bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of dextran sodium sulfate-induced experimental colitis by adoptive transfer of peritoneal cells
Authors: Liu Ting , Ren Jun , Wang Wei , Wei Xia-wei , Shen Guo-bo , Liu Yan-tong , Luo Min , Xu Guang-chao , Shao Bin , Deng Sen-yi , He Zhi-yao , Liang Xiao , Liu Yu , Wen Yan-Zhu , Xiang Rong , Yang Li , Deng Hong-xin , Wei Yu-quan 
Published: November 2015

AbstractThe adoptive transfer of the natural regulatory B cells and macrophages should be a useful treatment for inflammation and autoimmune disease. However, it is usually difficult to isolate these cells from the tissues and expand them. Here, we investigated the feasibility of adoptively transferring peritoneal cells (PCs) as a treatment for DSS-induced colitis. We found that peritoneal cavity can provide an easily accessible site for harvesting enough number of PCs, namely, two-dose PCs for the treatment from a mouse in one operation. Adoptive therapy of these cells from healthy mice or those with disease is effectively in reducing the disease activity score. The natural B cells and macrophages of the infused PCs can selectively migrate to lesion sites and regulate the expression of Stat3, NF−κB, Smad3 and Smad7. Additionally, PCs exert dual activity of IL-10 and TGF-β secreted spontaneously by both peritoneal B cells and macrophages, which in turn enhance the induction of regulatory B cells and Macrophages in microenvironment of inflammation. Moreover, PCs can re-establish immunological tolerance in the OVA-immunized mice. Thus, our findings provide a new strategy for colitis therapy and could be of importance in additional exploration of other inflammation and autoimmune diseases therapy.
A quantitative proteomic approach for unveiling novel mechanisms associated with MeHg-induced toxicity: effects on the methylation cycle
Authors: Cabezas-Sanchez Pablo , Garcia-Calvo Estefania , Camara Carmen , Luque-Garcia Jose L. 
Published: November 2015

Abstract
Methylmercury (MeHg) is still a major threat for human health and the environment due to its extremely high toxicity that mainly affects the nervous system. Despite the great efforts made during the last few decades, the specific molecular mechanisms involved in MeHg-induced toxicity are still not completely unveiled. In this work we explored such mechanisms using neuroblastoma cells (Neuro-2a) and SILAC as a quantitative proteomic approach. We found that exposure of Neuro-2a cells to 2 mg L−1 MeHg for 8 h decreased the cell viability to 70% and caused significant changes in the morphology of the cells, specially regarding neurite development. Our proteomic results showed different proteins altered upon MeHg exposure that helped to identify pathways related to the toxicity exerted by MeHg. Specifically, we have found that MeHg affects the methylation cycle by inhibiting the expression of key enzymes including MTHFD1 and MTR. Moreover, we demonstrate that inhibition of MTHFD1 is not observed when exposing the cells to inorganic Hg and other heavy metals such as Pb or Cu. Thus, this work sets the stage for dissecting a specific molecular mechanism for MeHg-induced toxicity.
Metabolomics screening identifies reducedL-carnitine to be associated with progressive emphysema
Authors: Conlon Thomas M. , Bartel Jörg , Ballweg Korbinian , Günter Stefanie , Prehn Cornelia , Krumsiek Jan , Meiners Silke , Theis Fabian J. , Adamski Jerzy , Eickelberg Oliver , Yildirim Ali Önder 
Published: November 2015

Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis, small airway remodelling and emphysema. Emphysema is the destruction of alveolar structures, leading to enlarged airspaces and reduced surface area impairing the ability for gaseous exchange. To further understand the pathological mechanisms underlying progressive emphysema, we used MS-based approaches to quantify the lung, bronchoalveolar lavage fluid (BALF) and serum metabolome during emphysema progression in the established murine porcine pancreatic elastase (PPE) model on days 28, 56 and 161, compared with PBS controls. Partial least squares (PLS) analysis revealed greater changes in the metabolome of lung followed by BALF rather than serum during emphysema progression. Furthermore, we demonstrate for the first time that emphysema progression is associated with a reduction in lung-specific L-carnitine, a metabolite critical for transporting long-chain fatty acids into the mitochondria for their subsequent β-oxidation. In vitro, stimulation of the alveolar epithelial type II (ATII)-like LA4 cell line with L-carnitine diminished apoptosis induced by both PPE and H2O2. Moreover, PPE-treated mice demonstrated impaired lung function compared with PBS-treated controls (lung compliance; 0.067±0.008 ml/cmH20 compared with 0.035±0.005 ml/cmH20, P&lt;0.0001), which improved following supplementation with L-carnitine (0.051±0.006, P&lt;0.01) and was associated with a reduction in apoptosis. In summary, our results provide a new insight into the role of L-carnitine and, importantly, suggest therapeutic avenues for COPD.
Identification and characterization of the zosA gene involved in copper uptake in Bacillus subtilis 168
Authors: Fukuhara Takahiro , Kobayashi Kazuo , Kanayama Yousuke , Enomoto Shu-ichi , Kondo Taeko , Tsunekawa Naoki , Nemoto Michiko , Ogasawara Naotake , Inagaki Kenji , Tamura Takashi 
Published: November 2015

Abstract
dl-Penicillamine, a copper-specific metal chelator, remarkably suppressed the growth of Bacillus subtilis 168 when added to a synthetic medium under Cu2+ limitation. DNA microarray and screening of 2,602 knockout mutants showed that the zosA gene was de-repressed in the presence of 0.1% dl-penicillamine, and that the zosA mutant was sensitive to dl-penicillamine medium. The zosA mutant delayed the growth under Cu-limitation even without the chelator, and the sensitivity to dl-penicillamine was reversed by induction using 0.3 mM IPTG and the Pspac promoter inserted directly upstream of the zosA gene. Furthermore, the zosA mutant showed elevated tolerance of excessive Cu2+ but not of excessive Zn2+ added to LB and synthetic media. Homology modeling of the ZosA protein suggested that the protein can fold itself into essential domains for constituting a metal transporting ATPase. Our study suggests that zosA is a candidate gene involved in copper uptake.
Lovastatin for the Treatment of Adult Patients With Dengue: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Whitehorn James , Nguyen Chau Van Vinh , Khanh Lam Phung , Kien Duong Thi Hue , Quyen Nguyen Than Ha , Tran Nguyen Thi Thanh , Hang Nguyen Thuy , Truong Nguyen Thanh , Hue Tai Luong Thi , Cam Huong Nguyen Thi , Nhon Vo Thanh , Van Tram Ta , Farrar Jeremy , Wolbers Marcel , Simmons Cameron P. , Wills Bridget 
Published: November 2015

Abstract
Background.  Dengue endangers billions of people in the tropical world, yet no therapeutic is currently available. In part, the severe manifestations of dengue reflect inflammatory processes affecting the vascular endothelium. In addition to lipid lowering, statins have pleiotropic effects that improve endothelial function, and epidemiological studies suggest that outcomes from a range of acute inflammatory syndromes are improved in patients already on statin therapy.
Methods.  Following satisfactory review of a short pilot phase (40 mg lovastatin vs placebo in 30 cases), we performed a randomized, double-blind, placebo-controlled trial of 5 days of 80 mg lovastatin vs placebo in 300 Vietnamese adults with a positive dengue NS1 rapid test presenting within 72 hours of fever onset. The primary outcome was safety. Secondary outcomes included comparisons of disease progression rates, fever clearance times, and measures of plasma viremia and quality of life between the treatment arms.
Results.  Adverse events occurred with similar frequency in both groups (97/151 [64%] placebo vs 82/149 [55%] lovastatin; P = .13), and were in keeping with the characteristic clinical and laboratory features of acute dengue. We also observed no difference in serious adverse events or any of the secondary outcome measures.
Conclusions.  We found lovastatin to be safe and well tolerated in adults with dengue. However, although the study was not powered to address efficacy, we found no evidence of a beneficial effect on any of the clinical manifestations or on dengue viremia. Continuing established statin therapy in patients who develop dengue is safe.
Chinese Clinical Trials Registration.  ISRCTN03147572.
ID Learning Unit—Diagnostics Update: Current Laboratory Methods for Rapid Pathogen Identification in Patients With Bloodstream Infections
Authors: Rubach Matthew P. , Hanson Kimberly E. 
Published: November 2015

Abstract
Diagnostic assays that rapidly identify bloodstream pathogens have the potential to improve patient outcomes and antibiotic stewardship efforts. Current tests are based on the detection of nucleic acids that are specific to a targeted pathogen or based on organism identification using mass spectrometry. Most rapid assays require a positive blood culture as their sample input and expedite pathogen identification by 24–72 hours. For those assays that also report detection of drug resistance markers, information on antimicrobial resistance is expedited by 48–96 hours. This learning unit reviews the basic principles of rapid microorganism identification assays for bloodstream infections with the aim of assisting clinicians in the interpretation and optimal utilization of test results.
Influence of Myelography and Postmyelographic CT on Therapeutic Decisions in Degenerative Diseases of the Cervical Spine
Authors: Westermaier Thomas , Doerr Christina , Stetter Christian , Linsenmann Thomas , Koehler Stefan , Eriskat Joerg , Solymosi Laszlo , Ernestus Ralf-Ingo 
Published: November 2015

Study Design:
A retrospective analysis of clinical records and radiologic imaging by 3 independent reviewers to assess the indication for surgical treatment with and without myelography and postmyelographic computed tomography (MCT).

Objective:
To evaluate whether myelography and MCT obtained in addition to magnetic resonance imaging (MRI) influence therapeutic decisions in degenerative diseases of the cervical spine.

Summary of Background Data:
MRI has become the standard examination in spinal diseases. The role of myelography and MCT is not clearly defined in the modern diagnostic setup. In many departments, they are used if MRI leaves some diagnostic uncertainty. It has not been examined yet whether additional myelography and MCT change therapeutic strategies.

Materials and Methods:
Three investigators independently reviewed the anonymized clinical data and image files of 105 patients who had all undergone MRI, myelography, and MCT. They determined their treatment decisions after each of 2 assessment rounds based on the following: (1) MRI and, if available, native CT, and plain radiographs. (2) Additional myelography and MCT. The intraobserver variability was the primary endpoint.

Results:
Myelography and MCT had been performed in multilevel disease, recurrent complaints after surgery, or if MRI had not revealed a clear finding. The intraobserver variability was 26.3% and varied markedly between the 3 investigators (17%–41 %). It was the highest in cases of multilevel disease. If noninvasive imaging included native CT and plain radiographs, the intraobserver variability was significantly reduced to 10.3%.

Conclusions:
In unclear cases of degenerative disorders of the cervical spine, particularly multilevel stenosis, myelography and MCT add relevant information for therapeutic decisions in more than a quarter of the patients in comparison with MRI as the sole diagnostic modality, and changes therapeutic strategies. However, a significant part of the information drawn out of myelography and MCT can be obtained by a completion of noninvasive examinations (native CT and radiographs).
Safety of Propofol Used as a Rescue Agent During Colonoscopy
Authors: Okeke Francis C. , Shaw Spencer , Hunt Kristel K. , Korsten Mark A. , Rosman Alan S. 
Published: November 2015

Goal:
The goal of this study was to evaluate the safety of propofol when used by gastroenterologists in patients who have an inadequate response to standard sedation (narcotics and benzodiazepines).

Background:
Many patients fail to achieve adequate sedation from narcotics and benzodiazepines during colonoscopy. The administration of propofol for colonoscopy is increasing, although its use by gastroenterologists is controversial.

Study:
We performed a retrospective review of our hospital’s colonoscopy records from January 2006 to December 2009 to identify 403 subjects undergoing screening colonoscopies who required propofol (20 to 30 mg every 3 min as needed) because of inadequate response to standard sedation. We also randomly selected 403 controls undergoing screening colonoscopies from the same time period that only required standard sedation. The incidence of adverse effects was then compared.

Results:
There were no major adverse events in either group. The rates of minor adverse events in the propofol and control group were 0.02 and 0.01, respectively (P=0.56). Adverse effects in the propofol group included: transient hypotension (n=1), nausea/vomiting (n=3), agitation (n=2), and rash (n=1). Adverse effects seen with standard sedation included: transient hypotension (n=2), nausea/vomiting (n=1), and oversedation (n=2). Patients who received propofol were more likely to be younger, had a history of illicit drug use, and a longer procedure time (P<0.05).

Conclusions:
Adjunctive propofol administered by gastroenterologist for conscious sedation was not associated with increased incidence of adverse events. It may be of value in patients who do not respond to conventional sedation.
Centralizing content and distributing labor: a community model for curating the very long tail of microbial genomes
Authors: Putman Tim , Burgstaller Sebastian , Waagmeester Andra , Wu Chunlei , Su Andrew I. , Good Benjamin M. 
Published: November 2015

AbstractThe last 20 years of advancement in DNA sequencing technologies have led to the sequencing of thousands of microbial genomes, creating mountains of genetic data. While our efficiency in generating the data improves almost daily, applying meaningful relationships between the taxonomic and genetic entities requires a new approach. Currently, the knowledge is distributed across a fragmented landscape of resources from government-funded institutions such as NCBI and Uniprot to topic-focused databases like the ODB3 database of prokaryotic operons, to the supplemental table of a primary publication. A major drawback to large scale, expert curated databases is the expense of maintaining and extending them over time. No entity apart from a major institution with stable long-term funding can consider this, and their scope is limited considering the magnitude of microbial data being generated daily. Wikidata is an, openly editable, semantic web compatible framework for knowledge representation. It’s a project of the Wikimedia Foundation and offers knowledge integration capabilities ideally suited to the challenge of representing the exploding body of information about microbial genomics. We are developing a microbial specific data model, based on Wikidata’s semantic web compatibility, that represents bacterial species, strains and the gene and gene products that define them. Currently, we have loaded 1736 gene items and 1741 protein items for two strains of the human pathogenic bacteriaChlamydia trachomatisand used this subset of data as an example of the empowering utility of this model. In our next phase of development we will expand by adding another 118 bacterial genomes and their gene and gene products, totaling over ~900,000 additional entities. This aggregation of knowledge will be a platform for community-driven collaboration, allowing the networking of microbial genetic data through the sharing of knowledge by both the data and domain expert.
Maternal expression of the novel centrosome assembly factor Wdr8 is required for vertebrate embryonic mitosis and development
Authors: Inoue Daigo , Stemmer Manuel , Thumberger Thomas , Wittbrodt Joachim , Gruss Oliver J. 
Published: November 2015

AbstractThe assembly of the first centrosome occurs upon fertilisation when the male centrioles recruit pericentriolar material (PCM) from the egg cytoplasm. While inaccuracy in the assembly of centrosomes leads to infertility and abnormal embryogenesis, the mechanism that ensures accurate assembly in vertebrate embryos remains obscure. Here we applied a CRISPR-Cas9-mediated gene knockout to show that Wdr8, a novel centrosomal protein, is maternally essential for PCM assembly during embryonic mitoses of medaka (Oryzias latipes). Maternal/zygotic Wdr8-null (Wdr8−/−) blastomeres exhibit severe defects in PCM assembly that cause them to divide asymmetrically and develop multipolar mitotic spindles and aneuploidy. We demonstrate that Wdr8 interacts via its WD40 domains with the centriolar satellite protein SSX2IP. Strikingly, exogenously provided Wdr8 fully rescues Wdr8−/−embryos to adulthood, except in variants with mutations in the WD40 domains. This combination of targeted gene inactivation andin vivoreconstitution of the maternally essential Wdr8-SSX2IP complex reveals an essential link between maternal PCM and the stability of the zygotic genome in the early vertebrate embryo.
Environmental unpredictability and inbreeding depression select for mixed dispersal syndromes
Authors: Hidalgo Jorge , de Casas Rafael Rubio , Muñoz Miguel Á. 
Published: November 2015

AbstractBackground:Mixed dispersal syndromes have historically been regarded as bet-hedging mechanisms that enhance survival in unpredictable environments, ensuring that some propagules stay in the maternal environment while others can potentially colonize new sites. However, this entails paying the costs of both dispersal and non-dispersal. Propagules that disperse are likely to encounter unfavorable conditions for establishment, while non-dispersing propagules might form populations of close relatives burdened with inbreeding. Here, we investigate the conditions under which mixed dispersal syndromes emerge and are evolutionarily stable, taking into account the risks of both environmental unpredictability and inbreeding.Results:Using mathematical and computational modeling we show that high dispersal propensity is favored whenever temporal environmental unpredictability is low and inbreeding depression high, whereas mixed dispersal syndromes are adaptive under conditions of high environmental unpredictability, but more particularly if also inbreeding depression is small. Although pure dispersers can be selected for under some circumstances, mixed dispersal provides the optimal strategy under most parameterizations of our models, indicating that this strategy is likely to be favored under a wide variety of conditions. Furthermore, populations exhibiting any single phenotype go inevitably extinct when environmental and genetic costs are high, whilst mixed strategies can maintain viable populations even under such conditions.Conclusions:Our models support the hypothesis that the interplay between inbreeding depression and environmental unpredictability shapes dispersal syndromes, often resulting in mixed strategies. Moreover, mixed dispersal seems to facilitate persistence whenever conditions are critical or nearly critical for survival.
Rising out of the ashes: additive genetic variation for susceptibility toHymenoscyphus fraxineusinFraxinus excelsior
Authors: Muñoz F. , Marçais B. , Dufour J. , Dowkiw A. 
Published: November 2015

AbstractSince the early 1990s, ash dieback due to the invasive ascomyceteHymenoscyphus fraxineusis threateningFraxinus excelsiorin most of its natural range. Previous studies reported significant levels of genetic variability for susceptibility inF. excelsioreither in field or inoculation experiments. The present study was based on a field experiment planted in 1995, fifteen years before onset of the disease. Crown and collar status were monitored on 788 trees from 23 open-pollinated progenies originating from 3 French provenances. Susceptibility was modeled using a Bayesian approach where spatio-temporal effects were explicitly taken into account. Moderate narrow-sense heritability was found for Crown Dieback (CD, h2=0.42). This study is first to show that Collar Lesions are also heritable (h2=0.49 for prevalence and h2=0.42 for severity) and that there is significant genetic correlation (r=0.40) between the severities of both symptoms. There was no evidence for differences between Provenances. Family effects were detected, but computing Individual Breeding Values (IBV) showed that most of the genetic variation lies within families. In agreement with previous reports, early flushing correlates with better crown status. Consequences of these results in terms of management and breeding are discussed.
Characterization of expression quantitative trait loci in extensively phenotyped pedigrees ascertained for bipolar disorder
Authors: Peterson C. , Service S. , Jasinska A. , Gao F. , Zelaya I. , Teshiba T. , Bearden C. , Reus V. , Macaya G. , López-Jaramillo C. , Bogomolov M. , Benjamini Y. , Eskin E. , Coppola G. , Freimer N. , Sabatti C. 
Published: November 2015

ABSTRACTThe observation that variants regulating gene expression (expression quantitative trait loci, eQTL) are at a high frequency among SNPs associated with complex traits has made the genome-wide characterization of gene expression an important tool in genetic mapping studies of such traits. As part of a study to identify genetic loci contributing to bipolar disorder and a wide range of BP-related quantitative traits in members of 26 pedigrees from Costa Rica and Colombia, we measured gene expression in lymphoblastoid cell lines derived from 786 pedigree members. The study design enabled us to comprehensively reconstruct the genetic regulatory network in these families, provide estimates of heritability, identify eQTL, evaluate missing heritability for the eQTL, and quantify the number of different alleles contributing to any given locus.
Species sorting along a subsidy gradient alters community stability
Authors: Mucarella Mario E. , Jones Stuart E. , Lennon Jay T. 
Published: November 2015

ABSTRACTThe movement of resources between terrestrial and aquatic habitats has strong effects on ecological processes in recipient ecosystems. Allochthonous inputs modify the quality and quantity of the available resource pool in ways that may alter the composition and stability of recipient communities. Inputs of terrestrial dissolved organic carbon (tDOC) into aquatic ecosystems represent a large influx of resources that has the potential to affect local communities, especially microorganisms. To evaluate the effects terrestrial inputs on aquatic microbial community composition and stability, we manipulated the supply rate of tDOC to a set of experimental ponds. Along the tDOC supply gradient, we measured changes in diversity and taxon-specific changes in abundance and activity. We then determined community stability by perturbing each pond using a pulse of inorganic nutrients and measuring changes in composition and activity (i.e., responsiveness) along the gradient. Terrestrial DOC supply significantly altered the composition of the active microbial community. The composition of the active bacterial community changed via decreases in richness and evenness as well as taxon-specific changes in abundance and activity indicating species sorting along the gradient. Likewise, the responsiveness of the active bacterial community decreased along the gradient, which led to a more stable active community. We did not, however, observe these changes in diversity and stability in the total community (i.e., active and inactive organisms), which suggests that tDOC supply modifies microbial community stability through functional not structural changes. Together, these results show that altered aquatic terrestrial linkages can have profound effects on the activity and stability of the base of the food web and thus can alter ecosystem functioning.