1,026 research outputs found
Mercapturate Pathway in the Tubulocentric Perspective of Diabetic Kidney Disease
BACKGROUND: The recent growing evidence that the proximal tubule underlies the
early pathogenesis of diabetic kidney disease (DKD) is unveiling novel and
promising perspectives. This pathophysiological concept links tubulointerstitial
oxidative stress, inflammation, hypoxia, and fibrosis with the progression of
DKD. In this new angle for DKD, the prevailing molecular mechanisms on proximal
tubular cells emerge as an innovative opportunity for prevention and management
of DKD as well as to improve diabetic dysmetabolism.
SUMMARY: The mercapturate pathway (MAP) is a classical metabolic detoxification
route for xenobiotics that is emerging as an integrative circuitry detrimental to
resolve tubular inflammation caused by endogenous electrophilic species. Herein
we review why and how it might underlie DKD. Key Messages: MAP is a hallmark of
proximal tubular cell function, and cysteine-S-conjugates might represent targets
for early intervention in DKD. Moreover, the biomonitoring of urinary
mercapturates from metabolic inflammation products might be relevant for the
implementation of preventive/management strategies in DKD.info:eu-repo/semantics/publishedVersio
A chemical survey of exoplanets with ARIEL
Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio
Cyclophilin B Interacts with Sodium-Potassium ATPase and Is Required for Pump Activity in Proximal Tubule Cells of the Kidney
Cyclophilins (Cyps), the intracellular receptors for Cyclosporine A (CsA), are responsible for peptidyl-prolyl cis-trans isomerisation and for chaperoning several membrane proteins. Those functions are inhibited upon CsA binding. Albeit its great benefits as immunosuppressant, the use of CsA has been limited by undesirable nephrotoxic effects, including sodium retention, hypertension, hyperkalemia, interstial fibrosis and progressive renal failure in transplant recipients. In this report, we focused on the identification of novel CypB-interacting proteins to understand the role of CypB in kidney function and, in turn, to gain further insight into the molecular mechanisms of CsA-induced toxicity. By means of yeast two-hybrid screens with human kidney cDNA, we discovered a novel interaction between CypB and the membrane Na/K-ATPase β1 subunit protein (Na/K-β1) that was confirmed by pull-down, co-immunoprecipitation and confocal microscopy, in proximal tubule-derived HK-2 cells. The Na/K-ATPase pump, a key plasma membrane transporter, is responsible for maintenance of electrical Na+ and K+ gradients across the membrane. We showed that CypB silencing produced similar effects on Na/K-ATPase activity than CsA treatment in HK-2 cells. It was also observed an enrichment of both alpha and beta subunits in the ER, what suggested a possible failure on the maturation and routing of the pump from this compartment towards the plasma membrane. These data indicate that CypB through its interaction with Na/K-β1 might regulate maturation and trafficking of the pump through the secretory pathway, offering new insights into the relationship between cyclophilins and the nephrotoxic effects of CsA
Studying the Underlying Event in Drell-Yan and High Transverse Momentum Jet Production at the Tevatron
We study the underlying event in proton-antiproton collisions by examining
the behavior of charged particles (transverse momentum pT > 0.5 GeV/c,
pseudorapidity |\eta| < 1) produced in association with large transverse
momentum jets (~2.2 fb-1) or with Drell-Yan lepton-pairs (~2.7 fb-1) in the
Z-boson mass region (70 < M(pair) < 110 GeV/c2) as measured by CDF at 1.96 TeV
center-of-mass energy. We use the direction of the lepton-pair (in Drell-Yan
production) or the leading jet (in high-pT jet production) in each event to
define three regions of \eta-\phi space; toward, away, and transverse, where
\phi is the azimuthal scattering angle. For Drell-Yan production (excluding the
leptons) both the toward and transverse regions are very sensitive to the
underlying event. In high-pT jet production the transverse region is very
sensitive to the underlying event and is separated into a MAX and MIN
transverse region, which helps separate the hard component (initial and
final-state radiation) from the beam-beam remnant and multiple parton
interaction components of the scattering. The data are corrected to the
particle level to remove detector effects and are then compared with several
QCD Monte-Carlo models. The goal of this analysis is to provide data that can
be used to test and improve the QCD Monte-Carlo models of the underlying event
that are used to simulate hadron-hadron collisions.Comment: Submitted to Phys.Rev.
Measurement of the Production Cross Section and Search for Anomalous and Couplings in Collisions at TeV
This Letter describes the current most precise measurement of the boson
pair production cross section and most sensitive test of anomalous
and couplings in collisions at a center-of-mass energy of 1.96
TeV. The candidates are reconstructed from decays containing two charged
leptons and two neutrinos, where the charged leptons are either electrons or
muons. Using data collected by the CDF II detector from 3.6 fb of
integrated luminosity, a total of 654 candidate events are observed with an
expected background contribution of events. The measured total
cross section is pb, which is in good agreement
with the standard model prediction. The same data sample is used to place
constraints on anomalous and couplings.Comment: submitted to Phys. Rev. Let
Measurement of CP-violation asymmetries in D0 to Ks pi+ pi-
We report a measurement of time-integrated CP-violation asymmetries in the
resonant substructure of the three-body decay D0 to Ks pi+ pi- using CDF II
data corresponding to 6.0 invfb of integrated luminosity from Tevatron ppbar
collisions at sqrt(s) = 1.96 TeV. The charm mesons used in this analysis come
from D*+(2010) to D0 pi+ and D*-(2010) to D0bar pi-, where the production
flavor of the charm meson is determined by the charge of the accompanying pion.
We apply a Dalitz-amplitude analysis for the description of the dynamic decay
structure and use two complementary approaches, namely a full Dalitz-plot fit
employing the isobar model for the contributing resonances and a
model-independent bin-by-bin comparison of the D0 and D0bar Dalitz plots. We
find no CP-violation effects and measure an asymmetry of ACP = (-0.05 +- 0.57
(stat) +- 0.54 (syst))% for the overall integrated CP-violation asymmetry,
consistent with the standard model prediction.Comment: 15 page
Intratumoral Injection of Propionibacterium acnes Suppresses Malignant Melanoma by Enhancing Th1 Immune Responses
Malignant melanoma (MM) is an aggressive cutaneous malignancy associated with poor prognosis; many putatively therapeutic agents have been administered, but with mostly unsuccessful results. Propionibacterium acnes (P. acnes) is an aerotolerant anaerobic gram-positive bacteria that causes acne and inflammation. After being engulfed and processed by phagocytes, P. acnes induces a strong Th1-type cytokine immune response by producing cytokines such as IL-12, IFN-γ and TNF-α. The characteristic Th2-mediated allergic response can be counteracted by Th1 cytokines induced by P. acnes injection. This inflammatory response induced by P. acnes has been suggested to have antitumor activity, but its effect on MM has not been fully evaluated
Observation of the Baryonic Flavor-Changing Neutral Current Decay Lambda_b -> Lambda mu+ mu-
We report the first observation of the baryonic flavor-changing neutral
current decay Lambda_b -> Lambda mu+ mu- with 24 signal events and a
statistical significance of 5.8 Gaussian standard deviations. This measurement
uses ppbar collisions data sample corresponding to 6.8fb-1 at sqrt{s}=1.96TeV
collected by the CDF II detector at the Tevatron collider. The total and
differential branching ratios for Lambda_b -> Lambda mu+ mu- are measured. We
find B(Lambda_b -> Lambda mu+ mu-) = [1.73+-0.42(stat)+-0.55(syst)] x 10^{-6}.
We also report the first measurement of the differential branching ratio of B_s
-> phi mu+ mu- using 49 signal events. In addition, we report branching ratios
for B+ -> K+ mu+ mu-, B0 -> K0 mu+ mu-, and B -> K*(892) mu+ mu- decays.Comment: 8 pages, 2 figures, 4 tables. Submitted to Phys. Rev. Let
Measurement of the Dipion Mass Spectrum in X(3872) -> J/Psi Pi+ Pi- Decays
We measure the dipion mass spectrum in X(3872)--> J/Psi Pi+ Pi- decays using
360 pb-1 of pbar-p collisions at 1.96 TeV collected with the CDF II detector.
The spectrum is fit with predictions for odd C-parity (3S1, 1P1, and 3DJ)
charmonia decaying to J/Psi Pi+ Pi-, as well as even C-parity states in which
the pions are from Rho0 decay. The latter case also encompasses exotic
interpretations, such as a D0-D*0Bar molecule. Only the 3S1 and J/Psi Rho
hypotheses are compatible with our data. Since 3S1 is untenable on other
grounds, decay via J/Psi Rho is favored, which implies C=+1 for the X(3872).
Models for different J/Psi-Rho angular momenta L are considered. Flexibility in
the models, especially the introduction of Rho-Omega interference, enable good
descriptions of our data for both L=0 and 1.Comment: 7 pages, 4 figures -- Submitted to Phys. Rev. Let
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