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991.
992.
TRIM16 controls assembly and degradation of protein aggregates by modulating the p62‐NRF2 axis and autophagy 下载免费PDF全文
Kautilya Kumar Jena Parej Nath Biswajit Das Pradyumna Kumar Sahoo Abdul Ahad Gulam Hussain Syed Sunil K Raghav Shantibhusan Senapati Swati Chauhan Santosh Chauhan 《The EMBO journal》2018,37(18)
Sequestration of protein aggregates in inclusion bodies and their subsequent degradation prevents proteostasis imbalance, cytotoxicity, and proteinopathies. The underlying molecular mechanisms controlling the turnover of protein aggregates are mostly uncharacterized. Herein, we show that a TRIM family protein, TRIM16, governs the process of stress‐induced biogenesis and degradation of protein aggregates. TRIM16 facilitates protein aggregate formation by positively regulating the p62‐NRF2 axis. We show that TRIM16 is an integral part of the p62‐KEAP1‐NRF2 complex and utilizes multiple mechanisms for stabilizing NRF2. Under oxidative and proteotoxic stress conditions, TRIM16 activates ubiquitin pathway genes and p62 via NRF2, leading to ubiquitination of misfolded proteins and formation of protein aggregates. We further show that TRIM16 acts as a scaffold protein and, by interacting with p62, ULK1, ATG16L1, and LC3B, facilitates autophagic degradation of protein aggregates. Thus, TRIM16 streamlines the process of stress‐induced aggregate clearance and protects cells against oxidative/proteotoxic stress‐induced toxicity in vitro and in vivo. Taken together, this work identifies a new mechanism of protein aggregate turnover, which could be relevant in protein aggregation‐associated diseases such as neurodegeneration. 相似文献
993.
Po-Huang Liang Wen-Ling Lin Han-Yu Hsieh Tsung-Yi Lin Chun-Hsu Chen Sunil K. Tewary Hsiao-Lin Lee Shuo-Fu Yuan Barbara Yang Jyun-Yu Yao Meng-Chiao Ho 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(3):513-521
Background
An array of glycoside hydrolases with multiple substrate specificities are required to digest plant cell wall polysaccharides. Cel5E from Clostridium thermocellum and Cel5A from Thermotoga maritima are two glycoside hydrolase family 5 (GH5) enzymes with high sequence and structural similarity, but notably possess different substrate specificities; the former is a bifunctional cellulase/xylanase and the latter is a cellulase/mannanase. A specific loop in TmCel5A, Tmloop, is one of the most structurally divergent regions compared to CtCel5E and interacts with substrates, suggesting the importance for mannan recognition.Method
A Tmloop inserted CtCel5E and its related mutants were produced to investigate the role of Tmloop in catalysis. Crystal structure of CtCel5E-TmloopF267A followed by site-direct mutagenesis reveals the mechanism. RtCelB, a homolog with Tmloop was identified to have mannanase activity.Result
Tmloop incorporation enables CtCel5E to gain mannanase activity. Tyr270, His277, and Trp282 in the Tmloop are indispensable for CtCel5E-Tmloop catalysis, and weakening hydrophobic environment near the Tmloop enhances enzyme kcat. Using our newly identified loop motif to search for structurally conserved homologs in other subfamilies of GH5, we identified RtCelB. This homolog, originally annotated as a cellulase also possesses mannanase and xylanase activities.Conclusion
Our studies show that Tmloop enhances GH5 enzyme promiscuity and plays a role in catalysis.General significance
The study identified a loop of GH5 for mannan recognition and catalysis. Weakening the hydrophobic environment near the loop can also enhance the enzyme catalytic rate. Our findings provide a new insight on mannan recognition and activity enhancement of GH5. 相似文献994.
Sunil R. Vaidya Venkat S. Hamde Neelakshi S. Kumbhar Atul M. Walimbe 《Microbiology and immunology》2018,62(4):243-247
995.
Summary Maize (Zea mays L. cv. Ganga-2) plants were grown in pot culture on a loamy alluvial soil of Lucknow district (India) alkalinized to graded
levels of ESP (Exchangeable Sodium Percentage) ranging from 15.5 to 55.3. Before sowing maize seeds the soil was fertilised
with NPK, Fe, Mn and Cu. At and above ESP 34 Zn-deficiency symptoms first appeared at 30 days. The symptoms gradually became
pronounced with increase in age and at 60 days they were found even at ESP 15.5. The severity of symptoms was related to increase
in sodicity. Alkalinization of soils depressed available soil Zn and tissue Zn and increased tissue ratios of Na/Zn and P/Zn.
It also decreased the total plant content of Zn, Fe, Mn, Cu and even Na. Increase in soil sodicity increased both tissue concentration
and total content of P in plants upto ESP 34 beyond which it decreased it. Among different extractants, 0.1N HCl, DTPA pH 7.3 and EDTA-(NH4)2 CO3 pH 8.6, for measuring available soil Zn the latter showed best correlations with soil ESP (−), tissue P (−), P/Zn ratio (−),
dry matter yield (+) and tissue Zn (+). Tissue Zn was related to yield (+), tissue Na (−) and soil ESP (−). Mild, moderate,
severe and very severe Zn deficiency in maize was induced by soil ESP levels, 18, 25, 33 and 45, respectively. 相似文献
996.
Counter-immunoelectrophoresis was employed for the detection of Brucella antigen in stomach contents of aborted buffalo fetuses and antibody in aborted as well as apparently healthy in contact buffaloes. Five of 16 aborted cases were serologically positive for brucellosis but isolation of Brucella abortus was successful in only two cases. By counter-immunoelectrophoresis, Brucella antigen was detected in the fetal stomach contents of four serologically positive cases.
Of the 68 serum samples from in contact healthy buffaloes, 10 were positive with counter-immunoelectrophoresis: more than were detected by tube agglutination, Rose Bengal plate agglutination, complement fixation and agar gel precipitation test. 相似文献
Of the 68 serum samples from in contact healthy buffaloes, 10 were positive with counter-immunoelectrophoresis: more than were detected by tube agglutination, Rose Bengal plate agglutination, complement fixation and agar gel precipitation test. 相似文献
997.
998.
Kejuan Li Yue Yu Shuang Sun Ye Liu Sukant Garg Sunil C. Kaul Zhongfang Lei Ran Gao Renu Wadhwa Zhenya Zhang 《PloS one》2016,11(3)
Helicteres angustifolia L. is a shrub that forms a common ingredient of several cancer treatment recipes in traditional medicine system both in China and Laos. In order to investigate molecular mechanisms of its anticancer activity, we prepared aqueous extract of Helicteres
angustifolia L. Roots (AQHAR) and performed several in vitro assays using human normal fibroblasts (TIG-3) and osteosarcoma (U2OS). We found that AQHAR caused growth arrest/apoptosis of U2OS cells in a dose-dependent manner. It showed no cytotoxicity to TIG-3 cells at doses up to 50 μg/ml. Biochemical, imaging and cell cycle analyses revealed that it induces ROS signaling and DNA damage response selectively in cancer cells. The latter showed upregulation of p53, p21 and downregulation of Cyclin B1 and phospho-Rb. Furthermore, AQHAR-induced apoptosis was mediated by increase in pro-apoptotic proteins including cleaved PARP, caspases and Bax. Anti-apoptotic protein Bcl-2 showed decrease in AQHAR-treated U2OS cells. In vivo xenograft tumor assays in nude mice revealed dose-dependent suppression of tumor growth and lung metastasis with no toxicity to the animals suggesting that AQHAR could be a potent and safe natural drug for cancer treatment. 相似文献
999.
Yudan Liu Rayeheh Bahar Sunil Kalia Rachel Yuanshen Huang Arlie Phillips Mingwan Su Sen Yang Xuejun Zhang Pingyu Zhou Youwen Zhou 《PloS one》2016,11(4)
BackgroundThere is a wide variation in the reported prevalence of primary hyperhidrosis in the literature. Further, it is unknown if primary hyperhidrosis is a lifelong condition, or if demographical factors influence hyperhidrosis prevalence.ObjectivesThis study aims to examine the prevalence of hyperhidrosis in multiple ethnic groups from two ethnically diverse cities and to determine if the prevalence of primary hyperhidrosis changes according to age, gender, ethnicity, body mass index, and geographical locations.MethodsIn total, 1010 consecutive subjects attending dermatology outpatient clinics in Shanghai Skin Disease Hospital and 1018 subjects in Skin Care Center of Vancouver General Hospital were invited to fill out a questionnaire on their presenting concerns, demographical information, and sweating symptoms. The subjects were then classified to have primary hyperhidrosis using the criteria of International Hyperhidrosis Society, late-onset hyperhidrosis, or no-hyperhidrosis. The prevalence of primary HH and late-onset HH was calculated for the entire study population and in subgroups stratified according to age of examination, sex, ethnicity, presenting diagnosis, body mass index, and specific study cities. Multivariate logistic regression analyses were performed to assess the impact of these factors on HH prevalence.ResultsThe prevalence of primary hyperhidrosis is very similar in Shanghai and in Vancouver, at 14.5% and 12.3% respectively. In addition, 4.0% of subjects in Shanghai and 4.4% subjects in Vancouver suffer from late-onset HH. Primary HH has highest prevalence in those younger than 30 years of age, decreasing dramatically in later years. Caucasian subjects are at least 2.5 times more likely to develop axillary hyperhidrosis compared to Chinese subjects. Obesity does not have much influence on primary HH presentation, although it does increase significantly the development of late-onset HH. Finally, there is no major difference of hyperhidrosis between Chinese subjects in Shanghai and Vancouver.LimitationsThe data were gathered according to patients’ self-reports only and the sample size was relatively small in some groups after stratification for gender, ethnicity and age.ConclusionPrevalence of primary HH and late-onset HH is similar in dermatology outpatients independent of geographical locations. However, certain specific HH subtypes can show great variations according to ethnicity, age, body mass index and sex. 相似文献
1000.
A. Basel Al-Yousfi Peter G. Hannak James F. Strunk Wyn V. Davies Sunil I. Shah 《Soil & Sediment Contamination》2000,9(1):1-12
After determining at an early stage of the project that the future land use of this New Jersey chemical manufacturing site remain industrial in nature, the site was zoned according to risk. The chemicals of concern (COCs) at the site included relatively low levels of mono- and polynuclear aromatic hydrocarbons, chlorinated aliphatics, as well as other volatile and semivolatile compounds. Direct human exposure scenarios were the key to the mitigation of risks related to soils because the groundwater migration pathway was already interrupted using groundwater recovery. A focused remedial strategy was developed to ensure that the exposure pathways (inhalation, ingestion, and dermal contact) are alleviated and the remedial measures are protective to the workers operating and/or maintaining the site. The risk evaluation process included a preliminary risk assessment (Tier 1) based on a comparison with pertinent soil cleanup criteria, a prioritization analysis to rank zones, chemicals and pathways of concern, and an application of the Risk Based Corrective Action (RBCA) approach (Tier 2) for construction worker exposure scenario. The risk assessment identified selected areas that would benefit from remedial actions. Prioritization Analysis classified the site into five high-priority (comprising 97% of the total health-based risk), three medium-priority (contributing to remaining 2 to 3% of the risk), and adequately protected areas. The boundaries and volumes of affected areas were delineated based on confirmatory soil sampling and statistical analyses. The remedial technologies selected for the site have achieved appropriate reduction in risk to comply with all State regulations and include (in addition to the institutional controls): ??Capping the site where only immobilesemivolatile contaminants are present ??Excavation and on-site treatment of the soils impacted by volatile organic com pounds through ex situ low temperature desorption, or alternative “biopile” treatment and natural attenuation, and ??Excavation and off-site disposal of limited volumes of soils This risk-based, integral approach helped identify the real significance of contamination present at the site and facilitated the development of suitable and adequate remedies. Had not it been for this approach, the mere comparison with soil cleanup criteria would have unnecessarily resulted in denoting all areas as nuisance contributors, and thus requiring some actions. New Jersey Department of Environmental Protection (NJDEP) has approved this approach and contributed to its accomplishment. 相似文献