PEDIA: prioritization of exome data by image analysis.

PURPOSE: Phenotype information is crucial for the interpretation of genomic variants. So far it has only been accessible for bioinformatics workflows after encoding into clinical terms by expert dysmorphologists. METHODS: Here, we introduce an approach driven by artificial intelligence that uses portrait photographs for the interpretation of clinical exome data. We measured the value added by computer-assisted image analysis to the diagnostic yield on a cohort consisting of 679 individuals with 105 different monogenic disorders. For each case in the cohort we compiled frontal photos, clinical features, and the disease-causing variants, and simulated multiple exomes of different ethnic backgrounds. RESULTS: The additional use of similarity scores from computer-assisted analysis of frontal photos improved the top 1 accuracy rate by more than 20-89% and the top 10 accuracy rate by more than 5-99% for the disease-causing gene. CONCLUSION: Image analysis by deep-learning algorithms can be used to quantify the phenotypic similarity (PP4 criterion of the American College of Medical Genetics and Genomics guidelines) and to advance the performance of bioinformatics pipelines for exome analysis

Geomorphological and sedimentary processes of the glacially influenced northwestern Iberian continental margin and abyssal plains

The offshore region of northwestern Iberia offers an opportunity to study the impacts of along-slope processes on the morphology of a glacially influenced continental margin, which has traditionally been conceptually characterised by predominant down-slope sedimentary processes. High-resolution multibeam bathymetry, acoustic backscatter and ultrahigh-resolution seismic reflection profile data are integrated and analysed to describe the present-day and recent geomorphological features and to interpret their associated sedimentary processes. Seventeen large-scale seafloor morphologies and sixteen individual echo types, interpreted as structural features (escarpments, marginal platforms and related fluid escape structures) and depositional and erosional bedforms developed either by the influence of bottom currents (moats, abraded surfaces, sediment waves, contourite drifts and ridges) or by gravitational features (gullies, canyons, slides, channel-levee complexes and submarine fans), are identified for the first time in the study area (spanning ~90,000 km2 and water depths of 300m to 5 km). Different types of slope failures and turbidity currents are mainly observed on the upper and lower slopes and along submarine canyons and deep-sea channels. The middle slope morphologies are mostly determined by the actions of bottom currents (North Atlantic Central Water, Mediterranean Outflow Water, Labrador Sea Water and North Atlantic Deep Water), which thereby define the margin morphologies and favour the reworking and deposition of sediments. The abyssal plains (Biscay and Iberian) are characterised by pelagic deposits and channel-lobe systems (the Cantabrian and Charcot), although several contourite features are also observed at the foot of the slope due to the influence of the deepest water masses (i.e., the North Atlantic Deep Water and Lower Deep Water). Thiswork shows that the study area is the result of Mesozoic to present-day tectonics (e.g. themarginal platforms and structural highs). Therefore, tectonism constitutes a long-term controlling factor, whereas the climate, sediment supply and bottom currents play key roles in the recent short-term architecture and dynamics. Moreover, the recent predominant along-slope sedimentary processes observed in the studied northwestern Iberian Margin represent snapshots of the progressive stages and mixed deep-water system developments of the marginal platforms on passive margins and may provide information for a predictive model of the evolution of other similar margins.Departamento de Investigación y Prospectiva Geocientífica, Unidad de Tres Cantos, Instituto Geológico y Minero de España, EspañaDepartamento de Geología y Geoquímica, Universidad Autónoma de Madrid, EspañaDepartment of Earth Sciences, Royal Holloway University of London, Reino Unid

Acceso al suelo ejidal periurbano: análisis desde el capital social

Recientemente, el modo más recurrente para acceder al suelo ejidal en las periferias urbanas mexicanas es mediante mecanismos de compra-venta, estos procesos están caracterizados por la multiplicidad de actores, normas y marcos jurídicos, así como por la regulación de las instituciones formales e informales. En este trabajo se aborda dicho proceso a través del concepto de capital social, el cual ofrece elementos que permiten el reconocimiento y la sistematización en un contexto de periferia urbana convergente y transicional. Con base en una revisión de la literatura se hace una propuesta analítica de la compra-venta de tierras parceladas desde el capital social, se reconocen sus etapas, dimensiones, relaciones y elementos principales

Alprostadil suppresses angiogenesis in vitro and in vivo in the murine Matrigel plug assay

1. Prostaglandin E(1) (PGE(1), alprostadil) is used as a vasodilator for the treatment of peripheral vascular diseases. 2. Previous reports suggested a pro-angiogenic effect for PGE(1). 3. We studied the in vitro and in vivo effect of PGE(1), complexed with α-cyclodextrin, on the angiogenic process. Contrary to what was expected, we found that, in human umbilical vein endothelial cells (HUVECs), PGE(1) inhibited proliferation, migration and capillary-like structure formation in Matrigel. 4. By RT–PCR studies, the expression of the EP(2) and EP(3) subtypes of the PG receptor was detected in HUVECs. 5. PGE(1) alone stimulated adenylate cyclase activity at micromolar concentrations, while at nanomolar concentrations potentiated the forskolin-induced cAMP accumulation. 6. 8-Bromoadenosine-3′:5′-cyclic monophosphate (Br-cAMP) mimicked the inhibitory effect of PGE(1) on endothelial cell growth, motility and tube formation. 7. Sulprostone, an agonist at the EP(3) subtype of PG receptors, mimicked the in vitro anti-angiogenic effects of PGE(1), while butaprost, an EP(2) receptor agonist, had no effect. 8. Finally, in the plug assay model of angiogenesis in mice, PGE(1) showed a strong inhibitory effect on Matrigel neovascularization. 9. Thus, PGE(1) possesses strong anti-angiogenic activity in vitro and in vivo