A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndrome

Opitz-Kaveggia syndrome (also known as FG syndrome) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation. We report here that the original family for whom the condition is named and five other families have a recurrent mutation (2881C>T, leading to R961W) in MED12 (also called TRAP230 or HOPA), a gene located at Xq13 that functions as a thyroid receptor-associated protein in the Mediator complex.     

The coming-to-be of Hansen’s method

This article by Curtis Wilson is an account of the origin of Hansen’s powerful systematic method for finding contributions of higher order perturbations in celestial mechanics. Hansen’s method was developed in the course of improving on Laplace’s treatment of the mutual perturbations of Jupiter and Saturn. This method, an entirely new way of doing celestial mechanics when it first appeared, later made possible the successful treatment of the complicated motions of our moon (see Wilson 2010). In this paper Wilson gives a brief historical introduction followed by an account of relevant technical details of the Laplacian background, an account illustrating technical details in Hansen’s initial development in his Disquisitions of 1829, and a treatment illustrating details contributing to the achievement of Hansen’s more refined development in his Untersuchung of 1831. These details include conditional equations Hansen provides for checking the accuracy of calculations. Wilson also includes a detailed assessment showing the extraordinary improvement in empirical accuracy of Hansen’s treatment over the best earlier treatment of the Jupiter-Saturn  interactions.     

Chromatin-remodeling complex specificity and embryonic vascular development

Vascular development is a dynamic process that relies on the coordinated expression of numerous genes, but the factors that regulate gene expression during blood vessel development are not well defined. ATP-dependent chromatin-remodeling complexes are gaining attention for their specific temporal and spatial effects on gene expression during vascular development. Genetic mutations in chromatin-remodeling complex subunits are revealing roles for the complexes in vascular signaling pathways at discrete developmental time points. Phenotypic analysis of these models at various stages of vascular development will continue to expand our understanding of how chromatin remodeling impacts new blood vessel growth. Such research could also provide novel therapeutic targets for the treatment of vascular pathologies.     

The ATP-binding cassette family: a structural perspective

The ATP-binding cassette family is one of the largest groupings of membrane proteins, moving allocrites across lipid membranes, using energy from ATP. In bacteria, they reside in the inner membrane and are involved in both uptake and export. In eukaryotes, these transporters reside in the cell’s internal membranes as well as in the plasma membrane and are unidirectional—out of the cytoplasm. The range of substances that these proteins can transport is huge, which makes them interesting for structure–function studies. Moreover, their abundance in nature has made them targets for structural proteomics consortia. There are eight independent structures for ATP-binding cassette transporters, making this one of the best characterised membrane protein families. Our understanding of the mechanism of transport across membranes and membrane protein structure in general has been enhanced by recent developments for this family.     

6-Methoxymellein as a phytoalexin

Résumé Le dihydroisocoumarin (I) était considéré comme un « phytoalexin » produit par des carottes infectées deCeratocystis fimbriata. Mais l'isocoumarin (II), de structure apparentée ayant été dégagé d'une culture de ce champignon sur bouillon synthétique, on peut douter que (I) tire son origine des carottes.     

TRPV3 is a calcium-permeable temperature-sensitive cation channel

Transient receptor potential (TRP) proteins are cation-selective channels that function in processes as diverse as sensation and vasoregulation. Mammalian TRP channels that are gated by heat and capsaicin (>43 degrees C; TRPV1 (ref. 1)), noxious heat (>52 degrees C; TRPV2 (ref. 2)), and cooling (< 22 degrees C; TRPM8 (refs 3, 4)) have been cloned; however, little is known about the molecular determinants of temperature sensing in the range between approximately 22 degrees C and 40 degrees C. Here we have identified a member of the vanilloid channel family, human TRPV3 (hTRPV3) that is expressed in skin, tongue, dorsal root ganglion, trigeminal ganglion, spinal cord and brain. Increasing temperature from 22 degrees C to 40 degrees C in mammalian cells transfected with hTRPV3 elevated intracellular calcium by activating a nonselective cationic conductance. As in published recordings from sensory neurons, the current was steeply dependent on temperature, sensitized with repeated heating, and displayed a marked hysteresis on heating and cooling. On the basis of these properties, we propose that hTRPV3 is thermosensitive in the physiological range of temperatures between TRPM8 and TRPV1.