Characterisation of two snake toxin-targeting human monoclonal immunoglobulin G antibodies expressed in tobacco plants.

Current snakebite antivenoms are based on polyclonal animal-derived antibodies, which can neutralize snake venom toxins in envenomed victims, but which are also associated with adverse reactions. Therefore, several efforts within antivenom research aim to explore the utility of recombinant monoclonal antibodies, such as human immunoglobulin G (IgG) antibodies, which are routinely used in the clinic for other indications. In this study, the feasibility of using tobacco plants as bioreactors for expressing full-length human monoclonal IgG antibodies against snake toxins was investigated. We show that the plant-produced antibodies perform similarly to their mammalian cell-expressed equivalents in terms of in vitro binding. Complete neutralization was achieved by both the plant and mammalian cell-produced anti-α-cobratoxin antibody. The feasibility of using plant-based expression systems may potentially make it easier for laboratories in resource-poor settings to work with human monoclonal IgG antibodies

Strategies in 'snake venomics' aiming at an integrative view of compositional, functional, and immunological characteristics of venoms

This work offers a general overview on the evolving strategies for the proteomic analysis of snake venoms, and discusses how these may be combined through diverse experimental approaches with the goal of achieving a more comprehensive knowledge on the compositional, toxic, and immunological characteristics of venoms. Some recent developments in this field are summarized, highlighting how strategies have evolved from the mere cataloguing of venom components (proteomics/venomics), to a broader exploration of their immunological (antivenomics) and functional (toxicovenomics) characteristics. Altogether, the combination of these complementary strategies is helping to build a wider, more integrative view of the life-threatening protein cocktails produced by venomous snakes, responsible for thousands of deaths every year.Ministerio de Economía y Competitividad/[BFU2013-42833-P]//EspañaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP

The Indian cobra reference genome and transcriptome enables comprehensive identification of venom toxins

Snakebite envenoming is a serious and neglected tropical disease that kills ~100,000 people annually. High-quality, genome-enabled comprehensive characterization of toxin genes will facilitate development of effective humanized recombinant antivenom. We report a de novo near-chromosomal genome assembly of Naja naja, the Indian cobra, a highly venomous, medically important snake. Our assembly has a scaffold N50 of 223.35 Mb, with 19 scaffolds containing 95% of the genome. Of the 23,248 predicted protein-coding genes, 12,346 venom-gland-expressed genes constitute the \u27venom-ome\u27 and this included 139 genes from 33 toxin families. Among the 139 toxin genes were 19 \u27venom-ome-specific toxins\u27 (VSTs) that showed venom-gland-specific expression, and these probably encode the minimal core venom effector proteins. Synthetic venom reconstituted through recombinant VST expression will aid in the rapid development of safe and effective synthetic antivenom. Additionally, our genome could serve as a reference for snake genomes, support evolutionary studies and enable venom-driven drug discovery

Estimating a threshold price for CO2 emissions of buildings to improve their energy performance level. Case study of a new Spanish home

Energy consumption in homes produces CO2. In many countries, building regulations are being set to enable energy efficiency performance levels to be issued. In Spain, there is a regulated procedure to certify the energy performance of buildings according to their CO2 emissions. Consequently, some software tools have been design to simulate buildings and to obtain their energy consumption and CO2 emissions. In this paper the investment, maintenance and energy consumption costs are calculated for different energy performance levels and for various climatic zones, in a single-family home. According to the results, more energy efficient buildings imply higher construction and maintenance costs, which are not compensated by lower energy costs. Therefore, under current conditions, economic criteria do not support the improvement of the energy efficiency of a dwelling. Among the possible measures to promote energy efficiency, a price on CO2 emissions is to be suggested, including the social cost in the analysis. For this purpose, the cost-optimal methodology is used. In different scenarios for the discount rate y energy prices, various prices for CO2 are obtained, depending on the climatic zone and energy performance level.Ruá Aguilar, MJ.; Guadalajara Olmeda, MN. (2015). Estimating a threshold price for CO2 emissions of buildings to improve their energy performance level. Case study of a new Spanish home. Energy Efficiency. 8(2):183-203. doi:10.1007/s12053-014-9286-2S18320382AICIA. (2009). Escala de calificación energética. Edificios de nueva construcción. Madrid: Instituto para la Diversificación y Ahorro de la Energía, Ministerio de Industria, Turismo y Comercio.Al-Homoud, M. S. (2005). Performance characteristics and practical applications of common building thermal insulation materials. Building and Environment, 40(3), 353–360.Amecke, H. 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Facility maintenance: the manager’s practical guide and handbook. New York: AMACOM American Management Association. New York, NY 10019.Concerted Action EPBD (2008). Implementation of the energy performance of buildings directive. Country reports 2008. Brussels: Directorate General for Energy and Transport, European Commission (available at www.epbd.ca.eu and www.buildup.eu ).Concerted Action EPBD (2011). Implementing the energy performance of buildings directive. Country reports 2011. Brussels: European Union (available at www.epbd.ca.eu and www.buildup.eu ).Davies, H., & Wyatt, D. (2004). Appropriate use or method for durability and service life prediction. Building Research and Information, 32(6), 552–553.Dresner, S., & Ekins, P. (2006). Economic instruments to improve UK home energy efficiency without negative social impacts. Fiscal Studies, 27(1), 47–74.Drury, C. (2008). Management and cost accounting, 7th ed. London.Eurostat European Comission, Instituto de Diversificación y Ahorro de Energía (IDAE), Ministerio de Industria, Energía y Turismo (2011). Proyecto SECH-SPAHOUSEC. Análisis del consumo energético del sector residencial en España. Informe Final. Madrid.Fraunhofer Institute for Systems and Innovation Research ISI (Germany) (2012). Financing the energy efficient transformation of the building sector in the EU. Lessons from the ODYSSEE-MURE project.Garrido, N., Almecija, J. C., Folch, C., Martínez, I. (2011). Certificación energética de edificios. Grupo de Estudios de Energía para la Sostenibilidad (CEES). Cátedra Unesco Sostenibilidad, Universitat Politècnica de Catalunya. (Available at: upcommons.upc.edu/e-prints/bitstream/2117/11820/1/GAS Natural_090406.pdf).Gómez, J. M., & Esteban, M. A. (2010). Sostenibilidad en la edificación. Comparación de dos tipologías constructivas. Rendimiento de los recursos. Ingeniería de Edificación Universitat Politècnica de Catalunya. 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Cross-recognition of a pit viper (Crotalinae) polyspecific antivenom explored through high-density peptide microarray epitope mapping

Snakebite antivenom is a 120 years old invention based on polyclonal mixtures of antibodies purified from the blood of hyper-immunized animals. Knowledge on antibody recognition sites (epitopes) on snake venom proteins is limited, but may be used to provide molecular level explanations for antivenom cross-reactivity. In turn, this may help guide antivenom development by elucidating immunological biases in existing antivenoms. In this study, we have identified and characterized linear elements of B-cell epitopes from 870 pit viper venom protein sequences by employing a high-throughput methodology based on custom designed high-density peptide microarrays. By combining data on antibody-peptide interactions with multiple sequence alignments of homologous toxin sequences and protein modelling, we have determined linear elements of antibody binding sites for snake venom metalloproteases (SVMPs), phospholipases A2s (PLA2s), and snake venom serine proteases (SVSPs). The studied antivenom antibodies were found to recognize linear elements in each of the three enzymatic toxin families. In contrast to a similar study of elapid (non-enzymatic) neurotoxins, these enzymatic toxins were generally not recognized at the catalytic active site responsible for toxicity, but instead at other sites, of which some are known for allosteric inhibition or for interaction with the tissue target. Antibody recognition was found to be preserved for several minor variations in the protein sequences, although the antibody-toxin interactions could often be eliminated completely by substitution of a single residue. This finding is likely to have large implications for the cross-reactivity of the antivenom and indicate that multiple different antibodies are likely to be needed for targeting an entire group of toxins in these recognized sites.Novo Nordisk Foundation/[NNF13OC0005613]/NNF/DinamarcaNovo Nordisk Foundation/[NNF16OC0019248]/NNF/DinamarcaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP

Horse immunization with short-chain consensus α-neurotoxin generates antibodies against broad spectrum of elapid venomous species

Antivenoms are fundamental in the therapy for snakebites. In elapid venoms, there are toxins, e.g. short-chain α-neurotoxins, which are quite abundant, highly toxic, and consequently play a major role in envenomation processes. The core problem is that such α-neurotoxins are weakly immunogenic, and many current elapid antivenoms show low reactivity towards them. We have previously developed a recombinant consensus short-chain α-neurotoxin (ScNtx) based on sequences from the most lethal elapid venoms from America, Africa, Asia, and Oceania. Here we report that an antivenom generated by immunizing horses with ScNtx can successfully neutralize the lethality of pure recombinant and native short-chain α-neurotoxins, as well as whole neurotoxic elapid venoms from diverse genera such as Micrurus, Dendroaspis, Naja, Walterinnesia, Ophiophagus and Hydrophis. These results provide a proof-ofprinciple for using recombinant proteins with rationally designed consensus sequences as universal immunogens for developing next-generation antivenoms with higher effectiveness and broader neutralizing capacity.Universidad de Costa Rica/[741-B7-608]/UCR/Costa RicaDireccion General de Asuntos del Personal Academico/[IN203118]/DGAPA/MéxicoDireccion General de Asuntos del Personal Academico/[IN207218]/DGAPA/MéxicoUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP

The evolutionary psychology of leadership trait perception

Knowles, Kristen K. - ORCID 0000-0001-9664-9055 https://orcid.org/0000-0001-9664-9055Many researchers now approach the understanding of how facial characteristics shape the perception of leadership ability through the lens of human evolution. This approach considers what skills and characteristics would have been valuable for leaders to possess in our evolutionary history, including dominance, masculinity, and trustworthiness. Moreover, it gives an understanding about why rapid categorisation of these social cues from faces is adaptive. In this chapter, I present evolutionary arguments for social inferences based on faces, and discuss how our understanding of this categorisation has shifted away from purely associative phenomena towards evolved, innate processes. I explain how the perception of leadership ability in faces is linked to variance in facial morphology, and how these morphologies tell us something about the individuals who carry them. Specific facial cues relating to leadership-relevant traits are discussed, as well as the underlying biological systems that accompany these traits. I also explain the importance of context and individual differences on the prioritisation of seemingly disparate facial cues to leadership: dominance and trustworthiness. I also discuss recent findings in this area which further extend these concepts to examine cues to leadership in women’s faces, generally overlooked by evolutionary psychologists, and how political ideology can interact with these effects.https://doi.org/10.1007/978-3-319-94535-4_5pubpu

In vivo neutralization of the dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG monoclonal antibodies

The black mamba (Dendroaspis polylepis) is one of the most feared snake species of the African savanna. It has a potent, fast-acting neurotoxic venom comprised of dendrotoxins and α-neurotoxins associated with high fatality in untreated victims. Current antivenoms are both scarce on the African continent and present a number of drawbacks as they are derived from the plasma of hyper-immunized large mammals. Here, we describe the development of an experimental recombinant antivenom by a combined toxicovenomics and phage display approach. The recombinant antivenom is based on a cocktail of fully human immunoglobulin G (IgG) monoclonal antibodies capable of neutralizing dendrotoxin-mediated neurotoxicity of black mamba whole venom in a rodent model. Our results show the potential use of fully human monoclonal IgGs against animal toxins and the first use of oligoclonal human IgG mixtures against experimental snakebite envenoming.Novo Nordisk Foundation/[NNF16OC0019248]//DinamarcaHørslev Foundation/[203866]//DinamarcaOticon Foundation/[17-3802]//DinamarcaUniversidad de Costa Rica - Instituto Clodomiro Picado/[]//Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP

Causes and consequences of snake venom variation

Snake venoms are mixtures of toxins that vary extensively between and within snake species. This variability has serious consequences for the management of the world’s 1.8 million annual snakebite victims. Advances in ‘omic’ technologies have empowered toxinologists to comprehensively characterise snake venom compositions, unravel the molecular mechanisms that underpin venom variation, and elucidate the ensuing functional consequences. In this review, we describe how such mechanistic processes have resulted in suites of toxin isoforms that cause diverse pathologies in human snakebite victims, and we detail how variation in venom composition can result in treatment failure. Finally, we outline current therapeutic approaches designed to circumvent venom variation and deliver next-generation treatments for the world’s most lethal neglected tropical disease