Losing control to bad relatives.
Ontology highlight
ABSTRACT:
SUBMITTER: Afshar-Kharghan V
PROVIDER: S-EPMC8225919 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundDNA methylation is an epigenetic chromatin mark that allows heterochromatin formation and gene silencing. It has a fundamental role in preserving genome stability (including chromosome stability) by controlling both gene expression and chromatin structure. Therefore, the onset of an incorrect pattern of DNA methylation is potentially dangerous for the cells. This is particularly important with respect to repetitive elements, which constitute the third of the human genome.Main bodyRepetitive sequences are involved in several cell processes, however, due to their intrinsic nature, they can be a source of genome instability. Thus, most repetitive elements are usually methylated to maintain a heterochromatic, repressed state. Notably, there is increasing evidence showing that repetitive elements (satellites, long interspersed nuclear elements (LINEs), Alus) are frequently hypomethylated in various of human pathologies, from cancer to psychiatric disorders. Repetitive sequences' hypomethylation correlates with chromatin relaxation and unscheduled transcription. If these alterations are directly involved in human diseases aetiology and how, is still under investigation.ConclusionsHypomethylation of different families of repetitive sequences is recurrent in many different human diseases, suggesting that the methylation status of these elements can be involved in preservation of human health. This provides a promising point of view towards the research of therapeutic strategies focused on specifically tuning DNA methylation of DNA repeats.
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Project description:Adaptability and "emergent" properties are the dominant characteristics of complex systems, whether naturally occurring or engineered. Structurally, a complex system might be made up of a large number of simpler components, or it might be formed from hierarchies of smaller numbers of interacting subsystems and work together to produce a defined function. The nucleus of a cell has all of these features, many of which may become disrupted in cancer and other disease states. The general view is that cancer progresses gradually over time; cells become premalignant, then increasingly abnormal before they become cancerous. However, recent work by Stephens et al. (2011) has revealed that cancer can emerge much more rapidly. Based on DNA sequences from multiple cancer samples of various types, they show that cancer can arise suddenly from a single catastrophic event that causes massive genomic rearrangement.
| S-EPMC3260564 | biostudies-literature
Project description:Unwanted memories often enter conscious awareness when individuals confront reminders. People vary widely in their talents at suppressing such memory intrusions; however, the factors that govern suppression ability are poorly understood. We tested the hypothesis that successful memory control requires sleep. Following overnight sleep or total sleep deprivation, participants attempted to suppress intrusions of emotionally negative and neutral scenes when confronted with reminders. The sleep-deprived group experienced significantly more intrusions (unsuccessful suppressions) than the sleep group. Deficient control over intrusive thoughts had consequences: Whereas in rested participants suppression reduced behavioral and psychophysiological indices of negative affect for aversive memories, it had no such salutary effect for sleep-deprived participants. Our findings raise the possibility that sleep deprivation disrupts prefrontal control over medial temporal lobe structures that support memory and emotion. These data point to an important role of sleep disturbance in maintaining and exacerbating psychiatric conditions characterized by persistent, unwanted thoughts.
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Project description:In the UK, the majority of imported malaria infections occur in the London area among UK residents of African origin who travel to Africa visiting friends and relatives (VFRs). Effective malaria prevention measures are available but there is little understanding of the factors that enhance and constrain their use among VFRs.Semi-structured interviews were undertaken with Africans resident in London who visited friends and relatives in Nigeria and Ghana (n = 20) and with African VFRs recently treated for malaria (n = 6). Data collection took place between December 2007 and February 2011. Information on migration patterns and travel of respondents was collected and the data were analysed using a framework analysis approach.Knowledge of the link between mosquitoes and malaria was high. Factors influencing the use of mosquito avoidance methods included knowledge about the local environment, perceptions of the inevitability of contracting malaria, and a desire to fit with the norms of host families. Previous experience of bed nets, and the belief that more modern ways of preventing mosquito bites were available deterred people from using them. Chemoprophylaxis use was varied and influenced by: perceptions about continuing immunity to malaria; previous experiences of malaria illness; the cost of chemoprophylaxis; beliefs about the likely severity of malaria infections; the influence of friends in the UK; and, the way malaria is perceived and managed in Nigeria and Ghana. Malaria treatment was considered by many to be superior in Nigeria and Ghana than in the UK. A conceptual framework was developed to illustrate the manner in which these factors interact to affect malaria decisions.The use of malaria prevention among VFRs needs to be understood not only in terms of individual risk factors but also in relation to the context in which decisions are made. For VFRs, malaria decisions are undertaken across two distinct social and environmental contexts and within the structural constraints associated with each. Strategies for reducing the burden of malaria among VFRs that ignore this complexity are likely to face challenges. New approaches that take account of contextual as well as individual factors are required.
| S-EPMC4118190 | biostudies-other
Project description:Invasive species have great ecological and economic impacts and are difficult to control once established, making the ability to understand and predict invasive behavior highly desirable. Preemptive measures to prevent potential invasive species from reaching new habitats are the most economically and environmentally efficient form of management. Darwin's naturalization hypothesis predicts that invaders less related to native flora are more likely to be successful than those that are closely related to natives. Here we test this hypothesis, using the weed-rich thistle tribe, Cardueae, in the California Floristic Province, a biodiversity hotspot, as our study system. An exhaustive molecular phylogenetic approach was used, generating and examining more than 100,000 likely phylogenies of the tribe based on nuclear and chloroplast DNA markers, representing the most in-depth reconstruction of the clade to date. Branch lengths separating invasive and noninvasive introduced taxa from native California taxa were used to represent phylogenetic distances between these groups and were compared at multiple biogeographical scales to ascertain whether invasive thistles are more or less closely related to natives than noninvasive introduced thistles are. Patterns within this highly supported clade show that not only are introduced thistles more closely related to natives more likely to be invasive, but these invasive species are also evolutionarily closer to native flora than by chance. This suggests that preadaptive traits are important in determining an invader's success. Such rigorous molecular phylogenetic analyses may prove a fruitful means for furthering our understanding of biological invasions and developing predictive frameworks for screening potential invasive taxa.
| S-EPMC3816436 | biostudies-literature
Project description:We introduce a method of estimating disease prevalence from case-control family study data. Case-control family studies are performed to investigate the familial aggregation of disease; families are sampled via either a case or a control proband, and the resulting data contain information on disease status and covariates for the probands and their relatives. Here, we introduce estimators for overall prevalence and for covariate-stratum-specific (e.g., sex-specific) prevalence. These estimators combine the proportion of affected relatives of control probands with the proportion of affected relatives of case probands and are designed to yield approximately unbiased estimates of their population counterparts under certain commonly made assumptions. We also introduce corresponding confidence intervals designed to have good coverage properties even for small prevalences. Next, we describe simulation experiments where our estimators and intervals were applied to case-control family data sampled from fictional populations with various levels of familial aggregation. At all aggregation levels, the resulting estimates varied closely and symmetrically around their population counterparts, and the resulting intervals had good coverage properties, even for small sample sizes. Finally, we discuss the assumptions required for our estimators to be approximately unbiased, highlighting situations where an alternative estimator based only on relatives of control probands may perform better.
| S-EPMC2933418 | biostudies-literature
Project description:Object relative clauses are harder to process than subject relative clauses. Under Grillo's (2009) Generalized Minimality framework, complexity effects of object relatives are construed as intervention effects, which result from an interaction between locality constraints on movement (Relativized Minimality) and the sentence processing system. Specifically, intervention of the subject DP in the movement dependency is expected to generate a minimality violation whenever processing limitations render the moved object underspecified, resulting in compromised comprehension. In the present study, assuming Generalized Minimality, we compared the processing of object relatives with the processing of subject control in ditransitives, which, like object relatives, instantiates a syntactic dependency across an intervening DP. This comparison is justified by the current debate on whether Control should be analyzed as movement: if control involves movement of the controller DP, as proposed by Hornstein (1999), a parallel between the processing of object relatives and subject control in ditransitives may be anticipated on the basis of intervention. In addition, we explored whether general cognitive factors contribute to complexity effects ascribed to movement across a DP. Sixty-nine adult speakers of European Portuguese read sentences and answered comprehension probes in a self-paced reading task with moving-window display, comprising four experimental conditions: Subject Relatives; Object Relatives; Subject Control; Object Control. Furthermore, participants performed four supplementary tasks, serving as measures of resistance to interference, lexical knowledge, working memory capacity and lexical access ability. The results from the reading task showed that whereas object relatives were harder to process than subject relatives, subject control was not harder to process than object control, arguing against recent movement accounts of control. Furthermore, we found that whereas object relative complexity effects assessed by response times to comprehension probes interacted with Reading Span, object relative complexity effects assessed by comprehension accuracy and reading times did not interact with any of the supplementary tasks. We discuss these results in light of Generalized Minimality and the hypothesis of modularity in syntactic processing (Caplan and Waters, 1999).
| S-EPMC7884622 | biostudies-literature
Project description:Ovulated eggs possess maternal apoptotic execution machinery that is inhibited for a limited time. The fertilized eggs switch off this time bomb whereas aged unfertilized eggs and parthenogenetically activated eggs fail to stop the timer and die. To investigate the nature of the molecular clock that triggers the egg decision of committing suicide, we introduce here Xenopus eggs as an in vivo system for studying the death of unfertilized eggs. We report that after ovulation, a number of eggs remains in the female body where they die by apoptosis. Similarly, ovulated unfertilized eggs recovered in the external medium die within 72 h. We showed that the death process depends on both cytochrome c release and caspase activation. The apoptotic machinery is turned on during meiotic maturation, before fertilization. The death pathway is independent of ERK but relies on activating Bad phosphorylation through the control of both kinases Cdk1 and JNK. In conclusion, the default fate of an unfertilized Xenopus egg is to die by a mitochondrial dependent apoptosis activated during meiotic maturation.
| S-EPMC3156807 | biostudies-literature
Project description:Background: The monitoring and management of blood glucose concentration are standard practices in critical settings as hyperglycaemia has been shown close association with poorer outcomes. Several meta-analyses have revealed that intensive glucose control has no benefit in decreasing short-term mortality among critically ill patients, while the studies these meta-analyses have incorporated have been largely divergent. We aim to perform a more comprehensive meta-analysis addressing this problem to provide stronger evidence. Methods: We conducted comprehensive searches for relevant randomized controlled studies in online databases, including the Cochrane Library, EMBASE, and PubMed databases, up to September 1, 2018. The clinical data, which included all-cause mortality, severe hypoglycemia, need for RRT, infection resulting in sepsis, ICU mortality, 90-day mortality, 180-day mortality, and hospital and ICU lengths of stay, were screened and analyzed after data extraction. We applied odds ratios (ORs) to analyze dichotomous outcomes and mean differences for continuous outcomes with a random effects model. Results: A total of 57 RCTs involving a total of 21840 patients were finally included. Patients admitted to the ICU who underwent intensive glucose control showed significantly reduced all-cause mortality (OR: 0.89; 95% CI: 0.80-1.00; P=0.04; I2=32%), reduced infection rate (OR: 0.65, 95% CI: 0.51-0.82, P=0.0002; I2=47%), a lower occurrence of acquired sepsis (OR: 0.80, 95% CI: 0.65-0.99, P=0.04; I2=0%) and shortened length of ICU stay (MD: -0.70, 95% CI: -1.21--0.19, P=0.007, I2=70%) when compared to the same parameters as those treated with the usual care strategy. However, patients in the intensive glucose control group presented with a significantly higher risk of severe hypoglycemia (OR: 5.63, 95% CI: 4.02-7.87, P<0.00001; I2=67%). Conclusions: Critically ill patients undergoing intensive glucose control showed significantly reduced all-cause mortality, length of ICU stay and incidence of acquired infection and sepsis compared to the same parameters in patients treated with the usual care strategy, while the intensive glucose control strategy was associated with higher occurrence of severe hypoglycemic events.
| S-EPMC7097913 | biostudies-literature
Project description:ObjectivesBeing a caregiver of an older adult is often associated with poor psychological outcomes and stress. Individual differences, such as personality, may moderate responses to caregiving. In this study, we examined (a) personality and psychological health of family caregivers compared to non-caregivers and (b) tested interactions between caregiver status and personality (both domains and facets) in predicting psychological outcomes.MethodsData were from an online sample of caregivers of older relatives (N = 491; 71.9% females) and matched controls (N = 491). Participants completed the Big Five Inventory-2 and a comprehensive set of psychological health and well-being measures.ResultsCompared to non-caregivers, caregivers had higher neuroticism, lower energy level (extraversion facet) and higher compassion (agreeableness facet). They also reported higher depression, anxiety, loneliness, and lower well-being and life satisfaction. Personality traits and facets had strong associations with psychological outcomes, and these associations were similar across the two groups. Only a few significant interactions between caregiver status and personality were found: For instance, higher neuroticism (in particular, higher scores on anxiety and depression facets) exacerbated anxiety among caregivers.ConclusionsPersonality is a relevant correlate of psychological health. In the context of caregiving, its assessment may help to identify caregivers at risk of poor outcomes and inform intervention programs. Further research is needed to replicate the findings and investigate longitudinal interrelations among variables.
| S-EPMC7606331 | biostudies-literature