bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin-1β Produced in Response to Islet Autoantigen Presentation Differentiates T-Helper 17 Cells at the Expense of Regulatory T-Cells
Authors: Bertin-Maghit Sebastien , Pang Dimeng , O'Sullivan Brendan , Best Shannon , Duggan Emily , Paul Sanjoy , Thomas Helen , Kay Thomas W.H. , Harrison Leonard C. , Steptoe Raymond , Thomas Ranjeny 
Published: October 2010

OBJECTIVEThe effectiveness of tolerizing immunotherapeutic strategies, such as anti-CD40L or dendritic cells (DCs), is greater when administered to young nonobese diabetic (NOD) mice than at peak insulitis. RelBlo DCs, generated in the presence of an nuclear factor-κB inhibitor, induce T-regulatory (Treg) cells and suppress inflammation in a model of rheumatoid arthritis. Interleukin (IL)-1β is overexpressed in humans and mice at risk of type 1 diabetes, dysregulates Treg cells, and accelerates diabetes in NOD mice. We investigated the relationship between IL-1β production and the response to RelBlo DCs in the prediabetic period.RESEARCH DESIGN AND METHODSWe injected RelBlo DCs subcutaneously into 4- or 14-week-old NOD mice and tracked the incidence of diabetes and effect on Treg cell function. We measured the expression of proinflammatory cytokines by stimulated splenocytes and unstimulated islets from mice of different ages and strains and proliferative and cytokine responses of T effectors to Treg in vitro.RESULTSTolerizing RelBlo DCs significantly inhibited diabetes progression when administered to 4-week-old but not 14-week-old mice. IL-1β production by NOD splenocytes and mRNA expression by islets increased from 6 to 16 weeks of age when major histocompatibility complex (MHC)-restricted islet antigen presentation to autoreactive T-cells occurred. IL-1 reduced the capacity of Treg cells to suppress effector cells and promoted their conversion to Th17 cells. RelBlo DCs exacerbated the IL-1–dependent decline in Treg function and promoted Th17 conversion.CONCLUSIONSIL-1β, generated by islet-autoreactive cells in MHC-susceptible mice, accelerates diabetes by differentiating Th17 at the expense of Treg. Tolerizing DC therapies can regulate islet autoantigen priming and prevent diabetes, but progression past the IL-1β/IL-17 checkpoint signals the need for other strategies.
Resequencing and Analysis of Variation in the TCF7L2 Gene in African Americans Suggests That SNP rs7903146 Is the Causal Diabetes Susceptibility Variant
Authors: Palmer Nicholette D. , Hester Jessica M. , An S. Sandy , Adeyemo Adebowale , Rotimi Charles , Langefeld Carl D. , Freedman Barry I. , Ng Maggie C.Y. , Bowden Donald W. 
Published: October 2010

OBJECTIVE
Variation in the transcription factor 7-like 2 (TCF7L2) locus is associated with type 2 diabetes across multiple ethnicities. The aim of this study was to elucidate which variant in TCF7L2 confers diabetes susceptibility in African Americans.

RESEARCH DESIGN AND METHODS
Through the evaluation of tagging single nucleotide polymorphisms (SNPs), type 2 diabetes susceptibility was limited to a 4.3-kb interval, which contains the YRI (African) linkage disequilibrium (LD) block containing rs7903146. To better define the relationship between type 2 diabetes risk and genetic variation we resequenced this 4.3-kb region in 96 African American DNAs. Thirty-three novel and 13 known SNPs were identified: 20 with minor allele frequencies (MAF) &gt;0.05 and 12 with MAF &gt;0.10. These polymorphisms and the previously identified DG10S478 microsatellite were evaluated in African American type 2 diabetic cases (n = 1,033) and controls (n = 1,106).

RESULTS
Variants identified from direct sequencing and databases were genotyped or imputed. Fifteen SNPs showed association with type 2 diabetes (P &lt; 0.05) with rs7903146 being the most significant (P = 6.32 × 10−6). Results of imputation, haplotype, and conditional analysis of SNPs were consistent with rs7903146 being the trait-defining SNP. Analysis of the DG10S478 microsatellite, which is outside the 4.3-kb LD block, revealed consistent association of risk allele 8 with type 2 diabetes (odds ratio [OR] = 1.33; P = 0.022) as reported in European populations; however, allele 16 (MAF = 0.016 cases and 0.032 controls) was strongly associated with reduced risk (OR = 0.39; P = 5.02 × 10−5) in contrast with previous studies.

CONCLUSIONS
In African Americans, these observations suggest that rs7903146 is the trait-defining polymorphism associated with type 2 diabetes risk. Collectively, these results support ethnic differences in type 2 diabetes associations.
Molecular Mechanisms for Activation of the Agouti-Related Protein and Stimulation of Appetite
Authors: Ilnytska Olha , Stütz Adrian M. , Park-York MieJung , York David A. , Ribnicky David M. , Zuberi Aamir , Cefalu William T. , Argyropoulos George 
Published: October 2010

OBJECTIVE
The agouti-related protein (Agrp) is a powerful orexigenic peptide, but little is known about its transcriptional regulation. The objective of this study was to determine molecular mechanisms for the activation of hypothalamic Agrp and identify compounds that stimulate appetite.

RESEARCH DESIGN AND METHODS
We used promoter analyses methods, hypothalamic cell culture and transfection, immunohistochemistry, luciferase-expressing transgenic mice, in vivo bioluminescence, anitisense RNA, mouse feeding studies, indirect calorimetry, real-time PCR, and Western blots.

RESULTS
We found that the Krüppel-like factor 4 (Klf4) is a potent activator of Agrp by binding to a specific CACCC-box in its minimal promoter. We also found that an extract of tarragon, termed PMI-5011, activated hypothalamic Klf4 and Agrp. In vivo, PMI-5011 increased Agrp promoter activity in luciferase-expressing transgenic mice, increased hypothalamic Klf4 and Agrp expression, increased hypothalamic Orexin and melanin-concentrating hormone, increased food intake, reduced circulating insulin and leptin levels, attenuated energy expenditure, and enhanced body weight but only when using a high-fat diet.

CONCLUSIONS
These data show that Klf4 augmented hypothalamic Agrp by binding to a specific CACCC-box onto its minimal promoter. In addition, the tarragon extract PMI-5011 activated Klf4 and orexigenic neuropeptides and reduced peripheral insulin and leptin levels leading to positive energy balance.
The Protective Role of Smad7 in Diabetic Kidney Disease: Mechanism and Therapeutic Potential
Authors: Chen Hai Yong , Huang Xiao R. , Wang Wansheng , Li Jin Hua , Heuchel Rainer L. , Chung Arthur C.K. , Lan Hui Yao 
Published: October 2010

OBJECTIVE
Although Smad3 has been considered as a downstream mediator of transforming growth factor-β (TGF-β) signaling in diabetes complications, the role of Smad7 in diabetes remains largely unclear. The current study tests the hypothesis that Smad7 may play a protective role and has therapeutic potential for diabetic kidney disease.

RESEARCH DESIGN AND METHODS
Protective role of Smad7 in diabetic kidney disease was examined in streptozotocin-induced diabetic mice that have Smad7 gene knockout (KO) and in diabetic rats given Smad7 gene transfer using an ultrasound-microbubble-mediated technique.

RESULTS
We found that mice deficient for Smad7 developed more severe diabetic kidney injury than wild-type mice as evidenced by a significant increase in microalbuminuria, renal fibrosis (collagen I, IV, and fibronectin), and renal inflammation (interleukin-1β [IL-1β], tumor necrosis factor-α [TNF-α], monocyte chemoattractant protein-1 [MCP-1], intracellular adhesion molecule-1 [ICAM-1], and macrophages). Further studies revealed that enhanced renal fibrosis and inflammation in Smad7 KO mice with diabetes were associated with increased activation of both TGF-β/Smad2/3 and nuclear factor-κB (NF-κB) signaling pathways. To develop a therapeutic potential for diabetic kidney disease, Smad7 gene was transferred into the kidney in diabetic rats by an ultrasound-microbubble-mediated technique. Although overexpression of renal Smad7 had no effect on levels of blood glucose, it significantly attenuated the development of microalbuminuria, TGF-β/Smad3-mediated renal fibrosis such as collagen I and IV and fibronectin accumulation and NF-κB/p65-driven renal inflammation including IL-1β, TNF-α, MCP-1, and ICAM-1 expression and macrophage infiltration in diabetic rats.

CONCLUSIONS
Smad7 plays a protective role in diabetic renal injury. Overexpression of Smad7 may represent a novel therapy for the diabetic kidney complication.
High Connectivity Between Reduced Cortical Thickness and Disrupted White Matter Tracts in Long-Standing Type 1 Diabetes
Authors: Franc Daniel T. , Kodl Christopher T. , Mueller Bryon A. , Muetzel Ryan L. , Lim Kelvin O. , Seaquist Elizabeth R. 
Published: October 2010

OBJECTIVE
Previous studies have observed disruptions in brain white and gray matter structure in individuals with type 1 diabetes, and these structural differences have been associated with neurocognitive testing deficiencies. This study investigated the relationship between cerebral cortical thickness reductions and white matter microstructural integrity loss in a group of patients with type 1 diabetes and in healthy control subjects using diffusion tensor imaging (DTI).

RESEARCH DESIGN AND METHODS
Twenty-five subjects with type 1 diabetes for at least 15 years and 25 age- and sex-matched control subjects underwent structural T1 and proton-density and DTI on a 3.0 Tesla scanner. Fractional anisotropy measurements were made on major cerebral white matter tracts, and DTI tractography was performed to identify cortical regions with high connectivity to these tracts.

RESULTS
Posterior white matter tracts with reduced fractional anisotropy (optic radiations, posterior corona radiata, and the splenium region of the corpus callosum) were found to have high connectivity with a number of posterior cortical regions, including the cuneus, precuneus, fusiform, and posterior parietal cortical regions. A significant reduction in cortical thickness in the diabetic group was observed in the regions with high connectivity to the optic radiations and posterior corona radiata tracts (P &lt; 0.05).

CONCLUSIONS
The direct relationship between white and gray matter structural pathology has not been previously demonstrated in subjects with long-standing type 1 diabetes. The relationship between posterior white matter microstructural integrity disruption and lower cortical thickness demonstrated using a novel DTI connectivity technique suggests a common or interrelated pathophysiological mechanism in type 1 diabetes.
Effects of Acute Hyperglucagonemia on Hepatic and Intestinal Lipoprotein Production and Clearance in Healthy Humans
Authors: Xiao Changting , Pavlic Mirjana , Szeto Linda , Patterson Bruce W. , Lewis Gary F. 
Published: October 2010

OBJECTIVE
The metabolism of hepatic- and intestinally derived lipoproteins is regulated in a complex fashion by nutrients, hormones, and neurologic and other factors. Recent studies in animal models suggest an important role for glucagon acting via the glucagon receptor in regulating hepatic triglyceride (TG) secretion. Here we examined the direct effects of glucagon on regulation of hepatic and intestinal lipoprotein metabolism in humans.

RESEARCH DESIGN AND METHODS
Eight healthy men underwent two studies each, in random order, 4–6 weeks apart in which de novo lipogenesis, kinetics of larger VLDL1 TG, and kinetics of VLDL1 and smaller VLDL2 apolipoprotein (apo)B100 and B48 were studied using established stable isotope enrichment methods. Subjects were studied in the constant fed state under conditions of a pancreatic clamp (with infusion of somatostatin, insulin, and growth hormone) at either basal glucagon (BG study, 64.5 ± 2.1 pg/mL) or hyperglucagonemia (high glucagon [HG] study, 183.2 ± 5.1 pg/mL).

RESULTS
There were no significant differences in plasma concentration of VLDL1 or VLDL2 TG, apoB100 or apoB48 between BG and HG studies. There was, however, lower (P &lt; 0.05) VLDL1 apoB100 fractional catabolic rate (−39%) and production rate (−30%) in HG versus BG, but no difference in de novo lipogenesis or TG turnover, and glucagon had no effect on intestinal (B48-containing) lipoprotein metabolism.

CONCLUSIONS
Glucagon acutely regulates hepatic but not intestinal lipoprotein particle metabolism in humans both by decreasing hepatic lipoprotein particle production as well as by inhibiting particle clearance, with no net effect on particle concentration.
Levels of Oxidized LDL and Advanced Glycation End Products–Modified LDL in Circulating Immune Complexes Are Strongly Associated With Increased Levels of Carotid Intima-Media Thickness and Its Progression in Type 1 Diabetes
Authors: Lopes-Virella Maria F. , Hunt Kelly J. , Baker Nathaniel L. , Lachin John , Nathan David M. , Virella G. ,   the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group
Published: October 2010

OBJECTIVE
High cholesterol levels in circulating immune complexes (IC), surrogate markers of modified LDL, are associated with increased carotid intima-media thickness (IMT) and cardiovascular events in type 1 diabetes. Different modifications of LDL are involved in IC formation, but which of these are predictive of vascular events is not known. Therefore, we measured oxidized LDL (oxLDL), advanced glycation end products–modified LDL (AGE-LDL), and malondialdehyde-modified LDL (MDA-LDL) in IC and determined their relationship with increased carotid IMT and compared the strength of the association with that observed with conventional risk factors.

RESEARCH DESIGN AND METHODS
Levels of oxLDL, AGE-LDL, and MDA-LDL were measured in circulating IC isolated from sera of 479 patients of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort, collected at baseline. Internal and common carotid IMT were measured 8 and 14 years later by DCCT/EDIC.

RESULTS
OxLDL, AGE-LDL, and MDA-LDL levels in circulating IC were significantly correlated with diabetes duration, BMI, and lipid and blood pressure, but not with age. Multivariate logistic regression models indicated that individuals in the highest versus lowest quartile of oxLDL and AGE-LDL in IC had a 6.11-fold [confidence interval (CI) 2.51–14.8] and a 6.4-fold (CI 2.53–16.2) increase in the odds of having high carotid IMT, respectively, after adjusting for conventional risk factors. Parallel analyses resulted in odds ratios of 2.62 (CI 1.24, 5.55) for LDL-C, 1.45 (CI 0.69, 3.03) for diastolic blood pressure, and 2.33 (CI 1.09, 4.99) for A1C.

CONCLUSIONS
OxLDL and AGE-LDL in circulating IC were significantly associated with progression and increased levels of carotid IMT in type 1 diabetes.
Untreated Type 2 Diabetes and Its Complications Are Associated With Subcortical Infarctions
Authors: Roberts Rosebud O. , Kantarci Kejal , Geda Yonas E. , Knopman David S. , Przybelski Scott A. , Weigand Stephen D. , Petersen Ronald C. , Jack Clifford R. 
Published: October 2010

OBJECTIVE
To investigate the association of type 2 diabetes with subcortical infarctions.

RESEARCH DESIGN AND METHODS
We investigated this association in subjects with type 2 diabetes (case subjects; n = 93) and without type 2 diabetes (control subjects; n = 186), matched by age, sex, and years of education. Participants were a subset of the Mayo Clinic Study of Aging (median age 79 years) who had undergone magnetic resonance imaging.

RESULTS
The frequency of subcortical infarctions was 39% in case subjects and 29% in control subjects (odds ratio 1.59 [95% CI 0.91–2.75]). The association was stronger in case subjects without treatment (2.60 [1.11–6.08]) and in case subjects with diabetes-related complications (1.96 [1.02–3.74]) compared with control subjects.

CONCLUSIONS
These findings suggest that untreated type 2 diabetes and type 2 diabetes with complications are associated with subcortical infarctions.
Metformin and Cancer Occurrence in Insulin-Treated Type 2 Diabetic Patients
Authors: Monami Matteo , Colombi Claudia , Balzi Daniela , Dicembrini Ilaria , Giannini Stefano , Melani Cecilia , Vitale Valentina , Romano Desiderio , Barchielli Alessandro , Marchionni Niccolò , Rotella Carlo Maria , Mannucci Edoardo 
Published: October 2010

OBJECTIVE
Metformin is associated with reduced cancer-related morbidity and mortality. The aim of this study was to assess the effect of metformin on cancer incidence in a consecutive series of insulin-treated patients.

RESEARCH DESIGN AND METHODS
A nested case-control study was performed in a cohort of 1,340 patients by sampling, for each case subject, age-, sex-, and BMI-matched control subjects from the same cohort.

RESULTS
During a median follow-up of 75.9 months, 112 case patients who developed incident cancer and were compared with 370 control subjects. A significantly lower proportion of case subjects were exposed to metformin and sulfonylureas. After adjustment for comorbidity, glargine, and total insulin doses, exposure to metformin, but not to sulfonylureas, was associated with reduced incidence of cancer (odds ratio 0.46 [95% CI 0.25–0.85], P = 0.014 and 0.75 [0.39–1.45], P = 0.40, respectively).

CONCLUSIONS
The reduction of cancer risk could be a further relevant reason for maintaining use of metformin in insulin-treated patients.
Telipogon szmiti (Orchidaceae, Telipogoneae), a new species from Southern Ecuador
Authors: Szlachetko Dariusz , Mytnik-Ejsmont Joanna , Baranow Przemysław 
Published: October 2010

Telipogon szmiti (Orchidaceae, Telipogoneae), a new species from Southern Ecuador
A new species of the genus Telipogon from Southern Ecuador is formally described and illustrated. This species is related to T. fritillum and T. dalstroemii but is clearly distinguished from both of them by its different petals and lip structure.
Apophytes as invasive plants in the vegetation of Poland
Authors: Zając Maria , Zając Adam 
Published: October 2010

Apophytes as invasive plants in the vegetation of Poland
Apophytes are native synanthropic plants, i.e. those found in disturbed habitats. Some apophytes with a limited geographic range, which are native to one part of a country, migrate out of their natural communities as "invasive" plants. We selected from the group of apophytes in Poland (more than 220 species) examples of such plants, which after World War II colonized new areas and often new habitats. They include, for instance, coastal species of dunes and salt marshes, or plants used as ornamentals. Moreover, some species of fresh meadows in the south of Poland, are now found in the north in ruderal habitats. The speed of colonization is high, such that in the last 20 years, starting from a few locations, some have taken over almost the entire area of Poland. The expansion of apophytes can be much faster than that of anthropophytes because apophytes have a higher number of diaspores or a shorter period of adaptation in new localities.
Alien plants of the Podilski Tovtry National Nature Park (Ukraine)
Authors: Lyubinska Lyudmila 
Published: October 2010

Alien plants of the Podilski Tovtry National Nature Park (Ukraine)
The results of a study on alien plants of the Podilsky Tovtry National Nature Park are presented. The alien fraction of the Park's flora comprises 335 species of vascular plants. Its taxonomic structure, ecological and life forms and species primary geographical origin are analyzed.
Invasion of synanthropic plants into the forest vegetation of the Cedynia Landscape Park (NW Poland)
Authors: Stępień Edyta 
Published: October 2010

Invasion of synanthropic plants into the forest vegetation of the Cedynia Landscape Park (NW Poland)
The distribution of synanthropic plants was studied in the Cedynia Landscape Park (Cedyński Park Krajobrazowy), with particular reference to alien species and their capability to penetrate into forest ecosystems. The research was conducted by the cartogram method in the Atpol system (1-km grid squares). The Park is situated within the Western Pomeranian Province and includes two large woodland complexes: the Piasek Forest (Puszcza Piaskowa) and the Mieszkowice Forest (Lasy Mieszkowickie). The forest vegetation is exposed to various forms of human pressure. Results of this study show that the vascular flora of forests of the Park is composed of 609 species: 506_native taxa (277_non-synanthropic spontaneophytes and 229_apophytes) and 107_anthropophytes (49_archaeophytes, 48_kenophytes, and 9_diaphytes). Most synanthropic plants in the studied forests occur near roads, cottages, and river banks. Contributions of various historical-geographic groups to the total number of species varied between forest types, but apophyte species were usually most numerous. In contrast to some earlier reports, not only alien but also native species were found to be more diverse near forest roads than in the forest interior. Spontaneophytes are equally diverse, while apophytes are much more diverse near roads.
Taxonomic investigations of cyanobacterial and algal flora from the Southern Altai, East Kazakhstan
Authors: Caisová Lenka , Bešta Tomáš , Chlachula Jiří , Komárek Jiří , Husák Štěpán 
Published: October 2010

Taxonomic investigations of cyanobacterial and algal flora from the Southern Altai, East Kazakhstan
The study presents results of pilot investigations (2005-2007) of micro-vegetation biodiversity in marginally explored mountain and forest-steppe areas of southern Altai, East Kazakhstan. On the basis of morphological phenotypes and ecological demands a total of 351 taxa of cyanobacteria and algae were identified in the principal biotopes (rivers and streams, backwaters, irrigation channels, lakes, high-tundra periglacial and barren land settings, snow fields, and pedogenic /soil cover/environments) of the territorial topographic gradient of ca. 400-3900 m a.s.l. Microbiological records display a remarkable taxonomic variability, including several previously undescribed endemic species of algae adapted to locally specific geoenvironmental conditions. The present results show a major potential for future systematic phycological studies integrated in the complex nature monitoring and management strategy in protected areas of the Altai. The results also demonstrate a limited impact of modern human activity on the quality of local water sources with only minor present ecological risks in balance with the traditional lifestyles of pastoralist communities.
De novo sequencing and development of EST‐SSR for Gevuina avellana (Proteaceae), a nut tree from South America
Authors: Riegel Ricardo , Diaz Leila , Véliz Débora 
Published: October 2010

•Premise of the study: The aim of this study was to develop molecular tools to investigate the genetic structure and diversity of natural populations of Gevuina avellana (Molina, Proteaceae), the Chilean hazelnut. Simple sequence repeats (SSRs) derived from expressed sequence tags (EST‐SSRs) were developed, optimized, and characterized.•Methods and Results: The microsatellite‐containing sequences were selected from a cDNA library developed from the nut. The eight marker loci showed two to seven alleles in 60 unrelated trees, from two different natural populations. The observed heterozygosity (Ho) was 0.44, ranging from 0.07 to 0.92 for different loci. When the multilocus genotype of the eight EST‐SSRs was considered, all trees could be differentiated.•Conclusions: The newly identified EST‐SSRs in G. avellana and the multi‐pooling strategy involving eight markers will facilitate future studies of clone identification, genetic structure, and diversity.