Transcription factor AP-1 in esophageal squamous cell carcinoma: Alterations in activity and expression during Human Papillomavirus infection

<p>Abstract</p> <p>Background</p> <p>Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related deaths in Jammu and Kashmir (J&K) region of India. A substantial proportion of esophageal carcinoma is associated with infection of high-risk HPV type 16 and HPV18, the oncogenic expression of which is controlled by host cell transcription factor Activator Protein-1 (AP-1). We, therefore, have investigated the role of DNA binding and expression pattern of AP-1 in esophageal cancer with or without HPV infection.</p> <p>Methods</p> <p>Seventy five histopathologically-confirmed esophageal cancer and an equal number of corresponding adjacent normal tissue biopsies from Kashmir were analyzed for HPV infection, DNA binding activity and expression of AP-1 family of proteins by PCR, gel shift assay and immunoblotting respectively.</p> <p>Results</p> <p>A high DNA binding activity and elevated expression of AP-1 proteins were observed in esophageal cancer, which differed between HPV positive (19%) and HPV negative (81%) carcinomas. While JunB, c-Fos and Fra-1 were the major contributors to AP-1 binding activity in HPV negative cases, Fra-1 was completely absent in HPV16 positive cancers. Comparison of AP-1 family proteins demonstrated high expression of JunD and c-Fos in HPV positive tumors, but interestingly, Fra-1 expression was extremely low or nil in these tumor tissues.</p> <p>Conclusion</p> <p>Differential AP-1 binding activity and expression of its specific proteins between HPV - positive and HPV - negative cases indicate that AP-1 may play an important role during HPV-induced esophageal carcinogenesis.</p

Vitamins A & D Inhibit the Growth of Mycobacteria in Radiometric Culture

The role of vitamins in the combat of disease is usually conceptualized as acting by modulating the immune response of an infected, eukaryotic host. We hypothesized that some vitamins may directly influence the growth of prokaryotes, particularly mycobacteria. complex).Vitamins A and D cause dose-dependent inhibition of all three mycobacterial species studied. Vitamin A is consistently more inhibitory than vitamin D. The vitamin A precursor, β-carotene, is not inhibitory, whereas three vitamin A metabolites cause inhibition. Vitamin K has no effect. Vitamin E causes negligible inhibition in a single strain.We show that vitamin A, its metabolites Retinyl acetate, Retinoic acid and 13-cis Retinoic acid and vitamin D directly inhibit mycobacterial growth in culture. These data are compatible with the hypothesis that complementing the immune response of multicellular organisms, vitamins A and D may have heretofore unproven, unrecognized, independent and probable synergistic, direct antimycobacterial inhibitory activity

Comparative Performance of Private and Public Healthcare Systems in Low- and Middle-Income Countries: A Systematic Review

A systematic review conducted by Sanjay Basu and colleagues reevaluates the evidence relating to comparative performance of public versus private sector healthcare delivery in low- and middle-income countries

Apparent genetic redundancy facilitates ecological plasticity for nitrate transport

Aspergillus nidulans possesses two high-affinity nitrate transporters, encoded by the nrtA and the nrtB genes. Mutants expressing either gene grew normally on 1-10 mM nitrate as sole nitrogen source, whereas the double mutant failed to grow on nitrate concentrations up to 200 mM. These genes appear to be regulated coordinately in all growth conditions, growth stages and regulatory genetic backgrounds studied. Flux analysis of single gene mutants using (NO3-)-N-13 revealed that K-m values for the NrtA and NrtB transporters were similar to 100 and similar to 10 muM, respectively, while V-max values, though variable according to age, were similar to 600 and similar to 100 nmol/mg dry weight/h, respectively, in young mycelia. This kinetic differentiation may provide the necessary physiological and ecological plasticity to acquire sufficient nitrate despite highly variable external concentrations. Our results suggest that genes involved in nitrate assimilation may be induced by extracellular sensing of ambient nitrate without obligatory entry into the cell.</p

Effects of Soil Temperature and Nitrogen Status on Kinetics of 15NO3 Uptake by Roots of Field-grown Agropyron Desertorum

Plant NO8‐ acquisition is largely determined by root uptake capacity. Although root uptake capacity has been shown to be sensitive to both root temperature and previous nitrogen (N) supply in hydroponic systems, the uptake capacity response to similar environmental factors under field conditions has not been investigated. Using 15NO3−, root uptake capacities were determined in excised roots of Agropyron desertorum (Fisch. ex Link) Schult grown in the field at two soil temperatures and two N fertilization treatments. Variation in soil and root temperatures was achieved by application of clear plastic film or insulating mulch to the soil immediately around the target plants. Uptake rates were measured at six different assay solution concentrations (from 1 to 1000 μM external 15NO3− concentration range). Two months after the imposition of soil N and temperature treatments, a biphasic transport system (a high‐affinity) saturable phase and a low‐affinity transport phase) was apparent in low N‐treated plants. Nitrate uptake capacity in the low‐concentration range (1–500μM) was significantly reduced in N‐fertilized plants compared with unfertilized control plants and the effect was more pronounced at high (27 °C) than low (17 °C) soil and assay temperatures. Furthermore, high soil N status inhibited the expression of a low‐affinity NO3− transport system which was clearly apparent at external NO3− concentration ranges between 500 and 1000 mM in plants grown at low soil N. Prior soil N and temperature history may ultimately determine root ability to exploit NO3− flushes which can result from changes in soil environmental conditions