The ERCC6 Gene and Age-Related Macular Degeneration

Background: Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the developed countries and is caused by both environmental and genetic factors. A recent study (Tuo et al., PNAS) reported an association between AMD and a single nucleotide polymorphism (SNP) (rs3793784) in the ERCC6 (NM_000124) gene. The risk allele also increased ERCC6 expression. ERCC6 is involved in DNA repair and mutations in ERCC6 cause Cockayne syndrome (CS). Amongst others, photosensitivity and pigmentary retinopathy are hallmarks of CS. Methodology/Principal Findings: Separate and combined data from three large AMD case-control studies and a prospective population-based study (The Rotterdam Study) were used to analyse the genetic association between ERCC6 and AMD (2682 AMD cases and 3152 controls). We also measured ERCC6 mRNA levels in retinal pigment epithelium (RPE) cells of healthy and early AMD affected human donor eyes. Rs3793784 conferred a small increase in risk for late AMD in the Dutch population (The Rotterdam and AMRO-NL study), but this was not replicated in two non-European studies (AREDS, Columbia University). In addition, the AMRO-NL study revealed no significant association for 9 other variants spanning ERCC6. Finally, we determined that ERCC6 expression in the human RPE did not depend on rs3793784 genotype, but, interestingly, on AMD status: Early AMD-affected donor eyes had a 50% lower ERCC6 expression than healthy donor eyes (P = 0.018). Conclusions/Significance: Our meta analysis of four Caucasian cohorts does not replicate the reported association between SNPs in ERCC6 and AMD. Nevertheless, our findings on ERCC6 expression in the RPE suggest that ERCC6 may be functionally involved in AMD. Combining our data with those of the literature, we hypothesize that the AMD-related reduced transcriptional activity of ERCC6 may be caused by diverse, small and heterogeneous genetic and/or environmental determinants

The European Hematology Association Roadmap for European Hematology Research. A Consensus Document

Abstract The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at Euro 23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine sections in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients. Received December 15, 2015. Accepted January 27, 2016. Copyright © 2016, Ferrata Storti Foundatio

Density functional theory based screening of ternary alkali-transition metal borohydrides: A computational material design project

The dissociation of molecules, even the most simple hydrogen molecule, cannot be described accurately within density functional theory because none of the currently available functionals accounts for strong on-site correlation. This problem led to a discussion of properties that the local Kohn-Sham potential has to satisfy in order to correctly describe strongly correlated systems. We derive an analytic expression for the nontrivial form of the Kohn-Sham potential in between the two fragments for the dissociation of a single bond. We show that the numerical calculations for a one-dimensional two-electron model system indeed approach and reach this limit. It is shown that the functional form of the potential is universal, i.e., independent of the details of the two fragments.We acknowledge funding by the Spanish MEC (Grant No. FIS2007-65702-C02-01), “Grupos Consolidados UPV/EHU del Gobierno Vasco” (Grant No. IT-319-07), and the European Community through e-I3 ETSF project (Grant Agreement No. 211956).Peer reviewe

“Dit is sterk doepa daai” maar is dit al wat ons het?

This article was written by Prof. Willie Burger before he joined the University of PretoriaThe realisation of the effects of the so-called “linguistic turn” and different thought associated with deconstruction and postmodernism has been an important presence in Brink’s oeuvre since On the Contrary (1993). In Praying Mantis (2005) there is an important shift away from the kind of awareness that the world is constituted in language (as in Devil’s Valley (1998)). An uneasiness with the postmodern celebration of the idea that “the universe is made of stories, not of atoms” and that retelling and reinvention open up new possibilities of being lead to the problematisation of the idea that all narratives are equal and of the total rejection of the notion of truth. In Praying Mantis there are attempts to reach past language and to escape from the malaise caused by a certain reaction to the linguistic turn.http://explore.up.ac.za/record=b102650

Heildronk : uit Wynboer /

Opsomming: Artikels waarin die wynwêreld uit verskillende oogpunte benader word. Ter viering van die blad se 50ste bestaansjaar.Opsomming: Artikels waarin die wynwêreld uit verskillende oogpunte benader word. Ter viering van die blad se 50ste bestaansjaar.Olivier, Fani