RESUMO
Subterranean rodents of the genus Ctenomys (tuco-tucos) are endemic to South America and have experienced relatively recent radiation. There are about 67 recognized species that originated in approximately 1-2 MY. They stand out for their species richness, extraordinary chromosomal diversity, and wide range of habitat they occupy in the continent. Phylogenetic relationships among species of tuco-tucos have been challenging to resolve. Groups of closely-related species have been suggested, but their relationships must be resolved. This study estimates the phylogeny of the genus using massive sequencing, generating thousands of independent molecular markers obtained by RADseq, with a taxonomic sampling that includes 66% of the recognized species. The sequences obtained were mapped against the C. sociabilis genome, recovering up to 1,215 widely shared RAD loci with more than 19,000 polymorphic sites. Our new phylogenetic hypothesis corroborated the species groups previously proposed with cytochrome b gene sequences and provided a much greater resolution of the relationships among species groups. The frater group is sister to all other tuco-tucos, whereas some of the earlierliest proposals placed the sociabilis group as sister to all other tuco-tucos. Ctenomys leucodon, previously proposed as an independent lineage, is associated with the frater group with moderate statistical support. The magellanicus and mendocinus are sister groups in a major clade formed by the boliviensis, talarum, tucumanus, torquatus, and opimus groups. Ctenomys viperinus, included in the phylogeny for the first time, belongs to the tucumanus group. This multi-locus phylogenetic hypothesis provides insights into the historical biogeography of understanding this highly diverse genus.
Assuntos
Especiação Genética , Filogenia , Roedores , Animais , Roedores/genética , Roedores/classificação , Análise de Sequência de DNA , Genoma/genética , América do Sul , GenômicaRESUMO
Sex identification is a common objective in molecular ecology. While many vertebrates display sexual dimorphism, determining the sex can be challenging in certain situations, such as species lacking clear sex-related phenotypic characteristics or in studies using non-invasive methods. In these cases, DNA analyses serve as valuable tools not only for sex determination but also for validating sex assignment based on phenotypic traits. In this study, we developed a bioinformatic framework for sex assignment using genomic data obtained through GBS, and having an available closely related genome assembled at the chromosome level. Our method consists of two ad hoc indexes that rely on the different properties of the mammalian heteromorphic sex chromosomes. For this purpose, we mapped RAD-seq loci to a reference genome and then obtained missingness and coverage depth values for the autosomes and X and Y chromosomes of each individual. Our methodology successfully determined the sex of 165 fur seals that had been phenotypically sexed in a previous study and 40 sea lions sampled in a non-invasive way. Additionally, we evaluated the accuracy of each index in sequences with varying average coverage depths, with Index Y proving greater reliability and robustness in assigning sex to individuals with low-depth coverage. We believe that the approach presented here can be extended to any animal taxa with known heteromorphic XY/ZW sex chromosome systems and that it can tolerate various qualities of GBS sequencing data.
Assuntos
Genoma , Cromossomos Sexuais , Humanos , Animais , Reprodutibilidade dos Testes , Genoma/genética , Cromossomos Sexuais/genética , Cromossomo Y , Genômica , Mamíferos/genéticaRESUMO
Wound healing after skin injury is a complex process, particularly in equines where leg wounds are prevalent and their repair is complicated due to the anatomical characteristics. Conventional treatments are not effective enough. The umbilical cord offers an unlimited source of adult mesenchymal stem cells (ucMSCs) from Wharton's jelly tissue. The present study aims to demonstrate the safety and therapeutic potential of the allogeneic use of equine ucMSCs (e-ucMSCs) in the healing of severe equine leg wounds. The methods employed were the isolation, culture and expansion of e-ucMSCs. Flow cytometry and a PCR assay were used for cell characterization. This study included an immunomodulation assay, a murine pre-clinical trial and the first phase of an equine clinical trial. Our results showed that e-ucMSCs express a functional HLA-G homolog, EQMHCB2. In the immunomodulation assay, the e-ucMSCs inhibited the proliferation of activated equine peripheral blood mononuclear cells (e-PBMCs). In the murine pre-clinical trial, e-ucMSCs reduced healing time by 50%. In the equine clinical trial, the injection of e-ucMSCs into severe leg lesions improved the closure time and quality of the tissues involved, regenerating them without fibrous tissue scar formation. In conclusion, the results of this study suggest that e-ucMSCs can be used allogeneically for wound healing by creating a tolerogenic environment.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Células-Tronco Mesenquimais , Animais , Cavalos , Camundongos , Leucócitos Mononucleares , Cordão Umbilical , CicatrizRESUMO
This study investigated the quality of anaerobic (AnE) and oxic/anoxic (O/A) effluents from a continuous-feed structured-bed hybrid baffled reactor (SBHBR) treating dairy wastewater impacts on lettuce and cucumber germination. While sustainable technologies like SBHBR have successfully removed organic matter and total nitrogen from dairy wastewater, residual concentrations may still represent a risk to water resources. Therefore, phytotoxicity bioassays were conducted with lettuce and cucumber seeds in contact with effluent during early stages to evaluate the potential implications of dairy wastewater reuse in agriculture. The study also explored the potential of SBHBR technology in promoting water resource preservation and creating a sustainable energy and nutrient cycling system. The physicochemical parameters of both effluents were characterized, and the phytotoxicity was evaluated by measuring the germination index (GI), root length (RL), the number of germinated seeds (SG), and epicotyl elongation (EE) for both lettuce and cucumber. The study revealed that the O/A effluent demonstrated lower phytotoxicity than the AnE effluent. The mean results indicate that the O/A zone wastewater was more conducive to cucumber germination than the AnE zone. Moreover, a positive influence of organic matter in the effluent on root growth and epicotyl elongation in cucumber, as well as the presence of nitrogen on the germination index, in both plant species. These findings emphasize the importance of considering effluent characteristics for suitable irrigation, highlighting SBHBR's potential as an effective solution for treating and reusing dairy wastewater in agriculture. This approach helps conserve water resources and promote a sustainable energy and nutrient cycling system.
Assuntos
Cucumis sativus , Águas Residuárias , Germinação , Plantas , Agricultura , Nitrogênio/farmacologiaRESUMO
Latin America continues to be severely underrepresented in genomics research, and fine-scale genetic histories and complex trait architectures remain hidden owing to insufficient data1. To fill this gap, the Mexican Biobank project genotyped 6,057 individuals from 898 rural and urban localities across all 32 states in Mexico at a resolution of 1.8 million genome-wide markers with linked complex trait and disease information creating a valuable nationwide genotype-phenotype database. Here, using ancestry deconvolution and inference of identity-by-descent segments, we inferred ancestral population sizes across Mesoamerican regions over time, unravelling Indigenous, colonial and postcolonial demographic dynamics2-6. We observed variation in runs of homozygosity among genomic regions with different ancestries reflecting distinct demographic histories and, in turn, different distributions of rare deleterious variants. We conducted genome-wide association studies (GWAS) for 22 complex traits and found that several traits are better predicted using the Mexican Biobank GWAS compared to the UK Biobank GWAS7,8. We identified genetic and environmental factors associating with trait variation, such as the length of the genome in runs of homozygosity as a predictor for body mass index, triglycerides, glucose and height. This study provides insights into the genetic histories of individuals in Mexico and dissects their complex trait architectures, both crucial for making precision and preventive medicine initiatives accessible worldwide.
Assuntos
Bancos de Espécimes Biológicos , Genética Médica , Genoma Humano , Genômica , Hispânico ou Latino , Humanos , Glicemia/genética , Glicemia/metabolismo , Estatura/genética , Índice de Massa Corporal , Interação Gene-Ambiente , Marcadores Genéticos/genética , Estudo de Associação Genômica Ampla , Hispânico ou Latino/classificação , Hispânico ou Latino/genética , Homozigoto , México , Fenótipo , Triglicerídeos/sangue , Triglicerídeos/genética , Reino Unido , Genoma Humano/genéticaRESUMO
Demographic models of Latin American populations often fail to fully capture their complex evolutionary history, which has been shaped by both recent admixture and deeper-in-time demographic events. To address this gap, we used high-coverage whole-genome data from Indigenous American ancestries in present-day Mexico and existing genomes from across Latin America to infer multiple demographic models that capture the impact of different timescales on genetic diversity. Our approach, which combines analyses of allele frequencies and ancestry tract length distributions, represents a significant improvement over current models in predicting patterns of genetic variation in admixed Latin American populations. We jointly modeled the contribution of European, African, East Asian, and Indigenous American ancestries into present-day Latin American populations. We infer that the ancestors of Indigenous Americans and East Asians diverged â¼30 thousand years ago, and we characterize genetic contributions of recent migrations from East and Southeast Asia to Peru and Mexico. Our inferred demographic histories are consistent across different genomic regions and annotations, suggesting that our inferences are robust to the potential effects of linked selection. In conjunction with published distributions of fitness effects for new nonsynonymous mutations in humans, we show in large-scale simulations that our models recover important features of both neutral and deleterious variation. By providing a more realistic framework for understanding the evolutionary history of Latin American populations, our models can help address the historical under-representation of admixed groups in genomics research and can be a valuable resource for future studies of populations with complex admixture and demographic histories.
Assuntos
Genética Populacional , Genoma Humano , Humanos , América Latina , Genoma Humano/genética , Demografia , BrancosRESUMO
There is a wealth of information on early pharmacological supportive treatment for early rehabilitation following acute ischemic stroke. This review aims to provide healthcare professionals involved in rehabilitating patients with a summary of the available evidence to assist with decision-making in their daily clinical practice. A search for randomized clinical trials and observational studies published between 1/1/2000 and 28/8/2022 was performed using PubMed, Cochrane and Epistemonikos as search engines with language restriction to english and spanish. The selected studies included patients older than 18 with acute ischemic stroke undergoing early rehabilitation. The outcomes considered for efficacy were: motor function, language, and central pain. The selected pharmacological interventions were: cerebrolysin, levodopa, selegiline, amphetamines, fluoxetine, citalopram, escitalopram, antipsychotics, memantine, pregabalin, amitriptyline and lamotrigine. Evidence synthesis and evaluation were performed using the GRADE methodology. This review provided a summary of the evidence on pharmacological supportive care in early rehabilitation of post-acute ischemic stroke patients. This will make it possible to improve current recommendations with the aim of collaborating with health decision-making for this population.
Existe una gran cantidad de información sobre el tratamiento de apoyo farmacológico temprano para la rehabilitación posterior a un accidente cerebrovascular isquémico agudo. El objetivo de esta revisión es ofrecer a los profesionales de la salud involucrados en la rehabilitación de los pacientes un resumen de la evidencia disponible que colabore con la toma de decisiones en su práctica clínica diaria. Se realizó una búsqueda de ensayos clínicos aleatorizados y estudios observacionales publicados entre el 1/1/2000 y el 28/8/2022 utilizando como motor de búsqueda PubMed, Cochrane y Epistemonikos con restricción de idioma a ingles y español. Los estudios seleccionados incluyeron pacientes mayores de 18 años con un accidente cerebrovascular isquémico agudo sometidos a rehabilitación temprana. Los desenlaces considerados para eficacia fueron: función motora, lenguaje y dolor. Las intervenciones farmacológicas seleccionadas fueron: cerebrolisina, levodopa, selegilina, anfetaminas, fluoxetina, citalopram, escitalopram, antipsicóticos, memantine, pregabalina, amitriptilina y lamotrigina. Se realizó síntesis y evaluación de la evidencia utilizando metodología GRADE. Esta revisión proporcionó un resumen de evidencia sobre el tratamiento de apoyo farmacológico en la neuro-rehabilitación temprana de pacientes post accidente cerebrovascular isquémico agudo. Esto permitirá mejorar las recomendaciones actuales con el objetivo de colaborar con la toma de decisiones en salud para esta población.
Assuntos
Antipsicóticos , AVC Isquêmico , Medicina , Humanos , Amitriptilina , CitalopramRESUMO
Resumen Existe una gran cantidad de información sobre el tratamiento de apoyo farmacológico temprano para la rehabilitación posterior a un accidente cerebrovascular isquémico agudo. El objetivo de esta revisión es ofrecer a los profesionales de la salud involucrados en la rehabilitación de los pacientes un resumen de la evidencia disponible que colabore con la toma de decisiones en su práctica clínica diaria. Se realizó una búsqueda de ensayos clínicos aleatorizados y estudios observacionales publicados entre el 1/1/2000 y el 28/8/2022 utilizando como motor de búsqueda PubMed, Cochrane y Epistemonikos con restricción de idioma a ingles y español. Los estudios seleccionados incluyeron pacientes mayores de 18 años con un accidente cerebrovascular isquémico agudo sometidos a rehabilitación temprana. Los desenlaces considerados para eficacia fueron: función motora, lenguaje y dolor. Las intervenciones farmacológicas seleccionadas fueron: cerebrolisina, levodopa, selegilina, anfetaminas, fluoxetina, citalopram, escitalopram, antipsicóticos, memantine, pregabalina, amitriptilina y lamotrigina. Se realizó síntesis y evaluación de la evidencia utilizando metodología GRADE. Esta revisión proporcionó un resumen de evidencia sobre el tratamiento de apoyo farmacológico en la neuro-rehabilitación temprana de pacientes post accidente cerebrovascular isquémico agudo. Esto permitirá mejorar las recomendaciones actuales con el objetivo de colaborar con la toma de decisiones en salud para esta población.
Abstract There is a wealth of information on early pharmacological supportive treatment for early rehabilitation following acute ischemic stroke. This review aims to provide healthcare professionals involved in rehabilitating patients with a summary of the available evidence to assist with decision-making in their daily clinical practice. A search for randomized clinical trials and observational studies published between 1/1/2000 and 28/8/2022 was performed using PubMed, Cochrane and Epistemonikos as search engines with language restriction to english and spanish. The selected studies included patients older than 18 with acute ischemic stroke undergoing early rehabilitation. The outcomes considered for efficacy were: motor function, language, and central pain. The selected pharmacological interventions were: cerebrolysin, levodopa, selegiline, amphetamines, fluoxetine, citalopram, escitalopram, antipsychotics, memantine, pregabalin, amitriptyline and lamotrigine. Evidence synthesis and evaluation were performed using the GRADE methodology. This review provided a summary of the evidence on pharmacological supportive care in early rehabilitation of post-acute ischemic stroke patients. This will make it possible to improve current recommendations with the aim of collaborating with health decision-making for this population.
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La edad materna avanzada guarda relación directamente proporcional con el riesgo de complicaciones obstétricas y no obstétricas durante la gestación, tanto para la gestante como para el feto. Esto es particularmente importante debido a que a las tasas de fecundidad de las mujeres de mayor edad han aumentado. En Estados Unidos, el 10% del primer nacimiento y el 20% de todos los nacimientos ocurren en mujeres con 35 años o más. Históricamente la edad materna avanzada se ha definido como una edad mayor o igual a 35 años, punto de corte que sustentado en la disminución de la fecundidad y el mayor riesgo de anomalías genéticas en la descendencia de las mujeres mayores a esta edad. Sin embargo, los efectos relacionados al aumento de edad son continuos y el riesgo es mayor mientras mayor sea la edad al momento de la concepción más que como efecto de pasar el umbral de los 35 años. Diferentes investigaciones han mostrado que las gestantes añosas tienen mayor riesgo de complicaciones tempranas de la gestación como aborto espontáneo, embarazo ectópico, anomalías cromosómicas y malformaciones congénitas, así como, preeclampsia, diabetes gestacional, patología placentaria, parto pretérmino, peso bajo al nacer, mortalidad perinatal, embarazo múltiple, parto distócico, parto por cesárea y mortalidad materna. En este artículo se revisa publicaciones recientes sobre el tema y se incluye estadística de un importante hospital de Lima, Perú, y de la Encuesta Nacional de Demografía y Salud Familiar - ENDES 2022.
Advanced maternal age is directly proportional to the risk of obstetric and nonobstetric complications during gestation, both for the pregnant woman and the fetus. This is particularly important because the fertility rates of older women have increased. In the US, 10% of first births and 20% of all births occur to women 35 years of age or older. Historically, advanced maternal age has been defined as an age greater than or equal to 35 years, a cutoff point that is supported by declining fertility and the increased risk of genetic abnormalities in the offspring of women older than this age. However, the effects related to increasing age are continuous and the risk is greater the older the age at conception rather than as an effect of passing the 35 years threshold. Research has shown that older pregnant women are at increased risk of early pregnancy complications such as miscarriage, ectopic pregnancy, chromosomal abnormalities and congenital malformations, as well as, preeclampsia, gestational diabetes, placental pathology, preterm delivery, low birth weight, perinatal mortality, multiple pregnancy, dystocic delivery, cesarean delivery and maternal mortality. This article reviews recent publications on the subject and includes statistics from a major hospital in Lima, Peru, and from the National Demographic and Family Health Survey - ENDES, 2022.
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Resumen El accidente cerebrovascular (ACV) constituye la principal causa de discapacidad de origen neuro- lógico en los adultos mayores a 40 años y la cuarta causa de muerte en Argentina. En los últimos diez años las publicaciones indexadas relacionadas al tratamiento del ACV isquémico fueron más numerosas que las de ACV hemorrágico. El objetivo de este material es proporcionar recomendaciones locales y actualiza- das del abordaje de pacientes con hematoma intraparenquimatoso espontáneo durante la internación. Para la redacción de este manuscrito se convocó a especialistas en esta enfermedad que conformaron grupos de trabajo. Se plantearon 10 tópicos centrales expresados como epidemiologia, atención inicial, imágenes, tratamiento de la presión arterial, reversión de antitrombóticos, indicación de cirugía, profilaxis anticonvulsivante, pronóstico, prevención de complicaciones y reinicio de antitrombóticos. De cada tópico se plantearon mediante preguntas PICO los interrogantes más frecuentes de la práctica diaria. Luego de una revisión sistemática de la literatura, se generaron recomendaciones evaluadas mediante sistema GRADE y consensuadas entre autores y pacientes.
Abstract Stroke is the leading cause of neurological disability in people over 40 years of age and the fourth leading cause of death in Argentina. In the last ten years, the indexed publications related to the treatment of ischemic stroke were more numerous than those of hemorrhagic stroke. The objective of this material is to provide local and updated recommendations for the management of patients with spontaneous intracere- bral hemorrhage during hospitalization. For the writing of this manuscript, diferent specialists were convened to form working groups. Ten central topics expressed as epidemiology, initial care, imaging, blood pressure treatment, reversal of antithrombotics, indication for surgery, seizure prophylaxis, prognosis, prevention of complications and resumption of antithrombotics were raised. For each topic, the most frequent questions of daily practice were raised through PICO questions. After a systematic review of the literature, recommendations were generated, evaluated using the GRADE system and agreed between authors and patients.
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Stroke is the leading cause of neurological disability in people over 40 years of age and the fourth leading cause of death in Argentina. In the last ten years, the indexed publications related to the treatment of ischemic stroke were more numerous than those of hemorrhagic stroke. The objective of this material is to provide local and updated recommendations for the management of patients with spontaneous intracerebral hemorrhage during hospitalization. For the writing of this manuscript, diferent specialists were convened to form working groups. Ten central topics expressed as epidemiology, initial care, imaging, blood pressure treatment, reversal of antithrombotics, indication for surgery, seizure prophylaxis, prognosis, prevention of complications and resumption of antithrombotics were raised. For each topic, the most frequent questions of daily practice were raised through PICO questions. After a systematic review of the literature, recommendations were generated, evaluated using the GRADE system and agreed between authors and patients.
El accidente cerebrovascular (ACV) constituye la principal causa de discapacidad de origen neurológico en los adultos mayores a 40 años y la cuarta causa de muerte en Argentina. En los últimos diez años las publicaciones indexadas relacionadas al tratamiento del ACV isquémico fueron más numerosas que las de ACV hemorrágico. El objetivo de este material es proporcionar recomendaciones locales y actualizadas del abordaje de pacientes con hematoma intraparenquimatoso espontáneo durante la internación. Para la redacción de este manuscrito se convocó a especialistas en esta enfermedad que conformaron grupos de trabajo. Se plantearon 10 tópicos centrales expresados como epidemiologia, atención inicial, imágenes, tratamiento de la presión arterial, reversión de antitrombóticos, indicación de cirugía, profilaxis anticonvulsivante, pronóstico, prevención de complicaciones y reinicio de antitrombóticos. De cada tópico se plantearon mediante preguntas PICO los interrogantes más frecuentes de la práctica diaria. Luego de una revisión sistemática de la literatura, se generaron recomendaciones evaluadas mediante sistema GRADE y consensuadas entre autores y pacientes.
Assuntos
Fibrinolíticos , Acidente Vascular Cerebral , Humanos , Adulto , Pessoa de Meia-Idade , Fibrinolíticos/uso terapêutico , Hemorragia Cerebral/terapia , Acidente Vascular Cerebral/etiologia , Pressão Sanguínea/fisiologia , HospitalizaçãoRESUMO
The population of Mexico has a considerable genetic substructure due to both its pre-Columbian diversity and due to genetic admixture from post-Columbian trans-oceanic migrations. The latter primarily originated in Europe and Africa, but also, to a lesser extent, in Asia. We analyze previously understudied genetic connections between Asia and Mexico to infer the timing and source of this genetic ancestry in Mexico. We identify the predominant origin within Southeast Asia-specifically western Indonesian and non-Negrito Filipino sources-and we date its arrival in Mexico to approximately 13 generations ago (1620 CE). This points to a genetic legacy from the seventeenth century Manila galleon trade between the colonial Spanish Philippines and the Pacific port of Acapulco. Indeed, within Mexico we observe the highest level of this trans-Pacific ancestry in Acapulco, located in the state of Guerrero. This colonial Spanish trade route from East Asia to Europe was centred on Mexico and appears in historical records, but its legacy has been largely ignored. Identities and stories were suppressed due to slavery, assimilation of the immigrants as 'Indios' and incomplete historical records. Here we characterize this understudied Mexican ancestry. This article is part of the theme issue 'Celebrating 50 years since Lewontin's apportionment of human diversity'.
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Povo Asiático , Variação Genética , Ásia , Sudeste Asiático , Genética Populacional , Humanos , México , FilipinasRESUMO
Cancer immunotherapies based mainly on the blockade of immune-checkpoint (IC) molecules by anti-IC antibodies offer new alternatives for treatment in oncological diseases. However, a considerable proportion of patients remain unresponsive to them. Hence, the development of novel clinical immunotherapeutic approaches and/or targets are crucial.W In this context, targeting the immune-checkpoint HLA-G/ILT2/ILT4 has caused great interest since it is abnormally expressed in several malignancies generating a tolerogenic microenvironment. Here, we used CRISPR/Cas9 gene editing to block the HLA-G expression in two tumor cell lines expressing HLA-G, including a renal cell carcinoma (RCC7) and a choriocarcinoma (JEG-3). Different sgRNA/Cas9 plasmids targeting HLA-G exon 1 and 2 were transfected in both cell lines. Downregulation of HLA-G was reached to different degrees, including complete silencing. Most importantly, HLA-G - cells triggered a higher in vitro response of immune cells with respect to HLA-G + wild type cells. Altogether, we demonstrated for the first time the HLA-G downregulation through gene editing. We propose this approach as a first step to develop novel clinical immunotherapeutic approaches in cancer.
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Edição de Genes/métodos , Antígenos HLA-G/genética , Antígenos HLA-G/metabolismo , Sistemas CRISPR-Cas , Linhagem Celular Tumoral , Antígenos HLA-G/imunologia , Humanos , Imunoterapia/métodos , RNA Guia de Cinetoplastídeos , TransfecçãoRESUMO
BACKGROUND: Biocontrol strategies are of significant concern for their application in crops. Various green practices have been designed, but almost all of them had delivery constraints. In particular, to design biocontrol strategies against Sclerotium oryzae in flooded rice fields, the active agent should be retained on the plant leaves by spreading application, nevertheless the direct application onto the water produces the biocontrol agent dilution. An effective delivery model was needed. This work aimed to evaluate the effects of chitosan molecular weight on the formation of positively charged Pseudomonas fluorescens-chitosan complex as a floating microcarrier against Sclerotium oryzae. To this end, three different sizes of chitosan [molecular weights (MWs) 20 000, 250 000, and 1 250 000 g mol-1 ] at different pH values (4, 6, and 7) were tested. The electrostatic interaction was analyzed through ζ-potential measurement. An adjustment of the experimental values was carried out for making predictions. The bacteria antifungal activity into the carrier with different chitosan MWs was analyzed. RESULTS: Our results suggest that it is possible to form a bacteria-chitosan complex with a net positive charge under condition that improve bacteria incorporation to the microcarrier technology without harming bacteria viability and antifungal activity. Thus, high chitosan MW (1 250 000 g mol-1 ) at pH 6 is preferable for microcarrier technology. CONCLUSION: Our findings provide relevant information about bacteria-chitosan interaction and may be useful in biocontrol programs that involved these two components as well as situations in which bacteria adsorption to an anionic carrier or anionic surface is desirable.
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Quitosana , Oryza , Ascomicetos , Bactérias , Peso MolecularRESUMO
Current Genome-Wide Association Studies (GWAS) rely on genotype imputation to increase statistical power, improve fine-mapping of association signals, and facilitate meta-analyses. Due to the complex demographic history of Latin America and the lack of balanced representation of Native American genomes in current imputation panels, the discovery of locally relevant disease variants is likely to be missed, limiting the scope and impact of biomedical research in these populations. Therefore, the necessity of better diversity representation in genomic databases is a scientific imperative. Here, we expand the 1,000 Genomes reference panel (1KGP) with 134 Native American genomes (1KGP + NAT) to assess imputation performance in Latin American individuals of mixed ancestry. Our panel increased the number of SNPs above the GWAS quality threshold, thus improving statistical power for association studies in the region. It also increased imputation accuracy, particularly in low-frequency variants segregating in Native American ancestry tracts. The improvement is subtle but consistent across countries and proportional to the number of genomes added from local source populations. To project the potential improvement with a higher number of reference genomes, we performed simulations and found that at least 3,000 Native American genomes are needed to equal the imputation performance of variants in European ancestry tracts. This reflects the concerning imbalance of diversity in current references and highlights the contribution of our work to reducing it while complementing efforts to improve global equity in genomic research.
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Introducción: la fístula dural arteriovenosa espinal (FDAVE) es una enfermedad vascular rara, de etiología desconocida y frecuentemente subdiagnosticada. El tratamiento puede ser microquirúrgico o endovascular. Material y Método: Análisis retrospectivo de una serie de 8 pacientes consecutivos con FDAVE tratados por microcirugía entre 2010 y 2020. Fueron evaluados parámetros como edad, sexo, cuadro clínico pre y postoperatorio medido con las escalas de Aminoff-Logue y Rankin modificada. Los estudios diagnósticos con RMN (Resonancia Magnética Nuclear), ARM (Angio Resonancia Magnética) y ADM (Angiografía Digital Medular) se utilizaron para determinar nivel lesional y resultados quirúrgicos. Resultados: Fueron operados 8 pacientes (7 masculinos y 1 femenino) con un promedio de edad de 58 años. El tiempo de evolución del cuadro clínico al diagnóstico fue menor a 12 meses salvo un caso de 32 meses. Las FDAVE fueron localizadas en: 6 a nivel dorsal entre D6 y D12, una en L2 y la última en S1 (5 derechas y 3 izquierdas). La arteria de Adamkiewicz se identificó en: 4 casos en L1, 2 en D12, 1 en D10 y un caso en D7 (6 izquierdas y 2 derechas). De los 8 pacientes operados, 3 fueron embolizados previamente. La evolución postoperatoria del cuadro neurológico fue: 2 de 8 permanecieron estables y 6 de 8 mejoraron uno o más puntos en la escala de Rankin modificada; no hubo complicaciones en el postoperatorio. Todos los pacientes mejoraron las imágenes en RMN diferida y la ADM luego de los 6 meses fue negativa. El seguimiento promedio fue de 48 meses con un rango de 11 a 116 meses, ningún paciente presentó recidiva de la FDAVE. Conclusiones: El tratamiento quirúrgico de las FDAVE es un método muy eficaz, de baja morbilidad y menor tasa de recurrencia comparado con el tratamiento endovascular.
Introduction: Spinal dural arteriovenous fistula (SDAVF) is a rare vascular disease, of unknown etiology and frequently underdiagnosed. Treatment can be microsurgical or endovascular. Material and Method: Retrospective analysis of a series of 8 SDAVF patients treated by microsurgery between 2010 and 2020. Parameters including age, sex, pre and postoperative clinical condition were analyzed according to modified Aminoff-Logue and modified Rankin scales. Diagnostic studies such as MRI (Magnetic Resonance Imaging), MRA (Magnetic Resonance Angiogram) and spinal DSA (Digital Subtraction Angiography), were evaluated for lesion level, as were surgical results. Results: Eight patients (7 male and 1 female), average age of 58 years were operated. The interval from symptom onset to diagnosis was less than 12 months in all cases except one (32 months). SDAVF locations were thoracic in 6 cases between T6 and T12, at L2 in one and at S1 in one case (5 on the right and 3 on the left). The Adamkiewicz artery was identified in: 4 cases at L1, 2 at D12, 1 at D10 and in one case at D7 (6 left-sided and 2 right-sided). Three of the 8 patients operated had undergone prior embolization. Postoperative neurological outcomes showed: 2 patients remained stable and 6 had improved one or more points on the modified Rankin scale; no postoperative complications were observed. Follow-up MRI images improved in all cases and spinal DSA was negative at six months. Average follow-up was 48 months (range 11 to 116 months), no patient presented recurrence. Conclusions: Microsurgical treatment of SDAVF proved to be efficient, with low morbidity and lower recurrence rates compared to endovascular results.
Assuntos
Humanos , Fístula , Doenças da Medula Espinal , Doenças Vasculares , Angiografia , Malformações Vasculares do Sistema Nervoso Central , MicrocirurgiaRESUMO
The stem cell niche has a strong influence in the differentiation potential of human pluripotent stem cells with integrins playing a major role in communicating cells with the extracellular environment. However, it is not well understood how interactions between integrins and the extracellular matrix are involved in cardiac stem cell differentiation. To evaluate this, we performed a profile of integrins expression in two stages of cardiac differentiation: mesodermal progenitors and cardiomyocytes. We found an active regulation of the expression of different integrins during cardiac differentiation. In particular, integrin α5 subunit showed an increased expression in mesodermal progenitors, and a significant downregulation in cardiomyocytes. To analyze the effect of α5 subunit, we modified its expression by using a CRISPRi technique. After its downregulation, a significant impairment in the process of epithelial-to-mesenchymal transition was seen. Early mesoderm development was significantly affected due to a downregulation of key genes such as T Brachyury and TBX6. Furthermore, we observed that repression of integrin α5 during early stages led to a reduction in cardiomyocyte differentiation and impaired contractility. In summary, our results showed the link between changes in cell identity with the regulation of integrin α5 expression through the alteration of early stages of mesoderm commitment.
Assuntos
Células-Tronco Embrionárias Humanas/citologia , Integrina alfa5/genética , Miócitos Cardíacos/citologia , Sistemas CRISPR-Cas , Diferenciação Celular , Linhagem Celular , Regulação para Baixo , Regulação da Expressão Gênica no Desenvolvimento , Células HEK293 , Células-Tronco Embrionárias Humanas/metabolismo , Humanos , Miócitos Cardíacos/metabolismo , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/metabolismo , Nicho de Células-TroncoRESUMO
Equid alphaherpesvirus 1 (EHV-1) infection causes abortion, respiratory disease, perinatal deaths and neurological disorders in horses. The natural infection and available vaccines provide only partial and short-lived protection against reinfections. In the present study, we analyzed the ability of purified baculovirus-expressed glycoprotein D (gD) administered by different routes to induce protective immunity in BALB/c mice after challenge with the EHV-1 AR8 strain. Clinical signs varied among the different groups of mice immunized by parenteral routes, and, although gD induced a specific serum IgG response, it did not prevent the virus from reaching the lungs. Intranasally immunized mice showed no clinical signs, and virus isolation from lungs, histological lesions and antigen detection by immunohistochemistry were negative. In addition, by this route, gD did not stimulate the production of serum IgG and IgA. However, a specific IgA response in the respiratory tract was confirmed in intranasally immunized mice. Thus, we conclude that the mucosal immune response could reduce the initial viral attachment and prevent the virus from reaching the lungs. Our findings provide additional data to further study new immunization strategies in the natural host.
La infección con alfaherpesvirus equino 1 (EHV-1) causa abortos, enfermedad respiratoria, muertes perinatales y desórdenes neurológicos en equinos. La infección natural y las vacunas disponibles solo proporcionan protección parcial y de corta duración contra las reinfecciones. En el presente estudio se analizó la inducción de inmunidad protectiva de la glicoproteina D (gD) expresada en baculovirus y purificada al ser administrada por diferentes rutas en ratones BALB/c desafiados con la cepa AR8 de EHV-1. Los signos clínicos fueron variables entre los grupos de ratones inmunizados por rutas parenterales y, aunque la gD indujo respuesta especifica de IgG en suero, no logró prevenir la llegada del virus al pulmón. En los ratones inmunizados intranasalmente no se observaron signos clinicos ni lesiones histopatológi-cas, y el aislamiento viral y la detección de antigenos por inmunohistoquímica en pulmón fueron negativos. Además, por esta ruta la gD no estimuló la producción de IgG y de IgA en suero. Sin embargo se confirmó la respuesta de IgA especifica en el tracto respiratorio de ratones inmunizados intranasalmente. Esta respuesta inmune mucosal podría haber reducido la unión inicial del virus a la célula huésped y, de este modo, prevenir la llegada del virus al pulmón. Nuestros hallazgos proporcionan un aporte para continuar estudiando nuevas estrategias de inmunización en el huésped natural.
Assuntos
Doenças Respiratórias/imunologia , Glicoproteínas/imunologia , Herpesvirus Equídeo 1/patogenicidade , Imuno-Histoquímica/veterinária , Imunização/veterinária , Cavalos/imunologia , Imunidade/efeitos dos fármacosRESUMO
Stroke is the third cause of death and the first cause of disability in Argentina. Ischemic events constitute 80% of cases. It requires the implementation of systematized protocols that allow reducing the time of care, morbidity and mortality. Specialists from nine medical societies related to the care of patients with cerebrovascular disease participated in the consensus. A separate agenda was agreed upon in chapters and for the writing of them, work groups were formed with members of different medical specialties. The level of recommendation was discussed and agreed upon for each topic based on the best clinical evidence available for each of them. An adaptation to the local scope of the recommendations was made when it was considered necessary.The American Heart Association system was used to draft the recommendations and their level of evidence. The correction and editing were done by five external reviewers, who did not participate in the writing and with extensive experience in vascular pathology. Once the preliminary document was finalized, a general meeting was held with all the members of the working groups and the reviewers to reach final recommendations. The consensus covers the management of ischemic stroke in the pre-hospital phase, initial evaluation in the emergency center, recanalization therapies (thrombolysis and/ or mechanical thrombectomy), decompressive craniectomy, neuroimaging and clinical care in the hospital.
El accidente cerebrovascular es la tercera causa de muerte y la primera de discapacidad en la Argentina. Los eventos isquémicos constituyen el 80% de los casos. Los accidentes vasculares cerebrales requieren la implementación de protocolos sistematizados que permitan reducir los tiempos en la atención, la morbilidad y mortalidad. En el consenso participaron especialistas de nueve sociedades médicas relacionadas con la atención de pacientes con enfermedad cerebrovascular. Se consensuó un temario separado en capítulos y para la redacción de los mismos se conformaron grupos de trabajo con miembros de diferentes especialidades médicas. Se discutió y acordó para cada tema el nivel de recomendación en base a la mejor evidencia clínica disponible para cada tópico. Se realizó una adaptación al ámbito local de las recomendaciones cuando se consideró necesario. El sistema de la American Heart Association se utilizó para redactar las recomendaciones y su grado de evidencia. La corrección y edición fue realizada por cinco revisores externos, que no participaron en la redacción y con amplia experiencia en enfermedad vascular. Finalizado el documento preliminar, se organizó una reunión general con todos los integrantes de los grupos de trabajo y los revisores para redactar las recomendaciones definitivas. El consenso abarca la atención del paciente con accidente cerebrovascular isquémico en la fase pre-hospitalaria, evaluación inicial en la central de emergencias, terapias de recanalización (trombolisis y/o trombectomía mecánica), craniectomía descompresiva, neuroimágenes y cuidados clínicos en la internación.