The thesis aims to provide a systematic, structured and evidence-based view of the internationalisation of Chinese NGOs and examine their role in Chinese international development by primarily... Show moreThe thesis aims to provide a systematic, structured and evidence-based view of the internationalisation of Chinese NGOs and examine their role in Chinese international development by primarily studying 28 Chinese NGOs based on fieldwork, interviews and analysis of organizational discourses. The thesis has shown that the major characteristic of the autonomy of Chinese NGOs is that the Chinese state’s influence does not come directly from its interventions in the operations of Chinese NGOs as there are limited direct policies, funding and other operational intervention from the Chinese government related to internationalisation. Instead, the Chinese state’s influence is embedded in the existing regulatory system regarding NGO registration and supervision and in the sources of legitimacy for internationalisation, a phenomenon dubbed as “embedded internationalisation”. The process of Chinese NGOs’ internationalisation is not sufficiently autonomous from the influence of the Chinese state and corporations and, thus, cannot offer a viable alternative to China’s mainstream international development landscape. Instead, Chinese NGOs have played a complementary role, as they have enriched the varieties of China’s aid and development cooperation and promoted China’s soft power. Show less
The circadian timing system is highly integrated with the sleep-wake regulation system. This thesis focuses on how different pharmacological treatments influence the sleep regulation system and the... Show moreThe circadian timing system is highly integrated with the sleep-wake regulation system. This thesis focuses on how different pharmacological treatments influence the sleep regulation system and the circadian timing rhythm in two murine models. In the first animal model, which is presented in Chapter 2 and 3, we implanted EEG/EMG electrodes in freely moving Brown Norway rats. We chose this rat strain because it is pigmented and therefore a more representative model than the more mainstream rat strains which are usually albino rats. This study aimed to investigate the effect of caffeine, sleep deprivation and ketamine on sleep and circadian-controlled activity under constant darkness. In the second animal model, which is presented in Chapter 4 and 5, we implanted EEG/EMG or Multi-unit electrodes in chemotherapy-induced fatigue mice. All the results from this thesis and future perspectives were discussed in Chapter 6. We are able to see how disruption of sleep and the circadian clock adversely affect health and may contribute to many diseases in modern society. In this thesis, these studies provide a better understanding of these drugs influence the circadian timing system and sleep-wake regulation and maybe new treatment approaches for antidepressant therapy and cancer related fatigue. Show less
Background Acute exacerbations of chronic inflammatory lung diseases, such as chronic obstructive pulmonary disease (COPD), are frequently associated with rhinovirus (RV) infections. Despite these... Show moreBackground Acute exacerbations of chronic inflammatory lung diseases, such as chronic obstructive pulmonary disease (COPD), are frequently associated with rhinovirus (RV) infections. Despite these associations, the pathogenesis of virus-induced exacerbations is incompletely understood. We aimed to investigate effects of cigarette smoke (CS), a primary risk factor for COPD, on RV infection in airway epithelium and identify novel mechanisms related to these effects. Methods Primary bronchial epithelial cells (PBEC) from COPD patients and controls were differentiated by culture at the air-liquid interface (ALI) and exposed to CS and RV-A16. Bulk RNA sequencing was performed using samples collected at 6 and 24 h post infection (hpi), and viral load, mediator and l-lactate levels were measured at 6, 24 and 48hpi. To further delineate the effect of CS on RV-A16 infection, we performed growth differentiation factor 15 (GDF15) knockdown, l-lactate and interferon pre-treatment in ALI-PBEC. We performed deconvolution analysis to predict changes in the cell composition of ALI-PBEC after the various exposures. Finally, we compared transcriptional responses of ALI-PBEC to those in nasal epithelium after human RV-A16 challenge. Results CS exposure impaired antiviral responses at 6hpi and increased viral replication at 24 and 48hpi in ALI-PBEC. At 24hpi, CS exposure enhanced expression of RV-A16-induced epithelial interferons, inflammation-related genes and CXCL8. CS exposure increased expression of oxidative stress-related genes, of GDF15, and decreased mitochondrial membrane potential. GDF15 knockdown experiments suggested involvement of this pathway in the CS-induced increase in viral replication. Expression of glycolysis-related genes and l-lactate production were increased by CS exposure, and was demonstrated to contribute to higher viral replication. No major differences were demonstrated between COPD and non-COPD-derived cultures. However, cellular deconvolution analysis predicted higher secretory cells in COPD-derived cultures at baseline. Conclusion Altogether, our findings demonstrate that CS exposure leads to higher viral infection in human bronchial epithelium by altering not only interferon responses, but likely also through a switch to glycolysis, and via GDF15related pathways. Show less
Next to the Pareto dominance relation, alternative order relations can be useful in many-objective optimization. In particular, it is interesting to extend the Pareto dominance relation in order to... Show moreNext to the Pareto dominance relation, alternative order relations can be useful in many-objective optimization. In particular, it is interesting to extend the Pareto dominance relation in order to make more pairs comparable and decrease the size of the optimal set (for discrete approximations in continuous optimization or discrete problems), which tends to grow exponentially with an increasing number of objectives. Here, we review some basic concepts in order theory with a focus on the concept of an order extension. Moreover, we will define and discuss properties of some orders that have been proposed as alternatives to the Pareto dominance relation in the context of dealing with larger number of objective functions. The chapter compares the different concepts and reveals commonalities between them. It will be shown that many of the order extensions proposed are special cases of cone orders. Therefore, the chapter puts particular emphasize on the concept of dominance cones and demonstrates how different ways of defining dominance cones, such as by means of angles or by trade-offs, can be mapped onto each other. Show less
The wide production and use of metallic nanomaterials (MNMs) leads to increased emissions into the aquatic environments and induces high potential risks. Experimentally evaluating the (eco)toxicity... Show moreThe wide production and use of metallic nanomaterials (MNMs) leads to increased emissions into the aquatic environments and induces high potential risks. Experimentally evaluating the (eco)toxicity of MNMs is time-consuming and expensive due to the multiple environmental factors, the complexity of material properties, and the species diversity. Machine learning (ML) models provide an option to deal with heterogeneous data sets and complex relationships. The present study established an in silico model based on a machine learning properties-environmental conditions-multi species-toxicity prediction model (ML-PEMST) that can be applied to predict the toxicity of different MNMs toward multiple aquatic species. Feature importance and interaction analysis based on the random forest method indicated that exposure duration, illumination, primary size, and hydrodynamic diameter were the main factors affecting the ecotoxicity of MNMs to a variety of aquatic organisms. Illumination was demonstrated to have the most interaction with the other features. Moreover, incorporating additional detailed information on the ecological traits of the test species will allow us to further optimize and improve the predictive performance of the model. This study provides a new approach for ecotoxicity predictions for organisms in the aquatic environment and will help us to further explore exposure pathways and the risk assessment of MNMs. Show less
Due to special properties, nano-TiO2 will interact with heavy metals and other pollutants in water, thus affecting the environmental behavior and ecotoxicity of these pollutants. However, the exact... Show moreDue to special properties, nano-TiO2 will interact with heavy metals and other pollutants in water, thus affecting the environmental behavior and ecotoxicity of these pollutants. However, the exact manner in which nano-TiO2 affects the bioaccumulation mechanisms of heavy metals is still unclear now. In the present study, quantitative structure bioaccumulation relationship (QSBAR) models were established to explore the relationships between physicochemical parameters of heavy metals and their accumulation in Daphnia magna in the absence and presence of nano-TiO2 at low metal exposure concentrations. The results showed that different physicochemical parameters affected the bioaccumulation of metals in Daphnia magna. The metal accumulation could be described by means of a Comprehensive Parameter composed of seven parameters, i.e., atomic number (AN), relative atomic weight (AW), atomic radius (AR), atomic ionization potential (AN/ΔIP), covalent index (X2r), second ionization energy (I2) and electrochemical potential (E0), in the absence of nano-TiO2, whereas the metal accumulation increased with the increase in Van Der Waals radius (rw) of metals in the presence of nano-TiO2. It was demonstrated that the bioaccumulation mechanism of the metals to Daphnia magna changed in the presence of nano-TiO2. Moreover, the bioaccumulation of more than 85% of the metals increased in the presence of nano-TiO2, but it increased differently for different metals. The present study provides an alternative approach to understand the mechanism of heavy metal bioaccumulation at low metal exposure concentrations and the effect of nano-TiO2 on metal bioaccumulation. Show less
Thaler, M.; Wang, Y.; Does, A.M. van der; Faiz, A.; Ninaber, D.K.; Ogando, N.S.; ... ; Hemert, M.J. van 2023
The consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can range from asymptomatic to fatal disease. Variations in epithelial susceptibility to SARS-CoV-2... Show moreThe consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can range from asymptomatic to fatal disease. Variations in epithelial susceptibility to SARS-CoV-2 infection depend on the anatomical location from the proximal to distal respiratory tract. However, the cellular biology underlying these variations is not completely understood. Thus, air-liquid interface cultures of well-differentiated primary human tracheal and bronchial epithelial cells were employed to study the impact of epithelial cellular composition and differentiation on SARS-CoV-2 infection by transcriptional (RNA sequencing) and immunofluorescent analyses. Changes of cellular composition were investigated by varying time of differentiation or by using specific compounds. We found that SARS-CoV-2 primarily infected not only ciliated cells but also goblet cells and transient secretory cells. Viral replication was impacted by differences in cellular composition, which depended on culturing time and anatomical origin. A higher percentage of ciliated cells correlated with a higher viral load. However, DAPT treatment, which increased the number of ciliated cells and reduced goblet cells, decreased viral load, indicating the contribution of goblet cells to infection. Cell entry factors, especially cathepsin L and transmembrane protease serine 2, were also affected by differentiation time. In conclusion, our study demonstrates that viral replication is affected by changes in cellular composition, especially in cells related to the mucociliary system. This could explain in part the variable susceptibility to SARS-CoV-2 infection between individuals and between anatomical locations in the respiratory tract. (c) 2023 The Author(s). Published by S. Karger AG, Basel Show less
Grafton-Waters, S.; Mao, J.; Mehdipour, M.; Branduardi-Raymont, G.; Page, M.; Kaastra, J.S.; ... ; Ebrero, J. 2023
Net Ecosystem Production (NEP) of forests is the net carbon dioxide (CO2) fluxes between land and the atmosphere due to forests' biogeochemical processes. NEP varies with natural drivers such as... Show moreNet Ecosystem Production (NEP) of forests is the net carbon dioxide (CO2) fluxes between land and the atmosphere due to forests' biogeochemical processes. NEP varies with natural drivers such as precipitation, air temperature, solar radiation, plant functional type (PFT), and soil texture, which affect the gross primary production and ecosystem respiration, and thus the net C sequestration. It is also known that deposition of sulphur and nitrogen influences NEP in forest ecosystems. These drivers' respective, unique effects on NEP, however, are often difficult to be individually identified by conventional bivariate analysis. Here we show that by analyzing 22 forest sites with 231 site-year data acquired from FLUXNET database across Europe for the years 2000-2014, the individual, unique effects of these drivers on annual forest CO2 fluxes can be disentangled using Generalized Additive Models (GAM) for nonlinear regression analysis. We show that S and N deposition have substantial impacts on NEP, where S deposition above 5 kg S ha(-1) yr(-1) can significantly reduce NEP, and N deposition around 22 kg N ha(-1) yr(-1) has the highest positive effect on NEP. Our results suggest that air quality management of S and N is crucial for maintaining healthy biogeochemical functions of forests to mitigate climate change. Furthermore, the empirical models we developed for estimating NEP of forests can serve as a forest management tool in the context of climate change mitigation. Potential applications include the assessment of forest carbon fluxes in the REDD+ framework of the UNFCCC. Show less
Covalently acting compounds experience a strong interest within chemical biology both as molecular probes in studies of fundamental biological mechanisms and/or as novel drug candidates. In this... Show moreCovalently acting compounds experience a strong interest within chemical biology both as molecular probes in studies of fundamental biological mechanisms and/or as novel drug candidates. In this context, the identification of new classes of reactive groups is particularly important as these can expose novel reactivity modes and, consequently, expand the ligandable proteome. Here, we investigated the electrophilic reactivity of the 3-acyl-5-hydroxy-1,5-dihydro-2H-pyrrole-2-one (AHPO) scaffold, a heterocyclic motif that is e.g. present in various bioactive natural products. Our investigations were focused on the compound MT-21 - a simplified structural analogue of the natural product epolactaene - which is known to have both neurotrophic activity and ability to trigger apoptotic cell death. We found that the central N-acyl hemiaminal group of MT-21 can function as an electrophilic centre enabling divergent reactivity with both amine- and thiokbased nucleophiles, which furthermore translated to reactivity with proteins in both cell lysates and live cells. We found that in live cells MT-21 strongly engaged the lipid transport protein fatty acid-binding protein 5 (FABP5) by direct binding to a cysteine residue in the bottom of the ligand binding pocket. Through preparation of a series of MT-21 derivatives, we probed the specificity of this interaction which was found to be strongly dependent on subtle structural changes. Our study suggests that MT-21 may be employed as a tool compound in future studies of the biology of FABP5, which remains incompletely understood. Furthermore, our study has also made dear that other natural products containing the AHPO-motif may likewise possess covalent reactivity and that this property may underlie their biological activity. Show less
Xu, N.; Kang, J.; Ye, Y.; Zhang, Q.; Ke, M.; Wang, Y.; ... ; Qian, H. 2022
With the rapid development of nanotechnology in agriculture, there is increasing urgency to assess the impacts of nanoparticles (NPs) on the soil environment. This study merged raw high-throughput... Show moreWith the rapid development of nanotechnology in agriculture, there is increasing urgency to assess the impacts of nanoparticles (NPs) on the soil environment. This study merged raw high-throughput sequencing (HTS) data sets generated from 365 soil samples to reveal the potential ecological effects of NPs on soil microbial community by means of metadata analysis and machine learning methods. Metadata analysis showed that treatment with nanoparticles did not have a significant impact on the alpha diversity of the microbial community, but significantly altered the beta diversity. Unfortunately, the abundance of several beneficial bacteria, such as Dyella, Methylophilus, Streptomyces, which promote the growth of plants, and improve pathogenic resistance, was reduced under the addition of synthetic nanoparticles. Furthermore, metadata demonstrated that nanoparticles treatment weakened the biosynthesis ability of cofactors, carriers, and vitamins, and enhanced the degradation ability of aromatic compounds, amino acids, etc. This is unfavorable for the performance of soil functions. Besides the soil heterogeneity, machine learning uncovered that a) the exposure time of nanoparticles was the most important factor to reshape the soil microbial community, and b) long-term exposure decreased the diversity of microbial community and the abundance of beneficial bacteria. This study is the first to use a machine learning model and metadata analysis to investigate the relationship between the properties of nanoparticles and the hazards to the soil microbial community from a macro perspective. This guides the rational use of nanoparticles for which the impacts on soil microbiota are minimized. Show less
Nanomaterials (NMs) are able to interact with natural organic matter (NOM) such that NOM is adsorbed on the surface of NMs to form an ecological corona (eco-corona). The formation of an eco-corona... Show moreNanomaterials (NMs) are able to interact with natural organic matter (NOM) such that NOM is adsorbed on the surface of NMs to form an ecological corona (eco-corona). The formation of an eco-corona can greatly influence the behavior, risk and fate of NMs in the environment. A systematic understanding of the impacts of an eco-corona on the hazards of NMs is crucial for NMs risk assessment in the aquatic environment. Herein, the mechanisms of the formation of an eco-corona were reviewed based on the representative literatures and their generality was discussed on the basis of the type of NMs, the type of NOM and the environmental conditions. The effects of an eco-corona on the bioaccumulation and toxicity of NMs for aquatic organisms were systematically discussed through reported studies. The results showed that an eco-corona could alter the toxicity of NMs by changing the dissolution of NMs, adhesion of NMs and the damages to bio-membranes, internalization, and the generation of NMs-induced reactive oxygen species. The dual effects of an eco-corona on the toxicity/accumulation of NMs were widely present because of the complex molecular composition of NOM, the diverse types of NMs, and the variable environmental conditions. The effects of an eco-corona on the fate and the effects of other pollutants (such as metals and organic pollutants) were also carefully reviewed. The results showed that more research is needed to investigate the effect of an eco-corona through the development of novel techniques, mathematical modeling, and mesocosm studies. Show less
