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To investigate changes in culinary practices associated with the arrival of farming, we analysed the organic residues of over 1,000 pottery vessels from hunter-gatherer-fisher and early agricultural sites across Northern Europe from the Lower Rhine Basin to the Northeastern Baltic. Here, pottery was widely used by hunter-gatherer-fishers prior to the introduction of domesticated animals and plants. Overall, there was surprising continuity in the way that hunter-gatherer-fishers and farmers used pottery. Both aquatic products and wild plants remained prevalent, a pattern repeated consistently across the study area. We argue that the rapid adaptation of farming communities to exploit coastal and lagoonal resources facilitated their northerly expansion, and in some cases, hunting, gathering, and fishing became the most dominant subsistence strategy. Nevertheless, dairy products frequently appear in pottery associated with the earliest farming groups often mixed with wild plants and fish. Interestingly, we also find compelling evidence of dairy products in hunter-gatherer-fisher Ertebølle pottery, which predates the arrival of domesticated animals. We propose that Ertebølle hunter-gatherer-fishers frequently acquired dairy products through exchange with adjacent farming communities prior to the transition. The continuity observed in pottery use across the transition to farming contrasts with the analysis of human remains which shows substantial demographic change through ancient DNA and, in some cases, a reduction in marine consumption through stable isotope analysis. We postulate that farmers acquired the knowledge and skills they needed to succeed from local hunter-gatherer-fishers but without substantial admixture.
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Agricultura , Arqueologia , Animais , Humanos , Europa (Continente) , Fazendas , FazendeirosRESUMO
From age 5 to 7, there are remarkable improvements in children's cognitive abilities ("5-7 shift"). In many countries, including Germany, formal schooling begins in this age range. It is, thus, unclear to what extent exposure to formal schooling contributes to the "5-7 shift." In this longitudinal study, we investigated if schooling acts as a catalyst of maturation. We tested 5-year-old children who were born close to the official cutoff date for school entry and who were still attending a play-oriented kindergarten. One year later, the children were tested again. Some of the children had experienced their first year of schooling whereas the others had remained in kindergarten. Using 2 functional magnetic resonance imaging tasks that assessed episodic memory formation (i.e., subsequent memory effect), we found that children relied strongly on the medial temporal lobe (MTL) at both time points but not on the prefrontal cortex (PFC). In contrast, older children and adults typically show subsequent memory effects in both MTL and PFC. Both children groups improved in their memory performance, but there were no longitudinal changes nor group differences in neural activation. We conclude that successful memory formation in this age group relies more heavily on the MTL than in older age groups.
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Educação , Memória/fisiologia , Envelhecimento/fisiologia , Encéfalo/diagnóstico por imagem , Criança , Pré-Escolar , Escolaridade , Feminino , Alemanha , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Memória Episódica , Rememoração Mental , Jogos e Brinquedos , Córtex Pré-Frontal/fisiologia , Lobo Temporal/fisiologiaRESUMO
The oral 13C-bicarbonate technique (o13CBT) can be used for short-term measurements of CO2 production (RCO2) and energy expenditure (EEx). The method relies on appropriate estimates for the respiratory quotient (RQ) and recovery factor (RF) of 13C. Four Retriever dogs were included in four experiments to validate the o13CBT against indirect calorimetry (IC), and determine RQ and RF; Expt. 1: feeding different protein:fat:carbohydrate ratios [in % of metabolisable energy]: 25:33:42 in a maintenance (Mnt.) diet; 38:26:36 in a high-protein high-fibre (HFibre) diet and 27:56:17 in a high-fat (HFat) diet, simultaneously with start of measurements (T0); Expt. 2: the Mnt. diet at T0 or 4 h postprandial (T4); Expt. 3: T4 at different ambient temperatures, 22°C and 15°C; Expt. 4: T4 after 1 h physical activity. The RCO2 and EEx were determined from the respiration chamber measurements made simultaneously with IC and the o13CBT (o13CBTonline), and in Expts. 1 and 2, also on two consecutive days using o13CBT with collection of breath into breath bags (o13CBTbreathbags). The RQ values obtained at T0 reflected dietary compositions, with the highest least square mean (LSM) of 0.954 for the Mnt. diet, 0.905 for the HFibre and 0.877 for the HFat diet (p < 0.05). An increased interval between meal and measurement period decreased RQ significantly (p < 0.05) in Expt. 2, LSM being 0.954 at T0 and 0.909 at T4. Ambient temperature (Expt. 3) and physical activity (Expt. 4) did not influence postprandial RQ. The RF values were not significantly affected by diet (Expt. 1). Measurements starting at T0 (Expt. 2) resulted in higher (p < 0.05) RF values than at T4 (LSM = 0.971 and 0.836, respectively). The ambient temperatures (Expt. 3) did not influence postprandial RF. However, when dogs were physically active prior to measurements (Expt. 4), RF values (LSM = 1.019) were higher (p < 0.05) than when resting only (LSM = 0.836). Calculations based on RQ and RF determined in each experiment resulted in RCO2 and EEx values which were not different regardless of method used, except for Expt. 1 where EEx-values [kJ · kg BW-0.75 · d-1] were higher (p < 0.05) when measured with o13CBTbreathbags (460) than by IC (421) and o13CBTonline (420). Provided accurate RQ and RF values, the o13CBTbreathbags can be used as an independent and minimally invasive research tool to determine EEx in dogs under carefully standardised conditions.
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Bicarbonatos , Dieta , Ração Animal/análise , Animais , Calorimetria Indireta/veterinária , Dieta/veterinária , Cães , Metabolismo EnergéticoRESUMO
BACKGROUND: Chromosome 8q24 has emerged as an important genetic susceptibility region for several cancers, including prostate cancer; however, little is known about the contribution of DNA methylation in this region to risk. METHODS: We prospectively evaluated DNA methylation at 8q24 in relation to prostate cancer using pre-diagnostic blood samples from 694 prostate cancer cases (including 172 aggressive cases) and 703 controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We used logistic regression to estimate odds ratios and 95% confidence intervals. RESULTS: Although none remained significant after adjustment for multiple testing (q>0.05), of the 50 CpG sites meeting quality control, we identified 8 sites that were nominally associated with prostate cancer (Ptrend<0.05), including 6 correlated (Spearman ρ: 0.20-0.52) sites in POU5F1B and 2 intergenic sites (most significant site: Chr8:128428897 in POU5F1B, Ptrend=0.01). We also identified two correlated (ρ=0.39) sites in MYC (Chr8:128753187 and Chr8:128753154) that were associated with aggressive (Ptrend=0.02 and 0.03), but not non-aggressive disease (Ptrend=0.70 and 0.20; Pheterogeneity=0.01 and 4.6 × 10-3). These findings persisted after adjustment for the top 8q24 prostate cancer variants in our study. CONCLUSIONS: Although requiring replication, our findings provide some evidence that 8q24 DNA methylation levels may be associated with prostate cancer risk.
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Cromossomos Humanos Par 8 , Metilação de DNA , DNA/sangue , Genes myc , Proteínas de Homeodomínio/genética , Neoplasias da Próstata/genética , Idoso , Estudos de Casos e Controles , Ilhas de CpG , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de RiscoRESUMO
Domestication is a multifaceted evolutionary process, involving changes in individual genes, genetic interactions, and emergent phenotypes. There has been extensive discussion of the phenotypic characteristics of plant domestication, and recent research has started to identify the specific genes and mutational mechanisms that control domestication traits. However, there is an apparent disconnect between the simple genetic architecture described for many crop domestication traits, which should facilitate rapid phenotypic change under selection, and the slow rate of change reported from the archeobotanical record. A possible explanation involves the middle ground between individual genetic changes and their expression during development, where gene-by-gene (epistatic) and gene-by-environment interactions can modify the expression of phenotypes and opportunities for selection. These aspects of genetic architecture have the potential to significantly slow the speed of phenotypic evolution during crop domestication and improvement. Here we examine whether epistatic and gene-by-environment interactions have shaped how domestication traits have evolved. We review available evidence from the literature, and we analyze two domestication-related traits, shattering and flowering time, in a mapping population derived from a cross between domesticated foxtail millet and its wild progenitor. We find that compared with wild progenitor alleles, those favored during domestication often have large phenotypic effects and are relatively insensitive to genetic background and environmental effects. Consistent selection should thus be able to rapidly change traits during domestication. We conclude that if phenotypic evolution was slow during crop domestication, this is more likely due to cultural or historical factors than epistatic or environmental constraints.
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Produtos Agrícolas/genética , Epistasia Genética , Interação Gene-Ambiente , Genes de Plantas/genética , Flores/genética , Flores/fisiologia , Loci Gênicos/genética , Fenótipo , Característica Quantitativa HerdávelRESUMO
BACKGROUND: Development of crop varieties with high nitrogen use efficiency (NUE) is crucial for minimizing N loss, reducing environmental pollution and decreasing input cost. Maize is one of the most important crops cultivated worldwide and its productivity is closely linked to the amount of fertilizer used. A survey of the transcriptomes of shoot and root tissues of a maize hybrid line and its two parental inbred lines grown under sufficient and limiting N conditions by mRNA-Seq has been conducted to have a better understanding of how different maize genotypes respond to N limitation. RESULTS: A different set of genes were found to be N-responsive in the three genotypes. Many biological processes important for N metabolism such as the cellular nitrogen compound metabolic process and the cellular amino acid metabolic process were enriched in the N-responsive gene list from the hybrid shoots but not from the parental lines' shoots. Coupled to this, sugar, carbohydrate, monosaccharide, glucose, and sorbitol transport pathways were all up-regulated in the hybrid, but not in the parents under N limitation. Expression patterns also differed between shoots and roots, such as the up-regulation of the cytokinin degradation pathway in the shoots of the hybrid and down-regulation of that pathway in the roots. The change of gene expression under N limitation in the hybrid resembled the parent with the higher NUE trait. The transcript abundances of alleles derived from each parent were estimated using polymorphic sites in mapped reads in the hybrid. While there were allele abundance differences, there was no correlation between these and the expression differences seen between the hybrid and the two parents. CONCLUSIONS: Gene expression in two parental inbreds and the corresponding hybrid line in response to N limitation was surveyed using the mRNA-Seq technology. The data showed that the three genotypes respond very differently to N-limiting conditions, and the hybrid clearly has a unique expression pattern compared to its parents. Our results expand our current understanding of N responses and will help move us forward towards effective strategies to improve NUE and enhance crop production.
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Quimera/genética , Genoma de Planta , Nitrogênio/metabolismo , Zea mays/genética , Zea mays/metabolismo , Quimera/crescimento & desenvolvimento , Quimera/metabolismo , Citocininas/metabolismo , Regulação para Baixo , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Proteínas de Transporte de Monossacarídeos/genética , Proteínas de Transporte de Monossacarídeos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Brotos de Planta/genética , Brotos de Planta/metabolismo , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/metabolismo , Transcriptoma , Regulação para Cima , Zea mays/crescimento & desenvolvimentoRESUMO
BACKGROUND: Genomic technologies such as genetic testing and precision treatments are rapidly becoming routine in oncology care, and nurses play an increasingly important role in supporting the growing demands for genomics-informed healthcare. Policy infrastructure such as competencies, standards, scope of practice statements, and education and curriculum frameworks are urgently needed to guide these practice and education changes. PURPOSE: This study is part of a larger three-phase project to develop recommendations and catalyze action for genomics-informed oncology nursing education and practice for the Canadian Association of Nurses in Oncology and the Canadian Association of Schools of Nursing. This phase aimed to enhance understanding of policy needs and action drivers for genomics-informed oncology nursing education and practice through the perspectives of Canadian oncology nurses and patient partners. METHODS: Interpretive description methodology guided the study. Twenty semi-structured virtual interviews were conducted; 17 with oncology nurses in various domains of practice, and three with patient partner representatives. Data collection and analysis occurred concurrently. RESULTS: Our analysis identified three themes: 1) nurses and patients recognize that it is time for action, 2) nurses and patients see advantages to executing intentional, strategic, and collaborative policy development, and 3) leadership and advocacy are required to drive action. CONCLUSION: Nursing policy infrastructure is required to increase genomic literacy, support nurses in providing safe patient care, and establish clear roles, responsibilities, and accountabilities within the interdisciplinary team. Strong leadership and advocacy at the practice, organizational, and systems levels are vital to accelerating action.
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A regulated stress response is essential for healthy child growth and development trajectories. We conducted a cluster-randomized trial in rural Bangladesh (funded by the Bill & Melinda Gates Foundation, ClinicalTrials.gov NCT01590095) to assess the effects of an integrated nutritional, water, sanitation, and handwashing intervention on child health. We previously reported on the primary outcomes of the trial, linear growth and caregiver-reported diarrhea. Here, we assessed additional prespecified outcomes: physiological stress response, oxidative stress, and DNA methylation (N = 759, ages 1-2 years). Eight neighboring pregnant women were grouped into a study cluster. Eight geographically adjacent clusters were block-randomized into the control or the combined nutrition, water, sanitation, and handwashing (N + WSH) intervention group (receiving nutritional counseling and lipid-based nutrient supplements, chlorinated drinking water, upgraded sanitation, and handwashing with soap). Participants and data collectors were not masked, but analyses were masked. There were 358 children (68 clusters) in the control group and 401 children (63 clusters) in the intervention group. We measured four F2-isoprostanes isomers (iPF(2α)-III; 2,3-dinor-iPF(2α)-III; iPF(2α)-VI; 8,12-iso-iPF(2α)-VI), salivary alpha-amylase and cortisol, and methylation of the glucocorticoid receptor (NR3C1) exon 1F promoter including the NGFI-A binding site. Compared with control, the N + WSH group had lower concentrations of F2-isoprostanes isomers (differences ranging from -0.16 to -0.19 log ng/mg of creatinine, P < 0.01), elevated post-stressor cortisol (0.24 log µg/dl; P < 0.01), higher cortisol residualized gain scores (0.06 µg/dl; P = 0.023), and decreased methylation of the NGFI-A binding site (-0.04; P = 0.037). The N + WSH intervention enhanced adaptive responses of the physiological stress system in early childhood.
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Metilação de DNA , Epigênese Genética , Desinfecção das Mãos , Saneamento , Humanos , Feminino , Bangladesh , Masculino , Lactente , Pré-Escolar , Gravidez , Estresse Oxidativo , Estresse Fisiológico , População Rural , Adulto , Diarreia/prevenção & controle , Receptores de Glucocorticoides/metabolismo , Receptores de Glucocorticoides/genéticaRESUMO
BACKGROUND: Hundreds of millions of children in low- and middle-income countries are exposed to chronic stressors, such as poverty, poor sanitation and hygiene, and sub-optimal nutrition. These stressors can have physiological consequences for children and may ultimately have detrimental effects on child development. This study explores associations between biological measures of chronic stress in early life and developmental outcomes in a large cohort of young children living in rural Bangladesh. METHODS: We assessed physiologic measures of stress in the first two years of life using measures of the hypothalamic-pituitary-adrenal (HPA) axis (salivary cortisol and glucocorticoid receptor gene methylation), the sympathetic-adrenal-medullary (SAM) system (salivary alpha-amylase, heart rate, and blood pressure), and oxidative status (F2-isoprostanes). We assessed child development in the first two years of life with the MacArthur-Bates Communicative Development Inventories (CDI), the WHO gross motor milestones, and the Extended Ages and Stages Questionnaire (EASQ). We compared development outcomes of children at the 75th and 25th percentiles of stress biomarker distributions while adjusting for potential confounders using generalized additive models, which are statistical models where the outcome is predicted by a potentially non-linear function of predictor variables. RESULTS: We analyzed data from 684 children (49% female) at both 14 and 28 months of age; we included an additional 765 children at 28 months of age. We detected a significant relationship between HPA axis activity and child development, where increased HPA axis activity was associated with poor development outcomes. Specifically, we found that cortisol reactivity (coefficient -0.15, 95% CI (-0.29, -0.01)) and post-stressor levels (coefficient -0.12, 95% CI (-0.24, -0.01)) were associated with CDI comprehension score, post-stressor cortisol was associated with combined EASQ score (coefficient -0.22, 95% CI (-0.41, -0.04), and overall glucocorticoid receptor methylation was associated with CDI expression score (coefficient -0.09, 95% CI (-0.17, -0.01)). We did not detect a significant relationship between SAM activity or oxidative status and child development. CONCLUSIONS: Our observations reveal associations between the physiological evidence of stress in the HPA axis with developmental status in early childhood. These findings add to the existing evidence exploring the developmental consequences of early life stress.
Assuntos
Desenvolvimento Infantil , Hidrocortisona , Criança , Humanos , Pré-Escolar , Feminino , Masculino , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Receptores de Glucocorticoides/metabolismo , Bangladesh , Sistema Hipófise-Suprarrenal/metabolismo , Biomarcadores/metabolismo , Saliva/metabolismo , Estresse Psicológico/metabolismoRESUMO
Background: Hundreds of millions of children in low- and middle-income countries are exposed to chronic stressors, such as poverty, poor sanitation and hygiene, and sub-optimal nutrition. These stressors can have physiological consequences for children and may ultimately have detrimental effects on child development. This study explores associations between biological measures of chronic stress in early life and developmental outcomes in a large cohort of young children living in rural Bangladesh. Methods: We assessed physiologic measures of stress in the first two years of life using measures of the hypothalamic-pituitary-adrenal (HPA) axis (salivary cortisol and glucocorticoid receptor gene methylation), the sympathetic-adrenal-medullary (SAM) system (salivary alpha-amylase, heart rate, and blood pressure), and oxidative status (F2-isoprostanes). We assessed child development in the first two years of life with the MacArthur-Bates Communicative Development Inventories (CDI), the WHO gross motor milestones, and the Extended Ages and Stages Questionnaire (EASQ). We compared development outcomes of children at the 75th and 25th percentiles of stress biomarker distributions while adjusting for potential confounders (hereafter referred to as contrasts) using generalized additive models, which are statistical models where the outcome is predicted by a potentially non-linear function of predictor variables. Results: We analyzed data from 684 children (49% female) at both 14 and 28 months of age; we included an additional 765 children at 28 months of age. We observed 135 primary contrasts of the differences in child development outcomes at the 75th and 25th percentiles of stress biomarkers, where we detected significant relationships in 5 out of 30 contrasts (17%) of HPA axis activity, 1 out of 30 contrasts (3%) of SAM activity, and 3 out of 75 contrasts (4%) of oxidative status. These findings revealed that measures of HPA axis activity were associated with poor development outcomes. We did not find consistent evidence that markers of SAM system activity or oxidative status were associated with developmental status. Conclusions: Our observations reveal associations between the physiological evidence of stress in the HPA axis with developmental status in early childhood. These findings add to the existing evidence exploring the developmental consequences of early life stress.
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Aversive events sometimes turn into intrusive memories. However, prior evidence indicates that such memories can be controlled via a mechanism of retrieval suppression. Here, we test the hypothesis that suppression exerts a sustained influence on memories by deteriorating their neural representations. This deterioration, in turn, would hinder their subsequent reactivation and thus impoverish the vividness with which they can be recalled. In an fMRI study, participants repeatedly suppressed memories of aversive scenes. As predicted, this process rendered the memories less vivid. Using a pattern classifier, we observed that suppression diminished the neural reactivation of scene information both globally across the brain and locally in the parahippocampal cortices. Moreover, the decline in vividness was associated with reduced reinstatement of unique memory representations in right parahippocampal cortex. These results support the hypothesis that suppression weakens memories by causing a sustained reduction in the potential to reactivate their neural representations.
Assuntos
Imageamento por Ressonância Magnética , Rememoração Mental , Encéfalo/fisiologia , Mapeamento Encefálico , Humanos , Rememoração Mental/fisiologiaRESUMO
Genomics is having a profound impact on every aspect of healthcare. To support nurses to develop genomic literacy and integrate genomics into care, an engagement framework was created. The framework uses principles of nursing intraprofessional collaboration, the knowledge-to-action cycle and the diffusion of innovations theory. This framework was used to identify six key priorities for action and leadership strategies to accelerate and sustain the nurses' engagement with genomics. With leadership and genomic literacy, nurses can fully participate in the creation and implementation of new care pathways, deliver education, advance research linked to genomics and improve patient experience and health outcomes.
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Competência Clínica , Liderança , Canadá , Genômica/educação , Conhecimentos, Atitudes e Prática em Saúde , HumanosRESUMO
Mucopolysaccharidosis type IIIA (MPS IIIA, Sanfilippo syndrome) is a fatal inherited lysosomal storage disease accompanied by progressive neurologic degeneration. The gene underlying MPS IIIA, SGSH, encodes a lysosomal enzyme, N-sulfoglucosamine sulfohydrolase (sulfamidase). Mutational analysis of a large cohort of MPS IIIA patients showed a correlation of the missense mutation p.Ser298Pro and a slowly progressive course of the disease. We report here on the expression of the mutant p.Ser298Pro sulfamidase in BHK cells retaining low residual activity. Pulse-chase experiments showed that rapid degradation is responsible for the low steady state level of the mutant protein. Processing and secretion of p.Ser298Pro sulfamidase suggests that small amounts of the newly synthesized enzyme are transported to lysosomes. Most of the mutant sulfamidase exits the endoplasmic reticulum for proteasomal degradation. The ability to predict the clinical course of MPS IIIA in patients with the p.Ser298Pro mutation, as well as the residual enzymatic activity, and the reduced stability of the mutant sulfamidase suggest that this subgroup of patients is especially well suited to early sulfamidase replacement therapy or treatment with selective pharmacological chaperones.
Assuntos
Hidrolases/genética , Hidrolases/metabolismo , Mucopolissacaridose III/enzimologia , Mucopolissacaridose III/genética , Fenótipo , Complexo de Endopeptidases do Proteassoma/metabolismo , Adolescente , Adulto , Substituição de Aminoácidos/genética , Animais , Linhagem Celular , Criança , Pré-Escolar , Cricetinae , Estabilidade Enzimática/genética , Feminino , Estudos de Associação Genética , Humanos , Masculino , Mutação/genética , Adulto JovemRESUMO
Epidemiological studies have established obesity as a critical risk factor for postmenopausal breast cancer (post-BC), whereas a reverse association holds prior to menopause. A significant scientific gap exists in understanding the mechanism(s) underpinning this epidemiological phenomenon, particularly the reverse association between obesity and premenopausal breast cancer (pre-BC). This study aimed to understand how folate metabolism and DNA methylation inform the association between obesity and pre-BC. Fifty normal breast tissue samples were collected from premenopausal women who underwent reduction mammoplasty. We modified the Lactobacillus Casei microbiological folate assay and measured folate levels in our breast tissue samples. The DNA methylation of LINE-1, a biomarker of genome-wide methylation, and the expression of a panel of breast cancer-related genes was measured by pyrosequencing and real-time PCR. We found that a high BMI is associated with an increase of folate levels in mammary tissue, with an increase of 2.65 ng/g of folate per every 5-unit increase of BMI (p < 0.05). LINE-1 DNA methylation was significantly associated with BMI (p < 0.05), and marginally associated with folate concentration (p = 0.087). A high expression of SFRP1 was observed in subjects with high BMI or high folate status (p < 0.05). This study demonstrated that, in premenopausal women, obesity is associated with increased mammary folate status, genome-wide DNA methylation and SFRP1 gene expression. Our findings indicated that the improved folate and epigenetic status represents a novel mechanism responsible for the reverse association between obesity and pre-BC.
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Neoplasias da Mama , Metilação de DNA , Índice de Massa Corporal , Neoplasias da Mama/genética , Feminino , Ácido Fólico , Expressão Gênica , Humanos , Obesidade/genéticaRESUMO
It is still debated whether suppressing the retrieval of unwanted memories causes forgetting and whether this constitutes a beneficial mechanism. To shed light on these 2 questions, we scrutinize the evidence for such suppression-induced forgetting (SIF) and examine whether it is deficient in psychological disorders characterized by intrusive thoughts. Specifically, we performed a focused meta-analysis of studies that have used the think/no-think procedure to test SIF in individuals either affected by psychological disorders or exhibiting high scores on related traits. Overall, across 96 effects from 25 studies, we found that avoiding retrieval leads to significant forgetting in healthy individuals, with a small to moderate effect size (0.28, 95% CI [0.14, 0.43]). Importantly, this effect was indeed larger than for more anxious (-0.21, 95% CI [-0.41, -0.02]) or depressed individuals (0.05, 95% CI [-0.19, 0.29])-though estimates for the healthy may be inflated by publication bias. In contrast, individuals with a stronger repressive coping style showed greater SIF (0.42, 95% CI [0.32, 0.52]). Furthermore, moderator analyses revealed that SIF varied with the exact suppression mechanism that participants were instructed to engage. For healthy individuals, the effect sizes were considerably larger when instructions induced specific mechanisms of direct retrieval suppression or thought substitution than when they were unspecific. These results suggest that intact suppression-induced forgetting is a hallmark of psychological well-being, and that inducing more specific suppression mechanisms fosters voluntary forgetting. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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Transtornos Mentais/psicologia , Repressão Psicológica , Adulto , Feminino , Humanos , MasculinoRESUMO
Increasing evidence suggests a role of epigenetic mechanisms at chromosome 8q24, an important cancer genetic susceptibility region, in prostate cancer. We investigated whether MYC DNA methylation at 8q24 (six CpG sites from exon 3 to the 3' UTR) in prostate tumor was associated with tumor aggressiveness (based on Gleason score, GS), and we incorporated RNA expression data to investigate the function. We accessed radical prostatectomy tissue for 50 Caucasian and 50 African American prostate cancer patients at the University of Maryland Medical Center, selecting an equal number of GS 6 and GS 7 cases per group. MYC DNA methylation was lower in tumor than paired normal prostate tissue for all six CpG sites (median difference: -14.74 to -0.20 percentage points), and we observed similar results for two nearby sites in The Cancer Genome Atlas (p < 0.0001). We observed significantly lower methylation for more aggressive (GS 7) than less aggressive (GS 6) tumors for three exon 3 sites (for CpG 212 (chr8:128753145), GS 6 median = 89.7%; GS 7 median = 85.8%; p-value = 9.4 × 10-4). MYC DNA methylation was not associated with MYC expression, but was inversely associated with PRNCR1 expression after multiple comparison adjustment (q-value = 0.04). Findings suggest that prostate tumor MYC exon 3 hypomethylation is associated with increased aggressiveness.
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Biomarcadores Tumorais/genética , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Proteínas Proto-Oncogênicas c-myc/genética , Adulto , Idoso , Estudos de Coortes , Ilhas de CpG/genética , Metilação de DNA , Epigênese Genética , Éxons/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Próstata/cirurgia , Prostatectomia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , RNA Longo não Codificante/genéticaRESUMO
The photodynamic bactericidal effect of the photoactive dyes acriflavine neutral, rose bengal, phloxine B, and malachite green (oxalate salt) at concentrations of 5 to 5,000 microg/ml against two gram-negative strains (Escherichia coli LJH 128 and Salmonella Typhimurium C1058), two gram-positive strains (Bacillus sp. C578 and Listeria monocytogenes LJH 375), and yeast (Saccharomyces cerevisiae C1172) was investigated. Incubation of the investigated bacteria with acriflavine neutral under illumination resulted in a significant reduction in cell numbers compared with dark incubation. Rose bengal caused a significant killing effect for bacteria incubated both in the dark and under illumination. Malachite green was active against gram-positive bacteria under illumination and did not affect gram-negative bacteria or yeasts. Incubation with phloxine B resulted in a significant decline in cell numbers for gram-positive bacteria, both in the dark and under illumination; gram-negative bacteria and yeasts were unaffected. Conjugation of rose bengal and phloxine B with poly(vinyl amine) resulted in an enhanced bactericidal effect during both dark and light incubation. This was explained by electrostatic interaction of the polymer with the cell surface, which resulted in closer contact of the photoactive dye and cell. No killing effect was observed for yeasts incubated with dye conjugates. Filter paper treated with dye-poly(vinyl amine) conjugates showed high photodynamic bactericidal activity against the bacterial strains, but not against the yeasts. The extent of bacterial killing depended on the nature and concentration of the dye conjugate and the type of microorganism. The presented data suggest that a photodynamic approach for constructing "self-decontaminating" materials has potential.
Assuntos
Corantes/farmacologia , Manipulação de Alimentos/métodos , Indústria de Processamento de Alimentos/métodos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Bacillus/efeitos dos fármacos , Bacillus/crescimento & desenvolvimento , Bacillus/efeitos da radiação , Contagem de Colônia Microbiana , Qualidade de Produtos para o Consumidor , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Sinergismo Farmacológico , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/efeitos da radiação , Doenças Transmitidas por Alimentos/prevenção & controle , Humanos , Listeria monocytogenes/efeitos dos fármacos , Listeria monocytogenes/crescimento & desenvolvimento , Listeria monocytogenes/efeitos da radiação , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/crescimento & desenvolvimento , Saccharomyces cerevisiae/efeitos da radiação , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/crescimento & desenvolvimento , Salmonella typhimurium/efeitos da radiaçãoRESUMO
Early life stress (ELS) or alcohol consumption can influence DNA methylation and affect gene expression. Monoamine oxidase A (Maoa) encodes the enzyme that metabolizes monoaminergic neurotransmitters crucial for the stress response, alcohol reward, and reinforcement. Previously, we reported lower Maoa expression in the nucleus accumbens and dorsal striatum of male rats exposed to ELS during the first three postnatal weeks, and to voluntary alcohol consumption in adulthood, compared with controls. The present study continued to investigate the effect of ELS and alcohol consumption on Maoa methylation, and its relation to Maoa expression in these animals. We selected candidate CpGs after performing next-generation bisulfite sequencing of the Maoa promoter, intron 1-5, and exons 5 and 6, together composed of 107 CpGs (5'-cytosine-phosphate-guanosine-3'), in a subgroup of rats. Pyrosequencing was used to analyze the methylation of 10 candidate CpGs in the promoter and intron 1 in the entire sample. ELS and alcohol displayed an interactive effect on CpG-specific methylation in the dorsal striatum. CpG-specific methylation correlated with Maoa expression, corticosterone levels, and alcohol consumption in a brain region-specific manner. CpG-specific methylation in the Maoa promoter was a potential moderator of the interaction of ELS with alcohol consumption on Maoa expression in the NAc. However, the findings were sparse, did not survive correction for multiple testing, and the magnitude of differences in methylation levels was small. In conclusion, CpG-specific Maoa methylation in the promoter and intron 1 may associate with ELS, alcohol consumption, and Maoa expression in reward-related brain regions.
Assuntos
Consumo de Bebidas Alcoólicas/genética , Metilação de DNA , Privação Materna , Monoaminoxidase/genética , Estresse Psicológico , Animais , Ilhas de CpG , Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Masculino , Núcleo Accumbens/metabolismo , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas , Controle de Qualidade , Ratos , Ratos Wistar , RecompensaRESUMO
Mucopolysaccharidosis type IIIA (MPS IIIA, Sanfilippo A syndrome) is caused by mutations in the N-sulfoglucosamine sulfohydrolase (SGSH) gene and the resulting defective lysosomal degradation of the glycosaminoglycan heparan sulfate. The onset and progression of the disease are highly variable. Seventy-five mutations distributed over the SGSH gene have been described. We here report on the analysis of the natural course of the disease in 54 MPS IIIA patients through the use of a detailed questionnaire and four-point scoring system and an examination of the underlying mutations. By assessing the degree of developmental regression over time a group of seven patients with a slowly progressive course of the disease were identified. In these seven patients and in 3 other mildly affected patients the missense mutation c.892T>C (p.Ser298Pro) was found on one allele. These patients showed a lower frequency and later onset of the typical symptoms of the disease. The onset of regression in speech abilities and cognitive functions were delayed by 0.7 and 0.8 years, respectively, and the onset of regression of motor functions occurred 6.1 years later than in all other MPS IIIA patients. Severe regression in speech, cognitive and motor functions were delayed by 5, 5.9, and 11.2 years, respectively. These data suggest that in MPS IIIA patients carrying the mutation p.Ser298Pro a slowly progressive phenotype can be predicted and this may have an important impact on parental counselling and therapeutic interventions.
Assuntos
Hidrolases/genética , Mucopolissacaridose III/genética , Mutação , Prolina/genética , Serina/genética , Adolescente , Adulto , Criança , Pré-Escolar , Progressão da Doença , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Mucopolissacaridose III/fisiopatologia , FenótipoRESUMO
Collagenous lectins are a family of soluble pattern recognition receptors that play an important role in innate immune resistance to infectious disease. Through recognition of carbohydrate motifs on the surface of pathogens, some collagenous lectins can activate the lectin pathway of complement, providing an effective means of host defense. Genetic polymorphisms in collagenous lectins have been shown in several species to predispose animals to a variety of infectious diseases. Infectious diseases are an important cause of morbidity in horses, however little is known regarding the role of equine collagenous lectins. Using a high-throughput, targeted re-sequencing approach, the relationship between genetic variation in equine collagenous lectin genes and susceptibility to disease was investigated. DNA was isolated from tissues obtained from horses submitted for post-mortem examination. Animals were divided into two populations, those with infectious or autoinflammatory diseases (nâ¯=â¯37) and those without (nâ¯=â¯52), and then subdivided by dominant pathological process for a total of 21 pools, each containing 4-5 horses. DNA was extracted from each horse and pooled in equimolar amounts, and the exons, introns, upstream (approximately 50â¯kb) and downstream (approximately 3â¯kb) regulatory regions for the 11 equine collagenous lectin genes and related MASP genes were targeted for re-sequencing. A custom target capture kit was used to prepare a sequencing library, which was sequenced on an Illumina MiSeq. After implementing quality control filters, 4559 variants were identified. Of these, 92 were present in the coding regions (43 missense, 1 nonsense, and 48 synonymous), 1414 in introns, 3029 in the upstream region, and 240 in the downstream region. In silico analysis of the missense short nucleotide variants identified 12 mutations with potential to disrupt collagenous lectin protein structure or function, 280 mutations located within predicted transcription factor binding sites, and 95 mutations located within predicted microRNA binding elements. Analysis of allelic association identified 113 mutations that segregated between the infectious/autoinflammatory and non-infectious populations. The variants discovered in this experiment represent potential genetic contributors to disease susceptibility of horses, and will serve as candidates for further population-level genotyping. This study contributes to the growing body of evidence that pooled, high-throughput sequencing is a viable strategy for cost-effective variant discovery.