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151.
Induced Levels of Heat Shock Proteins in a dnaK Mutant of Lactococcus lactis 总被引:1,自引:0,他引:1
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Birgit Koch Mogens Kilstrup Finn K. Vogensen Karin Hammer 《Journal of bacteriology》1998,180(15):3873-3881
The bacterial heat shock response is characterized by the elevated expression of a number of chaperone complexes and proteases, including the DnaK-GrpE-DnaJ and the GroELS chaperone complexes. In order to investigate the importance of the DnaK chaperone complex for growth and heat shock response regulation in Lactococcus lactis, we have constructed two dnaK mutants with C-terminal deletions in dnaK. The minor deletion of 65 amino acids in the dnaKΔ2 mutant resulted in a slight temperature-sensitive phenotype. BK6, containing the larger deletion of 174 amino acids (dnaKΔ1), removing the major part of the inferred substrate binding site of the DnaK protein, exhibited a pronounced temperature-sensitive phenotype and showed altered regulation of the heat shock response. The expression of the heat shock proteins was increased at the normal growth temperature, measured as both protein synthesis rates and mRNA levels, indicating that DnaK could be involved in the regulation of the heat shock response in L. lactis. For Bacillus subtilis, it has been found (A. Mogk, G. Homuth, C. Scholz, L. Kim, F. X. Schmid, and W. Schumann, EMBO J. 16:4579–4590, 1997) that the activity of the heat shock repressor HrcA is dependent on the chaperone function of the GroELS complex and that a dnaK insertion mutant has no effect on the expression of the heat shock proteins. The present data from L. lactis suggest that the DnaK protein could be involved in the maturation of the homologous HrcA protein in this bacterium. 相似文献
152.
Claudia S. Bauer Christoph Plieth Birgit Bethmann Ondina Popescu Ulf-Peter Hansen Wilhelm Simonis Gerald Sch?nknecht 《Plant physiology》1998,117(2):545-557
The divalent cation Sr2+ induced repetitive transient spikes of the cytosolic Ca2+ activity [Ca2+]cy and parallel repetitive transient hyperpolarizations of the plasma membrane in the unicellular green alga Eremosphaera viridis. [Ca2+]cy measurements, membrane potential measurements, and cation analysis of the cells were used to elucidate the mechanism of Sr2+-induced [Ca2+]cy oscillations. Sr2+ was effectively and rapidly compartmentalized within the cell, probably into the vacuole. The [Ca2+]cy oscillations cause membrane potential oscillations, and not the reverse. The endoplasmic reticulum (ER) Ca2+-ATPase blockers 2,5-di-tert-butylhydroquinone and cyclopiazonic acid inhibited Sr2+-induced repetitive [Ca2+]cy spikes, whereas the compartmentalization of Sr2+ was not influenced. A repetitive Ca2+ release and Ca2+ re-uptake by the ER probably generated repetitive [Ca2+]cy spikes in E. viridis in the presence of Sr2+. The inhibitory effect of ruthenium red and ryanodine indicated that the Sr2+-induced Ca2+ release from the ER was mediated by a ryanodine/cyclic ADP-ribose type of Ca2+ channel. The blockage of Sr2+-induced repetitive [Ca2+]cy spikes by La3+ or Gd3+ indicated the necessity of a certain influx of divalent cations for sustained [Ca2+]cy oscillations. Based on these data we present a mathematical model that describes the baseline spiking [Ca2+]cy oscillations in E. viridis. 相似文献
153.
FSH and testosterone exert different regulatory effects on the seminiferous epithelium; they act through multiple and complex signaling routes to direct the development of the germ cells into mature spermatozoa. In addition to their well-known pathways of action, both hormones have recently been recognized to have new signaling routes that are linked to the Ca(2+) ion, including, among others, the regulation of cell proliferation by FSH and the regulation of cell migration by testosterone. 相似文献
154.
Ceftaroline is a new cephalosporin active against Methicillin-resistant Staphylococcus aureus (MRSA). Based on a representative collection of clinical S. aureus isolates from Germany, supplemented with isolates of clonal lineages ST228 and ST239, we demonstrate the in-vitro susceptibility towards ceftaroline prior to its introduction into clinical use for a total of 219 isolates. Susceptibility testing was performed by broth microdilution, disc diffusion and Etest, respectively. Results were interpreted according to EUCAST guidelines and showed considerable variance in dependence on clonal affiliation of the isolates tested. Among isolates of widespread hospital-associated lineages we found a high proportion of clinical isolates with MICs close to the EUCAST breakpoint (MIC50/90 1.0/1.5 mg/L); currently, interpretation of these “borderline” MICs is complicated by a lack of concordant susceptibility testing methods and reasonable breakpoint determination. Isolates of clonal lineages ST228 and ST239 demonstrated increased MIC50/90 values of 2.5/3.33 mg/L. Sequencing of mecA revealed no association of resistance to a specific mecA polymorphism, but rather reveals two regions in the non-penicillin-binding domain of PbP2a which displayed different combinations of mutations putatively involved in resistance development. This study provides national baseline data to (i) adjust susceptibility testing methods and current breakpoints to clinical and epidemiological requirements, (ii) evaluate current breakpoints with respect to therapeutic outcome and (iii) monitor further resistance evolution. 相似文献
155.
156.
Genomic Resources Development Consortium Wolfgang Arthofer Laura Bertini Carla Caruso Francesco Cicconardi Lynda F. Delph Peter D. Fields Minoru Ikeda Yuki Minegishi Silvia Proietti Heike Ritthammer Birgit C. Schlick‐Steiner Florian M. Steiner Gregor A. Wachter Herbert C. Wagner Laura A. Weingartner 《Molecular ecology resources》2015,15(4):1014-1015
157.
Genomic Resources Development Consortium P. Álvarez Wolfgang Arthofer Maria M. Coelho D. Conklin A. Estonba Ana R. Grosso S. J. Helyar J. Langa Miguel P. Machado I. Montes Joana Pinho Alexander Rief Manfred Schartl Birgit C. Schlick‐Steiner Julia Seeber Florian M. Steiner C. Vilas 《Molecular ecology resources》2015,15(6):1510-1512
158.
Jun Wang Tobias Sinnberg Heike Niessner Rebecca Dölker Birgit Sauer Wolfgang E. Kempf Friedegund Meier Nick Leslie Birgit Schittek 《Pigment cell & melanoma research》2015,28(5):572-589
Inhibition of the mitogen‐activated protein kinase (MAPK) pathway is a major advance in the treatment of metastatic melanoma. However, its therapeutic success is limited by the rapid emergence of drug resistance. The insulin‐like growth factor‐1 receptor (IGF‐1R) is overexpressed in melanomas developing resistance toward the BRAFV600 inhibitor vemurafenib. Here, we show that hyperactivation of BRAF enhances IGF‐1R expression. In addition, the phosphatase activity of PTEN as well as heterocellular contact to stromal cells increases IGF‐1R expression in melanoma cells and enhances resistance to vemurafenib. Interestingly, PTEN‐negative melanoma cells escape IGF‐1R blockade by decreased expression of the receptor, implicating that only in melanoma patients with PTEN‐positive tumors treatment with IGF‐1R inhibitors would be a suitable strategy to combat therapy resistance. Our data emphasize the crosstalk and therapeutic relevance of microenvironmental and tumor cell‐autonomous mechanisms in regulating IGF‐1R expression and by this sensitivity toward targeted therapies. 相似文献
159.
160.
Jorge Esparza-Gordillo Anja Matanovic Ingo Marenholz Anja Bauerfeind Klaus Rohde Katja Nemat Min-Ae Lee-Kirsch Magnus Nordenskj?ld Marten C. G. Winge Thomas Keil Renate Krüger Susanne Lau Kirsten Beyer Birgit Kalb Bodo Niggemann Norbert Hübner Heather J. Cordell Maria Bradley Young-Ae Lee 《PLoS genetics》2015,11(3)
Epidemiological studies suggest that allergy risk is preferentially transmitted through mothers. This can be due to genomic imprinting, where the phenotype effect of an allele depends on its parental origin, or due to maternal effects reflecting the maternal genome''s influence on the child during prenatal development. Loss-of-function mutations in the filaggrin gene (FLG) cause skin barrier deficiency and strongly predispose to atopic dermatitis (AD). We investigated the 4 most prevalent European FLG mutations (c.2282del4, p.R501X, p.R2447X, and p.S3247X) in two samples including 759 and 450 AD families. We used the multinomial and maximum-likelihood approach implemented in the PREMIM/EMIM tool to model parent-of-origin effects. Beyond the known role of FLG inheritance in AD (R1meta-analysis = 2.4, P = 1.0 x 10−36), we observed a strong maternal FLG genotype effect that was consistent in both independent family sets and for all 4 mutations analysed. Overall, children of FLG-carrier mothers had a 1.5-fold increased AD risk (S1 = 1.50, Pmeta-analysis = 8.4 x 10−8). Our data point to two independent and additive effects of FLG mutations: i) carrying a mutation and ii) having a mutation carrier mother. The maternal genotype effect was independent of mutation inheritance and can be seen as a non-genetic transmission of a genetic effect. The FLG maternal effect was observed only when mothers had allergic sensitization (elevated allergen-specific IgE antibody plasma levels), suggesting that FLG mutation-induced systemic immune responses in the mother may influence AD risk in the child. Notably, the maternal effect reported here was stronger than most common genetic risk factors for AD recently identified through genome-wide association studies (GWAS). Our study highlights the power of family-based studies in the identification of new etiological mechanisms and reveals, for the first time, a direct influence of the maternal genotype on the offspring’s susceptibility to a common human disease. 相似文献