Molecular biology international最新文献_第6页

The Continuing Evolution of HIV-1 Therapy: Identification and Development of Novel Antiretroviral Agents Targeting Viral and Cellular Targets. HIV-1治疗的持续发展:针对病毒和细胞靶点的新型抗逆转录病毒药物的鉴定和开发。

Molecular biology international Pub Date : 2012-01-01 Epub Date: 2012-07-10 DOI: 10.1155/2012/401965

Tracy L Hartman, Robert W Buckheit

{"title":"The Continuing Evolution of HIV-1 Therapy: Identification and Development of Novel Antiretroviral Agents Targeting Viral and Cellular Targets.","authors":"Tracy L Hartman, Robert W Buckheit","doi":"10.1155/2012/401965","DOIUrl":"https://doi.org/10.1155/2012/401965","url":null,"abstract":"During the past three decades, over thirty-five anti-HIV-1 therapies have been developed for use in humans and the progression from monotherapeutic treatment regimens to today's highly active combination antiretroviral therapies has had a dramatic impact on disease progression in HIV-1-infected individuals. In spite of the success of AIDS therapies and the existence of inhibitors of HIV-1 reverse transcriptase, protease, entry and fusion, and integrase, HIV-1 therapies still have a variety of problems which require continued development efforts to improve efficacy and reduce toxicity, while making drugs that can be used throughout both the developed and developing world, in pediatric populations, and in pregnant women. Highly active antiretroviral therapies (HAARTs) have significantly delayed the progression to AIDS, and in the developed world HIV-1-infected individuals might be expected to live normal life spans while on lifelong therapies. However, the difficult treatment regimens, the presence of class-specific drug toxicities, and the emergence of drug-resistant virus isolates highlight the fact that improvements in our therapeutic regimens and the identification of new and novel viral and cellular targets for therapy are still necessary. Antiretroviral therapeutic strategies and targets continue to be explored, and the development of increasingly potent molecules within existing classes of drugs and the development of novel strategies are ongoing.","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/401965","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30801783","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: 40

Factors Important to the Prioritization and Development of Successful Topical Microbicides for HIV-1. 优选和开发成功的局部杀微生物剂治疗HIV-1的重要因素

Molecular biology international Pub Date : 2012-01-01 Epub Date: 2012-07-12 DOI: 10.1155/2012/781305

Karen W Buckheit, Robert W Buckheit

{"title":"Factors Important to the Prioritization and Development of Successful Topical Microbicides for HIV-1.","authors":"Karen W Buckheit, Robert W Buckheit","doi":"10.1155/2012/781305","DOIUrl":"https://doi.org/10.1155/2012/781305","url":null,"abstract":"Significant advancements in topical microbicide development have occurred since the prevention strategy was first described as a means to inhibit the sexual transmission of HIV-1. The lack of clinical efficacy of the first generation microbicide products has focused development attention on specific antiretroviral agents, and these agents have proven partially successful in human clinical trials. With greater understanding of vaginal and rectal virus infection, replication, and dissemination, better microbicide products and delivery strategies should result in products with enhanced potency. However, a variety of development gaps exist which relate to product dosing, formulation and delivery, and pharmacokinetics and pharmacodynamics which must be better understood in order to prioritize microbicide products for clinical development. In vitro, ex vivo, and in vivo models must be optimized with regard to these development gaps in order to put the right product at the right place, at the right time, and at the right concentration for effective inhibition of virus transmission. As the microbicide field continues to evolve, we must harness the knowledge gained from unsuccessful and successful clinical trials and development programs to continuously enhance our preclinical development algorithms.","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/781305","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30801784","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: 5

Genotoxicity studies performed in the ecuadorian population. 在厄瓜多尔人口中进行的遗传毒性研究。

Molecular biology international Pub Date : 2012-01-01 Epub Date: 2012-02-16 DOI: 10.1155/2012/598984

César Paz-Y-Miño, Nadia Cumbal, María Eugenia Sánchez

{"title":"Genotoxicity studies performed in the ecuadorian population.","authors":"César Paz-Y-Miño, Nadia Cumbal, María Eugenia Sánchez","doi":"10.1155/2012/598984","DOIUrl":"10.1155/2012/598984","url":null,"abstract":"Genotoxicity studies in Ecuador have been carried out during the past two decades. The focuses of the research were mainly the area of environmental issues, where the populations have been accidentally exposed to contaminants and the area of occupational exposure of individuals at the workplace. This paper includes studies carried out in the population of the Amazon region, a zone known for its rich biodiversity as well as for the ecological damage caused by oil spills and chemical sprayings whose consequences continue to be controversial. Additionally, we show the results of studies comprised of individuals occupationally exposed to toxic agents in two very different settings: flower plantation workers exposed to pesticide mixtures and X-ray exposure of hospital workers. The results from these studies confirm that genotoxicity studies can help evaluate current conditions and prevent further damage in the populations exposed to contaminants. As such, they are evidence of the need for biomonitoring employers at risk, stricter law enforcement regarding the use of pesticides, and increasingly conscientious oil extraction activities.","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3306904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30571331","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

Restriction of Retroviral Replication by Tetherin/BST-2. Tetherin/BST-2对逆转录病毒复制的限制

Molecular biology international Pub Date : 2012-01-01 Epub Date: 2012-07-02 DOI: 10.1155/2012/424768

Jason Hammonds, Jaang-Jiun Wang, Paul Spearman

引用次数: 12

Three-Dimensional Molecular Modeling of a Diverse Range of SC Clan Serine Proteases. 多种SC族丝氨酸蛋白酶的三维分子建模。

Molecular biology international Pub Date : 2012-01-01 Epub Date: 2012-11-19 DOI: 10.1155/2012/580965

Aparna Laskar, Aniruddha Chatterjee, Somnath Chatterjee, Euan J Rodger

{"title":"Three-Dimensional Molecular Modeling of a Diverse Range of SC Clan Serine Proteases.","authors":"Aparna Laskar, Aniruddha Chatterjee, Somnath Chatterjee, Euan J Rodger","doi":"10.1155/2012/580965","DOIUrl":"https://doi.org/10.1155/2012/580965","url":null,"abstract":"Serine proteases are involved in a variety of biological processes and are classified into clans sharing structural homology. Although various three-dimensional structures of SC clan proteases have been experimentally determined, they are mostly bacterial and animal proteases, with some from archaea, plants, and fungi, and as yet no structures have been determined for protozoa. To bridge this gap, we have used molecular modeling techniques to investigate the structural properties of different SC clan serine proteases from a diverse range of taxa. Either SWISS-MODEL was used for homology-based structure prediction or the LOOPP server was used for threading-based structure prediction. The predicted models were refined using Insight II and SCRWL and validated against experimental structures. Investigation of secondary structures and electrostatic surface potential was performed using MOLMOL. The structural geometry of the catalytic core shows clear deviations between taxa, but the relative positions of the catalytic triad residues were conserved. Evolutionary divergence was also exhibited by large variation in secondary structure features outside the core, differences in overall amino acid distribution, and unique surface electrostatic potential patterns between species. Encompassing a wide range of taxa, our structural analysis provides an evolutionary perspective on SC clan serine proteases.","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/580965","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31097416","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: 6

TRIM5 and the Regulation of HIV-1 Infectivity. TRIM5与HIV-1感染的调控

Molecular biology international Pub Date : 2012-01-01 Epub Date: 2012-05-30 DOI: 10.1155/2012/426840

Jeremy Luban

引用次数: 22

A Prevalence of Imprinted Genes within the Total Transcriptomes of Human Tissues and Cells. 印迹基因在人体组织和细胞总转录组中的普遍存在。

Molecular biology international Pub Date : 2012-01-01 Epub Date: 2012-09-11 DOI: 10.1155/2012/793506

Sergey V Anisimov

{"title":"A Prevalence of Imprinted Genes within the Total Transcriptomes of Human Tissues and Cells.","authors":"Sergey V Anisimov","doi":"10.1155/2012/793506","DOIUrl":"https://doi.org/10.1155/2012/793506","url":null,"abstract":"Genomic imprinting is an epigenetic phenomenon that causes a differential expression of paternally and maternally inherited alleles of a subset of genes (the so-called imprinted genes). Imprinted genes are distributed throughout the genome and it is predicted that about 1% of the human genes may be imprinted. It is recognized that the allelic expression of imprinted genes varies between tissues and developmental stages. The current study represents the first attempt to estimate a prevalence of imprinted genes within the total human transcriptome. In silico analysis of the normalized expression profiles of a comprehensive panel of 173 established and candidate human imprinted genes was performed, in 492 publicly available SAGE libraries. The latter represent human cell and tissue samples in a variety of physiological and pathological conditions. Variations in the prevalence of imprinted genes within the total transcriptomes (ranging from 0.08% to 4.36%) and expression profiles of the individual imprinted genes are assessed. This paper thus provides a useful reference on the size of the imprinted transcriptome and expression of the individual imprinted genes.","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/793506","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30921950","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: 2

RASSF1A and the Taxol Response in Ovarian Cancer. RASSF1A与卵巢癌紫杉醇反应。

Molecular biology international Pub Date : 2012-01-01 Epub Date: 2012-04-03 DOI: 10.1155/2012/263267

Susannah Kassler, Howard Donninger, Michael J Birrer, Geoffrey J Clark

{"title":"RASSF1A and the Taxol Response in Ovarian Cancer.","authors":"Susannah Kassler, Howard Donninger, Michael J Birrer, Geoffrey J Clark","doi":"10.1155/2012/263267","DOIUrl":"https://doi.org/10.1155/2012/263267","url":null,"abstract":"The RASSF1A tumor suppressor gene is frequently inactivated by promoter methylation in human tumors. The RASSF1A protein forms an endogenous complex with tubulin and promotes the stabilization of microtubules. Loss of RASSF1A expression sensitizes cells to microtubule destabilizing stimuli. We have observed a strong correlation between the loss of RASSF1A expression and the development of Taxol resistance in primary ovarian cancer samples. Thus, we sought to determine if RASSF1A levels could dictate the response to Taxol and whether an epigenetic therapy approach might be able to reverse the Taxol resistant phenotype of RASSF1A negative ovarian tumor cells. We found that knocking down RASSF1A expression in an ovarian cancer cell line inhibited Taxol-mediated apoptosis and promoted cell survival during Taxol treatment. Moreover, using a combination of small molecule inhibitors of DNA Methyl Transferase enzymes, we were able restore RASSF1A expression and Taxol sensitivity. This identifies a role for RASSF1A in modulating the tumor response to Taxol and provides proof of principal for the use of epigenetic therapy to overcome Taxol resistance.","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/263267","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40196398","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: 24

The Impact of Macrophage Nucleotide Pools on HIV-1 Reverse Transcription, Viral Replication, and the Development of Novel Antiviral Agents. 巨噬细胞核苷酸池对HIV-1逆转录、病毒复制和新型抗病毒药物开发的影响

Molecular biology international Pub Date : 2012-01-01 Epub Date: 2012-07-01 DOI: 10.1155/2012/625983

Christina Gavegnano, Edward M Kennedy, Baek Kim, Raymond F Schinazi

{"title":"The Impact of Macrophage Nucleotide Pools on HIV-1 Reverse Transcription, Viral Replication, and the Development of Novel Antiviral Agents.","authors":"Christina Gavegnano, Edward M Kennedy, Baek Kim, Raymond F Schinazi","doi":"10.1155/2012/625983","DOIUrl":"https://doi.org/10.1155/2012/625983","url":null,"abstract":"Macrophages are ubiquitous and represent a significant viral reservoir for HIV-1. Macrophages are nondividing, terminally differentiated cells, which have a unique cellular microenvironment relative to actively dividing T lymphocytes, all of which can impact HIV-1 infection/replication, design of inhibitors targeting viral replication in these cells, emergence of mutations within the HIV-1 genome, and disease progression. Scarce dNTPs drive rNTP incorporation into the proviral DNA in macrophages but not lymphocytes. Furthermore, the efficacy of a ribose-based inhibitor that potently inhibits HIV-1 replication in macrophages, has prompted a reconsideration of the previously accepted dogma that 2'-deoxy-based inhibitors demonstrate effective inhibition of HIV-1 replication. Additionally, higher levels of dUTP and rNTP incorporation in macrophages, and lack of repair mechanisms relative to lymphocytes, provide a further mechanistic understanding required to develop targeted inhibition of viral replication in macrophages. Together, the concentrations of dNTPs and rNTPs within macrophages comprise a distinctive cellular environment that directly impacts HIV-1 replication in macrophages and provides unique insight into novel therapeutic mechanisms that could be exploited to eliminate virus from these cells.","PeriodicalId":74217,"journal":{"name":"Molecular biology international","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/625983","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30774701","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: 42

The SARAH Domain of RASSF1A and Its Tumor Suppressor Function. RASSF1A的SARAH结构域及其抑瘤功能

Molecular biology international Pub Date : 2012-01-01 Epub Date: 2012-04-09 DOI: 10.1155/2012/196715

Claudia Dittfeld, Antje M Richter, Katrin Steinmann, Antje Klagge-Ulonska, Reinhard H Dammann

引用次数: 33