bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Xenobiotic-Sensing Nuclear Receptors Pregnane X Receptor, Constitutive Androstane Receptor, and Orphan Nuclear Receptor Hepatocyte Nuclear Factor 4α in the Regulation of Human Steroid-/Bile Acid-Sulfotransferase
Authors: Echchgadda Ibtissam , Song Chung S. , Oh Taesung , Ahmed Mohamed , De La Cruz Isidro John , Chatterjee Bandana 
Published: June 2007

AbstractThe nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are the primary transcription factors coordinating induced expression of the enzymes and proteins directing oxidative, conjugative, and transport phases of endobiotic and xenobiotic metabolism, whereas hepatocyte nuclear factor 4α (HNF4α), a regulator of hepatic lipid homeostasis, can modify the PXR/CAR response. Steroid- and bile acid-sulfotransferase (SULT2A1) promotes phase II metabolism through its sulfonating action on certain endobiotics, including steroids and bile acids, and on diverse xenobiotics, including therapeutic drugs. This study describes characterization of a PXR- and CAR-inducible composite element in the human SULT2A1 promoter and its synergistic interaction with HNF4α. Inverted and direct repeats of AG(G/T)TCA (IR2 and DR4), both binding to PXR and CAR, define the composite element. Differential recognition of the composite element by PXR and CAR is evident because single-site mutation at either IR2 or DR4 in the natural gene abolished the PXR response, whereas mutations at both repeats were necessary to abrogate completely the CAR response. The composite element conferred xenobiotic response to a heterologous promoter, and the cognate ligands induced PXR and CAR recruitment to the chromatin-associated response region. An HNF4α element adjacent to the −30 position enhanced basal promoter activity. Although functioning as a synergizer, the HNF4α element was not essential for the PXR/CAR response. An emerging role of SULT2A1 in lipid and caloric homeostasis suggests that illumination on the regulatory interactions driving human SULT2A1 expression may reveal new avenues to control certain metabolic disorders.
The Nuclear Receptor-Coactivator Interaction Surface as a Target for Peptide Antagonists of the Peroxisome Proliferator-Activated Receptors
Authors: Mettu Niharika B. , Stanley Thomas B. , Dwyer Mary A. , Jansen Michelle S. , Allen John E. , Hall Julie M. , McDonnell Donald P. 
Published: June 2007

AbstractThe peroxisome proliferator-activated receptors (PPARα, PPARδ, and PPARγ) constitute a family of nuclear receptors that regulates metabolic processes involved in lipid and glucose homeostasis. Although generally considered to function as ligand-regulated receptors, all three PPARs exhibit a high level of constitutive activity that may result from their stimulation by intracellularly produced endogenous ligands. Consequently, complete inhibition of PPAR signaling requires the development of inverse agonists. However, the currently available small molecule antagonists for the PPARs function only as partial agonists, or their efficacy is not sufficient to inhibit the constitutive activity of these receptors. Due to the lack of efficacious antagonists that interact with the ligand-binding domain of the PPARs, we decided to target an interaction that is central to nuclear receptor-mediated gene transcription: the nuclear receptor-coactivator interaction. We utilized phage display technology to identify short LXXLL-containing peptides that bind to the PPARs. Analysis of these peptides revealed a consensus binding motif consisting of HPLLXXLL. Cross-screening of these peptides for binding to other nuclear receptors enabled the identification of a high-affinity PPAR-selective peptide that has the ability to repress PPARγ1-dependent transcription of transfected reporter genes. Most importantly, when introduced into HepG2 cells, the peptide inhibited the expression of endogenous PPARγ1 target genes, adipose differentiation-related protein and mitochondrial 3-hydroxy-3-methylglutaryl coenzyme A synthase 2. This work lends support for the rational development of peptidomimetics that block receptor-mediated transcription by targeting the nuclear receptor-coactivator interaction surface.
A cognitive perspective on Singaporean primary school pupils' use of reading strategies in learning to read in English
Authors: Zhang Lawrence Jun. , Gu Peter Yongqi. , Hu Guangwei. 
Published: June 2007

Background. This study is conducted in Singapore, where learning to read in English is regarded as essential because it is offered as a First Language (L1) subject in the curriculum and is stipulated as the medium of instruction in the education system, and the mother tongues are offered as Second Language (L2) subjects, although the majority still learn English as an L2.Aims. The paper reports on the reading strategies used by Singaporean primary school pupils from a cognitive perspective, which is part of a larger study that aims to investigate these pupils' language learning strategies.Sample. The participants were 18 pupils from three neighbourhood primary schools, in grades Primary 4, 5 and 6.Method. The data were collected from high‐ and low‐proficiency pupils at each of the three grades in each school, who read two texts at each level. Grounded in an information‐processing theory and based on successful experiences of scholars using think‐aloud for data collection, we asked the pupils to read and report what they were thinking about while reading. The think‐aloud protocols were recorded, transcribed verbatim, coded and analysed.Results. The results suggest that participants' flexible and appropriate use of reading strategies varies according to language proficiency and grade level, with the high‐proficiency group outperforming its lower‐proficiency counterpart and the high‐graders outnumbering the lower‐graders in terms of the number of strategies that they used. These differences were also exemplified with qualitative findings from case studies.Conclusions. The use of reading strategies differs according to proficiency levels, and the quality of pupils' strategy‐use patterns has more significant implications for understanding efficient reading among primary school pupils.
Attitudes of young people towards depression and mania
Authors: Wolkenstein Larissa , Meyer Thomas D. 
Published: June 2007

Objectives. Despite the known effects of stigma on people suffering from affective disorders, no study so far has investigated and compared attitudes of the general public towards depression and mania. Furthermore, we were interested if it makes a difference if one asks a sample about its own attitudes or the assumed opinions of ‘others’.Design. We used an experimental and randomized design.Methods. People were faced either with a case vignette describing a man with current symptoms of depression or mania. Randomly people (N=387, age 16–34 years) were asked for their own attitudes or for the attitudes of the public in general.Results. Attitudes towards an individual with a current manic episode turned out to be significantly more negative than towards a person with current depression. Interestingly, the attitudes of the general public were reported to be more negative than the personal attitudes.Conclusions. While depression is still associated with negative attitudes, this first study looking at manic symptoms as well finds that this seems to be even more so for manic episodes indicating bipolar disorder. It seems recommended to concentrate efforts to reduce stigmatization of the mentally ill more intensively on the bipolar spectrum of affective disorders. Furthermore, testable hypotheses have to be derived why individuals attribute less favourable attitudes to the general public when compared with their own attitudes. The question is if there is a general bias towards social desirability when people are asked for their opinion.
SORCS1: A Novel Human Type 2 Diabetes Susceptibility Gene Suggested by the Mouse
Authors: Goodarzi Mark O. , Lehman Donna M. , Taylor Kent D. , Guo Xiuqing , Cui Jinrui , Quiñones Manuel J. , Clee Susanne M. , Yandell Brian S. , Blangero John , Hsueh Willa A. , Attie Alan D. , Stern Michael P. , Rotter Jerome I. 
Published: June 2007

OBJECTIVE—A small number of susceptibility genes for human type 2 diabetes have been identified by candidate gene analysis or positional cloning. Genes found to influence diabetes or related traits in mice are likely to be susceptibility genes in humans. SorCS1 is the gene identified as responsible for the mouse chromosome 19 T2dm2 quantitative trait locus for fasting insulin levels, acting via impaired insulin secretion and increased islet disruption in obese females. Genes that impair compensatory insulin secretion in response to obesity-induced insulin resistance may be particularly relevant to human diabetes. Thus, we sought to determine whether variation in the human SORCS1 gene was associated with diabetes-related traits.
RESEARCH DESIGN AND METHODS—We assessed the contribution of variation in SORCS1 to human insulin–related traits in two distinct Mexican-American cohorts. One cohort (the Mexican-American Coronary Artery Disease [MACAD] cohort) consisted of nondiabetic individuals, allowing assessment of genetic association with subclinical intermediate insulin-related traits; the second cohort (the San Antonio Family Diabetes Study [SAFADS]) contained individuals with diabetes, allowing association analyses with overt disease.
RESULTS—We first found association of SORCS1 single nucleotide polymorphisms and haplotypes with fasting insulin levels and insulin secretion in the MACAD cohort. Similar to our results in the mice, the genetic association was strongest in overweight women. We then observed association with diabetes risk and age at diagnosis in women of the SAFADS cohort.
CONCLUSIONS—Identification of SORCS1 as a novel gene affecting insulin secretion and diabetes risk is likely to provide important insight into the biology of obesity-induced type 2 diabetes.
Incretin Levels and Effect Are Markedly Enhanced 1 Month After Roux-en-Y Gastric Bypass Surgery in Obese Patients With Type 2 Diabetes
Authors: Laferrère Blandine , Heshka Stanley , Wang Krystle , Khan Yasmin , McGinty James , Teixeira Julio , Hart Allison B. , Olivan Blanca 
Published: June 2007

OBJECTIVE— Limited data on patients undergoing Roux-en-Y gastric bypass surgery (RY-GBP) suggest that an improvement in insulin secretion after surgery occurs rapidly and thus may not be wholly accounted for by weight loss. We hypothesized that in obese patients with type 2 diabetes the impaired levels and effect of incretins changed as a consequence of RY-GBP.RESEARCH DESIGN AND METHODS— Incretin (gastric inhibitory peptide [GIP] and glucagon-like peptide-1 [GLP-1]) levels and their effect on insulin secretion were measured before and 1 month after RY-GBP in eight obese women with type 2 diabetes and in seven obese nondiabetic control subjects. The incretin effect was measured as the difference in insulin secretion (area under the curve [AUC]) in response to an oral glucose tolerance test (OGTT) and to an isoglycemic intravenous glucose test.RESULTS— Fasting and stimulated levels of GLP-1 and GIP were not different between control subjects and patients with type 2 diabetes before the surgery. One month after RY-GBP, body weight decreased by 9.2 ± 7.0 kg, oral glucose-stimulated GLP-1 (AUC) and GIP peak levels increased significantly by 24.3 ± 7.9 pmol · l−1 · min−1 (P &lt; 0.0001) and 131 ± 85 pg/ml (P = 0.007), respectively. The blunted incretin effect markedly increased from 7.6 ± 28.7 to 42.5 ± 11.3 (P = 0.005) after RY-GBP, at which it time was not different from that for the control subjects (53.6 ± 23.5%, P = 0.284).CONCLUSIONS— These data suggest that early after RY-GBP, greater GLP-1 and GIP release could be a potential mediator of improved insulin secretion.
Prognostic Impact of Metabolic Syndrome by Different Definitions in a Population With High Prevalence of Obesity and Diabetes
Authors: de Simone Giovanni , Devereux Richard B. , Chinali Marcello , Best Lyle G. , Lee Elisa T. , Galloway James M. , Resnick Helaine E. ,   for the Strong Heart Study Investigators
Published: June 2007

OBJECTIVE— This study analyzed which definition of the metabolic syndrome is more predictive of cardiovascular events in both diabetic and nondiabetic members of a population-based sample.
RESEARCH DESIGN AND METHODS— A 10-year, longitudinal follow-up of the Strong Heart Study cohort has been evaluated. The analysis included 3,945 participants (2,384 female) with complete data (1,700 with diabetes and 1,468 with arterial hypertension) for evaluation of metabolic syndrome. Those with prevalent cardiovascular disease were excluded (n = 287, of whom 127 were female). Prevalence of metabolic syndrome was assessed based on the World Health Organization (WHO), the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III, and International Diabetes Federation (IDF) definitions. The main outcome was 10-year incidence of combined fatal and nonfatal cardiovascular events, including stroke, coronary heart disease, and congestive heart failure.
RESULTS— Fatal and nonfatal cardiovascular events occurred in 1,120 participants. After adjusting for age, sex, and diabetes, metabolic syndrome by all definitions was significantly associated with higher incidence of cardiovascular events (all P &lt; 0.0001). In nondiabetic individuals, incident cardiovascular event rates were about 30–40% higher in those with metabolic syndrome, without a significant difference among definitions (0.03 &lt; P &lt; 0.001), and remained significant in WHO and NCEP ATP III definitions even after further adjustment for obesity, hypertension, and low HDL cholesterol. In the diabetic group, metabolic syndrome risk for cardiovascular events was greatest using the WHO definition (P &lt; 0.002 vs. other models).
CONCLUSIONS— In individuals without diabetes, metabolic syndrome is associated with incident cardiovascular disease, especially with WHO and NCEP ATP III definitions. Metabolic syndrome also predicts higher cardiovascular event rates in diabetic participants, a prediction that is greatest using the WHO definition.
Monounsaturated Fat–Rich Diet Prevents Central Body Fat Distribution and Decreases Postprandial Adiponectin Expression Induced by a Carbohydrate-Rich Diet in Insulin-Resistant Subjects
Authors: Paniagua J.A. , de la Sacristana A. Gallego , Romero I. , Vidal-Puig A. , Latre J.M. , Sanchez E. , Perez-Martinez P. , Lopez-Miranda J. , Perez-Jimenez F. 
Published: June 2007

OBJECTIVE— Central obesity is associated with insulin resistance through factors that are not fully understood. We studied the effects of three different isocaloric diets on body fat distribution, insulin sensitivity, and peripheral adiponectin gene expression.
RESEARCH DESIGN AND METHODS— Eleven volunteers, offspring of obese type 2 diabetic patients with abdominal fat deposition, were studied. These subjects were considered insulin resistant as indicated by Matsuda index values &lt;4 after an oral glucose tolerance test, and they maintained A1C &lt;6.5% without therapeutic intervention. All subjects underwent three dietary periods of 28 days each in a crossover design: 1) diet enriched in saturated fat (SAT), 2) diet rich in monounsaturated fat (MUFA) (Mediterranean diet), and 3) diet rich in carbohydrates (CHOs).
RESULTS— Weight, body composition, and resting energy expenditure remained unchanged during the three sequential dietary periods. Using dual-energy X-ray absorptiometry we observed that when patients were fed a CHO-enriched diet, their fat mass was redistributed toward the abdominal depot, whereas periphery fat accumulation decreased compared with isocaloric MUFA-rich and high-SAT diets (ANOVA P &lt; 0.05). Changes in fat deposition were associated with decreased postprandial mRNA adiponectin levels in peripheral adipose tissue and lower insulin sensitivity index values from a frequently sampled insulin-assisted intravenous glucose tolerance test in patients fed a CHO-rich diet compared with a MUFA-rich diet (ANOVA P &lt; 0.05).
CONCLUSIONS— An isocaloric MUFA-rich diet prevents central fat redistribution and the postprandial decrease in peripheral adiponectin gene expression and insulin resistance induced by a CHO-rich diet in insulin-resistant subjects.
Prospective Study of Type 1 and Type 2 Diabetes and Risk of Stroke Subtypes
Authors: Janghorbani Mohsen , Hu Frank B. , Willett Walter C. , Li Tricia Y. , Manson Joann E. , Logroscino Giancarlo , Rexrode Kathryn M. 
Published: June 2007

OBJECTIVE— The aim of this study was to examine the relationship between type 1 and type 2 diabetes and risk of stroke subtypes in women.
RESEARCH DESIGN AND METHODS— We followed 116,316 women aged 30–55 years in 1976 through 2002 for incidence of stroke. At baseline and through biennial follow-up, women were asked about their history and treatment of diabetes and other potential risk factors for stroke.
RESULTS— During 2.87 million person-years of follow-up, 3,463 incident strokes occurred. In multivariate analyses, the incidence of total stroke was fourfold higher in women with type 1 diabetes (relative risk [RR] 4.7 [95% CI 3.3–6.6]) and twofold higher among women with type 2 diabetes (1.8 [1.7–2.0]) than for nondiabetic women. The multivariate RR of ischemic stroke was increased sixfold (6.3 [4.0–9.8]) in type 1 diabetes and twofold (2.3 [2.0–2.6]) in type 2 diabetes. Risks for large-artery infarction and lacunar stroke were similar. Type 1 diabetes was also significantly associated with the risk of hemorrhagic stroke (3.8 [1.2–11.8]), but type 2 diabetes was not (1.0 [0.7–1.4]).
CONCLUSIONS— Both type 1 and type 2 diabetes are associated with substantially increased risks of total and most subtypes of stroke.
Six-Year Incidence of Proteinuria in Type 1 Diabetic African Americans
Authors: Roy Monique S. , Affouf Mahmoud , Roy Alec 
Published: June 2007

OBJECTIVE— We sought to report the 6-year incidence of proteinuria and associated risk factors in African Americans with type 1 diabetes.
RESEARCH DESIGN AND METHODS— African Americans (n = 483) with type 1 diabetes were reexamined in a 6-year follow-up study. Proteinuria and creatinuria were measured in 4-h timed urine specimens obtained at initial and follow-up visits. Other evaluations included a structured clinical interview, ocular examination, masked grading of seven stereoscopic fundus photographs, blood pressure measurements, blood assays, and administration of the Beck Depression Inventory (BDI).
RESULTS— Over the 6-year period, 117 (42.9%) of the 473 patients at risk developed “any” proteinuria, defined as either microalbuminuria (26.0%) or overt (16.9%) proteinuria; 87 (23.5%) progressed from micro- or no albuminuria to overt proteinuria and 39 (8.7%) to end-stage renal disease; and 40 (20.6%) regressed. Peak incidence of any proteinuria occurred for patients who were 10–14 years of age or had 5–10 years of diabetes duration at baseline. Multiple regression analysis showed that baseline albumin excretion rate (AER), systemic hypertension, blood cholesterol, and high BDI depression scores were significant and independent risk factors for incidence of any proteinuria.
CONCLUSIONS— In African Americans with type 1 diabetes, the 6-year incidence of proteinuria is high, particularly among young patients and those with a relatively short duration of diabetes at baseline. Baseline AER is the strongest predictor for incidence of any proteinuria.
Asymmetric Dimethylarginine Predicts Cardiovascular Events in Patients With Type 2 Diabetes
Authors: Krzyzanowska Katarzyna , Mittermayer Friedrich , Wolzt Michael , Schernthaner Guntram 
Published: June 2007

OBJECTIVE— Circulating concentrations of an endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), are elevated in patients with increased cardiovascular risk. We hypothesized that ADMA predicts cardiovascular events and enhances risk prediction independent of established risk markers in patients with type 2 diabetes.
RESEARCH DESIGN AND METHODS— This prospective cohort study included 125 patients with type 2 diabetes. ADMA, l-arginine, high-sensitivity C-reactive protein (CRP), and routine clinical parameters were determined at baseline. First occurrence of cardiovascular events (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, stroke, carotid revascularization, or all-cause mortality) was defined as a composite end point.
RESULTS— During a median follow-up of 21 (interquartile range 11–27) months, 84 events occurred in 48 patients. According to multivariate Cox regression analysis, patients with baseline ADMA or CRP in the highest tertile had a significantly increased hazard ratio for incident cardiovascular events compared with those with ADMA or CRP in tertile 1 (2.37 [95% CI 1.05–5.35], P = 0.038, and 3.63 [1.59–8.28], P = 0.002). Assessing the joint effect of ADMA and CRP revealed that patients with either ADMA or CRP or both in the highest tertile had increased hazard ratios for cardiovascular events compared with patients with neither ADMA nor CRP in the highest tertile before and after adjustment for possible confounders (hazard ratio 4.59 [95% CI 2.07–10.15], P &lt; 0.001).
CONCLUSIONS— ADMA predicted cardiovascular events and enhanced the predictive role of CRP in patients with type 2 diabetes. ADMA therefore could improve cardiovascular risk assessment in patients with type 2 diabetes.
Central Obesity Is an Independent Risk Factor for Albuminuria in Nondiabetic South Asian Subjects
Authors: Chandie Shaw Prataap K. , Berger Stefan P. , Mallat Marko , Frölich Marijke , Dekker Friedo W. , Rabelink Ton J. 
Published: June 2007

OBJECTIVE— South Asians have a high prevalence of central obesity. When the diagnosis of diabetes is made, they have a very high risk of developing renal failure. In the current study, we explored the hypothesis that central obesity is associated with the development of renal injury, before the manifestation of diabetes.
RESEARCH DESIGN AND METHODS— We invited first-degree nondiabetic relatives of South Asian type 2 diabetic patients for investigation of microalbuminuria and diabetes. Subjects who used antihypertensive or antidiabetic medication were excluded. We performed a glucose tolerance test according to the classic World Health Organization criteria. A total of 205 subjects were normoglycemic; we excluded 25 subjects because of impaired glucose tolerance, and 30 subjects were excluded because of de novo diabetes. Central obesity was measured by waist-to-hip ratio (WHR). Albuminuria was measured as albumin-to-creatinine ratio (ACR) in the early-morning urine.
RESULTS— Central obesity was independently related with albuminuria in the 205 normoglycemic subjects. We found no relation of fasting blood glucose or systolic blood pressure with albuminuria. Multivariate analysis for the presence of increased albuminuria (median ACR &gt;0.31 mg/mmol) showed a relative risk of 4.1 for the highest versus the lowest tertile of WHR (P = 0.002).
CONCLUSIONS— Central obesity is an early and independent risk factor for increased albuminuria in normoglycemic South Asian subjects. This could explain the high incidence of diabetic renal disease in South Asians, probably by the mechanism of insulin resistance and endothelial dysfunction in the pre-diabetic state.