356 research outputs found
Pkd2 dosage influences cellular repair responses following ischemia-reperfusion injury
Autosomal dominant polycystic kidney disease (ADPKD) results from mutations in either PKD1 or PKD2 and accounts for 10% of all patients on renal replacement therapy. The kidney disease phenotype is primarily characterized by cyst formation, but there are also prominent interstitial changes (inflammation, apoptosis, proliferation, and fibrosis). Using a model of unilateral ischemia-reperfusion injury, we tested the hypothesis that Pkd2 heterozygous kidneys are more sensitive to injury and that this could lead to interstitial inflammation and fibrosis. Baseline tubular proliferation in heterozygous kidneys was twofold higher than in wild-type kidneys. The magnitude and duration of tubular and interstitial proliferative responses was consistently greater in injured heterozygous compared with wild-type kidneys at all time points. Conversely, tubular p21 expression in heterozygotes was lower at baseline and following injury at all time points. Significantly more neutrophils and macrophages were detected in injured Pkd2 heterozygous kidneys at 2 days, correlating with increased expression of the cytokines interleukin (IL)-1 beta and keratinocyte-derived chemokine and resulting in interstitial fibrosis at 28 days. We conclude that Pkd2 dosage influences both susceptibility and nature of the repair responses following injury. Polycystin-2 is therefore likely to play multiple roles in regulating tubular cell viability, repair, and remodeling in the mature kidney
Characterization and observation of animals responsible for rabies post-exposure treatment in Phnom Penh, Cambodia
In order to provide relevant therapeutic answers to human patients exposed to risk of rabies infection
who visit the lnstitut Pasteur du Cambodge for post-exposure treatment and to improve control of
rabies in Cambodia, a pilot study was carried out in Phnom Penh Province in November and December
1997 with three objectives: characterization of the population of animals responsible for the exposure
to rabies, observation of the animals concerned, and confirmation of the presence of rabies
virus in the province. Between 18 November 1997 and 19 December 1997, 409 of the 741 patients
treated at the lnstitut Pasteur du Cambodge because of an exposure to a known rabies vector were
included in the study. The animals concerned were: 401 dogs (98 %), six monkeys (1 ,5 %) and two
cats (0,5%). Three-hundred-and-seventy of the animals (90,5%) were owned, 4 (1 %) were unowned
but were available for characterization and observation, and 35 (8,6 %) had an unknown ownership
status and were not available for further study. The exposures occurred on private property in 84% of
the cases, and 80 of the 370 owned animals (22 %) lived in the same home as had the patient. The
374 animals with known ownership status were examined. Five were already dead and two of these
five dogs had presented clinical signs typical of those of rabies. The male:female sex ratio of the dogs
was 2,1: 1. The 369 live animals were placed under observation for 10 d immediately after exposure
of the humans had taken place. At the end of the period none of the animals had developed clinical
signs of rabies, three had died of diseases other than rabies, and one was lost. Tests for the rabies
nucleocapsid antigen were positive in two cases (the two suspected rabid dogs), confirming the presence
of rabies in Phnom Penh Province. Consequently, we recommend measures to improve the
control of rabies in Cambodia.The articles have been scanned in colour with a HP Scanjet 5590; 600dpi.
Adobe Acrobat v.9 was used to OCR the text and also for the merging and conversion to the final presentation PDF-format.mn201
Spin density wave dislocation in chromium probed by coherent x-ray diffraction
We report on the study of a magnetic dislocation in pure chromium. Coherent
x-ray diffraction profiles obtained on the incommensurate Spin Density Wave
(SDW) reflection are consistent with the presence of a dislocation of the
magnetic order, embedded at a few micrometers from the surface of the sample.
Beyond the specific case of magnetic dislocations in chromium, this work may
open up a new method for the study of magnetic defects embedded in the bulk.Comment: 8 pages, 7 figure
Global Phase Diagram of the Kondo Lattice: From Heavy Fermion Metals to Kondo Insulators
We discuss the general theoretical arguments advanced earlier for the T=0
global phase diagram of antiferromagnetic Kondo lattice systems, distinguishing
between the established and the conjectured. In addition to the well-known
phase of a paramagnetic metal with a "large" Fermi surface (P_L), there is also
an antiferromagnetic phase with a "small" Fermi surface (AF_S). We provide the
details of the derivation of a quantum non-linear sigma-model (QNLsM)
representation of the Kondo lattice Hamiltonian, which leads to an effective
field theory containing both low-energy fermions in the vicinity of a Fermi
surface and low-energy bosons near zero momentum. An asymptotically exact
analysis of this effective field theory is made possible through the
development of a renormalization group procedure for mixed fermion-boson
systems. Considerations on how to connect the AF_S and P_L phases lead to a
global phase diagram, which not only puts into perspective the theory of local
quantum criticality for antiferromagnetic heavy fermion metals, but also
provides the basis to understand the surprising recent experiments in
chemically-doped as well as pressurized YbRh2Si2. We point out that the AF_S
phase still occurs for the case of an equal number of spin-1/2 local moments
and conduction electrons. This observation raises the prospect for a global
phase diagram of heavy fermion systems in the Kondo-insulator regime. Finally,
we discuss the connection between the Kondo breakdown physics discussed here
for the Kondo lattice systems and the non-Fermi liquid behavior recently
studied from a holographic perspective.Comment: (v3) leftover typos corrected. (v2) Published version. 32 pages, 4
figures. Section 7, on the connection between the Kondo lattice systems and
the holographic models of non-Fermi liquid, is expanded. (v1) special issue
of JLTP on quantum criticalit
Discovery and characterization of a specific inhibitor of serine-threonine kinase cyclin-dependent kinase-like 5 (CDKL5) demonstrates role in hippocampal CA1 physiology
Pathological loss-of-function mutations in cyclin-dependent kinase-like 5 (CDKL5) cause CDKL5 deficiency disorder (CDD), a rare and severe neurodevelopmental disorder associated with severe and medically refractory early-life epilepsy, motor, cognitive, visual, and autonomic disturbances in the absence of any structural brain pathology. Analysis of genetic variants in CDD has indicated that CDKL5 kinase function is central to disease pathology. CDKL5 encodes a serine-threonine kinase with significant homology to GSK3β, which has also been linked to synaptic function. Further, Cdkl5 knock-out rodents have increased GSK3β activity and often increased long-term potentiation (LTP). Thus, development of a specific CDKL5 inhibitor must be careful to exclude cross-talk with GSK3β activity. We synthesized and characterized specific, high-affinity inhibitors of CDKL5 that do not have detectable activity for GSK3β. These compounds are very soluble in water but blood-brain barrier penetration is low. In rat hippocampal brain slices, acute inhibition of CDKL5 selectively reduces postsynaptic function of AMPA-type glutamate receptors in a dose-dependent manner. Acute inhibition of CDKL5 reduces hippocampal LTP. These studies provide new tools and insights into the role of CDKL5 as a newly appreciated key kinase necessary for synaptic plasticity. Comparisons to rodent knock-out studies suggest that compensatory changes have limited the understanding of the roles of CDKL5 in synaptic physiology, plasticity, and human neuropathology
Spin-Charge Separation in the Model: Magnetic and Transport Anomalies
A real spin-charge separation scheme is found based on a saddle-point state
of the model. In the one-dimensional (1D) case, such a saddle-point
reproduces the correct asymptotic correlations at the strong-coupling
fixed-point of the model. In the two-dimensional (2D) case, the transverse
gauge field confining spinon and holon is shown to be gapped at {\em finite
doping} so that a spin-charge deconfinement is obtained for its first time in
2D. The gap in the gauge fluctuation disappears at half-filling limit, where a
long-range antiferromagnetic order is recovered at zero temperature and spinons
become confined. The most interesting features of spin dynamics and transport
are exhibited at finite doping where exotic {\em residual} couplings between
spin and charge degrees of freedom lead to systematic anomalies with regard to
a Fermi-liquid system. In spin dynamics, a commensurate antiferromagnetic
fluctuation with a small, doping-dependent energy scale is found, which is
characterized in momentum space by a Gaussian peak at (, ) with
a doping-dependent width (, is the doping
concentration). This commensurate magnetic fluctuation contributes a
non-Korringa behavior for the NMR spin-lattice relaxation rate. There also
exits a characteristic temperature scale below which a pseudogap behavior
appears in the spin dynamics. Furthermore, an incommensurate magnetic
fluctuation is also obtained at a {\em finite} energy regime. In transport, a
strong short-range phase interference leads to an effective holon Lagrangian
which can give rise to a series of interesting phenomena including linear-
resistivity and Hall-angle. We discuss the striking similarities of these
theoretical features with those found in the high- cuprates and give aComment: 70 pages, RevTex, hard copies of 7 figures available upon request;
minor revisions in the text and references have been made; To be published in
July 1 issue of Phys. Rev. B52, (1995
Particle-Vortex Duality and the Modular Group: Applications to the Quantum Hall Effect and Other 2-D Systems
We show how particle-vortex duality implies the existence of a large
non-abelian discrete symmetry group which relates the electromagnetic response
for dual two-dimensional systems in a magnetic field. For conductors with
charge carriers satisfying Fermi statistics (or those related to fermions by
the action of the group), the resulting group is known to imply many, if not
all, of the remarkable features of Quantum Hall systems. For conductors with
boson charge carriers (modulo group transformations) a different group is
predicted, implying equally striking implications for the conductivities of
these systems, including a super-universality of the critical exponents for
conductor/insulator and superconductor/insulator transitions in two dimensions
and a hierarchical structure, analogous to that of the quantum Hall effect but
different in its details. Our derivation shows how this symmetry emerges at low
energies, depending only weakly on the details of dynamics of the underlying
systems.Comment: 22 pages, LaTeX, 2 figures, uses revte
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