Heterologous Prime Boost Regimes with N-terminal Peptides of Ag85B Induces Better Protection than Ag85B and BCG in Murine Model of Tuberculosis

Limited experimental evidences are available on the use of peptides as vaccines to boost BCG induced immunity for protection against tuberculosis. The present study therefore evaluated protective efficacy of booster dose of N-terminal peptides of Ag85B, using prime boost approaches in murine model of tuberculosis. Using earlier established subcutaneous murine model of TB in our laboratory, we compared the protective vaccination efficacy of peptides of Ag85B with that of booster dose of whole Ag85B and BCG by evaluating both antibody and cell-mediated immune response. Groups of mice primed by BCG and boosted with Ag85B peptides showed limited pulmonary bacillary burden and reduced lung pathology after challenge with virulent dose of Mycobacterium tuberculosis in mice. Significant levels (p < 0.001) of BCG specific antibodies (anti-BCG, anti-PPD) and T cell-specific cytokines were observed in Ag85B peptides boosted mice compared to Ag85B and BCG. Ag85B and BCG boosted mice however showed significant protection compared to single BCG dose and unvaccinated control groups. Our result suggests that prime boost strategy using N-terminal peptides of Ag85B may improve immunogenicity of BCG against TB. Such peptides may be attractive candidates for boosting waning BCG induced immune response in near future. However study demands further work including improvisation in experimental designs to justify the results.     

Improved shoot regeneration system through leaf derived callus and nodule culture of Sansevieria cylindrica

Long-term culture establishment and efficient in vitro regeneration protocol for Sansevieria cylindrica Bojer ex Hook was developed using leaf derived callus and nodule culture. Profuse callus induction on leaf discs was achieved on Murashige and Skoog (MS) medium supplemented with 10 μM indole-3-butyric acid (IBA), while a high frequency of nodulation was induced on 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) containing media. Shoot regeneration ability from cultured tissues occurred at varying degrees on all media. Through callus culture a maximum of 17.6 ± 0.14 shoots per culture was formed on medium containing 5μM 6-benzyladenine (BA) and 2 μM α-naphthaleneacetic acid (NAA). Among nodule cultures, the 2,4-D generated nodules were more proliferative and regenerative as compared to 2,4,5-T induced nodules and a maximum of 25 ± 0.16 shoots per culture was produced on a medium containing 5 μM BA plus 1 μM NAA. The regenerated shoots were successfully rooted on a semi-solid half strength MS medium containing 5 μM IBA with an average root number 3.5 ± 0.18 and root length 6.5 ± 0.14 cm. The regenerative ability of callus tissues was steady upto one year, while the nodules retained the totipotency to regenerate on optimal medium even after 3 years of subculturing. The histological sections of nodules confirm the typical anatomy exhibiting the vascular elements in bundles with well demarcated cortex and epidermal covering.     

Heavy drinking relates to positive valence ratings of alcohol cues

A positive family history of alcohol use disorders (FH) is a robust predictor of personal alcohol abuse and dependence. Exposure to problem-drinking models is one mechanism through which family history influences alcohol-related cognitions and drinking patterns. Similarly, exposure to alcohol advertisements is associated with alcohol involvement and the relationship between affective response to alcohol cues and drinking behavior has not been well established. In addition, the collective contribution that FH, exposure to different types of problem-drinking models (e.g. parents, peers) and personal alcohol use have on appraisal of alcohol-related stimuli has not been evaluated with a large sample. We investigated the independent effects of FH, exposure to problem-drinking models and personal alcohol use on valence ratings of alcohol pictures in a college sample. College students (n = 227) completed measures of personal drinking and substance use, exposure to problem-drinking models, FH and ratings on affective valence of 60 alcohol pictures. Greater exposure to non-familial problem-drinkers predicted greater drinking among college students (beta = 0.17, P < 0.01). However, personal drinking was the only predictor of valence ratings of alcohol pictures (beta = -0.53, P < 0.001). Personal drinking level predicted valence ratings of alcohol cues over and above FH, exposure to problem-drinking models and demographic characteristics. This suggests that positive affective responses to alcohol pictures are more a function of personal experience (i.e. repeated heavy alcohol use) than vicarious learning.     

Control of visuotemporal attention by inferior parietal and superior temporal cortex

The human cortical visual system is organized into major pathways: a dorsal stream projecting to the superior parietal lobe (SPL), considered to be critical for visuospatial perception or on-line control of visually guided movements, and a ventral stream leading to the inferotemporal cortex, mediating object perception. Between these structures lies a large region, consisting of the inferior parietal lobe (IPL) and superior temporal gyrus (STG), the function of which is controversial. Lesions here can lead to spatial neglect, a condition associated with abnormal visuospatial perception as well as impaired visually guided movements, suggesting that the IPL+STG may have largely a "dorsal" role. Here, we use a nonspatial task to examine the deployment of visuotemporal attention in focal lesion patients, with or without spatial neglect. We show that, regardless of the presence of neglect, damage to the IPL+STG leads to a more prolonged deployment of visuotemporal attention compared to lesions of the SPL. Our findings suggest that the human IPL+STG makes an important contribution to nonspatial perception, and this is consistent with a role that is neither strictly "dorsal" nor "ventral". We propose instead that the IPL+STG has a top-down control role, contributing to the functions of both dorsal and ventral visual systems.     

Exome sequencing followed by large-scale genotyping fails to identify single rare variants of large effect in idiopathic generalized epilepsy

Idiopathic generalized epilepsy (IGE) is a complex disease with high heritability, but little is known about its genetic architecture. Rare copy-number variants have been found to explain nearly 3% of individuals with IGE; however, it remains unclear whether variants with moderate effect size and frequencies below what are reliably detected with genome-wide association studies contribute significantly to disease risk. In this study, we compare the exome sequences of 118 individuals with IGE and 242 controls of European ancestry by using next-generation sequencing. The exome-sequenced epilepsy cases include study subjects with two forms of IGE, including juvenile myoclonic epilepsy (n = 93) and absence epilepsy (n = 25). However, our discovery strategy did not assume common genetic control between the subtypes of IGE considered. In the sequence data, as expected, no variants were significantly associated with the IGE phenotype or more specific IGE diagnoses. We then selected 3,897 candidate epilepsy-susceptibility variants from the sequence data and genotyped them in a larger set of 878 individuals with IGE and 1,830 controls. Again, no variant achieved statistical significance. However, 1,935 variants were observed exclusively in cases either as heterozygous or homozygous genotypes. It is likely that this set of variants includes real risk factors. The lack of significant association evidence of single variants with disease in this two-stage approach emphasizes the high genetic heterogeneity of epilepsy disorders, suggests that the impact of any individual single-nucleotide variant in this disease is small, and indicates that gene-based approaches might be more successful for future sequencing studies of epilepsy predisposition.