A broadband cavity-enhanced spectrometer for atmospheric trace gas measurements and Rayleigh scattering cross sections in the cyan region (470–540 nm)

An incoherent broadband cavity-enhanced absorption spectroscopy (IBBCEAS) instrument for quantification of atmospheric trace gases that absorb in the cyan region of the electromagnetic spectrum (470 to 540&thinsp;nm), including NO2 and I2, is described. The instrument uses a light-emitting diode coupled to a 1&thinsp;m optical cavity consisting of a pair of mirrors in stable resonator configuration. Transmitted light is monitored using a grating spectrometer and charge-coupled device array detector. The average mirror reflectivity was determined from the N2∕He and Ar∕He ratios of scattering coefficients and was ∼99.98&thinsp;% at its maximum, yielding an effective optical path length of 6.3&thinsp;km. Cross sections of N2, O2, air, Ar, CO2, and CH4 scattering and of O4 absorption were measured and agree with literature values within the measurement uncertainty. Trace gas mixing ratios were retrieved using the spectral fitting software DOASIS (DOAS intelligent system) from 480 to 535&thinsp;nm. Under laboratory conditions, the 60&thinsp;s, 1σ measurement precisions were ±124 and ±44&thinsp;pptv for NO2 and I2, respectively. The IBBCEAS instrument sampled ambient air in Ucluelet, BC, Canada, in July 2015. IBBCEAS retrievals agreed with independent measurements of NO2 by blue diode laser cavity ring-down spectroscopy (r2=0.975), but ambient I2 concentrations were below the detection limit.</p

Pathogenic Connexin-31 Forms Constitutively Active Hemichannels to Promote Necrotic Cell Death

Mutations in Connexin-31 (Cx31) are associated with multiple human diseases including erythrokeratodermia variabilis (EKV). The molecular action of Cx31 pathogenic mutants remains largely elusive. We report here that expression of EKV pathogenic mutant Cx31R42P induces cell death with necrotic characteristics. Inhibition of hemichannel activity by a connexin hemichannel inhibitor or high extracellular calcium suppresses Cx31R42P-induced cell death. Expression of Cx31R42P induces ER stress resulting in reactive oxygen species (ROS) production, in turn, to regulate gating of Cx31R42P hemichannels and Cx31R42P induced cell death. Moreover, Cx31R42P hemichannels play an important role in mediating ATP release from the cell. In contrast, no hemichannel activity was detected with cells expressing wildtype Cx31. Together, the results suggest that Cx31R42P forms constitutively active hemichannels to promote necrotic cell death. The Cx31R42P active hemichannels are likely resulted by an ER stress mediated ROS overproduction. The study identifies a mechanism of EKV pathogenesis induced by a Cx31 mutant and provides a new avenue for potential treatment strategy of the disease

Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells

Cellular functions accompanying establishment of premature senescence in methotrexate-treated human colon cancer C85 cells are deciphered in the present study from validated competitive expression microarray data, analyzed with the use of Ingenuity Pathways Analysis (IPA) software. The nitrosative/oxidative stress, inferred from upregulated expression of inducible nitric oxide synthase (iNOS) and mitochondrial dysfunction-associated genes, including monoamine oxidases MAOA and MAOB, β-amyloid precursor protein (APP) and presenilin 1 (PSEN1), is identified as the main determinant of signaling pathways operating during senescence establishment. Activation of p53-signaling pathway is found associated with both apoptotic and autophagic components contributing to this process. Activation of nuclear factor κB (NF-κB), resulting from interferon γ (IFNγ), integrin, interleukin 1β (IL-1β), IL-4, IL-13, IL-22, Toll-like receptors (TLRs) 1, 2 and 3, growth factors and tumor necrosis factor (TNF) superfamily members signaling, is found to underpin inflammatory properties of senescent C85 cells. Upregulation of p21-activated kinases (PAK2 and PAK6), several Rho molecules and myosin regulatory light chains MYL12A and MYL12B, indicates acquisition of motility by those cells. Mitogen-activated protein kinase p38 MAPK β, extracellular signal-regulated kinases ERK2 and ERK5, protein kinase B AKT1, as well as calcium, are identified as factors coordinating signaling pathways in senescent C85 cells

Deficient activation of CD95 (APO-1/ Fas)-mediated apoptosis: a potential factor of multidrug resistance in human renal cell carcinoma

The pronounced resistance of human renal cell carcinoma (RCC) to anticancer-induced apoptosis has primarily been related to the expression of P-glycoprotein and effective drug detoxification mechanisms. Because the CD95 system has recently been identified as a key mediator of anticancer drug-induced apoptosis, we analysed the contribution of the CD95 system to chemotherapy-induced apoptosis in four newly established RCC cell lines. Here, we demonstrate that all RCC cell lines expressed CD95-receptor and -ligand. Exposure to agonistic anti-CD95 antibodies resulted in induction of apoptosis and significant (P< 0.05) reduction of cell number in three out of four cell lines, indicating that the essential components for CD95-mediated apoptosis were present and functionally intact in the majority of these RCC cell lines. Moreover, treatment of cultures with bleomycin or topotecan, a novel topoisomerase I inhibitor with little substrate affinity for P-glycoprotein, led to induction of apoptosis and significant (P< 0.05) dose-dependent reduction of cell number in all RCC cell lines. Both anticancer drugs also induced upregulation of CD95 ligand expression in all cell lines. Additionally, augmentation of CD95 receptor expression was found in three RCC cell lines, including one p53-mutated cell line, whereas another p53-mutated cell line showed no or only a weak CD95 receptor upregulation after exposure to topotecan or bleomycin, respectively. Despite this upregulation of CD95 receptor and ligand, antagonistic antibodies directed against CD95 receptors or ligands could not inhibit induction of apoptosis by topotecan and bleomycin in any cell line. Thus, although a functionally intact CD95 signalling cascade is present in most RCC cell lines, the anticancer drugs topotecan and bleomycin that induce upregulation of CD95 receptor and ligand fail to effectively activate CD95-mediated apoptosis. This deficient activation of CD95-mediated apoptosis might be an important additional factor for the multidrug resistance phenotype of human RCCs. © 2000 Cancer Research Campaig

Nitrate radicals and biogenic volatile organic compounds: Oxidation, mechanisms, and organic aerosol

Oxidation of biogenic volatile organic compounds (BVOC) by the nitrate radical (NO3) represents one of the important interactions between anthropogenic emissions related to combustion and natural emissions from the biosphere. This interaction has been recognized for more than 3 decades, during which time a large body of research has emerged from laboratory, field, and modeling studies. NO3-BVOC reactions influence air quality, climate and visibility through regional and global budgets for reactive nitrogen (particularly organic nitrates), ozone, and organic aerosol. Despite its long history of research and the significance of this topic in atmospheric chemistry, a number of important uncertainties remain. These include an incomplete understanding of the rates, mechanisms, and organic aerosol yields for NO3-BVOC reactions, lack of constraints on the role of heterogeneous oxidative processes associated with the NO3 radical, the difficulty of characterizing the spatial distributions of BVOC and NO3 within the poorly mixed nocturnal atmosphere, and the challenge of constructing appropriate boundary layer schemes and non-photochemical mechanisms for use in state-of-The-Art chemical transport and chemistry-climate models. This review is the result of a workshop of the same title held at the Georgia Institute of Technology in June 2015. The first half of the review summarizes the current literature on NO3-BVOC chemistry, with a particular focus on recent advances in instrumentation and models, and in organic nitrate and secondary organic aerosol (SOA) formation chemistry. Building on this current understanding, the second half of the review outlines impacts of NO3-BVOC chemistry on air quality and climate, and suggests critical research needs to better constrain this interaction to improve the predictive capabilities of atmospheric models.The authors acknowledge support from the International Global Atmospheric Chemistry project (IGAC), the US National Science Foundation (NSF grants AGS-1541331 and AGS-1644979), and Georgia Tech College of Engineering and College of Sciences for support of the workshop on nitrate radicals and biogenic hydrocarbons that led to this review article. N. L. Ng acknowledges support from NSF CAREER AGS-1555034 and US Environmental Protection Agency STAR (Early Career) RD-83540301. S. S. Brown acknowledges support from the NOAA Atmospheric Chemistry, Carbon Cycle and Climate program. A. T. Archibald and B. Ouyang thank NERC for funding through NE/M00273X/1. E. Atlas acknowledges NSF grant AGS-0753200. R. C. Cohen acknowledges NSF grant AGS-1352972. J. N. Crowley acknowledges the Max Planck Society. J. L. Fry, D. A. Day, and J. L. Jimenez acknowledge support from the NOAA Climate Program Office’s AC4 program, award no. NA13OAR4310063 (Colorado)/NA13OAR4310070 (Reed). N. M. Donahue acknowledges NSF AGS-1447056. M. I. Guzman wishes to acknowledge support from NSF CAREER award (CHE-1255290). J. L. Jimenez and D. A. Day acknowledge support from NSF AGS-1360834 and EPA 83587701-0. R. McLaren acknowledges NSERC grant RGPIN/183982-2012. H. Herrmann, A. Tilgner, and A. Mutzel acknowledge the DARK KNIGHT project funded by DFG under HE 3086/25-1. B. Picquet-Varrault acknowledges support from the French National Agency for Research (project ONCEM-ANR-12-BS06-0017-01). R. H. Schwantes acknowledges NSF AGS-1240604. Y. Rudich and S. S. Brown acknowledge support from the USA-Israel Binational Science Foundation (BSF) grant no. 2012013. Y. Rudich acknowledges support from the Henri Gutwirth Foundation. J. Mao acknowledges support from the NOAA Climate Program Office grant no. NA13OAR4310071. J. A. Thornton acknowledges support from NSF AGS 1360745. B. H. Lee was supported by the NOAA Climate and Global Change Postdoctoral Fellowship. R. A. Zaveri acknowledges support from the US Department of Energy (DOE) Atmospheric System Research (ASR) program under contract DE-AC06-76RLO 1830 at Pacific Northwest National Laboratory