Project description:The development of the fetal heart is exquisitely controlled by a multitude of factors, ranging from humoral to mechanical forces. The gatekeeper regulating many of these factors is the placenta, an external fetal organ. As such, resistance within the placental vascular bed has a direct influence on the fetal circulation and therefore, the developing heart. In addition, the placenta serves as the interface between the mother and fetus, controlling substrate exchange and release of hormones into both circulations. The intricate relationship between the placenta and fetal heart is appreciated in instances of clinical placental pathology. Abnormal umbilical cord insertion is associated with congenital heart defects. Likewise, twin-to-twin transfusion syndrome, where monochorionic twins have unequal sharing of their placenta due to inter-twin vascular anastomoses, can result in cardiac remodeling and dysfunction in both fetuses. Moreover, epidemiological studies have suggested a link between placental phenotypic traits and increased risk of cardiovascular disease in adult life. To date, the mechanistic basis of the relationships between the placenta, fetal heart development and later risk of cardiac dysfunction have not been fully elucidated. However, studies using environmental exposures and gene manipulations in experimental animals are providing insights into the pathways involved. Likewise, surgical instrumentation of the maternal and fetal circulations in large animal species has enabled the manipulation of specific humoral and mechanical factors to investigate their roles in fetal cardiac development. This review will focus on such studies and what is known to date about the link between the placenta and heart development.
Project description:Central nervous processing of environmental stimuli requires integration of sensory information with ongoing autonomic control of cardiovascular function. Rhythmic feedback of cardiac and baroreceptor activity contributes dynamically to homeostatic autonomic control. We examined how the processing of brief somatosensory stimuli is altered across the cardiac cycle to evoke differential changes in bodily state. Using functional magnetic resonance imaging of brain and noninvasive beat-to-beat cardiovascular monitoring, we show that stimuli presented before and during early cardiac systole elicited differential changes in neural activity within amygdala, anterior insula and pons, and engendered different effects on blood pressure. Stimulation delivered during early systole inhibited blood pressure increases. Individual differences in heart rate variability predicted magnitude of differential cardiac timing responses within periaqueductal gray, amygdala and insula. Our findings highlight integration of somatosensory and phasic baroreceptor information at cortical, limbic and brainstem levels, with relevance to mechanisms underlying pain control, hypertension and anxiety.
Project description:In previous research, we detected that children and adolescents who were diagnosed with ADHD showed deficits in both complex auditory processing of musical stimuli and in musical performance when compared to controls. In this study, we were interested in whether we could detect similar or distinct findings when we use foreign speech perception tasks. Therefore, we recruited musically naïve participants (n = 25), music-educated participants (n = 25) and participants diagnosed with ADHD (n = 25) who were assessed for their short-term memory (STM) capacity and the ability to discriminate music and speech stimuli and we collected self-ratings of the participants' music and language performances. As expected, we found that young adults with ADHD show deficits in the perception of complex music and difficult speech perception stimuli. We also found that STM capacity was not impaired in young adults with ADHD and may not persist into young adulthood. In addition, subjective self-estimation about the participants' language and music performances revealed that the ADHD group overestimated their performance competence relatively compared to both control groups. As a result, the findings of our study suggest that individuals diagnosed with ADHD require a special training program that not only focuses on improving performance in perceptual skills of music and language but also requires metacognitive training to develop realistic self-assessment skills.
Project description:Intervention1: Tablet Ivabradine: Oral Ivabradine 5mg was given one hour before surgery
Control Intervention1: tablet multivitamin: oral multivitamin(one tablet) one hour before surgery
Primary outcome(s): Haemodynamics changesTimepoint: up to 10 min after laryngoscopy and intubation
Study Design: Randomized, Parallel Group, Placebo Controlled Trial
Method of generating randomization sequence:Computer generated randomization Method of allocation concealment:Sequentially numbered, sealed, opaque envelopes Blinding and masking:Participant, Investigator and Outcome Assessor Blinded
Project description:Studies of longevity rely on baseline life expectancy of reference genotypes measured in standardized conditions. Variation among labs, protocols, and genotypes makes longevity intervention studies difficult to compare. Furthermore, extending lifespan under suboptimal conditions or that of a short-lived genotype may be of a lesser theoretical and translational value than extending the maximal possible lifespan. Daphnia is becoming a model organism of choice for longevity research complementing data obtained on traditional models. In this study, we report longevity of several genotypes of a long-lived species D. magna under a variety of protocols, aiming to document the highest lifespan, factors reducing it, and parameters that change with age and correlate with longevity. Combining longevity data from 25 experiments across two labs, we report a strong intraspecific variation, moderate effects of group size and medium composition, and strong genotype-by-environment interactions with respect to food level. Specifically, short-lived genotypes show no caloric restriction (CR) effect, while long-lived ones expand their lifespan even further under CR. We find that the CR non-responsive clones show little correlation between longevity and two measures of lipid peroxidation. In contrast, the long-lived, CR-responsive clones show a positive correlation between longevity and lipid hydroperoxide abundance, and a negative correlation with MDA concentration. This indicates differences among genotypes in age-related accumulation and detoxification of LPO products and their effects on longevity. Our observations support the hypothesis that a long lifespan can be affected by CR and levels of oxidative damage, while genetically determined short lifespan remains short regardless.
Project description:The dataset was used to study the effect of 2 hours of western classical music concert performance on the peripheral blood microRNA transcriptome in professional musicians.
Project description:TP53 is the most frequently mutated gene in human cancer. Functionally, p53 is activated by a host of stress stimuli and, in turn, governs an exquisitely complex anti-proliferative transcriptional program that touches upon a bewildering array of biological responses. Despite the many unveiled facets of the p53 network, a clear appreciation of how and in what contexts p53 exerts its diverse effects remains unclear. How can we interpret p53's disparate activities and the consequences of its dysfunction to understand how cell type, mutation profile, and epigenetic cell state dictate outcomes, and how might we restore its tumor-suppressive activities in cancer?
Project description:Previous studies investigating to what extent students in elementary schools defend their victimized classmates typically treated defending as an individual characteristic. Defending should, however, be seen as a directed dyadic relationship between a victim and a defender, who are embedded multiple positive and negative relationships with each other and their classmates. Accordingly, in the present study defending was investigated using social network analysis. More specifically, it was investigated to what extent defending relationships co-occurred with friendship and dislike relationships involving not only the victim and the defender but also other classmates. Bivariate Exponential Random Graph Models (ERGMs) were used to analyze the defending-friendship and defending-dislike relationships in seven grade-three classrooms. As hypothesized, the results indicated that victimized students were likely to be defended by students who they perceive as friends or who perceive them as friends. Moreover, defending was likely to occur when the victim and (potential) defender had the same friends. Victimized students were unlikely to be defended by classmates whom they disliked or who had indicated to dislike them. Finally, defending was likely to occur between students who disliked the same classmates.
Project description:In a field where structure has finally begun to have a real impact, a series of new structures over the last two years have further extended our understanding of some of the critical regulatory events of the complement system. Notably, information has begun to flow from larger assemblies of components which allow insight into the often transient assemblies critical to complement regulation at the cell surface. This review will summarise the key structures determined since the last International Complement Workshop and the insights these have given us, before highlighting some questions that still require molecular frameworks to drive understanding.