Functional relatedness between the E1a and E1b regions of group C and group D human adenoviruses

The functional relatedness of the transforming genes (E1a and E1b) of adenovirus type 9 (group D) which induces mammary tumors in rats and those of the non-tumorigenic adenoviruses, Ad2 and Ad5 (group C) was examined. Transfection of established rat embryo cells with a DNA segment containing the E1a and E1b regions of Ad9 resulted in efficient transformation; similar results have been shown for group A, B and C Ads. In contrast to Ads of group A, B and C, Ad9 DNA containing the E1 region or the entire viral genome was unable to transform primary baby rat kidney (BRK) cells. The functional relatedness of genes encoded within the E1 region was compared using a mutant complementation assay in which various group C mutants defective in the entire E1 region or in the E1a or E1b regions alone as well as mutants defective exclusively within the 19K or 58K T antigens coding regions of E1b were coinfected with wild type (wt) Ad9 and tested for group C mutant DNA replication, virus production, or expression of early and late genes. These studies have shown that a defect in the entire E1 region of Ad2 could only be complemented poorly by Ad9; our earlier studies have shown that coinfection with Ad12 (group A) or Ad7 (group B) resulted in efficient complementation (Brusca and Chinnadurai (1981) J. Virol. 39, 300-305). Further analysis indicated that a defect in the E1a region could be complemented by the group D E1a region. The level of E1a complementation as judged by mutant DNA replication and activation of expression of mutant early viral genes was about one-fourth to one-fifth the level in 293 cells that constitutively express Ad5 E1a and E1b regions. Our results indicate that a defect in the E1b 19K T antigen, which leads to degradation of intracellular DNA in infected cells, could be complemented by the group D protein. However, a defect in the E1b 58K T antigen could not be efficiently complemented by the group D protein. Coinfection of group C mutants defective in the 58K T antigen and Ad9 wt did not lead to an increase in the mutant viral production. Furthermore, in cells coinfected with the 58K T antigen mutants and Ad9 wt there was a large reduction in the accumulation of group C late cytoplasmic RNA. The observed complementation defect of Ad9 in supporting multiplication of group C mutants defective in the entire E1 region may therefore be a cumulative effect of both E1a and E1b regions.     

L-Ascorbic Acid and α-Tocopherol Reduces Hepatotoxicity Associated with Arsenic Trioxide Chemotherapy by Modulating Nrf2 and Bcl2 Transcription Factors in Chang liver Cells

Arsenic trioxide (As₂O₃) is a promising new regimen for the treatment of acute promyelocytic leukemia (APL). The induction of oxidative stress mediated by reactive oxygen species (ROS) and excessive intracellular calcium influx are the main reasons behind As₂O₃ toxicity. Since liver is the major organ for xenobiotic metabolism, it is always under stress. Antioxidant vitamins such as L-Ascorbic acid (L-AA) and α-Tocopherol (α-TOC) have been proposed to have beneficial effects against a variety of pathological conditions and are known by their free radical scavenging properties. The present study evaluates the curative efficacy of L-AA and α-TOC against As₂O₃ toxicity using immortalized human Chang liver cells. Our results suggest that L-AA (100 µM) and α-TOC (50 µM) recovered As₂O₃ (10 µM) cytotoxicity. Furthermore, As₂O₃ treatment showed an increase in lipid peroxidation and depletion in antioxidant status, mitochondrial trans membrane potential and values of total antioxidant capacity. Cotreatment of antioxidant vitamins with As₂O₃ resulted in a significant reversal of oxidative stress markers. Our findings substantiate the effect of antioxidant vitamins in protecting the hepatocytes from oxidative stress which may be attributed through Nrf2 (Nuclear factor erythroid 2-related factor 2) mediated upregulation of Bcl2 (B-cell lymphoma 2) expression.     

The HLA-G Genetic Contribution to Bipolar Disorder: A Trans-Ethnic Replication

Bipolar disorder (BD) is frequently associated with immune dysfunctions. Studying the genetic diversity of the immuno-modulatory human leukocyte antigen (HLA)-G locus in a French BD cohort, we previously reported an association between a functionally relevant 14 bp Ins/Del polymorphism and BD risk. The present study investigated the genetic and expression diversities of HLA-G in a geographically distinct South Indian population-group BD patients, as well as the influence of exposure to the neurotropic Toxoplasma gondii pathogen. Three functionally relevant HLA-G polymorphisms, i.e. HLA-G 14 bp Ins/Del (rs66554220), +3142G>C (rs1063320) and +3187A>G (rs9380142) were genotyped by polymerase chain reaction (PCR) and real-time PCR. Sub-samples of BD patients and healthy controls (HC) were investigated for plasma levels of soluble HLA-G (sHLA-G) isoforms, as well as circulating stigma of T. gondii infection.

Findings indicate: (i) the frequency of the HLA-G 14 bp Del/Del genotype was higher in BD cases, as compared to HC; (ii) the HLA-G + 3142 C allele and CC genotype were more prevalent in BD patients than in HC; (iii) sHLA-G levels were significantly higher in BD cases, especially in females and in the early onset sub-group; and (iv) the InsGA haplotype was more prevalent in HC.

Our findings further support the genetic contribution of HLA-G to BD risk, as well as indicate relevant expression profiles. Such data may also indicate a potential developmental role in BD etiology, given that HLA-G is an important immune regulator from the intrauterine period and across development.     

A Review on Joint Carotid Intima-Media Thickness and Plaque Area Measurement in Ultrasound for Cardiovascular/Stroke Risk Monitoring: Artificial Intelligence Framework

Journal of Digital Imaging - Cardiovascular diseases (CVDs) are the top ten leading causes of death worldwide. Atherosclerosis disease in the arteries is the main cause of the CVD, leading to...     

Inhibition of fungal NADP+-isocitrate dehydrogenase by citric acid

The variations observed during earlier studies in the activity of NADP⁺-isocitrate dehydrogenase (EC. 1.1.1.42) in a strain of Aspergillus niger were found to be related to the extent of washing of mycelium. As a result the mycelium washed four times with phosphate buffer (0.05 M, pH 7.5), the enzyme activity present in 4 and 8 days old fungal mycelia increased five- and two-fold, respectively. In vivo studies showed a complete loss of enzyme activity in mycelia resuspended in HCl-KCl buffer (0.02 M, pH 2.2) containing citric acid (13 mM or more). The in vitro studies revealed 50% loss of enzyme activity in presence of 3.6 to 5.2 mM citric acid. However, in case of Aspergillus niger ATCC 1015, which produced less citric acid than the above strain, a much higher citric acid concentration (13 to 26 mM) was required to cause 50% loss of enzyme activity. These findings suggest a correlation between citric acid inhibition of NADP⁺-isocitrate dehydrogenase and the ability of A. niger to accumulate citric acid in the medium.     

Effect of acute hypobaric hypoxia on fatty acid metabolism in rat lung

Exposure of male albino rats in the weight range of 70-200 g to 25,000 ft of simulated altitude for 6 h at 32 degrees C caused an increase in plasma free fatty acids with decreased oxidation of palmitic acid-1-14C in lung slices of hypoxic rats. The in vivo esterification of palmitic acid-1-14C to form truglycerides, phosphatidylcholine and phosphatidylethanolamine was also low indicating decreased utilization of fatty acids by hypoxic lungs. De novo lipogenesis was observed to decreased to decrease because of decreased fatty acid biosynthesis as judged from acetate---14C incorporation. The specific activities of triglycerides, phosphatidylcholine and free cholesterol were also decreased. The decreased incorporation into phosphatidylcholine affected the incorporation into phosphatidylcholine of alveolar surfactant (2,000 g sediment fraction). The results are discussed in view of possible decreased energy status of hypoxic lungs.