bluuebunny/crossref_metadata_2025_split huggingface dataset:
gem-1 Encodes an SLC16 Monocarboxylate Transporter-Related Protein That Functions in Parallel to the gon-2 TRPM Channel During Gonad Development in Caenorhabditis elegans
Authors: Kemp Benedict J , Church Diane L , Hatzold Julia , Conradt Barbara , Lambie Eric J 
Published: December 2008

Abstract
The gon-2 gene of Caenorhabditis elegans encodes a TRPM cation channel required for gonadal cell divisions. In this article, we demonstrate that the gonadogenesis defects of gon-2 loss-of-function mutants (including a null allele) can be suppressed by gain-of-function mutations in the gem-1 (gon-2extragenic modifier) locus. gem-1 encodes a multipass transmembrane protein that is similar to SLC16 family monocarboxylate transporters. Inactivation of gem-1 enhances the gonadogenesis defects of gon-2 hypomorphic mutations, suggesting that these two genes probably act in parallel to promote gonadal cell divisions. GEM-1∷GFP is expressed within the gonadal precursor cells and localizes to the plasma membrane. Therefore, we propose that GEM-1 acts in parallel to the GON-2 channel to promote cation uptake within the developing gonad.
Extensive Long-Range and Nonsyntenic Linkage Disequilibrium in Livestock Populations: Deconstruction of a Conundrum
Authors: Lipkin E , Straus K , Stein R Tal , Bagnato A , Schiavini F , Fontanesi L , Russo V , Medugorac I , Foerster M , Sölkner J , Dolezal M , Medrano J F , Friedmann A , Soller M 
Published: December 2008

AbstractGreat interest was aroused by reports, based on microsatellite markers, of high levels of statistically significant long-range and nonsyntenic linkage disequilibrium (LD) in livestock. Simulation studies showed that this could result from population family structure. In contrast, recent SNP-based studies of livestock populations report much lower levels of LD. In this study we show, on the basis of microsatellite data from four cattle populations, that high levels of long-range LD are indeed obtained when using the multi-allelic D′ measure of LD. Long-range and nonsyntenic LD are exceedingly low, however, when evaluated by the standardized chi-square measure of LD, which stands in relation to the predictive ability of LD. Furthermore, specially constructed study populations provided no evidence for appreciable LD resulting from family structure at the grandparent level. We propose that the high statistical significance and family structure effects observed in the earlier studies are due to the use of large sample sizes, which accord high statistical significance to even slight deviations from asymptotic expectations under the null hypothesis. Nevertheless, even after taking sample size into account, our results indicate that microsatellites testify to the presence of usable LD at considerably wider separation distances than SNPs, suggesting that use of SNP haplotypes may considerably increase the usefulness of a given fixed SNP array.
Polymorphism Due to Multiple Amino Acid Substitutions at a Codon Site Within Ciona savignyi
Authors: Donmez Nilgun , Bazykin Georgii A , Brudno Michael , Kondrashov Alexey S 
Published: December 2008

Abstract
We compared two haploid genotypes of one Ciona savignyi individual and identified codons at which these genotypes differ by two nonsynonymous substitutions. Using the C. intestinalis genome as an outgroup, we showed that both substitutions tend to occur in the same genotype. Only in 53 (34.4%) of 154 codons, one substitution occurred in each of the two genotypes, although 77 (50%) of such codons are to be expected if substitutions were independent. We considered two feasible evolutionary causes for the observed pattern: substitutions driven by positive selection and compensatory substitutions, as well as several potential biases. However, none of these explanations is fully compelling, and data on multiple genotypes of C. savignyi would help to elucidate the causes of this pattern.
Stem Cells, Their Niches and the Systemic Environment: An Aging Network
Authors: Drummond-Barbosa Daniela 
Published: December 2008

Abstract
Stem cells have a fascinating biology and offer great prospects for therapeutic applications, stimulating intense research on what controls their properties and behavior. Although there have been significant advances in our understanding of how local microenvironments, or niches, control the maintenance and activity of stem cells, it is much less well understood how stem cells sense and respond to variable external, physiological, or tissue environments. This review focuses on the multidirectional interactions among stem cells, niches, tissues, and the systemic environment and on potential ideas for how changes in this network of communication may relate to the aging process.
A Genomewide Analysis of the Cinnamyl Alcohol Dehydrogenase Family in Sorghum [Sorghum bicolor(L.) Moench] IdentifiesSbCAD2as theBrown midrib6Gene
Authors: Saballos Ana , Ejeta Gebisa , Sanchez Emiliano , Kang ChulHee , Vermerris Wilfred 
Published: December 2008

AbstractThe content and composition of the plant cell wall polymer lignin affect plant fitness, carbon sequestration potential, and agro-industrial processing. These characteristics, are heavily influenced by the supply of hydroxycinnamyl alcohol precursors synthesized by the enzyme cinnamyl alcohol dehydrogenase (CAD). In angiosperms, CAD is encoded by a multigene family consisting of members thought to have distinct roles in different stages of plant development. Due to the high sequence similarity among CAD genes, it has been challenging to identify and study the role of the individual genes without a genome sequence. Analysis of the recently released sorghum genome revealed the existence of 14 CAD-like genes at seven genomic locations. Comparisons with maize and rice revealed subtle differences in gene number, arrangement, and expression patterns. Sorghum CAD2 is the predominant CAD involved in lignification based on the phylogenetic relationship with CADs from other species and genetic evidence showing that a set of three allelic brown midrib (bmr) lignin mutants contained mutations in this gene. The impact of the mutations on the structure of the protein was assessed using molecular modeling based on X-ray crystallography data of the closely related Arabidopsis CAD5. The modeling revealed unique changes in structure consistent with the observed phenotypes of the mutants.
Recently Trained General Pediatricians: Perspectives on Residency Training and Scope of Practice
Authors: Freed Gary L. , Dunham Kelly M. , Switalski Kara E. , Jones M. Douglas , McGuinness Gail A. ,   and the Research Advisory Committee of the American Board of Pediatrics
Published: December 2008

OBJECTIVE. Because of the increase in both the prevalence and complexity of chronic diseases in children, there is heightened awareness of the need for general pediatricians to be prepared to comanage their patients with chronic disorders with subspecialists. It is not known currently how well prepared general pediatricians believe themselves to be for these roles after residency training. This study was conducted to determine the perspectives of recently trained general pediatricians in practice regarding their decisions on residency choice, career choice, and adequacy of training.METHODS. A random sample of 600 generalists whose initial application for general pediatric certification occurred between 2002 and 2003 (4–5 years out of training) and 600 generalists who applied for board certification between 2005 and 2006 and who were not currently enrolled in or had completed subspecialty training (1–2 years out of training) received a structured questionnaire by mail. The survey focused on decision-making in selection of residency programs, strength of residency training in preparation for clinical care, and scope of practice.RESULTS. The overall response rate was 76%. The majority of generalists reported that their residency training was adequate in most subspecialty areas. However, a large proportion of generalists indicated that they could have used additional training in mental health (62% [n = 424]), sports medicine (51% [n = 345]), oral health (52% [n = 356]), and developmental/behavioral pediatrics (48% [n = 326]). Most generalist respondents reported that they are comfortable comanaging cases requiring subspecialty care with a subspecialist. However, generalist respondents without local access to subspecialists were more likely to report that they are comfortable managing patients who require subspecialty care.CONCLUSIONS. The training of general pediatricians, and the needs for their adequate preparation to care for patients, should be a dynamic process. As the nature and epidemiology of pediatric care change, our educational system must change as well.
Antenatal Betamethasone and Fetal Growth in Prematurely Born Children: Implications for Temperament Traits at the Age of 2 Years
Authors: Pesonen Anu-Katriina , Räikkönen Katri , Lano Aulikki , Peltoniemi Outi , Hallman Mikko , Kari M. Anneli 
Published: December 2008

OBJECTIVE. We explored whether repeated dose of antenatal betamethasone and variation in intrauterine growth of prematurely born children predict temperament characteristics at the age of 2 years.
PATIENTS AND METHODS. The patients (n = 142) were prematurely born children (mean gestational age: 31.0 weeks; range: 24.6–35.0 weeks) who participated in a randomized and blinded trial testing the effects of a repeated dose of antenatal betamethasone in imminent preterm birth. Fetal growth was estimated as weight, length, and head circumference in SDs according to Finnish growth charts. Parents assessed their toddlers' temperament with 201 items of the Early Childhood Temperament Questionnaire (mean child corrected age: 2.1 years).
RESULTS. No significant main effects of repeated betamethasone on toddler temperament existed. However, a significant interaction between study group and duration of exposure to betamethasone emerged; those exposed to a repeated dose for &gt;24 hours before delivery were more impulsive. One-SD increases in weight, length, and head circumference at birth were associated with 0.14- to 0.19-SD lower levels of negative affectivity (fearfulness, anger proneness, and sadness); 1-SD increases in length, weight, and head circumference at birth were associated with 0.14- to 0.18-SD higher levels of effortful control (self-regulation).
CONCLUSIONS. Repeated antenatal betamethasone did not induce alterations in toddler temperament. The results, however, suggest that a longer duration of exposure is associated with higher impulsivity scores. Regardless of betamethasone exposure, slower fetal growth exerted influences on temperament. Our findings indicate prenatal programming of psychological development and imply that more attention is needed to support the development of infants born at the lower end of the fetal growth distribution.
Muscle-Derived Angiopoietin-Like Protein 4 Is Induced by Fatty Acids via Peroxisome Proliferator–Activated Receptor (PPAR)-δ and Is of Metabolic Relevance in Humans
Authors: Staiger Harald , Haas Carina , Machann Jürgen , Werner Roman , Weisser Melanie , Schick Fritz , Machicao Fausto , Stefan Norbert , Fritsche Andreas , Häring Hans-Ulrich 
Published: December 2008

OBJECTIVE— Long-chain fatty acids (LCFAs) contribute to metabolic homeostasis in part via gene regulation. This study's objective was to identify novel LCFA target genes in human skeletal muscle cells (myotubes).
RESEARCH DESIGN AND METHODS— In vitro methods included culture and treatment of human myotubes and C2C12 cells, gene array analysis, real-time RT-PCR, Western blotting, ELISA, chromatin immunoprecipitation, and RNA interference. Human subjects (two cohorts) were characterized by oral glucose tolerance test, hyperinsulinemic-euglycemic clamp, magnetic resonance imaging and spectroscopy, and standard blood analyses (glucose, insulin, C-peptide, and plasma lipids).
RESULTS— We show here that ANGPTL4 (encoding angiopoietin-like protein 4) represents a prominent LCFA-responsive gene in human myotubes. LCFA activated peroxisome proliferator-activated receptor (PPAR)-δ, but not PPAR-α or -γ, and pharmacological activation of PPAR-δ markedly induced ANGPTL4 production and secretion. In C2C12 myocytes, knockdown of PPARD, but not of PPARG, blocked LCFA-mediated ANGPTL4 induction, and LCFA treatment resulted in PPAR-δ recruitment to the ANGPTL4 gene. In addition, pharmacological PPAR-δ activation induced LIPE (encoding hormone-sensitive lipase), and this response crucially depended on ANGPTL4, as revealed by ANGPTL4 knockdown. In a human cohort of 108 thoroughly phenotyped subjects, plasma ANGPTL4 positively correlated with fasting nonesterified fatty acids (P = 0.0036) and adipose tissue lipolysis (P = 0.0012). Moreover, in 38 myotube donors, plasma ANGPTL4 levels and adipose tissue lipolysis in vivo were reflected by basal myotube ANGPTL4 expression in vitro (P = 0.02, both).
CONCLUSIONS— ANGPTL4 is produced by human myotubes in response to LCFA via PPAR-δ, and muscle-derived ANGPTL4 seems to be of systemic relevance in humans.
Lipoic Acid Synthase (LASY)
Authors: Padmalayam Indira , Hasham Sumera , Saxena Uday , Pillarisetti Sivaram 
Published: December 2008

OBJECTIVE—Lipoic acid synthase (LASY) is the enzyme that is involved in the endogenous synthesis of lipoic acid, a potent mitochondrial antioxidant. The aim of this study was to study the role of LASY in type 2 diabetes.
RESEARCH DESIGN AND METHODS—We studied expression of LASY in animal models of type 2 diabetes. We also looked at regulation of LASY in vitro under conditions that exist in diabetes. Additionally, we looked at effects of LASY knockdown on cellular antioxidant status, inflammation, mitochondrial function, and insulin-stimulated glucose uptake.
RESULTS—LASY expression is significantly reduced in tissues from animal models of diabetes and obesity compared with age- and sex-matched controls. In vitro, LASY mRNA levels were decreased by the proinflammatory cytokine tumor necrosis factor (TNF)-α and high glucose. Downregulation of the LASY gene by RNA interference (RNAi) reduced endogenous levels of lipoic acid, and the activities of critical components of the antioxidant defense network, increasing oxidative stress. Treatment with exogenous lipoic acid compensated for some of these defects. RNAi-mediated downregulation of LASY induced a significant loss of mitochondrial membrane potential and decreased insulin-stimulated glucose uptake in skeletal muscle cells. In endothelial cells, downregulation of LASY aggravated the inflammatory response that manifested as an increase in both basal and TNF-α–induced expression of the proinflammatory cytokine, monocyte chemoattractant protein-1 (MCP-1). Overexpression of the LASY gene ameliorated the inflammatory response.
CONCLUSIONS—Deficiency of LASY results in an overall disturbance in the antioxidant defense network, leading to increased inflammation, insulin resistance, and mitochondrial dysfunction.
Reduced Adipose Tissue Oxygenation in Human Obesity
Authors: Pasarica Magdalena , Sereda Olga R. , Redman Leanne M. , Albarado Diana C. , Hymel David T. , Roan Laura E. , Rood Jennifer C. , Burk David H. , Smith Steven R. 
Published: December 2008

OBJECTIVE— Based on rodent studies, we examined the hypothesis that increased adipose tissue (AT) mass in obesity without an adequate support of vascularization might lead to hypoxia, macrophage infiltration, and inflammation.
RESEARCH DESIGN AND METHODS— Oxygen partial pressure (AT pO2) and AT temperature in abdominal AT (9 lean and 12 overweight/obese men and women) was measured by direct insertion of a polarographic Clark electrode. Body composition was measured by dual-energy X-ray absorptiometry, and insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Abdominal subcutaneous tissue was used for staining, quantitative RT-PCR, and chemokine secretion assay.
RESULTS— AT pO2 was lower in overweight/obese subjects than lean subjects (47 ± 10.6 vs. 55 ± 9.1 mmHg); however, this level of pO2 did not activate the classic hypoxia targets (pyruvate dehydrogenase kinase and vascular endothelial growth factor [VEGF]). AT pO2 was negatively correlated with percent body fat (R = −0.50, P &lt; 0.05). Compared with lean subjects, overweight/obese subjects had 44% lower capillary density and 58% lower VEGF, suggesting AT rarefaction (capillary drop out). This might be due to lower peroxisome proliferator–activated receptor γ1 and higher collagen VI mRNA expression, which correlated with AT pO2 (P &lt; 0.05). Of clinical importance, AT pO2 negatively correlated with CD68 mRNA and macrophage inflammatory protein 1α secretion (R = −0.58, R = −0.79, P &lt; 0.05), suggesting that lower AT pO2 could drive AT inflammation in obesity.
CONCLUSIONS— Adipose tissue rarefaction might lie upstream of both low AT pO2 and inflammation in obesity. These results suggest novel approaches to treat the dysfunctional AT found in obesity.
Bimodal Distribution of Glucose Is Not Universally Useful for Diagnosing Diabetes
Authors: Vistisen Dorte , Colagiuri Stephen , Borch-Johnsen Knut ,   on behalf of the DETECT-2 Collaboration
Published: December 2008

OBJECTIVE—Bimodality in the distribution of glucose has been used to define the cut point for the diagnosis of diabetes. Previous studies on bimodality have primarily been in populations with a high prevalence of type 2 diabetes, including one study in a white Caucasian population. All studies included participants with known diabetes. The aim of this study was to assess whether a bimodal structure is a general phenomenon in fasting plasma glucose (FPG) and 2-h plasma glucose that is useful for deriving a common cut point for diabetes in populations of different origin, both including and excluding known diabetes.
RESEARCH DESIGN AND METHODS—The Evaluation of Screening and Early Detection Strategies for Type 2 Diabetes and Impaired Glucose Tolerance (DETECT-2) project is an international collaboration pooling surveys from all continents. These studies include surveys in which plasma glucose was measured during an oral glucose tolerance test; in total, 43 studies (135,383 participants) from 27 countries were included. A mixture of two normal distributions was fitted to plasma glucose levels, and a cut point for normal glycemia was estimated as their intersection. In populations with a biologically meaningful cut point, bimodality was tested for significance.
RESULTS—Distributions of FPG and 2-h plasma glucose did not, in general, produce bimodal structures useful for deriving cut points for diabetes. When present, the cut points produced were inconsistent over geographical regions.
CONCLUSIONS—Deriving cut points for normal glycemia from distributions of FPG and 2-h plasma glucose does not appear to be suitable for defining diagnostic cut points for diabetes.
Lower Serum Creatinine Is a New Risk Factor of Type 2 Diabetes
Authors: Harita Nobuko , Hayashi Tomoshige , Sato Kyoko Kogawa , Nakamura Yoshiko , Yoneda Takeshi , Endo Ginji , Kambe Hiroshi 
Published: December 2008

OBJECTIVE—Because skeletal muscle is one of the target tissues for insulin, skeletal muscle mass might be associated with type 2 diabetes. Serum creatinine is a possible surrogate marker of skeletal muscle mass. The purpose of this study was to determine whether serum creatinine level is associated with type 2 diabetes.
RESEARCH DESIGN AND METHODS—The study participants were nondiabetic Japanese men (n = 8,570) aged 40–55 years at entry. Type 2 diabetes was diagnosed if fasting plasma glucose was ≥126 mg/dl or if participants were taking oral hypoglycemic medication or insulin.
RESULTS—During the 4-year follow-up period, 877 men developed type 2 diabetes. Lower serum creatinine was associated with an increased risk of type 2 diabetes. The multiple-adjusted odds ratio for those who had serum creatinine levels between 0.40 and 0.60 mg/dl was 1.91 (95% CI 1.44–2.54) compared with those who had levels between 0.71 and 0.80 mg/dl.
CONCLUSIONS—Lower serum creatinine increased the risk of type 2 diabetes.
Higher Prevalence of Retinopathy in Diabetic Patients of South Asian Ethnicity Compared With White Europeans in the Community
Authors: Raymond Neil T. , Varadhan Lakshminarayanan , Reynold Dilini R. , Bush Kate , Sankaranarayanan Sailesh , Bellary Srikanth , Barnett Anthony H. , Kumar Sudhesh , O'Hare J. Paul ,   on behalf of the UK Asian Diabetes Study Retinopathy Study Group
Published: December 2008

OBJECTIVE—The purpose of this study was to compare prevalence and risk factors for diabetic retinopathy among U.K. residents of South Asian or white European ethnicity.
RESEARCH DESIGN AND METHODS—This was a community-based cross-sectional study involving 10 general practices; 1,035 patients with type 2 diabetes were studied: 421 of South Asian and 614 of white European ethnicity. Diabetic retinopathy, sight-threatening retinopathy, maculopathy, and previous laser photocoagulation therapy were assessed after grading of retinal photographs. Data were collected on risk factors including age, duration, and treatment of diabetes, blood pressures, serum total cholesterol, and A1C.
RESULTS—Patients of South Asian ethnicity had significantly higher systolic (144 vs. 137 mmHg, P &lt; 0.0001) and diastolic (84 vs. 74 mmHg, P &lt; 0.0001) blood pressure, A1C (7.9 vs. 7.5%, P &lt; 0.0001), and total cholesterol (4.5 vs. 4.2 mmol/l, P &lt; 0.0001). Diabetic retinopathy was detected in 414 (40%) patients (189 South Asian [45%] versus 225 white European [37%]; P = 0.0078). Sight-threatening retinopathy was detected in 142 (14%) patients (68 South Asian [16%] versus 74 white European [12%]; P = 0.0597). After adjustment for confounders, there were significantly elevated risks of any retinopathy and maculopathy for South Asian versus white European patients.
CONCLUSIONS—Patients of South Asian ethnicity had a significantly higher prevalence of diabetic retinopathy and maculopathy, with significantly elevated systolic and diastolic blood pressure, A1C, and total cholesterol; lower attained age; and younger age at diagnosis. Earlier onset of disease and higher levels of modifiable risk factors make early detection of diabetes, annual referral for retinal screening, and intensive risk factor control key elements in addressing this health inequality.
A comparison of arsenic mobility in Phaseolus vulgaris, Mentha aquatica, and Pteris cretica rhizosphere
Authors: Száková Jiřina , Tlustoš Pavel , Goessler Walter , Findenig Silvia , Richtrová Eva , Balík Jiří 
Published: December 2008

Abstract
The ability of Phaseolus vulgaris, Mentha aquatica, and Pteris cretica to release arsenic (As) species from contaminated soil was tested in rhizobox experiments in three soils differing in their physicochemical parameters and total and mobile As concentration. Relatively low uptake of arsenic by P. vulgaris and M. aquatica resulted in very low and ambiguous changes in rhizosphere soil compared to bulk soil. However, there were observed differences in the distribution of the mobile As portion in soil to individual As species as affected by plant species and/or plantation conditions of these plants. Higher percentage of mobile arsenite in mint rhizosphere seems to be related to more reducing conditions during cultivation of these wetland plants. P. cretica planted in the soils containing between 36 and 1436 mg As kg−1 was able to accumulate between 80 and 500 mg As kg−1 in aboveground biomass. The extractable concentrations of As compounds in rhizosphere soil of P. cretica showed a clear depletion of arsenate (representing more than 90% of extractable arsenic) with the distance from plant roots. However, the As uptake mechanisms, as well as As transformation within hyperaccumulating fern plants, differ substantially from those in higher plants. Therefore the finding of suitable higher plant tolerant to the As soil contamination with good ability to accumulate As in aboveground biomass remains for the further research.