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    Krill Oil and Its Bioactive Components as a Potential Therapy for Inflammatory Bowel Disease: Insights from In Vivo and In Vitro Studies

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    Krill oil is extracted from krill, a small crustacean in the Antarctic Ocean. It has received growing attention because of krill oil’s unique properties and diverse health benefits. Recent experimental and clinical studies suggest that it has potential therapeutic benefits in preventing the development of a range of chronic conditions, including inflammatory bowel disease (IBD). Krill oil is enriched with long-chain n-3 polyunsaturated fatty acids, especially eicosapentaenoic and docosahexaenoic acids, and the potent antioxidant astaxanthin, contributing to its therapeutic properties. The possible underlying mechanisms of krill oil’s health benefits include anti-inflammatory and antioxidant actions, maintaining intestinal barrier functions, and modulating gut microbiota. This review aims to provide an overview of the beneficial effects of krill oil and its bioactive components on intestinal inflammation and to discuss the findings on the molecular mechanisms associated with the role of krill oil in IBD prevention and treatment

    Extracellular Vesicles in Pathophysiology: A Prudent Target That Requires Careful Consideration

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    Extracellular vesicles (EVs) are membrane-bound particles released by cells to perform multitudes of biological functions. Owing to their significant implications in diseases, the pathophysiological role of EVs continues to be extensively studied, leading research to neglect the need to explore their role in normal physiology. Despite this, many identified physiological functions of EVs, including, but not limited to, tissue repair, early development and aging, are attributed to their modulatory role in various signaling pathways via intercellular communication. EVs are widely perceived as a potential therapeutic strategy for better prognosis, primarily through utilization as a mode of delivery vehicle. Moreover, disease-associated EVs serve as candidates for the targeted inhibition by pharmacological or genetic means. However, these attempts are often accompanied by major challenges, such as off-target effects, which may result in adverse phenotypes. This renders the clinical efficacy of EVs elusive, indicating that further understanding of the specific role of EVs in physiology may enhance their utility. This review highlights the essential role of EVs in maintaining cellular homeostasis under different physiological settings, and also discusses the various aspects that may potentially hinder the robust utility of EV-based therapeutics

    Alterations in tryptophan metabolism and de novo NAD+ biosynthesis within the microbiota-gut-brain axis in chronic intestinal inflammation

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    Background: Inflammatory bowel disease is an incurable and idiopathic disease characterized by recurrent gastrointestinal tract inflammation. Tryptophan metabolism in mammalian cells and some gut microbes comprise intricate chemical networks facilitated by catalytic enzymes that affect the downstream metabolic pathways of de novo nicotinamide adenine dinucleotide (NAD+) synthesis. It is hypothesized that a correlation exists between tryptophan de novo NAD+ synthesis and chronic intestinal inflammation. Methods: Transcriptome analysis was performed using high-throughput sequencing of mRNA extracted from the distal colon and brain tissue of Winnie mice with spontaneous chronic colitis and C57BL/6 littermates. Metabolites were assessed using ultra-fast liquid chromatography to determine differences in concentrations of tryptophan metabolites. To evaluate the relative abundance of gut microbial genera involved in tryptophan and nicotinamide metabolism, we performed 16S rRNA gene amplicon sequencing of fecal samples from C57BL/6 and Winnie mice. Results: Tryptophan and nicotinamide metabolism-associated gene expression was altered in distal colons and brains of Winnie mice with chronic intestinal inflammation. Changes in these metabolic pathways were reflected by increases in colon tryptophan metabolites and decreases in brain tryptophan metabolites in Winnie mice. Furthermore, dysbiosis of gut microbiota involved in tryptophan and nicotinamide metabolism was evident in fecal samples from Winnie mice. Our findings shed light on the physiological alterations in tryptophan metabolism, specifically, its diversion from the serotonergic pathway toward the kynurenine pathway and consequential effects on de novo NAD+ synthesis in chronic intestinal inflammation. Conclusion: The results of this study reveal differential expression of tryptophan and nicotinamide metabolism-associated genes in the distal colon and brain in Winnie mice with chronic intestinal inflammation. These data provide evidence supporting the role of tryptophan metabolism and de novo NAD+ synthesis in IBD pathophysiology

    Roadside disturbance promotes plant communities with arbuscular mycorrhizal associations in mountain regions worldwide

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    We assessed the impact of road disturbances on the dominant mycorrhizal types in ecosystems at the global level and how this mechanism can potentially lead to lasting plant community changes. We used a database of coordinated plant community surveys following mountain roads from 894 plots in 11 mountain regions across the globe in combination with an existing database of mycorrhizal–plant associations in order to approximate the relative abundance of mycorrhizal types in natural and disturbed environments. Our findings show that roadside disturbance promotes the cover of plants associated with arbuscular mycorrhizal (AM) fungi. This effect is especially strong in colder mountain environments and in mountain regions where plant communities are dominated by ectomycorrhizal (EcM) or ericoid-mycorrhizal (ErM) associations. Furthermore, non-native plant species, which we confirmed to be mostly AM plants, are more successful in environments dominated by AM associations. These biogeographical patterns suggest that changes in mycorrhizal types could be a crucial factor in the worldwide impact of anthropogenic disturbances on mountain ecosystems. Indeed, roadsides foster AM-dominated systems, where AM-fungi might aid AM-associated plant species while potentially reducing the biotic resistance against invasive non-native species, often also associated with AM networks. Restoration efforts in mountain ecosystems will have to contend with changes in the fundamental make-up of EcM- and ErM plant communities induced by roadside disturbance

    Supported decision-making and the Disability Royal Commission

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    Throughout its proceedings and in its Final Report, the Royal Commission into Violence, Abuse, Neglect and Exploitation of People with Disability gave considerable prominence to supported decision-making as a means for achieving the human rights of people with disabilities. It sought input on supported decision-making from people with lived experience, roundtables, public hearings, and commissioned independent research on supported decision-making and proposals for reform. Practical challenges raised at the roundtables and by witnesses included the resources needed for education, training, and capacity building, and the challenge of finding supporters for people who were isolated. Evidence was given that legal reform was only one aspect of what was needed to embed supported decision-making into sectors and services to improve the lives of people with cognitive disabilities. The Commission’s Final Report endorsed a set of national supported decision-making principles, with many of these principles underpinned by the evidence received and commissioned research. However, overall, the Commission’s recommendations were overly focused on reform of guardianship and administration systems, and implementation guidance was lacking. The Commission also missed an opportunity to recommend legislative and practice reform beyond guardianship systems, into multiple services and sectors including the National Disability Insurance Scheme, the health system, and the public sector more widely

    Do dental anxiety and satisfaction with dental professionals modify the association between affordability and dental service use? A population-based longitudinal study of Australian adults

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    Objectives: This study aimed to assess the association between affordability in terms of difficulty paying dental bills in Australian dollars and dental service use in the presence of sociodemographic confounders, and to assess the role of dental anxiety and satisfaction with dental professionals as mediators. The second aim was to investigate how dental anxiety and satisfaction with dental professionals modify the association between affordability and use of dental services in Australian adults. Methods: Longitudinal data from the Australian National Study of Adult Oral Health (2004–06 and 2017–18) was used. Poisson regression and path analysis were conducted to determine the association between affordability and frequency of use of dental services. Effect measure modification (EMM) analysis was performed by stratification of dental anxiety and satisfaction with dental professionals. Results: The study included 1698 Australian adults and identified that the prevalence of low frequency of dental visits was 20% more for those who had difficulty paying dental bills. Adults with dental anxiety (prevalence ratio [PR] = 1.14) and those who were dissatisfied with dental professionals (PR = 1.17) had a higher prevalence of low frequency of dental visits in the presence of difficulty paying dental bills. This indicated that dental anxiety and dissatisfaction with dental professionals were effect modifiers on this pathway. Conclusions: Adults who experience dental anxiety and dissatisfaction with dental professionals are more likely to avoid dental visits when faced with difficulty paying dental bills. However, it is important to note that these associations do not necessarily imply a causal relationship.</p

    Subjective wellbeing of autistic adolescents and young adults: A cross sectional study

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    Subjective wellbeing (SWB) represents an individual's perception of wellness that is supported by homeostatic mechanisms. These mechanisms are proposed to be maintained by low negative affect and high positive affect, although less is known about these mechanisms and SWB in autism. The current cross-sectional study aimed to compare patterns of positive affect, negative affect (Positive Affect and Negative Affect Scale), and SWB (Personal Wellbeing Index-School Children) between autistic (n = 53) and non-autistic (n = 49) individuals aged 10–22 years (Mage = 13.97, SD = 3.13). Between-group t-tests revealed that compared with same-age peers, autistic participants scored lower SWB overall (p < 0.001). In both groups average SWB scores fell into the higher range, however, autistic participants were three-times more likely to fall below this range when compared to non-autistic participants. Negative affect had a higher intercept in the autistic sample, but no difference in slopes were observed. A hierarchical multiple regression revealed that diagnosis, positive affect, and negative affect significantly predicted SWB in our sample. Between-group t-tests found no significant difference in positive affect or negative affect across age between the autistic and non-autistic samples. In autistic participants, positive affect increased across age as SWB decreased, whilst negative affect remained stable, a pattern inconsistent with homeostatic SWB. The current study is overall consistent with the homeostatic explanation for SWB within autism; however, we identified potential differences between autistic and non-autistic participants in the contribution of positive affect and negative affect to homeostatic protect mood across development

    Difficult at dusk? Illuminating the debate on cricket ball visibility

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    Objectives: Investigate the visibility of new and old red, white and pink cricket balls under lighting and background conditions experienced during a day–night cricket match. Design: We modelled the luminance contrast signals available for a typical observer for a ball against backgrounds in a professional cricket ground, at different times of day. Methods: Spectral reflectance (light reflected as a function of wavelength) was derived from laboratory measurements of new and old red, white and pink balls. We also gathered spectral measurements from backgrounds (pitch, grass, sightscreens, crowd, sky) and spectral illuminance during a day–night match (natural afternoon light, through dusk to night under floodlights) from Lord's Cricket Ground (London, UK). The luminance contrast of the ball relative to the background was calculated for each combination of ball, time of day, and background surface. Results: Old red and old pink balls may offer little or no contrast against the grass, pitch and crowd. New pink balls can also be of low contrast against the crowd at dusk, as can pink and white balls (of any age) against the sky at dusk. Conclusions: Reports of difficulties with visibility of the pink ball are supported by our data. However, our modelling also shows that difficulties with visibility may also be expected under certain circumstances for red and white balls. The variable conditions in a cricket ground and the changing colour of an ageing ball make maintaining good visibility of the ball a challenge when playing day–night matches.</p

    A Novel Fluorogenic Probe Reveals Lipid Droplet Dynamics in ME/CFS Fibroblasts

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    Lipid droplets (LDs) are dynamic cellular organelles that play an essential role in lipid metabolism and storage. LD dysregulation has been implicated in various diseases. However, investigations into the cellular LD dynamics under disease conditions have been rarely reported, possibly due to the absence of high performing LD imaging agents. Here a novel fluorogenic probe, AM‐QTPA, is reported for specific LD imaging. AM‐QTPA demonstrates viscosity sensitivity and aggregation‐induced emission enhancement characteristics. It is live cell permeable and can specifically light up LDs in cells, with low background noise and superior signals that can be quantified. After validation in cell model with LD accumulation induced by oleic acid treatment, AM‐QTPA is applied in a small proof‐of‐concept number of human fibroblast samples derived from people diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a complex and debilitating disease with unknown cause. The results indicate the presence of larger but fewer LDs in ME/CFS fibroblasts compared to the healthy counterparts, accompanying with frequent LD‐mitochondria contacts, suggesting potential upregulation of lipolysis in ME/CFS connective tissue like fibroblasts. Overall, AM‐QTPA provides new understanding of the anomalous LD dynamics in disease status, which, potentially, will facilitate in‐depth investigation of the pathogenesis of ME/CFS.</p

    Low-Temperature X-ray Microanalysis Sheds New Light on Mineral Nutrition Aspects of Insect Leaf Galling

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    Manipulation of host plant physiology by leaf-galling insects is a multifaceted process. Among fundamental knowledge gaps surrounding this scientifically intriguing phenomenon is the appropriation of plant mineral nutrients and moisture for galling advantage. Small, soluble mineral ions and watery cell contents in dense gall tissues risk disruption during routine sample preparations. In this study, an X-ray microanalysis was applied to investigate gall mineral nutrition. Morphologically diverse leaf galls were sampled from three Australian rainforest tree species. Using cryo-analytical scanning electron microscopy, real-time X-ray analytical maps of cellular mineral nutrients and water were integrated with anatomical images of gall and leaf cross-sectional surfaces. A comparison of host-leaf and gall anatomies bore direct evidence of drastic changes to leaf cells through the galling process. Distinct "wet"and "dry"regions within galls were anatomically and/or chemically differentiated, suggesting specific functionality. "Wet"regions comprising hydrated cells including soft gall-cavity linings where larvae are known to feed contained soluble plant mineral nutrients, while C-rich "dry"tissues largely devoid of mineral nutrients likely contribute structural support. Mapping immobile nutrients such as Mn may provide a means of "matching"specific gall cell types to those in ungalled host-leaf tissues. The findings here provided otherwise inaccessible insights into leaf-gall mineral nutrition.</p

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