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1.
J Neurochem ; 166(5): 790-808, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37534523

RESUMO

Development of the mammalian neocortex requires proper inside-out migration of developing cortical neurons from the germinal ventricular zone toward the cortical plate. The mechanics of this migration requires precise coordination of different cellular phenomena including cytoskeleton dynamics, membrane trafficking, and cell adhesion. The small GTPases play a central role in all these events. The small GTPase Rab21 regulates migration and neurite growth in developing neurons. Moreover, regulators and effectors of Rab21 have been implicated in brain pathologies with cortical malformations, suggesting a key function for the Rab21 signaling pathway in cortical development. Mechanistically, it has been posited that Rab21 influences cell migration by controlling the trafficking of endocytic vesicles containing adhesion molecules. However, direct evidence of the participation of Rab21 or its mechanism of action in the regulation of cortical migration is still incomplete. In this study, we demonstrate that Rab21 plays a critical role in the differentiation and migration of pyramidal neurons by regulating the levels of the amyloid precursor protein on the neuronal cell surface. Rab21 loss of function increased the levels of membrane-exposed APP, resulting in impaired cortical neuronal differentiation and migration. These findings further our understanding of the processes governing the development of the cerebral cortex and shed light onto the molecular mechanisms behind cortical development disorders derived from the malfunctioning of Rab21 signaling effectors.


Assuntos
GTP Fosfo-Hidrolases , Neocórtex , Animais , GTP Fosfo-Hidrolases/metabolismo , Córtex Cerebral/metabolismo , Neurônios/metabolismo , Neocórtex/metabolismo , Movimento Celular/fisiologia , Precursor de Proteína beta-Amiloide/metabolismo , Mamíferos/metabolismo
2.
Sensors (Basel) ; 22(21)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36365981

RESUMO

An experimental procedure for characterizing the size-of-source effect (SSE) is proposed. Such an effect is the cause of one of the main influence variables generating uncertainty in the measurement, both in calibration and use, of direct reading radiation thermometers (RT). The procedure and uncertainty calculation described in the paper are aligned in terms of metrological traceability, with the requirements generally imposed to ensure the accuracy of measurements in industry and science. Results of application and validation of this particular procedure with equipment, including black body (BB) sources normally used in radiation thermometry calibration laboratories in the industrial field, are shown.


Assuntos
Termômetros , Termometria , Calibragem , Laboratórios , Incerteza , Termometria/métodos
4.
Cancer Med ; 13(5): e6923, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38491824

RESUMO

BACKGROUND AND STUDY AIMS: Our aim was to determine the impact of the SARS-CoV-2 pandemic on the diagnosis and prognosis of colorectal cancer (CRC). PATIENTS AND METHODS: This prospective cohort study included individuals diagnosed with CRC between March 13, 2019 and June 20, 2021 across 21 Spanish hospitals. Two time periods were compared: prepandemic (from March 13, 2019 to March 13, 2020) and pandemic (from March 14, 2020 to June 20, 2021, lockdown period and 1 year after lockdown). RESULTS: We observed a 46.9% decrease in the number of CRC diagnoses (95% confidence interval (CI): 45.1%-48.7%) during the lockdown and 29.7% decrease (95% CI: 28.1%-31.4%) in the year after the lockdown. The proportion of patients diagnosed at stage I significantly decreased during the pandemic (21.7% vs. 19.0%; p = 0.025). Centers that applied universal preprocedure SARS-CoV-2 PCR testing experienced a higher reduction in the number of colonoscopies performed during the pandemic post-lockdown (34.0% reduction; 95% CI: 33.6%-34.4% vs. 13.7; 95% CI: 13.4%-13.9%) and in the number of CRCs diagnosed (34.1% reduction; 95% CI: 31.4%-36.8% vs. 26.7%; 95% CI: 24.6%-28.8%). Curative treatment was received by 87.5% of patients diagnosed with rectal cancer prepandemic and 80.7% of patients during the pandemic post-lockdown period (p = 0.002). CONCLUSIONS: The COVID-19 pandemic has led to a decrease in the number of diagnosed CRC cases and in the proportion of stage I CRC. The reduction in the number of colonoscopies and CRC diagnoses was higher in centers that applied universal SARS-CoV-2 PCR screening before colonoscopy. In addition, the COVID-19 pandemic has affected curative treatment of rectal cancers.


Assuntos
COVID-19 , Neoplasias Colorretais , Neoplasias Retais , Humanos , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias , Estudos Prospectivos , Controle de Doenças Transmissíveis , Prognóstico , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Estudos Retrospectivos , Teste para COVID-19
5.
Cells ; 11(8)2022 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-35455998

RESUMO

Neurons are highly polarized cells requiring precise regulation of trafficking and targeting of membrane proteins to generate and maintain different and specialized compartments, such as axons and dendrites. Disruption of the Golgi apparatus (GA) secretory pathway in developing neurons alters axon/dendritic formation. Therefore, detailed knowledge of the mechanisms underlying vesicles exiting from the GA is crucial for understanding neuronal polarity. In this study, we analyzed the role of Brefeldin A-Ribosylated Substrate (CtBP1-S/BARS), a member of the C-terminal-binding protein family, in the regulation of neuronal morphological polarization and the exit of membrane proteins from the Trans Golgi Network. Here, we show that BARS is expressed during neuronal development in vitro and that RNAi suppression of BARS inhibits axonal and dendritic elongation in hippocampal neuronal cultures as well as largely perturbed neuronal migration and multipolar-to-bipolar transition during cortical development in situ. In addition, using plasma membrane (PM) proteins fused to GFP and engineered with reversible aggregation domains, we observed that expression of fission dominant-negative BARS delays the exit of dendritic and axonal membrane protein-containing carriers from the GA. Taken together, these data provide the first set of evidence suggesting a role for BARS in neuronal development by regulating post-Golgi membrane trafficking.


Assuntos
Complexo de Golgi , Neurônios , Axônios/metabolismo , Complexo de Golgi/metabolismo , Proteínas de Membrana/metabolismo , Neurônios/fisiologia , Rede trans-Golgi/metabolismo
6.
Cogn Behav Neurol ; 24(2): 93-8, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21677576

RESUMO

OBJECTIVE: To evaluate the relationship between the autonomic nervous system basal state and performance in decision-making tasks. BACKGROUND: The link between performance in decision-making tasks and acute changes in autonomic parameters during their execution has been extensively investigated. However, there is lacking evidence regarding the relationship between decision making and basal autonomic state. METHODS: Resting autonomic nervous system activity in 18 healthy individuals was assessed by means of heart rate variability (HRV) analysis before conducting 3 different decision-making tasks: an ambiguous one, the Iowa Gambling Task; a test that assesses risk-taking behavior, the Game of Dice Task; and a test that assesses reversal learning behavior, the Reversal Learning Task. The tasks were administered in a random manner. RESULTS: There was a direct correlation between the Iowa Gambling Task net score and the resting low frequency HRV (r = 0.73; P < 0.001), which is strongly influenced by sympathetic activity. No correlations were found between HRV and the Game of Dice Task net score or the Reversal Learning Task last error trial. CONCLUSIONS: The results are compatible with the idea that a higher basal activation of autonomic nervous system is beneficial for subsequent decision-making process.


Assuntos
Sistema Nervoso Autônomo/fisiologia , Tomada de Decisões/fisiologia , Assunção de Riscos , Adulto , Idoso , Emoções/fisiologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Reversão de Aprendizagem/fisiologia
8.
Aging Cell ; 19(1): e13050, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31625260

RESUMO

While NLRP3-inflammasome has been implicated in cardiovascular diseases, its role in physiological cardiac aging is largely unknown. During aging, many alterations occur in the organism, which are associated with progressive impairment of metabolic pathways related to insulin resistance, autophagy dysfunction, and inflammation. Here, we investigated the molecular mechanisms through which NLRP3 inhibition may attenuate cardiac aging. Ablation of NLRP3-inflammasome protected mice from age-related increased insulin sensitivity, reduced IGF-1 and leptin/adiponectin ratio levels, and reduced cardiac damage with protection of the prolongation of the age-dependent PR interval, which is associated with atrial fibrillation by cardiovascular aging and reduced telomere shortening. Furthermore, old NLRP3 KO mice showed an inhibition of the PI3K/AKT/mTOR pathway and autophagy improvement, compared with old wild mice and preserved Nampt-mediated NAD+ levels with increased SIRT1 protein expression. These findings suggest that suppression of NLRP3 prevented many age-associated changes in the heart, preserved cardiac function of aged mice and increased lifespan.


Assuntos
Sistema Cardiovascular/fisiopatologia , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Longevidade , Masculino , Camundongos , Transdução de Sinais
9.
Behav Brain Res ; 288: 11-9, 2015 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-25882724

RESUMO

Hemispheric specialization in affective responses has received little attention in the literature. This is a fundamental variable to understand circuit dynamics of networks subserving emotion. In this study we put to test a modified "valence" hypothesis of emotion processing, considering that sadness and happiness are processed by each hemisphere in relation to dominance for language and handedness. Mood induction and language activation during functional magnetic resonance imaging (fMRI) were used in 20 right-handed and 20 nonright-handed subjects, focusing on interconnected regions known to play critical roles in affective responses: subgenual cingulate cortex, amygdala, and anterior insular cortex. We observed a consistent relationship between lateralization of affective processing, motor dexterity, and language in individuals with clear right-handedness. Sadness induces a greater activation of right-hemisphere cortical structures in right-handed, left-dominant individuals, which is not evident in nonright-handed subjects who show no consistent hemispheric dominance for language. In anterior insula, right-handed individuals displayed reciprocal activation of either hemisphere depending upon mood valence, whereas amygdala activation was predominantly left-sided regardless of mood valence. Nonright-handed individuals exhibited less consistent brain lateralization of affective processing regardless of language and motor dexterity lateralization. In contrast with traditional views on emotion processing lateralization, hemispheric specialization in affective responses is not a unitary process but is specific to the brain structure being activated.


Assuntos
Encéfalo/fisiologia , Emoções/fisiologia , Lateralidade Funcional/fisiologia , Idioma , Destreza Motora/fisiologia , Adulto , Mapeamento Encefálico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Estimulação Luminosa , Percepção Visual/fisiologia
11.
Psychiatry Res ; 221(1): 30-6, 2014 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-24262801

RESUMO

Personality disorders are common in nonpsychotic siblings of patients with schizophrenia, and some personality traits in this group may be associated with an increased risk for full-blown psychosis. We sought to establish if faulty right-hemisphere activation induced by social cognitive tasks, as previously described in patients with schizophrenia, is associated with specific personality symptoms in their unaffected siblings. We observed that cluster B personality symptoms in this group were inversely related to activation in the right temporo parietal junction (rTPJ, a structure critical in social cognitive processing) in response to a basic emotion processing task and also to social competence, whereas in contrast to our initial hypothesis, cluster A traits were not associated with right hemisphere activation during emotion processing or with social competence. These findings suggest the existence of clinical traits in at-risk individuals which share a common neurobiological substrate with schizophrenia, in regards to social performance.


Assuntos
Encéfalo/fisiopatologia , Emoções/fisiologia , Esquizofrenia/fisiopatologia , Comportamento Social , Personalidade Tipo B , Adulto , Estudos de Casos e Controles , Predisposição Genética para Doença , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Transtornos da Personalidade/complicações , Inventário de Personalidade , Estimulação Luminosa , Transtornos Psicóticos/complicações , Esquizofrenia/complicações , Esquizofrenia/genética , Psicologia do Esquizofrênico , Irmãos
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