Molecular biology international最新文献

{"title":"DNA in 3R: Repair, Replication, and Recombination.","authors":"Frédéric Coin, Bernardo Reina-San-Martin, Giuseppina Giglia-Mari, Mark Berneburg","doi":"10.1155/2012/658579","DOIUrl":"https://doi.org/10.1155/2012/658579","url":null,"abstract":"This special issue entitled “DNA in 3R: Repair, Replication, and Recombination” is dedicated to biological processes that preserve the integrity of our genome. These phenomena have attracted broad interest among a large community of scientists that cross disciplines from mathematics, physics, chemistry, and biology to clinical scientists. DNA is continuously exposed to a range of damaging agents, including reactive cellular metabolites, environmental chemicals, ionizing radiation, and UV light. The biochemical consequences of DNA lesions are diverse and range from obstruction of fundamental cellular pathways like transcription and replication to fixation of mutations. Cellular misfunctioning, cell death, aging, and cancer are the phenotypical consequences of DNA damages accumulation in the genome. Fortunately, an intricate set of genome surveillance mechanisms function to counteract genomic insults. Among these mechanisms, base excision repair and nucleotide excision repair are both dedicated to the removal of single-strand lesions contrary to double-strand break repair. Additionally, some specialized polymerases can temporarily take over lesion-arrested DNA polymerases during S-phase, in a mutagenic mechanism called translesion synthesis. Such polymerases only work if a more reliable system, such as homologous recombination, cannot avoid stumbled DNA replication. These DNA repair mechanisms function in conjunction with an intricate machinery of damage sensors, responsible of a series of phosphorylations and chromatin modifications that signal to the rest of the cell the presence of lesions on the DNA. Together DNA repair mechanisms and DNA damage signaling systems form a molecular shield against genomic instability called DNA Damage Response system. Hence, we have tried to integrate several papers that present a synergy that emerge when researchers from different fields put their forces together into a common goal, trying to improve human health. We thank the contributors for their work and the many reviewers who served conscientiously and tirelessly to assure an issue that meets the standards. \u0000 \u0000 \u0000Frederic Coin \u0000 \u0000Bernardo Reina-San-Martin \u0000 \u0000Giuseppina Giglia-Mari \u0000 \u0000Mark Berneburg","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/10.1155/2012/658579","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40191932","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}

{"title":"ASGR1 and ASGR2, the Genes that Encode the Asialoglycoprotein Receptor (Ashwell Receptor), Are Expressed in Peripheral Blood Monocytes and Show Interindividual Differences in Transcript Profile.","authors":"Rebecca Louise Harris,&nbsp;Carmen Wilma van den Berg,&nbsp;Derrick John Bowen","doi":"10.1155/2012/283974","DOIUrl":"https://doi.org/10.1155/2012/283974","url":null,"abstract":"<p><p>Background. The asialoglycoprotein receptor (ASGPR) is a hepatic receptor that mediates removal of potentially hazardous glycoconjugates from blood in health and disease. The receptor comprises two proteins, asialoglycoprotein receptor 1 and 2 (ASGR1 and ASGR2), encoded by the genes ASGR1 and ASGR2. Design and Methods. Using reverse transcription amplification (RT-PCR), expression of ASGR1 and ASGR2 was investigated in human peripheral blood monocytes. Results. Monocytes were found to express ASGR1 and ASGR2 transcripts. Correctly spliced transcript variants encoding different isoforms of ASGR1 and ASGR2 were present in monocytes. The profile of transcript variants from both ASGR1 and ASGR2 differed among individuals. Transcript expression levels were compared with the hepatocyte cell line HepG2 which produces high levels of ASGPR. Monocyte transcripts were 4 to 6 orders of magnitude less than in HepG2 but nonetheless readily detectable using standard RT-PCR. The monocyte cell line THP1 gave similar results to monocytes harvested from peripheral blood, indicating it may provide a suitable model system for studying ASGPR function in this cell type. Conclusions. Monocytes transcribe and correctly process transcripts encoding the constituent proteins of the ASGPR. Monocytes may therefore represent a mobile pool of the receptor, capable of reaching sites remote from the liver.</p>","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/10.1155/2012/283974","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30856280","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}

{"title":"Cellular cofactors of lentiviral integrase: from target validation to drug discovery.","authors":"Oliver Taltynov,&nbsp;Belete A Desimmie,&nbsp;Jonas Demeulemeester,&nbsp;Frauke Christ,&nbsp;Zeger Debyser","doi":"10.1155/2012/863405","DOIUrl":"https://doi.org/10.1155/2012/863405","url":null,"abstract":"<p><p>To accomplish their life cycle, lentiviruses make use of host proteins, the so-called cellular cofactors. Interactions between host cell and viral proteins during early stages of lentiviral infection provide attractive new antiviral targets. The insertion of lentiviral cDNA in a host cell chromosome is a step of no return in the replication cycle, after which the host cell becomes a permanent carrier of the viral genome and a producer of lentiviral progeny. Integration is carried out by integrase (IN), an enzyme playing also an important role during nuclear import. Plenty of cellular cofactors of HIV-1 IN have been proposed. To date, the lens epithelium-derived growth factor (LEDGF/p75) is the best studied cofactor of HIV-1 IN. Moreover, small molecules that block the LEDGF/p75-IN interaction have recently been developed for the treatment of HIV infection. The nuclear import factor transportin-SR2 (TRN-SR2) has been proposed as another interactor of HIV IN-mediating nuclear import of the virus. Using both proteins as examples, we will describe approaches to be taken to identify and validate novel cofactors as new antiviral targets. Finally, we will highlight recent advances in the design and the development of small-molecule inhibitors binding to the LEDGF/p75-binding pocket in IN (LEDGINs).</p>","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/10.1155/2012/863405","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30863785","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}

{"title":"Combined RASSF1A and RASSF2A Promoter Methylation Analysis as Diagnostic Biomarker for Bladder Cancer.","authors":"Wei Meng,&nbsp;Alexander Huebner,&nbsp;Ahmad Shabsigh,&nbsp;Arnab Chakravarti,&nbsp;Tim Lautenschlaeger","doi":"10.1155/2012/701814","DOIUrl":"https://doi.org/10.1155/2012/701814","url":null,"abstract":"<p><p>Promoter hypermethylation, a widely studied epigenetic event known to influence gene expression levels, has been proposed as a potential biomarker in multiple types of cancer. Clinical diagnostic biomarkers are needed for reliable prediction of bladder cancer recurrence. In this paper, DNA promoter methylation of five C-terminal Ras-association family members (RASSF1A, RASSF2A, RASSF4, RASSF5, and RASSF6) was studied in 64 formalin-fixed paraffin-embedded (FFPE) bladder cancer and normal adjacent tissues using methylation-specific high-resolution melting (MS-HRM) analysis. Results showed that 73% (30/41) of transitional cell carcinoma, 100% (3/3) of squamous cell carcinoma, and 100% (4/4) of small cell carcinoma demonstrated promoter methylation of the RASSF1A or RASSF2A gene, but only 6% (1/16) of normal tissues had promoter methylation of RASSF genes. Testing positive for hypermethylation of RASSF1A or RASSF2A promoter provided 77% sensitivity and 94% specificity for identification of cancer tissues with an area under the curve of 0.854, suggesting that promoter methylation analysis of RASSF1A and RASSF2A genes has potential for use as a recurrence biomarker for bladder cancer patients.</p>","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/10.1155/2012/701814","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40180716","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}

{"title":"Pathogenetic and Prognostic Significance of Inactivation of RASSF Proteins in Human Hepatocellular Carcinoma.","authors":"Diego F Calvisi,&nbsp;Matthias Evert,&nbsp;Frank Dombrowski","doi":"10.1155/2012/849874","DOIUrl":"https://doi.org/10.1155/2012/849874","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is one of the most frequent solid tumors worldwide, with limited treatment options and a dismal prognosis. Thus, there is a strong need to expand the basic and translational research on this deadly disease in order to improve the prognosis of HCC patients. Although the etiologic factors responsible for HCC development have been identified, the molecular pathogenesis of liver cancer remains poorly understood. Recent evidence has shown the frequent downregulation of Ras association domain family (RASSF) proteins both in the early and late stages of hepatocarcinogenesis. Here, we summarize the data available on the pathogenetic role of inactivation of RASSF proteins in liver cancer, the molecular mechanisms responsible for suppression of RASSF proteins in HCC, and the possible clinical implications arising from these discoveries. Altogether, the data indicate that inactivation of the RASSF1A tumor suppressor is ubiquitous in human liver cancer, while downregulation of RASSF2 and RASSF5 proteins is limited to specific HCC subsets. Also, the present findings speak in favour of therapeutic strategies aimed at reexpressing RASSF1A, RASSF2, and RASSF5 genes and/or inactivating the RASSF cellular inhibitors for the treatment of human liver cancer.</p>","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/10.1155/2012/849874","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40196399","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}

{"title":"RASSF Family Proteins.","authors":"Geoffrey J Clark,&nbsp;Shairaz Baksh,&nbsp;Farida Latif,&nbsp;Dae-Sik Lim","doi":"10.1155/2012/938916","DOIUrl":"https://doi.org/10.1155/2012/938916","url":null,"abstract":"1 JG Brown Cancer Center, University of Louisville, 417 CTR Building, 505 S. Hancock Street, Louisville, KY 40202, USA 2Division of Hematology/Oncology, Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, 3-055 Katz Group Centre for Pharmacy and Health Research, 113 Street 87 Avenue, Edmonton, AB, Canada T6G 2E1 3School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK 4National Creative Research Initiatives Center for Cell Division and Differentiation, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 373-1 Guseoung-D, Yuseong-G, Daejeon 305-701, Republic of Korea","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/10.1155/2012/938916","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31150972","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}

{"title":"HIV Assembly and Budding: Ca(2+) Signaling and Non-ESCRT Proteins Set the Stage.","authors":"Lorna S Ehrlich,&nbsp;Carol A Carter","doi":"10.1155/2012/851670","DOIUrl":"https://doi.org/10.1155/2012/851670","url":null,"abstract":"<p><p>More than a decade has elapsed since the link between the endosomal sorting complex required for transport (ESCRT) machinery and HIV-1 protein trafficking and budding was first identified. L domains in HIV-1 Gag mediate recruitment of ESCRT which function in bud abscission releasing the viral particle from the host cell. Beyond virus budding, the ESCRT machinery is also involved in the endocytic pathway, cytokinesis, and autophagy. In the past few years, the number of non-ESCRT host proteins shown to be required in the assembly process has also grown. In this paper, we highlight the role of recently identified cellular factors that link ESCRT machinery to calcium signaling machinery and we suggest that this liaison contributes to setting the stage for productive ESCRT recruitment and mediation of abscission. Parallel paradigms for non-ESCRT roles in virus budding and cytokinesis will be discussed.</p>","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/10.1155/2012/851670","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30740167","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}

{"title":"Retroviral env glycoprotein trafficking and incorporation into virions.","authors":"Tsutomu Murakami","doi":"10.1155/2012/682850","DOIUrl":"https://doi.org/10.1155/2012/682850","url":null,"abstract":"<p><p>Together with the Gag protein, the Env glycoprotein is a major retroviral structural protein and is essential for forming infectious virus particles. Env is synthesized, processed, and transported to certain microdomains at the plasma membrane and takes advantage of the same host machinery for its trafficking as that used by cellular glycoproteins. Incorporation of Env into progeny virions is probably mediated by the interaction between Env and Gag, in some cases with the additional involvement of certain host factors. Although several general models have been proposed to explain the incorporation of retroviral Env glycoproteins into virions, the actual mechanism for this process is still unclear, partly because structural data on the Env protein cytoplasmic tail is lacking. This paper presents the current understanding of the synthesis, trafficking, and virion incorporation of retroviral Env proteins.</p>","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/10.1155/2012/682850","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30774703","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}

{"title":"Interleukin-1 Two-Locus Haplotype Is Strongly Associated with Severe Chronic Periodontitis among Yemenis.","authors":"Nezar Noor Al-Hebshi,&nbsp;Amat-Alrahman Ahmed Shamsan,&nbsp;Mohammed Sultan Al-Ak'hali","doi":"10.1155/2012/231309","DOIUrl":"10.1155/2012/231309","url":null,"abstract":"<p><p>Aim. To assess IL-1A C[-889]T and IL-1B C[3954]T genotypes as well as haplotypes in relation to sever chronic periodontitis (SCP) among Yemenis. Materials and Methods. 40 cases with SCP and 40 sex- and age-matched controls were included; all were nonsmokers and free of systemic diseases. Genotyping at each locus was performed using an established PCR-RFLP assay. The Haploview and SimHap software were used to assess data for Hardy-Weinberg's equilibrium (HWE) and linkage disequilibrium (LD) and to obtain subject-level haplotypes. Multiple logistic regression was used to seek for associations in dominant, additive, and recessive models. Results. Mean plaque index (MPI) showed the strongest association with SCP (OR = 16). A significant LD was observed in the cases (D' = 0.80 and r(2) = 0.47). The genotype at each locus showed significant association with SCP in the recessive model (TT versus TC + CC) even after adjustment for MPI (OR = 6.29 & 461, resp.). The C-T haplotype conferred protection against SCP in a dominant manner (OR = 0.16). On the other hand, the T-T haplotype in double dose (recessive model) showed strong association with CP (OR = 15.6). Conclusions. IL-1 two-locus haplotype is associated with SCP in Yemenis. Haplotype-based analysis may be more suited for use in genetic association studies of periodontitis.</p>","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/10.1155/2012/231309","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30750241","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}

{"title":"The Impact of HIV Genetic Polymorphisms and Subtype Differences on the Occurrence of Resistance to Antiretroviral Drugs.","authors":"Mark A Wainberg,&nbsp;Bluma G Brenner","doi":"10.1155/2012/256982","DOIUrl":"https://doi.org/10.1155/2012/256982","url":null,"abstract":"The vast majority of reports on drug resistance deal with subtype B infections in developed countries, and this is largely due to historical delays in access to antiretroviral therapy (ART) on a worldwide basis. This notwithstanding the concept that naturally occurring polymorphisms among different non-B subtypes can affect HIV-1 susceptibility to antiretroviral drugs (ARVs) is supported by both enzymatic and virological data. These findings suggest that such polymorphisms can affect both the magnitude of resistance conferred by some major mutations as well as the propensity to acquire certain resistance mutations, even though such differences are sometimes difficult to demonstrate in phenotypic assays. It is mandatory that tools are optimized to assure accurate measurements of drug susceptibility in non-B subtypes and to recognize that each subtype may have a distinct resistance profile and that differences in resistance pathways may also impact on cross-resistance and the choice of regimens to be used in second-line therapy. Although responsiveness to first-line therapy should not theoretically be affected by considerations of viral subtype and drug resistance, well-designed long-term longitudinal studies involving patients infected by viruses of different subtypes should be carried out.","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/10.1155/2012/256982","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30760213","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}