Residential change of the Ukrainian population in the city of Windsor, Ontario from 1951 to 1991.

The spatial residential patterns of Ukrainians in Windsor, Ontario are examined for the two census years of 1951 and 1991. In addition, comparisons are made between census Ukrainians and the three study groups of parishioners of Sts. Vladimir and Olga Ukrainian Catholic Church, parishioners of St. Vladimir Ukrainian Orthodox Cathedral and non-affiliated Ukrainians. The spatial residential patterns of the Ukrainian community have evolved from being highly concentrated in 1951 to significantly dispersed by 1991. Three factors of personal, cultural and societal are studied for their effect on the choice of residential location of the three study groups. Employment of Ukrainians during the 1950s in the automotive industry resulted in residential locations in low class neighbourhoods near the factories. A Ukrainian community developed in which social and spiritual needs were met through the establishment of traditional institutions. Over time, with no new Ukrainian immigration and increased association with mainstream society, residential concentrations of Ukrainians began to disperse.Dept. of Geography. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis1995 .M82. Source: Masters Abstracts International, Volume: 34-06, page: 2205. Adviser: Ihor Stebelsky. Thesis (M.A.)--University of Windsor (Canada), 1995

XPO1 inhibition by selinexor induces potent cytotoxicity against high grade bladder malignancies.

Treatment options for high grade urothelial cancers are limited and have remained largely unchanged for several decades. Selinexor (KPT-330), a first in class small molecule that inhibits the nuclear export protein XPO1, has shown efficacy as a single agent treatment for numerous different malignancies, but its efficacy in limiting bladder malignancies has not been tested. In this study we assessed selinexor-dependent cytotoxicity in several bladder tumor cells and report that selinexor effectively reduced XPO1 expression and limited cell viability in a dose dependent manner. The decrease in cell viability was due to an induction of apoptosis and cell cycle arrest. These results were recapitulated in in vivo studies where selinexor decreased tumor growth. Tumors treated with selinexor expressed lower levels of XPO1, cyclin A, cyclin B, and CDK2 and increased levels of RB and CDK inhibitor p27, a result that is consistent with growth arrest. Cells expressing wildtype RB, a potent tumor suppressor that promotes growth arrest and apoptosis, were most susceptible to selinexor. Cell fractionation and immunofluorescence studies showed that selinexor treatment increased nuclear RB levels and mechanistic studies revealed that RB ablation curtailed the response to the drug. Conversely, limiting CDK4/6 dependent RB phosphorylation by palbociclib was additive with selinexor in reducing bladder tumor cell viability, confirming that RB activity has a role in the response to XPO1 inhibition. These results provide a rationale for XPO1 inhibition as a novel strategy for the treatment of bladder malignancies

E2F mediates dihydrofolate reductase promoter activation and multiprotein complex formation in human cytomegalovirus infection.

The adenovirus immediate-early protein E1A activates the adenovirus E2 promoter and several cellular gene promoters through transcription factor E2F. The immediate-early proteins of human cytomegalovirus (HCMV) can complement an E1A-deficient adenovirus mutant and activate the adenovirus E2 promoter. HCMV also has been shown to activate the adenovirus E2 promoter. On the basis of these findings, we have investigated whether HCMV can activate the promoter of the cellular dihydrofolate reductase (DHFR) gene, which requires E2F binding for maximal promoter activity. We show that HCMV activates the DHFR promoter and that products of the HCMV major immediate-early gene region mediate the activation of the promoter specifically through the E2F site. We used gel mobility shift assays to search for potential molecular mechanisms for this activation and found an "infection-specific" multimeric complex that bound to the E2F sites in the DHFR and E2 promoters in extracts from HCMV-infected cells but not in extracts from uninfected cells. Several antibodies against HCMV immediate-early gene products had no effect on this infection-specific complex. Subsequently, the complex was found to contain E2F, cyclin A, p33cdk2, and p107 and to be similar to S-phase-specific complexes that recently have been identified in several cell types. A functional role for the binding of the cyclin A-p33cdk2 complex to cellular gene promoters has yet to be demonstrated; however, HCMV infection causes the induction of both cellular DNA replication and transcription of growth-related genes containing E2F sites in their promoters. The findings described above therefore may relate to both of these effects of HCMV infection. We also provide evidence that some of the molecular events associated with adenovirus infection are different from those associated with HCMV infection

Targeted suppression of AR-V7 using PIP5K1α inhibitor overcomes enzalutamide resistance in prostate cancer cells

One mechanism of resistance of prostate cancer (PCa) to enzalutamide (MDV3100) treatment is the increased expression of AR variants lacking the ligand binding-domain, the best characterized of which is AR-V7. We have previously reported that Phosphatidylinositol-4-phosphate 5-kinase alpha (PIP5Kα), is a lipid kinase that links to CDK1 and AR pathways. The discovery of PIP5Kα inhibitor highlight the potential of PIP5K1α as a drug target in PCa. In this study, we show that AR-V7 expression positively correlates with PIP5K1α in tumor specimens from PCa patients. Overexpression of AR-V7 increases PIP5K1α, promotes rapid growth of PCa in xenograft mice, whereas inhibition of PIP5K1α by its inhibitor ISA-2011B suppresses the growth and invasiveness of xenograft tumors overexpressing AR-V7. PIP5K1α is a key co-factor for both AR-V7 and AR, which are present as protein-protein complexes predominantly in the nucleus of PCa cells. In addition, PIP5K1α and CDK1 influence AR-V7 expression also through AKT-associated mechanism dependent on PTEN-status. ISA-2011B disrupts protein stabilization of AR-V7 which is dependent on PIP5K1α, leading to suppression of invasive growth of AR-V7-high tumors in xenograft mice. Our study suggests that combination of enzalutamide and PIP5K1α may have a significant impact on refining therapeutic strategies to circumvent resistance to antiandrogen therapies

Recent advances in γ-aminobutyric acid (GABA) properties in pulses: An overview

Beans, peas, and lentils are all types of pulses that are extensively used as foods around the world due to their beneficial effects on human health including their low glycemic index, cholesterol lowering effects, ability to decrease the risk of heart diseases and their protective effects against some cancers. These health benefits are a result of their components such as bioactive proteins, dietary fibers, slowly digested starches, minerals and vitamins, and bioactive compounds. Among these bioactive compounds, γ-aminobutyric acid (GABA), a non-proteinogenic amino acid with numerous reported health benefits (e.g. anti-diabetic and hypotensive effects, depression and anxiety reduction) is of particular interest. GABA is primarily synthesized in plant tissues by the decarboxylation of L-glutamic acid in the presence of glutamate decarboxylase (GAD). It is widely reported that during various processes including enzymatic treatment, gaseous treatment (e.g. with carbon dioxide), and fermentation (with lactic acid bacteria), GABA content increases in the plant matrix. The objective of this review paper is to highlight the current state of knowledge on the occurrence of GABA in pulses with special focus on mechanisms by which GABA levels are increased and the analytical extraction and estimation methods for this bioactive phytochemical

Nuclear MET requires ARF and is inhibited by carbon nanodots through binding to phospho-tyrosine in prostate cancer

Nuclear receptor tyrosine kinases (nRTKs) are aberrantly upregulated in many types of cancers, but the regulation of nRTK remains unclear. We previously showed androgen deprivation therapy (ADT) induces nMET in castration-resistant prostate cancer (CRPC) specimens. Through gene expression microarray profiles reanalysis, we identified that nMET signaling requires ARF for CRPC growth in Pten/Trp53 conditional knockout mouse model. Accordingly, aberrant MET/nMET elevation correlates with ARF in human prostate cancer (PCa) specimens. Mechanistically, ARF elevates nMET through binding to MET cytoplasmic domain to stabilize MET. Furthermore, carbon nanodots resensitize cancer cells to MET inhibitors through DNA damage response. The inhibition of phosphorylation by carbon nanodots was identified through binding to phosphate group of phospho-tyrosine via computational calculation and experimental assay. Thus, nMET is essential to precision therapy of MET inhibitor. Our findings reveal for the first time that targeting nMET axis by carbon nanodots can be a novel avenue for overcoming drug resistance in cancers especially prostate cancer