The role of non-parenchymal cells in liver growth

The main non-parenchymal cells of the liver, Kupffer cells, sinusoidal endothelial cells and stellate cells, participate in liver growth with respect to both their own proliferation, and effects on hepatocyte proliferation. In the well-characterised paradigm of 70% partial hepatectomy, they undergo DNA synthesis and cell division 20-24h later than the hepatocyte population. They exert both positive and negative influences on hepatocyte proliferation, including provision of an extracellular matrix-bound reservoir of hepatocyte growth factor that is activated after damage; priming of hepatocytes for DNA synthesis through rapid generation of TNF-alpha and IL-6; and generation of factors at later time points that curb hepatocyte DNA synthesis (IL-1, TGF-beta) and initiate reconstruction and reformation of matrix proteins.     

GREG cells, a dysferlin-deficient myogenic mouse cell line

The dysferlinopathies (e.g. LGMD2b, Myoshi myopathy) are progressive, adult-onset muscle wasting syndromes caused by mutations in the gene coding for dysferlin. Dysferlin is a large (~200kDa) membrane-anchored protein, required for maintenance of plasmalemmal integrity in muscle fibers. To facilitate analysis of dysferlin function in muscle cells, we have established a dysferlin-deficient myogenic cell line (GREG cells) from the A/J mouse, a genetic model for dysferlinopathy. GREG cells have no detectable dysferlin expression, but proliferate normally in growth medium and fuse into functional myotubes in differentiation medium. GREG myotubes exhibit deficiencies in plasma membrane repair, as measured by laser wounding in the presence of FM1-43 dye. Under the wounding conditions used, the majority (~66%) of GREG myotubes lack membrane repair capacity, while no membrane repair deficiency was observed in dysferlin-normal C2C12 myotubes, assayed under the same conditions. We discuss the possibility that the observed heterogeneity in membrane resealing represents genetic compensation for dysferlin deficiency.     

Naturally-occurring genetic variants in human DC-SIGN increase HIV-1 capture, cell-transfer and risk of mother-to-child transmission

Background

Mother-to-child transmission (MTCT) is the main cause of HIV-1 infection in children worldwide. Dendritic cell–specific ICAM-3 grabbing-nonintegrin (DC-SIGN, also known as CD209) is an HIV-1 receptor that enhances its transmission to T cells and is expressed on placental macrophages.

Methods and Findings

We have investigated the association between DC-SIGN genetic variants and risk of MTCT of HIV-1 among Zimbabwean infants and characterized the impact of the associated mutations on DC-SIGN expression and interaction with HIV-1. DC-SIGN promoter (p-336C and p-201A) and exon 4 (198Q and 242V) variants were all significantly associated with increased risk of intrauterine (IU) HIV-1 infection. Promoter variants decreased DC-SIGN expression both in vitro and in placental CD163⁺ macrophages (Hofbauer cells) of HIV-1 unexposed infants but not of HIV-1 exposed infants. The exon 4 protein-modifying mutations increased HIV-1 capture and transmission to T cells in vitro.

Conclusion

This study provides compelling evidence to support an important role of DC-SIGN in IU HIV-1 infection.     

Evolution of jasmonate and salicylate signal crosstalk

The evolution of land plants approximately 470 million years ago created a new adaptive zone for natural enemies (attackers) of plants. In response to attack, plants evolved highly effective, inducible defense systems. Two plant hormones modulating inducible defenses are salicylic acid (SA) and jasmonic acid (JA). Current thinking is that SA induces resistance against biotrophic pathogens and some phloem feeding insects and JA induces resistance against necrotrophic pathogens, some phloem feeding insects and chewing herbivores. Signaling crosstalk between SA and JA commonly manifests as a reciprocal antagonism and may be adaptive, but this remains speculative. We examine evidence for and against adaptive explanations for antagonistic crosstalk, trace its phylogenetic origins and provide a hypothesis-testing framework for future research on the adaptive significance of SA-JA crosstalk.     

Thermal energy conduction in a honey bee comb due to cell-heating bees

Theoretical analysis and numerical calculations are performed to characterize the unsteady two-dimensional conduction of thermal energy in an idealized honey bee comb. The situation explored corresponds to a comb containing a number of brood cells occupied by pupae. These cells are surrounded by other cells containing pollen which, in turn, are surrounded (above) by cells containing honey and (below) by vacant cells containing air. Up to five vacant cells in the brood region can be occupied by cell-heating bees which, through the isometrical contraction of their flight muscles, can generate sufficient energy to raise their body temperatures by a few degrees. In this way, the cell-heating bees alter the heat flux and temperature distributions in the brood region so as to maintain conditions that benefit the pupae. The calculations show that the number of cell-heating bees significantly affects the magnitude, time rate of change, and spatial distribution of temperature throughout the comb. They also reveal a vertically aligned asymmetry in the spatial distribution of temperature that is due to the large heat capacity and thermal conductivity of honey relative to air, whereby air-filled cells experience larger temperature increases than honey-filled cells. Analysis shows that convection and radiation represent negligible modes of thermal energy transfer at all levels in the problem considered. Also, because of its small thickness, the wax wall of a comb cell simultaneously presents negligible resistance to conduction heat transfer normal to it and very large resistance along it. As a consequence the walls of a cell play no thermal role, but simply serve as mechanical supports for the materials they contain.     

Complementary roles for histone deacetylases 1, 2, and 3 in differentiation of pluripotent stem cells

Abstract In eukaryotic cells, covalent modifications to core histones contribute to the establishment and maintenance of cellular phenotype via regulation of gene expression. Histone acetyltransferases (HATs) cooperate with histone deacetylases (HDACs) to establish and maintain specific patterns of histone acetylation. HDAC inhibitors can cause pluripotent stem cells to cease proliferating and enter terminal differentiation pathways in culture. To better define the roles of individual HDACs in stem cell differentiation, we have constructed "dominant-negative" stem cell lines expressing mutant, Flag-tagged HDACs with reduced enzymatic activity. Replacement of a single residue (His→Ala) in the catalytic center reduced the activity of HDACs 1 and 2 by 80%, and abolished HDAC3 activity; the mutant HDACs were expressed at similar levels and in the same multiprotein complexes as wild-type HDACs. Hexamethylene bisacetamide-induced MEL cell differentiation was potentiated by the individual mutant HDACs, but only to 2%, versus 60% for an HDAC inhibitor, sodium butyrate, suggesting that inhibition of multiple HDACs is required for full potentiation. Cultured E14.5 cortical stem cells differentiate to neurons, astrocytes, and oligodendrocytes upon withdrawal of basic fibroblast growth factor. Transduction of stem cells with mutant HDACs 1, 2, or 3 shifted cell fate choice toward oligodendrocytes. Mutant HDAC2 also increased differentiation to astrocytes, while mutant HDAC1 reduced differentiation to neurons by 50%. These results indicate that HDAC activity inhibits differentiation to oligodendrocytes, and that HDAC2 activity specifically inhibits differentiation to astrocytes, while HDAC1 activity is required for differentiation to neurons.     

Subpopulation Characteristics of Egg-Contaminating Salmonella enterica serovar Enteritidis as Defined by the Lipopolysaccharide O Chain

Characterization of Salmonella enterica serovar Enteritidis was refined by incorporating new data from isolates obtained from avian sources, from the spleens of naturally infected mice, and from the United Kingdom into an existing lipopolysaccharide (LPS) O-chain compositional database. From least to greatest, the probability of avian isolates producing high-molecular-mass LPS O chain ranked as follows: pooled kidney, liver, and spleen; intestine; cecum; ovary and oviduct; albumen; yolk; and whole egg. Mouse isolates were most like avian intestinal samples, whereas United Kingdom isolates were most like those from the avian reproductive tract and egg. Non-reproductive tract organ isolates had significant loss of O chain. Isogenic isolates that varied in ability to make biofilm and to be orally invasive produced different O-chain structures at 25°C but not at 37°C. Hens infected at a 91:9 biofilm-positive/-negative colony phenotype ratio yielded only the negative phenotype from eggs. These results indicate that the environment within the hen applies stringent selection pressure on subpopulations of S. enterica serovar Enteritidis at certain points in the infection pathway that ends in egg contamination. The avian cecum, rather than the intestines, is the early interface between the environment and the host that supports emergence of subpopulation diversity. These results suggest that diet and other factors that alter cecal physiology should be investigated as a means to reduce egg contamination.     

Assessment of the biological health of the Brantas River, East Java, Indonesia using the Australian River Assessment System (AUSRIVAS) methodology

This study aimed to evaluate the applicability of the Australian River Assessment System (AUSRIVAS) bioassessment methodology to assess the biological health of streams in the upper-middle Brantas River catchment, East Java, Indonesia. A total of 84 `minimally disturbed' reference sites were selected and sampled for macroinvertebrates in riffle habitats. Sampling of macroinvertebrates and identification to family level was conducted by local biologists following intensive training, and under supervision. A quality control protocol was introduced to ensure the data were reliable and reproducible. A suite of `potential predictor' and `monitoring' environmental variables were also measured at each site. The macroinvertebrate data were used to develop a predictive AUSRIVAS model for the upper-middle Brantas river, and the model was then used to assess the `health' of 15 test sites in the catchment. Bioassessment outputs – Observed (O)/Expected (E) ratios – were found to be broadly related to measures of physical disturbance from land use and riparian degradation. Through the process of local reference site selection and sampling, model development, validation and subsequent use, the Australian AUSRIVAS rapid bioassessment method was assessed as being highly applicable to the upper-middle catchment sections of Indonesian river systems.