151 research outputs found
Rpd3l contributes to the DNA damage sensitivity of saccharomyces cerevisiae checkpoint mutants
DNA replication forks that are stalled by DNA damage activate an S-phase checkpoint that prevents irreversible fork arrest and cell death. The increased cell death caused by DNA damage in budding yeast cells lacking the Rad53 checkpoint protein kinase is partially suppressed by deletion of the EXO1 gene. Using a whole-genome sequencing approach, we identified two additional genes, RXT2 and RPH1, whose mutation can also partially suppress this DNA damage sensitivity. We provide evidence that RXT2 and RPH1 act in a common pathway, which is distinct from the EXO1 pathway. Analysis of additional mutants indicates that suppression works through the loss of the Rpd3L histone deacetylase complex. Our results suggest that the loss or absence of histone acetylation, perhaps at stalled forks, may contribute to cell death in the absence of a functional checkpoint.Cancer Research UK FC001066UK Medical Research Council FC001066Wellcome Trust FC001066European Molecular Biology Organization ALTF 263–2011European Research Council Advanced 669424-CHROMORE
Evolving in Collaboration: Electronic Thesis and Dissertation Workflows in North Carolina
Thirty-seven colleges and universities in North Carolina offer advanced degrees, and most require a thesis or dissertation. The websites of thirteen (35%) indicate they accept or require electronic submission of dissertations and/or theses (ETD). How do these institutions handle the interdepartmental communication and collaboration needs of ETD programs? To begin answering this question, this study examines current practices among ETD administrators in North Carolina and in current national literature, paying special attention to communication, collaboration, workflows, and divisions of labor. The literature review surveys current (since 2003) library and higher education articles on topics related to collaboration, workflows, and divisions of labor in ETD programs. Then the authors use a brief web survey (sixteen questions) that was emailed to twenty-three individuals identified on institutional websites as being involved in the ETD program. Fifty percent of recipients completed the survey, and the results tend to support common themes found in the literature: ETD depositories require a great variety of skill sets and thus will involve multiple departments; libraries and graduate schools are primary players, but not exclusively, in ETD workflows; and communication and collaboration between departments are important from start to finish
Connecting a Community through a Family Literacy Project and Virtual Writing Collaboration: University Students Facilitate Access to Literature during the Pandemic
The importance of accessing and sharing children’s literature took on new meaning as educators pivoted to remote and online learning models over the course of the past school year. In light of the pandemic, College of Education pre-service educators enrolled in a Fall 2020 Language and Literacy Development course (which is usually scheduled to meet face-to-face twice a week) was re-structured as hybrid, where a group of students were scheduled to meet partially face-to-face and partially online on a weekly basis. I planned to adapt my family literacy project collaboration with a local community center, an academic service learning assignment that I incorporate each semester as part of the course. A second community literacy project embedded in the course involved reading and discussing Look both ways: A tale told in ten blocks (Reynolds, 2019), short stories that detail experiences of middle school characters on their walk home from school. My original plan was for both middle school students and pre-service educators to draft personal place-based writing short stories- inspired by the mentor text- and participate in writing conferences. Instead, Zoom sessions were conducted in which both sets of students virtually conferenced about their writing pieces when schedules allowed. In this manner, authentic conversations about writing were being cultivated through a virtual approach
Evolving in Collaboration: Electronic Thesis and Dissertation Workflows in North Carolina
Thirty-seven colleges and universities in North Carolina offer advanced degrees, and most require a thesis or dissertation. The websites of thirteen (35%) indicate they accept or require electronic submission of dissertations and/or theses (ETD). How do these institutions handle the interdepartmental communication and collaboration needs of ETD programs? To begin answering this question, this study examines current practices among ETD administrators in North Carolina and in current national literature, paying special attention to communication, collaboration, workflows, and divisions of labor. The literature review surveys current (since 2003) library and higher education articles on topics related to collaboration, workflows, and divisions of labor in ETD programs. Then the authors use a brief web survey (sixteen questions) that was emailed to twenty-three individuals identified on institutional websites as being involved in the ETD pro-gram. Fifty percent of recipients completed the survey, and the results tend to support common themes found in the literature: ETD depositories require a great variety of skill sets and thus will involve multiple departments; libraries and graduate schools are primary players, but not exclu-sively, in ETD workflows; and communication and collaboration between departments are im-portant from start to finish
Current ETD practices and workflows in North Carolina
How do institutions offering electronic theses and dissertations (ETD) handle the inter-departmental communication and collaboration needs of such programs? This study examines current practices among ETD administrators in North Carolina and in current national literature, with special attention to communication, collaboration, workflows, and divisions of labor
Prospectus, February 13, 1981
BLIZZARD HITS MIDWEST, ILLINOIS AND PARKLAND; Markland discusses new $15 million waste operation; Attention!; Letters to the Editor: Student upset, Student says college is security; It\u27s time to buy Girl Scout cookies; Gardenas at Parkland; S.N.A.P. holds monthly meetings; Women and Drugs forum; Serious problems face Reagan administration; PC has first Ag Conference; Help out the BSA; Astronomy Club; Mark Twain Tonight at Assembly Hall; Springsteen thrills capacity crowd; Gaucho hits charts; Classifieds; Top 30; Sales booming for jeans; Friends of Animals begins nationwide campaign; Saturday is Valentine\u27s Day...; PC Announcements...; The Dinner Party at Parkland February 18; Stroke Club has Valentine\u27s party; PC sponsors workshop; Women\u27s program has workshop; Parkland offers EMT course; German Club lists schedule; Cobras try to beat Kankakee a second time; Scoreboard; Ice Capades stars unite; Parkland College Results Student Government Elections February 4-5, 1981; Cobras beat Danville; Illinois faces Ohio State; Freddy off to good start; Record now 19-2 with loss to Millikin; Fast Freddy Contest; IM\u27s underway; Cobras upset by ICC, 51-48https://spark.parkland.edu/prospectus_1981/1029/thumbnail.jp
Overlapping genetic susceptibility variants between three autoimmune disorders: rheumatoid arthritis, type 1 diabetes and coeliac disease
INTRODUCTION: Genome wide association studies, replicated by numerous well powered validation studies, have revealed a large number of loci likely to play a role in susceptibility to many multifactorial diseases. It is now well established that some of these loci are shared between diseases with similar aetiology. For example, a number of autoimmune diseases have been associated with variants in the PTPN22, TNFAIP3 and CTLA4 genes. Here we have attempted to define overlapping genetic variants between rheumatoid arthritis (RA), type 1 diabetes (T1D) and coeliac disease (CeD). METHODS: We selected eight SNPs previously identified as being associated with CeD and six T1D-associated SNPs for validation in a sample of 3,962 RA patients and 3,531 controls. Genotyping was performed using the Sequenom MassArray platform and comparison of genotype and allele frequencies between cases and controls was undertaken. A trend test P-value < 0.004 was regarded as significant. RESULTS: We found statistically significant evidence for association of the TAGAP locus with RA (P = 5.0 Ă— 10-4). A marker at one other locus, C1QTNF6, previously associated with T1D, showed nominal association with RA in the current study but did not remain statistically significant at the corrected threshold. CONCLUSIONS: In exploring the overlap between T1D, CeD and RA, there is strong evidence that variation within the TAGAP gene is associated with all three autoimmune diseases. Interestingly a number of loci appear to be specific to one of the three diseases currently studied suggesting that they may play a role in determining the particular autoimmune phenotype at presentation
Tumor tissue levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and outcome following adjuvant chemotherapy in premenopausal lymph node-positive breast cancer patients: A retrospective study
<p>Abstract</p> <p>Background</p> <p>We have previously demonstrated that high tumor tissue levels of TIMP-1 are associated with no or limited clinical benefit from chemotherapy with CMF and anthracyclines in metastatic breast cancer patients. Here, we extend our investigations to the adjuvant setting studying outcome after adjuvant chemotherapy in premenopausal lymph node-positive patients. We hypothesize that TIMP-1 high tumors are less sensitive to chemotherapy and accordingly that high tumor tissue levels are associated with shorter survival.</p> <p>Methods</p> <p>From our original retrospectively collected tumor samples we selected a group of 525 pre-menopausal lymph node-positive patients (adjuvant treatment: CMF, 324 patients; anthracycline-based, 99 patients; no adjuvant chemotherapy, 102 patients). TIMP-1 levels were measured using ELISA in cytosolic extracts of frozen primary tumors. TIMP-1 was analyzed as a continuous variable and as a dichotomized one using the median TIMP-1 concentration as a cut point between high and low TIMP-1 groups. We analyzed the benefit of adjuvant CMF and anthracyclines in univariate and multivariable survival models; endpoints were disease-free (DFS) and overall survival (OS).</p> <p>Results</p> <p>In this selected cohort of high-risk patients, and in the subgroup of patients receiving no adjuvant therapy, TIMP-1 was not associated with prognosis. In the subgroup of patients treated with anthracyclines, when analyzed as a continuous variable we observed a tendency for increasing TIMP-1 levels to be associated with shorter DFS (multivariable analysis, HR 1.75, 95% CI 1.00-3.07, P = 0.05) and a significant association between increasing TIMP-1 and shorter OS in both univariate (HR 3.52, 95% CI 1.54-8.06, P = 0.003) and multivariable analyses (HR 4.19, 95% CI 1.67-10.51, P = 0.002). No statistically significant association between TIMP-1 and DFS was observed in the CMF-treated patients although high TIMP-1 was associated with shorter OS when analyzed as a dichotomized variable (HR 1.64, 95% CI 1.02-2.65, P = 0.04).</p> <p>Conclusion</p> <p>In the subgroup of patients receiving adjuvant chemotherapy we found an association between shorter survival after treatment in TIMP-1 high patients compared with TIMP-1 low patients, especially in patients receiving anthracycline-based therapy. This suggests that high tumor tissue levels of TIMP-1 might be associated with reduced benefit from classical adjuvant chemotherapy. Our findings should be validated in larger prospective studies.</p
Spirocycle MmpL3 Inhibitors with Improved hERG and Cytotoxicity Profiles as Inhibitors of Mycobacterium tuberculosis Growth
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