Evolution and chemical consequences of lightning-produced NOx observed in the North Atlantic upper troposphere

Airborne observations of NO during the Subsonics Assessment Ozone and Nitrogen Oxides Experiment (SONEX) reveal episodes of high NOx in the upper troposphere believed to be associated with lightning. Linkage to specific periods of lightning activity is possible through back trajectories and data from the National Lightning Detection Network. Lagrangian model calculations are used to explore the evolution of these high NOx plumes over the 1-2 days between their introduction and subsequent sampling by NASA's DC-8 aircraft. Simulations include expected changes in HNO3, H2O2, CH3OOH, HO2, and OH. Depending on the time of injection and dilution rate, initial NOx concentrations are estimated to range from 1 to 7 ppbv. Similar to many previous studies, simulated HNO3 concentrations tend to be greater than observations. Several possible explanations for this difference are explored. H2O2 observations are shown to be consistent with removal in convective activity. While it is possible that upper tropospheric CH3OOH is enhanced by convection, simulations show such increases in CH3OOH can be short-lived (e.g., < 12 hours) with no perceptible trace remaining at the time of sampling. High NO levels further prevent elevated levels of CH3OOH from propagating into increases in H2O2. HO2 is suppressed through reaction with NO in all cases. Simulated increases in OH exceeded a factor of 2 for some cases, but for the highest NOx levels, loss of OH via OH+NO2 offset production from HO2+NO. Additional increases in OH of 30-60% could result from convection of CH3OOH. A final point of discussion concerns how the chemistry within these plumes, their long-range transport, and their potential importance in sustaining background NOx far from source regions present a challenge to global and regional model simulations. Copyright 2000 by the American Geophysical Union

A model independent and rephase invariant parametrization of CP violation

The phenomenological description of the neutral B meson system is proposed in terms of the fundamental CP-violating observables and within a rephasing invariant formalism. This generic formalism can select the time-dependent and time-integrated asymmetries which provide the basic tools to discriminate the different kinds of possible CP-violating effects in dedicated experimental B-meson facilities.Comment: 19 pages, Plain Te

Experiment to Characterize Aircraft Volatile Aerosol and Trace-Species Emissions (EXCAVATE)

The Experiment to Characterize Aircraft Volatile and Trace Species Emissions (EXCAVATE) was conducted at Langley Research Center (LaRC) in January 2002 and focused upon assaying the production of aerosols and aerosol precursors by a modern commercial aircraft, the Langley B757, during ground-based operation. Remaining uncertainty in the postcombustion fate of jet fuel sulfur contaminants, the need for data to test new theories of particle formation and growth within engine exhaust plumes, and the need for observations to develop air quality models for predicting pollution levels in airport terminal areas were the primary factors motivating the experiment. NASA's Atmospheric Effects of Aviation Project (AEAP) and the Ultra Effect Engine Technology (UEET) Program sponsored the experiment which had the specific objectives of determining ion densities; the fraction of fuel S converted from S(IV) to S(VI); the concentration and speciation of volatile aerosols and black carbon; and gas-phase concentrations of long-chain hydrocarbon and PAH species, all as functions of engine power, fuel composition, and plume age

Chronic kidney disease and neurological disorders: are uraemic toxins the missing piece of the puzzle?

Chronic kidney disease (CKD) perturbs the crosstalk with others organs, with the interaction between the kidneys and the heart having been studied most intensively. However, a growing body of data indicates that there is an association between kidney dysfunction and disorders of the central nervous system. In epidemiological studies, CKD is associated with a high prevalence of neurological complications, such as cerebrovascular disorders, movement disorders, cognitive impairment and depression. Along with traditional cardiovascular risk factors (such as diabetes, inflammation, hypertension and dyslipidaemia), non-traditional risk factors related to kidney damage (such as uraemic toxins) may predispose patients with CKD to neurological disorders. There is increasing evidence to show that uraemic toxins, for example indoxyl sulphate, have a neurotoxic effect. A better understanding of factors responsible for the elevated prevalence of neurological disorders among patients with CKD might facilitate the development of novel treatments. Here, we review (i) the potential clinical impact of CKD on cerebrovascular and neurological complications, (ii) the mechanisms underlying the uraemic toxins' putative action (based on pre-clinical and clinical research) and (iii) the potential impact of these findings on patient care

Multi-systemic alterations by chronic exposure to a low dose of bisphenol a in drinking water: Effects on inflammation and nad+-dependent deacetylase sirtuin1 in lactating and weaned rats

Bisphenol A (BPA) is largely used as a monomer in some types of plastics. It accumulates in tissues and fluids and is able to bypass the placental barrier, affecting various organs and systems. Due to huge developmental processes, children, foetuses, and neonates could be more sensitive to BPA-induced toxicity. To investigate the multi-systemic effects of chronic exposure to a low BPA dose (100 µg/L), pregnant Wistar rats were exposed to BPA in drinking water during gestation and lactation. At weaning, newborn rats received the same treatments as dams until sex maturation. Free and conjugated BPA levels were measured in plasma and adipose tissue; the size of cerebral ventricles was analysed in the brain; morpho-functional and molecular analyses were carried out in the liver with a focus on the expression of inflammatory cytokines and Sirtuin 1 (Sirt1). Higher BPA levels were found in plasma and adipose tissue from BPA treated pups (17 PND) but not in weaned animals. Lateral cerebral ventricles were significantly enlarged in lactating and weaned BPA-exposed animals. In addition, apart from microvesicular steatosis, liver morphology did not exhibit any statistically significant difference for morphological signs of inflammation, hypertrophy, or macrovesicular steatosis, but the expression of inflammatory cytokines, Sirt1, its natural antisense long non-coding RNA (Sirt1-AS LncRNA) and histone deacetylase 1 (Hdac1) were affected in exposed animals. In conclusion, chronic exposure to a low BPA dose could increase the risk for disease in adult life as a consequence of higher BPA circulating levels and accumulation in adipose tissue during the neonatal period

Chronic exposure to low dose of bisphenol A impacts on the first round of spermatogenesis via SIRT1 modulation.

Spermatogenesis depends on endocrine, autocrine and paracrine communications along the hypothalamus-pituitary-gonad axis. Bisphenol A (BPA), an estrogen-mimic endocrine disrupting chemical, is an environmental contaminant used to manufacture polycarbonate plastics and epoxy resins with toxic effects for male reproduction. Here we investigated whether the chronic exposure to low BPA doses affects spermatogenesis through the modulation of SIRT1, a NAD+-dependent deacetylase involved in the progression of spermatogenesis, with outcomes on apoptosis, oxidative stress, metabolism and energy homeostasis. BPA exposure via placenta first, and lactation and drinking water later, affected the body weight gain in male offspring at 45 postnatal days and the first round of spermatogenesis, with impairment of blood testis barrier, reactive oxygen species production, DNA damage and decreased expression of SIRT1. The analysis of SIRT1 downstream molecular pathways revealed the increase of acetyl-p53Lys370, γH2AX foci, the decrease of oxidative stress defenses and the higher apoptotic rate in the testis of treated animals, with partial rescue at sex maturation. In conclusion, SIRT1 pathways disruption after BPA exposure can have serious consequences on the first round of spermatogenesis

Neuropeptide Y as a risk factor for cardiorenal disease and cognitive dysfunction in chronic kidney disease: translational opportunities and challenges

Neuropeptide Y (NPY) is a 36-amino-acid peptide member of a family also including peptide YY and pancreatic polypeptide, which are all ligands to Gi/Go coupled receptors. NPY regulates several fundamental biologic functions including appetite/satiety, sex and reproduction, learning and memory, cardiovascular and renal function and immune functions. The mesenteric circulation is a major source of NPY in the blood in man and this peptide is considered a key regulator of gut-brain cross talk. A progressive increase in circulating NPY accompanies the progression of chronic kidney disease (CKD) toward kidney failure and NPY robustly predicts cardiovascular events in this population. Furthermore, NPY is suspected as a possible player in accelerated cognitive function decline and dementia in patients with CKD and in dialysis patients. In theory, interfering with the NPY system has relevant potential for the treatment of diverse diseases from cardiovascular and renal diseases to diseases of the central nervous system. Pharmaceutical formulations for effective drug delivery and cost, as well as the complexity of diseases potentially addressable by NPY/NPY antagonists, have been a problem until now. This in part explains the slow progress of knowledge about the NPY system in the clinical arena. There is now renewed research interest in the NPY system in psychopharmacology and in pharmacology in general and new studies and a new breed of clinical trials may eventually bring the expected benefits in human health with drugs interfering with this system

Cognitive disorders in patients with chronic kidney disease: specificities of clinical assessment

Neurocognitive disorders are frequent among chronic kidney disease (CKD) patients. Identifying and characterizing cognitive impairment (CI) can help to assess the ability of adherence to CKD risk reduction strategy, identify potentially reversible causes of cognitive decline, modify pharmacotherapy, educate the patient and caregiver and provide appropriate patient and caregiver support. Numerous factors are associated with the development and progression of CI in CKD patients and various conditions can influence the results of cognitive assessment in these patients. Here we review clinical warning signs that should lead to cognitive screening; conditions frequent in CKD at risk to interfere with cognitive testing or performance, including specificities of cognitive assessment in dialysis patients or after kidney transplantation; and available tests for screening and observed cognitive patterns in CKD patients

Reversal of <i>MYB </i>-dependent suppression of <i>MAFB </i>expression overrides leukaemia phenotype in MLL-rearranged AML

Abstract The transcription factor MYB plays a pivotal role in haematopoietic homoeostasis and its aberrant expression is involved in the genesis and maintenance of acute myeloid leukaemia (AML). We have previously demonstrated that not all AML subtypes display the same dependency on MYB expression and that such variability is dictated by the nature of the driver mutation. However, whether this difference in MYB dependency is a general trend in AML remains to be further elucidated. Here, we investigate the role of MYB in human leukaemia by performing siRNA-mediated knock-down in cell line models of AML with different driver lesions. We show that the characteristic reduction in proliferation and the concomitant induction of myeloid differentiation that is observed in MLL-rearranged and t(8;21) leukaemias upon MYB suppression is not seen in AML cells with a complex karyotype. Transcriptome analyses revealed that MYB ablation produces consensual increase of MAFB expression in MYB-dependent cells and, interestingly, the ectopic expression of MAFB could phenocopy the effect of MYB suppression. Accordingly, in silico stratification analyses of molecular data from AML patients revealed a reciprocal relationship between MYB and MAFB expression, highlighting a novel biological interconnection between these two factors in AML and supporting new rationales of MAFB targeting in MLL-rearranged leukaemias