ROS from menadione induces astrocytic damage: protective effects of apocynin

Abstract only availableOxidative stress is a core cause of neurodegenerative diseases such as Alzheimer's disease. When cells are under oxidative stress, they will produce a high amount of reactive oxygen species (ROS). ROS are small and highly reactive and include compounds such as oxygen ions, free radicals, and peroxides. Understanding what triggers oxidative stress and how to ameliorate its damaging effects is a crucial step in discovering a cure for Alzheimer's disease. Menadione, a vitamin precursor of K2, is an oxidative compound that is capable of delivering ROS to the cells. Apocynin, a natural organic compound that has been isolated from Picrorhiza curroa grown in the Himalayan Mountains, is an inhibitor of NADPH oxidase, an enzyme for ROS production in cells. In this experiment, we studied whether apocynin may neutralize the effects of menadione using an immortalized astrocyte cell line DITNC. Astrocytes are glial cells that play a crucial role in the brain by providing necessary nutrient to surrounding neurons. We had three sample groups and treated each group with different drugs. The first group was the control, the second group was treated with menadione, and the third group was treated with both menadione and apocynin. After treating the cells, we recorded morphological changes of the cells by taking pictures of each sample group at three different time intervals (30 min, 1 and 2 hours). In addition to the morphological evidence, we also did a MTT assay to assess cell viability and later a data analysis based on the result from the MTT test. MTT assay measures mitochondrial activity and thus indirectly measures cell viability. Both morphological data and MTT analysis showed menadione caused DITNC cell damage with decreased mitochondrial activity. When cells are treated with menadione, they formed processes, shrink, and then round up. We also found apocynin protects against the oxidative damage caused by menadione to a certain extent. Since apocynin is an inhibitor of NADPH oxidase, this also indicates oxidative stress is generated by NADPH oxidase, suggesting apocynin may be a potential means to treat Alzheimer's disease.Alzheimer disease program project grant 2P01 AG018357 to G. Su

Understanding and distinguishing three time scale oscillations

A variety of bursting and spiking patterns arise in models for respiratory neurons [1] and other neurons associated with hormone release [2]. These models often feature quantities evolving on distinct time scales, such as fast voltage and slower ion current activation or inactivation variables. Furthermore, such systems may combine multiple interacting oscillatory mechanisms, such as intrinsic calcium oscillations together with a calcium-dependent, voltage-gated membrane potential oscillation mechanism.\ud \ud Motivated by the activity observed in these models, the goal of this project is to understand bursting dynamics in three time scale systems. We are particularly interested in knowing how much of the complication in burst patterns results from the presence of three or more timescales in the system and how much is, rather, a reflection of the models being relatively high dimensional nonlinear systems with many parameters. With this motivation, we construct a model consisting of two copies of Morris-Lecar equations with three time scales. By considering two viewpoints within the realm of geometric singular perturbation theory, we explain the mechanisms underlying the bursting dynamics of our model system, making use of computed critical manifold, superslow manifold and bifurcations. To elucidate which characteristics truly represent three time scale features, we investigate certain reductions to two time scales and the parameter dependence of solution features in the three time scale framework.\ud \ud Our results in this area may be useful for characterizing, developing models of, and analyzing models of experimental data. Moreover, they provide useful information for future modeling studies, where a determination needs to be made about how many time scales to include in a model to represent some given experimental data

Data assimilation of OMI NO2 observations for improving air quality forecast over Europe

This paper concerns the improvements of NO2 forecast due to satellite data assimilation. The Ozone Monitoring Instrument (OMI) aboard NASA Aura satellite provides observations of NO2 columns for air quality study. These satellite observations are assimilated, with the optimal-interpolation method, in an air quality model from Polyphemus, in order to improve NO2 forecasts in Europe. Good consistency is seen in the comparisons of model simulations, satellite data and ground observations before assimilation. The model results with and without assimilation are then compared with ground observations for evaluating the assimilation effects. It is found that in winter the errors between model data and ground observations have been reduced after assimilation, indicating a better NO2 forecast can be obtained using satellite observations. Such improvements are not found in summer, which is probably due to the shorter life time and higher temporal variability of NO2 in the warmer season

Ge-Photodetectors for Si-Based Optoelectronic Integration

High speed photodetectors are a key building block, which allow a large wavelength range of detection from 850 nm to telecommunication standards at optical fiber band passes of 1.3–1.55 μm. Such devices are key components in several applications such as local area networks, board to board, chip to chip and intrachip interconnects. Recent technological achievements in growth of high quality SiGe/Ge films on Si wafers have opened up the possibility of low cost Ge-based photodetectors for near infrared communication bands and high resolution spectral imaging with high quantum efficiencies. In this review article, the recent progress in the development and integration of Ge-photodetectors on Si-based photonics will be comprehensively reviewed, along with remaining technological issues to be overcome and future research trends

Comparison of Pharmacopuncture, Aquapuncture and Acepromazine for Sedation of Horses

Pharmacopuncture, the injection of subclinical doses of drugs into acupoints reduces drug undesirable side effects, residues in animal consumption products and treatment costs in large animals. Acepromazine (Acp) produces several undesirable effects, such as hypotension. Previous studies with the injection of 1/10 of Acp dose in dog acupoints showed its advantage for sedation, minimizing undesirable effects. Eight horses were randomly submitted to four different treatment protocols according to a Latin Square double-blind design: (i) 0.1 ml kg−1 of saline subcutaneously injected at the cervical region, (ii) 0.1 mg kg−1 of Acp injected subcutaneously at the cervical region, (iii) 0.01 ml kg−1 of saline injected into GV1 acupoint (aquapuncture) and (iv) 0.01 mg kg−1 of Acp injected into GV1 acupoint (pharmacopuncture). Heart rate, respiratory rate, head height and degree of sedation were measured before and at 30, 60 and 90 min after treatments. Signs of sedation were observed in all treated groups at 30 min and only in 1/10Acp-GV1 at 60 min after the treatments. Only the group treated with 0.1 mg kg−1 of Acp s.c. had significantly lower values of head height at 30 min. Respiratory rate tended to reduce in all groups but was significantly lower only in horses treated with 0.1 mg kg−1 of Acp s.c. Heart rate remained unchanged in all groups. Acp-pharmacopuncture on GV1 in horses produced a mild sedation when compared with the conventional dose of Acp. More investigations are necessary to determine the optimal dosage of Acp-pharmacopuncture for sedation in horses

Impact of CT-apelin and NT-proBNP on identifying non-responders to cardiac resynchronization therapy

CONTEXT: Assessment of response to cardiac resynchronization therapy (CRT) is essential. OBJECTIVE: To assess the predictive value of CT-apelin together with NT-proBNP in patients undergoing CRT. METHODS: Serum CT-apelin and NT-proBNP were measured by ELISA before, and 6-month after CRT. Primary endpoint was non-response (<4% increase in LVEF) after 6-month. RESULTS: From 81 patients, 15 proved to be non-responders. Six-month CT-apelin was superior compared to NT-proBNP in identifying non-responders by multivariate ROC (CT-apelin:p = 0.01, NT-proBNP:p = 0.13) and by logistic regression (CT-apelin:p = 0.01, NT-proBNP:p = 0.41) analyzes. CONCLUSION: Six-month CT-apelin might be valuable novel biomarker in identifying non-responders to CRT that was superior to NT-proBNP

Women and leadership in higher education in China: discourse and the discursive construction of identity

Prior research indicates that just 4.5 percent of mainland China’s higher educational institution leaders are female. This article extends theory and research by drawing attention to identity and Discourse as an important, yet under-researched, aspect of the problem of women’s underrepresentation in higher education leadership. Drawing on in-depth qualitative interviews with nine female academics in Chinese universities and informed by discursive approaches to identity and constructionist views, we analyze how women construct multiple identities, the interplay of identities, and the influence of broader societal Discourses of gender and leadership. The findings highlight the interplay between competing multiple identities, and illustrate how the women’s identities are shaped and constrained by dominant historical and cultural Discourses in Chinese society, which results in identity regulation (Alvesson and Billing 2009), notably identity positioning that is congruent with social norms and conventions. A key finding is that the female academics reject the leader identity. This is true for those in middle management positions, as well as women in early career stages, who might otherwise aspire to leadership. Implications for the leadership pipeline in China’s universities is discussed and recommendations are made for future research directions

Forms of Understanding of XAI-Explanations

Explainability has become an important topic in computer science and artificial intelligence, leading to a subfield called Explainable Artificial Intelligence (XAI). The goal of providing or seeking explanations is to achieve (better) 'understanding' on the part of the explainee. However, what it means to 'understand' is still not clearly defined, and the concept itself is rarely the subject of scientific investigation. This conceptual article aims to present a model of forms of understanding in the context of XAI and beyond. From an interdisciplinary perspective bringing together computer science, linguistics, sociology, and psychology, a definition of understanding and its forms, assessment, and dynamics during the process of giving everyday explanations are explored. Two types of understanding are considered as possible outcomes of explanations, namely enabledness, 'knowing how' to do or decide something, and comprehension, 'knowing that' -- both in different degrees (from shallow to deep). Explanations regularly start with shallow understanding in a specific domain and can lead to deep comprehension and enabledness of the explanandum, which we see as a prerequisite for human users to gain agency. In this process, the increase of comprehension and enabledness are highly interdependent. Against the background of this systematization, special challenges of understanding in XAI are discussed

Arabidopsis DXO1 links RNA turnover and chloroplast function independently of its enzymatic activity

The DXO family of proteins participates in eukaryotic mRNA 5'-end quality control, removal of non-canonical NAD+ cap and maturation of fungal rRNA precursors. In this work, we characterize the Arabidopsis thaliana DXO homolog, DXO1. We demonstrate that the plant-specific modification within the active site negatively affects 5'-end capping surveillance properties of DXO1, but has only a minor impact on its strong deNADding activity. Unexpectedly, catalytic activity does not contribute to striking morphological and molecular aberrations observed upon DXO1 knockout in plants, which include growth and pigmentation deficiency, global transcriptomic changes and accumulation of RNA quality control siRNAs. Conversely, these phenotypes depend on the plant-specific N-terminal extension of DXO1. Pale-green coloration of DXO1-deficient plants and our RNA-seq data reveal that DXO1 affects chloroplast-localized processes. We propose that DXO1 mediates the connection between RNA turnover and retrograde chloroplast-to-nucleus signaling independently of its deNADding properties