Digital training plays a major role in the initial training for preschool, primary, and high school teachers in Quebec, Canada. Since the mastery of information and communications technology (ICT) is prescriptive, measures have been implemented in university teacher training programs to ensure its development. Nevertheless, after this training, pre-service teachers' (PSTs') ability to transfer competency to a real context remains uncertain. We identified PSTs' levels of mastery of digital tools and competency, as well as their pedagogical usage of them during their school practicums. We sought to ascertain whether they were ready to organize collaborative learning activities with their students. Their mastery of digital tools did not go beyond the level of "good," except for tools related to office suites. They perceived themselves as having average mastery of the ability to integrate ICT. In addition, the transfer to a professional context is progressing via the pedagogical usage of ICT reported by PSTs during their school practicums. We observed moderate correlations between the mastery of collaborative and communication tools and of collaborative teaming activities.

Rare variants in at least 10 genes, including BRCA1, BRCA2, PALB2, ATM, and CHEK2, are associated with increased risk of breast cancer; however, these variants, in combination with common variants identified through genome-wide association studies, explain only a fraction of the familial aggregation of the disease. To identify further susceptibility genes, we performed a two-stage whole-exome sequencing study. In the discovery stage, samples from 1528 breast cancer cases enriched for breast cancer susceptibility and 3733 geographically matched unaffected controls were sequenced. Using five different filtering and gene prioritization strategies, 198 genes were selected for further validation. These genes, and a panel of 32 known or suspected breast cancer susceptibility genes, were assessed in a validation set of 6211 cases and 6019 controls for their association with risk of breast cancer overall, and by estrogen receptor (ER) disease subtypes, using gene burden tests applied to loss-of-function and rare missense variants. Twenty genes showed nominal evidence of association (p-value < 0.05) with either overall or subtype-specific breast cancer. Our study had the statistical power to detect susceptibility genes with effect sizes similar to ATM, CHEK2, and PALB2, however, it was underpowered to identify genes in which susceptibility variants are rarer or confer smaller effect sizes. Larger sample sizes would be required in order to identify such genes.

Background We identified two families with Paget's disease of bone (PDB) linked to the p.Pro392Leu mutation within the SQSTM1 gene displaying a possible digenism. This study aimed at identifying this second genetic variant cosegregating with the p.Pro392Leu mutation and at characterizing its impact on the clinical and cellular phenotypes of PDB. Methods Whole exome sequencing was performed in one patient per family and two healthy controls. We compared clinical characteristics of PDB in 14 relatives from the two families. The osteoclastic phenotype was compared in in vitro differentiated osteoclasts from 31 participants carrying the DOCK6 and/or SQSTM1 variants. Tridimensional models of SQSTM1 and DOCK6 proteins were generated to evaluate the impact of these variants on their stability and flexibility. Statistical analyses were performed with Graphpad prism. Results Whole-exome sequencing allowed us to identify the p.Val45Ile missense variant in the DOCK6 gene in patients. In both families, the mean age at PDB diagnosis was delayed in pagetic patients carrier of the p.Val45Ile variant alone compared to those carrying the p.Pro392Leu mutation alone (67 vs. 44 years, P = 0.03). Although both p.Val45Ile and p.Pro392Leu variants gave rise to a pagetic phenotype of osteoclast versus healthy controls, the p.Val45Ile variant was found to attenuate the severity of the osteoclastic phenotype of PDB caused by the p.Pro392Leu mutation when both variants were present. The DOCK6 mRNA expression was higher in carriers of the p.Val45Ile variant than in pagetic patients without any mutations and healthy controls. Structural bioinformatics analyses suggested that the p.Pro392Leu mutation might rigidify the UBA domain and thus decrease its possible intramolecular interaction with a novel domain, the serum response factor–transcription factor (SRF-TF)-like domain, whereas the p.Val45Ile variant may decrease SRF-TF-like activity. Conclusion The p.Val45Ile variant may attenuate the severity of the clinical phenotype of PDB in patient carriers of both variants. In vitro, the rare variant of the DOCK6 may have a modifier effect on the p.Pro392Leu mutation, possibly via its effect on the SRF-TF-like.

Recent evidence suggests that genetic and epigenetic mechanisms might be associated with acquired resistance to cancer therapies. The aim of this study was to assess the association of genome-wide genetic and epigenetic alterations with the response to anti-HER2 agents in HER2-positive breast cancer patients. PubMed was screened for articles published until March 2021 on observational studies investigating the association of genome-wide genetic and epigenetic alterations, measured in breast cancer tissues or blood, with the response to targeted treatment in HER2-positive breast cancer patients. Sixteen studies were included in the review along with ours, in which we compared the genome-wide DNA methylation pattern in breast tumor tissues of patients who acquired resistance to treatment (case group, n = 6) to that of patients who did not develop resistance (control group, n = 6). Among genes identified as differentially methylated between the breast cancer tissue of cases and controls, one of them, PRKACA, was also reported as differentially expressed in two studies included in the review. Although included studies were heterogeneous in terms of methodology and study population, our review suggests that genes of the PI3K pathway may play an important role in developing resistance to anti-HER2 agents in breast cancer patients. Genome-wide genetic and epigenetic alterations measured in breast cancer tissue or blood might be promising markers of resistance to anti-HER2 agents in HER2-positive breast cancer patients. Further studies are needed to confirm these data.

IntroductionThe administration of trastuzumab has led to significant improvement in survival of HER2‐positive breast cancer patients in the adjuvant and metastatic settings. Trastuzumab resistance, however, has been increasingly recognized as a major obstacle. Recent evidence suggests that epigenetic mechanisms might be associated with acquired resistance to cancer therapies. Aim of this study was to explore the association between genome‐wide DNA methylation pattern in breast cancer tissue and the response to trastuzumab.Patients and methodsDNA methylation pattern was assessed in breast cancer tissues of trastuzumab‐treated HER2‐positive breast cancer patients who acquired resistance to treatment (case group, n=6) and compared to that of trastuzumab‐treated HER2‐positive breast cancer patients who did not develop resistance (control group, n=6) using the Illumina Infinium HumanMethylation450 BeadChip. Cases were matched to controls for several factors. Bioinformatics analyses were performed using the R statistical environment (robust linear regression method) to identify differentially methylated genes (DMGs) (FDR < 0.05) between case and control groups.ResultsCompared to the control group, in the matched case group we identified 879 hypermethylated and 293 hypomethylated genes. The differentially methylated set of genes was enriched in molecular and cellular functions associated with cellular movement (P=8.02E‐07) as well as cell death and survival (P=4.24E‐09). Pathways associated with ERK/MAPK signaling and regulation of the epithelial‐mesenchymal transition were overrepresented (P=2.13E‐05, and P=2.43E‐03, respectively). Among the DMGs we observed AGPAT1, a gene related to the PI3K‐mTOR pathway which has been reported to be implicated with trastuzumab resistance in addition to be differentially expressed between HER2‐positive breast cancer patients who responded to trastuzumab and those who acquired resistance.ConclusionsAlthough our sample size was small, we observed DMGs associated with the response to trastuzumab. These data need to be confirmed in a larger prospective cohort of trastuzumab‐treated HER2‐positive breast cancer patients.Support or Funding InformationDF received doctoral fellowships from the Fonds de recherché du Québec – Santé (FRQS) and the Laval University Cancer Research Center. CD is a recipient of the Canadian Breast Cancer Foundation‐Canadian Cancer Society Development award (award #703003) and the FRQS Research Scholar.This study was supported by the Fondation des Hôpitaux Enfant Jésus – St‐Sacrement. Clinical specimens were provided by the Fondation du cancer du sein du Québec and the Banque de tissus et de données of the Réseau de recherche sur le cancer of the FRQS, which is affiliated with the Canadian Tumour Repository Network.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Fast identification of microbial species in clinical samples is essential to provide an appropriate antibiotherapy to the patient and reduce the prescription of broad-spectrum antimicrobials leading to antibioresistances. MALDI-TOF-MS technology has become a tool of choice for microbial identification but has several drawbacks: it requires a long step of bacterial culture before analysis (≥24 h), has a low specificity and is not quantitative. We developed a new strategy for identifying bacterial species in urine using specific LC-MS/MS peptidic signatures. In the first training step, libraries of peptides are obtained on pure bacterial colonies in DDA mode, their detection in urine is then verified in DIA mode, followed by the use of machine learning classifiers (NaiveBayes, BayesNet and Hoeffding tree) to define a peptidic signature to distinguish each bacterial species from the others. Then, in the second step, this signature is monitored in unknown urine samples using targeted proteomics. This method, allowing bacterial identification in less than 4 h, has been applied to fifteen species representing 84% of all Urinary Tract Infections. More than 31,000 peptides in 190 samples were quantified by DIA and classified by machine learning to determine an 82 peptides signature and build a prediction model. This signature was validated for its use in routine using Parallel Reaction Monitoring on two different instruments. Linearity and reproducibility of the method were demonstrated as well as its accuracy on donor specimens. Within 4h and without bacterial culture, our method was able to predict the predominant bacteria infecting a sample in 97% of cases and 100% above the standard threshold. This work demonstrates the efficiency of our method for the rapid and specific identification of the bacterial species causing UTI and could be extended in the future to other biological specimens and to bacteria having specific virulence or resistance factors.

This paper presents a research project in science education that is positioned at the intersection of computer science and context in learning. The main objective is to improve learning process by creating a software tool that participates, from the inception to the achievement, in the design of leaning scenarios, based on context effects, and, to show that context effects’ learning is an efficient method in the development of student’s knowledge regarding a concept. The software will compute differences between two – or more – external contexts based on specific parameters, related to the phenomenon or object that students are expected to study. The elaboration of the calculator (“the MazCalc”) is conducted using the design based research theory, meaning that several iterations of learning field experiments are conducted in order to collect relevant data which are used for the tool creation. In this paper, the design of the scenario involves students from North America and from the French West Indies and the concept studied is about geothermal energy. The instantiation of the context calculator is made with the geothermal object of study, and the differences are computed in the calculator between the two contexts mentioned. This example makes possible to validate the link between context effects predicted and observed, and also to study the impact of external context on the learning process. This study has been conducted thanks to the GEOTREF project support.

Exposure to solar ultraviolet type B (UVB), through the induction of cyclobutane pyrimidine dimer (CPD), is the major risk factor for cutaneous cancer. Cells respond to UV-induced CPD by triggering the DNA damage response (DDR) responsible for signaling DNA repair, programmed cell death and cell cycle arrest. Underlying mechanisms implicated in the DDR have been extensively studied using single acute UVB irradiation. However, little is known concerning the consequences of chronic low-dose of UVB (CLUV) on the DDR. Thus, we have investigated the effect of a CLUV pre-stimulation on the different stress response pathways. We found that CLUV pre-stimulation enhances CPD repair capacity and leads to a cell cycle delay but leave residual unrepaired CPD. We further analyzed the consequence of the CLUV regimen on general gene and protein expression. We found that CLUV treatment influences biological processes related to the response to stress at the transcriptomic and proteomic levels. This overview study represents the first demonstration that human cells respond to chronic UV irradiation by modulating their genotoxic stress response mechanisms.

Epithelial ovarian cancer (EOC) is a disease responsible for more deaths among women in the Western world than all other gynecologic malignancies. There is urgent need for new therapeutic targets and a better understanding of EOC initiation and progression. We have previously identified the polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) gene, a member of the GaINAc-transferases (GaINAc-Ts) gene family, as hypomethylated and overexpressed in high-grade serous EOC tumors, compared to low malignant potential EOC tumors and normal ovarian tissues. This data also suggested for a role of GALNT3 in aberrant EOC glycosylation, possibly implicated in disease progression. To evaluate differential glycosylation in EOC caused by modulations in GALNT3 expression, we used a metabolic labeling strategy for enrichment and mass spectrometry-based characterization of glycoproteins following GALNT3 gene knockdown (KD) in A2780s EOC cells. A total of 589 differentially expressed glycoproteins were identified upon GALNT3 Ka Most identified proteins were involved in mechanisms of cellular metabolic functions, post-translational modifications, and some have been reported to be implicated in EOC etiology.The GALNT3-dependent glycoproteins identified by this metabolic labeling approach support the oncogenic role of GALNT3 in EOC dissemination and may be pursued as novel EOC biomarkers and/or therapeutic targets. Biological significance: Knowledge of the O-glycoproteome has been relatively elusive, and the functions of the individual polypeptide GaINAc-Ts have been poorly characterized. Alterations in GaINAc-Ts expression were shown to provide huge variability in the )-glycoproteome in various pathologies, including cancer. The application of a chemical biology approach for the metabolic labeling and subsequent characterization of O-glycoproteins in EOC using the Ac(4)GaINAz metabolite has provided a strategy allowing for proteomic discovery of GaINAc-Ts specific functions. Our study supports an essential role of one of the GaINAc-Ts GALNT3, in EOC dissemination, including its implication in modulating PTMs and EOC metabolism. Our approach validates the use of the applied metabolic strategy to identify important functions of GaINAc-Ts in normal and pathological conditions (C). 2016 Elsevier B.V. All rights reserved.