p120-Catenin Mediates Inflammatory Responses in the Skin

SummaryAlthough p120-catenin regulates adherens junction (AJ) stability in cultured cells, genetic studies in lower eukaryotes have not revealed a role for this protein in vivo. Using conditional targeting in mice, we show that p120 null neonatal epidermis exhibits reduced intercellular AJ components but no overt disruption in barrier function or intercellular adhesion. As the mice age, however, they display epidermal hyperplasia and chronic inflammation, typified by hair degeneration and loss of body fat. Using skin engraftments and anti-inflammatory drugs, we show that these features are not attributable to reductions in junctional cadherins and catenins, but rather NFkB activation. Both in vivo and in vitro, p120 null epidermal cells activate nuclear NFkB, triggering a cascade of proinflammatory NFkB targets. Although the underlying mechanism is likely complex, we show that p120 affects NFkB activation and immune homeostasis in part through regulation of Rho GTPases. These findings provide important new insights into p120 function

Growing Scale-Free Networks with Tunable Clustering

We extend the standard scale-free network model to include a ``triad formation step''. We analyze the geometric properties of networks generated by this algorithm both analytically and by numerical calculations, and find that our model possesses the same characteristics as the standard scale-free networks like the power-law degree distribution and the small average geodesic length, but with the high-clustering at the same time. In our model, the clustering coefficient is also shown to be tunable simply by changing a control parameter - the average number of triad formation trials per time step.Comment: Accepted for publication in Phys. Rev.

MAPT R406W increases tau T217 phosphorylation in absence of amyloid pathology

OBJECTIVE: Tau hyperphosphorylation at threonine 217 (pT217) in cerebrospinal fluid (CSF) has recently been linked to early amyloidosis and could serve as a highly sensitive biomarker for Alzheimer\u27s disease (AD). However, it remains unclear whether other tauopathies induce pT217 modifications. To determine if pT217 modification is specific to AD, CSF pT217 was measured in AD and other tauopathies. METHODS: Using immunoprecipitation and mass spectrometry methods, we compared CSF T217 phosphorylation occupancy (pT217/T217) and amyloid-beta (Aβ) 42/40 ratio in cognitively normal individuals and those with symptomatic AD, progressive supranuclear palsy, corticobasal syndrome, and sporadic and familial frontotemporal dementia. RESULTS: Individuals with AD had high CSF pT217/T217 and low Aβ42/40. In contrast, cognitively normal individuals and the majority of those with 4R tauopathies had low CSF pT217/T217 and normal Aβ 42/40. We identified a subgroup of individuals with increased CSF pT217/T217 and normal Aβ 42/40 ratio, most of whom were MAPT R406W mutation carriers. Diagnostic accuracies of CSF Aβ 42/40 and CSF pT217/T217, alone and in combination were compared. We show that CSF pT217/T217 × CSF Aβ 42/40 is a sensitive composite biomarker that can separate MAPT R406W carriers from cognitively normal individuals and those with other tauopathies. INTERPRETATION: MAPT R406W is a tau mutation that leads to 3R+4R tauopathy similar to AD, but without amyloid neuropathology. These findings suggest that change in CSF pT217/T217 ratio is not specific to AD and might reflect common downstream tau pathophysiology common to 3R+4R tauopathies

Network Landscape from a Brownian Particle's Perspective

Given a complex biological or social network, how many clusters should it be decomposed into? We define the distance $d_{i,j}$ from node $i$ to node $j$ as the average number of steps a Brownian particle takes to reach $j$ from $i$. Node $j$ is a global attractor of $i$ if $d_{i,j}\leq d_{i,k}$ for any $k$ of the graph; it is a local attractor of $i$, if $j\in E_i$ (the set of nearest-neighbors of $i$) and $d_{i,j}\leq d_{i,l}$ for any $l\in E_i$. Based on the intuition that each node should have a high probability to be in the same community as its global (local) attractor on the global (local) scale, we present a simple method to uncover a network's community structure. This method is applied to several real networks and some discussion on its possible extensions is made.Comment: 5 pages, 4 color-figures. REVTeX 4 format. To appear in PR

Measuring the dark side (with weak lensing)

We introduce a convenient parametrization of dark energy models that is general enough to include several modified gravity models and generalized forms of dark energy. In particular we take into account the linear perturbation growth factor, the anisotropic stress and the modified Poisson equation. We discuss the sensitivity of large scale weak lensing surveys like the proposed DUNE satellite to these parameters. We find that a large-scale weak-lensing tomographic survey is able to easily distinguish the Dvali-Gabadadze-Porrati model from LCDM and to determine the perturbation growth index to an absolute error of 0.02-0.03.Comment: 19 pages, 11 figure

Post-operative cognitive function following general versus regional anesthesia, a systematic review

The effect of anesthetic technique on postoperative outcomes remains in question. This systematic review compares the role of regional versus general anesthesia, with a particular focus on postoperative cognitive function. Potentially relevant articles were identified by searching publicly available computerized databases for this systematic review. Any surgical procedure was accepted with the exception of cardiac, carotid, and neurosurgical procedures. Any regional anesthetic technique was accepted unless combined with a general anesthetic or in conjunction with propofol as a sedative. Any measure of postoperative cognitive function was accepted as long as it was performed no sooner than 7 days postoperatively. Sixteen studies met inclusion criteria and were included in the final analysis. Three studies showed some difference in cognitive function between regional and general anesthesia, whereas the remaining 13 showed no difference between regional and general anesthesia on postoperative cognitive function

Random graphs with arbitrary degree distributions and their applications

Recent work on the structure of social networks and the internet has focussed attention on graphs with distributions of vertex degree that are significantly different from the Poisson degree distributions that have been widely studied in the past. In this paper we develop in detail the theory of random graphs with arbitrary degree distributions. In addition to simple undirected, unipartite graphs, we examine the properties of directed and bipartite graphs. Among other results, we derive exact expressions for the position of the phase transition at which a giant component first forms, the mean component size, the size of the giant component if there is one, the mean number of vertices a certain distance away from a randomly chosen vertex, and the average vertex-vertex distance within a graph. We apply our theory to some real-world graphs, including the world-wide web and collaboration graphs of scientists and Fortune 1000 company directors. We demonstrate that in some cases random graphs with appropriate distributions of vertex degree predict with surprising accuracy the behavior of the real world, while in others there is a measurable discrepancy between theory and reality, perhaps indicating the presence of additional social structure in the network that is not captured by the random graph.Comment: 19 pages, 11 figures, some new material added in this version along with minor updates and correction

Investigation of radioactivity-induced backgrounds in EXO-200

The search for neutrinoless double-beta decay (0{\nu}{\beta}{\beta}) requires extremely low background and a good understanding of their sources and their influence on the rate in the region of parameter space relevant to the 0{\nu}{\beta}{\beta} signal. We report on studies of various {\beta}- and {\gamma}-backgrounds in the liquid- xenon-based EXO-200 0{\nu}{\beta}{\beta} experiment. With this work we try to better understand the location and strength of specific background sources and compare the conclusions to radioassay results taken before and during detector construction. Finally, we discuss the implications of these studies for EXO-200 as well as for the next-generation, tonne-scale nEXO detector.Comment: 9 pages, 7 figures, 3 table