398 research outputs found
Warm-Season Grass Establishment as Affected by Post-Planting Atrazine Application
Atrazine [6-chloro-N-ethyl-N’-methylethyl)-1,3,5-triazine-2,4-diamine] provides effective weed control during big bluestem (Andropogon gerardii Vitman) and switchgrass (Panicum virgatrum L.) establishment. However, most other desirable warm-season grasses are susceptible to atrazine injury at establishment. The objective of this study was to determine if atrazine applications after seedling would affect susceptible warm-season grass establishment. Big bluestem, switchgrass, Indiangrass [Sorghastrum nutans (L.) Nash], sideoats grama [Bouteloua curtipendula (Michx.) Torr.], and little bluestem [Schizachyrium scoparium (Michx.) Nash] were needed into greenhouse flats or field plots and 2.2 kg a.i. atrazine/ha applied at 0 (atrazine control), 7, 14, or 21 days after planting. An untreated control was used also. In greenhouse experiments, indiangrass and sideoats grama plant survival increased when atrazine applications were delayed. Switchgrass, big bluestem, and little bluestem plant survival was not affected by atrazine application. Field studies were conducted in 1983, 1985, and 1986 using the same soil type, grass species, and application periods as the greenhouse study. Delaying atrazine application 7 or more days after planting generally favored survival of indiangrass and sideoats grama. Big bluestem, switchgrass, and little bluestem were not affected by atrazine treatment. Delaying the application of atrazine may favor the survival of atrazine sensitive species. However, further researcher needs to be conducted on various soil types and environmental conditions before this can be a recommended practice
The longevity and reversibility of quiescence in Schizosaccharomyces pombe are dependent upon the HIRA histone chaperone
Quiescence (G0) is a reversible non-dividing state that facilitates cellular survival in adverse conditions. Here, we demonstrate that the HIRA histone chaperone complex is required for the reversibility and longevity of nitrogen starvation-induced quiescence in Schizosaccharomyces pombe. The HIRA protein, Hip1 is not required for entry into G0 or the induction of autophagy. Although hip1Δ cells retain metabolic activity in G0, they rapidly lose the ability to resume proliferation. After a short period in G0 (1 day), hip1Δ mutants can resume cell growth in response to the restoration of a nitrogen source but do not efficiently reenter the vegetative cell cycle. This correlates with a failure to induce the expression of MBF transcription factor-dependent genes that are critical for S phase. In addition, hip1Δ G0 cells rapidly progress to a senescent state in which they can no longer re-initiate growth following nitrogen source restoration. Analysis of a conditional hip1 allele is consistent with these findings and indicates that HIRA is required for efficient exit from quiescence and prevents an irreversible cell cycle arrest
A novel preoperative model to predict 90-day surgical mortality in patients considered for renal cell carcinoma surgery
Introduction
Surgical benefits for renal cell carcinoma must be weighed against competing causes of mortality, especially in the elderly patient population. We used a large cancer registry to evaluate the impact of patient and cancer-specific factors on 90-day mortality (90DM). A nomogram to predict the odds of short-term mortality was created.
Materials and Methods
The National Cancer Database was queried to identify all patients with clinically localized, nonmetastatic disease treated with partial or radical nephrectomy. Using a random sample of 60%, multiple logistic regression with 90DM outcomes were performed to identify preoperative variables associated with mortality. Variables included age, sex, race, co-morbidity score, tumor size, and presence of a thrombus. A nomogram was created and tested on the remaining 40% of patients to predict 90DM.
Results
183,407 patients met inclusion criteria. Overall 90DM for the cohort was 1.9%. All preoperative variables significantly influenced the risk of 90DM. Patient age was by far the strongest predictor. Nomogram scores ranged from 0 to 12. Compared to patients with 0 to 1 points, those with 2 to 3 (odds ratio [OR] 2.89, 2.42–3.46; P 6 (OR 12.86, 10.83–15.27; P 80 years of age alone placed patients into the highest risk of surgical mortality.
Conclusions
Management of localized kidney cancer must consider competing causes of mortality, especially in elderly patients with multiple co-morbidities. We present a preoperative tool to calculate risk of surgical short-term mortality to aid surgeon–patient counseling
Native Nephrectomy with Renal Transplantation Decreases Hypertension Medication Requirements in Autosomal Dominant Polycystic Kidney Disease
Purpose
We assessed hypertensive control after native nephrectomy and renal transplantation in patients with autosomal dominant polycystic kidney disease.
Materials and Methods
Blood pressure control was studied retrospectively in 118 patients with autosomal dominant polycystic kidney disease who underwent renal transplantation between 2003 and 2013. Overall 54 patients underwent transplantation alone (group 1) and 64 underwent transplantation with concurrent ipsilateral nephrectomy (group 2). Of these 64 patients 32 underwent ipsilateral nephrectomy only (group 2a) and 32 underwent eventual delayed contralateral native nephrectomy (group 2b). The number of antihypertensive drugs and defined daily dose of each antihypertensive was recorded at transplantation and up to 36-month followup.
Results
Comparing preoperative to postoperative medications at 12, 24 and 36-month followup, transplantation with concurrent ipsilateral nephrectomy had a greater decrease in quantity (−1.2 vs −0.5 medications, p=0.008; −1.1 vs −0.3, p=0.007 and −1.2 vs −0.4, p=0.03, respectively) and defined daily dose of antihypertensive drug (−3.3 vs −1.0, p=0.0008; −2.9 vs −1.0, p=0.006 and −2.7 vs −0.6, p=0.007, respectively) than transplantation alone at each point. Native nephrectomy continued to be a predictor of hypertensive requirements on multivariable analysis (p <0.0001). The mean decrease in number of medications in group 2b from after ipsilateral nephrectomy to 12 months after contralateral nephrectomy was −0.6 (p=0.0005) and the mean decrease in defined daily dose was −0.6 (p=0.009).
Conclusions
In patients with autosomal dominant polycystic kidney disease undergoing renal transplantation, concurrent ipsilateral native nephrectomy is associated with a significant decrease in the quantity and defined daily dose of antihypertensive drugs needed for hypertension control. Delayed contralateral native nephrectomy is associated with improved control of blood pressure to an even greater degree
A central role for TOR signalling in a yeast model for juvenile CLN3 disease
Yeasts provide an excellent genetically tractable eukaryotic system for investigating the function of genes in their biological context, and are especially relevant for those conserved genes that cause disease. We study the role of btn1, the orthologue of a human gene that underlies an early onset neurodegenerative disease (juvenile CLN3 disease, neuronal ceroid lipofuscinosis (NCLs) or Batten disease) in the fission yeast Schizosaccharomyces pombe. A global screen for genetic interactions with btn1 highlighted a conserved key signalling hub in which multiple components functionally relate to this conserved disease gene. This signalling hub includes two major mitogen-activated protein kinase (MAPK) cascades, and centers on the Tor kinase complexes TORC1 and TORC2. We confirmed that yeast cells modelling CLN3 disease exhibit features consistent with dysfunction in the TORC pathways, and showed that modulating TORC function leads to a comprehensive rescue of defects in this yeast disease model. The same pathways may be novel targets in the development of therapies for the NCLs and related diseases
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Whole-genome microarrays of fission yeast: characteristics, accuracy, reproducibility, and processing of array data
Background: The genome of the fission yeast Schizosaccharomyces pombe has recently been sequenced, setting the stage for the post-genomic era of this increasingly popular model organism. We have built fission yeast microarrays, optimised protocols to improve array performance, and carried out experiments to assess various characteristics of microarrays.|Results: We designed PCR primers to amplify specific probes (180-500 bp) for all known and predicted fission yeast genes, which are printed in duplicate onto separate regions of glass slides together with control elements (similar to13,000 spots/slide). Fluorescence signal intensities depended on the size and intragenic position of the array elements, whereas the signal ratios were largely independent of element properties. Only the coding strand is covalently linked to the slides, and our array elements can discriminate transcriptional direction. The microarrays can distinguish sequences with up to 70% identity, above which cross-hybridisation contributes to the signal intensity. We tested the accuracy of signal ratios and measured the reproducibility of array data caused by biological and technical factors. Because the technical variability is lower, it is best to use samples prepared from independent biological experiments to obtain repeated measurements with swapping of fluorochromes to prevent dye bias. We also developed a script that discards unreliable data and performs a normalization to correct spatial artefacts.|Conclusions: This paper provides data for several microarray properties that are rarely measured. The results define critical parameters for microarray design and experiments and provide a framework to optimise and interpret array data. Our arrays give reproducible and accurate expression ratios with high sensitivity. The scripts for primer design and initial data processing as well as primer sequences and detailed protocols are available from our website
Systematic screen for mutants resistant to TORC1 inhibition in fission yeast reveals genes involved in cellular ageing and growth
Target of rapamycin complex 1 (TORC1), which controls growth in response to nutrients, promotes ageing in multiple organisms. The fission yeast Schizosaccharomyces pombe emerges as a valuable genetic model system to study TORC1 function and cellular ageing. Here we exploited the combinatorial action of rapamycin and caffeine, which inhibit fission yeast growth in a TORC1-dependent manner. We screened a deletion library, comprising ∼84% of all non-essential fission yeast genes, for drug-resistant mutants. This screen identified 33 genes encoding functions such as transcription, kinases, mitochondrial respiration, biosynthesis, intra-cellular trafficking, and stress response. Among the corresponding mutants, 5 showed shortened and 21 showed increased maximal chronological lifespans; 15 of the latter mutants showed no further lifespan increase with rapamycin and might thus represent key targets downstream of TORC1. We pursued the long-lived sck2 mutant with additional functional analyses, revealing that the Sck2p kinase functions within the TORC1 network and is required for normal cell growth, global protein translation, and ribosomal S6 protein phosphorylation in a nutrient-dependent manner. Notably, slow cell growth was associated with all long-lived mutants while oxidative-stress resistance was not
<i>Schizosaccharomyces pombe</i> Pol II transcription elongation factor ELL functions as part of a rudimentary super elongation complex
ELL family transcription factors activate the overall rate of RNA polymerase II (Pol II) transcription elongation by binding directly to Pol II and suppressing its tendency to pause. In metazoa, ELL regulates Pol II transcription elongation as part of a large multisubunit complex referred to as the Super Elongation Complex (SEC), which includes P-TEFb and EAF, AF9 or ENL, and an AFF family protein. Although orthologs of ELL and EAF have been identified in lower eukaryotes including Schizosaccharomyces pombe, it has been unclear whether SEClike complexes function in lower eukaryotes. In this report, we describe isolation from S. pombe of an ELL-containing complex with features of a rudimentary SEC. This complex includes S. pombe Ell1, Eaf1, and a previously uncharacterized protein we designate Ell1 binding protein 1 (Ebp1), which is distantly related to metazoan AFF family members. Like the metazoan SEC, this S. pombe ELL complex appears to function broadly in Pol II transcription. Interestingly, it appears to have a particularly important role in regulating genes involved in cell separation
Php4 Is a Key Player for Iron Economy in Meiotic and Sporulating Cells
Meiosis is essential for sexually reproducing organisms, including the fission yeast Schizosaccharomyces
pombe. In meiosis, chromosomes replicate once in a diploid precursor cell (zygote), and then
segregate twice to generate four haploid meiotic products, named spores in yeast. In S. pombe, Php4 is
responsible for the transcriptional repression capability of the heteromeric CCAAT-binding factor to negatively
regulate genes encoding iron-using proteins under low-iron conditions. Here, we show that the
CCAAT-regulatory subunit Php4 is required for normal progression of meiosis under iron-limiting conditions.
Cells lacking Php4 exhibit a meiotic arrest at metaphase I. Microscopic analyses of cells expressing
functional GFP-Php4 show that it colocalizes with chromosomal material at every stage of meiosis under low
concentrations of iron. In contrast, GFP-Php4 fluorescence signal is lost when cells undergo meiosis under
iron-replete conditions. Global gene expression analysis of meiotic cells using DNA microarrays identified
137 genes that are regulated in an iron- and Php4-dependent manner. Among them, 18 genes are
expressed exclusively during meiosis and constitute new putative Php4 target genes, which include
hry1+ and mug14+. Further analysis validates that Php4 is required for maximal and timely repression of
hry1+ and mug14+ genes. Using a chromatin immunoprecipitation approach, we show that Php4 specifically
associates with hry1+ and mug14+ promoters in vivo. Taken together, the results reveal that in iron-starved
meiotic cells, Php4 is essential for completion of the meiotic program since it participates in global gene
expression reprogramming to optimize the use of limited available iron
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