Regulation of brain endothelial barrier function by microRNAs in health and neuroinflammation

Brain endothelial cells constitute the major cellular element of the highly specialized blood–brain barrier (BBB) and thereby contribute to CNS homeostasis by restricting entry of circulating leukocytes and blood-borne molecules into the CNS. Therefore, compromised function of brain endothelial cells has serious consequences for BBB integrity. This has been associated with early events in the pathogenesis of several disorders that affect the CNS, such as multiple sclerosis, HIV-associated neurologic disorder, and stroke. Recent studies demonstrate that brain endothelial microRNAs play critical roles in the regulation of BBB function under normal and neuroinflammatory conditions. This review will focus on emerging evidence that indicates that brain endothelial microRNAs regulate barrier function and orchestrate various phases of the neuroinflammatory response, including endothelial activation in response to cytokines as well as restoration of inflamed endothelium into a quiescent state. In particular, we discuss novel microRNA regulatory mechanisms and their contribution to cellular interactions at the neurovascular unit that influence the overall function of the BBB in health and during neuroinflammatio

Chemical abundances of damped Lyman alpha systems in the XQ-100 survey

The XQ-100 survey has provided high signal-noise spectra of 100 redshift 3-4.5 quasars with the X-Shooter spectrograph. The metal abundances for 13 elements in the 41 damped Lyman alpha systems (DLAs) identified in the XQ-100 sample are presented, and an investigation into abundances of a variety of DLA classes is conducted. The XQ-100 DLA sample contains five DLAs within 5000 km/s of their host quasar (proximate DLAs; PDLAs) as well as three sightlines which contain two DLAs within 10,000 km/s of each other along the same line-of-sight (multiple DLAs; MDLAs). Combined with previous observations in the literature, we demonstrate that PDLAs with logN(HI)<21.0 show lower [S/H] and [Fe/H] (relative to intervening systems with similar redshift and N(HI)), whilst higher [S/H] and [Si/H] are seen in PDLAs with logN(HI)>21.0. These abundance discrepancies are independent of their line-of-sight velocity separation from the host quasar, and the velocity width of the metal lines (v90). Contrary to previous studies, MDLAs show no difference in [alpha/Fe] relative to single DLAs matched in metallicity and redshift. In addition, we present follow-up UVES data of J0034+1639, a sightline containing three DLAs, including a metal-poor DLA with [Fe/H]=-2.82 (the third lowest [Fe/H] in DLAs identified to date) at z=4.25. Lastly we study the dust-corrected [Zn/Fe], emphasizing that near-IR coverage of X-Shooter provides unprecedented access to MgII, CaII and TiII lines (at redshifts 3-4) to provide additional evidence for subsolar [Zn/Fe] ratio in DLAs.Comment: Accepted to MNRAS. 19 pages plus Appendix material (102 pages total

Effect of pretreatment with low-frequency ultrasound on quality parameters in gulupa (Passiflora edulis sims) pulp

The Gulupa (Passiflora edulis f. edulis Sims) is an expression of South America’s tropics’ biodiversity, and a source of B vitamins and amino acids. It is a climacteric export fruit for which it is necessary to incorporate emerging technologies for its conservation and transport. This work investigated the effect of ultrasound on gulupa pulp and verified the stability of the characters of interest in the shelf life of 20 days. Six treatments and a control sample were used, evaluated in triplicate, and varied in frequency (30 and 40 kHz) with an exposure time of 10, 20, and 30 min. A statistical analysis of unidirectional variances and Dunnett’s test was used. It was found that the ultrasound treatments did not affect the pH or the titratable acidity. Soluble solid results presented a significant increase (p &lt; 0.05) (from 13.4 to 14.8% w/v) in the antioxidant capacity (from 1.13 to 1.54 µmol Trolox Equivalent (TE)/g by the ABTS•+ (2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) Cationic Radical Assay and from 3.3 to 3.7 µmol TE/g by the DPPH· (2,2-diphenyl-1-picrilhydrazil) Radical Scavenging Assay). During the shelf life, ascorbic acid was the parameter that varied most (p &lt; 0.05). It decreased from 42.7 to 21.6 mg ascorbic acid/100 g of pulp in the control sample. However, a smaller decrease was observed (23.8–24.5 mg ascorbic acid/100 g of pulp) in the 40 kHz treatments. The smallest global color difference (∆E) for the control was found in the 40 kHz treatment at 30 min through the entire shelf life (day 0 to 20). Ultrasound treatment offers a new strategy to improve and extend the shelf life of chilled gulupa pulp

Viral Coinfections in Kawasaki Disease: A Meta-analysis.

CONTEXT: Viral infections are suspected triggers in Kawasaki disease (KD); however, a specific viral trigger has not been identified. OBJECTIVES: In children with KD, to identify (1) overall prevalence of viral infections; (2) prevalence of specific viruses; and (3) whether viral positivity was associated with coronary artery aneurysms (CAAs) or refractoriness to intravenous immunoglobin (IVIG). DATA SOURCES: We searched Embase, Medline, and Cochrane databases and gray literature. STUDY SELECTION: Eligible studies were conducted between 1999 and 2019, and included children diagnosed with KD who underwent viral testing. DATA EXTRACTION: Two investigators independently reviewed full-text articles to confirm eligibility, extract data, appraise for bias, and assess evidence quality for outcomes using the Grading of Recommendations Assessment Development and Evaluation criteria. We defined viral positivity as number of children with a positive viral test divided by total tested. Secondary outcomes were CAA (z score ≥2.5) and IVIG refractoriness (fever ≥36 hours after IVIG). RESULTS: Of 3189 unique articles identified, 54 full-text articles were reviewed, and 18 observational studies were included. Viral positivity weighted mean prevalence was 30% (95% confidence interval [CI], 14-51) and varied from 5% to 66%, with significant between-study heterogeneity. Individual virus positivity was highest for rhinovirus (19%), adenovirus (10%), and coronavirus (7%). Odds of CAA (odds ratio, 1.08; 95% CI, 0.75-1.56) or IVIG refractoriness (odds ratio, 0.88; 95% CI, 0.58-1.35) did not differ on the basis of viral status. LIMITATIONS: Low or very low evidence quality. CONCLUSIONS: Viral infection was common with KD but without a predominant virus. Viral positivity was not associated with CAAs or IVIG refractoriness

The effect of acute sleep extension vs active recovery on post exercise recovery kinetics in rugby union players

Background Elite rugby players experience poor sleep quality and quantity. This lack of sleep could compromise post-exercise recovery. Therefore, it appears central to encourage sleep in order to improve recovery kinetics. However, the effectiveness of an acute ergogenic strategy such as sleep extension on recovery has yet to be investigated among athletes. Aim To compare the effects of a single night of sleep extension to an active recovery session (CON) on post-exercise recovery kinetics. Methods In a randomised cross-over design, 10 male rugby union players participated in two evening training sessions (19:30) involving collision activity, 7-days apart. After each session, participants either extended their sleep to 10 hours or attended an early morning recovery session (07:30). Prior to (PRE), immediately after (POST 0 hour [h]), 14h (POST 14) and 36h (POST 36) post training, neuromuscular, perceptual and cognitive measures of fatigue were assessed. Objective sleep parameters were monitored two days before the training session and over the two-day recovery period. Results The training session induced substantial decreases in countermovement jump mean power and wellness across all time points, while heart rate recovery decreased at POST 0 in both conditions. Sleep extension resulted in greater total sleep time (effect size [90% confidence interval]: 5.35 [4.56 to 6.14]) but greater sleep fragmentation than CON (2.85 [2.00 to 3.70]). Between group differences highlight a faster recovery of cognitive performance following sleep extension (-1.53 [-2.33 to -0.74]) at POST 14, while autonomic function (-1.00 [-1.85 to -0.16]) and upper-body neuromuscular function (-0.78 [-1.65 to 0.08]) were better in CON. However, no difference in recovery status between groups was observed at POST 36. Conclusion The main finding of this study suggests that sleep extension could affect cognitive function positively but did not improve neuromuscular function the day after a late exercise bout.</p

Near-Infrared Polarimetric Adaptive Optics Observations of NGC 1068: A torus created by a hydromagnetic outflow wind

We present J' and K' imaging linear polarimetric adaptive optics observations of NGC 1068 using MMT-Pol on the 6.5-m MMT. These observations allow us to study the torus from a magnetohydrodynamical (MHD) framework. In a 0.5" (30 pc) aperture at K', we find that polarisation arising from the passage of radiation from the inner edge of the torus through magnetically aligned dust grains in the clumps is the dominant polarisation mechanism, with an intrinsic polarisation of 7.0%$\pm$2.2%. This result yields a torus magnetic field strength in the range of 4$-$82 mG through paramagnetic alignment, and 139$^{+11}_{-20}$ mG through the Chandrasekhar-Fermi method. The measured position angle (P.A.) of polarisation at K$'$ is found to be similar to the P.A. of the obscuring dusty component at few parsec scales using infrared interferometric techniques. We show that the constant component of the magnetic field is responsible for the alignment of the dust grains, and aligned with the torus axis onto the plane of the sky. Adopting this magnetic field configuration and the physical conditions of the clumps in the MHD outflow wind model, we estimate a mass outflow rate $\le$0.17 M$_{\odot}$ yr$^{-1}$ at 0.4 pc from the central engine for those clumps showing near-infrared dichroism. The models used were able to create the torus in a timescale of $\geq$10$^{5}$ yr with a rotational velocity of $\leq$1228 km s$^{-1}$ at 0.4 pc. We conclude that the evolution, morphology and kinematics of the torus in NGC 1068 can be explained within a MHD framework.Comment: 14 pages, 4 figures, Accepted by MNRA

Current research into brain barriers and the delivery of therapeutics for neurological diseases: a report on CNS barrier congress London, UK, 2017.

This is a report on the CNS barrier congress held in London, UK, March 22-23rd 2017 and sponsored by Kisaco Research Ltd. The two 1-day sessions were chaired by John Greenwood and Margareta Hammarlund-Udenaes, respectively, and each session ended with a discussion led by the chair. Speakers consisted of invited academic researchers studying the brain barriers in relation to neurological diseases and industry researchers studying new methods to deliver therapeutics to treat neurological diseases. We include here brief reports from the speakers

Validity, reliability, and the contributing physical characteristics of a modified 15m prone Yo-Yo Intermittent Recovery Test Level-1 test in elite female rugby league players

This study aims to establish the validity and reliability of the prone Yo-YoIRL1 in elite female rugby league players (part one) and determine the anthropometric and physical characteristics contributing to 15m prone Yo-YoIRL1 performance (part two). Part one, 21 subjects completed one Yo-YoIRL1, one 20m and two 15m prone Yo-YoIRL1 tests over four sessions, with 7–14 days in-between. Part two, ten subjects completed a testing battery, including body mass, height, dual-energy x-ray absorptiometry, isometric mid-thigh pull, isometric bench-press, 10m and 20m sprints and an incremental treadmill test (V˙O2max). The 15m prone YoYoIRL1 demonstrated poor reliability with a typical error of 68m (21%) and a smallest worthwhile change of 54m (9%). Validity analysis found the prone versions of the YoYoIRL1 were not sensitive measures of intermittent running performance. Both prone YoYoIRL1 test distances demonstrated large mean bias (76% and -37% respectively) and typical error of the estimate (19% and 21%, respectively) in comparison to the YoYoIRL1. Body mass (r = -0.89), lean mass (r = -0.64), body fat % (r = -0.68), V˙O2max (l∙min-1) (r = -0.64), IMTP (r = -0.69), IBP (r = -0.15), 10m (r = -0.77) and 20m (r = -0.72) momentum displayed large negative relationships with 15m prone Yo-YoIRL1 performance. Due to the poor validity of the 20m prone YoYoIRL1, the poor validity and reliability of the 15m prone YoYoIRL1, and the anthropometric and physical characteristics which negatively impact performance, practitioners should reconsider the use of the prone YoYoIRL1 test to monitor high intensity intermittent running performance

Latest developments in data analysis tools for disruption prediction and for the exploration of multimachine operational spaces.

In the last years significant efforts have been devoted to the development of advanced data analysis tools to both predict the occurrence of disruptions and to investigate the operational spaces of devices, with the long term goal of advancing the understanding of the physics of these events and to prepare for ITER. On JET the latest generation of the disruption predictor called APODIS has been deployed in the real time network during the last campaigns with the new metallic wall. Even if it was trained only with discharges with the carbon wall, it has reached very good performance, with both missed alarms and false alarms in the order of a few percent (and strategies to improve the performance have already been identified). Since for the optimisation of the mitigation measures, predicting also the type of disruption is considered to be also very important, a new clustering method, based on the geodesic distance on a probabilistic manifold, has been developed. This technique allows automatic classification of an incoming disruption with a success rate of better than 85%. Various other manifold learning tools, particularly Principal Component Analysis and Self Organised Maps, are also producing very interesting results in the comparative analysis of JET and ASDEX Upgrade (AUG) operational spaces, on the route to developing predictors capable of extrapolating from one device to another