Calcineurin signaling and membrane lipid homeostasis regulates iron mediated multidrug resistance mechanisms in Candida albicans

We previously demonstrated that iron deprivation enhances drug susceptibility of Candida albicans by increasing membrane fluidity which correlated with the lower expression of ERG11 transcript and ergosterol levels. The iron restriction dependent membrane perturbations led to an increase in passive diffusion and drug susceptibility. The mechanisms underlying iron homeostasis and multidrug resistance (MDR), however, are not yet resolved. To evaluate the potential mechanisms, we used whole genome transcriptome and electrospray ionization tandem mass spectrometry (ESI-MS/MS) based lipidome analyses of iron deprived Candida cells to examine the new cellular circuitry of the MDR of this pathogen. Our transcriptome data revealed a link between calcineurin signaling and iron homeostasis. Among the several categories of iron deprivation responsive genes, the down regulation of calcineurin signaling genes including HSP90, CMP1 and CRZ1 was noteworthy. Interestingly, iron deprived Candida cells as well as iron acquisition defective mutants phenocopied molecular chaperone HSP90 and calcineurin mutants and thus were sensitive to alkaline pH, salinity and membrane perturbations. In contrast, sensitivity to above stresses did not change in iron deprived DSY2146 strain with a hyperactive allele of calcineurin. Although, iron deprivation phenocopied compromised HSP90 and calcineurin, it was independent of protein kinase C signaling cascade. Notably, the phenotypes associated with iron deprivation in genetically impaired calcineurin and HSP90 could be reversed with iron supplementation. The observed down regulation of ergosterol (ERG1, ERG2, ERG11 and ERG25) and sphingolipid biosynthesis (AUR1 and SCS7) genes followed by lipidome analysis confirmed that iron deprivation not only disrupted ergosterol biosynthesis, but it also affected sphingolipid homeostasis in Candida cells. These lipid compositional changes suggested extensive remodeling of the membranes in iron deprived Candida cells. Taken together, our data provide the first novel insight into the intricate relationship between cellular iron, calcineurin signaling, membrane lipid homeostasis and drug susceptibility of Candida cells

Low Energy X-ray Photons Induced Changes in Lexan Films

40 keV Synchrotron X-ray photons were made to fall on Lexan polycarbonate films at different exposure time. The low energy X-ray photons assisted modification in terms of physico-chemical properties of Lexan films were studied using Fourier Transform Infrared (FTIR) spectrophotometer, X-Ray Diffractogram (XRD), Vicker’s Microhardness Tester,Scanning Electron Microscope (SEM) and Contact Angle Meter. FTIR result mainly includes decrease in the C=C stretching and C-C stretching of aromatics after irradiation. XRD analysis shows a slight decrease in the crystallinity after irradiation. Vicker’s microhardness test reveals the decrement in microhardness of Lexan films after irradiation. SEM result shows irradiation induced changes in the surface morphology. Contact angle measurement shows increase in the water contact angle in irradiated Lexan films

Low Energy X-ray Photons Induced Changes in Lexan Films

706-71040 keV Synchrotron X-ray photons were made to fall on Lexan polycarbonate films at different exposure time. The low energy X-ray photons assisted modification in terms of physico-chemical properties of Lexan films were studied using Fourier Transform Infrared (FTIR) spectrophotometer, X-Ray Diffractogram (XRD), Vicker’s Microhardness Tester, Scanning Electron Microscope (SEM) and Contact Angle Meter. FTIR result mainly includes decrease in the C=C stretching and C-C stretching of aromatics after irradiation. XRD analysis shows a slight decrease in the crystallinity after irradiation. Vicker’s microhardness test reveals the decrement in microhardness of Lexan films after irradiation. SEM result shows irradiation induced changes in the surface morphology. Contact angle measurement shows increase in the water contact angle in irradiated Lexan films

Salinity Stress Effects on Growth and Nitrate Assimilation in Bean Seedlings Likely to be Mediated via Nitric Oxide

Background : Salinity stress usually imposes adverse effects on plant systems, but the severity depends upon plant species, growth status and genotype, nutritional and environmental conditions etc. Present study analyses salinity effects on growth and in vivo nitrate reductase activity (NRA) in Phaseolus vulgaris seedlings to work out the mechanism. Results : Supply of 10-200 mM NaCl with 10 mM KNO3 for 24 h in continuous light reduced the overall growth of the bean seedlings, with perfect –ve correlation for seedling weight, root length and shoot length. Salinity effect with 10 mM NH4Cl was lesser and with 10 mM NH4NO3 was intermediary. NaCl treatment with 10 mM KNO3 reduced the fresh wt of the root as well as shoot tissue but increased in vivo NRA exerting strong correlation and more prominent effect in the root tissue. Very high NaCl concentration prominently increased NRA at 1, 10 and 50 mM KNO3 showing inverse gradation in effect. Salt treatment with NH4NO3, reduced the in vivo NRA of the root tissue, but the stress parameters, like proline and peroxidase were increased. Conclusions : The salinity stress effects on NRA are less severe with NH4+, more prominent for root and more effective at low NO3- concentration. Inverse correlation between decrease in fresh mass and increase in NRA with salinity suggests the involvement of NR in the synthesis of nitric oxide and the observed effect of stress is the balance of two factors reduced assimilatory effect and increased nitric oxide stress

Comparison of daily and intermittent anti tubercular treatment in achieving sputum negativity in newly diagnosed sputum positive Pulmonary tuberculosis patients

Introduction: Tuberculosis is a major health problem in India. Sputum positive pulmonary tuberculosis patients expel bacilli for a variable period after the start of treatment. The period of infectivity depends on the drugs, dosage and interval period. Achieving sputum negativity helps in reducing secondary cases. Aim: Comparison of the effectiveness of daily and intermittent anti tubercular treatment in achieving sputum negativity in newly diagnosed sputum positive pulmonary tuberculosis patients without comorbidities. Methods: A prospective study was carried out in BJMC and SGH, Pune. 71 sputum positive pulmonary tuberculosis patients were included in the study. 35 patients received daily treatment and 36 patients received intermittent treatment. Patients were followed up on 15th, 30th, 45th and 60th day of treatment. Results: Mean duration of sputum conversion was 29 days in daily treatment and 44 days in intermittent treatment. Patients on daily regimen have sputum conversion about 15 days earlier as compared to intermittent regimen. (p<0.05). Conclusion: Patients on daily treatment are sputum negative 15 days prior to patients on intermittent treatment. Using daily treatment will decrease the period of communicability. Thus daily treatment will decrease the incidence and prevalence of the disease in a country with heavy burden of tuberculosis. A cost effective approach will be daily treatment during intensive phase and intermittent treatment during continuation phase