Proteogenomic analysis of acute myeloid leukemia associates relapsed disease with reprogrammed energy metabolism both in adults and children

Despite improvement of current treatment strategies and novel targeted drugs, relapse and treatment resistance largely determine the outcome for acute myeloid leukemia (AML) patients. To identify the underlying molecular characteristics, numerous studies have been aimed to decipher the genomic- and transcriptomic landscape of AML. Nevertheless, further molecular changes allowing malignant cells to escape treatment remain to be elucidated. Mass spectrometry is a powerful tool enabling detailed insights into proteomic changes that could explain AML relapse and resistance. Here, we investigated AML samples from 47 adult and 22 pediatric patients at serial time-points during disease progression using mass spectrometry-based in-depth proteomics. We show that the proteomic profile at relapse is enriched for mitochondrial ribosomal proteins and subunits of the respiratory chain complex, indicative of reprogrammed energy metabolism from diagnosis to relapse. Further, higher levels of granzymes and lower levels of the anti-inflammatory protein CR1/CD35 suggest an inflammatory signature promoting disease progression. Finally, through a proteogenomic approach, we detected novel peptides, which present a promising repertoire in the search for biomarkers and tumor-specific druggable targets. Altogether, this study highlights the importance of proteomic studies in holistic approaches to improve treatment and survival of AML patients.Peer reviewe

Genome-wide association for milk production and lactation curve parameters in Holstein dairy cows

The aim of this study was to identify genomic regions associated with 305-day milk yield and lactation curve parameters on primiparous (n = 9,910) and multiparous (n = 11,158) Holstein cows. The SNP solutions were estimated using a weighted single-step genomic BLUP approach and imputed high-density panel (777k) genotypes. The proportion of genetic variance explained by windows of 50 consecutive SNP (with an average of 165 Kb) was calculated, and regions that accounted for more than 0.50% of the variance were used to search for candidate genes. Estimated heritabilities were 0.37, 0.34, 0.17, 0.12, 0.30 and 0.19, respectively, for 305-day milk yield, peak yield, peak time, ramp, scale and decay for primiparous cows. Genetic correlations of 305-day milk yield with peak yield, peak time, ramp, scale and decay in primiparous cows were 0.99, 0.63, 0.20, 0.97 and -0.52, respectively. The results identified three windows on BTA14 associated with 305-day milk yield and the parameters of lactation curve in primi- and multiparous cows. Previously proposed candidate genes for milk yield supported by this work include GRINA, CYHR1, FOXH1, TONSL, PPP1R16A, ARHGAP39, MAF1, OPLAH and MROH1, whereas newly identified candidate genes are MIR2308, ZNF7, ZNF34, SLURP1, MAFA and KIFC2 (BTA14). The protein lipidation biological process term, which plays a key role in controlling protein localization and function, was identified as the most important term enriched by the identified genes

Expert-based development of a generic HACCP-based risk management system to prevent critical negative energy balance in dairy herds

The objective of this study was to develop a generic risk management system based on the Hazard Analysis and Critical Control Point (HACCP) principles for the prevention of critical negative energy balance (NEB) in dairy herds using an expert panel approach. In addition, we discuss the advantages and limitations of the system in terms of implementation in the individual dairy herd. For the expert panel, we invited 30 researchers and advisors with expertise in the field of dairy cow feeding and/or health management from eight European regions. They were invited to a Delphi-based set-up that included three inter-correlated questionnaires in which they were asked to suggest risk factors for critical NEB and to score these based on 'effect' and 'probability'. Finally, the experts were asked to suggest critical control points (CCPs) specified by alarm values, monitoring frequency and corrective actions related to the most relevant risk factors in an operational farm setting. A total of 12 experts (40 %) completed all three questionnaires. Of these 12 experts, seven were researchers and five were advisors and in total they represented seven out of the eight European regions addressed in the questionnaire study. When asking for suggestions on risk factors and CCPs, these were formulated as 'open questions', and the experts' suggestions were numerous and overlapping. The suggestions were merged via a process of linguistic editing in order to eliminate doublets. The editing process revealed that the experts provided a total of 34 CCPs for the 11 risk factors they scored as most important. The consensus among experts was relatively high when scoring the most important risk factors, while there were more diverse suggestions of CCPs with specification of alarm values and corrective actions. We therefore concluded that the expert panel approach only partly succeeded in developing a generic HACCP for critical NEB in dairy cows. We recommend that the output of this paper is used to inform key areas for implementation on the individual dairy farm by local farm teams including farmers and their advisors, who together can conduct herd-specific risk factor profiling, organise the ongoing monitoring of herd-specific CCPs, as well as implement corrective actions when CCP alarm values are exceeded

2017 Research & Innovation Day Program

A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1004/thumbnail.jp

Characterization and performance analysis of InAs/GaSb T2SL photodetector for LWIR/VLWIR spectral domain

International audienc

Characterization and performance analysis of InAs/GaSb T2SL photodetector for LWIR/VLWIR spectral domain

International audienc

Emergency Medicine Procedures: A Review of Approved Instructional Resources from the World of Free Open Access Medical Education.

The Academic Life in Emergency Medicine (ALiEM) Approved Instructional Resources (AIR) Series was created in 2014 to address the Free Open Access Medical Education (FOAM) movements decentralized nature and lack of inherent peer review. The AIR series provides a topic-based, curated list of online educational content vetted by academic emergency medicine (EM) faculty that meets individualized interactive instruction criteria for EM trainees. Relevant FOAM resources were identified from the top 50 FOAM websites using the Social Media Index and then scored by EM faculty using a validated instrument to identify the highest quality posts related to a topic. This article reviews FOAM resources pertaining to EM procedures that were labeled as an Approved Instructional Resource or Honorable Mention using the AIR series methodology

Minority Carrier Lifetime and Photoluminescence Studies of Antimony-Based Superlattices

In this paper, we have used the OMR technique to study the minority carrier lifetimes in three InAs/GaSb-photoluminescence (PL) structures with different number of periods in the absorber: 300, 400 and 600 periods respectively. The feasibility of using a visible 643 nm laser source with short penetration depth for lifetime measurements was studied by comparing the achieved results to measurements performed on the same samples with a 1550 nm IR laser source, which penetrates much deeper into the sample. Despite the differences in excitation wavelengths and penetration depths, the results from both measurements were very similar. This indicates that the diffusion length is long enough to facilitate a homogeneous distribution of excess carriers in the material

Photoluminescence Study of Long Wavelength Superlattice Infrared Detectors

In this paper, the relation between the photoluminescence (PL) intensity and the PL peak wavelength was studied. A linear decrease of the PL intensity with increasing cut-off wavelength of long wavelength infrared CBIRDs was observed at 77 K and the trend remained unchanged in the temperature range 10 - 77 K. This relation between the PL intensity and the peak wavelength can be favorably used for comparison of the optical quality of samples with different PL peak wavelengths. A strong increase of the width of the PL spectrum in the studied temperature interval was observed, which was attributed to thermal broadening