161 research outputs found

    Orbital evidence for clay and acidic sulfate assemblages on Mars based on mineralogical analogs from Rio Tinto, Spain

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    Outcrops of hydrated minerals are widespread across the surface of Mars, with clay minerals and sulfates being commonly identified phases. Orbitally-based reflectance spectra are often used to classify these hydrated components in terms of a single mineralogy, although most surfaces likely contain multiple minerals that have the potential to record local geochemical conditions and processes. Reflectance spectra for previously identified deposits in Ius and Melas Chasma within the Valles Marineris, Mars, exhibit an enigmatic feature with two distinct absorptions between 2.2 and 2.3 ”m. This spectral ‘doublet’ feature is proposed to result from a mixture of hydrated minerals, although the identity of the minerals has remained ambiguous. Here we demonstrate that similar spectral doublet features are observed in airborne, field, and laboratory reflectance spectra of rock and sediment samples from Rio Tinto, Spain. Combined visible-near infrared reflectance spectra and X-ray diffraction measurements of these samples reveal that the doublet feature arises from a mixture of Al-phyllosilicate (illite or muscovite) and jarosite. Analyses of orbital data from the Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) shows that the martian spectral equivalents are also consistent with mixtures of Al-phyllosilicates and jarosite, where the Al-phyllosilicate may also include kaolinite and/or halloysite. A case study for a region within Ius Chasma demonstrates that the relative proportions of the Al-phyllosilicate(s) and jarosite vary within one stratigraphic unit as well as between stratigraphic units. The former observation suggests that the jarosite may be a diagenetic (authigenic) product and thus indicative of local pH and redox conditions, whereas the latter observation may be consistent with variations in sediment flux and/or fluid chemistry during sediment deposition.Organismic and Evolutionary Biolog

    DHODH modulates transcriptional elongation in the neural crest and melanoma

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    Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma1. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation

    Construction kits or virtual worlds; management applications of E2E models

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    Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Journal of Marine Systems 109/110 (2013): 103-108, doi:10.1016/j.jmarsys.2011.10.016.We review briefly the diversity of modeling activity that comes under the rubric of end-to-end (E2E) models, but the focus of this paper – of joint concern to researchers and to managers - is on applications to management and decision making. The models and applications span a range from “construction kits” that identify particular management issues and use comparisons across ecosystems; to “virtual worlds” that immerse managers in the details of strategic evaluations for particular systems. The general conclusion is that “application” is not a straightforward transition from theory to practice but a complex interactive process.This review is based on the proceedings of a workshop, held at Woods Hole Oceanographic Institution, 19-22 April 2010, as part of CAMEO (Comparative Analysis of Marine Ecosystem Organization), a program supported jointly by NOAA (U.S. National Oceanic and Atmospheric Agency) and NSF (U.S. National Science Foundation)

    Internal validation of STRmixℱ – A multi laboratory response to PCAST

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    We report a large compilation of the internal validations of the probabilistic genotyping software STRmixℱ. Thirty one laboratories contributed data resulting in 2825 mixtures comprising three to six donors and a wide range of multiplex, equipment, mixture proportions and templates. Previously reported trends in the LR were confirmed including less discriminatory LRs occurring both for donors and non-donors at low template (for the donor in question) and at high contributor number. We were unable to isolate an effect of allelic sharing. Any apparent effect appears to be largely confounded with increased contributor number

    ‘Fourth places’: the Contemporary Public Settings for Informal Social Interaction among Strangers.

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    This paper introduces ‘fourth places’ as an additional category of informal social settings alongside ‘third places’ (Oldenburg 1989). Through extensive empirical fieldwork on where and how social interaction among strangers occurs in the public and semi-public spaces of a contemporary masterplanned neighbourhood, this paper reveals that ‘fourth places’ are closely related to ‘third places’ in terms of social and behavioural characteristics, involving a radical departure from the routines of home and work, inclusivity, and social comfort. However, the activities, users, locations and spatial conditions that support them are very different. They are characterized by ‘in-betweenness’ in terms of spaces, activities, time and management, as well as a great sense of publicness. This paper will demonstrate that the latter conditions are effective in breaking the ‘placelessness’ and ‘fortress’ designs of newly designed urban public spaces and that, by doing so, they make ‘fourth places’ sociologically more open in order to bring strangers together. The recognition of these findings problematizes well-established urban design theories and redefines several spatial concepts for designing public space. Ultimately, the findings also bring optimism to urban design practice, offering new insights into how to design more lively and inclusive public spaces. Keywords: ‘Fourth places’, Informal Public Social Settings, Social Interaction, Strangers, Public Space Design

    Bioenergetic status modulates motor neuron vulnerability and pathogenesis in a zebrafish model of spinal muscular atrophy

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    Degeneration and loss of lower motor neurons is the major pathological hallmark of spinal muscular atrophy (SMA), resulting from low levels of ubiquitously-expressed survival motor neuron (SMN) protein. One remarkable, yet unresolved, feature of SMA is that not all motor neurons are equally affected, with some populations displaying a robust resistance to the disease. Here, we demonstrate that selective vulnerability of distinct motor neuron pools arises from fundamental modifications to their basal molecular profiles. Comparative gene expression profiling of motor neurons innervating the extensor digitorum longus (disease-resistant), gastrocnemius (intermediate vulnerability), and tibialis anterior (vulnerable) muscles in mice revealed that disease susceptibility correlates strongly with a modified bioenergetic profile. Targeting of identified bioenergetic pathways by enhancing mitochondrial biogenesis rescued motor axon defects in SMA zebrafish. Moreover, targeting of a single bioenergetic protein, phosphoglycerate kinase 1 (Pgk1), was found to modulate motor neuron vulnerability in vivo. Knockdown of pgk1 alone was sufficient to partially mimic the SMA phenotype in wild-type zebrafish. Conversely, Pgk1 overexpression, or treatment with terazosin (an FDA-approved small molecule that binds and activates Pgk1), rescued motor axon phenotypes in SMA zebrafish. We conclude that global bioenergetics pathways can be therapeutically manipulated to ameliorate SMA motor neuron phenotypes in vivo

    A genome-wide association study of anorexia nervosa.

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    Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field

    Correlation analysis of the transcriptome of growing leaves with mature leaf parameters in a maize RIL population

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