5,172 research outputs found
Deficiency of NOX1 or NOX4 Prevents Liver Inflammation and Fibrosis in Mice through Inhibition of Hepatic Stellate Cell Activation.
Reactive oxygen species (ROS) produced by nicotinamide adenine dinucleotide phosphate oxidase (NOX) play a key role in liver injury and fibrosis. Previous studies demonstrated that GKT137831, a dual NOX1/4 inhibitor, attenuated liver fibrosis in mice as well as pro-fibrotic genes in hepatic stellate cells (HSCs) as well as hepatocyte apoptosis. The effect of NOX1 and NOX4 deficiency in liver fibrosis is unclear, and has never been directly compared. HSCs are the primary myofibroblasts in the pathogenesis of liver fibrosis. Therefore, we aimed to determine the role of NOX1 and NOX4 in liver fibrosis, and investigated whether NOX1 and NOX4 signaling mediates liver fibrosis by regulating HSC activation. Mice were treated with carbon tetrachloride (CCl4) to induce liver fibrosis. Deficiency of either NOX1 or NOX4 attenuates liver injury, inflammation, and fibrosis after CCl4 compared to wild-type mice. NOX1 or NOX4 deficiency reduced lipid peroxidation and ROS production in mice with liver fibrosis. NOX1 and NOX4 deficiency are approximately equally effective in preventing liver injury in the mice. The NOX1/4 dual inhibitor GKT137831 suppressed ROS production as well as inflammatory and proliferative genes induced by lipopolysaccharide (LPS), platelet-derived growth factor (PDGF), or sonic hedgehog (Shh) in primary mouse HSCs. Furthermore, the mRNAs of proliferative and pro-fibrotic genes were downregulated in NOX1 and NOX4 knock-out activated HSCs (cultured on plastic for 5 days). Finally, NOX1 and NOX4 protein levels were increased in human livers with cirrhosis compared with normal controls. Thus, NOX1 and NOX4 signaling mediates the pathogenesis of liver fibrosis, including the direct activation of HSC
Local pore size correlations determine flow distributions in porous media
The relationship between the microstructure of a porous medium and the
observed flow distribution is still a puzzle. We resolve it with an analytical
model, where the local correlations between adjacent pores, which determine the
distribution of flows propagated from one pore downstream, predict the flow
distribution. Numerical simulations of a two-dimensional porous medium verify
the model and clearly show the transition of flow distributions from
-function-like via Gaussians to exponential with increasing disorder.
Comparison to experimental data further verifies our numerical approach.Comment: 5 pages, 3 figures, supplemental materia
DM-PhyClus: A Bayesian phylogenetic algorithm for infectious disease transmission cluster inference
Background. Conventional phylogenetic clustering approaches rely on arbitrary
cutpoints applied a posteriori to phylogenetic estimates. Although in practice,
Bayesian and bootstrap-based clustering tend to lead to similar estimates, they
often produce conflicting measures of confidence in clusters. The current study
proposes a new Bayesian phylogenetic clustering algorithm, which we refer to as
DM-PhyClus, that identifies sets of sequences resulting from quick transmission
chains, thus yielding easily-interpretable clusters, without using any ad hoc
distance or confidence requirement. Results. Simulations reveal that DM-PhyClus
can outperform conventional clustering methods, as well as the Gap procedure, a
pure distance-based algorithm, in terms of mean cluster recovery. We apply
DM-PhyClus to a sample of real HIV-1 sequences, producing a set of clusters
whose inference is in line with the conclusions of a previous thorough
analysis. Conclusions. DM-PhyClus, by eliminating the need for cutpoints and
producing sensible inference for cluster configurations, can facilitate
transmission cluster detection. Future efforts to reduce incidence of
infectious diseases, like HIV-1, will need reliable estimates of transmission
clusters. It follows that algorithms like DM-PhyClus could serve to better
inform public health strategies
Skating on a Film of Air: Drops Impacting on a Surface
Drops impacting on a surface are ubiquitous in our everyday experience. This
impact is understood within a commonly accepted hydrodynamic picture: it is
initiated by a rapid shock and a subsequent ejection of a sheet leading to
beautiful splashing patterns. However, this picture ignores the essential role
of the air that is trapped between the impacting drop and the surface. Here we
describe a new imaging modality that is sensitive to the behavior right at the
surface. We show that a very thin film of air, only a few tens of nanometers
thick, remains trapped between the falling drop and the surface as the drop
spreads. The thin film of air serves to lubricate the drop enabling the fluid
to skate on the air film laterally outward at surprisingly high velocities,
consistent with theoretical predictions. Eventually this thin film of air must
break down as the fluid wets the surface. We suggest that this occurs in a
spinodal-like fashion, and causes a very rapid spreading of a wetting front
outwards; simultaneously the wetting fluid spreads inward much more slowly,
trapping a bubble of air within the drop. Our results show that the dynamics of
impacting drops are much more complex than previously thought and exhibit a
rich array of unexpected phenomena that require rethinking classical paradigms.Comment: 4 pages, 4 figure
Plyler Children: 21st Century Challenges with Judicial-Policy Implementation Affecting Immigrant Children in New Jersey
Denying unauthorized immigrant children access to a free public education through incomplete judicial policy implementation may lead to an illiterate underclass. Communicating, implementing, and enforcing Plyler v. Doe school registration documentation requirements continue to be difficult at the district level. In 2008, an ACLU study in New Jersey found that 187 of 516 school districts were mandating inappropriate documentation from parents registering their children. Separation of powers requires that executive agencies proactively implement transformative judicial decisions
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