1,516 research outputs found
Protein Kinase C-δ Mediates Neuronal Apoptosis in the Retinas of Diabetic Rats via the Akt Signaling Pathway
OBJECTIVE—Protein kinase C (PKC)-δ, an upstream regulator of the Akt survival pathway, contributes to cellular dysfunction in the pathogenesis of diabetes. Herein, we examined the role of PKC-δ in neuronal apoptosis through Akt in the retinas of diabetic rats
Epigenetic liquid biopsies for minimal residual disease, what’s around the corner?
Liquid biopsy assays for minimal residual disease (MRD) are used to monitor and inform oncological treatment and predict the risk of relapse in cancer patients. To-date, most MRD assay development has focused on targeting somatic mutations. However, epigenetic changes are more frequent and universal than genetic alterations in cancer and circulating tumor DNA (ctDNA) retains much of these changes. Here, we review the epigenetic signals that can be used to detect MRD, including DNA methylation alterations and fragmentation patterns that differentiate ctDNA from noncancerous circulating cell-free DNA (ccfDNA). We then summarize the current state of MRD monitoring; highlight the advantages of epigenetics over genetics-based approaches; and discuss the emerging paradigm of assaying both genetic and epigenetic targets to monitor treatment response, detect disease recurrence, and inform adjuvant therapy
Hydrodynamic coupling and rotational mobilities near planar elastic membranes
We study theoretically and numerically the coupling and rotational
hydrodynamic interactions between spherical particles near a planar elastic
membrane that exhibits resistance towards shear and bending. Using a
combination of the multipole expansion and Faxen's theorems, we express the
frequency-dependent hydrodynamic mobility functions as a power series of the
ratio of the particle radius to the distance from the membrane for the self
mobilities, and as a power series of the ratio of the radius to the
interparticle distance for the pair mobilities. In the quasi-steady limit of
zero frequency, we find that the shear- and bending-related contributions to
the particle mobilities may have additive or suppressive effects depending on
the membrane properties in addition to the geometric configuration of the
interacting particles relative to the confining membrane. To elucidate the
effect and role of the change of sign observed in the particle self and pair
mobilities, we consider an example involving a torque-free doublet of
counterrotating particles near an elastic membrane. We find that the induced
rotation rate of the doublet around its center of mass may differ in magnitude
and direction depending on the membrane shear and bending properties. Near a
membrane of only energetic resistance toward shear deformation, such as that of
a certain type of elastic capsules, the doublet undergoes rotation of the same
sense as observed near a no-slip wall. Near a membrane of only energetic
resistance toward bending, such as that of a fluid vesicle, we find a reversed
sense of rotation. Our analytical predictions are supplemented and compared
with fully resolved boundary integral simulations where a very good agreement
is obtained over the whole range of applied frequencies.Comment: 14 pages, 7 figures. Revised manuscript resubmitted to J. Chem. Phy
Au+Au Reactions at the AGS: Experiments E866 and E917
Particle production and correlation functions from Au+Au reactions have been
measured as a function of both beam energy (2-10.7AGeV) and impact parameter.
These results are used to probe the dynamics of heavy-ion reactions, confront
hadronic models over a wide range of conditions and to search for the onset of
new phenomena.Comment: 12 pages, 14 figures, Talk presented at Quark Matter '9
Quantum Smoluchowski equation: Escape from a metastable state
We develop a quantum Smoluchowski equation in terms of a true probability
distribution function to describe quantum Brownian motion in configuration
space in large friction limit at arbitrary temperature and derive the rate of
barrier crossing and tunneling within an unified scheme. The present treatment
is independent of path integral formalism and is based on canonical
quantization procedure.Comment: 10 pages, To appear in the Proceedings of Statphys - Kolkata I
Production of phi Mesons in Au+Au Collisions at 11.7 A GeV/c
We report on a measurement of phi-meson production in Au+Au collisions at a
beam momentum of 11.7 A GeV/c by Experiment E917 at the AGS. The measurement
covers the midrapidity region 1.2 < y < 1.6. Transverse-mass spectra and the
rapidity distribution are presented as functions of centrality characterized by
the number of participant projectile nucleons. The yield of phi's per
participant projectile nucleon increases strongly in central collisions in a
manner similar to that observed for kaons.Comment: 12 pages, 3 table, 14 eps figures which use \includegraphics, revtex
4, revised version submitted to Phys. Rev.
Rare coding SNP in DZIP1 gene associated with late-onset sporadic Parkinson's disease
We present the first application of the hypothesis-rich mathematical theory
to genome-wide association data. The Hamza et al. late-onset sporadic
Parkinson's disease genome-wide association study dataset was analyzed. We
found a rare, coding, non-synonymous SNP variant in the gene DZIP1 that confers
increased susceptibility to Parkinson's disease. The association of DZIP1 with
Parkinson's disease is consistent with a Parkinson's disease stem-cell ageing
theory.Comment: 14 page
Reversing Blood Flows Act through klf2a to Ensure Normal Valvulogenesis in the Developing Heart
Heart valve anomalies are some of the most common congenital heart defects, yet neither the genetic nor the epigenetic forces guiding heart valve development are well understood. When functioning normally, mature heart valves prevent intracardiac retrograde blood flow; before valves develop, there is considerable regurgitation, resulting in reversing (or oscillatory) flows between the atrium and ventricle. As reversing flows are particularly strong stimuli to endothelial cells in culture, an attractive hypothesis is that heart valves form as a developmental response to retrograde blood flows through the maturing heart. Here, we exploit the relationship between oscillatory flow and heart rate to manipulate the amount of retrograde flow in the atrioventricular (AV) canal before and during valvulogenesis, and find that this leads to arrested valve growth. Using this manipulation, we determined that klf2a is normally expressed in the valve precursors in response to reversing flows, and is dramatically reduced by treatments that decrease such flows. Experimentally knocking down the expression of this shear-responsive gene with morpholine antisense oligonucleotides (MOs) results in dysfunctional valves. Thus, klf2a expression appears to be necessary for normal valve formation. This, together with its dependence on intracardiac hemodynamic forces, makes klf2a expression an early and reliable indicator of proper valve development. Together, these results demonstrate a critical role for reversing flows during valvulogenesis and show how relatively subtle perturbations of normal hemodynamic patterns can lead to both major alterations in gene expression and severe valve dysgenesis
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