Ceramide triggers budding of exosome vesicles into multivesicular endosomes

Intraluminal vesicles of multivesicular endosomes are either sorted for cargo degradation into lysosomes or secreted as exosomes into the extracellular milieu. The mechanisms underlying the sorting of membrane into the different populations of intraluminal vesicles are unknown. Here, we find that cargo is segregated into distinct subdomains on the endosomal membrane and that the transfer of exosome-associated domains into the lumen of the endosome did not depend on the function of the ESCRT (endosomal sorting complex required for transport) machinery, but required the sphingolipid ceramide. Purified exosomes were enriched in ceramide, and the release of exosomes was reduced after the inhibition of neutral sphingomyelinases. These results establish a pathway in intraendosomal membrane transport and exosome formation.     

Nod2 mutation in Crohn's disease potentiates NF-kappaB activity and IL-1beta processing

Variants of NOD2, an intracellular sensor of bacteria-derived muramyl dipeptide (MDP), increase susceptibility to Crohn's disease (CD). These variants are thought to be defective in activation of nuclear factor kappaB (NF-kappaB) and antibacterial defenses, but CD clinical specimens display elevated NF-kappaB activity. To illuminate the pathophysiological function of NOD2, we introduced such a variant to the mouse Nod2 locus. Mutant mice exhibited elevated NF-kappaB activation in response to MDP and more efficient processing and secretion of the cytokine interleukin-1beta (IL-1beta). These effects are linked to increased susceptibility to bacterial-induced intestinal inflammation and identify NOD2 as a positive regulator of NF-kappaB activation and IL-1beta secretion.     

Forming electrical networks in three dimensions by self-assembly

Self-assembly of millimeter-scale polyhedra, with surfaces patterned with solder dots, wires, and light-emitting diodes, generated electrically functional, three-dimensional networks. The patterns of dots and wires controlled the structure of the networks formed; both parallel and serial connections were generated.     

Subnanometer-Diameter Wires Isolated in a Polymer Matrix by Fast Polymerization

The preparation and analysis of inorganic-organic polymer nanocomposites consisting of inorganic nanowires and multiwire "cables" in a random-coil organic polymer host is reported. Dissolution of inorganic (LiMo3Se3)n wires in a strongly coordinating monomer, vinylene carbonate, and the use of a rapid polymerization in the presence of a cross-linking agent produce nanocomposites without phase separation. Polymerization of dilute solutions yields a material containing mostly (Mo3Se3(-))n mono- and biwires, 6 to 20 angstroms in diameter and 50 to 100 nanometers long. Polymerization of more concentrated liquid crystalline solutions yields a nanocomposite containing oriented multiwire cables, 20 to 40 angstroms in diameter and up to 1500 nanometers long, that display optical anisotropy and electrical conductivity.     

Expression of interleukin-10 activity by Epstein-Barr virus protein BCRF1

Cytokine synthesis inhibitory factor (CSIF; interleukin-10), a product of mouse TH2 T cell clones that inhibits synthesis of cytokines by mouse TH1 T cell clones, exhibits extensive sequence similarity to an uncharacterized open reading frame in the Epstein-Barr virus BCRF1. Recombinant BCRF1 protein mimics the activity of interleukin-10, suggesting that BCRF1 may have a role in the interaction of the virus with the host's immune system.     

Magnetoreception in honeybees

Magnetoreception by honeybees (Apis mellifera) is demonstrated by such activities as comb building and homing orientation, which are affected by the geomagnetic field. In other magnetoreceptive species, iron oxide crystals in the form of magnetite have been shown to be necessary for primary detection of magnetic fields. Here it is shown that trophocytes, which are apparently the only iron granule-containing cells in honeybees, contain super-paramagnetic magnetite. These cells are innervated by the nervous system, which suggests that trophocytes might be primarily responsible for magnetoreception. Electron microscopy also shows cytoskeletal attachments to the iron granule membrane.     

Neural systems responding to degrees of uncertainty in human decision-making

Much is known about how people make decisions under varying levels of probability (risk). Less is known about the neural basis of decision-making when probabilities are uncertain because of missing information (ambiguity). In decision theory, ambiguity about probabilities should not affect choices. Using functional brain imaging, we show that the level of ambiguity in choices correlates positively with activation in the amygdala and orbitofrontal cortex, and negatively with a striatal system. Moreover, striatal activity correlates positively with expected reward. Neurological subjects with orbitofrontal lesions were insensitive to the level of ambiguity and risk in behavioral choices. These data suggest a general neural circuit responding to degrees of uncertainty, contrary to decision theory.     

Association of the HL-A7 cross-reacting group with a specific reaginic antibody response in allergic man

A relatively small proportion (17 percent) of individuals highly allergic to ragweed were found to develop marked reaginic (immunoglobulin E-mediated) skin sensitivity to a minor ragweed pollen allergen Ra5 (molecular weight 5200). Sensitivity to Ra5 was significantly associated with the possession of a major histocompatibility antigen of the HL-A7 cross-reacting group. This appears to be the first evidence of a strong association between a specific immune response and a specific group of closely related HL-A antigens in man.