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1.
Healthcare (Basel) ; 12(2)2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38255015

RESUMO

The relationship between attentional resources and functionality in individuals with intellectual disabilities (IDs) is clinically relevant. This study aimed to examine the possible relationship between the degree of ID and attentional resources, and to evaluate whether attentional resources predict the performance of basic and instrumental activities of daily living (ADL) in individuals with mild and moderate ID. This study, which employed a descriptive, cross-sectional, observational design, was conducted between July 2019 and May 2020. The sample consisted of 166 individuals divided into three groups: moderate ID, mild ID, and those without ID. These groups were compared for attentional functions (p < 0.001), obtaining an effect size ranging from medium to large. The results indicated that 40% of the variance in basic ADL performance was explained by the age of the participants, degree of disability, and sustained attention in individuals with ID. Additionally, 64% of the variance in instrumental ADL performance was explained by sustained, divided, and executive attention. Therefore, attentional resources appear to be associated with the performance of basic and instrumental ADL in individuals with mild and moderate ID.

2.
Children (Basel) ; 10(10)2023 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-37892351

RESUMO

School anxiety depends on multiple factors that occur directly or indirectly in the teaching-learning process, such as going to the blackboard in class or reporting low grades at home. Other factors that influence school climate are social skills and coping strategies. That said, the aim of this research was to analyze the sources of school anxiety, coping strategies, and social skills in Italian secondary school students through an artificial neural network. For this purpose, a quantitative and ex post facto design was used in which the Inventory of School Anxiety (IAES), the Coping Scale for Children (EAN), and the Questionnaire for the Evaluation of Social Skills student version (EHS-A) were administered. The results showed that cognitive avoidance and behavioral avoidance coping strategies, together with the lack of social skills in students, are the variables that contributed the most to school anxiety scores in the artificial neural network. The conclusions revolve around the need to develop primary prevention programs.

3.
Healthcare (Basel) ; 11(17)2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37685408

RESUMO

Institutionalized individuals with intellectual disabilities have few opportunities to participate in instrumental activities of daily living (IADLs), which probably affects higher cognitive functions, or vice versa. The objectives of this study were to evaluate the possible difference in the ability to perform IADLs and executive functioning between individuals with and without intellectual disabilities and to determine if executive functions are associated with the performance of IADLs in people with intellectual disabilities. This was a multi-center cross-sectional study, conducted between July 2019 and May 2020. Participants with intellectual disabilities were recruited from four centers for people with intellectual disabilities. Adults without these disabilities were gathered from several community centers. The sample consisted of 90 individuals with moderate intellectual disabilities and 79 individuals with no intellectual disability. Executive functions were evaluated using the Wechsler Adult Intelligence Scale-WAIS-IV, the INECO Frontal Screening test, the Semantic Verbal Fluency Test, and the Behavioural Assessment of the Dysexecutive Syndrome-BADS-Scale. The performance of the IADLs was assessed by the Lawton and Brody Scale. The results showed that the higher the function in instrumental activities, the lower the impairment of executive functions. Executive functions accounted for 81% of the total variance in the ability to perform the IADLs. In conclusion, individuals with moderate intellectual disabilities demonstrated limitations in executing the IADLs, which were partially associated with low performance in executive functions. This information could help in the development of evidence-based intervention programs and facilitate the formulation of appropriate support strategies to enhance participation in these activities.

4.
Healthcare (Basel) ; 11(18)2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37761677

RESUMO

Adaptive sports could produce multiple health benefits in people with physical disabilities. The aim is to evaluate if adaptive sports practice has an influence on physical and mental quality of life. A meta-analysis was performed using electronic databases and other sources. A within- and between-group analysis for physical and mental quality of life was conducted. Standardized mean difference (SMD) was used as a measure of the mean size effect. The statistical heterogeneity, the risk of bias, and the quality of evidence were evaluated. Eight studies met the inclusion criteria and four of them were included in the meta-analysis. In mental quality of life, significant differences were observed in the within-group analysis (SMD = 0.71, p < 0.001) and between people practicing adaptive sports and those not engaging in them (SMD = 0.62, p = 0.009). In physical quality of life, significant differences were also found between pre- and post-practice of adaptive sports (SMD = 1.03, p = 0.007). The engagement in adaptive sports showed a positive impact on the mental quality of life among adults with physical disabilities. However, the positive effect of adaptive sports practice on physical quality of life was shown only in the pre-post-test analysis. Further studies are required to validate the obtained findings.

5.
Healthcare (Basel) ; 11(16)2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37628534

RESUMO

Suicidal behavior among young people has become an increasingly relevant topic after the COVID-19 pandemic and constitutes a public health problem. This study aimed to examine the variables associated with suicide risk and determine their predictive capacity. The specific objectives were: (1) to analyze the relationship between suicide risk and model variables and (2) to design an artificial neural network (ANN) with predictive capacity for suicide risk. The sample comprised 337 youths aged 18-33 years. An ex post facto design was used. The results showed that emotional attention, followed by problem solving and perfectionism, were variables that contributed the most to the ANN's predictive capacity. The ANN achieved a hit rate of 85.7%, which is much higher than chance, and with only 14.3% of incorrect cases. This study extracted relevant information on suicide risk and the related risk and protective factors via artificial intelligence. These data will be useful for diagnosis as well as for psycho-educational guidance and prevention. This study was one of the first to apply this innovative methodology based on an ANN design to study these variables.

6.
Front Psychol ; 14: 1214892, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37492445

RESUMO

Mathematics and statistical skills are crucial to daily life. However, many students found mathematics difficult to learn and understand. This research aimed to find relationships between mathematics and statistical attitudes and emotional dimensions, such as anxiety or self-efficacy. The sample consisted of two groups: the first group was formed by 276 Spanish students (75.7% female with an average age of 19.92 years) from different degrees at the University of Granada and the second one by agroup of 19 secondary school students from of a Secondary School in Granada, Spain (57.9% male students between 14 and 16 years of age from a public school). The instruments applied were a scale of attitude toward mathematics, a scale of attitude toward statistics, a scale to assess mathematical anxiety, and a scale to assess self-efficacy. An artificial neural network for the backpropagation algorithm was designed using dependent variable. The results showed a negative impact of anxiety on those attitudes, while self-efficacy had a positive impact on those mentioned attitudes. Therefore, emotional education is important in the well-being, and teaching in mathematics. The usefulness of the innovative neural network analysis in predicting the constructs evaluated in this study can be highlighted.

7.
Artigo em Inglês | MEDLINE | ID: mdl-35409533

RESUMO

Affective-sexual and gender diversity is an increasingly distinctive and extended reality and should be acknowledged and respected. From a psychosocial and educational point of view, it is appropriate to review young people's attitudes and knowledge regarding this, relating them to aspects such as empathy, violence, or bullying, to implement quality education in the early stages of primary education. The main objective of this study was to analyze the relationship between empathy levels, attitudes toward transsexuality, and bullying among Spanish university students. The sample consisted of 247 students. Instruments were administered to evaluate negative attitudes toward transsexual people, gender ideology, transphobia, bullying, and empathy. Inverse relationships were found between transphobia and empathy. Regression analysis demonstrated the predictive ability of empathy on attitudes toward transsexual people. The results of this study are expected to increase awareness in society and encourage appropriate, satisfactory, or tolerable coexistence, in which all individuals can be free to live and express themselves. While the results indicated that the quality of life of transgender people has comparatively improved, there is still a long way to go.


Assuntos
Bullying , Empatia , Adolescente , Atitude , Bullying/psicologia , Identidade de Gênero , Humanos , Qualidade de Vida
8.
Front Psychol ; 13: 815853, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35295381

RESUMO

Artificial intelligence (AI) is a useful predictive tool for a wide variety of fields of knowledge. Despite this, the educational field is still an environment that lacks a variety of studies that use this type of predictive tools. In parallel, it is postulated that the levels of self-esteem in the university environment may be related to the strategies implemented to solve problems. For these reasons, the aim of this study was to analyze the levels of self-esteem presented by teaching staff and students at university (N = 290, 73.1% female) and to design an algorithm capable of predicting these levels on the basis of their coping strategies, resilience, and sociodemographic variables. For this purpose, the Rosenberg Self-Esteem Scale (RSES), the Perceived Stress Scale (PSS), and the Brief Resilience Scale were administered. The results showed a relevant role of resilience and stress perceived in predicting participants' self-esteem levels. The findings highlight the usefulness of artificial neural networks for predicting psychological variables in education.

9.
Eur J Investig Health Psychol Educ ; 11(4): 1205-1220, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34698121

RESUMO

It is necessary for the university environment to contribute to the improvement of the attention paid to affective-sexual, bodily, and gender diversity. This research deals with how, by means of a teaching innovation program, competences for affective-sexual diversity were developed. Specifically, negative attitudes towards diversity, knowledge, and degree of empathy on these issues before and after the implementation of the program are compared. The degree of satisfaction, perceived usefulness, and fulfillment of the objectives proposed in the program were also evaluated. An ex post facto design was used. The participants in this study were 129 students belonging to Educational Sciences and Psychology, out of 2400 who benefited from the innovation program. The results showed an increase in competences related to the attention to diversity, with the improvement of attitudes and knowledge about affective-sexual diversity after the application of the program. It is concluded that this type of innovation program, with quality training, contributes to the improvement of coexistence and the prevention of gender violence in university classrooms, eliminating stereotypes and negative attitudes towards diversity.

10.
Nat Commun ; 12(1): 3896, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34162837

RESUMO

Tumor cells may share some patterns of gene expression with their cell of origin, providing clues into the differentiation state and origin of cancer. Here, we study the differentiation state and cellular origin of 1300 childhood and adult kidney tumors. Using single cell mRNA reference maps of normal tissues, we quantify reference "cellular signals" in each tumor. Quantifying global differentiation, we find that childhood tumors exhibit fetal cellular signals, replacing the presumption of "fetalness" with a quantitative measure of immaturity. By contrast, in adult cancers our assessment refutes the suggestion of dedifferentiation towards a fetal state in most cases. We find an intimate connection between developmental mesenchymal populations and childhood renal tumors. We demonstrate the diagnostic potential of our approach with a case study of a cryptic renal tumor. Our findings provide a cellular definition of human renal tumors through an approach that is broadly applicable to human cancer.


Assuntos
Neoplasias Renais/genética , Rim/metabolismo , RNA Mensageiro/genética , RNA-Seq/métodos , Análise de Célula Única/métodos , Transcriptoma , Adulto , Algoritmos , Criança , Feto/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Rim/embriologia , Neoplasias Renais/embriologia , Neoplasias Renais/metabolismo , Modelos Genéticos , Transdução de Sinais/genética
11.
Front Psychol ; 12: 647964, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34017287

RESUMO

The COVID-19 global health emergency has greatly impacted the educational field. Faced with unprecedented stress situations, professors, students, and families have employed various coping and resilience strategies throughout the confinement period. High and persistent stress levels are associated with other pathologies; hence, their detection and prevention are needed. Consequently, this study aimed to design a predictive model of stress in the educational field based on artificial intelligence that included certain sociodemographic variables, coping strategies, and resilience capacity, and to study the relationship between them. The non-probabilistic snowball sampling method was used, involving 337 people (73% women) from the university education community in south-eastern Spain. The Perceived Stress Scale, Stress Management Questionnaire, and Brief Resilience Scale were administered. The Statistical Package for the Social Sciences (version 24) was used to design the architecture of artificial neural networks. The results found that stress levels could be predicted by the synaptic weights of coping strategies and timing of the epidemic (before and after the implementation of isolation measures), with a predictive capacity of over 80% found in the neural network model. Additionally, direct and significant associations were identified between the use of certain coping strategies, stress levels, and resilience. The conclusions of this research are essential for effective stress detection, and therefore, early intervention in the field of educational psychology, by discussing the influence of resilience or lack thereof on the prediction of stress levels. Identifying the variables that maintain a greater predictive power in stress levels is an effective strategy to design more adjusted prevention programs and to anticipate the needs of the community.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33810020

RESUMO

The present study aims analyze the risk factors that lead to high levels of burnout among nurses and physicians and the protective factors that prevent them. Thus, it is also intended to explore the possible correlation between physical and verbal violence produced at work and the symptoms derived from burnout. Methods: The search was carried out on the Scopus, PubMed and Web of Science databases between 2000 and 2019 (on which date the bibliographic search ends). Descriptive studies estimating the prevalence of workplace violence and risk and protective factors and burnout were included. An adapted version of the Downs and Black quality checklist was used for article selection. 89.6 percent of the studies analysed were in the health sector. There is a significant correlation between burnout symptoms and physical violence at work. On the one hand, the risk factors that moderate this correlation were of structural/organisational type (social support, quality of the working environment, authoritarian leadership, little autonomy or long working days, etc.) and personal type (age, gender, nationality or academic degree, etc.). On the other hand, protective factors were the quality of the working environment, mutual support networks or coping strategies. The results were analysed in-depth and intervention strategies were proposed.


Assuntos
Esgotamento Profissional , Médicos , Violência no Trabalho , Esgotamento Profissional/epidemiologia , Esgotamento Psicológico , Estudos Transversais , Humanos , Fatores de Proteção , Fatores de Risco , Local de Trabalho
13.
Artigo em Inglês | MEDLINE | ID: mdl-33546459

RESUMO

Anxiety disorders and suicide are commonly under-recognized issues that can be a public health problem. Adolescents are among the most affected population groups and studying them can prevent serious health problems. These two elements are related, but at the same time, they can only be understood from a multifactorial point of view, so other related variables such as emotional intelligence, empathy, or coping strategies are key to understand their effect on the population. In this study, a series of methods to measure the variables of interest were applied to a specific group of adolescents to determine their mental health levels, focusing on suicide and anxiety episodes. The results reflected average levels with a tendency to be high in the case of anxiety and nonalarming levels in terms of suicide risk, both parameters presenting more worrying values in women. In turn, the correlation between suicide and anxiety was demonstrated considering the other variables (coping strategies, empathy, emotional intelligence, and prosociality). This research has relevant implications for the diagnosis, orientation, and design of psychoeducational and clinical interventions that contribute to the improvement of their well-being and quality of life.


Assuntos
Empatia , Ideação Suicida , Adaptação Psicológica , Adolescente , Ansiedade/epidemiologia , Transtornos de Ansiedade , Inteligência Emocional , Feminino , Humanos , Qualidade de Vida
14.
Artigo em Inglês | MEDLINE | ID: mdl-32867132

RESUMO

The present study forms part of the project "Cross-disciplinary education for sexual, body, and gender diversity" (Code 419). The aim of this study was to analyze the role played by the psychoeducational variables involved in burnout (resilience, self-efficacy, self-esteem, emotional intelligence, empathy, and everyday stress) on attitudes toward sexual and gender diversity rights. Participants comprised 170 university students undertaking a degree in primary education. Instruments were administered to assess the constructs analyzed, ensuring informed consent, voluntary participation, anonymity, and data confidentiality. An ex post facto design was employed to determine whether attitudes toward sexual and gender diversity rights are influenced by the possible relationships and role of these variables. We found statistically significant associations between students' attitudes toward sexual and gender diversity at all three levels (sociocultural, relational, and personal) and the variable of burnout. Attitudes towards gender sexual orientation and gender identity rights influence burnout, and vice versa. As we ponder deeply about how these factors influence one another, we can shift our perspectives in a way that builds social harmony. It is important to learn how exactly these influences work, and this knowledge translates into making teaching strategies more effective to help raise awareness about guaranteeing rights for all. At the personal level of students' attitudes toward sexual and gender diversity/equality, we found positive correlations between this level and the total score for the variable of resilience and with its factor of personal competence. The data obtained will be of use for future psychoeducational assessment and intervention programs related to an education in sexual orientation and gender identity rights that are aimed at developing socio-emotional competencies and attention to diversity with the ultimate goal of improving social harmony by dismantling stereotypes and raising awareness of the importance of the variables of resilience, self-efficacy, self-esteem, emotional intelligence, empathy, and everyday stress which highlights how "education is an instrument of social transformation".


Assuntos
Empatia , Identidade de Gênero , Resiliência Psicológica , Autoeficácia , Estresse Psicológico , Atitude , Diversidade Cultural , Inteligência Emocional , Feminino , Humanos , Masculino , Estudantes , Inquéritos e Questionários , Universidades
15.
Artigo em Inglês | MEDLINE | ID: mdl-32630816

RESUMO

Determining what factors influence the psychological well-being of undergraduate university students may provide valuable information to inform the development of intervention programs and targeted learning activities. The objective of this study was to investigate the correlation between psychological well-being in university students and their self-reported learning styles and methodologies, social skills, emotional intelligence, anxiety, empathy and self-concept. The final sample consisted of 149 Spanish university students, with an average age of 21.59 years (SD = 4.64). Psychological well-being dimensions, along with learning style and methodology preferences, social skills, level of social responsibility, emotional intelligence, state and trait anxiety, empathy and levels of self-concept were measured using a series of validated self-report scales. The results indicate that the total variance explained by the university students' psychological well-being factors were as follows: i) self-acceptance dimension (R2 = 0.586, F(6,99) = 23.335, p < 0.001); ii) positive relationships dimension (R2 = 0.520, F(6,99) = 17.874, p < 0.001); iii) autonomy dimension (R2 = 0.313, F(4,101) = 11.525, p < 0.001); iv) environmental mastery dimension (R2 = 0.489, F(4,101) = 24.139, p < 0.001); v) personal growth dimension (R2 = 0.354, F(4,101) = 13.838, p < 0.001); and vi) purpose-in-life dimension (R2 = 0.439, F(4,101) = 19.786, p < 0.001). The study findings may be used to inform new educational policies and interventions aimed at improving the psychological well-being of university students in the international context.


Assuntos
Inteligência Emocional , Saúde Mental , Universidades , Adulto , Transtornos de Ansiedade , Empatia , Humanos , Estudantes , Adulto Jovem
16.
Front Psychol ; 10: 1689, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447720

RESUMO

The main objective of the present research is to analyze the relationship of levels of self-efficacy and anxiety, coping strategies, and emotional intelligence in Spanish university students. This study has a cross-sectional design. The sample was composed of 258 university students recruited from three academic areas. Descriptive, bivariate, and multivariate regression analyses were performed. Significant bivariate analysis showed a significant inverse correlation between self-efficacy and state anxiety (r = -0.340) and trait anxiety (r = -0.466). In addition, a direct correlation was found between self-efficacy and the coping strategies of problem-solving (r = 0.312), emotional expression (r = 0.133), cognitive restructuring (r = 0.195), social withdrawal (r = 0.103), and coping with a situation (r = 0.303), as well as with the emotional intelligence dimensions of emotional clarity (r = 0.397) and repair mood (r = 0.347). Multivariate regression analysis showed that trait anxiety, problem-solving, emotional expression, social withdrawal, and emotional clarity were significantly related to the dependent variable, predicting 39% of total variance on levels of general perceived self-efficacy. In conclusion, this paper contributes to a better understanding of the related factors to general perceived self-efficacy in undergraduate students.

17.
Front Psychol ; 10: 2889, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31920897

RESUMO

INTRODUCTION: Burnout syndrome has been characterized as a process of chronic responses to occupational stress in certain employee groups. However, this phenomenon has also been reported in other participant groups including university students. The Maslach Burnout Inventory-Student Survey (MBI-SS), composed of the Exhaustion, Cynicism and Efficacy subscales, was used to evaluate burnout in this sample group while the Utrecht Work Engagement Scale (UWES) was used to gather data related to engagement, a positive psychology construct composed of the three factors, namely vigor, dedication, and absorption. To date, no studies considered these factors in relation to occupational therapy students. This begs the question, is there a relationship between occupational therapy students' self-reported levels of burnout and engagement? OBJECTIVES: The study objectives are to (1) ascertain the self-reported levels of burnout and engagement in a sample of Australian Occupational undergraduate therapy students, and (2) analyze the sociodemographic, occupational and academic characteristic associated with these levels. METHODS: Participants were 225 Australian undergraduate occupational therapy students from Monash University completed the MBI-SS and the UWES for students. Descriptive, bivariate and multiple linear regression analyses were performed. RESULTS: Regarding MBI-SS burnout dimensions, exhaustion was associated with age, year level of enrolment and hours of direct time spent working on occupational therapy studies, explaining 15% of its variance. Cynicism and efficacy were associated with age, year level of enrolment and hours of indirect time, accounting for 16% of its variance. For the UWES engagement dimensions, year level of enrolment and hours of indirect time spent working on occupational therapy studies were significant predictors of vigor, explaining 27% its variance while while age, gender, year level of enrolment, hours of indirect time spent working on occupational therapy studies, and hours spend per week engaged in self-care activities accounted for 23% of the variance of dedication. Finally, age, year level of enrolment, and hours of indirect time spent working on occupational therapy studies explained 27% of the variance of absorption. CONCLUSION: The results indicate that a number of demographic and academic study variables are significantly associated with burnout syndrome and education engagement reported by undergraduate occupational therapy students.

18.
Cell Metab ; 28(6): 866-880.e15, 2018 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-30146486

RESUMO

The role of fatty acid synthesis in endothelial cells (ECs) remains incompletely characterized. We report that fatty acid synthase knockdown (FASNKD) in ECs impedes vessel sprouting by reducing proliferation. Endothelial loss of FASN impaired angiogenesis in vivo, while FASN blockade reduced pathological ocular neovascularization, at >10-fold lower doses than used for anti-cancer treatment. Impaired angiogenesis was not due to energy stress, redox imbalance, or palmitate depletion. Rather, FASNKD elevated malonyl-CoA levels, causing malonylation (a post-translational modification) of mTOR at lysine 1218 (K1218). mTOR K-1218 malonylation impaired mTOR complex 1 (mTORC1) kinase activity, thereby reducing phosphorylation of downstream targets (p70S6K/4EBP1). Silencing acetyl-CoA carboxylase 1 (an enzyme producing malonyl-CoA) normalized malonyl-CoA levels and reactivated mTOR in FASNKD ECs. Mutagenesis unveiled the importance of mTOR K1218 malonylation for angiogenesis. This study unveils a novel role of FASN in metabolite signaling that contributes to explaining the anti-angiogenic effect of FASN blockade.


Assuntos
Ácido Graxo Sintase Tipo I/fisiologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Malonil Coenzima A/metabolismo , Neovascularização Retiniana/patologia , Serina-Treonina Quinases TOR/metabolismo , Acetil-CoA Carboxilase/antagonistas & inibidores , Animais , Linhagem Celular Tumoral , Proliferação de Células , Ácido Graxo Sintase Tipo I/antagonistas & inibidores , Ácido Graxo Sintase Tipo I/genética , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Orlistate/uso terapêutico , Processamento de Proteína Pós-Traducional , Neovascularização Retiniana/tratamento farmacológico
19.
Cell Metab ; 28(6): 881-894.e13, 2018 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-30146488

RESUMO

Little is known about the metabolism of quiescent endothelial cells (QECs). Nonetheless, when dysfunctional, QECs contribute to multiple diseases. Previously, we demonstrated that proliferating endothelial cells (PECs) use fatty acid ß-oxidation (FAO) for de novo dNTP synthesis. We report now that QECs are not hypometabolic, but upregulate FAO >3-fold higher than PECs, not to support biomass or energy production but to sustain the tricarboxylic acid cycle for redox homeostasis through NADPH regeneration. Hence, endothelial loss of FAO-controlling CPT1A in CPT1AΔEC mice promotes EC dysfunction (leukocyte infiltration, barrier disruption) by increasing endothelial oxidative stress, rendering CPT1AΔEC mice more susceptible to LPS and inflammatory bowel disease. Mechanistically, Notch1 orchestrates the use of FAO for redox balance in QECs. Supplementation of acetate (metabolized to acetyl-coenzyme A) restores endothelial quiescence and counters oxidative stress-mediated EC dysfunction in CPT1AΔEC mice, offering therapeutic opportunities. Thus, QECs use FAO for vasculoprotection against oxidative stress-prone exposure.


Assuntos
Carnitina O-Palmitoiltransferase/metabolismo , Metabolismo Energético , Ácidos Graxos/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , NADP/metabolismo , Receptor Notch1/metabolismo , Animais , Proliferação de Células , Células HEK293 , Homeostase , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Oxirredução , Estresse Oxidativo
20.
Nature ; 561(7721): 63-69, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30158707

RESUMO

Glutamine synthetase, encoded by the gene GLUL, is an enzyme that converts glutamate and ammonia to glutamine. It is expressed by endothelial cells, but surprisingly shows negligible glutamine-synthesizing activity in these cells at physiological glutamine levels. Here we show in mice that genetic deletion of Glul in endothelial cells impairs vessel sprouting during vascular development, whereas pharmacological blockade of glutamine synthetase suppresses angiogenesis in ocular and inflammatory skin disease while only minimally affecting healthy adult quiescent endothelial cells. This relies on the inhibition of endothelial cell migration but not proliferation. Mechanistically we show that in human umbilical vein endothelial cells GLUL knockdown reduces membrane localization and activation of the GTPase RHOJ while activating other Rho GTPases and Rho kinase, thereby inducing actin stress fibres and impeding endothelial cell motility. Inhibition of Rho kinase rescues the defect in endothelial cell migration that is induced by GLUL knockdown. Notably, glutamine synthetase palmitoylates itself and interacts with RHOJ to sustain RHOJ palmitoylation, membrane localization and activation. These findings reveal that, in addition to the known formation of glutamine, the enzyme glutamine synthetase shows unknown activity in endothelial cell migration during pathological angiogenesis through RHOJ palmitoylation.


Assuntos
Células Endoteliais/enzimologia , Células Endoteliais/patologia , Glutamato-Amônia Ligase/metabolismo , Glutamina/biossíntese , Neovascularização Patológica , Actinas/metabolismo , Animais , Movimento Celular , Células Endoteliais/metabolismo , Feminino , Glutamato-Amônia Ligase/deficiência , Glutamato-Amônia Ligase/genética , Glutamato-Amônia Ligase/fisiologia , Células HEK293 , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/enzimologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Lipoilação , Camundongos , Ácido Palmítico/metabolismo , Processamento de Proteína Pós-Traducional , Fibras de Estresse/metabolismo , Proteínas rho de Ligação ao GTP/química , Proteínas rho de Ligação ao GTP/metabolismo , Quinases Associadas a rho/metabolismo
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