Broadly neutralizing antibodies against emerging delta-coronaviruses.

Porcine deltacoronavirus (PDCoV) spillovers were recently detected in children with acute undifferentiated febrile illness, underscoring recurrent zoonoses of divergent coronaviruses. To date, no vaccines or specific therapeutics are approved for use in humans against PDCoV. To prepare for possible future PDCoV epidemics, we isolated human spike (S)-directed monoclonal antibodies from transgenic mice and found that two of them, designated PD33 and PD41, broadly neutralized a panel of PDCoV variants. Cryo-electron microscopy structures of PD33 and PD41 in complex with the PDCoV receptor-binding domain and S ectodomain trimer provide a blueprint of the epitopes recognized by these mAbs, rationalizing their broad inhibitory activity. We show that both mAbs inhibit PDCoV by competitively interfering with host APN binding to the PDCoV receptor-binding loops, explaining the mechanism of viral neutralization. PD33 and PD41 are candidates for clinical advancement, which could be stockpiled to prepare for possible future PDCoV outbreaks.

Light-sensitive phosphorylation regulates retinal IMPDH1 activity and filament assembly.

Inosine monophosphate dehydrogenase (IMPDH) is the rate-limiting enzyme in guanosine triphosphate (GTP) synthesis and assembles into filaments in cells, which desensitizes the enzyme to feedback inhibition and boosts nucleotide production. The vertebrate retina expresses two splice variants IMPDH1(546) and IMPDH1(595). In bovine retinas, residue S477 is preferentially phosphorylated in the dark, but the effects on IMPDH1 activity and regulation are unclear. Here, we generated phosphomimetic mutants to investigate structural and functional consequences of S477 phosphorylation. The S477D mutation resensitized both variants to GTP inhibition but only blocked assembly of IMPDH1(595) filaments. Cryo-EM structures of both variants showed that S477D specifically blocks assembly of a high-activity assembly interface, still allowing assembly of low-activity IMPDH1(546) filaments. Finally, we discovered that S477D exerts a dominant-negative effect in cells, preventing endogenous IMPDH filament assembly. By modulating the structure and higher-order assembly of IMPDH, S477 phosphorylation acts as a mechanism for downregulating retinal GTP synthesis in the dark when nucleotide turnover is decreased.

Revistas médicas de América Latina descontinuadas de Scopus

Scopus es una de las bases de datos de literatura científica de mayor cobertura global y regional. El ranking Scimago Journal Rank, basado en datos de Scopus, clasifica dentro del ámbito de la Medicina 49 áreas temáticas específicas. Los objetivos del artículo fueron identificar las características de las revistas de Medicina de América Latina que estuvieron indizadas en Scopus pero que fueron descontinuadas y determinar los motivos por los que fueron excluidas de la base de datos durante la última década. Los hallazgos muestran que para el período 2013-2022 un total de 745 revistas se descontinuaron a nivel global; 21 de estas revistas fueron de América Latina y el Caribe, de las cuales 14 revistas corresponden a las áreas de la Medicina. En conclusión, la mayoría de revistas descontinuadas en la última década en Scopus se excluyeron por problemas de publicación; mientras que las revistas de América Latina por razones de métricas de rendimiento.

Scopus is one of the scientific literature databases with the greatest global and regional reach. Scimago Journal Rank, based on Scopus data, classifies 49 specific subject areas within the field of Medicine. The objectives of the article were to identify the characteristics of the Latin American medicine journals that were indexed in Scopus, but that were discontinued, and to determine the reasons why they were excluded from the database during the last decade. The findings show that for 2013-2022 period a total of 745 journals were discontinued globally; 21 of these journals were from Latin America and the Caribbean, 14 of them were journals of the Medicine areas. In conclusion, the majority of journals discontinued in the last decade in Scopus were excluded due to publication problems; while Latin American journals for reasons of performance metrics.

Broad receptor tropism and immunogenicity of a clade 3 sarbecovirus.

Although Rhinolophus bats harbor diverse clade 3 sarbecoviruses, the structural determinants of receptor tropism along with the antigenicity of their spike (S) glycoproteins remain uncharacterized. Here, we show that the African Rhinolophus bat clade 3 sarbecovirus PRD-0038 S has a broad angiotensin-converting enzyme 2 (ACE2) usage and that receptor-binding domain (RBD) mutations further expand receptor promiscuity and enable human ACE2 utilization. We determine a cryo-EM structure of the PRD-0038 RBD bound to Rhinolophus alcyone ACE2, explaining receptor tropism and highlighting differences with SARS-CoV-1 and SARS-CoV-2. Characterization of PRD-0038 S using cryo-EM and monoclonal antibody reactivity reveals its distinct antigenicity relative to SARS-CoV-2 and identifies PRD-0038 cross-neutralizing antibodies for pandemic preparedness. PRD-0038 S vaccination elicits greater titers of antibodies cross-reacting with vaccine-mismatched clade 2 and clade 1a sarbecoviruses compared with SARS-CoV-2 S due to broader antigenic targeting, motivating the inclusion of clade 3 antigens in next-generation vaccines for enhanced resilience to viral evolution.

Light-sensitive phosphorylation regulates enzyme activity and filament assembly of human IMPDH1 retinal splice variants.

Inosine monophosphate dehydrogenase (IMPDH) is the rate-limiting enzyme in de novo guanosine triphosphate (GTP) synthesis and is controlled by feedback inhibition and allosteric regulation. IMPDH assembles into micron-scale filaments in cells, which desensitizes the enzyme to feedback inhibition by GTP and boosts nucleotide production. The vertebrate retina expresses two tissue-specific splice variants IMPDH1(546) and IMPDH1(595). IMPDH1(546) filaments adopt high and low activity conformations, while IMPDH1(595) filaments maintain high activity. In bovine retinas, residue S477 is preferentially phosphorylated in the dark, but the effects on IMPDH1 activity and regulation are unclear. Here, we generated phosphomimetic mutants to investigate structural and functional consequences of phosphorylation in IMPDH1 variants. The S477D mutation re-sensitized both variants to GTP inhibition, but only blocked assembly of IMPDH1(595) filaments and not IMPDH1(546) filaments. Cryo-EM structures of both variants showed that S477D specifically blocks assembly of the high activity assembly interface, still allowing assembly of low activity IMPDH1(546) filaments. Finally, we discovered that S477D exerts a dominant-negative effect in cells, preventing endogenous IMPDH filament assembly. By modulating the structure and higher-order assembly of IMPDH, phosphorylation at S477 acts as a mechanism for downregulating retinal GTP synthesis in the dark, when nucleotide turnover is decreased. Like IMPDH1, many other metabolic enzymes dynamically assemble filamentous polymers that allosterically regulate activity. Our work suggests that posttranslational modifications may be yet another layer of regulatory control to finely tune activity by modulating filament assembly in response to changing metabolic demands.

Broad receptor tropism and immunogenicity of a clade 3 sarbecovirus.

Although Rhinolophus bats harbor diverse clade 3 sarbecoviruses, the structural determinants of receptor tropism along with the antigenicity of their spike (S) glycoproteins remain uncharacterized. Here, we show that the African Rinolophus bat clade 3 sarbecovirus PRD-0038 S has a broad ACE2 usage and that RBD mutations further expand receptor promiscuity and enable human ACE2 utilization. We determined a cryoEM structure of the PRD-0038 RBD bound to R. alcyone ACE2, explaining receptor tropism and highlighting differences with SARS-CoV-1 and SARS-CoV-2. Characterization of PRD-0038 S using cryoEM and monoclonal antibody reactivity revealed its distinct antigenicity relative to SARS-CoV-2 and identified PRD-0038 cross-neutralizing antibodies for pandemic preparedness. PRD-0038 S vaccination elicited greater titers of antibodies cross-reacting with vaccine-mismatched clade 2 and clade 1a sarbecoviruses compared to SARS-CoV-2 S due to broader antigenic targeting, motivating the inclusion of clade 3 antigens in next-generation vaccines for enhanced resilience to viral evolution.

Neutralization, effector function and immune imprinting of Omicron variants.

Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain1 (RBD) of the spike protein. The effects of these mutations on viral infection and transmission and the efficacy of vaccines and therapies remains poorly understood. Here we demonstrate that recently emerged BQ.1.1 and XBB.1.5 variants bind host ACE2 with high affinity and promote membrane fusion more efficiently than earlier Omicron variants. Structures of the BQ.1.1, XBB.1 and BN.1 RBDs bound to the fragment antigen-binding region of the S309 antibody (the parent antibody for sotrovimab) and human ACE2 explain the preservation of antibody binding through conformational selection, altered ACE2 recognition and immune evasion. We show that sotrovimab binds avidly to all Omicron variants, promotes Fc-dependent effector functions and protects mice challenged with BQ.1.1 and hamsters challenged with XBB.1.5. Vaccine-elicited human plasma antibodies cross-react with and trigger effector functions against current Omicron variants, despite a reduced neutralizing activity, suggesting a mechanism of protection against disease, exemplified by S309. Cross-reactive RBD-directed human memory B cells remained dominant even after two exposures to Omicron spikes, underscoring the role of persistent immune imprinting.

Discrimination of foreign bodies in quinoa (Chenopodium quinoa Willd.) grains using convolutional neural networks with a transfer learning approach.

The rising interest in quinoa (Chenopodium quinoa Willd.) is due to its high protein content and gluten-free condition; nonetheless, the presence of foreign bodies in quinoa processing facilities is an issue that must be addressed. As a result, convolutional neural networks have been adopted, mostly because of their data extraction capabilities, which had not been utilized before for this purpose. Consequently, the main objective of this work is to evaluate convolutional neural networks with a learning transfer for foreign bodies identification in quinoa samples. For experimentation, quinoa samples were collected and manually split into 17 classes: quinoa grains and 16 foreign bodies. Then, one thousand images were obtained from each class in RGB space and transformed into four different color spaces (L*a*b*, HSV, YCbCr, and Gray). Three convolutional neural networks (AlexNet, MobileNetv2, and DenseNet-201) were trained using the five color spaces, and the evaluation results were expressed in terms of accuracy and F-score. All the CNN approaches compared showed an F-score ranging from 98% to 99%; both color space and CNN structure were found to have significant effects on the F-score. Also, DenseNet-201 was the most robust architecture and, at the same time, the most time-consuming. These results evidence the capacity of CNN architectures to be used for the discrimination of foreign bodies in quinoa processing facilities.

Human PRPS1 filaments stabilize allosteric sites to regulate activity.

The universally conserved enzyme phosphoribosyl pyrophosphate synthetase (PRPS) assembles filaments in evolutionarily diverse organisms. PRPS is a key regulator of nucleotide metabolism, and mutations in the human enzyme PRPS1 lead to a spectrum of diseases. Here we determine structures of human PRPS1 filaments in active and inhibited states, with fixed assembly contacts accommodating both conformations. The conserved assembly interface stabilizes the binding site for the essential activator phosphate, increasing activity in the filament. Some disease mutations alter assembly, supporting the link between filament stability and activity. Structures of active PRPS1 filaments turning over substrate also reveal coupling of catalysis in one active site with product release in an adjacent site. PRPS1 filaments therefore provide an additional layer of allosteric control, conserved throughout evolution, with likely impact on metabolic homeostasis. Stabilization of allosteric binding sites by polymerization adds to the growing diversity of assembly-based enzyme regulatory mechanisms.

Impacto científico y temático de la Rev. Cuerpo Méd. HNAAA: un análisis bibliométrico, 2011-2020

Introducción: El Perú posee un gran número revistas de áreas biomédicas, pero solo algunas han logrado visibilizar e indizar sus publicaciones en diferentes medios de indización de alcance global. Objetivo: Analizar las características de publicación de la Revista del Cuerpo Médico Hospital Nacional Almanzor Aguinaga Asenjo (Chiclayo) a partir de indicadores bibliométricos. Material y métodos: Estudio descriptivo que analiza 587 registros bibliográficos de los artículos publicados en la revista durante 2011-2020, a partir de indicadores de impacto científico y análisis de términos. Resultados: La mayor producción de artículos corresponde a originales (60%; X̅=66). Los artículos publicados sobre medicina general obtuvieron más impacto en años anteriores. Los temas más frecuentes fueron estudios sobre pacientes de hospitales de Chiclayo, Lambayeque con casos de covid-19. Conclusiones: La Revista del Cuerpo Médico HNAAA se perfila como una publicación seriada de importancia para visibilizar la producción nacional y local por la cobertura temática en especialidades médicas de relevancia regional que publica.

Background: There are several journals about biomedical areas in Peru, however only a few have managed to make their publications avisible and indexed in different global indexing media. Objective: To analyze the main publication characteristics from Revista del Cuerpo Médico Hospital Nacional Almanzor Aguinaga Asenjo (Chiclayo) based on bibliometric methods. Material and methods: Descriptive study that analyzes 587 articles published by the journal from 2011 to 2020, based on bibliometric methods and indicators: citations, scientific impact and co-word analysis. Results: Original articles were the highest types of document published (60%; X̅=66). Published research articles on general medicine received more impact in previous years than the recents. Most frequent topic analyzed were studies about patients from hospitals in Chiclayo city (Lambayeque) with covid-19 clinical cases. Conclusion: Revista del Cuerpo Médico HNAAA is emerging as an important serial publication to make local, national, and international production visible due to thematic coverage in relevant medical specialties.

IMPDH1 retinal variants control filament architecture to tune allosteric regulation.

Inosine-5'-monophosphate dehydrogenase (IMPDH), a key regulatory enzyme in purine nucleotide biosynthesis, dynamically assembles filaments in response to changes in metabolic demand. Humans have two isoforms: IMPDH2 filaments reduce sensitivity to feedback inhibition, while IMPDH1 assembly remains uncharacterized. IMPDH1 plays a unique role in retinal metabolism, and point mutants cause blindness. Here, in a series of cryogenic-electron microscopy structures we show that human IMPDH1 assembles polymorphic filaments with different assembly interfaces in extended and compressed states. Retina-specific splice variants introduce structural elements that reduce sensitivity to GTP inhibition, including stabilization of the extended filament form. Finally, we show that IMPDH1 disease mutations fall into two classes: one disrupts GTP regulation and the other has no effect on GTP regulation or filament assembly. These findings provide a foundation for understanding the role of IMPDH1 in retinal function and disease and demonstrate the diverse mechanisms by which metabolic enzyme filaments are allosterically regulated.

Características de las revistas científicas biomédicas indexadas a Latindex-Perú / Characteristics of biomedical journals indexed in Latindex-Perú

Introducción: En la actualidad no hay estudios que evalúen específicamente el estado de las revistas biomédicas peruanas sobre la base de criterios como el uso de softwares de proceso editorial o el tipo de artículo predominante en las publicaciones. Se desea que una revista científica biomédica tenga, en más de la mitad de sus páginas, artículos originales. Objetivo: Describir las características generales y editoriales, y la producción científica, de las revistas biomédicas peruanas indexadas en Latindex-Perú a partir de 2015. Métodos: Estudio descriptivo transversal. Se incluyeron revistas peruanas de Ciencias de la Salud encontradas en el directorio Sistema Regional de Información en Línea para Revistas Científicas de América Latina, el Caribe, España y Portugal (Latindex). La población estuvo formada por 44 revistas científicas biomédicas peruanas, con temática Ciencias de la Salud (medicina humana, odontología, enfermería, farmacia y bioquímica). El listado de estas se obtuvo mediante el motor de búsquedas avanzadas de Latindex. Resultados: Se describieron características generales: localización, tipo de organización editora, periodicidad, formato de publicación de los artículos, uso de DOI y OJS, revisión por pares y h-index. El 54,4 por ciento de las revistas tuvo su organización encargada en una universidad y el 86,3 por ciento utilizó el OJS. La sede editorial del 68,18 por ciento de las revistas fue Lima. Conclusiones: Las revistas presentan una tendencia a adaptarse al OJS, publican principalmente artículos originales y casos clínicos, y utilizan la revisión por pares como criterio de calidad editorial(AU)

Introduction: Currently, there are no studies for assessing, specifically, the status of Peruvian biomedical journals based on criteria such as the use of editorial process software or the predominant type of articles in the publications. It is desired that a biomedical journal has, in more than half of its pages, original articles. Objective: To describe the general and editorial characteristics, as well as the scientific production, of the Peruvian biomedical journals indexed in Latindex-Peru as of 2015. Methods: Descriptive and cross-sectional study. Peruvian health sciences journals were included, from the Regional Cooperative Online Information System for Scholarly Journals from Latin America, the Caribbean, Spain and Portugal (Latindex). The population was made up of 44 Peruvian biomedical journals, under the topic health sciences (human medicine, dental medicine, nursing, pharmacy and biochemistry). The list of these was obtained through the Latindex advanced search engine. Results: General characteristics were described: location, type of publishing organization, periodicity, article publication format, use of DOI and OJS, peer review and h-index. 54.4 percent of the journals had a university as their responsible and 86.3 percent used OJS. The editorial venue of 68.18 percent of the journals was in Lima. Conclusions: The journals have a tendency to adapt to OJS. They publish mainly original articles and clinical cases, and use peer review as a criterion for editorial quality(AU)

Cryo-EM structures of CTP synthase filaments reveal mechanism of pH-sensitive assembly during budding yeast starvation.

Many metabolic enzymes self-assemble into micron-scale filaments to organize and regulate metabolism. The appearance of these assemblies often coincides with large metabolic changes as in development, cancer, and stress. Yeast undergo cytoplasmic acidification upon starvation, triggering the assembly of many metabolic enzymes into filaments. However, it is unclear how these filaments assemble at the molecular level and what their role is in the yeast starvation response. CTP Synthase (CTPS) assembles into metabolic filaments across many species. Here, we characterize in vitro polymerization and investigate in vivo consequences of CTPS assembly in yeast. Cryo-EM structures reveal a pH-sensitive assembly mechanism and highly ordered filament bundles that stabilize an inactive state of the enzyme, features unique to yeast CTPS. Disruption of filaments in cells with non-assembly or pH-insensitive mutations decreases growth rate, reflecting the importance of regulated CTPS filament assembly in homeotstasis.

Structural basis for isoform-specific inhibition of human CTPS1.

Cytidine triphosphate synthase 1 (CTPS1) is necessary for an effective immune response, as revealed by severe immunodeficiency in CTPS1-deficient individuals [E. Martin et al], [Nature] [510], [288-292] ([2014]). CTPS1 expression is up-regulated in activated lymphocytes to expand CTP pools [E. Martin et al], [Nature] [510], [288-292] ([2014]), satisfying increased demand for nucleic acid and lipid synthesis [L. D. Fairbanks, M. Bofill, K. Ruckemann, H. A. Simmonds], [J. Biol. Chem. ] [270], [29682-29689] ([1995]). Demand for CTP in other tissues is met by the CTPS2 isoform and nucleoside salvage pathways [E. Martin et al], [Nature] [510], [288-292] ([2014]). Selective inhibition of the proliferative CTPS1 isoform is therefore desirable in the treatment of immune disorders and lymphocyte cancers, but little is known about differences in regulation of the isoforms or mechanisms of known inhibitors. We show that CTP regulates both isoforms by binding in two sites that clash with substrates. CTPS1 is less sensitive to CTP feedback inhibition, consistent with its role in increasing CTP levels in proliferation. We also characterize recently reported small-molecule inhibitors, both CTPS1 selective and nonselective. Cryo-electron microscopy (cryo-EM) structures reveal these inhibitors mimic CTP binding in one inhibitory site, where a single amino acid substitution explains selectivity for CTPS1. The inhibitors bind to CTPS assembled into large-scale filaments, which for CTPS1 normally represents a hyperactive form of the enzyme [E. M. Lynch et al], [Nat. Struct. Mol. Biol.] [24], [507-514] ([2017]). This highlights the utility of cryo-EM in drug discovery, particularly for cases in which targets form large multimeric assemblies not amenable to structure determination by other techniques. Both inhibitors also inhibit the proliferation of human primary T cells. The mechanisms of selective inhibition of CTPS1 lay the foundation for the design of immunosuppressive therapies.

Structural basis for broad coronavirus neutralization.

Three highly pathogenic ß-coronaviruses have crossed the animal-to-human species barrier in the past two decades: SARS-CoV, MERS-CoV and SARS-CoV-2. To evaluate the possibility of identifying antibodies with broad neutralizing activity, we isolated a monoclonal antibody, termed B6, that cross-reacts with eight ß-coronavirus spike glycoproteins, including all five human-infecting ß-coronaviruses. B6 broadly neutralizes entry of pseudotyped viruses from lineages A and C, but not from lineage B, and the latter includes SARS-CoV and SARS-CoV-2. Cryo-EM, X-ray crystallography and membrane fusion assays reveal that B6 binds to a conserved cryptic epitope located in the fusion machinery. The data indicate that antibody binding sterically interferes with the spike conformational changes leading to membrane fusion. Our data provide a structural framework explaining B6 cross-reactivity with ß-coronaviruses from three lineages, along with a proof of concept for antibody-mediated broad coronavirus neutralization elicited through vaccination. This study unveils an unexpected target for next-generation structure-guided design of a pan-ß-coronavirus vaccine.

Coordination of phage genome degradation versus host genome protection by a bifunctional restriction-modification enzyme visualized by CryoEM.

Restriction enzymes that combine methylation and cleavage into a single assemblage and modify one DNA strand are capable of efficient adaptation toward novel targets. However, they must reliably cleave invasive DNA and methylate newly replicated unmodified host sites. One possible solution is to enforce a competition between slow methylation at a single unmodified host target, versus faster cleavage that requires multiple unmodified target sites in foreign DNA to be brought together in a reaction synapse. To examine this model, we have determined the catalytic behavior of a bifunctional type IIL restriction-modification enzyme and determined its structure, via cryoelectron microscopy, at several different stages of assembly and coordination with bound DNA targets. The structures demonstrate a mechanism in which an initial dimer is formed between two DNA-bound enzyme molecules, positioning the endonuclease domain from each enzyme against the other's DNA and requiring further additional DNA-bound enzyme molecules to enable cleavage.

Percepción de las madres adolescentes respecto al uso de métodos anticonceptivos en comunidades anexas en región de la selva, 2018 / Perception of adolescent mothers regarding the use of contraceptive methods in communities annexed in jungle region, 2018

Introducción:La selva peruana es un área geográfica con una alta tasa de natalidad, a su vez se encuentra la mayor proporción de madres adolescentes; ENDES reveló que en el país solo el 28,4% de las mujeres adolescentes ha usado alguna vez métodos anticonceptivos.Objetivo:Identificar cual es la percepción de las madres adolescentes respecto al uso de métodos anticonceptivos en comunidades anexas al distrito de Masisea-Ucayali en el 2018. Material y Métodos: Estudio cualitativo de tipo "fenomenológico". La población estudiada estuvo conformada por las madres adolescentes de entre 12-19 años. Se obtuvo una muestra de 13 personas mediante un muestreo teórico cualitativo. Se utilizó un análisis comparativo constante para analizar y sacar conclusiones de los datos de la entrevista. La Resultados: mayoría de las mujeres participantes del estudio tienen conocimientos básicos sobre los métodos anticonceptivos; por otro lado, la perspectiva que tienen frente a estos se ve influenciada por diversos factores. Uno de los factores de mayor relevancia en la percepción es la experiencia de las participantes referida a los efectos secundarios de los anticonceptivos sobretodo hormonales; un segundo factor de relevancia es la opinión de la pareja frente a su uso, ya que el 100% de las mujeres con pareja refirieron consultar a su pareja antes de usar algún anticonceptivo. Nuestro estudio concluye que la perspectiva de las Conclusiones: participantes es influida por el contexto socio cultural; asimismo, se reconoce al centro de salud de la localidad como principal difusor de información referente a métodos anticonceptivos.

Introduction:The Peruvian jungle is a geographical area with a high birth rate, and it has the highest proportion of teenage mothers; DHS revealed that only 28.4% of teenage women in the country have ever used contraception. To identify the perception of adolescent Objective:mothers regarding the use of contraceptive methods in communities annexed to the district of Masisea-Ucayaliin2018.Qualitativestudyofthe MaterialsandMethods:"Phenomenological" type The population studied was made up of adolescent mothers between 12-19 years of age. Asample of 13 people was obtained by means of a qualitative theoretical sampling. Aconstant comparative analysis was used to analyze and draw conclusions from the interview data.Most of the women participating in the study have basic knowledge Results:about contraceptive methods; on the other hand, their perspective on these methods is influenced by various factors. One of the most relevant factors in the perception is the experience of the participants regarding the side effects of contraceptives, especially hormonal ones; a second relevant factor is the opinion of the couple regarding their use, since 100% of the women with a partner referred to consult their partner before using any contraceptive. :Our study concludes that the perspective of the participants is Conclusionsinfluenced by the socio-cultural context; likewise, the local health center is recognized as the main disseminator of information regarding contraceptive methods

Structural basis for broad coronavirus neutralization.

Three highly pathogenic ß-coronaviruses crossed the animal-to-human species barrier in the past two decades: SARS-CoV, MERS-CoV and SARS-CoV-2. SARS-CoV-2 has infected more than 64 million people worldwide, claimed over 1.4 million lives and is responsible for the ongoing COVID-19 pandemic. We isolated a monoclonal antibody, termed B6, cross-reacting with eight ß-coronavirus spike glycoproteins, including all five human-infecting ß-coronaviruses, and broadly inhibiting entry of pseudotyped viruses from two coronavirus lineages. Cryo-electron microscopy and X-ray crystallography characterization reveal that B6 binds to a conserved cryptic epitope located in the fusion machinery and indicate that antibody binding sterically interferes with spike conformational changes leading to membrane fusion. Our data provide a structural framework explaining B6 cross-reactivity with ß-coronaviruses from three lineages along with proof-of-concept for antibody-mediated broad coronavirus neutralization elicited through vaccination. This study unveils an unexpected target for next-generation structure-guided design of a pan-coronavirus vaccine.

Percepción de las madres adolescentes respecto al uso de métodos anticonceptivos en comunidades anexas en región de la selva ,2018 / Perception of adolescent mothers regarding the use of contraceptive methods in communities annexed in jungle region, 2018

RESUMEN Introducción: La selva peruana es un área geográfica con una alta tasa de natalidad, a su vez se encuentra la mayor proporción de madres adolescentes; ENDES reveló que en el país solo el 28,4% de las mujeres adolescentes ha usado alguna vez métodos anticonceptivos. Objetivo: Identificar cual es la percepción de las madres adolescentes respecto al uso de métodos anticonceptivos en comunidades anexas al distrito de Masisea-Ucayali en el 2018. Material y Métodos: Estudio cualitativo de tipo "fenomenológico". La población estudiada estuvo conformada por las madres adolescentes de entre 12-19 años. Se obtuvo una muestra de 13 personas mediante un muestreo teórico cualitativo. Se utilizó un análisis comparativo constante para analizar y sacar conclusiones de los datos de la entrevista. Resultados: La mayoría de las mujeres participantes del estudio tienen conocimientos básicos sobre los métodos anticonceptivos; por otro lado, la perspectiva que tienen frente a estos se ve influenciada por diversos factores. Uno de los factores de mayor relevancia en la percepción es la experiencia de las participantes referida a los efectos secundarios de los anticonceptivos sobretodo hormonales; un segundo factor de relevancia es la opinión de la pareja frente a su uso, ya que el 100% de las mujeres con pareja refirieron consultar a su pareja antes de usar algún anticonceptivo. Conclusiones: Nuestro estudio concluye que la perspectiva de las participantes es influida por el contexto socio cultural; asimismo, se reconoce al centro de salud de la localidad como principal difusor de información referente a métodos anticonceptivos.

ABSTRACT Introduction: The Peruvian jungle is a geographical area with a high birth rate, and it has the highest proportion of teenage mothers; DHS revealed that only 28.4% of teenage women in the country have ever used contraception. Objective: To identify the perception of adolescent mothers regarding the use of contraceptive methods in communities annexed to the district of Masisea-Ucayali in 2018. Materials and Methods: Qualitative study of the "Phenomenological" type The population studied was made up of adolescent mothers between 12-19 years of age. A sample of 13 people was obtained by means of a qualitative theoretical sampling. A constant comparative analysis was used to analyze and draw conclusions from the interview data. Results: Most of the women participating in the study have basic knowledge about contraceptive methods; on the other hand, their perspective on these methods is influenced by various factors. One of the most relevant factors in the perception is the experience of the participants regarding the side effects of contraceptives, especially hormonal ones; a second relevant factor is the opinion of the couple regarding their use, since 100% of the women with a partner referred to consult their partner before using any contraceptive. Conclusions: Our study concludes that the perspective of the participants is influenced by the socio-cultural context; likewise, the local health center is recognized as the main disseminator of information regarding contraceptive methods.