Chronic granulomatous disease: a review of the infectious and inflammatory complications

Chronic Granulomatous Disease is the most commonly encountered immunodeficiency involving the phagocyte, and is characterized by repeated infections with bacterial and fungal pathogens, as well as the formation of granulomas in tissue. The disease is the result of a disorder of the NADPH oxidase system, culminating in an inability of the phagocyte to generate superoxide, leading to the defective killing of pathogenic organisms. This can lead to infections with Staphylococcus aureus, Psedomonas species, Nocardia species, and fungi (such as Aspergillus species and Candida albicans). Involvement of vital or large organs can contribute to morbidity and/or mortality in the affected patients. Major advances have occurred in the diagnosis and treatment of this disease, with the potential for gene therapy or stem cell transplantation looming on the horizon.     

Malarial infection develops mitochondrial pathology and mitochondrial oxidative stress to promote hepatocyte apoptosis

Activation of the mitochondrial apoptosis pathway by oxidative stress has been implicated in hepatocyte apoptosis during malaria. Because mitochondria are the source and target of reactive oxygen species (ROS), we have investigated whether hepatocyte apoptosis is linked to mitochondrial pathology and mitochondrial ROS generation during malaria. Malarial infection induces mitochondrial pathology by inhibiting mitochondrial respiration, dehydrogenases, and transmembrane potential and damaging the ultrastructure as evident from transmission electron microscopic studies. Mitochondrial GSH depletion and formation of protein carbonyl indicate that mitochondrial pathology is associated with mitochondrial oxidative stress. Fluorescence imaging of hepatocytes documents intramitochondrial superoxide anion (O₂^?) generation during malaria. O₂^? inactivates mitochondrial aconitase to release iron from iron–sulfur clusters, which forms the hydroxyl radical (OH) interacting with H₂O₂ produced concurrently. Malarial infection inactivates mitochondrial aconitase, and carbonylation of aconitase is evident from Western immunoblotting. The release of iron has been documented by fluorescence imaging of hepatocytes using Phen Green SK, and mitochondrial OH generation has been confirmed. During malaria, the depletion of cardiolipin and formation of the mitochondrial permeability transition pore favor cytochrome c release to activate caspase-9. Interestingly, mitochondrial OH generation correlates with the activation of both caspase-9 and caspase-3 with the progress of malarial infection, indicating the critical role of OH.     

Leaf gas exchange,water relations and photosystem-II functionality depict anisohydric behavior of drought-stressed mulberry (Morus indica, cv. V1) in the hot semi-arid steppe agroclimate of Southern India

The present study was undertaken to characterize leaf gas exchange physiology and photoacclimation characteristics in drought-stressed mulberry cultivar V1 (Morus indica L.) grown under the hot semi-arid steppe agroclimate of Southern India. The experiment was conducted in year 2009 during peak summer months (April–June). Mulberry plants, grown in short rotation coppice system, were subjected to two irrigation regimes: the control plot received a regulated full-rate irrigation (weekly 2–3 times) and the drought-stressed plot received a regulated deficit irrigation (irrigated only once in a fortnight). Net photosynthesis, transpiration, stomatal conductance, leaf water potential (Ψ_L) and photosytem-II (PS II) efficiency were examined. In spite of significant down-regulation in leaf gas exchange, the drought-stressed stands still exhibited a considerable rate of photosynthesis along with significant concomitant decrease in Ψ_L, more conspicuously during midday (12.00–13.00 h) depicting rather low stomatal control on Ψ_L, a behavior characterized as ‘anisohydric’. The PS II structural and functional integrity was well-maintained, even in the drought-stressed plants. However, apparent photoacclimatory changes were recorded in drought-exposed stands including decrease in electron transport and enhanced thermal dissipation from PS II. Overall, our data demonstrate some of the important driving leaf-level mechanisms adopted by mulberry cultivar V1 to tolerate drought stress and sustain photosynthesis.     

Probiotics L. acidophilus and B. clausii Modulate Gut Microbiota in Th1- and Th2-Biased Mice to Ameliorate Salmonella Typhimurium-Induced Diarrhea

Gut microbiota play important role in maintaining health. Probiotics are believed to augment it further. We aimed at comparing effects of probiotics, Lactobacillus acidophilus (LA) and Bacillus clausii (BC) (a) on the gut microbiota abundance and diversity and (b) their contributions to control intestinal dysbiosis and inflammation in Th1- and Th2-biased mice following Salmonella infection. We report how could gut microbiota and the differential immune bias (Th1 or Th2) of the host regulate host responses when challenged with Salmonella typhimurium in the presence and absence of either of the probiotics. LA was found to be effective in ameliorating the microbial dysbiosis and inflammation caused by Salmonella infection, in Th1 (C57BL/6) and Th2 (BALB/c)-biased mouse. BC was able to ameliorate Salmonella-induced dysbiosis and inflammation in Th2 but not in Th1-biased mouse. These results may support probiotics LA as a treatment option in the case of Salmonella infection.

     

Tracheal branch repopulation precedes induction of the Drosophila dorsal air sac primordium

The dorsal air sacs supply oxygen to the flight muscles of the Drosophila adult. This tracheal organ grows from an epithelial tube (the air sac primordium (ASP)) that arises during the third larval instar (L3) from a wing-disc-associated tracheal branch. Since the ASP is generated by a program of both morphogenesis and cell proliferation and since the larval tracheal branches are populated by cells that are terminally differentiated, the provenance of its progenitors has been uncertain. Here, we show that, although other larval tracheae are remodeled after L3, most tracheal branches in the tracheal metamere associated with the wing disc (Tr2) are precociously repopulated with imaginal tracheoblasts during L3. Concurrently, the larval cells in Tr2 undergo head involution defective (hid)-dependent programmed cell death. In BX-C mutant larvae, the tracheal branches of the Tr3 metamere are also repopulated during L3. Our results show that repopulation of the larval trachea is a prerequisite for FGF-dependent induction of cell proliferation and tubulogenesis in the ASP and that homeotic selector gene function is necessary for the temporal and spatial control of tracheal repopulation.     

Environments of the four tryptophans in the extracellular domain of human tissue factor: comparison of results from absorption and fluorescence difference spectra of tryptophan replacement mutants with the crystal structure of the wild-type protein.

The local environments of the four tryptophan residues of the extracellular domain of human tissue factor (sTF) were assessed from difference absorption and fluorescence spectra. The difference spectra were derived by subtracting spectra from single Trp-to-Phe or Trp-to-Tyr replacement mutants from the corresponding spectrum of the wild-type protein. Each of the mutants was capable of enhancing the proteolytic activity of factor VIIa showing that the mutations did not introduce major structural changes, although the mutants were more susceptible to denaturation by guanidinium chloride. The difference spectra indicate that the Trp residues are buried to different extents within the protein matrix. This evaluation was compared with the x-ray crystal structure of sTF. There is excellent agreement between predictions from the difference spectra and the environments of the Trp residues observed in the x-ray crystal structure, demonstrating that difference absorption and particularly fluorescence spectra derived from functional single-Trp replacement mutants can be used to obtain information about the local environments of individual Trp residues in multi-tryptophan proteins.