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Protein methylation and stress granules: posttranslational remodeler or innocent bystander? 蛋白质甲基化和应激颗粒:翻译后重塑者还是无辜的旁观者?
Molecular biology international Pub Date : 2011-01-01 Epub Date: 2011-02-24 DOI: 10.4061/2011/137459
Wen Xie, Robert B Denman
{"title":"Protein methylation and stress granules: posttranslational remodeler or innocent bystander?","authors":"Wen Xie,&nbsp;Robert B Denman","doi":"10.4061/2011/137459","DOIUrl":"https://doi.org/10.4061/2011/137459","url":null,"abstract":"<p><p>Stress granules contain a large number of post-translationally modified proteins, and studies have shown that these modifications serve as recruitment tags for specific proteins and even control the assembly and disassembly of the granules themselves. Work originating from our laboratory has focused on the role protein methylation plays in stress granule composition and function. We have demonstrated that both asymmetrically and symmetrically dimethylated proteins are core constituents of stress granules, and we have endeavored to understand when and how this occurs. Here we seek to integrate this data into a framework consisting of the currently known post-translational modifications affecting stress granules to produce a model of stress granule dynamics that, in turn, may serve as a benchmark for understanding and predicting how post-translational modifications regulate other granule types.</p>","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3196864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30260430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 36
Arsenic biotransformation as a cancer promoting factor by inducing DNA damage and disruption of repair mechanisms. 砷生物转化作为癌症促进因子通过诱导DNA损伤和破坏修复机制。
Molecular biology international Pub Date : 2011-01-01 Epub Date: 2011-08-02 DOI: 10.4061/2011/718974
Victor D Martinez, Emily A Vucic, Marta Adonis, Lionel Gil, Wan L Lam
{"title":"Arsenic biotransformation as a cancer promoting factor by inducing DNA damage and disruption of repair mechanisms.","authors":"Victor D Martinez,&nbsp;Emily A Vucic,&nbsp;Marta Adonis,&nbsp;Lionel Gil,&nbsp;Wan L Lam","doi":"10.4061/2011/718974","DOIUrl":"https://doi.org/10.4061/2011/718974","url":null,"abstract":"<p><p>Chronic exposure to arsenic in drinking water poses a major global health concern. Populations exposed to high concentrations of arsenic-contaminated drinking water suffer serious health consequences, including alarming cancer incidence and death rates. Arsenic is biotransformed through sequential addition of methyl groups, acquired from s-adenosylmethionine (SAM). Metabolism of arsenic generates a variety of genotoxic and cytotoxic species, damaging DNA directly and indirectly, through the generation of reactive oxidative species and induction of DNA adducts, strand breaks and cross links, and inhibition of the DNA repair process itself. Since SAM is the methyl group donor used by DNA methyltransferases to maintain normal epigenetic patterns in all human cells, arsenic is also postulated to affect maintenance of normal DNA methylation patterns, chromatin structure, and genomic stability. The biological processes underlying the cancer promoting factors of arsenic metabolism, related to DNA damage and repair, will be discussed here.</p>","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3200225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30260841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 61
The Role of miRNAs as Key Regulators in the Neoplastic Microenvironment. mirna在肿瘤微环境中的关键调控作用
Molecular biology international Pub Date : 2011-01-01 Epub Date: 2011-04-06 DOI: 10.4061/2011/839872
K K Wentz-Hunter, J A Potashkin
{"title":"The Role of miRNAs as Key Regulators in the Neoplastic Microenvironment.","authors":"K K Wentz-Hunter,&nbsp;J A Potashkin","doi":"10.4061/2011/839872","DOIUrl":"https://doi.org/10.4061/2011/839872","url":null,"abstract":"<p><p>The neoplastic microenvironment has been recognized to play a critical role in the development of cancer. Although a large body of evidence has established the importance of the cancer microenvironment, the manners of crosstalk between it and the cancer cells still remains unclear. Emerging mechanisms of communication include microRNAs (miRNAs). miRNAs are small noncoding RNA molecules that are involved in the posttranscriptional regulation of mRNA. Both intracellular and circulating miRNAs are differentially expressed in cancer and some of these alterations have been correlated with clinical patient outcomes. The role of miRNAs in the tumor microenvironment has only recently become a focus of research, however. In this paper, we discuss the influence of miRNAs on the tumor microenvironment as it relates to cancer progression. We conclude that miRNAs are a critical component in understanding invasion and metastasis of cancer cells.</p>","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4061/2011/839872","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30260842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 33
Bioinformatic Analysis of Leishmania donovani Long-Chain Fatty Acid-CoA Ligase as a Novel Drug Target. 作为新型药物靶点的利什曼原虫长链脂肪酸-CoA 连接酶的生物信息学分析
Molecular biology international Pub Date : 2011-01-01 Epub Date: 2011-07-19 DOI: 10.4061/2011/278051
Jaspreet Kaur, Rameshwar Tiwari, Arun Kumar, Neeloo Singh
{"title":"Bioinformatic Analysis of Leishmania donovani Long-Chain Fatty Acid-CoA Ligase as a Novel Drug Target.","authors":"Jaspreet Kaur, Rameshwar Tiwari, Arun Kumar, Neeloo Singh","doi":"10.4061/2011/278051","DOIUrl":"10.4061/2011/278051","url":null,"abstract":"<p><p>Fatty acyl-CoA synthetase (fatty acid: CoA ligase, AMP-forming; (EC 6.2.1.3)) catalyzes the formation of fatty acyl-CoA by a two-step process that proceeds through the hydrolysis of pyrophosphate. Fatty acyl-CoA represents bioactive compounds that are involved in protein transport, enzyme activation, protein acylation, cell signaling, and transcriptional control in addition to serving as substrates for beta oxidation and phospholipid biosynthesis. Fatty acyl-CoA synthetase occupies a pivotal role in cellular homeostasis, particularly in lipid metabolism. Our interest in fatty acyl-CoA synthetase stems from the identification of this enzyme, long-chain fatty acyl-CoA ligase (LCFA) by microarray analysis. We found this enzyme to be differentially expressed by Leishmania donovani amastigotes resistant to antimonial treatment. In the present study, we confirm the presence of long-chain fatty acyl-CoA ligase gene in the genome of clinical isolates of Leishmania donovani collected from the disease endemic area in India. We predict a molecular model for this enzyme for in silico docking studies using chemical library available in our institute. On the basis of the data presented in this work, we propose that long-chain fatty acyl-CoA ligase enzyme serves as an important protein and a potential target candidate for development of selective inhibitors against leishmaniasis.</p>","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3198602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30259754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Copper and its complexes in medicine: a biochemical approach. 医学上的铜及其络合物:生化方法。
Molecular biology international Pub Date : 2011-01-01 Epub Date: 2011-06-15 DOI: 10.4061/2011/594529
Isidoros Iakovidis, Ioannis Delimaris, Stylianos M Piperakis
{"title":"Copper and its complexes in medicine: a biochemical approach.","authors":"Isidoros Iakovidis,&nbsp;Ioannis Delimaris,&nbsp;Stylianos M Piperakis","doi":"10.4061/2011/594529","DOIUrl":"https://doi.org/10.4061/2011/594529","url":null,"abstract":"<p><p>The fundamental role of copper and the recognition of its complexes as important bioactive compounds in vitro and in vivo aroused an ever-increasing interest in these agents as potential drugs for therapeutic intervention in various diseases. The vast array of information available for their bioinorganic properties and mode of action in several biological systems, combined with the new opportunities offered by the flourishing technologies of medicinal chemistry, is creating an exciting scenario for the development of a novel generation of highly active drugs with minimized side effects which could add significantly to the current clinical research and practice. In this paper we attempt to summarize all the available-to-date information on these issues.</p>","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4061/2011/594529","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30260837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 251
Cryptolepine-Induced Cell Death of Leishmania donovani Promastigotes Is Augmented by Inhibition of Autophagy. 隐tolepine诱导的多诺瓦利什曼原虫原生体细胞死亡通过抑制自噬而增强。
Molecular biology international Pub Date : 2011-01-01 Epub Date: 2011-03-03 DOI: 10.4061/2011/187850
Souvik Sengupta, Sayan Chowdhury, Somdeb Bosedasgupta, Colin W Wright, Hemanta K Majumder
{"title":"Cryptolepine-Induced Cell Death of Leishmania donovani Promastigotes Is Augmented by Inhibition of Autophagy.","authors":"Souvik Sengupta,&nbsp;Sayan Chowdhury,&nbsp;Somdeb Bosedasgupta,&nbsp;Colin W Wright,&nbsp;Hemanta K Majumder","doi":"10.4061/2011/187850","DOIUrl":"https://doi.org/10.4061/2011/187850","url":null,"abstract":"<p><p>Leishmania donovani are the causative agents of visceral leishmaniasis worldwide. Lack of vaccines and emergence of drug resistance warrants the need for improved drug therapy and newer therapeutic intervention strategies against leishmaniasis. In the present study, we have investigated the effect of the natural indoloquinoline alkaloid cryptolepine on L. donovani AG83 promastigotes. Our results show that cryptolepine induces cellular dysfunction in L. donovani promastigotes, which leads to the death of this unicellular parasite. Interestingly, our study suggest that cryptolepine-induced cell death of L. donovani is counteracted by initial autophagic features elicited by the cells. For the first time, we show that autophagy serves as a survival mechanism in response to cryptolepine treatment in L. donovani promastigotes and inhibition of autophagy causes an early increase in the amount of cell death. This study can be exploited for designing better drugs and better therapeutic strategies against leishmaniasis in future.</p>","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3195846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30260433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 27
Role of cAMP Signaling in the Survival and Infectivity of the Protozoan Parasite, Leishmania donovani. cAMP信号在原虫多诺瓦利什曼原虫存活和感染中的作用。
Molecular biology international Pub Date : 2011-01-01 Epub Date: 2011-06-05 DOI: 10.4061/2011/782971
Arunima Biswas, Arijit Bhattacharya, Pijush K Das
{"title":"Role of cAMP Signaling in the Survival and Infectivity of the Protozoan Parasite, Leishmania donovani.","authors":"Arunima Biswas,&nbsp;Arijit Bhattacharya,&nbsp;Pijush K Das","doi":"10.4061/2011/782971","DOIUrl":"https://doi.org/10.4061/2011/782971","url":null,"abstract":"<p><p>Leishmania donovani, while invading macrophages, encounters striking shift in temperature and pH (from 22°C and pH 7.2 to 37°C and pH 5.5), which act as the key environmental trigger for differentiation, and increases cAMP level and cAMP-mediated responses. For comprehensive understanding of cAMP signaling, we studied the enzymes related to cAMP metabolism. A stage-specific and developmentally regulated isoform of receptor adenylate cyclase (LdRACA) showed to regulate differentiation-coupled induction of cAMP. The soluble acidocalcisomal pyrophosphatase, Ldvsp1, was the major isoform regulating cAMP level in association with LdRACA. A differentially expressed soluble cytosolic cAMP phosphodiesterase (LdPDEA) might be related to infection establishment by shifting trypanothione pool utilization bias toward antioxidant defense. We identified and cloned a functional cAMP-binding effector molecule from L. donovani (a regulatory subunit of cAMP-dependent protein kinase, LdPKAR) that may modulate metacyclogenesis through induction of autophagy. This study reveals the significance of cAMP signaling in parasite survival and infectivity.</p>","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3200087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30260840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 20
Establishment of Methylation-Specific PCR for the Mouse p53 Gene. 小鼠p53基因甲基化特异性PCR的建立。
Molecular biology international Pub Date : 2011-01-01 Epub Date: 2011-12-12 DOI: 10.4061/2011/938435
Ryuji Okazaki, Akira Ootsuyama, Yasuhiro Yoshida, Toshiyuki Norimura
{"title":"Establishment of Methylation-Specific PCR for the Mouse p53 Gene.","authors":"Ryuji Okazaki,&nbsp;Akira Ootsuyama,&nbsp;Yasuhiro Yoshida,&nbsp;Toshiyuki Norimura","doi":"10.4061/2011/938435","DOIUrl":"https://doi.org/10.4061/2011/938435","url":null,"abstract":"<p><p>Methylation-specific PCR (MSP) of the mouse p53 gene has not yet been reported. We searched the CpG islands, sequenced the bisulfited DNA, and designed PCR primers for methylation and unmethylation sites. DNA from a young mouse produced a strong PCR product with the unmethylated primer and a weaker band with the methylated primer. DNA from an old mouse produced bands of similar intensities with both primers. In radiation-induced tumors, DNA from an old mouse yielded similar bands with both types of primers. We suggest that MSP is a valuable technique for the epigenetic study of the mouse p53 gene.</p>","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3238407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30353522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Molecular Characterization and SNP Detection of CD14 Gene of Crossbred Cattle. 杂交牛CD14基因的分子特征及SNP检测。
Molecular biology international Pub Date : 2011-01-01 Epub Date: 2011-10-25 DOI: 10.4061/2011/507346
Aruna Pal, Arjava Sharma, T K Bhattacharya, P N Chatterjee, A K Chakravarty
{"title":"Molecular Characterization and SNP Detection of CD14 Gene of Crossbred Cattle.","authors":"Aruna Pal,&nbsp;Arjava Sharma,&nbsp;T K Bhattacharya,&nbsp;P N Chatterjee,&nbsp;A K Chakravarty","doi":"10.4061/2011/507346","DOIUrl":"https://doi.org/10.4061/2011/507346","url":null,"abstract":"<p><p>CD14 is an important molecule for innate immunity that can act against a wide range of pathogens. The present paper has characterized CD14 gene of crossbred (CB) cattle (Bos indicus×Bos taurus). Cloning and sequence analysis of CD14 cDNA revealed 1119 nucleotide long open reading frame encoding 373 amino acids protein and 20 amino acids signal peptide. CB cattle CD14 gene exhibited a high percentage of nucleotide identity (59.3-98.1%) with the corresponding mammalian homologs. Cattle and buffalo appear to have diverged from a common ancestor in phylogenetic analysis. 25 SNPs with 17 amino acid changes were newly reported and the site for mutational hot-spot was detected in CB cattle CD14 gene. Non-synonymous substitutions exceeding synonymous substitutions indicate the evolution of this protein through positive selection among domestic animals. Predicted protein structures obtained from deduced amino acid sequence indicated CB cattle CD14 molecule to be a receptor with horse shoe-shaped structure. The sites for LPS binding, LPS signalling, leucine-rich repeats, putative N-linked glycosylation, O-linked glycosylation, glycosyl phosphatidyl inositol anchor, disulphide bridges, alpha helix, beta strand, leucine rich nuclear export signal, leucine zipper and domain linker were predicted. Most of leucine and cysteine residues remain conserved across the species.</p>","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3205722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30295500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 41
Screening the MayBridge Rule of 3 Fragment Library for Compounds That Interact with the Trypanosoma brucei myo-Inositol-3-Phosphate Synthase and/or Show Trypanocidal Activity. 筛选与布氏锥虫肌醇-3-磷酸合酶相互作用和/或显示杀锥虫活性的化合物的MayBridge规则3片段文库。
Molecular biology international Pub Date : 2011-01-01 Epub Date: 2011-05-17 DOI: 10.4061/2011/389364
Louise L Major, Terry K Smith
{"title":"Screening the MayBridge Rule of 3 Fragment Library for Compounds That Interact with the Trypanosoma brucei myo-Inositol-3-Phosphate Synthase and/or Show Trypanocidal Activity.","authors":"Louise L Major,&nbsp;Terry K Smith","doi":"10.4061/2011/389364","DOIUrl":"https://doi.org/10.4061/2011/389364","url":null,"abstract":"<p><p>Inositol-3-phosphate synthase (INO1) has previously been genetically validated as a drug target against Trypanosoma brucei, the causative agent of African sleeping sickness. Chemical intervention of this essential enzyme could lead to new therapeutic agents. Unfortunately, no potent inhibitors of INO1 from any organism have been reported, so a screen for potential novel inhibitors of T. brucei INO1was undertaken. Detection of inhibition of T. brucei INO1 is problematic due to the nature of the reaction. Direct detection requires differentiation between glucose-6-phosphate and inositol-3-phosphate. Coupled enzyme assays could give false positives as potentially they could inhibit the coupling enzyme. Thus, an alternative approach of differential scanning fluorimetry to identify compounds that interact with T. brucei INO1 was employed to screen ~670 compounds from the MayBridge Rule of 3 Fragment Library. This approach identified 38 compounds, which significantly altered the T(m) of TbINO1. Four compounds showed trypanocidal activity with ED50s in the tens of micromolar range, with 2 having a selectivity index in excess of 250. The trypanocidal and general cytotoxicity activities of all of the compounds in the library are also reported, with the best having ED50S of ~20 μM against T. brucei.</p>","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3199943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30259757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 13
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