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71.
S Haege C Einer S Thiele W Mueller S Nietzsche A Lupp F Mackay S Schulz R Stumm 《PloS one》2012,7(8):e42814
Background
The CXCL12/CXCR4 axis is involved in kidney development by regulating formation of the glomerular tuft. Recently, a second CXCL12 receptor was identified and designated CXCR7. Although it is established that CXCR7 regulates heart and brain development in conjunction with CXCL12 and CXCR4, little is known about the influence of CXCR7 on CXCL12 dependent kidney development.Methodology/Principal Findings
We provided analysis of CXCR7 expression and function in the developing mouse kidney. Using in situ hybridization, we identified CXCR7 mRNA in epithelial cells including podocytes at all nephron stages up to the mature glomerulus. CXCL12 mRNA showed a striking overlap with CXCR7 mRNA in epithelial structures. In addition, CXCL12 was detected in stromal cells and the glomerular tuft. Expression of CXCR4 was complementary to that of CXCR7 as it occurred in mesenchymal cells, outgrowing ureteric buds and glomerular endothelial cells but not in podocytes. Kidney examination in CXCR7 null mice revealed ballooning of glomerular capillaries as described earlier for CXCR4 null mice. Moreover, we detected a severe reduction of CXCR4 protein but not CXCR4 mRNA within the glomerular tuft and in the condensed mesenchyme. Malformation of the glomerular tuft in CXCR7 null mice was associated with mesangial cell clumping.Conclusions/Significance
We established that there is a similar glomerular pathology in CXCR7 and CXCR4 null embryos. Based on the phenotype and the anatomical organization of the CXCL12/CXCR4/CXCR7 system in the forming glomerulus, we propose that CXCR7 fine-tunes CXCL12/CXCR4 mediated signalling between podocytes and glomerular capillaries. 相似文献72.
Villar S Ortiz-Cuaran S Abedi-Ardekani B Gouas D Nogueira da Costa A Plymoth A Khuhaprema T Kalalak A Sangrajrang S Friesen MD Groopman JD Hainaut P 《PloS one》2012,7(6):e37707
Primary Liver Cancer (PLC) is the leading cause of death by cancer among males in Thailand and the 3(rd) among females. Most cases are hepatocellular carcinoma (HCC) but cholangiocarcinomas represent between 4 and 80% of liver cancers depending upon geographic area. Most HCC are associated with chronic infection by Hepatitis B Virus while a G → T mutation at codon 249 of the TP53 gene, R249S, specific for exposure to aflatoxin, is detected in tumors for up to 30% of cases. We have used Short Oligonucleotide Mass Analysis (SOMA) to quantify free circulating R249S-mutated DNA in plasma using blood specimens collected in a hospital case:control study. Plasma R249S-mutated DNA was detectable at low concentrations (≥ 67 copies/mL) in 53 to 64% of patients with primary liver cancer or chronic liver disease and in 19% of controls. 44% of patients with HCC and no evidence of cirrhosis had plasma concentrations of R249S-mutated DNA ≥ 150 copies/mL, compared to 21% in patients with both HCC and cirrhosis, 22% in patients with cholangiocarcinoma, 12% in patients with non-cancer chronic liver disease and 3% of subjects in the reference group. Thus, plasma concentrations of R249S-mutated DNA ≥ 150 copies/mL tended to be more common in patients with HCC developing without pre-existing cirrhosis (p = 0.027). Overall, these results support the preferential occurrence of R249S-mutated DNA in HCC developing in the absence of cirrhosis in a context of HBV chronic infection. 相似文献
73.
Understanding the principles of calmodulin (CaM) activation of target enzymes will help delineate how this seemingly simple molecule can play such a complex role in transducing Ca (2+)-signals to a variety of downstream pathways. In the work reported here, we use biochemical and biophysical tools and a panel of CaM constructs to examine the lobe specific interactions between CaM and CaMKII necessary for the activation and autophosphorylation of the enzyme. Interestingly, the N-terminal lobe of CaM by itself was able to partially activate and allow autophosphorylation of CaMKII while the C-terminal lobe was inactive. When used together, CaMN and CaMC produced maximal CaMKII activation and autophosphorylation. Moreover, CaMNN and CaMCC (chimeras of the two N- or C-terminal lobes) both activated the kinase but with greater K act than for wtCaM. Isothermal titration calorimetry experiments showed the same rank order of affinities of wtCaM > CaMNN > CaMCC as those determined in the activity assay and that the CaM to CaMKII subunit binding ratio was 1:1. Together, our results lead to a proposed sequential mechanism to describe the activation pathway of CaMKII led by binding of the N-lobe followed by the C-lobe. This mechanism contrasts the typical sequential binding mode of CaM with other CaM-dependent enzymes, where the C-lobe of CaM binds first. The consequence of such lobe specific binding mechanisms is discussed in relation to the differential rates of Ca (2+)-binding to each lobe of CaM during intracellular Ca (2+) oscillations. 相似文献
74.
Substrate cleavage analysis of furin and related proprotein convertases. A comparative study 总被引:2,自引:0,他引:2
Remacle AG Shiryaev SA Oh ES Cieplak P Srinivasan A Wei G Liddington RC Ratnikov BI Parent A Desjardins R Day R Smith JW Lebl M Strongin AY 《The Journal of biological chemistry》2008,283(30):20897-20906
We present the data and the technology, a combination of which allows us to determine the identity of proprotein convertases (PCs) related to the processing of specific protein targets including viral and bacterial pathogens. Our results, which support and extend the data of other laboratories, are required for the design of effective inhibitors of PCs because, in general, an inhibitor design starts with a specific substrate. Seven proteinases of the human PC family cleave the multibasic motifs R-X-(R/K/X)-R downward arrow and, as a result, transform proproteins, including those from pathogens, into biologically active proteins and peptides. The precise cleavage preferences of PCs have not been known in sufficient detail; hence we were unable to determine the relative importance of the individual PCs in infectious diseases, thus making the design of specific inhibitors exceedingly difficult. To determine the cleavage preferences of PCs in more detail, we evaluated the relative efficiency of furin, PC2, PC4, PC5/6, PC7, and PACE4 in cleaving over 100 decapeptide sequences representing the R-X-(R/K/X)-R downward arrow motifs of human, bacterial, and viral proteins. Our computer analysis of the data and the follow-on cleavage analysis of the selected full-length proteins corroborated our initial results thus allowing us to determine the cleavage preferences of the PCs and to suggest which PCs are promising drug targets in infectious diseases. Our results also suggest that pathogens, including anthrax PA83 and the avian influenza A H5N1 (bird flu) hemagglutinin precursor, evolved to be as sensitive to PC proteolysis as the most sensitive normal human proteins. 相似文献
75.
The thyroid hormone receptor-alpha (TRalpha) gene encoding TRalpha1 controls deoxyribonucleic acid damage-induced tissue repair 总被引:1,自引:0,他引:1
Kress E Rezza A Nadjar J Samarut J Plateroti M 《Molecular endocrinology (Baltimore, Md.)》2008,22(1):47-55
The thyroid hormone (TH) controls, via its nuclear receptor, TH receptor-alpha1 (TRalpha1), intestinal crypt cell proliferation in the mouse. In order to understand whether this receptor also plays a role in intestinal regeneration after DNA damage, we applied a protocol of gamma-ray irradiation and monitored cell proliferation and apoptosis at several time points. In wild-type mice, the dose of 8 Gy induced cell cycle arrest and apoptosis in intestinal crypts a few hours after irradiation. This phenomenon reverted 48 h after irradiation. TRalpha(0/0) mutant mice displayed a constant low level of proliferating cells and a high apoptosis rate during the period of study. At the molecular level, in TRalpha(0/0) animals we observed a delay in the p53 phosphorylation induced by DNA damage. In our search for the expression of the protein kinases responsible for p53 phosphorylation upon irradiation, we have focused on DNA-dependent protein kinase catalytic subunit (DNA-PKcs). The number of cells expressing DNA-PKcs in crypts remained high 48 h after irradiation, specifically in TRalpha mutants. Altogether, in TRalpha(0/0) animals the rate of apoptosis in crypt cells remained high, apparently due to an elevated number of cells still presenting DNA damage. In conclusion, the TRalpha gene plays a role in crypt cell homeostasis by regulating the rate of cell renewal and apoptosis induced by DNA damage. 相似文献
76.
Seifert L Chehensse A Tourny-Chollet C Lemaitre F Chollet D 《Journal of strength and conditioning research / National Strength & Conditioning Association》2008,22(5):1670-1676
This study analyzed the relationship between breathing pattern and arm coordination symmetry in 11 expert male swimmers who performed the front crawl at their 100-m race pace using seven randomized breathing patterns. Two indexes of coordination (IdCP and IdCNP) and a symmetry index (SI) based on the difference of IdCP - IdCNP were calculated. IdCP calculated the lag time between the beginning of arm propulsion on the nonpreferential breathing side and the end of arm propulsion on the preferential breathing side; IdCNP did the converse. The IdCP and IdCNP comparisons and the SI showed coordination asymmetries among the seven breathing patterns. Specifically, breathing to the preferential side led to an asymmetry, in contrast to the other breathing patterns, and the asymmetry was even greater when the swimmer breathed to his nonpreferential side. These findings highlight the effect of breathing laterality in that coordination was symmetric in patterns with breathing that was bilateral, axed (as in breathing with a frontal snorkel), or removed (as in apnea). One practical application is that arm coordination asymmetry can be prevented or reduced by using breathing patterns that balance the coordination. 相似文献
77.
Drosophila suzukii Matsumura (Diptera: Drosophilidae) is a harmful invasive fruit pest, which is currently spreading in Europe. Since its arrival in 2008, the spotted wing drosophila has caused major losses in several soft-skinned fruit crops. This critical situation urgently requires efficient practices of residue-free pest control. In the present laboratory study, entomopathogenic nematodes (EPNs) were investigated for their ability to infect larvae and pupae of D. suzukii within directly sprayed fruit, fruit placed on soil, and soil. Steinernema feltiae Filipjev (Rhabditida: Steinernematidae), and Steinernema carpocapsae Weiser (Rhabditida: Steinernematidae) were more efficient at infecting soil-pupating host larvae than Heterorhabditis bacteriophora Poinar (Rhabditida: Heterorhabditidae) at application rates ranging from 25 to 400 EPN cm?2. Applied as a soil drench, S. feltiae and S. carpocapsae were able to infect D. suzukii larvae in the soil as well as hidden inside fruit. Direct application of EPNs on the fruit was less successful, although emergence of flies was significantly reduced. 相似文献
78.
79.
Francois-Didier Boyer Alexandre de Saint Germain Jean-Bernard Pouvreau Guillaume Clave Jean-Paul Pillot Amelie Roux Amanda Rasmussen Stephen Depuydt Dominique Lauresserguesh Nicolas Frei dit Frey Thomas S.A. Heugebaert Christian V. Stevens Danny Geelen Sofie Goormachtig Catherine Rameau 《植物生理与分子生物学学报》2014,(4):675-690
Strigolactones (SLs) are known not only as plant hormones, but also as rhizosphere signals for establishing symbiotic and parasitic interactions. The design of new specific SL analogs is a challenging goal in understanding the basic plant biology and is also useful to control plant architectures without favoring the development of parasitic plants. Two different molecules (23 (3'-methyI-GR24), 31 (thia-3'-methyl-debranone-like molecule)) already described, and a new one (AR36), for which the synthesis is presented, are biologically compared with the well-known GR24 and the recently identified CISA-1. These different structures emphasize the wide range of parts attached to the D-ring for the bioactivity as a plant hormone. These new compounds possess a common dimethylbutenolide motif but their structure varies in the ABC part of the molecules: 23 has the same ABC part as GR24, while 31 and AR36 carry, respectively, an aromatic ring and an acyclic carbon chain. Detailed information is given for the bioactivity of such derivatives in strigolactone synthesis or in perception mutant plants (pea rmsl and rms4, Arabidopsis max2 and, max4) for different hormonal functions along with their action in the rhizosphere on arbuscular mycorrhizal hyphal growth and parasitic weed germination. 相似文献
80.
Stephen J Kolb Amelie K Gubitz Robert F Olszewski Jr Elizabeth Ottinger Charlotte J Sumner Kenneth H Fischbeck Gideon Dreyfuss 《BMC neurology》2006,6(1):6-5