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1.
Cell Rep ; 41(2): 111483, 2022 10 11.
Article in English | MEDLINE | ID: mdl-36223737

ABSTRACT

The critical role of AMPA receptor (AMPAR) trafficking in long-term potentiation (LTP) of excitatory synaptic transmission is now well established, but the underlying molecular mechanism is still uncertain. Recent research suggests that PSD-95 captures AMPARs via an interaction with the AMPAR auxiliary subunits-transmembrane AMPAR regulatory proteins (TARPs). To determine if such interaction is a core minimal component of the AMPAR trafficking and LTP mechanism, we engineered artificial binding partners, which individually were biochemically and functionally dead but which, when expressed together, rescue binding and both basal synaptic transmission and LTP. These findings establish the TARP/PSD-95 complex as an essential interaction underlying AMPAR trafficking and LTP.


Subject(s)
Long-Term Potentiation , Receptors, AMPA , Disks Large Homolog 4 Protein/metabolism , Long-Term Potentiation/physiology , Nuclear Proteins/metabolism , Receptors, AMPA/metabolism , Synapses/metabolism , Synaptic Transmission/physiology
2.
eNeuro ; 7(6)2020.
Article in English | MEDLINE | ID: mdl-33004417

ABSTRACT

Larval zebrafish possess a number of molecular and genetic advantages for rigorous biological analyses of learning and memory. These advantages have motivated the search for novel forms of memory in these animals that can be exploited for understanding the cellular and molecular bases of vertebrate memory formation and consolidation. Here, we report a new form of behavioral sensitization in zebrafish larvae that is elicited by an aversive chemical stimulus [allyl isothiocyanate (AITC)] and that persists for ≥30 min. This form of sensitization is expressed as enhanced locomotion and thigmotaxis, as well as elevated heart rate. To characterize the neural basis of this nonassociative memory, we used transgenic zebrafish expressing the fluorescent calcium indicator GCaMP6 (Chen et al., 2013); because of the transparency of larval zebrafish, we could optically monitor neural activity in the brain of intact transgenic zebrafish before and after the induction of sensitization. We found a distinct brain area, previously linked to locomotion, that exhibited persistently enhanced neural activity following washout of AITC; this enhanced neural activity correlated with the behavioral sensitization. These results establish a novel form of memory in larval zebrafish and begin to unravel the neural basis of this memory.


Subject(s)
Memory , Zebrafish , Animals , Animals, Genetically Modified , Larva , Locomotion
3.
Ces med. vet. zootec ; 13(3): 308-328, sep.-dic. 2018. tab, graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1055704

ABSTRACT

Resumen El sarcoide equino es la neoplasia más común de los équidos y representa más de la mitad de las neoplasias de la piel de los caballos. El objetivo del presente trabajo fue realizar una compilación del conocimiento actual sobre etiología, fisiopatología, diagnóstico y tratamiento de esta patología. El agente etiológico del sarcoide equino es el virus del papiloma bovino tipo 1 y 2 que afecta a équidos de todas las razas, sexos y edades. El traumacutáneo, la presencia de vectores como insectos y algunos haplotipos genéticos son potenciales factores de riego. Se diagnostica a partir de la apariencia clínica, clasificándose en 6 tipos diferentes. La confirmación del diagnóstico se realiza mediante histopatología y las alternativas terapéuticas disponibles son muy variadas incluyendo cirugía, quimioterapia, radioterapia, inmunoterapia y otras. En conclusión, ésta es una patología de curso impredecible, no existiendo tratamiento efectivo por sí solo, ya que existe una alta probabilidad de recurrencia y solo el empleo de nuevas modalidades terapéuticas combinadas permite obtener mejores resultados. La prevención probablemente se verá facilitada en el futuro por el desarrollo de vacunas contra el virus del papiloma bovino.


Abstract The equine sarcoid is the most common neoplasm of equidae and represents more than half of the skin neoplasms of horses. The objective of the present work was to make a compilation of current knowledge about etiology, pathophysiology, diagnosis and treatment of this pathology. The etiological agent of the equine sarcoid is the bovine papilloma virus type 1 and 2 which affects equines of all races, sexes and ages. Cutaneous trauma, the presence of vectors such as insects and some genetic haplotypes are potential risk factors. It is diagnosed from the clinical appearance, classified into 6 different types. The confirmation of the diagnosis is made by histopathology and the therapeutic alternatives available are very varied, including surgery, chemotherapy, radiotherapy, immunotherapy and others. In conclusion, this is a pathology of unpredictable course, there is no effective treatment by itself, since there is a high probability of recurrence and only the use of new combined therapeutic modalities allows to obtain better results. Prevention will likely be facilitated in the future by the development of vaccines against the bovine papilloma virus.


Resumo O sarcoide eqüino é a neoplasia mais comum dos equídeos e representa mais da metade das neoplasias de pele dos equinos. O objetivo do presente trabalho foi fazer uma compilação dos conhecimentos atuais sobre etiologia, fisiopatologia, diagnóstico e tratamento desta patologia. O agente etiológico do sarcoide eqüino é o papilomavírus bovino tipo 1 e 2, que afeta equinos de todas as raças, sexos e idades. Trauma cutâneo, a presença de vetores como insetos e alguns haplótipos genéticos são fatores de risco potenciais. É diagnosticado a partir da aparência clínica, classificada em 6 tipos diferentes. A confirmação do diagnóstico é feita pela histopatologia e as alternativas terapêuticas disponíveis são muito variadas, incluindo cirurgia, quimioterapia, radioterapia, imunoterapia e outras. Em conclusão, esta é uma patologia de curso imprevisível, não há tratamento efetivo por si só, uma vez que há uma alta probabilidade de recorrência e apenas o uso de novas modalidades terapêuticas combinadas permite obter melhores resultados. A prevenção provavelmente será facilitada no futuro pelo desenvolvimento de vacinas contra o vírus do papiloma bovino.

4.
Pregnancy Hypertens ; 13: 161-165, 2018 Jul.
Article in English | MEDLINE | ID: mdl-30177046

ABSTRACT

OBJECTIVES: Several criteria have been proposed to categorize the risk of preeclampsia, with notable differences between these criteria. We compared the discriminatory accuracy of criteria for categorizing preeclampsia risk established by four institutions, namely, the World Health Organization (WHO), National Institute for Health and Care Excellence (NICE), American College of Obstetricians and Gynecologists (ACOG), and National Center for Technological Excellence in Health (CENETEC), and estimated the concordance between these criteria. STUDY DESIGN: We performed a secondary data analysis of 590 Mexican obstetric patients who received prenatal care in primary care between 2016 and 2017; 160 had a diagnosis of preeclampsia. MAIN OUTCOME MEASURES: We estimated the true (TP) and false positive (FP) fractions, positive (PPV) and negative predictive values (NPV), positive (LR+) and negative (LR-) likelihood ratios, diagnostic odds ratio (DOR), area under the receiver operating characteristic curve (AUROC), and Kappa coefficient with corresponding 95% confidence intervals (CIs). RESULTS: Only the WHO criteria, followed by the NICE criteria, had the greatest number of accuracy indicators with ideal or acceptable results: TP 83.6%, PPV 60.5%, NPV 90.3%, DOR 14.3, and AUROC 0.79 and TP 84.5%, PPV 51.0%, NPV 90.3%, DOR 9.7, and AUROC 0.74, respectively. The Kappa coefficient between WHO and NICE criteria was 0.78 (95% CI 0.71-0.85). CONCLUSIONS: The discriminatory accuracies of the WHO and NICE criteria were superior to those of the ACOG and CENETEC criteria for classifying preeclampsia risk. Their concordance was good; thus, both criteria seem appropriate for screening preeclampsia in primary care.


Subject(s)
Decision Support Techniques , Pre-Eclampsia/diagnosis , Pre-Eclampsia/etiology , Adult , Female , Humans , Mexico , Predictive Value of Tests , Pregnancy , Pregnancy Outcome , Primary Health Care , Prognosis , Risk Assessment , Risk Factors , Young Adult
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