Optineurin downregulation induces endoplasmic reticulum stress, chaperone-mediated autophagy, and apoptosis in pancreatic cancer cells

Pancreatic ductal adenocarcinoma (PDAC) shows a high level of basal autophagy. Here we investigated the role of optineurin (OPTN) in PDAC cell lines, which is a prominent member of the autophagy system. To that purpose, mining of publically available databases showed that OPTN is highly expressed in PDAC and that high levels of expression are related to reduced survival. Therefore, the role of OPTN on proliferation, migration, and colony formation was investigated by transient knockdown in Miapaca, BXPC3, and Suit2-007 human PDAC cells. Furthermore, gene expression modulation in response to OPTN knockdown was assessed by microarray. The influence on cell cycle distribution and cell death signaling cascades was followed by FACS, assays for apoptosis, RT-PCR, and western blot. Finally, autophagy and ROS induction were screened by acridine orange and DCFH-DA fluorescent staining respectively. OPTN knockdown caused significant inhibition of colony formation, increased migration and no significant effect on proliferation in Miapaca, BXPC3 and Suit2-007 cells. The microarray showed modulation of 293 genes in Miapaca versus 302 in Suit2-007 cells, of which 52 genes overlapped. Activated common pathways included the ER stress response and chaperone-mediated autophagy, which was confirmed at mRNA and protein levels. Apoptosis was activated as shown by increased levels of cleaved PARP, Annexin V binding and nuclear fragmentation. OPTN knockdown caused no increased vacuole formation as assessed by acridine orange. Also, there was only marginally increased ROS production. Combination of OPTN knockdown with the autophagy inducer erufosine or LY294002, an inhibitor of autophagy, showed additive effects, which led us to hypothesize that they address different pathways. In conclusion, OPTN knockdown was related to activation of ER stress response and chaperone-mediated autophagy, which tend to confine the damage caused by OPTN knockdown and thus question its value for PDAC therapy

Modeling the effects of climate and land use change on carbon and trace gas budgets over the Amazon Region using NASA satellite products.

Abstract ID: 14. Publicado também on-line

Terrestrial Carbon Sinks in the Brazilian Amazon and Cerrado Region Predicted from MODIS Satellite Data and Ecosystem Modeling

A simulation model based on satellite observations of monthly vegetation cover from the Moderate Resolution Imaging Spectroradiometer (MODIS) was used to estimate monthly carbon fluxes in terrestrial ecosystems of Brazilian Amazon and Cerrado regions over the period 2000-2004. Net ecosystem production (NEP) flux for atmospheric CO2 in the region for these years was estimated. Consistently high carbon sink fluxes in terrestrial ecosystems on a yearly basis were found in the western portions of the states of Acre and Rondonia and the northern portions of the state of Par a. These areas were not significantly impacted by the 2002-2003 El Nino event in terms of net annual carbon gains. Areas of the region that show periodically high carbon source fluxes from terrestrial ecosystems to the atmosphere on yearly basis were found throughout the state of Maranhao and the southern portions of the state of Amazonas. As demonstrated though tower site comparisons, NEP modeled with monthly MODIS Enhanced Vegetation Index (EVI) inputs closely resembles the measured seasonal carbon fluxes at the LBA Tapajos tower site. Modeling results suggest that the capacity for use of MODIS Enhanced Vegetation Index (EVI) data to predict seasonal uptake rates of CO2 in Amazon forests and Cerrado woodlands is strong

Distribution of Hydrogen Peroxide In the Northwest Pacific Ocean

[1] Hydrogen peroxide (H2O2) is a reactive oxygen intermediate involved in the cycling of metals and dissolved organic matter. Because little is known of its distribution in the North Pacific Ocean, we determined H2O2 in surface waters continuously and obtained vertical profiles at nine stations during a cruise from Japan to Hawaii. Surface water H2O2 varied from less than 10 to more than 250 nmol dm(-3). A diel cycle in surface water H2O2 (similar to 25 nmol dm(-3)) was observed only on one day during the monthlong cruise. This is contrary to expectations based on the usual assumption of photo-production as the dominant input of H2O2. Experiments were also conducted during the cruise to examine both photo-production and dark decay. The net rate of photo-production at a station near Hawaii was determined to be 8 nmol dm(-3) h(-1), similar to rates reported for the central Atlantic Ocean and Antarctic. However, this maximum estimate of photo-production is also similar to probable rates of H2O2 input by other mechanisms ( biological production and rain). The pseudo-first-order rate constant for dark decay varied from 0.1 to 0.2 d(-1), which is toward the low end of previous reports of H2O2 decay rates, and was observed to increase proportionately to the dissolved organic carbon concentration. Taken together, these results suggest that photo-production of H2O2 in open ocean waters may be less important than previously thought and therefore H2O2 is likely less of an indicator of the photo-chemical reactivity of surface waters than hoped for. Furthermore, we observed that the H2O2 inventory for the upper 200 m of the water column has a maximum at midlatitudes. We suggest that this results from diminished inputs at high latitude as well as increased decay rates at low latitudes

Humic Substances Enhance Chlorothalonil Phototransformation via Photoreduction and Energy Transfer

ABSTRACT: The photodegradation of chlorothalonil, a polychlorinated aromatic fungicide widely used in agriculture, was investigated under ultraviolet–visible irradiation in the presence and absence of different humic substances that significantly enhance the chlorothalonil phototransformation. On the basis of a kinetic model, an analytical study, the effect of scavengers, the chlorothalonil phosphorescence measurement, and varying irradiation conditions, it was possible to demonstrate that this accelerating effect is due to their capacity to reduce the chlorothalonil triplet state via H-donor reaction and to energy transfer from the triplet humic to ground state chlorothalonil. Energy transfer occurs at wavelengths below 450 nm and accounts for up to 30% of the reaction in deoxygenated medium upon irradiation with polychromatic light (300–450 nm). This process is more important with Elliott humic and fulvic acids and with humic acids extracted from natural carbonaceous material than with Nordic NOM and Pahokee peat humic acids. The obtained results are of high relevance to understanding the processes involved in chlorothalonil phototransformation and the photoreactivity of humic substances. Chlorothalonil is one of the rare molecules shown to react by energy transfer from excited humic substances

Business ethics : practical proposals

While most people agree that the inculcation of ethical awareness is desirable, the means of stimulating this awareness vary among companies, industries and cultures. The fundamental question surrounding the difference between social responsibility and ethics is addressed. Guidelines for establishing ethical priorities from both the individual, group and organisational perspectives are provided. <br /

Controlled growth of the self-modulation of a relativistic proton bunch in plasma

A long, narrow, relativistic charged particle bunch propagating in plasma is subject to the self-modulation (SM) instability. We show that SM of a proton bunch can be seeded by the wakefields driven by a preceding electron bunch. SM timing reproducibility and control are at the level of a small fraction of the modulation period. With this seeding method, we independently control the amplitude of the seed wakefields with the charge of the electron bunch and the growth rate of SM with the charge of the proton bunch. Seeding leads to larger growth of the wakefields than in the instability case.info:eu-repo/semantics/publishedVersio

The success of the Montreal Protocol in mitigating interactive effects of stratospheric ozone depletion and climate change on the environment

The Montreal Protocol and its Amendments have been highly effective in protecting the stratospheric ozone layer, preventing global increases in solar ultraviolet-B radiation (UV-B; 280-315 nm) at Earth's surface, and reducing global warming. While ongoing and projected changes in UV-B radiation and climate still pose a threat to human health, food security, air and water quality, terrestrial and aquatic ecosystems, and construction materials and fabrics, the Montreal Protocol continues to play a critical role in protecting Earth's inhabitants and ecosystems by addressing many of the United Nations Sustainable Development Goals.Non peer reviewe

United Nations Environment Programme (UNEP), Questions and Answers about the Effects of Ozone Depletion, UV Radiation, and Climate on Humans and the Environment. Supplement of the 2022 Assessment Report of the UNEP Environmental Effects Assessment Panel

This collection of Questions & Answers (Q&As) was prepared by the Environmental Effects Assessment Panel (EEAP) of the Montreal Protocol under the umbrella of the United Nations Environment Programme (UNEP). The document complements EEAP’s Quadrennial Assessment 2022 (https://ozone. unep.org/science/assessment/eeap) and provides interesting and useful information for policymakers, the general public, teachers, and scientists, written in an easy-to-understand language