Structural relationships between the endogenous volatile urinary metabolites of experimentally diabetic rats and certain neurotoxins

Summary High resolution glass capillary gas chromatography and GC/MS were utilized to examine qualitative and quantitative variations from normal of urinary volatile metabolites of long-term alloxan and streptozotocin diabetic rats. Volatile metabolites were structurally compared with known neurotoxins to examine any possible relationship between these metabolites and the development of the diabetic polyneuropathy.Acknowledgment. This research was supported by grant No. 24349 from the National Institute of General Medical Sciences, U.S. Public Health Service.     

A comparison of the degree of chimaerism produced when allogeneic cells from four different tissues are used to create tolerance in the mouse

Résumé La tolérance immunologique produite chez la souris avec les cellules de foie d'embryon, ou des cellules de rate, de tissus lymphoïdes ou de moelle osseuse d'adulte, a été comparée au degré de chimérisme. Le foie d'embryon a produit le plus haut degré de chimérisme (10,7%).     

The regeneration of accessory limb parts following epidermal cap transplantation in urodeles

Résumé Les événements morphogénétiques qui suivent le greffage d'un blastème apical à la face préaxiale d'un membre antérieur en voie régénératrice, chezAmbystoma, sont tout à fait normaux, mais le niveau où se localise le régénérat accessoire est différent selon l'espèce utilisé. Ces résultats sont discutés au point de vue du stimulus d'agrégation des cellules appartenant au régénérat accessoire.

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This work was supported by a research grant (NB 04128) from the National Institute of Neurological Diseases and Blindness, National Institutes of Health.     

Evolution of the extracellular space in immature nervous tissue

Resumen En el cerebelo de rata recién nacida existen espacios extracelulares mayores que 1000 Å los cuales progresivamente se reducen hasta que en la tercera semana, como en el adulto, las celulas y fibras se hallan separadas por endiduras de 150–200 Å. Estas observaciones indican que el reducido espacio usualmente hallado en el adulto no es un artificio tecnico como ha sido sugerido por algunos autores.     

TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function

Progressive kidney failure is a genetically and clinically heterogeneous group of disorders. Podocyte foot processes and the interposed glomerular slit diaphragm are essential components of the permeability barrier in the kidney. Mutations in genes encoding structural proteins of the podocyte lead to the development of proteinuria, resulting in progressive kidney failure and focal segmental glomerulosclerosis. Here, we show that the canonical transient receptor potential 6 (TRPC6) ion channel is expressed in podocytes and is a component of the glomerular slit diaphragm. We identified five families with autosomal dominant focal segmental glomerulosclerosis in which disease segregated with mutations in the gene TRPC6 on chromosome 11q. Two of the TRPC6 mutants had increased current amplitudes. These data show that TRPC6 channel activity at the slit diaphragm is essential for proper regulation of podocyte structure and function.     

A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2

We report heterozygous mutations in the genes encoding either type I or type II transforming growth factor beta receptor in ten families with a newly described human phenotype that includes widespread perturbations in cardiovascular, craniofacial, neurocognitive and skeletal development. Despite evidence that receptors derived from selected mutated alleles cannot support TGFbeta signal propagation, cells derived from individuals heterozygous with respect to these mutations did not show altered kinetics of the acute phase response to administered ligand. Furthermore, tissues derived from affected individuals showed increased expression of both collagen and connective tissue growth factor, as well as nuclear enrichment of phosphorylated Smad2, indicative of increased TGFbeta signaling. These data definitively implicate perturbation of TGFbeta signaling in many common human phenotypes, including craniosynostosis, cleft palate, arterial aneurysms, congenital heart disease and mental retardation, and suggest that comprehensive mechanistic insight will require consideration of both primary and compensatory events.     

The structure of the myosin VI motor reveals the mechanism of directionality reversal

Here we solve a 2.4-A structure of a truncated version of the reverse-direction myosin motor, myosin VI, that contains the motor domain and binding sites for two calmodulin molecules. The structure reveals only minor differences in the motor domain from that in plus-end directed myosins, with the exception of two unique inserts. The first is near the nucleotide-binding pocket and alters the rates of nucleotide association and dissociation. The second unique insert forms an integral part of the myosin VI converter domain along with a calmodulin bound to a novel target motif within the insert. This serves to redirect the effective 'lever arm' of myosin VI, which includes a second calmodulin bound to an 'IQ motif', towards the pointed (minus) end of the actin filament. This repositioning largely accounts for the reverse directionality of this class of myosin motors. We propose a model incorporating a kinesin-like uncoupling/docking mechanism to provide a full explanation of the movements of myosin VI.     

Imaging the Indian subcontinent beneath the Himalaya

The rocks of the Indian subcontinent are last seen south of the Ganges before they plunge beneath the Himalaya and the Tibetan plateau. They are next glimpsed in seismic reflection profiles deep beneath southern Tibet, yet the surface seen there has been modified by processes within the Himalaya that have consumed parts of the upper Indian crust and converted them into Himalayan rocks. The geometry of the partly dismantled Indian plate as it passes through the Himalayan process zone has hitherto eluded imaging. Here we report seismic images both of the decollement at the base of the Himalaya and of the Moho (the boundary between crust and mantle) at the base of the Indian crust. A significant finding is that strong seismic anisotropy develops above the decollement in response to shear processes that are taken up as slip in great earthquakes at shallower depths. North of the Himalaya, the lower Indian crust is characterized by a high-velocity region consistent with the formation of eclogite, a high-density material whose presence affects the dynamics of the Tibetan plateau.