Structural decoding of netrin-4 reveals a regulatory function towards mature basement membranes

Netrins, a family of laminin-related molecules, have been proposed to act as guidance cues either during nervous system development or the establishment of the vascular system. This was clearly demonstrated for netrin-1 via its interaction with the receptors DCC and UNC5s. However, mainly based on shared homologies with netrin-1, netrin-4 was also proposed to play a role in neuronal outgrowth and developmental/pathological angiogenesis via interac- tions with netrin-1 receptors. Here, we present the high-resolution structure of netrin-4, which shows unique features in comparison with netrin-1, and show that it does not bind directly to any of the known netrin-1 receptors. We show that netrin-4 disrupts laminin networks and basement membranes (BMs) through high-affinity binding to the laminin g1 chain. We hypothesize that this laminin-related function is essential for the previously described effects on axon growth promotion and angiogenesis. Our study unveils netrin-4 as a non-enzymatic extracellular matrix protein actively disrupting pre-existing BMs

Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain

Back pain is the #1 cause of years lived with disability worldwide, yet surprisingly little is known regarding the biology underlying this symptom. We conducted a genome-wide association study (GWAS) meta-analysis of ch

Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance

Brain malformations involving the corpus callosum are common in children with developmental disabilities. We identified DCC mutations in four families and five sporadic individuals with isolated agenesis of the corpus callosum (ACC) without intellectual disability. DCC mutations result in variable dominant phenotypes with decreased penetrance, including mirror movements and ACC associated with a favorable developmental prognosis. Possible phenotypic modifiers include the type and location of mutation and the sex of the individual

Updating the approaches to define susceptibility and resistance to anti-tuberculosis agents: implications for diagnosis and treatment

11 páginas, 2 figuras, 1 tablaInappropriately high breakpoints have resulted in systematic false-susceptible AST results to anti-TB drugs. MIC, PK/PD and clinical outcome data should be combined when setting breakpoints to minimise the emergence and spread of antimicrobial resistance.I. Comas was supported by PID2019-104477RB-I00 from the Spanish Science Ministry and by ERC (CoG 101001038)Peer reviewe

Universal Mosaicing using Pipe Projection

Video mosaicing is commonly used to increase the visual field of view by pasting together many video frames. Existing mosaicing methods are effective only in very limited cases where the image motion is almost a uniform translation or the camera performs a pure pan. Forward camera motion or camera zoom are very problematic for traditional mosaicing. A mosaicing methodology..

Mosaicing with Generalized Strips

Video mosaicing is commonly used to increase the effective visual field of view. Existing mosaicing methods are based on image alignment, and are effective only in very limited cases. To overcome most restrictions, mosaicing is presented in this paper as a process of collecting strips. Strips which are perpendicular to the optical flow are cut out of the images, and are warped so that within each strip the optical flow will be parallel. These strips are then pasted into the mosaic. This approach enables to define mosaicing even for cases of forward motion and for zoom. View interpolation, generating dense intermediate views, is used to overcome parallax effects. 1 Introduction An introduction and a survey of mosaicing methods can be found in [6]. We will only give a brief introduction focusing on the aspects relevant to this work. Early mosaicing methods were used for aerial and satellite images. In both cases the objects in the scene are distant from the camera, and camera motion co..