Statistical inference of the time-varying structure of gene-regulation networks

Background  

Biological networks are highly dynamic in response to environmental and physiological cues. This variability is in contrast to conventional analyses of biological networks, which have overwhelmingly employed static graph models which stay constant over time to describe biological systems and their underlying molecular interactions.     

Inhibitors of lipoprotein(a) assembly

Compounds of the general structure A and B were investigated for their activity as lipoprotein(a), [Lp(a)], assembly (coupling) inhibitors. SAR around the amino acid derivatives (structure A) gave compound 14-6 as a potent coupling inhibitor. Oral dosing of compound 14-6 to Lp(a) transgenic mice and cymologous monkeys resulted in a>30% decrease in plasma Lp(a) levels after 1-2 weeks of treatment at 100 mg/kg/day.     

Immunolocalization of the sea urchin sperm receptor in eggs and maturing ovaries

The sperm receptor from Strongylocentrotus purpuratus eggs is a high molecular weight proteoglycan-like molecule that inhibits fertilization species-specifically in a competition bioassay. A preparation of highly active sperm receptor that contained one major N-terminal sequence was used to generate polyclonal antibody in rabbits. This antibody species-specifically inhibited fertilization at low concentrations without interfering with fertilization envelope elevation. On immunofluorescence microscopy, the antibody recognized determinants on the mature egg cell surface and in the cortical granules just beneath the surface. Preabsorption of the antibody with the calcium-soluble fraction of the exudate from cortical granules rendered the antibody specific for the cell surface in mature eggs and still able to inhibit fertilization at the same concentrations as before treatment with cortical granule exudate. With antibody preabsorbed with cortical granule and by counting antibody-gold particles viewed by electron microscopy, sperm receptor was almost undetectable on the cell surface of immature oocytes in preseason ovaries, present on the cell surface and intracellularly in immature oocytes of ovaries collected at the beginning or at the height of the spawning season, and present only on the cell surface of mature oocytes in the lumen of the ovaries. Our results indicate that receptor is synthesized early in oogenesis and is rapidly moved to the egg cell surface.     

Function of Lysosomes and Lysosomal Enzymes in the Senescing Corolla of the Morning Glory (Ipomoea purpurea)

The rapid senescence of the Ipomoea corolla is characterizedby the breakdown of protein and nucleic acids. At the onsetof wilting the activities of deoxyribonuclease (DNase), ribonuclease(RNase), and ß-glucosidase are increased dramatically,while other hydrolytic activities such as the actions of protease,aminopeptidase, -glucosidase, phosphatase, esterase, and -amylaseare only slightly changed. Isolated corolla discs show a course of senescence similar tothat of the intact organ. When floating on solutions of cycloheximidethe activities of DNase, RNase, and ß-glucosidasedo not increase. Actinomycin D inhibits the increase in RNaseactivity. It is concluded that protein synthesis is a prerequisitefor the changes in these enzyme activities in the senescingcorolla. The function of the lysosomal compartment in the process ofsenescence is illustrated by electron micrographs showing theautophagic activity of vacuoles. The last phase of senescenceis characterized by the breakdown of the tonoplast and completedigestion of the cytoplasmic constituents in the autolysingcells.