JNK regulates FoxO-dependent autophagy in neurons

The cJun N-terminal kinase (JNK) signal transduction pathway is implicated in the regulation of neuronal function. JNK is encoded by three genes that play partially redundant roles. Here we report the creation of mice with targeted ablation of all three Jnk genes in neurons. Compound JNK-deficient neurons are dependent on autophagy for survival. This autophagic response is caused by FoxO-induced expression of Bnip3 that displaces the autophagic effector Beclin-1 from inactive Bcl-XL complexes. These data identify JNK as a potent negative regulator of FoxO-dependent autophagy in neurons.     

Comparative genomic analysis of simple sequence repeats in three Plasmodium species

Simple sequence repeats (SSRs) are known to be responsible for genetic complexities and play major roles in gene and genome evolution. To this respect, malaria parasites are known to have rapidly evolving and complex genomes with complicated and differential pathogenic behaviors. Hence, by studying the whole genome comparative SSRs patterns, one can understand genomic complexities and differential evolutionary patterns of these species. We herein utilized the whole genome sequence information of three Plasmodium species, Plasmodium falciparum, Plasmodium vivax, and Plasmodium knowlesi, to comparatively analyze genome-wide distribution of SSRs. The study revealed that despite having the smallest genome size, P. falciparum bears the highest SSR content among the three Plasmodium species. Furthermore, distribution patterns of different SSRs types (e.g., mono, di, tri, tetra, penta, and hexa) in term of relative abundance and relative density provide evidences for greater accumulation of di-repeats and marked decrease of mono-repeats in P. falciparum in comparison to other two species. Overall, the types and distribution of SSRs in P. falciparum genome was found to be different than that of P. vivax and P. knowlesi. The latter two species have quite similar SSR organizations in many aspects of the data. The results were discussed in terms of comparative SSR patterns among the three Plasmodium species, uniqueness of P. falciparum in SSR organization and general pattern of evolution of SSRs in Plasmodium.     

Mouse monoclonal antibodies to anthrax edema factor protect against infection

Bacillus anthracis is the causative agent of anthrax, and the tripartite anthrax toxin is an essential element of its pathogenesis. Edema factor (EF), a potent adenylyl cyclase, is one of the toxin components. In this work, anti-EF monoclonal antibodies (MAb) were produced following immunization of mice, and four of the antibodies were fully characterized. MAb 3F2 has an affinity of 388 pM, was most effective for EF detection, and appears to be the first antibody reported to neutralize EF by binding to the catalytic C(B) domain. MAb 7F10 shows potent neutralization of edema toxin activity in vitro and in vivo; it targets the N-terminal protective antigen binding domain. The four MAb react with three different domains of edema factor, and all were able to detect purified edema factor in Western blot analysis. None of the four MAb cross-reacted with the lethal factor toxin component. Three of the four MAb protected mice in both a systemic edema toxin challenge model and a subcutaneous spore-induced foreleg edema model. A combination of three of the MAb also significantly delayed the time to death in a third subcutaneous spore challenge model. This appears to be the first direct evidence that monoclonal antibody-mediated neutralization of EF alone is sufficient to delay anthrax disease progression.     

Regeneration and characterization of adult mouse hippocampal neurons in a defined in vitro system

Although the majority of human illnesses occur during adulthood, most of the available in vitro disease models are based upon cells obtained from embryonic/fetal tissues because of the difficulties involved with culturing adult cells. Development of adult mouse neuronal cultures has a special significance because of the abundance of transgenic disease models that use this species. In this study a novel cell culture method has been developed that supports the long-term survival and physiological regeneration of adult mouse hippocampal cells in a serum-free defined environment. In this well-defined, controlled system, adult mouse hippocampal cells survived for up to 21 days in culture. The cultured cells exhibited typical hippocampal neuronal morphology and electrophysiological properties after recovery from the trauma of dissociation, and stained positive for the expected neuronal markers. This system has great potential as an investigative tool for in vitro studies of adult diseases, the aging brain or transgenic models of age-associated disorders.     

Medulloblastomas: a correlative study of MIB-1 proliferation index along with expression of c-Myc,ERBB2, and anti-apoptotic proteins along with histological typing and clinical outcome

Background  Medulloblastoma (MB) is the most common pediatric brain tumor. It is however rare in adults. The genetic and protein expression profile of medulloblastoma is complex, which is worthwhile in terms of prognostication and development or selection of targeted therapy. Aims and objectives  The aims and objectives to correlate the MIB-1 proliferation index and protein expression profiles of c-Myc, ERBB2, and anti-apoptotic proteins (Bcl2 and Bcl-xL) in tumor cells with histological subtypes and clinical outcome. Methods and material  In 50 cases, histopathological subtyping was done, and protein expression profiling by immunohistochemical technique was performed by stains for MIB-1, Bcl2, Bcl-xL, c-Myc, and ERBB2 in 30 cases. The findings were correlated with histological types and patient’s average follow-up data. Results  Histological subtypes were similar to that described in literatures. The average expression of Bcl2, Bcl-xL, MIB-1, c-Myc, and ERBB2 were as follows: 50.38%, 38.18%, 59.03%, 46.16%, and 59.62%, respectively. Bcl2 expression showed statistically significant correlation with progress-free survival (PFS) [p = 0.046], while ERBB2 and MIB-1 showed a trend of higher expression in progressive disease. The protein expression pattern did not correlate with histological subtypes. Conclusion  Though Bcl-2, ERBB2, and MIB-1 LI came out to be potential markers of aggressive behavior, c-Myc did not correlate with PFS in MB.