Publications by authors named "Keefer K"

Transient receptor potential channel TRPM2 is highly expressed in many cancers and involved in regulation of key physiological processes including mitochondrial function, bioenergetics, and oxidative stress. In Stage 4 non-MYCN amplified neuroblastoma patients, high TRPM2 expression is associated with worse outcome. Here, neuroblastoma cells with high TRPM2 expression demonstrated increased migration and invasion capability.

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Transient receptor potential channel melastatin 2 (TRPM2) is highly expressed in cancer and has an essential function in preserving viability through maintenance of mitochondrial function and antioxidant response. Here, the role of TRPM2 in cell survival was examined in neuroblastoma cells with TRPM2 deletion with CRISPR technology. Viability was significantly decreased in TRPM2 knockout after doxorubicin treatment.

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Transient receptor potential melastatin 2 (TRPM2) ion channel has an essential function in maintaining cell survival following oxidant injury. Here, we show that TRPM2 is highly expressed in acute myeloid leukemia (AML). The role of TRPM2 in AML was studied following depletion with CRISPR/Cas9 technology in U937 cells.

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Trait Emotional Intelligence (EI)-related competencies are in growing demand in educational and vocational settings. The present study assesses the developmental dynamics of trait EI in emerging adulthood by capitalizing on the inclusion of a measure of trait EI in the National Longitudinal Survey of Children and Youth (NLSCY) called the Emotional Quotient Inventory: Mini (EQ-i: Mini). A sample of 1064 young adults (50% female) from ages 20-21 to 24-25 years was used to assess 4-year rank-order stability and mean-level change of trait EI, as well as whether the EQ-i: Mini functions equivalently over time (longitudinal measurement invariance).

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Transient receptor potential melastatin channel subfamily member 2 (TRPM2) has an essential role in protecting cell viability through modulation of oxidative stress. TRPM2 is highly expressed in cancer. When TRPM2 is inhibited, mitochondria are dysfunctional, ROS levels are increased, and cell viability is reduced.

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Trait Emotional Intelligence (EI) is a constellation of emotional self-perceptions and dispositions related to perceiving, understanding, using, and managing emotions of self and others. Although higher trait EI has been implicated in post-secondary success among university students. There is lack of evidence for whether it predicts the pursuit of post-secondary education (PSE) in emerging adulthood.

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Patients with non-Hodgkin's lymphoma (NHL) receiving rituximab-containing chemotherapy are at risk of developing respiratory complications, but comprehensive information on these complications and their impact on survival is lacking. We performed a retrospective cohort analysis on 123 NHL patients who received rituximab-containing chemotherapy between 2009 and 2016 in order to describe the incidence, etiologies and effect on survival of respiratory complications defined by new or worsening respiratory symptoms requiring diagnostic work-up or hospitalization. Thirty patients (24%) developed respiratory complications during a follow-up time of 825 (555-1338) days after chemotherapy.

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Transient receptor potential melastatin channel subfamily member 2 (TRPM2) has an essential function in cell survival and is highly expressed in many cancers. Inhibition of TRPM2 in neuroblastoma by depletion with CRISPR technology or expression of dominant negative TRPM2-S has been shown to significantly reduce cell viability. Here, the role of proline-rich tyrosine kinase 2 (Pyk2) in TRPM2 modulation of neuroblastoma viability was explored.

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The early stages of protein misfolding remain incompletely understood, as most mammalian proteinopathies are only detected after irreversible protein aggregates have formed. Cross-seeding, where one aggregated protein templates the misfolding of a heterologous protein, is one mechanism proposed to stimulate protein aggregation and facilitate disease pathogenesis. Here, we demonstrate the existence of cross-seeding as a crucial step in the formation of the yeast prion [PSI ], formed by the translation termination factor Sup35.

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Molecular chaperones are responsible for managing protein folding from translation through degradation. These crucial machines ensure that protein homeostasis is optimally maintained for cell health. However, 'too much of a good thing' can be deadly, and the excess of chaperones can be toxic under certain cellular conditions.

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Alexithymia is a clinically relevant personality construct characterized by difficulties identifying and describing feelings, externally oriented thinking, and impoverished imaginal processes. Previous taxometric investigations provided evidence that alexithymia is best conceptualized as a continuous dimension rather than a discrete type, at least when assessed with the self-report 20-Item Toronto Alexithymia Scale. The aim of the current study was to test the categorical versus dimensional structure of alexithymia using the recently developed Toronto Structured Interview for Alexithymia.

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Hypomorphic mutations are a valuable tool for both genetic analysis of gene function and for synthetic biology applications. However, current methods to generate hypomorphic mutations are limited to a specific organism, change gene expression unpredictably, or depend on changes in spatial-temporal expression of the targeted gene. Here we present a simple and predictable method to generate hypomorphic mutations in model organisms by targeting translation elongation.

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The nascent polypeptide-associated complex (NAC) is a highly conserved but poorly characterized triad of proteins that bind near the ribosome exit tunnel. The NAC is the first cotranslational factor to bind to polypeptides and assist with their proper folding. Surprisingly, we found that deletion of NAC subunits in Saccharomyces cerevisiae rescues toxicity associated with the strong [PSI+] prion.

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Transient receptor potential melastatin 2 (TRPM2) ion channel has an essential function in modulating cell survival following oxidant injury and is highly expressed in many cancers including neuroblastoma. Here, in xenografts generated from neuroblastoma cells in which TRPM2 was depleted with CRISPR/Cas9 technology and in in vitro experiments, tumor growth was significantly inhibited and doxorubicin sensitivity increased. The hypoxia-inducible transcription factor 1/2α (HIF-1/2α) signaling cascade including proteins involved in oxidant stress, glycolysis, and mitochondrial function was suppressed by TRPM2 depletion.

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Propylene glycol (PG) is used as a solvent in numerous medications, including trimethoprim/sulfamethoxazole (TMP/SMX) and lorazepam, and is metabolized in the liver to lactic acid. Cases of lactic acidosis related to PG toxicity have been described and always involved large doses of benzodiazepines and PG. We present the first case of severe lactic acidosis after a 3-day course of TMP/SMX alone, involving allegedly safe amounts of PG.

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The Toronto Structured Interview for Alexithymia (TSIA) has been translated into Dutch, German, and Italian and validated in clinical and nonclinical populations. In order to make valid comparisons across different population groups, it is important to establish measurement equivalence across variables such as language, gender, and clinical status. Our objective in this study was to establish measurement equivalence in relation to language (English, Dutch, German, and Italian), gender, and clinical status (non-clinical, psychiatric, and medical) using differential item functioning (DIF).

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Certain coping strategies alleviate stress and promote positive psychological outcomes, whereas others exacerbate stress and promote negative psychological outcomes. However, the efficacy of any given coping strategy may also depend on personal resiliency. This study examined whether personal resiliency moderated the effects of task-oriented, avoidance-oriented, and emotion-oriented coping strategies on measures of depression, anxiety, stress, positive affect, negative affect, and satisfaction with life.

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The calcium-permeable ion channel TRPM2 is highly expressed in a number of cancers. In neuroblastoma, full-length TRPM2 (TRPM2-L) protected cells from moderate oxidative stress through increased levels of forkhead box transcription factor 3a (FOXO3a) and superoxide dismutase 2. Cells expressing the dominant negative short isoform (TRPM2-S) had reduced FOXO3a and superoxide dismutase 2 levels, reduced calcium influx in response to oxidative stress, and enhanced reactive oxygen species, leading to decreased cell viability.

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The present study examined the link between problematic gambling and gambling related cognitions (GRCs) in a large sample of adolescents with (N = 266) and without (N = 1,738) special education needs (SEN) between the ages of 14 and 18 years attending several high schools in eastern central Ontario. The adolescents with SENs were identified as having various learning disorders and/or internalizing and externalizing problems [e.g.

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Amid the growing efforts to promote positive youth development, trait emotional intelligence (TEI) has emerged as an important protective factor in the processes of resilience and adaptation. The inclusion of a brief form of the Emotional Quotient Inventory-Youth Version (EQi:YV-Brief) in the Canadian National Longitudinal Survey of Children and Youth (NLSCY) presents a unique opportunity to study the developmental dynamics of TEI during the transition from childhood to adolescence. However, before drawing any inferences about construct continuity and change, researchers must establish that the EQi:YV-Brief functions equivalently over time.

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A new scaling law model is presented to rapidly simulate thermal blooming and turbulence effects on high energy laser propagation, producing results approaching the quality normally only available using wave-optics code, but at much faster speed. The model convolves irradiance patterns originating from two distinct scaling law models, one with a proficiency in thermal blooming effects and the other in turbulence. To underscore the power of the new model, results are verified for typical, realistic scenarios by direct comparison with wave optics simulation.

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The present study examined the factor structure of the Gambling Related Cognitions Scale (GRCS); (Raylu and Oei in Addiction 99:757-769, 2004) in a large sample of adolescents (N = 1,490) between the ages of 16 and 18 years (630 males, 860 females) attending several high schools in central Ontario. Problem gambling was measured using the DSM-IV-J (Fisher in J Gambl Stud 8:263-285, 1992). A 5-factor GRCS model was found to have the best fit to the data, and gambling-related cognitions were found to be powerful predictors of disordered gambling among adolescents.

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The second member of the transient receptor potential-melastatin channel family (TRPM2) is expressed in the heart and vasculature. TRPM2 channels were expressed in the sarcolemma and transverse tubules of adult left ventricular (LV) myocytes. Cardiac TRPM2 channels were functional since activation with H2O2 resulted in Ca(2+) influx that was dependent on extracellular Ca(2+), was significantly higher in wild-type (WT) myocytes compared with TRPM2 knockout (KO) myocytes, and inhibited by clotrimazole in WT myocytes.

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The present study examined the prevalence of disordered gambling behaviours in a community-based sample of adolescents (N = 532) living in eastern central Ontario. Of particular interest was examining the hypothesis that adolescents with learning disorders are at elevated risk for disordered gambling. Rates of disordered gambling in male adolescents with learning disorders were found to be significantly higher than adolescents without learning problems, even after controlling for negative affectivity and ADHD symptomatology.

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