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Antibiotic resistance is a major challenge to modern medicine. Intraspecies and interspecies dissemination of antibiotic resistance genes among bacteria can occur through horizontal gene transfer. Competence-mediated gene transfer has been reported to contribute to the spread of antibiotic resistance genes in Streptococcus pneumoniae. Induction of the competence regulon is mediated by a 17-amino acid peptide pheromone called the competence stimulating peptide (CSP). Thus, synthetic analogs that competitively inhibit CSPs may reduce horizontal gene transfer. We performed saturated alanine scanning mutagenesis and other amino acid substitutions on CSP1 to screen for analogs that disable genetic transformation in S. pneumoniae. Substitution of the glutamate residue at the first position created analogs that could competitively inhibit CSP1-mediated competence development in a concentration-dependent manner. Additional substitutions of the negatively-charged glutamate residue with amino acids of different charge, acidity and hydrophobicity, as well as enantiomeric D-glutamate, generated analogs that efficiently outcompeted CSP1, suggesting the importance of negative charge and enantiomericity of the first glutamate residue for the function of CSP1. Collectively, these results indicate that glutamate residue at the first position is important for the ability of CSP1 to induce ComD, but is dispensable for the peptide to bind the receptor. Furthermore, these results demonstrate the potential applicability of competitive CSP analogs to control horizontal transfer of antibiotic resistance genes in S. pneumoniae. 相似文献
854.
Rongxue Zhang Hong Chen Mei Duan Fugui Zhu Jiangqi Wen Jiangli Dong Tao Wang 《The Plant journal : for cell and molecular biology》2019,98(4):680-696
Recent studies on E3 of endoplasmic reticulum (ER)‐associated degradation (ERAD) in plants have revealed homologs in yeast and animals. However, it remains unknown whether the plant ERAD system contains a plant‐specific E3 ligase. Here, we report that MfSTMIR, which encodes an ER‐membrane‐localized RING E3 ligase that is highly conserved in leguminous plants, plays essential roles in the response of ER and salt stress in Medicago. MfSTMIR expression was induced by salt and tunicamycin (Tm). mtstmir loss‐of‐function mutants displayed impaired induction of the ER stress‐responsive genes BiP1/2 and BiP3 under Tm treatment and sensitivity to salt stress. MfSTMIR promoted the degradation of a known ERAD substrate, CPY*. MfSTMIR interacted with the ERAD‐associated ubiquitin‐conjugating enzyme MtUBC32 and Sec61‐translocon subunit MtSec61γ. MfSTMIR did not affect MtSec61γ protein stability. Our results suggest that the plant‐specific E3 ligase MfSTMIR participates in the ERAD pathway by interacting with MtUBC32 and MtSec61γ to relieve ER stress during salt stress. 相似文献
855.
Dong-Ning Gao Yang Yang Qiang Yan Xiao-Yun Wang Wen-Shan Duan 《Plasma Physics Reports》2017,43(2):212-217
Theoretical studies are carried out for ion acoustic solitons in multicomponent nonuniform plasma considering the dust size distribution. The Korteweg?de Vries equation for ion acoustic solitons is given by using the reductive perturbation technique. Two special dust size distributions are considered. The dependences of the width and amplitude of solitons on dust size parameters are shown. It is found that the properties of a solitary wave depend on the shape of the size distribution function of dust grains. 相似文献
856.
In a study to evaluate the structural elements essential for the antidiabetic activity of flavonoids, we synthesized two series of flavonoids, 5,7‐dihydroxyflavanones and 5,7‐dihydroxyflavones. In a screening for potential antidiabetic activity, most of the flavonoids showed a remarkable in vitro activity, and compounds 1f, 2d , and 3c were significantly more effective than the positive control, metformin. The biological activity was mainly affected by structural modification at the ring B moiety of the flavonoid skeleton. The results suggest that 5,7‐dihydroxyflavonoids can be considered as promising candidates in the development of new antidiabetic lead compounds. 相似文献
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858.
Inhibition of Telomere Recombination by Inactivation of KEOPS Subunit Cgi121 Promotes Cell Longevity
DNA double strand break (DSB) is one of the major damages that cause genome instability and cellular aging. The homologous recombination (HR)-mediated repair of DSBs plays an essential role in assurance of genome stability and cell longevity. Telomeres resemble DSBs and are competent for HR. Here we show that in budding yeast Saccharomyces cerevisiae telomere recombination elicits genome instability and accelerates cellular aging. Inactivation of KEOPS subunit Cgi121 specifically inhibits telomere recombination, and significantly extends cell longevity in both telomerase-positive and pre-senescing telomerase-negative cells. Deletion of CGI121 in the short-lived yku80tel mutant restores lifespan to cgi121Δ level, supporting the function of Cgi121 in telomeric single-stranded DNA generation and thus in promotion of telomere recombination. Strikingly, inhibition of telomere recombination is able to further slow down the aging process in long-lived fob1Δ cells, in which rDNA recombination is restrained. Our study indicates that HR activity at telomeres interferes with telomerase to pose a negative impact on cellular longevity. 相似文献
859.
M. Xu W. Duan P. G. Fan B. H. Wu L. J. Wang L. Ma D. D. Archbold S. H. Li 《Russian Journal of Plant Physiology》2014,61(3):397-408
Low sink demand provided by pod removal and stem girdling of beans (Vicia faba, cv. Daqingshan) (-Sink) induced a significantly lower net photosynthetic rate (P n), stomatal conductance (g s), internal CO2 concentration (C i), and transpiration rate (E) compared with pod and root sink retention (CK). This depression in P n was due to stomatal limitation. Low sink demand of -Sink plants resulted in a higher leaf sucrose content, but a lower sucrose content in guard cells. Moreover, the significant accumulation of H2O2 and ABA were observed in both leaves and guard cells of -Sink plants. The most intensive electron dense deposit of cerium perhydroxides, produced by H2O2 reaction with cerium chloride, was present in the cell walls, especially the dorsal walls of guard cells. Immunogold electron-microscopy localization of ABA showed that ABA was distributed in ventral walls of guard cells and the intercellular space of mesophyll cells of -Sink leaves in contrast to CK plants. Application of exogenous sucrose to isolated bean leaves increased H2O2 and ABA contents. H2O2 and ABA in leaves was likely generated by two independently regulated pathways, each affected by the high sucrose concentration induced by low sink demand. Increased sucrose in leaves in response to low sink demand may have caused the increase of H2O2 and ABA, and their accumulation in mesophyll cells and guard cells was likely the primary cause for stomatal closure under low sink demand. 相似文献
860.
Yongmei Yang Ailin Qu Jingkang Liu Rui Wang Yingjie Liu Gang Li Weili Duan Qian Fang Xiumei Jiang Lili Wang Guixi Zheng Lutao Du Xin Zhang Chuanxin Wang 《PloS one》2015,10(8)
MiR-210 is the master hypoxamir that generally exhibits oncogenic properties in most human solid tumors including bladder cancer (BC). However, it remains unknown about the clinical significance of circulating miR-210 levels in BC. In this study, we found that serum miR-210 was up-regulated in patients with BC, and serum levels of miR-210 increased with advancing stage and grade. Moreover, serum miR-210 expression was found to be significantly reduced in paired post-operative samples and elevated in most patients with relapsed BC. Taken together, our data suggest that serum miR-210 could be a potential noninvasive biomarker for screening, predicting and monitoring BC. 相似文献