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.     

The origin and direction of industrial R&D in India

This paper surveys the trends in industrial R&D in India over the last two decades. It shows that there has been a rapid rise in R&D expenditure and a shift in its composition towards in-house corporate R&D and away from R&D in government laboratories, which is explained by the laboratories' lack of market orientation and manufacturing experience. According to cross-section studies of corporate R&D, larger companies aim towards larger technological advances and take a longer view; but the overall composition of corporate R&D shows no discernible change. This apparent inconsistency is explained by the development of the technology market. Much R&D was triggered off by the need for import replacement arising from import controls till 1965 and later by the need for product diversification in the recession. But construction of new plants and mechanization for speeding up operations, activities where sustained R&D can yield large firms a steady flow of innovations, were unimportant or infrequent, and the demand for technology they gave rise to was largely met by imports.     

Ladder realizations of multivariable positive real functions

Necessary and sufficient conditions are obtained for the realization of an m-variable positive real function (PRF) as the impedence function of a resistively-terminated ladder network of m lossless two-ports connected in cascade. Each two-port is a single-variable lossless ladder with all of its transmission zeros either at the origin or at finity. Conditions are also obtained when each of the two-ports is a Fujisawa-type lowpass ladder.