Vectored antibody gene delivery protects against Plasmodium falciparum sporozoite challenge in mice

Malaria caused by Plasmodium falciparum kills nearly one million children each year and imposes crippling economic burdens on families and nations worldwide. No licensed vaccine exists, but infection can be prevented by antibodies against the circumsporozoite protein (CSP), the major surface protein of sporozoites, the form of the parasite injected by mosquitoes. We have used vectored immunoprophylaxis (VIP), an adeno-associated virus-based technology, to introduce preformed antibody genes encoding anti-P. falciparum CSP mAb into mice. VIP vector-transduced mice exhibited long-lived mAb expression at up to 1,200 µg/mL in serum, and up to 70% were protected from both i.v. and mosquito bite challenge with transgenic Plasmodium berghei rodent sporozoites that incorporate the P. falciparum target of the mAb in their CSP. Serum antibody levels and protection from mosquito bite challenge were dependent on the dose of the VIP vector. All individual mice expressing CSP-specific mAb 2A10 at 1 mg/mL or more were completely protected, suggesting that in this model system, exceeding that threshold results in consistent sterile protection. Our results demonstrate the potential of VIP as a path toward the elusive goal of immunization against malaria

Sitio Web con nivel de accesibilidad A para las Unidades Educativas y Colegios de la ciudad de Cuenca, Ecuador

La accesibilidad Web hace referencia a un diseño Web que va a permitir que diversas personas puedan percibir, entender, navegar e interactuar con la Web, aportando a su vez contenidos. El objetivo de este artículo es desarrollar un prototipo de un sitio Web con nivel de accesibilidad A, basándose en un análisis preliminar del estándar ISO/IEC 40500:2012 para las unidades educativas y Colegios de la ciudad de Cuenca, Ecuador. Para lograr el objetivo, primero se realizó un análisis preliminar del estándar ISO/IEC 40500:2012 en las 24 instituciones educativas de la ciudad de Cuenca que cuentan con un sitio Web, posteriormente se diseñó la arquitectura de un sitio Web accesible para personas con discapacidad visual y se desarrolló el prototipo de un sitio Web accesible. Se evaluó el prototipo del sitio Web mediante la herramienta Examinator. En los resultados obtenidos se identificaron diversos fallos en los criterios de conformidad, los cuales fueron corregidos y en la cuarta evaluación se logró obtener el resultado esperado de 10

MED 25 años: el nacimiento de una idea hecha realidad

Nos sentimos honrados y agradecidos de tener la oportunidad de contar la historia nunca antes contada sobre cómo surgió Med. Honrados por haber sido los estudiantes que fundaron la revista y agradecidos con todos aquellos que en estos 25 años han mantenido vivo ese sueño casi inalcanzable de tener un órgano de difusión científica de la Facultad de Medicina de la Universidad Militar Nueva Granada y el Hospital Militar Central. Gracias a 25 años de esfuerzos continuos, la esencia de Med sigue intacta, ser una revista médica propia, en busca de la excelencia, de todos y para todos

Floral Morphogenesis: Stochastic Explorations of a Gene Network Epigenetic Landscape

In contrast to the classical view of development as a preprogrammed and deterministic process, recent studies have demonstrated that stochastic perturbations of highly non-linear systems may underlie the emergence and stability of biological patterns. Herein, we address the question of whether noise contributes to the generation of the stereotypical temporal pattern in gene expression during flower development. We modeled the regulatory network of organ identity genes in the Arabidopsis thaliana flower as a stochastic system. This network has previously been shown to converge to ten fixed-point attractors, each with gene expression arrays that characterize inflorescence cells and primordial cells of sepals, petals, stamens, and carpels. The network used is binary, and the logical rules that govern its dynamics are grounded in experimental evidence. We introduced different levels of uncertainty in the updating rules of the network. Interestingly, for a level of noise of around 0.5–10%, the system exhibited a sequence of transitions among attractors that mimics the sequence of gene activation configurations observed in real flowers. We also implemented the gene regulatory network as a continuous system using the Glass model of differential equations, that can be considered as a first approximation of kinetic-reaction equations, but which are not necessarily equivalent to the Boolean model. Interestingly, the Glass dynamics recover a temporal sequence of attractors, that is qualitatively similar, although not identical, to that obtained using the Boolean model. Thus, time ordering in the emergence of cell-fate patterns is not an artifact of synchronous updating in the Boolean model. Therefore, our model provides a novel explanation for the emergence and robustness of the ubiquitous temporal pattern of floral organ specification. It also constitutes a new approach to understanding morphogenesis, providing predictions on the population dynamics of cells with different genetic configurations during development

Gelatin–chitosan–PVA hydrogels and their application in agriculture

This work demonstrated the ability of a fabrication process in the preparation of gelatin-chitosan-PVA hydrogels for potential agricultural applications. The hydrogels showed a dense, tridimensional, interconnected and reticulated structure that was more evident in the hydrogel loaded with inulin. The hydrogels showed a water absorption capacity of ≤12 times its mass. FTIR and light microscopy demonstrated that the hydrogels were biodegradable. The percentage of degradation of hydrogels in inoculated soil was higher than in sterile soil using the soil burial test. Hydrogel loaded with inulin was found to be capable of inducing resistance in chili plants against Phytophthora capsici.ITESO, A.C

General Gauge Mediation at the Weak Scale

We completely characterize General Gauge Mediation (GGM) at the weak scale by solving all IR constraints over the full parameter space. This is made possible through a combination of numerical and analytical methods, based on a set of algebraic relations among the IR soft masses derived from the GGM boundary conditions in the UV. We show how tensions between just a few constraints determine the boundaries of the parameter space: electroweak symmetry breaking (EWSB), the Higgs mass, slepton tachyons, and left-handed stop/sbottom tachyons. While these constraints allow the left-handed squarks to be arbitrarily light, they place strong lower bounds on all of the right-handed squarks. Meanwhile, light EW superpartners are generic throughout much of the parameter space. This is especially the case at lower messenger scales, where a positive threshold correction to $m_h$ coming from light Higgsinos and winos is essential in order to satisfy the Higgs mass constraint.Comment: 43 pages, 20 figures, mathematica package included in the sourc

Histopathology, microbiology and the inflammatory process associated with Sarcoptes scabiei infection in the Iberian ibex, Capra pyrenaica

© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.[EN]Background: Sarcoptic mange has been identified as the most significant infectious disease affecting the Iberian ibex (Capra pyrenaica). Despite several studies on the effects of mange on ibex, the pathological and clinical picture derived from sarcoptic mange infestation is still poorly understood. To further knowledge of sarcoptic mange pathology, samples from ibex were evaluated from histological, microbiological and serological perspectives. Methods: Samples of skin, non-dermal tissues and blood were collected from 54 ibex (25 experimentally infected, 15 naturally infected and 14 healthy). Skin biopsies were examined at different stages of the disease for quantitative cellular, structural and vascular changes. Sixteen different non-dermal tissues of each ibex were taken for histological study. Acetylcholinesterase and serum amyloid A protein levels were evaluated from blood samples from ibex with different lesional grade. Samples of mangy skin, suppurative lesions and internal organs were characterized microbiologically by culture. Bacterial colonies were identified by a desorption/ionization time-of-flight mass spectrometry system (MALDI TOF/TOF). Results: The histological study of the skin lesions revealed serious acanthosis, hyperkeratosis, rete ridges, spongiotic oedema, serocellular and eosinophilic crusts, exocytosis foci, apoptotic cells and sebaceous gland hyperplasia. The cellular response in the dermis was consistent with type I and type IV hypersensitivity responses. The most prominent histological findings in non-dermal tissues were lymphoid hyperplasia, leukocytosis, congestion and the presence of amyloid deposits. The increase in serum concentrations of acetylcholinesterase and amyloid A protein correlated positively with the establishment of the inflammatory response in mangy skin and the presence of systemic amyloidosis. A wide variety of bacterial agents were isolated and the simultaneous presence of these in mangy skin, lymph nodes and internal organs such as lungs, liver, spleen and kidney was compatible with a septicaemic pattern of infection. Conclusions: The alteration of biomarkers of inflammation and its implication in the pathogenesis of the disease and development of lesions in non-dermal tissues and septicaemic processes are serious conditioners for the survival of the mangy ibex. This severe clinical picture could be an important factor when considering the decision to eliminate animals that exceed a certain disease threshold from a population.SIThis study was funded by MINECO from the Spanish Government (grant numbers CGL2012-40043-C0-01, CGL2012-40043-CO2-02 and CGL2016-80543-P). The authors’ research activities are partially funded by the PAIDI Research Group RNM-118 from Junta de Andalucia. José Espinosa was supported by a PhD Grant (grant number ECC/1402/2013: BES-2013-063931). This study is part of the project "Bases biológicas para la gestión de la sarna sarcóptica en la cabra montés (Capra pyrenaica) de Sierra Nevada"

KM3NeT broadcast optical data transport system

[EN] The optical data transport system of the KM3NeT neutrino telescope at the bottom of the Mediterranean Sea will provide more than 6000 optical modules in the detector arrays with a point-to-point optical connection to the control stations onshore. The ARCA and ORCA detectors of KM3NeT are being installed at a depth of about 3500 m and 2500 m, respectively and their distance to the control stations is about 100 kilometers and 40 kilometers. In particular, the two detectors are optimised for the detection of cosmic neutrinos with energies above about 1 TeV (ARCA) and for the detection of atmospheric neutrinos with energies in the range 1 GeV-1 TeV (ORCA). The expected maximum data rate is 200 Mbps per optical module. The implemented optical data transport system matches the layouts of the networks of electro-optical cables and junction boxes in the deep sea. For efficient use of the fibres in the system the technology of Dense Wavelength Division Multiplexing is applied. The performance of the optical system in terms of measured bit error rates, optical budget are presented. The next steps in the implementation of the system are also discussed.The authors acknowledge the Foton Institute for providing all the reports concerning the cited measure-ments performed at the their facilities in the years 2014-2015 during the Phase I architecture design. The authors acknowledge the financial support of the funding agencies: Agence Nationale de la Recherche (contract ANR-15-CE31-0020) , Centre National de la Recherche Scientifique (CNRS) , Commission Europenne (FEDER fund and Marie Curie Program) , Institut Universitaire de France (IUF) , LabEx UnivEarthS (ANR-10-LABX-0023 and ANR-18-IDEX-0001) , Paris Ile-de-France Region, France; Deutsche Forschungsgemeinschaft (DFG), Germany; The General Secretariat of Research and Innovation (GSRI), Greece Istituto Nazionale di Fisica Nucleare (INFN) , Ministero dell'Universite della Ricerca (MIUR), PRIN 2017 program (Grant NAT-NET 2017W4HA7S) Italy; Ministry of Higher Education, Scientific Research and Innovation, Morocco, and the Arab Fund for Economic and Social Development, Kuwait; Nederlandse organisatie voor Wetenschappelijk Onderzoek (NWO), the Netherlands; The National Science Centre, Poland (2021/41/N/ST2/01177) ; National Authority for Scientific Research (ANCS), Romania; Ministerio de Ciencia, Innovacion, Investigacion y Universidades (MCIU) : Programa Estatal de Generacion de Conocimiento (refs. PGC2018-096663-B-C41,-A-C42,-B-C43,-B-C44 and refs. PID2021-124591NB-C41,-C42,-C43) (MCIU/FEDER, Generalitat Valenciana: Prometeo (PROMETEO/2020/019) , Grisolia (refs. GRISOLIA/2018/119,/2021/192) and GenT (refs. CIDEGENT/2018/034,/2019/043,/2020/049,/2021/023) programs, Junta de Andalucia (ref. A-FQM-053-UGR18) , La Caixa Foundation (ref. LCF/BQ/IN17/11620019) , EU: MSC program (ref. 101025085) , Spain; Maria Zambrano program within the framework of grants for retaining in the Spanish university system (Spanish Ministry of Universities, funded by the European Union, NextGenerationEU) .Aiello, S.; Albert, A.; Alves Garre, S.; Ambrosone, A.; Aly, Z.; Ameli, F.; Anghinolfi, M.... (2023). KM3NeT broadcast optical data transport system. Journal of Instrumentation. 18(2). https://doi.org/10.1088/1748-0221/18/02/T0200118

Determining the neutrino mass ordering and oscillation parameters with KM3NeT/ORCA

[EN] The next generation of water Cherenkov neu-trino telescopes in the Mediterranean Sea are under con- struction offshore France (KM3NeT/ORCA) and Sicily (KM3NeT/ARCA). The KM3NeT/ORCA detector features an energy detection threshold which allows to collect atmo- spheric neutrinos to study flavour oscillation. This paper reports the KM3NeT/ORCA sensitivity to this phenomenon. The event reconstruction, selection and classification are described. The sensitivity to determine the neutrino mass ordering was evaluated and found to be 4.4¿ if the true order- ing is normal and 2.3¿ if inverted, after 3 years of data taking. The precision to measure ¿m² and ¿¿¿ were also estimated and found to be 85.10¿¿ eV² and (¿¹.¿ -3.1)¿ for normal neu- trino mass ordering and, 75.10¿¿ eV² and (¿².¿ -7.0)¿ for inverted ordering. Finally, a unitarity test of the leptonic mixing matrix by measuring the rate of tau neutrinos is described. Three years of data taking were found to be sufficient to exclude ¿The authors acknowledge the financial support of the funding agencies: Agence Nationale de la Recherche (contract ANR-15-CE31-0020), Centre National de la Recherche Scientifique (CNRS), Commission Europeenne (FEDER fund and Marie Curie Program), Institut Universitaire de France (IUF), LabEx UnivEarthS (ANR-10-LABX-0023 and ANR-18-IDEX-0001), Paris Ile-de-France Region, France; Shota Rustaveli National Science Foundation of Georgia (SRNSFG, FR-18-1268), Georgia; Deutsche Forschungsgemeinschaft (DFG), Germany; The General Secretariat of Research and Technology (GSRT), Greece; Istituto Nazionale di Fisica Nucleare (INFN), Ministero dell'Universita e della Ricerca (MIUR), PRIN 2017 program (Grant NAT-NET 2017W4HA7S) Italy; Ministry of Higher Education Scientific Research and Professional Training, ICTP through Grant AF-13, Morocco; Nederlandse organisatie voor Wetenschappelijk Onderzoek (NWO), the Netherlands; The National Science Centre, Poland (2015/18/E/ST2/00758); National Authority for Scientific Research (ANCS), Romania; Ministerio de Ciencia, Innovacion, Investigacion y Universidades (MCIU): Programa Estatal de Generacion de Conocimiento (refs. PGC2018-096663-B-C41, -A-C42, -B-C43, -B-C44) (MCIU/FEDER), Severo Ochoa Centre of Excellence and MultiDark Consolider (MCIU), Junta de Andalucia (ref. SOMM17/6104/UGR), Generalitat Valenciana: Grisolia (ref. GRISOLIA/2018/119) and GenT (ref. CIDEGENT/2018/034 and CIDEGENT/2019/043) programs, La Caixa Foundation (ref. LCF/BQ/IN17/11620019), EU: MSC program (ref. 713673), Spain.Aiello, S.; Albert, A.; Alves Garre, S.; Aly, Z.; Ambrosone, A.; Ameli, F.; Andre, M.... (2022). Determining the neutrino mass ordering and oscillation parameters with KM3NeT/ORCA. The European Physical Journal C. 82(1):1-16. https://doi.org/10.1140/epjc/s10052-021-09893-011682