6,110 research outputs found
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 from node to node as
the average number of steps a Brownian particle takes to reach from .
Node is a global attractor of if for any of
the graph; it is a local attractor of , if (the set of
nearest-neighbors of ) and for any . 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
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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
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