233 research outputs found
Dynamical generation of a nontrivial index on the fuzzy 2-sphere
In the previous paper hep-th/0312199 we studied the 't Hooft-Polyakov (TP)
monopole configuration in the U(2) gauge theory on the fuzzy 2-sphere and
showed that it has a nonzero topological charge in the formalism based on the
Ginsparg-Wilson relation. In this paper, by showing that the TP monopole
configuration is stabler than the U(2) gauge theory without any condensation in
the Yang-Mills-Chern-Simons matrix model, we will present a mechanism for
dynamical generation of a nontrivial index. We further analyze the instability
and decay processes of the U(2) gauge theory and the TP monopole configuration.Comment: Latex2e, 30 pages, 4 figures, the topological charge for a monopole
configuration is corrected, reference added, the final version to appear in
Physical Review D (the typos mentioned in the erratum are corrected
Patch Materials for Pulmonary Artery Arterioplasty and Right Ventricular Outflow Tract Augmentation: A Review
Patch augmentation of the right ventricular outflow tract (RVOT) and pulmonary artery (PA) arterioplasty are relatively common procedures in the surgical treatment of patients with congenital heart disease. To date, several patch materials have been applied with no agreed upon clinical standard. Each patch type has unique performance characteristics, cost, and availability. There are limited data describing the various advantages and disadvantages of different patch materials. We performed a review of studies describing the clinical performance of various RVOT and PA patch materials and found a limited but growing body of literature. Short-term clinical performance has been reported for a multitude of patch types, but comparisons are limited by inconsistent study design and scarce histologic data. Standard clinical criteria for assessment of patch efficacy and criteria for intervention need to be applied across patch types. The field is progressing with improvements in outcomes due to newer patch technologies focused on reducing antigenicity and promoting neotissue formation which may have the ability to grow, remodel, and repair
FE65 as a link between VLDLR and APP to regulate their trafficking and processing
<p>Abstract</p> <p>Background</p> <p>Several studies found that FE65, a cytoplasmic adaptor protein, interacts with APP and LRP1, altering the trafficking and processing of APP. We have previously shown that FE65 interacts with the ApoE receptor, ApoER2, altering its trafficking and processing. Interestingly, it has been shown that FE65 can act as a linker between APP and LRP1 or ApoER2. In the present study, we tested whether FE65 can interact with another ApoE receptor, VLDLR, thereby altering its trafficking and processing, and whether FE65 can serve as a linker between APP and VLDLR.</p> <p>Results</p> <p>We found that FE65 interacted with VLDLR using GST pull-down and co-immunoprecipitation assays in COS7 cells and in brain lysates. This interaction occurs via the PTB1 domain of FE65. Co-transfection with FE65 and full length VLDLR increased secreted VLDLR (sVLDLR); however, the levels of VLDLR C-terminal fragment (CTF) were undetectable as a result of proteasomal degradation. Additionally, FE65 increased cell surface levels of VLDLR. Moreover, we identified a novel complex between VLDLR and APP, which altered trafficking and processing of both proteins. Furthermore, immunoprecipitation results demonstrated that the presence of FE65 increased the interaction between APP and VLDLR <it>in vitro </it>and <it>in vivo</it>.</p> <p>Conclusions</p> <p>These data suggest that FE65 can regulate VLDLR trafficking and processing. Additionally, the interaction between VLDLR and APP altered both protein's trafficking and processing. Finally, our data suggest that FE65 serves as a link between VLDLR and APP. This novel interaction adds to a growing body of literature indicating trimeric complexes with various ApoE Receptors and APP.</p
A putative relay circuit providing low-threshold mechanoreceptive input to lamina I projection neurons via vertical cells in lamina II of the rat dorsal horn
Background:
Lamina I projection neurons respond to painful stimuli, and some are also activated by touch or hair movement. Neuropathic pain resulting from peripheral nerve damage is often associated with tactile allodynia (touch-evoked pain), and this may result from increased responsiveness of lamina I projection neurons to non-noxious mechanical stimuli. It is thought that polysynaptic pathways involving excitatory interneurons can transmit tactile inputs to lamina I projection neurons, but that these are normally suppressed by inhibitory interneurons. Vertical cells in lamina II provide a potential route through which tactile stimuli can activate lamina I projection neurons, since their dendrites extend into the region where tactile afferents terminate, while their axons can innervate the projection cells. The aim of this study was to determine whether vertical cell dendrites were contacted by the central terminals of low-threshold mechanoreceptive primary afferents.
Results:
We initially demonstrated contacts between dendritic spines of vertical cells that had been recorded in spinal cord slices and axonal boutons containing the vesicular glutamate transporter 1 (VGLUT1), which is expressed by myelinated low-threshold mechanoreceptive afferents. To confirm that the VGLUT1 boutons included primary afferents, we then examined vertical cells recorded in rats that had received injections of cholera toxin B subunit (CTb) into the sciatic nerve. We found that over half of the VGLUT1 boutons contacting the vertical cells were CTb-immunoreactive, indicating that they were of primary afferent origin.
Conclusions:
These results show that vertical cell dendritic spines are frequently contacted by the central terminals of myelinated low-threshold mechanoreceptive afferents. Since dendritic spines are associated with excitatory synapses, it is likely that most of these contacts were synaptic. Vertical cells in lamina II are therefore a potential route through which tactile afferents can activate lamina I projection neurons, and this pathway could play a role in tactile allodynia
Point defects and clustering in uranium dioxide by LSDA+U calculations
A comprehensive investigation on point defects and their clustering behavior
in nonstoichiometric uranium dioxide UO2+x is carried out using LSDA+U method
based on density functional theory. Accurate energetic information and charge
transfers available so far are obtained. With these energies that have improved
more than 50% over that of pure GGA and LDA, we show the density functional
theory predicts the predominance of oxygen defects over uranium ones at any
compositions, which is possible only after treated the localized 5f electrons
properly. Calculations also suggest an upper bound of x~0.03 for oxygen
clusters to start off. The volume change induced by point uranium defects is
monotonic but nonlinear, whereas for oxygen defects, increase x always reduces
the system volume linearly, except dimers that require extra space for
accommodation, which has been identified as meta-stable ionic molecule. Though
oxygen dimers usually occupy Willis O'' sites and mimic a single oxygen in
energetics and charge state, they are rare at ambient conditions. Its
decomposition process and vibrational properties have been studied carefully.
To obtain a general clustering mechanism in anion-excess fluorites
systematically, we also analyze the local stabilities of possible basic
clustering modes of oxygen defects. The result shows an unified way to
understand the structure of Willis type and cuboctahedral clusters in UO2+x and
beta-U4O9. Finally we generalize the point defect model to the independent
clusters approximation to include clustering effects, the impact on defect
populations is discussed.Comment: 20 pages, 12 figure
Intracellular Trafficking of the Amyloid β-Protein Precursor (APP) Regulated by Novel Function of X11-Like
Background: Amyloid beta (A beta), a causative peptide of Alzheimer's disease, is generated by intracellular metabolism of amyloid beta-protein precursor (APP). In general, mature APP (mAPP, N- and O-glycosylated form) is subject to successive cleavages by alpha- or beta-, and gamma-secretases in the late protein secretory pathway and/or at plasma membrane, while immature APP (imAPP, N-glycosylated form) locates in the early secretory pathway such as endoplasmic reticulum or cis-Golgi, in which imAPP is not subject to metabolic cleavages. X11-like (X11L) is a neural adaptor protein composed of a phosphotyrosine-binding (PTB) and two C-terminal PDZ domains. X11L suppresses amyloidogenic cleavage of mAPP by direct binding of X11L through its PTB domain, thereby generation of A beta lowers. X11L expresses another function in the regulation of intracellular APP trafficking. Methodology: In order to analyze novel function of X11L in intracellular trafficking of APP, we performed a functional dissection of X11L. Using cells expressing various domain-deleted X11L mutants, intracellular APP trafficking was examined along with analysis of APP metabolism including maturation (O-glycosylation), processing and localization of APP. Conclusions: X11L accumulates imAPP into the early secretory pathway by mediation of its C-terminal PDZ domains, without being bound to imAPP directly. With this novel function, X11L suppresses overall APP metabolism and results in further suppression of Ab generation. Interestingly some of the accumulated imAPP in the early secretory pathway are likely to appear on plasma membrane by unidentified mechanism. Trafficking of imAPP to plasma membrane is observed in other X11 family proteins, X11 and X11L2, but not in other APP-binding partners such as FE65 and JIP1. It is herein clear that respective functional domains of X11L regulate APP metabolism at multiple steps in intracellular protein secretory pathways
Arabidopsis thaliana PGR7 Encodes a Conserved Chloroplast Protein That Is Necessary for Efficient Photosynthetic Electron Transport
A significant fraction of a plant's nuclear genome encodes chloroplast-targeted proteins, many of which are devoted to the assembly and function of the photosynthetic apparatus. Using digital video imaging of chlorophyll fluorescence, we isolated proton gradient regulation 7 (pgr7) as an Arabidopsis thaliana mutant with low nonphotochemical quenching of chlorophyll fluorescence (NPQ). In pgr7, the xanthophyll cycle and the PSBS gene product, previously identified NPQ factors, were still functional, but the efficiency of photosynthetic electron transport was lower than in the wild type. The pgr7 mutant was also smaller in size and had lower chlorophyll content than the wild type in optimal growth conditions. Positional cloning located the pgr7 mutation in the At3g21200 (PGR7) gene, which was predicted to encode a chloroplast protein of unknown function. Chloroplast targeting of PGR7 was confirmed by transient expression of a GFP fusion protein and by stable expression and subcellular localization of an epitope-tagged version of PGR7. Bioinformatic analyses revealed that the PGR7 protein has two domains that are conserved in plants, algae, and bacteria, and the N-terminal domain is predicted to bind a cofactor such as FMN. Thus, we identified PGR7 as a novel, conserved nuclear gene that is necessary for efficient photosynthetic electron transport in chloroplasts of Arabidopsis
Stress-induced galectin-1 influences immune tolerance in the spleen and thymus by modulating CD45 immunoreactive lymphocytes
A Chaperonin Subunit with Unique Structures Is Essential for Folding of a Specific Substrate
Type I chaperonins are large, double-ring complexes present in bacteria (GroEL),
mitochondria (Hsp60), and chloroplasts (Cpn60), which are involved in mediating
the folding of newly synthesized, translocated, or stress-denatured proteins. In
Escherichia coli, GroEL comprises 14 identical subunits and
has been exquisitely optimized to fold its broad range of substrates. However,
multiple Cpn60 subunits with different expression profiles have evolved in
chloroplasts. Here, we show that, in Arabidopsis thaliana, the
minor subunit Cpn60β4 forms a heterooligomeric Cpn60 complex with
Cpn60α1 and Cpn60β1–β3 and is specifically required for the
folding of NdhH, a subunit of the chloroplast NADH dehydrogenase-like complex
(NDH). Other Cpn60β subunits cannot complement the function of Cpn60β4.
Furthermore, the unique C-terminus of Cpn60β4 is required for the full
activity of the unique Cpn60 complex containing Cpn60β4 for folding of NdhH.
Our findings suggest that this unusual kind of subunit enables the Cpn60 complex
to assist the folding of some particular substrates, whereas other dominant
Cpn60 subunits maintain a housekeeping chaperonin function by facilitating the
folding of other obligate substrates
Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies.
The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15-18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20-22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.The EPIC Norfolk study (DOI 10.22025/2019.10.105.00004) has received funding from the Medical Research Council (MR/N003284/1 and MC-UU_12015/1) and Cancer Research UK (C864/A14136). NJW, NGF, and FI were supported by the Medical Research Council Epidemiology Unit core funding [MC_UU_12015/1 and MC_UU_12015/5]. NJW and NGF acknowledge support from the National Institute for Health Research Cambridge Biomedical Research Centre [IS-BRC-1215-20014] and NJW is an NIHR Senior Investigator
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