Common variation at 6p21.31 (BAK1) influences the risk of chronic lymphocytic leukemia

We performed a meta-analysis of 3 genome-wide association studies to identify additional common variants influencing chronic lymphocytic leukemia (CLL) risk. The discovery phase was composed of genome-wide association study data from 1121 cases and 3745 controls. Replication analysis was performed in 861 cases and 2033 controls. We identified a novel CLL risk locus at 6p21.33 (rs210142; intronic to the BAK1 gene, BCL2 antagonist killer 1; P = 9.47 × 10(-16)). A strong relationship between risk genotype and reduced BAK1 expression was shown in lymphoblastoid cell lines. This finding provides additional support for polygenic inheritance to CLL and provides further insight into the biologic basis of disease development.     

Genetic Variants in Toll-Like Receptor 2 (TLR2), TLR4, TLR9, and FCγ Receptor II Are Associated with Antibody Response to Quadrivalent Meningococcal Conjugate Vaccine in HIV-Infected Youth

This study examined the association of host genetic variants with the antibody response to the quadrivalent meningococcal conjugate vaccine (MCV4) in HIV-infected youth. Genetic variants associated with severity of meningococcal disease, including the IgG Fc receptor (FCγRII)-A484T, interleukin-10 (IL-10)-A1082G, -C819T, and -C627A, IL-4-C589T, mannose binding lectin-2 (MBL2)-A/O, -H/L, -P/Q, and -X/Y, toll-like receptor 2 (TLR2)-G2408A, TLR4-A12874G and -C13174T, and TLR9-T1237C and -T1486C were determined by real-time PCR (RT-PCR) for 271 HIV-infected subjects (median, 17 years). Response was defined as a ≥4-fold increase from entry in bactericidal antibody titers to each serogroup. Generalized estimating equation (GEE) models were used to evaluate the association of allelic variants with the immunologic response to all serogroups within each subject with and without adjusting for CD4 percentage and HIV viral load. At week 4, but not after, subjects with TLR2-2408-G/A versus -G/G genotypes and the TLR4-12874-A/A genotype were more likely to achieve a ≥4-fold increase overall in the four serogroups (unadjusted P of 0.006 and adjusted P of 0.008 and unadjusted P of 0.008 and adjusted P of 0.019, respectively). At week 28, the TLR9-1237 T allele was associated with enhanced antibody response (T allele versus C/C, unadjusted P of 0.014 and adjusted P of 0.009), which was maintained at week 72 (unadjusted and adjusted P of 0.008). At week 72, the FcγRII-131Arg allotype was associated with a ≥4-fold increase in antibody titer versus those with His/His (unadjusted P of 0.009; adjusted P of <0.001). These findings suggest that for HIV-infected youth, the initial antibody response to MCV4 is associated with variants in TLR2 and TLR4 while the long-term response is associated with genetic polymorphisms in TLR9 and FcγRIIa.     

Antibiotics produced by Streptomyces

Streptomyces is a genus of Gram-positive bacteria that grows in various environments, and its shape resembles filamentous fungi. The morphological differentiation of Streptomyces involves the formation of a layer of hyphae that can differentiate into a chain of spores. The most interesting property of Streptomyces is the ability to produce bioactive secondary metabolites, such as antifungals, antivirals, antitumorals, anti-hypertensives, immunosuppressants, and especially antibiotics. The production of most antibiotics is species specific, and these secondary metabolites are important for Streptomyces species in order to compete with other microorganisms that come in contact, even within the same genre. Despite the success of the discovery of antibiotics, and advances in the techniques of their production, infectious diseases still remain the second leading cause of death worldwide, and bacterial infections cause approximately 17 million deaths annually, affecting mainly children and the elderly. Self-medication and overuse of antibiotics is another important factor that contributes to resistance, reducing the lifetime of the antibiotic, thus causing the constant need for research and development of new antibiotics.