bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gestational Age and Birth Weight and the Risk of Childhood Type 1 Diabetes: A Population-Based Cohort and Sibling Design Study
Authors: Khashan Ali S. , Kenny Louise C. , Lundholm Cecilia , Kearney Patricia M. , Gong Tong , McNamee Roseanne , Almqvist Catarina 
Published: October 2015

OBJECTIVE
We investigated the effects of gestational age, birth weight, small for gestational age (SGA), and large for gestational age (LGA) on risk of childhood type 1 diabetes.

RESEARCH DESIGN AND METHODS
We conducted a population-based cohort study of all singleton live births in Sweden between 1973 and 2009 and a sibling control study. Perinatal data were extracted from the Swedish Medical Birth Register. Children with type 1 diabetes diagnosis were identified from the Swedish National Patient Register. Log-linear Poisson regression and conditional logistic regression were used for data analysis.

RESULTS
The study cohort consisted of 3,624,675 singleton live births (42,411,054 person-years). There were 13,944 type 1 diabetes cases during the study period. The sibling control study consisted of 11,403 children with type 1 diabetes and 17,920 siblings. Gestational age between 33 and 36 weeks (relative risk [RR] 1.18 [95% CI 1.09, 1.28) and 37 and 38 weeks (RR 1.12 [95% CI 1.07, 1.17]) was associated with type 1 diabetes in the cohort study and remained significant in the sibling control study. SGA (RR 0.83 [95% CI 0.75, 0.93]) and LGA (RR 1.14 [95% CI 1.04, 1.24]) were associated with type 1 diabetes in the cohort study. The SGA association remained unchanged in the sibling study, while the LGA association disappeared. Very low birth weight was associated with a reduced risk of type 1 diabetes.

CONCLUSIONS
The findings suggest a small association between gestational age and type 1 diabetes that is not likely due to familial confounding factors. Gestational age and type 1 diabetes may be related to insulin resistance due to early life growth restriction or altered gut microbiota in preterm babies.
Positivity for Zinc Transporter 8 Autoantibodies at Diagnosis Is Subsequently Associated With Reduced β-Cell Function and Higher Exogenous Insulin Requirement in Children and Adolescents With Type 1 Diabetes
Authors: Juusola Matilda , Parkkola Anna , Härkönen Taina , Siljander Heli , Ilonen Jorma , Åkerblom Hans K. , Knip Mikael ,   the Childhood Diabetes in Finland Study Group
Published: October 2015

OBJECTIVE
This study assessed the relationship between autoantibodies against zinc transporter 8 (ZnT8A) and disease characteristics at diagnosis of type 1 diabetes and during the first 2 years.

RESEARCH DESIGN AND METHODS
Children, younger than 15 years of age (n = 723) who were newly diagnosed with diabetes, were analyzed for ZnT8A, other diabetes-associated autoantibodies, HLA DR-DQ alleles, and metabolic status, which was monitored by pH, plasma glucose, and occurrence of ketoacidosis at diagnosis and through follow-up of C-peptide concentrations, exogenous insulin dose, and glycosylated hemoglobin for 2 years after the diagnosis.

RESULTS
ZnT8A positivity was detected in 530 children (73%). Positivity for ZnT8A was associated with older age (median 8.9 vs. 8.2 years, P = 0.002) and more frequent ketoacidosis (24% vs. 15%, P = 0.013). Children carrying the HLA DR3 allele were less often ZnT8A positive (66% vs. 77%, P = 0.002) than others. ZnT8A-positive children had lower serum C-peptide concentrations (P = 0.008) and higher insulin doses (P = 0.012) over time than their ZnT8A-negative peers.

CONCLUSIONS
Positivity for ZnT8A at diagnosis seems to reflect a more aggressive disease process before and after diagnosis.
Pourquoi punir les discours de haine ?
Authors: Girard Charles 
Published: October 2015

Les démocraties sont confrontées au dilemme suivant : faut-il limiter la liberté d’expression pour assurer l’égalité des citoyens ? Si la liberté d’expression est constitutive de la démocratie, les discours de haine menacent l’égalité de statut des citoyens appartenant au groupe dénigré. La répression des discours de haine est donc justifiée par la liberté d’expression réellement égale pour tous, ce qui impose une appréciation fine du contexte sociohistorique.
Deux poids, deux mesures ?
Authors: Bleich Erik , Roussin Juliette 
Published: October 2015

Contre l’idée d’une justice qui ferait du « deux poids, deux mesures », l’examen des arrêts de la Cour de cassation relatifs aux discours de haine entre 1972 et 2012 montre que les discours islamophobes sont tout autant réprimés que les autres discours racistes. Sur la base de la loi de 1972 contre le racisme, la plus haute cour française considère que l’humour n’excuse pas toutes les provocations, mais que la liberté des discours politiques doit être protégée.
Des mots qui blessent dans un monde globalisé
Authors: van Noorloos Marloes , Buton-Maquet Kevin 
Published: October 2015

Le contexte global des communications complique l’interprétation des discours de haine. La « quenelle » est-elle antisémite ou bien un simple geste de défi au pouvoir ? Une attaque de l’islam revient-elle à attaquer les musulmans ? Les satires servent-elles toujours un projet d’émancipation ? Ces difficultés imposent de s’accorder sur une définition claire des discours de haine.
Doute conspirationniste et regard critique
Authors: Ledoux Aurélie , Padis Marc-Olivier 
Published: October 2015

Alors que les tenants de la théorie du complot revendiquent l’héritage critique de la modernité, ils en accomplissent le dévoiement dogmatique. Le regard critique porté sur les images en offre un exemple frappant : les arguments complotistes s’appuient sur la certitude que les images ( Jfk , 11 Septembre, ou Charlie ) parlent d’elles-mêmes. Il est donc politiquement impératif de distinguer doute conspirationniste et pensée critique.
Le style paranoïaque à l’ère numérique
Authors: Padis Marc-Olivier 
Published: October 2015

Le style paranoïaque de la scène médiatique française témoigne d’un affaiblissement des normes du débat démocratique dû au nouveau contexte numérique (les espaces d’expression personnelle et les calculateurs des modes de vie). Pourtant, l’expression publique relève d’une demande de participation démocratique louable. Mais quels sont les médiateurs de ces nouvelles attentes ?
Retour vers le futur transhumaniste
Authors: Le Dévédec Nicolas 
Published: October 2015

L’aspiration à améliorer les performances des êtres humains grâce aux sciences et aux techniques s’inscrit-elle dans l’héritage des Lumières d’une perfectibilité humaine ? Si le transhumanisme est bien la continuation du projet moderne de maîtrise de la nature, il fait abstraction des considérations éthiques, sociales et politiques qui le portaient. Le transhumanisme est donc l’idéologie propre aux sociétés de la compétition individualiste.
Natural IgM Switches the Function of Lipopolysaccharide-Activated Murine Bone Marrow–Derived Dendritic Cells to a Regulatory Dendritic Cell That Suppresses Innate Inflammation
Authors: Lobo Peter I. , Schlegel Kailo H. , Bajwa Amandeep , Huang Liping , Kurmaeva Elvira , Wang Binru , Ye Hong , Tedder Thomas F. , Kinsey Gilbert R. , Okusa Mark D. 
Published: October 2015

Abstract
We have previously shown that polyclonal natural IgM protects mice from renal ischemia/reperfusion injury (IRI) by inhibiting the reperfusion inflammatory response. We hypothesized that a potential mechanism involved IgM modulation of dendritic cells (DC), as we observed high IgM binding to splenic DC. To test this hypothesis, we pretreated bone marrow–derived DC (BMDC) with polyclonal murine or human IgM prior to LPS activation and demonstrated that 0.5 × 106 IgM/LPS-pretreated BMDC, when injected into wild-type C57BL/6 mice 24 h before renal ischemia, protect mice from developing renal IRI. We show that this switching of LPS-activated BMDC to a regulatory phenotype requires modulation of BMDC function that is mediated by IgM binding to nonapoptotic BMDC receptors. Regulatory BMDC require IL-10 and programmed death 1 as well as downregulation of CD40 and p65 NF-κB phosphorylation to protect in renal IRI. Blocking the programmed death ligand 1 binding site just before i.v. injection of IgM/LPS-pretreated BMDC or using IL-10 knockout BMDC fails to induce protection. Similarly, IgM/LPS-pretreated BMDC are rendered nonprotective by increasing CD40 expression and phosphorylation of p65 NF-κB. How IgM/LPS regulatory BMDC suppress in vivo ischemia-induced innate inflammation remains to be determined. However, we show that suppression is dependent on other in vivo regulatory mechanisms in the host, that is, CD25+ T cells, B cells, IL-10, and circulating IgM. There was no increase in Foxp3+ regulatory T cells in the spleen either before or after renal IRI. Collectively, these findings show that natural IgM anti-leukocyte Abs can switch BMDC to a regulatory phenotype despite the presence of LPS that ordinarily induces BMDC maturation.
WDR82 Negatively Regulates Cellular Antiviral Response by Mediating TRAF3 Polyubiquitination in Multiple Cell Lines
Authors: Zhu Kun , Wang Xiang , Ju Lin-Gao , Zhu Yuan , Yao Jie , Wang Yanyi , Wu Min , Li Lian-Yun 
Published: October 2015

Abstract
Upon virus infection, retinoic acid–inducible gene I–like receptors in host cells recognize viral RNA and activate type I IFN expression. Previously, we identified WD repeat domain (WDR) 5 as one positive regulator for pathway activation. In this study, we report that WDR82, a homolog protein of WDR5, acts opposite to WDR5 and inhibits the activation of the retinoic acid–inducible gene I signaling pathway. WDR82 overexpression inhibits virus-triggered pathway activation, whereas its knockdown enhances induced IFN-β expression. WDR82 is localized on the mitochondria, and its first N-terminal WD40 domain is critical for localization. WDR82 interacts with TNFR-associated factor (TRAF) 3, and its overexpression promotes K48-linked, but not K63-linked, polyubiquitination on TRAF3. Furthermore, WDR82 knockdown inhibits viral replication in the cell, whereas its overexpression has the opposite effect. Interestingly, WDR82 regulates Sendai virus–induced IFNB1 expression in a cell type–specific manner. Taken together, our findings demonstrate that WDR82 is a negative regulator of virus-triggered type I IFNs pathway through mediating TRAF3 polyubiquitination status and stability on mitochondria.
CD11c/CD18 Signals Very Late Antigen-4 Activation To Initiate Foamy Monocyte Recruitment during the Onset of Hypercholesterolemia
Authors: Foster Greg A. , Xu Lu , Chidambaram Alagu A. , Soderberg Stephanie R. , Armstrong Ehrin J. , Wu Huaizhu , Simon Scott I. 
Published: October 2015

AbstractRecruitment of foamy monocytes to inflamed endothelium expressing VCAM-1 contributes to the development of plaque during atherogenesis. Foamy CD11c+ monocytes arise in the circulation during the onset of hypercholesterolemia and recruit to nascent plaque, but the mechanism of CD11c/CD18 and very late Ag-4 (VLA-4) activation and cooperation in shear-resistant cell arrest on VCAM-1 are ill defined. Within 1 wk of the onset of a Western high-fat diet (WD) in apolipoprotein E–deficient mice, an inflammatory subset of foamy monocytes emerged that made up one fourth of the circulating population. These cells expressed ∼3-fold more CD11c/CD18 and 50% higher chemokine receptors than nonfoamy monocytes. Recruitment from blood to a VCAM-1 substrate under shear stress was assessed ex vivo using a unique artery-on-a-chip microfluidic assay. It revealed that foamy monocytes from mice on a WD increased their adhesiveness over 5 wk, rising to twice that of mice on a normal diet or CD11c−/− mice fed a WD. Shear-resistant capture of foamy human or mouse monocytes was initiated by high-affinity CD11c, which directly activated VLA-4 adhesion via phosphorylated spleen tyrosine kinase and paxillin within focal adhesion complexes. Lipid uptake and activation of CD11c are early and critical events in signaling VLA-4 adhesive function on foamy monocytes competent to recruit to VCAM-1 on inflamed arterial endothelium.
Myeloid Cell–Restricted Insulin/IGF-1 Receptor Deficiency Protects against Skin Inflammation
Authors: Knuever Jana , Willenborg Sebastian , Ding Xiaolei , Akyüz Mehmet D. , Partridge Linda , Niessen Carien M. , Brüning Jens C. , Eming Sabine A. 
Published: October 2015

Abstract
Myeloid cells are key regulators of tissue homeostasis and disease. Alterations in cell-autonomous insulin/IGF-1 signaling in myeloid cells have recently been implicated in the development of systemic inflammation and insulin-resistant diabetes mellitus type 2 (DM). Impaired wound healing and inflammatory skin diseases are frequent DM-associated skin pathologies, yet the underlying mechanisms are elusive. In this study, we investigated whether myeloid cell–restricted IR/IGF-1R signaling provides a pathophysiologic link between systemic insulin resistance and the development of cutaneous inflammation. Therefore, we generated mice lacking both the insulin and IGF-1 receptor in myeloid cells (IR/IGF-1RMKO). Whereas the kinetics of wound closure following acute skin injury was similar in control and IR/IGF-1RMKO mice, in two different conditions of dermatitis either induced by repetitive topical applications of the detergent SDS or by high-dose UV B radiation, IR/IGF-1RMKO mice were protected from inflammation, whereas controls developed severe skin dermatitis. Notably, whereas during the early phase in both inflammatory conditions the induction of epidermal proinflammatory cytokine expression was similar in control and IR/IGF-1RMKO mice, during the late stage, epidermal cytokine expression was sustained in controls but virtually abrogated in IR/IGF-1RMKO mice. This distinct kinetic of epidermal cytokine expression was paralleled by proinflammatory macrophage activation in controls and a noninflammatory phenotype in mutants. Collectively, our findings provide evidence for a proinflammatory IR/IGF-1R–dependent pathway in myeloid cells that plays a critical role in the dynamics of an epidermal–dermal cross-talk in cutaneous inflammatory responses, and may add to the mechanistic understanding of diseases associated with disturbances in myeloid cell IR/IGF-1R signaling, including DM.
Pak2 Controls Acquisition of NKT Cell Fate by Regulating Expression of the Transcription Factors PLZF and Egr2
Authors: O’Hagan Kyle L. , Zhao Jie , Pryshchep Olga , Wang Chyung-Ru , Phee Hyewon 
Published: October 2015

Abstract
NKT cells constitute a small population of T cells developed in the thymus that produce large amounts of cytokines and chemokines in response to lipid Ags. Signaling through the Vα14-Jα18 TCR instructs commitment to the NKT cell lineage, but the precise signaling mechanisms that instruct their lineage choice are unclear. In this article, we report that the cytoskeletal remodeling protein, p21-activated kinase 2 (Pak2), was essential for NKT cell development. Loss of Pak2 in T cells reduced stage III NKT cells in the thymus and periphery. Among different NKT cell subsets, Pak2 was necessary for the generation and function of NKT1 and NKT2 cells, but not NKT17 cells. Mechanistically, expression of Egr2 and promyelocytic leukemia zinc finger (PLZF), two key transcription factors for acquiring the NKT cell fate, were markedly diminished in the absence of Pak2. Diminished expression of Egr2 and PLZF were not caused by aberrant TCR signaling, as determined using a Nur77-GFP reporter, but were likely due to impaired induction and maintenance of signaling lymphocyte activation molecule 6 expression, a TCR costimulatory receptor required for NKT cell development. These data suggest that Pak2 controls thymic NKT cell development by providing a signal that links Egr2 to induce PLZF, in part by regulating signaling lymphocyte activation molecule 6 expression.
Type I IFNs Act upon Hematopoietic Progenitors To Protect and Maintain Hematopoiesis during Pneumocystis Lung Infection in Mice
Authors: Prigge Justin R. , Hoyt Teri R. , Dobrinen Erin , Capecchi Mario R. , Schmidt Edward E. , Meissner Nicole 
Published: October 2015

Abstract
Although acquired bone marrow failure (BMF) is considered a T cell–mediated autoimmune disease, few studies have considered contributing roles of innate immune deviations following otherwise innocuous infections as a cause underlying the immune defects that lead to BMF. Type I IFN signaling plays an important role in protecting hematopoiesis during systemic stress responses to the opportunistic fungal pathogen Pneumocystis. During Pneumocystis lung infection, mice deficient in both lymphocytes and type I IFN receptor (IFrag−/−) develop rapidly progressing BMF associated with accelerated hematopoietic cell apoptosis. However, the communication pathway eliciting the induction of BMF in response to this strictly pulmonary infection has been unclear. We developed a conditional-null allele of Ifnar1 and used tissue-specific induction of the IFrag−/− state and found that, following Pneumocystis lung infection, type I IFNs act not only in the lung to prevent systemic immune deviations, but also within the progenitor compartment of the bone marrow to protect hematopoiesis. In addition, transfer of sterile-filtered serum from Pneumocystis-infected mice as well as i.p. injection of Pneumocystis into uninfected IFrag−/− mice induced BMF. Although specific cytokine deviations contribute to induction of BMF, immune-suppressive treatment of infected IFrag−/− mice ameliorated its progression but did not prevent loss of hematopoietic progenitor functions. This suggested that additional, noncytokine factors also target and impair progenitor functions; and interestingly, fungal β-glucans were also detected in serum. In conclusion, our data demonstrate that type 1 IFN signaling protects hematopoiesis within the bone marrow compartment from the damaging effects of proinflammatory cytokines elicited by Pneumocystis in the lung and possibly at extrapulmonary sites via circulating fungal components.
Sex Differences in Plasmacytoid Dendritic Cell Levels of IRF5 Drive Higher IFN-α Production in Women
Authors: Griesbeck Morgane , Ziegler Susanne , Laffont Sophie , Smith Nikaïa , Chauveau Lise , Tomezsko Phillip , Sharei Armon , Kourjian Georgio , Porichis Filippos , Hart Meghan , Palmer Christine D. , Sirignano Michael , Beisel Claudia , Hildebrandt Heike , Cénac Claire , Villani Alexandra-Chloé , Diefenbach Thomas J. , Le Gall Sylvie , Schwartz Olivier , Herbeuval Jean-Philippe , Autran Brigitte , Guéry Jean-Charles , Chang J. Judy , Altfeld Marcus 
Published: October 2015

AbstractIncreased IFN-α production contributes to the pathogenesis of infectious and autoimmune diseases. Plasmacytoid dendritic cells (pDCs) from females produce more IFN-α upon TLR7 stimulation than pDCs from males, yet the mechanisms underlying this difference remain unclear. In this article, we show that basal levels of IFN regulatory factor (IRF) 5 in pDCs were significantly higher in females compared with males and positively correlated with the percentage of IFN-α–secreting pDCs. Delivery of recombinant IRF5 protein into human primary pDCs increased TLR7-mediated IFN-α secretion. In mice, genetic ablation of the estrogen receptor 1 (Esr1) gene in the hematopoietic compartment or DC lineage reduced Irf5 mRNA expression in pDCs and IFN-α production. IRF5 mRNA levels furthermore correlated with ESR1 mRNA levels in human pDCs, consistent with IRF5 regulation at the transcriptional level by ESR1. Taken together, these data demonstrate a critical mechanism by which sex differences in basal pDC IRF5 expression lead to higher IFN-α production upon TLR7 stimulation in females and provide novel targets for the modulation of immune responses and inflammation.
Factors Influencing the Choice of Marketing Outlets among Small-Scale Pineapple Farmers in Kericho County, Kenya
Authors: Sigei Geoffrey , K. Hillary Bett , K. Jonah Kiprop , O. Timothy Odipo 
Published: October 2015

<p>Markets act as pivotal point in the agricultural transformation process. Access to market plays crucial role in exploiting the marketing opportunities for the pineapple farmers. In the study area, the strategies to unlock the market access among pineapple farmers are wanting and these have resulted to limited marketing outlets. This study therefore seeks to determine the factors influencing the choice of pineapple marketing outlets in Bureti district. The cross-sectional data were collected from a sample of 100 small-scale pineapple farmers. Data was analyzed using descriptive and Multinomial Logit model. The results showed that gender, group marketing, pineapple produce, price information, marketing under contract and vehicle ownership significantly influenced the choice of pineapple marketing outlets. The study has potential policy implication of improving the pineapple marketing performance and the welfare of the farmer. </p>
Afghanistan and its Economy
Authors: Eltezam Zabioullah A. 
Published: October 2015

AbstractAfghanistan is one of the least developed countries of the world. United States of America and several other nations spent hundreds of billions of dollars during the last 13 years to strengthen her economy and security but due to pervasive corruption the country could not absorb the aid effectively. As long as Afghanistan remains resistant to change, and corruption and lawlessness continue to hurt the country, the badly needed foreign assistance, no matter how colossal, will not make much difference.In this paper, the author explains the historical, geographical and political factors that have plagued and still hinder economic development of Afghanistan. The paper briefly explains land, population, resources and economic aggregates in addition to the historical events that have caused the progress to remain slow. Some recommendations are made at the end.
Large‐Scale Identification of the Arginine Methylome by Mass Spectrometry
Authors: Sylvestersen Kathrine B. , Nielsen Michael L. 
Published: November 2015

AbstractThe attachment of one or more methylation groups to the side chain of arginine residues is a regulatory mechanism for cellular proteins. Recent advances in mass spectrometry−based characterization allow comprehensive identification of arginine methylation sites by peptide‐level enrichment strategies. Described in this unit is a 4‐day protocol for enrichment of arginine‐methylated peptides and subsequent identification of thousands of distinct sites by mass spectrometry. Specifically, the protocol explains step‐by‐step sample preparation, enrichment using commercially available antibodies, prefractionation using strong cation exchange, and identification using liquid chromatography coupled to tandem mass spectrometry. A strategy for relative quantification is described using stable isotope labeling by amino acids in cell culture (SILAC). Approaches for analysis of arginine methylation site occupancy are also discussed. Collectively, the unit describes the essential parameters required for a successful and comprehensive experiment detailing the arginine methylome. © 2015 by John Wiley & Sons, Inc.