Cdc48 and Cofactors Npl4-Ufd1 Are Important for G1 Progression during Heat Stress by Maintaining Cell Wall Integrity in Saccharomyces cerevisiae

The ubiquitin-selective chaperone Cdc48, a member of the AAA (ATPase Associated with various cellular Activities) ATPase superfamily, is involved in many processes, including endoplasmic reticulum-associated degradation (ERAD), ubiquitin- and proteasome-mediated protein degradation, and mitosis. Although Cdc48 was originally isolated as a cell cycle mutant in the budding yeast Saccharomyces cerevisiae, its cell cycle functions have not been well appreciated. We found that temperature-sensitive cdc48-3 mutant is largely arrested at mitosis at 37°C, whereas the mutant is also delayed in G1 progression at 38.5°C. Reporter assays show that the promoter activity of G1 cyclin CLN1, but not CLN2, is reduced in cdc48-3 at 38.5°C. The cofactor npl4-1 and ufd1-2 mutants also exhibit G1 delay and reduced CLN1 promoter activity at 38.5°C, suggesting that Npl4-Ufd1 complex mediates the function of Cdc48 at G1. The G1 delay of cdc48-3 at 38.5°C is a consequence of cell wall defect that over-activates Mpk1, a MAPK family member important for cell wall integrity in response to stress conditions including heat shock. cdc48-3 is hypersensitive to cell wall perturbing agents and is synthetic-sick with mutations in the cell wall integrity signaling pathway. Our results suggest that the cell wall defect in cdc48-3 is exacerbated by heat shock, which sustains Mpk1 activity to block G1 progression. Thus, Cdc48-Npl4-Ufd1 is important for the maintenance of cell wall integrity in order for normal cell growth and division

Breast cancer screening program in canada: successes and challenges Programas de detección temprana de cáncer de mama en canadá: avances y obstáculos

This paper describes breast screening program development in Canada and the current status of screening in Canada. Programs have been implemented in most of Canada, beginning in the late 1980's. Certain components are common to all the programs, but others, such as personal invitation letters for recruitment and clinical breast examination vary across the country. Key successes in organized breast screening in Canada include the development of a comprehensive set of screening performance indicators, which are reported on regularly, and the downward trend in mortality rates observed over the past 20 years. Challenges include the continued prevalence of opportunistic screening; the need to better manage follow-up; dealing with changing evidence; and supporting informed decision-making about screening. Approaches to breast screening are dependent on the health care services available in countries, but regardless of the approach, good evaluation is necessary.Este artículo describe el desarrollo de la detección temprana de cáncer de mama en Canadá así como la situación actual de los programas de detección de cáncer en el mismo país. En su gran mayoría, estos programas de detección han sido implementados desde comienzos de los años ochenta. Algunos elementos de estos programas representan denominadores comunes en todos ellos. Sin embargo existen otros elementos -tales como invitaciones personales para reclutamiento y exámenes clínicos de mama, que difieren dependiendo de cada jurisdicción. Algunos de los avances en los programas organizados de detección temprana de cáncer de mama en Canadá incluyen la existencia de indicadores de evaluación de desempeño, sobre los cuales se reporta de forma regular. En base a estos indicadores se puede observar una tendencia descendente en los índices de mortalidad en los últimos 20 años. Algunas de las dificultades incluyen la persistencia de detección oportunística, la necesidad de gerenciar el efectivo seguimiento de pacientes, gerenciar el constante cambio de evidencia, así como el proveer asistencia en la toma de decisiones relacionadas a la detección temprana de cáncer. Las prácticas focalizadas en mejorar la detección temprana de cáncer dependen de los servicios de salud existentes en cada país. Sin embargo e independientemente de la orientación utilizada, la necesidad de evaluar el desempeño de los programas es un elemento vital

Endoscopic Follow-Up of Positive Fecal Occult Blood Testing in the Ontario FOBT Project

BACKGROUND: The Ontario FOBT Project is a pilot study of fecal occult blood testing (FOBT) for colorectal cancer screening conducted among age-eligible volunteers (50 to 75 years) in 12 of 37 public health regions in Ontario

Cancer Care Ontario Colonoscopy Standards: Standards and evidentiary base

Colorectal cancer (CRC) is the most common cause of non-tobacco-related cancer deaths in Canadian men and women, accounting for 10% of all cancer deaths. An estimated 7800 men and women will be diagnosed with CRC, and 3250 will die from the disease in Ontario in 2007. Given that CRC incidence and mortality rates in Ontario are among the highest in the world, the best opportunity to reduce this burden of disease would be through screening. The present report describes the findings and recommendations of Cancer Care Ontario’s Colonoscopy Standards Expert Panel, which was convened in March 2006 by the Program in Evidence-Based Care. The recommendations will form the basis of the quality assurance program for colonoscopy delivered in support of Ontario’s CRC screening program