IGFBP6 contributes to vascular resilience
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Coastal wetland resilience through local, regional and global conservation
Coastal wetlands, including tidal marshes, mangrove forests and tidal flats, support the livelihoods of millions of people. Understanding the resilience of coastal wetlands to the increasing number and intensity of anthropogenic threats (such as habitat conversion, pollution, fishing and climate change) can inform what conservation actions will be effective. In this Review, we synthesize anthropogenic threats to coastal wetlands and their resilience through the lens of scale. Over decades and centuries, anthropogenic threats have unfolded across local, regional and global scales, reducing both the extent and quality of coastal wetlands. The resilience of existing coastal wetlands is driven by their quality, which is modulated by both physical conditions (such as sediment supply) and ecological conditions (such as species interactions operating from local through to global scales). Protection and restoration efforts, however, are often localized and focus on the extent of coastal wetlands. The future of coastal wetlands will depend on an improved understanding of their resilience, and on society’s actions to enhance both their extent and quality across different scales.
Astrocytic cannabinoid receptor 1 promotes resilience by dampening stress-induced blood–brain barrier alterations
Blood–brain barrier (BBB) alterations contribute to stress vulnerability and the development of depressive behaviors. In contrast, neurovascular adaptations underlying stress resilience remain unclear. Here we report that high expression of astrocytic cannabinoid receptor 1 (CB1) in the nucleus accumbens (NAc) shell, particularly in the end-feet ensheathing blood vessels, is associated with resilience during chronic social stress in adult male mice. Viral-mediated overexpression of Cnr1 in astrocytes of the NAc shell results in baseline anxiolytic effects and dampens stress-induced anxiety- and depression-like behaviors in male mice. It promotes the expression of vascular-related genes and reduces astrocyte inflammatory response and morphological changes following an immune challenge with the cytokine interleukin-6, linked to stress susceptibility and mood disorders. Physical exercise and antidepressant treatment increase the expression of astrocytic Cnr1 in the perivascular region in male mice. In human tissue from male donors with major depressive disorder, we observe loss of CNR1 in the NAc astrocytes. Our findings suggest a role for the astrocytic endocannabinoid system in stress responses via modulation of the BBB.
Hybrid model of tumor growth, angiogenesis and immune response yields strategies to improve antiangiogenic therapy
Solid tumors harbor a complex and dynamic microenvironment that hinders the delivery and efficacy of therapeutic interventions. In this study, we developed and utilized a hybrid, discrete-continuous mathematical model to explore the interplay between solid tumor growth, immune response, tumor-induced angiogenesis, and antiangiogenic drugs. By integrating published data with anti-angiogenic drugs, we elucidate three primary mechanisms by which anti-angiogenesis influences tumor progression and treatment outcomes: reduction in tumor growth rate by mitigating and temporally delaying angiogenesis, normalization of blood vessel structure and function, and improving immune cell extravasation and activation. Our results indicate a significant increase in functional blood vessels and perfusion following anti-angiogenic treatment, which in turn improves the intratumoral distribution of immune cells. The normalization window, or optimal time frame for anti-angiogenic drug administration, and the dose of the drug arise naturally in the model and are highlighted as crucial factors in maximizing treatment benefits. Prolonged anti-angiogenic treatment triggers cancer cell migration into healthy tissue and induces immunosuppression due to hypoxia, potentially leading to negative effects because these cancer cells will rapidly proliferate upon treatment termination. In conclusion, the positive contribution of anti-angiogenic treatment must balance the possible negative effects by choosing a proper treatment protocol as well as combining it with proper anti-cancer treatment. Our findings provide valuable insights and a framework for the design of protocols with anti-angiogenic treatment, targeted immunotherapy, and non-targeted anti-cancer therapies.
Hypertension inhibition by Dubosiella newyorkensis via reducing pentosidine synthesis
Gut dysbiosis has been associated with hypertension. Herein, we aimed to discover the potential association between gut microbiota and high-salt diet (HSD) induced endothelial dysfunction in conventional hypertensive mice. Dubosiella newyorkensis was found highly sensitive to salt in HSD-induced hypertension. The salt-sensitive nature of Dubosiella newyorkensis was confirmed by bacteria culture in vitro. Oral Dubosiella newyorkensis in HSD-induced hypertensive mice decreased blood pressure, inhibited activation of vascular endothelium, attenuated inflammation and alleviated intestinal vascular barrier injury. Similar effects of Dubosiella newyorkensis were observed in germ-free mice. Interestingly, serum pentosidine was found to function as a biomarker for Dubosiella newyorkensis in response to HSD in both metabolic modes. Supplement of pentosidine, deteriorated hypertension and vascular endothelial damage. Differential genes enriched in the glycerophospholipid metabolism were markedly altered in cultured bacteria. Our study has identified Dubosiella newyorkensis as a new salt-sensitive gut microbe that inhibits pentosidine production thereby alleviating hypertension.
Protein signatures predict coral resilience and survival to thermal bleaching events
Coral bleaching events from thermal stress are increasing globally in duration, frequency, and intensity. While bleaching can cause mortality, some corals survive, reacquire symbionts, and recover. We experimentally bleached Montipora capitata to examine molecular and physiological differences between corals that recover (resilient) and those that die (susceptible). Corals were collected and monitored for eight months post-bleaching to identify genets with long-term resilience. Using an integrated systems-biology approach that included quantitative proteomics, 16S rRNA sequencing to characterize the coral microbiome, total coral lipids, symbiont community composition and density, we explored molecular-level mechanisms of tolerance in corals pre- and post-bleaching. Prior to thermal stress, resilient corals have a more diverse microbiome and abundant proteins essential for carbon acquisition, symbiont retention, and pathogen resistance. Protein signatures of susceptible corals showed early symbiont rejection and utilized urea for carbon and nitrogen. Our results reveal molecular factors for surviving bleaching events and identify diagnostic protein biomarkers for reef management and restoration.
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