Search

The purpose of this study was to analyze the perceptions of Korean English as a Foreign Language (EFL) university students toward teacher-generated educational videos and the recommendations they have for improving their effectiveness. While playing short video clips is now common practice in many EFL classes, few teachers choose to generate their own educational videos and little research has been done on how to create effective educational videos for EFL learners. Nine Korean university students participated in this study with qualitative data being collected from a focus group and semi-structured interviews. The videos shown to the students were viewed on the YouTube website during class and were created by their teacher and the author of this paper. The results show that the students find the videos helpful and effective for improving their English, although it is recommended to limit the time spent in class watching videos as students would rather spend time practicing the language. Other opinions and recommendations are grounded in cognitive load theory. The implications of this study suggest that teachers should consider creating their own educational videos and suggestions are made of how to create effective presentations.

Gene Rearrangement Frequencies in WGS Cohort

Detected chromatin interactions in all 12 tumour and 5 benign samples.

Sequencing metrics as calculated by HiCUP for all Hi-C libraries generated in this study.

SV breakpoints detected by Hi-C in each tumour sample.

XLS file - 38K

AR Gene Alterations in WGS Cohort

Simple and complex SVs reconstructed from SV breakpoints.

Purpose:PTEN deletions in prostate cancer are associated with tumor aggression and poor outcome. Recent studies have implicated PTEN as a determinant of homologous recombination (HR) through defective RAD51 function. Similar to BRCA1/2-defective tumor cells, PTEN-null prostate and other cancer cells have been reported to be sensitive to PARP inhibitors (PARPi). To date, no direct comparison between PTEN and RAD51 expression in primary prostate tumors has been reported.Experimental Design: Prostate cancer cell lines and xenografts with known PTEN status (22RV1-PTEN+/+, DU145-PTEN+/−, PC3-PTEN−/−) and H1299 and HCT116 cancer cells were used to evaluate how PTEN loss affects RAD51 expression and PARPi sensitivity. Primary prostate cancers with known PTEN status were analyzed for RAD51 expression.Results:PTEN status is not associated with reduced RAD51 mRNA or protein expression in primary prostate cancers. Decreased PTEN expression did not reduce RAD51 expression or clonogenic survival following PARPi among prostate cancer cells that vary in TP53 and PTEN. PARPi sensitivity instead associated with a defect in MRE11 expression. PTEN-deficient cells had only mild PARPi sensitivity and no loss of HR or RAD51 recruitment. Clonogenic cell survival following a series of DNA damaging agents was variable: PTEN-deficient cells were sensitive to ionizing radiation, mitomycin-C, UV, H2O2, and methyl methanesulfonate but not to cisplatin, camptothecin, or paclitaxel.Conclusions: These data suggest that the relationship between PTEN status and survival following DNA damage is indirect and complex. It is unlikely that PTEN status will be a direct biomarker for HR status or PARPi response in prostate cancer clinical trials. Clin Cancer Res; 18(4); 1015–27. ©2011 AACR.

Compartmentalization changes in tumours is not associated with widespread differential gene expression.

Supplementary Figures and descriptions for Supplementary Tables

PDF file - 183K

PDF file - 88K

Structural variant detection from Hi-C data.

Assembly of structural variants involving enhancer-hijacking events.

Individual TAD calls in all 12 tumour and 5 benign samples.

PDF file - 89K

Sample processing and TAD similarity between samples.

CCR Translation for This Article from PTEN Deletion in Prostate Cancer Cells Does Not Associate with Loss of RAD51 Function: Implications for Radiotherapy and Chemotherapy

PDF file - 31K

Summary statistics for TAD counts in all 12 tumour and 5 benign samples, across multiple window sizes.

PDF file - 185K

H3K27ac peaks identified in each of the 12 primary PCa patients. Raw sequencing data as previously published was remapped to the hg38 reference genome.

Characterization of chromatin interactions in benign and tumour tissue.

Patients and Tissues

Prostate cancer is a heterogeneous disease whose progression is linked to genome instability. However, the impact of this instability on the noncoding genome and its three-dimensional organization to aid progression is unclear. Using primary benign and tumor tissue, we find a high concordance in higher-order three-dimensional genome organization. This concordance argues for constraints to the topology of prostate tumor genomes. Nonetheless, we identified changes in focal chromatin interactions, typical of loops bridging noncoding cis-regulatory elements, and showed how structural variants can induce these changes to guide cis-regulatory element hijacking. Such events resulted in opposing differential expression of genes found at antipodes of rearrangements. Collectively, these results argue that changes to focal chromatin interactions, as opposed to higher-order genome organization, allow for aberrant gene regulation and are repeatedly mediated by structural variants in primary prostate cancer.Significance:This work showcases how the noncoding genome can be hijacked by focal insults to its three-dimensional organization that contribute to prostate cancer oncogenesis.

Relationship between inter-chromosomal rearrangements and differential gene expression.

AR Gene Rearrangement Calls in AR-Targeted Cohort

Clinical information of samples involved in this study.

Prostate cancer is a heterogeneous disease whose progression is linked to genome instability. However, the impact of this instability on the noncoding genome and its three-dimensional organization to aid progression is unclear. Using primary benign and tumor tissue, we find a high concordance in higher-order three-dimensional genome organization. This concordance argues for constraints to the topology of prostate tumor genomes. Nonetheless, we identified changes in focal chromatin interactions, typical of loops bridging noncoding cis-regulatory elements, and showed how structural variants can induce these changes to guide cis-regulatory element hijacking. Such events resulted in opposing differential expression of genes found at antipodes of rearrangements. Collectively, these results argue that changes to focal chromatin interactions, as opposed to higher-order genome organization, allow for aberrant gene regulation and are repeatedly mediated by structural variants in primary prostate cancer. Significance: This work showcases how the noncoding genome can be hijacked by focal insults to its three-dimensional organization that contribute to prostate cancer oncogenesis.

Blank

Analysis of DNA methylation is a valuable tool to understand disease progression and is increasingly being used to create diagnostic and prognostic clinical biomarkers. While conversion of cytosine to 5-methylcytosine (5mC) commonly results in transcriptional repression, further conversion to 5-hydroxymethylcytosine (5hmC) is associated with transcriptional activation. Here we perform the first study integrating whole-genome 5hmC with DNA, 5mC, and transcriptome sequencing in clinical samples of benign, localized, and advanced prostate cancer. 5hmC is shown to mark activation of cancer drivers and downstream targets. Furthermore, 5hmC sequencing revealed profoundly altered cell states throughout the disease course, characterized by increased proliferation, oncogenic signaling, dedifferentiation, and lineage plasticity to neuroendocrine and gastrointestinal lineages. Finally, 5hmC sequencing of cell-free DNA from patients with metastatic disease proved useful as a prognostic biomarker able to identify an aggressive subtype of prostate cancer using the genes TOP2A and EZH2, previously only detectable by transcriptomic analysis of solid tumor biopsies. Overall, these findings reveal that 5hmC marks epigenomic activation in prostate cancer and identify hallmarks of prostate cancer progression with potential as biomarkers of aggressive disease. Significance: In prostate cancer, 5-hydroxymethylcytosine delineates oncogene activation and stage-specific cell states and can be analyzed in liquid biopsies to detect cancer phenotypes. See related article by Wu and Attard, p. 3880

The solid electrolyte interphase (SEI) that forms on Li-ion battery anodes is critical to their long-term performance, however observing SEI forma- tion processes at the buried electrode-electrolyte interface is a significant challenge. Here we show that operando soft X-ray absorption spectroscopy in total electron yield mode can resolve the chemical evolution of the SEI during electrochemical formation in a Li-ion cell, with nm-scale interface sensitivity. O, F, and Si K-edge spectra, acquired as a function of potential, reveal when key reactions occur on high-capacity amorphous Si anodes cycled with and without fluoroethylene carbonate (FEC). The sequential formation of inorganic (LiF) and organic (-(C=O)O-) components is thereby revealed, and results in layering of the SEI. The addition of FEC leads to SEI formation at higher potentials which is implicated in the rapid healing of SEI defects and the improved cycling performance observed. Operando TEY-XAS offers new insights into the formation mechanisms of electrode-electrolyte interphases and their stability for a wide variety of electrode materials and electrolyte formulations.

Context Translational research in uro-oncology depends on the availability of high-quality biospecimens and associated data to advance precision medicine and improve clinical outcomes. Procurement, storage, and annotation of these specimens represent critical steps towards this end. Objective To review best-practice experiences gained via the McCain GU BioBank, a repository of more than 750 000 biospecimens obtained from more than 16 000 patients attending clinics at the University Health Network in Toronto, Canada. Evidence acquisition The review summarizes our experiences at a large single-institution genitourinary oncology biorepository. Evidence synthesis Key findings are placed in the context of emerging trends in genitourinary oncology, with a focus on integration of molecular profiling and clinical data with traditional biorepository management. Proposed approaches provide high-quality biospecimens with comprehensive and reliable clinical data that can fuel innovation and discovery in research. Conclusions Biorepositories are vital for improving clinical outcomes and advancing personalized medicine. High-quality biospecimens and their associated clinical data are crucial for validation of biomarkers in oncology. Efforts to procure, store, and annotate clinical specimens represent critical steps in translational research. Elements such as biobank size, biospecimen types, disease cohorts, predetermined collection protocols, broad informed consent, sample handling and storage protocols, and available infrastructure directly influence the effectiveness and capacity of a biobank. Patient summary Biorepositories, or biobanks, are facilities that store biospecimens such as blood, urine, or tissue (usually collected from humans) for use in research. Biobanks have become an important resource in medical research, as they provide high-quality specimens to support different types of contemporary research such as genomics, biomarker discovery, and personalized medicine. Clinical management and treatment of genitourinary cancers, such as prostate, kidney, and bladder cancers, are particularly suited for biomarker research. The provision of biospecimens and their associated clinical data have become crucial for validation of biomarkers in these cancers.