bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrauterine Exposure to Maternal Diabetes Is Associated With Higher Adiposity and Insulin Resistance and Clustering of Cardiovascular Risk Markers in Indian Children
Authors: Krishnaveni Ghattu V. , Veena Sargoor R. , Hill Jacqueline C. , Kehoe Sarah , Karat Samuel C. , Fall Caroline H.D.
Published: November 2009

OBJECTIVE

To test the hypothesis that maternal gestational diabetes increases cardiovascular risk markers in Indian children.

RESEARCH DESIGN AND METHODS

Anthropometry, blood pressure, and glucose/insulin concentrations were measured in 514 children at 5 and 9.5 years of age (35 offspring of diabetic mothers [ODMs], 39 offspring of diabetic fathers [ODFs]). Children of nondiabetic parents were control subjects.

RESULTS

At age 9.5 years, female ODMs had larger skinfolds (P < 0.001), higher glucose (30 min) and insulin concentrations, and higher homeostasis model assessment (HOMA) of insulin resistance and systolic blood pressure (P < 0.05) than control subjects. Male ODMs had higher HOMA (P < 0.01). Associations were stronger than at age 5 years. Female ODFs had larger skinfolds and male ODFs had higher HOMA (P < 0.05) than control subjects; associations were weaker than for ODMs. Associations between outcomes in control subjects and parental BMI, glucose, and insulin concentrations were similar for mothers and fathers.

CONCLUSIONS

The intrauterine environment experienced by ODMs increases diabetes and cardiovascular risk over genetic factors; the effects strengthen during childhood.
Decaffeinated Coffee and Glucose Metabolism in Young Men
Authors: Greenberg James A. , Owen David R. , Geliebter Allan
Published: November 2009

OBJECTIVE

The epidemiological association between coffee drinking and decreased risk of type 2 diabetes is strong. However, caffeinated coffee acutely impairs glucose metabolism. We assessed acute effects of decaffeinated coffee on glucose and insulin levels.

RESEARCH DESIGN AND METHODS

This was a randomized, cross-over, placebo-controlled trial of the effects of decaffeinated coffee, caffeinated coffee, and caffeine on glucose, insulin, and glucose-dependent insulinotropic polypeptide (GIP) levels during a 2-h oral glucose tolerance test (OGTT) in 11 young men.

RESULTS

Within the first hour of the OGTT, glucose and insulin were higher for decaffeinated coffee than for placebo (P < 0.05). During the whole OGTT, decaffeinated coffee yielded higher insulin than placebo and lower glucose and a higher insulin sensitivity index than caffeine. Changes in GIP could not explain any beverage effects on glucose and insulin.

CONCLUSIONS

Some types of decaffeinated coffee may acutely impair glucose metabolism but less than caffeine.
Aspirin Is Associated With Reduced Cardiovascular and All-Cause Mortality in Type 2 Diabetes in a Primary Prevention Setting
Authors: Ong Greg , Davis Timothy M.E. , Davis Wendy A.
Published: November 2009

OBJECTIVE

To determine whether regular aspirin use (≥75 mg/day) is independently associated with cardiovascular disease (CVD) and all-cause mortality in community-based patients with type 2 diabetes and no history of CVD.

RESEARCH DESIGN AND METHODS

Of the type 2 diabetic patients recruited to the longitudinal observational Fremantle Diabetes Study, 651 (50.3%) with no prior CVD history at entry between 1993 and 1996 were followed until death or the end of June 2007, representing a total of 7,537 patient-years (mean ± SD 11.6 ± 2.9 years). Cox proportional hazards modeling was used to determine independent baseline predictors of CVD and all-cause mortality including regular aspirin use.

RESULTS

There were 160 deaths (24.6%) during follow-up, with 70 (43.8%) due to CVD. In Kaplan-Meier survival analysis, there was no difference in either CVD or all-cause mortality in aspirin users versus nonusers (P = 0.52 and 0.94, respectively, by log-rank test). After adjustment for significant variables in the most parsimonious Cox models, regular aspirin use at baseline independently predicted reduced CVD and all-cause mortality (hazard ratio [HR] 0.30 [95% CI 0.09–0.95] and 0.53 [0.28–0.98[, respectively; P ≤ 0.044). In subgroup analyses, aspirin use was independently associated with reduced all-cause mortality in those aged ≥65 years and men.

CONCLUSIONS

Regular low-dose aspirin may reduce all-cause and CVD mortality in a primary prevention setting in type 2 diabetes. All-cause mortality reductions are greatest in men and in those aged ≥65 years. The present observational data support recommendations that aspirin should be used in primary CVD prevention in all but the lowest risk patients.
Mine Spoil Prairies Expand Critical Habitat for Endangered and Threatened Amphibian and Reptile Species
Authors: Lannoo Michael  J. , Kinney Vanessa  C. , Heemeyer Jennifer L. , Engbrecht Nathan  J. , Gallant Alisa  L. , Klaver Robert  W.
Published: November 2009

Coal extraction has been occurring in the Midwestern United States for over a century. Despite the pre-mining history of the landscape as woodlands, spent surface coalfields are often reclaimed to grasslands. We assessed amphibian and reptile species on a large tract of coal spoil prairie and found 13 species of amphibians (nine frog and four salamander species) and 19 species of reptiles (one lizard, five turtle, and 13 snake species). Two state-endangered and three state species of special concern were documented. The amphibian diversity at our study site was comparable to the diversity found at a large restored prairie situated 175 km north, within the historic prairie peninsula.
Variation of Natural Streamflow since 1470 in the Middle Yellow River, China
Authors: Miao Chi-Yuan , Ni Jin-Ren
Published: November 2009

Nowadays, as the available water resources throughout the World are becoming depleted, in order to manage and plan water resource better, more and more attention is being paid into the fluctuating characteristics of water discharges. However, the preexisting research was mainly focused on the last half century. In this paper, the natural streamflow observed since 1470 at the Sanmenxia station in the middle Yellow River basin was collected, and the methods of variation coefficient, moving average, Mann-Kendall test and wavelet transform were applied to analyze the dynamic characteristics of the streamflow. The results showed that, (1) between 1470 and 2007, the natural streamflow changed 200–919 ×108 m3, and water discharge varied moderately; (2) in the middle Yellow River basin, it appears that the most severe and most persistent droughts during circa 1868–1990, the periods of 1470s–1490s, 1920s–1930s and 1990s–2000s also presented the condition of sustained low flows; (3) the natural streamflow series shows increasing and decreasing trends during the periods of 1470–1880 and 1881–2007, respectively, but both trends are not significant at >95% confidence; in addition, it is still found the streamflow series shows abrupt changes circa 1845, 1935 and 1960, respectively; (4) within a 250-year scale, there are circa 11, 26, 67 and 120-year periods for natural streamflow at the Sanmenxia station, and the periodicity of the 120-year one is the strongest. The dynamic characteristics of natural streamflow is the comprehensive result by many influencing factors, such as precipitation, temperature, El Niño-Southern Oscillation, sunspots, human activity etc.
Detection of Cypress Canopies in the Florida Panhandle Using Subpixel Analysis and GIS
Authors: Wang Jialing , Lang Paul  A.
Published: November 2009

In this study, multitemporal subpixel analysis was used to identify cypress canopies from Landsat 7 ETM+ imagery. One spring and one fall image were selected for each of two sites, an eastern one centered on Tallahassee, FL and a western one centered on Panama City, FL. Signatures derived from the two eastern images were applied on the two western images that served as the control images for accuracy assessment. Results indicated that multitemporal subpixel analysis greatly improved the classification accuracy and signatures developed from one scene could be used to the subpixel classification of another scene with caution.
Investigating the Impacts of Landuse-landcover (LULC) Change in the Pearl River Delta Region on Water Quality in the Pearl River Estuary and Hong Kong’s Coast
Authors: Zhang Yuanzhi , Wang Yufei , Wang Yunpeng , Xi Hongyan
Published: November 2009

Water quality information in the coastal region of Hong Kong and the Pearl River Estuary (PRE) is of great concern to the local community. Due to great landuse-landcover (LULC) changes with rapid industrialization and urbanization in the Pearl River Delta (PRD) region, water quality in the PRE has worsened during the last 20 years. Frequent red tide and harmful algal blooms have occurred in the estuary and its adjacent coastal waters since the 1980s and have caused important economic losses, also possibly threatening to the coastal environment, fishery, and public health in Hong Kong. In addition, recent literature shows that water nutrients in Victoria Harbor of Hong Kong have been proven to be strongly influenced by both the Pearl River and sewage effluent in the wet season (May to September), but it is still unclear how the PRE diluted water intrudes into Victoria Harbor. Due to the cloudy and rainy conditions in the wet season in Hong Kong, ASAR images will be used to monitor the PRE river plumes and track the intruding routes of PRE water nutrients. In this paper, we first review LULC change in the PRD and then show our preliminary results to analyze water quality spatial and temporal information from remote observations with different sensors in the coastal region and estuary. The study will also emphasizes on time series of analysis of LULC trends related to annual sediment yields and critical source areas of erosion for the PRD region since the 1980s.
Ferric Reducing Antioxidant Power and Square Wave Voltammetry for Assay of Low Molecular Weight Antioxidants in Blood Plasma: Performance and Comparison of Methods
Authors: Pohanka Miroslav , Bandouchova Hana , Sobotka Jakub , Sedlackova Jana , Soukupova Ivana , Pikula Jiri
Published: November 2009

The purpose of the present study was to employ two methods—square wave voltammetry (SWV) performed on screen printed sensors and ferric reducing antioxidant power (FRAP)—as suitable tools for the assay of low-molecular-weight antioxidants (LMWAs). LMWAs were assayed by both methods and the resulting data were statistically compared. Plasma samples from five Cinereous vultures accidentally intoxicated with lead were used to represent real biological matrices with different levels of LMWAs. Blood was collected from the birds prior to and one month after treatment with Ca-EDTA. SWV resulted in two peaks. The first peak, with the potential value of 466 ± 15 mV, was recognized as ascorbic and uric acids, while the second one (743 ± 30 mV) represented glutathione, tocopherol, ascorbic acid and in a minor effect by uric acid, too. Contribution of individual antioxidants was recognized by separate assays of LMWA standards. Correlation between peaks 1 and 2 as well as the sum of the two peaks and FRAP was analysed. While peak 1 and the sum of peaks were in close correlation to FRAP results (correlation coefficient of 0.97), the relation between peak 2 and FRAP may be expressed using a correlation coefficient of 0.64. The determination of thiols by the Ellman assay confirmed the accuracy of SWV. Levels of glutathione and other similar structures were stable in the chosen model and it may be concluded that SWV is appropriate for assay of LMWAs in plasma samples. The methods employed in the study were advantageous in minimal sample volume consumption and fast acquisition of results.
An expedient and new synthesis of pyrrolo[1,2-b]pyridazine derivatives
Authors: Sagyam Rajeshwar Reddy , Buchikonda Ravinder , Pitta Jaya Prakash , Vurimidi Himabindu , Padi Pratap Reddy , Ghanta Mahesh Reddy
Published: November 2009

The reaction of 2-[2-(4-fluorophenyl)-2-oxo-1-phenylethyl]-4-methyl-3-oxo-pentanoic acid phenylamide with tertiary butyl carbazate and subsequent condensation of the resulting carbamate derivative with a chalcone provided a facile new approach to pyrrolo[1,2-b]pyridazine derivatives.
Initial evaluation of the Roche COBAS TaqMan HIV-1 v2.0 assay for determining viral load in HIV-infected individuals
Authors: Taylor Ninon , Schmid Ilse , Egle Alexander , Greil Richard , Patsch Wolfgang , Oberkofer Hannes
Published: November 2009

Background

HIV type-1 (HIV-1) genetic diversity poses a challenge for the development of diagnostic tests based on nucleic acid amplification, which can be overcome, at least in part, by targeting multiple genomic regions. The new Roche Diagnostics COBAS TaqMan (CTM) HIV-1 v2.0 assay uses multiplex real-time PCR detection of sequences in the long terminal repeat and gag regions within the HIV-1 genome.

Methods

We conducted initial comparative testing of HIV-1 viral load values in plasma samples from HIV-1-infected individuals using the Abbott RealTime HIV-1 (Abbott RT HIV-1), and the Roche CTM v1.0 and CTM v2.0 real-time PCR amplification systems, with a particular focus on patients previously undetectable or underestimated with the CTM v1.0 assay.

Results

The new Roche CTM v2.0 assay showed excellent agreement with the other two assays over a wide dynamic range ( r=0.9685). The assay also allowed accurate determination of viral load levels in individuals infected with HIV-1 isolates that were found falsely negative or underestimated with the Roche CTM v1.0 assay because of mutations within the gag region.

Conclusions

The reliability and accuracy of the CTM v2.0 assay is similar to the Abbott RT HIV-1 assay. The implementation of a multiplex real-time PCR approach in the CTM v2.0 is a significant improvement in viral load testing in comparison with the CTM v1.0 assay.
Agreement Between Quantiferon-TB Gold Test and Tuberculin Skin Test in the Identification of Latent Tuberculosis Infection in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis
Authors: INANC NEVSUN , AYDIN SIBEL ZEHRA , KARAKURT SAIT , ATAGUNDUZ PAMIR , YAVUZ SULE , DIRESKENELI HANER
Published: November 2009

Objective.

To compare the Quantiferon-TB Gold test (QTF-G) with the tuberculin skin test (TST) for the detection of latent tuberculosis infection (LTBI) among patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS), with reevaluation of the patients treated with tumor necrosis factor-α (TNF-α) antagonists in the followup.

Methods.

The study involved 140 consecutive patients, 82 with RA and 58 with AS. Thirty patients were evaluated with QTF-G for detection of LTBI before and after 6 months of TNF-α antagonist treatment. QTF-G was also performed on 49 healthy controls. QTF-G results were recorded as positive, negative, or indeterminate. A positive TST was defined as ≥ 5 mm for RA and AS.

Results.

The percentages of positive QTF-G were comparable in RA and AS (37% vs 32%). The rate of positive QTF-G in healthy controls (29%) was also similar to RA and AS. In contrast to QTF-G results, a high rate of TST positivity was observed in AS compared to RA (82% vs 55%; p = 0.02). The total agreement between QTF-G and TST was observed to be 61% (κ = 0.29) in the whole group, 70% (κ = 0.42) in RA, and 49% (κ = 0.14) in AS. After 6 months of treatment with TNF-α antagonists, a high rate of QTF-G change was observed in patients with indeterminate results (23% vs 3%; p = 0.03).

Conclusion.

The comparable prevalence of LTBI among the study groups according to QTF-G supports the view that QTF-G is less susceptible to external factors than TST. Sequential testing for QTF-G in patients with indeterminate or negative results may also be helpful in discriminating LTBI better.
Association of Interleukin 23 Receptor Polymorphisms with Anti-Topoisomerase-I Positivity and Pulmonary Hypertension in Systemic Sclerosis
Authors: AGARWAL SANDEEP K. , GOURH PRAVITT , SHETE SANJAY , PAZ GENE , DIVECHA DIPAL , REVEILLE JOHN D. , ASSASSI SHERVIN , TAN FILEMON K. , MAYES MAUREEN D. , ARNETT FRANK C.
Published: November 2009

Objective.

IL23Rhas been identified as a susceptibility gene for development of multiple autoimmune diseases. We investigated the possible association ofIL23Rwith systemic sclerosis (SSc), an autoimmune disease that leads to the development of cutaneous and visceral fibrosis.

Methods.

We tested 9 single-nucleotide polymorphisms (SNP) inIL23Rfor association with SSc in a cohort of 1402 SSc cases and 1038 controls.IL23RSNP tested were previously identified as SNP showing associations with inflammatory bowel disease.

Results.

Case-control comparisons revealed no statistically significant differences between patients and healthy controls with any of theIL23Rpolymorphisms. Analyses of subsets of SSc patients showed that rs11209026 (Arg381Gln variant) was associated with anti-topoisomerase I antibody (ATA)-positive SSc (p = 0.001)) and rs11465804 SNP was associated with diffuse and ATA-positive SSc (p = 0.0001, p = 0.0026, respectively). These associations remained significant after accounting for multiple comparisons using the false discovery rate method. Wild-type genotype at both rs11209026 and rs11465804 showed significant protection against the presence of pulmonary hypertension (PHT). (p = 3×10−5, p = 1×10−5, respectively).

Conclusion.

Polymorphisms inIL23Rare associated with susceptibility to ATA-positive SSc and protective against development of PHT in patients with SSc.
G Protein-Coupled Receptor 43 Is Essential for Neutrophil Recruitment during Intestinal Inflammation
Authors: Sina Christian , Gavrilova Olga , Förster Matti , Till Andreas , Derer Stefanie , Hildebrand Friederike , Raabe Björn , Chalaris Athena , Scheller Jürgen , Rehmann Ateequr , Franke Andre , Ott Stephan , Häsler Robert , Nikolaus Susanna , Fölsch Ulrich R. , Rose-John Stefan , Jiang Hui-Ping , Li Jun , Schreiber Stefan , Rosenstiel Philip
Published: November 2009

Molecular danger signals attract neutrophilic granulocytes (polymorphonuclear leukocytes (PMNs)) to sites of infection. The G protein-coupled receptor (GPR) 43 recognizes propionate and butyrate and is abundantly expressed on PMNs. The functional role of GPR43 activation for in vivo orchestration of immune response is unclear. We examined dextrane sodium sulfate (DSS)-induced acute and chronic intestinal inflammatory response in wild-type and Gpr43-deficient mice. The severity of colonic inflammation was assessed by clinical signs, histological scoring, and cytokine production. Chemotaxis of wild-type and Gpr43-deficient PMNs was assessed through transwell cell chemotactic assay. A reduced invasion of PMNs and increased mortality due to septic complications were observed in acute DSS colitis. In chronic DSS colitis, Gpr43−/− animals showed diminished PMN intestinal migration, but protection against inflammatory tissue destruction. No significant difference in PMN migration and cytokine secretion was detected in a sterile inflammatory model. Ex vivo experiments show that GPR43-induced migration is dependent on activation of the protein kinase p38α, and that this signal acts in cooperation with the chemotactic cytokine keratinocyte chemoattractant. Interestingly, shedding of L-selectin in response to propionate and butyrate was compromised in Gpr43−/− mice. These results indicate a critical role for GPR43-mediated recruitment of PMNs in containing intestinal bacterial translocation, yet also emphasize the bipotential role of PMNs in mediating tissue destruction in chronic intestinal inflammation.
Tc17 CD8 T Cells: Functional Plasticity and Subset Diversity
Authors: Yen Hung-Rong , Harris Timothy J. , Wada Satoshi , Grosso Joseph F. , Getnet Derese , Goldberg Monica V. , Liang Kai-Li , Bruno Tullia C. , Pyle Kristin J. , Chan Siaw-Li , Anders Robert A. , Trimble Cornelia L. , Adler Adam J. , Lin Tzou-Yien , Pardoll Drew M. , Huang Ching-Tai , Drake Charles G.
Published: November 2009

IL-17-secreting CD8 T cells (Tc17) have been described in several settings, but little is known regarding their functional characteristics. While Tc1 cells produced IFN-γ and efficiently killed targets, Tc17 cells lacked lytic function in vitro. Interestingly, the small numbers of IFN-γ-positive or IL-17/IFN-γ-double-positive cells generated under Tc17 conditions also lacked lytic activity and expressed a similar pattern of cell surface proteins to IL-17-producing cells. As is the case for Th17 (CD4) cells, STAT3 is important for Tc17 polarization, both in vitro and in vivo. Adoptive transfer of highly purified, Ag-specific IL-17-secreting Tc17 cells into Ag-bearing hosts resulted in near complete conversion to an IFN-γ-secreting phenotype and substantial pulmonary pathology, demonstrating functional plasticity. Tc17 also accumulated to a greater extent than did Tc1 cells, suggesting that adoptive transfer of CD8 T cells cultured in Tc17 conditions may have therapeutic potential for diseases in which IFN-γ-producing cells are desired.
Early Response of Mucosal Epithelial Cells duringToxoplasma gondiiInfection
Authors: Ju Chia-Hsin , Chockalingam Annapoorani , Leifer Cynthia A.
Published: November 2009

The innate immune response of mucosal epithelial cells during pathogen invasion plays a central role in immune regulation in the gut. Toxoplasma gondii is a protozoan intracellular parasite that is usually transmitted through oral infection. Although much of the information on immunity to T. gondii has come from i.p. infection models, more recent studies have revealed the importance of studying immunity following infection through the natural peroral route. Oral infection studies have identified many of the key players in the intestinal response; however, they have relied on responses detected days to weeks following infection. Much less is known about how the gut epithelial layer senses and reacts during initial contact with the pathogen. Given the importance of epithelial cells during pathogen invasion, this study uses an in vitro approach to isolate the key players and examine the early response of intestinal epithelial cells during infection by T. gondii. We show that human intestinal epithelial cells infected with T. gondii elicit rapid MAPK phosphorylation, NF-κB nuclear translocation, and secretion of IL-8. Both ERK1/2 activation and IL-8 secretion responses were shown to be MyD88 dependent and TLR2 was identified to be involved in the recognition of the parasite regardless of the parasite genotype. Furthermore, we were able to identify additional T. gondii-regulated genes in the infected cells using a pathway-focused array. Together, our findings suggest that intestinal epithelial cells were able to recognize T. gondii during infection, and the outcome is important for modulating intestinal immune responses.
Hematopoietic Lineage Cell-Specific Protein 1 Is Recruited to the Immunological Synapse by IL-2-Inducible T Cell Kinase and Regulates Phospholipase Cγ1 Microcluster Dynamics during T Cell Spreading
Authors: Carrizosa Esteban , Gomez Timothy S. , Labno Christine M. , Klos Dehring Deborah A. , Liu Xiaohong , Freedman Bruce D. , Billadeau Daniel D. , Burkhardt Janis K.
Published: November 2009

Productive T cell activation requires efficient reorganization of the actin cytoskeleton. We showed previously that the actin-regulatory protein, hematopoietic lineage cell-specific protein 1 (HS1), is required for the stabilization of F-actin and Vav1 at the immunological synapse and for efficient calcium responses. The Tec family kinase IL-2-inducible T cell kinase (Itk) regulates similar aspects of T cell activation, suggesting that these proteins act in the same pathway. Using video microscopy, we show that T cells lacking Itk or HS1 exhibited similar defects in actin responses, extending unstable lamellipodial protrusions upon TCR stimulation. HS1 and Itk could be coimmunoprecipitated from T cell lysates, and GST-pulldown studies showed that Itk’s Src homology 2 domain binds directly to two phosphotyrosines in HS1. In the absence of Itk, or in T cells overexpressing an Itk Src homology 2 domain mutant, HS1 failed to localize to the immunological synapse, indicating that Itk serves to recruit HS1 to sites of TCR engagement. Because Itk is required for phospholipase C (PLC)γ1 phosphorylation and calcium store release, we examined the calcium signaling pathway in HS1−/− T cells in greater detail. In response to TCR engagement, T cells lacking HS1 exhibited diminished calcium store release, but TCR-dependent PLCγ1 phosphorylation was intact, indicating that HS1’s role in calcium signaling is distinct from that of Itk. HS1-deficient T cells exhibited defective cytoskeletal association of PLCγ1 and altered formation of PLCγ1 microclusters. We conclude that HS1 functions as an effector of Itk in the T cell actin-regulatory pathway, and directs the spatial organization of PLCγ1 signaling complexes.
Dominant Expression of the Inhibitory FcγRIIB Prevents Antigen Presentation by Murine Plasmacytoid Dendritic Cells
Authors: Flores Marcella , Desai Dharmesh D. , Downie Matthew , Liang Bitao , Reilly Michael P. , McKenzie Steven E. , Clynes Raphael
Published: November 2009

Plasmacytoid dendritic cells (pDCs) are key regulators of the innate immune response, yet their direct role as APCs in the adaptive immune response is unclear. We found that unlike conventional DCs, immune complex (IC) exposed murine pDCs neither up-regulated costimulatory molecules nor activated Ag-specific CD4+ and CD8+ T cells. The inability of murine pDCs to promote T cell activation was due to inefficient proteolytic processing of internalized ICs. This defect in the IC processing capacity of pDCs results from a lack of activating FcγR expression (FcγRI, III, IV) and the dominant expression of the inhibitory receptor FcγRIIB. Consistent with this idea, transgenic expression of the activating human FcγRIIA gene, not present in the mouse genome, recapitulated the human situation and rescued IC antigenic presentation capacity by murine pDCs. The selective expression of FcγRIIB by murine pDCs was not strain dependent and was maintained even following stimulation with TLR ligands and inflammatory cytokines. The unexpected difference between the mouse and human in the expression of activating/inhibitory FcγRs has implications for the role of pDCs in Ab-modulated autoimmunity and anti-viral immunity.
β Cell-Specific CD4+ T Cell Clonotypes in Peripheral Blood and the Pancreatic Islets Are Distinct
Authors: Li Li , He Qiuming , Garland Alaina , Yi Zuoan , Aybar Lydia T. , Kepler Thomas B. , Frelinger Jeffrey A. , Wang Bo , Tisch Roland
Published: November 2009

Type 1 diabetes is an autoimmune disease mediated by β cell-specific CD4+ and CD8+ T cells. Tracking β cell-specific T cells is one approach to monitor the diabetogenic response in at risk or diabetic individuals. Such analyses, however, are limited to PBL because T cells infiltrating the pancreatic islets are normally inaccessible. A key issue is whether peripheral β cell-specific T cells accurately reflect those cells infiltrating the target tissue. We investigated the properties of CD4+ T cells specific for a mimetic epitope recognized by the BDC2.5 clonotypic TCR in NOD mice. Soluble IAg7-Ig (sIAg7-Ig) multimer complexes covalently linked to a mimetic BDC peptide (sIAg7-mBDC) were used to identify or isolate CD4+ T cells from PBL and the islets of NOD mice. A temporal increase in sIAg7-mBDC binding (g7-mBDC+) T cells corresponding with the progression of β cell autoimmunity was detected in both PBL and islets in NOD female mice. In contrast to T cells in PBL, however, the majority of islet g7-mBDC+ T cells exhibited a type 1 phenotype, and mediated diabetes upon transfer into NOD.scid recipients. TCR-β and CDR-β gene usage of single islet-infiltrating g7-mBDC+ CD4+ T cells from individual NOD mice showed a restricted repertoire dominated by one or two clones typically expressing TCR β-chain variable TRBV-15. In contrast, a distinct and diverse TCR repertoire was detected for PBL-derived g7-mBDC+ T cells. These results demonstrate that PBL and islet CD4+ T cells specific for a given β cell epitope can differ regarding pathogenicity and TCR repertoire.
Role of T Cell TGFβ Signaling and IL-17 in Allograft Acceptance and Fibrosis Associated with Chronic Rejection
Authors: Faust Susan M. , Lu Guanyi , Marini Bernard L. , Zou Weiping , Gordon David , Iwakura Yoichiro , Laouar Yasmina , Bishop D. Keith
Published: November 2009

Chronic allograft rejection (CR) is the main barrier to long-term transplant survival. CR is a progressive disease defined by interstitial fibrosis, vascular neointimal development, and graft dysfunction. The underlying mechanisms responsible for CR remain poorly defined. TGFβ has been implicated in promoting fibrotic diseases including CR, but is beneficial in the transplant setting due to its immunosuppressive activity. To assess the requirement for T cell TGFβ signaling in allograft acceptance and the progression of CR, we used mice with abrogated T cell TGFβ signaling as allograft recipients. We compared responses from recipients that were transiently depleted of CD4+ cells (that develop CR and express intragraft TGFβ) with responses from mice that received anti-CD40L mAb therapy (that do not develop CR and do not express intragraft TGFβ). Allograft acceptance and suppression of graft-reactive T and B cells were independent of T cell TGFβ signaling in mice treated with anti-CD40L mAb. In recipients transiently depleted of CD4+ T cells, T cell TGFβ signaling was required for the development of fibrosis associated with CR, long-term graft acceptance, and suppression of graft-reactive T and B cell responses. Furthermore, IL-17 was identified as a critical element in TGFβ-driven allograft fibrosis. Thus, IL-17 may provide a therapeutic target for preventing graft fibrosis, a measure of CR, while sparing the immunosuppressive activity of TGFβ.
Taking Advantage: High-Affinity B Cells in the Germinal Center Have Lower Death Rates, but Similar Rates of Division, Compared to Low-Affinity Cells
Authors: Anderson Shannon M. , Khalil Ashraf , Uduman Mohamed , Hershberg Uri , Louzoun Yoram , Haberman Ann M. , Kleinstein Steven H. , Shlomchik Mark J.
Published: November 2009

B lymphocytes producing high-affinity Abs are critical for protection from extracellular pathogens, such as bacteria and parasites. The process by which high-affinity B cells are selected during the immune response has never been elucidated. Although it has been shown that high-affinity cells directly outcompete low-affinity cells in the germinal center (GC), whether there are also intrinsic differences between these cells has not been addressed. It could be that higher affinity cells proliferate more rapidly or are more likely to enter cell cycle, thereby outgrowing lower affinity cells. Alternatively, higher affinity cells could be relatively more resistant to cell death in the GC. By comparing high- and low-affinity B cells for the same Ag, we show here that low-affinity cells have an intrinsically higher death rate than do cells of higher affinity, even in the absence of competition. This suggests that selection in the GC reaction is due at least in part to the control of survival of higher affinity B cells and not by a proliferative advantage conferred upon these cells compared with lower affinity B cells. Control over survival rather than proliferation of low- and high-affinity B cells in the GC allows greater diversity not only in the primary response but also in the memory response.
Atomic Structure and Electrical Properties of In(Te) Nanocontacts on CdZnTe(110) by Scanning Probe Microscopy
Authors: Cohen‐Taguri Gili , Sinkevich Ori , Levinshtein Mario , Ruzin Arie , Goldfarb Ilan
Published: November 2009

Understanding complex correlations between the macroscopic device performance (largely dependent on the character of the metal–semiconductor contact) and the metallurgy of contact formation on the atomic level in cadmium zinc telluride (CdZnTe) radiation detectors remains a formidable challenge. In this work, an effort towards bridging that macro–nano knowledge gap is made by conducting a series of controlled experiments aimed at correlating electrical properties of the In contact to n‐type CdZnTe(110) surface with the step‐by‐step process of contact formation. This can only be achieved by using high spatial resolution techniques, capable of conducting highly localized measurements on the nano‐ and sub‐nanoscale, such as scanning probe microscopy. Scanning tunneling microscopy is used in situ to monitor the behavior of various In atom coverages on an atomically flat and ordered CdZnTe surface under well‐controlled molecular beam epitaxial conditions in ultra‐high vacuum. Electrical derivatives of atomic force microscopy are used to measure the electrical contact properties, such as contact potential difference and spreading resistance in torsion resonance tunneling mode. It is concluded that In atoms preferentially reacted with Te atomic‐rows already at room temperature, forming nanometric patches of indium–telluride Schottky‐type contacts. The methods developed in this study, in terms of both nanocontact fabrication and characterization (especially in terms of electrical properties) should benefit basic and applied research of any metal–semiconductor system.
Multifunctional Fluorene‐Based Oligomers with Novel Spiro‐Annulated Triarylamine: Efficient, Stable Deep‐Blue Electroluminescence, Good Hole Injection, and Transporting Materials with Very High Tg
Authors: Jiang Zuoquan , Liu Zhongyin , Yang Chuluo , Zhong Cheng , Qin Jingui , Yu Gui , Liu Yunqi
Published: November 2009

A series of fluorene‐based oligomers with novel spiro‐annulated triarylamine structures, namely DFSTPA, TFSTPA, and TFSDTC, are synthesized by a Suzuki cross‐coupling reaction. The spiro‐configuration molecular structures lead to very high glass transition temperatures (197–253 °C) and weak intermolecular interactions, and consequently the structures retain good morphological stability and high fluorescence quantum efficiencies(0.69–0.98). This molecular design simultaneously solves the spectral stability problems and hole‐injection and transport issues for fluorene‐based blue‐light‐emitting materials. Simple double‐layer electroluminescence (EL) devices with a configuration of ITO/TFSTPA (device A) or TFSDTC (device B)/ TPBI/LiF/Al, where TFSTPA and TFSDTC serve as hole‐transporting blue‐light‐emitting materials, show a deep‐blue emission with a peak around 432 nm, and CIE coordinates of (0.17, 0.12) for TFSTPA and (0.16, 0.07) for TFSDTC, respectively, which are very close to the National Television System Committee (NTSC) standard for blue (0.15, 0.07). The maximum current efficiency/external quantum efficiencies are 1.63 cd A−1/1.6% for device A and 1.91 cd A−1/2.7% for device B, respectively. In addition, a device with the structure ITO/DFSTPA/Alq3/LiF/Al, where DFSTPA acts as both the hole‐injection and ‐transporting material, is shown to achieve a good performance, with a maximum luminance of 14 047 cd m−2, and a maximum current efficiency of 5.56 cd A−1. These values are significantly higher than those of devices based on commonly usedN,N′‐di(1‐naphthyl)‐N,N′‐diphenyl‐[1,1′‐biphenyl]‐4,4′‐diamine (NPB) as the hole‐transporting layer (11 738 cd m−2 and 3.97 cd A−1) under identical device conditions.
Spatial patterns and evolutionary processes in southern South America: A study of dental morphometric variation
Authors: Bernal Valeria , Perez S. Ivan , Gonzalez Paula N. , Sardi Marina L. , Pucciarelli Héctor M.
Published: November 2009

The purpose of this article is to examine the patterns of evolutionary relationships between human populations from the later Late Holocene (1,500–100 years BP) of southern South America on the basis of dental morphometric data. We tested the hypotheses that the variation observed in this region would be explained by the existence of populations with different phylogenetic origin or differential action of gene flow and genetic drift. In this study, we analyzed permanent teeth from 17 samples of male and female adult individuals from throughout southern South America. We measured mesiodistal and buccolingual diameters at the base of the crown, along the cement–enamel junction. The results of multiple regression analysis and a mantel correlogram indicate the existence of spatial structure in dental shape variation, as the D2 Mahalanobis distance between samples increases with increasing geographical distance between them. In addition, the correlation test results show a trend toward reduction of the internal variation of samples with increasing latitude. The detected pattern of dental variation agrees with the one expected as an outcome of founder serial effects related to an expansion of range during the initial occupation of southern South America. Am J Phys Anthropol, 2010. © 2009 Wiley‐Liss, Inc.
Influence of microwave heating on the kinetic of acrylic acid polymerization and crosslinking
Authors: Jovanovic Jelena , Adnadjevic Borivoj
Published: November 2009

Kinetics of isothermal formation of poly (acrylic acid) (PAA) hydrogels through polymerization of acrylic acid and crosslinking of the PAA formed in a conventionally heated reaction system and in a microwave heated reaction system were investigated. It was found that in the microwave heated system the reaction rate constant of PAA hydrogel formation significantly increased (from 32 to 43 times) when compared with the conventionally heated system. The isothermal kinetics of the PAA hydrogel formation during the microwave process could be described by the so‐called first‐order chemical reaction kinetics model. In contrast, the so‐called second‐order chemical reaction rate model could best describe the isothermal kinetics of the PAA hydrogel formation during the conventionally heated process. Also, in the microwave heated system, the reaction kinetics of the PAA hydrogel formation and its kinetic parameters changed, that is, the activation energy (Ea) decreased by about 19% and the pre‐exponential factor (lnA) decreased by 2.2 times. The decrease in activation energy, change in entropy of activation energy, and decrease in the pre‐exponential value of PAA hydrogel formation under microwave heating are caused with increased energy of the reactive species when compared with their energy in thermal activation. Increased energy of the reactive species is a consequence of rapid transfer and absorption of the energy of microwave field to the existing reactive species. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
New Phylogenetic Analysis of the Family Elephantidae Based on Cranial‐Dental Morphology
Authors: Todd Nancy E.
Published: November 2009

In 1973, Vincent Maglio published a seminal monograph on the evolution of the Elephantidae, in which he revised and condensed the 100+ species named by Henry Fairfield Osborn in 1931. Michel Beden further revised the African Elephantidae in 1979, but little systematic work has been done on the family since this publication. With addition of new specimens and species and revisions of chronology, a new analysis of the phylogeny and systematics of this family is warranted. A new, descriptive character dataset was generated from studies of modern elephants for use with fossil species. Parallel evolution in cranial and dental characters in all three lineages of elephants creates homoplastic noise in cladistic analysis, but new inferences about evolutionary relationships are possible. In this analysis, earlyLoxodontaand early AfricanMammuthusare virtually indistinguishable in dental morphology. TheElephaslineage is not monophyletic, and results from this analysis suggest multiple migration events out of Africa into Eurasia, and possibly back into Africa. New insight into the origin of the three lineages is also proposed, withStegotetrabelodonleading to theMammuthuslineage, andPrimelephasas the ancestor ofLoxodontaandElephas. These new results suggest a much more complex picture of elephantid origins, evolution, and paleogeography. Anat Rec, 2010. © 2009 Wiley‐Liss, Inc.
Polarized Light Microscopic Analysis of Bone Formation After Inhibition of Cyclooxygenase 1 and 2
Authors: Retamoso Luciana Borges , Montagner Francisco , Camargo Elisa Souza , Vitral Roberto Willer Farinazzo , Tanaka Orlando Motohiro
Published: November 2009

Potassium diclofenac is a potent nonsteroidal anti‐inflammatory drug (NSAID) and COX isoforms (COX‐1 and COX‐2) inhibitor. Quantitative analysis of birefringence with polarized light microscopy is a useful method to investigate the macromolecular orientation and organization of collagen fibers in connective tissues. The aim of this research was to analyze the collagen structure and maturation in bone formed after potassium diclofenac administration, during first molar orthodontic movement. Sixty Wistar rats were divided in two equal groups (N = 30): control (C) and potassium diclofenac (PD). The animals in Group C received 0.9% saline solution and the PD group received potassium diclofenac Cataflam® (5 mg/kg). Animals were sacrificed 3, 7, or 14 days after a NiTi unilateral closed‐coil spring was stretched between the upper right first molar and the incisors. The first molar area was fixed, decalcified, and histologically processed using picrosirius pigment. The collagen birefringence of bone turnover was analyzed by phase retardation. Two‐way ANOVA and Tukey's test showed that optical retardation was influenced by time and treatment. There was increase in the collagen organization over time. On the third day, the C group showed better collagen organization than the PD group. Potassium diclofenac interfered in collagen maturation, reducing fibril organization in the initial phase of orthodontic movement. Anat Rec, 2010. © 2009 Wiley‐Liss, Inc.
Platinum‐Decorated Ruthenium Nanoparticles for Enhanced Methanol Electrooxidation
Authors: Chen Ching‐Hsiang , Sarma Loka Subramanyam , Wang Di‐Yan , Lai Feng‐Ju , Al Andra Cun‐Cun , Chang Shi‐Hong , Liu Din‐Goa , Chen Chia‐Chun , Lee Jyh‐Fu , Hwang Bing‐Joe
Published: November 2009

A promising electrocatalyst based on the reduction of Pt2+ ions on the surface of hexagonally close‐packed (hcp) Ru core nanoparticles has been prepared by a redox–transmetalation process. This simple synthetic process generates a Pt‐on‐Ru catalyst with a lower Pt content than commercially available PtRu electrocatalysts and with a long‐range ordered hcp structure, which can significantly reduce the Pt loading. X‐Ray absorption spectroscopy of the Pt‐on‐Ru catalyst reveals pronounced electronic modifications when compared to the commercial PtRu black catalyst. The Pt‐on‐Ru catalyst exhibits a higher mass‐specific current than the PtRu black catalyst in solution in 0.5 M H2SO4 with 10 vol. % CH3OH under the conditions of rotating disk experiments. Further optimization of this synthetic procedure may yield even more active electrocatalysts with a significant reduction in noble metal loadings.
Total Synthesis, Characterization, and Conformational Analysis of the Naturally Occurring Hexadecapeptide Integramide A and a Diastereomer
Authors: De Zotti Marta , Damato Francesca , Formaggio Fernando , Crisma Marco , Schievano Elisabetta , Mammi Stefano , Kaptein Bernard , Broxterman Quirinus B. , Felock Peter J. , Hazuda Daria J. , Singh Sheo B. , Kirschbaum Jochen , Brückner Hans , Toniolo Claudio
Published: November 2009

Integramide A is a 16‐amino acid peptide inhibitor of the enzyme HIV‐1 integrase. We have recently reported that the absolute stereochemistries of the dipeptide sequence near the C terminus are L‐Iva14‐D‐Iva15. Herein, we describe the syntheses of the natural compound and its D‐Iva14‐L‐Iva15 diastereomer, and the results of their chromatographic/mass spectrometric analyses. We present the conformational analysis of the two compounds and some of their synthetic intermediates of different main‐chain length in the crystal state (by X‐ray diffraction) and in solvents of different polarities (using circular dichroism, FTIR absorption, and 2D NMR techniques). These data shed light on the mechanism of inhibition of HIV‐1 integrase, which is an important target for anti‐HIV therapy.
The Interaction of Zinc(II) and Hydroxamic Acids and a Metal‐Triggered Lossen Rearrangement
Authors: Ducháčková Lucie , Roithová Jana
Published: November 2009

The structure and reactivity of a complex of zinc(II), water, acetic acid, and acetohydroxamic acid, in which one of the acids is deprotonated, is investigated by means of mass spectrometry, labeling studies, and density functional calculations to unravel the exceptional binding properties of hydroxamic acids towards zinc‐containing enzymes at the molecular level. It is shown that acetohydroxamic acid is deprotonated in the complex, whereas acetic acid is present in its neutral form. The binding energies of the ligands towards zinc increase in the following order: water<acetic acid<acetohydroxamic acid. The structure of the complex and its fragmentation provide experimental evidence for the proposed mode of operation of drugs based on hydroxamic acids. Furthermore, coordinatively unsaturated complexes of zinc and acetohydroxamic acid undergo a zinc‐assisted Lossen rearrangement followed by elimination of water if acetohydroxamic acid is present as a neutral ligand, or by loss of methylisocyanate if acetohydroxamic acid is deprotonated.
Altered balance of γ‐aminobutyric acidergic and glutamatergic afferent inputs in rostral ventrolateral medulla‐projecting neurons in the paraventricular nucleus of the hypothalamus of renovascular hypertensive rats
Authors: Biancardi Vinicia Campana , Campos Ruy Ribeiro , Stern Javier Eduardo
Published: November 2009

An imbalance of excitatory and inhibitory functions has been shown to contribute to numerous pathological disorders. Accumulating evidence supports the idea that a change in hypothalamic γ‐aminobutyric acid (GABA)‐ergic inhibitory and glutamatergic excitatory synaptic functions contributes to exacerbated neurohumoral drive in prevalent cardiovascular disorders, including hypertension. However, the precise underlying mechanisms and neuronal substrates are still not fully elucidated. In the present study, we combined quantitative immunohistochemistry with neuronal tract tracing to determine whether plastic remodeling of afferent GABAergic and glutamatergic inputs into identified RVLM‐projecting neurons of the hypothalamic paraventricular nucleus (PVN‐RVLM) contributes to an imbalanced excitatory/inhibitory function in renovascular hypertensive rats (RVH). Our results indicate that both GABAergic and glutamatergic innervation densities increased in oxytocin‐positive, PVN‐RVLM (OT‐PVN‐RVLM) neurons in RVH rats. Despite this concomitant increase, time‐dependent and compartment‐specific differences in the reorganization of these inputs resulted in an altered balance of excitatory/inhibitory inputs in somatic and dendritic compartments. A net predominance of excitatory over inhibitory inputs was found in OT‐PVN‐RVLM proximal dendrites. Our results indicate that, along with previously described changes in neurotransmitter release probability and postsynaptic receptor function, remodeling of GABAergic and glutamatergic afferent inputs contributes as an underlying mechanism to the altered excitatory/inhibitory balance in the PVN of hypertensive rats. J. Comp. Neurol. 518:567–585, 2010. © 2009 Wiley‐Liss, Inc.