There are two schools of thought regarding the cyclooxygenase (COX) isoform
active in the vasculature. Using urinary prostacyclin markers some groups have
proposed that vascular COX-2 drives prostacyclin release. In contrast, we and
others have found that COX-1, not COX-2, is responsible for vascular
prostacyclin production. Our experiments have relied on immunoassays to detect
the prostacyclin breakdown product, 6-keto-PGF1α and antibodies to
detect COX-2 protein. Whilst these are standard approaches, used by many
laboratories, antibody-based techniques are inherently indirect and have been
criticized as limiting the conclusions that can be drawn. To address this
question, we measured production of prostanoids, including
6-keto-PGF1α, by isolated vessels and in the circulation
in vivo using liquid chromatography tandem mass
spectrometry and found values essentially identical to those obtained by
immunoassay. In addition, we determined expression from the
Cox2 gene using a knockin reporter mouse in which
luciferase activity reflects Cox2 gene expression. Using this
we confirm the aorta to be essentially devoid of Cox2 driven
expression. In contrast, thymus, renal medulla, and regions of the brain and gut
expressed substantial levels of luciferase activity, which correlated well with
COX-2-dependent prostanoid production. These data are consistent with the
conclusion that COX-1 drives vascular prostacyclin release and puts the sparse
expression of Cox2 in the vasculature in the context of the
rest of the body. In doing so, we have identified the thymus, gut, brain and
other tissues as target organs for consideration in developing a new
understanding of how COX-2 protects the cardiovascular system. 相似文献
Objective: The presence of appetite hormones, namely glucagon‐like peptide‐1 (GLP‐1), peptide YY (PYY), and leptin in breast milk may be important in infant feeding regulation and infant growth. This study evaluated whether concentrations of GLP‐1, PYY, and leptin change across a single feeding (from fore‐ to hindmilk), and are associated with maternal and infant anthropometrics. Design and Methods: Thirteen postpartum women (mean ± SD: 25.6 ± 4.5 years, 72.0 ± 11.9 kg) provided fore‐ and hindmilk samples 4‐5 weeks after delivery and underwent measurements of body weight and composition by Dual X‐ray Absorptiometry. GLP‐1, PYY, and leptin concentrations were measured using radioimmunoassay, and milk fat content was determined by creamatocrit. Results: Concentration of GLP‐1 and content of milk fat was higher in hindmilk than foremilk (P ≤ 0.05). PYY and leptin concentrations did not change between fore‐ and hindmilk. Both leptin concentration and milk fat content were correlated with indices of maternal adiposity, including body mass index (r = 0.65‐0.85, P < 0.02), and fat mass (r = 0.65‐0.84, P < 0.02). Hindmilk GLP‐1 was correlated with infant weight gain from birth to 6 months (r = ?0.67, P = 0.034). Conclusion: The presence of appetite hormones in breast milk may be important in infant appetite and growth regulation. 相似文献
Symptomatic pulmonary embolism (PE) is a major cause of cardiovascular death and morbidity. Estimated prevalence and incidence of atrial fibrillation (AF) in developed countries are between 388–661 per 100,000, and 90–123 per 100,000 person-years respectively. However, the prevalence and incidence of AF in patients presenting with an acute PE and its predictors are not clear.
Methods
Individual patient clinical details were retrieved from a database containing all confirmed acute PE presentations to a tertiary institution from 2001–2012. Prevalence and incidence of AF was tracked from a population registry by systematically searching for AF during any hospital admission (2000–2013) based on International Classification of Disease (ICD-10) code.
Results
Of the 1,142 patients included in this study, 935 (81.9%) had no AF during index PE admission whilst 207 patients had documented baseline AF (prevalence rate 18,126 per 100,000; age-adjusted 4,672 per 100,000). Of the 935 patients without AF, 126 developed AF post-PE (incidence rate 2,778 per 100,000 person-years; age-adjusted 984 per 100,000 person-years). Mean time from PE to subsequent AF was 3.4 ± 2.9 years. Total mortality (mean follow-up 5.0 ± 3.7 years) was 42% (n = 478): 35% (n = 283), 59% (n = 119) and 60% (n = 76) in the no AF, baseline AF and subsequent AF cohorts respectively. Independent predictors for subsequent AF after acute PE include age (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.04–1.08, p<0.001), history of congestive cardiac failure (HR 1.88, 95% CI 1.12–3.16, p = 0.02), diabetes (HR 1.72, 95% CI 1.07–2.77, p = 0.02), obstructive sleep apnea (HR 4.83, 1.48–15.8, p = 0.009) and day-1 serum sodium level during index PE admission (HR 0.94, 95% CI 0.90–0.98, p = 0.002).
Conclusions
Patients presenting with acute PE have a markedly increased age-adjusted prevalence and subsequent incidence of AF. Screening for AF may be of importance post-PE. 相似文献
Detecting loci under selection is an important task in evolutionary biology. In conservation genetics detecting selection is key to investigating adaptation to the spread of infectious disease. Loci under selection can be detected on a spatial scale, accounting for differences in demographic history among populations, or on a temporal scale, tracing changes in allele frequencies over time. Here we use these two approaches to investigate selective responses to the spread of an infectious cancer—devil facial tumor disease (DFTD)—that since 1996 has ravaged the Tasmanian devil (Sarcophilus harrisii). Using time-series ‘restriction site associated DNA’ (RAD) markers from populations pre- and post DFTD arrival, and DFTD free populations, we infer loci under selection due to DFTD and investigate signatures of selection that are incongruent among methods, populations, and times. The lack of congruence among populations influenced by DFTD with respect to inferred loci under selection, and the direction of that selection, fail to implicate a consistent selective role for DFTD. Instead genetic drift is more likely driving the observed allele frequency changes over time. Our study illustrates the importance of applying methods with different performance optima e.g. accounting for population structure and background selection, and assessing congruence of the results. 相似文献
Mutagenesis via treatment of seeds with chemical mutagens such as ethyl methanesulfonate (EMS) has been widely used for crop improvement. However, this approach is not suitable for some crop species such as clonally propagated crops and allogamous perennial plants characteristically with high levels of genome heterozygosity and a long life cycle. Here, we report direct treatment of in vitro-induced peach shoot tip tissues with EMS for generation of mutations in peach, a perennial, woody fruit tree. We optimized EMS dosage and exposure time and found that treatment of the explants with 0.2 % EMS for 16 h was optimal for generation of genetic variations. So far we have generated nearly 2000 peach seedlings. Typical EMS-induced phenotypic variations were present in the seedlings. Next generation sequencing and subsequent data analyses were performed to monitor the efficiency of mutagenesis. The mutation rate was estimated to be one mutation per 150 kilobase pairs in the mutagenized population, suggesting effectiveness of this method in inducing mutagenesis in peach. Taken together, our data open an avenue for the generation of mutant populations suitable for crop improvement in allogamous perennial plants including fruit trees and clonally propagated plants.
Metabolic alterations in prostate cancer (PC) are associated with progression and aggressiveness. However, the underlying mechanisms behind PC metabolic functions are unknown. The authors’ group recently reported on the important role of centromere protein F (CENPF), a protein associated with the centromere–kinetochore complex and chromosomal segregation during mitosis, in PC MRI visibility. This study focuses on discerning the role of CENPF in metabolic perturbation in human PC3 cells. A series of bioinformatics analyses shows that CENPF is one gene that is strongly associated with aggressive PC and that its expression is positively correlated with metastasis. By identifying and reconstructing the CENPF network, additional associations with lipid regulation are found. Further untargeted metabolomics analysis using gas chromatography‐time‐of‐flight‐mass spectrometry reveals that silencing of CENPF alters the global metabolic profiles of PC cells and inhibits cell proliferation, which suggests that CENPF may be a critical regulator of PC metabolism. These findings provide useful scientific insights that can be applied in future studies investigating potential targets for PC treatment. 相似文献
Diffuse reflectance spectroscopy (DRS) is a noninvasive, fast, and low‐cost technology with potential to assist cancer diagnosis. The goal of this study was to test the capability of our physiological model, a computational Monte Carlo lookup table inverse model, for nonmelanoma skin cancer diagnosis. We applied this model on a clinical DRS dataset to extract scattering parameters, blood volume fraction, oxygen saturation and vessel radius. We found that the model was able to capture physiological information relevant to skin cancer. We used the extracted parameters to classify (basal cell carcinoma [BCC], squamous cell carcinoma [SCC]) vs actinic keratosis (AK) and (BCC, SCC, AK) vs normal. The area under the receiver operating characteristic curve achieved by the classifiers trained on the parameters extracted using the physiological model is comparable to that of classifiers trained on features extracted via Principal Component Analysis. Our findings suggest that DRS can reveal physiologic characteristics of skin and this physiologic model offers greater flexibility for diagnosing skin cancer than a pure statistical analysis. Physiological parameters extracted from diffuse reflectance spectra data for nonmelanoma skin cancer diagnosis. 相似文献