286 research outputs found
Atopic children with cystic fibrosis have increased urinary leukotriene E<sub>4</sub> concentrations and more severe pulmonary disease
No full textBackground: We investigated the hypothesis that cysteinyl leukotriene (LT) production is altered in atopic patients with cystic fibrosis (CF). Methods: Urinary LTE4 was measured in two groups of children with CF: atopic (ACF group, n = 22) and nonatopic (NACF group, n = 13); and in two groups of unaffected children, those with atopic asthma (AA group, n = 11) and nonatopic normal control subjects (NN group, n = 12). Results: Atopic groups excreted significantly more urinary LTE4 (geometric means [95% confidence intervals] in picomoles per millimole creatinine), ACF group: 104 (73-147) and AA group: 195 (136-282) compared with NACF group: 19 (9-39) and NN group: 27 (15-48). The ACF group had significantly more airflow obstruction than the NACF group, with forced expiratory volume in 1 second (percent predicted, mean ± SD) in ACF: 58 ± 21 versus NACF: 81 ± 23, and forced vital capacity (percent predicted, mean ± SD) 72 ± 17 versus 87 ± 23, respectively. There were significant correlations between the degree of airflow obstruction, bronchodilator responsiveness, and urinary LTE4 concentration within the entire CF group. We used multiple regression analysis to assess the respective influence of age, atopy, sensitization to Aspergillus fumigatus, and colonization with Pseudomonas aeruginosa on urinary LTE4 concentration. The atopic state was the only significant variable associated with urinary LTE4 production in subjects with CF. Conclusions: The similarities in urinary LTE4 between ACF and AA groups suggest that the atopic state is the prime determinant of urinary LTE4 excretion. Enhanced cysteinyl LT production associated with atopy in CF may increase the severity of pulmonary disease.</p
Sputum tumour necrosis factor-alpha and leukotriene concentrations in cystic fibrosis.
No full textIt is postulated that a vigorous host inflammatory response in the cystic fibrosis lung contributes to lung injury. Tumour necrosis factor-α (TNF-α) may play a part in that process and in the generation of leukotrienes. Therefore, the relationships between sputum TNF-α, leukotriene concentration, and lung function abnormalities in 16 children with cystic fibrosis were investigated. Each subject provided sputum samples and performed spirometry. TNF-α was measured by enzyme linked immunosorbent assay; individual leukotrienes were separated using high performance liquid chromatography and quantified by radioimmunoassay. The geometric mean concentration of TNF-α was 129.7 pg/ml and 95% confidence interval 48.2 to 348.3. Mean (SEM) leukotriene B4 (LTB4) was 97.8 (22.9) pmol/g and total cysteinyl leukotrienes were 60.9 (14.8) pmol/g. Mean (SD) forced expiratory volume in one second (FEV1) of the group was 53 (15)% of predicted and forced vital capacity (FVC) was 65 (14)% of predicted. There was a significant positive correlation between TNF-α and both LTB4 and the total cysteinyl leukotriene sputum content. An inverse relationship existed between TNF-α and FEV1 and FVC. Moreover, a negative correlation was observed between sputum LTB4 and FEV1 and FVC. These results suggest that TNF-α and the leukotrienes may participate in the airways inflammation and airflow obstruction observed in cystic fibrosis subjects and support the hypothesis that TNF-α. upregulates the 5-lipoxygenase pathway in vivo.</p
The DNA methylome of human sperm is distinct from blood with little evidence for tissue-consistent obesity associations
No full textEpidemiological research suggests that paternal obesity may increase the risk of fathering small for gestational age offspring. Studies in non-human mammals indicate that such associations could be mediated by DNA methylation changes in spermatozoa that influence offspring development in utero. Human obesity is associated with differential DNA methylation in peripheral blood. It is unclear, however, whether this differential DNA methylation is reflected in spermatozoa. We profiled genome-wide DNA methylation using the Illumina MethylationEPIC array in a cross-sectional study of matched human blood and sperm from lean (discovery n = 47; replication n = 21) and obese (n = 22) males to analyse tissue covariation of DNA methylation, and identify obesity-associated methylomic signatures. We found that DNA methylation signatures of human blood and spermatozoa are highly discordant, and methylation levels are correlated at only a minority of CpG sites (~1%). At the majority of these sites, DNA methylation appears to be influenced by genetic variation. Obesity-associated DNA methylation in blood was not generally reflected in spermatozoa, and obesity was not associated with altered covariation patterns or accelerated epigenetic ageing in the two tissues. However, one cross-tissue obesity-specific hypermethylated site (cg19357369; chr4:2429884; P = 8.95 × 10^{-8}; 2% DNA methylation difference) was identified, warranting replication and further investigation. When compared to a wide range of human somatic tissue samples (n = 5,917), spermatozoa displayed differential DNA methylation across pathways enriched in transcriptional regulation. Overall, human sperm displays a unique DNA methylation profile that is highly discordant to, and practically uncorrelated with, that of matched peripheral blood. We observed that obesity was only nominally associated with differential DNA methylation in sperm, and therefore suggest that spermatozoal DNA methylation is an unlikely mediator of intergenerational effects of metabolic traits
Histone lactylation: a new epigenetic mark in the malaria parasite Plasmodium
No full textEpigenetic processes play important roles in the biology of the malaria parasite Plasmodium falciparum. Here, we characterised a new epigenetic mark, histone lactylation, for the first time in Plasmodium: it was found in two human malaria parasites, P. falciparum and P. knowlesi, and also in vivo in two rodent malaria models, P. yoelii and P. berghei. Histones were increasingly lactylated in response to elevated lactate levels in vitro and in vivo, making this mark uniquely well-placed to act as a metabolic sensor, since severe falciparum malaria characteristically leads to hyperlactataemia in the human host. Mass spectrometry showed that lysines on several parasite histones could be lactylated, as well as many non-histone chromatin proteins. Histone lactylation was less abundant and less inducible in P. knowlesi than P. falciparum, suggesting that P. falciparum may have evolved particular epigenetic responses to this characteristic feature of its pathology. Finally, in the rodent model P. yoelii, hyperlactataemia correlated with parasite transcriptomic programmes that suggested metabolic ‘dormancy’
Novel DNA methylation profiles associated with key gene regulation and transcription pathways in blood and placenta of growth-restricted neonates
No full textFetal growth is determined by the feto-placental genome interacting with the maternal in utero environment. Failure of this interplay leads to poor placental development and fetal growth restriction (FGR), which is associated with future metabolic disease. We investigated whether whole genome methylation differences existed in umbilical cord blood and placenta, between gestational-matched, FGR, and appropriately grown (AGA) neonates. Using the Infinium HumanMethylation450 BeadChip®, we found that DNA from umbilical cord blood of FGR born at term (n = 19) had 839 differentially methylated positions (DMPs) that reached genome-wide significance compared with AGA (n = 18). Using gestational age as a continuous variable, we identified 76,249 DMPs in cord blood (adj. P 10% and 25 genes were co-methylated more than twice within 1000 base pairs. Gene Ontology (GO) analysis of DMPs supported their involvement in gene regulation and transcription pathways related to organ development and metabolic function. A similar profile of DMPs was found across different cell types in the cord blood. At term, no DMPs between FGR and AGA placentae reached genome-wide significance, validated with an external dataset. GO analysis of 284 pre-term, placental DMPs associated with autophagy, oxidative stress and hormonal responses. Growth restricted neonates have distinct DNA methylation profiles in pre-term placenta and in cord blood at birth, which may predispose to future adult disease
Global and regional emission estimates for HCFC-22
No full textHCFC-22 (CHClF[subscript 2], chlorodifluoromethane) is an ozone-depleting substance (ODS) as well as a significant greenhouse gas (GHG). HCFC-22 has been used widely as a refrigerant fluid in cooling and air-conditioning equipment since the 1960s, and it has also served as a traditional substitute for some chlorofluorocarbons (CFCs) controlled under the Montreal Protocol. A low frequency record on tropospheric HCFC-22 since the late 1970s is available from measurements of the Southern Hemisphere Cape Grim Air Archive (CGAA) and a few Northern Hemisphere air samples (mostly from Trinidad Head) using the Advanced Global Atmospheric Gases Experiment (AGAGE) instrumentation and calibrations. Since the 1990s high-frequency, high-precision, in situ HCFC-22 measurements have been collected at these AGAGE stations. Since 1992, the Global Monitoring Division of the National Oceanic and Atmospheric Administration/Earth System Research Laboratory (NOAA/ESRL) has also collected flasks on a weekly basis from remote sites across the globe and analyzed them for a suite of halocarbons including HCFC-22. Additionally, since 2006 flasks have been collected approximately daily at a number of tower sites across the US and analyzed for halocarbons and other gases at NOAA. All results show an increase in the atmospheric mole fractions of HCFC-22, and recent data show a growth rate of approximately 4% per year, resulting in an increase in the background atmospheric mole fraction by a factor of 1.7 from 1995 to 2009. Using data on HCFC-22 consumption submitted to the United Nations Environment Programme (UNEP), as well as existing bottom-up emission estimates, we first create globally-gridded a priori HCFC-22 emissions over the 15 yr since 1995. We then use the three-dimensional chemical transport model, Model for Ozone and Related Chemical Tracers version 4 (MOZART v4), and a Bayesian inverse method to estimate global as well as regional annual emissions. Our inversion indicates that the global HCFC-22 emissions have an increasing trend between 1995 and 2009. We further find a surge in HCFC-22 emissions between 2005 and 2009 from developing countries in Asia – the largest emitting region including China and India. Globally, substantial emissions continue despite production and consumption being phased out in developed countries currently.NASA Upper Atmospheric Research Program (Grant NNX11AF17G
Emissions of ozone-depleting halocarbons from China
No full textNational emission inventories of ozone-depleting substances (ODS) play a key role in the control mechanisms of the Montreal Protocol's emission reduction plans. New quasi-continuous ground-based atmospheric measurements allow us to estimate China's current emissions of the most effective ODS. This serves as an independent validation of China's ODS consumption data reported to the United Nations Environment Programme (UNEP). Emissions of most first-generation ODS have declined in recent years, suggesting compliance with the regulations of China's advanced phase-out program. In contrast the emissions of some second-generation ODS have increased. Because China is currently one of the largest consumers of first generation ODS, the country's upcoming complete phase-out will be crucial for the rate of decline of atmospheric ODS hence the eventual recovery of the stratospheric ozone. Citation: Vollmer, M. K., et al. (2009), Emissions of ozone-depleting halocarbons from China, Geophys. Res. Lett., 36, L15823, doi:10.1029/2009GL038659
338. Comparing characteristics and survival outcomes of adolescent and young adults to mature patients with colorectal cancer
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