bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fine‐tuning the P. pastoris iMT1026 genome‐scale metabolic model for improved prediction of growth on methanol or glycerol as sole carbon sources
Authors: Tomàs‐Gamisans Màrius , Ferrer Pau , Albiol Joan 
Published: November 2017

SummaryThe methylotrophic yeast Pichia pastoris (Komagataella spp.) is widely used as cell factory for recombinant protein production. In the past recent years, important breakthroughs in the systems‐level quantitative analysis of its physiology have been achieved. This wealth of information has allowed the development of genome‐scale metabolic models, which make new approaches possible for host cell and bioprocess engineering. Nevertheless, the predictive accuracy of the previous consensus model required to be upgraded and validated with new experimental data sets for P. pastoris growing on glycerol or methanol as sole carbon sources, two of the most relevant substrates for this cell factory. In this study, we have characterized P. pastoris growing in chemostat cultures using glycerol or methanol as sole carbon sources over a wide range of growth rates, thereby providing physiological data on the effect of growth rate and culture conditions on biomass macromolecular and elemental composition. In addition, these data sets were used to improve the performance of the P. pastoris consensus genomic‐scale metabolic model iMT1026. Thereupon, new experimentally determined bounds, including the representation of biomass composition for these growth conditions, have been incorporated. As a result, here, we present version 3 (v3.0) of the consensus P. pastoris genome‐scale metabolic model as an update of the iMT1026 model. The v3.0 model was validated for growth on glycerol and methanol as sole carbon sources, demonstrating improved prediction capabilities over an extended substrate range including two biotechnologically relevant carbon sources.
Effects of combined helium pre/post‐conditioning on the brain and heart in a rat resuscitation model
Authors: Aehling C. , Weber N. C. , Zuurbier C. J. , Preckel B. , Galmbacher R. , Stefan K. , Hollmann M. W. , Popp E. , Knapp J. 
Published: November 2017

BackgroundThe noble gas helium induces cardio‐ and neuroprotection by pre‐ and post‐conditioning. We investigated the effects of helium pre‐ and post‐conditioning on the brain and heart in a rat resuscitation model.MethodsAfter approval by the Animal Care Committee, 96 Wistar rats underwent cardiac arrest for 6 min induced by ventricular fibrillation. Animals received 70% helium and 30% oxygen for 5 min before cardiac arrest and for 30 min after restoration of spontaneous circulation (ROSC). Control animals received 70% nitrogen and 30% oxygen. Hearts and brains were excised after 2, 4 h or 7 days. Neurological degeneration was evaluated using TUNEL and Nissl staining in the hippocampal CA‐1 sector. Cognitive function after 7 days was detected with the tape removal test. Molecular targets were measured by infrared western blot. Data are shown as median [Interquartile range].ResultsHelium treatment resulted in significantly less apoptosis (TUNEL positive cells/100 pixel 73.5 [60.3–78.6] vs.78.2 [70.4–92.9] P = 0.023). Changes in Caveolin‐3 expression in the membrane fraction and Hexokinase‐II in the mitochondrial fraction were observed in the heart. Caveolin‐1 expression of treated animals significantly differed from control animals in the membrane fraction of the heart and brain after ROSC.ConclusionTreatment with helium reduced apoptosis in our resuscitation model. Differential expression levels of Caveolin‐1, Caveolin‐3 and Hexokinase II in the heart were found after helium pre‐ and post‐conditioning. No beneficial effects were seen on neurofunctional outcome.
Age of Alcohol Initiation and Progression to Binge Drinking in Adolescence: A Prospective Cohort Study
Authors: Aiken Alexandra , Clare Philip J. , Wadolowski Monika , Hutchinson Delyse , Najman Jackob M. , Slade Tim , Bruno Raimondo , McBride Nyanda , Kypri Kypros , Mattick Richard P. 
Published: November 2017

BackgroundEarly alcohol initiation is common and has been associated with the development of alcohol problems. Yet, past research on the association of age of initiation with later problem drinking has produced inconsistent findings. Using prospective data from the Australian Parental Supply of Alcohol Longitudinal Study cohort, this study examined age of alcohol initiation, and of first drunkenness, and associations with subsequent drinking in adolescence.MethodsA total of 1,673 parent–child dyads recruited through Australian secondary schools completed annual surveys for 5 years (grades 7 to 11). Limiting the sample to those adolescents who had initiated alcohol use by age 17 (n = 839), multinomial logistic regression models were used to examine associations between (i) age of initiation to alcohol use (consuming at least 1 full serve) and (ii) age of first drunkenness, and 2 outcomes: (i) binge drinking (consuming >4 standard drinks on a single occasion), and (ii) the total number of alcoholic drinks consumed in the past year, adjusted for a range of potential child, parent, family, and peer covariates.ResultsFifty percent of adolescents reported alcohol use and 36% reported bingeing at wave 5 (mean age 16.9 years), and the mean age of initiation to alcohol use for drinkers was 15.1 years. Age of initiation was significantly associated with binge drinking and total quantity of alcohol consumed in unadjusted and adjusted models. Age of first drunkenness was associated with total quantity of alcohol consumed in unadjusted models but not adjusted models and was not associated with subsequent bingeing.ConclusionsInitiating alcohol use earlier in adolescence is associated with an increased risk of binge drinking and higher quantity of consumption in late secondary school, supporting an argument for delaying alcohol initiation for as long as possible to reduce the risk for problematic use in later adolescence and the alcohol‐related harms that may accompany this use.
Ecophysiological responses of six coastal dune species along the eastern seaboard of South Africa
Authors: Naidoo Gonasageran 
Published: November 2017

AbstractEcophysiological responses of six co‐occurring dune species were investigated in a field study to determine whether they exhibit similar functional traits in response to environmental stressors. The species included Brachylaena discolor DC, Chrysanthemoides monilifera (L.), Scaevola plumieri (L.) Vahl, Canavalia maritima (Aubl.) Thouars, Gazania rigens (L.) Gaertn. and Cyperus esculentis L. Carbon dioxide exchange was saturated at 1,800 μmol m−2 s−1 in S. plumieri and at 1,000–1,300 μmol m−2 s−1 in the others. Maximal CO2 exchange occurred during mid‐morning. Midday stomatal closure occurred in S. plumieri, C. monilifera and B. discolor, while stomatal regulation was achieved by maintaining low conductance. Photoinhibition was minimized by efficient mechanisms for light dissipation. Species such as S. plumieri, C. maritima and B. discolor exhibited sclerophylly, a trait for survival in saline and nutrient‐ and water‐deficient environments. Concentrations of Na+ and Cl−1 were high in C. monilifera, G. rigens, B. discolor and S. plumieri, while the high C:N ratio in S. plumieri and C. esculentis suggested nitrogen deficiency. The responses of the six species to environmental stressors in terms of light use, gas exchange, ion and water relations and degree of sclerophylly suggest similar strategies for survival in the dune environment.
The Humanitarian War Against Migrant Smugglers at Sea
Authors: Garelli Glenda , Tazzioli Martina 
Published: November 2017

AbstractThis paper engages with the military‐humanitarian technology of migration management from the vantage point of the European Union Naval Force Mediterranean (EUNAVFOR MED) “Operation Sophia”, the naval and air force intervention deployed by the EU in the Central Southern Mediterranean to disrupt “the business model of human smuggling and trafficking” while “protecting life at sea”. We look at the military‐humanitarian mode of migration management that this operation performs from three vantage points: logistics, with a focus on the infrastructure of migrant travels; subjectivity, looking at the migrant profiles this operation works through; and epistemology, building on the mission's first stage of intelligence and data gathering. Through this multi‐focal approach, we illuminate the productivity of this military‐humanitarian approach to the migration crisis in the Mediterranean.
Exposure‐response relationship of certolizumab pegol induction and maintenance therapy in patients with Crohn's disease
Authors: Vande Casteele N. , Feagan B. G. , Vermeire S. , Yassine M. , Coarse J. , Kosutic G. , Sandborn W. J. 
Published: November 2017

SummaryBackgroundTherapeutic drug monitoring may optimize therapy for Crohn's disease (CD).AimTo use a population pharmacokinetic model that accounts for the time‐varying nature of covariates to simulate certolizumab pegol (CZP) concentrations to evaluate the exposure‐response relationship for CZP in Crohn's disease.MethodsAdults (N = 2157) with Crohn's disease were treated with CZP in nine clinical trials. Simulated CZP concentrations were compared to outcomes at weeks 6 and 26, including Crohn's disease activity index (CDAI) response (decrease from baseline ≥ 100 points), remission (CDAI ≤ 150), C‐reactive protein (CRP) ≤ 5 mg/L, faecal calprotectin (FC) ≤ 250 μg/g, and a composite endpoint of CDAI ≤ 150 and FC ≤ 250 μg/g. Multivariable analyses identified covariates associated with outcomes and receiver operating characteristic analyses determined optimal CZP concentrations.ResultsCZP concentrations at weeks 2, 4 and 6 were higher in patients with clinical response, remission, CRP ≤ 5 mg/L or FC ≤ 250 μg/g at week 6 than without. In multivariable analyses, higher CZP concentrations at week 6 were associated with the composite outcome at weeks 6 and 26 (P < .001). Although the exposure‐response relationship varied among patients, approximate CZP concentrations of at least 36.1 μg/mL (positive predictive value [PPV] 22.8% and negative predictive value [NPV] 92.7%) and at least 14.8 μg/mL (PPV 28.0% and NPV 90.4%) at weeks 6 and 12 were associated with weeks 6 and 26 outcomes.ConclusionsAn exposure‐response relationship was apparent for CZP in Crohn's disease and achieving higher CZP concentrations may increase the likelihood of attaining efficacy outcomes, but this remains to be evaluated prospectively.
Urological dysfunction in young women: an inheritance of childhood?
Authors: Costantini Elisabetta , Illiano Ester , Giannitsas Konstantinos , Prestipino Marco , Pastore Antonio Luigi , Carbone Antonio , Palleschi Giovanni , Balsamo Raffaele , Natale Franca , Villari Donata , Bini Vittorio , Maruccia Serena , Filocamo Maria‐Teresa , Zucchi Alessandro 
Published: November 2017

ObjectiveTo investigate the correlation of a history of lower urinary tract symptomatology during childhood with lower urinary tract dysfunction in young adult women.Subjects and MethodsThis was a multicentre, prospective, case–control study conducted between April 2013 and November 2015. A total of 300 women, aged 18–40 years, participated. The case group comprised women attending urogynaecology clinics for various lower urinary tract complaints and the control group was recruited from a healthy population. Exclusion criteria were designed to avoid common causes of lower urinary tract dysfunction and symptoms and included diabetes mellitus, neurological disease and pelvic inflammatory disease. All women completed a self‐administered 77‐item questionnaire, exploring childhood urological and bowel history, as well as current urological, bowel and sexual symptoms. Statistical analysis was performed using chi‐squared and Fisher's exact tests to compare categorical variables. Multivariate logistic regression models were fit for the prediction of the adult outcomes, incorporating as explanatory variables all those that showed a significant P value in bivariate analysis. P values < 0.05 were considered statistically significant.ResultsWomen with childhood urinary voiding and storage symptoms had a higher prevalence of these symptoms in adult life compared with women without such history. Women with urinary tract infections (UTIs) during childhood had a higher incidence of adult UTIs compared with women without this problem in childhood.ConclusionsLower urinary tract dysfunction in childhood seems to ‘persist’ in young adult life but the implications of this finding in clinical practice need to be defined in future studies.
Spatial analysis of cirques from three regions of Iceland: implications for cirque formation and palaeoclimate
Authors: Ipsen Heather A. , Principato Sarah M. , Grube Rachael E. , Lee Jessica F. 
Published: November 2017

This study is a quantitative analysis of cirques in three regions of Iceland: Tröllaskagi, the East Fjords and Vestfirðir. Using Google Earth and the National Land Survey of Iceland Map Viewer, we identified 347 new cirques on Tröllaskagi and the East Fjords region, and combined these data with 100 cirques previously identified on Vestfirðir. We used ArcGIS to measure length, width, aspect, latitude and distance to coastline of each cirque. Palaeo‐equilibrium‐line altitudes (palaeo‐ELAs) of palaeo‐cirque glaciers were calculated using the altitude‐ratio method, cirque‐floor method and minimum‐point method. The mean palaeo‐ELA values in Tröllaskagi, the East Fjords and Vestfirðir are 788, 643 and 408 m a.s.l, respectively. Interpolation maps of palaeo‐ELAs demonstrate a positive relationship between palaeo‐ELA and distance to coastline. A positive relationship between palaeo‐ELA and latitude is observed on Vestfirðir, a negative relationship is observed on Tröllaskagi and no statistically significant relationship is present on the East Fjords. The modal orientation of cirques on Tröllaskagi and Vestfirðir is northeast, while orientation of cirques in the East Fjords is north. Palaeo‐wind reconstructions for the LGM show that modal aspect is aligned with the prevailing north‐northeast wind directions, although aspect measurements demonstrate wide dispersion. Cirque length is similar on Tröllaskagi and the East Fjords, but cirques are approximately 200 m shorter in Vestfirðir. Cirque widths are similar in all three regions. Comparisons with a global data set show that cirques in Iceland are smaller and more circular than cirques in other regions of the world. Similar to glaciers in Norway and Kamchatka, our results demonstrate that access to a moisture source is a key parameter in determining palaeo‐ELAs in Iceland. Temperatures interpreted from palaeo‐ELA depressions suggest that these cirques may have been glaciated as recently as the Little Ice Age.
A case study on a generalist service delivery model for street children in Durban, South Africa: Insights from the capability approach
Authors: Van Raemdonck Laura , Seedat‐Khan Mariam 
Published: November 2017

AbstractThis paper adopts a qualitative case study on the generalist service delivery model of I‐Care, a Durban‐based non‐governmental organization that works with male street children. Fifteen face‐to‐face interviews were conducted with 10 I‐Care employees and 5 former street children. A focus group was set up with I‐Care employees. Although existing literature is forthright about a generalist approach for children at risk, it remains unclear how to implement this approach in practice. This paper reviews a continuity of 5 fundamental social work practices for working with street children: (a) outreach work, (b) child–family and child–community mediation, (c) transitory care centres and programmes, (d) brokerage, and (e) mentorship and follow‐ups. The study analyses how these practices contribute to the capability and agency expansion of the street children and outlines challenges that service providers and former street children experience. The main challenges acknowledged are balancing between the agency and protection of street children and the adaptation of children to street life. The study proposes intervention strategies to overcome these challenges.
ERK5 plays an essential role in gestational beta‐cell proliferation
Authors: Chen Congde , Wu Suichun , Lin Xiaokun , Wu Dazhou , Fischbach Shane , Xiao Xiangwei 
Published: November 2017

AbstractObjectivesRestoring a functional beta‐cell mass is a fundamental goal in treating diabetes. A complex signalling pathway network coordinates the regulation of beta‐cell proliferation, although a role forERK5 in this network has not been reported. This question was addressed in this study.Materials and methodsWe studied the activation of extracellular‐signal‐regulated kinase 5 (ERK5) in pregnant mice, a well‐known mouse model of increased beta‐cell proliferation. A specific inhibitor ofERK5 activation,BIX02189, was intraperitoneally injected into the pregnant mice to suppressERK5 signalling. Beta‐cell proliferation was determined by quantification of Ki‐67+beta cells. Beta‐cell apoptosis was determined byTUNELassay. The extent of beta‐cell proliferation was determined by beta‐cell mass. The alteration ofERK5 activation and CyclinD1 levels in purified mouse islets was examined by Western blotting.ResultsExtracellular‐signal‐regulated kinase 5 phosphorylation, which representsERK5 activation, was significantly upregulated in islets from pregnant mice. Suppression ofERK5 activation byBIX02189 in pregnant mice significantly reduced beta‐cell proliferation, without affecting beta‐cell apoptosis, resulting in increases in random blood glucose levels and impairment of glucose response of the mice.ERK5 seemed to activate CyclinD1 to promote gestational beta‐cell proliferation.ConclusionsExtracellular‐signal‐regulated kinase 5 plays an essential role in the gestational augmentation of beta‐cell proliferation.ERK5 may be a promising target for increasing beta‐cell mass in diabetes patients.
Low level laser therapy induces increased viability and proliferation in isolated cancer cells
Authors: Kara C. , Selamet H. , Gökmenoğlu C. , Kara N. 
Published: November 2017

AbstractObjectivesLow level laser therapy (LLLT), which stimulates natural biological processes in the application region, is frequently used in dental treatments. The aim of our study was to evaluate the effects of LLLT which could activate precancerous cells or increase existing cancerous tissue in case of clinically undetectable situations.Materials and methodsSaos‐2 osteoblast‐like osteosarcoma cells and A549 human lung carcinoma cells were used. Twenty‐four hours after preparation of cell culture plates, laser irradiation was performed 1, 2 and 3 times according to the test groups using Nd:YAG laser with the power output 0.5, 1, 2 and 3 W. Cell proliferation analysis was performed by MTT assay at the 24th hour following the last laser applications.ResultsGenerally, it was observed that the proliferation rates increased as the number of applications increased, when compared to the controls, especially in those cases in which the irradiation was performed 2 or 3 times more.ConclusionThe findings of this study have led to the conclusion that LLLT increases cancer cell proliferation, depending on the power output level of the laser and the number of applications. In addition to the proliferation and mitotic activity of the cancer tissue cells, we concluded that LLLT, which is frequently used in dental practice, could activate precancerous cells or increase existing cancerous tissue.
Revisiting chronic rejection following living donor liver transplantation in the tacrolimus era: A single center experience
Authors: Choudhary Narendra Singh , Saraf Neeraj , Saigal Sanjiv , Gautam Dheeraj , Rastogi Amit , Goja Sanjay , Bhangui Prashant , Srinivasan Thiagrajan , Yadav Sanjay Kumar , Soin Arvinder 
Published: November 2017

AbstractBackground and AimsChronic rejection (CR) is an uncommon but important cause of graft dysfunction, leading to graft loss and often requires retransplantation. This study evaluates the incidence and outcome of the patients with CR at a large living donor liver transplant (LDLT) center.MethodsData of patients with CR were retrospectively analyzed in 1232 adult (age >18 years) LDLT on tacrolimus (mainly)‐based immunosuppression. Sirolimus/everolimus (mammalian target of rapamycin [mTOR] inhibitors) was added to baseline immunosuppression as rescue therapy in patients with CR. Data are shown as median (interquartile range [IQR]).ResultsTwenty‐three patients (22 males), aged 42 (IQR 45‐56) years, had biopsy‐proven chronic rejection at 21 (8‐44) months after liver transplantation. The incidence of chronic rejection was 1.9% in this cohort. The patients with CR (n = 23) had a significantly higher incidence of cytomegalovirus (CMV) viremia, acute cellular rejection, and history of anastomotic biliary strictures as compared to patients without CR. Five patients were noncompliant with immunosuppression before the diagnosis of CR. Twelve patients (52%) responded to addition of mTOR inhibitors, whereas 11 did not respond and had poor outcome.ConclusionThe incidence of chronic rejection is low in LDLT. Treatment with mTOR inhibitors can reverse graft dysfunction in approximately half of the patients.
Calcium hydroxide regulates transcription of the bone sialoprotein gene via a calcium‐sensing receptor in osteoblast‐like ROS 17/2.8 cells
Authors: Wang Shuang , Noda Keisuke , Yang Yuanyuan , Shen Zhengyan , Chen Zhen , Ogata Yorimasa 
Published: November 2017

Bone sialoprotein (BSP) is a glycoprotein associated with mineralized tissues. In this study, we investigated the regulation of Bsp transcription by calcium hydroxide [Ca(OH)2] in rat osteosarcoma‐derived osteoblast‐like ROS 17/2.8 cells and stromal bone marrow cells. Application of Ca(OH)2 (0.4 mM) increased the levels of runt‐related transcription factor 2 (Runx2) and BspmRNAs at 3 and 6 h and the level of BSP protein at 12 h. Transient transfection analyses were performed using chimeric constructs encompassing different regions of the rat Bsp gene promoter ligated to a luciferase reporter gene. It was found that Ca(OH)2 increased the luciferase activities of the pLUC3 and pLUC4 constructs. Introduction of 2‐bp mutations to the luciferase construct showed that the effects of Ca(OH)2 were mediated by cAMP response‐element (CRE) and fibroblast growth factor 2 (FGF2) response element (FRE). Luciferase activities induced by Ca(OH)2 were blocked by protein kinase C (PKC), protein kinase A (PKA), phosphoinositide‐3‐kinase (PI3‐K), and extracellular signal‐regulated kinase 1/2 (ERK1/2) inhibitors and by calcium‐sensing receptor (CASR) antagonists. Gel‐shift analyses showed that Ca(OH)2 increased binding of nuclear protein to CRE and FRE. Dexamethasone‐induced mineralization in stromal bone marrow cells was abrogated by CASR antagonists. These studies demonstrate that Ca(OH)2 regulates Bsp transcription via the CASR by targeting CRE and FRE in the rat Bsp gene promoter.