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The Greatwall kinase inhibits PP2A-B55 phosphatase activity during mitosis to stabilise critical Cdk1-driven mitotic phosphorylation. Although Greatwall represents a potential oncogene and prospective therapeutic target, our understanding of the cellular and molecular consequences of chemical Greatwall inactivation remains limited. To address this, we introduce C-604, a highly selective Greatwall inhibitor, and characterise both immediate and long-term cellular responses to the chemical attenuation of Greatwall activity. We demonstrate that Greatwall inhibition causes systemic destabilisation of the mitotic phosphoproteome, premature mitotic exit and pleiotropic cellular pathologies. Importantly, we show that the cellular and molecular abnormalities associated with reduced Greatwall activity are specifically dependent on the B55α isoform, rather than other B55 variants, underscoring PP2A-B55α phosphatases as key mediators of the cytotoxic effects of Greatwall-targeting agents in human cells. Additionally, we establish that sensitivity to Greatwall inhibition varies in different cell line models and that dependency on Greatwall activity reflects the balance between Greatwall and B55α expression levels. Our findings highlight Greatwall dependency as a cell-specific vulnerability and propose the B55α-to-Greatwall expression ratio as a predictive biomarker of cellular responses to Greatwall-targeted therapeutics. The authors develop and characterise a selective Greatwall inhibitor, C-604, and show that its cytotoxicity stems from PP2A-B55α hyperactivation. They identify B55α and Greatwall levels as biomarkers of responses to Greatwall-targeted therapy.

Patient concerns about hospital hygiene have resulted in nurses at Cumbria Infirmary developing welcome cards, to reassure patients about the general cleanliness of wards and to encourage patients to speak to a nurse in charge about any anxiety they have about the risk of hospital-acquired infections. [(BNI unique abstract)] 0 references

The Greatwall kinase inhibits PP2A-B55 phosphatase activity during mitosis to stabilise critical Cdk1-driven mitotic phosphorylation. Although Greatwall represents a potential oncogene and prospective therapeutic target, our understanding of cellular and molecular consequences of chemical Greatwall inactivation remains limited. To address this, we introduce C-604, a highly selective Greatwall inhibitor, and characterise both immediate and long-term cellular responses to the chemical attenuation of Greatwall activity. We demonstrate that Greatwall inhibition causes systemic destabilisation of the mitotic phosphoproteome, premature mitotic exit and pleiotropic cellular pathologies. Importantly, we demonstrate that the cellular and molecular abnormalities linked to reduced Greatwall activity are specifically dependent on the B55α isoform rather than other B55 variants, underscoring PP2A-B55α phosphatases as key mediators of cytotoxic effects of Greatwall-targeting agents in human cells. Additionally, we show that sensitivity to Greatwall inhibition varies in different cell line models and that dependency on Greatwall activity reflects the balance between Greatwall and B55α expression levels. Our findings highlight Greatwall dependency as a cell-specific vulnerability and propose the B55α-to-Greatwall expression ratio as a predictive biomarker of cellular responses to Greatwall-targeted therapeutics.

Mary Fay Bourgoin's article [\"You Can't Be a Mother and 'Have It All,'\" Outlook, Nov. 27] is the last straw. I am sick and tired of women who have no responsibility for paying rent and putting food on the table implying that I am shortchanging my child by not being home all day.

The purpose of this study is to investigate change, planned or unplanned, which has occurred in Catholic schools because of non-Catholic students in attendance. Respondents include school staff, Catholic parents and non-Catholic parents in selected urban and suburban Catholic schools. A new instrument, the Catholic School Participants' Scale, was devised to suit the purposes of the study. Major findings are: (1) Catholic parents and non-Catholic parents patronize Catholic schools for basically the same reasons; the academic program and teaching of moral and spiritual values are ranked first and second, respectively, as primary reasons for parents selecting Catholic schools. Unexpectedly, student safety is ranked as the least important reason by both parent groups. (2) Dissatisfaction is expressed with the quality of education in public schools by both parent groups. (3) No major changes have occurred in school religion programs, prayer services, or sacramental programs because of non-Catholic children in attendance; furthermore, the majority of respondents indicate they do not wish to see future change occur. (4) Social studies curricula, parental involvement, tuition fees, and discipline remain unchanged despite the presence of non-Catholic children. Results show that parents and staff share attitudes of care, concern, and respect (solicitude) which are part of the affective atmosphere of Catholic schools. Respondents express satisfaction with the academic program in Catholic schools but share a common concern about a feeling of exclusion evidenced by non-Catholic children when Catholic students are being prepared for the sacraments of Holy Eucharist, Penance, and Confirmation. Results of the study imply that, although Catholic schools should keep doing what they do so well, planned change will enable them to maintain the integrity of their religiously oriented educational program and still educate non-Catholic children. Since this is the first study which concentrates on non-Catholic children in Catholic schools, additional research is recommended on Catholic school enrollment trends, academic achievements, and attitudes of school staff and pastors. Future studies should include schools of religious denominations other than Catholic to determine whether change has occurred because of students of various religious backgrounds in attendance.