Petrographic and geochemical characterization of seep carbonate from Alaminos Canyon,Gulf of Mexico

Seep carbonates were collected from the Alaminos Canyon lease area, Gulf of Mexico. The carbonates are present as slabs and blocks. Bivalve shell and foraminifer are the dominant bioclasts in carbonate. Pores are common and usually filled with acicular aragonite crystals. XRD investigation shows that aragonite is the dominate mineral （98%）. Peloids, clotted microfabirc and botryoidal aragonite are developed in carbonate and suggest a genesis linked with bacterial degradation of the hydrocarbons. The δ^13C value of bioclasts in carbonate is from -4.9‰ to -0.6‰, indicating that the carbon source is mainly from sea water as well as the small portion incorporation of the seep hydrocarbon. The microcrystalline and sparite aragonite shows the δ^13C value from -31.3‰ to -23.4‰, suggesting that their carbon is derived mainly from microbial degradation of crude oil. ^14C analyses give the radiocarbon age of about 10 ka. Rare earth elements （REE） analyses of the 5% HNO3-treated solution of the carbonates show that the total REE content of the carbonates is low, that is from 0.752 to 12.725 μg·g^-1. The shale-normalized REE patterns show significantly negative Ce anomalies. This suggests that cold seep carbonate is most likely formed in a relatively aerobic environment.     

Germline gain-of-function mutations in SOS1 cause Noonan syndrome

Noonan syndrome, the most common single-gene cause of congenital heart disease, is characterized by short stature, characteristic facies, learning problems and leukemia predisposition. Gain-of-function mutations in PTPN11, encoding the tyrosine phosphatase SHP2, cause approximately 50% of Noonan syndrome cases. SHP2 is required for RAS-ERK MAP kinase (MAPK) cascade activation, and Noonan syndrome mutants enhance ERK activation ex vivo and in mice. KRAS mutations account for <5% of cases of Noonan syndrome, but the gene(s) responsible for the remainder are unknown. We identified missense mutations in SOS1, which encodes an essential RAS guanine nucleotide-exchange factor (RAS-GEF), in approximately 20% of cases of Noonan syndrome without PTPN11 mutation. The prevalence of specific cardiac defects differs in SOS1 mutation-associated Noonan syndrome. Noonan syndrome-associated SOS1 mutations are hypermorphs encoding products that enhance RAS and ERK activation. Our results identify SOS1 mutants as a major cause of Noonan syndrome, representing the first example of activating GEF mutations associated with human disease and providing new insights into RAS-GEF regulation.     

Paraneoplastic myasthenic syndrome IgG inhibits 45Ca2+ flux in a human small cell carcinoma line

Certain cancers exert unexplained remote effects on the nervous system. Small cell carcinoma (SCC) of the lung, a tumour capable of spike electrogenesis and which is of possible neural crest origin, is present in approximately 70% of patients with the Lambert-Eaton myasthenic syndrome (LEMS), a disorder characterized by fatigable muscle weakness. Patients with this syndrome have a defect in the (Ca2+-dependent) quantal release of acetylcholine from motor nerve terminals evoked by a nerve impulse or by high K+ (ref.5), and a decreased number of presynaptic active zone particles. The physiological and morphological features of the syndrome can be transferred to mice by the patients' IgG, consistent with an autoantibody interfering with the function of voltage-dependent Ca2+ channels. Here we demonstrate that K+-induced 45Ca2+ flux in a cultured human SCC line is significantly reduced by LEMS IgG, suggesting that in SCC-LEMS an autoantibody to tumour Ca2+-channel determinants is triggered; its cross-reaction with similar determinants at the motor nerve terminal could lead to the remote neurological syndrome.     

The synthesis and in vivo assembly of functional antibodies in yeast

The yeast Saccharomyces cerevisiae can synthesize, process and secrete higher eukaryotic proteins. We have investigated the expression of immunoglobulin chains in yeast and demonstrate here the synthesis, processing and secretion of light and heavy chains, the glycosylation of heavy chain, the intracellular localization of these foreign proteins by immunofluorescence, and the detection of functional antibodies in cells co-expressing both chains. This may provide the basis of a microbial fermentation process for the production of monoclonal antibodies. The co-expression of light and heavy chains in Escherichia coli has been reported but functional antibodies were not assembled in vivo. Furthermore, only low-level assembly of these chains was found in vitro.