Easing the Transition From Middle School to High School for Long-term English Learners

The research question addressed in this project was, how do educational stakeholders help to create a successful transition from middle school to high school for our long-term English learners? The author of this capstone documented her personal experience as a middle school teacher of long-term English learners who inspired her to research strategies and methods to help support students in their transition from middle school to high school. The available research on transitioning students from middle school to high school merged with English learner theories and research created a framework for a curriculum unit for eighth grade long-term English learners. This unit features various activities and lessons that help prepare students for a more successful transition into high school based upon four main learning objectives, including three academic language objectives

DC-SIGN as a model of pathogen recognition receptor : interaction with the envelope glycoproteins of HIV-1 and Ebola virus and the role in viral pathogenesis

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Microbiología, leída el 04-07-2014Las lectinas de tipo C juegan un papel importante como receptores de reconocimiento de los carbohidratos derivados de patógenos por el sistema inmunológico. El receptor DC-SIGN fue inicialmente identificado en el año 2000 por Geijtenbeek y cols. como el factor de la unión del VIH-1, que capturaba la envoltura viral y facilitaba la infección. Durante años, se llevaron a cabo múltiples estudios para caracterizar el papel biológico de DC-SIGN. Se ha demostrado que DC-SIGN juega un papel en la respuesta del sistema inmunológico. Por otro lado, se ha señalado que DC-SIGN tiene un papel como un receptor para los patógenos. DC-SIGN reconoce las glicoproteínas que contienen un numero alto de los N-carbohidratos presentes en manera multivalente en la superficie de diferentes patógenos. Se ha sugerido que DC-SIGN puede mejorar la entrada viral y la infección directa en el proceso referido como infección en cis, así como también puede capturar y transmitir las partículas virales a células susceptibles en el proceso denominado como infección en trans. En nuestro estudio hemos estandarizado y evaluado el modelo celular de la infección mediada por DC-SIGN por el virus y la utilidad del nuestro modelo de infección como una plataforma de monitorización de las estrategias antivirales dirigidas frente DC-SIGN. Por otra parte, hemos tratado de estudiar la implicación del receptor DC-SIGN en la patogénesis de los virus de Ébola y del VIH-1. A pesar del papel de DC-SIGN en la entrada del virus de Ébola y la difusión inicial del virus, en nuestro estudio encontramos significativamente mayor uso de DC-SIGN por la cepa no patógena de Ébola Reston en comparación con la cepa más virulenta Ébola Zaire. Este hallazgo podría indicar que DC-SIGN en el caso de Ébola Reston esta involucrado en un control inmunitario más eficaz. En el caso del VIH-1, hemos encontrado que las glicoproteínas de la envoltura del VIH-1 de los controladores virológicos, especialmente los Controladores Virémicos (VC), utilizan DC-SIGN más eficientemente en el experimento de trans-infección en comparación con los pacientes con enfermedad crónica. En el grupo de los VC, la significativamente mayor trans-infección observada podría indicar que DC-SIGN participa en la detección viral, presentación y control inmunológico más que en la difusión viral, como en el caso de trans-infección por Ébola Reston.Depto. de Inmunología, Oftalmología y ORLFac. de MedicinaTRUEunpu

Virus-like glycodendrinanoparticles displaying quasi-equivalent nested polyvalency upon glycoprotein platforms potently block viral infection

Ligand polyvalency is a powerful modulator of protein–receptor interactions. Host–pathogen infection interactions are often mediated by glycan ligand–protein interactions, yet its interrogation with very high copy number ligands has been limited to heterogenous systems. Here we report that through the use of nested layers of multivalency we are able to assemble the most highly valent glycodendrimeric constructs yet seen (bearing up to 1,620 glycans). These constructs are pure and well-defined single entities that at diameters of up to 32 nm are capable of mimicking pathogens both in size and in their highly glycosylated surfaces. Through this mimicry these glyco-dendri-protein-nano-particles are capable of blocking (at picomolar concentrations) a model of the infection of T-lymphocytes and human dendritic cells by Ebola virus. The high associated polyvalency effects (β>106, β/N ~102–103) displayed on an unprecedented surface area by precise clusters suggest a general strategy for modulation of such interactions.España MICINN CTQ2008-01694España MICINN CTQ2011-2341

Multivalent glycoconjugates as vaccines and potential drug candidates

Pathogens adhere to the host cells during the first steps of infection through multivalent interactions which involve protein–glycan recognition. Multivalent interactions are also involved at different stages of immune response. Insights into these multivalent interactions generate a way to use suitable carbohydrate ligands that are attached to a basic scaffold consisting of e.g., dendrimer, polymer, nanoparticle, etc., with a suitable linker. Thus a multivalent architecture can be obtained with controllable spatial and topology parameters which can interfere with pathogen adhesion. Multivalent glycoconjugates bearing natural or unnatural carbohydrate antigen epitopes have also been used as carbohydrate based vaccines to stimulate an innate and adaptive immune response. Designing and synthesizing an efficient multivalent architecture with optimal ligand density and a suitable linker is a challenging task. This review presents a concise report on the endeavors to potentially use multi- and polyvalent glycoconjugates as vaccines as well as anti-infectious and anti-inflammatory drug candidates

Antiviral Activity of Self‐Assembled Glycodendro[60]fullerene Monoadducts

A series of amphiphilic glycodendro[60]fullerene monoadducts were efficiently synthesized using the CuAAC “click chemistry” approach. These glycodendrofullerenes can self‐assemble in aqueous media, in a process favoured through π‐ π interactions between the [60]fullerene moieties. This aggregation process leads to big and well‐defined compact micelles with a uniform size and spherical‐shape. The supramolecular aggregate was characterized using electronic microscopy (SEM and TEM), light scattering methods (DLS) and X‐ray methodologies (SAXS and XRD). The antiviral efficiency of these aggregates has been tested in an experimental infection assay using Ebola virus glycoprotein (EboGP) pseudotyped viral particles on Jurkat cells overexpressing DC‐SIGN and it is observed an improvement of the IC50 value with respect to other systems endowed with a higher number of carbohydrate ligands

Synthesis of giant globular multivalent glycofullerenes as potent inhibitors in a model of Ebola virus infection

The use of multivalent carbohydrate compounds to block cell-surface lectin receptors is a promising strategy to inhibit the entry of pathogens into cells and could lead to the discovery of novel antiviral agents. One of the main problems with this approach, however, is that it is difficult to make compounds of an adequate size and multivalency to mimic natural systems such as viruses. Hexakis adducts of [60]fullerene are useful building blocks in this regard because they maintain a globular shape at the same time as allowing control over the size and multivalency. Here we report water-soluble tridecafullerenes decorated with 120 peripheral carbohydrate subunits, so-called ‘superballs’, that can be synthesized efficiently from hexakis adducts of [60]fullerene in one step by using copper-catalysed azide–alkyne cycloaddition click chemistry. Infection assays show that these superballs are potent inhibitors of cell infection by an artificial Ebola virus with half-maximum inhibitory concentrations in the subnanomolar range

Design, synthesis and biological evaluation of 3-hydroxyquinazoline-2,4(1H,3H)-diones as dual inhibitors of HIV-1 reverse transcriptase-associated RNase H and integrase

A novel series of 3-hydroxyquinazoline-2,4(1H,3H)-diones derivatives has been designed and synthesized. Their biochemical characterization revealed that most of the compounds were effective inhibitors of HIV-1 RNase H activity at sub to low micromolar concentrations. Among them, II-4 was the most potent in enzymatic assays, showing an IC50 value of 0.41 ± 0.13 μM, almost five times lower than the IC50 obtained with β-thujaplicinol. In addition, II-4 was also effective in inhibiting HIV-1 IN strand transfer activity (IC50 = 0.85 ± 0.18 μM) but less potent than raltegravir (IC50 = 71 ± 14 nM). Despite its relatively low cytotoxicity, the efficiency of II-4 in cell culture was limited by its poor membrane permeability. Nevertheless, structure-activity relationships and molecular modeling studies confirmed the importance of tested 3-hydroxyquinazoline-2,4(1H,3H)-diones as useful leads for further optimization.Financial support from the National Natural Science Foundation of China (NSFC No. 81273354), the Key Project of NSFC for International Cooperation (No. 81420108027), the Key Research and Development Project of Shandong Province (No. 2017CXGC1401), the Young Scholars Program of Shandong University (YSPSDU No. 2016WLJH32, to P. Z.), the Major Project of Science and Technology of Shandong Province (No. 2015ZDJS04001) is gratefully acknowledged. Work in Madrid was supported by grant BIO2016-76716-R (AEI/FEDER, UE) (Spanish Ministry of Economy, Industry and Competitiveness) and an institutional grant of Fundación Ramón Areces. The technical assistance of Mr. Kris Uyttersprot, and Mrs. Kristien Erven, for the HIV experiments is gratefully acknowledged.Peer reviewe

Preclinical immune efficacy against SARS-CoV-2 beta B.1.351 variant by MVA-based vaccine candidates

17 Pág.The constant appearance of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoCs) has jeopardized the protective capacity of approved vaccines against coronavirus disease-19 (COVID-19). For this reason, the generation of new vaccine candidates adapted to the emerging VoCs is of special importance. Here, we developed an optimized COVID-19 vaccine candidate using the modified vaccinia virus Ankara (MVA) vector to express a full-length prefusion-stabilized SARS-CoV-2 spike (S) protein, containing 3 proline (3P) substitutions in the S protein derived from the beta (B.1.351) variant, termed MVA-S(3Pbeta). Preclinical evaluation of MVA-S(3Pbeta) in head-to-head comparison to the previously generated MVA-S(3P) vaccine candidate, expressing a full-length prefusion-stabilized Wuhan S protein (with also 3P substitutions), demonstrated that two intramuscular doses of both vaccine candidates fully protected transgenic K18-hACE2 mice from a lethal challenge with SARS-CoV-2 beta variant, reducing mRNA and infectious viral loads in the lungs and in bronchoalveolar lavages, decreasing lung histopathological lesions and levels of proinflammatory cytokines in the lungs. Vaccination also elicited high titers of anti-S Th1-biased IgGs and neutralizing antibodies against ancestral SARS-CoV-2 Wuhan strain and VoCs alpha, beta, gamma, delta, and omicron. In addition, similar systemic and local SARS-CoV-2 S-specific CD4+ and CD8+ T-cell immune responses were elicited by both vaccine candidates after a single intranasal immunization in C57BL/6 mice. These preclinical data support clinical evaluation of MVA-S(3Pbeta) and MVA-S(3P), to explore whether they can diversify and potentially increase recognition and protection of SARS-CoV-2 VoCs.The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by Fondo COVID-19 grant COV20/00151 (Spanish Health Ministry, Instituto de Salud Carlos III (ISCIII)), Fondo Supera COVID-19 grant (Crue Universidades-Banco Santander), and Spanish Research Council (CSIC) grant 202120E079 (to JG-A); CSIC grant 2020E84, la Caixa Banking Foundation grant CF01-00008, Ferrovial, and MAPFRE donations (to ME); and Spanish Ministry of Science and Innovation (MCIN)/Spanish Research Agency (AEI)/10.13039/501100011033 grant (PID2020-114481RB-I00; to JG-A and ME). This research work was also funded by the European Commission-Next Generation EU, through CSIC’s Global Health Platform (PTI Salud Global) (to JG-A and ME). JG-A and ME acknowledges financial support from the Spanish State Research Agency, AEI/10.13039/501100011033, through the “Severo Ochoa” Programme for Centres of Excellence in R&D (SEV-2013-0347, SEV-2017-0712). JC acknowledges MCIN and CSIC support (project number 202020E079). RD received grants from ISCIII (FIS PI2100989), the European Commission Horizon 2020 Framework Programme (Project VIRUSCAN FETPROACT-2016: 731868 and Project EPIC-CROWN-2: 101046084), and Fundacioín Caixa-Health Research HR18-00469 (Project StopEbola).Peer reviewe

Dendritic Cell‐Mediated Cross‐Priming by a Bispecific Neutralizing Antibody Boosts Cytotoxic T Cell Responses and Protects Mice against SARS‐CoV‐2

SARS-CoV-2 B.1.351 and B.1.167.2 viruses used in this study were obtained through the European Virus Archive Global (EVA-GLOBAL) project that has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 653316. SARS-CoV-2 B.1 (MAD6 isolate) was kindly provided by José M. Honrubia and Luis Enjuanes (CNB-CSIC, Madrid, Spain). The authors thank Centro de Investigación en Sanidad Animal (CISA)-Instituto Nacional de Investigaciones Agrarias (INIA-CSIC) (Valdeolmos, Madrid, Spain) for the BSL-3 facilities. Research in LAV laboratory was funded by the BBVA Foundation (Ayudas Fundación BBVA a Equipos de Investigación Científica SARS-CoV-2 y COVID19); the MCIN/AEI/10.13039/501100011033 (PID2020-117323RB-I00 and PDC2021-121711-I00), partially supported by the European Regional Development Fund (ERDF); the Carlos III Health Institute (ISCIII) (DTS20/00089), partially supported by the ERDF, the Spanish Association Against Cancer (AECC 19084); the CRIS Cancer Foundation (FCRISIFI-2018 and FCRIS-2021-0090), the Fundación Caixa-Health Research (HR21-00761 project IL7R_LungCan), and the Comunidad de Madrid (P2022/BMD-7225 NEXT_GEN_CART_MAD-CM). Work in the DS laboratory was funded by the CNIC; the European Union’s Horizon 2020 research and innovation program under grant agreement ERC-2016-Consolidator Grant 725091; MCIN/AEI/10.13039/501100011033 (PID2019-108157RB); Comunidad de Madrid (B2017/BMD-3733 Immunothercan-CM); Atresmedia (Constantes y Vitales prize); Fondo Solidario Juntos (Banco Santander); and “La Caixa” Foundation (LCF/PR/HR20/00075). The CNIC was supported by the ISCIII, the MCIN and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (CEX2020- 001041-S funded by MCIN/AEI/10.13039/501100011033). Research in RD laboratory was supported by the ISCIII (PI2100989) and CIBERINFEC; the European Commission Horizon 2020 Framework Programme (grant numbers 731868 project VIRUSCAN FETPROACT-2016, and 101046084 project EPIC-CROWN-2); and the Fundación CaixaHealth Research (grant number HR18-00469 project StopEbola). Research in CNB-CSIC laboratory was funded by Fondo Supera COVID19 (Crue Universidades-Banco Santander) grant, CIBERINFEC, and Spanish Research Council (CSIC) grant 202120E079 (to J.G.-A.), CSIC grant 2020E84 (to M.E.), MCIN/AEI/10.13039/501100011033 (PID2020- 114481RB-I00 to J.G-A. and M.E.), and by the European CommissionNextGenerationEU, through CSIC’s Global Health Platform (PTI Salud Global) to J.G.-A. and M.E. Work in the CIB-CSIC laboratory was supported by MCIN/AEI/10.13039/501100011033 (PID2019-104544GB-I00 and 2023AEP105 to CA, and PID2020-113225GB-I00 to F.J.B.). Cryo-EM data were collected at the Maryland Center for Advanced Molecular Analyses which was supported by MPOWER (The University of Maryland Strategic Partnership). I.H.-M. receives the support of a fellowship from la Caixa Foundation (ID 100010434, fellowship code: LCF/BQ/IN17/11620074) and from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 71367. L.R.-P. was supported by a predoctoral fellowship from the Immunology Chair, Universidad Francisco de Vitoria/Merck.S