Effects of the mutations Ala30 to Pro and Ala53 to Thr on the physical and morphological properties of α-synuclein protein implicated in Parkinson's disease

Abstractα-Synuclein (α-syn) protein has been found in association with the pathological lesions of a number of neurodegenerative diseases. Recently, mutations in the α-syn gene have been reported in families susceptible to an inherited form of Parkinson's disease. We report here that human wild-type α-syn, PD-linked mutant α-syn(Ala30Pro) and mutant α-syn(Ala53Thr) proteins can self-aggregate and form amyloid-like filaments. The mutant α-syn forms more β-sheet and mature filaments than the wild-type protein. These findings suggest that accumulation of α-syn as insoluble deposits of amyloid may play a major role in the pathogenesis of these neurodegenerative diseases

Liver fibrosis markers and all cause mortality in people with type 2 diabetes:a population based study (The Ayrshire Diabetes Outcomes Cohort (ADOC) Study)

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Study of Mill Island ice core (East Antarctica): A sensitive site for high resolution ocean climate signals?

第2回極域科学シンポジウム　氷床コアセッション 11月16日（水） 国立極地研究所 2階大会議

Antarctic Volcanic Flux Ratios from Law Dome Ice Cores

Explosive volcanic eruptions can inject large quantities of sulphur dioxide into the stratosphere. The aerosols that result from oxidation of the sulphur dioxide can produce significant cooling of the troposphere by reflecting or absorbing solar radiation. It is possible to obtain an estimate of the relative stratospheric sulphur aerosol concentration produced by different volcanoes by comparing sulphuric acid fluxes determined by analysis of polar ice cores. Here, we use a non-sea-salt sulphate time series derived from three well-dated Law Dome ice cores to investigate sulphuric acid flux ratios for major eruptions over the period AD 1301-1995. We use additional data from other cores to investigate systematic spatial variability in the ratios. Only for the Kuwae eruption (Law Dome ice date AD 1459.5) was the H2SO4 flux larger than that deposited by Tambora (Law Dome ice date AD 1816.7)

High-precision Dating of Volcanic Events (A.D. 1301–1995) Using Ice Cores from Law Dome, Antarctica

A record of volcanic activity over the period A.D. 1301–1995 has been extracted from three Law Dome ice cores (East Antarctica). The record dating is unambiguous at the annual level from A.D. 1807 to 1995 and has an uncertainty of ±1 year at A.D. 1301. Signals from 20 eruptions are preserved in the record, including those of two unknown eruptions with acid deposition beginning in A.D. 1810.8 and A.D. 1685.8. The beginning of the ice core signal from the A.D. 1815 Tambora eruption is observed in the austral summer of A.D. 1816/1817. The mean observed stratospheric transport and deposition time to Law Dome from the eruption site is 1.5 years (σ = 0.6 years) from 11 well-dated eruptions. The largest eruption observed in the Law Dome record has its maximum in A.D. 1460 with volcanic sulfate deposition beginning in the austral winter of A.D. 1459. This event is also observed in other ice core records and is attributed to the volcano Kuwae, with an eruption date in the range A.D. 1455.9–1459.9 if all sources of error are considered. This is at least three years later than the date previously ascribed by dendrochronological and historical studies

Post-Depositional Movement of Methanesulphonic Acid at Law Dome, Antarctica, and the Influence of Accumulation Rate

A series of ice cores from sites with different snow-accumulation rates across Law Dome, East Antarctica, was investigated for methanesulphonic acid (MSA) movement. The precipitation at these sites (up to 35 km apart) is influenced by the same air masses, the principal difference being the accumulation rate. At the low-accumulation-rate W20k site (0.17 in ice equivalent), MSA was completely relocated from the summer to winter layer. Moderate movement was observed at the intermediate-accumulation-rate site (0.7 in ice equivalent), Dome Summit South (DSS), while there was no evidence of movement at the high-accumulation-rate DE08 site (1.4 in ice equivalent). The main DSS record of MSA covered the epoch AD 1727-2000 and was used to investigate temporal post-depositional changes. Co-deposition of MSA and sea-salt ions was observed of the surface layers, outside of the main summer MSA peak, which complicates interpretation of these peaks as evidence of movement in deeper layers. A seasonal study of the 273 year DSS record revealed MSA migration predominantly from summer into autumn (in the up-core direction), but this migration was suppressed during the Tambora (1815) and unknown (1809) volcanic eruption period, and enhanced during an epoch (1770-1800) with high summer nitrate levels. A complex interaction between the gradients in nss-sulphate, nitrate and sea salts (which are influenced by accumulation rate) is believed to control the rate and extent of movement of MSA

Effectiveness of a community football programme on improving physiological markers of health in a hard-to-reach male population: the role of exercise intensity

© 2015 Taylor & Francis. The present study evaluated the effectiveness of participation in recreational football during a community health programme, on physiological markers of health within a hard to reach population. Nine men (Age: 33 ± 9 years, Mass: 75.4 ± 13.7 kg, Height: 1.74 ± 0.07 m and Body Fat: 19 ± 2%) were recruited to participate in the study in collaboration with an English Premier League Football Club. Participants completed the 12-week football-based programme which included two coached football sessions each week. Physiological tests for blood pressure, resting heart rate, cholesterol and an anthropometrical test for body composition were completed at three time points during the study (Weeks – 1, 6 and 12) in an attempt to evaluate the impact of the intervention on health. During each training session, measurements of intensity (%HRmax, identified from the yoyo intermittent level 1 test), duration and rating of perceived exertion were made. The 12-week programme (mean HRmax throughout programme = 75 ± 4% beats min−1; mean RPE throughout programme = 6 ± 1) elicited few changes in physiological markers of health with the only significant change been a decrease in resting heart rate from weeks 6 to 12 (87 ± 22 beats min−1 at week-6, to 72 ± 17 beats min−1; p < 0.05). These data would suggest that the current community football-related health project was not effective in improving physiological markers of health, but was able to maintain their level of health. A lack of improvement may be due to the low intensity of sessions and a lack of coach education for the promotion of sessions that aim to improve health

Evaluating the use of a 22-pathogen TaqMan array card for rapid diagnosis of respiratory pathogens in Intensive Care

Introduction. Pneumonia is highly prevalent in intensive care units (ICUs), with high associated mortality. Empirical treatment prioritizes breadth of coverage while awaiting laboratory diagnosis, often at the expense of antimicrobial stewardship. Microarrays use multiple parallel polymerase chain reactions to enable a rapid syndromic approach to laboratory diagnosis. Aim. To evaluate the clinical and laboratory implications of introducing a bespoke 22-pathogen TaqMan Array Card (TAC) for rapid pathogen detection in deep respiratory samples from adult ICUs. Methodology. TAC results from all ICU patients prospectively tested over a 9-month period at Cambridge’s Clinical Microbiology and Public Health Laboratory were compared to those of corresponding conventional microbiological assays (culture-, PCR- or serology-based) in terms of result agreement and time-to-result availability. Clinical impact was assessed by retrospective review of medical records. Results. Seventy-one patients were included [45 (63 %) male, median age 59). Overall result agreement was 94 %, with TAC detecting more pathogens than conventional methods. TAC detected Streptococcus pneumoniae more readily than culture (7 vs 0 cases; P=0.02). TAC did not detect Aspergillus spp. in eight culture- or galactomannan-positive cases. The median turnaround time (1 day) was significantly shorter than that of bacterial/fungal culture, Pneumocystis jirovecii PCR and galactomannan testing (each 3 days; P<0.001), atypical bacteria serology (13 days; P<0.001) and Mycobacterium tuberculosis culture (46 days; P<0.001). Earlier result availability prompted discontinuation of unnecessary antimicrobials in 15/71 (21 %) cases, but had no bearing on patient isolation/deisolation. Conclusion. TAC provided greater overall yield of pathogen detection and faster turnaround times, permitting earlier discontinuation of unnecessary antimicrobials.A. C. M. is supported by a Wellcome Trust Clinical Research Career Development Fellowship (WT 2055214/Z/16/Z)

Changes in Black Carbon Deposition to Antarctica from Two Ice Core Records, A.D. 1850-2000

Continuous flow analysis was based on a steady sample flow and in-line detection of BC and other chemical substances as described in McConnell et al. (2007). In the cold room, previously cut one meter ice core sticks of 3x3cm, are melted continuously on a heated melter head specifically designed to eliminate contamination from the atmosphere or by the external parts of the ice. The melted ice from the most inner part of the ice stick is continuously pumped by a peristaltic pump and carried to a clean lab by Teflon lines. The recorded signal is continuous, integrating a sample volume of about 0.05 mL, for which the temporal resolution depends on the speed of melting, ice density and snow accumulation rate at the ice core drilling site. For annual accumulation derived from the WAIS and Law Dome ice cores, we assumed ~3.1 cm water equivalent uncertainty in each year's accumulation from short scale spatial variability (glaciological noise) which was determined from several measurements of annual accumulation in multiple parallel ice cores notably from the WAIS Divide ice core site (Banta et al., 2008) and from South Pole site (McConnell et al., 1997; McConnell et al., 2000). Refractory black carbon (rBC) concentrations were determined using the same method as in (Bisiaux et al., 2011) and adapted to continuous flow measurements as described by (McConnell et al., 2007). The technique uses a single particle intracavity laser induced incandescence photometer (SP2, Droplet Measurement Technologies, Boulder, Colorado) coupled to an ultrasonic nebulizer/desolvation (CETAC UT5000) Flow Injection Analysis (FIA). All analyses, sample preparation etc, were performed in a class 100 cleanroom using anti contamination "clean techniques". The samples were not acidified