The Role of Proteasome Inhibition in Nonsmall Cell Lung Cancer

Lung cancer therapy with current available chemotherapeutic agents is mainly palliative. For these and other reasons there is now a great interest to find targeted therapies that can be effective not only palliating lung cancer or decreasing treatment-related toxicity, but also giving hope to cure these patients. It is already well known that the ubiquitin-proteasome system like other cellular pathways is critical for the proliferation and survival of cancer cells; thus, proteosome inhibition has become a very attractive anticancer therapy. There are several phase I and phase II clinical trials now in non-small cell lung cancer and small cell lung cancer using this potential target. Most of the trials use bortezomib in combination with chemotherapeutic agents. This paper tends to make a state-of-the-art review based on the available literature regarding the use of bortezomib as a single agent or in combination with chemotherapy in patients with lung cancer

Carotenoids in Cassava Roots

Vitamin A deficiency (VAD) is a preventable tragedy that affects millions of people, particularly in sub-Saharan Africa. A large proportion of these people rely on diets based on cassava as a source of calories. During the last two decades, significant efforts have been made to identify sources of germplasm with high pro-vitamin A carotenoids (pVAC) and then use them to develop cultivars with a nutritional goal of 15 μg g−1 of β-carotene (fresh weight basis) and good agronomic performance. The protocols for sampling roots and quantifying carotenoids have been improved. Recently, NIR predictions began to be used. Retention of carotenoids after different root processing methods has been measured. Bioavailability studies suggest high conversion rates. Genetic modification has also been achieved with mixed results. Carotenogenesis genes have been characterized and their activity in roots measured

Tratamiento por fermentación anaerobia de las vinazas producidas en la fabricación de alcohol

Con el fin de disminuir su carga contaminante, las vinazas se sometieron a tratamiento en cuatro reactores tipo filtro anaerobio de flujo ascendente, los cuales se evaluaron bajo diferentes condiciones de tiempo de retención hidráulico TRH y de carga orgánica. Para una Demanda Química de Oxígeno DQO, afluente de 5000 a 30000 mg/1 y TRH de 3.0 días o más, se obtuvieron eficiencias de remoción superiores a 90% en términos de DQO. Para una DQO afluente constante de 20000 mg/1 y TRH de 1.3 días, se alcanzaron eficiencias entre 75-80%

Down-regulation of endothelial TLR4 signalling after apo A-I gene transfer contributes to improved survival in an experimental model of lipopolysaccharide-induced inflammation

The protective effects of high-density lipoprotein (HDL) under lipopolysaccharide (LPS) conditions have been well documented. Here, we investigated whether an effect of HDL on Toll-like receptor 4 (TLR4) expression and signalling may contribute to its endothelial-protective effects and to improved survival in a mouse model of LPS-induced inflammation and lethality. HDL cholesterol increased 1.7-fold (p < 0.005) and lung endothelial TLR4 expression decreased 8.4-fold (p < 0.005) 2 weeks after apolipoprotein (apo) A-I gene transfer. Following LPS administration in apo A-I gene transfer mice, lung TLR4 and lung MyD88 mRNA expression, reflecting TLR4 signalling, were 3.0-fold (p < 0.05) and 2.1-fold (p < 0.05) lower, respectively, than in LPS control mice. Concomitantly, LPS-induced lung neutrophil infiltration, lung oedema and mortality were significantly attenuated following apo A–I transfer. In vitro, supplementation of HDL or apo A–I to human microvascular endothelial cells-1 24 h before LPS administration reduced TLR4 expression, as assessed by fluorescent-activated cell sorting, and decreased the LPS-induced MyD88 mRNA expression and NF-κB activity, independently of LPS binding. In conclusion, HDL reduces TLR4 expression and signalling in endothelial cells, which may contribute significantly to the protective effects of HDL in LPS-induced inflammation and lethality

High-throughput phenotyping and improvements in breeding cassava for increased carotenoids in the roots

Past research developed reliable equations to base selections for high β-carotene on near-infrared spectroscopy (NIR) predictions (100 genotypes d−1) rather than with high-performance liquid chromatography (HPLC) (<10 samples d−1). During recent harvest, CIAT made selections based on NIR predictions for the first time. This innovation produced valuable information that will help other cassava (Manihot esculenta Crantz) breeding programs. A total of 284 samples were analyzed with NIR and HPLC for total β-carotene (TBC) and by the oven method for dry matter content (DMC). Results indicated that NIR reliably predicted TBC and DMC. In addition, 232 genotypes grown in preliminary yield trials (PYTs) were harvested at 8.5 and 10.5 mo after planting (one plant per genotype and age) and root quality traits analyzed (by NIR only). Repeatability of results at the two ages was excellent, suggesting reliable results from NIR. In contrast to previous reports, age of the plant did not influence carotenoids content in the roots. The availability of a high-throughput NIR protocol allowed comparing results (for the first time) from seedling and cloned plants from the same genotype. Results showed very little relationship for DMC between seedling and cloned plants (R2 = 0.09). There was a much better association for TBC (R2 = 0.48) between seedling and cloned plants. It is postulated that variation in the environmental conditions when seedling and cloned plants (from the same genotype) may be responsible for these weak associations. Important changes in selection strategies have been implemented to overcome problems related to a lengthy harvesting season. (Résumé d'auteur

A global observational analysis to understand changes in air quality during exceptionally low anthropogenic emission conditions

This global study, which has been coordinated by the World Meteorological Organization Global Atmospheric Watch (WMO/GAW) programme, aims to understand the behaviour of key air pollutant species during the COVID-19 pandemic period of exceptionally low emissions across the globe. We investigated the effects of the differences in both emissions and regional and local meteorology in 2020 compared with the period 2015-2019. By adopting a globally consistent approach, this comprehensive observational analysis focuses on changes in air quality in and around cities across the globe for the following air pollutants PM2.5, PM10, PMC (coarse fraction of PM), NO2, SO2, NOx, CO, O-3 and the total gaseous oxidant (O-X = NO2 + O-3) during the pre-lockdown, partial lockdown, full lockdown and two relaxation periods spanning from January to September 2020. The analysis is based on in situ ground-based air quality observations at over 540 traffic, background and rural stations, from 63 cities and covering 25 countries over seven geographical regions of the world. Anomalies in the air pollutant concentrations (increases or decreases during 2020 periods compared to equivalent 2015-2019 periods) were calculated and the possible effects of meteorological conditions were analysed by computing anomalies from ERA5 reanalyses and local observations for these periods. We observed a positive correlation between the reductions in NO2 and NOx concentrations and peoples' mobility for most cities. A correlation between PMC and mobility changes was also seen for some Asian and South American cities. A clear signal was not observed for other pollutants, suggesting that sources besides vehicular emissions also substantially contributed to the change in air quality. As a global and regional overview of the changes in ambient concentrations of key air quality species, we observed decreases of up to about 70% in mean NO2 and between 30% and 40% in mean PM2.5 concentrations over 2020 full lockdown compared to the same period in 2015-2019. However, PM2.5 exhibited complex signals, even within the same region, with increases in some Spanish cities, attributed mainly to the long-range transport of African dust and/or biomass burning (corroborated with the analysis of NO2/CO ratio). Some Chinese cities showed similar increases in PM2.5 during the lockdown periods, but in this case, it was likely due to secondary PM formation. Changes in O-3 concentrations were highly heterogeneous, with no overall change or small increases (as in the case of Europe), and positive anomalies of 25% and 30% in East Asia and South America, respectively, with Colombia showing the largest positive anomaly of similar to 70%. The SO2 anomalies were negative for 2020 compared to 2015-2019 (between similar to 25 to 60%) for all regions. For CO, negative anomalies were observed for all regions with the largest decrease for South America of up to similar to 40%. The NO2/CO ratio indicated that specific sites (such as those in Spanish cities) were affected by biomass burning plumes, which outweighed the NO2 decrease due to the general reduction in mobility (ratio of similar to 60%). Analysis of the total oxidant (OX = NO2 + O-3) showed that primary NO2 emissions at urban locations were greater than the O-3 production, whereas at background sites, O-X was mostly driven by the regional contributions rather than local NO2 and O-3 concentrations. The present study clearly highlights the importance of meteorology and episodic contributions (e.g., from dust, domestic, agricultural biomass burning and crop fertilizing) when analysing air quality in and around cities even during large emissions reductions. There is still the need to better understand how the chemical responses of secondary pollutants to emission change under complex meteorological conditions, along with climate change and socio-economic drivers may affect future air quality. The implications for regional and global policies are also significant, as our study clearly indicates that PM2.5 concentrations would not likely meet the World Health Organization guidelines in many parts of the world, despite the drastic reductions in mobility. Consequently, revisions of air quality regulation (e.g., the Gothenburg Protocol) with more ambitious targets that are specific to the different regions of the world may well be required.Peer reviewe

Near-infrared spectroscopy applications for high-throughput phenotyping for cassava and yam: a review

Open Access Article; Published online: 12 Aug 2020The review aimed to identify the different high‐throughput phenotyping (HTP) techniques that used for quality evaluation in cassava and yam breeding programmes, and this has provided insights towards the development of metrics and their application in cassava and yam improvements. A systematic review of the published research articles involved the use of NIRS in analysing the quality traits of cassava and yam was carried out, and Scopus, Science Direct, Web of Sciences and Google Scholar were searched. The results of the review established that NIRS could be used in understanding the chemical constituents (carbohydrate, protein, vitamins, minerals, carotenoids, moisture, starch, etc.) for high‐throughput phenotyping. This study provides preliminary evidence of the application of NIRS as an efficient and affordable procedure for HTP. However, the feasibility of using mid‐infrared spectroscopy (MIRS) and hyperspectral imaging (HSI) in combination with the NIRS could be further studied for quality traits phenotyping

Hypofibrinolysis in diabetes: a therapeutic target for the reduction of cardiovascular risk

An enhanced thrombotic environment and premature atherosclerosis are key factors for the increased cardiovascular risk in diabetes. The occlusive vascular thrombus, formed secondary to interactions between platelets and coagulation proteins, is composed of a skeleton of fibrin fibres with cellular elements embedded in this network. Diabetes is characterised by quantitative and qualitative changes in coagulation proteins, which collectively increase resistance to fibrinolysis, consequently augmenting thrombosis risk. Current long-term therapies to prevent arterial occlusion in diabetes are focussed on anti-platelet agents, a strategy that fails to address the contribution of coagulation proteins to the enhanced thrombotic milieu. Moreover, antiplatelet treatment is associated with bleeding complications, particularly with newer agents and more aggressive combination therapies, questioning the safety of this approach. Therefore, to safely control thrombosis risk in diabetes, an alternative approach is required with the fibrin network representing a credible therapeutic target. In the current review, we address diabetes-specific mechanistic pathways responsible for hypofibrinolysis including the role of clot structure, defects in the fibrinolytic system and increased incorporation of anti-fibrinolytic proteins into the clot. Future anti-thrombotic therapeutic options are discussed with special emphasis on the potential advantages of modulating incorporation of the anti-fibrinolytic proteins into fibrin networks. This latter approach carries theoretical advantages, including specificity for diabetes, ability to target a particular protein with a possible favourable risk of bleeding. The development of alternative treatment strategies to better control residual thrombosis risk in diabetes will help to reduce vascular events, which remain the main cause of mortality in this condition