Drosophila DJ-1 Mutants Are Selectively Sensitive to Environmental Toxins Associated with Parkinson’s Disease

SummaryParkinson’s disease (PD) is a common neurodegenerative disorder that displays both sporadic and inherited forms [1]. Exposure to several common environmental toxins acting through oxidative stress has been shown to be associated with PD [2]. One recently identified inherited PD gene, DJ-1, may have a role in protection from oxidative stress [3–10], thus potentially linking a genetic cause with critical environmental risk factors. To develop an animal model that would allow integrative study of genetic and environmental influences, we have generated Drosophila lacking DJ-1 function. Fly DJ-1 homologs exhibit differential expression: DJ-1β is ubiquitous, while DJ-1α is predominantly expressed in the male germline. DJ-1α and DJ-1β double knockout flies are viable, fertile, and have a normal lifespan; however, they display a striking selective sensitivity to those environmental agents, including paraquat and rotenone, linked to PD in humans. This sensitivity results primarily from loss of DJ-1β protein, which also becomes modified upon oxidative stress. These studies demonstrate that fly DJ-1 activity is selectively involved in protection from environmental oxidative insult in vivo and that the DJ-1β protein is biochemically responsive to oxidative stress. Study of these flies will provide insight into the critical interplay of genetics and environment in PD

Off-Nominal Planning for the Cryogenic Vacuum Test of the JWST Optical Telescope Element/Integrated Science Instrument Module at JSC

The cryogenic thermal vacuum/thermal balance test of the James Webb Space Telescope (JWST) combined Optical Telescope Element (OTE)/Integrated Science Instrument Module (ISIM), known as the OTIS, at the Johnson Space Center (JSC) Chamber A in 2017 was likely the most complex test ever performed by NASA for an unmanned mission. The test of the combined flight Optical Telescope and ISIM elements was prefaced by years of modifications to chamber facilities, and included three extensive precursor tests of non-flight and flight hardware to establish safe and optimal test operational procedures. One critical part of the test preparation was planning for off-nominal events that could arise, including appropriate responses. In some cases, assurance of personnel and payload safety required modification of original test hardware and procedures which had to be validated before the final test could begin. This planning proved especially prescient for the OTIS test, as Hurricane Harvey struck the Houston area during the test in August 2017, and consequences for the precious payload could have been severe. This paper describes the extent of the thermal off-nominal planning undertaken for the OTIS test, including including safing for hurricanes, and some real-life effects of Hurricane Harvey on the test conduct. Documentation of the consequences and mitigations for these events are discussed. The importance of off-nominal planning for future thermal vacuum/thermal balance tests is illustrated

SAVVY Vaginal Gel (C31G) for Prevention of HIV Infection: A Randomized Controlled Trial in Nigeria

The objective of this trial was to determine the effectiveness of 1.0% C31G (SAVVY) in preventing male-to-female vaginal transmission of HIV infection among women at high risk.This was a Phase 3, double-blind, randomized, placebo-controlled trial. Participants made up to 12 monthly follow-up visits for HIV testing, adverse event reporting, and study product supply. The study was conducted between September 2004 and December 2006 in Lagos and Ibadan, Nigeria, where we enrolled 2153 HIV-negative women at high risk of HIV infection. Participants were randomized 1 ratio 1 to SAVVY or placebo. The effectiveness endpoint was incidence of HIV infection as indicated by detection of HIV antibodies in oral mucosal transudate (rapid test) or blood (ELISA), and confirmed by Western blot or PCR testing. We observed 33 seroconversions (21 in the SAVVY group, 12 in the placebo group). The Kaplan-Meier estimates of the cumulative probability of HIV infection at 12 months were 0.028 in the SAVVY group and 0.015 in the placebo group (2-sided p-value for the log-rank test of treatment effect 0.121). The point estimate of the hazard ratio was 1.7 for SAVVY versus placebo (95% confidence interval 0.9, 3.5). Because of lower-than-expected HIV incidence, we did not observe the required number of HIV infections (66) for adequate power to detect an effect of SAVVY. Follow-up frequencies of adverse events, reproductive tract adverse events, abnormal pelvic examination findings, chlamydial infections and vaginal infections were similar in the study arms. No serious adverse event was attributable to SAVVY use.SAVVY did not reduce the incidence of HIV infection. Although the hazard ratio was higher in the SAVVY than the placebo group, we cannot conclude that there was a harmful treatment effect of SAVVY

Compendium of Single Event Effects Results for Candidate Spacecraft Electronics for NASA

Susceptibility of a variety of candidate spacecraft electronics to proton and heavy ion induced single event effects is studied. Devices tested include digital, linear bipolar, and hybrid devices

Optics and Quantum Electronics

Contains table of contents for Section 2 and reports on eighteen research projects.National Science Foundation (Grant EET 87-00474)Joint Services Electronics Program (Contract DAAL03-86-K-0002)Joint Services Electronics Program (Contract DAALO3-89-C-0001)Charles Stark Draper Laboratory (Grant DL-H-285408)Charles Stark Draper Laboratory (Grant DL-H-2854018)National Science Foundation (Grant EET 87-03404)National Science Foundation (Grant ECS 84-06290)U.S. Air Force - Office of Scientific Research (Contract F49620-88-C-0089)AT&T Bell FoundationNational Science Foundation (Grant ECS 85-52701)National Institutes of Health (Grant 5-RO1-GM35459)Massachusetts General Hospital (Office of Naval Research Contract N00014-86-K-0117)Lawrence Livermore National Laboratory (Subcontract B048704

The status of the world's land and marine mammals: diversity, threat, and knowledge

Knowledge of mammalian diversity is still surprisingly disparate, both regionally and taxonomically. Here, we present a comprehensive assessment of the conservation status and distribution of the world's mammals. Data, compiled by 1700+ experts, cover all 5487 species, including marine mammals. Global macroecological patterns are very different for land and marine species but suggest common mechanisms driving diversity and endemism across systems. Compared with land species, threat levels are higher among marine mammals, driven by different processes (accidental mortality and pollution, rather than habitat loss), and are spatially distinct (peaking in northern oceans, rather than in Southeast Asia). Marine mammals are also disproportionately poorly known. These data are made freely available to support further scientific developments and conservation action

Precision mouse models with expanded tropism for human pathogens

A major limitation of current humanized mouse models is that they primarily enable the analysis of human-specific pathogens that infect hematopoietic cells. However, most human pathogens target other cell types, including epithelial, endothelial and mesenchymal cells. Here, we show that implantation of human lung tissue, which contains up to 40 cell types, including nonhematopoietic cells, into immunodeficient mice (lung-only mice) resulted in the development of a highly vascularized lung implant. We demonstrate that emerging and clinically relevant human pathogens such as Middle East respiratory syndrome coronavirus, Zika virus, respiratory syncytial virus and cytomegalovirus replicate in vivo in these lung implants. When incorporated into bone marrow/liver/thymus humanized mice, lung implants are repopulated with autologous human hematopoietic cells. We show robust antigen-specific humoral and T-cell responses following cytomegalovirus infection that control virus replication. Lung-only mice and bone marrow/liver/thymus-lung humanized mice substantially increase the number of human pathogens that can be studied in vivo, facilitating the in vivo testing of therapeutics

Модель професійної культури юриста: критерії та підходи

В статті визначається модель професійної культури

Jonson\u27s Acoustic-Oriented Dramaturgy in the First Folio Playtexts of \u3ci\u3eEpicoene\u3c/i\u3e and \u3ci\u3eThe Alchemist\u3c/i\u3e

One significant yet understudied aspect of the First Folio printings of Epicoene and The Alchemist is that their marginal stage directions highlight the importance of Jonson\u27s acoustic-oriented dramaturgy to both plays. In light of Jonson\u27s recurrent associations between exposure to noise pollution and the threat of plague, this essay reads Jonson\u27s acoustic-oriented dramaturgy in i\u3eEpicoene and The Alchemist as a direct engagement with the contemporary plague-time performance settings of both plays. Moreover, when considered alongside the numerous site-specific engagements of both printed playtexts, what becomes clear is that Jonson\u27s acoustic-oriented dramaturgy assumes an important satirical dimension directed at these plays’ earliest London audiences. First, in part through his acoustic manipulation of the indoor performance environments of the Whitefriars and Blackfriars theaters, Jonson satirically critiques the fantasies of social exclusivity embodied by Morose and Lovewit. Equally importantly, by drawing dramaturgical inspiration from the ambivalent experience of playgoing during an ongoing plague outbreak, Jonson also critiques the fantasies of social exclusivity evident among his plague-time comedies’ well-to-do London audiences