Sorghum Genome Sequencing by Methylation Filtration

Sorghum bicolor is a close relative of maize and is a staple crop in Africa and much of the developing world because of its superior tolerance of arid growth conditions. We have generated sequence from the hypomethylated portion of the sorghum genome by applying methylation filtration (MF) technology. The evidence suggests that 96% of the genes have been sequence tagged, with an average coverage of 65% across their length. Remarkably, this level of gene discovery was accomplished after generating a raw coverage of less than 300 megabases of the 735-megabase genome. MF preferentially captures exons and introns, promoters, microRNAs, and simple sequence repeats, and minimizes interspersed repeats, thus providing a robust view of the functional parts of the genome. The sorghum MF sequence set is beneficial to research on sorghum and is also a powerful resource for comparative genomics among the grasses and across the entire plant kingdom. Thousands of hypothetical gene predictions in rice and Arabidopsis are supported by the sorghum dataset, and genomic similarities highlight evolutionarily conserved regions that will lead to a better understanding of rice and Arabidopsis

The Improving Rural Cancer Outcomes Trial: a cluster-randomised controlled trial of a complex intervention to reduce time to diagnosis in rural cancer patients in Western Australia.

BACKGROUND: Rural Australians have poorer survival for most common cancers, due partially to later diagnosis. Internationally, several initiatives to improve cancer outcomes have focused on earlier presentation to healthcare and timely diagnosis. We aimed to measure the effect of community-based symptom awareness and general practice-based educational interventions on the time to diagnosis in rural patients presenting with breast, prostate, colorectal or lung cancer in Western Australia. METHODS: 2 × 2 factorial cluster randomised controlled trial. Community Intervention: cancer symptom awareness campaign tailored for rural Australians. GP intervention: resource card with symptom risk assessment charts and local cancer referral pathways implemented through multiple academic detailing visits. Trial Area A received the community symptom awareness and Trial Area B acted as the community campaign control region. Within both Trial Areas general practices were randomised to the GP intervention or control. PRIMARY OUTCOME: total diagnostic interval (TDI). RESULTS: 1358 people with incident breast, prostate, colorectal or lung cancer were recruited. There were no significant differences in the median or ln mean TDI at either intervention level (community intervention vs control: median TDI 107.5 vs 92 days; ln mean difference 0.08 95% CI -0.06-0.23 P=0.27; GP intervention vs control: median TDI 97 vs 96.5 days; ln mean difference 0.004 95% CI -0.18-0.19 P=0.99). There were no significant differences in the TDI when analysed by factorial design, tumour group or sub-intervals of the TDI. CONCLUSIONS: This is the largest trial to test the effect of community campaign or GP interventions on timeliness of cancer diagnosis. We found no effect of either intervention. This may reflect limited dose of the interventions, or the limited duration of follow-up. Alternatively, these interventions do not have a measurable effect on time to cancer diagnosis

Machine for In-Line Valve Seat Inspection on Automotive Engines

ME450 Capstone Design and Manufacturing Experience: Fall 2007Auto-makers wish to improve the quality of newly assembled engine valve seats without sacrificing time and production levels. Currently, they use dial gauges and hard gauges to manually measure seat geometry. This process is time consuming and does not offer sufficient repeatability (due to human error in measurements). In response, we will use a laser sensor capable of making high accuracy measurements of seat geometry. Our main task will be to design and fabricate a mechanism that positions the sensor around the valve seats quickly and accurately. The intended outcome will be an automated, accurate, and quick way of ensuring 100% seat inspection.NSF Engineering Research Center for Reconfigurable Manufacturing Systemshttp://deepblue.lib.umich.edu/bitstream/2027.42/57934/1/ME450F07Project5_report.pd

Adapting and optimizing Problem Adaptation Therapy (PATH) for people with mild-moderate dementia and depression

Objective To adapt and optimize problem adaptation therapy for depression in dementia by grounding it in the lives of people with dementia, caregivers and clinicians. Methods A person-centered qualitative approach was taken to elicit the unique cognitive, psychological and social needs of people with dementia relevant to the adaptation of the intervention. A two-stage design was used: the first involved interviews and focus groups to identify priorities and concerns surrounding depression in dementia, the second trialling of the adapted intervention. Participants Ten people with dementia and nine caregivers participated in individual interviews, 35 healthcare practitioners and clinical academics with experience of working with dementia participated in focus groups. Results The findings highlight the importance of addressing key themes that typified the experience of depression among people with dementia including: a profound sense of isolation and role loss, the feeling of being both a burden and poorly understood, polarized thinking, interpersonal tensions, diverging views among carers and people with dementia about their capabilities, and changeability in cognitive ability and mood. These themes were used to inform adaptation of the intervention manual, ensuring that its content and delivery addressed the concerns of both people with depression and dementia and those who support them. Conclusion Implications for PATH included a focus on facilitating open communication, supporting the continuation of valued roles, and improving confidence

Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line

The SK-BR-3 cell line is one of the most important models for HER2+ breast cancers, which affect one in five breast cancer patients. SK-BR-3 is known to be highly rearranged, although much of the variation is in complex and repetitive regions that may be underreported. Addressing this, we sequenced SK-BR-3 using long-read single molecule sequencing from Pacific Biosciences and develop one of the most detailed maps of structural variations (SVs) in a cancer genome available, with nearly 20,000 variants present, most of which were missed by short-read sequencing. Surrounding the important ERBB2 oncogene (also known as HER2), we discover a complex sequence of nested duplications and translocations, suggesting a punctuated progression. Full-length transcriptome sequencing further revealed several novel gene fusions within the nested genomic variants. Combining long-read genome and transcriptome sequencing enables an in-depth analysis of how SVs disrupt the genome and sheds new light on the complex mechanisms involved in cancer genome evolution

Annotation of <i>Arabidopsis</i> by Sorghum MF Versus Rice Gene Sequences

<p>Shown are the number of <i>Arabidopsis</i> proteins that are matched in a TBLASTN comparison to the sorghum MF set (blue) versus the rice gene sequences (yellow). The <i>Arabidopsis</i> proteins, after having known repetitive elements removed (see <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0030013#s3" target="_blank">Materials and Methods</a>), have been categorized as either hypothetical or known based on the definition line. <i>Arabidopsis</i> proteins were considered supported if they matched with an E-value less than or equal to 1 × 10⁻⁸. Sb, S. bicolor MF set; Osj:seq, <i>Oryza sativa japonica</i> gene sequences.</p

Genome Reduction

<p>MF reduces the sorghum genome by 66% in sampling a hypomethylated space of approximately 247 Mb (green) and filtering out 488 Mb (red) of the 735-Mb sorghum genome.</p

Secondary Structure of Predicted MiRNAs

<p>Predicted hairpin secondary structure of miRNA MIR156a from rice and the newly discovered ortholog from sorghum. The 21-nucleotide MIR156a sequence is highlighted in red.</p