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  • 1
    Publication Date: 2008-04-22
    Description: Metabolic phenotypes are the products of interactions among a variety of factors-dietary, other lifestyle/environmental, gut microbial and genetic. We use a large-scale exploratory analytical approach to investigate metabolic phenotype variation across and within four human populations, based on 1H NMR spectroscopy. Metabolites discriminating across populations are then linked to data for individuals on blood pressure, a major risk factor for coronary heart disease and stroke (leading causes of mortality worldwide). We analyse spectra from two 24-hour urine specimens for each of 4,630 participants from the INTERMAP epidemiological study, involving 17 population samples aged 40-59 in China, Japan, UK and USA. We show that urinary metabolite excretion patterns for East Asian and western population samples, with contrasting diets, diet-related major risk factors, and coronary heart disease/stroke rates, are significantly differentiated (P 〈 10(-16)), as are Chinese/Japanese metabolic phenotypes, and subgroups with differences in dietary vegetable/animal protein and blood pressure. Among discriminatory metabolites, we quantify four and show association (P 〈 0.05 to P 〈 0.0001) of mean 24-hour urinary formate excretion with blood pressure in multiple regression analyses for individuals. Mean 24-hour urinary excretion of alanine (direct) and hippurate (inverse), reflecting diet and gut microbial activities, are also associated with blood pressure of individuals. Metabolic phenotyping applied to high-quality epidemiological data offers the potential to develop an area of aetiopathogenetic knowledge involving discovery of novel biomarkers related to cardiovascular disease risk.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holmes, Elaine -- Loo, Ruey Leng -- Stamler, Jeremiah -- Bictash, Magda -- Yap, Ivan K S -- Chan, Queenie -- Ebbels, Tim -- De Iorio, Maria -- Brown, Ian J -- Veselkov, Kirill A -- Daviglus, Martha L -- Kesteloot, Hugo -- Ueshima, Hirotsugu -- Zhao, Liancheng -- Nicholson, Jeremy K -- Elliott, Paul -- R01 HL084228/HL/NHLBI NIH HHS/ -- R01 HL50490/HL/NHLBI NIH HHS/ -- England -- Nature. 2008 May 15;453(7193):396-400. doi: 10.1038/nature06882. Epub 2008 Apr 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics (SORA), Faculty of Medicine, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18425110" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Alanine/urine ; Animals ; Blood Pressure/*physiology ; Cardiovascular Diseases/metabolism ; China ; *Diet ; Dietary Proteins/pharmacology ; Female ; Great Britain ; Hippurates/urine ; Humans ; Intestines/microbiology ; Japan ; Magnetic Resonance Spectroscopy ; Male ; Metabolism/*physiology ; Middle Aged ; Phenotype ; Principal Component Analysis ; Time Factors ; United States ; Vegetables/chemistry
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2005-09-06
    Description: Antisense transcription (transcription from the opposite strand to a protein-coding or sense strand) has been ascribed roles in gene regulation involving degradation of the corresponding sense transcripts (RNA interference), as well as gene silencing at the chromatin level. Global transcriptome analysis provides evidence that a large proportion of the genome can produce transcripts from both strands, and that antisense transcripts commonly link neighboring "genes" in complex loci into chains of linked transcriptional units. Expression profiling reveals frequent concordant regulation of sense/antisense pairs. We present experimental evidence that perturbation of an antisense RNA can alter the expression of sense messenger RNAs, suggesting that antisense transcription contributes to control of transcriptional outputs in mammals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Katayama, S -- Tomaru, Y -- Kasukawa, T -- Waki, K -- Nakanishi, M -- Nakamura, M -- Nishida, H -- Yap, C C -- Suzuki, M -- Kawai, J -- Suzuki, H -- Carninci, P -- Hayashizaki, Y -- Wells, C -- Frith, M -- Ravasi, T -- Pang, K C -- Hallinan, J -- Mattick, J -- Hume, D A -- Lipovich, L -- Batalov, S -- Engstrom, P G -- Mizuno, Y -- Faghihi, M A -- Sandelin, A -- Chalk, A M -- Mottagui-Tabar, S -- Liang, Z -- Lenhard, B -- Wahlestedt, C -- RIKEN Genome Exploration Research Group -- Genome Science Group (Genome Network Project Core Group) -- FANTOM Consortium -- New York, N.Y. -- Science. 2005 Sep 2;309(5740):1564-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Genome Exploration Research Group, RIKEN Genomic Sciences Centre (GSC), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16141073" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Gene Expression Regulation ; *Genome ; Humans ; Mice/*genetics ; RNA Interference ; RNA, Antisense/*biosynthesis ; RNA, Messenger/biosynthesis ; *Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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