39,703 research outputs found
Charge Frustration Effects in Capacitively Coupled Two-Dimensional Josephson-Junction Arrays
We investigate the quantum phase transitions in two capacitively coupled
two-dimensional Josephson-junction arrays with charge frustration. The system
is mapped onto the S=1 and anisotropic Heisenberg antiferromagnets near
the particle-hole symmetry line and near the maximal-frustration line,
respectively, which are in turn argued to be effectively described by a single
quantum phase model. Based on the resulting model, it is suggested that near
the maximal frustration line the system may undergo a quantum phase transition
from the charge-density wave to the super-solid phase, which displays both
diagonal and off- diagonal long-range order.Comment: 6 pages, 6 figures, to appear in Phys. Rev.
Microglia: Key Players in Retinal Ageing and Neurodegeneration
Microglia are the resident immune cells of the central nervous system (CNS) and play a key role in maintaining the normal function of the retina and brain. During early development, microglia migrate into the retina, transform into a highly ramified phenotype, and scan their environment constantly. Microglia can be activated by any homeostatic disturbance that may endanger neurons and threaten tissue integrity. Once activated, the young microglia exhibit a high diversity in their phenotypes as well as their functions, which relate to either beneficial or harmful consequences. Microglial activation is associated with the release of cytokines, chemokines, and growth factors that can determine pathological outcomes. As the professional phagocytes in the retina, microglia are responsible for the clearance of pathogens, dead cells, and protein aggregates. However, their phenotypic diversity and phagocytic capacity is compromised with ageing. This may result in the accumulation of protein aggregates and myelin debris leading to retinal neuroinflammation and neurodegeneration. In this review, we describe microglial phenotypes and functions in the context of the young and ageing retina, and the mechanisms underlying changes in ageing. Additionally, we review microglia-mediated retinal neuroinflammation and discuss the mechanisms of microglial involvement in retinal neurodegenerative diseases
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The E3 ubiquitin ligase IDOL regulates synaptic ApoER2 levels and is important for plasticity and learning.
Neuronal ApoE receptors are linked to learning and memory, but the pathways governing their abundance, and the mechanisms by which they affect the function of neural circuits are incompletely understood. Here we demonstrate that the E3 ubiquitin ligase IDOL determines synaptic ApoER2 protein levels in response to neuronal activation and regulates dendritic spine morphogenesis and plasticity. IDOL-dependent changes in ApoER2 abundance modulate dendritic filopodia initiation and synapse maturation. Loss of IDOL in neurons results in constitutive overexpression of ApoER2 and is associated with impaired activity-dependent structural remodeling of spines and defective LTP in primary neuron cultures and hippocampal slices. IDOL-deficient mice show profound impairment in experience-dependent reorganization of synaptic circuits in the barrel cortex, as well as diminished spatial and associative learning. These results identify control of lipoprotein receptor abundance by IDOL as a post-transcriptional mechanism underlying the structural and functional plasticity of synapses and neural circuits
Variational formulas of higher order mean curvatures
In this paper, we establish the first variational formula and its
Euler-Lagrange equation for the total -th mean curvature functional
of a submanifold in a general Riemannian manifold
for . As an example, we prove that closed
complex submanifolds in complex projective spaces are critical points of the
functional , called relatively -minimal submanifolds,
for all . At last, we discuss the relations between relatively -minimal
submanifolds and austere submanifolds in real space forms, as well as a special
variational problem.Comment: 13 pages, to appear in SCIENCE CHINA Mathematics 201
Current-voltage characteristics of the two-dimensional XY model with Monte Carlo dynamics
Current-voltage characteristics and the linear resistance of the
two-dimensional XY model with and without external uniform current driving are
studied by Monte Carlo simulations. We apply the standard finite-size scaling
analysis to get the dynamic critical exponent at various temperatures. From
the comparison with the resistively-shunted junction dynamics, it is concluded
that is universal in the sense that it does not depend on details of
dynamics. This comparison also leads to the quantification of the time in the
Monte Carlo dynamic simulation.Comment: 5 pages in two columns including 5 figures, to appear in PR
-minimal surface and manifold with positive -Bakry-\'{E}mery Ricci curvature
In this paper, we first prove a compactness theorem for the space of closed
embedded -minimal surfaces of fixed topology in a closed three-manifold with
positive Bakry-\'{E}mery Ricci curvature. Then we give a Lichnerowicz type
lower bound of the first eigenvalue of the -Laplacian on compact manifold
with positive -Bakry-\'{E}mery Ricci curvature, and prove that the lower
bound is achieved only if the manifold is isometric to the -shpere, or the
-dimensional hemisphere. Finally, for compact manifold with positive
-Bakry-\'{E}mery Ricci curvature and -mean convex boundary, we prove an
upper bound for the distance function to the boundary, and the upper bound is
achieved if only if the manifold is isometric to an Euclidean ball.Comment: 15 page
Pituitary Adenylate-Cyclase Activating Polypeptide Regulates Hunger- and Palatability-Induced Binge Eating
While pituitary adenylate cyclase activating polypeptide (PACAP) signaling in the hypothalamic ventromedial nuclei (VMN) has been shown to regulate feeding, a challenge in unmasking a role for this peptide in obesity is that excess feeding can involve numerous mechanisms including homeostatic (hunger) and hedonic-related (palatability) drives. In these studies, we first isolated distinct feeding drives by developing a novel model of binge behavior in which homeostatic-driven feeding was temporally separated from feeding driven by food palatability. We found that stimulation of the VMN, achieved by local microinjections of AMPA, decreased standard chow consumption in food-restricted rats (e.g., homeostatic feeding); surprisingly, this manipulation failed to alter palatable food consumption in satiated rats (e.g., hedonic feeding). In contrast, inhibition of the nucleus accumbens (NAc), through local microinjections of GABA receptor agonists baclofen and muscimol, decreased hedonic feeding without altering homeostatic feeding. PACAP microinjections produced the site-specific changes in synaptic transmission needed to decrease feeding via VMN or NAc circuitry. PACAP into the NAc mimicked the actions of GABA agonists by reducing hedonic feeding without altering homeostatic feeding. In contrast, PACAP into the VMN mimicked the actions of AMPA by decreasing homeostatic feeding without affecting hedonic feeding. Slice electrophysiology recordings verified PACAP excitation of VMN neurons and inhibition of NAc neurons. These data suggest that the VMN and NAc regulate distinct circuits giving rise to unique feeding drives, but that both can be regulated by the neuropeptide PACAP to potentially curb excessive eating stemming from either drive
Deregulation of HDAC5 by Viral Interferon Regulatory Factor 3 Plays an Essential Role in Kaposi's Sarcoma-Associated Herpesvirus-Induced Lymphangiogenesis.
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent for Kaposi's sarcoma (KS), which is one of the most common HIV-associated neoplasms. The endothelium is the thin layer of squamous cells where vascular blood endothelial cells (BECs) line the interior surface of blood vessels and lymphatic endothelial cells (LECs) are in direct contact with lymphatic vessels. The KS lesions contain a prominent compartment of neoplastic spindle morphology cells that are closely related to LECs. Furthermore, while KSHV can infect both LECs and BECs in vitro, its infection activates genetic programming related to lymphatic endothelial cell fate, suggesting that lymphangiogenic pathways are involved in KSHV infection and malignancy. Here, we report for the first time that viral interferon regulatory factor 3 (vIRF3) is readily detected in over 40% of KS lesions and that vIRF3 functions as a proangiogenic factor, inducing hypersprouting formation and abnormal growth in a LEC-specific manner. Mass spectrometry analysis revealed that vIRF3 interacted with histone deacetylase 5 (HDAC5), which is a signal-responsive regulator for vascular homeostasis. This interaction blocked the phosphorylation-dependent cytosolic translocation of HDAC5 and ultimately altered global gene expression in LECs but not in BECs. Consequently, vIRF3 robustly induced spindle morphology and hypersprouting formation of LECs but not BECs. Finally, KSHV infection led to the hypersprouting formation of LECs, whereas infection with a ΔvIRF3 mutant did not do so. Collectively, our data indicate that vIRF3 alters global gene expression and induces a hypersprouting formation in an HDAC5-binding-dependent and LEC-specific manner, ultimately contributing to KSHV-associated pathogenesis.IMPORTANCE Several lines of evidences indicate that KSHV infection of LECs induces pathological lymphangiogenesis and that the results resemble KS-like spindle morphology. However, the underlying molecular mechanism remains unclear. Here, we demonstrated that KSHV vIRF3 is readily detected in over 40% of various KS lesions and functions as a potent prolymphangiogenic factor by blocking the phosphorylation-dependent cytosolic translocation of HDAC5, which in turn modulates global gene expression in LECs. Consequently, vIRF3-HDAC5 interaction contributes to virus-induced lymphangiogenesis. The results of this study suggest that KSHV vIRF3 plays a crucial role in KSHV-induced malignancy
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