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101.
Pradel N Santini CL Ye CY Fevat L Gérard F Alami M Wu LF 《Biochemical and biophysical research communications》2003,306(3):786-791
Proteins are exported across the bacterial cytoplasmic membrane either as unfolded precursors via the Sec machinery or in folded conformation via the Tat system. The ribose-binding protein (RBP) of Escherichia coli is a Sec-pathway substrate. Intriguingly, it exhibits fast folding kinetics and its export is independent of SecB, a general chaperone protein dedicated for protein secretion. In this study, we found that the quantity of RBP was significantly reduced in the periplasm of tat mutants, which was restored by in trans expression of the tatABC genes. Pulse-chase experiments showed that significant amount of wild-type RBP was processed in a secY mutant in the presence of azide (SecA inhibitor), whereas the processing of a slow folding RBP derivative was almost completely blocked under the same conditions. These results would suggest that under the Sec-defective conditions the export of a portion of folded RBP could be rescued by the Tat system. 相似文献
102.
Meriem Bennabi Richard Delorme José Oliveira Catherine Fortier Mohamed Lajnef Wahid Boukouaci Jean-Paul Feugeas Fran?ois Marzais Alexandru Gaman Dominique Charron Bijan Ghaleh Rajagopal Krishnamoorthy Marion Leboyer Ryad Tamouza 《PloS one》2015,10(9)
Introduction
In autism spectrum disorders (ASD), complex gene-environment interactions contribute to disease onset and progress. Given that gastro-intestinal dysfunctions are common in ASD, we postulated involvement of microbial dysbiosis in ASD and investigated, under a case-control design, the influence of DNA polymorphisms in the CLEC7A gene that encodes a pivotal fungal sensor, Dectin-1.Material and methods
DNAs from 478 ASD patients and 351 healthy controls (HC) were analyzed for the CLEC7A rs16910631G/A and rs2078178 A/G single nucleotide polymorphisms (SNPs). Differences in the distribution of allele, genotype and haplotype by Chi-square testing and nonparametric analysis by Kruskal-Wallis/Mann–Whitney tests, where appropriate, were performed. The free statistical package R.2.13 software was used for the statistical analysis.Results
We found that the CLEC7A rs2078178 G allele and GG genotype were more prevalent in HC as compared to ASD but failed to reach statistical significance for the latter (pc = 0.01, 0.06 respectively). However, after phenotype-based stratification, the CLEC7A rs2078178 G allele and GG genotype were found to be significantly more frequent in the Asperger group as compared to other ASD subsets (pc = 0.02, 0.01), a finding reinforced by haplotype analysis (rs2078178/rs16910631 G-G/G-G) (pc = 0.002). Further, intellectual quotient (IQ)-based stratification of ASD patients revealed that IQ values increase linearly along the CLEC7A rs2078178 AA, AG and GG genotypes (p = 0.05) and in a recessive manner (GG vs. AA+AG p = 0.02), further confirmed by haplotype distribution (CLEC7A rs2078178-16910631; A-G/A-G, A-G/G-G and G-G/G-G, p = 0.02, G-G/G-G vs. others, p = 0.01).Conclusion
Our data suggest that the genetic diversity of CLEC7A gene influences the ASD phenotype by behaving as a disease specifier and imply that the genetic control of innate immune response could determine the ASD phenotype. 相似文献103.
José Oliveira Bruno Etain Mohamed Lajnef Nora Hamdani Meriem Bennabi Djaouida Bengoufa Aparna Sundaresh Arij Ben Chaabane Frank Bellivier Chantal Henry Jean-Pierre Kahn Dominique Charron Rajagopal Krishnamoorthy Marion Leboyer Ryad Tamouza 《PloS one》2015,10(3)
Gene-environment interactions may play an important role in modulating the impact of early-life stressful events on the clinical course of bipolar disorder (BD), particularly associated to early age at onset. Immune dysfunction is thought to be an important mechanism linking childhood trauma with early-onset BD, thus the genetic diversity of immune-related loci may account for an important part of the interindividual susceptibility to this severe subform. Here we investigated the potential interaction between genetic variants of Toll-like receptors 2 (TLR2) and 4 (TLR4), major innate immune response molecules to pathogens, and the childhood trauma questionnaire (CTQ) in age at onset of BD. We recruited 531 BD patients (type I and II or not otherwise specified), genotyped for the TLR2 rs4696480 and rs3804099 and TLR4 rs1927914 and rs11536891 single-nucleotide polymorphisms and recorded for history of childhood trauma using the CTQ. TLR2 and TLR4 risk genotype carrier state and history of childhood emotional, physical and sexual abuses were evaluated in relation to age at onset as defined by the age at first manic or depressive episode. We observed a combined effect of TLR2 rs3804099 TT genotype and reported sexual abuse on determining an earlier age at onset of BD by means of a Kaplan-Meier survival curve (p = 0.002; corrected p = 0.02). Regression analysis, however, was non-significant for the TLR2-CTQ sexual abuse interaction term. The negative effects of childhood sexual abuse on age at onset of BD may be amplified in TLR2 rs3804099 risk genotype carriers through immune-mediated pathways. Clinical characteristics of illness severity, immune phenotypes and history of early life infectious insults should be included in future studies involving large patient cohorts. 相似文献
104.
Meriem Khairoun Mieke van den Heuvel Bernard M. van den Berg Oana Sorop Rients de Boer Nienke S. van Ditzhuijzen Ingeborg M. Bajema Hans J. Baelde Malu Zandbergen Dirk J. Duncker Ton J. Rabelink Marlies E. J. Reinders Wim J. van der Giessen Joris I. Rotmans 《PloS one》2015,10(4)
Background
Diabetes mellitus (DM) is associated with a range of microvascular complications including diabetic nephropathy (DN). Microvascular abnormalities in the kidneys are common histopathologic findings in DN, which represent one manifestation of ongoing systemic microvascular damage. Recently, sidestream dark-field (SDF) imaging has emerged as a noninvasive tool that enables one to visualize the microcirculation. In this study, we investigated whether changes in the systemic microvasculature induced by DM and an atherogenic diet correlated spatiotemporally with renal damage.Methods
Atherosclerotic lesion development was triggered in streptozotocin-induced DM pigs (140 mg/kg body weight) by administering an atherogenic diet for approximately 11 months. Fifteen months following induction of DM, microvascular morphology was visualized in control pigs (n = 7), non-diabetic pigs fed an atherogenic diet (ATH, n = 5), and DM pigs fed an atherogenic diet (DM+ATH, n = 5) using SDF imaging of oral mucosal tissue. Subsequently, kidneys were harvested from anethesized pigs and the expression levels of well-established markers for microvascular integrity, such as Angiopoietin-1 (Angpt1) and Angiopoietin-2 (Angpt2) were determined immunohistochemically, while endothelial cell (EC) abundance was determined by immunostaining for von Willebrand factor (vWF).Results
Our study revealed an increase in the capillary tortuosity index in DM+ATH pigs (2.31±0.17) as compared to the control groups (Controls 0.89±0.08 and ATH 1.55±0.11; p<0.05). Kidney biopsies showed marked glomerular lesions consisting of mesangial expansion and podocyte lesions. Furthermore, we observed a disturbed Angpt2/ Angpt1balance in the cortex of the kidney, as evidenced by increased expression of Angpt2 in DM+ATH pigs as compared to Control pigs (p<0.05).Conclusion
In the setting of DM, atherogenesis leads to the augmentation of mucosal capillary tortuosity, indicative of systemic microvascular damage. Concomitantly, a dysbalance in renal angiopoietins was correlated with the development of diabetic nephropathy. As such, our studies strongly suggest that defects in the systemic microvasculature mirror the accumulation of microvascular damage in the kidney. 相似文献105.
Sonia Jemli Mamdouh Ben-Ali Hajer Ben-Hlima Bassem Khemakhem Samir Bejar 《Biologia》2012,67(4):636-643
The cyclodextrin glucanotransferase from Paenibacillus pabuli US132 (US132 CGTase) was engineered using a rational approach in an attempt to provide it with anti-staling properties comparable to those of the commercial maltogenic amylase (Novamyl). The study aimed to concurrently decrease the cyclization activity and increase the hydrolytic activity of US132 CGTase. A five-residue loop (PAGFS) was inserted, alone or with the substitution of essential residues for cyclization (G180, L194 and Y195), mimicking the case of Novamyl. The findings indicate that, unlike the case of the CGTase of Thermoanerobacterium thermosulfurigenes strain EM1 whose initial high hydrolytic activity was exceptional, these mutations completely abolished the cyclization and hydrolytic activities of the US132 CGTase. This suggests that those mutations are not able to convert conventional CGTases, whose hydrolytic activities are very weak, into hydrolases. Accordingly, and for the first time, a structural barrier at subsite ?3 was advanced as an influential factor which might explain the low hydrolytic activity of conventional CGTases. 相似文献
106.
107.
Changes in vessel anatomy in response to mechanical loading in six species of tropical trees 总被引:3,自引:0,他引:3
It is well known that trees adapt their supportive tissues to changes in loading conditions, yet little is known about how the vascular anatomy is modified in this process. We investigated this by comparing more and less mechanically loaded sections in six species of tropical trees with two different rooting morphologies. We measured the strain, vessel size, frequency and area fraction and from this calculated the specific conductivity, then measured the conductivity, modulus of elasticity and yield stress. The smallest vessels and the lowest vessel frequency were found in the parts of the trees subjected to the greatest stresses or strains. The specific conductivity varied up to two orders of magnitude between mechanically loaded and mechanically unimportant parts of the root system. A trade-off between conductivity and stiffness or strength was revealed, which suggests that anatomical alterations occur in response to mechanical strain. By contrast, between-tree comparisons showed that average anatomical features for the whole tree seemed more closely related to their ecological strategy. 相似文献
108.
Nolivos S Touzain F Pages C Coddeville M Rousseau P El Karoui M Le Bourgeois P Cornet F 《Nucleic acids research》2012,40(12):5535-5545
Bacteria use the global bipolarization of their chromosomes into replichores to control the dynamics and segregation of their genome during the cell cycle. This involves the control of protein activities by recognition of specific short DNA motifs whose orientation along the chromosome is highly skewed. The KOPS motifs act in chromosome segregation by orienting the activity of the FtsK DNA translocase towards the terminal replichore junction. KOPS motifs have been identified in γ-Proteobacteria and in Bacillus subtilis as closely related G-rich octamers. We have identified the KOPS motif of Lactococcus lactis, a model bacteria of the Streptococcaceae family harbouring a compact and low GC% genome. This motif, 5'-GAAGAAG-3, was predicted in silico using the occurrence and skew characteristics of known KOPS motifs. We show that it is specifically recognized by L. lactis FtsK in vitro and controls its activity in vivo. L. lactis KOPS is thus an A-rich heptamer motif. Our results show that KOPS-controlled chromosome segregation is conserved in Streptococcaceae but that KOPS may show important variation in sequence and length between bacterial families. This suggests that FtsK adapts to its host genome by selecting motifs with convenient occurrence frequencies and orientation skews to orient its activity. 相似文献
109.
? Premise of the study: Gravitropic movements are unexpected mechanical processes that could disturb tree design allometries derived from the physics of nonliving bodies. We investigated whether the scaling law of gravitropic performance (power of -2 of stem diameter) derived from integrative biomechanical modeling is disturbed by ontogeny or environment, then discuss the silvicultural and dendroecological consequences. ? Methods: In a beech (Fagus sylvatica) plantation, four plots with different initial planting densities evolved without any intervention for 26 yr. Regular tree inventories and a silvicultural model were used to monitor competition over time in each plot. The radial production of tension wood was quantified using a cross-section of the stems at 1.30-m height, and an integrative biomechanical model computed the tree gravitropic performance over time. ? Key results: All trees developed tension wood over the whole period, with higher amounts at the youngest age, resulting in theoretical lean corrections of ca. 20-30° on the first 4 m of the stem over the whole period. The scaling law of gravitropic performance is slightly larger than the power of -2 of stem diameter. ? Conclusions: Gravitropic performance in forest ecosystems is mainly limited by size (diameter). Ontogenic acclimation of tension wood formation allows the youngest trees to be more reactive. No additional effect of spacing was found. However, silviculture influences size and, therefore, tree reactivity at a given age. Such results will be helpful for dendroecological approaches that use wood as a marker of environmental disturbances or a trait linked to plant strategies. 相似文献