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1.
Nat Commun ; 12(1): 6187, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34702855

RESUMO

Attention-deficit hyperactivity disorder (ADHD) is a common childhood-onset psychiatric disorder characterized by inattention, impulsivity and hyperactivity. ADHD exhibits substantial heritability, with rare monogenic variants contributing to its pathogenesis. Here we demonstrate familial ADHD caused by a missense mutation in CDH2, which encodes the adhesion protein N-cadherin, known to play a significant role in synaptogenesis; the mutation affects maturation of the protein. In line with the human phenotype, CRISPR/Cas9-mutated knock-in mice harboring the human mutation in the mouse ortholog recapitulated core behavioral features of hyperactivity. Symptoms were modified by methylphenidate, the most commonly prescribed therapeutic for ADHD. The mutated mice exhibited impaired presynaptic vesicle clustering, attenuated evoked transmitter release and decreased spontaneous release. Specific downstream molecular pathways were affected in both the ventral midbrain and prefrontal cortex, with reduced tyrosine hydroxylase expression and dopamine levels. We thus delineate roles for CDH2-related pathways in the pathophysiology of ADHD.


Assuntos
Antígenos CD/genética , Antígenos CD/metabolismo , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Caderinas/genética , Caderinas/metabolismo , Animais , Antígenos CD/química , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Caderinas/química , Criança , Dopamina/metabolismo , Perfilação da Expressão Gênica , Homozigoto , Humanos , Locomoção/efeitos dos fármacos , Masculino , Metilfenidato/uso terapêutico , Camundongos , Mutação , Neurônios/metabolismo , Córtex Pré-Frontal/metabolismo , Conformação Proteica , Irmãos , Transmissão Sináptica/efeitos dos fármacos , Vesículas Sinápticas/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo
2.
Gig Sanit ; 94(7): 37-40, 2015.
Artigo em Russo | MEDLINE | ID: mdl-26856138

RESUMO

In the paper there are presented data of field observations of the spectrum of viruses, contained in the waste waters. The studies were performed on the territory of the city and the territory unfavorable for hepatitis A. In the territory of the big city by RT-PCR in the waste liquid the enterovirus RNA was detected in 45% of samples; astroviruses--90%; noroviruses--80% and 15% of rotaviruses. Samples from 2 wells were slightly positive for the presence of HCV RNA A. In the waste liquid on the territory, unfavorable for viral hepatitis A, in 100% of the samples there were determined noro- and astroviruses RNA and adenovirus DNA, in 75%--enterovirus RNA; 50%--HAV RNA and a 25%--rotavirus RNA.


Assuntos
Enteropatias , Vírus de RNA/isolamento & purificação , Viroses , Águas Residuárias , Abastecimento de Água/normas , Reservatórios de Doenças/virologia , Monitoramento Epidemiológico , Humanos , Enteropatias/epidemiologia , Enteropatias/etiologia , Enteropatias/prevenção & controle , Enteropatias/virologia , Federação Russa/epidemiologia , Viroses/epidemiologia , Viroses/etiologia , Viroses/prevenção & controle , Viroses/virologia , Vírus/classificação , Vírus/patogenicidade , Águas Residuárias/análise , Águas Residuárias/virologia , Qualidade da Água/normas
3.
Gig Sanit ; (5): 92-5, 2009.
Artigo em Russo | MEDLINE | ID: mdl-20000100

RESUMO

The paper outlines materials on how to improve a method for indication of water viral pollution in different water objects of the environment, by applying a MFM filtration module based on tangentially radial-mode water microfiltration and viral concentration on the positively charged membranes, by using the secondary stage of concentration. Experimental and full-scale studies have demonstrated that this method for virus isolation has a high effectiveness and is based on the employment of the materials made in Russia. This determines its rapid introduction into the system for the sanitary-virological monitoring of practical laboratories of various departments, which will favor the higher efficiency of epidemiological surveillance as an integral part of nonspecific prophylactic measures of virus infections of water etiology.


Assuntos
Saneamento/instrumentação , Viroses/prevenção & controle , Vírus/isolamento & purificação , Microbiologia da Água/normas , Poluentes da Água/análise , Purificação da Água/instrumentação , Água/análise , Monitoramento Ambiental/métodos , Desenho de Equipamento , Humanos , Reprodutibilidade dos Testes , Viroses/virologia
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