Metabolite Fingerprinting in Transgenic Nicotiana tabacum Altered by the Escherichia coli Glutamate Dehydrogenase Gene

With about 200 000 phytochemicals in existence, identifying those of biomedical significance is a mammoth task. In the postgenomic era, relating metabolite fingerprints, abundances, and profiles to genotype is also a large task. Ion analysis using Fourier transformed ion cyclotron resonance mass spectrometry (FT-ICR-MS) may provide a high-throughput approach to measure genotype dependency of the inferred metabolome if reproducible techniques can be established. Ion profile inferred metabolite fingerprints are coproducts. We used FT-ICR-MS-derived ion analysis to examine gdhA (glutamate dehydrogenase (GDH; EC 1.4.1.1)) transgenic Nicotiana tabacum (tobacco) carrying out altered glutamate, amino acid, and carbon metabolisms, that fundamentally alter plant productivity. Cause and effect between gdhA expression, glutamate metabolism, and plant phenotypes was analyzed by [Formula: see text] labeling of amino acid fractions, and by FT-ICR-MS analysis of metabolites. The gdhA transgenic plants increased (13)N labeling of glutamate and glutamine significantly. FT-ICR-MS detected 2 012 ions reproducible in 2 to 4 ionization protocols. There were 283 ions in roots and 98 ions in leaves that appeared to significantly change abundance due to the measured GDH activity. About 58% percent of ions could not be used to infer a corresponding metabolite. From the 42% of ions that inferred known metabolites we found that certain amino acids, organic acids, and sugars increased and some fatty acids decreased. The transgene caused increased ammonium assimilation and detectable ion variation. Thirty-two compounds with biomedical significance were altered in abundance by GDH including 9 known carcinogens and 14 potential drugs. Therefore, the GDH transgene may lead to new uses for crops like tobacco

The case for an HIV cure and how to get there

In light of the increasing global burden of new HIV infections, growing financial requirements, and shifting funding landscape, the global health community must accelerate the development and delivery of an HIV cure to complement existing prevention modalities. An effective curative intervention could prevent new infections, overcome the limitations of antiretroviral treatment, combat stigma and discrimination, and provide a sustainable financial solution for pandemic control. We propose steps to plan for an HIV cure now, including defining a target product profile and establishing the HIV Cure Africa Acceleration Partnership (HCAAP), a multidisciplinary public-private partnership that will catalyse and promote HIV cure research through diverse stakeholder engagement. HCAAP will convene stakeholders, including people living with HIV, at an early stage to accelerate the design, social acceptability, and rapid adoption of HIV-cure products

Integrated Medical Model Project - Overview and Summary of Historical Application

Introduction: The Integrated Medical Model (IMM) Project represents one aspect of NASA's Human Research Program (HRP) to quantitatively assess medical risks to astronauts for existing operational missions as well as missions associated with future exploration and commercial space flight ventures. The IMM takes a probabilistic approach to assessing the likelihood and specific outcomes of one hundred medical conditions within the envelope of accepted space flight standards of care over a selectable range of mission capabilities. A specially developed Integrated Medical Evidence Database (iMED) maintains evidence-based, organizational knowledge across a variety of data sources. Since becoming operational in 2011, version 3.0 of the IMM, the supporting iMED, and the expertise of the IMM project team have contributed to a wide range of decision and informational processes for the space medical and human research community. This presentation provides an overview of the IMM conceptual architecture and range of application through examples of actual space flight community questions posed to the IMM project. Methods: Figure 1 [see document] illustrates the IMM modeling system and scenario process. As illustrated, the IMM computational architecture is based on Probabilistic Risk Assessment techniques. Nineteen assumptions and limitations define the IMM application domain. Scenario definitions include crew medical attributes and mission specific details. The IMM forecasts probabilities of loss of crew life (LOCL), evacuation (EVAC), quality time lost during the mission, number of medical resources utilized and the number and type of medical events by combining scenario information with in-flight, analog, and terrestrial medical information stored in the iMED. In addition, the metrics provide the integrated information necessary to estimate optimized in-flight medical kit contents under constraints of mass and volume or acceptable level of mission risk. Results and Conclusions: Historically, IMM simulations support Science and Technology planning, Exploration mission planning, and ISS program operations by supplying simulation support, iMED data information, and subject matter expertise to Crew Health and Safety and the HRP. Upcoming release of IMM version 4.0 seeks to provide enhanced functionality to increase the quality of risk decisions made using the IMM through a more accurate representation of the real world system

Integrated Medical Model Overview

The Integrated Medical Model (IMM) Project represents one aspect of NASA's Human Research Program (HRP) to quantitatively assess medical risks to astronauts for existing operational missions as well as missions associated with future exploration and commercial space flight ventures. The IMM takes a probabilistic approach to assessing the likelihood and specific outcomes of one hundred medical conditions within the envelope of accepted space flight standards of care over a selectable range of mission capabilities. A specially developed Integrated Medical Evidence Database (iMED) maintains evidence-based, organizational knowledge across a variety of data sources. Since becoming operational in 2011, version 3.0 of the IMM, the supporting iMED, and the expertise of the IMM project team have contributed to a wide range of decision and informational processes for the space medical and human research community. This presentation provides an overview of the IMM conceptual architecture and range of application through examples of actual space flight community questions posed to the IMM project

The KiVa antibullying program in primary schools in Chile, with and without the digital game component: study protocol for a randomized controlled trial.

BACKGROUND: Bullying is a major problem worldwide and Chile is no exception. Bullying is defined as a systematic aggressive behavior against a victim who cannot defend him or herself. Victims suffer social isolation and psychological maladjustment, while bullies have a higher risk for conduct problems and substance use disorders. These problems appear to last over time. The KiVa antibullying program has been evaluated in Finland and other European countries, showing preventive effects on victimization and self-reported bullying. The aims of this study are (1) to develop a culturally appropriate version of the KiVa material and (2) to test the effectiveness of the KiVa program, with and without the online game, on reducing experiences of victimization and bullying behavior among vulnerable primary schools in Santiago (Chile), using a cluster randomized controlled trial (RCT) design with three arms: (1) full KiVa program group, (2) partial KiVa (without online game) program group and (3) control group. METHODS AND DESIGN: This is a three-arm, single-blind, cluster randomized controlled trial (RCT) with a target enrolment of 1495 4th and 5th graders attending 13 vulnerable schools per arm. Students in the full and partial KiVa groups will receive universal actions: ten 2-h lessons delivered by trained teachers during 1 year; they will be exposed to posters encouraging them to support victims and behave constructively when witnessing bullying; and a person designated by the school authorities will be present in all school breaks and lunchtimes using a visible KiVa vest to remind everybody that they are in a KiVa school. KiVa schools also will have indicated actions, which consist of a set of discussion groups with the victims and with the bullies, with proper follow-up. Only full KiVa schools will also receive an online game which has the aim to raise awareness of the role of the group in bullying, increase empathy and promote strategies to support victimized peers. Self-reported victimization, bullying others and peer-reported bullying actions, psychological and academic functioning, and sense of school membership will be measured at baseline and 12 months after randomization. DISCUSSION: This is the first cluster RCT of the KiVa antibullying program in Latin America. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT02898324 . Registered on 8 September 2016

Belongingness in early secondary school: Key factors that primary and secondary schools need to consider

© 2015 Vaz et al. It is unknown if, and how, students redefine their sense of school belongingness after negotiating the transition to secondary school. The current study used longitudinal data from 266 students with, and without, disabilities who negotiated the transition from 52 primary schools to 152 secondary schools. The study presents the 13 most significant personal student and contextual factors associated with belongingness in the first year of secondary school. Student perception of school belongingness was found to be stable across the transition. No variability in school belongingness due to gender, disability or household-socio-economic status (SES) was noted. Primary school belongingness accounted for 22% of the variability in secondary school belongingness. Several personal student factors (competence, coping skills) and school factors (low-level classroom task-goal orientation), which influenced belongingness in primary school, continued to influence belongingness in secondary school. In secondary school, effort-goal orientation of the student and perception of their school's tolerance to disability were each associated with perception of school belongingness. Family factors did not influence belongingness in secondary school. Findings of the current study highlight the need for primary schools to foster belongingness among their students at an early age, and transfer students' belongingness profiles as part of the handover documentation. Most of the factors that influenced school belongingness before and after the transition to secondary are amenable to change

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

HIV-1 Pre-Integration Complexes Selectively Target Decondensed Chromatin in the Nuclear Periphery

Integration of the double-stranded DNA copy of the HIV-1 genome into host chromosomal DNA is a requirement for efficient viral replication. Integration preferentially occurs within active transcription units, however chromosomal site specificity does not correlate with any strong primary sequence. To investigate whether the nuclear architecture may affect viral integration we have developed an experimental system where HIV-1 viral particles can be visualized within the nuclear compartment. Fluorescently labeled HIV-1 virions were engineered by fusing integrase, the viral protein that catalyzes the integration reaction, to fluorescent proteins. Viral tests demonstrate that the infectivity of fluorescent virions, including the integration step, is not altered as compared to wild-type virus. 3-D confocal microscopy allowed a detailed analysis of the spatial and temporal distribution of the pre-integration complexes (PICs) within the nucleus at different moments following infection; the fluorescently labeled PICs preferentially distribute in decondensed areas of the chromatin with a striking positioning in the nuclear periphery, while heterochromatin regions are largely disfavored. These observations provide a first indication of how the nuclear architecture may initially orient the selection of retroviral integration sites

A Q-methodology study of flare help-seeking behaviours and different experiences of daily life in rheumatoid arthritis

© 2014 Lin et al.; licensee BioMed Central Ltd. Background: Previous studies have not addressed rheumatoid arthritis (RA) patients' help-seeking behaviours for RA flares, and only one small qualitative study has addressed how patients experience daily life on current treatment regimes. Thus, this study aims to identify clusters of opinion related to RA patients' experiences of daily life on current treatments, and their help-seeking behaviours for RA flares. Methods: Using Q-methodology (a methodology using qualitative and quantitative methods to sort people according to subjective experience), two separate studies were conducted with the same sample of RA patients (mean age 55, 73% female). Thirty participants sorted 39 statements about daily life (Q-study 1) and 29 participants separately sorted 23 statements about flare help-seeking (Q-study 2). Data were examined using Q-factor analysis. Results: Daily life with RA (Q-study 1): Three factors relating to the experience of living with RA were extracted and explained. Patients belonging to Factor A (mean age 62, 86% female) use effective self-management techniques to control the daily impact of RA. Those in Factor B (mean age 55, 75% male) struggle to self-manage and cope. Whilst patients in Factor C (mean age 42, 100% female) prioritise life responsibilities over their RA, reporting less impact. Flare help-seeking (Q-study 2): Two factors explaining the experience of flare help-seeking (unrelated to the factors from Q-study 1) were extracted and explained. Factor X (68.8% on biologics) reported seeking help quickly, believing the medical team is there to help. Factor Y (0% on biologics) delay help-seeking, concerned about wasting the rheumatologist's time, believing they should manage alone. All participants agreed they sought help due to intense pain and persistent, unmanageable symptoms. Conclusions: Patients with different characteristics appear to manage RA life in different ways and men may struggle more than women. Whilst all patients are prompted to seek help by persistent, unmanageable symptoms, some delay help-seeking. Further research is needed to quantify the severity of daily symptoms, the level of symptoms needed for patients to define themselves as in flare and to understand the support needs of RA men

Protocol for a randomised controlled trial of a school based cognitive behaviour therapy (CBT) intervention to prevent depression in high risk adolescents (PROMISE)

<p>Abstract</p> <p>Background</p> <p>Depression in adolescents is a significant problem that impairs everyday functioning and increases the risk of severe mental health disorders in adulthood. Relatively few adolescents with depression are identified and referred for treatment indicating the need to investigate alternative preventive approaches.</p> <p>Study Design</p> <p>A pragmatic cluster randomised controlled trial evaluating the effectiveness of a school based prevention programme on symptoms of depression in "high risk" adolescents (aged 12-16). The unit of allocation is year groups (n = 28) which are assigned to one of three conditions: an active intervention based upon cognitive behaviour therapy, attention control or treatment as usual. Assessments will be undertaken at screening, baseline, 6 months and 12 months. The primary outcome measure is change on the Short Mood and Feeling Questionnaire at 12 months. Secondary outcome measures will assess changes in negative thoughts, self esteem, anxiety, school connectedness, peer attachment, alcohol and substance misuse, bullying and self harm.</p> <p>Discussion</p> <p>As of August 2010, all 28 year groups (n = 5023) had been recruited and the assigned interventions delivered. Final 12 month assessments are scheduled to be completed by March 2011.</p> <p>Trial Registration</p> <p>ISRCTN19083628</p