bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stepwise modifications of genetic parts reinforce the secretory production of nattokinase in Bacillus subtilis
Authors: Cui Wenjing , Suo Feiya , Cheng Jintao , Han Laichuang , Hao Wenliang , Guo Junling , Zhou Zhemin 
Published: July 2018

SummaryNattokinase (NK) is an important serine‐protease with direct fibrinolytic activity involving the prevention of cardiovascular disease as an antithrombotic agent. Dozens of studies have focused on the characterization of intrinsic novel promoters and signal peptides to the secretory production of recombinant proteins in Bacillus subtilis. However, intrinsic genetic elements have several drawbacks, which cannot mediate the production of NK to the desired level. In this study, the genetic elements, which were used to overproduce the recombinant secretory NK, were rationally modified in B. subtilis in a stepwise manner. The first step was to select a suitable signal peptide for the highly efficient secretion of NK. By comparison of the secretory levels mediated by two different signal peptides, which were encoded by the genes of a minor extracellular protease epr (SPepr) and cell‐wall associated protease wapA (SPwapA), respectively, SPwapA was verified as the superior secretory element. Second, P04, which was a synthetic promoter screened from an array of mutants based on the promoter cloned from the operon of a quorum‐sensing associated gene srfA (PsrfA), was paired to SPwapA. The secretory level of NK was obviously augmented by the combination of these two genetic elements. Third, the cis‐acting element CodY‐binding sequence positioned at the 5′UTR was deleted (yielding P08), and thus the secretory level was significantly elevated. The activity of NK, which was defined as fibrinolytic units (FU), reached to a level of 270 FU ml−1. Finally, the superior genetic element composed of P08 and SPwapA was utilized to overproduce NK in the host B. subtilis WB800, which was able to produce the secretory NK at 292 FU ml−1. The strategy established in this study can not only be used to overproduce NK in B. subtilis but also might be a promising pipeline to modify the genetic element for the synthetic secretory system.
Ghrelin modulates mesolimbic reactivity to alcohol cues in alcohol‐addicted subjects: a functional imaging study
Authors: Koopmann Anne , Bach Patrick , Schuster Rilana , Bumb Jan Malte , Vollstädt‐Klein Sabine , Reinhard Iris , Rietschel Marcella , Witt Stephanie H. , Wiedemann Klaus , Kiefer Falk 
Published: July 2018

AbstractGhrelin has been shown to be involved in the pathophysiology of alcohol dependence, affecting alcohol self‐administration and craving. However, the mechanism of action in alcohol dependence still has to be determined. We thus investigated whether ghrelin is associated with mesolimbic cue reactivity to alcohol cues and alcohol craving in recently detoxified alcohol‐addicted subjects. We included 41 recently detoxified alcohol‐dependent individuals. Functional magnetic resonance imaging (fMRI) was used to study mesolimbic cue reactivity during the presentation of alcohol‐related pictures. Additionally, we assessed patients' alcohol craving using the Alcohol Urge Questionnaire and a visual analogue scale. Plasma concentrations of total and acylated (activated) ghrelin were measured in parallel to the fMRI session. The association between ghrelin plasma concentrations, mesolimbic cue reactivity and alcohol craving was assessed by performing correlation and mediation analyses. Alcohol‐induced brain response in a network of brain clusters, including the right and left ventral striatum, showed a significant positive association with acylated ghrelin plasma concentration. Additionally, acylated ghrelin was significantly associated with craving. Mediation analyses showed that the association between acylated ghrelin plasma concentration and alcohol craving is mediated by a cue‐induced brain response in the ventral striatum. Based on the finding that ghrelin modulates mesolimbic reactivity to alcohol cues, the following should be considered: If alcohol craving and the appetitive status were interrelated, this has to be taken into account when implementing fMRI studies for addictive disorders. Moreover, appetite regulation seems to represent a valid treatment target for reducing cue reactivity in addictive disorders.
Associations between repeated ultrasound measures of fetal growth and biomarkers of maternal oxidative stress and inflammation in pregnancy
Authors: Ferguson Kelly K. , Kamai Elizabeth M. , Cantonwine David E. , Mukherjee Bhramar , Meeker John D. , McElrath Thomas F. 
Published: July 2018

ProblemPerturbations in normal fetal growth during pregnancy are associated with poor child and adult health outcomes. Inflammation and oxidative stress are recognized as important mechanisms in preeclampsia and preterm birth but have been examined less in relation to fetal growth. We hypothesized that maternal inflammation and oxidative stress in pregnancy would be associated with reduced fetal growth and sought to identify windows of vulnerability.Method of studyIn a secondary analysis of 482 women from the LIFECODES birth cohort study, we measured inflammation (C‐reactive protein [CRP] and the cytokines IL‐1β, IL‐6, IL‐10, and TNF‐α) and oxidative stress (8‐isoprostane and 8‐hydroxydeoxyguanosine [8‐OHdG]) biomarkers in plasma and urine, respectively, at four time points during pregnancy. We examined associations between repeated measures of each marker and ultrasound (head and abdominal circumference, femur length, and a summary measure of estimated fetal weight) as well as delivery (birthweight) metrics of growth.ResultsIn adjusted repeated‐measures models, an interquartile range (IQR) increase in CRP was associated with a 0.12 standard deviation decrease in fetal weight z‐score (95% confidence interval, CI, −0.21, −0.02), which corresponds to approximately 50 g at 40‐week gestation. The association was greatest in magnitude (ie, most negative) with CRP measured later in pregnancy. Oxidative stress markers were not associated with fetal weight, although both were inversely associated with head circumference and femur length.ConclusionInflammation and oxidative stress markers measured later in pregnancy were associated with reduced fetal growth as measured by repeated ultrasound scans.
Malignancy and mortality in paediatric‐onset inflammatory bowel disease: a 3‐year prospective, multinational study from the paediatric IBD Porto group of ESPGHAN
Authors: Joosse M. E. , Aardoom M. A. , Kemos P. , Turner D. , Wilson D. C. , Koletzko S. , Martin‐de‐Carpi J. , Fagerberg U. L. , Spray C. , Tzivinikos C. , Sladek M. , Shaoul R. , Roma‐Giannikou E. , Bronsky J. , Serban D. E. , Ruemmele F. M. , Garnier‐Lengline H. , Veres G. , Hojsak I. , Kolho K. L. , Davies I. H. , Aloi M. , Lionetti P. , Hussey S. , Veereman G. , Braegger C. P. , Trindade E. , Wewer A. V. , Hauer A. C. , de Vries A. C. H. , Sigall Boneh R. , Sarbagili Shabat C. , Levine A. , de Ridder L. ,   the Paediatric IBD Porto group of ESPGHAN
Published: July 2018

SummaryBackgroundRisk benefit strategies in managing inflammatory bowel diseases (IBD) are dependent upon understanding the risks of uncontrolled inflammation vs those of treatments. Malignancy and mortality in IBD have been associated with disease‐related inflammation and immune suppression, but data are limited due to their rare occurrence.AimTo identify and describe the most common causes of mortality, types of cancer and previous or current therapy among children and young adults with paediatric‐onset IBD.MethodsInformation on paediatric‐onset IBD patients diagnosed with malignancy or mortality was prospectively collected via a survey in 25 countries over a 42‐month period. Patients were included if death or malignancy occurred after IBD diagnosis but before the age of 26 years.ResultsIn total, 60 patients were identified including 43 malignancies and 26 fatal cases (9 due to cancer). Main causes of fatality were malignancies (n = 9), IBD or IBD‐therapy related nonmalignant causes (n = 10; including 5 infections), and suicides (n = 3). Three cases, all fatal, of hepatosplenic T‐cell lymphoma were identified, all were biologic‐naïve but thiopurine‐exposed. No other haematological malignancies were fatal. The 6 other fatal cancer cases included 3 colorectal adenocarcinomas and 3 cholangiocarcinomas (CCAs). Primary sclerosing cholangitis (PSC) was present in 5 (56%) fatal cancers (1 colorectal carcinoma, 3 CCAs and 1 hepatosplenic T‐cell lymphoma).ConclusionsWe report the largest number of paediatric‐onset IBD patients with cancer and/or fatal outcomes to date. Malignancies followed by infections were the major causes of mortality. We identified PSC as a significant risk factor for cancer‐associated mortality. Disease‐related adenocarcinomas were a commoner cause of death than lymphomas.
Impairment of bone marrow endothelial progenitor cells in acute graft‐versus‐host disease patients after allotransplant
Authors: Cao Xie‐Na , Kong Yuan , Song Yang , Shi Min‐Min , Zhao Hong‐Yan , Wen Qi , Lyu Zhong‐Shi , Duan Cai‐Wen , Wang Yu , Xu Lan‐Ping , Zhang Xiao‐Hui , Huang Xiao‐Jun 
Published: July 2018

SummaryGraft‐versus‐host disease (GVHD) is a major complication after allogeneic haematopoietic stem cell transplantation (allo‐HSCT) that is frequently associated with bone marrow (BM) suppression, and clinical management is challenging. BM endothelial progenitor cells (EPCs) play crucial roles in the regulation of haematopoiesis and thrombopoiesis. However, little is known regarding the functional roles of BM EPCs in acute GVHD (aGVHD) patients. In the current prospective case‐control study, reduced and dysfunctional BM EPCs, characterized by decreased migration and angiogenesis capacities and increased levels of reactive oxygen species (ROS) and apoptosis, were found in aGVHD patients compared with those without aGVHD. Moreover, lower frequency and increased levels of ROS, apoptosis and DNA damage, but reduced colony‐forming unit‐plating efficiency were found in BM CD34+ cells of aGVHD patients compared with those without aGVHD. The severity of aGVHD and GVHD‐mediated cytopenia was associated with BM EPC impairment in aGVHD patients. In addition, the EPC impairment positively correlated with ROS level. Taken together, our results suggest that reduced and dysfunctional BM EPCs may be involved in the pathogenesis of aGVHD. Although these findings require validation, our data indicate that improvement of BM EPCs may represent a promising therapeutic approach for aGVHD patients.
Overall survival of children and adolescents with mature B cell non‐Hodgkin lymphoma who had refractory or relapsed disease during or after treatment with FAB/LMB 96: A report from the FAB/LMB 96 study group
Authors: Cairo Mitchell , Auperin Anne , Perkins Sherrie L. , Pinkerton Ross , Harrison Lauren , Goldman Stanton , Patte Catherine 
Published: July 2018

SummaryWe determined the risk factors associated with poor survival in children and adolescents with de novo mature B cell non‐Hodgkin lymphoma (B‐NHL) who had refractory or relapsed disease during or after the French‐American‐British mature lymphoma B (FAB/LMB) 96 multi‐agent chemotherapy. Among the 1 111 registered on study, 104 patients (9·4%) had refractory disease or disease relapse after first complete remission. Among these 104 patients, 28 (27%) patients had refractory disease and 76 (73%) had relapsed disease. The estimated 1‐ and 2‐year overall survival (OS) (95% confidence interval) was 31·5% (23·3–41·0%) and 22·3% (15·3–31·4%), respectively. Prognostic analysis of OS using a Cox multivariate model showed that factors independently associated with OS included lactate dehydrogenase ≥2 upper normal limit [hazard ratio (HR) = 2·86 (1·57–5·2), P = 0·0006]; time to failure (>6 months) [HR = 0·59 (0·36–0·97), P = 0·038]; and failure in bone marrow [HR = 2·78 (1·65–4·68), P = 0·0001]. New therapeutic strategies are required to significantly reduce refractory disease and disease relapse in patients with newly diagnosed mature B‐NHL and, more importantly, there is a critical need to develop novel retrieval approaches in patients with chemotherapy‐resistant disease.
Shareholders of the World United? Organized Labour's Preferences on Corporate Governance under Pension Fund Capitalism in the United States, United Kingdom and France
Authors: Bridgen Paul , Naczyk Marek 
Published: July 2018

AbstractThis article considers whether organized labour's engagement with shareholder activism represents a shift in unions’ traditional stakeholder preferences on corporate governance under pension fund capitalism. It does so in light of recent critiques of the class power thesis of corporate governance which suggest greater fluidity and fragmentation in labour's approach. Adopting a diverse case study strategy to compare organized labour's actions in the United States, United Kingdom and France, the article explains these activities as innovative strategies, similar to other revitalization initiatives, designed to advance traditional agendas by alternative means. The article thus concludes that, while organized labour's shareholder activism is unexpected under the class power thesis, its core preferences remain largely unchanged.
Nevertheless They Persisted: Gendered Frameworks and Socialization Advantages in Indian Professional Service Firms
Authors: Ballakrishnen Swethaa S. 
Published: July 2018

AbstractThis article uses the Indian case to offer nuance to narratives about the gendered experience of professional work. I find that while gendered constructs certainly infiltrate all workspaces, there remain occupational and organizational differences in the ways in which women experience their environments. Particularly, while Indian women lawyers overall are more disadvantaged than their international counterparts, the experience of women lawyers in very elite law firms is more favorable than both their local and global peers. A confluence of factors might be responsible for this unusual experience of professional work, but this article highlights the importance of one set of supply side dynamics: the variations in socializing experiences and expectations before entry into these firms. In doing so, it adds to the literature that suggests the importance of not just enrollment parity, but also early training and institutional socialization for gender egalitarian professional outcomes.
Some node ordering methods for the K2 algorithm
Authors: Aghdam Rosa , Rezaei Tabar Vahid , Pezeshk Hamid 
Published: July 2018

AbstractInferring Bayesian network structure from data is a challenging issue, and many researchers have been working on this problem. The K2 is a well‐known order‐dependent algorithm to learn Bayesian network. The result of the algorithm is not robust since it achieves different network structure if node orderings are permuted. Consequently, choosing suitable sequential node ordering for the input of the K2 algorithm is a challenging task. In this work, some deterministic methods for selecting a suitable sequential node ordering are introduced. The effectiveness of these methods benchmarked through the Asia, Alarm, Car, and Insurance networks. The results indicate that the methods based on the concept of mutual information and entropy are suitable for finding a sequential node ordering and considerably improves the precision of network inference. The source code and selected data sets are available onhttp://profiles.bs.ipm.ir/softwares/ordering/.
Changes in bone microarchitecture following kidney transplantation—Beyond bone mineral density
Authors: Sharma Ashish K. , Toussaint Nigel D. , Elder Grahame J. , Rajapakse Chamith S. , Holt Stephen G. , Baldock Paul , Robertson Patricia L. , Ebeling Peter R. , Sorci Olivia R. , Masterson Rosemary 
Published: July 2018

AbstractBone disease in kidney transplant recipients (KTRs) is characterized by bone mineral density (BMD) loss but bone microarchitecture changes are poorly defined. In this prospective cohort study, we evaluated bone microarchitecture using non‐invasive imaging modalities; high‐resolution magnetic resonance imaging (MRI), peripheral quantitative computed tomography (pQCT), dual energy X‐ray absorptiometry (DXA), and the trabecular bone score (TBS) following kidney transplantation. Eleven KTRs (48.3 ± 11.2 years) underwent MRI (tibia), pQCT (radius) and DXA at baseline and 12 months post–transplantation. Transiliac bone biopsies, performed at transplantation, showed 70% of patients with high/normal bone turnover. Compared with baseline, 12‐month MRI showed deterioration in indices of trabecular network integrity—surface to curve ratio (S/C; −15%, P = 0.03) and erosion index (EI; +19%, P = 0.01). However, cortical area increased (+10.3%, P = 0.04), with a non‐significant increase in cortical thickness (CtTh; +7.8%, P = 0.06). At 12 months, parathyroid hormone values (median 10.7 pmol/L) correlated with improved S/C (r = 0.75, P = 0.009) and EI (r = −0.71, P = 0.01) while osteocalcin correlated with CtTh (r = 0.72, P = 0.02) and area (r = 0.70, P = 0.02). TBS decreased from baseline (−5.1%, P = 0.01) with no significant changes in BMD or pQCT. These findings highlight a post–transplant deterioration in trabecular bone quality detected by MRI and TBS, independent of changes in BMD, underlining the potential utility of these modalities in evaluating bone microarchitecture in KTRs.
Plant niche breadths along environmental gradients and their relationship to plant functional traits
Authors: Schellenberger Costa David , Gerschlauer Friederike , Kiese Ralf , Fischer Markus , Kleyer Michael , Hemp Andreas 
Published: July 2018

AbstractAimsWe tested whether plant species niche breadths decrease with increasing species richness due to competition on temperature, precipitation and disturbance gradients. We assumed that niche optima, niche breadth and niche volume are related to plant functional traits, indicating competitive ability and adaptation to environmental stress. Finally, we wanted to identify habitats dominated by species with small niche breadths most prone to environmental change.LocationSouthern slopes of Mount Kilimanjaro, Tanzania.MethodsWe calculated species distribution models for 1,492 plant species based on the presence/absence data on 969 plots using generalized linear models. We derived niche breadths, optima and volumes and investigated their relationship with plant functional traits with principal component regression to account for high trait correlations.ResultsNiche breadths of individual species increased with elevation, precipitation and disturbance. Averaged community elevation niche breadth and niche volume decreased with increasing species richness. Plant functional traits explained about 40% and 50% of the variation in niche optima and breadths, respectively. Size and growth traits were significant predictors of niche breadths on all gradients, whereas traits indicating reproductive strategy were not significant on the precipitation gradient.Main conclusionsOur results support the notion of decreasing niche breadth with increasing temperature, possibly a result of competition due to increased diversification rates and hence species richness. However, the complexity of the niche breadth–species richness patterns on the other gradients shows that additional covariables shape species niche breadths apart from competition. Plant species with narrow niche breadths dominated natural savannas around Mount Kilimanjaro, indicating strong sensitivity to the ongoing conversion of savanna to fields and grasslands.
Effect of days postburning and calcium oxide on the fermentation, aerobic stability and nutritional characteristics of sugarcane silage for finishing Nellore steers
Authors: Roth Anna Paula T. P. , Siqueira Gustavo R. , Rabelo Carlos H. S. , Moretti Matheus H. , Härter Carla J. , Resende Flávio D. , Reis Ricardo A. 
Published: July 2018

AbstractIn this study, the effects of days postburning and calcium oxide (CaO) on the fermentation, aerobic stability and nutritional characteristics of sugarcane silages for finishing Nellore steers were investigated. Silages were prepared in minisilos from in natura and burned sugarcane that remained in the field 1 and 10 days postburning (1‐day burned and 10‐day burned, respectively). Next, forages were left untreated or treated with CaO (10 g/kg fresh forage). Compared to that in untreated silages, CaO application increased the dry‐matter (DM) recovery of in natura, 1‐day and 10‐day burned silages (p < 0.001) by 67, 179 and 209 g/kg DM respectively. The CaO treatment increased (p < 0.001) the aerobic stability of the in natura and 10‐day burned silages by 62.7 and 24.7 hr respectively. In a feedlot experiment, feeding 1‐day burned silage reduced DM intake of steers throughout the feedlot period (0–93 days; p < 0.05) compared with that of steers fed in natura silage diet, but the average daily gain (ADG) was lower (p = 0.006) only during the adaptation period (−0.16 kg/day; 0–28 days). The CaO application decreased DM intake (p = 0.007; −1.17 kg/day) and ADG (p < 0.001; −0.13 kg/day) of steers only during the adaptation period likely owing to low silage palatability caused by increased Ca and butyric acid concentrations (≥11.6 g/kg DM). We recommend feeding beef cattle with CaO‐treated burned sugarcane silages in low‐dietary concentration because of its high butyric acid concentration.
Factor VIII activity of BAY 94‐9027 is accurately measured with most commonly used assays: Results from an international laboratory study
Authors: Church N. , Leong L. , Katterle Y. , Ulbrich H.‐F. , Noerenberg I. , Kitchen S. , Michaels L. A. 
Published: July 2018

IntroductionDiscrepancies in the measurement of modified factor VIII (FVIII) products have been recognized, highlighting the need for adjustments in clinical laboratory practices to ensure effective monitoring of patients treated with these products, particularly using the one‐stage (activated partial thromboplastin time [aPTT]) assay.AimTo assess the ability of clinical laboratories to measure the activity of BAY 94‐9027, a PEGylated extended half‐life FVIII product, using routine (predominantly one‐stage) assays in clinical laboratoriesMethodsBlinded samples of FVIII‐deficient plasma spiked with defined levels of BAY 94‐9027 and a recombinant FVIII product comparator were provided to 52 clinical laboratories that routinely conduct FVIII testing. Samples were provided at 3 concentrations (low, medium and high), and laboratories analysed the samples using routine in‐house one‐stage and, when available, chromogenic assays. Acceptable spiked recovery (accuracy) of the local laboratory methods to measure BAY 94‐9027 was the primary endpoint of the study.ResultsAccurate FVIII measurements were obtained at all concentrations for both products using the chromogenic assay and most of the commonly used one‐stage reagents, both ellagic acid and silica based. Two specific silica‐based reagents, APTT‐SP and PTT‐A, underestimated BAY 94‐9027 levels at all concentrations, consistent with previous findings.ConclusionsFVIII activity of BAY 94‐9027 was accurately measured with most commonly used one‐stage assays used in routine clinical practice. The chromogenic assay was also accurate. It is recommended that clinical laboratories identify and avoid specific inappropriate reagents, such as the APTT‐SP and PTT‐A, in their one‐stage assays for FVIII monitoring.