University of East Anglia

About: University of East Anglia is a education organization based out in Norwich, Norfolk, United Kingdom. It is known for research contribution in the topics: Population & Climate change. The organization has 13250 authors who have published 37504 publications receiving 1669060 citations. The organization is also known as: UEA.

COI1 links jasmonate signalling and fertility to the SCF ubiquitin-ligase complex in Arabidopsis.

Abstract: Jasmonates (JAs) regulate Arabidopsis thaliana wound and defence responses, pollen development, and stress-related growth inhibition. Significantly, each of these responses requires COI1, an F-box protein. Other F-box proteins interact with SKP1 and cullin proteins to form SCF complexes that selectively recruit regulatory proteins targeted for ubiquitination. To determine whether COI1 also functions in an SCF complex, we have characterized Arabidopsis proteins that bind to COI1. An Arabidopsis cDNA expression library was screened in yeast for clones that produce proteins which can bind to COI1. We recovered two SKP1 homologues and a histone deacetylase. The Arabidopsis F-box protein TIR1 interacted with SKP1 proteins, but not with the histone deacetylase. Mutant COI1 proteins revealed that the F-box is required for interaction with SKP1s, but that sequences in leucine-rich repeat domains are required for interaction with the histone deacetylase. Epitope-tagged COI1 was introduced into Arabidopsis plants and cell cultures. Co-immunoprecipitation experiments confirmed the interaction in planta of COI1 with SKP1-like proteins and histone deacetylase, and also indicated that COI1 interacted with cullin. These results suggest that COI1 forms an SCFCOI1 complex in vivo. COI1 is therefore expected to form a functional E3-type ubiquitin ligase in plants and to regulate expression of jasmonate responsive genes, possibly by targeted ubiquitination of a histone deacetylase.

Signatures of adaptation to obligate biotrophy in the Hyaloperonospora arabidopsidis genome

Abstract: Many oomycete and fungal plant pathogens are obligate biotrophs, which extract nutrients only from living plant tissue and cannot grow apart from their hosts. Although these pathogens cause substantial crop losses, little is known about the molecular basis or evolution of obligate biotrophy. Here, we report the genome sequence of the oomycete Hyaloperonospora arabidopsidis (Hpa), an obligate biotroph and natural pathogen of Arabidopsis thaliana. In comparison with genomes of related, hemibiotrophic Phytophthora species, the Hpa genome exhibits dramatic reductions in genes encoding (i) RXLR effectors and other secreted pathogenicity proteins, (ii) enzymes for assimilation of inorganic nitrogen and sulfur, and (iii) proteins associated with zoospore formation and motility. These attributes comprise a genomic signature of evolution toward obligate biotrophy.

DHODH modulates transcriptional elongation in the neural crest and melanoma

Abstract: Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma1. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation.

Epidemiology of systemic vasculitis: A ten‐year study in the United Kingdom

Abstract: Objective To describe the epidemiology of the primary systemic vasculitides (PSV; Wegener's granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis, polyarteritis nodosa) in a well-defined population over a 10-year period. Methods An inception cohort of patients from the Norwich Health Authority (NHA) who were >15 years of age and had PSV first diagnosed between January 1, 1988 and December 31, 1997 was collected. Incidence rates were adjusted for age and sex to the 1992 population. The prevalence of PSV in this cohort was estimated on December 31, 1997. Patients were classified according to the American College of Rheumatology 1990 vasculitis criteria and the Chapel Hill Consensus definitions. Results Eighty-two NHA residents fulfilled the inclusion criteria. There were 47 men and 35 women, with a mean age of 62.9 years (median 65.0 years). The overall annual incidence of PSV among NHA residents was 19.8/million (95% confidence interval [95% CI] 15.8–24.6). The point prevalence on December 31, 1997 was 144.5/million (95% CI 110.4–185.3). PSV was more common in males (23.5/million; 95% CI 17.3–31.3) than females (16.4/million; 95% CI 11.4–22.8). The age- and sex-specific incidence showed a clear increase with age, with an overall peak in the 65–74 year age group (60.1/million). Conclusion In our study population, the annual incidence of PSV is slowly increasing with time and the incidence is greatest in the elderly.