Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses.

Adjuvants are critical for improving the quality and magnitude of adaptive immune responses to vaccination. Lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccines have shown great efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the mechanism of action of this vaccine platform is not well-characterized. Using influenza virus and SARS-CoV-2 mRNA and protein subunit vaccines, we demonstrated that our LNP formulation has intrinsic adjuvant activity that promotes induction of strong T follicular helper cell, germinal center B cell, long-lived plasma cell, and memory B cell responses that are associated with durable and protective antibodies in mice. Comparative experiments demonstrated that this LNP formulation outperformed a widely used MF59-like adjuvant, AddaVax. The adjuvant activity of the LNP relies on the ionizable lipid component and on IL-6 cytokine induction but not on MyD88- or MAVS-dependent sensing of LNPs. Our study identified LNPs as a versatile adjuvant that enhances the efficacy of traditional and next-generation vaccine platforms.

Development of an mRNA-lipid nanoparticle vaccine against Lyme disease.

Lyme disease is the most common vector-borne infectious disease in the United States, in part because a vaccine against it is not currently available for humans. We propose utilizing the lipid nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) platform to generate a Lyme disease vaccine like the successful clinical vaccines against SARS-CoV-2. Of the antigens expressed by Borrelia burgdorferi, the causative agent of Lyme disease, outer surface protein A (OspA) is the most promising candidate for vaccine development. We have designed and synthesized an OspA-encoding mRNA-LNP vaccine and compared its immunogenicity and protective efficacy to an alum-adjuvanted OspA protein subunit vaccine. OspA mRNA-LNP induced superior humoral and cell-mediated immune responses in mice after a single immunization. These potent immune responses resulted in protection against bacterial infection. Our study demonstrates that highly efficient mRNA vaccines can be developed against bacterial targets.

A Gulf in lockdown: How an enforced ban on recreational vessels increased dolphin and fish communication ranges.

From midnight of 26 March 2020, New Zealand became one of the first countries to enter a strict lockdown to combat the spread of COVID-19. The lockdown banned all non-essential services and travel both on land and sea. Overnight, the country's busiest coastal waterway, the Hauraki Gulf Marine Park, became devoid of almost all recreational and non-essential commercial vessels. An almost instant change in the marine soundscape ensued, with ambient sound levels in busy channels dropping nearly threefold the first 12 h. This sudden drop led fish and dolphins to experience an immediate increase in their communication ranges by up to an estimated 65%. Very low vessel activity during the lockdown (indicated by the presence of vessel noise over the day) revealed new insights into cumulative noise effects from vessels on auditory masking. For example, at sites nearer Auckland City, communication ranges increased approximately 18 m (22%) or 50 m (11%) for every 10% decrease in vessel activity for fish and dolphins, respectively. However, further from the city and in deeper water, these communication ranges were increased by approximately 13 m (31%) or 510 m (20%). These new data demonstrate how noise from small vessels can impact underwater soundscapes and how marine animals will have to adapt to ever-growing noise pollution.

A Multi-Targeting, Nucleoside-Modified mRNA Influenza Virus Vaccine Provides Broad Protection in Mice.

Influenza viruses are respiratory pathogens of public health concern worldwide with up to 650,000 deaths occurring each year. Seasonal influenza virus vaccines are employed to prevent disease, but with limited effectiveness. Development of a universal influenza virus vaccine with the potential to elicit long-lasting, broadly cross-reactive immune responses is necessary for reducing influenza virus prevalence. In this study, we have utilized lipid nanoparticle-encapsulated, nucleoside-modified mRNA vaccines to intradermally deliver a combination of conserved influenza virus antigens (hemagglutinin stalk, neuraminidase, matrix-2 ion channel, and nucleoprotein) and induce strong immune responses with substantial breadth and potency in a murine model. The immunity conferred by nucleoside-modified mRNA-lipid nanoparticle vaccines provided protection from challenge with pandemic H1N1 virus at 500 times the median lethal dose after administration of a single immunization, and the combination vaccine protected from morbidity at a dose of 50 ng per antigen. The broad protective potential of a single dose of combination vaccine was confirmed by challenge with a panel of group 1 influenza A viruses. These findings support the advancement of nucleoside-modified mRNA-lipid nanoparticle vaccines expressing multiple conserved antigens as universal influenza virus vaccine candidates.

Assessing auditory masking for management of underwater anthropogenic noise.

Masking is often assessed by quantifying changes, due to increasing noise, to an animal's communication or listening range. While the methods used to measure communication or listening ranges are functionally similar if used for vocalizations, they differ in their approaches: communication range is focused on the sender's call, while the listening range is centered on the listener's ability to perceive any signal. How these two methods differ in their use and output is important for management recommendations. Therefore it was investigated how these two methods may alter the conclusions of masking assessments based on Atlantic cod calls in the presence of a commercial air gun array. The two methods diverged with increasing distance from the masking noise source with maximum effects lasting longer between air gun pulses in terms of communication range than listening range. Reductions in the cod's communication ranges were sensitive to fluctuations in the call's source level. That instability was not observed for the listening range. Overall, changes to the cod's communication range were more conservative but very sensitive to the call source level. A high level of confidence in the call is therefore required, while confidence in the receiver's audiogram and soundscape is required for the listening range method.

Relationship between vertical stiffness and soft-tissue injuries in professional Australian football.

Soft-tissue injuries are common in Australian football. Recently, literature has identified non-modifiable and modifiable risk factors, including vertical stiffness (Kvert). However, limitations regarding measurement frequency and duration exist; thus, further information is required about the role of Kvert as a modifiable risk factor for injury. This study examined the seasonal variation in Kvert and its relationship to soft-tissue injuries in professional Australian football. The mean Kvert and bilateral asymmetry were assessed and compared between injured and non-injured players. For the seasonal analysis, 56 players were tested across two seasons with no variation in bilateral asymmetry evident (p= 0.33). While there were generally no changes in Kvert, the value from the end of the second pre-season revealed 5% lower values than the mean of two seasons (p= 0.02). Considering the injury analysis, 21 lower-body soft-tissue injuries were recorded from 18 participants. No differences were recorded for mean Kvert between the injured and non-injured groups (p= 0.16-0.76). When assessing Kvert asymmetry, the injured group displayed a 4.5% higher value than the non-injured group at the end of the pre-season test (p= 0.03) but not at other time-points (p= 0.16-0.99). Higher Kvert bilateral asymmetry measures after the pre-season appear to be related to lower-body soft-tissue injury in professional Australian footballers. Medical and conditioning staff should consider this measure when trying to mitigate the onset of injury or identify at-risk players.

Sounds of Arctic cod (Boreogadus saida) in captivity: A preliminary description.

Sounds produced by Arctic cod were recorded for the first time and suggest passive acoustic monitoring (PAM) can be an effective additional tool for the study and management of the species. Each of the 38 calls detected in three different aquatic facilities consisted of a single grunt with 6 to 12 pulses and a mean duration of 289 ms. Call frequency ranged between 59 and 234 Hz, with a mean peak frequency of 107 Hz. These preliminary data suggest Arctic cod can be distinguished from other gadids, but additional studies of sympatric species are needed before PAM can be confidently adopted.

Noise characterization of a subsea tidal kite.

This paper presents the first noise measurements of a quarter-scale subsea tidal kite (anchored to the sea floor by a tether and flying in a figure-eight configuration in the water column) operating in field conditions. Challenges in the measurement and post-processing of the data are detailed. Results are presented for three operating conditions of the kite: (1) varying turbine rotations per minute (RPM), (2) varying kite speed, and (3) a twisted tether. Turbine RPM was identified as the main parameter influencing noise emissions.

The echolocation transmission beam of free-ranging Indo-Pacific humpback dolphins (Sousa chinensis).

While the transmission beam of odontocetes has been described in a number of studies, the majority of them that have measured the transmission beam in two dimensions were focused on captive animals. Within the current study, a dedicated cross hydrophone array with nine elements was used to investigate the echolocation transmission beam of free-ranging Indo-Pacific humpback dolphins. A total of 265 on-axis clicks were analyzed, from which the apparent peak to peak source levels ranged between 168 to 207 dB (mean 184.5 dB ± 6.6 dB). The 3-dB beam width along the horizontal and vertical plane was 9.6° and 7.4°, respectively. Measured separately, the directivity index of the horizontal and vertical plane was 12.6 and 13.5 dB, respectively, and the overall directivity index (both planes combined) was 29.5 dB. The beam shape was slightly asymmetrical along the horizontal and vertical axis. Compared to other species, the characteristics of the transmitting beam of Indo-Pacific humpback dolphins were relatively close to the bottlenose dolphin (Tursiops truncatus), likely due to the similarity in the peak frequency and waveform of echolocation clicks and comparable body sizes of the two species.

Differences in Physical Capacity Between Junior and Senior Australian Footballers.

Kelly, SJ, Watsford, ML, Austin, DJ, Spurrs, RW, Pine, MJ, and Rennie, MJ. Differences in physical capacity between junior and senior Australian footballers. J Strength Cond Res 31(11): 3059-3066, 2017-The purpose of this study was to profile and compare anthropometric and physical capacities within elite junior and senior Australian football (AF) players of various chronological ages and stages of athletic development. Seventy-nine players, including junior and senior AF players from one professional club, were profiled using 11 assessments. Junior players were divided into 2 groups based on chronological age (under 16 and 18 years) and senior players according to years since drafted to a professional AF team (1-2 years, 3-7 years, and 8+ years). Parametric data were assessed using a 1-way analysis of variance (ANOVA), whereas nonparametric data were assessed using a Kruskal-Wallis ANOVA. The magnitude difference between players was measured using the Hopkins' effect size (ES). Significant differences were evident between under-16 players and all senior player groups for anthropometric (p = 0.001-0.019/ES = 1.25-2.13), absolute strength (p = 0.001-0.01/ES = 1.82-4.46), and relative strength (p = 0.001-0.027/ES = 0.84-3.55). The under-18 players displayed significantly lower absolute strength (p = 0.001-0.012/ES = 1.82-3.79) and relative strength (p = 0.001-0.027/ES = 0.85-4.00) compared with the 3-7 and 8+ players. Significant differences were evident between the under-16 players and senior player groups for explosive jumping and throwing tests (p = 0.001-0.017/ES = 1.03-2.99). Minimal differences were evident between all player groups for running assessments; however, the under-16 players were significantly slower compared with the 8+ players for the 3-km time trial (p < 0.02/ES = 1.31), whereas both junior player groups covered significantly less distance during the Yo-Yo IR2 (p < 0.02/ES = 1.19 and 1.60). Results of this study display a significant deficit in strength between junior and senior AF players.

Effects of Underwater Turbine Noise on Crab Larval Metamorphosis.

The development of marine tidal turbines has advanced at a rapid rate over the last decade but with little detailed understanding of the potential noise impacts on invertebrates. Previous research has shown that underwater reef noise plays an important role in mediating metamorphosis in many larval crabs and fishes. New research suggests that underwater estuarine noise may also mediate metamorphosis in estuarine crab larvae and that the noise emitted from underwater tidal and sea-based wind turbines may significantly influence larval metamorphosis in estuarine crabs.

Movement Profiles, Match Events, and Performance in Australian Football.

Johnston, RJ, Watsford, ML, Austin, D, Pine, MJ, and Spurrs, RW. Movement profiles, match events, and performance in Australian football. J Strength Cond Res 30(8): 2129-2137, 2016-This study examined the relationship between movement demands, match events, and match performance in professional Australian football. Data were collected from 19 players using global positioning system units during 2 Australian Football League seasons. A range of movement demands and instantaneous power measures were collected. The players were divided into high-caliber (HC, ≥17/20) and low-caliber (LC, ≤8/20) groups based on the rating score by their coaches. A Mann-Whitney U-test, independent samples t-test, and effect sizes were used to determine whether any differences existed between the 2 groups. The HC group had a significantly higher match duration (7.2%), higher total distance (9.6%), and covered more distance and spent more time high-speed running per minute (12.7 and 11.9%). Although not significant, the effect sizes revealed that the HC group tended to have a higher mean metabolic power output (2.6%) and spent more time at the high power zone (7.9%). For the match event data, the HC group had significantly more involvements with the football. The results demonstrated the higher physical demands placed on the HC group. The findings suggest that analyzing instantaneous power measures can provide valuable information about the physical demands placed on team sport athletes to coaches and conditioning staff.

Movement Demands and Metabolic Power Comparisons Between Elite and Subelite Australian Footballers.

This study examined the differences in movement demands and metabolic power output of elite and subelite Australian football (AF) players and quantified the movement profiles of a subelite AF competition. Movement variables were collected from AF players using Global Positioning System devices over 2 AF League (elite) and North East Australian Football League (NEAFL, subelite) seasons. A total of 500 files were collected from 37 elite and subelite nomadic AF players. NEAFL players covered 13,547 m at an average speed of 124.5 m·min(-1). Elite players performed more high-speed running (5.7-6.3%) and high acceleration and deceleration efforts (1.9-14.7%, p ≤ 0.05). The elite players had a higher mean metabolic power output (3.2%) and time spent at the very high power zone (15.9%, p ≤ 0.05). In contrast, elite players recorded a lower total match duration than the subelite players (4%, p ≤ 0.05). The contrasting amount of high-intensity activities performed by the 2 groups demonstrates the need to alter the training programs of subelite players to ensure they are capable of meeting the demands of elite football. The differences in match duration suggest that reducing subelite players' match time through increasing their rotations would assist the replication of movement profiles of elite players.

An Examination of the Relationship Between Movement Demands and Rating of Perceived Exertion in Australian Footballers.

This study aimed to determine whether a relationship existed between movement demands, match events, and perceptual match load, as determined by rating of perceived exertion (RPE) in professional Australian footballers. The movement variables were collected between 1 and 22 times using global positioning system units from 21 players during the 2011 and 2012 Australian Football League seasons. A range of movement demands and match events were collected to obtain a complete insight into the physical demands and work rates of these athletes. These data were separated into the high-load (HL, ≥9) and low-load (LL, ≤8) RPE groups. A Mann-Whitney U-test, independent samples t-test, and effect sizes were used to determine whether any differences existed between the 2 groups and the size of the difference. The results revealed that the HL groups covered more distance, spent more time, and produced more efforts at the high deceleration zone (2.4-6.7%). Further, the HL group had more possessions and disposals of the football than the LL group (9.2-29.6%). The findings have highlighted the importance of monitoring accelerations, decelerations, and instantaneous power outputs to obtain a comprehensive insight into the physical demands placed on team sport athletes. Furthermore, the results demonstrate that training sessions should involve a focus on drills that are composed of both skill development and physical stimulus element.

Validity and interunit reliability of 10 Hz and 15 Hz GPS units for assessing athlete movement demands.

The purpose of this study was to assess the validity and interunit reliability of 10 Hz (Catapult) and 15 Hz (GPSports) Global Positioning System (GPS) units and investigate the differences between these units as measures of team sport athlete movement demands. A team sport simulation circuit was completed by 8 trained male participants. The movement demands examined included: total distance covered (TD), average peak speed, and the distance covered, time spent, and the number of efforts performed low-speed running (0.00-13.99 km · h(-1)), high-speed running (14.00-19.99 km · h(-1)), and very high-speed running (>20.00 km · h(-1)). The degree of difference between the 10 Hz and the 15 Hz GPS units and validity was assessed using a paired samples t-test. Pearson's correlations were also used for validity assessment. Interunit reliability was established using percentage typical error of measurement (%TEM) and intraclass correlations. The findings revealed that 10 Hz GPS units were a valid (p > 0.05) and reliable (%TEM = 1.3%) measure of TD. In contrast, the 15 Hz GPS units exhibited lower validity for TD and average peak speed. Further, as the speed of movement increased the level of error for the 10 Hz and 15 Hz GPS units increased (%TEM = 0.8-19.9). The findings from this study suggest that comparisons should not be undertaken between 10 Hz and 15 Hz GPS units. In general, the 10 Hz GPS units measured movement demands with greater validity and interunit reliability than the 15 Hz units, however, both 10 Hz and 15 Hz units provided the improved measures of movement demands in comparison to 1 Hz and 5 Hz GPS units.

Not so silent spectators: How spectator vessels at international sailing regattas alter marine soundscapes.

International sailing regattas are major sporting events often held within coastal marine environments which overlap with the habitats of marine species. Although races are confined to courses, the popularity of these events can attract large spectator flotillas, sometimes composed of hundreds of motorized vessels. Underwater noise from these flotillas can potentially alter soundscapes experienced by marine species. To understand how these flotillas may alter soundscapes, acoustic recordings were taken around racecourses during the 36th America's Cup in the Hauraki Gulf, New Zealand in 2021. Sustained increases in broadband underwater sound levels during the regatta (up to 17 dB re 1 µPa rms; 0.01-24 kHz) that extended beyond racecourse boundaries (>8.5 km) and racing hours were observed; very likely attributable to the increase in regatta-related vessel activity. Underwater noise pollution from spectator flotillas attending larger regattas should be considered during event planning stages, particularly when events occur in ecologically significance areas.

Seasonal variation of leg stiffness in professional Australian rules footballers.

Leg stiffness (Kleg) is an important component to consider in both performance and injury in the Australian Football League (AFL). Kleg has not yet been examined longitudinally throughout an entire AFL season. A unilateral hop test was used to measure Kleg in the left and right legs of 25 professional AFL players (24.9 ± 4.3 years, 86.8 ± 8.1 kg, 187.0 ± 7.3 cm). Kleg was assessed at least once per month for each participant. Furthermore, the session rate of perceived exertion method was used to quantify the average weekly training loads experienced by the participants. One-way analysis of variance revealed no significant difference between the average monthly bilateral Kleg scores; however, average weekly training loads varied between 1,400 and 2,000 AU, depending on the training period. Thirteen participants were randomly selected to perform hop tests on 2 consecutive weeks. Reliability tests revealed these measurements to have a typical error of the measurement of 4.15% and an intraclass correlation of 0.8, proving the methods to be reliable. Although training intensity appears to vary, Kleg does not fluctuate significantly across an entire AFL season, suggesting that weekly training loads between 1,400 and 2,000 AU may be prescribed without the risk of fluctuating stiffness levels.

Impact of small boat sound on the listening space of Pempheris adspersa, Forsterygion lapillum, Alpheus richardsoni and Ovalipes catharus.

Anthropogenic stressors, such as plastics and fishing, are putting coastal habitats under immense pressure. However, sound pollution from small boats has received little attention given the importance of sound in the various life history strategies of many marine animals. By combining passive acoustic monitoring, propagation modelling, and hearing threshold data, the impact of small-boat sound on the listening spaces of four coastal species was determined. Listening space reductions (LSR) were greater for fishes compared to crustaceans, for which LSR varied by day and night, due to their greater hearing abilities. Listening space also varied by sound modality for the two fish species, highlighting the importance of considering both sound pressure and particle motion. The theoretical results demonstrate that boat sound hinders the ability of fishes to perceive acoustic cues, advocating for future field-based research on acoustic cues, and highlighting the need for effective mitigation and management of small-boat sound within coastal areas worldwide.

Acoustic Presence of Cetaceans in the Miaodao Archipelago, China.

Once an important cetacean habitat, the Miaodao Archipelago has been altered by human-induced disturbances over several decades. While cetacean diversity is known to have decreased, no recent data on species diversity around Miaodao are known to exist. Capitalizing on the high vocal activity of cetaceans, three passive acoustic surveys, including towed and stationary types, were undertaken to detect the presence of species-specific vocalizations in May 2021, October 2021, and July 2022, as most cetacean sightings occurred during May and August in recent years. The results revealed that the East Asian finless porpoise is the sole cetacean species that can be reliably observed around the archipelago, as no other species were detected. The acoustic data also revealed potentially clumped distributions of finless porpoises with some seasonal variation. While not acoustically detected during any of the surveys, humpback whales, minke whales, and killer whales have been visually sighted in the region. The lack of acoustic detection of these species suggests that they are likely to be temporary visitors to the region, or at least exhibit strong seasonality in their presence within the region. These new data provide the latest snapshot of cetacean presence around the Miaodao Archipelago that can help inform future research and conservation.