Targeting of the c-Abl tyrosine kinase to mitochondria in endoplasmic reticulum stress-induced apoptosis

The ubiquitously expressed c-Abl tyrosine kinase localizes to the nucleus and cytoplasm. Using confocal microscopy, we demonstrated that c-Abl colocalizes with the endoplasmic reticulum (ER)-associated protein grp78. Expression of c-Abl in the ER was confirmed by immunoelectron microscopy. Subcellular fractionation studies further indicate that over 20% of cellular c-Abl is detectable in the ER. The results also demonstrate that induction of ER stress with calcium ionophore A23187, brefeldin A, or tunicamycin is associated with translocation of ER-associated c-Abl to mitochondria. In concert with targeting of c-Abl to mitochondria, cytochrome c is released in the response to ER stress by a c-Abl-dependent mechanism, and ER stress-induced apoptosis is attenuated in c-Abl-deficient cells. These findings indicate that c-Abl is involved in signaling from the ER to mitochondria and thereby the apoptotic response to ER stress.     

Rock phosphate solubilization under alkaline conditions byAspergillus japonicus andA. foetidus

Aspergillus japonicus andA. foetidus were found to solubilize, five types of Indian rock phosphates at pH 8 and 9. Solubilization was higher in the presence of pyrite than in controls lacking either pyrite or fungal, inoculum. Both the aspergilli were found to be good pyrite solubilizers and could grow over a wide pH range. Solubilization of rock phosphates was the result of organic acid release and pyrite oxidation.     

Conservation,propagation, and redistribution (CPR) of Hill’s thistle: paradigm for plant species at risk

Cryopreservation is a valuable tool that could potentially create an alternate plant preservation strategy for species at risk such as Hill’s thistle. The present study is focused on a successful paradigm involving conservation, propagation and redistribution (CPR), emaphasizing the usefulness of cryopreservation techniques for plant conservation using Hill’s thistle (Cirsium hillii. (Canby) Fernald). A cryopreservation protocol was established using the droplet-vitrification method for 5-week-old shoot tips of in vitro grown cultures. More than 90% of shoot tips showed regrowth and nearly all regenerated plants were able to survive in the greenhouse. The survival, growth, and development of plants from cryopreserved shoot buds and their performance in field conditions were all comparable or better than the plants from non-cryopreserved buds. Reintroduced plants flowered following overwintering and the magnitude of flowering was site dependent with ca. 80% flowering observed in one site. The site dependent flowering patterns were assessed using phytohormone profiling and compared to herbivory, a common biotic stressor of these plants. Lower tryptophan concentrations led to higher flowering except in alvars, where the limestone resisted root penetration resulting in poor flowering. The presence of tryptamine in the greenhouse acclimatized or alvar field leaves suggested the preparedness of the plants for herbivory/grazing. Serotonin and melatonin concentrations were lower in flowering plants and in sites where the biotic/abiotic stress was minimal. This study provides evidence of the effectiveness of the CPR model in species recovery programs for endangered species. Physiological characterization of plants developed from cryopreserved tissues can be useful for fundamental and applied research in stress adaptation and reproductive biology of plants.

     

A detailed model and Monte Carlo simulation for predicting DIP genome length distribution in baculovirus infection of insect cells

Baculoviruses have enormous potential for use as biopesticides to control insect pest populations without the adverse environmental effects posed by the widespread use of chemical pesticides. However, continuous baculovirus production is susceptible to DNA mutation and the subsequent production of defective interfering particles (DIPs). The amount of DIPs produced and their genome length distribution are of great interest not only for baculoviruses but for many other DNA and RNA viruses. In this study, we elucidate this aspect of virus replication using baculovirus as an example system and both experimental and modeling studies. The existing mathematical models for the virus replication process consider DIPs as a lumped quantity and do not consider the genome length distribution of the DIPs. In this study, a detailed population balance model for the cell‐virus culture is presented, which predicts the genome length distribution of the DIP population along with their relative proportion. The model is simulated using the kinetic Monte Carlo algorithm, and the results agree well with the experimental results. Using this model, a practical strategy to maintain the DIP fraction to near to its maximum and minimum limits has been demonstrated.     

Synthetic Antimicrobial Peptide Polybia MP-1 (Mastoparan) Inhibits Growth of Antibiotic Resistant Pseudomonas aeruginosa Isolates From Mastitic Cow Milk

International Journal of Peptide Research and Therapeutics - Antimicrobial peptides (AMPs) offer a potent and effective alternative for treatment of antibiotic resistant microbes. Mastoparans or...     

The role of adipose tissue-associated macrophages and T lymphocytes in the pathogenesis of inflammatory bowel disease

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders of the gastrointestinal tract that affect more than 3 million people worldwide, but the pathological etiology is still unknown. The overall purpose of our investigations was to elucidate the possibility of pathological causes of IBD, and therefore, we determined the difference of inflammatory cytokine profiles in adipose tissue macrophages (ATMs) and T lymphocytes (ATTs) obtained near active lesions of IBD; investigated whether the alteration in ATM activation induces genes involved in collagen formation; and evaluated the effects of fatty acid oxidation inhibitors on factors involved in inflammation and collagen production by ATMs in IBD. Adipose tissues (ATs) were collected near active lesions and also at the margin of resected segments of the bowel from IBD patients with ulcerative colitis (UC) and CD (n = 14/group). Normal appearing ATs from control subjects (n = 14) who had colon resection for adenocarcinoma were collected as far away from the cancer lesion as possible to rule out possible changes. Compared with inactive disease lesions, ATMs and ATTs from active lesions released more IL-6, IL-4 and IL-13. Treatments of cytokine IL-4 and/or IL-13 to ATMs reduced iNOS expression but increased Arg-I expression which were exacerbated when treated with T cell- and adipocyte-conditioned medium. However, fatty acid oxidation inhibitors prevented the effects of cytokines IL-4 and/or IL-13 on iNOS and Arg-I expressions. This study was the first to show the effect of IL-4 and IL-13 on collagen formation, through iNOS and Arg-I expressions, that was exacerbated in a condition that mimics in vivo condition of active lesions. Moreover, our study was the first to provide potential benefits of fatty acid oxidation inhibitors to ATMs on preventing collagen formation; thus, providing therapeutic implications for individuals with intestinal fibrosis and stricture lesions, although future study should be guaranteed to elucidate the underlying mechanisms.     

Synthesis of azatricyclodiones & octahydro-benzo[f]isoindoles and their antimicrobial evaluation

A series of azatricyclodiones and octahydro-benzo[f]isoindoles have been synthesized by (4+2) Diels-Alder cycloaddition of maleimides with furfuryl amine. Reaction of azatricyclodiones with isocyanates led to the respective ureides. All of the compounds were screened against a number of bacteria and fungi. One of the compounds (2) displayed moderate antitubercular activity while two compounds (2) and (4) inhibited the fungal growth at 25 μg/mL.     

Toxicity of cypermethrin: hsp70 as a biomarker of response in transgenic Drosophila

Heat shock protein induction is often associated with a cellular response to a harmful environment or to adverse life conditions. The main aims of our study were (1) to evaluate the cytotoxic potential of cypermethrin; and (2) to investigate the suitability of stress-induced heat shock protein Hsp70 as a biomarker for environmental pollutants in transgenic Drosophila melanogaster (Hsp70-lacZ)Bg⁹. Different concentrations of cypermethrin (0.002, 0.2, 0.5 and 50.0 p.p.m.) were mixed with food. Third instar larvae of transgenic Drosophila melanogaster were allowed to feed on these mixtures for different time intervals (2, 4, 6, 12, 24 and 48h). Following feeding, hsp70 induction and tissue damage were evaluated. In the highest concentration treatment group (50 p.p.m.), 100% larval mortality was recorded after 12 h exposure. Hsp70 was found to be induced even at the lowest concentration (0.002 p.p.m.) of the insecticide, while tissue damage was observed in the larvae exposed for 48 h. While an insignificant decline in hsp70 expression was observed in the larvae exposed to cypermethrin at a dietary concentration of 0.002 p.p.m. after 48 h compared with those exposed for 24 h, in the next two higher concentrations of the toxicant, a similar but significant decline in hsp70 expression was evident in the exposed larvae after 48 h. The present study reveals the cytotoxic potential of cypermethrin and further proposes that hsp70 induction in transgenic Drosophila melanogaster could be used as a sensitive biomarker in risk assessment.