Mechanisms of anti-atherosclerotic functions of soy-based diets

Soy-based diets have been reported to protect against the development of atherosclerosis. However, the underlying mechanism(s) for this protection remains unknown. Although atherosclerosis was traditionally considered a disease associated with impaired lipid metabolism, in recent years the inflammatory components of atherosclerosis have been explored. Recent studies have convincingly delineated that uncontrolled chronic inflammation is the principal contributing factor for the initiation and progression of atherosclerosis. Interaction between activated monocytes and vascular endothelial cells is an early event in atherogenesis. The adhesion of leukocytes, including monocytes, to the inflamed-vascular endothelium and their transmigration into intima initiate the inflammatory processes. Following transmigration, monocytes in the intima are transformed to macrophages, which take up oxidized-LDL (oxLDL) to generate lipid-laden macrophages, also known as foam cells. Hence, in this review article the inflammatory processes associated with atherosclerosis and possible anti-inflammatory functions of soy-based diets contributing to the prevention of atherosclerosis are presented.     

Identification of Medically Actionable Secondary Findings in the 1000 Genomes

The American College of Medical Genetics and Genomics (ACMG) recommends that clinical sequencing laboratories return secondary findings in 56 genes associated with medically actionable conditions. Our goal was to apply a systematic, stringent approach consistent with clinical standards to estimate the prevalence of pathogenic variants associated with such conditions using a diverse sequencing reference sample. Candidate variants in the 56 ACMG genes were selected from Phase 1 of the 1000 Genomes dataset, which contains sequencing information on 1,092 unrelated individuals from across the world. These variants were filtered using the Human Gene Mutation Database (HGMD) Professional version and defined parameters, appraised through literature review, and examined by a clinical laboratory specialist and expert physician. Over 70,000 genetic variants were extracted from the 56 genes, and filtering identified 237 variants annotated as disease causing by HGMD Professional. Literature review and expert evaluation determined that 7 of these variants were pathogenic or likely pathogenic. Furthermore, 5 additional truncating variants not listed as disease causing in HGMD Professional were identified as likely pathogenic. These 12 secondary findings are associated with diseases that could inform medical follow-up, including cancer predisposition syndromes, cardiac conditions, and familial hypercholesterolemia. The majority of the identified medically actionable findings were in individuals from the European (5/379) and Americas (4/181) ancestry groups, with fewer findings in Asian (2/286) and African (1/246) ancestry groups. Our results suggest that medically relevant secondary findings can be identified in approximately 1% (12/1092) of individuals in a diverse reference sample. As clinical sequencing laboratories continue to implement the ACMG recommendations, our results highlight that at least a small number of potentially important secondary findings can be selected for return. Our results also confirm that understudied populations will not reap proportionate benefits of genomic medicine, highlighting the need for continued research efforts on genetic diseases in these populations.     

Production of insulin-like growth factor-II (MSA) by endoderm-like cells derived from embryonal carcinoma cells: possible mediator of embryonic cell growth

The present study was carried out to determine if an insulin-like growth factor (IGF) type activity might be produced by embryonal carcinoma-derived cells. The cell line used to condition growth medium for the isolation of secreted growth factors was a newly established Dif 5 cell type. Dif 5 cells are a differentiated endoderm-like cell type derived from F9 embryonal carcinoma cells (which possess properties similar to mouse embryonic stem cells) following extensive exposure to retinoic acid. When growth medium conditioned by Dif 5 cells is chromatographed on Sephadex G-75 in 1 M acetic acid two peaks of activity are observed which compete for specific [125I]iodo multiplication stimulating activity (MSA) binding to PYS cells. MSA is the rat homologue of human IGF-II. The high molecular weight fraction (Mr approximately 60K) apparently corresponds to IGF-binding protein as determined by its ability to bind [125I]iodo-MSA. The low molecular weight fraction (Mr approximately 8K) is biologically active as this fraction stimulates [3H]thymidine incorporation into serum-starved chick embryo fibroblasts. Radioimmunoassay data indicate that the IGF-like activity produced by Dif 5 cells is more closely related to IGF-II than to IGF-I. Undifferentiated embryonal carcinoma stem cell lines (F9, Nulli, and PCC4) produced little of this MSA-like activity, while PYS-2 (parietal endoderm-like) cells produced about 16 ng MSA/10(6) cells/24 hr as determined by radioimmunoassay. Dif 5 and PSA-5E (visceral endoderm-like) cells, are found to secrete significant amounts of MSA into the growth medium (30-50 ng MSA/10(6) cells/24 hr). These findings offer further support to a proposal that MSA (IGF-II) produced by endoderm cells, particularly visceral endoderm, may serve as an early embryonic growth factor.     

Embryogenesis and plant regeneration of Medicago spp. in tissue culture

Ten cultivars and breeding lines from two species of alfalfa (Medicago media and M. sativa) were screened for their ability to produce embryos and plantlets from the root and hypocotyl under three different tissue culture protocols. The three protocols differed in basal salt composition, vitamins, hormones and cytokinin additions. That protocol having a high 2–4,D low cytokinin induction step gave the highest percentage of embryogenic calli in some cultivars and lines. M. media cultivars and breeding lines had a high percentage of embryoid formation. M. sativa cultivars gave no embryoid formation. Two M. media breeding lines (Br1 and Le1), which were intermediate in the percentage of embryogenic calli formed from explants, had the highest number of regenerated plants established in soil. The creeping rooted M. media cultivar Heinrichs produced the highest percentage of embryogenic calli from explants but most of these embryoids were abnormal and failed to grow in soil or vermiculite. Accordingly, successful regeneration is directly related to the quality and quantity of the embryoids produced. Respectively: Biotechnology Department, Alberta Research Council, Agriculture Canada, Beaverlodge, Alberta, and University of Alberta, Edmonton, Alberta, Canada     

Waterbirds and substrate quality of the Pichavaram wetlands,southern India

The water and mud characteristics of the six types of wetlands in Pichavaram were compared in order to determine whether the habitat of waterbird species was characterized by them. Waterbird species richness was most influenced by mud phosphorus levels. Variation in water pH was the principal factor that determined waterbird diversity. The water level mainly determined the density of waterbirds. Levels of pH and nitrites in the water also appeared to influence significant variations in waterbird diversity and density, respectively. Bottom substrate variables, viz. pH and phosphorus levels, were also significantly correlated with the density and richness of waterbirds, respectively. Water quality factors, viz. pH and nitrite and mud pH and phosphorus, were correlated with the abundance, while water depth was correlated with the accessibility of prey to the birds.     

Chloramphenicol acetyltransferase, a cytoplasmic protein is incompatible for export from Bacillus subtilis.

Bacillus subtilis cells expressing a hybrid protein (Lvsss-Cat) consisting of the B. amyloliquefaciens levansucrase signal peptide fused to B. pumilus chloramphenicol acetyltransferase (Cat) are unable to export Cat protein into the growth medium. A series of tripartite protein fusions was constructed by inserting various lengths of the Cat sequences between the levansucrase signal peptide and staphylococcal protein A or Escherichia coli alkaline phosphatase. Biochemical characterization of the various Cat protein fusions revealed that multiple regions in the Cat protein were causing the export defect.     

Secretion of streptavidin from Bacillus subtilis.

Streptavidin is an extracellular tetrameric protein produced by Streptomyces avidinii. A series of hybrid gene fusions consisting of Bacillus signal peptide coding regions fused to the mature streptavidin sequence were constructed. B. subtilis strains harboring these plasmids accumulate a tetrameric streptavidin in the growth medium. The properties of the streptavidin produced by B. subtilis are similar to those of the streptavidin produced by S. avidinii. B. subtilis strains carrying the various fusions can be grown to a high cell density in a biotin-free medium. Thus, B. subtilis represents an alternate host system for the production of streptavidin.     

Urease catalysis and structure: X. Alternate bonding-site isozymes of jackbean urease

Three previously uncharacterized, nongenetic urease isozymes have been analyzed by sucrose density gradient sedimentation, gel electrophoresis, and chemical reactivity. The full complement of isozymes could be reliably generated by choosing appropriate levels of NaCl, pH, and ethylene glycol, and was stable for several days in dilute solution. The three forms of interest were found to be quaternary isomers of other isozymes, but differed from them qualitatively in their bonding sites, with disulfide bonds being substituted for noncovalent bonds. The separation of these isomer-pairs during sedimentation and electrophoresis cannot be readily explained by differences in size or charge, but must rather arise from a difference in shape. A simple two-dimensional model can provide the appropriate molecular architecture to satisfy these requirements: Only one of the two half-units in each α-urease molecule undergoes disulfide bonding during polymerization, and it does so with two adjacent molecules, thus producing asymmetric polymers from symmetric starting components.