Evidence for the use of cannabis-based medicines in osteoarthritis: a scoping review.

The purpose of this study was to conduct a scoping review to describe the evidence on the efficacy and safety of using cannabis-based medicines for osteoarthritis. The review was conducted following the framework proposed by Arksey and O'Malley and reported following PRISMA extension for scoping reviews guidelines. We conducted a comprehensive search across various databases including MEDLINE, Embase, Cochrane Library, CINAHL, Scopus, and Proquest, spanning from inception of each database to March 2023. We retrieved 2533 citations, and after deduplication, title and abstract screening, and full-text screening, 10 articles were included for analysis. These studies were composed of randomized-controlled trials (n = 4/10), cross-sectional surveys (n = 3/10), case studies (n = 2/10), and a cohort study (n = 1/10). Evidence for using cannabis-based medicines was mixed, with just 60% (n = 6/10) of included studies reporting statistically significant improvements in pain. Studies with larger samples sizes and longer durations of exposure did not find significant benefits for pain. The few adverse effects reported were generally mild and affected a minority of participants. Several studies also discovered that cannabis-based medicines were associated with a reduction in opioid use. Currently available data on the use of cannabis-based medicines in osteoarthritis is insufficient to make recommendations. Future research should address concerns regarding small sample sizes and short treatment durations to provide a more robust evidence base. Key Points • Current evidence remains mixed; studies that found a positive benefit with using cannabis-based medicines had limitations with small sample sizes and short durations of exposure • The use of cannabis-based medicines in osteoarthritis appears to be generally well tolerated, adverse effects are mild and experienced by a minority of participants • Cannabis-based medicines may decrease the use of opioids in patients with osteoarthritis • Future research should address the gaps in long-term efficacy and safety data.

Dimethyl sulfoxide as a novel therapy in a murine model of acute lung injury.

INTRODUCTION: The endothelial glycocalyx on the luminal surface of endothelial cells contributes to the permeability barrier of the pulmonary vasculature. Dimethyl sulfoxide (DMSO) has a disordering effect on plasma membranes, which prevents the formation of ordered membrane domains important in the shedding of the endothelial glycocalyx. We hypothesized that DMSO would protect against protein leak by preserving the endothelial glycocalyx in a murine model of acute respiratory distress syndrome (ARDS). METHODS: C57BL/6 mice were given ARDS via intratracheally administered lipopolysaccharide (LPS). Dimethyl sulfoxide (220 mg/kg) was administered intravenously for 4 days. Animals were sacrificed postinjury day 4 after bronchoalveolar lavage (BAL). Bronchoalveolar lavage cell counts and protein content were quantified. Lung sections were stained with fluorescein isothiocyanate-labeled wheat germ agglutinin to quantify the endothelial glycocalyx. Human umbilical vein endothelial cells (HUVECs) were exposed to LPS. Endothelial glycocalyx was measured using fluorescein isothiocyanate-labeled wheat germ agglutinin, and co-immunoprecipitation was performed to measure interaction between sheddases and syndecan-1. RESULTS: Dimethyl sulfoxide treatment resulted in greater endothelial glycocalyx staining intensity in the lung when compared with sham (9,641 vs. 36,659 arbitrary units, p < 0.001). Total BAL cell counts were less for animals receiving DMSO (6.93 × 10 6 vs. 2.49 × 10 6 cells, p = 0.04). The treated group had less BAL macrophages (189.2 vs. 76.9 cells, p = 0.02) and lymphocytes (527.7 vs. 200.0 cells, p = 0.02). Interleukin-6 levels were lower in DMSO treated. Animals that received DMSO had less protein leak in BAL (1.48 vs. 1.08 µg/µL, p = 0.02). Dimethyl sulfoxide prevented LPS-induced endothelial glycocalyx loss in HUVECs and reduced the interaction between matrix metalloproteinase 16 and syndecan-1. CONCLUSION: Systemically administered DMSO protects the endothelial glycocalyx in the pulmonary vasculature, mitigating pulmonary capillary leak after acute lung injury. Dimethyl sulfoxide also results in decreased inflammatory response. Dimethyl sulfoxide reduced the interaction between matrix metalloproteinase 16 and syndecan-1 and prevented LPS-induced glycocalyx damage in HUVECs. Dimethyl sulfoxide may be a novel therapeutic for ARDS.

Blood epigenome-wide association studies of suicide attempt in adults with bipolar disorder.

Suicide attempt (SA) risk is elevated in individuals with bipolar disorder (BD), and DNA methylation patterns may serve as possible biomarkers of SA. We conducted epigenome-wide association studies (EWAS) of blood DNA methylation associated with BD and SA. DNA methylation was measured at >700,000 positions in a discovery cohort of n = 84 adults with BD with a history of SA (BD/SA), n = 79 adults with BD without history of SA (BD/non-SA), and n = 76 non-psychiatric controls (CON). EWAS revealed six differentially methylated positions (DMPs) and seven differentially methylated regions (DMRs) between BD/SA and BD/non-SA, with multiple immune-related genes implicated. There were no epigenome-wide significant differences when BD/SA and BD/non-SA were each compared to CON, and patterns suggested that epigenetics differentiating BD/SA from BD/non-SA do not differentiate BD/non-SA from CON. Weighted gene co-methylation network analysis and trait enrichment analysis of the BD/SA vs. BD/non-SA contrast further corroborated immune system involvement, while gene ontology analysis implicated calcium signalling. In an independent replication cohort of n = 48 BD/SA and n = 47 BD/non-SA, fold changes at the discovery cohort's significant sites showed moderate correlation across cohorts and agreement on direction. In both cohorts, classification accuracy for SA history among individuals with BD was highest when methylation at the significant CpG sites as well as information from clinical interviews were combined, with an AUC of 88.8% (CI = 83.8-93.8%) and 82.1% (CI = 73.6-90.5%) for the combined epigenetic-clinical classifier in the discovery and replication cohorts, respectively. Our results provide novel insight to the role of immune system functioning in SA and BD and also suggest that integrating information from multiple levels of analysis holds promise to improve risk assessment for SA in adults with BD.

Effect of marine heatwaves and warming on kelp microbiota influence trophic interactions.

The range-expansion of tropical herbivores due to ocean warming can profoundly alter temperate reef communities by overgrazing the seaweed forests that underpin them. Such ecological interactions may be mediated by changes to seaweed-associated microbiota in response to warming, but empirical evidence demonstrating this is rare. We experimentally simulated ocean warming and marine heatwaves (MHWs) to quantify effects on two dominant temperate seaweed species and their microbiota, as well as grazing by a tropical herbivore. The kelp Ecklonia radiata's microbiota in sustained warming and MHW treatments was enriched with microorganisms associated with seaweed disease and tissue degradation. In contrast, the fucoid Sargassum linearifolium's microbiota was unaffected by temperature. Consumption by the tropical sea-urchin Tripneustes gratilla was greater on Ecklonia where the microbiota had been altered by higher temperatures, while Sargassum's consumption was unaffected. Elemental traits (carbon, nitrogen), chemical defences (phenolics) and tissue bleaching of both seaweeds were generally unaffected by temperature. Effects of warming and MHWs on seaweed holobionts (host plus its microbiota) are likely species-specific. The effect of increased temperature on Ecklonia's microbiota and subsequent increased consumption suggest that changes to kelp microbiota may underpin kelp-herbivore interactions, providing novel insights into potential mechanisms driving change in species' interactions in warming oceans.

Dimethyl malonate protects the lung in a murine model of acute respiratory distress syndrome.

BACKGROUND: Succinate is a proinflammatory citric acid cycle metabolite that accumulates in tissues during pathophysiological states. Oxidation of succinate after ischemia-reperfusion leads to reversal of the electron transport chain and generation of reactive oxygen species. Dimethyl malonate (DMM) is a competitive inhibitor of succinate dehydrogenase, which has been shown to reduce succinate accumulation. We hypothesized that DMM would protect against inflammation in a murine model of ARDS. METHODS: C57BL/6 mice were given ARDS via 67.7 µg of intratracheally administered lipopolysaccharide. Dimethyl malonate (50 mg/kg) was administered via tail vein injection 30 minutes after injury, then daily for 3 days. The animals were sacrificed on day 4 after bronchoalveolar lavage (BAL). Bronchoalveolar lavage cell counts were performed to examine cellular influx. Supernatant protein was quantified via Bradford protein assay. Animals receiving DMM (n = 8) were compared with those receiving sham injection (n = 8). Cells were fixed and stained with FITC-labeled wheat germ agglutinin to quantify the endothelial glycocalyx (EGX). RESULTS: Total cell counts in BAL was less for animals receiving DMM (6.93 × 10 6 vs. 2.46 × 10 6 , p = 0.04). The DMM group had less BAL macrophages (168.6 vs. 85.1, p = 0.04) and lymphocytes (527.7 vs. 248.3; p = 0.04). Dimethyl malonate-treated animals had less protein leak in BAL than sham treated (1.48 vs. 1.15 µg/µl, p = 0.03). Treatment with DMM resulted in greater staining intensity of the EGX in the lung when compared with sham (12,016 vs. 15,186 arbitrary units, p = 0.03). Untreated animals had a greater degree of weight loss than treated animals (3.7% vs. 1.1%, p = 0.04). Dimethyl malonate prevented the upregulation of monocyte chemoattractant protein-1 (1.66 vs. 0.92 RE, p = 0.02) and ICAM-1 (1.40 vs. 1.01 RE, p = 0.05). CONCLUSION: Dimethyl malonate reduces lung inflammation and capillary leak in ARDS. This may be mediated by protection of the EGX and inhibition of monocyte chemoattractant protein-1 and ICAM-1. Dimethyl malonate may be a novel therapeutic for ARDS.

Tropical Storms and Hurricanes in New Orleans Lead to Increased Rates of Violent Injury.

OBJECTIVE: The effects of named weather storms on the rates of penetrating trauma is poorly understood with only case reports of single events currently guiding public health policy. This study examines whether tropical storms and hurricanes contribute to trauma services and volume. METHODS: This was a cross-sectional review of tropical storms/hurricanes affecting New Orleans, Louisiana, during hurricane seasons (June 1-November 30) from 2010-2021, and their association with the rate of penetrating trauma. Authors sought to determine how penetrating trauma rates changed during hurricane seasons and associate them with demographic variables. RESULTS: There were 5531 penetrating injuries, with 412 (7.4%) occurring during landfall and 554 (10.0%) in the aftermath. Black/African Americans were the most affected. There was an increase in the rate of penetrating events during landfall (3.4 events/day) and aftermath (3.5 events/day) compared to the baseline (2.8 events/day) (P = < 0.001). Using multivariate analysis, wind speed was positively related to firearm injury, whereas the rainfall total was inversely related to firearm violence rates during landfall and aftermath periods. Self-harm was positively related to distance from the trauma center. CONCLUSIONS: Cities at risk for named weather storms may face increasing gun violence in the landfall and aftermath periods. Black/African Americans are most affected, worsening existing disparities. Self-harm may also increase following these weather events.

Blood epigenome-wide association studies of suicide attempt in adults with bipolar disorder.

Suicide attempt (SA) risk is elevated in individuals with bipolar disorder (BD), and DNA methylation patterns may serve as possible biomarkers of SA. We conducted epigenome-wide association studies (EWAS) of blood DNA methylation associated with BD and SA. DNA methylation was measured at > 700,000 positions in a discovery cohort of n = 84 adults with BD with a history of SA (BD/SA), n = 79 adults with BD without history of SA (BD/non-SA), and n = 76 non-psychiatric controls (CON). EWAS revealed six differentially methylated positions (DMPs) and seven differentially methylated regions (DMRs) between BD/SA and BD/non-SA, with multiple immune-related genes implicated. There were no epigenome-wide significant differences when BD/SA and BD/non-SA were each compared to CON, and patterns suggested that epigenetics differentiating BD/SA from BD/non-SA do not differentiate BD/non-SA from CON. Weighted gene co-methylation network analysis and trait enrichment analysis of the BD/SA vs. BD/non-SA contrast further corroborated immune system involvement, while gene ontology analysis implicated calcium signalling. In an independent replication cohort of n = 48 BD/SA and n = 47 BD/non-SA, fold-changes at the discovery cohort's significant sites showed moderate correlation across cohorts and agreement on direction. In both cohorts, classification accuracy for SA history among individuals with BD was highest when methylation at the significant CpG sites as well as information from clinical interviews were combined, with an AUC of 88.8% (CI = 83.8-93.8%) and 82.1% (CI = 73.6-90.5%) for the combined epigenetic-clinical predictor in the discovery and replication cohorts, respectively. Our results provide novel insight to the role of immune system functioning in SA and BD and also suggest that integrating information from multiple levels of analysis holds promise to improve risk assessment for SA in adults with BD.

The one-week prevalence of neck pain and low back pain in post-secondary students at two Canadian institutions.

BACKGROUND: Low back and neck pain are common in the general population, but the prevalence among Canadian post-secondary students is not well known. We aimed to determine the one-week prevalence of neck pain (NP) and low back pain (LBP) among postsecondary students in Canada. METHODS: We conducted a cross-sectional study of students enrolled in the Faculty of Health Sciences and Faculty of Education at Ontario Tech University, and the Canadian Memorial Chiropractic College (CMCC) in the Fall of 2017. Neck and low back pain intensity in the past week were measured with the 11-point numerical rating scale. We report the cumulative, gender- and institution-specific one-week prevalence (95% CI) of any pain (1-10/10) and moderate to severe pain (≥ 3/10). RESULTS: The one-week prevalence of any neck pain ranged from 45.4% (95% CI: 38.4, 52.4) in the Faculty of Education to 76.9% (95% CI: 72.9, 80.4) at CMCC. The one-week prevalence of neck pain ≥3/10 ranged from 44.4% (95% CI: 37.5, 51.4) in the Faculty of Education to 58.4% (95% CI: 54.0, 62.7) at CMCC. The one-week prevalence of any low back pain ranged from 60.9% (95% CI: 53.8, 67.5) in the Faculty of Education to 69.0% (95% CI: 64.8, 73.0) at CMCC, and the one-week prevalence of low back pain ≥ 3/10 ranged from 47.8% (95% CI: 43.4, 52.2) at CMCC to 55.1% (95% CI: 51.2, 58.9) in the Faculty of Health Sciences. The prevalence of any back or neck pain and pain ≥ 3/10 was consistently higher in females than males, with the largest difference seen for neck pain at CMCC. CONCLUSION: Most post-secondary students in our samples experienced LBP and NP in the past week. Overall, the one-week prevalence of NP and LBP was higher among chiropractic students and among females. This study should draw attention to school administrators about the burden of NP and LBP in post-secondary students.

Association between the epigenetic lifespan predictor GrimAge and history of suicide attempt in bipolar disorder.

Bipolar disorder (BD) has been previously associated with premature mortality and aging, including acceleration of epigenetic aging. Suicide attempts (SA) are greatly elevated in BD and are associated with decreased lifespan, biological aging, and poorer clinical outcomes. We investigated the relationship between GrimAge, an epigenetic clock trained on time-to-death and associated with mortality and lifespan, and SA in two independent cohorts of BD individuals (discovery cohort - controls (n = 50), BD individuals with (n = 77, BD/SA) and without (n = 67, BD/non-SA) lifetime history of SA; replication cohort - BD/SA (n = 48) and BD/non-SA (n = 47)). An acceleration index for the GrimAge clock (GrimAgeAccel) was computed from blood DNA methylation (DNAm) and compared between groups with multiple general linear models. Differences in epigenetic aging from the discovery cohort were validated in the independent replication cohort. In the discovery cohort, controls, BD/non-SA, and BD/SA significantly differed on GrimAgeAccel (F = 5.424, p = 0.005), with the highest GrimAgeAccel in BD/SA (p = 0.004, BD/SA vs. controls). Within the BD individuals, BD/non-SA and BD/SA differed on GrimAgeAccel in both cohorts (p = 0.008) after covariate adjustment. Finally, DNAm-based surrogates revealed possible involvement of plasminogen activator inhibitor 1, leptin, and smoking pack-years in driving accelerated epigenetic aging. These findings pair with existing evidence that not only BD, but also SA, may be associated with an accelerated biological aging and provide putative biological mechanisms for morbidity and premature mortality in this population.

In defence of falling: the onomastics and ethics of "therapeutic" falls in rehabilitation.

Aim: Despite efforts towards a more just culture, rehabilitation providers still experience shame and trauma when their patients fall. This paper proposes a shift in philosophy in how we classify, communicate and learn from falls, and joins the growing literature in which falls in rehab are not seen as something to be avoided at all costs, but rather as part of the recovery journey for some patients.Methods: Patients who understand and are willing to take on the risks of falling are more likely to collaborate with their care team to practice higher-risk activities, such as walking to the bathroom independently at night, as part of their recovery. If a fall takes place in this context, we argue that it should be considered a "therapeutic" fall.Results: This paper details some of the clinical and ethical approaches to supporting a care environment where values-and potential conflicts-about the benefits and challenges of risk-taking are recognized. An expanded concept of a therapeutic fall may help patients and providers take a more balanced and nuanced approach to promoting safety while maximising independence.Conclusion: The goal of this work is to offer rehabilitation patients greater opportunities to make autonomous decisions about their mobility, and lay the groundwork for a more successful transition home.IMPLICATIONS FOR REHABILITATIONDespite best efforts, patients are often less active than they or their rehabilitation team might wish them to be.An expanded concept of a "therapeutic" fall may help patients and providers take a more balanced and nuanced approach to promoting safety while maximising independence.Rehabilitation is the right environment to support shared decision-making about risk that better prepares patients and families for the often challenging transition back to community living.This works represents a shift in philosophy in how we classify, communicate and learn from falls, and joins the growing literature in which falls are not something to be avoided at all costs, but can instead be part of the journey to recovery.

Epigenetic GrimAge acceleration and cognitive impairment in bipolar disorder.

Bipolar disorder (BD) has been previously associated with clinical signs of premature aging, including accelerated epigenetic aging in blood and brain, and a steeper age-related decline in cognitive function. However, the clinical drivers and cognitive correlates of epigenetic aging in BD are still unknown. We aimed to investigate the relationship between multiple measures of epigenetic aging acceleration with clinical, functioning, and cognitive outcomes in patients with BD and controls. Blood genome-wide DNA methylation levels were measured in BD patients (n = 153) and matched healthy controls (n = 50) with the Infinium MethylationEPIC BeadChip (Illumina). Epigenetic age estimates were calculated using an online tool, including the recently developed lifespan predictor GrimAge, and analyzed with generalized linear models controlling for demographic variables and blood cell proportions. BD was significantly associated with greater GrimAge acceleration (AgeAccelGrim, ß=0.197, p = 0.009), and significant group-dependent interactions were found between AgeAccelGrim and blood cell proportions (CD4+ T-lymphocytes, monocytes, granulocytes, and B-cells). Within patients, higher AgeAccelGrim was associated with worse cognitive function in multiple domains (short-term affective memory (ß=-0.078, p = 0.030), short-term non-affective memory (ß=-0.088, p = 0.018), inhibition (ß=0.064, p = 0.046), and problem solving (ß=-0.067, p = 0.034)), age of first diagnosis with any mood disorder (ß=-0.076, p = 0.039) or BD (ß=-0.102, p = 0.016), as well as with current non-smoking status (ß=-0.392, p < 0.001). Overall, our findings support the contribution of epigenetic factors to the aging-related cognitive decline and premature mortality reported in BD patients, with an important driving effect of smoking in this population.

Is the Intestinal Bacterial Community in the Australian Rabbitfish Siganus fuscescens Influenced by Seaweed Supplementation or Geography?

We recently demonstrated that dietary supplementation with seaweed leads to dramatic improvements in immune responses in S. fuscescens, a candidate species for aquaculture development in Asia. Here, to assess whether the immunostimulatory effect was facilitated by changes to the gut microbiome, we investigated the effects of those same seaweed species and four commercial feed supplements currently used in aquaculture on the bacterial communities in the hindgut of the fish. Since we found no correlations between the relative abundance of any particular taxa and the fish enhanced innate immune responses, we hypothesised that S. fuscescens might have a core microbiome that is robust to dietary manipulation. Two recently published studies describing the bacteria within the hindgut of S. fuscescens provided an opportunity to test this hypothesis and to compare our samples to those from geographically distinct populations. We found that, although hindgut bacterial communities were clearly and significantly distinguishable between studies and populations, a substantial proportion (55 of 174 taxa) were consistently detected across all populations. Our data suggest that the importance of gut microbiota to animal health and the extent to which they can be influenced by dietary manipulations might be species-specific or related to an animals' trophic level.

Host genetics, phenotype and geography structure the microbiome of a foundational seaweed.

Interactions between hosts and their microbiota are vital to the functioning and resilience of macro-organisms. Critically, for hosts that play foundational roles in communities, understanding what drives host-microbiota interactions is essential for informing ecosystem restoration and conservation. We investigated the relative influence of host traits and the surrounding environment on microbial communities associated with the foundational seaweed Phyllospora comosa. We quantified 16 morphological and functional phenotypic traits, including host genetics (using 354 single nucleotide polymorphisms) and surface-associated microbial communities (using 16S rRNA gene amplicon sequencing) from 160 individuals sampled from eight sites spanning Phyllospora's entire latitudinal distribution (1,300 km). Combined, these factors explained 54% of the overall variation in Phyllospora's associated microbial community structure, much of which was related to the local environment (~32%). We found that putative "core" microbial taxa (i.e., present on all Phyllospora individuals sampled) exhibited slightly higher associations with host traits when compared to "variable" taxa (not present on all individuals). We identified several key genetic loci and phenotypic traits in Phyllospora that were strongly related to multiple microbial amplicon sequence variants, including taxa with known associations to seaweed defence, disease and tissue degradation. This information on how host-associated microbial communities vary with host traits and the environment enhances our current understanding of how "holobionts" (hosts plus their microbiota) are structured. Such understanding can be used to inform management strategies of these important and vulnerable habitats.

Molecular analysis of a fungal disease in the habitat-forming brown macroalga Phyllospora comosa (Fucales) along a latitudinal gradient.

Infectious diseases affecting habitat-forming species can have significant impacts on population dynamics and alter the structure and functioning of marine ecosystems. Recently, a fungal infection was described as the causative agent of necrotic lesions on the stipe of the forest-forming macroalga Phyllospora comosa, a disease named "stipe rot" (SR). Here, we developed a quantitative PCR (qPCR) method for rapid detection and quantification of this pathogen, which was applied to evaluate the level of SR infection in eight P. comosa populations spanning the entire latitudinal distribution of this species along southeastern Australia. We also investigated the relationship between the abundance and prevalence of Stipe Rot Fungus (SRF) and potential host chemical defenses as well as its relationship with morphological and ecophysiological traits of P. comosa. qPCR estimates of SRF abundance reflected the levels of infection estimated by visual assessment, with higher numbers of SRF copies being observed in individuals showing high or intermediate levels of visual symptoms of SR. Concordance of conventional PCR and visual assessments was 92 and 94%, respectively, compared to qPCR detection. SRF prevalence was positively related to fucoxanthin content and herbivory, but not significant related to other traits measured (phlorotannin content, total length, thallus diameter, stipe width, number of branches, frond width, fouling, bleaching, gender, and photosynthetic efficiency). These results provide confidence for previous reports of this disease based upon visual assessments only, contribute to the development of monitoring and conservation strategies for safeguarding P. comosa forests, and generate insights into potential factors influencing host-pathogen interactions in this system.

Application of omics research in seaweeds with a focus on red seaweeds.

Targeted 'omics' research for seaweeds, utilizing various computational and informatics frameworks, has the potential to rapidly develop our understanding of biological processes at the molecular level and contribute to solutions for the most pressing environmental and social issues of our time. Here, a systematic review into the current status of seaweed omics research was undertaken to evaluate the biological diversity of seaweed species investigated (red, green and brown phyla), the levels to which the work was undertaken (from full genome to transcripts, proteins or metabolites) and the field of research to which it has contributed. We report that from 1994 to 2021 the majority of seaweed omics research has been performed on the red seaweeds (45% of total studies), with more than half of these studies based upon two genera Pyropia and Gracilaria. A smaller number of studies examined brown seaweed (key genera Saccharina and Sargassum) and green seaweed (primarily Ulva). Overall, seaweed omics research is most highly associated with the field of evolution (46% of total studies), followed by the fields of ecology, natural products and their biosynthesis, omics methodology and seaweed-microbe interactions. Synthesis and specific outcomes derived from omics studies in the red seaweeds are provided. Together, these studies have provided a broad-scale interrogation of seaweeds, facilitating our ability to answer fundamental queries and develop applied outcomes. Crucial to the next steps will be establishing analytical tools and databases that can be more broadly utilized by practitioners and researchers across the globe because of their shared interest in the key seaweed genera.

Seaweed dietary supplements enhance the innate immune response of the mottled rabbitfish, Siganus fuscescens.

Disease is one of the major bottlenecks for aquaculture development, costing the industry in excess of US $6 billion each year. The increase in pressure to phase out some traditional approaches to disease control (e.g. antibiotics) is pushing farmers to search for alternatives to treat and prevent disease outbreaks, which do not have detrimental consequences (e.g. antibiotic resistance). We tested the effects of eleven seaweed species and four established fish immunostimulants on the innate immune response (cellular and humoral immunity) of the rabbitfish Siganus fuscescens. All supplements including different seaweeds from the three groups (Chlorophyta, Phaeophyta and Rhodophyta) were included in the fish pellet at 3% (by weight) and had variably positive effects across the four innate immune parameters we measured compared to control fish. Diets supplemented with the red seaweed Asparagopsis taxiformis and the brown seaweed Dictyota intermedia led to the largest boosts in humoral and cellular innate immune defences, including particularly significant increases in haemolytic activity. Diets supplemented with Ulva fasciata also led to promising positive effects on the fish innate immune responses. We conclude that dietary seaweed supplements can boost the immune response of S. fuscescens and thus the top three species highlighted in this study should be further investigated for this emerging aquaculture species and other fish species.

Genomic vulnerability of a dominant seaweed points to future-proofing pathways for Australia's underwater forests.

Globally, critical habitats are in decline, threatening ecological, economic and social values and prompting calls for 'future proofing' efforts that enhance resilience to climate change. Such efforts rely on predicting how neutral and adaptive genomic patterns across a species' distribution will change under future climate scenarios, but data is scant for most species of conservation concern. Here, we use seascape genomics to characterise genetic diversity, structure and gene-environmental associations in a dominant forest-forming seaweed, Phyllospora comosa, along its entire latitudinal (12° latitude), and thermal (~14°C) range. Phyllospora showed high connectivity throughout its central range, with evidence of genetic structure and potential selection associated with sea surface temperatures (SSTs) at its rear and leading edges. Rear and leading-edge populations harboured only half the genetic diversity of central populations. By modelling genetic turnover as a function of SST, we assessed the genomic vulnerability across Phyllospora's distributional range under climate change scenarios. Despite low diversity, range-edge populations were predicted to harbour beneficial adaptations to marginal conditions and overall adaptability of the species may be compromised by their loss. Assisted gene flow from range edge populations may be required to enhance adaptation and increase resilience of central and leading-edge populations under warming oceans. Understanding genomic vulnerability can inform proactive restoration and future-proofing strategies for underwater forests and ensure their persistence in changing oceans.

Kelp forests.

Vergés and Campbell introduce the kelp forest ecosystem.

Binding Interactions of Ergotamine and Dihydroergotamine to 5-Hydroxytryptamine Receptor 1B (5-HT1b) Using Molecular Dynamics Simulations and Dynamic Network Analysis.

Ergotamine (ERG) and dihydroergotamine (DHE), common migraine drugs, have small structural differences but lead to clinically important distinctions in their pharmacological profiles. For example, DHE is less potent than ERG by about 10-fold at the 5-hydroxytrptamine receptor 1B (5-HT1B). Although the high-resolution crystal structures of the 5-HT1B receptor with both ligands have been solved, the high similarity between these two complex structures does not sufficiently explain their activity differences and the activation mechanism of the receptor. Hence, an examination of the dynamic motion of both drugs with the receptor is required. In this study, we ran a total of 6.0 µs molecular dynamics simulations on each system. Our simulation data show the subtle variations between the two systems in terms of the ligand-receptor interactions and receptor secondary structures. More importantly, the ligand and protein root-mean-square fluctuations (RMSFs) for the two systems were distinct, with ERG having a trend of lower RMSF values, indicating it to be bound tighter to 5-HT1B with less fluctuations. The molecular mechanism-general born surface area (MM-GBSA) binding energies illustrate this further, proving ERG has an overall stronger MM-GBSA binding energy. Analysis of several different microswitches has shown that the 5-HT1B-ERG complex is in a more active conformation state than 5-HT1B-DHE, which is further supported by the dynamic network model, with reference to mutagenesis data with the critical nodes and the first three low-energy modes from the normal mode analysis. We also identify Trp3276.48 and Phe3316.52 as key residues involved in the active state 5-HT1B for both ligands. Using the detailed dynamic information from our analysis, we made predictions for possible modifications to DHE and ERG that yielded five derivatives that might have more favorable binding energies and reduced structural fluctuations.