Tennantryan4423

Interestingly, phorbol ester-induced nucleo-cytoplasmic translocation of the lncRNA in monocytic THP-1 cells resulted in a reduction of ALOX12 protein without a concomitant change in its mRNA level. This indicated ALOX12-AS1 operates via an antisense-sense duplex-mediated translational downregulation mechanism. This deduction was validated by demonstrating sense/antisense duplex formation and an association of the duplex with ribosomal proteins in HEK293 cells. Overall, this study revealed a hitherto unknown mechanism of antisense lncRNA-mediated translational downregulation of ALOX12 that adds to the existing regulatory mechanisms for the modulation of potent bioactive lipid mediators that contribute to both health and disease.White matter deterioration is associated with cognitive impairment in healthy aging and Alzheimer's disease. It is critical to identify interventions that can slow down white matter deterioration. So far, clinical trials have failed to demonstrate the benefits of aerobic exercise on the adult white matter using diffusion Magnetic Resonance Imaging. Here, we report the effects of a 6-month aerobic walking and dance interventions (clinical trial NCT01472744) on white matter integrity in healthy older adults (n = 180, 60-79 years) measured by changes in the ratio of calibrated T1- to T2-weighted images (T1w/T2w). Specifically, the aerobic walking and social dance interventions resulted in positive changes in the T1w/T2w signal in late-myelinating regions, as compared to widespread decreases in the T1w/T2w signal in the active control. Notably, in the aerobic walking group, positive change in the T1w/T2w signal correlated with improved episodic memory performance. Lastly, intervention-induced increases in cardiorespiratory fitness did not correlate with change in the T1w/T2w signal. Together, our findings suggest that white matter regions that are vulnerable to aging retain some degree of plasticity that can be induced by aerobic exercise training. In addition, we provided evidence that the T1w/T2w signal may be a useful and broadly accessible measure for studying short-term within-person plasticity and deterioration in the adult human white matter.The positron emission tomography (PET) radioligand [11C]UCB-J binds to synaptic vesicle protein 2A (SV2A) and is used to investigate synaptic density in the living brain. Clinical studies have indicated reduced [11C]UCB-J binding in Alzheimer's disease (AD) and Parkinson's disease (PD) brains compared to healthy controls. Still, it is unknown whether [11C]UCB-J PET can visualise synaptic loss in mouse models of these disorders. Such models are essential for understanding disease pathology and for evaluating the effects of novel disease-modifying drug candidates. In the present study, synaptic density in transgenic models of AD (ArcSwe) and PD (L61) was studied using [11C]UCB-J PET. Data were acquired during 60 min after injection, and time-activity curves (TACs) in different brain regions and the left ventricle of the heart were generated based on the dynamic PET images. The [11C]UCB-J brain concentrations were expressed as standardised uptake value (SUV) over time. The area under the SUV curve (AUC), the ratio of AUC in the brain to that in the heart (AUCbrain/blood), and the volume of distribution (VT) obtained by kinetic modelling using the heart TAC as input were compared between transgenic and age-matched wild type (WT) mice. The L61 mice displayed 11-13% lower AUCbrain/blood ratio and brain VT generated by kinetic modeling compared to the control WT mice. In general, also transgenic ArcSwe mice tended to show lower [11C]UCB-J brain exposure than age-matched WT controls, but variation within the different animal groups was high. Older WT mice (18-20 months) showed lower [11C]UCB-J brain exposure than younger WT mice (8-9 months). Together, these data imply that [11C]UCB-J PET reflects synaptic density in mouse models of neurodegeneration and that inter-subject variation is large. In addition, the study suggested that model-independent AUCbrain/blood ratio can be used to evaluate [11C]UCB-J binding as an alternative to full pharmacokinetic modelling.Diffusion MRI is a valuable tool for probing tissue microstructure in the brain noninvasively. Today, model-based techniques are widely available and used for white matter characterisation where their development is relatively mature. Conversely, tissue modelling in grey matter is more challenging, and no generally accepted models exist. With advances in measurement technology and modelling efforts, a clinically viable technique that reveals salient features of grey matter microstructure, such as the density of quasi-spherical cell bodies and quasi-cylindrical cell projections, is an exciting prospect. As a step towards capturing the microscopic architecture of grey matter in clinically feasible settings, this work uses a biophysical model that is designed to disentangle the diffusion signatures of spherical and cylindrical structures in the presence of orientation heterogeneity, and takes advantage of B-tensor encoding measurements, which provide additional sensitivity compared to standard single diffusion eses.Neural oscillations are fundamental mechanisms of the human brain that enable coordinated activity of different brain regions during perceptual and cognitive processes. A frontotemporal network generated by means of gamma oscillations and comprising the auditory cortex (AC) and the anterior cingulate cortex (ACC) has been shown to be involved in the cognitively demanding auditory information processing. This study aims to reveal patterns of functional and effective connectivity within this network in healthy subjects by means of simultaneously recorded electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). We simultaneously recorded EEG and fMRI in 28 healthy subjects during the performance of a cognitively demanding auditory choice reaction task. Connectivity between the ACC and AC was analysed employing EEG and fMRI connectivity measures. We found a significant BOLD signal correlation between the ACC and AC, a significant task-dependant increase of fMRI connectivity (gPPI) and a significant increase in functional coupling in the gamma frequency range between these regions (LPS), which was increased in top-down direction (granger analysis). EEG and fMRI connectivity measures were positively correlated. The results of these study point to a role of a top-down influence of the ACC on the AC executed by means of gamma synchronisation. The replication of fMRI connectivity patterns in simultaneously recorded EEG data and the correlation between connectivity measures from both domains found in our study show, that brain connectivity based on the synchronisation of gamma oscillations is mirrored in fMRI connectivity patterns.The past few years have witnessed rapid progress in the field of RNA modifications. As the most prevailing modification on eukaryotic mRNA, m6A is characterized to play a vital role in various cellular activities. However, limitations of the detection method impede functional studies of m6A. Here we introduce m6A-REF-seq, a powerful and straightforward method to identify m6A at single-nucleotide resolution. m6A-REF-seq relies on the recognition of RNA endonuclease MazF towards m6A at the ACA motif, providing an orthogonal method independent of the m6A antibody being adopted by most of current methods. We describe a detailed protocol to perform m6A-REF-seq, including NGS library construction and sequencing data analysis. In particular, we describe an optimized assay to validate individual m6A sites identified by m6A-REF-seq, which can also be applied to detect any candidate m6A sites.Despite extensive research on the development and risk factors of chronic pain, the process of recovery from chronic pain in later life has been rarely studied. this website We estimated the recovery rate of moderate to severe chronic pain (chronic pain of moderate or severe severity or interfering with usual activities) among older adults and investigated predictors of recovery. Leveraging the longitudinal Health and Retirement Study 2006-2016 data (6 waves), we estimated the biennial national attrition-adjusted recovery rate of moderate to severe chronic pain among 6,132 US adults aged 65-75 at baseline. Generalized estimating equation Poisson models examined pain-related, sociodemographic, psychosocial and health-related factors in relation to recovery within any 2-year interval using longitudinal lagged design. Between 2006-2016, the prevalence of moderate to severe chronic pain increased from 28% to 33% with the incidence increasing from 14% to 18% and the recovery rate approximately 30%. Previous chronic pain duration, age, chronic diseases and a personality trait (agreeableness) were associated with a lower probability of recovery. Greater financial wealth and physical activity, better sleep quality and self-reported health were associated with a greater probability of recovery. Interventions that improve physical activity and sleep quality may be important avenues for reducing chronic pain burden among older adults. Perspective Our longitudinal findings suggested that recovery from moderate to severe chronic pain is common in later life and we further identified several key factors associated with this recovery process. Future research should consider the potential of interventions that improve physical activity and sleep quality to enhance recovery among older adults.This study investigated whether there are gender differences in attention to bodily expressions of pain and core emotions. Three experiments are reported using the attentional dot probe task. Images of men and women displaying bodily expressions, including pain, were presented. The task was used to determine whether participants' attention was drawn towards or away from target expressions. Inconsistent evidence was found for an attentional bias towards body expressions, including pain. While biases were affected by gender, patterns varied across the Experiments. Experiment 1, which had a presentation duration of 500 ms, found a relative bias towards the location of male body expressions compared to female expressions. Experiments 2 and 3 varied stimulus exposure times by including both shorter and longer duration conditions (e.g., 100 vs. 500 vs. 1250 ms). In these experiments, a bias towards pain was confirmed. Gender differences were also found, especially in the longer presentation conditions. Expressive body postures captured the attention of women for longer compared to men. These results are discussed in light of their implications for why there are gender differences in attention to pain, and what impact this has on pain behaviour. PERSPECTIVE We show that men and women might differ in how they direct their attention towards bodily expressions, including pain. These results have relevance to understanding how carers might attend to the pain of others, as well as highlighting the wider role that social-contextual factors have in pain.Increasing emphasis on guidelines and prescription drug monitoring programs highlight the role of healthcare providers in pain treatment. Objectives of this study were to identify characteristics of key players and influence of opioid prescribers through construction of a referral network of patients with chronic pain. A retrospective cohort study was performed and patients with commercial or Medicaid coverage with chronic back, neck, or joint pain were identified using the Arkansas All-Payer Claims-Database. A social network comprised of providers connected by patient referrals based on 12-months of healthcare utilization following chronic pain was constructed. Network measures evaluated were indegree and eigen (referrals obtained), betweenness (involvement), and closeness centrality (reach). Outcomes included influence of providers, opioid prescribers, and brokerage status. Exposures included provider demographics, specialties and network characteristics. There were 51,941 chronic pain patients who visited 8,110 healthcare providers.