165 research outputs found
Podocytic PKC-Alpha Is Regulated in Murine and Human Diabetes and Mediates Nephrin Endocytosis
Background: Microalbuminuria is an early lesion during the development of diabetic nephropathy. The loss of high molecular weight proteins in the urine is usually associated with decreased expression of slit diaphragm proteins. Nephrin, is the major component of the glomerular slit diaphragm and loss of nephrin has been well described in rodent models of experimental diabetes as well as in human diabetic nephropathy. Methodology/Principal Findings: In this manuscript we analyzed the role of PKC-alpha (PKCa) on endocytosis of nephrin in podocytes. We found that treatment of diabetic mice with a PKCa-inhibitor (GĂ6976) leads to preserved nephrin expression and reduced proteinuria. In vitro, we found that high glucose stimulation would induce PKCa protein expression in murine and human podocytes. We can demonstrate that PKCa mediates nephrin endocytosis in podocytes and that overexpression of PKCa leads to an augmented endocytosis response. After PKC-activation, we demonstrate an inducible association of PKCa, PICK1 and nephrin in podocytes. Moreover, we can demonstrate a strong induction of PKCa in podocytes of patients with diabetic nephropathy. Conclusions/Significance: We therefore conclude that activation of PKCa is a pathomechanistic key event during the development of diabetic nephropathy. PKCa is involved in reduction of nephrin surface expression and therefore PKC
Living with a diagnosis of behavioural-variant frontotemporal dementia: The personâs experience.
YesResearch investigating behavioural-variant frontotemporal dementia has concentrated on identifying and quantifying peopleâs difficulties; yet few studies have considered how people with behavioural-variant frontotemporal dementia make sense of their difficulties. Five participants were interviewed and interpretive phenomenological analysis used to analyse the data. Two superordinate themes emerged: âBewildermentâ and âRelationships with othersâ. âBewildermentâ reflected the feelings of the participants from the start of their dementia, and was divided into two main themes (1) âAwareness of change: Whatâs the problem? and (2) Threats to self: This is not me. The superordinate theme, âRelationships with othersâ, reflected difficulties with social relationships and comprised two main themes (1) âFamily and friends: Things havenât changed⊠but do I say anything wrong?â and (2) Coping with threats to self: Blame others or just avoid them. The themes were discussed in relation to literature evaluating the difficulties associated with behavioural-variant frontotemporal dementia together with implications for clinical practice
Differential limit on the extremely-high-energy cosmic neutrino flux in the presence of astrophysical background from nine years of IceCube data
We report a quasi-differential upper limit on the extremely-high-energy (EHE)
neutrino flux above GeV based on an analysis of nine years of
IceCube data. The astrophysical neutrino flux measured by IceCube extends to
PeV energies, and it is a background flux when searching for an independent
signal flux at higher energies, such as the cosmogenic neutrino signal. We have
developed a new method to place robust limits on the EHE neutrino flux in the
presence of an astrophysical background, whose spectrum has yet to be
understood with high precision at PeV energies. A distinct event with a
deposited energy above GeV was found in the new two-year sample, in
addition to the one event previously found in the seven-year EHE neutrino
search. These two events represent a neutrino flux that is incompatible with
predictions for a cosmogenic neutrino flux and are considered to be an
astrophysical background in the current study. The obtained limit is the most
stringent to date in the energy range between and GeV. This result constrains neutrino models predicting a three-flavor
neutrino flux of $E_\nu^2\phi_{\nu_e+\nu_\mu+\nu_\tau}\simeq2\times 10^{-8}\
{\rm GeV}/{\rm cm}^2\ \sec\ {\rm sr}10^9\ {\rm GeV}$. A significant part
of the parameter-space for EHE neutrino production scenarios assuming a
proton-dominated composition of ultra-high-energy cosmic rays is excluded.Comment: The version accepted for publication in Physical Review
Investigation of two Fermi-LAT gamma-ray blazars coincident with high-energy neutrinos detected by IceCube
After the identification of the gamma-ray blazar TXS 0506+056 as the first
compelling IceCube neutrino source candidate, we perform a systematic analysis
of all high-energy neutrino events satisfying the IceCube realtime trigger
criteria. We find one additional known gamma-ray source, the blazar GB6
J1040+0617, in spatial coincidence with a neutrino in this sample. The chance
probability of this coincidence is 30% after trial correction. For the first
time, we present a systematic study of the gamma-ray flux, spectral and optical
variability, and multi-wavelength behavior of GB6 J1040+0617 and compare it to
TXS 0506+056. We find that TXS 0506+056 shows strong flux variability in the
Fermi-LAT gamma-ray band, being in an active state around the arrival of
IceCube-170922A, but in a low state during the archival IceCube neutrino flare
in 2014/15. In both cases the spectral shape is statistically compatible () with the average spectrum showing no indication of a significant
relative increase of a high-energy component. While the association of GB6
J1040+0617 with the neutrino is consistent with background expectations, the
source appears to be a plausible neutrino source candidate based on its
energetics and multi-wavelength features, namely a bright optical flare and
modestly increased gamma-ray activity. Finding one or two neutrinos originating
from gamma-ray blazars in the given sample of high-energy neutrinos is
consistent with previously derived limits of neutrino emission from gamma-ray
blazars, indicating the sources of the majority of cosmic high-energy neutrinos
remain unknown.Comment: 22 pages, 11 figures, 2 Table
Paper Trails: Following the Money
In many recent elections, the candidates who raise the most money have a better shot at winning, so candidates must raise millions of dollars to win an election. A top question to consider in all elections: Where is the money coming from?
Posting about the financing behind federal elections from In All Things - an online hub committed to the claim that the life, death, and resurrection of Jesus Christ has implications for the entire world.
http://inallthings.org/paper-trails-following-the-money
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