Lead optimisation of dehydroemetine for repositioned use in malaria

Drug repositioning offers an effective alternative to de novo drug design to tackle the urgent need for novel anti-malarial treatments. The anti-amoebic compound, emetine dihydrochloride, has been identified as a potent in-vitro inhibitor of the multi-drug resistant strain K1 of Plasmodium falciparum (IC50: 47 nM ± 2.1 nM). Dehydroemetine, a synthetic analogue of emetine dihydrochloride has been reported to have less cardiotoxic effects than emetine. The structures of two diastereomers of dehydroemetine were modelled on the published emetine binding site on cryo-EM structure 3J7A (Pf 80S ribosome in complex with emetine) and it was found that (-)-R,S-dehydroemetine mimicked the bound pose of emetine more closely than (-)-S,S-dehydroisoemetine. (-)-R,S-dehydroemetine (IC50 71.03 ± 6.1 nM) was also found to be highly potent against the multi-drug resistant K1 strain of P. falciparum in comparison with (-)-S,S-dehydroisoemetine (IC50 2.07 ± 0.26 μM), which loses its potency due to the change of configuration at C-1′. In addition to its effect on the asexual erythrocytic stages of P. falciparum, the compounds exhibited gametocidal properties with no cross-resistance against any of the multi-drug resistant strains tested. Drug interaction studies showed (-)-R,S-dehydroemetine to have synergistic antimalarial activity with atovaquone and proguanil. Emetine dihydrochloride, and (-)-R,S-dehydroemetine failed to show any inhibition of the hERG potassium channel and displayed activity on the mitochondrial membrane potential indicating a possible multi-modal mechanism of action. [Abstract copyright: Copyright © 2020 Panwar et al.

Genomic Evolution of Two Acinetobacter baumannii Clinical Strains from ST-2 Clones Isolated in 2000 and 2010 (ST-2_clon_2000 and ST-2_clon_2010)

Acinetobacter baumannii is a successful nosocomial pathogen due to its ability to persist in hospital environments by acquiring mobile elements such as transposons, plasmids, and phages. In this study, we compared two genomes of A. baumannii clinical strains isolated in 2000 (ST-2_clon_2000) and 2010 (ST-2_clon_2010) from GenBank project PRJNA308422

Report on fisheries mangement in international deep sea water and its biodiversity conservation

It is a repport on the FAO "Analysis and guide for the implementation of international and policy instruments related to deep sea fisheries and biodiversity conservation in ABJN (Areas Beyond National Jurisdiction)” of 27th June 2016

CompareML: A Novel Approach to Supporting Preliminary Data Analysis Decision Making

There are a large number of machine learning algorithms as well as a wide range of libraries and services that allow one to create predictive models. With machine learning and artificial intelligence playing a major role in dealing with engineering problems, practising engineers often come to the machine learning field so overwhelmed with the multitude of possibilities that they find themselves needing to address difficulties before actually starting on carrying out any work. Datasets have intrinsic properties that make it hard to select the algorithm that is best suited to some specific objective, and the ever-increasing number of providers together make this selection even harder. These were the reasons underlying the design of CompareML, an approach to supporting the evaluation and comparison of machine learning libraries and services without deep machine learning knowledge. CompareML makes it easy to compare the performance of different models by using well-known classification and regression algorithms already made available by some of the most widely used providers. It facilitates the practical application of methods and techniques of artificial intelligence that let a practising engineer decide whether they might be used to resolve hitherto intractable problems. Thus, researchers and engineering practitioners can uncover the potential of their datasets for the inference of new knowledge by selecting the most appropriate machine learning algorithm and determining the provider best suited to their data

Nitrogen fixation in the upwelling region off NW Iberia

Comunicación oralPicoplankton are the most abundant organisms in the ocean, often dominate planktonic biomass and primary production, and they could represent a substantial contribution to the global export of carbon. Nowadays, we have a limited understanding about the factors that control the picoplankton community structure. A recent analysis indicates that light and temperature are the main factors explaining Prochlorococcus and Synechococcus distributions, whereas nutrient concentrations play a minor role (Flombaum et al., PNAS 2013). Methodological difficulties to quantify mixing in the marine enviroments have motivated the use of indirect approaches to determine the input of nutrients into the euphotic zone, however, nutrient concentrations are not necessarily a proxy of nutrient supply. We present a large data set, including open-ocean and coastal regions, of simultaneous measurements of picoplankton abundance, temperature and irradiance, together with estimates of nutrient supply. The transport of nutrients across the nutricline was computed combining nutrient concentrations and small-scale turbulence observations collected with a microstructure profiler. Our preliminary results indicate that nutrient supply also plays a role in the distribution of functional groups of picoplankton in the ocean

Toward a holistic understanding of pastoralism

Pastoralism is globally significant in social, environmental and economic terms. However, it experiences crises rooted in misconceptions and poor interdisciplinary understanding, while being largely overlooked in international sustainability forums and agendas. Here we propose a transdisciplinary research approach to understand pastoralist transitions using i) social, economic and environmental dimensions, ii) diverse geographic contexts and scales to capture emerging properties, allowing for cross-system comparisons, and iii) timescales from the distant past to the present. We provide specific guidelines to develop indicators for this approach, within a social-ecological resilience analytical framework to understand change. Distinct systems undergo similar transitions over time, crossing critical thresholds and then either collapsing or recovering. Such an integrated view of multidimensional interactions improves understanding of possible tipping points, thereby supporting better-informed decision-making. The need for a paradigm shift in pastoralism science and policy is pressing. This research approach, including participatory methods, can provide the solutions urgently needed.Peer reviewe

Are technological projects reducing social inequalities and improving people's well-being? A capability approach analysis of renewable energy-based electrification projects in Cajamarca, Peru

This is an Accepted Manuscript of an article published by Taylor & Francis Group in Journal of Human Development and Capabilities on 18/11/2013, available online: http://dx.doi.org/10.1080/19452829.2013.837035".[EN] This paper analyses four renewable energy-based electrification projects that were implemented by the non-governmental organization Practical Action in the rural area of Cajamarca, Peru. Using the capability approach, the research examines the effect of the projects on the things people value. It confirms that projects provide different benefits to the communities (reducing air pollution caused by candles and kerosene, improving access to communication through television and radio, providing the possibility of night study under appropriate light, etc.), but also detects an expansion of the capabilities in other areas not considered by the non-governmental organization such as those related to religion, leisure or community participation. However, the expansion of capabilities is different for men and women. The study reveals the limitations of interventions designed to supply technology, electrification in this particular case, which do not take into account certain elements that can make the use of technology contribute unequally to the expansion of people's capabilities. The paper concludes that technological projects can generate inequalities, and some recommendations are presented in order to address these issues when planning interventions.We would like to thank the people from the Peruvian communities where the case study was implemented. Many thanks also to Practical Action-Peru for their collaboration, and to the Centro de Cooperación al Desarrollo of our University who granted this research through Adsideo 2010, and special thanks to José Sastre for his involvement during the fieldwork.Fernández-Baldor Martínez, Á.; Boni Aristizábal, A.; Lillo Rodrigo, P.; Hueso, A. (2014). Are technological projects reducing social inequalities and improving people's well-being? A capability approach analysis of renewable energy-based electrification projects in Cajamarca, Peru. Journal of Human Development and Capabilities. 15(1):13-27. https://doi.org/10.1080/19452829.2013.837035S132715

Lack of association between TLR4 rs4986790 polymorphism and risk of cardiovascular disease in patients with rheumatoid arthritis

This is copy of an article published in the DNA and cell biology 2012 © Mary Ann Liebert, Inc.; DNA and cell bilogy is available online at: http://online.liebertpub.comRheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased cardiovascular (CV) mortality. Toll-like receptor-4 (TLR4) activates the innate immune response via NF-kB pathway and mitogenactivated protein kinase signaling, leading to expression of proinflammatory cytokines and chemokines. The G allele of TLR4 rs4986790 (+ 896A > G, Asp299Gly) gene polymorphism has been implicated in reduction of risk of atherosclerosis. In this study, 1481 RA patients fulfilling the 1987 American College of Rheumatology (ACR) criteria were genotyped for the rs4986790 TLR4 variant to determine the influence of this variant in the risk of CV events in these patients. Also, HLA-DRB1 status was determined using molecular based methods. Moreover, potential influence of rs4986790 variant in the development of subclinical atherosclerosis was assessed in a subgroup of RA patients with no history of CV events by the measurement of surrogate markers of subclinical atherosclerosis. No statistically significant differences in allele or genotype frequencies for the rs4986790 variant between RA patients who experienced CV events or not were found. Likewise, no significant association between this gene variant and any of the surrogate markers of subclinical atherosclerosis was found. In summary, results in our study do not support the hypothesis that the rs4986790 (+ 896A > G, Asp299Gly) TLR4 variant may influence predisposition for subclinical atherosclerosis and clinically evident CV disease in RA patientsThis study was supported by two grants from Fondo de Investigaciones Sanitarias PI06-0024 and PS09/00748 (Spain). This work was partially supported by RETICS Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), within the VI PN de I +D+ i 2008–2011 (FEDER). M.G.B. is supported by a grant from Fundación Española de Reumatología (FER). R.L.M. is supported by a grant by IFIMAV, Santander (Spain)