patient clusters with distinct activity signatures for RA-relevant pathways. In the case of infliximab, we constructed a classifier of drug response that was highly accurate with an AUC/AUPR of 0.92/0.86. The most informative pathways in achieving this performance were the NFκB-, FcεRI- TCR-, and TNF signaling pathways. Similarly, the expression of the HMMR, PRPF4B, EVI2A, RAB27A, MALT1, SNX6, and IFIH1 genes contributed in predicting the patient outcome. Construction and analysis of normalized synovial transcriptomic compendia can provide useful insights for understanding RA-related pathway involvement and drug responses for individual patients. The efficacy of a predictive model for personalized drug response has been demonstrated and can be generalized to several drugs, co-morbidities, and other relevant features.
Label-free imaging of cholesterol and lipid distributions in model membranes
Authors: Donaldson Stephen H. , de Aguiar Hilton B. 
Published: March 2018

ABSTRACTOver recent decades, lipid membranes have become standard models for examining the biophysics and biochemistry of cell membranes. Interrogation of lipid domains within biomembranes is generally done with fluorescence microscopy via exogenous chemical probes. However, most fluorophores have limited partitioning tunability, with the majority segregating in the least biologically relevant domains (i.e., low-density liquid domains). Therefore, a molecular-level picture of the majority of non-labeled lipids forming the membrane is still elusive. Here, we present simple, label-free imaging of domain formation in lipid monolayers, with chemical selectivity in unraveling lipid and cholesterol composition in all domain types. Exploiting conventional vibrational contrast in spontaneous Raman imaging, combined with chemometrics analysis, allows for examination of ternary systems containing saturated lipids, unsaturated lipids, and cholesterol. We confirm features commonly observed by fluorescence microscopy, and provide an unprecedented analysis of cholesterol distribution at the single-membrane level.
Drosophilaegg-derived tyrosine phosphatase (EDTP): a novel target for improved survivorship to prolonged anoxia and cellular protein aggregates
Authors: Xiao Chengfeng , Qiu Shuang , Li Xiao , Luo Dan-Ju , Liu Gong-Ping 
Published: March 2018

AbstractDrosophilaegg-derived tyrosine phosphatase (EDTP), a lipid phosphatase that removes 3-position phosphate at the inositol ring, has dual functions in the oogenesis and the muscle performance during adult stages. A mammalian homologous geneMTMR14, which encodes the myotubularin-related protein 14, negatively regulates autophagy. Mutation ofEDTP/MTMR14, however, causes at least three deleterious consequences: (1) lethality in the early embryogenesis inDrosophila; (2) “jumpy” phenotype with apparently impaired motor functions; and (3) association with a rare genetic disorder called centronuclear myopathy. Here we show that flies carrying a heterozygousEDTPmutation had increased survivorship to prolonged anoxia; tissue-specific downregulation ofEDTPin non-muscle tissues, particularly motoneurons, extended the lifespan; and tissue-specific downregulation ofEDTPin motoneurons improved the survivorship to beta-amyloid peptides (Aβ42) and polyglutamine (polyQ) protein aggregates. MTMR14 expression was evident in the hippocampus and cortex in C57BL/6J and APP/PS1 mice. Compared with C57BL/6J mice, APP/PS1 mice had reduced MTMR14 in the cortex but not in the hippocampus. Hippocampal expression of MTMR14 was increased and plateaued at 9-17 months compared with 2-6 months in C57BL/6J mice. Aβ42 treatment increased the expression of MTMR14 in the primarily cultured hippocampal neurons of Sprague/Dawley rats and mouse Neuro2a neuroblasts. We demonstrated a novel approach of tissue-specific manipulation of the disease-associated geneEDTP/MTMR14for lifespan extension and the improvement of survivorship to cellular protein aggregates.
On expectation propagation for generalised, linear and mixed models
Authors: Kim Andy S.I. , Wand Matt P. 
Published: March 2018

SummaryExpectation propagation is a general approach to deterministic approximate Bayesian inference for graphical models, although its literature is confined mostly to machine learning applications. We investigate the utility of expectation propagation in generalised, linear, and mixed model settings. We show that, even though the algebra and computations are complicated, the notion of message passing on factor graphs affords streamlining of the required calculations and we list the algorithmic steps explicitly. Numerical studies indicate expectation propagation is marginally more accurate than a competing method for the models considered, but at the expense of bigger algebraic and computational overheads.
Stunting, starvation and refeeding: a review of forgotten 19th and early 20th century literature
Authors: Hermanussen M , Bogin B , Scheffler C 
Published: March 2018

AbstractAimTo scrutinize to what extent modern ideas about nutrition effects on growth are supported by historic observations in European populations.MethodWe reviewed 19th and early 20th century paediatric journals in the Staatsbibliothek zu Berlin, the third largest European library with an almost complete collection of the German medical literature. During a three‐day visit, we inspected 15 bookshelf meters of literature not available in electronic format.ResultsLate 19th and early 20th century breastfed European infants and children, independent of social strata, grew far below World Health Organisation (WHO) standards and 15–30% of adequately‐fed children would be classified as stunted by theWHOstandards. Historic sources indicate that growth in height is largely independent of the extent and nature of the diet. Height catch‐up after starvation was greater than catch‐up reported in modern nutrition intervention studies, and allowed for unimpaired adult height.ConclusionHistorical studies are indispensable to understand why stunting does not equate with undernutrition and why modern diet interventions frequently fail to prevent stunting. Appropriateness and effect size of modern nutrition interventions on growth need revision.
Effects of personal air pollution exposure on asthma symptoms, lung function and airway inflammation
Authors: Chambers L. , Finch J. , Edwards K. , Jeanjean A. , Leigh R. , Gonem S. 
Published: March 2018

SummaryBackgroundThere is evidence that air pollution increases the risk of asthma hospitalizations and healthcare utilization, but the effects on day‐to‐day asthma control are not fully understood.ObjectiveWe undertook a prospective single‐centre panel study to test the hypothesis that personal air pollution exposure is associated with asthma symptoms, lung function and airway inflammation.MethodsThirty‐two patients with a clinical diagnosis of asthma were provided with a personal air pollution monitor (Cairclip NO2/O3) which was kept on or around their person throughout the 12‐week follow‐up period. Ambient levels of NO2 and particulate matter were modelled based upon satellite imaging data. Directly measured ozone, NO2 and particulate matter levels were obtained from a monitoring station in central Leicester. Participants made daily electronic records of asthma symptoms, peak expiratory flow and exhaled nitric oxide. Spirometry and asthma symptom questionnaires were completed at fortnightly study visits. Data were analysed using linear mixed effects models and cross‐correlation.ResultsCairclip exposure data were of good quality with clear evidence of diurnal variability and a missing data rate of approximately 20%. We were unable to detect consistent relationships between personal air pollution exposure and clinical outcomes in the group as a whole. In an exploratory subgroup analysis, total oxidant exposure was associated with increased daytime symptoms in women but not men.Conclusions and clinical relevanceWe did not find compelling evidence that air pollution exposure impacts on day‐to‐day clinical control in an unselected asthma population, but further studies are required in larger populations with higher exposure levels. Women may be more susceptible than men to the effects of air pollution, an observation which requires confirmation in future studies.