Nanobodies Protecting From Lethal SARS-CoV-2 Infection Target Receptor Binding Epitopes Preserved in Virus Variants Other Than Omicron

The emergence of SARS-CoV-2 variants that escape from immune neutralization are challenging vaccines and antibodies developed to stop the COVID-19 pandemic. Thus, it is important to establish therapeutics directed toward multiple or specific SARS-CoV-2 variants. The envelope spike (S) glycoprotein of SARS-CoV-2 is the key target of neutralizing antibodies (Abs). We selected a panel of nine nanobodies (Nbs) from dromedary camels immunized with the receptor-binding domain (RBD) of the S, and engineered Nb fusions as humanized heavy chain Abs (hcAbs). Nbs and derived hcAbs bound with subnanomolar or picomolar affinities to the S and its RBD, and S-binding cross-competition clustered them in two different groups. Most of the hcAbs hindered RBD binding to its human ACE2 (hACE2) receptor, blocked cell entry of viruses pseudotyped with the S protein and neutralized SARS-CoV-2 infection in cell cultures. Four potent neutralizing hcAbs prevented the progression to lethal SARS-CoV-2 infection in hACE2-transgenic mice, demonstrating their therapeutic potential. Cryo-electron microscopy identified Nb binding epitopes in and out the receptor binding motif (RBM), and showed different ways to prevent virus binding to its cell entry receptor. The Nb binding modes were consistent with its recognition of SARS-CoV-2 RBD variants; mono and bispecific hcAbs efficiently bound all variants of concern except omicron, which emphasized the immune escape capacity of this latest variant.This work was partially funded by Ministerio de Ciencia e Innovación (MICIN; https://www.ciencia.gob.es/) and the Spanish Research Council (CSIC; https://www.csic.es/) under grants PIE-RD-COVID 19 (No 202020E079) and PTI+ Salud Global REC_EU (No SGL 2103051, NextGenerationEU) to LF, JMC, PG, and UG, and (No SGL 2103053, NextGenerationEU) to MM-A. This study was partially conducted within the CSIC Antiviral Screening Network, an infrastructure supported by NextGeneration EU funds (https://ec.europa.eu/info/strategy/recovery-plan-europe_es) from the European Union and the European Virus Archive Global (EVag) of the European Union’s Horizon 2020 (https://ec.europa.eu/programmes/horizon2020/en/home) research and innovation programme (No 871029) to PG and UG. EM facilities of CNB-CSIC were supported by Ministerio de Ciencia e Innovación (MICIN; https://www.ciencia.gob.es/), EU-FEDER (https://ec.europa.eu/regional_policy/es/funding/erdf/) CRIOMECORR project (ESFRI-2019-01-CSIC-16). JMC access to the European Synchrotron Radiation Facility (ESRF) CM01 line through the Iberian-BAG, and to the Instruct Image Processing Center (I2PC, http://i2pc.es/) by projects PID16168 and PID14989. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

EDUCACIÓN AMBIENTAL Y SOCIEDAD. SABERES LOCALES PARA EL DESARROLLO Y LA SUSTENTABILIDAD

Este texto contribuye al análisis científico de varias áreas del conocimiento como la filosofía social, la patología, la educación para el cuidado del medio ambiente y la sustentabilidad que inciden en diversas unidades de aprendizaje de la Licenciatura en Educación para la Salud y de la Maestría en Sociología de la SaludLas comunidades indígenas de la sierra norte de Oaxaca México, habitan un territorio extenso de biodiversidad. Sin que sea una área protegida y sustentable, la propia naturaleza de la región ofrece a sus visitantes la riqueza de la vegetación caracterizada por sus especies endémicas que componen un paisaje de suma belleza

Validación de material de apoyo audiovisual de diferentes danzas folclóricas chilenas

Tesis (Profesor de Educación Física, Licenciado en Educación)El folclore es parte de nuestra cultura, representa nuestras raíces y nos hace únicos en el mundo. Es por esto, que cada año se celebran las Fiestas Patrias donde los festejos y las tradiciones alcanzan su máxima expresión. En este contexto, la danza es una expresión artística que cobra protagonismo donde la coordinación y ritmo son importantes. Debido a las características anteriormente mencionadas, la danza se encuentra fuertemente ligada a la Educación Física y por este motivo fue incorporada como materia de estudio en el Ministerio de Educación (MINEDUC) y en la mayoría de los establecimientos educacionales, como unidad obligatoria en la asignatura Educación Física. Con el objetivo de crear un material educativo de fácil entendimiento para los alumnos, un grupo de estudiantes de Educación Física de la Universidad Andrés Bello desarrolló un DVD que incorporó información sobre las principales danzas tradicionales de Chile y su relación con las distintas zonas del país. El análisis sobre su impacto y efectividad en los alumnos, será materia de estudio en este seminario de grado a fin de establecer su potencial aporte a través de su implementación en centros educacionales. Durante el desarrollo de la investigación se llevará a cabo una encuesta enfocada a directivos, profesores y alumnos con el fin de obtener de primera fuente las impresiones de este trabajo realizado. La encuesta será realizada en cuatro colegios de Santiago: dos colegios particulares pagados de la comuna de Las Condes, un colegio particular pagado de la comuna de Vitacura y un cuarto colegio particular subvencionado de la comuna de La Pintana

Evaluation of the BD Phoenix Carbapenemase-Producing Organism Panels for the Detection of Carbapenemase Producers in <i>Escherichia coli, Klebsiella pneumoniae</i> and <i>Pseudomonas aeruginosa</i>

The classification of carbapenemases can help guide therapy. The present study evaluated the performance of the CPO detection test, included in the BD Phoenix™ NMIC-501 panel for the detection and classification of carbapenemases on the representative molecularly characterized strains collection from Mexico. Carbapenem non-susceptible isolates collected in Mexico were included. The clinical isolates (n = 484) comprised Klebsiella pneumoniae (n = 154), Escherichia coli (n = 150), and P. aeruginosa (n = 180). BD Phoenix CPO NMIC-504 and NMIC-501 panels were used for the identification of species, antimicrobial susceptibility tests, and detection of CPOs. For the detection of carbapenemase-encoding genes, E. coli and K. pneumoniae were evaluated using PCR assays for blaNDM-1, blaKPC, blaVIM, blaIMP, and blaOXA-48-like. For P. aeruginosa, blaVIM, blaIMP, and blaGES were detected using PCR. Regarding E. coli, the CPO panels had a sensitivity of 70% and specificity of 83.33% for the detection of a class B carbapenemase (blaNDM in the molecular test). Regarding K. pneumoniae, the panels had a sensitivity of 75% and specificity of 100% for the detection of a class A carbapenemase (blaKPC in the molecular test). The Phoenix NMIC-501 panels are reliable for detecting class B carbapenemases in E. coli. The carbapenemase classification in K. pneumoniae for class A carbapenemases has a high specificity and PPV; thus, a positive result is of high value

Active Surveillance of Antimicrobial Resistance and Carbapenemase-Encoding Genes According to Sites of Care and Age Groups in Mexico: Results from the INVIFAR Network

We analyzed the antimicrobial resistance (AMR) data of 6519 clinical isolates of Escherichia coli (n = 3985), Klebsiella pneumoniae (n = 775), Acinetobacter baumannii (n = 163), Pseudomonas aeruginosa (n = 781), Enterococcus faecium (n = 124), and Staphylococcus aureus (n = 691) from 43 centers in Mexico. AMR assays were performed using commercial microdilution systems (37/43) and the disk diffusion susceptibility method (6/43). The presence of carbapenemase-encoding genes was assessed using PCR. Data from centers regarding site of care, patient age, and clinical specimen were collected. According to the site of care, the highest AMR was observed in E. coli, K. pneumoniae, and P. aeruginosa isolates from ICU patients. In contrast, in A. baumannii, higher AMR was observed in isolates from hospitalized non-ICU patients. According to age group, the highest AMR was observed in the ≥60 years age group for E. coli, E. faecium, and S. aureus, and in the 19–59 years age group for A. baumannii and P. aeruginosa. According to clinical specimen type, a higher AMR was observed in E. coli, K. pneumoniae, and P. aeruginosa isolates from blood specimens. The most frequently detected carbapenemase-encoding gene in E. coli was blaNDM (84%)

A snapshot of antimicrobial resistance in Mexico. Results from 47 centers from 20 states during a six-month period.

AIM:We aimed to assess the resistance rates of antimicrobial-resistant, in bacterial pathogens of epidemiological importance in 47 Mexican centers. MATERIAL AND METHODS:In this retrospective study, we included a stratified sample of 47 centers, covering 20 Mexican states. Selected isolates considered as potential causatives of disease collected over a 6-month period were included. Laboratories employed their usual methods to perform microbiological studies. The results were deposited into a database and analyzed with the WHONET 5.6 software. RESULTS:In this 6-month study, a total of 22,943 strains were included. Regarding Gram-negatives, carbapenem resistance was detected in ≤ 3% in Escherichia coli, 12.5% in Klebsiella sp. and Enterobacter sp., and up to 40% in Pseudomonas aeruginosa; in the latter, the resistance rate for piperacillin-tazobactam (TZP) was as high as 19.1%. In Acinetobacter sp., resistance rates for cefepime, ciprofloxacin, meropenem, and TZP were higher than 50%. Regarding Gram-positives, methicillin resistance in Staphylococcus aureus (MRSA) was as high as 21.4%, and vancomycin (VAN) resistance reached up to 21% in Enterococcus faecium. Acinetobacter sp. presented the highest multidrug resistance (53%) followed by Klebsiella sp. (22.6%) and E. coli (19.4%). CONCLUSION:The multidrug resistance of Acinetobacter sp., Klebsiella sp. and E. coli and the carbapenem resistance in specific groups of enterobacteria deserve special attention in Mexico. Vancomycin-resistant enterococci (VRE) and MRSA are common in our hospitals. Our results present valuable information for the implementation of measures to control drug resistance

Libro de Proyectos Finales 2021 primer semestre

PregradoIngeniero CivilIngeniero de SistemasIngeniero ElectricistaIngeniero ElectrónicoIngeniero IndustrialIngeniero Mecánic