Medical Countermeasures for Radiation Induced Health Effects: Reports of an Interagency Panel Session Held at the NASA Human Research Program Investigator's Workshop, January 26, 2017

An Interagency Panel Session organized by the NASA Human Research Program Space Radiation Program Element (SRPE) was held during the NASA Human Research Program (HRP) Investigators Workshop (IWS) in Galveston, Texas on January 26, 2017 to identify complementary research areas that will advance the testing and development of medical countermeasures (MCM) in support of radioprotection and radiation mitigation on the ground and in space. There were several areas of common interest identified among the various participating agencies. This report provides a summary of the topics discussed by each agency along with potential areas of intersection for mutual collaboration opportunities. Common goals included repurposing of pharmaceuticals, neutraceuticals for use as radioprotectors and/or mitigators, low-dose/chronic exposure paradigms, late effects post-radiation exposure, mixed-field exposures of gamma-neutron, performance decrements, and methods to determine individual exposure levels

Incompatibility Systems in Switchgrass

Switchgrass (Panicum virgatum L.), a cross-pollinated perennial, produces very little or no seed when self-pollinated, indicating the presence of self-incompatibility mechanisms. Knowledge of self-incompatibility mechanisms is required to use germplasm effectively in a breeding program. The objective of this study was to characterize features of the incompatibility systems in switchgrass. Seed set and seed characteristics of reciprocal matings of tetraploid, octaploid, and tetraploid x octaploid plants were used as measures of incompatibility. Both bagged mutual pollination and manual emasculation and pollination methods were used to make crosses. The percentages of self-compatibility in the tetraploid and octaploid parent plants were 0.35 and 1.39%, respectively. Prefertilization incompatibility in switchgrass is apparently under gametophytic control, since there were significant differences in percentage of compatible pollen as measured by percentage of total seed set between reciprocal matings within ploidy levels. Results indicated that the prefertilization incompatibility system in switchgrass is similar to the S-Z incompatibility system found in other members of the Poaceae. A postfertilization incompatibility system also exists that inhibits intermatings among octaploid and tetraploid plants. In these interploidy crosses, two very distinctive types of abnormal seed were found. When the female parent was the tetraploid plant, the resulting seed was small and shriveled, while when the female parent was the octaploid, small seed with floury endosperm was obtained. These results are similar to those obtained for endosperm incompatibility due to the endosperm balance number system found in other species

How to Build Collective Capabilities: The 3C-Model for Grassroots-led Development

Capabilities need to be built from the bottom-up. Social innovations at the grassroots seek to present new solutions to existing social problems. However, since the poor suffer from limitations on their individual capabilities and agency, they engage in acts of collective agency to generate new collective capabilities that each individual alone would not be able to achieve. The question is: how can these acts of collective agency be initiated, supported and sustained in practice? What roles can development actors (such as the state, donors and NGOs) play in supporting these acts of collective agency? Drawing on the literature on social innovation, the capability approach, participation and empowerment, the paper argues that three crucial C-processes are integral conditions for promoting successful, scalable and sustainable social innovations at the grassroots, namely: (1) Conscientization; (2) Conciliation and (3) Collaboration. By linking the individual, collective and institutional levels of analysis, the paper demonstrates the importance of individual behavioural changes, collective agency and local institutional reforms for the success, sustainability and scalability of social innovations at the grassroots. The paper acknowledges conflict, capture and cooptation as potential limitations and recognizes the role of contextual factors in initiating, implementing and sustaining social innovations at the grassroots

Psychometric Evaluation of the Arabic Version of the Spiritual Well-Being Scale on a Sample of Jordanian Arab Christians

This paper assesses the psychometric properties of the Arabic version of the Spiritual Well-Being Scale (SWBS) in an Arab Christian sample by analyzing its internal structure. A convenience sample of 340 Arab Christians was recruited from the adult community population of northern Jordan. Data were collected through a self-completion, anonymous questionnaire distributed through church and community groups. Principal Components factor analysis, non-parametric bivariate statistics, and Cronbach's alpha were used to assess the psychometric properties of the total scale and its subscales. The findings broadly supported the factor structure of the SWBS in other Arab samples in that the scale consists of three factors, representing positive existential well-being, affiliation, and alienation subscales. In conclusion, these preliminary findings suggest that the Arabic version of the SWBS can be used as an instrument to measure levels of spiritual well-being in Arab Christian populations. </jats:p

Prevalence of self-harm among lesbian, gay, bisexual, and transgender adolescents: a comparison of personal and social adversity with a heterosexual sample in Ghana

Objectives We sought to estimate the prevalence of self-reported self-harm among adolescents identifying as lesbian, gay, bisexual, and transgender (LGBT) in Ghana, and compare self-reported personal and social adversities related to self-harm in this group to those in a random sample of heterosexual adolescents from the same locality. Results A total of 444 adolescents aged 13-21 years, comprising 74 LGBT adolescents and 370 heterosexual adolescents, provided data. The lifetime prevalence estimate of self-harm was higher in the LGBT group (47%) than the heterosexual group (23%). The LGBT group reported a higher rate of self-harm during the previous 12 months (45%), compared to the heterosexual group (18%). LGBT adolescents reported more alcohol and substance use and more personal social adversities, including various forms of victimisation, than heterosexual adolescents. They were no more likely to report difficulty in making and keeping friends or schoolwork problems than were heterosexual adolescents

Variants in STXBP3 are Associated with Very Early Onset Inflammatory Bowel Disease, Bilateral Sensorineural Hearing Loss and Immune Dysregulation

Background and aims: Very early onset inflammatory bowel disease [VEOIBD] is characterized by intestinal inflammation affecting infants and children less than 6 years of age. To date, over 60 monogenic aetiologies of VEOIBD have been identified, many characterized by highly penetrant recessive or dominant variants in underlying immune and/or epithelial pathways. We sought to identify the genetic cause of VEOIBD in a subset of patients with a unique clinical presentation. Methods: Whole exome sequencing was performed on five families with ten patients who presented with a similar constellation of symptoms including medically refractory infantile-onset IBD, bilateral sensorineural hearing loss and, in the majority, recurrent infections. Genetic aetiologies of VEOIBD were assessed and Sanger sequencing was performed to confirm novel genetic findings. Western analysis on peripheral blood mononuclear cells and functional studies with epithelial cell lines were employed. Results: In each of the ten patients, we identified damaging heterozygous or biallelic variants in the Syntaxin-Binding Protein 3 gene [STXBP3], a protein known to regulate intracellular vesicular trafficking in the syntaxin-binding protein family of molecules, but not associated to date with either VEOIBD or sensorineural hearing loss. These mutations interfere with either intron splicing or protein stability and lead to reduced STXBP3 protein expression. Knock-down of STXBP3 in CaCo2 cells resulted in defects in cell polarity. Conclusion: Overall, we describe a novel genetic syndrome and identify a critical role for STXBP3 in VEOIBD, sensorineural hearing loss and immune dysregulation.info:eu-repo/semantics/publishedVersio

Design and development of a peptide-based adiponectin receptor agonist for cancer treatment

<p>Abstract</p> <p>Background</p> <p>Adiponectin, a fat tissue-derived adipokine, exhibits beneficial effects against insulin resistance, cardiovascular disease, inflammatory conditions, and cancer. Circulating adiponectin levels are decreased in obese individuals, and this feature correlates with increased risk of developing several metabolic, immunological and neoplastic diseases. Thus, pharmacological replacement of adiponectin might prove clinically beneficial, especially for the obese patient population. At present, adiponectin-based therapeutics are not available, partly due to yet unclear structure/function relationships of the cytokine and difficulties in converting the full size adiponectin protein into a viable drug.</p> <p>Results</p> <p>We aimed to generate adiponectin-based short peptide that can mimic adiponectin action and be suitable for preclinical and clinical development as a cancer therapeutic. Using a panel of 66 overlapping 10 amino acid-long peptides covering the entire adiponectin globular domain (residues 105-254), we identified the 149-166 region as the adiponectin active site. Three-dimensional modeling of the active site and functional screening of additional 330 peptide analogs covering this region resulted in the development of a lead peptidomimetic, ADP 355 (H-DAsn-Ile-Pro-Nva-Leu-Tyr-DSer-Phe-Ala-DSer-NH₂). In several adiponectin receptor-positive cancer cell lines, ADP 355 restricted proliferation in a dose-dependent manner at 100 nM-10 μM concentrations (exceeding the effects of 50 ng/mL globular adiponectin). Furthermore, ADP 355 modulated several key signaling pathways (AMPK, Akt, STAT3, ERK1/2) in an adiponectin-like manner. siRNA knockdown experiments suggested that ADP 355 effects can be transmitted through both adiponectin receptors, with a greater contribution of AdipoR1. <it>In vivo</it>, intraperitoneal administration of 1 mg/kg/day ADP 355 for 28 days suppressed the growth of orthotopic human breast cancer xenografts by ~31%. The peptide displayed excellent stability (at least 30 min) in mouse blood or serum and did not induce gross toxic effects at 5-50 mg/kg bolus doses in normal CBA/J mice.</p> <p>Conclusions</p> <p>ADP 355 is a first-in-class adiponectin receptor agonist. Its biological activity, superior stability in biological fluids as well as acceptable toxicity profile indicate that the peptidomimetic represents a true lead compound for pharmaceutical development to replace low adiponectin levels in cancer and other malignancies.</p

Plant ARGONAUTEs: Features, Functions and Unknowns

ARGONAUTEs (AGOs) are the effector proteins in eukaryotic small RNA(sRNA)– based gene silencing pathways controlling gene expression and transposon activity. In plants, AGOs regulate key biological processes such as development, response to stress, genome structure and integrity, and pathogen defense. Canonical functions of plant AGO–sRNA complexes include the endonucleolytic cleavage or translational inhibition of target RNAs, and the methylation of target DNAs. Here, I provide a brief update on the major features, molecular functions and biological roles of plant AGOs. A special focus is given to the more recent discoveries related to emerging molecular or biological functions of plant AGOs, as well as to the major unknowns in the plant AGO field.This work was supported by an Individual Fellowship from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 655841 to A.C.Carbonell Olivares, A. (2017). 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