This report constitutes the sixth update of the human obesity gene map incorporating published results up to the end of October 1999. Evidence from the rodent and human obesity cases caused by single gene mutations, Mendelian disorders exhibiting obesity as a clinical feature, quantitative trait loci (QTL) uncovered in human genome‐wide scans and in crossbreeding experiments with mouse, rat, pig and chicken models, association and linkage studies with candidate genes and other markers is reviewed. Twenty‐five human cases of obesity can now be explained by variation in five genes. Twenty Mendelian disorders exhibiting obesity as one of their clinical manifestations have now been mapped. The number of different QTLs reported from animal models reaches now 98. Attempts to relate DNA sequence variation in specific genes to obesity phenotypes continue to grow, with 89 reports of positive associations pertaining to 40 candidate genes. Finally, 44 loci have linked to obesity indicators in genomic scans and other linkage study designs. The obesity gene map depicted in Figure 1 reveals that putative loci affecting obesity‐related phenotypes can be found on all autosomes, with chromosomes 14 and 21 showing each one locus only. The number of genes, markers, and chromosomal regions that have been associated or linked with human obesity phenotypes continues to increase and is now well above 200. Figure 1 Open in figure viewer PowerPoint The 1999 human obesity gene map. The map includes all putative obesity‐related phenotypes identified from the various lines of evidence reviewed in the article. The chromosomes and their regions are from the Gene Map of the Human Genome web site hosted by the National Center for Biotechnology Information, National Institutes of Health, Bethesda, MD (URL: http:www.ncbi.nlm.nih.gov ). The chromosome number and the size of each chromosome in megabases (Mb) are given at the top and bottom of the chromosomes, respectively. Loci abbreviations and full names are given in the Appendix. The abbreviations for QTLs are given in Table 4 . 相似文献
The objective is to generate milligram quantities of recombinant human 2C2 adrenergic receptor for X-ray crystallographic studies. It has been cloned in Saccharomyces cerevisiae, and the production level is at best about 13 pmol/mg of membrane protein, as estimated by radio-ligand binding assay. The receptor is solubilized with sucrose monolaurate followed by immunoaffinity purification and reconstitution into phospholipid vesicles. The efficiency of solubilization and immuno-purification are 60% and 91%, respectively. 相似文献
ADP-ribosylation is a post-translational modification catalyzed by writer enzymes – ADP-ribosyltransferases. The modification is part of many signaling events, can modulate the function and stability of target proteins, and often results in the recruitment of reader proteins that bind to the ADP-ribosyl groups. Erasers are integral actors in these signaling events and reverse the modification. ADP-ribosylation can be targeted with therapeutics and many inhibitors against writers exist, with some being in clinical use. Inhibitors against readers and erasers are sparser and development of these has gained momentum only in recent years. Drug discovery has been hampered by the lack of specific tools, however many significant advances in the methods have recently been reported. We discuss assays used in the field with a focus on methods allowing efficient identification of small molecule inhibitors and profiling against enzyme families. While human proteins are focused, the methods can be also applied to bacterial toxins and virus encoded erasers that can be targeted to treat infectious diseases in the future. 相似文献
Moose (Alces alces L.) prefer to browse Pinus sylvestris over other coniferous trees. One reason for this preference might be due to differences in the chemical composition of various coniferous plants, and/or differences in digestibility. We evaluated the in-sacco digestibility of P. sylvestris, Pinus contorta and Picea abies using a fistulated cow (Bos taurus). Additionally, we determined the chemical profile of the different plant species (with emphasis on specific phenolics) and we modified the concentration of the individual phenolic (+)catechin in plant material of P. sylvestris to test the influence of this particular phenolic on digestibility in vitro (IVDMD). The in-sacco experiment revealed the highest digestibility of dry matter, and neutral detergent fibre for P. sylvestris. In addition, the concentration of nitrogen was significantly higher, and the concentrations of total phenolics and condensed tannins were significantly lower in P. sylvestris than in the other species. Individual phenolics showed high variation but were low in P. sylvestris, whereas P. contorta and P. abies had at least one species-specific phenolic compound of high concentration each. We found no changes in the digestibility of samples in which we experimentally elevated (+)catechin content. 相似文献
The purpose of this study was to identify regions of the human genome linked to submaximal exercise heart rates in the sedentary state and in response to a standardized 20-wk endurance training program in blacks and whites of the HERITAGE Family Study. A total of 701 polymorphic markers covering the 22 autosomes were used in the genome-wide linkage scan, with 328 sibling pairs from 99 white nuclear families and 102 pairs from 115 black family units. Steady-state heart rates were measured at the relative intensity of 60% maximal oxygen uptake (HR60) and at the absolute intensity of 50 W (HR50). Baseline phenotypes were adjusted for age, sex, and baseline body mass index (BMI) and training responses (posttraining minus baseline, Delta) were adjusted for age, sex, baseline BMI, and baseline value of the phenotype. Two analytic strategies were used, a multipoint variance components and a regression-based multipoint linkage analysis. In whites, promising linkages (LOD > 1.75) were identified on 18q21-q22 for baseline HR50 (LOD = 2.64; P = 0.0002) and DeltaHR60 (LOD = 2.10; P = 0.0009) and on chromosome 2q33.3 for DeltaHR50 (LOD = 2.13; P = 0.0009). In blacks, evidence of promising linkage for baseline HR50 was detected with several markers within the chromosomal region 10q24-q25.3 (peak LOD = 2.43, P = 0.0004 with D10S597). The most promising regions for fine mapping in the HERITAGE Family Study were found on 2q33 for HR50 training response in whites, on 10q25-26 for baseline HR60 in blacks, and on 18q21-22 for both baseline HR50 and DeltaHR60 in whites. 相似文献
We tested the hypothesis that peroxisome proliferator-activated receptor-delta (PPARdelta) gene polymorphisms are associated with cardiorespiratory fitness and plasma lipid responses to endurance training. Associations between the PPARdelta exon 4 +15 C/T and exon 7 +65 A/G polymorphisms and maximal exercise capacity and plasma lipid responses to 20 wk of endurance training were investigated in healthy white (n = 477) and black (n = 264) subjects. In black subjects, the exon 4 +15 C/C homozygotes showed a smaller training-induced increase in maximal oxygen consumption (P = 0.028) than the C/T and T/T genotypes. Similarly, a lower training response in maximal power output was observed in the exon 4 +15 C/C homozygotes (P = 0.005) compared with the heterozygotes and the T/T homozygotes in black subjects, and a similar trend was evident in white subjects (P = 0.087). In white subjects, baseline apolipoprotein A-1 (Apo A-1)levels were higher in the exon 4 +15 C/C (P = 0.011) and exon 7 +65 G/G (P = 0.05) genotypes compared with those in the other genotypes. In white subjects, exon 4 +15 C/C (P = 0.0025) and exon 7 +65 G/G (P = 0.011) genotypes showed significantly greater increases in plasma high-density lipoprotein-cholesterol (HDL-C) levels with endurance training than in the other genotypes, whereas in black subjects the exon 4 +15 CC homozygotes tended to increase (P = 0.057) their Apo A-1 levels more than the T allele carriers. DNA sequence variation in the PPARdelta locus is a potential modifier of changes in cardiorespiratory fitness and plasma HDL-C in healthy individuals in response to regular exercise. 相似文献
There are no prospective studies that would have compared the relationships of different types of physical activity (PA) and sedentary behavior (SB) with academic skills among children. We therefore investigated the associations of different types of PA and SB with reading and arithmetic skills in a follow-up study among children.
Methods
The participants were 186 children (107 boys, 79 girls, 6–8 yr) who were followed-up in Grades 1–3. PA and SB were assessed using a questionnaire in Grade 1. Reading fluency, reading comprehension and arithmetic skills were assessed using standardized tests at the end of Grades 1–3.
Results
Among all children more recess PA and more time spent in SB related to academic skills were associated with a better reading fluency across Grades 1–3. In boys, higher levels of total PA, physically active school transportation and more time spent in SB related to academic skills were associated with a better reading fluency across the Grades 1–3. Among girls, higher levels of total PA were related to worse arithmetic skills across Grades 1–3. Moreover, total PA was directly associated with reading fluency and arithmetic skills in Grades 1–3 among girls whose parents had a university degree, whereas these relationships were inverse in girls of less educated parents.
Conclusions
Total PA, physically active school transportation and SB related to academic skills may be beneficial for the development of reading skills in boys, whereas factors that are independent of PA or SB may be more important for academic skills in girls.
The occurrence of variations in the spectrum of cardiovascular disease between different regions of the world and ethnic groups have been the subject of great interest. This study report the 24-h variation of myocardial infarction (MI) occurrence in patients recruited from CCU located in Argentina and Uruguay.
Methods
A cohort of 1063 patients admitted to the CCU within 24 h of the onset of symptoms of an acute MI was examined. MI incidence along the day was computed in 1 h-intervals.
Results
A minimal MI incidence between 03:00 and 07:00 h and the occurrence of a first maximum between 08:00 and 12:00 h and a second maximum between 15:00 and 22:00 h were verified. The best fit curve was a 24 h cosinor (acrophase ~ 19:00 h, accounting for 63 % of variance) together with a symmetrical gaussian bell (maximum at ~ 10:00 h, accounting for 37 % of variance). A similar picture was observed for MI frequencies among different excluding subgroups (older or younger than 70 years; with or without previous symptoms; diabetics or non diabetics; Q wave- or non-Q wave-type MI; anterior or inferior MI location). Proportion between cosinor and gaussian probabilities was maintained among most subgroups except for older patients who had more MI at the afternoon and patients with previous symptoms who were equally distributed among the morning and afternoon maxima.
Conclusion
The results support the existence of two maxima (at morning and afternoon hours) in MI incidence in the Argentine and Uruguayan population. 相似文献
