bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in Utilization and Discard of HCV Antibody-Positive Deceased Donor Kidneys in the Era of Direct-Acting Antiviral Therapy
Authors: Bowring Mary G. , Kucirka Lauren M. , Massie Allan B. , Ishaque Tanveen , Bae Sunjae , Shaffer Ashton A. , Garonzik Wang Jacqueline , Sulkowski Mark , Desai Niraj , Segev Dorry L. , Durand Christine M. 
Published: June 2018

BackgroundThe availability of direct-acting antiviral (DAA) therapy might have impacted use of hepatitis C virus (HCV)-infected (HCV+) deceased donor kidneys for transplantation.MethodsWe used 2005 to 2018 Scientific Registry of Transplant Recipients data to identify 18 936 candidates willing to accept HCV+ kidneys and 3348 HCV+ recipients of HCV+ kidneys. We compared willingness to accept, utilization, discard, and posttransplant outcomes associated with HCV+ kidneys between 2 treatment eras (interferon [IFN] era, January 1, 2005 to December 5, 2013 vs DAA era, December 6, 2013 to August 2, 2018). Models were adjusted for candidate, recipient, and donor factors where appropriate.ResultsIn the DAA era, candidates were 2.2 times more likely to list as willing to accept HCV+ kidneys (adjusted odds ratio,2.072.232.41;P< 0.001), and HCV+ recipients were 1.95 times more likely to have received an HCV+ kidney (adjusted odds ratio,1.761.952.16;P< 0.001). Median Kidney Donor Profile Index of HCV+ kidneys decreased from 77 (interquartile range [IQR], 59-90) in 2005 to 53 (IQR, 40-67) in 2017. Kidney Donor Profile Index of HCV− kidneys remained unchanged from 45 (IQR, 21-74) to 47 (IQR, 24-73). After adjustment, HCV+ kidneys were 3.7 times more likely to be discarded than HCV− kidneys in the DAA era (adjusted relative rate,3.363.674.02;P< 0.001); an increase from the IFN era (adjusted relative rate,2.783.023.27;P< 0.001). HCV+ kidney use was concentrated within a subset of centers; 22.5% of centers performed 75% of all HCV+ kidney transplants in the DAA era. Mortality risk associated with HCV+ kidneys remained unchanged (aHR,1.071.191.32in both eras).ConclusionsGiven the elevated risk of death on dialysis facing HCV+ candidates, improving quality of HCV+ kidneys, and DAA availability, broader utilization of HCV+ kidneys is warranted to improve access in this era of organ shortage.
Soil viruses are underexplored players in ecosystem carbon processing
Authors: Trubl Gareth , Jang Ho Bin , Roux Simon , Emerson Joanne B. , Solonenko Natalie , Vik Dean R. , Solden Lindsey , Ellenbogen Jared , Runyon Alexander T. , Bolduc Benjamin , Woodcroft Ben J. , Saleska Scott R. , Tyson Gene W. , Wrighton Kelly C. , Sullivan Matthew B. , Rich Virginia I. 
Published: June 2018

SummaryRapidly thawing permafrost harbors ~30–50% of global soil carbon, and the fate of this carbon remains unknown. Microorganisms will play a central role in its fate, and their viruses could modulate that impact via induced mortality and metabolic controls. Because of the challenges of recovering viruses from soils, little is known about soil viruses or their role(s) in microbial biogeochemical cycling. Here, we describe 53 viral populations (vOTUs) recovered from seven quantitatively-derived (i.e. not multiple-displacement-amplified) viral-particle metagenomes (viromes) along a permafrost thaw gradient. Only 15% of these vOTUs had genetic similarity to publicly available viruses in the RefSeq database, and ~30% of the genes could be annotated, supporting the concept of soils as reservoirs of substantial undescribed viral genetic diversity. The vOTUs exhibited distinct ecology, with dramatically different distributions along the thaw gradient habitats, and a shift from soil-virus-like assemblages in the dry palsas to aquatic-virus-like in the inundated fen. Seventeen vOTUs were linked to microbial hosts (in silico), implicating viruses in infecting abundant microbial lineages fromAcidobacteria, Verrucomicrobia, andDeltaproteoacteria, including those encoding key biogeochemical functions such as organic matter degradation. Thirty-one auxiliary metabolic genes (AMGs) were identified, and suggested viral-mediated modulation of central carbon metabolism, soil organic matter degradation, polysaccharide-binding, and regulation of sporulation. Together these findings suggest that these soil viruses have distinct ecology, impact host-mediated biogeochemistry, and likely impact ecosystem function in the rapidly changing Arctic.
Exploratory analyses suggest less cognitive decline with nilvadipine treatment in very mild Alzheimer’s disease subjects
Authors: Abdullah L , Crawford F , Langlois H , Tsolaki M , Börjesson-Hanson A , Olde Rikkert M , Pasquier F , Wallin A , Kennelly S , Hendrix S , Blennow K , Lawlor B , Mullan M 
Published: June 2018

AbstractBackgroundWe explored whether the effects of nilvadipine on cognition were influenced by baseline Alzheimer’s disease (AD) severity.MethodsExploratory analyses were performed on the modified intention-to-treat (mITT) dataset (n = 497) of a phase III randomized placebo-controlled trial to examine the response to nilvadipine in very mild, mild and moderate AD subjects. The outcome measures included total and subscale scores of the Alzheimer’s Disease Assessment Scale Cognitive 12 (ADAS-Cog 12), the Clinical Dementia Rating Scale sum of boxes (CDR-sb) and the AD composite score (ADCOMS), an outcome measure recently developed to detect treatment responses in subjects with prodromal AD. Cerebrospinal fluid (CSF) biomarkers Aβ38, Aβ40, Aβ42, total tau and P181 tau were measured in a subset of samples (n = 55). Regression analyses were adjusted for potential confounders and effect modifiers in order to examine the interactive effects of nilvadipine and AD severity on cognitive outcomes over 78-weeks.ResultsCompared to their respective placebo-controls, nilvadipine-treated, very mild AD subjects showed less decline, whereas moderate AD subjects showed greater decline on the ADAS-Cog 12. Also in very mild AD, a beneficial effect (as measured by ADCOMS), was detected in the nilvadipine treated group. Therapeutic effects of nilvadipine were also observed for a composite memory trait in very mild AD subjects and a composite language trait in mild AD subjects. CSF Aβ42/Aβ40 ratios were increased in mild AD and decreased in moderate AD patients treated with nilvadipine, compared to their respective controls.ConclusionThese data suggest that very mild AD subjects benefited from nilvadipine and that future clinical trials of nilvadipine in this population are required to confirm these findings.Trial RegistrationNCT02017340 Registered 20 December 2013,https://clinicaltrials.gov/ct2/show/NCT02017340EUDRACT Reference Number 2012-002764-27 Registered 04 February 2013,https://www.clinicaltrialsregister.eu/ctr-search/search?query=2012-002764-27
MITA couples with PI3K to regulate actin reorganization during BCR activation
Authors: Jing Yukai , Kang Danqing , Yang Lu , Jiang Panpan , Li Na , Cheng Jiali , Li Jingwen , Miller Heather , Ren Boxu , Gong Quan , Yin Wei , Liu Zheng , Mattila Pieta , Yu Bing , Liu Chaohong 
Published: June 2018

AbstractAs an adaptor protein, MITA has been extensively studied in innate immunity. However, its role in adaptive immunity as well as its underlying mechanism are not completely understood. We used MITA KO mice to study the effect of MITA deficiency on B cell development and differentiation, BCR signaling during BCR activation and humoral immune response. We found that MITA deficiency promotes the differentiation of marginal zone B cells, which is linked to the lupus-like autoimmune disease that develops in MITA KO mice. MITA is involved in BCR activation and negatively regulates the activation of CD19 and Btk and positively regulates the activation of SHIP. Interestingly, we found that the activation of WASP and accumulation of F-actin is enhanced in MITA KO B cells upon stimulation. Mechanistically, we found that MITA uses PI3K mediated by the CD19-Btk axis as a central hub to control the actin remodeling that, in turn, offers feedback to BCR signaling. Overall, our study has provided a new mechanism on how MITA regulates BCR signaling via feedback from actin reorganization, which may contribute to the effects of MITA on the humoral immune response.
Pivoting of microtubules driven by minus end directed motors leads to their alignment to form an interpolar bundle
Authors: Winters Lora , Ban Ivana , Prelogović Marcel , Pavin Nenad , Tolić Iva M. 
Published: June 2018

ABSTRACTAt the beginning of mitosis, the cell forms a spindle made of microtubules and associated proteins to segregate chromosomes. An important part of spindle architecture is a set of antiparallel microtubule bundles connecting the two spindle poles. A key question is how microtubules extending at arbitrary angles form an antiparallel interpolar bundle. Here we show that microtubules meet at an oblique angle and subsequently rotate into antiparallel alignment. By combining experiments with theory, we show that microtubules from each pole search for those from the opposite pole by performing random angular movement. Upon contact of two microtubules, they slide sideways along each other towards the minus end, which we interpret as the action of minus end directed Cut7/kinesin-5 motors. In conclusion, random rotational motion helps microtubules from the opposite poles to find each other and subsequent accumulation of motors allows them to generate forces that drive interpolar bundle formation.
Xylanolytic psychrotrophs from andosolic sedge fens and moss heaths in Iceland
Authors: Rickman Olivia J. , Sigurbjörnsdóttir M. Auður , Vilhelmsson Oddur 
Published: June 2018

AbstractNine xylanolytic bacterial strains were isolated from fen and heath soils in northern Iceland. They were found by 16S rRNA gene sequencing to belong to the generaPaenibacillus,Bacillus,Pseudomonas, andStenotrophomonas. Using a simple, plate-based semiquantitative assay with azo-crosslinked xylan as the substrate, it was determined that although isolated from cold environments, most of the strains displayed greater xylanolytic activity under mesophilic conditions, with only the paenibacilli displaying markedly cold-active xylanolytic activity. Indeed, for one isolate,Paenibacillus castaneaeOV2122, xylanolytic activity was only detected at 15°C and below under the conditions tested. Of the nine strains,Paenibacillus amylolyticusOV2121 displayed the greatest activity at 5°C. Glycohydrolase family-specific PCR indicated that the paenibacilli produced multiple xylanases of families 10 and 11, whereas a family 8 xylanase was detected inPseudomonas kilonensisAL1515, and a family 11 xylanase inStenotrophomonas rhizophilaAL1610.
Gas seepage pockmark microbiomes suggest the presence of sedimentary coal seams in the Öxarfjörður graben of NE-Iceland
Authors: Þorsteinsdóttir Guðný Vala , Blischke Anett , Sigurbjörnsdóttir M. Auður , Óskarsson Finnbogi , Arnarson Þórarinn Sveinn , Magnússon Kristinn P. , Vilhelmsson Oddur 
Published: June 2018

AbstractNatural gas seepage pockmarks are found off and onshore in the Öxarfjörður graben, NE Iceland. The bacterial communities of two onshore seepage sites were analysed by amplicon sequencing of 16S rDNA, along with determining the geochemical characteristics, hydrocarbon content and the carbon isotope composition of the sites.While one site was found to be characterised by biogenic origin of methane gas, with carbon isotope ratio δ13C [‰] = −63.2, high content of organic matter and complex hydrocarbons, the other site showed a mixed origin of the methane gas (δ13C [‰] = −26.6) with geothermal characteristics and lower organic matter content. While both sites harbouredProteobacteriaas the most abundant bacterial phyla, theDeltaproteobacteriawere more abundant at the geothermal site, and theAlphaproteobacteriaat the biogenic site. TheDehalococcoidiaclass of theChloroflexiphylum was abundant at the geothermal site while theAnaerolineaeclass was more abundant at the biogenic site. Bacterial strains from the seepage pockmarks were isolated on a variety of selective media targeting bacteria with bioremediation potential. A total of 106 strains were isolated and characterised, including representatives from the phylaProteobacteria, Bacterioidetes, Firmicutes, andActinobacteria. This article describes the first microbial study on gas seepage pockmarks in Iceland.
Planktonic interference and biofilm alliance between aggregation substance and endocarditis and biofilm associated pili inEnterococcus faecalis
Authors: Afonina Irina , Lim Xin Ni , Tan Rosalind , Kline Kimberly A. 
Published: June 2018

ABSTRACTLike many bacteria,Enterococcus faecalisencodes a number of adhesins involved in colonization or infection of different niches. Two well-studiedE. faecalisadhesins, aggregation substance (AS) and endocarditis and biofilm-associated pili (Ebp), both contribute to biofilm formation on abiotic surfaces and in endocarditis, suggesting they may be expressed at the same time. Because different regulatory pathways have been reported for AS and Ebp, here we examined if they are co-expressed on the same cells and the functional impact of co-expression on individual cells and within a population. We found that while Ebp are only expressed on a subset of cells, when Ebp and AS are expressed on the same cells, pili interfere with AS-mediated clumping and impede AS-mediated conjugative plasmid transfer during planktonic growth. However, when the population density increases, horizontal gene transfer rates normalize and are no longer affected by pilus expression. Instead, at higher cell densities during biofilm formation, Ebp and AS differentially contribute to biofilm development and structure, synergizing to promote maximal biofilm formation.
Pasakbumin A controls the growth of Mycobacterium tuberculosis by enhancing the autophagy and production of antibacterial mediators in mouse macrophages
Authors: Lee Hyo-Ji , Ko Hyun-Jeong , Kim Seung Hyun , Jung Yu-Jin 
Published: June 2018

AbstractTuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) and remains a major health problem worldwide. Thus, there is an urgent need to identify new and more effective drugs to treat emerging multidrug-resistant TB (MDR-TB) and to reduce the side effects of anti-TB drugs, such as liver toxicity and other detrimental changes. In this study, to develop a novel candidate drug for effective TB treatment with few side effects in the host, we selected pasakbumin A isolated from Eurycoma longifolia (E. longifolia) Jack, which protected host cells against Mtb infection-induced death. Pasakbumin A significantly inhibited intracellular Mtb growth by inducing autophagy via the ERK1/2-mediated signaling pathway in Mtb-infected macrophages. We further investigated whether pasakbumin A could be used as a potential adjuvant for TB treatment. Treatment with pasakbumin A and the anti-TB drug rifampicin (RMP) potently suppressed intracellular Mtb killing by promoting autophagy as well as TNF-α production via the ERK1/2- and NF-κB-mediated signaling pathways in Mtb-infected cells. Our results suggest that pasakbumin A could be developed as a novel anti-TB drug or host-directed therapeutic (HDT) strategy to protect against host cell death and improve host defense mechanisms against Mtb infection in macrophages.
The effect of a free radical scavenger on oxidation stress in partial bladder outlet obstruction and its relief in a rat model
Authors: Choo Min Soo , Piao SongZhe , Oh Seung-June 
Published: June 2018

AbstractAIMSTo investigate the effect of a free radical scavenger (tempol) after relief of partial bladder outlet obstruction (pBOO) on bladder function in a rat model.METHODSpBOO was induced in 50 eight-week-old female Sprague-Dawley rats and relieved 3 weeks later. The rats were divided randomly into 5 groups: sham-operated, tempol-treated for 1 week (Treat-1w) or 3 weeks (Treat-3w), and no treatment for 1 week (nonTreat-1w) or 3 weeks (nonTreat-3w). Awaken cystometrograms were obtained 1 or 3 weeks after relief according to the grouping. The bladders were isolated and weighed. H&E, Masson’s trichrome and TUNEL staining were used to analyze histological changes. The oxidative stress assessed using malondialdehyde. The expression of beta-3 adrenoreceptor was examined by Western blotting.RESULTSThe tempol-treated groups exhibited a significant decrease in the number of IDCs per voiding cycle (nonTreat-1w vs. Treat-1w, 1.18±0.82 vs. 0.36±0.40, P=0.010; nonTreat-3w vs. Treat-3w, 1.51±0.69 vs. 0.23±0.25, P=0.002). The thickness and collagen fiber deposition of the detrusor muscle layer was significantly decreased in the treated groups. Apoptosis detected was mainly observed in the urothelial cell layer, although the rate of apoptosis was significantly decreased in the treated groups (48.9±3.36% vs. 32.7±11.10%, P=0.024; 25.8±4.67% vs. 15.7±9.83%, P=0.314). The tempol-treated groups showed significant decreases in the MDA concentrations at both 1 and 3 weeks after relief. The expression of the beta-3 adrenoreceptor was increased in the tempol-treated rats.CONCLUSIONSIschemic reperfusion injury after relief of pBOO caused histological and functional changes in the bladder. Free radical scavenger treatment prevented this oxidative stress.
Detecting spatiotemporal pattern of tuberculosis and the relationship between ecological environment and tuberculosis, a spatial panel data analysis in Guangxi, China
Authors: Cui Zhezhe , Lin Dingwen , Chongsuvivatwong Virasakdi , Zhao Jinming , Lin Mei , Ou Jing , Zhao Jinghua 
Published: June 2018

AbstractGuangxi is one of the provinces having the highest reported incidence of tuberculosis (TB) in China. However, spatial and temporal pattern and causation of the situation are still unclear. In order to detect the spatiotemporal pattern of TB and the association with ecological environment factors in Guangxi Zhuang autonomous region, China, We performed a spatiotemporal analysis with prediction using time series analysis, Moran’s I global and local spatial autocorrelation statistics, and space-time scan statistics, to detect temporal and spatial clusters. Spatial panel models were employed to identify the influence factors. The time series analysis shows that the number of reported cases peaked in spring and summer and decreased in autumn and winter with the annual reported incidence of 113.1/100,000 population. Moran’s I global statistics were greater than 0 (0.363 – 0.536) during the study period. The most significant hot spots were mainly located in the central part. The east part exhibited a low-low relation. By spacetime scanning, the clusters identified were similar to that of the local autocorrelation statistics, and were clustered toward the early of 2016. Duration of sunshine, per capita gross domestic product (PGDP), the recovery rate of TB and participation rate of new cooperative medical care insurance in rural areas had a significant negative association with TB. In conclusion, the reported incidence of TB in Guangxi remains high. The main cluster was located in the central part of Guangxi, a region where promoting the productivity, improving TB treatment pathway and strengthening environmental protective measures (increasing sunshine exposure) are urgently needed.
Netrin-1 plays a role in the effect of 10 weeks moderate exercise on myocardial fibrosis in rats
Authors: Daliang Zhou , Hong Fu , Lifang Yu , Lingling Zhang , Lin Wei , Dapeng Li , Tianshu Zhang , Weimin Li 
Published: June 2018

AbstractThis study aimed to determine the effect of Netrin-1 and its receptor on acute myocardial infarction in rats after aerobic exercise.METHODS:Twenty-four rats were randomly divided into three groups: the sham group (n = 8); acute myocardial infarction model group (AMI)(n = 8); and aerobic exercise treatment after acute myocardial infarction group(ET) (n = 8). After 10 weeks, the levels of netrin-1, tumor necrosis factor alpha α(TNF-α), and interleukin 6(IL-6) in the serum were measured. The expression of matrix metalloproteinases 2 and 9(MMP2,9), and their inhibitor, tissue inhibitor of metalloproteinases 2(TIMP2), myocardial netrin-1, Deleted in colorectal cancer(DCC) receptor were evaluated. Histopathological were evaluated. The collagen volume fraction of myocardial tissues was also calculated.RESULTS:Compared to the sham group, the AMI group and ET groups showed increased levels of serum TNF-α, IL-6 and significantly reduced levels of netrin-1. Levels of TNF-α and IL-6 were significantly reduced in the ET group compared to the AMI group, whereas the level of netrin-1 was increased. The expression of myocardial MMP2,9 was significantly increased in the AMI group compared to the sham group, whereas that of myocardial netrin-1, inhibitor of TIMP2 and DCC receptor, was significantly reduced. Compared to AMI group, the ET group showed reduced expression of myocardial MMP2,9 proteins, whereas expression of myocardial netrin-1, inhibitor of TIMP2 and DCC receptor, was significantly increased. The collagen volume fraction of myocardial tissues was significantly increased in the AMI group and ET group compared to the sham group, with the greater increase being noted in the AMI group.CONCLUSIONS: Aerobic exercise could increase levels of serum netrin-1 myocardial netrin-1, and DCC receptor and reduced expression of myocardial MMP2,9 proteins, to improve the degree of fibrosis following myocardial infarction in rats.
Spatial transcriptomics ofC. elegansmales and hermaphrodites identifies novel fertility genes
Authors: Ebbing Annabel , Vertesy Abel , Betist Marco , Spanjaard Bastiaan , Junker Jan Philipp , Berezikov Eugene , van Oudenaarden Alexander , Korswagen Hendrik C. 
Published: June 2018

SummaryTo advance our understanding of the genetic programs that drive cell and tissue specialization, it is necessary to obtain a comprehensive overview of gene expression patterns. Here, we have used RNA tomography to generate the first high-resolution, anteroposterior gene expression maps ofC. elegansmales and hermaphrodites. To explore these maps, we have developed computational methods for discovering region and tissue-specific genes. Moreover, by combining pattern-based analysis with differential gene expression analysis, we have found extensive sex-specific gene expression differences in the germline and sperm. We have also identified genes that are specifically expressed in the male reproductive tract, including a group of uncharacterized genes that encode small secreted proteins that are required for male fertility. We conclude that spatial gene expression maps provide a powerful resource for identifying novel tissue-specific gene functions inC. elegans. Importantly, we found that expression maps from different animals can be precisely aligned, which opens up new possibilities for transcriptome-wide comparisons of gene expression patterns.
Structure of a human intramembrane ceramidase explains enzymatic dysfunction found in leukodystrophy
Authors: Vasiliauskaité-Brooks Ieva , Healey Robert D. , Rochaix Pascal , Sounier Rémy , Grison Claire , Waltrich-Augusto Thierry , Fortier Mathieu , Hoh François , Saied Essa M. , Arenz Christoph , Basu Shibom , Leyrat Cédric , Granier Sébastien 
Published: June 2018

AbstractAlkaline ceramidases (ACERs) are a class of poorly understood transmembrane enzymes controlling the homeostasis of ceramides. They are implicated in human pathophysiology, including progressive leukodystrophy, colon cancer as well as acute myeloid leukemia. We report here the crystal structure of the human ACER type 3 (ACER3). Together with computational studies, the structure reveals that ACER3 is an intramembrane enzyme with a seven transmembrane domain architecture and a catalytic Zn2+ binding site in its core, similar to adiponectin receptors. Interestingly, we uncover a Ca2+ binding site physically and functionally connected to the Zn2+ providing a structural explanation for the known regulatory role of Ca2+ on ACER3 enzymatic activity and for the loss of function in E33G-ACER3 mutant found in leukodystrophic patients.