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.     

Quinone tanning in Agnatha

Summary The buccal teeth and notochordal sheath of the marine hagfish,Petromyzon marinus (L.) are phenolically tanned like the cuticle of insects and other arthropods.Acknowledgments. We are grateful to Dr Bill Lovejoy for generously supplyingP. marinus L. A.R.V. is thankful to Prof. R.G. Michael for encouragement.Previously called A. Sannasi.     

On the contribution of boundaries towards strength in oxygen free high conductivity copper subjected to repetitive upsetting–extrusion

Oxygen free high conductivity (OFHC) copper was subjected to 1, 5, 10, 15 and 20 cycles of repetitive upsetting and extrusion (RUE) process at room temperature. Microstructure and microhardness in the RUE processed material were evaluated at specific locations and correlated with the equivalent plastic strain. The microhardness of the material was found to be independent of strain or number of RUE cycles at certain locations whereas it exhibited strain softening behaviour at certain locations even though significant grain refinement was achieved. This difference in behaviour is attributed to the varied strength contribution from different types of boundaries present in the material after deformation.     

Modeling the hot working behavior of near-α tita nium alloy IMI 834

The hot working behavior of near-a titanium alloy IMI 834 with a duplex starting microstructure was studied using the technique of processing map.The processing map was interpreted in terms of the microstrucmral processes occurring during deformation,based on the values of dimensionless parameter η which represents the energy dissipation through microstructural processes.An instability criterion（ξ<0） was also applied to demarcate the flow instability regions in the processing map.Both the parameters（η and ξ） were computed using the experimental data generated by carrying out hot compression tests over a range of temperatures（850-1060℃） and strain rates(3×10^-4-1/s).The deterministic domains observed under the investigated temperature and strain rate conditions were attributed to continuous dynamic recrystallization or globularisation of a lamellae,dynamic recrystallization and growth of β grains through microstructural observations.An unified strain compensated constitutive equation was established to describe the hot working behavior of the material in the selected temperature-strain rate range.The established constitutive equation was validated using standard statistical parameters such as correlation coefficient and average absolute relative error.     

ON and OFF pathways in Drosophila motion vision

Motion vision is a major function of all visual systems, yet the underlying neural mechanisms and circuits are still elusive. In the lamina, the first optic neuropile of Drosophila melanogaster, photoreceptor signals split into five parallel pathways, L1-L5. Here we examine how these pathways contribute to visual motion detection by combining genetic block and reconstitution of neural activity in different lamina cell types with whole-cell recordings from downstream motion-sensitive neurons. We find reduced responses to moving gratings if L1 or L2 is blocked; however, reconstitution of photoreceptor input to only L1 or L2 results in wild-type responses. Thus, the first experiment indicates the necessity of both pathways, whereas the second indicates sufficiency of each single pathway. This contradiction can be explained by electrical coupling between L1 and L2, allowing for activation of both pathways even when only one of them receives photoreceptor input. A fundamental difference between the L1 pathway and the L2 pathway is uncovered when blocking L1 or L2 output while presenting moving edges of positive (ON) or negative (OFF) contrast polarity: blocking L1 eliminates the response to moving ON edges, whereas blocking L2 eliminates the response to moving OFF edges. Thus, similar to the segregation of photoreceptor signals in ON and OFF bipolar cell pathways in the vertebrate retina, photoreceptor signals segregate into ON-L1 and OFF-L2 channels in the lamina of Drosophila.     

Visual transduction in Drosophila

The brain's capacity to analyse and interpret information is limited ultimately by the input it receives. This sets a premium on information capacity of sensory receptors, which can be maximized by optimizing sensitivity, speed and reliability of response. Nowhere is selection pressure for information capacity stronger than in the visual system, where speed and sensitivity can mean the difference between life and death. Phototransduction in flies represents the fastest G-protein-signalling cascade known. Analysis in Drosophila has revealed many of the underlying molecular strategies, leading to the discovery and characterization of signalling molecules of widespread importance.