Critical role of mitochondrial dysfunction and impaired mitophagy in diabetic nephropathy

Mitochondrial dynamics play a critical role in deciding the fate of a cell under normal and diseased condition. Recent surge of studies indicate their regulatory role in meeting energy demands in renal cells making them critical entities in the progression of diabetic nephropathy. Diabetes is remarkably associated with abnormal fuel metabolism, a basis for free radical generation, which if left unchecked may devastate the mitochondria structurally and functionally. Impaired mitochondrial function and their aberrant accumulation have been known to be involved in the manifestation of diabetic nephropathy, indicating perturbed balance of mitochondrial dynamics, and mitochondrial turnover. Mitochondrial dynamics emphasize the critical role of mitochondrial fission proteins such as mitochondrial fission 1, dynamin-related protein 1 and mitochondrial fission factor and fusion proteins including mitofusin-1, mitofusin-2 and optic atrophy 1. Clearance of dysfunctional mitochondria is aided by translocation of autophagy machinery to the impaired mitochondria and subsequent activation of mitophagy regulating proteins PTEN-induced putative kinase 1 and Parkin, for which mitochondrial fission is a prior event. In this review, we discuss recent progression in our understanding of the molecular mechanisms targeting reactive oxygen species mediated alterations in mitochondrial energetics, mitophagy related disorders, impaired glucose transport, tubular atrophy, and renal cell death. The molecular cross talks linking autophagy and renoprotection through an intervention of 5′-AMP-activated protein kinase, mammalian target of rapamycin, and SIRT1 factors are also highlighted here, as in-depth exploration of these pathways may help in deriving therapeutic strategies for managing diabetes provoked end-stage renal disease.     

Effect of olfactory and visual stimuli on the orientation of the 4th instar larvae of the stem borer Chilo partellus swinhoe (Lepidoptera: Pyralidae).

The orientational responses of 4th instar larvae of Chilo partellus to different sources of stimuli being artificial diet, leaves and stems of maize and sorghum were tested, under free choice and no-choice situations. Larvae were attracted to maize and sorghum in a moderate to high degree dependent on what choice they were given. The orientational preference of the larvae, offered a choice between the visual and the odour sources, depended upon their stimulating capacities which were represented by the percentages of individuals responding to the sources of stimuli. Odour played a greater role than visual stimuli in this close range attraction when the two competed with each other.     

Natural killer activity against human K562 tumour cells during Plasmodium cynomolgi malarial infection of rhesus monkeys

This study assessed the natural killer (NK) cell activity profile during Plasmodium cynomolgi infection in rhesus monkeys. There was a significant decrease in the NK cell activity in the peripheral blood leukocytes of infected monkeys during the early, ascending phase of infection. However, as the parasite load decreased, NK cell activity returned to normal levels. This could be correlated with the peak increase in lymphocyte counts. This indicated that a decrease in NK cell activity observed at an earlier stage during an active P. vivax malarial infection was a temporary phenomenon.     

Cytotoxic potential of ribonuclease and ribonuclease hybrid proteins

Pancreatic RNase injected into Xenopus oocytes abolishes protein synthesis at concentrations comparable to the toxin ricin yet has no effect on oocyte protein synthesis when added to the extracellular medium. Therefore RNase behaves like a potent toxin when directed into a cell. To explore the cytotoxic potential of RNase toward mammalian cells, bovine pancreatic ribonuclease A was coupled via a disulfide bond to human transferrin or antibodies to the transferrin receptor. The RNase hybrid proteins were cytotoxic to K562 human erythroleukemia cells in vitro with an IC50 around 10(-7) M whereas greater than 10(-5) M native RNase was required to inhibit protein synthesis. Cytotoxicity requires both components of the conjugate since excess transferrin or ribonuclease inhibitors added to the medium protected the cells from the transferrin-RNase toxicity. Compounds that interfere with transferrin receptor cycling and compartmentalization such as ammonium chloride decreased the cytotoxicity of transferrin-RNase. After a dose-dependent lag period inactivation of protein synthesis by transferrin-RNase followed a first-order decay constant. In a clonogenic assay that measures the extent of cell death 1 x 10(-6) M transferrin-RNase killed at least 4 logs or 99.99% of the cells whereas 70 x 10(-6) M RNase was nontoxic. These results show that RNase coupled to a ligand can be cytotoxic. Human ribonucleases coupled to antibodies also may exhibit receptor-mediated toxicities providing a new approach to selective cell killing possibly with less systemic toxicity and importantly less immunogenicity than the currently employed ligand-toxin conjugates.     

Isolation and characterization of four polycyclic aromatic hydrocarbon degrading bacteria from soil near an oil refinery

Four bacterial strains (I-IV) capable of optimum growth on 0·1% naphthalene, anthracene or a mixture of naphthalene and phenanthrene were isolated from soil near an oil refinery. Two isolates (I and II) were identified as belonging to the genus Micrococcus , while strains III and IV were identified as Pseudomonas and Atcaligenes respectively. All the isolates were found to bear high molecular weight plasmid DNA (isolate I and IV 89%, II 67·5% and III 92·1% of Λ DNA), which is presumed to aid in the metabolism of polycyclic aromatic hydrocarbons. The strains also showed appreciable growth at high concentrations of NaCl (up to 7·5%).     

Enterotoxigenicity of diarrhoeal isolates of Salmonella bareilly

Whole cell cultures, cell-free supernatants, and cell sonicates from ten strains of Salmonella bareilly induced fluid accumulation in ligated rabbit and rat ileal loops. All strains had an intracellular vascular permeability factor, half were suckling mouse positive indicating the presence of a heat-stable type of activity. The toxin(s), however, were Immunologically distinct from the heat-labile toxin of Escherichia coll LT and cholera toxin. Besides enterotoxigenicity, all strains exhibited potential Invasive character.The authors are with the Department of Microbiology, Panjab University, Chandigarh, India 160 014. M. Saxena is the corresponding author.     

Natural killer activity against human K562 tumour cells during Plasmodium cynomolgi malarial infection of rhesus monkeys

Abstract This study assessed the natural killer (NK) cell activity profile during Plasmodium cynomologi infection in rhesus monkeys. There was a significant decrease in the NK cell activity in the peripheral blood leukocytes of infected monkeys during the early, asending phase of infection. However, as the parasite load decreased, NK cell activity returned to normal levels. This could be correlated with the peak increase in lymphocyte counts. This indicated that a decrease in NK cell activity observed at an earlier stage during an active P. vivax malarial infection was a temporary phenomenon.     

In Vitro Multiplication of Phoenix dactylifera (L)

A method of microcloning via somatic embryogenesis was established in date palm (Phoenix dactylifera L) cultivars. The method has potential for commercial application. Embryogenic cultures were initiated from soft primordial tissues of 2-3-year-old female suckers. The system was optimized first for the genotype ’sayar’ and then its applicability was tested to other genotypes. A method of pre-acclimation using pre-acclimation chambers has been devised, which improved hardening survival greatly. More than 80 clones obtained from the genotype ’sayar’ have been shifted to field for agronomic evaluation.