Biochemistry Insights最新文献_第6页

A 20 Residues Motif Delineates the Furin Cleavage Site and its Physical Properties May Influence Viral Fusion 一个20残基基序描绘了Furin切割位点及其物理性质可能影响病毒融合

Biochemistry Insights Pub Date : 2009-01-01 DOI: 10.4137/BCI.S2049

S. Tian

{"title":"A 20 Residues Motif Delineates the Furin Cleavage Site and its Physical Properties May Influence Viral Fusion","authors":"S. Tian","doi":"10.4137/BCI.S2049","DOIUrl":"https://doi.org/10.4137/BCI.S2049","url":null,"abstract":"Furin is a proprotein convertase that proteolytically cleaves protein precursors to yield functional proteins. Efficient cleavage depends on the presence of a specific sequence motif on the substrate. Currently, the cleavage site motif is described as a four amino acid pattern: R-X-[K/R]-R⇓. However, not all furin cleavage recognition sites can be described by this pattern and not all R-X-[K/R]-R⇓ sites are cleaved by furin. Since many furin substrates are involved in the pathogenesis of viral infection and human diseases, it is important to accurately characterize the furin cleavage site motif. In this study, the furin cleavage site motif was characterized using statistical analysis. The data were interpreted within the 3D crystal structure of the furin catalytic domain. The results indicate that the furin cleavage site motif is comprised of about 20 residues, P14-P6′. Specific physical properties such as volume, charge, and hydrophilicity are required at specific positions. The furin cleavage site motif is divided into two parts: 1) one core region (8 amino acids, positions P6-P2′) packed inside the furin binding pocket; 2) two polar regions (8 amino acids, positions P7–P14; and 4 amino acids, positions P3′-P6′) located outside the furin binding pocket. The physical properties of the core region contribute to the binding strength of the furin substrate, while the polar regions provide a solvent accessible environment and facilitate the accessibility of the core region to the furin binding pocket. This furin cleavage site motif also revealed a dynamic relationship linking the evolution of physical properties in region P1′-P6′ of viral fusion peptides, furin cleavage efficacy, and viral infectivity.","PeriodicalId":8791,"journal":{"name":"Biochemistry Insights","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70684632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 43

Prolonged Treatment with Free Fatty Acids has Post Receptor Effect in Hepatic Insulin Resistance: Evidence that Fatty Acids, Oleate and Palmitate have Insignificant Effect on the Insulin Receptor Beta In Vivo and Ex Vivo primary Hepatocytes 游离脂肪酸长期治疗对肝脏胰岛素抵抗具有受体后效应:脂肪酸、油酸和棕榈酸酯对体内和离体原代肝细胞胰岛素受体β影响不显著的证据

Biochemistry Insights Pub Date : 2009-01-01 DOI: 10.4137/BCI.S2850

R. Ragheb, A. Medhat, G. Shanab, D. Seoudi, I. G. Fantus

{"title":"Prolonged Treatment with Free Fatty Acids has Post Receptor Effect in Hepatic Insulin Resistance: Evidence that Fatty Acids, Oleate and Palmitate have Insignificant Effect on the Insulin Receptor Beta In Vivo and Ex Vivo primary Hepatocytes","authors":"R. Ragheb, A. Medhat, G. Shanab, D. Seoudi, I. G. Fantus","doi":"10.4137/BCI.S2850","DOIUrl":"https://doi.org/10.4137/BCI.S2850","url":null,"abstract":"In the current study, we used immunoprecipitation and immunoblotting to examine the levels and phosphorylation status of the insulin receptor-beta subunit (IR-β), as well as the down stream target in PI3K pathway, total PKB/Akt as well as their phosphorylated forms. The assessment of FFAs treatment showed no direct and significant effect on the PI3K stimulation, specifically the IR-β in primary hepatic control cells treated with insulin. Cells treated with either oleate or palmitate (360 μM) showed no statistically significant values following insulin stimulation (P > 0.05). To further investigate the effect of both FFAs and high insulin (1 μg), we examined the effects of oleate and palmitate at 360 μM concentration on IR-β as well as PKB. There was no significant difference in the total protein levels and their phosphorylated forms in cells treated with or without oleate or plamitate. Interestingly, IR-β tyrosine phosphorylation showed a similar insignificant effect in vivo and ex vivo hepatic cells treated with oleate or palmitate in comparison to their controls in the fructose fed hamsters.","PeriodicalId":8791,"journal":{"name":"Biochemistry Insights","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70684383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Fast and Simple microRNA Northern Blots 快速和简单的microRNA Northern印迹

Biochemistry Insights Pub Date : 2009-01-01 DOI: 10.4137/BCI.S2257

Nham T Tran

引用次数: 5

Renal Toxicity of Mercuric Chloride at Different Time Intervals in Rats 不同时间间隔氯化汞对大鼠肾毒性的影响

Biochemistry Insights Pub Date : 2009-01-01 DOI: 10.4137/BCI.S2928

W.A. Al-Madani, N. J. Siddiqi, A. Alhomida

{"title":"Renal Toxicity of Mercuric Chloride at Different Time Intervals in Rats","authors":"W.A. Al-Madani, N. J. Siddiqi, A. Alhomida","doi":"10.4137/BCI.S2928","DOIUrl":"https://doi.org/10.4137/BCI.S2928","url":null,"abstract":"This study was undertaken to study the renal toxicity of mercuric chloride in rats at different periods of time. The following groups of rats were studied: i) control, ii) placebo, iii) rats injected with a single ip dose of 100 mg/kg body weight of 2, 3 dimercapto-1-propanesulfonic acid, iv) rats injected with a single ip dose of 100 mg/kg body weight of 2, 3 dimercapto-1-propanesulfonic acid (DMPS) followed by a single dose ip of 2.0 mg HgCl2/kg body weight one hour after DMPS injection v) rats injected with a single ip dose of 2.0 mg HgCl2/kg body weight. Results indicate that mercuric chloride was more toxic after 48 hours of its administration when compared to 24 hours. Mercuric chloride administration caused an impairment of renal function which was evident from a significant decrease in urine volume, urinary excretion of urea, creatinine and glomerular filteration rate (P < 0.001) when compared to other treated groups. There was an increased excretion of protein, albumin and γ–-glutamyltransferase in the urine of mercuric chloride treated rats. Administration of 2, 3 dimercapto-1-propanesulfonic acid before mercuric chloride treatment caused the altered indices to return to near normal levels.","PeriodicalId":8791,"journal":{"name":"Biochemistry Insights","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/BCI.S2928","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70684506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 18

Article Commentary: Capsaicin—the Hot and Spicy Diet Turned Mild and Effective by Glycosylation 文章评论:辣椒素-糖基化使辛辣饮食变得温和有效

Biochemistry Insights Pub Date : 2009-01-01 DOI: 10.4137/BCI.S3064

H. T. Simonsen

引用次数: 1

Immune- and Pollution-mediated DNA Damage in Two Wild Mya arenaria Clam Populations 两个野生砂蛤种群免疫和污染介导的DNA损伤

Biochemistry Insights Pub Date : 2009-01-01 DOI: 10.4137/BCI.S2935

F. Gagné, M. L. Martín-Díaz, C. Blaise

{"title":"Immune- and Pollution-mediated DNA Damage in Two Wild Mya arenaria Clam Populations","authors":"F. Gagné, M. L. Martín-Díaz, C. Blaise","doi":"10.4137/BCI.S2935","DOIUrl":"https://doi.org/10.4137/BCI.S2935","url":null,"abstract":"In aquatic environments, genotoxicity results from the effects of pollution combined with the inflammatory response triggered by the immune system. Indeed, the production of nitrosylated DNA and proteins are though to arise from the production of peroxinitrite during phagocytosis and inflammation. The purpose of this study was to examine new DNA biomarkers that differentiate between immune- and pollution-mediated genotoxicity in wild clam populations. Intertidal clam populations were sampled and analyzed for gonadal DNA strand breaks, DNA nitrosylation and xanthine oxidoreductase (XOR) activity (purine salvage pathway). The clam weight-to-shell-length ratio, the gonado-somatic index (GSI), age status, lipid peroxidation, xenobiotic conjugation activity (glutathione S-transferase (GST) and phagocytic activity were examined to shed light on their relationships with the observed genotoxic endpoints. XOR activity and DNA strand breaks were generally elevated at polluted sites and correlated significantly with clam weight-to-shell-length ratios and DNA nitrosylation. DNA nitrosylation was also higher at some sites and correlated significantly with phagocytic activity and with DNA strand breaks. This study showed that DNA strand breaks were associated with both immune-and pollution-mediated effects. This suggests that there is a loss of DNA repair capacity due to the combined effects of aging, pollution and immune response in wild clam populations that are impacted by anthropogenic activity.","PeriodicalId":8791,"journal":{"name":"Biochemistry Insights","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70685089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Targeted Cancer Therapy with Tumor Necrosis Factor-Alpha. 肿瘤坏死因子- α靶向治疗癌症。

Biochemistry Insights Pub Date : 2008-07-22

Weibo Cai, Zachary J Kerner, Hao Hong, Jiangtao Sun

{"title":"Targeted Cancer Therapy with Tumor Necrosis Factor-Alpha.","authors":"Weibo Cai, Zachary J Kerner, Hao Hong, Jiangtao Sun","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Tumor necrosis factor-alpha (TNF-α), a member of the TNF superfamily, was the first cytokine to be evaluated for cancer biotherapy. However, the clinical use of TNF-α is severely limited by its toxicity. Currently, TNF-α is administered only through locoregional drug delivery systems such as isolated limb perfusion and isolated hepatic perfusion. To reduce the systemic toxicity of TNF-α, various strategies have been explored over the last several decades. This review summarizes current state-of-the-art targeted cancer therapy using TNF-α. Passive targeting, cell-based therapy, gene therapy with inducible or tissue-specific promoters, targeted polymer-DNA complexes, tumor pre-targeting, antibody-TNF-α conjugate, scFv/TNF-α fusion proteins, and peptide/TNF-α fusion proteins have all been investigated to combat cancer. Many of these agents are already in advanced clinical trials. Molecular imaging, which can significantly speed up the drug development process, and nanomedicine, which can integrate both imaging and therapeutic components, has the potential to revolutionize future cancer patient management. Cooperative efforts from scientists within multiple disciplines, as well as close partnerships among many organizations/entities, are needed to quickly translate novel TNF-α-based therapeutics into clinical investigation.</p>","PeriodicalId":8791,"journal":{"name":"Biochemistry Insights","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2008-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3792586/pdf/nihms-518109.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31798924","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

A Changing Research and Publication Landscape for Biochemistry 变化中的生物化学研究和出版景观

Biochemistry Insights Pub Date : 2008-01-01 DOI: 10.4137/BCI.S0

G. Mocz

引用次数: 0

Targeted Cancer Therapy with Tumor Necrosis Factor-Alpha 肿瘤坏死因子- α靶向治疗癌症

Biochemistry Insights Pub Date : 2008-01-01 DOI: 10.4137/BCI.S901

W. Cai, Zachary J. Kerner, H. Hong, Jiangtao Sun

{"title":"Targeted Cancer Therapy with Tumor Necrosis Factor-Alpha","authors":"W. Cai, Zachary J. Kerner, H. Hong, Jiangtao Sun","doi":"10.4137/BCI.S901","DOIUrl":"https://doi.org/10.4137/BCI.S901","url":null,"abstract":"Tumor necrosis factor-alpha (TNF-α), a member of the TNF superfamily, was the first cytokine to be evaluated for cancer biotherapy. However, the clinical use of TNF-α is severely limited by its toxicity. Currently, TNF-α is administered only through locoregional drug delivery systems such as isolated limb perfusion and isolated hepatic perfusion. To reduce the systemic toxicity of TNF-α, various strategies have been explored over the last several decades. This review summarizes current state-of-the-art targeted cancer therapy using TNF-α. Passive targeting, cell-based therapy, gene therapy with inducible or tissue-specific promoters, targeted polymer-DNA complexes, tumor pre-targeting, antibody-TNF-α conjugate, scFv/TNF-α fusion proteins, and peptide/TNF-α fusion proteins have all been investigated to combat cancer. Many of these agents are already in advanced clinical trials. Molecular imaging, which can significantly speed up the drug development process, and nanomedicine, which can integrate both imaging and therapeutic components, has the potential to revolutionize future cancer patient management. Cooperative efforts from scientists within multiple disciplines, as well as close partnerships among many organizations/entities, are needed to quickly translate novel TNF-α-based therapeutics into clinical investigation.","PeriodicalId":8791,"journal":{"name":"Biochemistry Insights","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/BCI.S901","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70685276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 32

Use of a Combined Duplex PCR/Dot Blot Assay for more sensitive genetic characterization 使用双链聚合酶链反应/点印迹联合检测更敏感的遗传特征

Biochemistry Insights Pub Date : 2008-01-01 DOI: 10.4137/BCI.S872

E. Curry, S. L. Pratt, D. Kelley, D. R. Lapin, J. Gibbons

{"title":"Use of a Combined Duplex PCR/Dot Blot Assay for more sensitive genetic characterization","authors":"E. Curry, S. L. Pratt, D. Kelley, D. R. Lapin, J. Gibbons","doi":"10.4137/BCI.S872","DOIUrl":"https://doi.org/10.4137/BCI.S872","url":null,"abstract":"A reliable and sensitive method of genetic analysis is necessary to detect multiple specific nucleic acid sequences from samples containing limited template. The most widely utilized method of specific gene detection, polymerase chain reaction (PCR), imparts inconsistent results when assessing samples with restricted template, especially in a multiplex reaction when copies of target genes are unequal. This study aimed to compare two methods of PCR product analysis, fluorescent detection following agarose gel electrophoresis or dot blot hybridization with chemiluminescent evaluation, in the detection of a single copy gene (SRY) and a multicopy gene (β-actin). Bovine embryo sex determination was employed to exploit the limited DNA template available and the target genes of unequal copies. Primers were used either independently or together in a duplex reaction with purified bovine genomic DNA or DNA isolated from embryos. When used independently, SRY and β-actin products were detected on a gel at the equivalent of 4-cell or 1-cell of DNA, respectively; however, the duplex reaction produced visible SRY bands at the 256 cell DNA equivalent and β-actin products at the 64 cell DNA equivalent. Upon blotting and hybridization of the duplex PCR reaction, product was visible at the 1–4 cell DNA equivalent. Duplex PCR was also conducted on 186 bovine embryos and product was subjected to gel electrophoresis or dot-blot hybridization in duplicate. Using PCR alone, sex determination was not possible for 22.6% of the samples. Using PCR combined with dot blot hybridization, 100.0% of the samples exhibited either both the male specific and β-actin products or the β-actin signal alone, indicating that the reaction worked in all samples. This study demonstrated that PCR amplification followed by dot blot hybridization provided more conclusive results in the evaluation of samples with low DNA concentrations and target genes of unequal copies.","PeriodicalId":8791,"journal":{"name":"Biochemistry Insights","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70685530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5