Deciphering the Transcriptomic Heterogeneity of Duodenal Coeliac Disease Biopsies

Coeliac disease (CD) is a clinically heterogeneous autoimmune disease with variable presentation and progression triggered by gluten intake. Molecular or genetic factors contribute to disease heterogeneity, but the reasons for different outcomes are poorly understood. Transcriptome studies of tissue biopsies from CD patients are scarce. Here, we present a high-resolution analysis of the transcriptomes extracted from duodenal biopsies of 24 children and adolescents with active CD and 21 individuals without CD but with intestinal afflictions as controls. The transcriptomes of CD patients divide into three groups—a mixed group presenting the control cases, and CD-low and CD-high groups referring to lower and higher levels of CD severity. Persistence of symptoms was weakly associated with subgroup, but the highest marsh stages were present in subgroup CD-high, together with the highest cell cycle rates as an indicator of virtually complete villous atrophy. Considerable variation in inflammation-level between subgroups was further deciphered into immune cell types using cell type de-convolution. Self-organizing maps portrayal was applied to provide high-resolution landscapes of the CD-transcriptome. We find asymmetric patterns of miRNA and long non-coding RNA and discuss the effect of epigenetic regulation. Expression of genes involved in interferon gamma signaling represent suitable markers to distinguish CD from non-CD cases. Multiple pathways overlay in CD biopsies in different ways, giving rise to heterogeneous transcriptional patterns, which potentially provide information about etiology and the course of the disease

Subpopulations of anti-β2glycoprotein I antibodies with different pathogenic potential: fine specificity against the domains of β2glycoprotein I

Objective: Anti-β2glycoprotein I antibodies (a-β2GPI) are a laboratory criterion for the antiphospholipid syndrome (APS) and were demonstrated to be involved in the pathogenesis of APS. However, they can also be detected in asymptomatic subjects. It has been suggested that a-β2GPI against Domain1 (D1) associate with thrombosis, while those recognizing Domain4/5 (D4/5) have been identified in non-thrombotic conditions. We evaluate the specificity of a- β2GPI in different clinical situations. Methods: We studied 39 one-year-old healthy children born to mothers with systemic autoimmune diseases (SAD) (15 (38.4%) were born to mothers who were a-β2GPI positive), 33 children with atopic dermatitis (AD) and 55 patients with APS (50 adults and 5 paediatrics). All subjects were IgG a-β2GPI positive. IgG a-β2GPI were performed by homemade ELISA, while IgG a-β2GPI D1 and D4/5 were tested on research ELISAs containing recombinant β2GPI domains antigens. Results: One-year-old children and AD children displayed preferential reactivity for D4/5; patients with APS recognized preferentially D1. We also found a good correlation between a-β2GPI and D4/5 in one-year-old (r=0.853) and AD children (r=0.879) and between a-β2GPI and D1 in the APS group (r=0.575). No thrombotic events were recorded in both groups of children. Conclusions: A-β2GPI found in non-thrombotic conditions (healthy children born to mothers with SAD and AD children) mostly recognize D4/5, in contrast to the prevalent specificity for D1 in the APS group. The different specificity could at least partially explain the "innocent" profile of a-β2GPI in children

Gender differences in the temporal voice areas

There is not only evidence for behavioral differences in voice perception between female and male listeners, but also recent suggestions for differences in neural correlates between genders. The fMRI functional voice localizer (comprising a univariate analysis contrasting stimulation with vocal versus non-vocal sounds) is known to give robust estimates of the temporal voice areas (TVAs). However there is growing interest in employing multivariate analysis approaches to fMRI data (e.g. multivariate pattern analysis; MVPA). The aim of the current study was to localize voice-related areas in both female and male listeners and to investigate whether brain maps may differ depending on the gender of the listener. After a univariate analysis, a random effects analysis was performed on female (n = 149) and male (n = 123) listeners and contrasts between them were computed. In addition, MVPA with a whole-brain searchlight approach was implemented and classification maps were entered into a second-level permutation based random effects models using statistical non-parametric mapping (SnPM; Nichols & Holmes 2002). Gender differences were found only in the MVPA. Identified regions were located in the middle part of the middle temporal gyrus (bilateral) and the middle superior temporal gyrus (right hemisphere). Our results suggest differences in classifier performance between genders in response to the voice localizer with higher classification accuracy from local BOLD signal patterns in several temporal-lobe regions in female listeners

Evaluation of noise regression techniques in resting-state fMRI studies using data of 434 older adults

Subject motion is a well-known confound in resting-state functional MRI (rs-fMRI) and the analysis of functional connectivity. Consequently, several clean-up strategies have been established to minimize the impact of subject motion. Physiological signals in response to cardiac activity and respiration are also known to alter the apparent rs-fMRI connectivity. Comprehensive comparisons of common noise regression techniques showed that the Independent Component Analysis based strategy for Automatic Removal of Motion Artifacts (ICA-AROMA) was a preferred pre-processing technique for teenagers and adults. However, motion and physiological noise characteristics may differ substantially for older adults. Here, we present a comprehensive comparison of noise-regression techniques for older adults from a large multi-site clinical trial of exercise and intensive pharmacological vascular risk factor reduction. The Risk Reduction for Alzheimer\u27s Disease (rrAD) trial included hypertensive older adults (60-84 years old) at elevated risk of developing Alzheimer\u27s Disease (AD). We compared the performance of censoring, censoring combined with global signal regression, non-aggressive and aggressive ICA-AROMA, as well as the Spatially Organized Component Klassifikator (SOCK) on the rs-fMRI baseline scans from 434 rrAD subjects. All techniques were rated based on network reproducibility, network identifiability, edge activity, spatial smoothness, and loss of temporal degrees of freedom (tDOF). We found that non-aggressive ICA-AROMA did not perform as well as the other four techniques, which performed table with marginal differences, demonstrating the validity of these techniques. Considering reproducibility as the most important factor for longitudinal studies, given low false-positive rates and a better preserved, more cohesive temporal structure, currently aggressive ICA-AROMA is likely the most suitable noise regression technique for rs-fMRI studies of older adults

When and where to transfer for Bayesian network parameter learning

This work is supported by the European Research Council (ERC-2013-AdG339182-BAYES-KNOWLEDGE) and the European Union’s Horizon 2020 research and innovation programme under grant agreement No 640891. YZ is supported by China Scholarship Council (CSC)/Queen Mary Joint PhD scholarships and National Natural Science Foundation of China (61273322, 71471174)

Assessing hippocampal functional reserve in temporal lobe epilepsy:A multi-voxel pattern analysis of fMRI data

Assessing the functional reserve of key memory structures in the medial temporal lobes (MTL) of pre-surgical patients with intractable temporal lobe epilepsy (TLE) remains a challenge. Conventional functional MRI (fMRI) memory paradigms have yet to fully convince of their ability to confidently assess the risk of a post-surgical amnesia. An alternative fMRI analysis method, multi-voxel pattern analysis (MVPA), focuses on the patterns of activity across voxels in specific brain regions that are associated with individual memory traces. This method makes it possible to investigate whether the hippocampus and related structures contralateral to any proposed surgery are capable of laying down and representing specific memories. Here we used MVPA-fMRI to assess the functional integrity of the hippocampi and MTL in patients with long-standing medically refractory TLE associated with unilateral hippocampal sclerosis (HS). Patients were exposed to movie clips of everyday events prior to scanning, which they subsequently recalled during high-resolution fMRI. MTL structures were delineated and pattern classifiers were trained to learn the patterns of brain activity across voxels associated with each memory. Predictable patterns of activity across voxels associated with specific memories could be detected in MTL structures, including the hippocampus, on the side contralateral to the HS, indicating their functional viability. By contrast, no discernible memory representations were apparent in the sclerotic hippocampus, but adjacent MTL regions contained detectable information about the memories. These findings suggest that MVPA in fMRI memory studies of TLE can indicate hippocampal functional reserve and may be useful to predict the effects of hippocampal resection in individual patients

Low level of physical activity in women with rheumatoid arthritis is associated with cardiovascular risk factors but not with body fat mass - a cross sectional study

<p>Abstract</p> <p>Background</p> <p>As many patients with rheumatoid arthritis (RA) have increased fat mass (FM) and increased frequency of cardiovascular diseases we evaluated if total physical activity (MET-hours) had impact on body composition and cardiovascular risk factors in women with RA.</p> <p>Methods</p> <p>Sixty-one out-ward RA women, 60.8 (57.3-64.4) years, answered a self-administered questionnaire, to estimate total daily physical activity during the previous year. Physical activity level was given as metabolic equivalents (MET) × h/day. Diet content was assessed by a food frequency questionnaire and body composition by whole-body dual-energy X-ray absorptiometry. Blood lipids and antibodies against phosphorylcholine (anti-PC) were determined.</p> <p>Results</p> <p>Forty-one percent of the women had BMI > 25, 6% were centrally obese and 80% had FM% > 30%. The median (IQR) total physical activity was 40.0 (37.4-47.7), i.e. the same activity level as healthy Swedish women in the same age. Total physical activity did not significantly correlate with disease activity, BMI or FM%. Disease activity, BMI and FM% did not differ between those in the lowest quartile of total physical activity and those in the highest quartile. However, the women in the lowest quartile of physical activity had lower HDL (p = 0.05), Apo A1 (p = 0.005) and atheroprotective natural anti-PC (p = 0.016) and higher levels of insulin (p = 0.05) and higher frequency of insulin resistance than those in the highest quartile. Women in the lowest quartile consumed larger quantities of saturated fatty acids than those in the highest quartile (p = 0.042), which was associated with high oxidized low-density lipoprotein (oxLDL).</p> <p>Conclusion</p> <p>This cross sectional study demonstrated that RA women with fairly low disease activity, good functional capacity, high FM and high frequency of central obesity had the same total physical activity level as healthy Swedish women in the same age. The amount of total physical activity was not associated with functional capacity or body composition. However, low total physical activity was associated with dyslipidemia, insulin resistance, low levels of atheroprotective anti-PC and consumption of saturated fatty acids, which is of interest in the context of increased frequency of cardiovascular disease in RA.</p

The Psychology of Privacy in the Digital Age

Privacy is a psychological topic suffering from historical neglect – a neglect that is increasingly consequential in an era of social media connectedness, mass surveillance and the permanence of our electronic footprint. Despite fundamental changes in the privacy landscape, social and personality psychology journals remains largely unrepresented in debates on the future of privacy. By contrast, in disciplines like computer science and media and communication studies, engaging directly with socio- technical developments, interest in privacy has grown considerably. In our review of this interdisciplinary literature we suggest four domains of interest to psychologists. These are: sensitivity to individual differences in privacy disposition; a claim that privacy is fundamentally based in social interactions; a claim that privacy is inherently contextual; and a suggestion that privacy is as much about psychological groups as it is about individuals. Moreover, we propose a framework to enable progression to more integrative models of the psychology of privacy in the digital age, and in particular suggest that a group and social relations based approach to privacy is needed

An fMRI investigation of the relationship between future imagination and cognitive flexibility

While future imagination is largely considered to be a cognitive process grounded in default mode network activity, studies have shown that future imagination recruits regions in both default mode and frontoparietal control networks. In addition, it has recently been shown that the ability to imagine the future is associated with cognitive flexibility, and that tasks requiring cognitive flexibility result in increased coupling of the default mode network with frontoparietal control and salience networks. In the current study, we investigated the neural correlates underlying the association between cognitive flexibility and future imagination in two ways. First, we experimentally varied the degree of cognitive flexibility required during future imagination by manipulating the disparateness of episodic details contributing to imagined events. To this end, participants generated episodic details (persons, locations, objects) within three social spheres; during fMRI scanning they were presented with sets of three episodic details all taken from the same social sphere (Congruent condition) or different social spheres (Incongruent condition) and required to imagine a future event involving the three details. We predicted that, relative to the Congruent condition, future simulation in the Incongruent condition would be associated with increased activity in regions of the default mode, frontoparietal and salience networks. Second, we hypothesized that individual differences in cognitive flexibility, as measured by performance on the Alternate Uses Task, would correspond to individual differences in the brain regions recruited during future imagination. A task partial least squares (PLS) analysis showed that the Incongruent condition resulted in an increase in activity in regions in salience networks (e.g. the insula) but, contrary to our prediction, reduced activity in many regions of the default mode network (including the hippocampus). A subsequent functional connectivity (within-subject seed PLS) analysis showed that the insula exhibited increased coupling with default mode regions during the Incongruent condition. Finally, a behavioral PLS analysis showed that individual differences in cognitive flexibility were associated with differences in activity in a number of regions from frontoparietal, salience and default-mode networks during both future imagination conditions, further highlighting that the cognitive flexibility underlying future imagination is grounded in the complex interaction of regions in these networks