We carry out a detailed analysis of effects of flavor dependence of average transverse quark momentum inside a meson onJ/ψ→Pandϒ→Bctransition form factors and two-body weak hadronic decays ofJ/ψandϒemploying the factorization scheme. We predict the branching ratios of semileptonic and nonleptonic weak decays ofJ/ψandϒmesons in Cabibbo-angle-enhanced and Cabibbo-angle-suppressed modes.
In light of recent measurements of the H + + p y asymmetry and the branching ratio of Z -+ Z -y decay, we reinvestigate the single-quark-and two-quark-transition contributions to the weak radiative decays of hyperons. We find that a small contribution from single-quark transition, necessary for Z -+ H -y decay, enhances the Z + + p y decay asymmetry to around -0.59.
Calcium ions regulate a diversity of cellular functions in all eukaryotes. The cytosolic Ca concentration is tightly regulated at the physiological cytosolic concentration of 50-100 nm. The Toxoplasma gondii genome predicts the presence of several genes encoding potential Ca channels, pumps, and transporters. Many of these genes are weakly expressed and likely tightly regulated due to their potential impact to the physiology of the cell. Endogenous tagging has been widely used to localize proteins in T. gondii but low level of expression of many of them makes visualization of tags difficult and sometimes impossible. The use of high-performance tags for labeling proteins expressed at low level is ideal for investigating the localization of these gene products. We designed a Carboxy-terminus tagging plasmid containing the previously characterized "spaghetti monster-HA" (smHA) or "spaghetti monster-MYC" (smMYC) tags. These tags consist of 10 copies of a single epitope (HA or MYC) inserted into a darkened green fluorescence protein scaffold. We localized six proteins of various levels of expression. Clonal lines were isolated and validated by PCR, western blot, and immunofluorescence analyses. Some gene products were only visible when tagged with smHA and in one case the smHA revealed a novel localization previously undetected.
Inheritance of the single mitochondrial nucleoid (kinetoplast) in the trypanosome requires numerous proteins many of whose precise roles are unclear. By considering kinetoplast DNA (kDNA) as a template for cleavage into two equal-size networks, we predicted sets of mutant kinetoplasts associated with defects in each of five steps in the kinetoplast cycle. Comparison of these kinetoplasts with those obtained after gene knockdowns enabled assignment of proteins to five classes -kDNA synthesis, site of scission selection, scission, separation, and partitioning. These studies highlight how analysis of mutant kinetoplast phenotypes may be used to predict functional categories of proteins involved in biogenesis of kinetoplasts.
Lapatinib, an approved EGFR inhibitor, was explored as a starting point for the synthesis of new hits against Trypanosoma brucei, the causative agent of human African trypanosomiasis (HAT). Previous work culminated in 1 (NEU-1953), which was part of a series typically associated with poor aqueous solubility. In this report, we present various medicinal chemistry strategies that were used to increase the aqueous solubility and improve the physicochemical profile without sacrificing anti-trypanosome potency. To rank trypanocidal hits, a new assay (summarized in a *
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