bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Key Temporal Delay in the Circadian Cycle ofDrosophilaIs Mediated by a Nuclear Localization Signal in the Timeless Protein
Authors: Saez Lino , Derasmo Mary , Meyer Pablo , Stieglitz J , Young Michael W 
Published: April 2011

AbstractRegulated nuclear entry of the Period (PER) and Timeless (TIM) proteins, two components of the Drosophila circadian clock, is essential for the generation and maintenance of circadian behavior. PER and TIM shift from the cytoplasm to the nucleus daily, and the length of time that PER and TIM reside in the cytoplasm is an important determinant of the period length of the circadian rhythm. Here we identify a TIM nuclear localization signal (NLS) that is required for appropriately timed nuclear accumulation of both TIM and PER. Transgenic flies with a mutated TIM NLS produced circadian rhythms with a period of ∼30 hr. In pacemaker cells of the brain, PER and TIM proteins rise to abnormally high levels in the cytoplasm of timΔNLS mutants, but show substantially reduced nuclear accumulation. In cultured S2 cells, the mutant TIMΔNLS protein significantly delays nuclear accumulation of both TIM and wild-type PER proteins. These studies confirm that TIM is required for the nuclear localization of PER and point to a key role for the TIM NLS in the regulated nuclear accumulation of both proteins.
A Balance Between Euchromatic (JIL-1) and Heterochromatic [SU(VAR)2-5 and SU(VAR)3-9] Factors Regulates Position-Effect Variegation inDrosophila
Authors: Wang Chao , Girton Jack , Johansen Jørgen , Johansen Kristen M 
Published: April 2011

AbstractIn this study, we show that the haplo-enhancer effect of JIL-1 has the ability to counterbalance the haplo-suppressor effect of both Su(var)3-9 and Su(var)2-5 on position-effect variegation, providing evidence that a finely tuned balance between the levels of JIL-1 and the major heterochromatin components contributes to the regulation of gene expression.
Lack of Interleukin-1 Receptor I (IL-1RI) Protects Mice From High-Fat Diet–Induced Adipose Tissue Inflammation Coincident With Improved Glucose Homeostasis
Authors: McGillicuddy Fiona C. , Harford Karen A. , Reynolds Clare M. , Oliver Elizabeth , Claessens Mandy , Mills Kingston H.G. , Roche Helen M. 
Published: April 2011

OBJECTIVEHigh-fat diet (HFD)-induced adipose tissue inflammation is a critical feature of diet-induced insulin resistance (IR); however, the contribution of interleukin-1 receptor I (IL-1RI)-mediated signals to this phenotype has not been defined. We hypothesized that lack of IL-1RI may ameliorate HFD-induced IR by attenuating adipose tissue inflammation.RESEARCH DESIGN AND METHODSGlucose homeostasis was monitored in chow- and HFD-fed wild-type (WT) and IL-1RI−/− mice by glucose tolerance and insulin tolerance tests. Macrophage recruitment and cytokine signature of adipose tissue macrophages was evaluated. Insulin sensitivity and cytokine secretion from adipose explants was quantified. Cytokine secretion and adipocyte insulin sensitivity was measured in cocultures of WT or IL-1RI−/− macrophages with 3T3L1 adipocytes. Synergistic effects of IL-1β with tumor necrosis factor (TNF)-α on inflammation was monitored in WT and IL-1RI−/− bone-marrow macrophages and adipose explants.RESULTSLean and obese IL-1RI−/− animals exhibited enhanced glucose homeostasis by glucose tolerance test and insulin tolerance test. M1/M2 macrophage number in adipose tissue was comparable between genotypes; however, TNF-α and IL-6 secretion was lower from IL-1RI−/− adipose tissue macrophages. IL-1RI−/− adipose exhibited enhanced insulin sensitivity, elevated pAKT, lower cytokine secretion, and attenuated induction of phosphorylated signal transducer and activator of transcription 3 and suppressor of cytokine signaling molecule 3 after HFD. Coculture of WT, but not IL-1RI−/− macrophages, with 3T3L1 adipocytes enhanced IL-6 and TNF-α secretion, reduced adiponectin secretion, and impaired adipocyte insulin sensitivity. TNF-α and IL-1β potently synergized to enhance inflammation in WT macrophages and adipose, an effect lost in the absence of IL-1RI.CONCLUSIONSLack of IL-1RI protects against HFD-induced IR coincident with reduced local adipose tissue inflammation, despite equivalent immune cell recruitment.
Insulin Restores Gestational Diabetes Mellitus–Reduced Adenosine Transport Involving Differential Expression of Insulin Receptor Isoforms in Human Umbilical Vein Endothelium
Authors: Westermeier Francisco , Salomón Carlos , González Marcelo , Puebla Carlos , Guzmán-Gutiérrez Enrique , Cifuentes Fredi , Leiva Andrea , Casanello Paola , Sobrevia Luis 
Published: April 2011

OBJECTIVE
To determine whether insulin reverses gestational diabetes mellitus (GDM)–reduced expression and activity of human equilibrative nucleoside transporters 1 (hENT1) in human umbilical vein endothelium cells (HUVECs).

RESEARCH DESIGN AND METHODS
Primary cultured HUVECs from full-term normal (n = 44) and diet-treated GDM (n = 44) pregnancies were used. Insulin effect was assayed on hENT1 expression (protein, mRNA, SLC29A1 promoter activity) and activity (initial rates of adenosine transport) as well as endothelial nitric oxide (NO) synthase activity (serine1177 phosphorylation, l-citrulline formation). Adenosine concentration in culture medium and umbilical vein blood (high-performance liquid chromatography) as well as insulin receptor A and B expression (quantitative PCR) were determined. Reactivity of umbilical vein rings to adenosine and insulin was assayed by wire myography. Experiments were in the absence or presence of l-NG-nitro-l-arginine methyl ester (l-NAME; NO synthase inhibitor) or ZM-241385 (an A2A-adenosine receptor antagonist).

RESULTS
Umbilical vein blood adenosine concentration was higher, and the adenosine- and insulin-induced NO/endothelium-dependent umbilical vein relaxation was lower in GDM. Cells from GDM exhibited increased insulin receptor A isoform expression in addition to the reported NO–dependent inhibition of hENT1-adenosine transport and SLC29A1 reporter repression, and increased extracellular concentration of adenosine and NO synthase activity. Insulin reversed all these parameters to values in normal pregnancies, an effect blocked by ZM-241385 and l-NAME.

CONCLUSIONS
GDM and normal pregnancy HUVEC phenotypes are differentially responsive to insulin, a phenomenon where insulin acts as protecting factor for endothelial dysfunction characteristic of this syndrome. Abnormal adenosine plasma levels, and potentially A2A-adenosine receptors and insulin receptor A, will play crucial roles in this phenomenon in GDM.
Impact of Intranasal Insulin on Insulin Antibody Affinity and Isotypes in Young Children With HLA-Conferred Susceptibility to Type 1 Diabetes
Authors: Ryhänen Samppa J. , Härkönen Taina , Siljander Heli , Näntö-Salonen Kirsti , Simell Tuula , Hyöty Heikki , Ilonen Jorma , Veijola Riitta , Simell Olli , Knip Mikael 
Published: April 2011

OBJECTIVE
Despite promising results from studies on mouse models, intranasal insulin failed to prevent or delay the development of type 1 diabetes in autoantibody-positive children with HLA-conferred disease susceptibility. To analyze whether the insulin dose was inadequate to elicit an immunomodulatory response, we compared the changes observed in insulin antibody (IA) affinity and isotypes after treatment with nasal insulin or placebo.

RESEARCH DESIGN AND METHODS
Ninety-five children (47 in the placebo group and 48 in the insulin group of the total of 224 children randomized for the trial) with HLA-conferred susceptibility to type 1 diabetes derived from the intervention arm of the Finnish Type 1 Diabetes Prediction and Prevention study were included in these analyses. Blood samples drawn before or at the beginning of the treatment and after treatment for 3 and 6 months were analyzed for IA affinity and isotype-specific IAs (IgG1–4, IgA, IgM, and IgE).

RESULTS
IgG3- and IgA-IA levels (P = 0.031 and 0.015, respectively) and the number of IgG3-IA–positive subjects (P = 0.022) were significantly higher at 6 months after the initiation of the treatment in the insulin group. No significant differences were observed between the two groups in IA affinity or other IA isotypes.

CONCLUSIONS
The insulin dose administered induced a modest change in the IA isotype profile. The lack of impact of nasal insulin on IA affinity implies that the immune response of study subjects was already mature at the beginning of the intervention.
Utility of Hemoglobin A1c for Diagnosing Prediabetes and Diabetes in Obese Children and Adolescents
Authors: Nowicka Paulina , Santoro Nicola , Liu Haibei , Lartaud Derek , Shaw Melissa M. , Goldberg Rachel , Guandalini Cindy , Savoye Mary , Rose Paulina , Caprio Sonia 
Published: April 2011

OBJECTIVE
Hemoglobin A1c (A1C) has emerged as a recommended diagnostic tool for identifying diabetes and subjects at risk for the disease. This recommendation is based on data in adults showing the relationship between A1C with future development of diabetes and microvascular complications. However, studies in the pediatric population are lacking.

RESEARCH DESIGN AND METHODS
We studied a multiethnic cohort of 1,156 obese children and adolescents without a diagnosis of diabetes (male, 40%/female, 60%). All subjects underwent an oral glucose tolerance test (OGTT) and A1C measurement. These tests were repeated after a follow-up time of ∼2 years in 218 subjects.

RESULTS
At baseline, subjects were stratified according to A1C categories: 77% with normal glucose tolerance (A1C &lt;5.7%), 21% at risk for diabetes (A1C 5.7–6.4%), and 1% with diabetes (A1C &gt;6.5%). In the at risk for diabetes category, 47% were classified with prediabetes or diabetes, and in the diabetes category, 62% were classified with type 2 diabetes by the OGTT. The area under the curve receiver operating characteristic for A1C was 0.81 (95% CI 0.70–0.92). The threshold for identifying type 2 diabetes was 5.8%, with 78% specificity and 68% sensitivity. In the subgroup with repeated measures, a multivariate analysis showed that the strongest predictors of 2-h glucose at follow-up were baseline A1C and 2-h glucose, independently of age, ethnicity, sex, fasting glucose, and follow-up time.

CONCLUSIONS
The American Diabetes Association suggested that an A1C of 6.5% underestimates the prevalence of prediabetes and diabetes in obese children and adolescents. Given the low sensitivity and specificity, the use of A1C by itself represents a poor diagnostic tool for prediabetes and type 2 diabetes in obese children and adolescents.
One-Hour Postload Plasma Glucose Levels and Left Ventricular Mass in Hypertensive Patients
Authors: Sciacqua Angela , Miceli Sofia , Carullo Giuseppe , Greco Laura , Succurro Elena , Arturi Franco , Sesti Giorgio , Perticone Francesco 
Published: April 2011

OBJECTIVE
Left ventricular hypertrophy (LVH), an independent risk factor for cardiovascular (CV) morbidity and mortality, recognizes a multifactorial pathogenesis. A plasma glucose value ≥155 mg/dL for the 1-h postload plasma glucose during an oral glucose tolerance test (OGTT) identifies subjects with normal glucose tolerance (NGT) at high risk for type 2 diabetes. We addressed the question if glucose tolerance status, particularly 1-h postload plasma glucose levels, affects left ventricular mass (LVM) and cardiac geometry in essential hypertension.

RESEARCH DESIGN AND METHODS
We enrolled 767 never-treated hypertensive subjects, 393 women and 374 men (mean age 49.6 ± 8.5 years). All patients underwent an OGTT for the evaluation of glucose tolerance and standard echocardiography. LVM was calculated using the Devereux formula and normalized by body surface area (LVM index [LVMI]). Insulin sensitivity was assessed by the Matsuda index. Among all participants, 514 had NGT, 168 had impaired glucose tolerance (IGT), and 85 had type 2 diabetes. According to the 1-h postload plasma glucose cutoff point of 155 mg/dL, we divided normotolerant subjects into two groups: NGT &lt;155 mg/dL (n = 356) and NGT ≥155 mg/dL (n = 158).

RESULTS
Subjects in the NGT ≥155 mg/dL group had worse insulin sensitivity than subjects in the NGT &lt;155 mg/dL group (Matsuda index 63.9 vs. 88.8; P &lt; 0.0001). Men with NGT ≥155 mg/dL had a higher LVMI than men with NGT &lt;155 mg/dL (126.6 vs. 114.3 g/m2; P = 0.002) and a different LVH prevalence (41.1 vs. 25.8%; P &lt; 0.0001). At multiple regression analysis, 1-h glucose resulted in the major determinant of LVMI in normotolerant, IGT, and diabetic groups.

CONCLUSIONS
These data show that NGT ≥155 mg/dL subjects, compared with NGT &lt;155 mg/dL subjects, have a higher LVMI and a greater prevalence of LVH similar to that of IGT and diabetic patients.
La médiation de rue comme régulation des désordres urbains
Authors: Marlière Éric , Fontaine Séverine 
Published: April 2011

Résumé Les ruptures entre les jeunes dits « des cités » et les élus locaux se sont opérées progressivement depuis les années 1980. Elles se sont accentuées brutalement avec les émeutes de novembre 2005, comme le montrent les récentes échauffourées entre jeunes et police dans les cités populaires urbaines. Quelle que soit la culture politique de la commune, les élus locaux ont de plus en plus de mal à conserver de la crédibilité à l’égard d’une frange croissante de la jeunesse des quartiers populaires, celle qui se situe en marge. C’est le cas d’une municipalité « gauche » de la banlieue de Paris étudiée entre 2007 et 2008 qui voit une augmentation graduelle des tensions entre jeunes et institutions. Cette situation que l’on pourrait qualifier d’« explosive » amène les édiles municipaux à concevoir (avant les émeutes de 2005) un dispositif de médiation de rue composé d’adultes originaires des cités HLM qui composent la ville.
Dispositif d'insertion par le maraîchage biologique. Épreuve d'une nouvelle gouvernementalité
Authors: Muramatsu Kenjiro 
Published: April 2011

Résumé Le travail d’insertion socio-professionnelle montre un mode d’exercice caractéristique de la gouvernementalité néolibérale et contemporaine. Le cas d’un dispositif d’insertion par le maraîchage biologique en Belgique, étudié dans ce texte, vise par sa forme une « production du corps régulateur » combinant concrètement les enjeux de régulation de l’économie et de contrôle de l’individu. Ainsi, loin d’être un simple effet illusoire d’une idéologie, son lieu d’opération constitue un lieu central de légitimation de l’action du « social » inscrit dans une politique de l’État social actif. Suite à une mise en évidence d’éléments de cadrage discursif et normatif de l’action, nous examinerons des effets de ce cadrage à partir de la forme d’engagement des opérateurs dans leur espace d’activités concret. Le régime d’action compassionnel de ces travailleurs, combiné à celui civique, se trouve au cœur de l’épreuve politique et pratique de cette nouvelle gouvernementalité.
3.3 AERIAL RELEASE SYSTEM FOR TRICHOGRAMMA MINUTUM RILEY IN PLANTATION FORESTS
Authors: Hope C.A. , Nicholson S.A. , Churcher J.J. 
Published: April 2011

AbstractAn aerial dispersal system was developed for inundative release of insect eggs, Anagasta kuehniella (Zeller) and Sitotroga cerealella (Olivier), parasitized by Trichogramma minutum Riley. The equipment was used successfully in field tests over a 4-year period (1982–1985) in a coniferous plantation forest near Hearst, Ont. The release equipment consisted of simple electrical components, mechanical components from a small grain planter, and a centrifugal slinger used for aerial seeding of jack pine. The equipment was mounted on a Bell® 47 helicopter, flown at about 25 m above the ground. A swath width of 15 m was attained using this system. Application rates ranged from 12.3 to 263.0 g ♀ ♀ parasitoids per hectare (0.6–25 × 106 ♀ ♀ parasitoids per hectare) during the 4 years of tests.
3.4 DEPOSIT AND DISTRIBUTION OF TRICHOGRAMMA MINUTUM RILEY FOLLOWING AERIAL RELEASE
Authors: Smith S.M. , Wallace D.R. , Laing J.E. , Eden G.M. , Nicholson S.A. 
Published: April 2011

AbstractThe egg parasitoid, Trichogramma minutum Riley, was distributed by helicopter over forest stands near Hearst, Ont., to control the spruce budworm, Choristoneura fumiferana (Clemens). The quality of the parasitoids in terms of emergence, proportion of females, longevity, and fecundity was not affected by aerial release. Based on monitoring with deposit cards, at 10 m above ground, the helicopter had an effective swath width of ca. 10 m. Aerial release provided an uneven distribution of deposit on 1.0-ha plots, with significantly less parasitized material reaching the outer edges of each plot than in the centre; parasitism of sentinel egg masses within the plots corresponded to the distribution of deposit. Over 50% of the released material was deposited on the ground. Drift outside the plots was generally less than 25 m, never exceeding 100 m. The extent of drift was dependent on the application technique, and to a lesser extent, wind direction. Deposit cards provided an extensive rather than an intensive sampling method for monitoring the aerial distribution of T. minutum.
A REVISION OF THE NEOTROPICAL GENUS ONTHERUS ERICHSON (COLEOPTERA: SCARABAEIDAE, SCARABAEINAE)
Authors: Génier François 
Published: April 2011

AbstractThe species of the genus Ontherus, endemic to Latin America, are revised. A key in English and Spanish for the identification of adults of the 58 recognized species is provided. Three subgenera are recognized (Caelontherus nov., Planontherus nov. and Ontherus s.str.). The following 29 species are described as new: O. hadros, O. magnus, O. gilli, O. ashei, O. politus, O. sanctaemartae, O. tenuistriatus, O. obliquus, O. howdeni, O. diabolicus, O. pilatus, O. sextuberculatus, O. lunicollis, O. monilistriatus, O. pseudodidymus, O. rectus, O. pubens, O. ulcopygus, O. cambeforti, O. raptor, O. planus, O. edentulus, O. rectangulidens, O. lobifrons, O. androgynus, O. amplector, O. atlantidis, O. insolitus, O. stridulator. The following new synonymies are proposed (the first specific name being valid): O. kirschii Harold = O. elongatus Waterhouse; O. alexis (Blanchard) = O. didymus Erichson = O. glaucinus Erichson = O. nevinsoni Waterhouse; O. incisus (Kirsch) = O. thoracicus Waterhouse; O. azteca Harold = O. villosus Luederwaldt = O. strius Howden and Young; O. cephalotes Harold = O. quadrituberculatus Luederwaldt. The variety O. zikani var. carinicollis Luederwaldt is now recognized as a valid species. Species are arranged into groups according to their phylogenetic relationship, with a brief diagnosis given for each of the 11 groups of species. The following information is given for each species, when appropriate: detailed literature review, synonymy, description or redescription, illustration of important morphological characters, data of material studied, and geographic distribution.
Runx3 Is Required for Full Activation of Regulatory T Cells To Prevent Colitis-Associated Tumor Formation
Authors: Sugai Manabu , Aoki Koji , Osato Motomi , Nambu Yukiko , Ito Kosei , Taketo Makoto M. , Shimizu Akira 
Published: April 2011

Abstract
Inflammation is increasingly recognized as an essential component of tumorigenesis, which is promoted and suppressed by various T cell subsets acting in different ways. It was shown previously in Runx3-deficient mice that differentiation of CD8 T and NK cells is perturbed. In this study, we show that Runx3 is also required for proper differentiation and function of regulatory T cells. In Runx3-deficient mice, T cells were unable to inhibit inflammation and to suppress tumor development. As expected, recombination activating gene 2-deficient mice bearing Runx3-deficient lymphocytes spontaneously developed colon tumors. However, tumor formation was completely blocked by transfer of either regulatory T cells or CD8 T cells derived from wild-type mice to mutant mice or by housing mutant mice in a specific pathogen-free condition. These results indicate that Runx3-deficient lymphocytes and microorganisms act together to induce inflammation and consequently induce the development of colon tumors.
Posttranscriptional Regulation of IL-23 Expression by IFN-γ through Tristetraprolin
Authors: Qian Xuesong , Ning Huan , Zhang Jidong , Hoft Daniel F. , Stumpo Deborah J. , Blackshear Perry J. , Liu Jianguo 
Published: April 2011

Abstract
IL-23 plays an essential role in maintenance of IL-17–producing Th17 cells that are involved in the pathogenesis of several autoimmune diseases. Regulation of Th17 cells is tightly controlled by multiple factors such as IL-27 and IFN-γ. However, the detailed mechanisms responsible for IFN-γ–mediated Th17 cell inhibition are still largely unknown. In this study, we demonstrate that IFN-γ differentially regulates IL-12 and IL-23 production in both dendritic cells and macrophages. IFN-γ suppresses IL-23 expression by selectively targeting p19 mRNA stability through its 3′-untranslated region (3′UTR). Furthermore, IFN-γ enhances LPS-induced tristetraprolin (TTP) mRNA expression and protein production. Overexpression of TTP suppresses IL-23 p19 mRNA expression and p19 3′UTR-dependent luciferase activity. Additionally, deletion of TTP completely abolishes IFN-γ–mediated p19 mRNA degradation. We further demonstrate that IFN-γ suppresses LPS-induced p38 phosphorylation, and blockade of p38 MAPK signaling pathway with SB203580 inhibits IFN-γ– and LPS-induced p19 mRNA expression, whereas overexpression of p38 increases p19 mRNA expression via reducing TTP binding to the p19 3′UTR. Finally, inhibition of p38 phosphorylation by IFN-γ leads to TTP dephosphorylation that could result in stronger binding of the TTP to the adenosine/uridine-rich elements in the p19 3′UTR and p19 mRNA degradation. In summary, our results reveal a direct link among TTP, IFN-γ, and IL-23, indicating that IFN-γ–mediated Th17 cell suppression might act through TTP by increasing p19 mRNA degradation and therefore IL-23 inhibition.
IL-33 Shifts the Balance from Osteoclast to Alternatively Activated Macrophage Differentiation and Protects from TNF-α–Mediated Bone Loss
Authors: Zaiss Mario M. , Kurowska-Stolarska Mariola , Böhm Christina , Gary Regina , Scholtysek Carina , Stolarski Bartosz , Reilly James , Kerr Shauna , Millar Neal L. , Kamradt Thomas , McInnes Iain B. , Fallon Padraic G. , David Jean-Pierre , Liew Foo Y. , Schett Georg 
Published: April 2011

Abstract
IL-33 is a new member of the IL-1 family, which plays a crucial role in inflammatory response, enhancing the differentiation of dendritic cells and alternatively activated macrophages (AAM). Based on the evidence of IL-33 expression in bone, we hypothesized that IL-33 may shift the balance from osteoclast to AAM differentiation and protect from inflammatory bone loss. Using transgenic mice overexpressing human TNF, which develop spontaneous joint inflammation and cartilage destruction, we show that administration of IL-33 or an IL-33R (ST2L) agonistic Ab inhibited cartilage destruction, systemic bone loss, and osteoclast differentiation. Reconstitution of irradiated hTNFtg mice with ST2−/− bone marrow led to more bone loss compared with the chimeras with ST2+/+ bone marrow, demonstrating an important endogenous role of the IL-33/ST2L pathway in bone turnover. The protective effect of IL-33 on bone was accompanied by a significant increase of antiosteoclastogenic cytokines (GM-CSF, IL-4, and IFN-γ) in the serum. In vitro IL-33 directly inhibits mouse and human M-CSF/receptor activator for NF-κB ligand-driven osteoclast differentiation. IL-33 acts directly on murine osteoclast precursors, shifting their differentiation toward CD206+ AAMs via GM-CSF in an autocrine fashion. Thus, we show in this study that IL-33 is an important bone-protecting cytokine and may be of therapeutic benefit in treating bone resorption.