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991.
992.
Trombetta M Bonetti S Boselli M Turrini F Malerba G Trabetti E Pignatti P Bonora E Bonadonna RC 《PloS one》2012,7(3):e32755
Background
Genetic variability of the major subunit (CACNA1E) of the voltage-dependent Ca2+ channel CaV2.3 is associated to risk of type 2 diabetes, insulin resistance and impaired insulin secretion in nondiabetic subjects. The aim of the study was to test whether CACNA1E common variability affects beta cell function and/or insulin sensitivity in patients with newly diagnosed type 2 diabetes.Methodology/Principal Findings
In 595 GAD-negative, drug naïve patients (mean±SD; age: 58.5±10.2 yrs; BMI: 29.9±5 kg/m2, HbA1c: 7.0±1.3) with newly diagnosed type 2 diabetes we: 1. genotyped 10 tag SNPs in CACNA1E region reportedly covering ∼93% of CACNA1E common variability: rs558994, rs679931, rs2184945, rs10797728, rs3905011, rs12071300, rs175338, rs3753737, rs2253388 and rs4652679; 2. assessed clinical phenotypes, insulin sensitivity by the euglycemic insulin clamp and beta cell function by state-of-art modelling of glucose/C-peptide curves during OGTT. Five CACNA1E tag SNPs (rs10797728, rs175338, rs2184945, rs3905011 and rs4652679) were associated with specific aspects of beta cell function (p<0.05−0.01). Both major alleles of rs2184945 and rs3905011 were each (p<0.01 and p<0.005, respectively) associated to reduced proportional control with a demonstrable additive effect (p<0.005). In contrast, only the major allele of rs2253388 was related weakly to more severe insulin resistance (p<0.05).Conclusions/Significance
In patients with newly diagnosed type 2 diabetes CACNA1E common variability is strongly associated to beta cell function. Genotyping CACNA1E might be of help to infer the beta cell functional phenotype and to select a personalized treatment. 相似文献993.
The present study provides normative data from a sample of 257 healthy children and 608 adults on a modified version of the Five-Point Test (5PT). The 5PT is a structured and standardized test measuring figural fluency functions. Interrater reliability, test-retest-reliability and construct validity of this measure were analyzed. The sensitivity of the task for cognitive disturbances of patients with neurological diseases was proven by analyzing the test performance in the 5PT of patients with Parkinson''s disease. Finally, normative data stratified by age and corrected for education level is provided. The results of the present study confirm the value of the 5PT in the measurement of figural fluency functions in clinical examination and neuropsychological research. 相似文献
994.
J Lailson-Brito R Cruz PR Dorneles L Andrade Ade F Azevedo AB Fragoso LG Vidal MB Costa TL Bisi R Almeida DP Carvalho WR Bastos O Malm 《PloS one》2012,7(7):e42162
Top marine predators present high mercury concentrations in their tissues as consequence of biomagnification of the most toxic form of this metal, methylmercury (MeHg). The present study concerns mercury accumulation by Guiana dolphins (Sotalia guianensis), highlighting the selenium-mediated methylmercury detoxification process. Liver samples from 19 dolphins incidentally captured within Guanabara Bay (Rio de Janeiro State, Brazil) from 1994 to 2006 were analyzed for total mercury (THg), methylmercury (MeHg), total organic mercury (TOrgHg) and selenium (Se). X-ray microanalyses were also performed. The specimens, including from fetuses to 30-year-old dolphins, comprising 8 females and 11 males, presented high THg (0.53-132 μg/g wet wt.) and Se concentrations (0.17-74.8 μg/g wet wt.). Correlations between THg, MeHg, TOrgHg and Se were verified with age (p<0.05), as well as a high and positive correlation was observed between molar concentrations of Hg and Se (p<0.05). Negative correlations were observed between THg and the percentage of MeHg contribution to THg (p<0.05), which represents a consequence of the selenium-mediated methylmercury detoxification process. Accumulation of Se-Hg amorphous crystals in Kupffer Cells was demonstrated through ultra-structural analysis, which shows that Guiana dolphin is capable of carrying out the demethylation process via mercury selenide formation. 相似文献
995.
996.
Rasmus Ribel-Madsen Mario F. Fraga Stine Jacobsen Jette Bork-Jensen Ester Lara Vincenzo Calvanese Agustin F. Fernandez Martin Friedrichsen Birgitte F. Vind Kurt H?jlund Henning Beck-Nielsen Manel Esteller Allan Vaag Pernille Poulsen 《PloS one》2012,7(12)
Background
Monozygotic twins discordant for type 2 diabetes constitute an ideal model to study environmental contributions to type 2 diabetic traits. We aimed to examine whether global DNA methylation differences exist in major glucose metabolic tissues from these twins.Methodology/Principal Findings
Skeletal muscle (n = 11 pairs) and subcutaneous adipose tissue (n = 5 pairs) biopsies were collected from 53–80 year-old monozygotic twin pairs discordant for type 2 diabetes. DNA methylation was measured by microarrays at 26,850 cytosine-guanine dinucleotide (CpG) sites in the promoters of 14,279 genes. Bisulfite sequencing was applied to validate array data and to quantify methylation of intergenic repetitive DNA sequences. The overall intra-pair variation in DNA methylation was large in repetitive (LINE1, D4Z4 and NBL2) regions compared to gene promoters (standard deviation of intra-pair differences: 10% points vs. 4% points, P<0.001). Increased variation of LINE1 sequence methylation was associated with more phenotypic dissimilarity measured as body mass index (r = 0.77, P = 0.007) and 2-hour plasma glucose (r = 0.66, P = 0.03) whereas the variation in promoter methylation did not associate with phenotypic differences. Validated methylation changes were identified in the promoters of known type 2 diabetes-related genes, including PPARGC1A in muscle (13.9±6.2% vs. 9.0±4.5%, P = 0.03) and HNF4A in adipose tissue (75.2±3.8% vs. 70.5±3.7%, P<0.001) which had increased methylation in type 2 diabetic individuals. A hypothesis-free genome-wide exploration of differential methylation without correction for multiple testing identified 789 and 1,458 CpG sites in skeletal muscle and adipose tissue, respectively. These methylation changes only reached some percentage points, and few sites passed correction for multiple testing.Conclusions/Significance
Our study suggests that likely acquired DNA methylation changes in skeletal muscle or adipose tissue gene promoters are quantitatively small between type 2 diabetic and non-diabetic twins. The importance of methylation changes in candidate genes such as PPARGC1A and HNF4A should be examined further by replication in larger samples. 相似文献997.
998.
999.
Design and implementation of an environmental monitoring program is vital to assure the maintenance of acceptable quality conditions in a pharmaceutical manufacturing unit of human mesenchymal stem cells. Since sterility testing methods require 14 days and these cells are only viable for several hours, they are currently administered without the result of this test. Consequently environmental monitoring is a key element in stem cell banks for assuring low levels of potential introduction of contaminants into the cell products. The aim of this study was to qualitatively and quantitatively analyze the environmental microbiological quality in a pharmaceutical manufacturing unit of human mesenchymal stem cells production for use in advanced therapies. Two hundred and sixty one points were tested monthly during one year, 156 from air and 105 from surfaces. Among the 6264 samples tested, 231 showed contamination, 76.6% for bacteria and 23.4% for fungi. Microbial genuses isolated were Staphylococcus (89.7%), Microccocus (4.5%), Kocuria (3.2%) and Bacillus (2.6%). In the identification of fungi, three genuses were detected: Aspergillus (56%), Penicillium (26%) and Cladosporium (18%). The origin of the contamination was found to be due to personnel manipulation and air microbiota. For all sampling methods, alert limits were set and corrective measures suggested. 相似文献
1000.
Natasha Spadafora Lara Perrotta Jeroen Nieuwland Diego Albani M. Beatrice Bitonti Robert J. Herbert John H. Doonan Angela M. Marchbank Ilario Siciliano Anne Lentz Gr?nlund Dennis Francis Hilary J. Rogers 《Annals of botany》2012,110(8):1631-1639