Influence of southern hemispheric biomass burning on midtropospheric distributions of nonmethane hydrocarbons and selected halocarbons over the remote South Pacific

Aircraft measurements of nonmethane hydrocarbons (NMHCs) and halocarbons were made over the remote South Pacific Ocean during late August-early October 1996 for NASA's Global Tropospheric Experiment (GTE) Pacific Exploratory Mission-Tropics A (PEM-Tropics A). This paper discusses the large-scale spatial distributions of selected trace gases encountered during PEM-Tropics A. The PEM-Tropics A observations are compared to measurements made over the southwestern pacific in early November 1995 as part of Aerosol Characterization Experiment (ACE 1). Continental pollution in the form of layers containing elevated levels of O3 was observed during a majority of PEM-Tropics flights, as well as during several ACE 1 flights. The chemical composition of these air masses indicates that they were not fresh and were derived from nonurban combustion sources. The substantial impact of biomass burning on the vertical structure of the South Pacific troposphere is discussed. Copyright 1999 by the American Geophysical Union

Two-step OFFGEL approach for effective peptide separation compatible with iTRAQ labeling

Shotgun proteomic analyses are increasingly becoming methods of choice for complex samples. The development of effective methods for fractionating peptides to reduce the complexity of the sample before mass analysis is a key point in this strategy. The OFFGEL technology has recently become a tool of choice in proteomic analysis at peptide level. This OFFGEL electrophoresis (OGE) approach allows the in-solution separation of peptides from various biological sources by isoelectric focusing in highly resolved 24 fractions. It was also demonstrated that OGE technology is a filtering tool for pI-based validation of peptide identification. As peptide OGE is compatible with iTRAQ labeling, OGE is finding valuable applications in quantitative proteomics as well. The aim of this study is to explain a new 2D-OGE approach that improves the proteomic coverage of complex mixtures such as colorectal cell line lysates, and which is compatible with iTRAQ labeling

Burden of treatment for chronic illness: a concept analysis and review of the literature

Context Treatment burden, the burden associated with the treatment and management of chronic illness, has not yet been well articulated. Objective Using Rodgers' (1989, Journal of Advanced Nursing, 14, 330–335) method of concept analysis, this review describes the ways in which treatment burden has been conceptualized to define the concept and to develop a framework for understanding its attributes, antecedents and consequences. Methods Leading databases were searched electronically between the years 2002 and 2011. To ensure the review focused on actual observations of the concept of interest, articles that did not measure treatment burden (either qualitatively or quantitatively) were excluded. An inductive approach was used to identify themes related to the concept of treatment burden. Main results Thirty articles, identified from 1557 abstracts, were included in the review. The attributes of treatment burden include burden as a dynamic process, as a multidimensional concept, and comprising of both subjective and objective elements. Prominent predisposing factors (antecedents) include the person's age and gender, their family circumstances, possible comorbidity, high use of medications, characteristics of treatment and their relationship with their health-care provider. The most dominant consequences are poor health and well-being, non-adherence to treatment, ineffective resource use and burden on significant others. Furthermore, many of these consequences can also become antecedents, reflecting the cyclic and dynamic nature of treatment burden. Conclusion The findings underscore the need for researchers and health-care professionals to engage in collaborative discussions and make cooperative efforts to help alleviate treatment burden and tailor treatment regimens to the realities of people's daily lives

Screening of DUB activity and specificity by MALDI-TOF mass spectrometry

Deubiquitylases (DUBs) are key regulators of the ubiquitin system which cleave ubiquitin moieties from proteins and polyubiquitin chains. Several DUBs have been implicated in various diseases and are attractive drug targets. We have developed a sensitive and fast assay to quantify in vitro DUB enzyme activity using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Unlike other current assays, this method uses unmodified substrates, such as diubiquitin topoisomers. By analyzing 42 human DUBs against all diubiquitin topoisomers we provide an extensive characterization of DUB activity and specificity. Our results confirm the high specificity of many members of the OTU and JAMM DUB families and highlight that all USPs tested display low linkage selectivity. We also demonstrate that this assay can be deployed to assess the potency and specificity of DUB inhibitors by profiling 11 compounds against a panel of 32 DUBs

Assessment of the proliferative, apoptotic and cellular renovation indices of the human mammary epithelium during the follicular and luteal phases of the menstrual cycle

Introduction During the menstrual cycle, the mammary gland goes through sequential waves of proliferation and apoptosis. in mammary epithelial cells, hormonal and non-hormonal factors regulate apoptosis. To determine the cyclical effects of gonadal steroids on breast homeostasis, we evaluated the apoptotic index ( AI) determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling ( TUNEL) staining in human mammary epithelial cells during the spontaneous menstrual cycle and correlated it with cellular proliferation as determined by the expression of Ki-67 during the same period.Methods Normal breast tissue samples were obtained from 42 randomly selected patients in the proliferative ( n = 21) and luteal ( n = 21) phases. Menstrual cycle phase characterization was based on the date of the last and subsequent menses, and on progesterone serum levels obtained at the time of biopsy.Results the proliferation index ( PI), defined as the number of Ki-67-positive nuclei per 1,000 epithelial cells, was significantly larger in the luteal phase (30.46) than in the follicular phase (13.45; P = 0.0033). the AI was defined as the number of TUNEL-positive cells per 1,000 epithelial cells. the average AI values in both phases of the menstrual cycle were not statistically significant ( P = 0.21). However, the cell renewal index ( CRI = PI/AI) was significantly higher in the luteal phase ( P = 0.033). A significant cyclical variation of PI, AI and CRI was observed. PI and AI peaks occurred on about the 24th day of the menstrual cycle, whereas the CRI reached higher values on the 28th day.Conclusions We conclude that proliferative activity is dependent mainly on hormonal fluctuations, whereas apoptotic activity is probably regulated by hormonal and non-hormonal factors.Universidade Federal de São Paulo, Dept Gyneol, Mastol Div, São Paulo, BrazilStanford Univ, Sch Med, Dept Neurosurg, Stanford, CA 94305 USAAPC Pathol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Gyneol, Mastol Div, São Paulo, BrazilWeb of Scienc

Mathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms

Cancer cells depend on transcription of telomerase reverse transcriptase (TERT). Many transcription factors affect TERT, though regulation occurs in context of a broader network. Network effects on telomerase regulation have not been investigated, though deeper understanding of TERT transcription requires a systems view. However, control over individual interactions in complex networks is not easily achievable. Mathematical modelling provides an attractive approach for analysis of complex systems and some models may prove useful in systems pharmacology approaches to drug discovery. In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their respective promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analysed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR analysis of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3′-oxime (BIO) predicted unstable TERT repression dependent on noise and expression of JUN, corresponding with observations from a previous study. MYC expression is critical in TERT activation in the model, consistent with its well known function in endogenous TERT regulation. Loss of MYC caused complete TERT suppression in our model, substantially rescued only by co-suppression of AR. Interestingly expression was easily rescued under modelled Ets-factor gain of function, as occurs in TERT promoter mutation. RNAi targeting AR, JUN, MXD1, SP3, or TP53, showed that AR suppression does rescue endogenous TERT expression following MYC knockdown in these cells and SP3 or TP53 siRNA also cause partial recovery. The model therefore successfully predicted several aspects of TERT regulation including previously unknown mechanisms. An extrapolation suggests that a dominant stimulatory system may programme TERT for transcriptional stability

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

S

Proteomic identification and characterization of hepatic glyoxalase 1 dysregulation in non-alcoholic fatty liver disease

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. However, its molecular pathogenesis is incompletely characterized and clinical biomarkers remain scarce. The aims of these experiments were to identify and characterize liver protein alterations in an animal model of early, diet-related, liver injury and to assess novel candidate biomarkers in NAFLD patients. Methods: Liver membrane and cytosolic protein fractions from high fat fed apolipoprotein E knockout (ApoE−/−) animals were analyzed by quantitative proteomics, utilizing isobaric tags for relative and absolute quantitation (iTRAQ) combined with nano-liquid chromatography and tandem mass spectrometry (nLC-MS/MS). Differential protein expression was confirmed independently by immunoblotting and immunohistochemistry in both murine tissue and biopsies from paediatric NAFLD patients. Candidate biomarkers were analyzed by enzyme-linked immunosorbent assay in serum from adult NAFLD patients. Results: Through proteomic profiling, we identified decreased expression of hepatic glyoxalase 1 (GLO1) in a murine model. GLO1 protein expression was also found altered in tissue biopsies from paediatric NAFLD patients. In vitro experiments demonstrated that, in response to lipid loading in hepatocytes, GLO1 is first hyperacetylated then ubiquitinated and degraded, leading to an increase in reactive methylglyoxal. In a cohort of 59 biopsy-confirmed adult NAFLD patients, increased serum levels of the primary methylglyoxal-derived advanced glycation endproduct, hydroimidazolone (MG-H1) were significantly correlated with body mass index (r = 0.520, p < 0.0001). Conclusion: Collectively these results demonstrate the dysregulation of GLO1 in NAFLD and implicate the acetylation-ubquitination degradation pathway as the functional mechanism. Further investigation of the role of GLO1 in the molecular pathogenesis of NAFLD is warranted. Keywords: Non-alcoholic fatty liver disease, Glyoxalase, Methylglyoxal, Proteomics, iTRA

Tests of Lorentz symmetry using antihydrogen

Signals of CPT and Lorentz violation are possible in the context of spectroscopy using hydrogen and antihydrogen. We apply the Standard-Model Extension, a broad framework for Lorentz breaking in physics, to various transitions in the hydrogen and antihydrogen spectra. The results show an unsuppressed effect in the transition between the upper two hyperfine sublevels of the ground state of these systems. We also discuss related tests in Penning traps, and recent work on Lorentz violation in curved spacetime.Comment: 11pp, invited talk at PQE 37 Conference, Snowbird, Utah, USA, 2-6 Jan 200