Association of NIPA1 repeat expansions with amyotrophic lateral sclerosis in a large international cohort

NIPA1 (nonimprinted in Prader-Willi/Angelman syndrome 1) mutations are known to cause hereditary spastic paraplegia type 6, a neurodegenerative disease that phenotypically overlaps to some extent with amyotrophic lateral sclerosis (ALS). Previously, a genomewide screen for copy number variants found an association with rare deletions in NIPA1 and ALS, and subsequent genetic analyses revealed that long (or expanded) polyalanine repeats in NIPA1 convey increased ALS susceptibility. We set out to perform a large-scale replication study to further investigate the role of NIPA1 polyalanine expansions with ALS, in which we characterized NIPA1 repeat size in an independent international cohort of 3955 patients with ALS and 2276 unaffected controls and combined our results with previous reports. Meta-analysis on a total of 6245 patients with ALS and 5051 controls showed an overall increased risk of ALS in those with expanded (>8) GCG repeat length (odds ratio = 1.50, p = 3.8×10-5). Together with previous reports, these findings provide evidence for an association of an expanded polyalanine repeat in NIPA1 and ALS

Distribution and ecotoxicological significance of trace element contamination in a similar to 150 yr record of sediments in Lake Chaohu, Eastern China

This paper presents the concentrations, vertical profiles and possible sources of selected major and trace elements in a sediment core covering similar to 150 years of sedimentation in Lake Chaohu, eastern China. Element concentrations were measured by portable X-ray Fluorescence Spectroscopy (XRF) and were used to evaluate possible environmental consequences of the recent industrialization in China. Statistical analyses identify four groups: (1) organic carbon (OC), total nitrogen (TN), Pb, Zn, and As associated with the use of chemical fertilizers and pesticides; (2) Mn, Cr, Ni and Cu from industrial and mining activities; (3) Fe, Rb, K, Co, Ti and Ca influenced by post-depositional processes and land exploitation; and (4) Zr and Sr from the soil. The vertical profiles of elements placed in the first two groups show distinct increases in concentrations above depths of 20 cm (similar to 1978), coincident with the timing of industrialization in China, and the anthropogenic-derived fluxes are higher than the lithogenic-derived fluxes over the last three decades. With the exception of Zr and Sr, association of the measured metals with organic carbon and nitrogen suggests that organic matter may act as a carrier phase. The geoaccumulation index (I(geo)) reveals increased contamination from elements in the first two groups in recent years. Element concentrations, compared with the Effects Range-Low (ERL) and Effects Range-Median (ERM) levels set by NOAA, suggest that adverse biological effects from Ni contamination are very likely.</p

Comparison of Elemental Carbon in Lake Sediments Measured by Three Different Methods and 150-Year Pollution History in Eastern China

Concentrations of elemental carbon (EC) were measured in a 150 yr sediment record collected from Lake Chaohu in Anhui Province, eastern China, using three different thermal analytical methods: IMPROVE_A thermal optical reflectance (TOR), STN_thermal optical transmittance (TOT), and chemothermal oxidation (CTO). Distribution patterns for EC concentrations are different among the three methods, most likely due to the operational definition of EC and different temperature treatments prescribed for each method. However, similar profiles were found for high-temperature EC fractions among different methods. Historical soot(ToR) (high-temperature EC fractions measured by the IMPROVE_A TOR method) from Lake Chaohu exhibited stable low concentrations prior to the late 1970s and a sharp increase thereafter, corresponding well with the rapid industrialization of China in the last three decades. This may suggest that high-temperature thermal protocols are suitable for differentiating between soot and other carbon fractions. A similar soot(ToR) record was also obtained from Lake Taihu (similar to 200 km away), suggesting a regional source of soot. The ratio of char(ToR) (low-temperature EC fraction measured by the IMPROVE_A TOR method, after correction for pyrolysis) to sootToR in Lake Chaohu shows an overall decreasing trend, consistent with gradual changes in fuel use from wood burning to increasing fossil fuel combustions. Average higher char(ToR)/soot(ToR) was observed in Lake Taihu than in Lake Chaohu in the past 150 years, consistent with the longer and more extensive industrialization around the Taihu region.</p

H63D polymorphism in HFE is not associated with amyotrophic lateral sclerosis

The H63D polymorphism in HFE has frequently been associated with susceptibility to amyotrophic lateral sclerosis (ALS). Regarding the role of HFE in iron homeostasis, iron accumulation is considered an important process in ALS. Furthermore, novel therapeutic strategies are being developed targeting this process. Evidence for this genetic association is, however, limited to several small studies. For this reason we studied the H63D polymorphism in a large European cohort including 3962 ALS patients and 5072 control subjects from 7 countries. After meta-analysis of previous studies and current findings we conclude that the H63D polymorphism in HFE is not associated with susceptibility to ALS, age at disease onset, or survival.status: publishe