Tbata modulates thymic stromal cell proliferation and thymus function

By inhibiting Nedd8, Tbata suppresses thymic epithelial cell proliferation and thymus size in mice.Niche availability provided by stromal cells is critical to thymus function. Thymi with diminished function contain fewer stromal cells, whereas thymi with robust function contain proliferating stromal cell populations. Here, we show that the thymus, brain, and testes–associated gene (Tbata; also known as SPATIAL) regulates thymic epithelial cell (TEC) proliferation and thymus size. Tbata is expressed in thymic stromal cells and interacts with the enzyme Uba3, thereby inhibiting the Nedd8 pathway and cell proliferation. Thymi from aged Tbata-deficient mice are larger and contain more dividing TECs than wild-type littermate controls. In addition, thymic reconstitution after bone marrow transplantation occurred more rapidly in Rag2−/−Tbata−/− mice than in Rag2−/−Tbata+/+ littermate controls. These findings suggest that Tbata modulates thymus function by regulating stromal cell proliferation via the Nedd8 pathway

Evaluation of Leishmania donovani Protein Disulfide Isomerase as a Potential Immunogenic Protein/Vaccine Candidate against Visceral Leishmaniasis

In Leishmania species, Protein disulfide isomerase (PDI) - a redox chaperone, is reported to be involved in its virulence and survival. This protein has also been identified, through proteomics, as a Th1 stimulatory protein in the soluble lysate of a clinical isolate of Leishmania donovani (LdPDI). In the present study, the molecular characterization of LdPDI was carried out and the immunogenicity of recombinant LdPDI (rLdPDI) was assessed by lymphocyte proliferation assay (LTT), nitric oxide (NO) production, estimation of Th1 cytokines (IFN-γ and IL-12) as well as IL-10 in PBMCs of cured/endemic/infected Leishmania patients and cured L. donovani infected hamsters. A significantly higher proliferative response against rLdPDI as well as elevated levels of IFN-γ and IL-12 were observed. The level of IL-10 was found to be highly down regulated in response to rLdPDI. A significant increase in the level of NO production in stimulated hamster macrophages as well as IgG2 antibody and a low level of IgG1 in cured patient's serum was observed. Higher level of IgG2 antibody indicated its Th1 stimulatory potential. The efficacy of pcDNA-LdPDI construct was further evaluated for its prophylactic potential. Vaccination with this construct conferred remarkably good prophylactic efficacy (∼90%) and generated a robust cellular immune response with significant increases in the levels of iNOS transcript as well as TNF-α, IFN-γ and IL-12 cytokines. This was further supported by the high level of IgG2 antibody in vaccinated animals. The in vitro as well as in vivo results thus indicate that LdPDI may be exploited as a potential vaccine candidate against visceral Leishmaniasis (VL)

Elicitation of resistance and associated defense responses in trichoderma hamatum induced protection against pearl millet downy mildew pathogen

Endophytic Trichoderma hamatum UoM 13 isolated from pearl millet roots was evaluated for its efficiency to suppress downy mildew disease. Under laboratory conditions, T. hamatum seed treatment significantly enhanced pearl millet seed germination and seedling vigor. T. hamatum seed treatment resulted in systemic and durable immunity against pearl millet downy mildew disease under greenhouse and field conditions. T. hamatum treated seedlings responded to downy mildew infection with high lignification and callose deposition. Analysis of defense enzymes showed that T. hamatum treatment significantly enhanced the activities of glucanase, peroxidase, phenylalanine ammonia-lyase, and polyphenol oxidase in comparison to untreated control. RT-PCR analysis revealed differentially expressed transcripts of the defense enzymes and PR-proteins in treated, untreated, and checks, wherein PR-1, PR-5, and cell wall defense HRGPs were significantly over expressed in treated seedlings as against their lower expression in controls. T. hamatum treatment significantly stimulated endogenous salicylic acid ( SA) levels and significantly upregulated important SA biosynthesis gene isochorismate synthase. The results indicated that T. hamatum UoM13 treatment induces resistance corresponding to significant over expression of endogenous SA, important defense enzymes, PR-proteins, and HRGPs, suggesting that SA biosynthetic pathway is involved in pearl millet for mounting systemic immunity against downy mildew pathogen

Synthesis and characterization of metal-doped reduced graphene oxide composites, and their application in removal of Escherichia coli, arsenic and 4-nitrophenol

The aim of the present study is to synthesize dispersible reduced graphene oxide (RGO) via functionalization with metals and metal oxides and explore their potential applications in water purification. Graphene-based metal and metal oxide composites were synthesized hydrothermally using sodium borohydride as a reducing agent and sodium sorbate as a stabilizer. Single (Ag, Cu<inf>2</inf>O, and Fe<inf>3</inf>O<inf>4</inf>) and bimetallic (Ag-Cu<inf>2</inf>O, Ag-Fe<inf>3</inf>O<inf>4</inf>, and Cu<inf>2</inf>O-Fe<inf>3</inf>O<inf>4</inf>) nanoparticles were incorporated on the surface of RGO. The synthesized composites were characterized by various analytical methods. The inactivation of E. coli, the catalytic degradation of 4-nitrophenol, and the adsorption of As(V) were examined using the RGO composites.close1

Candida albicans PEP12 Is Required for Biofilm Integrity and In Vivo Virulence ▿

To investigate the role of the prevacuolar secretion pathway in biofilm formation and virulence in Candida albicans, we cloned and analyzed the C. albicans homolog of the Saccharomyces cerevisiae prevacuolar trafficking gene PEP12. C. albicans PEP12 encodes a deduced t-SNARE that is 28% identical to S. cerevisiae Pep12p, and plasmids bearing C. albicans PEP12 complemented the abnormal vacuolar morphology and temperature-sensitive growth of an S. cerevisiae pep12 null mutant. The C. albicans pep12 Δ null mutant was defective in endocytosis and vacuolar acidification and accumulated 40- to 60-nm cytoplasmic vesicles near the plasma membrane. Secretory defects included increased extracellular proteolytic activity and absent lipolytic activity. The pep12Δ null mutant was more sensitive to cell wall stresses and antifungal agents than the isogenic complemented strain or the control strain DAY185. Notably, the biofilm formed by the pep12Δ mutant was reduced in overall mass and fragmented completely upon the slightest disturbance. The pep12Δ mutant was markedly reduced in virulence in an in vitro macrophage infection model and an in vivo mouse model of disseminated candidiasis. These results suggest that C. albicans PEP12 plays a key role in biofilm integrity and in vivo virulence