Combined Synergistic Effects of Aqueous Extracts of Parquetina nigrescens, Camellia sinensis and Telfaria occidentalis on Bone Marrow Haemopoietic Multipotent Stem Cells Proliferation in Irradiated Guinea Pigs

Cancer which is one of the most threatening human diseases is most commonly treated by chemotherapy and radiotherapy. However, these therapies are not tumor-specific. Normal tissues, particularly the bone marrow (BM), are extremely vulnerable to cytotoxicity caused by these therapies. How rapidly patients recover from these treatment modalities greatly depends on the percentage of resting stem cells remaining after such treatment. Antidotes are required for the untoward side effects of these therapies. As a means to protect stem cells or help damaged stem cells to recover, the use of biological response modifiers (BRMs) has received attention. The use of fruits or vegetables has the benefits of providing a cocktail of many different phytochemicals with multiple actions including antioxidant and anti-inflammatory effects. Certain whole-food extracts, such as blueberry, dietary fatty acids, particularly oleic acid and linoleic acid have been reported recently to actively promote the proliferation of haemopoietic stem cells [1]

Survey of variation in human transcription factors reveals prevalent DNA binding changes

Sequencing of exomes and genomes has revealed abundant genetic variation affecting the coding sequences of human transcription factors (TFs), but the consequences of such variation remain largely unexplored. We developed a computational, structure-based approach to evaluate TF variants for their impact on DNA binding activity and used universal protein-binding microarrays to assay sequence-specific DNA binding activity across 41 reference and 117 variant alleles found in individuals of diverse ancestries and families with Mendelian diseases. We found 77 variants in 28 genes that affect DNA binding affinity or specificity and identified thousands of rare alleles likely to alter the DNA binding activity of human sequence-specific TFs. Our results suggest that most individuals have unique repertoires of TF DNA binding activities, which may contribute to phenotypic variation.National Human Genome Research Institute (U.S.) (Grant R01 HG003985

Assessing computational predictions of the phenotypic effect of cystathionine-beta-synthase variants

Accurate prediction of the impact of genomic variation on phenotype is a major goal of computational biology and an important contributor to personalized medicine. Computational predictions can lead to a better understanding of the mechanisms underlying genetic diseases, including cancer, but their adoption requires thorough and unbiased assessment. Cystathionine-beta-synthase (CBS) is an enzyme that catalyzes the first step of the transsulfuration pathway, from homocysteine to cystathionine, and in which variations are associated with human hyperhomocysteinemia and homocystinuria. We have created a computational challenge under the CAGI framework to evaluate how well different methods can predict the phenotypic effect(s) of CBS single amino acid substitutions using a blinded experimental data set. CAGI participants were asked to predict yeast growth based on the identity of the mutations. The performance of the methods was evaluated using several metrics. The CBS challenge highlighted the difficulty of predicting the phenotype of an ex vivo system in a model organism when classification models were trained on human disease data. We also discuss the variations in difficulty of prediction for known benign and deleterious variants, as well as identify methodological and experimental constraints with lessons to be learned for future challenges.status: publishe

Assessing computational predictions of the phenotypic effect of cystathionine-beta-synthase variants

Accurate prediction of the impact of genomic variation on phenotype is a major goal of computational biology and an important contributor to personalized medicine. Computational predictions can lead to a better understanding of the mechanisms underlying genetic diseases, including cancer, but their adoption requires thorough and unbiased assessment. Cystathionine-beta-synthase (CBS) is an enzyme that catalyzes the first step of the transsulfuration pathway, from homocysteine to cystathionine, and in which variations are associated with human hyperhomocysteinemia and homocystinuria. We have created a computational challenge under the CAGI framework to evaluate how well different methods can predict the phenotypic effect(s) of CBS single amino acid substitutions using a blinded experimental data set. CAGI participants were asked to predict yeast growth based on the identity of the mutations. The performance of the methods was evaluated using several metrics. The CBS challenge highlighted the difficulty of predicting the phenotype of an ex vivo system in a model organism when classification models were trained on human disease data. We also discuss the variations in difficulty of prediction for known benign and deleterious variants, as well as identify methodological and experimental constraints with lessons to be learned for future challenges