Curiosities: The Official Blog of Sheridan

Welcome to the book edition of Curiosities - the official blog of Sheridan. The book is a curated collection of blog posts from curiositites.sheridancollege.ca, which show the vibrancy and energy at Sheridan. Here you\u27ll find all things creative, intriguing and noteworthy. From the profound to the peculiar, the stories in this volume offer insight into different fields of study, explore the ways in which Sheridan contributes to the world, and spotlight the people who bring Sheridan to life. Feed your curiosity by visiting the blog regularly for the latest stories about Sheridan: curiositites.sheridancollege.cahttps://source.sheridancollege.ca/nonfaculty_adva_comm_book/1000/thumbnail.jp

Reliability of electromyography during 2000 m rowing ergometry

Purpose. This study aimed to investigate the reliability of surface electromyography (EMG) assessed at seven muscles during three repeated 2000 m rowing ergometer sessions. Methods. Twelve male well-trained rowers participated in a repeated measures design, performing three 2000 m rowing ergometer sessions interspersed by 3–7 days (S1, S2, S3). Surface electrodes were attached to the gastrocnemius, biceps femoris, gluteus maximus, erector spinae, vastus medialis, rectus abdominis and latissimus dorsi for EMG analysis. Results. No differences existed between 2000 m sessions for EMG amplitude for any of the seven muscles (p = 0.146–0.979). Mean coefficient of variation of EMG for 6 of 7 muscles was ‘acceptable’ (12.3–18.6%), although classed as ‘weak’ for gastrocnemius (28.6%). Mean intra-class correlation coefficient values across muscles ranged from ‘moderate’ to ‘very large’ (0.31–0.89). Within-session EMG activation rates of vastus medialis were greater during 0–500 m and 1500–2000 m segments, compared with 500–1000 m and 1000–1500 m (p < 0.05). Values for biceps femoris and gluteus maximus were significantly higher during 1500–2000 m compared to 500–1000 m and 1000–1500 m (p < 0.05). The general pattern was for higher activation rates during 0–500 m and 1500–2000 m compared to 500–1000 m and 1000–1500 m. However, there were no between-sessions differences in EMG for any of the 500 m segments (p > 0.05). Conclusion. Reliability of EMG values over repeated 2000 m sessions was generally ‘acceptable’. However, EMG was seemingly not sensitive enough to detect potential changes in neural activation between-sessions, with respect to changes in pacing strategy

Therapeutic targeting of the E3 ubiquitin ligase SKP2 in T-ALL

Timed degradation of the cyclin-dependent kinase inhibitor p27^(Kip1) by the E3 ubiquitin ligase F-box protein SKP2 is critical for T-cell progression into cell cycle, coordinating proliferation and differentiation processes. SKP2 expression is regulated by mitogenic stimuli and by Notch signaling, a key pathway in T-cell development and in T-cell acute lymphoblastic leukemia (T-ALL); however, it is not known whether SKP2 plays a role in the development of T-ALL. Here, we determined that SKP2 function is relevant for T-ALL leukemogenesis, whereas is dispensable for T-cell development. Targeted inhibition of SKP2 by genetic deletion or pharmacological blockade markedly inhibited proliferation of human T-ALL cells in vitro and antagonized disease in vivo in murine and xenograft leukemia models, with little effect on normal tissues. We also demonstrate a novel feed forward feedback loop by which Notch and IL-7 signaling cooperatively converge on SKP2 induction and cell cycle activation. These studies show that the Notch/SKP2/p27^(Kip1) pathway plays a unique role in T-ALL development and provide a proof-of-concept for the use of SKP2 as a new therapeutic target in T-cell acute lymphoblastic leukemia (T-ALL)

High-sensitivity visualisation of contaminants in heparin samples by spectral filtering of H-1 NMR spectra

A novel application of two-dimensional correlation analysis has been employed to filter H-1 NMR heparin spectra distinguishing acceptable natural variation and the presence of foreign species. Analysis of contaminated heparin samples, compared to a dataset of accepted heparin samples using two-dimensional correlation spectroscopic analysis of their 1-dimensional H-1 NMR spectra, allowed the spectral features of contaminants to be recovered with high sensitivity, without having to resort to more complicated NMR experiments. Contaminants, which exhibited features distinct from those of heparin and those with features normally hidden within the spectral mass of heparin could be distinguished readily. A heparin sample which had been pre-mixed with a known contaminant, oversulfated chondroitin sulfate (OSCS), was tested against the heparin reference library. It was possible to recover the 1 H NMR spectrum of the OSCS component through difference 2D-COS power spectrum analysis of as little as 0.25% (w/w) with ease, and of 2% (w/w) for more challenging contaminants, whose NMR signals fell under those of heparin. the approach shows great promise for the quality control of heparin and provides the basis for greatly improved regulatory control for the analysis of heparin, as well as other intrinsically heterogeneous and varied products.Wellcome TrustRoyal SocietyBBSRCFinlambardia SPA 'Fondo per la promozione di Accordi Istituzionali'Univ Liverpool, Sch Biol Sci, Liverpool L69 3BX, Merseyside, EnglandIst Ric Chim & Biochim G Ronzoni, I-20133 Milan, ItalyUNIFESP Universidade Federal de São Paulo, Dept Bioquim, Disciplina Biol Mol, BR-04044020 São Paulo, BrazilKeele Univ, Inst Sci & Technol Med, Keele ST5 5BG, Staffs, EnglandNatl Inst Biol Stand & Controls, Potters Bar EN6 3QG, Herts, EnglandUNIFESP Universidade Federal de São Paulo, Dept Bioquim, Disciplina Biol Mol, BR-04044020 São Paulo, BrazilWeb of Scienc

DNA methylation profiles and their relationship with cytogenetic status in adult acute myeloid leukemia

Background: Aberrant promoter DNA methylation has been shown to play a role in acute myeloid leukemia (AML) pathophysiology. However, further studies to discuss the prognostic value and the relationship of the epigenetic signatures with defined genomic rearrangements in acute myeloid leukemia are required. Methodology/Principal Findings: We carried out high-throughput methylation profiling on 116 de novo AML cases and we validated the significant biomarkers in an independent cohort of 244 AML cases. Methylation signatures were associated with the presence of a specific cytogenetic status. In normal karyotype cases, aberrant methylation of the promoter of DBC1 was validated as a predictor of the disease-free and overall survival. Furthermore, DBC1 expression was significantly silenced in the aberrantly methylated samples. Patients with chromosome rearrangements showed distinct methylation signatures. To establish the role of fusion proteins in the epigenetic profiles, 20 additional samples of human hematopoietic stem/progenitor cells (HSPC) transduced with common fusion genes were studied and compared with patient samples carrying the same rearrangements. The presence of MLL rearrangements in HSPC induced the methylation profile observed in the MLL-positive primary samples. In contrast, fusion genes such as AML1/ETO or CBFB/MYH11 failed to reproduce the epigenetic signature observed in the patients. Conclusions/Significance: Our study provides a comprehensive epigenetic profiling of AML, identifies new clinical markers for cases with a normal karyotype, and reveals relevant biological information related to the role of fusion proteins on the methylation signature

DNA Methylation Profiles and Their Relationship with Cytogenetic Status in Adult Acute Myeloid Leukemia

Aberrant promoter DNA methylation has been shown to play a role in acute myeloid leukemia (AML) pathophysiology. However, further studies to discuss the prognostic value and the relationship of the epigenetic signatures with defined genomic rearrangements in acute myeloid leukemia are required.We carried out high-throughput methylation profiling on 116 de novo AML cases and we validated the significant biomarkers in an independent cohort of 244 AML cases. Methylation signatures were associated with the presence of a specific cytogenetic status. In normal karyotype cases, aberrant methylation of the promoter of DBC1 was validated as a predictor of the disease-free and overall survival. Furthermore, DBC1 expression was significantly silenced in the aberrantly methylated samples. Patients with chromosome rearrangements showed distinct methylation signatures. To establish the role of fusion proteins in the epigenetic profiles, 20 additional samples of human hematopoietic stem/progenitor cells (HSPC) transduced with common fusion genes were studied and compared with patient samples carrying the same rearrangements. The presence of MLL rearrangements in HSPC induced the methylation profile observed in the MLL-positive primary samples. In contrast, fusion genes such as AML1/ETO or CBFB/MYH11 failed to reproduce the epigenetic signature observed in the patients.Our study provides a comprehensive epigenetic profiling of AML, identifies new clinical markers for cases with a normal karyotype, and reveals relevant biological information related to the role of fusion proteins on the methylation signature

Ticagrelor potentiates adenosine-induced stimulation of neutrophil chemotaxis and phagocytosis

In the PLATO study, ticagrelor was associated with fewer pulmonary infections and subsequent deaths than clopidogrel. Neutrophils are a first-line defence against bacterial lung infection; ticagrelor inhibits cellular uptake of adenosine, a known regulator of neutrophil chemotaxis and phagocytosis. We assessed whether the inhibition of adenosine uptake by ticagrelor influences neutrophil chemotaxis and phagocytosis. Neutrophils and erythrocytes were isolated from healthy volunteers. Concentration-dependent effects of adenosine on IL-8-induced neutrophil chemotaxis were investigated and the involved receptors identified using adenosine receptor antagonists. The modulatory effects of ticagrelor on adenosine-mediated changes in neutrophil chemotaxis and phagocytosis of Streptococcus pneumoniae were determined in the presence of erythrocytes to replicate physiological conditions of cellular adenosine uptake. Low-concentration adenosine (10-8 M) significantly increased IL-8-induced neutrophil chemotaxis (% neutrophil chemotaxis: adenosine 28.7%±4.4 vs. control 22.6%±2.4; p1 receptor. Erythrocytes attenuated the effect of adenosine, although this was preserved by ticagrelor and dipyridamole (another inhibitor of adenosine uptake) but not by control or by cangrelor. Similarly, in the presence of erythrocytes, a low concentration of adenosine (10-8 M) significantly increased neutrophil phagocytic index compared to control when ticagrelor was present (37.6±6.6 vs. 28.0±6.6; p=0.028) but had no effect in the absence of ticagrelor. We therefore conclude that the inhibition of cellular adenosine reuptake by ticagrelor potentiates the effects of a nanomolar concentration of adenosine on neutrophil chemotaxis and phagocytosis. This represents a potential mechanism by which ticagrelor could influence host defence against bacterial lung infection

DNA Methylation Profiles and Their Relationship with Cytogenetic Status in Adult Acute Myeloid Leukemia

Background: Aberrant promoter DNA methylation has been shown to play a role in acute myeloid leukemia (AML) pathophysiology. However, further studies to discuss the prognostic value and the relationship of the epigenetic signatures with defined genomic rearrangements in acute myeloid leukemia are required. Methodology/Principal Findings: We carried out high-throughput methylation profiling on 116 de novo AML cases and we validated the significant biomarkers in an independent cohort of 244 AML cases. Methylation signatures were associated with the presence of a specific cytogenetic status. In normal karyotype cases, aberrant methylation of the promoter of DBC1 was validated as a predictor of the disease-free and overall survival. Furthermore, DBC1 expression was significantly silenced in the aberrantly methylated samples. Patients with chromosome rearrangements showed distinct methylation signatures. To establish the role of fusion proteins in the epigenetic profiles, 20 additional samples of human hematopoietic stem/ progenitor cells (HSPC) transduced with common fusion genes were studied and compared with patient samples carrying the same rearrangements. The presence of MLL rearrangements in HSPC induced the methylation profile observed in the MLL-positive primary samples. In contrast, fusion genes such as AML1/ETO or CBFB/MYH11 failed to reproduce the epigenetic signature observed in the patients. Conclusions/Significance: Our study provides a comprehensive epigenetic profiling of AML, identifies new clinical markers for cases with a normal karyotype, and reveals relevant biological information related to the role of fusion proteins on the methylation signatur