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1.
Development ; 150(18)2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37721334

RESUMO

During neural development, cellular adhesion is crucial for interactions among and between neurons and surrounding tissues. This function is mediated by conserved cell adhesion molecules, which are tightly regulated to allow for coordinated neuronal outgrowth. Here, we show that the proprotein convertase KPC-1 (homolog of mammalian furin) regulates the Menorin adhesion complex during development of PVD dendritic arbors in Caenorhabditis elegans. We found a finely regulated antagonistic balance between PVD-expressed KPC-1 and the epidermally expressed putative cell adhesion molecule MNR-1 (Menorin). Genetically, partial loss of mnr-1 suppressed partial loss of kpc-1, and both loss of kpc-1 and transgenic overexpression of mnr-1 resulted in indistinguishable phenotypes in PVD dendrites. This balance regulated cell-surface localization of the DMA-1 leucine-rich transmembrane receptor in PVD neurons. Lastly, kpc-1 mutants showed increased amounts of MNR-1 and decreased amounts of muscle-derived LECT-2 (Chondromodulin II), which is also part of the Menorin adhesion complex. These observations suggest that KPC-1 in PVD neurons directly or indirectly controls the abundance of proteins of the Menorin adhesion complex from adjacent tissues, thereby providing negative feedback from the dendrite to the instructive cues of surrounding tissues.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Ligantes , Membrana Celular , Animais Geneticamente Modificados , Transporte Biológico , Caenorhabditis elegans/genética , Dendritos , Mamíferos , Proteínas de Membrana , Proteínas de Caenorhabditis elegans/genética
2.
Rev. salud pública ; 24(4)jul.-ago. 2022.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1536737

RESUMO

Objetivo Evaluar el conocimiento en el uso de Medicamentos de Uso Veterinario (MUV) de los productores ganaderos y personal involucrado en Bogotá y municipios aledaños. Métodos Se realizó un estudio de corte transversal a través de entrevistas a operarios y productores ganaderos de una muestra de 30 hatos lecheros localizados en 15 municipios cerca de Bogotá, Cundinamarca. Resultados Se identificó la implementación de prácticas para la administración de MUV, incluyendo parámetros que influencian su administración y conocimientos en las personas que los prescriben y administran. Se encontró que los medicamentos de mayor frecuencia fueron los antimicrobianos con 60,7%, entre los cuales se destaca el uso de penicilina y oxitetraciclina. Los MUV inyectables (parenterales) fueron las formas más frecuentes de aplicación con un 64,7%. Se identificaron 251 MUV en los hatos lecheros, de los cuales el 81,3% están compuestos por principios activos que requieren tiempo de retiro en leche y carne. Se destaca el rol del mayordomo en el cuidado animal a nivel diagnóstico y administración del tratamiento. Conclusión El presente estudio sugiere que el uso de MUV es implementado empíricamente en producciones lecheras y podría contribuir a mediano y largo plazo a la emergencia de cepas con resistencia a MUV.


Objective To evaluate the knowledge in the antibiotic stewardship practices in livestock producers and associated staff from Bogotá and neighboring municipalities. Methods A cross-sectional study was performed through interviews for livestock producers and staff in a sample of 30 dairy farms located in 15 municipalities near Bogota, Cundinamarca. We evaluated practice administration of veterinary drugs and knowledge in antibiotic stewardship by farm livestock managers in charge who prescribe and administer veterinary drugs. Results The most common veterinary drugs were antimicrobials with 60.7% such as penicillin and oxytetracycline. The injectable veterinary drugs (parenteral) were the most frequently used with 64.7%. We identified 251 veterinary drugs in the dairy farms where 81.3% of active compounds require withdrawal time in the milk and meat. The butler role in animal care was highlighted at diagnostic level and treatment compliance. Conclusion This study suggests that recommendations for veterinary drug stewardship remain empirically implemented in dairy farms which might lead to the future emergence of multidrug-resistant strains in the long and middle term.

3.
PLoS Biol ; 20(6): e3001684, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35727855

RESUMO

The ability to detect and respond to acute oxygen (O2) shortages is indispensable to aerobic life. The molecular mechanisms and circuits underlying this capacity are poorly understood. Here, we characterize the behavioral responses of feeding Caenorhabditis elegans to approximately 1% O2. Acute hypoxia triggers a bout of turning maneuvers followed by a persistent switch to rapid forward movement as animals seek to avoid and escape hypoxia. While the behavioral responses to 1% O2 closely resemble those evoked by 21% O2, they have distinct molecular and circuit underpinnings. Disrupting phosphodiesterases (PDEs), specific G proteins, or BBSome function inhibits escape from 1% O2 due to increased cGMP signaling. A primary source of cGMP is GCY-28, the ortholog of the atrial natriuretic peptide (ANP) receptor. cGMP activates the protein kinase G EGL-4 and enhances neuroendocrine secretion to inhibit acute responses to 1% O2. Triggering a rise in cGMP optogenetically in multiple neurons, including AIA interneurons, rapidly and reversibly inhibits escape from 1% O2. Ca2+ imaging reveals that a 7% to 1% O2 stimulus evokes a Ca2+ decrease in several neurons. Defects in mitochondrial complex I (MCI) and mitochondrial complex I (MCIII), which lead to persistently high reactive oxygen species (ROS), abrogate acute hypoxia responses. In particular, repressing the expression of isp-1, which encodes the iron sulfur protein of MCIII, inhibits escape from 1% O2 without affecting responses to 21% O2. Both genetic and pharmacological up-regulation of mitochondrial ROS increase cGMP levels, which contribute to the reduced hypoxia responses. Our results implicate ROS and precise regulation of intracellular cGMP in the modulation of acute responses to hypoxia by C. elegans.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Cálcio/metabolismo , GMP Cíclico/metabolismo , Proteínas Quinases Dependentes de GMP Cíclico/genética , Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Hipóxia , Oxigênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo
4.
EMBO Rep ; 23(7): e54163, 2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35586945

RESUMO

N-glycans are molecularly diverse sugars borne by over 70% of proteins transiting the secretory pathway and have been implicated in protein folding, stability, and localization. Mutations in genes important for N-glycosylation result in congenital disorders of glycosylation that are often associated with intellectual disability. Here, we show that structurally distinct N-glycans regulate an extracellular protein complex involved in the patterning of somatosensory dendrites in Caenorhabditis elegans. Specifically, aman-2/Golgi alpha-mannosidase II, a conserved key enzyme in the biosynthesis of specific N-glycans, regulates the activity of the Menorin adhesion complex without obviously affecting the protein stability and localization of its components. AMAN-2 functions cell-autonomously to allow for decoration of the neuronal transmembrane receptor DMA-1/LRR-TM with the correct set of high-mannose/hybrid/paucimannose N-glycans. Moreover, distinct types of N-glycans on specific N-glycosylation sites regulate DMA-1/LRR-TM receptor function, which, together with three other extracellular proteins, forms the Menorin adhesion complex. In summary, specific N-glycan structures regulate dendrite patterning by coordinating the activity of an extracellular adhesion complex, suggesting that the molecular diversity of N-glycans can contribute to developmental specificity in the nervous system.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Amantadina/metabolismo , Animais , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Dendritos/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Polissacarídeos/química , Polissacarídeos/metabolismo
5.
World J Pediatr ; 18(6): 373-382, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35476245

RESUMO

BACKGROUND: Since December 2019, the SARS-CoV-2 virus has been a global health issue. The main clinical presentation of this virus is a flu-like disease; however, patients with diverse neurologic manifestations have also been reported. In this review, we attempt to summarize, discuss and update the knowledge of the neurologic manifestations in the pediatric population affected by SARS-CoV-2 infection and the pandemic's effects in children with neurologic diseases. DATA SOURCES: This review analyzes studies found on the PubMed database using the following keywords: Neurologic manifestations COVID-19, Neurological COVID-19, coronavirus, SARS-CoV-2, pediatric COVID-19, COVID-19 in children, MIS-C, Pediatric Inflammatory Multisystem Syndrome, Guillain Barré Syndrome, Stroke, ADEM, and Anti-NMDA encephalitis. All studies cited were published between 2004 and 2022, and represent the most relevant articles in the field. The World Health Organization COVID-19 online dashboard was assessed to obtain updated epidemiological data. RESULTS: The most common neurologic symptoms in the pediatric population are headache, seizures, encephalopathy, and muscle weakness. These can be present during COVID-19 or weeks after recovering from it. Children who presented with multi-system inflammatory syndrome had a higher incidence of neurologic manifestations, which conferred a greater risk of morbidity and mortality. Several neuro-pathophysiological mechanisms have been proposed, including direct virus invasion, hyper-inflammatory reactions, multi-systemic failure, prothrombotic states, and immune-mediated processes. On the other hand, the COVID-19 pandemic has affected patients with neurologic diseases, making it challenging to access controls, treatment, and therapies. CONCLUSIONS: Various neurologic manifestations have been associated with children's SARS-CoV-2 infection. It is important to identify and give them proper and opportune treatment because they can be potentially grave and life-threatening; some can lead to long-lasting sequelae. Different neuro-pathophysiological mechanisms have been proposed, however, a causal relationship between SARS-CoV-2 infection and neurologic manifestations remains to be proven. Patients with neurologic diseases are especially affected by COVID-19, not only by the disease itself but also by its complications and pandemic management measures.


Assuntos
COVID-19 , Doenças do Sistema Nervoso , COVID-19/complicações , Criança , Humanos , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/etiologia , Neurologistas , Pandemias , SARS-CoV-2 , Convulsões , Síndrome de Resposta Inflamatória Sistêmica
6.
PLoS Genet ; 17(7): e1009475, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34197450

RESUMO

The assembly of neuronal circuits involves the migrations of neurons from their place of birth to their final location in the nervous system, as well as the coordinated growth and patterning of axons and dendrites. In screens for genes required for patterning of the nervous system, we identified the catp-8/P5A-ATPase as an important regulator of neural patterning. P5A-ATPases are part of the P-type ATPases, a family of proteins known to serve a conserved function as transporters of ions, lipids and polyamines in unicellular eukaryotes, plants, and humans. While the function of many P-type ATPases is relatively well understood, the function of P5A-ATPases in metazoans remained elusive. We show here, that the Caenorhabditis elegans ortholog catp-8/P5A-ATPase is required for defined aspects of nervous system development. Specifically, the catp-8/P5A-ATPase serves functions in shaping the elaborately sculpted dendritic trees of somatosensory PVD neurons. Moreover, catp-8/P5A-ATPase is required for axonal guidance and repulsion at the midline, as well as embryonic and postembryonic neuronal migrations. Interestingly, not all axons at the midline require catp-8/P5A-ATPase, although the axons run in the same fascicles and navigate the same space. Similarly, not all neuronal migrations require catp-8/P5A-ATPase. A CATP-8/P5A-ATPase reporter is localized to the ER in most, if not all, tissues and catp-8/P5A-ATPase can function both cell-autonomously and non-autonomously to regulate neuronal development. Genetic analyses establish that catp-8/P5A-ATPase can function in multiple pathways, including the Menorin pathway, previously shown to control dendritic patterning in PVD, and Wnt signaling, which functions to control neuronal migrations. Lastly, we show that catp-8/P5A-ATPase is required for localizing select transmembrane proteins necessary for dendrite morphogenesis. Collectively, our studies suggest that catp-8/P5A-ATPase serves diverse, yet specific, roles in different genetic pathways and may be involved in the regulation or localization of transmembrane and secreted proteins to specific subcellular compartments.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/fisiologia , Neurônios/fisiologia , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Animais , Animais Geneticamente Modificados , Axônios/fisiologia , Padronização Corporal , Proteínas de Caenorhabditis elegans/genética , Movimento Celular/genética , Dendritos/fisiologia , Retículo Endoplasmático/metabolismo , Proteínas de Membrana/metabolismo , Mutação , Via de Sinalização Wnt
7.
Cad Saude Publica ; 37(5): e00078820, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34076096

RESUMO

Historically, human migrations have determined the spread of many infectious diseases by promoting the emergence of temporal outbreaks between populations. We aimed to analyze health indicators, expenditure, and disability caused by tuberculosis (TB) and HIV/AIDS burden under the Colombian-Venezuelan migration flow focusing on the Northeastern border. A retrospective study was conducted using TB and HIV/AIDS data since 2009. We consolidated a database using official reports from the Colombian Surveillance System, World Health Organization, Indexmundi, the Global Health Observatory, IHME HIV atlas, and Joint United Nations Programme on HIV/AIDS (UNAIDS). Disability metrics regarding DALYs (disability adjusted life years) and YLDs (years lived with disability), were compared between countries. Mapping was performed on ArcGIS using official migration data of Venezuelan citizens. Our results indicate that TB profiles from Colombia and Venezuela are identical in terms of disease burden, except for an increase in TB incidence in the Colombian-Venezuelan border departments in recent years, concomitantly with the massive Venezuelan immigration since 2005. We identified a four-fold underfunding for the TB program in Venezuela, which might explain the low-testing rates for cases of multidrug-resistant TB (67%) and HIV/AIDS (60%), as well as extended hospital stays (150 days). We found a significant increase in DALYs of HIV/AIDS patients in Venezuela, specifically, 362.35 compared to 265.37 observed in Colombia during 2017. This study suggests that the Venezuelan massive migration and program underfunding might exacerbate the dual burden of TB and HIV in Colombia, especially towards the Colombian-Venezuelan border.


Assuntos
Infecções por HIV , Tuberculose , Brasil , Colômbia/epidemiologia , Emigração e Imigração , Infecções por HIV/epidemiologia , Humanos , Estudos Retrospectivos , Tuberculose/epidemiologia , Venezuela/epidemiologia
8.
Cad. Saúde Pública (Online) ; 37(5): e00078820, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1249447

RESUMO

Abstract: Historically, human migrations have determined the spread of many infectious diseases by promoting the emergence of temporal outbreaks between populations. We aimed to analyze health indicators, expenditure, and disability caused by tuberculosis (TB) and HIV/AIDS burden under the Colombian-Venezuelan migration flow focusing on the Northeastern border. A retrospective study was conducted using TB and HIV/AIDS data since 2009. We consolidated a database using official reports from the Colombian Surveillance System, World Health Organization, Indexmundi, the Global Health Observatory, IHME HIV atlas, and Joint United Nations Programme on HIV/AIDS (UNAIDS). Disability metrics regarding DALYs (disability adjusted life years) and YLDs (years lived with disability), were compared between countries. Mapping was performed on ArcGIS using official migration data of Venezuelan citizens. Our results indicate that TB profiles from Colombia and Venezuela are identical in terms of disease burden, except for an increase in TB incidence in the Colombian-Venezuelan border departments in recent years, concomitantly with the massive Venezuelan immigration since 2005. We identified a four-fold underfunding for the TB program in Venezuela, which might explain the low-testing rates for cases of multidrug-resistant TB (67%) and HIV/AIDS (60%), as well as extended hospital stays (150 days). We found a significant increase in DALYs of HIV/AIDS patients in Venezuela, specifically, 362.35 compared to 265.37 observed in Colombia during 2017. This study suggests that the Venezuelan massive migration and program underfunding might exacerbate the dual burden of TB and HIV in Colombia, especially towards the Colombian‐Venezuelan border.


Resumen: Históricamente, las migraciones humanas han determinado la expansión de muchas enfermedades infecciosas, promoviendo el surgimiento de brotes temporales en la población. Nuestro objetivo fue analizar indicadores de salud, gastos, así como la discapacidad causada por la tuberculosis (TB) y la carga del VIH/SIDA ante el flujo migratorio entre Colombia-Venezuela, centrándose en los departamentos fronterizos del nordeste. Se realizó un estudio retrospectivo usando datos sobre TB y VIH/SIDA desde 2009. Consolidamos una base de datos usando informes oficiales del Sistema de Vigilancia Colombiano, Organización Mundial de la Salud, Indexmundi, Observatorio Global de la Salud, IHME HIV atlas, y Programa Conjunto de las Naciones Unidas sobre el VIH/SIDA (ONUSIDA). Se midió la discapacidad en términos del DALYs (incapacidad ajustada por años de vida) y YLDs (años vividos con discapacidad) y se compararon entre ambos países. El mapeo se realizó en ArcGIS, usando datos oficiales de migración de ciudadanos venezolanos. Nuestros resultados indican que los perfiles de TB de Colombia y Venezuela son idénticos, en lo que se refiere a la carga de la enfermedad, excepto por el incremento en la incidencia de TB en los departamentos fronterizos de la frontera entre Colombia y Venezuela en años recientes, concomitantemente con la inmigración masiva venezolana desde 2005. Identificamos una cuadruplicación de la subfinanciación para el programa de TB en Venezuela, que podría explicar las bajas tasas de test para los casos multirresistentes a medicamentos contra la TB (67%) y VIH/SIDA (60%), al igual que las estancias prolongadas en el hospital (150 días). Hallamos un incremento significativo en DALYs de pacientes con VIH/SIDA en Venezuela, específicamente, 362,35 comparados con los 265,37 observados en Colombia durante 2017. Este estudio sugiere que la migración venezolana masiva y la subfinanciación del programa podrían haber exacerbado la doble carga de la TB y el VIH en Colombia, especialmente a través de la frontera entre Colombia y Venezuela.


Resumo: Historicamente, as migrações humanas determinaram a propagação de muitas doenças infecciosas ao facilitar surtos temporais entre populações. O estudo buscou analisar os indicadores sanitários e os gastos e taxas de incapacidade relacionados à tuberculose (TB) e à carga de HIV/aids no fluxo migratório entre Colômbia e Venezuela, com destaque para os departamentos (estados) da fronteira nordeste. Foi realizado um estudo retrospectivo de dados sobre TB e HIV/aids desde 2009. Consolidamos uma base de dados a partir de relatórios do Sistema de Vigilância da Colômbia, Organização Mundial da Saúde, Indexmundi, Observatório de Saúde Global, IHME HIV Atlas e Programa Conjunto das Nações Unidas sobre HIV/AIDS (UNAIDS). As métricas de incapacidade em termos de AVAIs (anos de vida ajustados para incapacidade) e AVIs (anos vividos com incapacidade) foram comparadas entre os dois países. O mapeamento foi realizado no ArcGIS, com dados oficiais sobre migração de cidadãos venezuelanos. Nossos resultados indicam que os perfis de TB da Colômbia e da Venezuela são idênticos em termos de carga de doença, exceto por um aumento da incidência de TB nos departamentos na fronteira entre os dois países em anos recentes, concomitantemente com a imigração venezuelana maciça desde 2005. Identificamos um subfinanciamento (por um fator de quatro) no programa de tuberculose da Venezuela, o que pode explicar as baixas taxas de testagem para casos de TB multirresistente (67%) e HIV/aids (60%), além das internações hospitalares prolongadas (150 dias). Encontramos um aumento significativo de AVAIs em pacientes de HIV/aids na Venezuela, especificamente 362,35 comparado com 265,37 na Colômbia em 2017. O estudo sugere que a migração maciça venezuelana e o subfinanciamento podem exacerbar a carga dupla de TB e HIV na Colômbia, principalmente na fronteira com a Venezuela.


Assuntos
Humanos , Tuberculose/epidemiologia , Infecções por HIV/epidemiologia , Venezuela/epidemiologia , Brasil , Estudos Retrospectivos , Colômbia/epidemiologia , Emigração e Imigração
9.
Mech Ageing Dev ; 192: 111360, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32976914

RESUMO

Recently, mutations in the RNA polymerase III subunit A (POLR3A) have been described as the cause of the neonatal progeria or Wiedemann-Rautenstrauch syndrome (WRS). POLR3A has important roles in transcription regulation of small RNAs, including tRNA, 5S rRNA, and 7SK rRNA. We aim to describe the cellular and molecular features of WRS fibroblasts. Cultures of primary fibroblasts from one WRS patient [monoallelic POLR3A variant c.3772_3773delCT (p.Leu1258Glyfs*12)] and one control patient were cultured in vitro. The mutation caused a decrease in the expression of wildtype POLR3A mRNA and POLR3A protein and a sharp increase in mutant protein expression. In addition, there was an increase in the nuclear localization of the mutant protein. These changes were associated with an increase in the number and area of nucleoli and to a high increase in the expression of pP53 and pH2AX. All these changes were associated with premature senescence. The present observations add to our understanding of the differences between Hutchinson-Gilford progeria syndrome and WRS and opens new alternatives to study cell senesce and human aging.


Assuntos
Retardo do Crescimento Fetal , Fibroblastos , Progéria , RNA Polimerase III , Proteína Supressora de Tumor p53/metabolismo , Nucléolo Celular/fisiologia , Células Cultivadas , Senescência Celular/fisiologia , Dano ao DNA , Retardo do Crescimento Fetal/genética , Retardo do Crescimento Fetal/patologia , Fibroblastos/fisiologia , Fibroblastos/ultraestrutura , Expressão Gênica , Humanos , Mutação , Progéria/genética , Progéria/patologia , RNA Polimerase III/genética , RNA Polimerase III/metabolismo , RNA Ribossômico 5S/metabolismo
10.
Elife ; 82019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30694177

RESUMO

Dendritic arbors are crucial for nervous system assembly, but the intracellular mechanisms that govern their assembly remain incompletely understood. Here, we show that the dendrites of PVD neurons in Caenorhabditis elegans are patterned by distinct pathways downstream of the DMA-1 leucine-rich transmembrane (LRR-TM) receptor. DMA-1/LRR-TM interacts through a PDZ ligand motif with the guanine nucleotide exchange factor TIAM-1/GEF in a complex with act-4/Actin to pattern higher order 4° dendrite branches by localizing F-actin to the distal ends of developing dendrites. Surprisingly, TIAM-1/GEF appears to function independently of Rac1 guanine nucleotide exchange factor activity. A partially redundant pathway, dependent on HPO-30/Claudin, regulates formation of 2° and 3° branches, possibly by regulating membrane localization and trafficking of DMA-1/LRR-TM. Collectively, our experiments suggest that HPO-30/Claudin localizes the DMA-1/LRR-TM receptor on PVD dendrites, which in turn can control dendrite patterning by directly modulating F-actin dynamics through TIAM-1/GEF.


Assuntos
Actinas/genética , Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/genética , Proteínas de Membrana/genética , Plasticidade Neuronal/genética , Proteína 1 Indutora de Invasão e Metástase de Linfoma de Células T/genética , Actinas/metabolismo , Animais , Caenorhabditis elegans/citologia , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Claudinas/genética , Claudinas/metabolismo , Regulação da Expressão Gênica , Proteínas de Membrana/metabolismo , Sistema Nervoso/citologia , Sistema Nervoso/crescimento & desenvolvimento , Sistema Nervoso/metabolismo , Neurogênese/genética , Neurônios/citologia , Neurônios/metabolismo , Domínios PDZ , Ligação Proteica , Transporte Proteico , Transmissão Sináptica , Proteína 1 Indutora de Invasão e Metástase de Linfoma de Células T/metabolismo , Proteínas rac1 de Ligação ao GTP/genética , Proteínas rac1 de Ligação ao GTP/metabolismo
11.
Dev Cell ; 48(2): 229-244.e4, 2019 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-30661986

RESUMO

The mechanisms that pattern and maintain dendritic arbors are key to understanding the principles that govern nervous system assembly. The activity of presynaptic axons has long been known to shape dendrites, but activity-independent functions of axons in this process have remained elusive. Here, we show that in Caenorhabditis elegans, the axons of the ALA neuron control guidance and extension of the 1° dendrites of PVD somatosensory neurons independently of ALA activity. PVD 1° dendrites mimic ALA axon guidance defects in loss-of-function mutants for the extracellular matrix molecule MIG-6/Papilin or the UNC-6/Netrin pathway, suggesting that axon-dendrite adhesion is important for dendrite formation. We found that the SAX-7/L1CAM cell adhesion molecule engages in distinct molecular mechanisms to mediate extensions of PVD 1° dendrites and maintain the ALA-PVD axon-dendritic fascicle, respectively. Thus, axons can serve as critical scaffolds to pattern and maintain dendrites through contact-dependent but activity-independent mechanisms.


Assuntos
Axônios/metabolismo , Moléculas de Adesão Celular/metabolismo , Dendritos/metabolismo , Plasticidade Neuronal/fisiologia , Animais , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo
12.
Bogotá; Hospital Universitario Centro Dermatológico Federico Lleras Acosta, E.S.E; Primera edición en español; 2019. 209 p. ilus, tab, graf, mapas.
Monografia em Espanhol | COLNAL, LILACS | ID: biblio-1146683

RESUMO

El libro resalta que la lepra continúa siendo una enfermedad presente en Colombia y que aún constituye un problema de salud pública importante por los costos sociales, económicos y de sufrimiento humano que conlleva. Sabiendo que la literatura sobre el tema es escasa en nuestro medio, este libro surge como una herramienta de consulta creada para médicos y otros profesionales de salud, con la certeza de que es preciso mejorar la oportunidad del diagnóstico. Siendo fundamental que, durante su proceso formativo, todos los profesionales de la salud adquieran conocimientos sobre dicha enfermedad, que cada día se hace más visible por sus secuelas y diagnóstico tardío.


The book highlights the fact that leprosy continues to be a disease present in Colombia and that it is still a major public health problem due to the social, economic and human suffering costs it entails. Knowing that the literature on the subject is scarce in our country, this book is intended as a reference tool for doctors and other health professionals, in the knowledge that it is necessary to improve the timeliness of diagnosis. It is essential that, during their training process, all health professionals acquire knowledge about this disease, which is becoming more and more visible every day due to its sequelae and late diagnosis.


Assuntos
Humanos , Animais , Masculino , Feminino , Criança , Colômbia , Hanseníase , Epidemiologia , Hanseníase/classificação , Hanseníase/genética , Hanseníase/história , Hanseníase/patologia , Hanseníase/epidemiologia , Mycobacterium leprae
13.
PLoS One ; 13(10): e0205015, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30273391

RESUMO

Channelopsins and photo-regulated ion channels make it possible to use light to control electrical activity of cells. This powerful approach has lead to a veritable explosion of applications, though it is limited to changing membrane voltage of the target cells. An enormous potential could be tapped if similar opto-genetic techniques could be extended to the control of chemical signaling pathways. Photopigments from invertebrate photoreceptors are an obvious choice-as they do not bleach upon illumination -however, their functional expression has been problematic. We exploited an unusual opsin, pScop2, recently identified in ciliary photoreceptors of scallop. Phylogenetically, it is closer to vertebrate opsins, and offers the advantage of being a bi-stable photopigment. We inserted its coding sequence and a fluorescent protein reporter into plasmid vectors and demonstrated heterologous expression in various mammalian cell lines. HEK 293 cells were selected as a heterologous system for functional analysis, because wild type cells displayed the largest currents in response to the G-protein activator, GTP-γ-S. A line of HEK cells stably transfected with pScop2 was generated; after reconstitution of the photopigment with retinal, light responses were obtained in some cells, albeit of modest amplitude. In native photoreceptors pScop2 couples to Go; HEK cells express poorly this G-protein, but have a prominent Gq/PLC pathway linked to internal Ca mobilization. To enhance pScop2 competence to tap into this pathway, we swapped its third intracellular loop-important to confer specificity of interaction between 7TMDRs and G-proteins-with that of a Gq-linked opsin which we cloned from microvillar photoreceptors present in the same retina. The chimeric construct was evaluated by a Ca fluorescence assay, and was shown to mediate a robust mobilization of internal calcium in response to illumination. The results project pScop2 as a potentially powerful optogenetic tool to control signaling pathways.


Assuntos
Luz , Opsinas/metabolismo , Transdução de Sinais/efeitos da radiação , Sequência de Aminoácidos , Animais , Cálcio/metabolismo , Carbacol/farmacologia , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/química , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Células HEK293 , Humanos , Potenciais da Membrana , Opsinas/classificação , Opsinas/genética , Técnicas de Patch-Clamp , Pectinidae/metabolismo , Filogenia , Domínios Proteicos , Retina/metabolismo , Retina/patologia , Alinhamento de Sequência , Transdução de Sinais/efeitos dos fármacos , Fosfolipases Tipo C/metabolismo
14.
Entramado ; 14(1): 232-240, ene.-jun. 2018. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1090173

RESUMO

RESUMEN El uso de pesticidas es una práctica común en la industria agrícola para erradicar plagas. El objetivo de esta revisión fue documentar el efec to de los pesticidas en la relación ecológica de las abejas con el medio ambiente y los sistemas de producción agropecuaria. Se revisaron las publicaciones científicas y académicas en Science-Direct, Scielo, JSTOR, Springerlink y Google académico. Se encontró que las abejas proveen de servicios ecosistémicos poco valorados a nivel productivo y económico y, de acuerdo con estimaciones globales sus pobla ciones se encuentran en declive. Las abejas exhiben hipersensibilidad a la mayoría de diferentes pesticidas (especialmente insecticidas). Además, padecen diferentes alteraciones fisiológicas a nivel del sistema nervioso, respecto a su ciclo reproductivo e inmunosupresión. En conclusión, existe evidencia respecto a los efectos tóxicos de los pesticidas que alteran colateralmente las cosechas, específicamente en el proceso de polinización mediada por abejas.


ABSTRACT The use of pesticides is a common practice used in agricultural production to eradicate bugs. The review's aim was to document the pesticide effect regarding bee ecologic relationship with environment and agricultural production systems. Scientific and academic reports were retrieved from Science-Direct, Scielo, JSTOR, Springerlink and Google scholar Findings reveal that bees provide ecosystem services which are not well evaluated and according to global estimations bee's populations are endangered. Bees present hypersusceptibility to several pesticides (insecticides). Although, bees suffer physiologic alterations including neuronal system, impairment in the reproductive cycle and immunosuppression. In conclusion, there is evidence about toxic effects of pesticides which collaterally impact crop productivity through bee-mediated pollination.


RESUMO O uso de pesticidas é uma prática comum na indústria agrícola para erradicar as pragas. O objetivo desta revisão foi documentar o efeito de pesticidas na relação ecológica das abelhas com o meio ambiente e sistemas de produção agrícola. As publicações científicas e acadêmicas em acadêmicos da Science-Direct, Scielo, JSTOR, Springerlink e Google foram revisadas. Descobriu-se que as abelhas fornecem serviços ecossistêmicos que são pouco valorizados em um nível produtivo e econômico e, de acordo com estimativas globais, suas populações estão em declínio. As abelhas exibem hipersensibilidade aos mais diferentes pesticidas (especialmente inseticidas). Além disso, sofrem diferentes alterações fisiológicas ao nível do sistema nervoso, no que diz respeito ao ciclo reprodutivo e à imunossupressão. Em conclusão, há evidências sobre os efeitos tóxicos de pesticidas que colateralmente alteram as culturas, especificamente no processo de polinização mediada por abelhas.

15.
Arch. med ; 17(2): http://revistasum.umanizales.edu.co/ojs/index.php/archivosmedicina/article/view/1979, 20171206.
Artigo em Espanhol | LILACS | ID: biblio-882273

RESUMO

Objetivo: evaluar la calidad de agua en pequeñas y medianas unidades de producción ganaderas de la región de Sumapaz (Cundinamarca, Colombia). Materiales y métodos: el muestreo se realizó colectando 50 mL de agua en bolsas estériles, para la determinación de contaminación microbiológica incluyendo presencia de aerobios mesófilos, coliformes totales, Escherichia coli y Pseudomonas sp. de acuerdo con los parámetros permisibles de potabilidad definidos en el decreto 1575 de 2007 del Ministerio de la Protección Social de la República de Colombia. Resultados: se evidenció contaminación microbiana en 16 (66,7%) de los 24 predios evaluados de acuerdo con la normatividad descrita. También, se detectó la presencia de aerobios mesófilos, coliformes totales, Escherichia coli y Pseudomonas sp. en al menos el 25% de los predios evaluados. Conclusiones: los hallazgos sugieren que el agua podría representar una fuente de contaminación microbiológica directa para la salud humana, producción pecuaria y a la vez afectar la cadena de comercialización de productos lácteos y cárnicos en la provincia del Sumapaz..(AU)


Objective: to assess water quality in small and medium livestock farms from the Sumapaz region. Materials and methods: 50 mL of water were collected in sterile bags, for determination of microbial contamination, presence of mesophilic aerobes, total coliforms, Escherichia coli and Pseudomonas sp. According to law 1575/2007 from The Ministry of Health. Results: microbial contamination was determined in 16 (66,7%) out of 24 farms. Altogether with presence of mesophilic aerobes, total coliforms, Escherichia coli and Salmonella sp in at least 25% of the evaluated farms. Conclusions:findings suggest that water could represent a source of microbial contamination for human health, livestock production and market chain of dairy and meat products in the Sumapaz province..(AU)


Assuntos
Bovinos , Qualidade da Água
16.
Medisur ; 15(4): 545-549, jul.-ago. 2017.
Artigo em Espanhol | LILACS | ID: biblio-894749

RESUMO

La cistitis glandular es una lesión proliferativa infrecuente, está compuesta de estructuras glandulares, columnares y células intestinales secretoras de mucina; se localizada dentro de la mucosa y submucosa de la vejiga. Se ha encontrado en pacientes de todas las edades, incluyendo niños. Para dar a conocer las características clínicas y anatomopatologicas de una enfermedad poco frecuente y por el interés que puede tener para residentes en formación se decidió presentar el caso de un paciente masculino, de color de piel negra, 21 años de edad con historia de disuria, aumento de la frecuencia miccional diurna, nocturna y urgencia, así como episodios repetidos de hematuria macroscópica, al que se le realizó el diagnóstico clínico de cistitis glandular confirmado por biopsia.


Glandular Cistitis is an infrequent proliferative lesion, it is composed of glandular structures , columnar and mucin-secreting intestinal cells.. It is located inside the bladder mucosa and submucosa. It has been found in patients of all ages, including children. To present the clinical and anatomopathological characteristics of a rare disease and the interest that it may have for in training residents, it was decided to present the case of a 21 year old black male patient, with a history of dysuria, Increased urinary frequency in the day, night and urgency, as well as repeated episodes of macroscopic hematuria, with clinical diagnosis of glandular cystitis confirmed by biopsy.

17.
PLoS Genet ; 10(9): e1004657, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25232734

RESUMO

Animals sample their environment through sensory neurons with often elaborately branched endings named dendritic arbors. In a genetic screen for genes involved in the development of the highly arborized somatosensory PVD neuron in C. elegans, we have identified mutations in kpc-1, which encodes the homolog of the proprotein convertase furin. We show that kpc-1/furin is necessary to promote the formation of higher order dendritic branches in PVD and to ensure self-avoidance of sister branches, but is likely not required during maintenance of dendritic arbors. A reporter for kpc-1/furin is expressed in neurons (including PVD) and kpc-1/furin can function cell-autonomously in PVD neurons to control patterning of dendritic arbors. Moreover, we show that kpc-1/furin also regulates the development of other neurons in all major neuronal classes in C. elegans, including aspects of branching and extension of neurites as well as cell positioning. Our data suggest that these developmental functions require proteolytic activity of KPC-1/furin. Recently, the skin-derived MNR-1/menorin and the neural cell adhesion molecule SAX-7/L1CAM have been shown to act as a tripartite complex with the leucine rich transmembrane receptor DMA-1 on PVD mechanosensory to orchestrate the patterning of dendritic branches. Genetic analyses show that kpc-1/furin functions in a pathway with MNR-1/menorin, SAX-7/L1CAM and DMA-1 to control dendritic branch formation and extension of PVD neurons. We propose that KPC-1/furin acts in concert with the 'menorin' pathway to control branching and growth of somatosensory dendrites in PVD.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiologia , Dendritos/metabolismo , Furina/genética , Células Receptoras Sensoriais/metabolismo , Sequência de Aminoácidos , Animais , Proteínas de Caenorhabditis elegans/química , Proteínas de Caenorhabditis elegans/metabolismo , Furina/química , Furina/metabolismo , Dados de Sequência Molecular , Mutação , Fenótipo , Alinhamento de Sequência
18.
Cell ; 155(2): 308-20, 2013 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-24120132

RESUMO

Sensory dendrites depend on cues from their environment to pattern their growth and direct them toward their correct target tissues. Yet, little is known about dendrite-substrate interactions during dendrite morphogenesis. Here, we describe MNR-1/menorin, which is part of the conserved Fam151 family of proteins and is expressed in the skin to control the elaboration of "menorah"-like dendrites of mechanosensory neurons in Caenorhabditis elegans. We provide biochemical and genetic evidence that MNR-1 acts as a contact-dependent or short-range cue in concert with the neural cell adhesion molecule SAX-7/L1CAM in the skin and through the neuronal leucine-rich repeat transmembrane receptor DMA-1 on sensory dendrites. Our data describe an unknown pathway that provides spatial information from the skin substrate to pattern sensory dendrite development nonautonomously.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Dendritos/metabolismo , Proteínas de Membrana/metabolismo , Neurônios/metabolismo , Sequência de Aminoácidos , Animais , Proteínas de Caenorhabditis elegans/genética , Clonagem Molecular , Técnicas de Silenciamento de Genes , Proteínas de Membrana/genética , Dados de Sequência Molecular , Alinhamento de Sequência
19.
Infectio ; 15(3): 177-183, sep. 2011. ilus, tab
Artigo em Inglês | LILACS, COLNAL | ID: lil-635691

RESUMO

Introduction: PCR detection offers a good opportunity to obtain fast results which is a priority in tuberculosis control programs. Objectives: We assayed an in-house PCR method based on the detection of mycobaterial IS6110 gene in clinical samples of patients with pulmonary and extrapulmonary tuberculosis to demonstrate its usefulness and reliability in the setting of a middle-resource region with high tuberculosis prevalence. Materials and methods: Pulmonary (n=317) and extrapulmonary (n=41) samples were collected from 358 patients with clinical suspicion of tuberculosis. All samples were processed to detect acid-fast bacilli by microscopy, culture on solid media and PCR. To remove PCR inhibitors, three washing steps of the decontaminated pellet were included before mycobacterial cell lysis. Results: The overall sensitivity was 96% in clinical samples, and specificity was 100% for our in-house method in pulmonary and extrapulmonary samples. No inhibition was found among samples that were PCR negative, but culture positive for Mycobacterium tuberculosis. No false positives were found. Conclusions: In-house PCR in a middle-income setting region, with simple and strictly controlled methods, could efficiently complement conventional bacteriological tools for the rapid diagnosis of tuberculosis, especially in paucibacillary and extrapulmonary samples.


Introducción. La prueba de PCR ofrece la posibilidad de obtener resultados rápidos, una prioridad para los programas de control de la tuberculosis. Objetivos.Evaluar el método de PCR basado en la detección del gen IS6110 de las micobacterias en muestras clínicas de pacientes con tuberculosis pulmonar y extrapulmonar, para demostrar su utilidad y confiabilidad en un sitio de desarrollo medio con alta prevalencia de tuberculosis. Materiales y métodos. Se recolectaron 317 muestras pulmonares y 41 de origen extrapulmonar, de 358 pacientes con sospecha clínica de tuberculosis. Todas las muestras se procesaron para detectar bacilos ácido-alcohol resistentes por microscopía, cultivo en medio sólido y PCR. Para eliminar los inhibidores de la PCR se lavaron tres veces antes de realizar la lisis de la pared de la micobacteria. Resultados. La sensibilidad total fue de 96% y la especificidad de 100% para este método "casero" en muestras pulmonares y extrapulmonares. No se encontró inhibición entre las muestras que fueron negativas por PCR pero con cultivo positivo para Mycobacterium tuberculosis. No se hallaron falsos positivos. Conclusiones. La implementación de la PCR "casera" en regiones de desarrollo intermedio como método simple y estrictamente controlado, podría complementar eficientemente las herramientas bacteriológicas tradicionales para el diagnóstico rápido de la tuberculosis, especialmente en muestras paucibacilares y de origen extrapulmonar.


Assuntos
Humanos , Tuberculose , Tuberculose Pulmonar , Reação em Cadeia da Polimerase , Manejo de Espécimes , Laboratórios , Mycobacterium tuberculosis
20.
Rev. salud pública ; 12(6): 1000-1009, dic. 2010. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-602848

RESUMO

Objetivo Determinar la prevalencia de tuberculosis (TB) infantil y los factores socio-demográficos asociados a esta población en el municipio de Armenia (Colombia). Metodología Se realizó un estudio descriptivo-retrospectivo en el cual se incluyeron pacientes con diagnóstico de TB menores de 14 años que fueron notificados al programa de TB en el municipio de Armenia y que iniciaron esquema de Tratamiento Acortado Estrictamente Supervisado (TAES) entre el 2000-2009. Resultados Se notificaron un total de 58 casos de TB, el mayor número de casos ocurrió en el 2009 (12 casos) seguido del 2008 (8 casos) y 2006 (7 casos) respectivamente, representando una elevada tasa de prevalencia (16,6 casos/100 000 habitantes). Las formas pulmonares tuvieron mayor proporción con 74 por ciento, de las cuales 34 por ciento fueron positivas a la baciloscopia (BK). El nexo epidemiológico se configuró en el 21 por ciento de los enfermos. En cuanto al egreso del programa de control de la TB el 5 por ciento de los pacientes finalizó con criterio de curado, 17 por ciento terminado, 4 por ciento transferidos, 7 por ciento fallecidos y en el 67 por ciento de los casos se desconoció el resultado del tratamiento. Conclusión La TB representa en la actualidad una causa importante de morbilidad y mortalidad infantil. Dada la buena cobertura de vacunación con BCG y que la mayoría de casos son pulmonares en este municipio, la alta tasa de casos de TB infantil estaría indicando fallas en la oportunidad para interrumpir transmisión reciente a partir de casos bacilíferos.


Objective To determine the childhood tuberculosis prevalence and its socio-demographics factors associated to this population in Armenia (Colombia). Methodology A retrospective-descriptive study was carried out; TB patients under the age of 14 years were included and notified to the TB control program in Armenia, those who started a Directly Observed Treatment Supervised (DOTS) scheme among from 2000 to 2009 years. Results 58 TB cases were described, most cases have occurred in 2009 (12 cases) followed by the 2008 (8 cases) and 2006 (7 cases) respectively. Thus, Armenia has a high rate of prevalence (16.6 cases/100 000 inhabitants). Pulmonary forms had greater proportion with 74 percent, of which 34 percent were positive to sputum examination revealed Acid-fast bacilli (AFB). Epidemiological link allowed confirmation of 21 percent of cases. TB treatment cohort revealed that 5 percent of patients were cured, finished 17 percent, transferred 4 percent, dead 7 percent and in 67 percent of cases the results were not documented. Conclusion Nowadays TB still an important cause of childhood morbidity and mortality. The good BCG vaccine covertures and the high prevalence of pulmonary forms in childhood TB indicates that the most plausible explanation for this high prevalence is a failure in early detection of bacilli positive patients to cut recent transmission in this municipality.


Assuntos
Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Tuberculose/epidemiologia , Vacina BCG , Colômbia/epidemiologia , Prevalência , Estudos Retrospectivos , Fatores de Risco , Fatores Socioeconômicos , Tuberculose/diagnóstico , Tuberculose/prevenção & controle , Vacinação/estatística & dados numéricos
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