Where do we go from here? An assessment of navigation performance using a compass versus a GPS unit

The Global Positioning System (GPS) looks set to replace the traditional map and compass for navigation tasks in military and civil domains. However, we may ask whether GPS has a real performance advantage over traditional methods. We present an exploratory study using a waypoint plotting task to compare the standard magnetic compass against a military GPS unit, for both expert and non-expert navigators. Whilst performance times were generally longer in setting up the GPS unit, once navigation was underway the GPS was more efficient than the compass. For mediumto long-term missions, this means that GPS could offer significant performance benefits, although the compass remains superior for shorter missions. Notwithstanding the performance times, significantly more errors, and more serious errors, occurred when using the compass. Overall, then, the GPS offers some clear advantages, especially for non-expert users. Nonetheless, concerns over the development of cognitive maps remain when using GPS technologies

The use of phylogeny to interpret cross-cultural patterns in plant use and guide medicinal plant discovery: an example from Pterocarpus (Leguminosae)

The study of traditional knowledge of medicinal plants has led to discoveries that have helped combat diseases and improve healthcare. However, the development of quantitative measures that can assist our quest for new medicinal plants has not greatly advanced in recent years. Phylogenetic tools have entered many scientific fields in the last two decades to provide explanatory power, but have been overlooked in ethnomedicinal studies. Several studies show that medicinal properties are not randomly distributed in plant phylogenies, suggesting that phylogeny shapes ethnobotanical use. Nevertheless, empirical studies that explicitly combine ethnobotanical and phylogenetic information are scarce.In this study, we borrowed tools from community ecology phylogenetics to quantify significance of phylogenetic signal in medicinal properties in plants and identify nodes on phylogenies with high bioscreening potential. To do this, we produced an ethnomedicinal review from extensive literature research and a multi-locus phylogenetic hypothesis for the pantropical genus Pterocarpus (Leguminosae: Papilionoideae). We demonstrate that species used to treat a certain conditions, such as malaria, are significantly phylogenetically clumped and we highlight nodes in the phylogeny that are significantly overabundant in species used to treat certain conditions. These cross-cultural patterns in ethnomedicinal usage in Pterocarpus are interpreted in the light of phylogenetic relationships.This study provides techniques that enable the application of phylogenies in bioscreening, but also sheds light on the processes that shape cross-cultural ethnomedicinal patterns. This community phylogenetic approach demonstrates that similar ethnobotanical uses can arise in parallel in different areas where related plants are available. With a vast amount of ethnomedicinal and phylogenetic information available, we predict that this field, after further refinement of the techniques, will expand into similar research areas, such as pest management or the search for bioactive plant-based compounds

Ancient Ethiopian genome reveals extensive Eurasian admixture throughout the African continent.

Characterizing genetic diversity in Africa is a crucial step for most analyses reconstructing the evolutionary history of anatomically modern humans. However, historic migrations from Eurasia into Africa have affected many contemporary populations, confounding inferences. Here, we present a 12.5× coverage ancient genome of an Ethiopian male ("Mota") who lived approximately 4500 years ago. We use this genome to demonstrate that the Eurasian backflow into Africa came from a population closely related to Early Neolithic farmers, who had colonized Europe 4000 years earlier. The extent of this backflow was much greater than previously reported, reaching all the way to Central, West, and Southern Africa, affecting even populations such as Yoruba and Mbuti, previously thought to be relatively unadmixed, who harbor 6 to 7% Eurasian ancestry.A.M. was supported by European Research Council (ERC) Consolidator Grant 647787 “LocalAdaptation”; R.P by ERC Starting Grant 263441, “ADNABIOARC”; M.H. by ERC Consolidator Grant 310763 “GeneFlow”; J.B. by the 2014 Research Fund (1.140113.01, 1.140064.01) of UNIST (Ulsan National Institute of Science and Technology) and Geromics internal research funding; J.T.S. by ERC Consolidator Grant 617627 “ADaPt”; K.W.A. by NSF award 1027607; D.G.B. by ERC Investigator Grant 295729-CodeX; V.S. by a scholarship from the Gates Cambridge Trust; and M.G.L. by a Biotechnology and Biological Sciences Research Council (BBSRC) DTP studentship. Permission for the archaeology was given by the Ethiopian Authority for Research and Conservation of Cultural Heritage and offices of the Ministry of Culture and Tourism for the Southern Nations, Nationalities, and Peoples Region. Raw reads from Mota are available for download through the National Center for Biotechnology Information, BioProject ID PRJNA295861, and the corresponding BAM and VCF files are available at africangenome.orgThis is the author accepted manuscript. The final version is available from AAAS via http://dx.doi.org/10.1126/science.aad287

What are the beliefs, attitudes and practices of front-line staff in long-term care (LTC) facilities related to osteoporosis awareness, management and fracture prevention?

<p>Abstract</p> <p>Background</p> <p>Compared to the general elderly population, those institutionalized in LTC facilities have the highest prevalence of osteoporosis and subsequently have higher incidences of vertebral and hip fractures. The goal of this study is to determine how well nurses at LTC facilities are educated to properly administer bisphosphonates. A secondary question assessed was the nurse's and PSW's attitudes and beliefs regarding the role and benefits of vitamin D for LTC patients.</p> <p>Methods</p> <p>Eight LTC facilities in Hamilton were surveyed, and all nurses were offered a survey. A total 57 registered nurses were surveyed. A 21 item questionnaire was developed to assess existing management practices and specific osteoporosis knowledge areas.</p> <p>Results</p> <p>The questionnaire assessed the nurse's and personal support worker's (PSWs) education on how to properly administer bisphosphonates by having them select all applicable responses from a list of options. These options included administering the drug before, after or with meals, given with or separate from other medications, given with juice, given with or without water, given with the patient sitting up, or finally given with the patient supine. Only 52% of the nurses and 8.7% of PSWs administered the drug properly, where they selected the options: (given before meals, given with water, given separate from all other medications, and given in a sitting up position). If at least one incorrect option was selected, then it was scored as an inappropriate administration. Bisphosphonates were given before meals by 85% of nurses, given with water by 90%, given separately from other medication by 71%, and was administered in an upright position by 79%. Only 52% of the nurses and 8.7% of PSWs surveyed were administering the drug properly. Regarding the secondary question, of the 57 nurses surveyed, 68% strongly felt their patients should be prescribed vitamin D supplements. Of the 124 PSWs who completed the survey, 44.4% strongly felt their patients should be prescribed vitamin D supplementation.</p> <p>Conclusion</p> <p>Bisphosphonates are quite effective in increasing the bone mineral density of LTC patients, and may reduce fracture rates, but it is only effective if properly administered. In our study, proper administration of bisphosphonate therapy was less than optimal. In summary, although the education of health providers has improved since the mid-1990's, this area still requires further attention and the subject of future quality assurance research.</p

A Lentivirus-Mediated Genetic Screen Identifies Dihydrofolate Reductase (DHFR) as a Modulator of β-Catenin/GSK3 Signaling

The multi-protein β-catenin destruction complex tightly regulates β-catenin protein levels by shuttling β-catenin to the proteasome. Glycogen synthase kinase 3β (GSK3β), a key serine/threonine kinase in the destruction complex, is responsible for several phosphorylation events that mark β-catenin for ubiquitination and subsequent degradation. Because modulation of both β-catenin and GSK3β activity may have important implications for treating disease, a complete understanding of the mechanisms that regulate the β-catenin/GSK3β interaction is warranted. We screened an arrayed lentivirus library expressing small hairpin RNAs (shRNAs) targeting 5,201 human druggable genes for silencing events that activate a β-catenin pathway reporter (BAR) in synergy with 6-bromoindirubin-3′oxime (BIO), a specific inhibitor of GSK3β. Top screen hits included shRNAs targeting dihydrofolate reductase (DHFR), the target of the anti-inflammatory compound methotrexate. Exposure of cells to BIO plus methotrexate resulted in potent synergistic activation of BAR activity, reduction of β-catenin phosphorylation at GSK3-specific sites, and accumulation of nuclear β-catenin. Furthermore, the observed synergy correlated with inhibitory phosphorylation of GSK3β and was neutralized upon inhibition of phosphatidyl inositol 3-kinase (PI3K). Linking these observations to inflammation, we also observed synergistic inhibition of lipopolysaccharide (LPS)-induced production of pro-inflammatory cytokines (TNFα, IL-6, and IL-12), and increased production of the anti-inflammatory cytokine IL-10 in peripheral blood mononuclear cells exposed to GSK3 inhibitors and methotrexate. Our data establish DHFR as a novel modulator of β-catenin and GSK3 signaling and raise several implications for clinical use of combined methotrexate and GSK3 inhibitors as treatment for inflammatory disease

Imaging of hydrothermal altered zones in Wadi Al-Bana, in southern Yemen, using remote sensing techniques and very low frequency–electromagnetic data

© 2019, Saudi Society for Geosciences. Economic mineralization and hydrothermally altered zones are areas of great economic interests. This study focusses on hydrothermal altered zones of high mineralization potentials in Wadi Al-Bana, in southern Yemen. An azimuthal very low frequency–electromagnetic (AVLF-EM) data acquisition was conducted in search for mineralization in the study area. The study integrated observations from geophysical field data with others extracted from object-oriented principal component analysis (PCA) to better map and understand mineralization in the investigated area. This technique was applied to two data sets, ASTER and Landsat 8 Operational Land Imager (OLI) imagery. The results of PCA revealed high accuracy in detecting alteration minerals and for mapping zones of high concentration of these minerals. The PCA-based distribution of selected alteration zones correlated spatially with high conductivity anomalies in the subsurface that were detected by VLF measurements. Finally, a GIS model was built and successfully utilized to categorize the resulted altered zones, into three levels. [Figure not available: see fulltext.]

Evidence for association between the HLA-DQA locus and abdominal aortic aneurysms in the Belgian population: a case control study

BACKGROUND: Chronic inflammation and autoimmunity likely contribute to the pathogenesis of abdominal aortic aneurysms (AAAs). The aim of this study was to investigate the role of autoimmunity in the etiology of AAAs using a genetic association study approach with HLA polymorphisms. METHODS: HLA-DQA1, -DQB1, -DRB1 and -DRB3-5 alleles were determined in 387 AAA cases (180 Belgian and 207 Canadian) and 426 controls (269 Belgian and 157 Canadian) by a PCR and single-strand oligonucleotide probe hybridization assay. RESULTS: We observed a potential association with the HLA-DQA1 locus among Belgian males (empirical p = 0.027, asymptotic p = 0.071). Specifically, there was a significant difference in the HLA-DQA1*0102 allele frequencies between AAA cases (67/322 alleles, 20.8%) and controls (44/356 alleles, 12.4%) in Belgian males (empirical p = 0.019, asymptotic p = 0.003). In haplotype analyses, marginally significant association was found between AAA and haplotype HLA-DQA1-DRB1 (p = 0.049 with global score statistics and p = 0.002 with haplotype-specific score statistics). CONCLUSION: This study showed potential evidence that the HLA-DQA1 locus harbors a genetic risk factor for AAAs suggesting that autoimmunity plays a role in the pathogenesis of AAAs

Genetic and Physical Interactions between Tel2 and the Med15 Mediator Subunit in Saccharomyces cerevisiae

International audienceBACKGROUND: In budding yeast, the highly conserved Tel2 protein is part of several complexes and its main function is now believed to be in the biogenesis of phosphatidyl inositol 3-kinase related kinases. PRINCIPAL FINDINGS: To uncover potentially novel functions of Tel2, we set out to isolate temperature-sensitive (ts) mutant alleles of TEL2 in order to perform genetic screenings. MED15/GAL11, a subunit of Mediator, a general regulator of transcription, was isolated as a suppressor of these mutants. The isolated tel2 mutants exhibited a short telomere phenotype that was partially rescued by MED15/GAL11 overexpression. The tel2-15 mutant was markedly deficient in the transcription of EST2, coding for the catalytic subunit of telomerase, potentially explaining the short telomere phenotype of this mutant. In parallel, a two-hybrid screen identified an association between Tel2 and Rvb2, a highly conserved member of the AAA+ family of ATPases further found by in vivo co-immunoprecipitation to be tight and constitutive. Transiently overproduced Tel2 and Med15/Gal11 associated together, suggesting a potential role for Tel2 in transcription. Other Mediator subunits, as well as SUA7/TFIIB, also rescued the tel2-ts mutants. SIGNIFICANCE: Altogether, the present data suggest the existence of a novel role for Tel2, namely in transcription, possibly in cooperation with Rvb2 and involving the existence of physical interactions with the Med15/Gal11 Mediator subunit

Structural and Functional Insights into Endoglin Ligand Recognition and Binding

Endoglin, a type I membrane glycoprotein expressed as a disulfide-linked homodimer on human vascular endothelial cells, is a component of the transforming growth factor (TGF)-β receptor complex and is implicated in a dominant vascular dysplasia known as hereditary hemorrhagic telangiectasia as well as in preeclampsia. It interacts with the type I TGF-β signaling receptor activin receptor-like kinase (ALK)1 and modulates cellular responses to Bone Morphogenetic Protein (BMP)-9 and BMP-10. Structurally, besides carrying a zona pellucida (ZP) domain, endoglin contains at its N-terminal extracellular region a domain of unknown function and without homology to any other known protein, therefore called the orphan domain (OD). In this study, we have determined the recognition and binding ability of full length ALK1, endoglin and constructs encompassing the OD to BMP-9 using combined methods, consisting of surface plasmon resonance and cellular assays. ALK1 and endoglin ectodomains bind, independently of their glycosylation state and without cooperativity, to different sites of BMP-9. The OD comprising residues 22 to 337 was identified among the present constructs as the minimal active endoglin domain needed for partner recognition. These studies also pinpointed to Cys350 as being responsible for the dimerization of endoglin. In contrast to the complete endoglin ectodomain, the OD is a monomer and its small angle X-ray scattering characterization revealed a compact conformation in solution into which a de novo model was fitted