Description: The Journal of Organic Chemistry DOI: 10.1021/jo401433q

Description: Background: Fungal pathogens cause devastating losses in economically important cereal crops by utilising pathogen proteins to infect host plants. Secreted pathogen proteins are referred to as effectors and have thus far been identified by selecting small, cysteine-rich peptides from the secretome despite increasing evidence that not all effectors share these attributes. Results: We take advantage of the availability of sequenced fungal genomes and present an unbiased method for finding putative pathogen proteins and secreted effectors in a query genome via comparative hidden Markov Model analyses followed by unsupervised protein clustering. Our method returns experimentally validated fungal effectors in Stagonospora nodorum and Fusarium oxysporum as well as the N-terminal Y/F/WxC-motif from the barley powdery mildew pathogen. Application to the cereal pathogen Fusarium graminearum reveals a secreted phosphorylcholine phosphatase that is characteristic of hemibiotrophic and necrotrophic cereal pathogens and shares an ancient selection process with bacterial plant pathogens. Three F. graminearum protein clusters are found with an enriched secretion signal. One of these putative effector clusters contains proteins that share a [SG]-P-C-[KR]-P sequence motif in the N-terminal and show features not commonly associated with fungal effectors. This motif is conserved in secreted pathogenic Fusarium proteins and a prime candidate for functional testing. Conclusions: Our pipeline has successfully uncovered conservation patterns, putative effectors and motifs of fungal pathogens that would have been overlooked by existing approaches that identify effectors as small, secreted, cysteine-rich peptides. It can be applied to any pathogenic proteome data, such as microbial pathogen data of plants and other organisms.

Description: Background: As greater numbers of us are living longer, it is increasingly important to understand how we can age healthily. Although old age is often stereotyped as a time of declining mental abilities and inflexibility, cognitive neuroscience reveals that older adults use neural and cognitive resources flexibly, recruiting novel neural regions and cognitive processes when necessary. Our aim in this project is to understand how age-related changes to neural structure and function interact to support cognitive abilities across the lifespan.Methods/DesignWe are recruiting a population-based cohort of 3000 adults aged 18 and over into Stage 1 of the project, where they complete an interview including health and lifestyle questions, a core cognitive assessment, and a self-completed questionnaire of lifetime experiences and physical activity. Of those interviewed, 700 participants aged 18-87 (100 per age decile) continue to Stage 2 where they undergo cognitive testing and provide measures of brain structure and function. Cognition is assessed across multiple domains including attention and executive control, language, memory, emotion, action control and learning. A subset of 280 adults return for in-depth neurocognitive assessment in Stage 3, using functional neuroimaging experiments across our key cognitive domains.Formal statistical models will be used to examine the changes that occur with healthy ageing, and to evaluate age-related reorganisation in terms of cognitive and neural functions invoked to compensate for overall age-related brain structural decline. Taken together the three stages provide deep phenotyping that will allow us to measure neural activity and flexibility during performance across a number of core cognitive functions. This approach offers hypothesis-driven insights into the relationship between brain and behaviour in healthy ageing that are relevant to the general population.DiscussionOur study is a unique resource of neuroimaging and cognitive measures relevant to change across the adult lifespan. Because we focus on normal age-related changes, our results may contribute to changing views about the ageing process, lead to targeted interventions, and reveal how normal ageing relates to frail ageing in clinicopathological conditions such as Alzheimer’s disease.