SpliceGrapher: detecting patterns of alternative splicing from RNA-Seq data in the context of gene models and EST data

We propose a method for predicting splice graphs that enhances curated gene models using evidence from RNA-Seq and EST alignments. Results obtained using RNA-Seq experiments in Arabidopsis thaliana show that predictions made by our SpliceGrapher method are more consistent with current gene models than predictions made by TAU and Cufflinks. Furthermore, analysis of plant and human data indicates that the machine learning approach used by SpliceGrapher is useful for discriminating between real and spurious splice sites, and can improve the reliability of detection of alternative splicing. SpliceGrapher is available for download at http://SpliceGrapher.sf.net

Reflections on the IPCC and global change science: time for a more (physical) geographical tradition

Over the last quarter of a century, physical geography has not been served well by the often homogenising influence of global change science, as exemplified by the structures and activities of the Intergovernmental Panel on Climate Change (IPCC). However, certain areas of physical geography may have been at fault in being too little, and too uncritically, engaged with international, interdisciplinary research programmes in global environmental change. Moving forward, physical geography should look towards an independently constituted framework that incorporates the complexities of landscape response to both external forcing and internal feedbacks and, above all, works with others to prevent the socio-spatial injustices associated with climate change from being realised

Genome-wide analysis of alternative splicing in Chlamydomonas reinhardtii

<p>Abstract</p> <p>Background</p> <p>Genome-wide computational analysis of alternative splicing (AS) in several flowering plants has revealed that pre-mRNAs from about 30% of genes undergo AS. <it>Chlamydomonas</it>, a simple unicellular green alga, is part of the lineage that includes land plants. However, it diverged from land plants about one billion years ago. Hence, it serves as a good model system to study alternative splicing in early photosynthetic eukaryotes, to obtain insights into the evolution of this process in plants, and to compare splicing in simple unicellular photosynthetic and non-photosynthetic eukaryotes. We performed a global analysis of alternative splicing in <it>Chlamydomonas reinhardtii </it>using its recently completed genome sequence and all available ESTs and cDNAs.</p> <p>Results</p> <p>Our analysis of AS using BLAT and a modified version of the Sircah tool revealed AS of 498 transcriptional units with 611 events, representing about 3% of the total number of genes. As in land plants, intron retention is the most prevalent form of AS. Retained introns and skipped exons tend to be shorter than their counterparts in constitutively spliced genes. The splice site signals in all types of AS events are weaker than those in constitutively spliced genes. Furthermore, in alternatively spliced genes, the prevalent splice form has a stronger splice site signal than the non-prevalent form. Analysis of constitutively spliced introns revealed an over-abundance of motifs with simple repetitive elements in comparison to introns involved in intron retention. In almost all cases, AS results in a truncated ORF, leading to a coding sequence that is around 50% shorter than the prevalent splice form. Using RT-PCR we verified AS of two genes and show that they produce more isoforms than indicated by EST data. All cDNA/EST alignments and splice graphs are provided in a website at <url>http://combi.cs.colostate.edu/as/chlamy</url>.</p> <p>Conclusions</p> <p>The extent of AS in <it>Chlamydomonas </it>that we observed is much smaller than observed in land plants, but is much higher than in simple unicellular heterotrophic eukaryotes. The percentage of different alternative splicing events is similar to flowering plants. Prevalence of constitutive and alternative splicing in <it>Chlamydomonas</it>, together with its simplicity, many available public resources, and well developed genetic and molecular tools for this organism make it an excellent model system to elucidate the mechanisms involved in regulated splicing in photosynthetic eukaryotes.</p

The clinical assessment study of the foot (CASF): study protocol for a prospective observational study of foot pain and foot osteoarthritis in the general population.

BACKGROUND: Symptomatic osteoarthritis (OA) affects approximately 10% of adults aged over 60 years. The foot joint complex is commonly affected by OA, yet there is relatively little research into OA of the foot, compared with other frequently affected sites such as the knee and hand. Existing epidemiological studies of foot OA have focussed predominantly on the first metatarsophalangeal joint at the expense of other joints. This three-year prospective population-based observational cohort study will describe the prevalence of symptomatic radiographic foot OA, relate its occurrence to symptoms, examination findings and life-style-factors, describe the natural history of foot OA, and examine how it presents to, and is diagnosed and managed in primary care. METHODS: All adults aged 50 years and over registered with four general practices in North Staffordshire, UK, will be invited to participate in a postal Health Survey questionnaire. Respondents to the questionnaire who indicate that they have experienced foot pain in the preceding twelve months will be invited to attend a research clinic for a detailed clinical assessment. This assessment will consist of: clinical interview; physical examination; digital photography of both feet and ankles; plain x-rays of both feet, ankles and hands; ultrasound examination of the plantar fascia; anthropometric measurement; and a further self-complete questionnaire. Follow-up will be undertaken in consenting participants by postal questionnaire at 18 months (clinic attenders only) and three years (clinic attenders and survey participants), and also by review of medical records. DISCUSSION: This three-year prospective epidemiological study will combine survey data, comprehensive clinical, x-ray and ultrasound assessment, and review of primary care records to identify radiographic phenotypes of foot OA in a population of community-dwelling older adults, and describe their impact on symptoms, function and clinical examination findings, and their presentation, diagnosis and management in primary care

Enhanced flight performance by genetic manipulation of wing shape in Drosophila

Insect wing shapes are remarkably diverse and the combination of shape and kinematics determines both aerial capabilities and power requirements. However, the contribution of any specific morphological feature to performance is not known. Using targeted RNA interference to modify wing shape far beyond the natural variation found within the population of a single species, we show a direct effect on flight performance that can be explained by physical modelling of the novel wing geometry. Our data show that altering the expression of a single gene can significantly enhance aerial agility and that the Drosophila wing shape is not, therefore, optimized for certain flight performance characteristics that are known to be important. Our technique points in a new direction for experiments on the evolution of performance specialities in animals

Benefits of restoring ecosystem services in urban areas

Cities are a key nexus of the relationship between people and nature and are huge centers of demand for ecosystem services and also generate extremely large environmental impacts. Current projections of rapid expansion of urban areas present fundamental challenges and also opportunities to design more livable, healthy and resilient cities (e.g. adaptation to climate change effects). We present the results of an analysis of benefits of ecosystem services in urban areas. Empirical analyses included estimates of monetary benefits from urban ecosystem services based on data from 25 urban areas in the USA, Canada, and China. Our results show that investing in ecological infrastructure in cities, and the ecological restoration and rehabilitation of ecosystems such as rivers, lakes, and woodlands occurring in urban areas, may not only be ecologically and socially desirable, but also quite often, economically advantageous, even based on the most traditional economic approaches.Peer reviewe

Liver resection or combined chemoembolization and radiofrequency ablation improve survival in patients with hepatocellular carcinoma

Background/ Aims: To evaluate the long-term outcome of surgical and non-surgical local treatments of patients with hepatocellular carcinoma (HCC). Methods: We stratified a cohort of 278 HCC patients using six independent predictors of survival according to the Vienna survival model for HCC (VISUM- HCC). Results: Prior to therapy, 224 HCC patients presented with VISUM stage 1 (median survival 18 months) while 29 patients were classified as VISUM stage 2 (median survival 4 months) and 25 patients as VISUM stage 3 (median survival 3 months). A highly significant (p < 0.001) improved survival time was observed in VISUM stage 1 patients treated with liver resection ( n = 52; median survival 37 months) or chemoembolization (TACE) and subsequent radiofrequency ablation ( RFA) ( n = 44; median survival 45 months) as compared to patients receiving chemoembolization alone (n = 107; median survival 13 months) or patients treated by tamoxifen only (n = 21; median survival 6 months). Chemoembolization alone significantly (p <= 0.004) improved survival time in VISUM stage 1 - 2 patients but not (p = 0.341) in VISUM stage 3 patients in comparison to those treated by tamoxifen. Conclusion: Both liver resection or combined chemoembolization and RFA improve markedly the survival of patients with HCC

The outcome of trachomatous trichiasis surgery in Ethiopia: risk factors for recurrence.

BACKGROUND: Over 1.2 million people are blind from trachomatous trichiasis (TT). Lid rotation surgery is the mainstay of treatment, but recurrence rates can be high. We investigated the outcomes (recurrence rates and other complications) of posterior lamellar tarsal rotation (PLTR) surgery, one of the two most widely practised TT procedures in endemic settings. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a two-year follow-up study of 1300 participants who had PLTR surgery, conducted by one of five TT nurse surgeons. None had previously undergone TT surgery. All participants received a detailed trachoma eye examination at baseline and 6, 12, 18 and 24 months post-operatively. The study investigated the recurrence rates, other complications and factors associated with recurrence. Recurrence occurred in 207/635 (32.6%) and 108/641 (16.9%) of participants with pre-operative major (>5 trichiatic lashes) and minor (5 lashes (major recurrence). Recurrence was greatest in the first six months after surgery: 172 cases (55%) occurring in this period. Recurrence was associated with major TT pre-operatively (OR 2.39, 95% CI 1.83-3.11), pre-operative entropic lashes compared to misdirected/metaplastic lashes (OR 1.99, 95% CI 1.23-3.20), age over 40 years (OR 1.59, 95% CI 1.14-2.20) and specific surgeons (surgeon recurrence risk range: 18%-53%). Granuloma occurred in 69 (5.7%) and notching in 156 (13.0%). CONCLUSIONS/SIGNIFICANCE: Risk of recurrence is high despite high volume, highly trained surgeons. However, the vast majority are minor recurrences, which may not have significant corneal or visual consequences. Inter-surgeon variation in recurrence is concerning; surgical technique, training and immediate post-operative lid position require further investigation