Methylation of histone H3 lysine 4 (H3K4) by Set1 complex/COMPASS is a hallmark of eukaryotic chromatin, but it remains poorly understood how this post-translational modification contributes to the ...regulation of biological processes like the cell cycle. Here, we report a H3K4 methylation-dependent pathway in Saccharomyces cerevisiae that governs toxicity toward benomyl, a microtubule destabilizing drug. Benomyl-sensitive growth of wild-type cells required mono- and dimethylation of H3K4 and Pho23, a PHD-containing subunit of the Rpd3L complex. Δset1 and Δpho23 deletions suppressed defects associated with ipl1-2 aurora kinase mutant, an integral component of the spindle assembly checkpoint during mitosis. Benomyl resistance of Δset1 strains was accompanied by deregulation of all four tubulin genes and the phenotype was suppressed by tub2-423 and Δtub3 mutations, establishing a genetic link between H3K4 methylation and microtubule function. Most interestingly, sine wave fitting and clustering of transcript abundance time series in synchronized cells revealed a requirement for Set1 for proper cell-cycle-dependent gene expression and Δset1 cells displayed delayed entry into S phase. Disruption of G1/S regulation in Δmbp1 and Δswi4 transcription factor mutants duplicated both benomyl resistance and suppression of ipl1-2 as was observed with Δset1 Taken together our results support a role for H3K4 methylation in the coordination of cell-cycle progression and proper assembly of the mitotic spindle during mitosis.
IntroductionThe COVID-19 pandemic has had both direct and indirect impacts on the health of populations worldwide. While racial/ethnic health inequities in COVID-19 infection are now well known (and ...ongoing), knowledge about the impact of COVID-19 pandemic management on non-COVID-19-related outcomes for Indigenous peoples is less well understood. This article presents the study protocol for the Health Research Council of New Zealand funded project ‘Mā te Mōhio ka Mārama: Impact of COVID-19 on Māori:non-Māori inequities’. The study aims to explore changes in access to healthcare, quality of healthcare and health outcomes for Māori, the Indigenous peoples of Aotearoa New Zealand (NZ) and non-Māori during the COVID-19 outbreak period across NZ.Methods and analysisThis observational study is framed within a Kaupapa Māori research positioning that includes Kaupapa Māori epidemiology. National datasets will be used to report on access to healthcare, quality of healthcare and health outcomes between Māori and non-Māori during the COVID-19 pandemic in NZ. Study periods are defined as (a) prepandemic period (2015–2019), (b) first pandemic year without COVID-19 vaccines (2020) and (c) pandemic period with COVID-19 vaccines (2021 onwards). Regional and national differences between Māori and non-Māori will be explored in two phases focused on identified health priority areas for NZ including (1) mortality, cancer, long-term conditions, first 1000 days, mental health and (2) rheumatic fever.Ethics and disseminationThis study has ethical approval from the Auckland Health Research Ethics Committee (AHREC AH26253). An advisory group will work with the project team to disseminate the findings of this project via project-specific meetings, peer-reviewed publications and a project-specific website. The overall intention of the project is to highlight areas requiring health policy and practice interventions to address Indigenous inequities in health resulting from COVID-19 pandemic management (both historical and in the future).
It is evident that COVID-19 will remain a public health concern in the coming years, largely driven by variants of concern (VOC). It is critical to continuously monitor vaccine effectiveness as new ...variants emerge and new vaccines and/or boosters are developed. Systematic surveillance of the scientific evidence base is necessary to inform public health action and identify key uncertainties. Evidence syntheses may also be used to populate models to fill in research gaps and help to prepare for future public health crises. This protocol outlines the rationale and methods for a living evidence synthesis of the effectiveness of COVID-19 vaccines in reducing the morbidity and mortality associated with, and transmission of, VOC of SARS-CoV-2.
Living evidence syntheses of vaccine effectiveness will be carried out over one year for (1) a range of potential outcomes in the index individual associated with VOC (pathogenesis); and (2) transmission of VOC. The literature search will be conducted up to May 2023. Observational and database-linkage primary studies will be included, as well as RCTs. Information sources include electronic databases (MEDLINE; Embase; Cochrane, L*OVE; the CNKI and Wangfang platforms), pre-print servers (medRxiv, BiorXiv), and online repositories of grey literature. Title and abstract and full-text screening will be performed by two reviewers using a liberal accelerated method. Data extraction and risk of bias assessment will be completed by one reviewer with verification of the assessment by a second reviewer. Results from included studies will be pooled via random effects meta-analysis when appropriate, or otherwise summarized narratively.
Evidence generated from our living evidence synthesis will be used to inform policy making, modelling, and prioritization of future research on the effectiveness of COVID-19 vaccines against VOC.
Purpose We used MAPP data to identify participants with urological chronic pelvic pain syndromes only or a chronic functional nonurological associated somatic syndrome in addition to urological ...chronic pelvic pain syndromes. We characterized these 2 subgroups and explored them using 3 criteria, including 1) MAPP eligibility criteria, 2) self-reported medical history or 3) RICE criteria. Materials and Methods Self-reported cross-sectional data were collected on men and women with urological chronic pelvic pain syndromes, including predominant symptoms, symptom duration and severity, nonurological associated somatic syndrome symptoms and psychosocial factors. Results Of 424 participants with urological chronic pelvic pain syndromes 162 (38%) had a nonurological associated somatic syndrome, including irritable bowel syndrome in 93 (22%), fibromyalgia in 15 (4%), chronic fatigue syndrome in 13 (3%) and multiple syndromes in 41 (10%). Of 233 females 103 (44%) had a nonurological associated somatic syndrome compared to 59 of 191 males (31%) (p = 0.006). Participants with a nonurological associated somatic syndrome had more severe urological symptoms and more frequent depression and anxiety. Of 424 participants 228 (54%) met RICE criteria. Of 228 RICE positive participants 108 (47%) had a nonurological associated somatic syndrome compared to 54 of 203 RICE negative patients (28%) with a nonurological associated somatic syndrome (p <0.001). Conclusions Nonurological associated somatic syndromes represent important clinical characteristics of urological chronic pelvic pain syndromes. Participants with a nonurological associated somatic syndrome have more severe symptoms, longer duration and higher rates of depression and anxiety. RICE positive patients are more likely to have a nonurological associated somatic syndrome and more severe symptoms. Because nonurological associated somatic syndromes are more common in women, future studies must account for this potential confounding factor in urological chronic pelvic pain syndromes.
•SELENE is a phase 3, placebo-controlled trial evaluating ibrutinib or placebo added to BR/R-CHOP for patients with R/R FL or MZL.•The addition of ibrutinib to BR or R-CHOP did not significantly ...improve the PFS.
Display omitted
The phase 3 SELENE study evaluated ibrutinib + chemoimmunotherapy (CIT; bendamustine and rituximab BR; or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone R-CHOP) for patients with relapsed/refractory (R/R) follicular lymphoma (FL) or marginal zone lymphoma (MZL). Adult patients who had received ≥1 prior line of CIT were randomized 1:1 to oral ibrutinib (560 mg) or placebo daily, plus 6 cycles of BR/R-CHOP. The primary end point was investigator-assessed progression-free survival (PFS). Overall, 403 patients were randomized to ibrutinib + CIT (n = 202) or placebo + CIT (n = 201). Most patients received BR (90.3%) and had FL (86.1%). With a median follow-up of 84 months, median PFS was 40.5 months in the ibrutinib + CIT arm and 23.8 months in the placebo + CIT arm (hazard ratio HR, 0.806; 95% confidence interval CI, 0.626-1.037; P = .0922). Median overall survival was not reached in either arm (HR, 0.980; 95% CI, 0.686-1.400). Grade ≥3 treatment-emergent adverse events (TEAEs) were reported in 85.6% and 75.4% of patients in the ibrutinib + CIT and placebo + CIT arms, respectively. In each arm, 13 patients had TEAEs leading to death. The addition of ibrutinib to CIT did not significantly improve PFS compared with placebo + CIT. The safety profile was consistent with known profiles of ibrutinib and CIT. This trial was registered at www.clinicaltrials.gov as #NCT01974440.
Measurement can develop in the earliest years from children's experience, and it readily lends itself to real-world application. Focusing on research and practice, NCTM's 2003 Yearbook presents ...current thinking about the learning and teaching of measurement, including students' understanding, the mathematics of measurement, estimation and approximation, connections, and pedagogy. The 331-page yearbook divides into two parts and twenty-four chapters, as follows. Part 1: "Elementary School," contains: Introduction (Michelle Stephan and JoAnne Mendiola); (1) Linear, Area, and Time Measurement in Prekindergarten to Grade 2 (Michelle Stephan and Douglas H. Clements); (2) Understanding Children's Developing Strategies and Concepts for Length (Jeffrey E. Barrett; Graham Jones; Carol Thornton; Sandra Dickson); (3) Making Connections with Powerful Ideas in the Measurement of Length (Nicola Yelland); (4) Developing the Building Blocks of Measurement with Young Children (Theresa J. Grant and Kate Kline); (5) Benchmarks as Tools for Developing Measurement Sense (Elana Joram); (6) Assessing and Developing Measurement with Young Children (Doug Clarke; Jill Cheeseman; Andrea McDonough; and Barbara Clark); (7) Count Me into Measurement: A Program for the Early Elementary School (Lynne Outhred; Michael Mitchelmore; Diane McPhail; and Peter Gould; (8) Developing an Understanding of Measurement in the Elementary Grades (Richard Lehrer; Linda Jaslow; and Carmen L. Curtis); (9) Understanding Students' Thinking about Area and Volume Measurement (Michael T. Battista); (10) Structuring a Rectangle: Teachers Write to Learn about Their Students' Thinking (Deborah Schifter and Janice Szymaszek); (11) About Students' Understanding and Learning the Concept of Surface Area (Cinzia Bonotto); (12) The Measurement of Time: Transitivity, Unit Iteration, and Conservation of Speed (Constance K. Kamii and Kathy Long); and (13) Bridging Yup'ik Ways of Measuring to Western Mathematics (Jerry Lipka; Tod Shockey; and Barbara Adams). Part 2: "Secondary School," contains: Introduction (Veronica Meeks and Robert F. Wheeler); (14) What Students Know about Measurement: Perspectives from the NAEP (Marilyn E. Strutchens; W. Gary Martin; and Patricia Ann Kenney); (15) Providing Opportunities for Students and Teachers to "Measure Up" (Melissa Boston and Margaret Smith); (16) Measuring Montana: An Episode in Estimation (Ted Hodgson; Linda Simonsen; Jennifer Lubek; and Lyle Anderson); (17) Estimation at Work (Thomasenia Lott Adams; and Gregory Harrell); (18) Exploring Measurement Concepts through Literature: Natural Links across Disciplines (Richard Austin; Denisse Thompson; and Charlene Beckmann); (19) Using the Geoboard to Enhance Measurement Instruction in the Secondary School Mathematics Classroom (Barbara A. Burns and Gail A. Brade); (20) Using Measurement to Develop Mathematical Reasoning at the Middle and High School Levels (Mary C. Enderson); (21) Is Our Teaching Measuring Up? Race-, SES-, and Gender-Related Gaps in Measurement Achievement (Sarah T. Lubienski); (22) Measurement, Representation, and Computer Models of Motion (Christopher Hartmann and Jeffrey Choppin); (23) Measuring the Unmeasurable: Using Technology to Study the Irrational (Maurice Burke); and (24) Measurement in Adult Education: Starting with Students' Understandings (Myriam Steinback; Mary Jane Schmitt; Martha Merson; and Esther Leonelli). The 77-page companion booklet, which not only illustrates some of the issues from the yearbook but also contains activities that go beyond the content, contains teaching notes and ready-to-use handouts. The booklet contains the following eighteen chapters: (1) A Word to Teachers; (2) Woolly Worms (Andrea McDonough; Jill Cheeseman; and Doug Clarke); (3) Teddy Counters (Andrea McDonough; Jill Cheeseman; and Doug Clarke); (4) Broken Rulers (Jeffrey Barnett and Sandra Dickson); (5) Benchmarks for Measurement Units (Elana Joram); (6) Measuring Volume Informally (Sinan Olkun); (7) Angle Measurements (George W. Bright); (8) Estimation (George W. Bright); (9) Greatest Perimeter (George W. Bright); (10) Measuring the Mountain State (Ted Hodgson); (11) Area of Kite: Teaching Notes (George W. Bright); (12) Making Rabbit Pens (Margaret S. Smith and Melissa Boston); (13) The Perimeter and Area of Similar Figures (Barbara A. Burns and Gail Brade); (14) Ratios--Surface Areas and Volumes (George W. Bright); (15) Look-Alike Rectangles (Suzanne Levin Weinberg); (16) Perimeter and Area of Similar Figures (Mary C. Enderson); (17) Determining Densities of Various Kinds of Wood (Joseph I. Stepans); and (18) Investigating Densities of Different Paper Materials (Joseph I. Stepans).
PDF
