Comet and close-approach asteroid mission study. volume 1- summary report final report

Comet and close-approach asteroid mission stud

Genetic regulation of mouse liver metabolite levels.

We profiled and analyzed 283 metabolites representing eight major classes of molecules including Lipids, Carbohydrates, Amino Acids, Peptides, Xenobiotics, Vitamins and Cofactors, Energy Metabolism, and Nucleotides in mouse liver of 104 inbred and recombinant inbred strains. We find that metabolites exhibit a wide range of variation, as has been previously observed with metabolites in blood serum. Using genome-wide association analysis, we mapped 40% of the quantified metabolites to at least one locus in the genome and for 75% of the loci mapped we identified at least one candidate gene by local expression QTL analysis of the transcripts. Moreover, we validated 2 of 3 of the significant loci examined by adenoviral overexpression of the genes in mice. In our GWAS results, we find that at significant loci the peak markers explained on average between 20 and 40% of variation in the metabolites. Moreover, 39% of loci found to be regulating liver metabolites in mice were also found in human GWAS results for serum metabolites, providing support for similarity in genetic regulation of metabolites between mice and human. We also integrated the metabolomic data with transcriptomic and clinical phenotypic data to evaluate the extent of co-variation across various biological scales

Antitrust and Competition Law Update: Agencies Send a Strong Message on HSR Filing

The Federal Trade Commission and Department of Justice’s Antitrust Division last week each announced enforcement actions against and settlements with parties that alleged failed to make required notifications of transactions under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended. Each case resulted in a significant fine (one of $800,000 and one of$1 million) and signaled the agencies’ intent to pursue vigorously parties that fail -- intentionally or negligently -- to meet their obligations under the HSR Act. Moreover, both cases address the scope of the HSR Act’s “investment only” exemption and show that the agencies construe it strictly to apply only when the acquiror’s interest and intent concerning the acquired firm is truly passive. Finally, these cases serve as a reminder that the Act’s filing requirements apply not only to purchases of an entire company or all of its assets, but also to any purchase of voting securities so long as certain thresholds are met -- whether or not the purchaser obtains any significant percentage ownershi

Stepwise evolution of a butterfly supergene via duplication and inversion

Supergenes maintain adaptive clusters of alleles in the face of genetic mixing. Although usually attributed to inversions, supergenes can be complex, and reconstructing the precise processes that led to recombination suppression and their timing is challenging. We investigated the origin of the BC supergene, which controls variation in warning coloration in the African monarch butterfly, Danaus chrysippus. By generating chromosome-scale assemblies for all three alleles, we identified multiple structural differences. Most strikingly, we find that a region of more than 1 million bp underwent several segmental duplications at least 7.5 Ma. The resulting duplicated fragments appear to have triggered four inversions in surrounding parts of the chromosome, resulting in stepwise growth of the region of suppressed recombination. Phylogenies for the inversions are incongruent with the species tree and suggest that structural polymorphisms have persisted for at least 4.1 Myr. In addition to the role of duplications in triggering inversions, our results suggest a previously undescribed mechanism of recombination suppression through independent losses of divergent duplicated tracts. Overall, our findings add support for a stepwise model of supergene evolution involving a variety of structural changes. This article is part of the theme issue ‘Genomic architecture of supergenes: causes and evolutionary consequences’

The role of morphological markedness in the processing of number and gender agreement in Spanish: an event-related potential investigation

Current morphological theory assumes that feature values, such as masculine and feminine or singular and plural, are asymmetrically represented. That is, one member of the opposition (e.g. feminine for gender, plural for number) is assumed to be marked, and the other one, unmarked. The present study examines how these asymmetries impact agreement resolution in Spanish. Agreement was manipulated between a noun acting as head of a relative clause and an adjective located inside the relative clause (e.g. catedral que parecía inmensa “cathedral that looked huge”). Half of the nouns were feminine (marked) and the other half, masculine (unmarked). Half of the nouns were used in the plural (marked) and the other half, in the singular (unmarked). Twenty-seven Spanish native speakers read 240 sentences while their brain activity was recorded with EEG and performed a grammaticality judgment. Results showed that both number and gender violations elicited a central-posterior P600, a component associated with syntactic repair, and a late anterior negativity, argued to reflect working memory costs. Only the P600 was affected by markedness. It started earlier for violations where the mismatching feature was marked. Moreover, it was larger for errors where the mismatching feature was marked, although this amplitude modulation only emerged for number, possibly due to differences in how number and gender cues were realized (i.e. both masculine and feminine showed overt inflection, but singular was uninflected relative to plural). These results suggest that the parser is sensitive to markedness asymmetries in the course of online processing

Factors associated with self-care activities among adults in the United Kingdom: a systematic review

Background: The Government has promoted self-care. Our aim was to review evidence about who uses self-tests and other self-care activities (over-the-counter medicine, private sector,complementary and alternative medicine (CAM), home blood pressure monitors). Methods: During April 2007, relevant bibliographic databases (Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Applied Social Sciences Index and Abstracts, PsycINFO,British Nursing Index, Allied and Complementary Medicine Database, Sociological Abstracts, International Bibliography of the Social Sciences, Arthritis and Complementary Medicine Database, Complementary and Alternative Medicine and Pain Database) were searched, and potentially relevant studies were reviewed against eligibility criteria. Studies were included if they were published during the last 15 years and identified factors, reasons or characteristics associated with a relevant activity among UK adults. Two independent reviewers used proformas to assess the quality of eligible studies. Results: 206 potentially relevant papers were identified, 157 were excluded, and 49 papers related to 46 studies were included: 37 studies were, or used data from questionnaire surveys, 36 had quality scores of five or more out of 10, and 27 were about CAM. Available evidence suggests that users of CAM and over-the-counter medicine are female, middle-aged, affluent and/or educated with some measure of poor health, and that people who use the private sector are affluent and/or educated. Conclusion: People who engage in these activities are likely to be affluent. Targeted promotion may, therefore, be needed to ensure that use is equitable. People who use some activities also appear to have poorer measures of health than non-users or people attending conventional services. It is, therefore, also important to ensure that self-care is not used as a second choice for people who have not had their needs met by conventional service

Pharmacoinformatic investigation of medicinal plants from East Africa

Medicinal plants have widely been used in the traditional treatment of ailments and have been proven effective. Their contribution still holds an important place in modern drug discovery due to their chemical, and biological diversities. However, the poor documentation of traditional medicine, in developing African countries for instance, can lead to the loss of knowledge related to such practices. In this study, we present the Eastern Africa Natural Products Database (EANPDB) containing the structural and bioactivity information of 1870 unique molecules isolated from about 300 source species from the Eastern African region. This represents the largest collection of natural products (NPs) from this geographical region, covering literature data of the period from 1962 to 2019. The computed physicochemical properties and toxicity profiles of each compound have been included. A comparative analysis of some physico-chemical properties like molecular weight, H-bond donor/acceptor, logP(o/w), etc. as well scaffold diversity analysis has been carried out with other published NP databases. EANPDB was combined with the previously published Northern African Natural Products Database (NANPDB), to form a merger African Natural Products Database (ANPDB), containing similar to 6500 unique molecules isolated from about 1000 source species (freely available at http://african-compounds.org). As a case study, latrunculins A and B isolated from the spongeNegombata magnifica(Podospongiidae) with previously reported antitumour activities, were identified via substructure searching as molecules to be explored as putative binders of histone deacetylases (HDACs)

An updated protocol for a systematic review of implementation-related measures

Abstract Background Implementation science is the study of strategies used to integrate evidence-based practices into real-world settings (Eccles and Mittman, Implement Sci. 1(1):1, 2006). Central to the identification of replicable, feasible, and effective implementation strategies is the ability to assess the impact of contextual constructs and intervention characteristics that may influence implementation, but several measurement issues make this work quite difficult. For instance, it is unclear which constructs have no measures and which measures have any evidence of psychometric properties like reliability and validity. As part of a larger set of studies to advance implementation science measurement (Lewis et al., Implement Sci. 10:102, 2015), we will complete systematic reviews of measures that map onto the Consolidated Framework for Implementation Research (Damschroder et al., Implement Sci. 4:50, 2009) and the Implementation Outcomes Framework (Proctor et al., Adm Policy Ment Health. 38(2):65-76, 2011), the protocol for which is described in this manuscript. Methods Our primary databases will be PubMed and Embase. Our search strings will be comprised of five levels: (1) the outcome or construct term; (2) terms for measure; (3) terms for evidence-based practice; (4) terms for implementation; and (5) terms for mental health. Two trained research specialists will independently review all titles and abstracts followed by full-text review for inclusion. The research specialists will then conduct measure-forward searches using the “cited by” function to identify all published empirical studies using each measure. The measure and associated publications will be compiled in a packet for data extraction. Data relevant to our Psychometric and Pragmatic Evidence Rating Scale (PAPERS) will be independently extracted and then rated using a worst score counts methodology reflecting “poor” to “excellent” evidence. Discussion We will build a centralized, accessible, searchable repository through which researchers, practitioners, and other stakeholders can identify psychometrically and pragmatically strong measures of implementation contexts, processes, and outcomes. By facilitating the employment of psychometrically and pragmatically strong measures identified through this systematic review, the repository would enhance the cumulativeness, reproducibility, and applicability of research findings in the rapidly growing field of implementation science