Tuning ion coordination preferences to enable selective permeation

Potassium (K-) channels catalyze K+ ion permeation across cellular membranes while simultaneously discriminating their permeation over Na+ ions by more than a factor of a thousand. Structural studies show bare K+ ions occupying the narrowest channel regions in a state of high coordination by all 8 surrounding oxygen ligands from the channel walls. As in most channels, the driving force for selectivity occurs when one ion is preferentially stabilized or destabilized by the channel compared to water. In the common view of mechanism, made vivid by textbook graphics, the driving force for selectivity in K- channels arises by a fit, whereby the channel induces K+ ions to leave water by offering an environment like water for K+, in terms of both energy and local structure. The implication that knowledge of local ion coordination in a liquid environment translates to design parameters in a protein ion channel, producing similar energetic stabilities, has gone unchallenged, presumably due in part to lack of consensus regarding ion coordination structures in liquid water. Growing evidence that smaller numbers and different arrangements of ligands coordinate K+ ions in liquid water, however, raises new questions regarding mechanism: how and why should ion coordination preferences change, and how does that alter the current notions of ion selectivity? Our studies lead to a new channelcentric paradigm for the mechanism of K+ ion channel selectivity. Because the channel environment is not liquid-like, the channel necessarily induces local structural changes in ion coordination preferences that enable structural and energetic differentiation between ions.Comment: Main manuscript: 12 pages, 6 figures. Supplementary information: 10 pages, 7 figure

Evaluation of projects funded by the European Commission and of the existing information of the GDs that might be relevant in the Territorial Intelligence field. Coordination Group WP4P "Projects" of CaENTI

International audienceThis communication makes a state of the activities carried out by the WP4P coordination group of the 4th work package "Fundamental methods" of the CAENTI, Coordination Action of the European Network of Territorial Intelligence. The WP4P concerns a technical issue, the evaluation of projects funded by the European Commission and of the existing information of the GDs that might be relevant in the territorial intelligence field. The first six months of the CAENTI were mainly devoted to the projects selection. A first task consisted in identifying the projects which are funded by the European Union and that can be considered as belonging to the territorial intelligence field. A first group of keywords was suggested to select them. The first selection essentially underlines projects that are linked to governance. We need to enlarge key words to make e new selection. The objective for 2007 is to organize a seminar that will gather the projects leaders of the most relevant projects about territorial action and the CAENTI territorial actors to deepen the principles and the practice of territorial intelligence with them. The identification of the information that the GD owns and that is relevant for territorial intelligence will be made in collaboration with the WP4I group that leads research activities about territorial information (WP4I), before making a survey of the GDs. During this conference, the WP4P should define and program its prospects

Genetic Testing and FOX News

Genetic testing is transforming kidney care, arguably with similar impact as the adoption of kidney biopsies in the 1950s. It is incumbent on nephrologists to teach the genetics of kidney disease and the accessibility of genetic testing. Proper usage of genetic testing can avoid “diagnostic odysseys” with multiple nonspecific investigations, some of them invasive like a kidney biopsy and repeated consultations with multiple different specialists [1]

Estimated central blood volume in cirrhosis

The estimated central blood volume (i.e., blood volume in the heart cavities, lungs and central arterial tree) was determined by multiplying cardiac output by circulatory mean transit time in 19 patients with cirrhosis and compared with sympathetic nervous activity and circulating level of atrial natriuretic factor. Arterial norepinephrine level, an index of overall sympathetic nervous activity (3.08 nmol/L in patients vs. 1.36 nmol/L in controls; p < 0.01) was negatively correlated (r = -0.54, p < 0.01) with estimated central blood volume (mean = 23 ml/kg in patients vs. 27 ml/kg in controls; p < 0.05). Similarly, renal venous norepinephrine level (an index of renal sympathetic tone; 4.26 nmol/L in patients vs. 1.78 nmol/L in controls; p < 0.01) was inversely correlated with estimated central blood volume (r = -0.53, n = 18, p < 0.02). No significant correlation could be established between arterial atrial natriuretic factor level (8.9 pmol/L in patients vs. 9.6 pmol/L in controls; not significant) and estimated central blood volume. Hemodynamic values were subsequently modified with oral propranolol (80 mg). During -adrenergic blockade, the mean estimated central blood volume was not altered significantly, except in six patients who exhibited decreases in mean arterial blood pressure (85 to 69 mm Hg; n = 6) and decreases in mean estimated central blood volume (23.2 to 20.6 ml/kg; n = 6, p < 0.05). Slight increases were observed in mean right atrial pressure (2.2 to 3.7 mm Hg; n = 14, p < 0.05); this change was positively correlated with the change in estimated central blood volume (r = 0.44, n = 14, p = 0.06). In conclusion, reduced estimated central blood volume probably unloads volume receptors and baroreceptors, thus provoking enhanced overall and renal sympathetic nervous activity and thereby contributing to increased water and salt retention in cirrhosis. During -adrenergic blockade estimated central blood volume changes correlated with alterations in preload and afterload. These findings indicate that central circulatory and arterial underfilling is a key element of the hemodynamic derangement observed in cirrhosis

NETWORK FOR MULTIMEDIA APPLICATION

International audienceFor the last four decades, the number and sophistication of electronic systems in vehicles have shown an exponential increase. One high-growth area is telematics systems-the convergence of mobile telecommunications and information processing in cars (radios, Web browsers, CD/DVD players, telematics, and infotainment systems). There is the need for a high-speed serial interface for future vehicles, able to share audio-video sources between all passengers and able to connect automotive electronic world with consumer electronic world. Different networks are available for multimedia automotive applications. Because of their capabilities IDB-1394b and Most are strong candidate. IDB 1394 is the automotive version of IEEE 1394 version b. It is designed for high-speed multimedia applications that require large amounts of information to be moved quickly in a vehicle. Key features include hot plug capability, compatibility with consumer electronics and the ability to use small, flexible, and inexpensive cables and connectors. Its flexible topology supports both branching and daisy-chaining of nodes. MOST (Media Oriented Systems Transport) is a Multimedia optical fiber system transport that is designed for the automotive environment. This paper presents the main characteristics of these two multimedia protocols. It includes the electrical characteristics, topology, transmission media, software layers… It includes as well some examples of applications and platform developmen

Inherited Disorders of Water Handling

Under normal circumstances, about 90% of the 180 L/day glomerular filtrate is constitutively reabsorbed in the proximal tubule and descending limb of Henle’s loop. According to the needs, the remaining 10% of the fluid is reabsorbed in the collecting duct by a tightly regulated process under control of arginine vasopressin (AVP). After binding of AVP to arginine vasopressin type 2 receptors (AVPR2) in the basolateral membrane of collecting duct cells, aquaporin-2 (AQP2) water channels are inserted into the luminal membrane of these cells, allowing water reabsorption and urine concentration. Disorders of water handling are characterized by disturbances of this AVP-regulated system. In congenital nephrogenic diabetes insipidus (NDI), the kidney cannot concentrate urine in response to AVP, as a result of loss-of-function mutations in genes encoding AVPR2 and AQP2, resulting in polyuria and polydipsia. In recent years, extensive research has led to increased understanding of the cellular defects in NDI, with important implications for future development of targeted treatment of the disorder, with hope for better outcomes in comparison to the conventional symptomatic therapy. The very rare nephrogenic syndrome of inappropriate antidiuresis (NSIAD), caused by gain-of-function mutations in the gene encoding AVPR2, is the mirror image of NDI. In this disorder, urinary dilution is impaired, independent of the presence or absence of AVP. In this chapter, the focus will be on the physiology of water handling in the collecting duct and on its disturbances in congenital NDI. The clinical details, differential diagnosis, genetics, and conventional and possible future therapies of NDI will be discussed in detail.</p

Aisey-et-Richecourt – Ancienne gare

Les récents travaux effectués dans la région de Jussey, pour la rectification et l’aménagement du réseau routier, ont fait apparaître de grandes coupes et décaper des formations quaternaires qui jusqu’alors étaient masquées et difficiles à étudier. La prospection de ces coupes a permis la découverte et la récupération d’un matériel lithique en place à base de quartzites taillés. L’interprétation géologique a bénéficié de la présence de cette industrie paléolithique qui constitue un nouveau re..

Contribution à l'étude sédimentologique du remplissage karstique de la Caverna Delle Fate (Ligurie Italienne). Essai chronostratigraphique

L'étude sédimentologique de la Caverna delle Fate s'inscrit dans le cadre d'une étude globale actuellement en cours. Cette étude à pour objectif de préciser le contexte et les conditions de l'occupation humaine de la grotte et plus généralement de la présence néandertalienne en Ligurie. Mais la fouille et l'étude du gisement de la Caverna delle Fate ont de particulier qu'elles ne concernent que les « témoins » préservés d'un remplissage fouillé il y a aujourd'hui un siècle. Les nouvelles fouilles entreprises depuis cinq ans, à l'origine de cette étude, sont une tentative bien difficile de reconstituer un puzzle dont il manque bon nombre de pièces. L'étude des processus sédimentaires à l'origine du remplissage ne peut donc être abordée qu'au travers d'une information très fragmentaire qui limite considérablement le champ de nos investigations

Chaffois – Tumulus de la carrière no 1

Situé vers une carrière qui progresse quotidiennement, un tumulus de faible hauteur était piétiné par les bovins qui enlevaient chaque jour un peu plus de la faible couche de terre qui recouvrait la tombe, surmontée d’ailleurs curieusement par un abreuvoir. Le décapage superficiel fit apparaître rapidement un amoncellement de gros blocs calcaires ramassés dans une moraine des environs ou sur le sol en place fortement délité. La terre végétale de recouvrement infiltrée ensuite au travers de la..