671 research outputs found

    Implementing Parent Engagement Policy in an Increasingly Culturally Diverse Community of New Immigrants: How New is “New”?

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    The Ontario Ministry of Education announced the Parent Engagement Policy for Ontario Schools in 2010. This policy aims to support parent engagement and provides a vision of its implementation at schools, boards, and the ministry. This mixed methods case study sheds light on its implementation and thus its implication by exploring the parent engagement experiences of parents and teachers. The study results reveal that the actual and desired levels of engagement are different between new immigrants and the established ornon-immigrant families, and that teacher education in parent engagement is desirable in optimizing parent partnerships

    Progeny of Germ Line Knockouts of \u3cem\u3eASI2\u3c/em\u3e, a Gene Encoding a Putative Signal Transduction Receptor in \u3cem\u3eTetrahymena Thermophila\u3c/em\u3e, Fail to Make the Transition from Sexual Reproduction to Vegetative Growth

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    The ciliated protozoan Tetrahymena has two nuclei: a germ line micronucleus and a somatic macronucleus. The transcriptionally active macronucleus has about 50 copies of each chromosome. At sexual reproduction (conjugation), the parental macronucleus is degraded and new macronucleus develops from a mitotic product of the zygotic micronucleus. Development of the macronucleus involves massive genome remodeling, including deletion of about 6000 specific internal eliminated sequences (IES) and multiple rounds of DNA replication. A gene encoding a putative signal transduction receptor, ASI2, (anlagen stage induced 2) is up-regulated during development of the new macronuclei (anlagen). Macronuclear ASI2 is nonessential for vegetative growth. Homozygous ASI2 germ line knockout cells with wild type parental macronuclei proceed through mating but arrest at late macronuclear anlagen development and die before the first post-conjugation fission. IES elimination occurs in these cells. Two rounds of postzygotic DNA replication occur normally in progeny of ASI2 germ line knockouts, but endoreduplication of the macronuclear genome is arrested. The germ line ASI2 null phenotype is rescued in a mating of a knockout strain with wild type cells

    Binimetinib inhibits MEK and is effective against neuroblastoma tumor cells with low NF1 expression.

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    BackgroundNovel therapies are needed for children with high-risk and relapsed neuroblastoma. We hypothesized that MAPK/ERK kinase (MEK) inhibition with the novel MEK1/2 inhibitor binimetinib would be effective in neuroblastoma preclinical models.MethodsLevels of total and phosphorylated MEK and extracellular signal-regulated kinase (ERK) were examined in primary neuroblastoma tumor samples and in neuroblastoma cell lines by Western blot. A panel of established neuroblastoma tumor cell lines was treated with increasing concentrations of binimetinib, and their viability was determined using MTT assays. Western blot analyses were performed to examine changes in total and phosphorylated MEK and ERK and to measure apoptosis in neuroblastoma tumor cells after binimetinib treatment. NF1 protein levels in neuroblastoma cell lines were determined using Western blot assays. Gene expression of NF1 and MEK1 was examined in relationship to neuroblastoma patient outcomes.ResultsBoth primary neuroblastoma tumor samples and cell lines showed detectable levels of total and phosphorylated MEK and ERK. IC50 values for cells sensitive to binimetinib ranged from 8 nM to 1.16 μM, while resistant cells did not demonstrate any significant reduction in cell viability with doses exceeding 15 μM. Sensitive cells showed higher endogenous expression of phosphorylated MEK and ERK. Gene expression of NF1, but not MEK1, correlated with patient outcomes in neuroblastoma, and NF1 protein expression also correlated with responses to binimetinib.ConclusionsNeuroblastoma tumor cells show a range of sensitivities to the novel MEK inhibitor binimetinib. In response to binimetinib, sensitive cells demonstrated complete loss of phosphorylated ERK, while resistant cells demonstrated either incomplete loss of ERK phosphorylation or minimal effects on MEK phosphorylation, suggesting alternative mechanisms of resistance. NF1 protein expression correlated with responses to binimetinib, supporting the use of NF1 as a biomarker to identify patients that may respond to MEK inhibition. MEK inhibition therefore represents a potential new therapeutic strategy for neuroblastoma

    A pharmacological and transcriptomic approach to exploring novel pain targets

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    Therapeutic opportunities for targeting cold pain pathways

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    Cold pain is a frequent symptom in neuropathic pain. Compared to other pain modalities, such as heat pain, the mechanisms behind physiological and pathological cold pain remain elusive. Moreover, it is becoming increasingly evident that cold pain pharmacology differs between various neuropathic pain conditions, making mechanism-directed treatment based on an understanding of the underlying pathophysiological mechanisms imperative to achieving clinical success. Here we review the processes of physiological and abnormal cold sensing, the pharmacology of cold nociception, cold hyperalgesia and cold allodynia, and provide an overview of cold pain syndromes and their current and potential treatments

    Comparative Studies Of The Biology, Life Tables And Water Balance Of The Turkestan Cockroach Blatta lateralis (Walker), German Cockroach Blattella germanica (L.) And Brown-Banded Cockroach Supella longipalpa (Fabricius) (Dictyoptera: Blattidae, Blattellidae)

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    The selected biological parameters such as adult longevity, fecundity and nymphal development of the Turkestan cockroach, Blatta lateralis (Walker) under laboratory controlled environment in comparison with the brown-banded cockroach, Supella longipalpa (Fabricius) and the German cockroach, Blattella germanica (L.) were studied. Results obtained demonstrated that the adult longevity of B. lateralis was the highest among the three cockroach species while the male to female ratio skewed towards the male with a ratio of 1.12:1.00. Among the three species, the adult females of B. lateralis were able to produce a significantly high number of oothecae (with a maximum number recorded at 39 oothecae) over their life span

    Progeny of germ line knockouts of ASI2, a gene encoding a putative signal transduction receptor in Tetrahymena thermophila, fail to make the transition from sexual reproduction to vegetative growth

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    AbstractThe ciliated protozoan Tetrahymena has two nuclei: a germ line micronucleus and a somatic macronucleus. The transcriptionally active macronucleus has about 50 copies of each chromosome. At sexual reproduction (conjugation), the parental macronucleus is degraded and new macronucleus develops from a mitotic product of the zygotic micronucleus. Development of the macronucleus involves massive genome remodeling, including deletion of about 6000 specific internal eliminated sequences (IES) and multiple rounds of DNA replication. A gene encoding a putative signal transduction receptor, ASI2, (anlagen stage induced 2) is up-regulated during development of the new macronuclei (anlagen). Macronuclear ASI2 is nonessential for vegetative growth. Homozygous ASI2 germ line knockout cells with wild type parental macronuclei proceed through mating but arrest at late macronuclear anlagen development and die before the first post-conjugation fission. IES elimination occurs in these cells. Two rounds of postzygotic DNA replication occur normally in progeny of ASI2 germ line knockouts, but endoreduplication of the macronuclear genome is arrested. The germ line ASI2 null phenotype is rescued in a mating of a knockout strain with wild type cells

    Coronary Collateral Growth: Clinical Perspectives and Recent Insights

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    This chapter summarizes recent research on the coronary collateral circulation. The chapter is focused on clinical perspectives and importance of a well-developed coronary collateral circulation, the mechanisms of growth induced by chemical factors and a role for stem cells in the process. Some discussion is devoted to the role of shear stress and mechanical signaling, but because this topic has been reviewed so extensively in the recent past, there is only small mention of its role in the growth of the coronary collateral circulation

    Emergent Prelabor Cesarean Birth in Solid Organ Transplant Recipients: Associated Risk Factors and Outcomes.

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    BACKGROUND: Pregnancies after solid-organ transplant are at a higher risk for antepartum admission and pregnancy complications, including cesarean birth. Emergent prelabor cesarean is associated with increased maternal and neonatal morbidity in other high-risk populations, but its incidence and impact in transplant recipients is not well understood OBJECTIVE: To characterize the risk factors and outcomes of emergency prelabor cesarean birth in kidney and liver transplant recipients STUDY DESIGN: Retrospective cohort study of all kidney and liver transplant recipients \u3e20 weeks\u27 gestation enrolled in the Transplant Pregnancy Registry International between 1976 and 2019. Participants admitted antepartum who required an emergency prelabor cesarean were compared to those admitted antepartum who underwent non-emergent birth. Primary outcomes were composite severe maternal morbidity and neonatal composite morbidity. Multivariable logistic regression was conducted for neonatal composite morbidity RESULTS: Of 1,979 births, 181 pregnancies (188 neonates) with an antepartum admission were included. 51 pregnancies (53 neonates, 28%) were delivered by emergent prelabor cesarean birth compared with 130 pregnancies (135 neonates, 72%) admitted antepartum who subsequently did not require emergent delivery. The most common indication for emergent delivery was non-reassuring fetal heart tracing (44 neonates, 86%). Pregnant people who underwent an emergent prelabor cesarean were less likely to birth at a transplant center (37.3% vs 41.5%, p=0.04) and had increased rates of chronic hypertension (33.3% vs 16.2%, p=0.02). There was no significant difference in severe maternal morbidity (3.9% vs 4.6%, p=0.84), though there was an increase in surgical site infection in the emergent prelabor cesarean cohort (3.9% vs 0%, p=0.02). Among those with an emergent prelabor cesarean, there was a significant increase in neonatal composite morbidity (43.4% vs 19.3%,
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