Low-motion fMRI data can be obtained in pediatric participants undergoing a 60-minute scan protocol

Performing functional magnetic resonance imaging (fMRI) scans of children can be a difficult task, as participants tend to move while being scanned. Head motion represents a significant confound in fMRI connectivity analyses. One approach to limit motion has been to use shorter MRI protocols, though this reduces the reliability of results. Hence, there is a need to implement methods to achieve high-quality, low-motion data while not sacrificing data quantity. Here we show that by using a mock scan protocol prior to a scan, in conjunction with other in-scan steps (weighted blanket and incentive system), it is possible to achieve low-motion fMRI data in pediatric participants (age range: 7–17 years old) undergoing a 60 min MRI session. We also observe that motion is low during the MRI protocol in a separate replication group of participants, including some with autism spectrum disorder. Collectively, the results indicate it is possible to conduct long scan protocols in difficult-to-scan populations and still achieve high-quality data, thus potentially allowing more reliable fMRI findings.

Functional Diversification of Replication Protein A Paralogs and Telomere Length Maintenance in Arabidopsis

Replication protein A (RPA) is essential for many facets of DNA metabolism. The RPA gene family expanded in Arabidopsis thaliana with five phylogenetically distinct RPA1 subunits (RPA1A-E), two RPA2 (RPA2A and B), and two RPA3 (RPA3A and B). RPA1 paralogs exhibit partial redundancy and functional specialization in DNA replication (RPA1B and RPA1D), repair (RPA1C and RPA1E), and meiotic recombination (RPA1A and RPA1C). Here, we show that RPA subunits also differentially impact telomere length set point. Loss of RPA1 resets bulk telomeres at a shorter length, with a functional hierarchy for replication group over repair and meiosis group RPA1 subunits. Plants lacking RPA2A, but not RPA2B, harbor short telomeres similar to the replication group. Telomere shortening does not correlate with decreased telomerase activity or deprotection of chromosome ends in rpa mutants. However, in vitro assays show that RPA1B2A3B unfolds telomeric G-quadruplexes known to inhibit replications fork progression. We also found that ATR deficiency can partially rescue short telomeres in rpa2a mutants, although plants exhibit defects in growth and development. Unexpectedly, the telomere shortening phenotype of rpa2a mutants is completely abolished in plants lacking the RTEL1 helicase. RTEL1 has been implicated in a variety of nucleic acid transactions, including suppression of homologous recombination. Thus, the lack of telomere shortening in rpa2a mutants upon RTEL1 deletion suggests that telomere replication defects incurred by loss of RPA may be bypassed by homologous recombination. Taken together, these findings provide new insight into how RPA cooperates with replication and recombination machinery to sustain telomeric DNA.

Genome-wide analysis of DNA methylation in hypertension-discordant monozygotic twins

Background: DNA methylation has great potential for identifying the aetiology of hypertension. The aim of this study was to explore the correlation between hypertension and DNA methylation using twins discordant for hypertension in China. Methods: In this study, 43 pairs of monozygotic twins discordant for hypertension (age 31.9-72.3 years; 67.4% male) from the Chinese National Twin Registry were recruited. Genome-wide DNA methylation was measured using the Illumina Human methylation EPIC Beadchip in whole-blood-derived DNA. Standardized questionnaires were used to collect twin data on the following variables: age, gender, socioeconomic level, lifestyle factors (including smoking, alcohol drinking, vegetable intake, and physical activity). Blood pressure, height, weight, and other anthropometric indicators were obtained by physical examination. Empirical Bayes paired moderated t-test was utilized to compare the methylation data within twin pairs. Results: Four suspected significant methylation sites, cg00950476, cg08041400, cg26733338, and cg08580087 were identified. All of these four sites locate on known loci, which were LINC01252, BDP1, SYT1, and ODZ4, respectively. The main function includes transcriptional regulation, learning and cognitive, neurodevelopment. The significant sites were further replicated among two different replication population, the first replication population contained 38 hypertension concordant monozygotic twin pairs and 38 non-hypertension concordant monozygotic twin pairs matched in age, sex, region, and birth order, and the second replication group included 21 MZ twin pairs discordant for hypertension . None of them, however, were significant. The methylation variation in the above sites may influence blood pressure, independent of genetic and early-life environmental factors. Conclusions: This study found four suspected methylation sites correlated with hypertension. However, all four sites failed the replication analysis. More hypertension-discordant monozygotic twin pairs are needed to replicate these findings in the future to explore the stability of the results.

Implementation of a pre- and in-scan system to minimize head motion in pediatric participants undergoing fMRI scans

BackgroundPerforming fMRI scans of children can be a difficult task, as participants tend to move while being scanned. Head motion represents a significant confound in functional magnetic resonance imaging (fMRI) connectivity analyses, and methods to limit the impact of movement on data quality are needed. One approach has been to use shorter MRI protocols, though this potentially reduces the reliability of the results.ObjectiveHere we describe steps we have taken to limit head motion in an ongoing fMRI study of children undergoing a 60 minute MRI scan protocol. Specifically, we have used a mock scan protocol that trains participants to lie still while being scanned. We provide a detailed protocol and describe other in-scanner measures we have implemented, including an incentive system and the use of a weighted blanket.Materials and methodsParticipants who received a formal mock scan (n = 12) were compared to participants who had an informal mock scan (n = 7). A replication group of participants (n = 16), including five with autism spectrum disorder, who received a formal mock scan were also compared to the informal mock scan group. The primary measure of interest was the mean frame-to-frame displacement across eight functional runs during the fMRI protocol.ResultsParticipants in the formal mock scan and replication group tended to exhibit more low-motion functional scans than the informal mock scan group (P < 0.05). Across different functional scan conditions (i.e. while watching movie clips, performing an attention task, and during resting-state scans), effect sizes tended to be large (Hedge’s g > 0.8).ConclusionResults indicate that with appropriate measures, it is possible to achieve low-motion fMRI data in younger participants undergoing a long scan protocol.

Associations in asthma between quantitative computed tomography and bronchial biopsy-derived airway remodelling

Airway remodelling in asthma remains poorly understood. This study aimed to determine the association of airway remodelling measured on bronchial biopsies with 1) lung function impairment and 2) thoracic quantitative computed tomography (QCT)-derived morphometry and densitometry measures of proximal airway remodelling and air trapping.Subjects were recruited from a single centre. Bronchial biopsy remodelling features that were the strongest predictors of lung function impairment and QCT-derived proximal airway morphometry and air trapping markers were determined by stepwise multiple regression. The best predictor of air trapping was validated in an independent replication group.Airway smooth muscle % was the only predictor of post-bronchodilator forced expiratory volume in 1 s (FEV1) % pred, while both airway smooth muscle % and vascularity were predictors of FEV1/forced vital capacity. Epithelial thickness and airway smooth muscle % were predictors of mean segmental bronchial luminal area (R2=0.12; p=0.02 and R2=0.12; p=0.015), whereas epithelial thickness was the only predictor of wall area % (R2=0.13; p=0.018). Vascularity was the only significant predictor of air trapping (R2=0.24; p=0.001), which was validated in the replication group (R2=0.19; p=0.031).In asthma, airway smooth muscle content and vascularity were both associated with airflow obstruction. QCT-derived proximal airway morphometry was most strongly associated with epithelial thickness and airway smooth muscle content, whereas air trapping was related to vascularity.

Node Detection Using High-Dimensional Fuzzy Parcellation Applied to the Insular Cortex

Several functional connectivity approaches require the definition of a set of regions of interest (ROIs) that act as network nodes. Different methods have been developed to define these nodes and to derive their functional and effective connections, most of which are rather complex. Here we aim to propose a relatively simple “one-step” border detection and ROI estimation procedure employing the fuzzyc-mean clustering algorithm. To test this procedure and to explore insular connectivity beyond the two/three-region model currently proposed in the literature, we parcellated the insular cortex of 20 healthy right-handed volunteers scanned in a resting state. By employing a high-dimensional functional connectivity-based clustering process, we confirmed the two patterns of connectivity previously described. This method revealed a complex pattern of functional connectivity where the two previously detected insular clusters are subdivided into several other networks, some of which are not commonly associated with the insular cortex, such as the default mode network and parts of the dorsal attentional network. Furthermore, the detection of nodes was reliable, as demonstrated by the confirmative analysis performed on a replication group of subjects.

Effect of White Noise on Disinhibition of Verbal Expression

Two groups each composed of 10 male Ss were required to tell E about an embarrassing situation, in nonsense language, under two conditions: with white noise masking their speech and without white noise. 16 of 20 Ss uttered more English words and 18 of 20 talked for a greater length of time in the white noise condition. Latency was not significantly affected by the white noise. The average number of syllables spoken per 15 sec. was significantly greater under white noise, for both groups combined and separately only for the second or replication group. The results are interpreted to indicate a process of disinhibition of speech under white noise.