Mated progeny production is a biomarker of aging in Caenorhabditis elegans

The relationships between reproduction and aging are important for understanding the mechanisms of aging and evaluating evolutionary theories of aging. To investigate the effects of progeny production on reproductive and somatic aging, we conducted longitudinal studies of Caenorhabditis elegans hermaphrodites. For mated wild-type animals that were not sperm limited and survived past the end of the reproductive period, high levels of cross-progeny production were positively correlated with delayed reproductive and somatic aging. In this group of animals, individuals that generated more cross progeny also reproduced and lived longer than individuals that generated fewer cross progeny. These results indicate that progeny production does not accelerate reproductive or somatic aging. This longitudinal study demonstrated that cumulative cross progeny production through day four is an early-stage biomarker that is a positive predictor of longevity. Furthermore, in mated animals, high levels of early cross progeny production were positively correlated with high levels of late cross progeny production, indicating that early progeny production does not accelerate reproductive aging. The relationships between progeny production and aging were further evaluated by comparing self-fertile hermaphrodites that generated relatively few self progeny with mated hermaphrodites that generated many cross progeny. The timing of age-related somatic degeneration was similar in these groups, suggesting progeny production does not accelerate somatic aging. These studies rigorously define relationships between progeny production, reproductive aging, and somatic aging and identify new biomarkers of C. elegans aging. These results indicate that some mechanisms or pathways control age-related degeneration of both reproductive and somatic tissues in C. elegans

The Anticonvulsant Ethosuximide Disrupts Sensory Function to Extend C. elegans Lifespan

Ethosuximide is a medication used to treat seizure disorders in humans, and we previously demonstrated that ethosuximide can delay age-related changes and extend the lifespan of the nematode Caenorhabditis elegans. The mechanism of action of ethosuximide in lifespan extension is unknown, and elucidating how ethosuximide functions is important for defining endogenous processes that influence lifespan and for exploring the potential of ethosuximide as a therapeutic for age-related diseases. To identify genes that mediate the activity of ethosuximide, we conducted a genetic screen and identified mutations in two genes, che-3 and osm-3, that cause resistance to ethosuximide-mediated toxicity. Mutations in che-3 and osm-3 cause defects in overlapping sets of chemosensory neurons, resulting in defective chemosensation and an extended lifespan. These findings suggest that ethosuximide extends lifespan by inhibiting the function of specific chemosensory neurons. This model is supported by the observation that ethosuximide-treated animals displayed numerous phenotypic similarities with mutants that have chemosensory defects, indicating that ethosuximide inhibits chemosensory function. Furthermore, ethosuximide extends lifespan by inhibiting chemosensation, since the long-lived osm-3 mutants were resistant to the lifespan extension caused by ethosuximide. These studies demonstrate a novel mechanism of action for a lifespan-extending drug and indicate that sensory perception has a critical role in controlling lifespan. Sensory perception also influences the lifespan of Drosophila, suggesting that sensory perception has an evolutionarily conserved role in lifespan control. These studies highlight the potential of ethosuximide and related drugs that modulate sensory perception to extend lifespan in diverse animals

Toward a sustainable biomedical research enterprise: Finding consensus and implementing recommendations

The US research enterprise is under significant strain due to stagnant funding, an expanding workforce, and complex regulations that increase costs and slow the pace of research. In response, a number of groups have analyzed the problems and offered recommendations for resolving these issues. However, many of these recommendations lacked follow-up implementation, allowing the damage of stagnant funding and outdated policies to persist. Here, we analyze nine reports published since the beginning of 2012 and consolidate over 250 suggestions into eight consensus recommendations made by the majority of the reports. We then propose how to implement these consensus recommendations, and we identify critical issues, such as improving workforce diversity and stakeholder interactions, on which the community has yet to achieve consensus

Cluster Multi-spacecraft Determination of AKR Angular Beaming

Simultaneous observations of AKR emission using the four-spacecraft Cluster array were used to make the first direct measurements of the angular beaming patterns of individual bursts. By comparing the spacecraft locations and AKR burst locations, the angular beaming pattern was found to be narrowly confined to a plane containing the magnetic field vector at the source and tangent to a circle of constant latitude. Most rays paths are confined within 15 deg of this tangent plane, consistent with numerical simulations of AKR k-vector orientation at maximum growth rate. The emission is also strongly directed upward in the tangent plane, which we interpret as refraction of the rays as they leave the auroral cavity. The narrow beaming pattern implies that an observer located above the polar cap can detect AKR emission only from a small fraction of the auroral oval at a given location. This has important consequences for interpreting AKR visibility at a given location. It also helps re-interpret previously published Cluster VLBI studies of AKR source locations, which are now seen to be only a subset of all possible source locations. These observations are inconsistent with either filled or hollow cone beaming models.Comment: 5 pages, 4 figures. Geophys. Res. Letters (accepted

First results from the Cluster wideband plasma wave investigation

International audienceIn this report we present the first results from the Cluster wideband plasma wave investigation. The four Cluster spacecraft were successfully placed in closely spaced, high-inclination eccentric orbits around the Earth during two separate launches in July – August 2000. Each spacecraft includes a wideband plasma wave instrument designed to provide high-resolution electric and magnetic field wave-forms via both stored data and direct downlinks to the NASA Deep Space Network. Results are presented for three commonly occurring magnetospheric plasma wave phenomena: (1) whistlers, (2) chorus, and (3) auroral kilometric radiation. Lightning-generated whistlers are frequently observed when the spacecraft is inside the plasmasphere. Usually the same whistler can be detected by all spacecraft, indicating that the whistler wave packet extends over a spatial dimension at least as large as the separation distances transverse to the magnetic field, which during these observations were a few hundred km. This is what would be expected for nonducted whistler propagation. No case has been found in which a strong whistler was detected at one spacecraft, with no signal at the other spacecraft, which would indicate ducted propagation. Whistler-mode chorus emissions are also observed in the inner region of the magnetosphere. In contrast to lightning-generated whistlers, the individual chorus elements seldom show a one-to-one correspondence between the spacecraft, indicating that a typical chorus wave packet has dimensions transverse to the magnetic field of only a few hundred km or less. In one case where a good one-to-one correspondence existed, significant frequency variations were observed between the spacecraft, indicating that the frequency of the wave packet may be evolving as the wave propagates. Auroral kilometric radiation, which is an intense radio emission generated along the auroral field lines, is frequently observed over the polar regions. The frequency-time structure of this radiation usually shows a very good one-to-one correspondence between the various spacecraft. By using the microsecond timing available at the NASA Deep Space Net-work, very-long-baseline radio astronomy techniques have been used to determine the source of the auroral kilometric radiation. One event analyzed using this technique shows a very good correspondence between the inferred source location, which is assumed to be at the electron cyclotron frequency, and a bright spot in the aurora along the magnetic field line through the source

Internal and near nozzle measurements of Engine Combustion Network "Spray G" gasoline direct injectors

[EN] Gasoline direct injection (GDI) sprays are complex multiphase flows. When compared to multi-hole diesel sprays, the plumes are closely spaced, and the sprays are more likely to interact. The effects of multi-jet interaction on entrainment and spray targeting can be influenced by small variations in the mass fluxes from the holes, which in turn depend on transients in the needle movement and small-scale details of the internal geometry. In this paper, we present a comprehensive overview of a multi-institutional effort to experimentally characterize the internal geometry and near-nozzle flow of the Engine Combustion Network (ECN) Spray G gasoline injector. In order to develop a complete pictitre of the near-nozzle flow, a standardized setup was shared between facilities. A wide range of techniques were employed, including both X-ray and visible-light diagnostics. The novel aspects of this work include both new experimental measurements, and a comparison of the results across different techniques and facilities. The breadth and depth of the data reveal phenomena which were not apparent from analysis of the individual data sets. We show that plume-to-plume variations in the mass fluxes from the holes can cause large-scale asymmetries in the entrainment field and spray structure. Both internal flow transients and small-scale geometric features can have an effect on the external flow. The sharp turning angle of the flow into the holes also causes an inward vectoring of the plumes relative to the hole drill angle, which increases with time due to entrainment of gas into a low-pressure region between the plumes. These factors increase the likelihood of spray collapse with longer injection durations.The X-ray experiments were performed at the 7-BM and 32-ID beam lines of the APS at Argonne National Laboratory. Use of the APS is supported by the U.S. Department of Energy (DOE) under Contract No. DE-AC02-06CH11357. Research was also performed at the Combustion Research Facility, Sandia National Laboratories, Livermore, California. Sandia National Laboratories is managed and operated by National Technology and Engineering Solutions of Sandia LLC, a wholly owned subsidiary of Honeywell International, Inc., for the U.S. Department of Energy National Nuclear Security Administration under contract DE-NA-0003525.Duke, DJ.; Kastengren, AL.; Matusik, KE.; Swantek, AB.; Powell, CF.; Payri, R.; Vaquerizo, D.... (2017). Internal and near nozzle measurements of Engine Combustion Network "Spray G" gasoline direct injectors. Experimental Thermal and Fluid Science. 88:608-621. https://doi.org/10.1016/j.expthermflusci.2017.07.015S6086218

ViPR: an open bioinformatics database and analysis resource for virology research

The Virus Pathogen Database and Analysis Resource (ViPR, www.ViPRbrc.org) is an integrated repository of data and analysis tools for multiple virus families, supported by the National Institute of Allergy and Infectious Diseases (NIAID) Bioinformatics Resource Centers (BRC) program. ViPR contains information for human pathogenic viruses belonging to the Arenaviridae, Bunyaviridae, Caliciviridae, Coronaviridae, Flaviviridae, Filoviridae, Hepeviridae, Herpesviridae, Paramyxoviridae, Picornaviridae, Poxviridae, Reoviridae, Rhabdoviridae and Togaviridae families, with plans to support additional virus families in the future. ViPR captures various types of information, including sequence records, gene and protein annotations, 3D protein structures, immune epitope locations, clinical and surveillance metadata and novel data derived from comparative genomics analysis. Analytical and visualization tools for metadata-driven statistical sequence analysis, multiple sequence alignment, phylogenetic tree construction, BLAST comparison and sequence variation determination are also provided. Data filtering and analysis workflows can be combined and the results saved in personal ‘Workbenches’ for future use. ViPR tools and data are available without charge as a service to the virology research community to help facilitate the development of diagnostics, prophylactics and therapeutics for priority pathogens and other viruses

Cluster in the Auroral Acceleration Region

Due to a fortuitous evolution of the Cluster orbit, the Cluster spacecraft penetrated for the first time in its mission the heart of Earth's auroral acceleration region (AAR) in December 2009 and January 2010. During this time a special AAR campaign was carried out by the various Cluster instrument teams with special support from ESA and NASA facilities. We present some of the first multi-spacecraft observations of the waves, particles and fields made during that campaign. The Cluster spacecraft configuration during these AAR passages was such that it allowed us to explore the differences in the signatures of waves, particles, and fields on the various spacecraft in ways not possible with single spacecraft. For example, one spacecraft was more poleward than the other three (C2), one was at higher altitude (C1), and one of them (0) followed another (C4) through the AAR on approximately the same track but delayed by three minutes. Their separations were generally on the order of a few thousand km or less and occasionally two of them were lying along the same magnetic field line. We will show some of the first analyses of the data obtained during the AAR campaign, where upward and downward current regions, and the waves specifically associated with those regions, as well as the auroral cavities, were observed similarly and differently on the various spacecraft, helping us to explore the spatial, as well as the temporal, aspects of processes occurring in the AAR