The Role of Mislocalized Phototransduction in Photoreceptor Cell Death of Retinitis Pigmentosa

Most of inherited retinal diseases such as retinitis pigmentosa (RP) cause photoreceptor cell death resulting in blindness. RP is a large family of diseases in which the photoreceptor cell death can be caused by a number of pathways. Among them, light exposure has been reported to induce photoreceptor cell death. However, the detailed mechanism by which photoreceptor cell death is caused by light exposure is unclear. In this study, we have shown that even a mild light exposure can induce ectopic phototransduction and result in the acceleration of rod photoreceptor cell death in some vertebrate models. In ovl, a zebrafish model of outer segment deficiency, photoreceptor cell death is associated with light exposure. The ovl larvae show ectopic accumulation of rhodopsin and knockdown of ectopic rhodopsin and transducin rescue rod photoreceptor cell death. However, knockdown of phosphodiesterase, the enzyme that mediates the next step of phototransduction, does not. So, ectopic phototransduction activated by light exposure, which leads to rod photoreceptor cell death, is through the action of transducin. Furthermore, we have demonstrated that forced activation of adenylyl cyclase in the inner segment leads to rod photoreceptor cell death. For further confirmation, we have also generated a transgenic fish which possesses a human rhodopsin mutation, Q344X. This fish and rd10 model mice show photoreceptor cell death caused by adenylyl cyclase. In short, our study indicates that in some RP, adenylyl cyclase is involved in photoreceptor cell death pathway; its inhibition is potentially a logical approach for a novel RP therapy

Nanofibers Technology: History and Developments

International audienc

Spatial heterogeneity of high-resolution Chalk groundwater geochemistry – Underground quarry at Saint Martin-le-Noeud, France

International audienceChalk groundwater is an important aquifer resource in France because it accounts for a production of 12 million m3 y-1 with a large proportion reserved for drinking water. Processes occurring in the unsaturated zone (UZ) and the overlying superficial formations have a high impact on Chalk groundwater geochemistry and require better understanding. The study site is a former underground Chalk quarry located near Beauvais (France) that extends over 1200 m in length, at a depth ranging from 20 to 30 m. The water table intersects the cavity creating 15 underground "lake" that give access to the Chalk groundwater. Lakes geochemistry has been studied: water samples were collected in July 2013 and major ion concentrations were analyzed. UZ and clay-with-flints thickness above each lake were estimated qualitatively using an electromagnetic sensor (EM31) and Underground GPS. The results unexpectedly showed that groundwater quality varied widely in spatial terms for both allochthonous and autochthonous ions (e.g., HCO3- ranged from 2.03 to 4.43 meq L-1, NO3- ranged from 0.21 to 1.33 meq L-1). Principal component analysis indicated the impact of agricultural land use on water quality, with the intake of NO3- as well as SO42-, Cl- and Ca2+. Chalk groundwater geochemistry is compared with the nature and structure of the UZ. We highlight correlations (1) between thick clay-with-flints layers and the ions Mg2+ and K+, and (2) between UZ thickness and Na+. In conclusion, this paper identifies various ion sources (agriculture, clay-with-flints and Chalk) and demonstrates different processes in the UZ: dissolution, ionic exchange and solute storage

Salt-Induced Universal Slowing Down of the Short-Time Self-Diffusion of a Globular Protein in Aqueous Solution

The short-time self-diffusion D of the globular model protein bovine serum albumin in aqueous (D2O) solutions has been measured comprehensively as a function of the protein and trivalent salt (YCl3) concentration, noted cp and cs, respectively. We observe that D follows a universal master curve D(cs,cp) = D(cs = 0,cp) g(cs/cp), where D(cs = 0,cp) is the diffusion coefficient in the absence of salt and g(cs/cp) is a scalar function solely depending on the ratio of the salt and protein concentration. This observation is consistent with a universal scaling of the bonding probability in a picture of cluster formation of patchy particles. The finding corroborates the predictive power of the description of proteins as colloids with distinct attractive ion-activated surface patches