Preliminary Studies on Immune Response and Viral Pathogenesis of Zika Virus in Rhesus Macaques

Zika Virus (ZIKV) is primarily transmitted through mosquito bites. It can also be transmitted during sexual intercourse and in utero from mother to fetus. To gain preliminary insight into ZIKV pathology and immune responses on route of transmission, rhesus macaques (RMs) were inoculated with ZIKV (PRVABC59) via intravaginal (IVAG) (n = 3) or subcutaneous (sub Q) (n = 2) routes. Systemic ZIKV infection was observed in all RMs, regardless of the route of inoculation. After 9 days postinfection (dpi), ZIKV was not detected in the plasma of IVAG- and sub-Q-inoculated RMs. Importantly, RMs harbored ZIKV up to 60 dpi in various anatomical locations. Of note, ZIKV was also present in several regions of the brain, including the caudate nucleus, parietal lobe, cortex, and amygdala. These observations appear to indicate that ZIKV infection may be systemic and persistent regardless of route of inoculation. In addition, we observed changes in key immune cell populations in response to ZIKV infection. Importantly, IVAG ZIKV infection of RMs is associated with increased depletion of CD11C hi myeloid cells, reduced PD-1 expression in NK cells, and elevated frequencies of Ki67⁺ CD8⁺ central memory cells as compared to sub Q ZIKV-infected RMs. These results need to interpreted with caution due to the small number of animals utilized in this study. Future studies involving large groups of animals that have been inoculated through both routes of transmission are needed to confirm our findings

Blood biomarkers indicate mild neuroaxonal injury and increased amyloid production after transient hypoxia during breath-hold diving

OBJECTIVE: To determine whether transient hypoxia during breath-hold diving causes neuronal damage or dysfunction or alters amyloid metabolism as measured by certain blood biomarkers. DESIGN: Sixteen divers competing in the national Swedish championship in breath-hold diving and five age-matched healthy control subjects were included. Blood samples were collected at baseline and over a course of 3 days where the divers competed in static apnea (STA), dynamic apnea without fins (DYN1) and dynamic apnea with fins (DYN2). MAIN OUTCOMES: Biomarkers reflecting brain injury and amyloid metabolism were analysed in serum (S-100β, NFL) and plasma (T-tau, Aβ42) using immunochemical methods. RESULTS: Compared to divers’ baseline, Aβ42 increased after the first event of static apnea (p = 0.0006). T-tau increased (p = 0.001) in STA vs baseline and decreased after one of the dynamic events, DYN2 (p = 0.03). Further, T-tau correlated with the length of the apneic time during STA (ρ = 0.7226, p = 0.004) and during DYN1 (ρ = 0.66, p = 0.01). CONCLUSION: The findings suggest that transient hypoxia may acutely increase the levels of Aβ42 and T-tau in plasma of healthy adults, further supporting that general hypoxia may cause mild neuronal dysfunction or damage and stimulate Aβ production

Solar Wind—Magnetosphere Coupling During Radial Interplanetary Magnetic Field Conditions: Simultaneous Multi-Point Observations

S. Toledo-Redondo and J. Fornieles acknowledge support of the Ministry of Economy and Competitiveness (MINECO) of Spain (grant FIS2017-90102-R) and of Ministry of Science and Innovation (grant PID2020-112805GA-I00). Research at IRAP was supported by CNRS, CNES, and the University of Toulouse. We acknowledge support of the ISSI teams MMS and Cluster observations of magnetic reconnection and Cold plasma of ionospheric in the Earth's magnetosphere, and of the ESAC Science faculty.In-situ spacecraft missions are powerful assets to study processes that occur in space plasmas. One of their main limitations, however, is extrapolating such local measurements to the global scales of the system. To overcome this problem at least partially, multi-point measurements can be used. There are several multi-spacecraft missions currently operating in the Earth's magnetosphere, and the simultaneous use of the data collected by them provides new insights into the large-scale properties and evolution of magnetospheric plasma processes. In this work, we focus on studying the Earth's magnetopause (MP) using a conjunction between the Magnetospheric Multiscale and Cluster fleets, when both missions skimmed the MP for several hours at distant locations during radial interplanetary magnetic field (IMF) conditions. The observed MP positions as a function of the evolving solar wind conditions are compared to model predictions of the MP. We observe an inflation of the magnetosphere (similar to 0.7 R-E), consistent with magnetosheath pressure decrease during radial IMF conditions, which is less pronounced on the flank (<0.2 R-E). There is observational evidence of magnetic reconnection in the subsolar region for the whole encounter, and in the dusk flank for the last portion of the encounter, suggesting that reconnection was extending more than 15 R-E. However, reconnection jets were not always observed, suggesting that reconnection was patchy, intermittent or both. Shear flows reduce the reconnection rate up to similar to 30% in the dusk flank according to predictions, and the plasma beta enhancement in the magnetosheath during radial IMF favors reconnection suppression by the diamagnetic drift.Ministry of Economy and Competitiveness (MINECO) of Spain FIS2017-90102-RSpanish Government PID2020-112805GA-I00Centre National de la Recherche Scientifique (CNRS)European CommissionCentre National D'etudes SpatialesUniversity of ToulouseESAC Science facult

Serum Neurofilament Light in American Football Athletes over the Course of a Season

Despite being underreported, American football boasts the highest incidence of concussion among all team sports, likely due to exposure to head impacts that vary in number and magnitude over the season. This study compared a biological marker of head trauma in American football athletes with non-contact sport athletes and examined changes over the course of a season. Baseline serum neurofilament light polypeptide (NFL) was measured after 9 weeks of no contact and compared with a non-contact sport. Serum NFL was then measured over the course of the entire season at eight time-points coincident with expected changes in likelihood of increased head impacts. Data were compared between starters (n = 11) and non-starters (n = 9). Compared with non-starters (mean ± standard deviation) (7.30 ± 3.57 pg•mL-1) and controls (6.75 ± 1.68 pg•mL-1), serum NFL in starters (8.45 ± 5.90 pg•mL-1) was higher at baseline (mean difference; ±90% confidence interval) (1.69; ± 1.96 pg•mL-1 and 1.15; ± 1.4 pg•mL-1, respectively). Over the course of the season, an increase (effect size [ES] = 1.8; p < 0.001) was observed post-camp relative to baseline (1.52 ± 1.18 pg•mL-1), which remained elevated until conference play, when a second increase was observed (ES = 2.6; p = 0.008) over baseline (4.82 ± 2.64 pg•mL-1). A lack of change in non-starters resulted in substantial differences between starters and non-starters over the course of the season. These data suggest that a season of collegiate American football is associated with elevations in serum NFL, which is indicative of axonal injury, as a result of head impacts

An environmentally benign antimicrobial nanoparticle based on a silver-infused lignin core

Silver nanoparticles have antibacterial properties, but their use has been a cause for concern because they persist in the environment. Here, we show that lignin nanoparticles infused with silver ions and coated with a cationic polyelectrolyte layer form a biodegradable and green alternative to silver nanoparticles. The polyelectrolyte layer promotes the adhesion of the particles to bacterial cell membranes and, together with silver ions, can kill a broad spectrum of bacteria, including Escherichia coli, Pseudomonas aeruginosa and quaternary-amine-resistant Ralstonia sp. Ion depletion studies have shown that the bioactivity of these nanoparticles is time-limited because of the desorption of silver ions. High-throughput bioactivity screening did not reveal increased toxicity of the particles when compared to an equivalent mass of metallic silver nanoparticles or silver nitrate solution. Our results demonstrate that the application of green chemistry principles may allow the synthesis of nanoparticles with biodegradable cores that have higher antimicrobial activity and smaller environmental impact than metallic silver nanoparticles

Electron Heating by Debye-Scale Turbulence in Guide-Field Reconnection

We report electrostatic Debye-scale turbulence developing within the diffusion region of asymmetric magnetopause reconnection with amoderate guide field using observations by the Magnetospheric Multiscale mission. We show that Buneman waves and beam modes cause efficient and fast thermalization of the reconnection electron jet by irreversible phase mixing, during which the jet kinetic energy is transferred into thermal energy. Our results show that the reconnection diffusion region in the presence of a moderate guide field is highly turbulent, and that electrostatic turbulence plays an important role in electron heating.Peer reviewe

Effect of Docosahexaenoic Acid on a Biomarker of Head Trauma in American Football

PURPOSE: American football athletes are exposed to subconcussive impacts over the course of the season resulting in elevations in serum neurofilament light (NFL), a biomarker of axonal injury. Docosahexaenoic acid (DHA) has been reported to reduce axonal trauma associated with traumatic brain injury in rodent models. However, the optimal dose in American football athletes is unknown. This study examined the effect of differing doses of DHA on serum NFL over the course of a season of American football. METHODS: In a randomized, double-blind, placebo-controlled, parallel design, 81 National Collegiate Athletic Association Division I American football athletes were assigned to ingest either 2, 4, 6 g·d−1 of DHA or placebo. Blood was sampled at specific times over the course of 189 d, coincident with changes in intensity, hours of contact, and likely changes in head impacts. Standardized magnitude-based inference was used to define outcomes. RESULTS: DHA supplementation increased plasma DHA in a dose-dependent manner (2 g·d⁻¹: mean difference from baseline; ±90% CL; 2 g·d⁻¹: 1.3; ±0.6; 4 g·d⁻¹: 1.6; ±0.7%; 6 g·d⁻¹: 1.6; ±0.7%; 6 g·d⁻¹) versus nonstarters (1398 ± 581 pg·mL⁻¹; P = 0.024). Irrespective of dose, supplemental DHA likely attenuated serum NFL coincident with increases in serum NFL by likely small and moderate magnitude (effect size = 0.4–0.7). CONCLUSIONS: Findings from this study, the first large-scale study examining potential prophylactic use of DHA in American football athletes, include identification of optimal dose of DHA, suggesting a neuroprotective effect of DHA supplementation

Large scale analysis of positional effects of single-base mismatches on microarray gene expression data

<p>Abstract</p> <p>Background</p> <p>Affymetrix GeneChips utilize 25-mer oligonucleotides probes linked to a silica surface to detect targets in solution. Mismatches due to single nucleotide polymorphisms (SNPs) can affect the hybridization between probes and targets. Previous research has indicated that binding between probes and targets strongly depends on the positions of these mismatches. However, there has been substantial variability in the effect of mismatch type across studies.</p> <p>Methods</p> <p>By taking advantage of naturally occurring mismatches between rhesus macaque transcripts and human probes from the Affymetrix U133 Plus 2 GeneChip, we collected the largest 25-mer probes dataset with single-base mismatches at each of the 25 positions on the probe ever used in this type of analysis.</p> <p>Results</p> <p>A mismatch at the center of a probe led to a greater loss in signal intensity than a mismatch at the ends of the probe, regardless of the mismatch type. There was a slight asymmetry between the ends of a probe: effects of mismatches at the 3' end of a probe were greater than those at the 5' end. A cross study comparison of the effect of mismatch types revealed that results were not in good agreement among different reports. However, if the mismatch types were consolidated to purine or pyrimidine mismatches, cross study conclusions could be generated.</p> <p>Conclusion</p> <p>The comprehensive assessment of the effects of single-base mismatches on microarrays provided in this report can be useful for improving future versions of microarray platform design and the corresponding data analysis algorithms.</p

Cluster and MMS simultaneous observations of magnetosheath high speed jets and their impact on the magnetopause

When the supersonic solar wind encounters the Earth's magnetosphere a shock, called bow shock, is formed and the plasma is decelerated and thermalized in the magnetosheath downstream from the shock. Sometimes, however, due to discontinuities in the solar wind, bow shock ripples or ionized dust clouds carried by the solar wind, high speed jets (HSJs) are observed in the magnetosheath. These HSJs have typically a Vx component larger than 200 km s−1 and their dynamic pressure can be a few times the solar wind dynamic pressure. They are typically observed downstream from the quasi-parallel bow shock and have a typical size around one Earth radius (RE) in XGSE. We use a conjunction of Cluster and MMS, crossing simultaneously the magnetopause, to study the characteristics of these HSJs and their impact on the magnetopause. Over 1 h 15 min interval in the magnetosheath, Cluster observed 21 HSJs. During the same period, MMS observed 12 HSJs and entered the magnetosphere several times. A jet was observed simultaneously by both MMS and Cluster and it is very likely that they were two distinct HSJs. This shows that HSJs are not localized into small regions but could span a region larger than 10 RE, especially when the quasi-parallel shock is covering the entire dayside magnetosphere under radial IMF. During this period, two and six magnetopause crossings were observed, respectively, on Cluster and MMS with a significant angle between the observation and the expected normal deduced from models. The angles observed range between from 11° up to 114°. One inbound magnetopause crossing observed by Cluster (magnetopause moving out at 142 km s−1) was observed simultaneous to an outbound magnetopause crossing observed by MMS (magnetopause moving in at −83 km s−1), showing that the magnetopause can have multiple local indentation places, most likely independent from each other. Under the continuous impacts of HSJs, the magnetopause is deformed significantly and can even move in opposite directions at different places. It can therefore not be considered as a smooth surface anymore but more as surface full of local indents. Four dust impacts were observed on MMS, although not at the time when HSJs are observed, showing that dust clouds would have been present during the observations. No dust cloud in the form of Interplanetary Field Enhancements was however observed in the solar wind which may exclude large clouds of dust as a cause of HSJs. Radial IMF and Alfvén Mach number above 10 would fulfill the criteria for the creation of bow shock ripples and the subsequent crossing of HSJs in the magnetosheath.publishedVersio