Atx1-like chaperones and their cognate P-type ATPases: copper-binding and transfer

Copper is an essential yet toxic metal ion. To satisfy cellular requirements, while, at the same time, minimizing toxicity, complex systems of copper trafficking have evolved in all cell types. The best conserved and most widely distributed of these involve Atx1-like chaperones and P_1B-type ATPase transporters. Here, we discuss current understanding of how these chaperones bind Cu(I) and transfer it to the Atx1-like N-terminal domains of their cognate transporter.     

Discovery of novel phenoxazinone derivatives as DKK1/LRP6 interaction inhibitors: Synthesis,biological evaluation and structure–activity relationships

Amino derivatives of NCI8642 were synthesized and evaluated as inhibitors of DKK1/LRP6 interactions. The new inhibitors were able to activate the Wnt signaling pathway as indicated by the increased levels of β-catenin, and decrease the DKK1-induced Tau phosphorylation at serine 396.     

DISC1 gene polymorphisms and the risk of schizophrenia in an Iranian population: A preliminary study

Background: Schizophrenia, schizoaffective disorder, and bipolar illness are common psychological disorders with high heritability and variable phenotypes. The disrupted in schizophrenia 1 ( DISC1) gene, on chromosome 1q42, has an essential role in neurite outgrowth and cell signaling. The purpose of this study was to investigate the association of three single-nucleotide polymorphisms (SNPs; rs6675281, rs2255340, and rs2738864) with schizophrenia disorder. These three SNPs were chosen as they had been used in most of the previous studies. Methods: In a case-control study of Iranian population for the first time 778 blood samples were collected including, 402 schizophrenic patients and 376 healthy controls. Genomic DNA was extracted from peripheral blood using DNA extraction kit (BioFlux Co). The genotypes of rs6675281, rs2255340, and rs2738864 were detected by nested allele-specific multiplex polymersae chain reaction (PCR). Results: Our data revealed that the three SNPs are significantly associated with schizophrenia (rs2255349 C>T: confidence interval (CI), 2.115 to 3.268; P = 0.0000 OR: 2.629; rs2738864 C>T: CI, 1.538 to 2.339; P = 0.0000 OR: 1.897; rs6675281 C>T: CI, 2.788 to 4.662; P = 0.0009241 OR: 3.605). Through applying the expectation-maximization (EM) algorithm, we calculated the haplotype frequency, and finally performed haplotype analysis with Bonferroni correction and data preprocessing methods and the results showed rs66875281 to have the highest association. Discussion: Our findings primarily showed that DISC1 gene polymorphisms contribute to schizophrenia risk and have a significant association with this disorder among Iranian population. The strategy was found to be easy, rapid, specific, and consistent for the co-occurring detection of the DISC1 polymorphisms. We could finally confirm that the polymorphisms are related to schizophrenia studied in Iranian population.     

Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer

The cellular energy and biomass demands of cancer drive a complex dynamic between uptake of extracellular FAs and their de novo synthesis. Given that oxidation of de novo synthesized FAs for energy would result in net-energy loss, there is an implication that FAs from these two sources must have distinct metabolic fates; however, hitherto, all FAs have been considered part of a common pool. To probe potential metabolic partitioning of cellular FAs, cancer cells were supplemented with stable isotope-labeled FAs. Structural analysis of the resulting glycerophospholipids revealed that labeled FAs from uptake were largely incorporated to canonical (sn-) positions on the glycerol backbone. Surprisingly, labeled FA uptake also disrupted canonical isomer patterns of the unlabeled lipidome and induced repartitioning of n-3 and n-6 PUFAs into glycerophospholipid classes. These structural changes support the existence of differences in the metabolic fates of FAs derived from uptake or de novo sources and demonstrate unique signaling and remodeling behaviors usually hidden from conventional lipidomics.     

Epilogue — Demography and anthropology

As a conclusion, this paper reviews briefly the content of the volume. The wealth of demographic data has not been adequately exploited in anthropology; this is why this publication is valuable in showing attempts to apply demographic data in a variety of anthropological problems. This symposium has explored many interesting points which we recall here. Yet it has also opened up a whole range of further questions on the material presented as well as in this broad field. Several directions of research could be developed, for instance, testing among human populations, over long periods, the ecological thoughts of ecosystems evolving as a cascade of instabilities, rather than a succession of equilibrium states. Let us also recall the pervasive nature of demographic facts in topics such as the energy cycle or the genetic structure and evolution of human populations.     

Competitive and facilitative relationships among three shrub species,and the role of browsing intensity and rooting depth in the Succulent Karoo,South Africa

Abstract. The nearest‐neighbour technique is used to infer competition and facilitation between the three most abundant species in a semi‐arid region of western South Africa. Relationships among the shrubs Leipoldtia schultzei and Ruschia robusta, which are leaf‐succulent members of the Mesembryanthemaceae (‘mesembs’) and Hirpicium alienatum a non‐succulent Asteraceae, were compared on two adjacent sites with different histories of browsing intensity. Competition was more prevalent and more important than facilitation. The only evidence for facilitation was found at the heavily‐browsed site where the palatable Hirpicium was larger under the unpalatable Leipoldtia. Generally the prevalence and importance of competition was reduced at the heavily‐browsed site. Strong evidence was obtained for intraspecific competition in each of the three species; also, competition was evident between the two mesembs, where Leipoldtia was competitively dominant over Ruschia, although neither species inhibited Hirpicium. Minimal competition between the mesembs and the asteraceous shrub was interpreted in terms of differentiation in rooting depth, and competition within the mesembs, in terms of overlap in rooting depth. The mesembs had the bulk of their roots in the top 5 cm of soil, while the asteraceous shrub had the bulk of its roots, and all its fine roots, at greater depths. The shallow‐rooted morphology of the mesembs is well adapted to utilize small rainfall events, which occur frequently in the Succulent Karoo, and do not penetrate the soil deeply. Modifications of existing methods are applied for analysing nearest‐neighbour interactions.