T-cell hybridoma bearing heavy chain variable region determinants producing (T,G)-A--L-specific helper factor

Thymus-derived lymphocytes (T cells) exert their regulatory effect (help or suppression) on the antibody production by B cells either by direct cell to cell interaction or by soluble mediators or factors. The low frequency of specific T cells, the heterogeneity of their responses and their relatively short life span have hampered the molecular characterization of the antigen recognition unit of T cells, and its structure is largely unknown. The lymphocyte hybridization technique, which has been found very useful for the production of B-cell hybridomas secreting specific monoclonal antibodies, has also been used for the generation of homogeneous and stable T-cell hybridomas with unlimited growth potential. So far the only specific effector function demonstrated in the established T hybridomas is the property to generate a factor(s) which suppresses antibody responses. We now describe the establishment of hybrid lines which exhibit characteristic T-cell markers. One of the hybridomas (denoted R-9) releases into the culture supernatant factor(s) with helper activity specific to the synthetic polypeptide (T,G)-A--L and bears surface determinants of the immunoglobulin heavy chain variable region (VH). Such hybrid cell lines are of great value for studies on the nature of the T-cell receptor.     

A new genus and four new species of onchidiid slugs from South-East Asia (Mollusca: Gastropoda: Pulmonata: Onchidiidae)

The taxonomy of the Onchidiidae has remained extremely confusing for decades. As part of an on-going systematic revision of the entire family, a new genus, Melayonchis Dayrat and Goulding gen. nov., and four new species (Melayonchis eloisae Dayrat sp. nov., Melayonchis siongkiati Dayrat and Goulding sp. nov., Melayonchis annae Dayrat sp. nov., and Melayonchis aileenae Dayrat and Goulding sp. nov.) are described. Species are delineated using an integrative approach, based on morphological characters and DNA sequences. First-hand field observations and pictures of live animals are provided in order to help future species identification. All four Melayonchis species live in mangrove forests. The geographic distribution of Melayonchis ranges from the Andaman Sea to the South China Sea through the Strait of Malacca. Records are based on entirely new collections from the Andaman Islands, Peninsular Malaysia, Singapore, Brunei Darussalam and Vietnam. The nomenclature of all existing onchidiid species- and genus-group names from that region is addressed, as well as intraspecific character variation within Melayonchis.

www.zoobank.org/urn:lsid:zoobank.org:pub:671922DB-C6C1-44A5-B2CD-A3A3127CB668     

ADAMTSL2 mutations in geleophysic dysplasia demonstrate a role for ADAMTS-like proteins in TGF-beta bioavailability regulation

Geleophysic dysplasia is an autosomal recessive disorder characterized by short stature, brachydactyly, thick skin and cardiac valvular anomalies often responsible for an early death. Studying six geleophysic dysplasia families, we first mapped the underlying gene to chromosome 9q34.2 and identified five distinct nonsense and missense mutations in ADAMTSL2 (a disintegrin and metalloproteinase with thrombospondin repeats-like 2), which encodes a secreted glycoprotein of unknown function. Functional studies in HEK293 cells showed that ADAMTSL2 mutations lead to reduced secretion of the mutated proteins, possibly owing to the misfolding of ADAMTSL2. A yeast two-hybrid screen showed that ADAMTSL2 interacts with latent TGF-beta-binding protein 1. In addition, we observed a significant increase in total and active TGF-beta in the culture medium as well as nuclear localization of phosphorylated SMAD2 in fibroblasts from individuals with geleophysic dysplasia. These data suggest that ADAMTSL2 mutations may lead to a dysregulation of TGF-beta signaling and may be the underlying mechanism of geleophysic dysplasia.     

Genetic and functional linkage between ADAMTS superfamily proteins and fibrillin-1: a novel mechanism influencing microfibril assembly and function

Tissue microfibrils contain fibrillin-1 as a major constituent. Microfibrils regulate bioavailability of TGFβ superfamily growth factors and are structurally crucial in the ocular zonule. FBN1 mutations typically cause the Marfan syndrome, an autosomal dominant disorder manifesting with skeletal overgrowth, aortic aneurysm, and lens dislocation (ectopia lentis). Infrequently, FBN1 mutations cause dominantly inherited Weill–Marchesani syndrome (WMS), isolated ectopia lentis (IEL), or the fibrotic condition, geleophysic dysplasia (GD). Intriguingly, mutations in ADAMTS [a disintegrin-like and metalloprotease (reprolysin-type) with thrombospondin type 1 motif] family members phenocopy these disorders, leading to recessive WMS (ADAMTS10), WMS-like syndrome (ADAMTS17), IEL (ADAMTSL4 and ADAMTS17) and GD (ADAMTSL2). An ADAMTSL2 founder mutation causes Musladin–Lueke syndrome, a fibrotic disorder in beagle dogs. The overlapping disease spectra resulting from fibrillin-1 and ADAMTS mutations, interaction of ADAMTS10 and ADAMTSL2 with fibrillin-1, and evidence that these ADAMTS proteins accelerate microfibril biogenesis, constitutes a consilience suggesting that some ADAMTS proteins evolved to provide a novel mechanism regulating microfibril formation and consequently cell behavior.