Proteasome Inhibition Represses Unfolded Protein Response and Nox4, Sensitizing Vascular Cells to Endoplasmic Reticulum Stress-Induced Death

Background: Endoplasmic reticulum (ER) stress has pathophysiological relevance in vascular diseases and merges with proteasome function. Proteasome inhibition induces cell stress and may have therapeutic implications. However, whether proteasome inhibition potentiates ER stress-induced apoptosis and the possible mechanisms involved in this process are unclear. Methodology/Principal Findings: Here we show that proteasome inhibition with MG132, per se at non-lethal levels, sensitized vascular smooth muscle cells to caspase-3 activation and cell death during ER stress induced by tunicamycin (Tn). This effect was accompanied by suppression of both proadaptive (KDEL chaperones) and proapoptotic (CHOP/GADD153) unfolded protein response markers, although, intriguingly, the splicing of XBP1 was markedly enhanced and sustained. In parallel, proteasome inhibition completely prevented ER stress-induced increase in NADPH oxidase activity, as well as increases in Nox4 isoform and protein disulfide isomerase mRNA expression. Increased Akt phosphorylation due to proteasome inhibition partially offset the proapoptotic effect of Tn or MG132. Although proteasome inhibition enhanced oxidative stress, reactive oxygen species scavenging had no net effect on sensitization to Tn or MG132-induced cell death. Conclusion/Relevance: These data indicate unfolded protein response-independent pathways whereby proteasome inhibition sensitizes vascular smooth muscle to ER stress-mediated cell death. This may be relevant to understand the therapeutic potential of such compounds in vascular disease associated with increased neointimal hyperplasia.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[04/13683-0]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[09/54764-6]Instituto Nacional de Ciencia e Tecnologia de Processos Redox em BioMedicina (Redoxoma, INCT, CNPq)Fundacao Zerbin

Analysis of histological frequency and pediatric cancer in Rondônia, Western Amazonia (Brazil)

Objective:Describe the histological and cancer frequency in children and adolescents attended at the Hospital de Base Dr. Ary Pinheiro and the Hospital de Barretos / Rondônia, Western Amazonia, in the years 2014 and 2015. Method: This is a descriptive, quantitative and transverse study. We used a structured instrument containing a series of variables, such as gender, age, histological types, more frequent neoplasms, lymphomas, leukemias, among others. We asked The Comitê de Ética em Pesquisa em Seres Humanos (Research Ethics Committee) to dispense the Informed Consent Form because the study did not require intervention on the patient or collection of biological material, and no possibility of constraints on patients and their relatives. Results: From 75 cases, 32 (42.7%) were female and 43 (57.3%) were male. Regarding the distribution of patients according to the age group, 21 (28.0%) were younger than 4 years, 12 (16.0%), 5 to 9 years, 17 (22.6%) from 10 to 14 and 25 (33.4%) from 15 to 19. The most frequent histological types by gender were leukemias of myeloproliferative diseases and myelodysplastic diseases with 30% and 50% new cases in the period, followed by lymphomas and reticuloendothelial neoplasms with 16.65% and 20, 0% of the histological types in the period. Leukemia in the hematopoietic and reticuloendothelial system (C42) is the most frequent cancer in both, female and male gender, with 47.5% of cancers in the biennium. The second group of cancers in children from 0 to 19 years old and location of the primary tumor is the encephalon carcinoma (C71), with 11.25% of the new cases. Conclusions: The results presented with their proper nuances are in agreement with the data of studies carried out in Brazil and in other countries

Magnetically controlled exciton transfer in hybrid quantum dot-quantum well nanostructures

A magnetophotoluminescence study of the carrier transfer with hybrid InAs/GaAs quantum dot(QD)-InGaAs quantum well (QW) structures is carried out where we observe an unsual dependence of the photoluminescence (PL) on the GaAs barrier thickness at strong magnetic field and excitation density. For the case of a thin barrier the QW PL intensity is observed to increase at the expense of a decrease in the QD PL intensity. This is attributed to changes in the interplane carrier dynamics in the QW and the wetting layer (WL) resulting from increasing the magnetic field along with changes in the coupling between QD excited states and exciton states in the QW and the WL

Protein Disulfide Isomerase and Host-Pathogen Interaction

Reactive oxygen species (ROS) production by immunological cells is known to cause damage to pathogens. Increasing evidence accumulated in the last decade has shown, however, that ROS (and redox signals) functionally regulate different cellular pathways in the host-pathogen interaction. These especially affect (i) pathogen entry through protein redox switches and redox modification (i.e., intra- and interdisulfide and cysteine oxidation) and (ii) phagocytic ROS production via Nox family NADPH oxidase enzyme and the control of phagolysosome function with key implications for antigen processing. The protein disulfide isomerase (PDI) family of redox chaperones is closely involved in both processes and is also implicated in protein unfolding and trafficking across the endoplasmic reticulum (ER) and towards the cytosol, a thiol-based redox locus for antigen processing. Here, we summarise examples of the cellular association of host PDI with different pathogens and explore the possible roles of pathogen PDIs in infection. A better understanding of these complex regulatory steps will provide insightful information on the redox role and coevolutional biological process, and assist the development of more specific therapeutic strategies in pathogen-mediated infections

Potencial de hibridação entre acessos de tomateiro para pré-melhoramento quanto à resistência à requeima.

O objetivo deste trabalho foi avaliar genitores com potencial de hibridação para o pré?melhoramento do tomateiro (Solanum lycopersicum) quanto à resistência à requeima. Foram utilizados seis acessos de tomateiro (BGH?2102, BGH?2117, BGH?2127, BGH?2130, BGH?2332 e BGH?2343) como genitores resistentes e 15 híbridos F1 originários destes genitores. Utilizou?se o delineamento de blocos ao acaso, com três repetições. As plantas foram inoculadas com uma mistura de esporângios de Phytophthora infestans , agente etiológico da requeima, na concentração de 5x10 3 esporângios mL ?1. A área abaixo da curva de progresso da doença foi utilizada para avaliar a resistência. Realizou?se a análise dialélica, tendo se considerado o efeito de genótipos como fixo. Estimou-se a capacidade geral e específica de combinação dos acessos. O padrão de resistência dos genitores e da maioria dos F1 foi o mesmo que o das testemunhas resistentes. Foram observados: variabilidade genética aditiva entre os genitores, predominância de efeitos gênicos não aditivos e desvios de dominância bidirecional no controle do caráter. A frequência de alelos favoráveis e divergentes para resistência à requeima é maior nos acessos BGH?2117, BGH?2127 e BGH?2343

Pathway to an excitonic coherence

This paper discusses the combined effects of optical excitation power, interface roughness, lattice temperature, and applied magnetic fields on the spin-coherence of excitonic states in GaAs/AlGaAs multiple quantum wells. For low optical powers, at lattice temperatures between 4 K and 50 K, the scattering with acoustic phonons and short-range interactions appear as the main decoherence mechanisms. Statistical fluctuations of the band-gap however become also relevant in this regime and we were able to deconvolute them from the decoherence contributions. The circularly polarized magneto-photoluminescence unveils a non-monotonic tuning of the coherence for one of the spin components at low magnetic fields. This effect has been ascribed to the competition between short-range interactions and spin-flip scattering, modulated by the momentum relaxation time

Effects of grid spacing on high-frequency precipitation variance in coupled high-resolution global ocean–atmosphere models

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Light, C., Arbic, B., Martin, P., Brodeau, L., Farrar, J., Griffies, S., Kirtman, B., Laurindo, L., Menemenlis, D., Molod, A., Nelson, A., Nyadjro, E., O’Rourke, A., Shriver, J., Siqueira, L., Small, R., & Strobach, E. Effects of grid spacing on high-frequency precipitation variance in coupled high-resolution global ocean–atmosphere models. Climate Dynamics, (2022): 1–27, https://doi.org/10.1007/s00382-022-06257-6.High-frequency precipitation variance is calculated in 12 different free-running (non-data-assimilative) coupled high resolution atmosphere–ocean model simulations, an assimilative coupled atmosphere–ocean weather forecast model, and an assimilative reanalysis. The results are compared with results from satellite estimates of precipitation and rain gauge observations. An analysis of irregular sub-daily fluctuations, which was applied by Covey et al. (Geophys Res Lett 45:12514–12522, 2018. https://doi.org/10.1029/2018GL078926) to satellite products and low-resolution climate models, is applied here to rain gauges and higher-resolution models. In contrast to lower-resolution climate simulations, which Covey et al. (2018) found to be lacking with respect to variance in irregular sub-daily fluctuations, the highest-resolution simulations examined here display an irregular sub-daily fluctuation variance that lies closer to that found in satellite products. Most of the simulations used here cannot be analyzed via the Covey et al. (2018) technique, because they do not output precipitation at sub-daily intervals. Thus the remainder of the paper focuses on frequency power spectral density of precipitation and on cumulative distribution functions over time scales (2–100 days) that are still relatively “high-frequency” in the context of climate modeling. Refined atmospheric or oceanic model grid spacing is generally found to increase high-frequency precipitation variance in simulations, approaching the values derived from observations. Mesoscale-eddy-rich ocean simulations significantly increase precipitation variance only when the atmosphere grid spacing is sufficiently fine (< 0.5°). Despite the improvements noted above, all of the simulations examined here suffer from the “drizzle effect”, in which precipitation is not temporally intermittent to the extent found in observations.Support for CXL’s effort on this project was provided by a Research Experiences for Undergraduates (REU) supplement for National Science Foundation (NSF) grant OCE-1851164 to BKA, which also provided partial support for PEM. In addition, BKA acknowledges NSF grant OCE-1351837, which provided partial support for AKO, Office of Naval Research grant N00014-19-1-2712 and NASA grants NNX17AH55G, which also provided partial support for ADN, and 80NSSC20K1135. JTF’s participation, and the SPURS-II buoy data, were funded by NASA grants 80NSSC18K1494 and NNX15AG20G