Mitochondria directly donate their membrane to form autophagosomes during a novel mechanism of parkin-associated mitophagy

BACKGROUND: Autophagy (macroautophagy), a cellular process of “self-eating”, segregates damaged/aged organelles into vesicles, fuses with lysosomes, and enables recycling of the digested materials. The precise origin(s) of the autophagosome membrane is unclear and remains a critical but unanswered question. Endoplasmic reticulum, mitochondria, Golgi complex, and the plasma membrane have been proposed as the source of autophagosomal membranes. FINDINGS: Using electron microscopy, immunogold labeling techniques, confocal microscopy, and flow cytometry we show that mitochondria can directly donate their membrane material to form autophagosomes. We expand upon earlier studies to show that mitochondria donate their membranes to form autophagosomes during basal and drug-induced autophagy. Moreover, electron microscopy and immunogold labeling studies show the first physical evidence of mitochondria forming continuous structures with LC3-labeled autophagosomes. The mitochondria forming these structures also stain positive for parkin, indicating that these mitochondrial-formed autophagosomes represent a novel mechanism of parkin-associated mitophagy. CONCLUSIONS: With the on-going debate regarding autophagosomal membrane origin, this report demonstrates that mitochondria can donate membrane materials to form autophagosomes. These structures may also represent a novel form of mitophagy where the mitochondria contribute to the formation of autophagosomes. This novel form of parkin-associated mitophagy may be a more efficient bio-energetic process compared with de novo biosynthesis of a new membrane, particularly if the membrane is obtained, at least partly, from the organelle being targeted for later degradation in the mature autolysosome

Selective Deuterium Ion Acceleration Using the Vulcan PW Laser

We report on the successful demonstration of selective acceleration of deuterium ions by target-normal sheath acceleration (TNSA) with a high-energy petawatt laser. TNSA typically produces a multi-species ion beam that originates from the intrinsic hydrocarbon and water vapor contaminants on the target surface. Using the method first developed by Morrison, et al.,$^{1}$ an ion beam with $>$99$\%$ deuterium ions and peak energy 14 MeV/nucleon is produced with a 200 J, 700 fs, $>10^{20} W/cm^{2}$ laser pulse by cryogenically freezing heavy water (D$_{2}$O) vapor onto the rear surface of the target prior to the shot. Within the range of our detectors (0-8.5$^{\circ}$), we find laser-to-deuterium-ion energy conversion efficiency of 4.3$\%$ above 0.7 MeV/nucleon while a conservative estimate of the total beam gives a conversion efficiency of 9.4$\%$.Comment: 5 pages, 5 figure

Ebola and Marburg virus matrix layers are locally ordered assemblies of VP40 dimers.

Filoviruses such as Ebola and Marburg virus bud from the host membrane as enveloped virions. This process is achieved by the matrix protein VP40. When expressed alone, VP40 induces budding of filamentous virus-like particles, suggesting that localization to the plasma membrane, oligomerization into a matrix layer, and generation of membrane curvature are intrinsic properties of VP40. There has been no direct information on the structure of VP40 matrix layers within viruses or virus-like particles. We present structures of Ebola and Marburg VP40 matrix layers in intact virus-like particles, and within intact Marburg viruses. VP40 dimers assemble extended chains via C-terminal domain interactions. These chains stack to form 2D matrix lattices below the membrane surface. These lattices form a patchwork assembly across the membrane and suggesting that assembly may begin at multiple points. Our observations define the structure and arrangement of the matrix protein layer that mediates formation of filovirus particles

Recent trends in hormone therapy utilization and breast cancer incidence rates in the high incidence population of Marin County, California

<p>Abstract</p> <p>Background</p> <p>Recent declines in invasive breast cancer have been reported in the US, with many studies linking these declines to reductions in the use of combination estrogen/progestin hormone therapy (EPHT). We evaluated the changing use of postmenopausal hormone therapy, mammography screening rates, and the decline in breast cancer incidence specifically for Marin County, California, a population with historically elevated breast cancer incidence rates.</p> <p>Methods</p> <p>The Marin Women's Study (MWS) is a community-based, prospective cohort study launched in 2006 to monitor changes in breast cancer, breast density, and personal and biologic risk factors among women living in Marin County. The MWS enrolled 1,833 women following routine screening mammography between October 2006 and July 2007. Participants completed a self-administered questionnaire that included items regarding historical hormone therapy regimen (estrogen only, progesterone only, EPHT), age of first and last use, total years of use, and reason(s) for stopping, as well as information regarding complementary hormone use. Questionnaire items were analyzed for 1,083 non-Hispanic white participants ages 50 and over. Breast cancer incidence rates were assessed overall and by tumor histology and estrogen receptor (ER) status for the years 1990-2007 using data from the Northern California Surveillance, Epidemiology and End Results (SEER) cancer registry.</p> <p>Results</p> <p>Prevalence of EPHT use among non-Hispanic white women ages 50 and over declined sharply from 21.2% in 1998 to 6.7% by 2006-07. Estrogen only use declined from 26.9% in 1998 to 22.4% by 2006-07. Invasive breast cancer incidence rates declined 33.4% between 2001 and 2004, with drops most pronounced for ER+ cancers. These rate reductions corresponded to declines of about 50 cases per year, consistent with population attributable fraction estimates for EPHT-related breast cancer. Self-reported screening mammography rates did not change during this period. Use of alternative or complementary agents did not differ significantly between ever and never hormone users. Of women who reported stopping EPHT in the past 5 years, 60% cited "health risks" or "news reports" as their primary reasons for quitting.</p> <p>Conclusion</p> <p>A dramatic reduction in EPHT use was followed temporally by a significant reduction in invasive and ER+ breast cancer rates among women living in Marin County, California.</p

The sedimentology, architecture and depositional setting of the fluvial Spireslack 1 Sandstone of the Midland Valley, Scotland: insights from Spireslack surface coal mine.

Spireslack surface coal mine exposes a section in the Carboniferous Lawmuir Formation (Brigantian) into the Upper Limestone Formation (Arnsbergian). This paper describes the stratigraphy exposed at Spireslack for the first time and, in so doing, names the Spireslack Sandstone, a distinctive erosively based, sandstone-dominated unit in the Upper Limestone Formation. The Spireslack Sandstone comprises two fluvial sandstone channel sets and an upper possibly fluvio-estuarine succession. From an analysis of their internal architectural elements, the channel sets are interpreted as a low sinuosity, sand-dominated, mixed load fluvial system in which avulsion and variations in sediment load played a significant role. The lower channel set appears confined to erosional palaeovalleys of limited lateral extent and significant relief. The upper channel set is much more laterally extensive and displays evidence of a generally lower sediment load with a greater degree of lateral accretion and flooding. Consequently, the Spireslack Sandstone may represent a system responding to base level changes of higher magnitude and longer duration than the glacioeustatic scale commonly attributed to Carboniferous fluvio-deltaic cycles. Spireslack Sandstone may represent an important correlative marker in the Carboniferous of the Midland Valley, and may provide an alternative analogue for some Carboniferous fluvial sandstone stratigraphical traps

An Integrated Web-based Decision Support System for Inter-Asset Streetworks Management

Streetworks are the activities conducted in streets such as building or repairing roads, installing or replacing buried utilities, or street furniture. Sustainable streetworks requires an integrated approach taking account of the complex inter-asset relationships between human activities, different city infrastructure assets and the environment. To facilitate decision making by relevant stakeholders, an integrated web-based decision support system is presented in this paper which combines experts' domain knowledge, multiple geospatial datasets and an inference engine for automated inference of potential consequences. Users' feedback collected from two workshops showed that the system is widely considered as a potentially useful tool for practitioners

A preliminary assessment of PM10 and TSP concentrations in Tuticorin, India

The respirable particulate matter (RPM; PM10) and total suspended particulate matter (TSP) concentrations in ambient air in Tuticorin, India, were preliminarily estimated. Statistical analyses on so-generated database were performed to infer frequency distributions and to identify dominant meteorological factor affecting the pollution levels. Both the RPM and TSP levels were well below the permissible limits set by the US Environmental Protection Agency. As expected, lognormal distribution always fit the data during the study period. However, fit with the normal was also acceptable except for very few seasons. The RPM concentrations ranged between 20.9 and 198.2 μg/m3, while the TSP concentrations varied from 51.5 to 333.3 μg/m3 during the study period. There was a better correlation between PM10–100 and TSP concentrations than that of PM10 (RPM) and TSP concentrations, but the correlation of RPM fraction was also acceptable. It was found that wind speed was the most important meteorological factor affecting the concentrations of the pollutants of present interest. Significant seasonal variations in the pollutant concentrations of present interest were found at 5% significance level except for TSP concentrations in the year 2006