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11.
12.
Risheg H Graham JM Clark RD Rogers RC Opitz JM Moeschler JB Peiffer AP May M Joseph SM Jones JR Stevenson RE Schwartz CE Friez MJ 《Nature genetics》2007,39(4):451-453
Opitz-Kaveggia syndrome (also known as FG syndrome) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation. We report here that the original family for whom the condition is named and five other families have a recurrent mutation (2881C>T, leading to R961W) in MED12 (also called TRAP230 or HOPA), a gene located at Xq13 that functions as a thyroid receptor-associated protein in the Mediator complex. 相似文献
13.
Komen JC Distelmaier F Koopman WJ Wanders RJ Smeitink J Willems PH 《Cellular and molecular life sciences : CMLS》2007,64(24):3271-3281
Refsum disease is a rare, inherited neurodegenerative disorder characterized by accumulation of the dietary branched-chain
fatty acid phytanic acid in plasma and tissues caused by a defect in the alphaoxidation pathway. The accumulation of phytanic
acid is believed to be the main pathophysiological cause of the disease. However, the exact mechanism(s) by which phytanic
acid exerts its toxicity have not been resolved. In this study, the effect of phytanic acid on mitochondrial respiration was
investigated. The results show that in digitonin-permeabilized fibroblasts, phytanic acid decreases ATP synthesis, whereas
substrate oxidation per se is not affected. Importantly, studies in intact fibroblasts revealed that phytanic acid decreases both the mitochondrial
membrane potential and NAD(P)H autofluorescence. Taken together, the results described here show that unesterified phytanic
acid exerts its toxic effect mainly through its protonophoric action, at least in human skin fibroblasts.
Received 4 August 2007; received after revision 26 September 2007; accepted 10 October 2007
J. C. Komen, F. Distelmaier: These authors contributed equally to this work. 相似文献
14.
Regulation of insulin receptor function 总被引:1,自引:0,他引:1
Youngren JF 《Cellular and molecular life sciences : CMLS》2007,64(7-8):873-891
Resistance to the biological actions of insulin contributes to the development of type 2 diabetes and risk of cardiovascular
disease. A reduced biological response to insulin by tissues results from an impairment in the cascade of phosphorylation
events within cells that regulate the activity of enzymes comprising the insulin signaling pathway. In most models of insulin
resistance, there is evidence that this decrement in insulin signaling begins with either the activation or substrate kinase
activity of the insulin receptor (IR), which is the only component of the pathway that is unique to insulin action. Activation
of the IR can be impaired by post-translational modifications of the protein involving serine phosphorylation, or by binding
to inhibiting proteins such as PC-1 or members of the SOCS or Grb protein families. The impact of these processes on the conformational
changes and phosphorylation events required for full signaling activity, as well as the role of these mechanisms in human
disease, is reviewed in this article.
Received 3 August 2006; received after revision 1 December 2006; accepted 8 January 2007 相似文献
15.
St Onge RP Mani R Oh J Proctor M Fung E Davis RW Nislow C Roth FP Giaever G 《Nature genetics》2007,39(2):199-206
Systematic genetic interaction studies have illuminated many cellular processes. Here we quantitatively examine genetic interactions among 26 Saccharomyces cerevisiae genes conferring resistance to the DNA-damaging agent methyl methanesulfonate (MMS), as determined by chemogenomic fitness profiling of pooled deletion strains. We constructed 650 double-deletion strains, corresponding to all pairings of these 26 deletions. The fitness of single- and double-deletion strains were measured in the presence and absence of MMS. Genetic interactions were defined by combining principles from both statistical and classical genetics. The resulting network predicts that the Mph1 helicase has a role in resolving homologous recombination-derived DNA intermediates that is similar to (but distinct from) that of the Sgs1 helicase. Our results emphasize the utility of small molecules and multifactorial deletion mutants in uncovering functional relationships and pathway order. 相似文献
16.
A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21 总被引:14,自引:0,他引:14
van Heel DA Franke L Hunt KA Gwilliam R Zhernakova A Inouye M Wapenaar MC Barnardo MC Bethel G Holmes GK Feighery C Jewell D Kelleher D Kumar P Travis S Walters JR Sanders DS Howdle P Swift J Playford RJ McLaren WM Mearin ML Mulder CJ McManus R McGinnis R Cardon LR Deloukas P Wijmenga C 《Nature genetics》2007,39(7):827-829
We tested 310,605 SNPs for association in 778 individuals with celiac disease and 1,422 controls. Outside the HLA region, the most significant finding (rs13119723; P = 2.0 x 10(-7)) was in the KIAA1109-TENR-IL2-IL21 linkage disequilibrium block. We independently confirmed association in two further collections (strongest association at rs6822844, 24 kb 5' of IL21; meta-analysis P = 1.3 x 10(-14), odds ratio = 0.63), suggesting that genetic variation in this region predisposes to celiac disease. 相似文献
17.
1 Results Acid-doped polybenzimidazoles[1] are particularly appealing because of high proton conductivity with no or low humidification and promising fuel cells performances. PBI, in fact, contains basic functional groups which can easily interact with strong oxo-acids, such as H3PO4 and H2SO4. The acid partially protonates the polymer and partially is freely dispersed in the polymer backbone, so allowing proton migration via Grotthuss mechanism along the anionic chains[2]. Anyway, a technological limit... 相似文献
18.
19.
Strell C Lang K Niggemann B Zaenker KS Entschladen F 《Cellular and molecular life sciences : CMLS》2007,64(24):3306-3316
The extravasation of leukocytes and tumor cells is a multi-step process with the involvement of various adhesion molecules
depending on the three steps rolling, adhesion, and diapedesis. We have developed an in vitro model, by which we investigated the rolling and adhesion of neutrophil granulocytes and MDA-MB-468 human breast carcinoma
cells to lung endothelial cells under physiological flow-conditions. We found that norepinephrine had an inhibitory function
on the fMLP-promoted adhesion of neutrophil granulocytes due to a down-regulation of β2-integrin. Furthermore, neutrophil
granulocytes serve as linking cells for the interaction of the MDA-MB-468 cells with the endothelium, which are both β2-integrin
negative, but express the β2-integrin ligand ICAM-1. In addition, we show here that N-cadherin is up-regulated on the endothelial
cells and on neutrophil granulocytes in response to fMLP. This up-regulation resulted in a significant increase of adherent
MDA-MB-468 cells, which are also N-cadherin positive.
Received 3 September 2007; received after revision 17 October 2007; accepted 22 October 2007 相似文献
20.
Advances in our understanding of cardiac development have fuelled research into cellular approaches to myocardial repair of
the damaged heart. In this collection of reviews we present recent advances into the basic mechanisms of heart development
and the resident and non-resident progenitor cell populations that are currently being investigated as potential mediators
of cardiac repair. Together these reviews illustrate that despite our current knowledge about how the heart is constructed,
caution and much more research in this exciting field is essential. The current momentum to evaluate the potential for cardiac
repair will in turn accelerate research into fundamental aspects of myocardial biology. 相似文献