Cytokine secretion via cholesterol-rich lipid raft-associated SNAREs at the phagocytic cup

Lipopolysaccharide-activated macrophages rapidly synthesize and secrete tumor necrosis factor alpha(TNF alpha) to prime the immune system. Surface delivery of membrane carrying newly synthesized TNF alpha is controlled and limited by the level of soluble N-ethylmaleimide-sensitive factor attachment protein receptor ( SNARE) proteins syntaxin 4 and SNAP-23. Many functions in immune cells are coordinated from lipid rafts in the plasma membrane, and we investigated a possible role for lipid rafts in TNF alpha trafficking and secretion. TNF alpha surface delivery and secretion were found to be cholesterol-dependent. Upon macrophage activation, syntaxin 4 was recruited to cholesterol-dependent lipid rafts, whereas its regulatory protein, Munc18c, was excluded from the rafts. Syntaxin 4 in activated macrophages localized to discrete cholesterol-dependent puncta on the plasma membrane, particularly on filopodia. Imaging the early stages of TNF alpha surface distribution revealed these puncta to be the initial points of TNF alpha delivery. During the early stages of phagocytosis, syntaxin 4 was recruited to the phagocytic cup in a cholesterol-dependent manner. Insertion of VAMP3-positive recycling endosome membrane is required for efficient ingestion of a pathogen. Without this recruitment of syntaxin 4, it is not incorporated into the plasma membrane, and phagocytosis is greatly reduced. Thus, relocation of syntaxin 4 into lipid rafts in macrophages is a critical and rate-limiting step in initiating an effective immune response.

Shift, scaling and derivative properties for the discrete cosine transform

A set of DCT domain properties for shifting and scaling by real amounts, and taking linear operations such as differentiation is described. The DCT coefficients of a sampled signal are subjected to a linear transform, which returns the DCT coefficients of the shifted, scaled and/or differentiated signal. The properties are derived by considering the inverse discrete transform as a cosine series expansion of the original continuous signal, assuming sampling in accordance with the Nyquist criterion. This approach can be applied in the signal domain, to give, for example, DCT based interpolation or derivatives. The same approach can be taken in decoding from the DCT to give, for example, derivatives in the signal domain. The techniques may prove useful in compressed domain processing applications, and are interesting because they allow operations from the continuous domain such as differentiation to be implemented in the discrete domain. An image matching algorithm illustrates the use of the properties, with improvements in computation time and matching quality.

Total cholesterol concentrations of the muscles in castrated Boer goats

Goat meat is an important source of animal protein and Boer goats are the most widespread breed of meat goats. Cholesterol in meat is a potential cause of human disease and little is known about the cholesterol concentration in different goat muscles. As animals gain bodyweight the amount of cholesterol in their tissues generally increases and can vary for different tissues. Therefore, the aim of this experiment was to determine the effect of slaughter weight and muscle type on total cholesterol concentrations in three muscles (longissimus thoracic, infraspinatus and biceps femoris) taken from castrated male Boer goats in Australia. The goats were grazed on a mixture of native pasture and Rhodes grass (Chloris gayana) and had access to lucerne and commercial goat pellets (CP 18%; ME 12.3 MJ/kg DM). The muscles were dissected from 24 goats slaughtered in groups of 4 or 5 animals at 30, 45, 60, 75 and 90 kg liveweight. Total cholesterol concentrations were then determined using high performance liquid chromatography (HPLC). Total cholesterol concentrations decreased (P < 0.01) with an increase in slaughter weight for the longissimus thoracic, infraspinatus and biceps femoris muscles. Significant differences (P < 0.01) were recorded in the total cholesterol concentrations for the three muscles studied. The average total cholesterol concentrations ranged from 55 to 60 mg/100 g for the longissimus thoracic, 69 to 88 mg/100g for infraspinatus and 65 to 82 mg/100 g for the biceps femoris muscles. These results are important for consumers of goat meat as total cholesterol concentrations vary between different muscles taken from animals slaughtered at different weights and the concentrations are higher in muscles taken from lighter and younger animals. Therefore, health conscious consumers of meat, concerned about the cholesterol content of their diet, should consume meat from the longissimus thoracic muscles of heavier or older goats. (c) 2005 Elsevier B.V. All rights reserved.

Mutant huntingtin inhibits clathrin-independent endocytosis and causes accumulation of cholesterol in vitro and in vivo.

We show that the mutant Huntington's disease (HD) protein (mhtt) specifically inhibits endocytosis in primary striatal neurons. Unexpectedly, mhtt does not inhibit clathrin-dependent endocytosis as was anticipated based on known interacting partners. Instead, inhibition occurs through a non-clathrin, caveolar-related pathway. Expression of mhtt inhibited internalization of BODIPY-lactosylceramide (LacCer), which is internalized by a caveolar-related mechanism. In contrast, endocytosis of Alexa Fluor 594-transferrin (Tfn) and epidermal growth factor, internalized through clathrin pathway, was unaffected by mhtt expression. Caveolin-1 (cav1), the major structural protein of caveolae binds cholesterol and is responsible for its trafficking inside cells. Mhtt interacts with cav-1 and caused a striking accumulation of intracellular cholesterol. Cholesterol accumulated in cultured neurons expressing mhtt in vitro and in brains of mhtt-expressing animals in vivo, and was observed after induction of mhtt expression in PC-12 cell lines. The accumulation occurred only when mhtt and cav1 were simultaneously expressed in cells. Knockdown of cav1 in mhtt-expressing neurons blocked cholesterol accumulation and restored LacCer endocytosis. Thus, mhtt and cav1 functionally interact to cause both cellular defects. These data provide the first direct link between mhtt and caveolar-related endocytosis and also suggest a possible mechanism for HD neurotoxicity where cholesterol homeostasis is perturbed.

Energy derivative market and derivative pricing via simulation

The deregulation of power industry worldwide has delivered the efficiency gains to the society; meanwhile, the intensity of competition has increased uncertainty and risks to market participants. Consequently, market participants are keen to hedge the market risks and maintain a competitive edge in the market; and this is a good explanation to the flourish of electricity derivative market. In this paper, the authors gave a comprehensive review of derivative contract pricing methods and proposed a new framework for energy derivative pricing to suit the needs of a deregulated electricity market