RESUMEN La apicultura, a nivel mundial, es de gran importancia, por el desempeño que realizan las abejas, como agentes polinizadores del 75 % de los cultivos, que garantizan la seguridad alimentaria ...de millones de personas. En Colombia, el sector apícola contribuye al fortalecimiento de la economía campesina y promueve la conservación de diferentes ecosistemas estratégicos. Respecto al municipio de Fortul, Arauca, cuenta con una importante zona de reserva forestal y una amplia variabilidad de ecosistemas, aptos para el desarrollo de la apicultura, actividad que, actualmente, se desarrolla por la asociación “Panaldemiel”, la cual, requiere un acompañamiento y fortalecimiento de las capacidades organizacionales y gerenciales. Es así, que el objeto de la presente investigación es “fortalecer la gestión administrativa de la Asociación de Apicultores “Panaldemiel”, del municipio de Fortul, Arauca”, estudio soportado en el método de investigación Acción-participación, bajo la estrategia de estudio de caso, que permite analizar la problemática en un contexto real, facilitando la obtención de información necesaria, para la formulación de herramientas estratégicas, encaminadas a dinamizar el proceso productivo y competitivo de la asociación, en el ámbito local y regional. Se concluye, que la asociación cuenta con un alto porcentaje de aspectos positivos internos y externos que la respalda, de manera significativa; sin embargo, se requiere de un compromiso gubernamental para mitigar la coyuntura de orden público que se vive en esta región.
Fortul – Arauca es un municipio que ha presentado problemas de conflicto armado causando atrasos sociales, económicos y tecnológicos especialmente en el sector agropecuario; en la región uno de los ...productos más representativos es el cacao, el cual se encuentra como alternativa para la sustitución de cultivos ilícitos; es así que el propósito del presente estudio es “diagnosticar el sector cacaotero del municipio Fortul bajo la metodología de acción participación”, destacando como resultado el logro en la creación de la Asociación de productores de cacao ASPROCAF del municipio de Fortul.
Cholera toxin (CT) is a potent adjuvant for mucosal vaccination; however, its mechanism of action has not been clarified completely. It is well established that peripheral monocytes differentiate ...into dendritic cells (DCs) both in vitro and in vivo and that monocytes are the in vivo precursors of mucosal CD103⁻ proinflammatory DCs. In this study, we asked whether CT had any effects on the differentiation of monocytes into DCs. We found that CT-treated monocytes, in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4), failed to differentiate into classical DCs (CD14low CD1ahigh) and acquired a macrophage-like phenotype (CD14high CD1alow). Cells differentiated in the presence of CT expressed high levels of major histocompatibility complex class I (MHC-I) and MHC-II and CD80 and CD86 costimulatory molecules and produced larger amounts of IL-1β, IL-6, and IL-10 but smaller amounts of tumor necrosis factor alpha (TNF-α) and IL-12 than did monocytes differentiated into DCs in the absence of CT. The enzymatic activity of CT was found to be important for the skewing of monocytes toward a macrophage-like phenotype (Ma-DCs) with enhanced antigen-presenting functions. Indeed, treatment of monocytes with scalar doses of forskolin (FSK), an activator of adenylate cyclase, induced them to differentiate in a dose-dependent manner into a population with phenotype and functions similar to those found after CT treatment. Monocytes differentiated in the presence of CT induced the differentiation of naïve T lymphocytes toward a Th2 phenotype. Interestingly, we found that CT interferes with the differentiation of monocytes into DCs in vivo and promotes the induction of activated antigen-presenting cells (APCs) following systemic immunization.
El presente artículo de revisión se basa en un estudio bibliográfico en el que se busca seleccionar analizar y sintetizar la literatura científicas sobre el marketing territorial como parte ...fundamental y estructural para el desarrollo del proyecto de investigación “Marketing territorial: una estrategia de desarrollo sostenible para las comunidades del corredor del roble en el municipio de Sotaquirá”, la revisión bibliográfica es de tipo documental de carácter científico, apoyada por las bases de datos como Scielo, Scopus, Dialnet, lens y el buscador de Google Académico, con un rango de búsqueda no menor a 5 años. Como resultados se evidencia que el marketing territorial ha generado las herramientas necesarias para ser utilizado como una estrategia de desarrollo social, económico, cultural y ambiental.
The SARS-CoV-2 spike (S) glycoprotein contains an immunodominant receptor-binding domain (RBD) targeted by most neutralizing antibodies (Abs) in COVID-19 patient plasma. Little is known about ...neutralizing Abs binding to epitopes outside the RBD and their contribution to protection. Here, we describe 41 human monoclonal Abs (mAbs) derived from memory B cells, which recognize the SARS-CoV-2 S N-terminal domain (NTD) and show that a subset of them neutralize SARS-CoV-2 ultrapotently. We define an antigenic map of the SARS-CoV-2 NTD and identify a supersite (designated site i) recognized by all known NTD-specific neutralizing mAbs. These mAbs inhibit cell-to-cell fusion, activate effector functions, and protect Syrian hamsters from SARS-CoV-2 challenge, albeit selecting escape mutants in some animals. Indeed, several SARS-CoV-2 variants, including the B.1.1.7, B.1.351, and P.1 lineages, harbor frequent mutations within the NTD supersite, suggesting ongoing selective pressure and the importance of NTD-specific neutralizing mAbs for protective immunity and vaccine design.
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•NTD-targeting antibodies are a key part of immunity to SARS-CoV-2•NTD neutralizing antibodies target a single antigenic site of vulnerability•Neutralizing NTD antibodies protect hamsters from SARS-CoV-2 challenge•Variants of concern have mutations in the NTD that escape neutralization
McCallum et al. identify a supersite in the N-terminal domain of SARS-CoV-2 spike protein that is targeted by neutralizing antibodies and exhibits mutation in response to selective pressure.
A novel variant of concern (VOC) named CAL.20C (B.1.427/B.1.429), which was originally detected in California, carries spike glycoprotein mutations S13I in the signal peptide, W152C in the N-terminal ...domain (NTD), and L452R in the receptor-binding domain (RBD). Plasma from individuals vaccinated with a Wuhan-1 isolate-based messenger RNA vaccine or from convalescent individuals exhibited neutralizing titers that were reduced 2- to 3.5-fold against the B.1.427/B.1.429 variant relative to wild-type pseudoviruses. The L452R mutation reduced neutralizing activity in 14 of 34 RBD-specific monoclonal antibodies (mAbs). The S13I and W152C mutations resulted in total loss of neutralization for 10 of 10 NTD-specific mAbs because the NTD antigenic supersite was remodeled by a shift of the signal peptide cleavage site and the formation of a new disulfide bond, as revealed by mass spectrometry and structural studies.
The recent emergence of SARS-CoV-2 variants of concern
and the recurrent spillovers of coronaviruses
into the human population highlight the need for broadly neutralizing antibodies that are not ...affected by the ongoing antigenic drift and that can prevent or treat future zoonotic infections. Here we describe a human monoclonal antibody designated S2X259, which recognizes a highly conserved cryptic epitope of the receptor-binding domain and cross-reacts with spikes from all clades of sarbecovirus. S2X259 broadly neutralizes spike-mediated cell entry of SARS-CoV-2, including variants of concern (B.1.1.7, B.1.351, P.1, and B.1.427/B.1.429), as well as a wide spectrum of human and potentially zoonotic sarbecoviruses through inhibition of angiotensin-converting enzyme 2 (ACE2) binding to the receptor-binding domain. Furthermore, deep-mutational scanning and in vitro escape selection experiments demonstrate that S2X259 possesses an escape profile that is limited to a single substitution, G504D. We show that prophylactic and therapeutic administration of S2X259 protects Syrian hamsters (Mesocricetus auratus) against challenge with the prototypic SARS-CoV-2 and the B.1.351 variant of concern, which suggests that this monoclonal antibody is a promising candidate for the prevention and treatment of emergent variants and zoonotic infections. Our data reveal a key antigenic site that is targeted by broadly neutralizing antibodies and will guide the design of vaccines that are effective against all sarbecoviruses.
Memory B cells persist for a lifetime and rapidly differentiate into antibody-producing plasmablasts and plasma cells upon antigen re-encounter. The clonal relationship and evolution of memory B ...cells and circulating plasmablasts is not well understood. Using single-cell sequencing combined with isolation of specific antibodies, we found that in two healthy donors, the memory B cell repertoire was dominated by large IgM, IgA and IgG2 clonal families, whereas IgG1 families, including those specific for recall antigens, were of small size. Analysis of multiyear samples demonstrated stability of memory B cell clonal families and revealed that a large fraction of recently generated plasmablasts was derived from long-term memory B cell families and was found recurrently. Collectively, this study provides a systematic description of the structure, stability and dynamics of the human memory B cell pool and suggests that memory B cells may be active at any time point in the generation of plasmablasts.
Understanding broadly neutralizing sarbecovirus antibody responses is key to developing countermeasures against SARS-CoV-2 variants and future zoonotic sarbecoviruses. We describe the isolation and ...characterization of a human monoclonal antibody, designated S2K146, that broadly neutralizes viruses belonging to SARS-CoV- and SARS-CoV-2-related sarbecovirus clades which use ACE2 as an entry receptor. Structural and functional studies show that most of the virus residues that directly bind S2K146 are also involved in binding to ACE2. This allows the antibody to potently inhibit receptor attachment. S2K146 protects against SARS-CoV-2 Beta challenge in hamsters and viral passaging experiments reveal a high barrier for emergence of escape mutants, making it a good candidate for clinical development. The conserved ACE2-binding residues present a site of vulnerability that might be leveraged for developing vaccines eliciting broad sarbecovirus immunity.
Dendritic cells (DCs) are the most potent antigen presenting cells and are therefore widely used in cancer immunotherapy. An optimal method for the generation of DCs for clinical use remains to be ...established. The aim of the study was to find a serum-free media (SFM) able to generate reproducible and functional cultures of DCs for clinical studies. We characterized immature and mature DCs cultured in SFM, CellGro DC and X-VIVO15, and serum media (SM), RPMI 1640+5% human serum or autologous serum. The expression of HLA-DR, CD86, CD83 was higher in SM-cultured DCs (SM-DCs) than SFM-derived DCs (SFM-DCs). Between SFM-DCs, CellGro-cultured DCs (CellGro-DCs) showed a higher expression and an improved up-regulation capacity of all molecules as compared with X-VIVO15-derived DCs (X-VIVO15-DCs). CellGro-DCs and SM-DCs showed a similar mannose receptor expression and related endocytic capacity tested by fluorescein isothiocyanate-dextran uptake. In contrast X-VIVO15-DCs expressed low levels of mannose receptor and were unable to endocyte fluorescein isothiocyanate-dextran. DCs cultured in all conditions stimulated a mix lymphocyte reaction, but CellGro-DCs and SM-DCs induced a more potent T-cell proliferation compared with X-VIVO15-DCs. Cytokine analysis showed that after maturation, all DC cultures produced IL-12p70 and IL-10 except for X-VIVO15-DCs which only produced the latter cytokine. SM-DCs and SFM-DCs induced a TH1 polarization in allogeneic naive T cells. In conclusion, a comparative analysis of DC performance generated in different conditions allows us to determine CellGro DC as the optimal medium for the generation of clinical grade DCs.
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