Effects of purposeful soccer heading on circulating small extracellular vesicle concentration and cargo

BackgroundConsidering the potential cumulative effects of repetitive head impact (HI) exposure, we need sensitive biomarkers to track short- and long-term effects. Circulating small extracellular vesicles (sEVs) (<200 nm) traffic biological molecules throughout the body and may have diagnostic value as biomarkers for disease. The purpose of this study was to identify the microRNA (miRNA) profile in circulating sEVs derived from human plasma following repetitive HI exposure.MethodsHealthy adult (aged 18–35 years) soccer players were randomly assigned to one of 3 groups: the HI group performed 10 standing headers, the leg impact group performed 10 soccer ball trapping maneuvers over 10 min, and the control group did not participate in any soccer drills. Plasma was collected before testing and 24 h afterward, and sEVs were isolated and characterized via nanoparticle tracking analysis. Next-generation sequencing was utilized to identify candidate miRNAs isolated from sEVs, and candidate microRNAs were analyzed via quantitative polymerase chain reaction. In silico target prediction was performed using TargetScan (Version 7.0; targetscan.org) and miRWalk (http://mirwalk.umm.uni-heidelberg.de/) programs, and target validation was performed using luciferase reporter vectors with a miR-7844-5p mimic in human embryonic kidney (HEK) 293T/17 cells.ResultsPlasma sEV concentration and size were not affected across time and group following repetitive HI exposure. After 24 h, the HI read count from next-generation sequencing showed a 4-fold or greater increase in miR-92b-5p, miR-423-5p, and miR-24-3p and a 3-fold or greater decrease in miR-7844-5p, miR-144-5p, miR-221-5p, and miR-22-3p. Analysis of quantitative polymerase chain reaction revealed that leg impact did not alter the candidate miRNA levels. To our knowledge, miR-7844-5p is a previously unknown miRNA. We identified 8 miR-7844-5p mRNA targets: protein phosphatase 1 regulatory inhibitor subunit 1B (PPP1R1B), LIM and senescent cell antigen-like domains 1 (LIMS1), autophagy-related 12 (ATG12), microtubule-associated protein 1 light chain 3 beta (MAP1LC3B), integrin subunit alpha-1 (ITGA1), mitogen-activated protein kinase 1 (MAPK1), glycogen synthase kinase 3β (GSK3β), and mitogen-activated protein kinase 8 (MAPK8).ConclusionCollectively, these data indicate repetitive HI exposure alters plasma sEV miRNA content, but not sEV size or number. Furthermore, for the first time we demonstrate that previously unknown miR-7844-5p targets mRNAs known to be involved in mitochondrial apoptosis, autophagy regulation, mood disorders, and neurodegenerative disease.     

EUROPEAN PUBLIC PERCEPTIONS OF SCIENCE

In this paper we explore the relationships between public interestin, knowledge of, and attitudes towards science and technologyand the level of industrialization in 12 countries of the EuropeanCommunity. Using the 1989 Eurobarometer survey no 31 (N=11,678),we constructed four scales measuring interest, knowledge, generalattitudes to science, and support for EC funded science foreach of the 12 EC countries. We found that overall factual scientificknowledge correlates moderately positively with interest andattitudes to science. For example the Netherlands and GreatBritain have relatively high levels of knowledge, interest,and support for science in general. Spain and Greece have relativelylow levels of knowledge, interest, and support for science ingeneral. However, the simple correlation hides more complexrelationships. First, the variance within and across countriesof knowledge, attitudes and interest increases with nationallevels of knowledge. This indicates greater degrees of polarizationof both support and interest. Second, the data indicates a post-industrialismeffect: knowledge, interest in, and attitudes to science showa curvilinear relationship with levels of industrialization.The decline of interest in science and the less positive attitudesin highly developed countries requires further exploration.Third, we found, that the consistency of the knowledge and theattitude measures declines as the national level of knowledgeincreases. We suggest that this reflects a knowledge-ignoranceparadox and knowledge specialization among informed populations.Support for EC level science follows a different pattern. Wefound that France, Italy, and Spain show high levels of supportfor EC level science. This is not the case in Great Britainand Germany. The pattern suggests that attitudes towards ECscience are formed on the basis of national level scientificstrength: if the national science base is strong, EC scienceinitiatives find less support and vice versa. These findingsrepresent a first step towards a comparative assessment of publicunderstanding of science in EC countries.     

Export restrictions,tax incentives and the national artistic patrimony

This paper analyses the main forms of government intervention used in the UK to protect the national artistic patrimony. It examines the two most common policy measures used in the art market ‐ export regulation and tax incentives ‐ and reports their use over an eight‐year period from 1990 to 1998. It also reviews the UK's collective obligations to patrimony internationally and specifically as a member of the European Union. This is the first time that these related topics have been considered as a whole.     

Water-clocks and time measurement in classical antiquity

The water-clock was the first mechanical device for time measurement to be used by the Greeks. Previously they had relied on sundials, or observation of the phases of the moon or the position of the sun in the zodiac to locate points of time within the day, month or year; and by the mid-fifth century BC they had made some progress with the difficult calendar problems due to the fact that the solar day, the lunar month, and the solar year are not commensurable with each other in whole numbers.     

On Linear Least-Squares Estimators for Continous-Time Stochastic Systems

The problem of least-squares state estimation of stochastic continuous-time linear systems is reconsidered. A concise derivation of the least-squares minimal-order estimator is presented using an innovations approach. An important result is the reinstatement of the problem in a least-squares estimation framework independent of deterministic observer theory. A second result is thus the clarification of previous approaches to the problem, particularly in relation to observer theory.