Anti-ALG2 monoclonal antibody, clone FQS23117(3)(C)

Standard ocean color data products from the Medium Resolution Imaging Spectrometer (MERIS) are compared with equivalent regional products in European seas exhibiting different bio-optical properties: the northern Adriatic Sea, the Baltic Sea and the Western Black Sea (ADRS, BLTS and BLKS, respectively). Investigated quantities are: 1) the algal-2 pigment index, alg2; 2) the composite-absorption coefficient of yellow substance and non-pigmented particles at 442 nm, a(dg); and 3) the concentration of the total suspended matter, TSM. Regional data products are created using ocean color inversion schemes based on MultiLayer Perceptron (MLP) neural nets trained with field measurements from the Coastal Atmosphere and Sea Time Series (CoASTS) and Bio-Optical mapping of Marine Properties (BiOMaP) programs. MLP input is the remote sensing reflectance Res at MERIS center-wavelengths specifically selected for different water types in view of minimizing the perturbing effects of inaccurate atmospheric correction on the retrieval of regional data products. A new method is also proposed to define the applicability of regional MLPs to input Res. Results indicate that MERIS alg2 values tend to overestimate the equivalent quantity computed with MLP regional algorithms. The agreement between MERIS and regional TSM data products is significantly better than that reported for alg2 and ad, especially for BLKS. Findings highlight the relevance of using regional inversion schemes to evaluate standard products over extended oceanographic regions as a complement to the analysis of match-ups between marine products measured in situ and derived from space-born data. (C) 2013 Elsevier Inc. All rights reserved.

Congenital myasthenic syndromes are a heterogeneous group of inherited disorders that arise from impaired signal transmission at the neuromuscular synapse. They are characterized by fatigable muscle weakness. We performed linkage analysis, whole-exome and whole-genome sequencing to determine the underlying defect in patients with an inherited limb-girdle pattern of myasthenic weakness. We identify ALG14 and ALG2 as novel genes in which mutations cause a congenital myasthenic syndrome. Through analogy with yeast, ALG14 is thought to form a multiglycosyltransferase complex with ALG13 and DPAGT1 that catalyses the first two committed steps of asparagine-linked protein glycosylation. We show that ALG14 is concentrated at the muscle motor endplates and small interfering RNA silencing of ALG14 results in reduced cell-surface expression of muscle acetylcholine receptor expressed in human embryonic kidney 293 cells. ALG2 is an alpha-1,3-mannosyltransferase that also catalyses early steps in the asparagine-linked glycosylation pathway. Mutations were identified in two kinships, with mutation ALG2p.Val68Gly found to severely reduce ALG2 expression both in patient muscle, and in cell cultures. Identification of DPAGT1, ALG14 and ALG2 mutations as a cause of congenital myasthenic syndrome underscores the importance of asparagine-linked protein glycosylation for proper functioning of the neuromuscular junction. These syndromes form part of the wider spectrum of congenital disorders of glycosylation caused by impaired asparagine-linked glycosylation. It is likely that further genes encoding components of this pathway will be associated with congenital myasthenic syndromes or impaired neuromuscular transmission as part of a more severe multisystem disorder. Our findings suggest that treatment with cholinesterase inhibitors may improve muscle function in many of the congenital disorders of glycosylation.