No abstract

SummaryTwo low phytic acid (lpa) mutants have been developed previously with the aim to improve the nutritional value of rice (Oryza sativa) grains. In the present study, the impacts of lpa mutations on grain composition and underlying molecular mechanisms were investigated.Comparative compositional analyses and metabolite profiling demonstrated that concentrations of both phytic acid (PA) and total phosphorus (P) were significantly reduced in lpa brown rice, accompanied by changes in other metabolites and increased concentrations of nutritionally relevant compounds. The lpa mutations modified the expression of a number of genes involved in PA metabolism, as well as in sulfate and phosphate homeostasis and metabolism.Map-based cloning and complementation identified the underlying lpa gene to be OsSULTR3;3. The promoter of OsSULTR3;3 is highly active in the vascular bundles of leaves, stems and seeds, and its protein is localized in the endoplasmic reticulum. No activity of OsSULTR3;3 was revealed for the transport of phosphate, sulfate, inositol or inositol 1,4,5 triphosphate by heterologous expression in either yeast or Xenopus oocytes.The findings reveal that OsSULTR3;3 plays an important role in grain metabolism, pointing to a new route to generate value-added grains in rice and other cereal crops.

DSTA4637A, a novel THIOMAB™ antibody antibiotic conjugate (TAC) against Staphylococcus aureus (S. aureus), is currently being investigated as a potential therapy against S. aureus infections. Structurally, TAC is composed of an anti-S. aureus antibody linked to a potent antibiotic, dmDNA31. The goal of the current study was to characterize the pharmacokinetics (PK) of TAC in mice, assess the effect of S. aureus infection on its PK, and evaluate its pharmacodynamics (PD) by measuring the bacterial load in various organs at different timepoints following TAC treatment. Plasma concentrations of 3 analytes, total antibody (TAb), antibody-conjugated dmDNA31 (ac-dmDNA31), and unconjugated dmDNA31, were measured in these studies. In non-infected mice (target antigen absent), following intravenous (IV) administration of a single dose of TAC, systemic concentration-time profiles of both TAb and ac-dmDNA31 were bi-exponential and characterized by a short distribution phase and a long elimination phase as expected for a monoclonal antibody-based therapeutic. Systemic exposures of both TAb and ac-dmDNA31 were dose proportional over the dose range tested (5 to 50 mg/kg). In a mouse model of systemic S. aureus infection (target antigen present), a single IV dose of TAC demonstrated PK behavior similar to that in the non-infected mice, and substantially reduced bacterial load in the heart, kidney, and bones on 7 and 14 d post dosing. These findings have increased our understanding of the PK and PK/PD of this novel molecule, and have shown that at efficacious dose levels the presence of S. aureus infection had minimal effect on TAC PK.

Psoralea corylifolia L. (Fabaceae) is a widely used medical plant in China. This study was designed to screen and identify bioactive compounds with anticancer activity from the seeds of Psoralea corylifolia L. One volatile fraction (fraction I) and three other fractions (fraction II, III, IV) from methanol extraction of P. corylifolia L. were obtained. Bioactivities of these fractions were evaluated by the cytotoxicity on KB, KBv200, K562, K562/ADM cancer cells with MTT assay. Major components in the active fraction were identified by HPLC/MSn. Fraction IV significantly inhibits the growth of cancer cells in a dose-dependent manner. The IC50 values were 21.6, 24.4, 10.0 and 26.9, respectively. Psoralen and isopsoralen, isolated from fraction IV, were subject to bioactive assay and presented a dose-dependent anticancer activity in four cancer cell lines (KB, KBv200, K562 and K562/ADM). The IC50 values of psoralen were 88.1, 86.6, 24.4 and 62.6, which of isopsoralen were 61.9, 49.4, 49.6 and 72.0, respectively. Apoptosis of tumor cell significantly increased after treated with psoralen and isopsoralen. Induction of apoptotic activity was confirmed by flow cytometry after staining with Annexin V/PI. These results suggested psoralen and isopsoralen contribute to anticancer effect of P. corylifolia L.