COL4A1 Mutations Cause Ocular Dysgenesis, Neuronal Localization Defects, and Myopathy in Mice and Walker-Warburg Syndrome in Humans

Muscle-eye-brain disease (MEB) and Walker Warburg Syndrome (WWS) belong to a spectrum of autosomal recessive diseases characterized by ocular dysgenesis, neuronal migration defects, and congenital muscular dystrophy. Until now, the pathophysiology of MEB/WWS has been attributed to alteration in dystroglycan post-translational modification. Here, we provide evidence that mutations in a gene coding for a major basement membrane protein, collagen IV alpha 1 (COL4A1), are a novel cause of MEB/WWS. Using a combination of histological, molecular, and biochemical approaches, we show that heterozygous Col4a1 mutant mice have ocular dysgenesis, neuronal localization defects, and myopathy characteristic of MEB/WWS. Importantly, we identified putative heterozygous mutations in COL4A1 in two MEB/WWS patients. Both mutations occur within conserved amino acids of the triple-helix-forming domain of the protein, and at least one mutation interferes with secretion of the mutant proteins, resulting instead in intracellular accumulation. Expression and posttranslational modification of dystroglycan is unaltered in Col4a1 mutant mice indicating that COL4A1 mutations represent a distinct pathogenic mechanism underlying MEB/WWS. These findings implicate a novel gene and a novel mechanism in the etiology of MEB/WWS and expand the clinical spectrum of COL4A1-associated disorders

Widespread drying of European peatlands in recent centuries

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this record Climate warming and human impacts are thought to be causing peatlands to dry,potentially converting them from sinks to sources of carbon. However, it is unclear whether the hydrological status of peatlands has moved beyond their natural envelope. Here we show that European peatlands have undergone substantial, widespread drying during the last ~300 years. We analyse testate amoeba-derived hydrological reconstructions from 31 peatlands across Britain, Ireland, Scandinavia and continental Europe to examine changes in peatland surface wetness during the last 2000 years. 60% of our study sites were drier during the period CE 1800-2000 than they have been for the last 600 years; 40% of sites were drier than they have been for 1000 years; and 24% of sites were drier than they have been for 2000 years. This marked recent transition in the hydrology of European peatlands is concurrent with compound pressures including climatic drying, warming and direct human impacts on peatlands, although these factors vary between regions and individual sites. Our results suggest that the wetness of many European peatlands may now be moving away from natural baselines. Our findings highlight the need for effective management and restoration of European peatlands.Natural Environment Research Council (NERC

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

The Bentheim Sandstone: Geology, petrophysics, varieties and it's use as dimension stone

The shallow-marine Bentheim Sandstone was deposited in one of the NW-SE trending basins north of the London-Brabant and Rhenish massifs during the Valanginian (Early Cretaceous). The Bentheim Sandstone forms an important reservoir rock for petroleum, but has also proven itself as a very durable natural stone quarried since about 1100 AD. This paper focuses on the geology and the petrophysics of the Bentheim Sandstone as a building stone. The Bentheim Sandstone is exposed in outcrops just east of the Dutch-German border, in the vicinity of Bad Bentheim and Gildehaus. Two varieties are distinguished, a pale yellow sandstone characteristic for the Gildehaus area and a darker, ochre and locally even reddish type. The red variety is found in an area around Bad Bentheim. In the red variety different generations of hematite coatings, from the early phase of burial history to later stages in the formation of the Bentheim Sandstone could be recognized in thin sections and on SEM images. Thick iron crusts along fault planes originated from the percolation of iron-rich groundwater in the joints crossing the sandstone beds. The historic use of the Bentheim Sandstone and the weathering aspects of the dimension stone are shortly dealt with