Interactions of SARS Coronavirus Nucleocapsid Protein with the host cell proteasome subunit p42

<p>Abstract</p> <p>Background</p> <p>Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spreads rapidly and has a high case-mortality rate. The nucleocapsid protein (NP) of SARS-CoV may be critical for pathogenicity. This study sought to discover the host proteins that interact with SARS-CoV NP.</p> <p>Results</p> <p>Using surface plasmon resonance biomolecular interaction analysis (SPR/BIA) and matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry, we found that only the proteasome subunit p42 from human fetal lung diploid fibroblast (2BS) cells bound to SARS-CoV NP. This interaction was confirmed by the glutathione S-transferase (GST) fusion protein pulldown technique. The co-localization signal of SARS-CoV NP and proteasome subunit p42 in 2BS cells was detected using indirect immunofluorescence and confocal microscopy. p42 is a subunit of the 26S proteasome; this large, multi-protein complex is a component of the ubiquitin-proteasome pathway, which is involved in a variety of basic cellular processes and inflammatory responses.</p> <p>Conclusion</p> <p>To our knowledge, this is the first report that SARS-CoV NP interacts with the proteasome subunit p42 within host cells. These data enhance our understanding of the molecular mechanisms of SARS-CoV pathogenicity and the means by which SARS-CoV interacts with host cells.</p

Anticardiolipin antibody and anti-beta(2) glycoprotein I antibody are potential risk markers of ischaemic stroke in Chinese adults

Objectives. aCL and anti-beta(2) glycoprotein I antibody (a beta(2)GPI) are autoantibodies associated with thromboembolic diseases. Here we investigated whether they are correlated with ischaemic cardiovascular disease in a Chinese population. Methods. Serum total aCL and a beta(2)GPI isotypes (IgA, IgG or IgM, separately) were measured in 11 015 Chinese adults. Differences of antibody level between disease and non-disease groups were examined by t-test. The correlation between antibody and ischaemic cardiovascular disease was determined by logistic regression analysis. Performance of risk prediction models employed aCL or a beta(2)GPI isotypes was evaluated by C statistic, net reclassification improvement index and integrated discrimination improvement. Results. Total aCL and a beta(2)GPI isotypes maintained low levels and increased with increasing age except total aCL and a beta(2)GPI IgG in participants older than 70 years. When distinguishing ischaemic cardiovascular disease by coronary heart disease (CHD) and ischaemic stroke, the stroke group had higher levels of aCL and a beta(2)GPI isotypes than the non-stroke group, while the CHD group only had a slightly higher a beta(2)GPI IgG than non-CHD groups. aCL and a beta(2)GPI were positively correlated with stroke but not with CHD, and improved the performance of conventional risk factors for stroke risk prediction, with C statistic from 0.769 (95% CI 0.744, 0.793) to 0.777 (95% CI 0.754, 0.800) (a beta(2)GPI IgG, P = 0.0091), and 0.778 (95% CI 0.754, 0.801) (a beta(2)GPI IgA, P = 0.0793). Stroke risk could be better reclassified by aCL and a beta(2)GPI, in association with both net reclassification improvement and integrated discrimination improvement statistics (P<0.05). Conclusion. aCL and a beta(2)GPI are associated with ischaemic stroke and have added value for stroke risk prediction

A Planar Underactuated Compaction Mechanism with Self-Adaptability for Automated Fiber Placement Heads

Automated fiber placement (AFP) systems accommodate complex-shaped structures by pressing fibers against the non-planar surfaces of mandrels, in which compaction mechanisms are of crucial significance. A conventional compaction mechanism utilizes an independent actuator with compacting rollers to conform surfaces. Compared with these mechanisms, underactuated mechanisms can improve self-adjustability and functionality. This research introduces the concept design and the analysis of a planar underactuated compaction mechanism for automated fiber placement heads. Firstly, the requirements and design premise are determined. Then, a novel planar underactuated compaction mechanism with a bistable structure is constructed based on the metamorphic design theory. Secondly, the analytical models are established to give insight into the motion characteristics of the mechanism. Moreover, the example and simulation results are presented to verify the conceptual design. Furthermore, the standard deviation of the contact force of the planar underactuated compaction mechanism is much lower than that of a conventional compaction mechanism under equal conditions. Finally, the potential application of the underactuated mechanisms is discussed. Thus, this research shows that the designed compaction mechanism increases the adjustability, robustness, and high repeatability in positioning and can be used to simplify the motion planning for AFP systems when producing complex structures

PM2.5 induced apoptosis in endothelial cell through the activation of the p53-bax-caspase pathway

Resenha de:VOMMARO, Gabriel; COMBES, Hélène. El clientelismo político:desde 1950 hasta nuestros días. Buenos Aires: Siglo XXI Editores,2016, 192 p. A obra resenhada apresenta um panorama didático e imprescindível dos estudos sobre o clientelismo, inclusive em sociedades contemporâneas. Representa uma contribuição fundamental para as ciências sociais, ao ampliar a perspectiva da denunciação, ressaltar que o clientelismo é noção dificilmente dissociada de uma intenção moral e, especialmente, indagar em que medida os diagnósticos intelectuais da patologia da política são mobilizados na condição de crítica, deslegitimação ou desqualificação das práticas dos oponentes na luta política

Development Dilemma of Primary Health Care Institutions: a Grounded Theory Study Based on Guilin City

Background Since the new medical reform, primary health care institutions have made remarkable achievements in the number of consultations and basic public health service projects, however, the problems including low quality and high mobility of personnel, weakened capacity and low efficiency of service still remain. Therefore, it has become an urgent task to solve the development dilemma of primary health care institutions. Objective To analyze the development dilemma of primary health care institutions and propose corresponding countermeasures. Methods From April to May 2021, the heads of 16 primary health care institutions in 6 counties and 2 districts in Guilin were selected using multi-stage sampling method to conduct semi-structured interviews, which mainly included resource allocation, service capacity building, health insurance policy implementation, and development dilemmas. NVivo 11.0 qualitative analysis software and the research method of ground theory were used to classify, ummarize and refine the original interview data at each level. Results A total of 38 initial concepts, 9 initial categories, 4 main categories, and 1 core category were extracted, and nodes of stagnation in four dimensions including &quot;resource allocation constraints&quot; &quot;obstruction of the path of three medical linkage&quot; &quot;deviation of functional positioning&quot; and &quot;accessibility lacking in medical community construction&quot; were obtained. Conclusion The development of primary health care institutions is constrained by a variety of factors, with resource allocation balance and compensation mechanism improvement as core issue, synergy of the three medical linkage paths as external condition, adjustment of functional positioning as key link, and the construction of close medical community as important approach

The size-dependent effects of silica nanoparticles on endothelial cell apoptosis through activating the p53-caspase pathway

With the growing production and applications of silica nanoparticles (SiNPs), human exposure to these nanoparticles continues to increase. However, the possible hazards that SiNP exposure may pose to human cardiovascular system and the underlying mechanisms remain unclear. In the present study, the flow cytometry was employed to investigate the potential of four sizes (10, 25, 50, 100 nm) of SiNPs to induce the apoptosis of human umbilical vein endothelial cells (HUVECs) in culture. The apoptotic pathway was also explored through the determination of the protein expression and/or activation of p53, Bcl-2, Bax, caspases-9, -7, -3, and PARP by western blot. The results showed that all the four sizes of SiNPs could significantly elicit apoptosis in HUVECs at the tested concentrations (1, 5, 25 mu g/mL), compared with the negative control (p &lt; 0.05, p &lt; 0.01). Moreover, the apoptotic rates were increased with the elevating levels and decreasing sizes of administrative SiNPs, showing both dose- and size-dependent effect relationships. Interestingly, the enhancing phosphorylation of p53 protein (Ser15), decreasing ratio of Bcl-2/Bax protein, and elevating activation of the downstream proteins, caspase-9, -7, -3 and PARP, were also observed with the decreasing sizes of tested SiNPs, indicating that the p53-caspase pathway is the main way of the SiNP-mediated apoptosis in HUVECs and that the size is an important parameter that determines the SiNPs' potential to induce cellular response. (C) 2017 Elsevier Ltd. All rights reserved