The Crystal Structures of Two Novel Cadmium-Picolinic Acid Complexes in Relation to the Solution Species

The crystal structures of two novel cadmium-picolinic acid complexes grown in aqueous solutions at selected pH values are reported. The structures are compared to expected solution species under the same conditions. The crystal structure of complex 1 exhibits a seven coordinate structure which contains a protonated picolinic acid ligand that bonds bidentately to the cadmium ion via both carboxylate oxygens. Two nitrates coordinate to the metal centre within the same plane, one monodentately and the other bidentately, and two water molecules are found in the axial positions. The structure of complex 2 shows cadmium bonded to three of N,O-bidentate picolinic acid ligands to produce a distorted octahedron.Keywords: Cadmium, picolinic acid, solution species, crystal structures, controlled pH PDF and supplementary file attached

Lymphocyte gene expression signatures from patients and mouse models of hereditary hemochromatosis reveal a function of HFE as a negative regulator of CD8+ T-lymphocyte activation and differentiation in vivo

Abnormally low CD8+ T-lymphocyte numbers is characteristic of some patients with hereditary hemochromatosis (HH), a MHC-linked disorder of iron overload. Both environmental and genetic components are known to influence CD8+ T-lymphocyte homeostasis but the role of the HH associated protein HFE is still insufficiently understood. Genome-wide expression profiling was performed in peripheral blood CD8+ T lymphocytes from HH patients selected according to CD8+ T-lymphocyte numbers and from Hfe-/- mice maintained either under normal or high iron diet conditions. In addition, T-lymphocyte apoptosis and cell cycle progression were analyzed by flow cytometry in HH patients. HH patients with low CD8+ T-lymphocyte numbers show a differential expression of genes related to lymphocyte differentiation and maturation namely CCR7, LEF1, ACTN1, NAA50, P2RY8 and FOSL2, whose expression correlates with the relative proportions of naïve, central and effector memory subsets. In addition, expression levels of LEF1 and P2RY8 in memory cells as well as the proportions of CD8+ T cells in G2/M cell cycle phase are significantly different in HH patients compared to controls. Hfe-/- mice do not show alterations in CD8+ T-lymphocyte numbers but differential gene response patterns. We found an increased expression of S100a8 and S100a9 that is most pronounced in high iron diet conditions. Similarly, CD8+ T lymphocytes from HH patients display higher S100a9 expression both at the mRNA and protein level. Altogether, our results support a role for HFE as a negative regulator of CD8+ T-lymphocyte activation. While the activation markers S100a8 and S100a9 are strongly increased in CD8+ T cells from both, Hfe-/- mice and HH patients, a differential profile of genes related to differentiation/maturation of CD8+ T memory cells is evident in HH patients only. This supports the notion that HFE contributes, at least in part, to the generation of low peripheral blood CD8+ T lymphocytes in HH

A critical role for endocytosis in Wnt signaling

BACKGROUND: The Wnt signaling pathway regulates many processes during embryonic development, including axis specification, organogenesis, angiogenesis, and stem cell proliferation. Wnt signaling has also been implicated in a number of cancers, bone density maintenance, and neurological conditions during adulthood. While numerous Wnts, their cognate receptors of the Frizzled and Arrow/LRP5/6 families and downstream pathway components have been identified, little is known about the initial events occurring directly after receptor activation. RESULTS: We show here that Wnt proteins are rapidly endocytosed by a clathrin- and dynamin-mediated process. While endocytosis has traditionally been considered a principal mechanism for receptor down-regulation and termination of signaling pathways, we demonstrate that interfering with clathrin-mediated endocytosis actually blocks Wnt signaling at the level of β-catenin accumulation and target gene expression. CONCLUSION: A necessary component of Wnt signaling occurs in a subcellular compartment distinct from the plasma membrane. Moreover, as internalized Wnts transit partially through the transferrin recycling pathway, it is possible that a "signaling endosome" serves as a nexus for activated Wnt pathway components

Trade-offs between vegetative growth and acorn production in Quercus lobata during a mast year: the relevance of crop size and hierarchical level within the canopy

The concept of trade-offs between reproduction and other fitness traits is a fundamental principle of life history theory. For many plant species, the cost of sexual reproduction affects vegetative growth in years of high seed production through the allocation of resources to reproduction at different hierarchical levels of canopy organization. We have examined these tradeoffs at the shoot and branch level in an endemic California oak, Quercus lobata, during a mast year. To determine whether acorn production caused a reduction in vegetative growth, we studied trees that were high and low acorn producers, respectively. We observed that in both low and high acorn producers, shoots without acorns located adjacent to reproductive shoots showed reduced vegetative growth but that reduced branch-level growth on acorn-bearing branches occurred only in low acorn producers. The availability of local resources, measured as previous year growth, was the main factor determining acorn biomass. These findings show that the costs of reproduction varied among hierarchical levels, suggesting some degree of physiological autonomy of shoots in terms of acorn production. Costs also differed among trees with different acorn crops, suggesting that trees with large acorn crops had more available resources to allocate for growth and acorn production and to compensate for immediate local costs of seed production. These findings provide new insight into the proximate mechanisms for mast-seeding as a reproductive strategy

Reliability of race assessment based on the race of the ascendants: a cross-sectional study

BACKGROUND: Race is commonly described in epidemiological surveys based on phenotypic characteristics. Training of interviewers to identify race is time-consuming and self identification of race might be difficult to interpret. The aim of this study was to determine the agreement between race definition based on the number of ascendants with black skin colour, with the self-assessment and observer's assessment of the skin colour. METHODS: In a cross-sectional study of 50 women aged 14 years or older, from an outpatient clinic of an University affiliated hospital, race was assessed through observation and the self-assignment of the colour of skin and by the number of black ascendants including parents and grandparents. Reliability was measured through Kappa coefficient. RESULTS: Agreement beyond chance between self-assigned and observed skin colour was excellent for white (0.75 95% CI 0.72–0.78) and black women (0.89 95% CI 0.71–0.79), but only good for participants with mixed colour (0.61 95% CI 0.58–0.64), resulting in a global kappa of 0.75 (95% CI 0.71–0.79). However, only a good agreement for mixed women was obtained. The presence of 3 or more black ascendants was highly associated with observed and self-assessed black skin colour. Most women self-assigned or observed as white had no black ascendants. CONCLUSIONS: The assessment of race based on the race of ascendants showed reasonable agreement with the ascertainment done by trained interviewers and with the self-report of race. This method may be considered for evaluation of race in epidemiological surveys, since it is less time-consuming than the evaluation by interviewers

Serratia marcescens internalization and replication in human bladder epithelial cells

BACKGROUND: Serratia marcescens, a frequent agent of catheterization-associated bacteriuria, strongly adheres to human bladder epithelial cells in culture. The epithelium normally provides a barrier between lumal organisms and the interstitium; the tight adhesion of bacteria to the epithelial cells can lead to internalization and subsequent lysis. However, internalisation was not shown yet for S. marcescens strains. METHODS: Elektronmicroscopy and the common gentamycin protection assay was used to assess intracellular bacteria. Via site directed mutagenesis, an hemolytic negative isogenic Serratia strain was generated to point out the importance of hemolysin production. RESULTS: We identified an important bacterial factor mediating the internalization of S. marcescens, and lysis of epithelial cells, as the secreted cytolysin ShlA. Microtubule filaments and actin filaments were shown to be involved in internalization. However, cytolysis of eukaryotic cells by ShlA was an interfering factor, and therefore hemolytic-negative mutants were used in subsequent experiments. Isogenic hemolysin-negative mutant strains were still adhesive, but were no longer cytotoxic, did not disrupt the cell culture monolayer, and were no longer internalized by HEp-2 and RT112 bladder epithelial cells under the conditions used for the wild-type strain. After wild-type S. marcescens became intracellular, the infected epithelial cells were lysed by extended vacuolation induced by ShlA. In late stages of vacuolation, highly motile S. marcescens cells were observed in the vacuoles. S. marcescens was also able to replicate in cultured HEp-2 cells, and replication was not dependent on hemolysin production. CONCLUSION: The results reported here showed that the pore-forming toxin ShlA triggers microtubule-dependent invasion and is the main factor inducing lysis of the epithelial cells to release the bacteria, and therefore plays a major role in the development of S. marcescens infections