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1.
Cell ; 172(5): 897-909.e21, 2018 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-29474918

RESUMEN

X-linked Dystonia-Parkinsonism (XDP) is a Mendelian neurodegenerative disease that is endemic to the Philippines and is associated with a founder haplotype. We integrated multiple genome and transcriptome assembly technologies to narrow the causal mutation to the TAF1 locus, which included a SINE-VNTR-Alu (SVA) retrotransposition into intron 32 of the gene. Transcriptome analyses identified decreased expression of the canonical cTAF1 transcript among XDP probands, and de novo assembly across multiple pluripotent stem-cell-derived neuronal lineages discovered aberrant TAF1 transcription that involved alternative splicing and intron retention (IR) in proximity to the SVA that was anti-correlated with overall TAF1 expression. CRISPR/Cas9 excision of the SVA rescued this XDP-specific transcriptional signature and normalized TAF1 expression in probands. These data suggest an SVA-mediated aberrant transcriptional mechanism associated with XDP and may provide a roadmap for layered technologies and integrated assembly-based analyses for other unsolved Mendelian disorders.


Asunto(s)
Trastornos Distónicos/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Genoma Humano , Transcriptoma/genética , Empalme Alternativo/genética , Elementos Alu/genética , Secuencia de Bases , Sistemas CRISPR-Cas/genética , Estudios de Cohortes , Familia , Femenino , Sitios Genéticos , Haplotipos/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Histona Acetiltransferasas/genética , Histona Acetiltransferasas/metabolismo , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Intrones/genética , Masculino , Repeticiones de Minisatélite/genética , Modelos Genéticos , Degeneración Nerviosa/genética , Degeneración Nerviosa/patología , Células-Madre Neurales/metabolismo , Neuronas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Elementos de Nucleótido Esparcido Corto , Factores Asociados con la Proteína de Unión a TATA/genética , Factores Asociados con la Proteína de Unión a TATA/metabolismo , Factor de Transcripción TFIID/genética , Factor de Transcripción TFIID/metabolismo
2.
Artículo en Inglés | MEDLINE | ID: mdl-38759113

RESUMEN

OBJECTIVES: We aimed to characterize the clinical and radiological features, and outcomes, of a large cohort of hypertrophic pachymeningitis (HP) patients from a single center. METHODS: We conducted a retrospective study at a tertiary referral center, encompassing patients diagnosed with HP between 2003 and 2022. The diagnosis of HP relied on the identification of thickening of the dura mater via magnetic resonance imaging (MRI) of the brain or spine. RESULTS: We included 74 patients with a mean age of 43.6 ± 14.2 years, of whom 37 (50%) were male. Among them, 32 (43.2%) had an immune-mediated origin, including 21 with granulomatosis with polyangiitis (GPA) (predominantly PR3-ANCA positive), four with systemic lupus erythematosus, three with IgG4-related disease, three with idiopathic HP, and one with rheumatoid arthritis. Non-immune-mediated HP accounted for 45 cases (56.8%). Within this category, 21 (28.4%) were infectious cases, with 14 being Mycobacterium tuberculosis infection (TB-HP), and 21 (28.4%) were malignancy-associated HP. Clinical and MRI characteristics exhibited variations among the four etiological groups. Hypoglycorrhachia was primarily observed in infectious and malignancy-associated HP. Immune-mediated HP was associated with a peripheral pattern of contrast enhancement and the Eiffel-by-night sign. MRI features strongly indicative of TB-HP included leptomeningeal involvement, brain parenchymal lesions, and arterial stroke. MPO-ANCA GPA was associated with a higher prevalence of spinal HP. CONCLUSIONS: Within our cohort, GPA and Mycobacterium tuberculosis emerged as the predominant causes of HP. We identified significant disparities in clinical and radiological features among different etiologies, which could have implications for diagnosis.

3.
Int J Mol Sci ; 20(6)2019 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-30889795

RESUMEN

The last decade has seen a rapid expansion of interest in extracellular vesicles (EVs) released by cells and proposed to mediate intercellular communication in physiological and pathological conditions. Considering that the genetic content of EVs reflects that of their respective parent cell, many researchers have proposed EVs as a source of biomarkers in various diseases. So far, the question of heterogeneity in given EV samples is rarely addressed at the experimental level. Because of their relatively small size, EVs are difficult to reliably isolate and detect within a given sample. Consequently, standardized protocols that have been optimized for accurate characterization of EVs are lacking despite recent advancements in the field. Continuous improvements in pre-analytical parameters permit more efficient assessment of EVs, however, methods to more objectively distinguish EVs from background, and to interpret multiple single-EV parameters are lacking. Here, we review EV heterogeneity according to their origin, mode of release, membrane composition, organelle and biochemical content, and other factors. In doing so, we also provide an overview of currently available and potentially applicable methods for single EV analysis. Finally, we examine the latest findings from experiments that have analyzed the issue at the single EV level and discuss potential implications.


Asunto(s)
Vesículas Extracelulares/metabolismo , Neoplasias/metabolismo , Humanos , Modelos Biológicos , Nanopartículas/química , Neoplasias/patología , Fenómenos Ópticos
4.
Glycobiology ; 24(2): 179-84, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24225883

RESUMEN

The invasion of host cells by the intracellular protozoan Trypanosoma cruzi requires interactions with host cell molecules, and the replication of the parasite requires escape from a parasitophorous vacuole into the host cell cytosol. Galectin-3, a member of ß-galactosidase-binding lectin family, has numerous extracellular and intracellular functions. In this study, we investigated the role of galectin-3 during the invasion and intracellular trafficking of T. cruzi extracellular amastigotes (EAs). Endogenous galectin-3 from mouse peritoneal macrophages accumulated around the pathogen during cell invasion by EAs. In addition, galectin-3 accumulated around parasites after their escape from the parasitophorous vacuole. Thus, galectin-3 behaved as a novel marker of phagolysosome lysis during the infection of host cells by T. cruzi.


Asunto(s)
Galectina 3/metabolismo , Trypanosoma cruzi/fisiología , Trypanosoma cruzi/patogenicidad , Animales , Transporte Biológico , Células Cultivadas , Citoplasma/parasitología , Células Madre Embrionarias/parasitología , Endocitosis , Humanos , Macrófagos Peritoneales/parasitología , Ratones , Ratones Endogámicos C57BL , Unión Proteica
5.
An Acad Bras Cienc ; 85(1): 113-35, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23538956

RESUMEN

A very large pterosaur (MN 6594-V) from the Romualdo Formation (Aptian/Albian), Santana Group, Araripe Basin, is described. The specimen is referred to Tropeognathus cf. T. mesembrinus mainly due to the presence of a low and blunt frontoparietal crest, the comparatively low number of teeth and the inclined dorsal part of the occipital region. Two distinct wingspan measurements for pterosaurs are introduced: the maximized wingspan (maxws), which essentially consists of doubling the addition of all wing elements and the length of the scapula or the coracoid (the smaller of the two), and the normal wingspan (nws), which applies a reducing factor (rfc) to the maximized wingspan to account for the natural flexures of the wing. The rfc suggested for pteranodontoids is 5%. In the case of MN 6594-V, the maxws and nws are 8.70 m and 8.26 m, respectively, making it the largest pterosaur recovered from Gondwana so far. The distal end of a larger humerus (MCT 1838-R) and a partial wing (MPSC R 1395) are also described showing that large to giant flying reptiles formed a significant part of the pterosaur fauna from the Romualdo Formation. Lastly, some comments on the nomenclatural stability of the Santana deposits are presented.


Asunto(s)
Dinosaurios/anatomía & histología , Dinosaurios/clasificación , Vuelo Animal , Fósiles , Animales , Brasil
6.
Proteomics ; 12(17): 2668-81, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22740317

RESUMEN

Intracellular peptides generated by the proteasome and oligopeptidases have been suggested to function in signal transduction and to improve insulin resistance in mice fed a high-caloric diet. The aim of this study was to identify specific intracellular peptides in the adipose tissue of Wistar rats that could be associated with the physiological and therapeutic control of glucose uptake. Using semiquantitative mass spectrometry and LC/MS/MS analyses, we identified ten peptides in the epididymal adipose tissue of the Wistar rats; three of these peptides were present at increased levels in rats that were fed a high-caloric Western diet (WD) compared with rats fed a control diet (CD). The results of affinity chromatography suggested that in the cytoplasm of epididymal adipose tissue from either WD or CD rats, distinctive proteins bind to these peptides. However, despite the observed increase in the WD animals, the evaluated peptides increased insulin-stimulated glucose uptake in 3T3-L1 adipocytes treated with palmitate. Thus, intracellular peptides from the adipose tissue of Wistar rats can bind to specific proteins and facilitate insulin-induced glucose uptake in 3T3-L1 adipocytes.


Asunto(s)
Tejido Adiposo/citología , Tejido Adiposo/metabolismo , Glucosa/metabolismo , Resistencia a la Insulina , Péptidos/análisis , Péptidos/metabolismo , Células 3T3 , Adipocitos/citología , Adipocitos/metabolismo , Secuencia de Aminoácidos , Animales , Cromatografía de Afinidad , Cromatografía Liquida , Ingestión de Energía , Insulina/metabolismo , Masculino , Ratones , Datos de Secuencia Molecular , Ácido Palmítico/metabolismo , Unión Proteica , Proteínas/metabolismo , Ratas , Ratas Wistar , Espectrometría de Masas en Tándem
7.
Proteomics ; 12(17): 2641-55, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22740335

RESUMEN

Protein interactions are crucial for most cellular process. Thus, rationally designed peptides that act as competitive assembly inhibitors of protein interactions by mimicking specific, determined structural elements have been extensively used in clinical and basic research. Recently, mammalian cells have been shown to contain a large number of intracellular peptides of unknown function. Here, we investigate the role of several of these natural intracellular peptides as putative modulators of protein interactions that are related to Ca(2+) -calmodulin (CaM) and 14-3-3ε, which are proteins that are related to the spatial organization of signal transduction within cells. At concentrations of 1-50 µM, most of the peptides that are investigated in this study modulate the interactions of CaM and 14-3-3ε with proteins from the mouse brain cytoplasm or recombinant thimet oligopeptidase (EP24.15) in vitro, as measured by surface plasmon resonance. One of these peptides (VFDVELL; VFD-7) increases the cytosolic Ca(2+) concentration in a dose-dependent manner but only if introduced into HEK293 cells, which suggests a wide biological function of this peptide. Therefore, it is exciting to suggest that natural intracellular peptides are novel modulators of protein interactions and have biological functions within cells.


Asunto(s)
Proteínas 14-3-3/metabolismo , Encéfalo/metabolismo , Calmodulina/metabolismo , Metaloendopeptidasas/metabolismo , Péptidos/metabolismo , Mapas de Interacción de Proteínas , Proteínas/metabolismo , Secuencia de Aminoácidos , Animales , Calcio/metabolismo , Células HEK293 , Humanos , Ratones , Ratones Endogámicos C57BL , Datos de Secuencia Molecular , Péptidos/química , Proteínas Recombinantes/metabolismo
8.
Int J Med Microbiol ; 302(1): 19-32, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21783413

RESUMEN

The facultative intracellular bacterial pathogens Listeria monocytogenes and Salmonella enterica have evolved multiple strategies to invade a large panel of mammalian cells. These pathogens use the host cell actin system for invasion and became a paradigm for the study of host-pathogen interactions and bacterial adaptation to mammalian hosts. The key signaling component that these pathogens use to orchestrate actin remodeling is the Arp2/3 complex, which is related to polymerization of actin filaments. These bacterial pathogens are able to trigger distinct invasion mechanisms. On the one hand, L. monocytogenes invade a host cell in a way dependent on the specific interactions between bacterial and host cell proteins, which in turn activate the host cell actin polymerizing machinery that culminates with bacterial internalization. Also, Listeria escapes from the newly formed parasitophorous vacuole and moves among adjacent cells by triggering actin polymerization. On the other hand, Salmonella invades a host cell by delivering into the cytoplasm virulence factors which directly interact with host regulators of actin polymerization which leads to bacterial uptake. Moreover, Salmonella avoids vacuole lyses and modulates the early and late endosomal markers presented in the vacuole membrane. This mini-review focuses on the different pathways that L. monocytogenes and S. enterica activate to modulate the actin cytoskeleton in order to invade, to form the parasitophorous vacuole, and to migrate inside host cells.


Asunto(s)
Actinas/metabolismo , Listeria monocytogenes/patogenicidad , Listeriosis/microbiología , Infecciones por Salmonella/microbiología , Salmonella enterica/patogenicidad , Citoesqueleto de Actina/metabolismo , Complejo 2-3 Proteico Relacionado con la Actina/metabolismo , Animales , Proteínas Bacterianas/metabolismo , Interacciones Huésped-Patógeno , Humanos , Listeria monocytogenes/fisiología , Polimerizacion , Salmonella enterica/fisiología , Transducción de Señal , Vacuolas/metabolismo , Vacuolas/microbiología , Factores de Virulencia/metabolismo
9.
Arch Med Res ; 53(2): 113-121, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34649738

RESUMEN

Latin America is experiencing a demographic and epidemiological transition, with an increase in non-communicable diseases such as cancer. One of the greatest advances in the therapeutic approach to cancer has been the discovery of immunotherapy, and specifically of checkpoint inhibitors (CPIs). Since inhibition of CTLA-4 and PD-1/PD-L1 enhances the immune response, cancer immunotherapies are associated with a new class of toxicities of autoimmune and/or autoinflammatory origin. These immune-related adverse events (irAEs) result in a broad spectrum of clinical events including rheumatic clinical syndromes, which may resemble classic rheumatic diseases. The most common rheumatic manifestations include inflammatory arthritis, myositis, vasculitis, and sicca syndrome. Recognizing rheumatologic irAEs is challenging due to the wide spectrum of clinical presentations that often do not fulfill traditional classification criteria of rheumatic diseases. A delayed diagnosis and treatment can lead to long-term disability, and disorders may become chronic and require ongoing immunosuppressive therapy. The management of irAEs includes the prompt detection and appropriate grading since their management is dictated by their severity. The growing use of CPIs, and the ensuing increase in irAEs, warrants an increasing collaboration between rheumatologists and oncologists. Understanding the pathophysiology, diagnosis, grading, and therapeutic implications of irAEs in patients with cancer is thus a requirement for Latin American oncologists and rheumatologists alike.


Asunto(s)
Miositis , Neoplasias , Enfermedades Reumáticas , Humanos , Inhibidores de Puntos de Control Inmunológico , Inmunoterapia/efectos adversos , Miositis/tratamiento farmacológico , Miositis/terapia , Neoplasias/tratamiento farmacológico , Enfermedades Reumáticas/diagnóstico , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/etiología
10.
Mol Ther Nucleic Acids ; 21: 1-12, 2020 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-32502938

RESUMEN

Most individuals affected with DYT1 dystonia have a heterozygous 3-bp deletion in the TOR1A gene (c.907_909delGAG). The mutation appears to act through a dominant-negative mechanism compromising normal torsinA function, and it is proposed that reducing mutant torsinA may normalize torsinA activity. In this study, we used an engineered Cas9 variant from Streptococcus pyogenes (SpCas9-VRQR) to target the mutation in the TOR1A gene in order to disrupt mutant torsinA in DYT1 patient fibroblasts. Selective targeting of the DYT1 allele was highly efficient with most common non-homologous end joining (NHEJ) edits, leading to a predicted premature stop codon with loss of the torsinA C terminus (delta 302-332 aa). Structural analysis predicted a functionally inactive status of this truncated torsinA due to the loss of residues associated with ATPase activity and binding to LULL1. Immunoblotting showed a reduction of the torsinA protein level in Cas9-edited DYT1 fibroblasts, and a functional assay using HSV infection indicated a phenotypic recovery toward that observed in control fibroblasts. These findings suggest that the selective disruption of the mutant TOR1A allele using CRISPR-Cas9 inactivates mutant torsinA, allowing the remaining wild-type torsinA to exert normal function.

11.
Psicol. ciênc. prof ; 43: e245027, 2023.
Artículo en Portugués | LILACS, Index Psi Revistas Técnico-Científicas | ID: biblio-1431133

RESUMEN

Este artigo versa sobre o processo de desligamento institucional por maioridade de jovens que residem em serviços de acolhimento. Aposta-se em uma política do sensível para visibilizar os encontros e desencontros que acontecem entre as e os jovens e as políticas públicas brasileiras. Para tanto, realizaram-se encontros com jovens que já haviam passado pelo processo de desligamento e com jovens que logo completariam 18 anos e teriam de sair das instituições de acolhimento. Para tornar visíveis essas existências, investiu-se na escrita de biografemas, inspirados na obra de Roland Barthes. Os conceitos de necropolítica e vidas precárias foram fundamentais para compreender as omissões do Estado no momento do desligamento. Verificou-se que o Estado pode maximizar a precariedade de algumas vidas, especialmente daquelas marcadas por características de raça, gênero e classe culturalmente marginalizados. Contudo, é também o encontro com as políticas públicas que garante melhores condições de vida para alguns, facilitando o acesso à universidade e ao mercado de trabalho. A pesquisa aponta que, diante do abandono, as e os jovens se fazem vagalumes, produzindo luminosidades em meio à escuridão e reivindicando o direito à vida.(AU)


This article discusses the process of institutional removal of young people that reside in foster care institutions for reaching adulthood. It relies on a politics of the sensitive to make visible the encounters and mismatches that take place between young people and Brazilian public policies. To do so, meetings were held with young people who had already experienced the removal process and with young people who would soon turn 18 and would have to leave the host institutions. To make these existences visible, this study invested in the writing of biographems, inspired by the works of Roland Barthes. The concepts of necropolitics and precarious lives were fundamental to understand the omissions of the State at the time of removal. It was also found that the State can maximize the precariousness of some lives, especially those marked by culturally marginalized race, gender, and class characteristics. However, it is also the encounter with public policies that ensures better living conditions for some, facilitating access to the university and the labor market. This research points out that, in the face of abandonment, young people become fireflies, producing luminosity amid the darkness and claiming the right to life.(AU)


Este artículo aborda el proceso de desconexión institucional justificado por la edad adulta de los jóvenes que residen en los servicios de acogida. Utilizamos una política sensible para hacer visibles las reuniones y los desajustes que tienen lugar entre los jóvenes y las políticas públicas brasileñas. Con este fin, se celebraron reuniones con los jóvenes que ya habían pasado por el proceso de desconexión institucional y también con los jóvenes que pronto cumplirían los 18 años y tendrían que abandonar las instituciones de acogida. Para hacer visibles estas existencias, se redactaron biografemas, inspirados en el trabajo de Roland Barthes. Los conceptos de necropolítica y vida precaria fueron fundamentales para comprender las omisiones del Estado en el momento de la desconexión. Se encontró que el Estado puede maximizar la precariedad de algunas vidas, principalmente de aquellas marcadas por características de raza, género y clase culturalmente marginadas. Sin embargo, el encuentro con las políticas también puede garantizar mejores condiciones de vida para algunos, facilitándoles el acceso a la universidad y al mercado laboral. Esta investigación señala que, ante el abandono, los jóvenes se convierten en luciérnagas, produciendo luminosidad en medio de la oscuridad y reclamando el derecho a la vida.(AU)


Asunto(s)
Humanos , Masculino , Femenino , Política Pública , Adolescente , Desinstitucionalización , Institucionalización , Orientación , Satisfacción Personal , Embarazo en Adolescencia , Prejuicio , Psicología , Seguridad , Autoimagen , Delitos Sexuales , Trastorno de la Conducta Social , Cambio Social , Control Social Formal , Problemas Sociales , Responsabilidad Social , Apoyo Social , Bienestar Social , Factores Socioeconómicos , Sociología , Desempleo , Violencia , Conducta y Mecanismos de Conducta , Trabajo Infantil , Biografías como Asunto , Aflicción , Custodia del Niño , Adaptación Psicológica , Movilidad Laboral , Organizaciones de Beneficencia , Maltrato a los Niños , Defensa del Niño , Niño Institucionalizado , Protección a la Infancia , Organizaciones , Salud , Salud Mental , Recolección de Datos , Esperanza de Vida , Mortalidad , Adolescente Institucionalizado , Coerción , Jóvenes sin Hogar , Crimen , Derecho Penal , Refugio , Conflictos Armados , Cultura , Cuidado en Custodia , Autonomía Personal , Obligaciones Morales , Poder Público , Muerte , Aplicación de la Ley , Menores , Poblaciones Vulnerables , Violaciones de los Derechos Humanos , Dependencia Psicológica , Crecimiento y Desarrollo , Educación , Empatía , Disciplina Laboral , Empleo , Proyectos de Inversión Social , Resiliencia Psicológica , Acoso Escolar , Racismo , Integración a la Comunidad , Tráfico de Drogas , Ajuste Emocional , Consumo de Alcohol en Menores , Conducta Criminal , Segregación Social , Sistemas de Apoyo Psicosocial , Fragilidad , Cuidados en el Hogar de Adopción , Supervivencia , Reincidencia , Libertad , Autoabandono , Abuso Emocional , Interacción Social , Ciudadanía , Apoyo Familiar , Desamparo Adquirido , Homicidio , Derechos Humanos , Renta , Delincuencia Juvenil , Mala Praxis
12.
Front Cell Dev Biol ; 6: 94, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30211159

RESUMEN

The blastocyst inner cell mass (ICM) that gives rise to a whole embryo in vivo can be derived and cultured in vitro as embryonic stem cells (ESCs), which retain full developmental potential. ICM cells receive, from diverse sources, complex molecular and spatiotemporal signals that orchestrate the finely-tuned processes associated with embryogenesis. Those instructions come, continuously, from themselves and from surrounding cells, such as those present in the trophectoderm and primitive endoderm (PrE). A key component of the ICM niche are the extracellular vesicles (EVs), produced by distinct cell types, that carry and transfer key molecules that regulate target cells and modulate cell renewal or cell fate. A growing number of studies have demonstrated the extracellular circulation of morphogens, a group of classical regulators of embryo development, are carried by EVs. miRNAs are also an important cargo of the EVs that have been implicated in tissue morphogenesis and have gained special attention due to their ability to regulate protein expression through post-transcriptional modulation, thereby influencing cell phenotype. This review explores the emerging evidence supporting the role of EVs as an additional mode of intercellular communication in early embryonic and ESCs differentiation.

13.
PLoS One ; 13(8): e0201305, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30118490

RESUMEN

BACKGROUND: The incidence of canine rabies cases in El Salvador has decreased in the last decade since the establishment of intense control programs, such as massive vaccination campaigns implemented by the Ministry of Health. Socioeconomic crises in recent years have limited the access to certain areas across the country and have impacted surveillance and prevention campaigns, which places the country at risk for a resurgence of canine rabies.We aimedto describe the spatiotemporal patterns of canine rabies and its association with critical social factors in El Salvador from 2005 to 2014. METHOD: We included 459 cases of canine rabies. Several socioeconomic, demographic, and surveillance variables were modeled using a Poisson regression to evaluate their associations with the incidence of canine rabies. Spatial scan statistics were adjusted or unadjusted with covariates and applied to identify statistically significant clusters of canine rabies. Finally, a canine rabies risk map was created. RESULTS: A positive association and higher risk of canine rabies were found for low poverty zones, where it is suspected that urban slums contribute to ongoing rabies transmission (RR = 7.74). Violence had a negative association with rabies (RR = 0.663), which is likely due to reporting bias. Significant clusters were identified in all five epidemiological regions, and the Eastern region had the highest risk (RR = 50.62). The influences of the selected variables in cluster detection were confirmed by the adjusted analysis. Higher-risk townships were distributed from the Western to the Eastern regions of the country. CONCLUSION: Social factors are determinants of rabies in El Salvador and play a major role in national spatial patterns of the disease. There are high-risk areas for canine rabies across the country, and there were two persistent rabies foci during the study period. Examining the role of social factors can provide better insight into rabies in vulnerable countries, and socioeconomic factors can be key elements in developing better policies and interventions for rabies control.


Asunto(s)
Enfermedades de los Perros/epidemiología , Pobreza , Rabia/epidemiología , Violencia , Animales , Perros , El Salvador/epidemiología , Humanos , Incidencia
14.
Stem Cell Rev Rep ; 14(2): 262-276, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29032399

RESUMEN

Extracellular vesicles (EVs) released by mouse embryonic stem cells (mESCs) are considered a source of bioactive molecules that modulate their microenvironment by acting on intercellular communication. Either intracellular endosomal machinery or their derived EVs have been considered a relevant system of signal circuits processing. Herein, we show that these features are found in mESCs. Ultrastructural analysis revealed structures and organelles of the endosomal system such as coated pits and endocytosis-related vesicles, prominent rough endoplasmic reticulum and Golgi apparatus, and multivesicular bodies (MVBs) containing either few or many intraluminal vesicles (ILVs) that could be released as exosomes to extracellular milieu. Besides, budding vesicles shed from the plasma membrane to the extracellular space is suggestive of microvesicle biogenesis in mESCs. mESCs and mouse blastocyst express specific markers of the Endosomal Sorting Complex Required for Transport (ESCRT) system. Ultrastructural analysis and Nanoparticle Tracking Analysis (NTA) of isolated EVs revealed a heterogeneous population of exosomes and microvesicles released by mESCs. These vesicles contain Wnt10b and the Notch ligand Delta-like 4 (DLL4) and also the co-chaperone stress inducible protein 1 (STI1) and its partner Hsp90. Wnt10b and Dll4 colocalize with EVs biogenesis markers in mESCs. Overall, the present study supports the function of the mESCs endocytic network and their EVs as players in stem cell biology.


Asunto(s)
Vesículas Extracelulares/metabolismo , Células Madre Embrionarias de Ratones/metabolismo , Animales , Línea Celular , Retículo Endoplásmico/metabolismo , Retículo Endoplásmico/ultraestructura , Vesículas Extracelulares/ultraestructura , Aparato de Golgi/metabolismo , Proteínas HSP90 de Choque Térmico/metabolismo , Proteínas de Choque Térmico/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Microscopía Electrónica de Transmisión , Células Madre Embrionarias de Ratones/ultraestructura , Cuerpos Multivesiculares/metabolismo
15.
Methods Mol Biol ; 1740: 1-15, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29388131

RESUMEN

Extracellular RNA (exRNA) has recently expanded as a highly important area of study in biomarker discovery and cancer therapeutics. exRNA consists of diverse RNA subpopulations that are normally protected from degradation by incorporation into membranous vesicles or by lipid/protein association. They are found circulating in biofluids, and have proven highly promising for minimally invasive diagnostic and prognostic purposes, particularly in oncology. Recent work has made progress in our understanding of exRNAs-from their biogenesis, compartmentalization, and vesicle packaging to their various applications as biomarkers and therapeutics, as well as the new challenges that arise in isolation and purification for accurate and reproducible analysis. Here we review the most recent advancements in exRNA research.


Asunto(s)
Espacio Extracelular/metabolismo , ARN/metabolismo , Animales , Vesículas Extracelulares/metabolismo , Humanos , MicroARNs/metabolismo , ARN Mensajero/metabolismo
16.
Sci Rep ; 8(1): 2324, 2018 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-29396398

RESUMEN

Most cases of early onset torsion dystonia (DYT1) are caused by a 3-base pair deletion in one allele of the TOR1A gene causing loss of a glutamate in torsinA, a luminal protein in the nuclear envelope. This dominantly inherited neurologic disease has reduced penetrance and no other medical manifestations. It has been challenging to understand the neuronal abnormalities as cells and mouse models which are heterozygous (Het) for the mutant allele are quite similar to wild-type (WT) controls. Here we found that patient fibroblasts and mouse neurons Het for this mutation showed significant differences from WT cells in several parameters revealed by infection with herpes simplex virus type 1 (HSV) which replicates in the nucleus and egresses out through the nuclear envelope. Using a red fluorescent protein capsid to monitor HSV infection, patient fibroblasts showed decreased viral plaque formation as compared to controls. Mouse Het neurons had a decrease in cytoplasmic, but not nuclear HSV fluorescence, and reduced numbers of capsids entering axons as compared to infected WT neurons. These findings point to altered dynamics of the nuclear envelope in cells with the patient genotype, which can provide assays to screen for therapeutic agents that can normalize these cells.


Asunto(s)
Fibroblastos/virología , Herpesvirus Humano 1/fisiología , Heterocigoto , Interacciones Huésped-Patógeno , Chaperonas Moleculares/genética , Neuronas/virología , Replicación Viral , Animales , Núcleo Celular/virología , Células Cultivadas , Citoplasma/virología , Humanos , Ratones , Proteínas Mutantes/genética , Ensayo de Placa Viral
17.
Braz J Microbiol ; 49(1): 144-147, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-28927874

RESUMEN

Many countries in the Americas have detected local transmission of multiple arboviruses that cause febrile illnesses. Therefore, laboratory testing has become an important tool for confirming the etiology of these diseases. The present study aimed to compare the sensitivity and specificity of three different Zika virus detection assays. One hundred serum samples from patients presenting with acute febrile symptoms were tested using a previously reported TaqMan® RT-qPCR assay. We used a SYBR® Green RT-qPCR and a conventional PCR methodologies to compare the results. Of the samples that were determined to be negative by the TaqMan® RT-qPCR assay, 100% (Kappa=0.670) were also found to be negative by SYBR® Green RT-qPCR based on Tm comparison; however, 14% (Kappa=0.035) were found to be positive by conventional PCR followed by agarose gel electrophoresis. The differences between the ZIKV strains circulating worldwide and the low viremia period can compromise diagnostic accuracy and thereby the accuracy of outbreak data. Therefore, improved assays are required to improve the diagnosis and surveillance of arbovirus.


Asunto(s)
Reacción en Cadena de la Polimerasa/métodos , Infección por el Virus Zika/virología , Virus Zika/aislamiento & purificación , Humanos , ARN Viral/genética , Sensibilidad y Especificidad , Virus Zika/clasificación , Virus Zika/genética , Infección por el Virus Zika/diagnóstico
18.
Sci Rep ; 8(1): 16034, 2018 10 30.
Artículo en Inglés | MEDLINE | ID: mdl-30375482

RESUMEN

In Africa, Old World Primates are involved in the maintenance of sylvatic circulation of ZIKV. However, in Brazil, the hosts for the sylvatic cycle remain unknown. We hypothesized that free-living NHPs might play a role in urban/periurban ZIKV dynamics, thus we undertook an NHP ZIKV investigation in two cities in Brazil. We identified ZIKV-positive NHPs and sequences obtained were phylogenetically related to the American lineage of ZIKV. Additionally, we inoculated four C. penicillata with ZIKV and our results demonstrated that marmosets had a sustained viremia. The natural and experimental infection of NHPs with ZIKV, support the hypothesis that NHPs may be a vertebrate host in the maintainance of ZIKV transmission/circulation in urban tropical settings. Further studies are needed to understand the role they may play in maintaining the urban cycle of the ZIKV and how they may be a conduit in establishing an enzootic transmission cycle in tropical Latin America.


Asunto(s)
Reservorios de Enfermedades/virología , Primates/virología , Infección por el Virus Zika/virología , Virus Zika/patogenicidad , Aedes/virología , África , Animales , Brasil , Humanos , Filogenia , Viremia , Infección por el Virus Zika/transmisión
19.
Psicol. soc. (Online) ; 34: e263894, 2022.
Artículo en Portugués | LILACS, Index Psi Revistas Técnico-Científicas | ID: biblio-1422445

RESUMEN

Resumo: Neste artigo objetiva-se discutir questões relacionadas aos encontros das crianças com a assistência social a partir de um recorte da pesquisa de mestrado realizada em um Serviço de Convivência e Fortalecimento de Vínculos. Apostamos nos traçados singulares da metodologia cartográfica para o acompanhamento dos acontecimentos cotidianos do serviço e para o exercício epistêmico de descolonização do pensamento. Pretendemos, assim, contextualizar os discursos vinculados às crianças consideradas público prioritário do serviço e objetos da política pública e refletir sobre a pandemia da Covid-19 que escancara as desigualdades sociais. Entendemos que o olhar crítico desde uma perspectiva parcial potencializa a desconstrução de discursos totalizantes e universais sobre as infâncias e propomos a escutação como aposta ética-estética-política de uma escuta menor em tempos e sistemas maiores, que podem brutalizar o cotidiano de trabalho nas políticas públicas.


Resumen: Este artículo tiene como objetivo discutir cuestiones relacionadas con los encuentros de los niños con la asistencia social, a partir de un fragmento de una investigación de maestría realizada en un Servicio de Convivencia y Fortalecimiento de Vínculos. Apostamos por las huellas únicas de la metodología cartográfica para el seguimiento de los acontecimientos cotidianos del servicio y para el ejercicio epistémico de descolonización del pensamiento. Pretendemos, por tanto, contextualizar los discursos vinculados a los niños considerados público prioritario del servicio y objeto de la política pública y reflexionar sobre la pandemia de la Covid-19, que abre las desigualdades sociales. Entendemos que la mirada crítica desde una perspectiva parcial potencia la deconstrucción de discursos totalizadores y universales sobre la infancia y proponemos la "escucha-acción" como una apuesta ético-estética-política de una escucha más pequeña en tiempos y sistemas más grandes que puede embrutecer el trabajo cotidiano en las políticas públicas.


Abstract: This article aims to discuss issues related to children's encounters with social assistance, based on an excerpt from a master's research carried out in the Service for Coexistence and Strengthening of Bonds. We bet on the unique traces of the cartographic methodology for the monitoring of the daily events of the service and for the epistemic exercise of decolonization of thought. We intend, therefore, to contextualize the speeches linked to children considered a priority public of the service and objects of public policy and to reflect on the Covid-19 pandemic that opens up social inequalities. We understand that the critical look from a partial perspective enhances the deconstruction of totalizing and universal discourses about childhood. Besides, we propose listening-action as an ethical-aesthetic-political bet of a smaller listening in larger times and systems, which can brutalize the daily work in public policies.


Asunto(s)
Humanos , Masculino , Femenino , Niño , Adolescente , Política Pública , Apoyo Social , Niño , Psicología Social , COVID-19
20.
Rev. enferm. UERJ ; 30jan. -dez. 2022.
Artículo en Inglés, Portugués | LILACS-Express | LILACS | ID: biblio-1399586

RESUMEN

Objetivo: descrever os efeitos da escuta terapêutica domiciliar junto a idosos com indicativo de depressão utilizando a técnica de solução de problemas. Método: estudo descritivo, intervencional de cunho qualitativo, com idosos de 60 anos ou mais e com indicativo de depressão. Os dados foram coletados entre outubro de 2017 a abril de 2018 e foi realizada em três etapas: seleção da amostra, intervenção domiciliar e avaliação final. Utilizou-se para análise o Discurso do Sujeito Coletivo. O estudo foi aprovado pelo Comitê de Ética em Pesquisa com Seres Humanos. Resultados: foram elaborados três discursos utilizando as ideias centrais: acolhimento; crescimento pessoal e reflexão sobre a vida. Conclusão: a escuta terapêutica no domicílio favoreceu o acolhimento, fortalecimento do vínculo profissional/paciente e reforçou de modo positivo os mecanismos assertivos das idosas. A Técnica de Solução de Problemas possibilitou o desenvolvimento de uma estratégia sistematizada e adequada para a aplicação da escuta terapêutica.


Objective: to describe the effects of therapeutic listening, using the problem-solving technique, in home visits to elderly people with signs of depression. Method: this qualitative, descriptive, interventional study with elderly people aged 60 years and over with an indication of depression proceeded in three stages: sample selection, home intervention, and final evaluation. Data were collected between October 2017 and April 2018 and analyzed using Collective Subject Discourse. The study was approved by the human research ethics committee. Results: three discourses were formulated using the central ideas: reception; personal growth and reflection on life. Conclusion: therapeutic listening at home favored receptiveness, a stronger bond with the patients and reinforced the elderly women's assertive mechanisms positively. The Problem-Solving Technique made it possible to develop a systematic strategy suited to applying therapeutic listening.


Objetivo: describir los efectos de la escucha terapéutica domiciliaria junto a personas mayores con signos de depresión, utilizando la técnica de resolución de problemas. Método: estudio descriptivo, intervencionista, de tipo cualitativo, junto a personas mayores de 60 años y con indicios de depresión. La recolección de datos se realizó entre octubre de 2017 y abril de 2018 y se llevó a cabo en tres etapas: selección de la muestra, intervención domiciliaria y evaluación final. Para el análisis, se utilizó el Discurso del Sujeto Colectivo. El estudio fue sometido al Comité de Ética en Investigación con Seres Humanos. Resultados: se han elaborado tres discursos utilizando las ideas centrales: acogimiento; crecimiento personal y reflexión sobre la vida. Conclusión: la escucha terapéutica en el domicilio favoreció la recepción, fortaleció el vínculo profesional/paciente y reforzó positivamente los mecanismos asertivos de las ancianas. La Técnica de Resolución de Problemas permitió desarrollar una estrategia sistematizada y adecuada a la aplicación de la escucha terapéutica.

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