CEP152 is a genome maintenance protein disrupted in Seckel syndrome

Functional impairment of DNA damage response pathways leads to increased genomic instability. Here we describe the centrosomal protein CEP152 as a new regulator of genomic integrity and cellular response to DNA damage. Using homozygosity mapping and exome sequencing, we identified CEP152 mutations in Seckel syndrome and showed that impaired CEP152 function leads to accumulation of genomic defects resulting from replicative stress through enhanced activation of ATM signaling and increased H2AX phosphorylation.     

The mas oncogene encodes an angiotensin receptor

The class of receptors coupled to GTP-binding proteins share a conserved structural motif which is described as a 'seven-transmembrane segment' following the prediction that these hydrophobic segments form membrane-spanning alpha-helices. Identified examples include the mammalian opsins, alpha 1-, alpha 2-, beta 1- and beta 2-adrenergic receptors, the muscarinic receptor family, the 5-HT1C-receptor, and the substance-K receptor. In addition, two mammalian genes have been identified that code for predicted gene products with sequence similarity to these receptors, but whose ligand specificity is unknown namely, G21 and the mas oncogene. The mas oncogene shows the greatest sequence similarity to the substance-K receptor, and on this basis it was predicted that it would encode a peptide receptor with mitogenic activity which would act through the inositol lipid signalling pathways. The mas oncogene product was transiently expressed in Xenopus oocytes, and stably expressed in a transfected mammalian cell line. The results demonstrate that the mas gene product is a functional angiotensin receptor.     

An IgG autoantibody which inactivates C1-inhibitor

Antibodies are considered to play a specific pathogenic role in certain disease states such as myasthenia gravis, Graves' disease and autoimmune haemolytic anaemia. Autoantibodies which interfere with the function of enzyme cascade systems have also been described in diseases such as acquired haemophilia (anti-factor VIII antibodies) and glomerulonephritis (C3 nephritic factor). The identification of these autoantibodies is crucial to an understanding of the aetiology of such diseases and is also of importance in revealing the inter-relationships of the immune system with other biological pathways. This is the first report of an immunoglobulin G (IgG) autoantibody reactive with C1-inhibitor (C1-Inh), a pivotal inhibitor of the inflammatory response which is known to inactivate proteins of the complement, kinin, fibrinolytic and 'contact phase' systems. This autoantibody was isolated from a patient with a novel variant of acquired angioedema and C1-Inh dysfunction. This finding highlights the involvement of the immune system in the pathogenesis of disorders characterized by the presence of dysfunctional inflammatory response proteins.     

Control of the behaviour of leaf-cutting ants by their ‘symbiotic’ fungus

There is an obligatory relationship between leaf-cutting ants of the generaAtta andAcromyrmex (Hymenoptera; Attini) and the fungus,Attamyces bromatificus Kreisel, for which they provide a substrate of cut plant material. We show that the ants learn to reject plant material that contains chemicals injurious to the fungus. After an initial period of acceptance, ants from laboratory nests stopped harvesting granular bait containing a fungicidal agent (cycloheximide) and orange peel. This rejection was maintained for many weeks. These colonies also rejected control bait containing no cycloheximide. Some generalisation of the response was observed; colonies rejecting orange granules also rejected grapefruit granules, although they still accepted blackcurrant granules. Rejection of fungicidal bait by colonies in the field was restricted to ants on foraging trails exposed to experimental bait. We conclude that a semiochemical from the fungus, circulated by trophallaxis and grooming, regulates the selection of plant material by foragers. The fungus gains more advantages from the symbiotic relationship than is often realised. The ants provide the fungus with housing, sanitation, defence against disease and predators, pre-selected food, and a means of dissemination, at the cost to itself of providing food for the ant brood.