Next-generation sequencing reveals substantial genetic contribution to dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia after Alzheimer's disease. Although an increasing number of genetic factors have been connected to this debilitating condition, the proportion of cases that can be attributed to distinct genetic defects is unknown. To provide a comprehensive analysis of the frequency and spectrum of pathogenic missense mutations and coding risk variants in nine genes previously implicated in DLB, we performed exome sequencing in 111 pathologically confirmed DLB patients. All patients were Caucasian individuals from North America. Allele frequencies of identified missense mutations were compared to 222 control exomes. Remarkably, ~ 25% of cases were found to carry a pathogenic mutation or risk variant in APP, GBA or PSEN1, highlighting that genetic defects play a central role in the pathogenesis of this common neurodegenerative disorder. In total, 13% of our cohort carried a pathogenic mutation in GBA, 10% of cases carried a risk variant or mutation in PSEN1, and 2% were found to carry an APP mutation. The APOE ε4 risk allele was significantly overrepresented in DLB patients (p-value < 0.001). Our results conclusively show that mutations in GBA, PSEN1, and APP are common in DLB and consideration should be given to offer genetic testing to patients diagnosed with Lewy body dementia

Measurement of Mass and Width of the W Boson at LEP

We report on measurements of the mass and total decay width of the W boson with the L3 detector at LEP. W-pair events produced in $\mathrm{e^+e^-}$ interactions between 161 GeV and 183 GeV centre-of-mass energy are selected in a data sample corresponding to a total luminosity of 76.7 pb$^{-1}$. Combining all final states in W-pair production, the mass and total decay width of the W boson are determined to be $\mathrm{M_W}=80.61\pm0.15$ GeV and $\Gamma_{\mathrm{W}}=1.97\pm0.38$ GeV, respectively

Genomic Risk Profiling of Ischemic Stroke: Results of an International Genome-Wide Association Meta-Analysis

Introduction: Familial aggregation of ischemic stroke derives from shared genetic and environmental factors. We present a meta-analysis of genome-wide association scans (GWAS) from 3 cohorts to identify the contribution of common variants to ischemic stroke risk.Methods: This study involved 1464 ischemic stroke cases and 1932 controls. Cases were genotyped using the Illumina 610 or 660 genotyping arrays; controls, with Illumina HumanHap 550Kv1 or 550Kv3 genotyping arrays. Imputation was performed with the 1000 Genomes European ancestry haplotypes (August 2010 release) as a reference. A total of 5,156,597 single-nucleotide polymorphisms (SNPs) were incorporated into the fixed effects meta-analysis. All SNPs associated with ischemic stroke (P < 1 x 10(-5)) were incorporated into a multivariate risk profile model.Results: No SNP reached genome-wide significance for ischemic stroke (P < 5 x 10(-8)). Secondary analysis identified a significant cumulative effect for age at onset of stroke (first versus fifth quintile of cumulative profiles based on SNPs associated with late onset, beta = 14.77 [10.85, 18.68], P = 5.5 x 10(-12)), as well as a strong effect showing increased risk across samples with a high propensity for stroke among samples with enriched counts of suggestive risk alleles (P < 5 x 10(-6)). Risk profile scores based only on genomic information offered little incremental prediction.Discussion: There is little evidence of a common genetic variant contributing to moderate risk of ischemic stroke. Quintiles based on genetic loading of alleles associated with a younger age at onset of ischemic stroke revealed a significant difference in age at onset between those in the upper and lower quintiles. Using common variants from GWAS and imputation, genomic profiling remains inferior to family history of stroke for defining risk. Inclusion of genomic (rare variant) information may be required to improve clinical risk profiling

Mineralogical and geochemical analysis of Fe-phases in drill-cores from the Triassic Stuttgart Formation at Ketzin CO₂ storage site before CO₂ arrival

Reactive iron (Fe) oxides and sheet silicate-bound Fe in reservoir rocks may affect the subsurface storage of CO2 through several processes by changing the capacity to buffer the acidification by CO2 and the permeability of the reservoir rock: (1) the reduction of three-valent Fe in anoxic environments can lead to an increase in pH, (2) under sulphidic conditions, Fe may drive sulphur cycling and lead to the formation of pyrite, and (3) the leaching of Fe from sheet silicates may affect silicate diagenesis. In order to evaluate the importance of Fe-reduction on the CO2 reservoir, we analysed the Fe geochemistry in drill-cores from the Triassic Stuttgart Formation (Schilfsandstein) recovered from the monitoring well at the CO2 test injection site near Ketzin, Germany. The reservoir rock is a porous, poorly to moderately cohesive fluvial sandstone containing up to 2–4 wt% reactive Fe. Based on a sequential extraction, most Fe falls into the dithionite-extractable Fe-fraction and Fe bound to sheet silicates, whereby some Fe in the dithionite-extractable Fe-fraction may have been leached from illite and smectite. Illite and smectite were detected in core samples by X-ray diffraction and confirmed as the main Fe-containing mineral phases by X-ray absorption spectroscopy. Chlorite is also present, but likely does not contribute much to the high amount of Fe in the silicate-bound fraction. The organic carbon content of the reservoir rock is extremely low (<0.3 wt%), thus likely limiting microbial Fe-reduction or sulphate reduction despite relatively high concentrations of reactive Fe-mineral phases in the reservoir rock and sulphate in the reservoir fluid. Both processes could, however, be fuelled by organic matter that is mobilized by the flow of supercritical CO2 or introduced with the drilling fluid. Over long time periods, a potential way of liberating additional reactive Fe could occur through weathering of silicates due to acidification by CO2

Moving carbon between spheres, the potential oxalate-carbonate pathway of Brosimum alicastrum Sw.; Moraceae.

Aims The Oxalate-Carbonate Pathway (OCP) is a biogeochemical process that transfers atmospheric CO2 into the geologic reservoir as CaCO3; however, until now all investigations on this process have focused on species with limited food benefits. This study evaluates a potential OCP associated with Brosimum alicastrum, a Neotropical species with agroforestry potential (ca. 70–200 kg-nuts yr−1), in the calcareous soils of Haiti and Mexico. Methods / results Enzymatic analysis demonstrated significant concentrations of calcium oxalate (5.97 % D.W.) were associated with B. alicastrum tissue in all sample sites. The presence of oxalotrophism was also confirmed with microbiological analyses in both countries. High concentrations of total calcium (>7 g kg−1) and lithogenic carbonate obscured the localised alkalinisation and identification of secondary carbonate associated with the OCP at most sample sites, except Ma Rouge, Haiti. Soils adjacent to subjects in Ma Rouge demonstrated an increase in pH (0.63) and CaCO3 concentration (5.9 %) that, when coupled with root-like secondary carbonate deposits in Mexico, implies that the OCP does also occur in calcareous soils. Conclusions Therefore this study confirms that the OCP also occurs in calcareous soils, adjacent to B. alicastrum, and could play a fundamental and un-accounted role in the global calcium-carbon coupled cycle

Development of Iron Speciation Reference Materials for Palaeoredox Analysis

The development and application of geochemical techniques to identify redox conditions in modern and ancient aquatic environments has intensified over recent years. Iron (Fe) speciation has emerged as one of the most widely used procedures to distinguish different redox regimes in both the water column and sediments, and is the main technique used to identify oxic, ferruginous (anoxic, Fe(II) containing) and euxinic (anoxic, sulfidic) water column conditions. However, an international sediment reference material has never been developed. This has led to concern over the consistency of results published by the many laboratories that now utilise the technique. Here, we report an interlaboratory comparison of four Fe speciation reference materials for palaeoredox analysis, which span a range of compositions and reflect deposition under different redox conditions. We provide an update of extraction techniques used in Fe speciation, and assess the effects of both test portion mass, and the use of different analytical procedures, on the quantification of different Fe fractions in sedimentary rocks. While atomic adsorption spectroscopy and inductively coupled plasma‐optical emission spectrometry produced comparable Fe measurements for all extraction stages, the use of ferrozine consistently underestimated Fe in the extraction step targeting mixed ferrous‐ferric minerals such as magnetite. We therefore suggest that the use of ferrozine is discontinued for this Fe pool. Finally, we report the combined data of four independent Fe speciation laboratories to characterise the Fe speciation composition of the reference materials. These reference materials are available to the community to provide an essential validation of in‐house Fe speciation measurements

Measurement of the Michel Parameters and the Average τ\tau-Neutrino Helicity from τ\tau Decays at LEP

Four of the Michel parameters and the average tau-neutrino helicity have been measured by analysing tau decay spectra in 147 \pb ~of data collected by the L3 detector. The decays \tte, ~\ttm, ~\ttp, ~\ttr ~and their charge conjugates were considered. The results: $\rho = 0.762 \pm 0.035$, $\eta = 0.27 \pm 0.14$, $\xi = 0.70 \pm 0.16$, $\xi\delta = 0.70 \pm0.11$ and $\xi_{h} = -1.032 \pm 0.031$ are consistent with a V$-$A structure for the weak charged current and lepton universality

Measurement of the Effective Weak Mixing Angle by Jet-Charge Asymmetry in Hadronic Decays of the Z Boson

The coupling of the Z boson to quarks is studied in a sample of about 3.5 million hadronic Z decays collected by the L3 experiment at LEP from 1991 to 1995. The forward-backward quark charge asymmet ry is measured by means of a jet charge technique. From the measured asymmetries, the effective weak mixing angle is determined to be \begin{center} $\STE = 0.2327 \pm 0.0012(\mbox{\emph{stat.}} ) \pm 0.0013(\mbox{\emph{syst.}

Single and multi-photon events with missing energy in e+e−e^+ e^- collisions at 161 GeV < s\sqrt{s} < 172 GeV

A search for single and multi-photon events with missing energy is performed using data collected at centre-of-mass energies between 161 GeV and 172 GeV for a total of 20.9 pb$^{-1}$ of integrated luminosity. The results obtained are used to derive the value for the $\nu\bar{\nu}\gamma(\gamma)$ cross section as well as upper limits on new physics processes

Study of Neutral-Current Four-Fermion and ZZ Production in e+e−e^+ e^- Collisions at s\sqrt{s}= 183 GeV

Study of Neutral--Current Four--Fermion and ZZ \\ Production in $\rm e^+ e^-$ Collisions at $\rm \sqrt{s}=$ 183 GeV A study of neutral--current four--fermion processes is performed using a data sample corresponding to 55.3~pb$^{-1}$ of integrated luminosity collected by the L3 detector at LEP at an average centre--of--mass energy of 183~\GeV. The neutral--current four--fermion cross sections for final states with a pair of charged leptons plus jets and with four charged leptons are measured to be consistent with the Standard Model predictions. Events with fermion pair masses close to the Z boson mass are selected in all observable final states and the ZZ production cross section is measured to be %\begin{center} $\rm \sigma_{ZZ} = 0.30 ^{+0.22\,\,+0.07}_{-0.16\,\,-0.03}\,\mathrm{pb},$ %\end{center} in agreement with the Standard Model expectation. No evidence for the existence of anomalous triple gauge boson ZZZ and ZZ$\gamma$ couplings is found and limits on these couplings are set