Annexin A2 mediates apical trafficking of renal Na(+)-K(+)-2Cl(-)-cotransporter

The furosemide-sensitive Na(+)-K(+)-2Cl(-)-cotransporter (NKCC2) is responsible for urine concentration, and helps maintain systemic salt homeostasis. Its activity depends on trafficking to, and insertion into, the apical membrane, as well as on phosphorylation of conserved N-terminal serine and threonine residues. Vasopressin (AVP), signaling via PKA and other kinases, activates NKCC2. Association of NKCC2 with lipid rafts facilitates its AVP-induced apical translocation and activation at the surface. Lipid raft microdomains typically serve as platforms for membrane proteins to facilitate their interactions with other proteins, but little is known about partners that interact with NKCC2. Yeast two-hybrid screening identified an interaction between NKCC2 and the cytosolic protein, annexin A2 (AnxA2). Annexins mediate lipid raft-dependent trafficking of transmembrane proteins, including the AVP-regulated water channel, aquaporin 2. Here, we demonstrate that AnxA2, which binds to phospholipids in a Ca(2+)-dependent manner and may organize microdomains, is co-distributed with NKCC2 to promote its apical translocation in response to AVP stimulation and low chloride hypotonic stress. NKCC2 and AnxA2 interact in a phosphorylation-dependent manner. Phosphomimetic AnxA2 carrying a mutant, Src-dependent phosphoacceptor (AnxA2-Y24D-GFP), enhanced surface expression and raft association of NKCC2 by 5-fold upon AVP stimulation, whereas PKC-dependent AnxA2-S26D-GFP did not. As the AnxA2 effect involved only non-phosphorylated NKCC2, it appears to affect NKCC2 trafficking. Overexpression or knockdown experiments further supported the role of AnxA2 in the apical translocation and surface expression of NKCC2. In summary, this study identifies AnxA2 as a lipid raft-associated trafficking factor for NKCC2 and provides mechanistic insight into the regulation of this essential cotransporter

The UTMOST Survey for Magnetars, Intermittent pulsars, RRATs and FRBs I: System description and overview

We describe the ongoing `Survey for Magnetars, Intermittent pulsars, Rotating radio transients and Fast radio bursts' (SMIRF), performed using the newly refurbished UTMOST telescope. SMIRF repeatedly sweeps the southern Galactic plane performing real-time periodicity and single-pulse searches, and is the first survey of its kind carried out with an interferometer. SMIRF is facilitated by a robotic scheduler which is capable of fully autonomous commensal operations. We report on the SMIRF observational parameters, the data analysis methods, the survey's sensitivities to pulsars, techniques to mitigate radio frequency interference and present some early survey results. UTMOST's wide field of view permits a full sweep of the Galactic plane to be performed every fortnight, two orders of magnitude faster than previous surveys. In the six months of operations from January to June 2018, we have performed $\sim 10$ sweeps of the Galactic plane with SMIRF. Notable blind re-detections include the magnetar PSR J1622$-$4950, the RRAT PSR J0941$-$3942 and the eclipsing pulsar PSR J1748$-$2446A. We also report the discovery of a new pulsar, PSR J1705$-$54. Our follow-up of this pulsar with the UTMOST and Parkes telescopes at an average flux limit of $\leq 20$ mJy and $\leq 0.16$ mJy respectively, categorizes this as an intermittent pulsar with a high nulling fraction of $< 0.002$Comment: Submitted to MNRAS, comments welcom

A New 5-Flavour LO Analysis and Parametrization of Parton Distributions in the Real Photon

New, radiatively generated, LO quark (u,d,s,c,b) and gluon densities in a real, unpolarized photon are presented. We perform a global 3-parameter fit, based on LO DGLAP evolution equations, to all available data for the structure function F2^gamma(x,Q^2). We adopt a new theoretical approach called ACOT(chi), originally introduced for the proton, to deal with the heavy-quark thresholds. This defines our basic model (CJKL model), which gives a very good description of the experimental data on F2^gamma(x,Q^2), for both Q^2 and x dependences. For comparison we perform a standard fit using the Fixed Flavour-Number Scheme (FFNS_CJKL model), updated with respect to the previous fits of this type. We show the superiority of the CJKL fit over the FFNS_CJKL one and other LO fits to the F2^gamma(x,Q^2) data. The CJKL model gives also the best description of the LEP data on the Q^2 dependence of the F2^gamma, averaged over various x-regions, and the F_2,c^gamma, which were not used directly in the fit. Finally, a simple analytic parametrization of the resulting parton densities obtained with the CJKL model is given.Comment: 43 pages, RevTeX4 using axodraw style, 3 tex and 12 postscript figures, version submitted to Phys. Rev. D, small text changes, one reference added, FORTRAN program available at http://www.fuw.edu.pl/~pjank/param.html and at http://www-zeuthen.desy.de/~alorca/id4.htm

General Stability Analysis of Synchronized Dynamics in Coupled Systems

We consider the stability of synchronized states (including equilibrium point, periodic orbit or chaotic attractor) in arbitrarily coupled dynamical systems (maps or ordinary differential equations). We develop a general approach, based on the master stability function and Gershgorin disc theory, to yield constraints on the coupling strengths to ensure the stability of synchronized dynamics. Systems with specific coupling schemes are used as examples to illustrate our general method.Comment: 8 pages, 1 figur

Social Interactions vs Revisions, What is important for Promotion in Wikipedia?

In epistemic community, people are said to be selected on their knowledge contribution to the project (articles, codes, etc.) However, the socialization process is an important factor for inclusion, sustainability as a contributor, and promotion. Finally, what does matter to be promoted? being a good contributor? being a good animator? knowing the boss? We explore this question looking at the process of election for administrator in the English Wikipedia community. We modeled the candidates according to their revisions and/or social attributes. These attributes are used to construct a predictive model of promotion success, based on the candidates's past behavior, computed thanks to a random forest algorithm. Our model combining knowledge contribution variables and social networking variables successfully explain 78% of the results which is better than the former models. It also helps to refine the criterion for election. If the number of knowledge contributions is the most important element, social interactions come close second to explain the election. But being connected with the future peers (the admins) can make the difference between success and failure, making this epistemic community a very social community too

Evaluation of the zucker diabetic fatty (ZDF) rat as a model for human disease based on urinary peptidomic profiles

Representative animal models for diabetes-associated vascular complications are extremely relevant in assessing potential therapeutic drugs. While several rodent models for type 2 diabetes (T2D) are available, their relevance in recapitulating renal and cardiovascular features of diabetes in man is not entirely clear. Here we evaluate at the molecular level the similarity between Zucker diabetic fatty (ZDF) rats, as a model of T2D-associated vascular complications, and human disease by urinary proteome analysis. Urine analysis of ZDF rats at early and late stages of disease compared to age- matched LEAN rats identified 180 peptides as potentially associated with diabetes complications. Overlaps with human chronic kidney disease (CKD) and cardiovascular disease (CVD) biomarkers were observed, corresponding to proteins marking kidney damage (eg albumin, alpha-1 antitrypsin) or related to disease development (collagen). Concordance in regulation of these peptides in rats versus humans was more pronounced in the CVD compared to the CKD panels. In addition, disease-associated predicted protease activities in ZDF rats showed higher similarities to the predicted activities in human CVD. Based on urinary peptidomic analysis, the ZDF rat model displays similarity to human CVD but might not be the most appropriate model to display human CKD on a molecular level

High pressure, quasi-isentropic compression experiments on the Omega laser

The high energy density of pulsed lasers can be used to generate shockless loading in solids to high pressures and compressions but low temperatures. We have used the Omega laser to extend the capabilities of this technique to multi-Mbar pressures and compressions approaching a factor of 2 in aluminum foils. The energy from a 3.7 ns laser pulse is used to drive a strong shock through a 200 {micro}m polystyrene disc. The disc material unloads from a high-pressure state and expands across a 300 {micro}m vacuum gap where it stagnates against the sample to produce a smooth, monotonically increasing load with rise times from a few to {approx} 20 ns. Ramped compression reasing waves having peak pressures of 14-200 GPa (0.14-2.0 Mbar) and peak compressions {rho}/{rho}{sub 0} of 1.1-2.0 were generated in the aluminum samples using laser pulse energies of 400 J to 2 kJ. Wave profiles from a series of successively thicker targets loaded to 120 GPa show the evolution of the high-pressure compression wave within the sample. The initial loading in the sample is shockless, and develops into a shock at a depth of 20-25 {micro}m. We compare these wave profiles with hydrodynamic simulations from which we extract material temperatures and plastic strain rates behind the compression wave. Limitations and future prospects for this new shockless loading technique are discussed