Shaping Skeletal Growth by Modular Regulatory Elements in the Bmp5 Gene

Cartilage and bone are formed into a remarkable range of shapes and sizes that underlie many anatomical adaptations to different lifestyles in vertebrates. Although the morphological blueprints for individual cartilage and bony structures must somehow be encoded in the genome, we currently know little about the detailed genomic mechanisms that direct precise growth patterns for particular bones. We have carried out large-scale enhancer surveys to identify the regulatory architecture controlling developmental expression of the mouse Bmp5 gene, which encodes a secreted signaling molecule required for normal morphology of specific skeletal features. Although Bmp5 is expressed in many skeletal precursors, different enhancers control expression in individual bones. Remarkably, we show here that different enhancers also exist for highly restricted spatial subdomains along the surface of individual skeletal structures, including ribs and nasal cartilages. Transgenic, null, and regulatory mutations confirm that these anatomy-specific sequences are sufficient to trigger local changes in skeletal morphology and are required for establishing normal growth rates on separate bone surfaces. Our findings suggest that individual bones are composite structures whose detailed growth patterns are built from many smaller lineage and gene expression domains. Individual enhancers in BMP genes provide a genomic mechanism for controlling precise growth domains in particular cartilages and bones, making it possible to separately regulate skeletal anatomy at highly specific locations in the body

Conflitos pela água em tempos de seca no Baixo Jaguaribe, Estado do Ceará

Este trabalho analisa os impactos ambientais e socioeconômicos da seca de 2012 a 2014 na microrregião do Baixo Jaguaribe do estado do Ceará, com o objetivo de compreender como a população reage à crise ambiental, seja pela aprendizagem e auto-organização a partir da experiência de escassez, seja pelo aumento dos conflitos por acesso à água. Verifica-se que houve o desaparecimento de lagoas e açudes equivalente a uma área de 300 km2, entre 2009 e 2014, em dois municípios da região. Ademais, pode-se destacar o surgimento de conflitos socioambientais em razão da escassez de água, mesmo em um dos territórios mais privilegiados do Semiárido com a presença de rios, lagoas e açudes. Há conflitos associados ao acesso e distribuição da água entre as empresas dos perímetros irrigados, os pequenos agricultores, a Região Metropolitana de Fortaleza, a população de municípios da região e o Movimento dos Trabalhadores Rurais sem Terra (MST)

The assessment of an existing RC framed structure: a case study on a collapsed building

The total collapse of a building in L’Aquila, Via D’Annunzio (D’Annunzio Street), located at about 6 km from the epicenter of the earthquake of April 6 2009, is here analyzed. The reinforced concrete moment-resisting frames were designed in the 1961 according to the Italian Seismic Code of 1937, and failed with a “pancake-type collapse”, with a very high death toll of 13 casualties. At the beginning of 2013, the first Author was appointed by the legal authority to investigate the reasons for the collapse. Studies were partly based on the on-site investigations performed during the summer 2009, including tests on the concrete properties, analysis of the ground properties and exam of parts of the collapsed structure recovered from the debris. Due to the lack of a complete set of design blueprints, the dimensions and positions of the columns, as well as the geometry of the reinforcement, were obtained by an on-site series of measurements during 2013. The range of variation of natural periods and modal shapes depending on the modeling assumptions have been determined through numerical analyses. The seismic excitation at the site, determined from the earthquake records and the ground properties coming from down-hole tests, has been provided in terms of time history and response spectrum. When all the factors affecting the seismic behavior are taken into account, the collapse of the building can be explained; the collapse mechanism resembles the modal shape of the first mode. The flaws of the original design, brought to light with this study, can be assumed as typical for the design time and provide clear indications on the critical points to be checked when assessing an RC frame of the sixties

An uncoupled approach for vehicle bridge interaction analysis

A formulation of the coupled equations of motion for the bridge-vehicle dynamic interaction problem is proposed. This is derived through the Lagrange’s equation and adopts a compatibility condition at the interface bridge-vehicle, assuming that the two systems are always in contact. The pavement roughness can be considered in a simple way, through a roughness profile either generated from a PSD spectrum or based on experimental data. The coupled equations are forcibly uncoupled, moving the coupling terms to the RHS of the equations as forcing terms. The equilibrium condition at the interface, stated by the action-reaction principle, is then imposed through an iterative solution. Two iteration strategies are developed in the time domain; leaving generality to the iterative approach, separate and uncoupled mechanical models for the vehicle and the bridge are adopted. Both strategies consider: (a) a vehicle moving on the bridge at constant velocity along a straight direction, transmitting vertical contact forces to the bridge; (b) the sum of contributions from the bridge deflection and the pavement roughness as prescribed motion at the wheels of the vehicle. Procedure WTH iterates over the whole time-history and relies on a general purpose FE code for the structure; an ad hoc code has been developed for the vehicle. Thus, the bridge is subjected to the time history of contact forces, the vehicle is subjected to the time history of prescribed displacements and velocities. Convergence on contact forces involves the rms values during the whole time history. Procedure STS is implemented in an ad hoc developed code that needs the stiffness and mass matrix of the structure as input data. A two-phase iteration strategy within each time step is adopted; in the predicting phase the vehicle is moved to the step final position, in the correcting phase the forces transmitted by the vehicle are updated with the current values of the bridge displacement and velocities. The convergence check involves the variation of contact forces from an iteration to the next one. The first numerical studies are performed on a simply supported RC bridge, considering a 3D, 7DOFs vehicle model and two simpler 2D, 1 DOF and 4DOFs ones

Role of iron load on fibrogenesis in chronic hepatitis C

BACKGROUND/AIMS: In chronic viral hepatitis, an enhanced iron load is related to lower response to interferon. Furthermore, iron, through the production of oxygen radicals, may stimulate hepatocyte necrosis and the activation of cells responsible for synthesis and deposition of extracellular matrix. We investigated the relationship between iron load, evaluated by serum assays, and liver fibrogenesis in chronic active viral hepatitis. METHODOLOGY: Serum iron, ferritin, transferrin saturation and serum markers of hepatic fibrogenesis (Laminin and the amino-terminal peptide of procollagen III-NPIIIP-) were assayed in 102 patients (47 females, 55 males, mean age 42.48 years) affected by chronic hepatitis C virus and in 81 healthy controls (47 males, 34 females). In hepatitis C virus patients (studied before alpha-interferon treatment) a semiquantitative score for portal inflammation, necrosis and fibrosis was applied to liver biopsy. RESULTS: Serum indices of iron load were higher in hepatitis C virus patients than in controls, and were higher in cirrhotic than in chronic hepatitis cases. Ferritin and serum iron were positively correlated with NPIIIP and laminin; moreover cases with ferritin levels over the normal limit for sex and age had higher levels of NPIIIP and laminin than cases with normal or poor iron status. CONCLUSIONS: Our data suggest that even a mild increase of iron load stimulates hepatic fibrogenesis, probably adding oxygen free radical injury to the damage of viral infection

A long term study of hepatitis G virus coinfection in chronic hepatitis B

Hepatology 1997; Suppl. 2: 321