Two classes of metabolites fromTheonella swinhoei are localized in distinct populations of bacterial symbionts

The marine spongeTheonella swinhoei (lithistid Family Theonellidae, Order Astrophorida) has yielded many important, bioactive natural products, most of which share structural features with bacterial natural products. The presence of microbial symbionts inT. swinhoei has been reported, and it was originally suggested that the cytotoxic macrolide swinholide A and many of the bioactive cyclic peptides fromT. swinhoei were all produced by symbiotic cyanobacteria. By transmission electron microscopy, we found four distinct cell populations to be consistently present inT. swinhoei: eukaryotic sponge cells, unicellular heterotrophic bacteria, unicellular cyanobacteria and filamentous heterotrophic bacteria. Purification and chemical analyses of each cell type showed the macrolide swinholide A to be limited to the mixed population of unicellular heterotrophic bacteria, and an anti-fungal cyclic peptide occurred only in the filamentous heterotrophic bacteria. Contrary to prior speculation, no major metabolites were located in the cyanobacteria or sponge cells.     

Alternative splicing and genome complexity.

Alternative splicing of mRNA allows many gene products with different functions to be produced from a single coding sequence. It has recently been proposed as a mechanism by which higher-order diversity is generated. Here we show, using large-scale expressed sequence tag (EST) analysis, that among seven different eukaryotes the amount of alternative splicing is comparable, with no large differences between humans and other animals.     

The influence of ethylene on primary attraction of the olive beetle,Phloeotribus scarabaeoides (Bern.) (Col., Scolytidae)

Two experiments have been carried out to verify the effect of ethylene on the primary attraction ofPhloeotribus scarabaeoides under both laboratory and field conditions. The experiments were based on the enhancement of ethylene production by olive branches and trunks after the application of (2-chloroethyl)phosphonic acid. Under laboratory conditions, the beetles' response was strongly stimulated on the treated branches. Under field conditions, the treatment aided the location of the olive wood by the flying beetles, and the attack density was significantly greater in the treated wood at the end of the experiment.     

The coconut pathosystem: weed hosts of nymphs of the American palm Cixiid Haplaxius crudus (Hemiptera: Fulgoroidea)

Lethal yellowing (LY) of coconut palm (Cocos nucifera L., Arecaceae) is a disease of economic importance that is caused by the phytoplasma ‘Candidatus Phytoplasma palmae’ and is transmitted by the planthopper Haplaxius crudus (Van Duzee) (Hemiptera: Cixiidae). This study explores the weeds used by H. crudus nymphs and other Cixiidae in a coconut pathosystem in southern Mexico. Nymphs were collected directly from the root system of each weed by hand or with the help of a vacuum after carefully opening the culm. This study included 11 species of weeds: nine Poaceae [Brachiaria decumbens Stapf, B. humidicola (Rendle) Schweick, B. mutica (Forssk.) Stapf, Digitaria abyssinica (Hochst. Ex A. Rich.) Stapf, Eustachys petraea (Sw.) Desv., Leersia hexandra Sw., Panicum laxum Sw., P. maximum Jacq., Paspalum notatum Flüggé]; one Cyperaceae [Cyperus ligularis L.], and one Portulacaceae: [Portulaca pilosa L.]. Brachiaria mutica, E. petraea, B. humidicola, P. maximum were identified as the principal host species for H. crudus nymphs. Brachiaria decumbens, D. abyssinica, and C. ligularis are new host records for the nymphs of H. crudus. Additionally, it was found that H. crudus may coexist with its cogeners H. skarphion Kramer (Cixiidae) and H. caldwelli Kramer (Cixiidae), on B. mutica. On C. ligularis, H. crudus may coexist with Oecleus snowi Ball (Cixiidae) nymphs. These results suggest that in the coconut pathosystem there is a complex of multitrophic interactions that should be considered in integrated management of LY.     

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.     

The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast

The autosomal recessive disorder Shwachman-Diamond syndrome, characterized by bone marrow failure and leukemia predisposition, is caused by deficiency of the highly conserved Shwachman-Bodian-Diamond syndrome (SBDS) protein. Here, we identify the function of the yeast SBDS ortholog Sdo1, showing that it is critical for the release and recycling of the nucleolar shuttling factor Tif6 from pre-60S ribosomes, a key step in 60S maturation and translational activation of ribosomes. Using genome-wide synthetic genetic array mapping, we identified multiple TIF6 gain-of-function alleles that suppressed the pre-60S nuclear export defects and cytoplasmic mislocalization of Tif6 observed in sdo1Delta cells. Sdo1 appears to function within a pathway containing elongation factor-like 1, and together they control translational activation of ribosomes. Thus, our data link defective late 60S ribosomal subunit maturation to an inherited bone marrow failure syndrome associated with leukemia predisposition.     

Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.