Cyclic GMP-AMP synthase (cGAS) detects cytosolic DNA during virus infection and induces an antiviral state. cGAS signals by synthesis of a second messenger, cyclic GMP-AMP (cGAMP), which activates ...stimulator of interferon genes (STING). We show that cGAMP is incorporated into viral particles, including lentivirus and herpesvirus virions, when these are produced in cGAS-expressing cells. Virions transferred cGAMP to newly infected cells and triggered a STING-dependent antiviral program.These effects were independent of exosomes and viral nucleic acids. Our results reveal a way by which a signal for innate immunity is transferred between cells, potentially accelerating and broadening antiviral responses. Moreover, infection of dendritic cells with cGAMP-loaded lentiviruses enhanced their activation. Loading viral vectors with cGAMP therefore holds promise for vaccine development.
We are glad to introduce the first Journal Club of volume five, the first issue. This edition is focused on relevant studies published in the last years in the field of eccentric training, chosen by ...our editorial board members and their colleagues. We hope to stimulate your curiosity in this field and to share with you the passion for the sport, seen also from a scientific point of view. The editorial board members wish you an inspiring lecture.
•New application of DBS (Dry Blood Spot) technology for the monitoring of mRNA response to intervention study.•Optimization of existing RNA isolation methodologies to enable multiplex mRNA detection ...using Nanostring.•Potential application of DBS for tracking biological outcomes in large, field-based intervention studies.
Monitoring immunological response to physical stressors in a field setting is challenging because existing methods require a laboratory visit and traditional blood collection via venipuncture. The purpose of this study was to determine if our optimized dry blood spot (DBS) methodology yields sufficient total RNA to quantify the effect of Baker’s Yeast Beta Glucan supplementation (BYBG; Wellmune; 250 mg/d) on post-exercise mRNA expression. Participants had venous DBS samples collected prior to (PRE), and immediately (POST), 2 (2H), and 4 (4H) hrs after completion of a 90 min run/walk trial in a hot, humid environment. Total RNA extracted from DBS was analyzed using a 574-plex Human Immunology mRNA panel (Nanostring). BYBG supplementation was associated with the increased expression of 12 mRNAs (LTB4R, PML, PRFM1, TNFRSF14, LCK, MYD88, STAT3, CCR1, TNFSF10, LILRB3, MME, and STAT6) and decreased expression of 4 mRNAs (MAP4K1, IKBKG, CD5, and IL4R) across all post-exercise time points. In addition to individually changed mRNA targets, we found eleven immune-response pathways that were significantly enriched by BYBG following exercise (TNF Family signaling, immunometabolism, oxidative stress, toll-like receptor (TLR) signaling, Treg differentiation, autophagy, chemokine signaling, complement system, Th2 differentiation, cytokine signaling, and innate immune). The present approach showed that DBS samples can be used to yield useful information about mRNA biomarkers in an intervention study. We have found that BYBG supplementation induces changes at the mRNA level that support the immune system and reduce susceptibility to opportunistic infection (i.e., upper respiratory tract infection) and facilitate improved physical recovery from exercise. Future studies may look to use DBS sampling for testing other nutritional, health, or medical interventions.
•Supplementation with BYBG altered the expression of 47 innate immune system mRNA in response.•Supplementation with BYBG intake may improve innate immune response to both DAMP and PAMP.•Multiplex ...mRNA detection can be an effective to measure small expression changes associated with an orally consumed nutritional compound.
Beta glucans are found in many natural sources, however, only Baker’s Yeast Beta Glucan (BYBG) has been well documented to have structure–function effects that are associated with improved innate immune response to stressors (e.g., exercise, infection, etc.). The purpose was to identify a BYBG-associated mRNA expression pattern following exercise. Participants gave IRB-approved consent and were randomized to BYBG (Wellmune®; N=9) or Placebo (maltodextrin; N=10) for 6-weeks prior to performing 90 min of whole-body exercise. Paxgene blood samples were collected prior to exercise (PRE), after exercise (POST), two hours after exercise (2H), and four hours after exercise (4H). Total RNA was isolated and analyzed for the expression of 770 innate immune response mRNA (730 mRNA targets; 40 housekeepers/controls; Nanostring nCounter). The raw data were normalized against housekeeping controls and expressed as Log2 fold change from PRE for a given condition. Significance was set at p < 0.05 with adjustments for multiple comparisons and false discovery rate. We identified 47 mRNA whose expression was changed after exercise with BYBG and classified them to four functional pathways: 1) Immune Cell Maturation (8 mRNA), 2) Immune Response and Function (5 mRNA), 3) Pattern Recognition Receptors and DAMP or PAMP Detection (25 mRNA), and 4) Detection and Resolution of Tissue Damage (9 mRNA). The identified mRNA whose expression was altered after exercise with BYBG may represent an innate immune response pattern and supports previous conclusions that BYBG improves immune response to a future sterile inflammation or infection.
Exercise-induced muscle injury and the subsequent release of Damage-Associated Molecular Patterns (DAMP) result in soreness and inflammation. Dietary supplements may accelerate the rate of recovery ...by supporting resolution of inflammation. The purpose of this study was to determine if methylsulfonylmethane (MSM) supplementation (30 d prior to exercise and during recovery) altered mRNA expression in LPS-exposed blood leukocytes after a bout of downhill running. Exercise consisted of 60 min of downhill running (−15% grade). Blood (baseline, pre-exercise, 4, 24, 48, and 72 h post-exercise) was diluted (1:10) and combined with LPS (20 µg/mL) for 24 h. Total RNA was isolated from leukocytes and analyzed for 574 immune-associated mRNA (Nanostring nCounter; ROSALIND.BIO). Data were expressed as log2 fold change from baseline for each condition (MSM and placebo). Compared to placebo, MSM supplementation was associated with an improved inflammation response (15 mRNA) and viral immune response (2 mRNA). The largest number of changes were found at 4 and 24 h post-exercise. The key finding in the present study is that MSM supplementation can improve inflammation management and the innate immune response after exercise.
ABSTRACTBridgeman, LA, McGuigan, MR, Gill, ND, and Dulson, DK. Relationships between concentric and eccentric strength and countermovement jump performance in resistance trained men. J Strength Cond ...Res 32(1)255–260, 2018—The purpose of this study was to investigate the relationships between concentric and eccentric peak force (PF) and countermovement jump (CMJ) performance in resistance trained men. Subjects were 12 men (mean ± SD; age25.4 ± 3.5 years; height177.2 ± 4.5 cm; mass84.0 ± 10.1 kg). The men were tested for concentric and eccentric PF using the Exerbotics squat device. Subjects then completed 3 CMJs to allow for the calculation of peak power (PP), peak ground reaction force, and jump height (JH). Correlations between the variables of interest were calculated using Pearson product-moment correlation coefficients. A large relationship was found between absolute concentric PF and absolute CMJ PP (r = 0.66, p ≤ 0.05). Absolute eccentric PF had a very large relationship with absolute CMJ PP and CMJ JH (r = 0.74, p < 0.01 and r = 0.74, p < 0.001, respectively). In addition, absolute eccentric PF was found to have a moderate relationship with relative CMJ PP (r = 0.58, p ≤ 0.05). Relative eccentric PF was had a very large relationship with relative CMJ PP and CMJ JH (r = 0.73, p < 0.001 and r = 0.79, p < 0.001, respectively). Based on these findings, strength and conditioning coaches and athletes who wish to enhance CMJ performance may wish to include exercises, which enhance lower-body eccentric strength within their training.
The aims of this study were (a) to investigate the acute effects of different drop jump (DJ) accentuated eccentric loading (AEL) protocols and (b) to investigate the effect of these AEL DJ protocols ...on subsequent countermovement jump (CMJ) performance. The subjects were 12 strength-trained athletes; initially, baseline CMJ performance was assessed and individual optimal DJ drop height identified. In subsequent weeks, subjects completed 1 set of 5 DJs with no additional load or an AEL of 10, 20, or 30% of their individual body mass (BM) using dumbbells to provide the extra load. After the AEL DJ protocols, 3 CMJs were completed after 2, 6, and 12 minutes rest. A generalized linear mixed model was used to investigate the effects of AEL load and time post-DJs on CMJ height, peak power, and ground reaction force. The 20% AEL condition resulted in greater CMJ height in comparison with all other conditions (p < 0.001). CMJ height was significantly greater after 2 and 6 minutes rest compared with 12 minutes (p < 0.001 and p ≤ 0.05 respectively). Greater peak power was also found during the CMJs after the 20% AEL condition compared with baseline, BM, and 10% AEL (p ≤ 0.05). In conclusion, 5 DJs with 20% AEL followed by a 2 minutes recovery period resulted in significant enhancement in CMJ height and peak power.
Herpesviruses encode a variety of proteins with the potential to disrupt chemokine signaling, and hence immune organization. However, little is known of how these might function in vivo. The B ...cell-tropic murine gammaherpesvirus-68 (MHV-68) is related to the Kaposi's sarcoma-associated herpesvirus (KSHV), but whereas KSHV expresses small chemokine homologues, MHV-68 encodes a broad spectrum chemokine binding protein (M3). Here we have analyzed the effect on viral pathogenesis of a targeted disruption of the M3 gene. After intranasal infection, an M3 deficiency had surprisingly little effect on lytic cycle replication in the respiratory tract or the initial spread of virus to lymphoid tissues. However, the amplification of latently infected B cells in the spleen that normally drives MHV-68-induced infectious mononucleosis failed to occur. Thus, there was a marked reduction in latent virus recoverable by in vitro reactivation, latency-associated viral tRNA transcripts detectable by in situ hybridization, total viral DNA load, and virus-driven B cell activation. In vivo CD8(+) T cell depletion largely reversed this deficiency, suggesting that the chemokine neutralization afforded by M3 may function to block effective CD8(+) T cell recruitment into lymphoid tissue during the expansion of latently infected B cell numbers. In the absence of M3, MHV-68 was unable to establish a normal latent load.
Background
Global positioning systems (GPS) imbedded with accelerometer systems (AS) are used in rugby union (RU) to collect information on absolute and relative distances, distances in different ...speed zones, high-speed running (HSR) distances, repeated high-intensity efforts (RHIE) and collisions and impacts. This information can be used to monitor match play which can then be used to plan training sessions. The objective of this review was to conduct a systematic review of studies which have reported the use of GPS and AS.
Methods
A systematic review of the use of GPS and AS in both age-grade and senior rugby was conducted. The authors systematically searched electronic databases from January 2010 until March 2020. Keywords included rugby union, GPS, global position* and microtechnology.
Results
A total of 51 studies met the eligibility criteria and were included in this review. There was a total of 34 studies utilising GPS and AS in senior RU players (mean ± SD; age 26.2 ± 1.9 years; height 185.7 ± 2.6 cm; mass 101.3 ± 4.2 kg) and 17 studies in age-grade RU players (mean ± SD; age 17.6 ± 1.5 years; height 182.1 ± 3.3 cm; mass 87.1 ± 8.6 kg). The results of this review highlighted that there are differences between backs and forwards and within these positions in these groups during both match play and training sessions. The backs covered greater total absolute, relative and HSR distance compared to forwards. Forwards are involved in more collisions and impacts than backs. When investigating the most intense periods of match play, studies in this review highlighted that the demands during these periods outweigh the average demands of the game. It was proposed that a rolling average over different time epochs is the best way to assess this and ensure that the most intense periods of play are assessed and monitored.
Conclusions
The information highlighted in this review can be used to help coaches assess performances in match play, allow them to plan appropriate training sessions and monitor training load.
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