839 research outputs found
The blind spots of secularization
No full textAccording to several international surveys Spain is among the western countries with the most negative views of Jews. While quantitative data on the topic accumulates, there is a significant lack of interpretative approaches that might explain the particular Spanish case. This paper presents the background, methodology and major results of a discussion group-based study on antisemitism, which was conducted in Spain in the autumn of 2009. The study identifies and locates in different socio-economic and ideological milieus the range of stereotypical discourses on Jews, Judaism and the Arab–Israeli conflict in Spain. Analysis of the group meetings shows that, despite growing secularization in Spanish society, the central explanatory variable for persisting and resurging antisemitism in this country is still religion in a broad cultural sense.N
Métricas de autor Alejandro Gómez Jaramillo
No full textInforme de las métricas de autor del Dr. Alejandro Gómez Jaramillo de las publicaciones indexadas en Google Académico cuyo objetivo es entregar un insumo para el fortalecimiento de las capacidades y potencialidades de los autores de la Universidad Santo Tomás en el posicionamiento y visibilidad de sus publicacionesReport of the author metrics Alejandro Gómez Jaramillo of the publications indexed in Google Scholar whose objective is to provide an input for the strengthening of the capacities and potentialities of the authors of the Santo Tomás University in the positioning and visibility of their publications.http://unidadinvestigacion.usta.edu.c
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Fantastic B-Cells and Where to Find Them
No full textSince the SARS-CoV-2 pandemic began in 2020, viral sequencing has documented the emergence of hundreds of individual mutations in the viral spike protein across numerous variants. With the drastic viral evolution over the past four years resulting in variants with greater than 60 mutations relative to the Wuhan strain the vaccine has been updated three times. Studies have demonstrated that repeated mRNA vaccination enhances the breadth of neutralization against diverse SARS-CoV-2 variants. However, the development of antibodies and humoral immune responses capable of neutralizing across the coronavirus family is poorly understood. The ongoing spread of COVID-19 underscores the importance of identifying and characterizing neutralizing monoclonal antibodies capable of neutralizing all variants. The fusion peptide (FP) region of the viral spike protein is a crucial target for neutralization given its broad cross reactivity and conservation among all the coronaviruses.
Here, we determine the ability of vaccine-mediated humoral immunity to keep pace with continued SARS-CoV-2 evolution. Updated vaccines increase neutralization breadth, but viral evolution continues to outpace them. Using newly developed depletion protocols we show that broadly neutralizing responses are often a result of receptor binding domain (RBD) specific antibodies, but some donors produce FP-specific responses that contribute to neutralization breadth. In a comprehensive ELISA study, we find that FP-specific antibodies arise only in response to natural infection and not vaccination. Next, we developed a novel protocol to isolate antigen-specific memory B-cells and monoclonal antibodies (mAbs) in less than 1 week. Using this highly efficient and effective protocol, we isolated 11 FP-specific antibodies with varying neutralization breadths. Finally, we designed a set of pseudoviral spike proteins to assess epitope and escape mutations for FP-specific antibodies. We found that mutations at S816 and F823 escape all FP-specific antibodies. Collectively, this work helps elucidate the co-evolution of the humoral immune response and the SARS-CoV-2 virus, suggesting that novel vaccine strategies are needed to end the spread of the virus and prevent further viral evolution. In this thesis we also present a roadmap for the selection of ideal donors for mAb isolation and offer a highly efficacious protocol for generation of mAbs from donor PBMCs.Medical Science
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Origins of a Humoral Immune Response: Characterizing Virus-specific Naive B cells
No full textInitial exposure to a pathogen elicits the production of pathogen-specific antibodies that may protect and eradicate the threat. The naive B cell repertoire is the starting material from which these protective antibodies arise, providing an enormously diverse substrate for the initial recognition of any pathogen or vaccine antigen. The composition of the naive repertoire, including frequency and binding strength for antigen, influences the quality of the initial pathogen response including the elicitation of immune memory. However, the human naive B cell repertoire remains largely undefined. Interrogating the abundance and specificity of this pre-immune repertoire can drive an understanding of how protective responses are mounted, especially for emerging pathogens to which we have no prior exposure. Here, we characterized naive B cell reactivity for viral antigens from SARS-CoV-2 and avian influenza virus.
For SARS-CoV-2, we characterized naive B cells specific for the receptor binding domain (RBD) from seronegative donors to understand their relative abundance, intrinsic affinity, potential for activation, and putative maturation pathways. We identified genetically diverse naive B cell receptors (BCRs) targeting distinct RBD epitopes, including the identification of a conserved mode of recognition shared with infection-induced antibodies. For representative naive BCRs, higher-affinity RBD interactions could be engineered through a single amino acid change, which conferred potent SARS-CoV-2 neutralization and suggested a potentially low threshold for naive B cells to acquire protective capabilities.
We also characterized avian influenza virus hemagglutinin (HA)-specific naive B cells with efforts focused on comparing the frequency, affinity, and neutralization potential between strain-specific B cells and those which cross-react to HAs circulating in the human population. We found that naive B cells targeting the HA head domain were at an elevated precursor frequency relative to cross-reactive clones. Further, a subset of HA head-specific antibodies neutralized H5 at germline and bound to HA at major antigenic sites previously characterized by H5 vaccine- and infection-elicited neutralizing antibodies.
This work expands our understanding of human B cell specificities for emerging pathogens to support the prediction of potential responses made upon zoonotic infection and the design of next generation vaccines aimed at engaging protective germline responses.Medical SciencesMedical Science
Genomic characterization of schizophrenia candidate gene regions
No full textSchizophrenia (SZ) is a severe mental disorder with a complex genetic etiology and a lifetime prevalence of ~0.55-1%. In this study, we extracted and analyzed data from 47 independent genomewide scans for linkage to SZ. The genome was partitioned into 22 schizophrenia candidate gene regions (SCRs) by applying three methods: single significant approach, disjoint approach, and smoothing method. For the single significant hit approach, an SCR was defined by the presence of a significant hit by extending 10 cM upstream and downstream of that hit. For the disjoint approach, we identified criteria-events based on clustering of hits within small regions by using a sliding window approach. For the smoothing method, we imputed a randomized range of p-values (0.001697≤p<1) for the genome scans without a suggestive or significant result at each 0.1 cM interval. We combined these p-values with the genome scan results using three methods: geometric mean method, Fisher’s method, and Stouffer’s method. We characterized each SCR by identifying the genes and genomic elements such as structural variations, regulatory elements, and functional noncoding RNAs. We also categorized the genes within SCRs. The total coverage of SCRs is 880 cM (739 Mb) with SCR sizes ranging from 18 cM to 87 cM. SCRs with multiple peaks were divided into smaller subregions. We developed a ranking system to identify and prioritize SZ candidate genes by assigning weights to each of the following criteria: (a) relative significance of a peak within an SCR, (b) annotated in SZ association studies and microarray analyses, and meta-analyses, (c) associated with phenotypes or diseases, and (d) located within or near other genetic elements. We identified functions/diseases and pathways that were most significantly associated with genes that had at least the same score or better than the top 10% of candidate genes after prioritization by utilizing the Ingenuity® Pathways Analysis (IPA). We generated an interactome for SZ based on the SZ candidate genes. We created a website (http://compgen.rutgers.edu/schiz) to disseminate information about our SCRs. Our procedure, which provides a novel approach to identify and prioritize candidate gene regions and genomic elements, is applicable to other complex diseases.Ph. D.Includes bibliographical referencesby Alejandro Q. Nato, Jr
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Receptor binding and antibody neutralization of emerging RNA viruses
No full textThe spillover of viral zoonotic pathogens into human populations is an ever present threat to public health. Preparedness for the threat of emerging viruses requires an understanding of viral pathogenesis and the development of effective treatments. Viral attachment and entry into host cells is the first critical step in viral infection. This step is the target of neutralizing antibodies that recognize viral receptor binding subunits to block infectivity. Here we use single B cell cloning to isolate monoclonal antibodies that target the receptor-binding subunits of two groups of emerging enveloped RNA viruses – arenaviruses and coronaviruses. For arenaviruses, we identify a key cross-neutralizing epitope in the receptor-binding subunit (GP1) of Junin virus and Machupo virus. For coronaviruses, we identify a critical neutralizing epitope on the S1 receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein and define pathways for neutralization escape while retaining receptor-binding activity. Alphaviruses are a group of less well studied emerging RNA viruses. We identify lipoprotein receptors as a novel class of evolutionarily conserved cellular receptors for encephalitic alphaviruses. Our work sets the stage for studies examining, in detail, the relationship between antibody neutralization and receptor-binding, which in turn may help inform the development of effective antiviral monoclonal antibodies.Medical SciencesMedical Science
Dichotomius (Dichotomius) telamon
No full textDichotomius (Dichotomius) telamon (Harold, 1869) (Figs. 3 A–B) Pinotus pelamon Harold, 1869a: 128 (original description). Type locality: Brésil [= Brazil]. Type series. The holotype (female) is deposited at the MNHN (examined, see Figs. 3 A–B). Remarks: According to Luederwaldt (1929) this species has a length of 30 mm. It is distributed in Brazil (Gillet 1911: 62; Vaz-de-Mello 2000: 193); and Guianas (Gillet 1911: 62; Vulcano & Pereira 1967: 585; Hielkema & Hielkema 2019: 53 as Dichotomius pelamon). The epithet “ pelamon ” was an involuntary and typographical error that the author himself corrected in the same year (see Harold 1869 b: 60).Published as part of Chamorro, William, Lopera-Toro, Alejandro & Rossini, Michele, 2021, A new species and distribution records of Dichotomius Hope, 1838 (Coleoptera Scarabaeidae: Scarabaeinae) in Colombia, pp. 193-206 in Zootaxa 4942 (2) on page 195, DOI: 10.11646/zootaxa.4942.2.3, http://zenodo.org/record/460044
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Broadly neutralizing antibody recognition of diverse HIV envelopes modulates effector function
No full textWhile neutralization of free virus is essential for protection against HIV transmission, the fragment crystallizable (Fc) region mediated functions of broadly neutralizing antibodies (bNAbs) have also been shown to be critical for protection in animal models, namely antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Multiple sites of vulnerability on the viral envelope (Env) have been described that serve as targets for bNAb binding to neutralize HIV. The diverse locations of these sites on Env suggest that they may result in differential accessibility of innate effector cells to bound bNAb. Effector cells utilize different FcRs to engage the Fc-region of an antibody to drive effector functions. As such, the accessibility of antibody Fc-regions when bound to a specific epitope may allow an antibody to effectively drive one effector function while a different epitope may be a more ideal target to mediate another.
Here, we determine how binding to five different sites of vulnerability influences the ability of innate immune cells to mediate antibody-dependent effector functions against Env-expressing target cells. Our results show that bNAb-mediated effector functions are dependent upon bNAb binding site, with V1V2-directed bNAbs engaging monocytes to efficiently drive ADCP while MPER and Interface-directed antibodies potently mediate ADCC. We found that CD4bs and V3-directed antibodies are effective mediators of both functions. Additionally, we find that the potency of a given antibody to mediate effector functions across diverse envelopes is driven by differential binding of FcRs, suggesting that antibody binding to its epitope can impact binding of innate cell receptors. Collectively, this work helps elucidate optimal vaccine targets capable of maximal effector functions, thereby informing future prevention strategies against HIV.Medical SciencesMedical Science
. 31 Año 10 (2013) enero-abril. Señales de humo
No full text- Editorial por Hugo Reynoso Urtiz. - 40 años Centro INAH Sonora por Alejandro Aguilar Zeleny. - De San Bernardo al Cuchujaqui, una Colección Arqueológica entre el Río Mayo y el Río Fuerte por Adriana Hinojo Hinojo y B. Eréndira Contreras Barragán. - La conformación sociodemográfica de la población de Sonora. Análisis diacrónico de su dinámica demográfica por Patricia Olga Hernández Espinoza. - Hachas y bifaciales. Colecciones arqueológicas decomisadas por ICE/HSI por Júpiter Martínez Martínez y Elisa Villalpando Canchola. A 100 años de la lucha por la legalidad del Estado de Sonora, marzo de 1913 por Juan José Gracida Romo. - Participación de los investigadores del Centro INAH Sonora en el IV Coloquio de Historia, Cultura y Medio Ambiente de Caborca por Esperanza Donjuan Villalpando. - El patrimonio arqueológico de Sonora, a través del Catálogo de Sitios Arqueológicos del Estado de Sonora por César Armando Quijada López y Tomás Pérez Reyes. - Mujeres yaquis en Francia por Raquel Padilla Ramos. - Tesis sobre los comcaac por Guadalupe Piña Ortiz
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Engineering Symbiotic Microbiota for in Situ Delivery of Therapeutic Proteins
No full textAs symbiotic members of the human microbiome, Lactobacilli are an emerging class of living biotherapeutic agents capable of sustained and targeted drug delivery of protein biologics to the many organs they naturally inhabit. However, progress to this end remains limited by the paucity of genetic tools for manipulating these bacteria. We used synthetic biology techniques to build a tunable, broad host range expression system, and applied in silico techniques for de novo design of robust, strain-optimized secretion signals that direct protein export. Together, these components provide an approach to rapidly engineer niche-adapted Lactobacilli for in situ delivery of therapeutic proteins. We leveraged this platform to engineer model symbionts from the gastrointestinal and female genital tracts to secrete single domain antibody fragments, as candidate vectors for IBD immunotherapy and HIV immunoprophylaxis. This work advances Lactobacillus as a vehicle for drug delivery, and serves as a platform to accelerate development of diverse, microbiome-based medicines capable of addressing myriad disease.Biophysic
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