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11.
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
12.
1 Results In this work, the ion conducting films of polyacrylonitrile (PAN) containing lithium triflate (LiCF3SO3) and sodium triflate (NaCF3SO3) were prepared by the solution casting technique. The ionic conductivity measurements were carried out using impedance spectroscopy. The room temperature conductivity for pure polyacrylonitrile film is 1.51×10-11 S·cm-1. The room temperature conductivity for the highest conducting film in the PAN-LiCF3SO3 and PAN-NaCF3SO3 systems is 1.51×10-5 and 7.99×10-6 S·cm-1, respectively. The conductivity-temperature studies were performed in the temperature range between 303 and 373 K. The results for the variation of the conductivity with temperature obeys the VTF law. The increase and decrease in the number of ions can be implied from the plots of dielectric constant, εr-frequency and dielectric loss, εi-frequency. 相似文献
13.
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
14.
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
15.
Wang E Lenferink A O'Connor-McCourt M 《Cellular and molecular life sciences : CMLS》2007,64(14):1752-1762
Genomic alterations lead to cancer complexity and form a major hurdle for comprehensive understanding of the molecular mechanisms underlying oncogenesis. In this review, we describe recent advances in studying cancer-associated genes from a systems biology point of view. The integration of known cancer genes onto protein and signaling networks reveals the characteristics of cancer genes within networks. This approach shows that cancer genes often function as network hub proteins which are involved in many cellular processes and form focal nodes in information exchange between many signaling pathways. Literature mining allows constructing gene-gene networks, in which new cancer genes can be identified. The gene expression profiles of cancer cells are used for reconstructing gene regulatory networks. By doing so, genes which are involved in the regulation of cancer progression can be picked up from these networks, after which their functions can be further confirmed in the laboratory. 相似文献
16.
Lindahl E Nyman U Melles E Sigmundsson K Ståhlberg M Wahren J Obrink B Shafqat J Joseph B Jörnvall H 《Cellular and molecular life sciences : CMLS》2007,64(4):479-486
Proinsulin C-peptide is known to bind specifically to cell membranes and to exert intracellular effects, but whether it is
internalized in target cells is unknown. In this study, using confocal microscopy and immunostained or rhodamine-labeled peptide,
we show that C-peptide is internalized and localized to the cytosol of Swiss 3T3 and HEK-293 cells. In addition, transport
into nuclei was found using the labeled peptide. The internalization was followed at 37°C for up to 1 h, and was reduced at
4°C and after preincubation with pertussis toxin. Hence, it is concluded to occur via an energy-dependent, pertussis toxin-sensitive
mechanism and without detectable degradation within the experimental time course. Surface plasmon resonance measurements demonstrated
binding of HEK-293 cell extract components to C-peptide, and subsequent elution of bound material revealed the components
to be intracellular proteins. The identification of C-peptide cellular internalization, intracellular binding proteins, absence
of rapid subsequent C-peptide degradation and apparent nuclear internalization support a maintained activity similar to that
of an intracrine peptide hormone. Hence, the data suggest the possibility of one further C-peptide site of action.
Received 31 October 2006; received after revision 27 December 2006; accepted 30 December 2006 相似文献
17.
V.A.帕瑟根 《国外科技新书评介》2007,(2):7-7
分子间的范德华力是十分微弱的,但可以说普遍的存在着,在很多体系中起着巨大的作用,在物理学、化学、生物学等学科中得到了广泛的研究。但怎样计算范德华力?如何考虑各种条件对范德华力的影响? 相似文献
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Infection of bacteria triggers innate immune defense reactions in Drosophila. So far, the only bacterial component known to be recognized by the insect innate immune system is peptidoglycan, one of
the most abundant constituents of the bacterial cell wall. Insects use peptidoglycan recognition proteins to detect peptidoglycan
and to activate innate immune responses. Such specialized peptidoglycan receptors appear to have evolved from phage enzymes
that hydrolyze bacterial cell walls. They are able to bind specific peptidoglycan molecules with distinct chemical moieties
and activate innate immune pathways by interacting with other signaling proteins. Recent X-ray crystallographic studies of
the peptidoglycan recognition proteins LCa, and LCx bound to peptidoglycan have provided structural insights into recognition
of peptidoglycan and activation of innate immunity in insects.
Received 28 December 2006; received after revision 2 February 2007; accepted 21 February 2007 相似文献