Assessing Volcanic Controls on Miocene Climate Change

The Miocene period saw substantially warmer Earth surface temperatures than today, particularly during a period of global warming called the Mid Miocene Climatic Optimum (MMCO; ∼17–15 Ma). However, the long-term drivers of Miocene climate remain poorly understood. By using a new continuous climate-biogeochemical model (SCION), we can investigate the interaction between volcanism, climate and biogeochemical cycles through the Miocene. We identify high tectonic CO2 degassing rates and further emissions associated with the emplacement of the Columbia River Basalt Group as the primary driver of the background warmth and the MMCO respectively. We also find that enhanced weathering of the basaltic terrane and input of explosive volcanic ash to the oceans are not sufficient to drive the immediate cooling following the MMCO and suggest that another mechanism, perhaps the change in ocean chemistry due to massive evaporite deposition, was responsible

Psychometric properties of burnout measures: a systematic review.

Occupational Burnout (OB) is currently measured through several Patient-Reported Outcome Measures (PROMs) and some of them have become widely used in occupational health research and practice. We, therefore, aimed to review and grade the psychometric validity of the five OB PROMs considered as valid for OB measure in mental health professionals (the Maslach Burnout Inventory (MBI), the Pines' Burnout Measure (BM), the Psychologist Burnout Inventory (PBI), the OLdenburg Burnout Inventory (OLBI) and the Copenhagen Burnout Inventory (CBI)). We conducted systematic literature searches in MEDLINE, PsycINFO and EMBASE databases. We reviewed studies published between January 1980 and September 2018 following a methodological framework, in which each step of PROM validation, the reference method, analytical technics and result interpretation criteria were assessed. Using the COnsensus-based Standards for the selection of health Measurement Instruments we evaluated the risk of bias in studies assessing content and criterion validity, structural validity, internal consistency, reliability, measurement error, hypotheses testing and responsiveness of each PROM. Finally, we assessed the level of evidence for the validity of each PROM using the GRADE approach. We identified 6541 studies, 19 of which were included for review. Fifteen studies dealt with MBI whereas BM, PBI, OLBI and CBI were each examined in only one study. OLBI had the most complete validation, followed by CBI, MBI, BM and PBI, respectively. When examining the result interpretation correctness, the strongest disagreement was observed for MBI (27% of results), BM (25%) and CBI (17%). There was no disagreement regarding PBI and OLBI. For OLBI and CBI, the quality of evidence for sufficient content validity, the crucial psychometric property, was moderate; for MBI, BM and PBI, it was very low. To be validly and reliably used in medical research and practice, PROM should exhibit robust psychometric properties. Among the five PROMs reviewed, CBI and, to a lesser extent, OLBI meet this prerequisite. The cross-cultural validity of these PROMs was beyond the scope of our work and should be addressed in the future. Moreover, the development of a diagnostic standard for OB would be helpful to assess the sensitivity and specificity of the PROMs and further reexamine their validity.The study protocol was registered in PROSPERO (CRD 42019124621)

Effect of Chemical Mutagens and Carcinogens on Gene Expression Profiles in Human TK6 Cells

Characterization of toxicogenomic signatures of carcinogen exposure holds significant promise for mechanistic and predictive toxicology. In vitro transcriptomic studies allow the comparison of the response to chemicals with diverse mode of actions under controlled experimental conditions. We conducted an in vitro study in TK6 cells to characterize gene expression signatures of exposure to 15 genotoxic carcinogens frequently used in European industries. We also examined the dose-responsive changes in gene expression, and perturbation of biochemical pathways in response to these carcinogens. TK6 cells were exposed at 3 dose levels for 24 h with and without S9 human metabolic mix. Since S9 had an impact on gene expression (885 genes), we analyzed the gene expression data from cells cultures incubated with S9 and without S9 independently. The ribosome pathway was affected by all chemical-dose combinations. However in general, no similar gene expression was observed among carcinogens. Further, pathways, i.e. cell cycle, DNA repair mechanisms, RNA degradation, that were common within sets of chemical-dose combination were suggested by clustergram. Linear trends in dose–response of gene expression were observed for Trichloroethylene, Benz[a]anthracene, Epichlorohydrin, Benzene, and Hydroquinone. The significantly altered genes were involved in the regulation of (anti-) apoptosis, maintenance of cell survival, tumor necrosis factor-related pathways and immune response, in agreement with several other studies. Similarly in S9+ cultures, Benz[a]pyrene, Styrene and Trichloroethylene each modified over 1000 genes at high concentrations. Our findings expand our understanding of the transcriptomic response to genotoxic carcinogens, revealing the alteration of diverse sets of genes and pathways involved in cellular homeostasis and cell cycle control

Epigenetic Factors in Cancer Risk: Effect of Chemical Carcinogens on Global DNA Methylation Pattern in Human TK6 Cells

In the current study, we assessed the global DNA methylation changes in human lymphoblastoid (TK6) cells in vitro in response to 5 direct and 10 indirect-acting genotoxic agents. TK6 cells were exposed to the selected agents for 24 h in the presence and/or absence of S9 metabolic mix. Liquid chromatography-mass spectrometry was used for quantitative profiling of 5-methyl-2′-deoxycytidine. The effect of exposure on 5-methyl-2′-deoxycytidine between control and exposed cultures was assessed by applying the marginal model with correlated residuals on % global DNA methylation data. We reported the induction of global DNA hypomethylation in TK6 cells in response to S9 metabolic mix, under the current experimental settings. Benzene, hydroquinone, styrene, carbon tetrachloride and trichloroethylene induced global DNA hypomethylation in TK6 cells. Furthermore, we showed that dose did not have an effect on global DNA methylation in TK6 cells. In conclusion we report changes in global DNA methylation as an early event in response to agents traditionally considered as genotoxic

Prenatal exposures and exposomics of asthma

This review examines the causal investigation of preclinical development of childhood asthma using exposomic tools. We examine the current state of knowledge regarding early-life exposure to non-biogenic indoor air pollution and the developmental modulation of the immune system. We examine how metabolomics technologies could aid not only in the biomarker identification of a particular asthma phenotype, but also the mechanisms underlying the immunopathologic process. Within such a framework, we propose alternate components of exposomic investigation of asthma in which, the exposome represents a reiterative investigative process of targeted biomarker identification, validation through computational systems biology and physical sampling of environmental medi

Isotopic constraints on the Cenozoic evolution of the carbon cycle

In the last few years, several models have been built to explore the Cenozoic evolution of the carbon and strontium cycles. Of particular interest is the study of the impact on the carbon cycle of major mountain uplifts such as the Himalayan orogeny. To explain the Cenozoic increase in the measured seawater strontium isotopic ratio, it was recently proposed that the Himalyan uplift could be responsible for an enhanced consumption of atmospheric CO2 by continental silicate weathering. Here, a new model of the carbon cycle evolution over Cenozoic times is presented. It calculates the various fluxes involved in the organic and inorganic components of the carbon cycle from the seawater delta C-13, the biological isotopic fractionation in the ocean and the seafloor spreading rate. The model equilibrates the budgets of the carbon and alkalinity cycles on the million year timescale, assuming as many previous investigators that the system remains close to equilibrium. The validity of this equilibrium approximation is examined critically. Various sensitivity experiments are performed in order to test the impact of the model parameters on the results. The calculated history of the carbonate deposition rate is consistent with the available reconstruction. The continental silicate weathering rate calculated by the model appears to be widely insensitive to the model parameters, showing three distinct evolutions over the Cenozoic. The model indeed suggests a time of relative constancy of the silicate weathering flux before 40 Ma, followed by a period of slow decrease until 15 Ma and finally a marked increase up to the present. In a progressively cooler world, this evolution may be interpreted as a change from a 'chemically' controlled to a 'physically' controlled weathering regime. The evolution of continental silicate weathering thus partly appears decoupled from the increase in the observed seawater strontium isotopic ratio. For this reason, the evolution of the calculated riverine Sr-87/ Sr-86 ratio shows a strong increase over the Cenozoic, from about 0.710 to 0.712. However, this increase may largely be reduced by considering the recycling of a pelagic carbonate reservoir increasing over the Cenozoic or by assuming that seafloor basalt weathering is a CO2- or climate-dependent process. (C) 1998 Elsevier Science B.V. All rights reserved

The Cenozoic evolution of the strontium and carbon cycles: Relative importance of continental erosion and mantle exchanges

The past variations of the seawater Sr-87/Sr-86 isotopic ratio are related to changes in the relative contribution of the mantle Sr input to the ocean and the Sr supply from continental weathering. Recently, it has been postulated that the Cenozoic increase in the seawater Sr-87/Sr-86 isotopic ratio was associated with the uplift of the Himalayan and Andean mountains at that time. These orogenies may have changed the Sr isotopic ratio of the continental rocks undergoing weathering (as a result of extensive metamorphism), increased the river flux of Sr through enhanced weathering in these regions and possibly caused the global climatic cooling trend of the Cenozoic. A model of the major geochemical cycles coupled to an energy balance climate model is used to explore the possible causes of the Mesozoic-Cenozoic fluctuations in the seawater Sr-87/Sr-86 isotopic ratio. The contribution of the mantle exchanges at mid-ocean ridges, of the recycling of seafloor carbonates through plate margin volcanism and of the alteration of seafloor basalts to the fluctuations of the seawater Sr-87/Sr-86 isotopic ratio are studied. Finally, this model tentatively describes the impact of the Himalayan orogeny on the geochemical cycles of Sr and C. Some possible effects of the extensive metamorphism associated with the India-Asia collision and of the Himalayan uplift are modelled. The model reproduces the Cenozoic increase of the seawater Sr-87/Sr-86 isotopic ratio. However, the impact of the Himalayan orogeny on the C cycle appears to be limited and insufficient to generate the global climatic cooling of the Cenozoic. Rather, in the model, the Cenozoic cooling is mostly due to the reduction of the CO2 emission from mid-ocean ridge volcanism and to changes in the chemical weathering rates in the rest of the world excluding the Himalayas

Balancing the Cenozoic carbon and alkalinity cycles: Constraints from isotopic records

A simple model of the carbon, alkalinity and strontium cycles is built up and used to interpret the carbon and strontium isotopic evolution of seawater over the Cenozoic as recorded in marine limestones. The idea that weathering fluxes have increased globally over the Cenozoic in response to the Himalayan uplift is critically examined. It is shown that such an increase of global weathering, postulated to explain the sharp increase in the Sr-87/Sr-86 ratio, is not compatible with the carbon isotopic record, if the budgets of carbon, alkalinity and strontium are considered simultaneously. Another scenario of the Cenozoic evolution of global weathering consistent with the carbon isotopic record is proposed in which the global weathering flux varies only slightly over the Cenozoic with a small increase between 15 Ma and the present. This second scenario appears more consistent with the reconstructed carbonate sedimentation rate and the evolution of the carbon isotopic fractionation in continental and oceanic environments