White light augments chemotherapeutic potential of cyclophosphamide: an in vitro study

Cyclophosphamide (CYC) is a known chemotherapeutic drug used widely for the treatment of leukemias, lymphomas and some solid tumors. Copper is an essential constituent of chromatin and its level is usually elevated in various malignancies. Combined modality chemotherapy involves the use of drug with other components for cancer treatment, such as radiation therapy or surgery. Photosensitizer anticancer drugs can be used in combination with light and may have synergistic effect on cancer. The present study is an attempt to show that CYC acts as prooxidant when used in combination with Cu(II) and white light. We hypothesize that CYC when given as a chemotherapeutic agent possibly interact with endogenous copper associated with chromatin of the cancer cells and generate ROS besides acting as DNA alkylating agent. Thus, during chemotherapy the oxidative stress is possibly generated by the drug through mobilizing endogenous Cu(II) which may attribute to the cytotoxic death of cancer cell.     

Population Structure of Peronospora effusa in the Southwestern United States

Peronospora effusa is an obligate pathogen that causes downy mildew on spinach and is considered the most economically important disease of spinach. The objective of the current research was to assess genetic diversity of known historical races and isolates collected in 2014 from production fields in Yuma, Arizona and Salinas Valley, California. Candidate neutral single nucleotide polymorphisms (SNPs) were identified by comparing sequence data from reference isolates of known races of the pathogen collected in 2009 and 2010. Genotypes were assessed using targeted sequencing on genomic DNA extracted directly from infected plant tissue. Genotyping 26 historical and 167 contemporary samples at 46 SNP loci revealed 82 unique multi-locus genotypes. The unique genotypes clustered into five groups and the majority of isolates collected in 2014 were genetically closely related, regardless of source location. The historical samples, representing several races, showed greater genetic differentiation. Overall, the SNP data indicate much of the genotypic variation found within fields was produced during asexual development, whereas overall genetic diversity may be influenced by sexual recombination on broader geographical and temporal scales.     

The RACK1 signal anchor protein from Trypanosoma brucei associates with eukaryotic elongation factor 1A: a role for translational control in cytokinesis

RACK1 is a WD-repeat protein that forms signal complexes at appropriate locations in the cell. RACK1 homologues are core components of ribosomes from yeast, plants and mammals. In contrast, a cryo-EM analysis of trypanosome ribosomes failed to detect RACK1, thus eliminating an important translational regulatory mechanism. Here we report that TbRACK1 from Trypanosoma brucei associates with eukaryotic translation elongation factor-1a (eEF1A) as determined by tandem MS of TAP-TbRACK1 affinity eluates, co-sedimentation in a sucrose gradient, and co-precipitation assays. Consistent with these observations, sucrose gradient purified 80S monosomes and translating polysomes each contained TbRACK1. When RNAi was used to deplete cells of TbRACK1, a shift in the polysome profile was observed, while the phosphorylation of a ribosomal protein increased. Under these conditions, cell growth became hypersensitive to the translational inhibitor anisomycin. The kinetoplasts and nuclei were misaligned in the postmitotic cells, resulting in partial cleavage furrow ingression during cytokinesis. Overall, these findings identify eEF1A as a novel TbRACK1 binding partner and establish TbRACK1 as a component of the trypanosome translational apparatus. The synergy between anisomycin and TbRACK1 RNAi suggests that continued translation is required for complete ingression of the cleavage furrow.     

Prevalence of hyperhomocysteinemia in healthy Indian doctors

Currently, hyperhomocysteinemia is a well-known risk factor for variety of vascular diseases. Prevalence of hyperhomocysteinemia increases with age. Hence, the present study was aimed to investigate the prevalence of hyperhomocysteinemia in healthy upper socio-economic class population in India. Total homocysteine (tHcy) concentration was determined in 1243 (906 men & 337 women) healthy Indian doctors with different age group. Using Third National Health and Nutrition Examination Survey (NHANES III) study criteria, the prevalence of hyperhomocysteinemia was 92.85% among men (>11.4 µmol/L) and 81.60% among women (>10.4 µmol/L). The prevalence of hyperhomocysteinemia was higher among men with mean tHcy concentration (21.96 ± 0.38 µmol/L) significantly higher (P<0.0001) than women (15.90 ± 0.39 µmol/L) (95% CI, 4.733- 7.376). Our study showed very high prevalence of hyperhomocysteinemia which may point to the future risk for various pathologies in the present subset of population. Further studies to look at the plasma levels of homocysteine lowering vitamins are warranted to prevent the future risk of vascular diseases.