KCNKØ: opening and closing the 2-P-domain potassium leak channel entails "C-type" gating of the outer pore.

Essential to nerve and muscle function, little is known about how potassium leak channels operate. KCNKØ opens and closes in a kinase-dependent fashion. Here, the transition is shown to correspond to changes in the outer aspect of the ion conduction pore. Voltage-gated potassium (VGK) channels open and close via an internal gate; however, they also have an outer pore gate that produces "C-type" inactivation. While KCNKØ does not inactivate, KCNKØ and VGK channels respond in like manner to outer pore blockers, potassium, mutations, and chemical modifiers. Structural relatedness is confirmed: VGK residues that come close during C-type gating predict KCNKØ sites that crosslink (after mutation to cysteine) to yield channels controlled by reduction and oxidization. We conclude that similar outer pore gates mediate KCNKØ opening and closing and VGK channel C-type inactivation despite their divergent structures and physiological roles

Sequence and function of the two P domain potassium channels: implications of an emerging superfamily.

A new superfamily of K+ channels has emerged in the past 2 years. Notable for possessing two pore-forming P domains in each subunit, members of the superfamily have been recognized through phylogeny from micro-organisms to humans. Four subfamilies of two P domain channels have been isolated thus far; among these are the first cloned examples of outward rectifier and open rectifier (or leak) K+ channels. The two P domain K+ channels offer a new perspective from which to glimpse the molecular basis for function and dysfunction of K+-selective ion channels

A molecular target for viral killer toxin: TOK1 potassium channels.

Killer strains of S. cerevisiae harbor double-stranded RNA viruses and secrete protein toxins that kill virus-free cells. The K1 killer toxin acts on sensitive yeast cells to perturb potassium homeostasis and cause cell death. Here, the toxin is shown to activate the plasma membrane potassium channel of S. cerevisiae, TOK1. Genetic deletion of TOK1 confers toxin resistance; overexpression increases susceptibility. Cells expressing TOK1 exhibit toxin-induced potassium flux; those without the gene do not. K1 toxin acts in the absence of other viral or yeast products: toxin synthesized from a cDNA increases open probability of single TOK1 channels (via reversible destabilization of closed states) whether channels are studied in yeast cells or X. laevis oocytes

Partial DNA Assembly: A Rate-Distortion Perspective

Earlier formulations of the DNA assembly problem were all in the context of perfect assembly; i.e., given a set of reads from a long genome sequence, is it possible to perfectly reconstruct the original sequence? In practice, however, it is very often the case that the read data is not sufficiently rich to permit unambiguous reconstruction of the original sequence. While a natural generalization of the perfect assembly formulation to these cases would be to consider a rate-distortion framework, partial assemblies are usually represented in terms of an assembly graph, making the definition of a distortion measure challenging. In this work, we introduce a distortion function for assembly graphs that can be understood as the logarithm of the number of Eulerian cycles in the assembly graph, each of which correspond to a candidate assembly that could have generated the observed reads. We also introduce an algorithm for the construction of an assembly graph and analyze its performance on real genomes.Comment: To be published at ISIT-2016. 11 pages, 10 figure

Rokhlin dimension: obstructions and permanence properties

This paper is a further study of finite Rokhlin dimension for actions of finite groups and the integers on C*-algebras, introduced by the first author, Winter, and Zacharias. We extend the definition of finite Rokhlin dimension to the nonunital case. This definition behaves well with respect to extensions, and is sufficient to establish permanence of finite nuclear dimension and Z-absorption. We establish K-theoretic obstructions to the existence of actions of finite groups with finite Rokhlin dimension (in the commuting tower version). In particular, we show that there are no actions of any nontrivial finite group on the Jiang-Su algebra or on the Cuntz algebra O_\infty with finite Rokhlin dimension in this sense.Comment: 33 pages, minor changes, to appear, Doc. Mat

Intrasheath subluxation of the peroneal tendons.

BACKGROUND: Dislocation or subluxation of the peroneal tendons out of the peroneal groove under a torn or avulsed superior peroneal retinaculum has been well described. We identified a new subgroup of patients with intrasheath subluxation of these tendons within the peroneal groove and with an otherwise intact retinaculum. METHODS: The cases of fifty-seven patients with painful snapping of the peroneal tendons posterior to the fibula were reviewed. Of these, forty-three had tendons that could be reproducibly subluxated out of the groove with a dorsiflexion-eversion maneuver of the ankle. Fourteen patients who could not subluxate the tendons out of the groove underwent a dynamic ultrasound examination of the tendons. While the same dorsiflexion and eversion maneuver was being performed, the tendons were seen to switch their relative positions (the peroneus longus came to lie deep to the peroneus brevis tendon) with a reproducible painful click. All fourteen patients underwent a peroneal groove-deepening procedure with retinacular reefing. Intraoperatively, thirteen patients were found to have a convex peroneal groove and all fourteen had an intact peroneal retinaculum. All patients subsequently underwent a follow-up dynamic ultrasound examination and an American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score evaluation at a minimum of twenty-four months after surgery. RESULTS: All fourteen patients were female, with an average age of thirty-five years. Two subtypes of intrasheath subluxation were found. Type A (ten patients) involved intact tendons with relative switching of their anatomic alignment. Type B (four patients) involved a longitudinal split within the peroneus brevis tendon through which the longus tendon subluxated. Intraoperative confirmation of the ultrasound findings was 100%. At an average follow-up interval of thirty-three months, the average AOFAS score had improved from 61 points preoperatively to 93 points, and the average score on the 10-cm visual analog pain scale had improved from 6.8 to 1.2. Follow-up ultrasound evaluation revealed healed tendons without persistent subluxation in thirteen patients. Nine patients rated the result as excellent, four rated it as good, and one rated it as fair. CONCLUSIONS: Patients with retrofibular pain and clicking of the peroneal tendons may not have demonstrable subluxation on physical examination and may have an intact superior peroneal retinaculum. They may have an intrasheath subluxation of the peroneal tendons, which can be confirmed with use of a dynamic ultrasound. Surgical repair of tendon tears combined with a peroneal groove-deepening procedure with retinacular reefing is a reproducibly effective procedure for this condition