50 research outputs found
Pathological Interaction between DNA Repair and Mitochondrial Dysfunction in ALS
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the degeneration of cortical and spinal cord motor neurons. Several mechanisms have been implicated in the pathogenesis of the disease, including mitochondrial dysfunction, oxidative stress, and genome instability. Recently, a combined role between impaired DNA repair and subsequent mitochondrial dysfunction has emerged as a novel pathological interaction in neurodegeneration. This is exemplified by mutations in the RNA-/DNA-binding proteins FUS and TDP-43 as well as superoxide dismutase 1 (SOD1) gene, all related to familial ALS. In this regard, evidence supports either downregulation or impaired recruitment of DNA repair enzymes in both nuclear and mitochondrial genomes. In addition, evidence also suggests a complex metabolic dysregulation as a critical component in the promotion of the disease. This chapter aims to integrate the molecular mechanisms of this pathological interplay and the possible role in cytosolic protein aggregation and cell death in motor neurons
Bosque de niebla. Gestión y educación ambiental como herramientas didácticas para su conservación
La investigación en estrategias de gestión en sistemas socioecológicos busca aportes al conocimiento para la protección de ecosistemas estratégicos como son los bosques de niebla y la comunicación que estos ejercen con la ciudad-región, como es el caso de bosque de niebla en el sector del Salto del Tequendama. Para ello se plantean diferentes miradas investigativas de diferentes profesionales que participaron en calidad de coinvestigadores, cuyos aportes significativos en las diferentes temáticas a los procesos investigativos, a través de diferentes aristas epistemológicas, se articulan alrededor de los siguientes ejes: ecología, ecopedagogía y recursos naturales, aulas ambientales, modelos pedagógicos en educación ambiental, didácticas ambientales y elementos de TIC. Todas estas son herramientas para desarrollar la educación ambiental y las experiencias pedagógicas por parte de algunos docentes en colegios del departamento de Cundinamarca, quienes dinamizaron proyectos Praes y experiencias educativas para la conservación de los recursos naturales. El elemento común en esto es conseguir que los actores de las comunidades educativas generaran procesos en los que la educación ambiental facilite y genere espacios participativos para el fomento de la protección y conservación de los recursos naturales, en especial de los bosques de niebla
Educación para el siglo XXI: Derechos humanos, ciudadanía y diversidad sexual
172 p. Libro ElectrónicoEste libro recoge el resultado de la sistematización del programa “Maestros y maestras que inspiran” de la línea de Derechos humanos, ciudadanía y diversidad sexual. Estos documentos contienen los relatos de los docentes participantes, como resultado del trabajo dentro y fuera de las aulas en diferentes colegios del Distrito Capital. Los docentes narran sus experiencias desde los diversos contextos, así como las diferentes metodologías utilizadas todas con el fin de forta-lecer la ciudadanía, no solo de sus estudiantes, sino de ellos mismos, de padres y madres de familia y la comunidad en general. Finalmente nos cuentan, cuáles fueron los principales logros y las recomendacio-nes para otros docentes que quieran seguir sus pasos
Mutational survivorship bias: The case of PNKP.
The molecular function of a protein relies on its structure. Understanding how variants alter structure and function in multidomain proteins is key to elucidate the generation of a pathological phenotype. However, one may fall into the logical bias of assessing protein damage only based on the variants that are visible (survivorship bias), which can lead to partial conclusions. This is the case of PNKP, an important nuclear and mitochondrial DNA repair enzyme with both kinase and phosphatase function. Most variants in PNKP are confined to the kinase domain, leading to a pathological spectrum of three apparently distinct clinical entities. Since proteins and domains may have a different tolerability to variation, we evaluated whether variants in PNKP are under survivorship bias. Here, we provide the evidence that supports a higher tolerance in the kinase domain even when all variants reported are deleterious. Instead, the phosphatase domain is less tolerant due to its lower variant rates, a higher degree of sequence conservation, lower dN/dS ratios, and the presence of more disease-propensity hotspots. Together, our results support previous experimental evidence that demonstrated that the phosphatase domain is functionally more necessary and relevant for DNA repair, especially in the context of the development of the central nervous system. Finally, we propose the term "Wald's domain" for future studies analyzing the possible survivorship bias in multidomain proteins
Anticuerpos contra Toxocara spp.en perros de la comunidad de Getsemaní de Heredia, Costa Rica
La toxocariasis es causada por el nématodo Toxocara canis
cuyo hospedero definitivo es el perro y otros cánidos. Es
considerada una de las zoonosis más importantes por su
impacto en salud pública. El ser humano puede infectarse
accidentalmente y desarrollar el síndrome de Larva Migrans
Visceral y Larva Migrans Ocular a veces con secuelas tan
severas como la ceguera. En nuestro país se han realizado
varios estudios coproparasitológicos en caninos de áreas
recreativas y playas reportándose prevalencias de
huevecillos de Toxocara canis alrededor del 7%. Sin
embargo, puede haber un subdiagnóstico por la forma
irregular de excreción de los huevecillos. El objetivo de este
estudio fue determinar la infección previa con Toxocara spp.
mediante la detección de anticuerpos IgG en perros de un
área urbano-marginal de Heredia.Toxocariasis is caused by the nematode Toxocara canis whose definitive host is the dog and other canids. It is considered one of the most important zoonoses due to its impact on public health. Humans can become infected accidentally and develop Visceral Larva Migrans and Ocular Larva Migrans syndrome, sometimes with sequelae as severe as blindness. In our country, several coproparasitological studies have been carried out in canines in recreational areas and beaches, reporting prevalences of Toxocara canis eggs around 7%. However, there may be an underdiagnosis due to the irregular form of egg excretion. The objective of this study was to determine previous infection with Toxocara spp. by detecting IgG antibodies in dogs from an urban-marginal area of Heredia.Escuela de Medicina Veterinari
Detecção de anticorpos anti-Toxocara spp. em caninos de uma comunidade periurbana na província de Heredia, Costa Rica
La toxocariasis es una enfermedad zoonótica cosmopolita causada por nemátodos del género Toxocara. Los
perros son hospedadores definitivos de Toxocara canis y pueden ser asintomáticos o presentar signos clínicos
inespecíficos. El ser humano puede infectarse y desarrollar diferentes patologías.
En Costa Rica, se ha realizado estudios de prevalencia de huevecillos de Toxocara spp. en muestras de suelo y
heces de caninos, pero no se ha investigado la prevalencia de anticuerpos contra este parásito en perros. Este
estudio tiene como objetivo analizar 55 sueros de caninos de una comunidad periurbana de Heredia, Costa
Rica, utilizando una prueba comercial para la detección de anticuerpos IgG anti-Toxocara spp. Además, se
utilizó la información obtenida, mediante un cuestionario aplicado a las personas poseedoras de los perros,
para conocer las prácticas de manejo con sus mascotas y el conocimiento sobre enfermedades zoonóticas.
Se determinó una seroprevalencia de 29%, lo cual evidencia que los caninos se infectaron con este parásito
en alguna etapa de su vida. Se comprueba un desconocimiento generalizado acerca de las enfermedades
zoonóticas por parte de los propietarios de los caninos; la mayoría de ellos aplicaba prácticas de manejo
inadecuadas, tales como: no recoger las heces de sus perros en sitios públicos, poca o ninguna atención
veterinaria para sus mascotas y protocolos de desparasitación de sus animales sin guía profesional ni registros
confiables, lo cual podría favorecer la infección de sus mascotas con parásitos zoonóticos.Toxocariasis is a cosmopolitan zoonotic disease caused by nematodes belonging to the genus To x o c a r a. Dogs are the definitive hosts of Toxocara canis and can develop non-specific clinical symptoms or remain asymptomatic. Humans can also become infected and develop different pathologies.
Prevalence studies on To x o c a r a spp. eggs in soil samples and canine feces were conducted in Costa Rica; however, the prevalence of antibodies against this parasite in dogs has not been investigated yet. This study aimed to analyze 55 canine sera from a peri-urban community in Heredia, Costa Rica, using a commercial test for the detection of IgG antibodies against To x o c a r a spp. In addition, dog owners were asked to fill out a questionnaire to know pet management practices and verify their knowledge of zoonotic diseases.A 29% seroprevalence was determined, evidencing that canines had been infected with this parasite at some point in their lives. A general lack of knowledge about zoonotic diseases was determined among the owners, and most of them showed inadequate pet management practices such as not collecting canine feces in public places, little or no veterinary care, and deworming protocols without professional guidance or reliable records which could favor infection with zoonotic parasites.A toxocaríase é uma doença zoonótica cosmopolita causada por nematóides do gênero Toxocara. Os cães são hospedeiros definitivos do Toxocara canis e podem ser assintomáticos ou mostrar sinais clínicos inespecíficos. O ser humano pode ser infectado e desenvolver diferentes patologias.Em Costa Rica, foram realizados estudos de prevalência de ovos de To x o c a r a spp. em amostras de solo e fezes de cães, mas a prevalência de anticorpos contra esse parasita em cães ainda não tem sido investigado. Este estudo tem como objetivo analisar 55 soros caninos de uma comunidade periurbana de Heredia, Costa Rica, utilizando um teste comercial para a detecção de anticorpos IgG anti-To x o c a r a spp. Além disso, as informações obtidas, através de um questionário aplicado aos donos dos cães, foram utilizadas para conhecer as práticas de manejo com seus animais de estimação e o conhecimento sobre doenças zoonóticas.Foi determinada uma soroprevalência de 29%, o que mostra que os caninos foram infectados com esse parasita em algum estágio de sua vida. Existe um desconhecimento geral sobre doenças zoonóticas por parte dos proprietários caninos; a maioria deles aplicava práticas inadequadas de manejo, tais como: não coletar as fezes de seus cães em locais públicos, pouca ou nenhuma atenção veterinária para seus animais de estimação e protocolos de desparasitação para seus animais sem orientação profissional ou registros confiáveis, o que poderia favorecer a infecção de seus animais de estimação com parasitas zoonóticos.Escuela de Medicina Veterinari
Recommended from our members
The lack of Tex44 causes severe subfertility with flagellar abnormalities in male mice
Acknowledgements: The authors would like to thank A. Schmitt from the Electron Microscopy Facility (Institut Cochin, Paris), R. Onifarasoaniaina from the HISTIM core facility (Institut Cochin, Paris), J. Lesieur and T. Guilbert from the IMAG’IC core facility (Institut Cochin, Paris). The authors thank P. Lorès, A.Touré and M. Whitfield for providing scientific advice.Funder: PHENOMIN; doi: http://dx.doi.org/10.13039/501100021419AbstractBy analyzing a mouse Interspecific Recombinant Congenic Strain (IRCS), we previously identified a quantitative trait locus (QTL), called Mafq1 on mouse chromosome 1, that is associated with male hypofertility and ultrastructural sperm abnormalities. Within this locus, we identified a new candidate gene that could be implicated in a reproductive phenotype: Tex44 (Testis-expressed protein 44). We thus performed a CRISPR/Cas9-mediated complete deletion of this gene in mice in order to study its function. Tex44-KO males were severely hypofertile in vivo and in vitro due to a drastic reduction of sperm motility which itself resulted from important morphological sperm abnormalities. Namely, Tex44-KO sperm showed a disorganized junction between the midpiece and the principal piece of the flagellum, leading to a 180° flagellar bending in this region. In addition, the loss of some axonemal microtubule doublets and outer dense fibers in the flagellum’s principal piece has been observed. Our results suggest that, in mice, TEX44 is implicated in the correct set-up of the sperm flagellum during spermiogenesis and its absence leads to flagellar abnormalities and consequently to severe male hypofertility.
Graphical Abstract</jats:p
The lack of Tex44 causes severe subfertility with flagellar abnormalities in male mice
Abstract By analyzing a mouse Interspecific Recombinant Congenic Strain (IRCS), we previously identified a quantitative trait locus (QTL), called Mafq1 on mouse chromosome 1, that is associated with male hypofertility and ultrastructural sperm abnormalities. Within this locus, we identified a new candidate gene that could be implicated in a reproductive phenotype: Tex44 (Testis-expressed protein 44). We thus performed a CRISPR/Cas9-mediated complete deletion of this gene in mice in order to study its function. Tex44-KO males were severely hypofertile in vivo and in vitro due to a drastic reduction of sperm motility which itself resulted from important morphological sperm abnormalities. Namely, Tex44-KO sperm showed a disorganized junction between the midpiece and the principal piece of the flagellum, leading to a 180° flagellar bending in this region. In addition, the loss of some axonemal microtubule doublets and outer dense fibers in the flagellum’s principal piece has been observed. Our results suggest that, in mice, TEX44 is implicated in the correct set-up of the sperm flagellum during spermiogenesis and its absence leads to flagellar abnormalities and consequently to severe male hypofertility. Graphical Abstrac