RESUMO
A-to-I RNA editing is a widespread epitranscriptomic phenomenon leading to the conversion of adenosines to inosines, which are primarily interpreted as guanosines by cellular machines. Consequently, A-to-I editing can alter splicing or lead to recoding of transcripts. As misregulation of editing can cause a variety of human diseases, A-to-I editing requires tight regulation of the extent of deamination, particularly in protein-coding regions. The bulk of A-to-I editing occurs cotranscriptionally. Thus, we studied A-to-I editing regulation in the context of transcription and pre-mRNA processing. We show that stimulation of transcription impacts editing levels. Activation of the transcription factor MYC leads to an up-regulation of A-to-I editing, particularly in transcripts that are suppressed upon MYC activation. Moreover, low pre-mRNA synthesis rates and low pre-mRNA expression levels support high levels of editing. We also show that editing levels greatly differ between nascent pre-mRNA and mRNA in a cellular system, as well as in mouse tissues. Editing levels can increase or decrease from pre-mRNA to mRNA and can vary across editing targets and across tissues, showing that pre-mRNA processing is an important layer of editing regulation. Several lines of evidence suggest that the differences emerge during pre-mRNA splicing. Moreover, actinomycin D treatment of primary neuronal cells and editing level analysis suggests that regulation of editing levels also depends on transcription.
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Edição de RNA , RNA Polimerase II , Precursores de RNA , Animais , Humanos , Camundongos , Adenosina Desaminase/genética , RNA Polimerase II/genética , Precursores de RNA/genética , Precursores de RNA/metabolismo , Splicing de RNA , RNA Mensageiro/metabolismo , Transcrição Gênica , Edição de RNA/genética , Edição de RNA/fisiologiaRESUMO
OBJECTIVE: The literature suggests that mentalizing deficits, insecure attachment, and higher levels of perceived stress are closely linked, however, the association between these constructs has not yet been investigated among Hungarian adults. In our study, we investigated the relationship between mentalization, attachment and perceived stress in a non-clinical adult sample. METHODS: In our study, 255 adults completed the Reflective Functioning Questionnaire (RFQ-R-7), the Experiences in Close Relationships questionnaire (ECR-R-HU) and the Perceived Stress Scale (PSS) after informed consent. In our analysis, we tested two simple mediation models. The independent variables differed in the two analyses, in the first one we used the attachment anxiety subscale, while in the second one, we used the attachment avoidance subscale of the ECR-R-HU questionnaire. In both of our models, the perceived stress (PSS) was the dependent variable, while hypomentalization was the mediator (RFQ7). RESULTS: The models were found to be significant. The direct path between attachment anxiety and perceived stress (c' = 0.11, p < .001, ß = 0.29) and indirect path through hypomentalizig also proved to be significant (∑ab = 0.04 [0.02 - 0.06], ß = 0.10). The direct path between attachment avoidance and perceived stress was significant (c' = 0.05, p = 0.04, ß = 0.12), however, the indirect path between attachment avoidance and perceived stress was not significant (∑ab = -0.004 [-0.02 - 0.01], ß = -0.01). CONCLUSIONS: Our results - taking our limitations into account - suggest that hypomentalization has a mediational effect on the relationship between attachment anxiety and perceived stress, while attachment avoidance is directly related to perceived stress. Our results have important practical implications for prevention and intervention.
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Mentalização , Testes Psicológicos , Adulto , Humanos , Ansiedade , Autorrelato , Estresse PsicológicoRESUMO
OBJECTIVE: We investigated the relationship between mentalisation, attachment and resilience in an adult sample. METHOD: 225 people completed the Reflective Function Questionnaire (RFQ-H), the Experiences in Close Relationships Questionnaire (ECR-R-HU), and the Connor-Davidson Resilience Questionnaire (CD-RISC) in our non-clinical study after informed consent. The analysis was controlled for gender of the respondents. RESULTS: The models were found to be significant in the mediator analysis. The path between attachment total score and hypomentalisation was significant (a=2.88, p<0.01, ß=0.32). The direct path between attachment total score and resilience was found to be significant (c'=-2.00, p<0.001, ß=-0.28). The relationship between hypomentalisation and resilience was also significant (b=-0.30, p<0.01, ß=-0.38). The indirect pathway between attachment and resilience through hypomentalisation was found to be significant (∑ab=-0.87 [-1.41 - -0.40], ß = 0.12). Thus, a high total attachment score through higher levels of hypomentalisation predicts lower resilience. Based on the standardized regression coefficients, hypomentalisation was the strongest predictor of resilience, and attachment was more strongly associated with resilience via direct than indirect means via hypomentalisation. CONCLUSIONS: Our results suggest - considering the limitations of our research - that attachment is related to resilience through mentalisation, and that mentalisation itself is a strong predictor of resilience. The practical implication of our results is that the use of mentalisation-based methods may be worth considering for individuals with lower levels of resilience.
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Resiliência Psicológica , Adulto , Humanos , Psicometria , Testes Psicológicos , Inquéritos e QuestionáriosRESUMO
AIMS: This paper aims to describe Roger Mulder's presentation on borderline personality disorder organized by the 23rd World Congress of Psychiatry, supplemented with relevant research results. METHODS: Mulder presents the diagnostic criteria of borderline personality disorder, its comorbidity, therapeutic considerations and the phenomenon of stigmatization related to the disorder. RESULTS: According to Mulder, the diagnostic criteria of borderline personality disorder are vague and it shows a very high comorbidity with other psychiatric disorders. Mulder draws attention to the fact that it was not possible to identify a borderline factor in previous research because the borderline symptoms disappeared during the analysis in a general ("g") personality disorder factor. According to Mulder, there is no specific psychotherapy that is effective only in borderline personality disorder, and the pharmacological treatment has also not proven to be effective in treating the core symptoms of borderline personality disorder. According to Mulder, the stigma associated with the diagnosis of borderline personality disorder hinders the recognition and treatment of other psychiatric or somatic difficulties of patients. CONCLUSION: according to Mulder, based on modern scientific standards, borderline personality disorder has no place in the classification, however, specialists still insist on the diagnosis.
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Transtorno da Personalidade Borderline , Humanos , Transtorno da Personalidade Borderline/diagnóstico , Transtorno da Personalidade Borderline/terapia , Transtornos da Personalidade/diagnóstico , Transtornos da Personalidade/epidemiologia , Psicoterapia/métodos , Comorbidade , Escalas de Graduação PsiquiátricaRESUMO
INTRODUCTION: The literature indicates that a more genuine parental reflective function positively relates to the child's well-being and adaptive parental cognitive emotion regulation strategies. However, this relationship has not been studied among Hungarian parents of adolescents. The present research aims to explore the relationship between parental mentalization, cognitive emotion regulation, and perception of children's quality of life among parents of 12- and 18-year-old adolescents. METHODS: In our cross-sectional, non-clinical study, 100 parents completed the Parental Reflective Function Questionnaire Adolescent Version (PRFQ-A), the Cognitive Emotion Regulation Questionnaire (CERQ), and the Quality of Life Questionnaire (ILK) after informed consent. In our mediator model, we chose the Quality of Life Questionnaire as a dependent variable and the Parental Reflective Functions Questionnaire Adolescent Version Certainty in Mental State subscale as an independent variable, and the mediator was the Positive Reappraisal subscale of the Cognitive Emotion Regulation Questionnaire. RESULTS: The direct path between the Certainty in Mental Conditions subscale and the Quality of Life Questionnaire (c'=1.63, p<.001, ß=0.33) was significant. However, the indirect pathway between the Certainty in Mental Conditions subscale and the Quality of Life Questionnaire through the Positive Reappraisal subscale was insignificant (∑ab=0.32 [-0.01- 0.65], ß=0.07). CONCLUSION: Our results suggest that parental mentalization plays a crucial role in the perception of child's well-being among parents of adolescents, which has practical implications.
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Regulação Emocional , Qualidade de Vida , Criança , Humanos , Adolescente , Estudos Transversais , Pais , Percepção , CogniçãoRESUMO
BACKGROUND: According to research, there is a negative association between emotion regulation, mentalization difficulties and quality of life among adolescents. However, no former study examined the relationship between these three constructs in a Hungarian adolescent sample. METHODS: In our non-clinical cross-sectional study, 122 adolescents answered a list of demographic questions and then completed the Reflective Function Questionnaire (RFQ-H), the Emotion Regulation Difficulties Questionnaire (DERS) and the Quality of Life Scale (ILK) after informed consent. In our mediator model, we chose the Reflective Function Questionnaire as the independent variable, the Emotional Regulation Difficulties Questionnaire as the mediator and the Quality of Life Scale as the dependent variable. RESULTS: There was a significant relationship between mentalization dysfunction and emotional regulation difficulties (a=0.39, p< .01, ß=0.44). The direct effect between mentalization difficulties and low quality of life was not significant (c'=0.02, p=.73, ß=0.03), while the indirect effect between mentalization dysfunction and low quality of life mediated by emotional regulation difficulties was significant (ab=0.22 [0.13-0.33], ß=0.25 [0.14-0.36]). CONCLUSION: Our results imply that emotional regulation mediates the relationship between mentalization and quality of life among the Hungarian adolescent sample, which have practical implications.
Assuntos
Regulação Emocional , Mentalização , Humanos , Adolescente , Estudos Transversais , Qualidade de VidaRESUMO
The RNA-editing protein ADAR is essential for early development in the mouse. Genetic evidence suggests that A to I editing marks endogenous RNAs as 'self'. Today, different Adar knockout alleles have been generated that show a common phenotype of apoptosis, liver disintegration, elevated immune response and lethality at E12.5. All the Adar knockout alleles can be rescued by a concomitant deletion of the innate immunity genes Mavs or Ifih1 (MDA5), albeit to different extents. This suggests multiple functions of ADAR. We analyze AdarΔ7-9 mice that show a unique growth defect phenotype when rescued by Mavs. We show that AdarΔ7-9 can form a truncated, unstable, editing deficient protein that is mislocalized. Histological and hematologic analysis of these mice indicate multiple tissue- and hematopoietic defects. Gene expression profiling shows dysregulation of Rps3a1 and Rps3a3 in rescued AdarΔ7-9. Consistently, a distortion in 40S and 60S ribosome ratios is observed in liver cells. This dysregulation is also seen in AdarΔ2-13; Mavs-/- but not in AdarE861A/E861A; Ifih1-/- mice, suggesting editing-independent functions of ADAR in regulating expression levels of Rps3a1 and Rps3a3. In conclusion, our study demonstrates the importance of ADAR in post-natal development which cannot be compensated by ADARB1.
Assuntos
Adenosina Desaminase/genética , Imunidade Inata/genética , Helicase IFIH1 Induzida por Interferon/genética , Proteínas Ribossômicas/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Alelos , Animais , Regulação da Expressão Gênica/genética , Fígado/metabolismo , Camundongos , Camundongos Knockout , Edição de RNA/genética , Proteínas de Ligação a RNA/genética , Subunidades Ribossômicas Maiores de Eucariotos/genética , Subunidades Ribossômicas Menores de Eucariotos/genética , Deleção de Sequência/genéticaRESUMO
INTRODUCTION: Parental reflective function is the ability of a parent to attribute mental states to their child and to themselves. In the English-speaking world, The Parental Reflective Functioning Questionnaire (PRFQ; Luyten, Mayes, Nijssens and Fonagy, 2017) is widely used for the measurement of this construct, the adolescent version of which can be used by parents of children aged 12-18. The aim of our research was to adapt the adolescent version of The Parental Reflective Functioning Questionnaire to Hungarian language and to analyze its factor structure. METHODS: In our cross-sectional, non-clinical study, 240 mothers completed the demographic form, the adolescent version of The Parental Reflective Functioning Questionnaire (PRFQ-A), and the Reflective Function Questionnaire (RFQ; Fonagy et al, 2016; Unoka et al, in press). RESULTS: Confirmatory factor analysis did not confirm the original three-factor structure. The principal component analysis resulted in a two-factor structure. Factors corresponded to the original questionnaire's certainty in mental states (Alpha=.81) and interest and curiosity subscales (Alpha=.70). When analyzing the relationship between parental reflective function and reflective function, the subscales of the parental reflective function questionnaire were examined with two types of median coding in addition to polar coding (higher values reflect more favorable reflective function). During the first median coding, the frequency of scores in the middle of the scales reflected optimal mentalization, while the frequency of extreme values on the scales corresponded to less favorable forms of reflective functioning - a category that included different kinds of mentalization deficits. With the second median coding, in addition to the optimal mentalization capacity subscale, hypermentalization and hypomentalization subscales were also created based on the frequency of the values achieved on (respectedly) the lower and the upper parts of the scales. The second median transcoding proved to be the most suitable for capturing the relationship between RFQ and PRFQ-A. CONCLUSION: The questionnaire proved to be a reliable measure on the Hungarian sample. Based on the results of the current study, we recommend using of the additional subscales of hypomentalization, optimal mentalization capacity, and hypermentalization.
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Idioma , Pais , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Hungria , Psicometria , Inquéritos e QuestionáriosRESUMO
An important correlate of mental health problems is mentalizing capacity, which appears to be particularly influential during adolescence. However, quality of life has not been studied in relation to mentalizing capacity among adolescents. This study aimed to translate the Reflective Function Questionnaire for Youth (RFQY) into Hungarian, present its psychometric properties, and assess its relationship with demographic characteristics, psychopathology and quality of life. A community sample of 384 youths aged 12-18 years completed the RFQY, the Measure of Quality of Life for Children and Adolescents, and the Strengths and Difficulties Questionnaire. First, we conducted an exploratory factor analysis with direct oblimin rotation on the RFQY items. Next, we assessed the associations between the RFQY and demographics, quality of life, and psychopathology. The EFA resulted in four factors: Internal-self, Internal-other, Self-other, and Strong emotions. The Cronbach's alpha coefficients of the scales were .81, .82, .67, and .80, respectively. The subscales were uniquely associated with psychopathology and quality of life. Our study provides the first psychometric support for the Hungarian version of the RFQY and indicates that adolescents suffering from internalizing, externalizing symptoms or lower levels of quality of life could benefit from interventions aimed at enhancing mentalizing capacity.
An important correlate of mental health problems is mentalizing capacity, which appears to be particularly influential during adolescence. However, quality of life has not been studied in relation to mentalizing capacity among adolescents. This study aimed to translate the Reflective Function Questionnaire for Youth (RFQY) into Hungarian, present its psychometric properties, and assess its relationship with demographic characteristics, psychopathology and quality of life. A community sample of 384 youths between the ages of 12 and 18 completed the RFQY, the Measure of Quality of Life for Children and Adolescents, and the Strengths and Difficulties Questionnaire. Our study provides the first psychometric support for the Hungarian version of the RFQY and indicates that adolescents suffering from internalizing, externalizing symptoms or lower levels of quality of life could benefit from interventions aimed at enhancing mentalizing capacity.
RESUMO
Spatially explicit, quantitative information on soil hydraulic properties is required in various modelling schemes. At European scale, EU-SoilHydroGrids proved its applicability in a number of studies, in ecological predictions, geological and hydrological hazard assessment, agri-environmental models, among others. Inspired by its continental antecedent, an analogous, but larger scale, national, 3D soil hydraulic database was elaborated for the territory of Hungary (HU-SoilHydroGrids) supported by various improvements (i-iv) in the computation process. Pedotransfer functions (PTFs) were built in the form of i) advanced machine learning methods and ensemble models, and trained on the ii) national soil hydrophysical dataset. The set of predictors used in PTFs was supplemented by iii) additional environmental auxiliary variables. Spatial layers of the soil hydraulic parameters were generated using iv) 100 m resolution information on primary soil properties, namely DOSoReMI.hu. HU-SoilHydroGrids provides information on the most frequently required soil hydraulic properties (water content at saturation, field capacity and wilting point, saturated hydraulic conductivity and van Genuchten parameters for the description of the moisture retention curve) with national coverage at 100 m spatial resolution down to 2 m depth for six GSM standard depth layers. The HU-SoilHydroGrids has significantly lower squared error in the case of describing the moisture retention curve and hydraulic conductivity than the EU-SoilHydroGrids. The derived 3D soil hydraulic database (ver1.0) is presently available in National Laboratory for Water Science and Water Safety for project partners in order to test its functional performance in describing hydrological and ecological processes.
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INTRODUCTION: According to the literature, mentalizing difficulties and insecure emotional attachment styles occur more frequently among adolescents with eating disorders. The role of mentalization in the relationship between emotional attachment styles and eating attitudes has not been investigated among Hungarian adolescents. OBJECTIVE: We investigated the relationship between mentalization, emotional attachment and eating attitudes among adolescents between 14 and 18 years of age. METHOD: After informed consent, 143 adolescents filled out the Reflective Functioning Questionnaire, the Experience in Close Relationship Scale, and the Eating Attitudes Test in our study. RESULTS: The direct path between the emotional attachment total score and dieting was not significant (c' = 0.01, p = 0.31, ß = 0.09), while the indirect path between emotional attachment and eating attitudes through mentalization uncertainty proved to be significant (∑ab = 0.01 [0.01-0.02], ß = 0.07). DISCUSSION: Our results suggest that the attachment style plays a role in dieting through mentalizing among adolescents. CONCLUSION: We recommend mentalization-based methods to change attitudes about dieting among adolescents. Orv Hetil. 2023; 164(2): 64-69.
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Emoções , Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Adolescente , Hungria , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The purpose of this study was to investigate cognitive emotion regulation in adolescents with chronic illness and their parents. METHODS: Eighty-five young people (mean = 15.86 years, standard deviation = ± 1.42, girls 65.88%) with chronic illnesses (inflammatory bowel disease n = 40 or type 1 diabetes n = 45), and their parents (mean = 46.06 years, 87.06% mother) completed the Cognitive Emotion Regulation Questionnaire (CERQ) for themselves and the Inventory of Quality of Life in Children and Adolescents (ILC) questionnaire adolescent and parent version. We conducted two hierarchical linear regression analyses with "enter" method. The CERQ scales and the diagnosis of chronic disease were chosen as independent variables, and the total ILC score in the first analysis and the ILC proxy score in the second analysis were chosen as dependent variables. RESULTS: Among adolescents, cognitive emotion regulation strategies such as self-blame, positive reappraisal, and catastrophizing have been proven to be predictors of their own quality of life; however, parental self-blame was also found to be a predictor of adolescents' quality of life. Parental rumination and positive refocusing have been shown to be predictors of how parents rate their child's quality of life. CONCLUSIONS: The present study sheds light on cognitive emotion regulation strategies in adolescents with chronic illness and their parents that have a significant impact on the development of young people's quality of life.
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Regulação Emocional , Adolescente , Criança , Feminino , Humanos , Qualidade de Vida/psicologia , Projetos Piloto , Emoções , Cognição , Inquéritos e Questionários , Doença CrônicaRESUMO
Összefoglaló. Bevezetés: A férfiakat érinto egyik leggyakoribb malignus ráktípus a prosztatarák. A Nemzeti Rákregiszter adatai alapján hazánkban évente több mint 4600 új eset kerül diagnosztizálásra. Célkituzés: A rákbetegek pszichoszociális háttere napjainkig alulvizsgált terület Magyarországon. A szerzok célja a magyar prosztatarákos férfiak szociodemográfiai, egészségi, mentális állapotának vizsgálata volt. Módszer: A vizsgálatban 100 prosztatarákos férfi vett részt, akiknek más urológiai betegsége nem volt, továbbá más daganatos betegségbol kifolyó kezelésben nem részesültek a kérdoív kitöltésekor. A részvétel anonim és önkéntes volt. A standard validált tesztek mellett - mint a Beck Depresszió Kérdoív, Rosenberg Önértékelés Skála - szociodemográfiai, egészségmagatartás- és életmód-kérdéscsoportokat tartalmazott kérdoívünk. Statisztikai analízis: Leíró statisztikát, khi-négyzet-próbát, lineáris regresszió analízist, Fisher-egzakt tesztet, kétmintás t-próbát végeztünk 95%-os valószínuségi szinten az SPSS 20.0 és a Microsoft Excel 2016-os programban. Eredmények: Az egészségi állapotot a lakhely településcsoportja (p = 0,024), az anyagi helyzet (p = 0,001), a krónikus betegség (p = 0,000), a fizikai aktivitás (p = 0,000) és az alkoholfogyasztás (p = 0,001) befolyásolta. A társas támogatás (p = 0,726) ellenben nem bizonyult befolyásoló tényezonek. A megkérdezettek 66%-a volt elhízott a BMI alapján. Helyesen csupán a megkérdezettek egyharmada táplálkozott a ma érvényes MDOSZ-ajánlás alapján. 62%-uk enyhén depressziósnak volt mondható a Beck Depresszió Kérdoív alapján, 73%-uk önértékelése azonban a Rosenberg Önértékelés Skála alapján átlagosnak volt mondható. Az életkorral nem nott sem a Depresszió Kérdoív pontszáma, sem az Önértékelés Skála pontszáma. Következtetés: Eredményeink alátámasztják, amit a hazai és a külföldi szakirodalom is mutat: az egészséget befolyásoló tényezoknek meghatározó szerepük van a daganatos megbetegedéssel éloknél is. A depresszió és az önértékelés közti összefüggés nem igazolódott a mintánkban. Orv Hetil. 2021; 162(10): 383-391. INTRODUCTION: Prostate cancer is one of the most common malignant cancers amongst men. More than 4600 men are diagnosed with prostate cancer every year in Hungary. OBJECTIVE: The psychosocial background of cancer patients is an underexamined area in Hungary. The aim of the authors was to obtain information on the sociodemographic status, health and mental status of Hungarian men with prostate cancer. METHOD: 100 prostate cancer patiens were included in the study who did not have any urologic diseases and did not go under any therapy due to any other type of cancer. The applied questionnaire was put together by the authors about sociodemographic and health status, lifestyle. The Beck's Depression Inventory and the Rosenberg Self-Esteem Scale were also used. STATISTICAL ANALYSIS: We used descriptive statistics, chi-square test, linear regression, Fisher's exact test, independent t-sample test on a 95% probability level in the SPSS 20.0 and Microsoft Excel 2016 softwers. RESULTS: The settlement classification (p = 0.024), financial status (p = 0.001), chronic illnesses (p = 0.000), physical activity (p = 0.000) and alcohol consumption (p = 0.001) affected the health status. Only one third of the respondents ate healthy according to the recommendations of the MDOSZ. 66% of the respondents were overweight. 62% of the respondents were depressed according to the Beck's Depression Inventory, however, 73% of them had average self-esteem measured by the Rosenberg Scale. We proved that with age either the depression score or the self-esteem score did not increase. CONCLUSION: Our results roughly mirror the national and international literature about health behavior. No connection was found between self-esteem and depression. Orv Hetil. 2021; 162(10): 383-391.
Assuntos
Comportamentos Relacionados com a Saúde , Neoplasias da Próstata , Humanos , Hungria , Masculino , Neoplasias da Próstata/terapia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Despite of the importance of soils in agronomy, to date no comprehensive assessment of cropping in Europe has been performed from the viewpoint of the soil variability and its relationship to cropping patterns. In order to fill this knowledge gap, we studied the cropping patterns in different soils of European climate zones with regards to the shares of their crop types in a comparative manner. The study highlights the main features of farming by soil in Europe. Farming by soil in this context means the consideration of soil characteristics when selecting crop types and cropping patterns. METHODS: We first assessed the dissimilarity between the cropping compositions of different pedoclimatic zones in Europe. Next, we assessed the differences of crop distribution in the climate zones by soil types and main crop types by analyzing the degree of association of crops to soil types. A detailed country scale assessment was performed using crops-specific soil productivity maps and land use survey data from Hungary. RESULTS: Results suggest that, in general, farmers consciously take pedoclimatic condition of farming into account when selecting their cropping patterns. In other words, farming by soil is a common practice in the different climatic regions of Europe. However, we have strong reasons to believe that soil suitability-based cropping is not practiced to its full potential over the continent. For example, the findings of our European assessment suggest that production areas of legumes are not always optimized for the local pedoclimatic conditions in some zones. These findings also underline that economic drivers are decisive, when farmers adopt their cropping (eg. oil crops on Albeluvsiols in Europe). Win-win situations of economic considerations and soil suitability based management are observed in all pedoclimatic zones of Europe. The country analysis shows that cropping is progressively practiced on more suitable areas, depending also the crop tolerance to variable pedoclimatic conditions In conclusion, we can assume that pedoclimatic conditions of cropping are respected in most of Europe and farmers crops according to edaphic conditions whenever economic considerations do not override the ecological concerns of farming.
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COVID-19 , Humanos , COVID-19/epidemiologia , Pandemias , Pessoal de Saúde/psicologia , SARS-CoV-2 , Depressão , AnsiedadeRESUMO
The cytoplasmic nucleotide oligomerization domain 2 (NOD2) receptor recognizes the bacterial cell wall component muramyl dipeptide (MDP). NOD2 ligation initiates the nuclear factor kappa B and the mitogen-activated protein kinase cascades. However, administering MDP alone is insufficient to elicit strong cytokine responses in various immune cells, including dendritic cells (DCs). Because the simultaneous presence of various microbial products and cytokines in inflamed tissues modulates DC function, we initiated this study to examine how interferon gamma (IFNγ), a central modulator of inflammation, affects the NOD2-mediated signaling pathway in human conventional DCs (cDCs). Synergistic stimulation of DCs with MDP and IFNγ increased the expression of CD40, CD80, CD83, CD86, and human leukocyte antigen DQ proteins and significantly elevated the production of pro-inflammatory cytokines IL-1ß, IL-6, IL-12, and tumour necrosis factor (TNF), as well as anti-inflammatory cytokine IL-10. Furthermore, the simultaneous presence of MDP and IFNγ was necessary to decrease IkBα protein levels. By investigating various mechanisms implicated in MDP- and IFNγ-mediated signaling pathways, we revealed that the increased production of pro-inflammatory cytokines is highly dependent on the X-linked inhibitor of apoptosis protein (XIAP) but not on cellular IAP1 and IAP2. We also found that the NOD2 signaling pathway is regulated by the mammalian target of rapamycin (mTOR) but is not affected by phosphatidylinositol-3 kinase or signal transducer and activator of transcription 1 inhibition. Our results demonstrate, for the first time, that IFNγ positively affects NOD2-mediated signaling in human cDCs, in a manner considerably dependent on XIAP and partially dependent on mTOR.