Vac8p, an Armadillo Repeat Protein, Coordinates Vacuole Inheritance With Multiple Vacuolar Processes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74978/1/j.1600-0854.2006.00458.x.pd

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Using Visual Analytics to Enhance Data Exploration and Knowledge Discovery in Financial Systemic Risk Analysis: The Multivariate Density Estimator

Analyzing and managing the risks in financial systems is necessary to maintain healthy global financial systems and economic wellbeing. However, the complexity of the financial system and the heterogeneity and volume of data sources needed for financial systemic risk analysis are currently overwhelming. Visual Analytics tools can be used to provide macroprudential supervisors with greater visibility into the health of financial systems by augmenting their information processing capabilities. To this end, we present a novel prototype design for a visual analytics tool that implements the multivariate density estimator of financial systemic risk, explaining how it addresses macroprudential supervisors' need for enhanced data exploration and knowledge discovery capabilities.publishedye

Effectiveness of an online self-management tool, OPERAS (an On-demand Program to EmpoweR Active Self-management), for people with rheumatoid arthritis: a research protocol

Background: Active self-management is a process where patients are fully engaged in managing their health in daily life by having access to contextualized health data and tailored guidance to support a healthy lifestyle. This study aims to determine whether an e-health intervention that incorporates symptom/disease activity monitoring and physical activity counselling can improve self-management ability in patients with rheumatoid arthritis (RA). Methods: The ‘Empowering active self-management of arthritis: Raising the bar with OPERAS (an On-demand Program to EmpoweR Active Self-management)’ project is a randomized controlled trial that uses a delayed control design. One hundred thirty-four participants with RA will be randomly assigned to start the intervention either immediately (immediate group) or 6 months later (delayed group). The intervention involves (1) use of a Fitbit-compatible web app to record and monitor their RA disease activity, symptoms, and time spent on physical activity and a Fitbit; (2) group education and individual counselling by a physiotherapist (PT); and (3) six phone calls with a PT. The primary outcome measure is self-management ability measured by the Patient Activation Measure. Secondary outcome measures include disease status, fatigue, pain, depressive symptoms, and characteristics of habitual behavior and also time spent in physical activity and sedentary activity with a wearable multi-sensor device (SenseWear Mini). After the 6-month intervention, we will interview a sample of participants to examine their experiences with the intervention. Discussion: The results of this study will help to determine whether this technology-enhanced self-management intervention improves self-management ability and health outcomes for people living with RA. A limitation of this study is that participants will need to self-report their symptoms, disease status, and treatment use through questionnaires on the OPERAS web app. The user-friendly interface, reminder emails from the research staff, and tailored guidance from PTs will encourage participants to actively engage with the app. Trial registration: Date of last update in ClinicalTrials.gov: January 2, 2019. ClinicalTrials.gov Identifier: NCT03404245.Medicine, Faculty ofOther UBCNon UBCFamily Practice, Department ofMedicine, Department ofOccupational Science and Occupational Therapy, Department ofPhysical Therapy, Department ofReviewedFacult

Changes observed in prostate biopsy practices in an inner city hospital with a high risk patient population following the 2012 USPSTF PSA screening recommendations

ABSTRACT Introduction: We compared characteristics of patients undergoing prostate biopsy in a high-risk inner city population before and after the 2012 USPSTF recommendation against PSA based prostate cancer screening to determine its effect on prostate biopsy practices. Materials and Methods: This was a retrospective study including patients who received biopsies after an abnormal PSA measurement from October 2008-December 2015. Patients with previously diagnosed prostate cancer were excluded. Chi-square tests of independence, two sample t-tests, Mann-Whitney U tests, and Fisher's exact tests were performed. Results: There were 202 and 208 patients in the pre-USPSTF and post-USPSTF recommendation cohorts, respectively. The post-USPSTF cohort had higher median PSA (7.8 versus 7.1ng/mL, p=0.05), greater proportion of patients who were black (96.6% versus 90.5%, p=0.01), and greater percentage of biopsy cores positive for disease (58% versus 29.5%, p<0.001). Multivariable analysis supported that the increase in PSA was independent of the increase in the proportion of patients who were black. The proportion of patients who were classified as D’Amico intermediate and high-risk disease increased in the post-USPSTF cohort and approached statistical significance (70.1% versus 58.8%, p=0.12). Conclusions: Our study suggests that the USPSTF recommendations may have led to an increase in pre-biopsy PSA as well as greater volume of disease. Also, a greater proportion of patients were being classified with intermediate or high risk disease. While the clinical significance of these findings is unknown, what the data suggests is somewhat troubling. Future research should further examine these changes in a larger cohort as well as resultant long-term outcomes

Efficacy of a Physical Activity Counselling Program with Use of Wearable Tracker in People with Inflammatory Arthritis : A Randomized Controlled Trial

Objectives. To assess the efficacy of a multi-faceted counselling intervention at improving physical activity participation and patient outcomes. Methods. We recruited people with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). In Weeks 1-8, the Immediate Group received education and counselling by a physiotherapist (PT), used a Fitbit and a web-application to obtain feedback about their physical activity, and received 4 follow-up calls from the PT. The Delay Group received the same intervention in Weeks 10-17. Participants were assessed at baseline, Week 9, 18 and 27. Primary outcome was time spent in moderate/vigorous physical activity (MVPA; in bouts of >10 mins) measured with a SenseWear. Secondary outcomes included step count, time in sedentary behaviour, pain, fatigue, mood, self management capacity, and habitual behaviours. Results. 118 participants enrolled. The adjusted mean difference in MVPA was 9.4 mins/day (95% CI: -0.5, 19.3, P=0.06). A significant effect was found in pain (-2.45; 95% CI: -4.78, -0.13, P=0.04), and perceived walking habit (0.54; 95% CI: 0.08, 0.99, P=0.02). The remaining secondary outcomes improved, but were not statistically significant. Post-hoc analysis revealed a significant effect in MVPA (14.3 mins/day; 95% CI: 2.3, 26.3) and pain (-4.05; 95% CI: -6.73, -1.36) in participants with RA, but not those with SLE. Conclusion. Counselling by a PT has potential to improve physical activity in people with inflammatory arthritis, but further study is needed to understand the intervention effect on different diseases. We found a significant improvement in pain, suggesting the intervention might have a positive effect on symptom management.Medicine, Faculty ofNon UBCMedicine, Department ofOccupational Science and Occupational Therapy, Department ofPhysical Therapy, Department ofReviewedFacultyResearcherPostdoctora

SETD1A modulates cell cycle progression through a miRNA network that regulates p53 target genes

Expression of the p53-inducible antiproliferative gene BTG2 is suppressed in many cancers in the absence of inactivating gene mutations, suggesting alternative mechanisms of silencing. Using a shRNA screen targeting 43 histone lysine methyltransferases (KMTs), we show that SETD1A suppresses BTG2 expression through its induction of several BTG2-targeting miRNAs. This indirect but highly specific mechanism, by which a chromatin regulator that mediates transcriptional activating marks can lead to the downregulation of a critical effector gene, is shared with multiple genes in the p53 pathway. Through such miRNA-dependent effects, SETD1A regulates cell cycle progression in vitro and modulates tumorigenesis in mouse xenograft models. Together, these observations help explain the remarkably specific genetic consequences associated with alterations in generic chromatin modulators in cancer

\u3ci\u3eDrosophila\u3c/i\u3e Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu