129 research outputs found
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Abstract not availabl
Dietary supplementation of cystinotic mice by lysine inhibits the megalin pathway and decreases kidney cystine content.
peer reviewedMegalin/LRP2 is a major receptor supporting apical endocytosis in kidney proximal tubular cells. We have previously reported that kidney-specific perinatal ablation of the megalin gene in cystinotic mice, a model of nephropathic cystinosis, essentially blocks renal cystine accumulation and partially preserves kidney tissue integrity. Here, we examined whether inhibition of the megalin pathway in adult cystinotic mice by dietary supplementation (5x-fold vs control regular diet) with the dibasic amino-acids (dAAs), lysine or arginine, both of which are used to treat patients with other rare metabolic disorders, could also decrease renal cystine accumulation and protect cystinotic kidneys. Using surface plasmon resonance, we first showed that both dAAs compete for protein ligand binding to immobilized megalin in a concentration-dependent manner, with identical inhibition curves by L- and D-stereoisomers. In cystinotic mice, 2-month diets with 5x-L-lysine and 5x-L-arginine were overall well tolerated, while 5x-D-lysine induced strong polyuria but no weight loss. All diets induced a marked increase of dAA urinary excretion, most prominent under 5x-D-lysine, without sign of kidney insufficiency. Renal cystine accumulation was slowed down approx. twofold by L-dAAs, and totally suppressed by D-lysine. We conclude that prolonged dietary manipulation of the megalin pathway in kidneys is feasible, tolerable and can be effective in vivo
Mechanism of primitive duct formation in the pancreas and submandibular glands: a role for SDF-1
BACKGROUND: The exocrine pancreas is composed of a branched network of ducts connected to acini. They are lined by a monolayered epithelium that derives from the endoderm and is surrounded by mesoderm-derived mesenchyme. The morphogenic mechanisms by which the ductal network is established as well as the signaling pathways involved in this process are poorly understood. RESULTS: By morphological analyzis of wild-type and mutant mouse embryos and using cultured embryonic explants we investigated how epithelial morphogenesis takes place and is regulated by chemokine signaling. Pancreas ontogenesis displayed a sequence of two opposite epithelial transitions. During the first transition, the monolayered and polarized endodermal cells give rise to tissue buds composed of a mass of non polarized epithelial cells. During the second transition the buds reorganize into branched and polarized epithelial monolayers that further differentiate into tubulo-acinar glands. We found that the second epithelial transition is controlled by the chemokine Stromal cell-Derived Factor (SDF)-1. The latter is expressed by the mesenchyme, whereas its receptor CXCR4 is expressed by the epithelium. Reorganization of cultured pancreatic buds into monolayered epithelia was blocked in the presence of AMD3100, a SDF-1 antagonist. Analyzis of sdf1 and cxcr4 knockout embryos at the stage of the second epithelial transition revealed transient defective morphogenesis of the ventral and dorsal pancreas. Reorganization of a globular mass of epithelial cells in polarized monolayers is also observed during submandibular glands development. We found that SDF-1 and CXCR4 are expressed in this organ and that AMD3100 treatment of submandibular gland explants blocks its branching morphogenesis. CONCLUSION: In conclusion, our data show that the primitive pancreatic ductal network, which is lined by a monolayered and polarized epithelium, forms by remodeling of a globular mass of non polarized epithelial cells. Our data also suggest that SDF-1 controls the branching morphogenesis of several exocrine tissues.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe
Transverse Momentum Dependent Parton Distribution/Fragmentation Functions at an Electron-Ion Collider
We present a summary of a recent workshop held at Duke University on Partonic
Transverse Momentum in Hadrons: Quark Spin-Orbit Correlations and Quark-Gluon
Interactions. The transverse momentum dependent parton distribution functions
(TMDs), parton-to-hadron fragmentation functions, and multi-parton correlation
functions, were discussed extensively at the Duke workshop. In this paper, we
summarize first the theoretical issues concerning the study of partonic
structure of hadrons at a future electron-ion collider (EIC) with emphasis on
the TMDs. We then present simulation results on experimental studies of TMDs
through measurements of single spin asymmetries (SSA) from semi-inclusive
deep-inelastic scattering (SIDIS) processes with an EIC, and discuss the
requirement of the detector for SIDIS measurements. The dynamics of parton
correlations in the nucleon is further explored via a study of SSA in D (`D)
production at large transverse momenta with the aim of accessing the unexplored
tri-gluon correlation functions. The workshop participants identified the SSA
measurements in SIDIS as a golden program to study TMDs in both the sea and
valence quark regions and to study the role of gluons, with the Sivers
asymmetry measurements as examples. Such measurements will lead to major
advancement in our understanding of TMDs in the valence quark region, and more
importantly also allow for the investigation of TMDs in the sea quark region
along with a study of their evolution.Comment: 44 pages 23 figures, summary of Duke EIC workshop on TMDs accepted by
EPJ
Double parton correlations and constituent quark models: a light front approach to the valence sector
An explicit evaluation of the double parton distribution functions (dPDFs), within a relativistic Light-Front approach to constituent quark models, is presented. dPDFs encode information on the correlations between two partons inside a target and represent the non-perturbative QCD ingredient for the description of double parton scattering in proton-proton collisions, a crucial issue in the search of new Physics at the LHC. Valence dPDFs are evaluated at the low scale of the model and the perturbative scale of the experiments is reached by means of QCD evolution. The present results show that the strong correlation effects present at the scale of the model are still sizable, in the valence region, at the experimental scale. At the low values of x presently studied at the LHC the correlations become less relevant, although they are still important for the spin-dependent contributions to unpolarized proton scattering
Single Spin Asymmetries in High Energy Reactions and Nonperturbative QCD Effects
We discuss some experimental and theoretical results on single spin
asymmetries (SSA) in high energy lepton-hadron and hadron-hadron reactions. In
particular, recent results on meson SSA obtained by HERMES are considered in
detail. We also discuss the SSA results obtained recently by COMPASS, as well
as those from BRAHMS, PHENIX and STAR. Special attention is paid to a possible
nonperturbative QCD mechanism that might be responsible for the observed meson
SSA. This mechanism originates from the spin-flip quark-gluon chromomagnetic
interaction induced by the complex topological structure of the QCD vacuum. We
argue that in semi-inclusive deep-inelastic scattering a large SSA is expected
not only for mesons but also for baryons due to strong nonperturbative final
state interactions between -diquark and -quark in the fragmenting
proton.Comment: 9 pages,8 figure
Probing exotic phenomena at the interface of nuclear and particle physics with the electric dipole moments of diamagnetic atoms: A unique window to hadronic and semi-leptonic CP violation
The current status of electric dipole moments of diamagnetic atoms which
involves the synergy between atomic experiments and three different theoretical
areas -- particle, nuclear and atomic is reviewed. Various models of particle
physics that predict CP violation, which is necessary for the existence of such
electric dipole moments, are presented. These include the standard model of
particle physics and various extensions of it. Effective hadron level combined
charge conjugation (C) and parity (P) symmetry violating interactions are
derived taking into consideration different ways in which a nucleon interacts
with other nucleons as well as with electrons. Nuclear structure calculations
of the CP-odd nuclear Schiff moment are discussed using the shell model and
other theoretical approaches. Results of the calculations of atomic electric
dipole moments due to the interaction of the nuclear Schiff moment with the
electrons and the P and time-reversal (T) symmetry violating
tensor-pseudotensor electron-nucleus are elucidated using different
relativistic many-body theories. The principles of the measurement of the
electric dipole moments of diamagnetic atoms are outlined. Upper limits for the
nuclear Schiff moment and tensor-pseudotensor coupling constant are obtained
combining the results of atomic experiments and relativistic many-body
theories. The coefficients for the different sources of CP violation have been
estimated at the elementary particle level for all the diamagnetic atoms of
current experimental interest and their implications for physics beyond the
standard model is discussed. Possible improvements of the current results of
the measurements as well as quantum chromodynamics, nuclear and atomic
calculations are suggested.Comment: 46 pages, 19 tables and 16 figures. A review article accepted for
EPJ
Segregation of Fluorescent Membrane Lipids into Distinct Micrometric Domains: Evidence for Phase Compartmentation of Natural Lipids?
Background: We recently reported that sphingomyelin (SM) analogs substituted on the alkyl chain by various fluorophores (e.g. BODIPY) readily inserted at trace levels into the plasma membrane of living erythrocytes or CHO cells and spontaneously concentrated into micrometric domains. Despite sharing the same fluorescent ceramide backbone, BODIPY-SM domains segregated from similar domains labelled by BODIPY-D-e-lactosylceramide (D-e-LacCer) and depended on endogenous SM.
Methodology/Principal Findings. We show here that BODIPY-SM further differed from BODIPY-D-e-LacCer or -glucosylceramide (GlcCer) domains in temperature dependence, propensity to excimer formation, association with a glycosylphosphatidylinositol (GPI)-anchored fluorescent protein reporter, and lateral diffusion by FRAP, thus demonstrating different lipid phases and boundaries. Whereas BODIPY-D-e-LacCer behaved like BODIPY-GlcCer, its artificial stereoisomer, BODIPY-L-t-LacCer, behaved like BODIPY- and NBD-phosphatidylcholine (PC). Surprisingly, these two PC analogs also formed micrometric patches yet preferably at low temperature, did not show excimer, never associated with the GPI reporter and showed major restriction to lateral diffusion when photobleached in large fields. This functional comparison supported a three-phase micrometric compartmentation, of decreasing order: BODIPY-GSLs > -SM > -PC (or artificial L-t-LacCer). Co-existence of three segregated compartments was further supported by double labelling experiments and was confirmed by additive occupancy, up to ~70% cell surface coverage. Specific alterations of BODIPY-analogs domains by manipulation of corresponding endogenous sphingolipids suggested that distinct fluorescent lipid partition might reflect differential intrinsic propensity of endogenous membrane lipids to form large assemblies.
Conclusions/Significance. We conclude that fluorescent membrane lipids spontaneously concentrate into distinct micrometric assemblies. We hypothesize that these might reflect preexisting compartmentation of endogenous PM lipids into non-overlapping domains of differential order: GSLs > SM > PC, resulting into differential self-adhesion of the two former, with exclusion of the latter
Uterine fibroids â whatâs new?
Uterine fibroids are the commonest benign tumours of women and affect all races with a cumulative lifetime risk of around 70%. Despite their high prevalence and the heavy economic burden of treatment, fibroids have received remarkably little attention compared to common female malignant tumours. This article reviews recent progress in understanding the biological nature of fibroids, their life cycle and their molecular genetic origins. Recent progress in surgical and interventional management is briefly reviewed, and medical management options, including treatment with selective progesterone receptor modulators, are also discussed
Strong Interaction Physics at the Luminosity Frontier with 22 GeV Electrons at Jefferson Lab
This document presents the initial scientific case for upgrading the
Continuous Electron Beam Accelerator Facility (CEBAF) at Jefferson Lab (JLab)
to 22 GeV. It is the result of a community effort, incorporating insights from
a series of workshops conducted between March 2022 and April 2023. With a track
record of over 25 years in delivering the world's most intense and precise
multi-GeV electron beams, CEBAF's potential for a higher energy upgrade
presents a unique opportunity for an innovative nuclear physics program, which
seamlessly integrates a rich historical background with a promising future. The
proposed physics program encompass a diverse range of investigations centered
around the nonperturbative dynamics inherent in hadron structure and the
exploration of strongly interacting systems. It builds upon the exceptional
capabilities of CEBAF in high-luminosity operations, the availability of
existing or planned Hall equipment, and recent advancements in accelerator
technology. The proposed program cover various scientific topics, including
Hadron Spectroscopy, Partonic Structure and Spin, Hadronization and Transverse
Momentum, Spatial Structure, Mechanical Properties, Form Factors and Emergent
Hadron Mass, Hadron-Quark Transition, and Nuclear Dynamics at Extreme
Conditions, as well as QCD Confinement and Fundamental Symmetries. Each topic
highlights the key measurements achievable at a 22 GeV CEBAF accelerator.
Furthermore, this document outlines the significant physics outcomes and unique
aspects of these programs that distinguish them from other existing or planned
facilities. In summary, this document provides an exciting rationale for the
energy upgrade of CEBAF to 22 GeV, outlining the transformative scientific
potential that lies within reach, and the remarkable opportunities it offers
for advancing our understanding of hadron physics and related fundamental
phenomena.Comment: Updates to the list of authors; Preprint number changed from theory
to experiment; Updates to sections 4 and 6, including additional figure
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