Protein Disulfide Isomerase A3 Regulates Influenza Neuraminidase Activity and Influenza Burden in the Lung

Influenza (IAV) neuraminidase (NA) is a glycoprotein required for the viral exit from the cell. NA requires disulfide bonds for proper function. We have recently demonstrated that protein disulfide isomerase (PDI)A3 is required for oxidative folding of IAV hemagglutinin (HA), and viral propagation. However, it not known whether PDIs are required for NA maturation or if these interactions represent a putative target for the treatment of influenza infection. We sought to determine whether PDIA3 is required for disulfide bonds of NA, its activity, and propagation of the virus. Requirement of disulfides for NA oligomerization and activity were determined using biotin switch and redox assays in WT and PDIA3^−/− in A549 cells. A PDI specific inhibitor (LOC14) was utilized to determine the requirement of PDIs in NA activity, IAV burden, and inflammatory response in A549 and primary mouse tracheal epithelial cells. Mice were treated with the inhibitor LOC14 and subsequently examined for IAV burden, NA activity, cytokine, and immune response. IAV-NA interacts with PDIA3 and this interaction is required for NA activity. PDIA3 ablation or inhibition decreased NA activity, viral burden, and inflammatory response in lung epithelial cells. LOC14 treatment significantly attenuated the influenza-induced inflammatory response in mice including the overall viral burden. These results provide evidence for PDIA3 inhibition suppressing NA activity, potentially providing a novel platform for host-targeted antiviral therapies.     

庭院时光 日本福冈某私人住宅

<正>小时候,孩子们的游乐场是房屋与房屋之间狭长的小路,是花园的边缘,是仓库的后巷,是废弃的工房。但当经济大发展将城市土地变得寸土寸金,钢筋水泥的商业森林便开始吞噬孩子们的领地。     

Effect of endogenous antioxidants of sesame seeds and sesame oil to the thermal stability of edible vegetable oils

Differently processed sesame seeds were used for the preparation of sesamol, seed extract, oil extract or unsaponifiable matter. Analysis of these sesame extracts revealed that dehulling and roasting of seeds had an adverse effect on their lignan and phenolic compounds content. Various concentrations of the extracts were incorporated in vegetable oils and their effectiveness in retarding the oxidative deterioration of oils was evaluated. Additionally, the formation of oxidation products in these oil samples was correlated with their antioxidant activity and their sesamol and phenolic compounds content. Results indicated that decomposition of phenolic compounds present in oil samples induced a significant reduction in their linoleic acid peroxidation inhibition capacity and a corresponding increase in their oxidative rancidity. Sesame seed extract was the most effective in protecting oils from oxidation, suggesting that seed extract, especially the one prepared from coated-unroasted sesame seeds, may have potential application as a source of natural antioxidants in oil industry.     

Ecological change associated with historic industrial activity in the St. Lawrence River at Cornwall,ON: A paleo-ecotoxicological assessment using subfossil chironomid assemblages

Twentieth-century historic industrial activity in Cornwall, ON loaded high amounts of metals and metalloids to the St. Lawrence River. Despite industrial improvements and the eventual closure of point-source polluters, sedimentary contamination in the Cornwall waterfront remains above provincial guidelines, causing concern for ecosystem management. We analysed chironomid (Order: Diptera) subfossils from modern-day surface-sediment samples and a sediment core from the Cornwall waterfront in order to better understand historic pollution impacts and potential recovery. Modern-day chironomid assemblages were diverse (48 genera, >70 species) and overall assemblage structure was weakly related to sedimentary zinc concentrations, with Procladius, Paratanytarsus, and Ablabesmyia identified as zinc-tolerant and Rheotanytarsus, Polypedilum and Paratendipes identified as zinc-sensitive. The sediment core showed peak total mercury (THg) concentrations were an order of magnitude higher than in modern-day surface sediments. In sections of the core below 10 cm in depth, THg concentrations were high (~30–50 µg/g) and chironomids were nearly absent from the record. Above 10 cm (c. 1980) THg concentrations decreased and chironomid taxa returned in low abundances. Subsequent intervals displayed an increase in diversity, abundance, and the relative abundance of metal-sensitive taxa. This study provides evidence of ecological change which co-occurs with Cornwall’s historic industrial activity and indicates progress toward related ecological goals identified in the current management strategy.     

光之舞 法国慕拉诺度假酒店

<正>位于法国巴黎玛莱区(Marais)的慕拉诺度假酒店(MURANO Resort),是巴黎市内的"城区度假地之首",那里的建筑将巴黎的魅力与内在的艺术张力表露无遗,这家酒店亦是那一区域的典范。它由克里斯汀·德瑞(Christine Derory)和雷蒙德·莫雷尔(Raymond Morel)这两位法国设计师联手设计。之前他们已经在法国和     

Making an impact: The influence of policies to reduce emissions from aviation on the business travel patterns of individual corporations

The contribution of aviation to global carbon dioxide (CO₂) emissions is projected to triple by 2050. As nations strive to meet CO₂ reduction targets, policy interventions to manage the growth of emissions arising from air travel are likely. Here, we investigate the potential influence of aviation emissions reduction policies on the business travel patterns of individual corporations. Using travel data from six UK-based companies, we find that increased ticket prices can deliver substantial emissions cuts, particularly on premium class flights, and may provide strong financial incentives to seek modal and/or technological alternatives to flying. We also find that corporations from different business sectors vary in their responsiveness to a range of policy options. Finally, we examine questionnaire data to determine whether companies more broadly are going beyond compliance to mitigate their environmental impact by managing travel-related emissions voluntarily. Although many corporations are measuring and reporting emissions, only a limited number are willing to implement in-house reduction policies prior to regulation.     

Characterization of Antibodies against Receptor Activity-Modifying Protein 1 (RAMP1): A Cautionary Tale

Calcitonin gene-related peptide (CGRP) is a key component of migraine pathophysiology, yielding effective migraine therapeutics. CGRP receptors contain a core accessory protein subunit: receptor activity-modifying protein 1 (RAMP1). Understanding of RAMP1 expression is incomplete, partly due to the challenges in identifying specific and validated antibody tools. We profiled antibodies for immunodetection of RAMP1 using Western blotting, immunocytochemistry and immunohistochemistry, including using RAMP1 knockout mouse tissue. Most antibodies could detect RAMP1 in Western blotting and immunocytochemistry using transfected cells. Two antibodies (844, ab256575) could detect a RAMP1-like band in Western blots of rodent brain but not RAMP1 knockout mice. However, cross-reactivity with other proteins was evident for all antibodies. This cross-reactivity prevented clear conclusions about RAMP1 anatomical localization, as each antibody detected a distinct pattern of immunoreactivity in rodent brain. We cannot confidently attribute immunoreactivity produced by RAMP1 antibodies (including 844) to the presence of RAMP1 protein in immunohistochemical applications in brain tissue. RAMP1 expression in brain and other tissues therefore needs to be revisited using RAMP1 antibodies that have been comprehensively validated using multiple strategies to establish multiple lines of convincing evidence. As RAMP1 is important for other GPCR/ligand pairings, our results have broader significance beyond the CGRP field.     

Modeling gender evolution and gap in science and technology using ecological dynamics

In this paper a model based on population biology is proposed in order to investigate the evolution of human resources (men and women) in science and technology as a share of labor market as well as the dynamics of their gap. An analytical and a simulation method using the Artificial Bee Colony optimization algorithm are described and used for the determination of the proposed model parameters. The presented model is applied to three case studies; Greece, Portugal and Europe-27.³ The accuracy of the obtained results is confirmed through comparison with actual data. In addition, the model can also be used to accurately forecast future trends. It is illustrated that the gender gap is continuously decreasing, while in the last years, women seem to outperform men in the field of science and technology. The estimation and forecasting ability of the model can be used as an extremely valuable tool for decision and policy makers.