Physics-guided machine learning from simulated data with different physical parameters

Knowledge and Information Systems - Physics-based models are widely used to study dynamical systems in a variety of scientific and engineering problems. However, these models are necessarily...     

Prevention, early detection, and treatment of breast cancer: a collaborative approach

Breast disorders are not only common and concerning, but in many cases, represent a real risk of death. Dealing knowledgeably with breast-related concerns is a priority for all HCPs and requires a thorough understanding of primary and secondary prevention strategies; first, to reduce the incidence of breast cancer, and second, to reduce the morbidity and mortality associated with the disease. Coordinated and supportive care for women diagnosed with breast cancer is essential to promote optimal health and well-being. The knowledgeable primary HCP, working collaboratively with a breast specialist, can help women achieve these goals.     

Metabolic role of cytoplasmic isozymes of 5,10-methylenetetrahydrofolate dehydrogenase in Saccharomyces cerevisiae

Saccharomyces cerevisiae possesses two cytosolic 5,10-methylenetetrahydrofolate (CH2-THF) dehydrogenases that differ in their redox cofactor specificity: an NAD-dependent dehydrogenase encoded by the MTD1 gene and an NADP-dependent activity as part of the trifunctional C1-THF synthase encoded by the ADE3 gene. The experiments described here were designed to define the metabolic roles of the NAD- and NADP-dependent CH2-THF dehydrogenases in one-carbon interconversions and de novo purine biosynthesis. Growth studies showed that the NAD-dependent CH2-THF dehydrogenase is interchangeable with the NADP-dependent CH2-THF dehydrogenase when flow of one-carbon units is in the oxidative direction but that it does not participate significantly when flux is in the reductive direction. 13C NMR experiments with [2-13C]glycine and unlabeled formate confirmed the latter conclusion. Direct measurements of cellular folate coenzyme levels revealed substantial levels of 10-formyl-THF (CHO-THF), the one-carbon donor used in purine synthesis, in the purine-requiring ade3 deletion strain. Thus, CHO-THF is necessary but not sufficient for de novo purine synthesis in yeast. Disruption of the MTD1 gene in this strain resulted in undetectable CHO-THF, indicating that the NAD-dependent CH2-THF dehydrogenase was responsible for CHO-THF production in the ade3 deletion strain. Finally, we examined the ability of wild-type and catalytically-inactive domains of the cytoplasmic C1-THF synthase to complement the adenine auxotrophy of the ade3 deletion strain. Both the dehydrogenase/cyclohydrolase (D/C) domain and the synthetase domain could functionally replace the full-length protein, but, at least for the D/C domain, complementation was not dependent on catalytic activity. These results reveal a catalytic role for the NAD-dependent CH2-THF dehydrogenase in the oxidation of cytoplasmic one-carbon units and indicate that the cytoplasmic C1-THF synthase plays both catalytic and noncatalytic roles in de novo purine biosynthesis in yeast.