THE RELATIONSHIP OF DIETARY FAT TO ATHEROSCLEROTIC DISEASE

Atherosclerosis is the Number One public health problem. Many factors have been implicated in the pathogenesis of this disease. Prominent among these factors is the amount and kind of fat in the diet. The evidence now appears to be conclusive that sufficient quantities of polyunsaturated fat in the diet, with proportional decrease in saturated fat, will result in major decrease in blood lipid. Some evidence indicates that such blood lipid lowering produces a desirable effect upon existing atherosclerosis. Much additional time and work will be required to clarify the prophylactic and therapeutic value of this type of dietary approach.     

Standardized experiments in mutant mice reveal behavioural similarity on 129S5 and C57BL/6J backgrounds

Behavioural analysis of mice carrying engineered mutations is widely used to identify roles of specific genes in components of the mammalian behavioural repertoire. The reproducibility and robustness of phenotypic measures has become a concern that undermines the use of mouse genetic models for translational studies. Contributing factors include low individual study power, non‐standardized behavioural testing, failure to address confounds and differences in genetic background of mutant mice. We have examined the importance of these factors using a statistically robust approach applied to behavioural data obtained from three mouse mutations on 129S5 and C57BL/6J backgrounds generated in a standardized battery of five behavioural assays. The largest confounding effect was sampling variation, which partially masked the genetic background effect. Our observations suggest that strong interaction of mutation with genetic background in mice in innate and learned behaviours is not necessarily to be expected. We found composite measures of innate and learned behaviour were similarly impacted by mutations across backgrounds. We determined that, for frequently used group sizes, a single retest of a significant result conforming to the commonly used P < 0.05 threshold results in a reproducibility of 60% between identical experiments. Reproducibility was reduced in the presence of strain differences. We also identified a P‐value threshold that maximized reproducibility of mutant phenotypes across strains. This study illustrates the value of standardized approaches for quantitative assessment of behavioural phenotypes and highlights approaches that may improve the translational value of mouse behavioural studies.     

Diversity of life strategies and population structure of Kamchatka mykiss <Emphasis Type="Italic">Parasalmo mykiss</Emphasis> in the ecosystems of small salmon rivers of various types

The diversity of life strategies and population structure of Kamchatka mykiss Parasalmo mykiss in the ecosystems of small salmon rivers of various types are considered. Hydrogeomorphological differences of the model rivers Kol and Kekhta are found. The preferred habitats are investigated, and their area is determined. It is shown that, in the Kol River, the mykiss having a resident life strategy predominated, and in the Kekhta River—the mykiss with migratory strategy. The key parameter controlling the prevalence of life strategies in each river is the ratio of the area of spawning grounds to the area of feeding grounds and their productivity. The hypothesis is confirmed that, in complex river systems, due to the diversity of biotopes and a higher productivity, the food resources are sufficient for maturation of mykiss and for realization of the resident life strategy (without migration to the sea for feeding). In small rivers of the channel type with their insufficient food resources, the specimens having a migratory life strategy prevail.     

Habitat Heterogeneity and Associated Microbial Community Structure in a Small-Scale Floodplain Hyporheic Flow Path

The Nyack floodplain is located on the Middle Fork of the Flathead River, an unregulated, pristine, fifth-order stream in Montana, USA, bordering Glacier National Park. The hyporheic zone is a nutritionally heterogeneous floodplain component harboring a diverse array of microbial assemblages essential in fluvial biogeochemical cycling, riverine ecosystem productivity, and trophic interactions. Despite these functions, microbial community structure in pristine hyporheic systems is not well characterized. The current study was designed to assess whether physical habitat heterogeneity within the hyporheic zone of the Nyack floodplain was sufficient to drive bacterial β diversity between three different hyporheic flow path locations. Habitat heterogeneity was assessed by measuring soluble reactive phosphorous, nitrate, dissolved organic carbon, dissolved oxygen, and soluble total nitrogen levels seasonally at surface water infiltration, advection, and exfiltration zones. Significant spatial differences were detected in dissolved oxygen and nitrate levels, and seasonal differences were detected in dissolved oxygen, nitrate, and dissolved organic carbon levels. Denaturing gradient gel electrophoresis (DGGE) and cell counts indicated that bacterial diversity increased with abundance, and DGGE fingerprints covaried with nitrate levels where water infiltrated the hyporheic zone. The ribosomal gene phylogeny revealed that hyporheic habitat heterogeneity was sufficient to drive β diversity between bacterial assemblages. Phylogenetic (P) tests detected sequence disparity between the flow path locations. Small distinct lineages of Firmicutes, Actinomycetes, Planctomycetes, and Acidobacteria defined the infiltration zone and α- and β-proteobacterial lineages delineated the exfiltration and advection zone communities. These data suggest that spatial habitat heterogeneity drives hyporheic microbial community development and that attempts to understand functional differences between bacteria inhabiting nutritionally heterogeneous hyporheic environments might begin by focusing on the biology of these taxa.     

Human Mesenchymal Stem Cells Self-Renew and Differentiate According to a Deterministic Hierarchy

Background

Mesenchymal progenitor cells (MPCs) have been isolated from a variety of connective tissues, and are commonly called “mesenchymal stem cells” (MSCs). A stem cell is defined as having robust clonal self-renewal and multilineage differentiation potential. Accordingly, the term “MSC” has been criticised, as there is little data demonstrating self-renewal of definitive single-cell-derived (SCD) clonal populations from a mesenchymal cell source.

Methodology/Principal Findings

Here we show that a tractable MPC population, human umbilical cord perivascular cells (HUCPVCs), was capable of multilineage differentiation in vitro and, more importantly, contributed to rapid connective tissue healing in vivo by producing bone, cartilage and fibrous stroma. Furthermore, HUCPVCs exhibit a high clonogenic frequency, allowing us to isolate definitive SCD parent and daughter clones from mixed gender suspensions as determined by Y-chromosome fluorescent in situ hybridization.

Conclusions/Significance

Analysis of the multilineage differentiation capacity of SCD parent clones and daughter clones enabled us to formulate a new hierarchical schema for MSC self-renewal and differentiation in which a self-renewing multipotent MSC gives rise to more restricted self-renewing progenitors that gradually lose differentiation potential until a state of complete restriction to the fibroblast is reached.