A Combinatorial approach: To design inhibitory molecules on Hemagglutinin protein of H1N1 virus (Swine Flu)

The Hemagglutinin (HA) is a protein of influenza A virus. It is present on the surface of influenza A virus and it is a glycoprotein. The HA is identified as potential drug target. H1N1 thiazolides, proved to be a potent drug in the inhibition of H1N1 replication. It is also known as inhibitor of other strains of influenza A virus. Thiazolide drug represses viral HA''s maturation at a level which exists just before the resistance from digestion of endoglycosidase-H and thereby it hampers, HA insertion in host membrane. Blocking the appropriate active site of hemagglutinin protein helps in the disease control. In the present work, we have generated diverse combinatorial library based ligands on known inhibitor thiazolides and they were used for virtual screening by Molegro virtual docker program. K-means clustering approach was used for finding new inhibitory molecules with more appropriate features. These resulted molecules are may be helpful in the treatment of swine flu and many other related diseases.     

alpha-Enolase binds to human plasminogen on the surface of Bacillus anthracis

alpha-enolase of Bacillus anthracis has recently been classified as an immunodominant antigen and a potent virulence factor determinant. alpha-enolase (2-phospho-d-glycerate hydrolase (EC 4.2.1.11), a key glycolytic metalloenzyme catalyzes the dehydration of d-(+)-2-phosphoglyceric acid to phosphoenolpyruvate. Interaction of surface bound alpha-enolase with plasminogen has been incriminated in tissue invasion for pathogenesis. B. anthracis alpha-enolase was expressed in Escherichia coli and the recombinant enzyme was purified to homogeneity that exhibited a K(m) of 3.3 mM for phosphoenolpyruvate and a V(max) of 0.506 microM min(- 1) mg(-1). B. anthracis whole cells and membrane vesicles probed with anti-enolase antibodies confirmed the surface localization of alpha-enolase. The specific interaction of alpha-enolase with human plasminogen (but not plasmin) evident from ELISA and the retardation in the native gel reinforced its role in plasminogen binding. Putative plasminogen receptors in B. anthracis other than enolase were also observed. This binding was found to be carboxypeptidase sensitive implicating the role of C-terminal lysine residues. The recombinant enolase displayed in vitro laminin binding, an important mammalian extracellular matrix protein. Plasminogen interaction conferred B. anthracis with a potential to in vitro degrade fibronectin and exhibit fibrinolytic phenotype. Therefore, by virtue of its interaction to host plasminogen and extracellular matrix proteins, alpha-enolase may contribute in augmenting the invasive potential of B. anthracis.     

Innate and specific gut-associated immunity and microbial interference

Certain bacterial species isolated from the gastrointestinal microbial communities release low-molecular-weight peptides into milk products using bacteria-derived proteases that degrade milk casein, and thereby generate peptides, triggering immune responses. The intestinal microbial communities contributes to the processing of food antigens in the gut. The present study was designed to investigate the immunomodulatory effects of microbial interference to determine whether casein degraded by probiotic bacteria-derived enzymes could modulate the cytokine production and peripheral blood mononuclear cells in atopic infants with cow or other synthetic milk allergy. Without hydrolyzation, casein reduced the production of interleukin-4, which indicates that probiotics modify the structure of potentially harmful antigens and thereby alter the mode of their immunogenicity. Intraluminal bacterial antigens have been reported to elicit specific responses in the gut-associated lymphoid tissue (GALT) through the binding capacity of intraluminal bacterial antigens to epithelial cells, which allows antigen entry via enterocytes and aids in evading the tolerance function in Peyer's patches. Such tonic immune responses in the GALT may allow control of the metabolic activity and balance of the gut microbial communities.     

Highly pathogenic simian immunodeficiency virus mne variants that emerge during the course of infection evolve enhanced infectivity and the ability to downregulate CD4 but not class I major histocompatibility complex antigens

The replicative, cytopathic, and antigenic properties of simian immunodeficiency virus (SIV) variants influence its replication efficiency in vivo. To further define the viral properties and determinants that may be important for high-level replication in vivo and progression to AIDS, we compared a minimally pathogenic SIVmne molecular clone with two highly pathogenic variants cloned from late stages of infection. Both variants had evolved greater infectivity than the parental clone due to mutations in nef. Interestingly, a pol determinant in one of the highly pathogenic variants also contributed to its increased infectivity. Furthermore, because replication in vivo may also be influenced by the ability of a virus to evade the cellular immune response of the host, we examined whether the variants were more capable of downregulating surface expression of class I major histocompatibility complex (MHC). Decreased MHC class I expression was not observed in cells infected with any of the viruses. Furthermore, the Nef proteins of the highly pathogenic variants only slightly reduced surface MHC class I expression in transfected cells, although they efficiently downregulated CD4. Together, these data demonstrate that mutations which can enhance viral infectivity, as well as CD4 downregulation, may be important for efficient replication of SIV in the host. However, Nef-mediated reduction of MHC class I expression does not appear to be critical for the increased in vivo replicative ability of highly pathogenic late variants.     

Critical factors governing the efficient direct organogenesis in green-fleshed kiwifruit (Actinidia deliciosa) [A. Chev.] var. deliciosa

In Vitro Cellular & Developmental Biology - Plant - The present study was focused towards determining the factors governing direct organogenesis in kiwifruit cultivar ‘Allison’....     

The validity of self-reported weight change among adolescents and young adults

Objective: To assess the association of weight change based on serial self‐reported vs. measured weights. Research Methods and Procedures: Two thousand two hundred eighty‐four male and 2476 female participants in the National Longitudinal Study of Adolescent Health who provided information on weight at Waves II and III and were at least 16 years of age were studied. Linear regression was used to assess predictors of the discrepancy between weight change based on self‐reported vs. measured weights. Logistic regression was used to identify predictors of self‐report correctly classifying participants in terms of weight change category. Results: Self‐reported weight was slightly lower than measured weight at Waves II and III, but weight change based on self‐reported weights underestimated true weight change by only 2.1 (female participants) to 2.8 (male participants) pounds. Overweight and obese female participants were consistent in their under‐reporting of their weight more than their leaner peers; thus, the discrepancy between weight change from Wave II to Wave III based on serial self‐reports vs. measured weights was significantly smaller among the obese female vs. healthy‐weight female participants (0.3‐ vs. 2.3‐pound underestimation, p < 0.05). Among the male participants, the same pattern was evident. African‐American ethnicity, Hispanic ethnicity, the level of physical activity, the hours per week watching television, and weight change efforts were not related to the discrepancy between weight change based on self‐reported vs. measured weights. Discussion: The discrepancy between weight change based on self‐report vs. measured weights was minor and not related to race, weight change efforts, activity, or inactivity, thus suggesting that much of the error is random.     

Race and gender differences in the association of dieting and gains in BMI among young adults

Objective: To assess the relationship between dieting and subsequent weight change and whether the association varies by gender or race/ethnicity. Research Methods and Procedures: Male (n = 4100) and female (n = 4302) participants in the National Longitudinal Study of Adolescent Health who provided information on weight and height at baseline and two follow‐up assessments and were not missing information on weight control strategies or race were studied. Generalized estimating equations were used to assess whether dieting to lose or maintain weight at Wave I or II predicted BMI (kg/m²) change between adolescence and young adulthood (Wave II to III). Analyses were stratified by gender and took sampling weights and clustering into account. Results: At Wave I, the mean age of the participants was 14.9 years. Approximately 29.3% of female participants and 9.8% of male participants reported dieting in Wave I or II. Fewer African Americans than whites (6.2% vs. 10.0% and 25.5% vs. 31.2%, p = 0.007 and p = 0.02, among males and females, respectively) reported dieting. Between Waves II and III, participants gained on average 3.3 kg/m². Independent of BMI gain during adolescence (Waves I to II), female participants who dieted to lose or maintain weight during adolescence made larger gains in BMI during the 5 years between Waves II and III (mean additional gain, 0.39 kg/m²; 95% confidence interval, 0.08 to 0.71) than their nondieting peers. The association was not significant among the male participants. The association was largest among African‐American female participants. Discussion: The results suggest that not only is dieting to lose weight ineffective, it is actually associated with greater weight gain, particularly among female adolescents. Female African‐American dieters made the largest BMI gains.