The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease

The recycling of the amyloid precursor protein (APP) from the cell surface via the endocytic pathways plays a key role in the generation of amyloid beta peptide (Abeta) in Alzheimer disease. We report here that inherited variants in the SORL1 neuronal sorting receptor are associated with late-onset Alzheimer disease. These variants, which occur in at least two different clusters of intronic sequences within the SORL1 gene (also known as LR11 or SORLA) may regulate tissue-specific expression of SORL1. We also show that SORL1 directs trafficking of APP into recycling pathways and that when SORL1 is underexpressed, APP is sorted into Abeta-generating compartments. These data suggest that inherited or acquired changes in SORL1 expression or function are mechanistically involved in causing Alzheimer disease.     

A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndrome

Opitz-Kaveggia syndrome (also known as FG syndrome) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation. We report here that the original family for whom the condition is named and five other families have a recurrent mutation (2881C>T, leading to R961W) in MED12 (also called TRAP230 or HOPA), a gene located at Xq13 that functions as a thyroid receptor-associated protein in the Mediator complex.     

I ain’t afraid of no ghost

This paper criticizes the traditional philosophical account of the quantization of gauge theories and offers an alternative. On the received view, gauge theories resist quantization because they feature distinct mathematical representatives of the same physical state of affairs. This resistance is overcome by a sequence of ad hoc modifications, justified in part by reference to semiclassical electrodynamics. Among other things, these modifications introduce ”ghosts”: particles with unphysical properties which do not appear in asymptotic states and which are said to be purely a notational convenience. I argue that this sequence of modifications is unjustified and inadequate, making it a poor basis for the interpretation of ghosts. I then argue that gauge theories can be quantized by the same method as any other theory. On this account, ghosts are not purely notation: they are coordinates on the classical configuration space of the theory—specifically, on its gauge structure. This interpretation does not fall prey to the standard philosophical arguments against the significance of ghosts, due to Weingard. Weingard’s argumentative strategy, properly applied, in fact tells in favor of ghosts’ physical significance.     

Synthesis of the 3D porous carbon-manganese oxide (3D-C@MnO) nanocomposite and its supercapacitor behavior study

A 3D porous carbon-manganese oxide ([email protected]) nanocomposite is successfully synthesized via a thermal plasma deposition method. The chemical bonds and compositions, phase structures, surface morphologies, etc. of as-obtained [email protected] nanocomposite were characterized by the various equipment, such as X-ray diffractometer, X-ray photoelectron spectroscopy, and electron microscopes. The electrochemical performances of the [email protected] nanocomposite electrode showed a specific capacitance of 780 F g^?1 at a current density of 2 A g^?1 and a capacitance retention rate of 99% after 5000 charge-discharge cycles at a high current density of 10 A g^?1. These excellent capacitive performances may be attributed to the encapsulation of MnO nanoparticles by porous carbon sheets in the [email protected] MnO nanocomposite structure. It is believed that the carbon-encapsulated MnO nanoparticles can be protected from a volume deformation during the charge adsorption/desorption cycle and can be electrically improved by the encapsulated carbon sheets, resulting in better overall capacitive performance. In addition, this study also demonstrates the practical applicability by assembling a supercapacitor using the as-obtained [email protected] nanocomposite to glow a light emitting diode.     

Antiinflammatory and analgesic effect of herbal cocktail Hongbaekjeong via inhibition of proinflammatory cytokines and prostaglandin E2 release

Though Hongbaekjeong(HBJ),a hebal mixture of three medicinal plants,has been traditionally used for arthritis and muscular pain,its scientific evidence still remains unclear.Thus,in the present study,analgesic and anti-inflammatory mechanism of HBJ was evaluated in vitro and in vivo.HBJ significantly reduced NO production and prostaglandin E2(PGE2)release and also attenuated the expression of cyclooxygenase 2(COX-2)in lipopolysaccharides(LPS)and interferon(IFN)-c treated RAW 264.7 cells.Furthermore,HBJ abrogated the production of proinflammatory cytokines such as interleukin(IL)1b,IL-6,IL-8 and monocyte chemoattractant protein-1(MCP-1)in LPS and IFN-c treated RAW 264.7 cells.In addition,HBJ significantly decreased the number of writhing syndrome induced by acetic acid,and also increased latency in hot-plate method and tail flick test in mice.Consistently,HBJ significantly reduced the edema volume in the hind paw of the rats with arthritis induced by Freund’s complete adjuvant(FCA)compared to untreated control.Collectively,our findings demonstrate the antiinflammatory and analgesic potential of HBJ via inhibition of proinflammatory cytokines and PGE2 release for treatment of arthritis and muscular pain.