Background: Expansion of the scope of pharmacists' activities in hospital is associated with reductions in adverse events and drug-related readmissions. However, the breadth of hospital pharmacists' clinical activities varies widely across Ontario due to provisions in the provincial . Few data exist defining expanded scope in institutions across Ontario.
View Article and Find Full Text PDFPurpose: High-throughput screening (HTS) platforms have been widely used to identify candidate anticancer drugs and drug-drug combinations; however, HTS-based identification of new drug-ionizing radiation (IR) combinations has rarely been reported. Herein, we developed an integrated approach including cell-based HTS and computational large-scale isobolographic analysis to accelerate the identification of radiosensitizing compounds acting strongly and more specifically on cancer cells.
Methods And Materials: In a 384-well plate format, 160 compounds likely to interfere with the cell response to radiation were screened on human glioblastoma (U251-MG) and cervix carcinoma (ME-180) cell lines, as well as on normal fibroblasts (CCD-19Lu).
Membrane-less organelles are condensates formed by phase separation whose functions often remain enigmatic. Upon oxidative stress, PML scaffolds Nuclear Bodies (NBs) to regulate senescence or metabolic adaptation. PML NBs recruit many partner proteins, but the actual biochemical mechanism underlying their pleiotropic functions remains elusive.
View Article and Find Full Text PDFDengue virus (DENV) is a mosquito-borne flavivirus responsible for dengue disease, a major human health concern for which no specific therapies are available. Like other viruses, DENV relies heavily on the host cellular machinery for productive infection. In this study, we performed a genome-wide CRISPR-Cas9 screen using haploid HAP1 cells to identify host genes important for DENV infection.
View Article and Find Full Text PDFThe steady-state localization of Golgi-resident glycosylation enzymes in the Golgi apparatus depends on a balance between anterograde and retrograde transport. Using the Retention Using Selective Hooks (RUSH) assay and high-content screening, we identified small molecules that perturb the localization of Mannosidase II (ManII) used as a model cargo for Golgi resident enzymes. In particular, we found that two compounds known as EGFR tyrosine kinase inhibitors, namely BML-265 and Tyrphostin AG1478 disrupt Golgi integrity and abolish secretory protein transport of diverse cargos, thus inducing brefeldin A-like effects.
View Article and Find Full Text PDFUsing a cell-based assay monitoring differential protein transport in the secretory pathway coupled to high-content screening, we have identified three molecules that specifically reduce the delivery of the major co-receptor for HIV-1, CCR5, to the plasma membrane. They have no effect on the closely related receptors CCR1 and CXCR4. These molecules are also potent in primary macrophages as they markedly decrease HIV entry.
View Article and Find Full Text PDFPhysiotherapists have been acknowledged as playing a vital role in the care of people living with chronic obstructive pulmonary disease (COPD), and this care includes providing patient education (PE). Yet very little is known about the issues critical to providing this PE. The purpose of this scoping review was to identify and map out the current knowledge about the content, processes, and overall effectiveness of the PE provided by physiotherapists for people living with COPD.
View Article and Find Full Text PDFBackground: RBM10 is an RNA binding protein involved in message stabilization and alternative splicing regulation. The objective of the research described herein was to identify novel targets of RBM10-regulated splicing. To accomplish this, we downregulated RBM10 in human cell lines, using small interfering RNAs, then monitored alternative splicing, using a reverse transcription-PCR screening platform.
View Article and Find Full Text PDFSignificance: Cellular metabolic activity impacts the production of reactive oxygen species (ROS), both positively through mitochondrial oxidative processes and negatively by promoting the production of reducing agents (including NADPH and reduced glutathione). A defined metabolic state in cancer cells is critical for cell growth and long-term self-renewal, and such state is intrinsically associated with redox balance. Promyelocytic leukemia protein (PML) regulates several biological processes, at least in part, through its ability to control the assembly of PML nuclear bodies (PML NBs).
View Article and Find Full Text PDFFasci et al proposed that a SENP1-mediated switch from SUMO2 to SUMO1 conjugation on Lys(65) in promyelocytic leukemia protein (PML) is required for arsenic-induced PML degradation, the basis for the antileukemic activity of arsenic. We found that PML or PML/RARA (retinoic acid receptor α) mutants that cannot be SUMO-conjugated on this specific site nevertheless underwent immediate arsenic-triggered SUMO modification. Moreover, these mutants were efficiently degraded in cells and even in vivo, demonstrating that SUMOylation of Lys(65) was dispensable for arsenic response.
View Article and Find Full Text PDFIn Vitro Cell Dev Biol Anim
March 2016
We previously examined the expression of Rbm5 during myoblast differentiation and found significantly more protein in the early stages of skeletal myoblast differentiation than during the later stages. We decided to determine if this elevated level was necessary for differentiation. Our hypothesis was that if high levels of Rbm5 protein expression were necessary for the initiation of skeletal myoblast differentiation, then inhibition of expression would prevent differentiation.
View Article and Find Full Text PDFBackground: RBM10 is an RNA binding protein involved in the regulation of transcription, alternative splicing and message stabilization. Mutations in RBM10, which maps to the X chromosome, are associated with TARP syndrome, lung and pancreatic cancers. Two predominant isoforms of RBM10 exist, RBM10v1 and RBM10v2.
View Article and Find Full Text PDFCentrosome amplification is a hallmark of human tumours. In flies, extra centrosomes cause spindle position defects that result in the expansion of the neural stem cell (NSC) pool and consequently in tumour formation. Here we investigated the consequences of centrosome amplification during mouse brain development and homeostasis.
View Article and Find Full Text PDFCordycepin (3' deoxyadenosine) has long been used in the study of in vitro assembled polyadenylation complexes, because it terminates the poly(A) tail and arrests the cleavage complex. It is derived from caterpillar fungi, which are highly prized in Chinese traditional medicine. Here we show that cordycepin specifically inhibits the induction of inflammatory mRNAs by cytokines in human airway smooth muscle cells without affecting the expression of control mRNAs.
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