Fate mapping neurons and glia derived from Dbx1-expressing progenitors in mouse preBotzinger complex

The brainstem preBotzinger complex (preBotC) generates the inspiratory breathing rhythm, and its core rhythmogenic interneurons are derived from Dbx1-expressing progenitors. To study the neural bases of breathing, tamoxifen-inducible Cre-driver mice and Cre-dependent reporters are used to identify, record, and perturb Dbx1 preBotC neurons. However, the relationship between tamoxifen administration and reporter protein expression in preBotC neurons and glia has not been quantified. To address this problem, we crossed mice that express tamoxifen-inducible Cre recombinase under the control of the Dbx1 gene (Dbx1(CreERT2)) with Cre-dependent fluorescent reporter mice (Rosa26(tdTomato)), administered tamoxifen at different times during development, and analyzed tdTomato expression in the preBotC of their offspring. We also crossed Rosa26(tdTomato) reporters with mice that constitutively express Cre driven by Dbx1 (Dbx1(Cre)) and analyzed tdTomato expression in the preBotC of their offspring for comparison. We show that Dbx1-expressing progenitors give rise to preBotC neurons and glia. Peak neuronal tdTomato expression occurs when tamoxifen is administered at embryonic day 9.5 (E9.5), whereas tdTomato expression in glia shows no clear relationship with tamoxifen timing. These results can be used to bias reporter protein expression in neurons (or glia). Tamoxifen administration at E9.5 labels 91% of Dbx1-derived neurons in the preBotC, yet only 48% of Dbx1-derived glia. By fate mapping Dbx1-expressing progenitors, this study illustrates the developmental assemblage of Dbx1-derived cells in preBotC, which can be used to design intersectional Cre/lox experiments that interrogate its cellular composition, structure, and function

Resolving candidate genes of mouse skeletal muscle QTL via RNA-Seq and expression network analyses

Peer reviewedPublisher PD

Recidivism Risk Assessment for Aboriginal Males: A Brief Review of the Scientific Literature

No level of violent recidivism is acceptable to Correctional Service of Canada staff or the Canadian public. Among other tools, CSC staff use counselling, supervision, education, and treatment programs to ensure the safe community reintegration of eligible offenders. The core method of determining risk for recidivism is an actuarially-based risk assessment instrument. The general process of contemporary risk assessment is outlined in this paper revealing a number of efficient and effective measures suitable for all male offender populations. Theory and research are reviewed showing that established risk prediction factors such as age, criminal history, anti-social peers, anti-social attitudes, and substance abuse predict criminal recidivism for all offenders regardless of cultural, racial, or geographic heritage. The majority of these validated risk assessment instruments have moderate predictive power for all male offenders. Seven of these instruments are individually reviewed with regard to their use with Aboriginal groups. This paper concludes with recommendations for further research on risk assessment among cultural groups

Randomized phase II study investigating pazopanib versus weekly paclitaxel in relapsed or progressive urothelial cancer

Purpose: Two previous single-arm trials have drawn conflicting conclusions regarding the activity of pazopanib in urothelial cancers after failure of platinum-based chemotherapy. Patients and Methods: This randomized (1:1) open-label phase II trial compared the efficacy of pazopanib 800 mg orally with paclitaxel (80 mg/m2 days 1, 8, and 15 every 28 days) in the second-line setting. The primary end point was overall survival (OS). Results: Between August 2012 and October 2014, 131 patients, out of 140 planned, were randomly assigned. The study was terminated early on the recommendation of the independent data monitoring committee because of futility. Final analysis after the preplanned number of deaths (n = 110) occurred after a median follow-up of 18 months. One hundred fifteen deaths had occurred at the final data extract presented here. Median OS was 8.0 months for paclitaxel (80% CI, 6.9 to 9.7 months) and 4.7 months for pazopanib (80% CI, 4.2 to 6.4 months). The hazard ratio (HR) adjusted for baseline stratification factors was 1.28 (80% CI, 0.99 to 1.67; one-sided P = .89). Median progression-free survival was 4.1 months for paclitaxel (80% CI, 3.0 to 5.6 months) and 3.1 months for pazopanib (80% CI, 2.7 to 4.6 months; HR, 1.09; 80% CI, 0.85 to 1.40; one-sided P = .67). Discontinuations for toxicity occurred in 7.8% and 23.1% for paclitaxel and pazopanib, respectively. Conclusion: Pazopanib did not have greater efficacy than paclitaxel in the second-line treatment of urothelial cancers. There was a trend toward superior OS for paclitaxel

Oxidation of tertiary amine-derivatized surfaces to control protein adhesion

Selective oxidation of omega-tertiary amine self-assembled thiol monolayers to tertiary amine N-oxides is shown to transform the adhesion of model proteins lysozyme and fibrinogen upon them. Efficient preparation of both secondary and tertiary linker amides as judged by X-ray photoelectron spectroscopy (XPS) and water droplet contact angle was achieved with an improved amide bond formation on gold quartz crystal microbalance (QCM) sensors using 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl hexafluorophosphate methanaminium uronium (HATU). Oxidation with hydrogen peroxide was similarly assessed, and adhesion of lysozyme and fibrinogen from phosphate buffered saline was then assayed by QCM and imaged by AFM. Tertiary amine-functionalized sensors adsorbed multilayers of aggregated lysozyme, whereas tertiary amine N-oxides and triethylene glycol-terminated monolayers are consistent with small protein aggregates. The surface containing a dimethylamine N-oxide headgroup and ethyl secondary amide linker showed the largest difference in adsorption of both proteins. Oxidation of tertiary amine decorated surfaces therefore holds the potential for selective deposition of proteins and cells through masking and other patterning techniques