bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated genomic and prospective clinical studies show the importance of modular pleiotropy for disease susceptibility, diagnosis and treatment
Authors: Gustafsson Mika , Edström Måns , Gawel Danuta , Nestor Colm E , Wang Hui , Zhang Huan , Barrenäs Fredrik , Tojo James , Kockum Ingrid , Olsson Tomas , Serra-Musach Jordi , Bonifaci Núria , Pujana Miguel Angel , Ernerudh Jan , Benson Mikael 
Published: February 2014

Abstract
Background
Translational research typically aims to identify and functionally validate individual, disease-specific genes. However, reaching this aim is complicated by the involvement of thousands of genes in common diseases, and that many of those genes are pleiotropic, that is, shared by several diseases.

Methods
We integrated genomic meta-analyses with prospective clinical studies to systematically investigate the pathogenic, diagnostic and therapeutic roles of pleiotropic genes. In a novel approach, we first used pathway analysis of all published genome-wide association studies (GWAS) to find a cell type common to many diseases.

Results
The analysis showed over-representation of the T helper cell differentiation pathway, which is expressed in T cells. This led us to focus on expression profiling of CD4+ T cells from highly diverse inflammatory and malignant diseases. We found that pleiotropic genes were highly interconnected and formed a pleiotropic module, which was enriched for inflammatory, metabolic and proliferative pathways. The general relevance of this module was supported by highly significant enrichment of genetic variants identified by all GWAS and cancer studies, as well as known diagnostic and therapeutic targets. Prospective clinical studies of multiple sclerosis and allergy showed the importance of both pleiotropic and disease specific modules for clinical stratification.

Conclusions
In summary, this translational genomics study identified a pleiotropic module, which has key pathogenic, diagnostic and therapeutic roles.
Novel 3D micro- and nanofabrication method using thermally activated selective topography equilibration (TASTE) of polymers
Authors: Schleunitz Arne , Guzenko Vitaliy A , Messerschmidt Martin , Atasoy Hakan , Kirchner Robert , Schift Helmut 
Published: February 2014

Abstract
Micro- and nanostructures with three-dimensional (3D) shapes are needed for a variety of applications in optics and fluidics where structures with both smooth and sharp features enhance the performance and functionality. We present a novel method for the generation of true 3D surfaces based on thermally activated selective topography equilibration (TASTE). This technique allows generating almost arbitrary sloped, convex and concave profiles in the same polymer film with dimensions in micro- and nanometer scale. We describe its principal mechanism exemplified by pre-patterned poly (methyl methacrylate) resist which is exposed to high energy electrons prior to a thermal annealing step enabling the selective transformation of stepped contours into smooth surfaces. From this we conclude, that TASTE not only offers an enormous degree of freedom for future process variations, but also will advance the patterning capabilities of current standard 3D micro- and nanofabrication methods.
mTOR limits the recruitment of CD11b+Gr1+Ly6Chigh myeloid-derived suppressor cells in protecting against murine immunological hepatic injury
Authors: Zhang Yan , Bi Yujing , Yang Hui , Chen Xi , Liu Huanrong , Lu Yun , Zhang Zhengguo , Liao Jiongbo , Yang Shan , Chu Yiwei , Yang Ruifu , Liu Guangwei 
Published: February 2014

AbstractThe mTOR pathway integrates diverse environmental inputs, including immune signals and metabolic cues, to direct the innate and adaptive immune responses. MDSCs are a heterogeneous cell population that plays a crucial regulatory effect in immune-related diseases. However, whether mTOR signaling affects the functions of MDSCs remains largely unknown. Here, we show that mTOR signaling is a pivotal negative determinant of MDSC recruitment in IMH disease. In the context of IMH, inhibition of mTOR with rapamycin in CD11b+Gr1+ MDSCs mediates protection against IMH and serves as a functional, suppressive immune modulator that results in increased CD11b+Gr1+Ly6Chigh MDSC recruitment to inflammatory sites. In agreement with this, mTOR down-regulation promotes CD11b+Gr1+Ly6Chigh MDSC migration in vitro and in vivo. Mechanistically, mTOR activity down-regulation in MDSCs induced iNOS expression and NO production. Pharmacologic inhibition of iNOS completely eliminated MDSC recruitment. This study identifies MDSCs as an essential component for protection against IMH following rapamycin treatment. Rapamycin treatment or mTOR inhibition promotes CD11b+Gr1+Ly6Chigh MDSC recruitment and is critically required for protection against hepatic injury. This study further validates the targeting of mTOR signaling as a potential therapeutic approach to IMH-related diseases.
Insulin elicits a ROS-activated and an IP3-dependent Ca2+ release; both impinge on GLUT4 translocation
Authors: Contreras-Ferrat Ariel , Llanos Paola , Vásquez César , Espinosa Alejandra , Osorio-Fuentealba César , Arias-Calderon Manuel , Lavandero Sergio , Klip Amira , Hidalgo Cecilia , Jaimovich Enrique 
Published: February 2014

Insulin signaling includes generation of low levels of H2O2; however, its origin and contribution to insulin-stimulated glucose transport are unknown. We tested the impact of H2O2 on insulin-dependent glucose transport and GLUT4 translocation in skeletal muscle cells. H2O2 increased GLUT4myc translocation, an effect additive to that of insulin. The anti-oxidants N-acetyl L-cysteine and Trolox, the p47phox/NOX2 NADPH oxidase inhibitory peptide gp91-ds-tat or p47phox knockdown each reduced insulin-dependent GLUT4myc translocation. Importantly, gp91-ds-tat suppressed insulin-dependent H2O2 production. A ryanodine-receptor (RyR) channel agonist stimulated GLUT4myc translocation and insulin stimulated RyR1-mediated Ca2+ release by promoting RyR1 S-glutathionylation.
This pathway acts in parallel to insulin-mediated stimulation of inositol-1,4,5-trisphosphate (IP3) activated Ca2+ channels, enacted through activation of phosphatidylinositol 3-kinase and its downstream target phospholipase C, resulting in Ca2+ transfer to the mitochondria. An inhibitor of IP3 receptors, Xestospongin B, reduced both insulin-dependent IP3 production and GLUT4myc translocation. We propose that, in addition to the canonical α,β phosphatidylinositol 3-kinase to Akt pathway, insulin engages both RyR-mediated Ca2+ release and IP3 receptor-mediated mitochondrial Ca2+ uptake, and that these signals jointly stimulate glucose uptake.
Preparation of Polyimide–Cellulose Composite Using Oligoimide with Ethynyl Terminals
Authors: Shirata Tomoya , Kon Tatsuki , Sasaki Keiko , Oishi Yoshiyuki , Shibasaki Yuji 
Published: February 2014

Abstract
A soluble imide oligomer (IO) (repeating number; 2 and 4) having N-phenylated melamine units and phenylethynyl terminals was prepared, and the application to polyimide composites with cellulose (CEL) crystals derived from pulp (CELp) or Halocynthia (CELh) with or without a modifier was investigated. The CELh additive up to 0.5 wt % was easily dispersed in IO matrix in solution, and thermostable (glass-transition temperature, ca. 285 °C) transparent tough film (tensile strength, ca. 169 MPa; elongation at break, ca. 8.9%; tensile modulus, ca. 4.6 GPa) was obtained, while the addition of a modifier such as cetyltrimethylammonium bromide and poly(ethylene glycol) derivatives was necessary to obtain a similar tough film for the CELp additive.
Study protocol for examining job strain as a risk factor for severe unipolar depression in an individual participant meta-analysis of 14 European cohorts
Authors: Madsen Ida E. H. , Hannerz Harald , Nyberg Solja T. , Magnusson Hanson Linda L. , Ahola Kirsi , Alfredsson Lars , Batty G. David , Bjorner Jakob B. , Borritz Marianne , Burr Hermann , Dragano Nico , Ferrie Jane E. , Hamer Mark , Jokela Markus , Knutsson Anders , Koskenvuo Markku , Koskinen Aki , Leineweber Constanze , Nielsen Martin L. , Nordin Maria , Oksanen Tuula , Pejtersen Jan H. , Pentti Jaana , Salo Paula , Singh-Manoux Archana , Suominen Sakari , Theorell Töres , Toppinen-Tanner Salla , Vahtera Jussi , Väänänen Ari , Westerholm Peter J. M , Westerlund Hugo , Fransson Eleonor , Heikkilä Katriina , Virtanen Marianna , Rugulies Reiner , Kivimäki Mika ,   for the IPD-Work Consortium
Published: February 2014

Background: Previous studies have shown that gainfully employed individuals with high work demands and low control at work (denoted “job strain”) are at increased risk of common mental disorders, including depression. Most existing studies have, however, measured depression using self-rated symptom scales that do not necessarily correspond to clinically diagnosed depression. In addition, a meta-analysis from 2008 indicated publication bias in the field. Methods: This study protocol describes the planned design and analyses of an individual participant data meta-analysis, to examine whether job strain is associated with an increased risk of clinically diagnosed unipolar depression based on hospital treatment registers. The study will be based on data from approximately 120,000 individuals who participated in 14 studies on work environment and health in 4 European countries. The self-reported working conditions data will be merged with national registers on psychiatric hospital treatment, primarily hospital admissions. Study-specific risk estimates for the association between job strain and depression will be calculated using Cox regressions. The study-specific risk estimates will be pooled using random effects meta-analysis. Discussion: The planned analyses will help clarify whether job strain is associated with an increased risk of clinically diagnosed unipolar depression. As the analysis is based on pre-planned study protocols and an individual participant data meta-analysis, the pooled risk estimates will not be influenced by selective reporting and publication bias. However, the results of the planned study may only pertain to severe cases of unipolar depression, because of the outcome measure applied.
Rapid and inexpensive body fluid identification by RNA profiling-based multiplex High Resolution Melt (HRM) analysis
Authors: Hanson Erin K. , Ballantyne Jack 
Published: February 2014

Positive identification of the nature of biological material present on evidentiary items can be crucial for understanding the circumstances surrounding a crime. However, traditional protein-based methods do not permit the identification of all body fluids and tissues, and thus molecular based strategies for the conclusive identification of all forensically relevant biological fluids and tissues need to be developed. Messenger RNA (mRNA) profiling is an example of such a molecular-based approach. Current mRNA body fluid identification assays involve capillary electrophoresis (CE) or quantitative RT-PCR (qRT-PCR) platforms, each with its own limitations. Both platforms require the use of expensive fluorescently labeled primers or probes. CE-based assays require separate amplification and detection steps thus increasing the analysis time. For qRT-PCR assays, only 3-4 markers can be included in a single reaction since each requires a different fluorescent dye.To simplify mRNA profiling assays, and reduce the time and cost of analysis, we have developed single- and multiplex body fluid High Resolution Melt (HRM) assays for the identification of common forensically relevant biological fluids and tissues. The incorporated biomarkers include IL19 (vaginal secretions), IL1F7 (skin), ALAS2 (blood), MMP10 (menstrual blood), HTN3 (saliva) and TGM4 (semen). The HRM assays require only unlabeled PCR primers and a single saturating intercalating fluorescent dye (Eva Green). Each body-fluid-specific marker can easily be identified by the presence of a distinct melt peak. Usually, HRM assays are used to detect variants or isoforms for a single gene target. However, we have uniquely developed duplex and triplex HRM assays to permit the simultaneous detection of multiple targets per reaction. Here we describe the development and initial performance evaluation of the developed HRM assays. The results demonstrate the potential use of HRM assays for rapid, and relatively inexpensive, screening of biological evidence.
The Mandarin LVS construction: Verb lexical semantics and grammatical aspect
Authors: Chen Ying , Jing-Schmidt Zhuo 
Published: February 2014

AbstractTwo empirical studies – a verb elicitation experiment and a collostructional analysis – were conducted to investigate the Mandarin LVS construction with respect to the lexical semantics of the verb and its collocation with grammatical aspect. Converging evidence from both studies indicates strong schematicity and productivity in the verb category of the LVS construction. Although most exemplars fall into a few major lexical semantic clusters, there are more low-frequency marginal exemplars than previously recognized, reinforcing the constructional schema in an essentially radial category. In addition to the lexical semantic regularity of the verb slot, both studies showed the existence of high-frequency tokens with prototype status. As far as grammatical aspect is concerned, the converging evidence indicates that the LVS category is compatible not only with the durative aspect, but also with the perfective as well as the resultative and directional lexical aspect. The attraction of grammatical aspect to the verb of LVS is graded rather than absolute, with some mutual selection patterns more typical than others. The two grammatical aspects as marked by the durative -zhe and the perfective -le are non-interchangeable.
Unpacking noun-noun compounds: Interpreting novel and conventional foodnames in isolation and on food labels
Authors: Smith Viktor , Barratt Daniel , Zlatev Jordan 
Published: February 2014

AbstractIn two complementary experiments we took an integrated approach to a set of tightly interwoven, yet rarely combined questions concerning the spontaneous interpretation of novel (unfamiliar) noun-noun compounds (NNCs) when encountered in isolation, and possible (re)interpretations of novel as well as conventional (familiar) NNCs when encountered in verbo-visual context. To enhance ecological validity, we mirrored our research questions in real-life concerns on the naming of commercial food products and the risk of consumers being misled by the names that producers give to them, focusing on the Danish food market and using Danish NNCs. Specifically, we addressed a highly productive type of compound food names where the modifier denotes a geographical entity and the head denotes a type of food, e.g. Hawaii pizza. Our findings contribute new evidence to central issues of (cognitive) linguistic theory concerning the relations between semantics and pragmatics, as well as system and usage, and psycholinguistic issues concerning the processing of NNCs. New insights and methodological tools are also provided for supporting future best practices in the field of food naming and labelling.
Influence of toasting treatment on permeability of six wood species for enological use
Authors: Acuña Luis , Gonzalez Daniel , de la Fuente Javier , Moya Laura 
Published: February 2014

Abstract
The major physical properties and permeability of six wood species, namely, Castanea sativa, Prunus avium, Robinia pseudoacacia, Fraxinus excelsior, Quercus alba, and Quercus petraea, have been investigated from the enological point of view. With permeability studies in focus, impregnation and evaporation losses were assessed by means of a hydroalcoholic solution similar to wine. Both native and toasted woods were tested, as toasting is a common pretreatment for barrels destined to be used in wine aging. Evaporation losses of all species, with and without treatment, follow a positively sloped linear model with R
2 adjusted ≥90%, whereas losses by impregnation followed an asymptotic model with R
2 values ≥80%. The effects of toasting are species specific. It was observed that the impregnation and evaporation losses decrease significantly in the species C. sativa, R. pseudoacacia, Q. alba, and P. avium. It is remarkable that toasted F. excelsior has total losses much higher than the other woods tested; thus, toasting of this type of wood is not recommendable for manufacturing wood staves for winemaking.
Risk behaviors related to violence and injury among school-going adolescents in Karnataka, Southern India
Authors: Swain Subhashisa , Mohanan Padma , Sanah Noore , Sharma Vikram , Ghosh Deboporna 
Published: February 2014

Abstract
Background: Adolescence is a crucial stage of life. The development and practice of various risk behaviors predisposes the risk of getting injured and consequences in later life.
Study methods: This cross-sectional study was conducted among 381 adolescents (15–19 years) studying in different schools and colleges of Udupi. The Youth Risk Behavior Survey (YRBS), Center for Disease Control (CDC) Questionnaire and the Atlanta Questionnaire and Guidelines was adopted for data collection. Behaviors such as poor obeying traffic rules while driving, violence at school premises, and suicidal thoughts of the participants were explored. Univariate analysis followed by multivariate logistic regression was done to estimate the predictors of violence-related behavior using the Statistical Packages for Social Sciences (SPSS) v. 20.
Results: In our study, 27.03% of students (total=381) had knowledge of traffic rules in detail, where 65% drove a motorized vehicle. Nearly 75% of students did not use a helmet or seatbelt while driving and 17% used a mobile phone for either talking or texting while driving. Considering all violence risk behaviors, 33.07% of students had at least and 18% had at least two violence-related risk behaviors. Nearly 21.78% thought of hitting somebody, 16.34% of boys and 9.5% of girls carried sharp objects to school, 18.81% of boys and 10.39% of girls damaged or stole other students’ property, 18.37% bullied others in the past month at the school campus, and 11.32% were involved in serious fights. Out of 381 students, 114 (30.32%) were bullied, 10% had been slapped intentionally, and 18% of girls felt unsafe to go out of their home because of threat compared with 15% of boys. In total, 71 (18.93%) students thought of suicide and 22 of them attempted it. Logistic regression showed that boys [odds ratio (OR): 1.72, 95% confidence interval (CI): 1.02–2.93) and students of 16 years of age (OR: 3.02, 95% CI: 1.06–9.02) affected or victimized by violent activities at school (OR: 3.23, 95% CI: 1.76–5.93) and bullied by others (OR: 2.6, 95% CI: 1.55–4.36) were determining factors for violence-related behaviors after adjusting for other variables.
Conclusion: There is a need to identify students at risk and for intervention addressing the risk factors. Further qualitative studies could provide more insight.
Effect of life skills training on physical activity patterns amongst school adolescents in Delhi: a non-randomized interventional study
Authors: Anand Tanu , Ingle Gopal Krishna , Meena Gajendra Singh , Kishore Jugal , Yadav Sangita 
Published: February 2014

Abstract
Background: Effect of life skills on physical activity behavior of adolescents is little explored.
Objective: To assess impact of life-skills training on the level of physical activity amongst adolescents.
Methods: A nonrandomized interventional study with a control group. All students studying in Class IX and XI of two schools in Delhi were included. Data was collected at baseline, 15 days and 3 months after the life-skills training. Two life-skills training sessions were conducted for each standard following collection of baseline data.
Results: There were 180 students in the intervention and 183 students in the control group. A significant increase was noted in the level of light-moderate, vigorous physical activity, and stretching and strengthening exercises (p<0.001) in an intervention group over the period of 3 months following the training. The number of students enrolled in physical education classes also increased.
Conclusions: A skills-based approach helped to improve the level of physical activity amongst the school adolescents.
Absence of antibodies against Bordetella pertussis in pregnant women and newborns in the state of Nuevo Leon
Authors: Villarreal-Pérez Jesús Zacarías , Ramírez-Aranda José Manuel , Rodríguez-Rodríguez Irasema , Perales-Dávila José , García-Elizondo Francisco Javier , Gómez-Gómez Celina , Galindo-Galindo Edgar , Rodríguez-Moreno Marco Antonio , Ballesteros-Elizondo Romelia 
Published: February 2014

Abstract

Aims: To assess placental transfer of antibodies to the child at birth and at 2 months of age.

Materials and methods: For the quantification of anti-PT IgG antibodies, we used an indirect enzyme-linked immunosorbent assay standardized by The National Institute of Epidemiologic Diagnosis and Reference (InDRE). Samples were considered negative from 0 to 48 IU/mL, indeterminate from 49 to 93 IU/mL and positive at ≥94 IU/mL. We performed a cross-sectional assessment of anti-PT IgG antibody levels in the mother, umbilical cord, and child.

Results: There was a higher concentration of IgG anti-TP in the umbilical cord (4.3%) and in the mother (1.4%), but a total absence was observed in the child (0%).

Conclusion: The vulnerability of children to Bordetella pertussis shows the need to implement effective immunization strategies, whether actively, in the child, or passively through the mother, adolescents, and adults who are in contact with the child.
Melatonin deprival modifies follicular and corpus luteal growth dynamics in a sheep model
Authors: Manca Maria Elena , Manunta Maria Lucia , Spezzigu Antonio , Torres-Rovira Laura , Gonzalez-Bulnes Antonio , Pasciu Valeria , Piu Peter , Leoni Giovanni G , Succu Sara , Chesneau Didier , Naitana Salvatore , Berlinguer Fiammetta 
Published: February 2014

This study assessed the effect of melatonin deprival on ovarian status and function in sheep. Experimental procedures were carried out within two consecutive breeding seasons. Animals were divided into two groups: pinealectomised (n=6) and sham-operated (n=6). The completeness of the pineal gland removal was confirmed by the plasma concentration of melatonin. Ovarian status was monitored by ovarian ultrasonography for 1 year to study reproductive seasonality. Follicular and corpus luteal growth dynamics were assessed during an induced oestrous cycle. As the effects of melatonin on the ovary may also be mediated by its antioxidant properties, plasma Trolox equivalent antioxidant capacity (TEAC) was determined monthly for 1 year. Pinealectomy significantly extended the breeding season (310±24.7 vs 217.5±24.7 days in controls;P<0.05). Both pinealectomised and sham-operated ewes showed a well-defined wave-like pattern of follicle dynamics; however, melatonin deficiency caused fewer waves during the oestrous cycle (4.3±0.2 vs 5.2±0.2;P<0.05), because waves were 1 day longer when compared with the controls (7.2±0.3 vs 6.1±0.3;P<0.05). The mean area of the corpora lutea (105.4±5.9 vs 65.4±5.9 mm2;P<0.05) and plasma progesterone levels (7.1±0.7 vs 4.9±0.6 ng/ml;P<0.05) were significantly higher in sham-operated ewes compared with pinealectomised ewes. In addition, TEAC values were significantly lower in pinealectomised ewes compared with control ones. These data suggest that melatonin, besides exerting its well-known role in the synchronisation of seasonal reproductive fluctuations, influences the growth pattern of the follicles and the steroidogenic capacity of the corpus luteum.Free Italian abstractAn Italian translation of this abstract is freely available athttp://www.reproduction-online.org/content/147/6/885/suppl/DC1.