Tribute to Prof. Geoffrey Burnstock: his contribution to acupuncture

Purinergic Signalling -     

KDM5A silencing transcriptionally suppresses the FXYD3-PI3K/AKT axis to inhibit angiogenesis in hepatocellular cancer via miR-433 up-regulation

Hepatocellular cancer (HCC) has been reported to belong to one of the highly vascularized solid tumours accompanied with angiogenesis of human umbilical vein endothelial cells (HUVECs). KDM5A, an attractive drug target, plays a critical role in diverse physiological processes. Thus, this study aims to investigate its role in angiogenesis and underlying mechanisms in HCC. ChIP-qPCR was utilized to validate enrichment of H3K4me3 and KDM5A on the promotor region of miR-433, while dual luciferase assay was carried out to confirm the targeting relationship between miR-433 and FXYD3. Scratch assay, transwell assay, Edu assay, pseudo-tube formation assay and mice with xenografted tumours were conducted to investigate the physiological function of KDM5A-miR-433-FXYD3-PI3K-AKT axis in the progression of HCC after loss- and gain-function assays. KDM5A p-p85 and p-AKT were highly expressed but miR-433 was down-regulated in HCC tissues and cell lines. Depletion of KDM5A led to reduced migrative, invasive and proliferative capacities in HCC cells, including growth and a lowered HUVEC angiogenic capacity in vitro. Furthermore, KDM5A suppressed the expression of miR-433 by demethylating H3K4me3 on its promoterregion. miR-433 negatively targeted FXYD3. Depleting miR-433 or re-expressing FXYD3 restores the reduced migrative, invasive and proliferative capacities, and lowers the HUVEC angiogenic capacity caused by silencing KDM5A. Therefore, KDM5A silencing significantly suppresses HCC tumorigenesis in vivo, accompanied with down-regulated miR-433 and up-regulated FXYD3-PI3K-AKT axis in tumour tissues. Lastly, KDM5A activates the FXYD3-PI3K-AKT axis to enhance angiogenesis in HCC by suppressing miR-433.     

Nanoparticle formulation of mycophenolate mofetil achieves enhanced efficacy against hepatocellular carcinoma by targeting tumour-associated fibroblast

Hepatocellular carcinoma (HCC) is one of the most aggressive tumours with marked fibrosis. Mycophenolate mofetil (MMF) was well-established to have antitumour and anti-fibrotic properties. To overcome the poor bioavailability of MMF, this study constructed two MMF nanosystems, MMF-LA@DSPE-PEG and MMF-LA@PEG-PLA, by covalently conjugating linoleic acid (LA) to MMF and then loading the conjugate into polymer materials, PEG_5k-PLA_8k and DSPE- PEG_2k, respectively. Hepatocellular carcinoma cell lines and C57BL/6 xenograft model were used to examine the anti-HCC efficacy of nanoparticles (NPs), whereas NIH-3T3 fibroblasts and highly-fibrotic HCC models were used to explore the anti-fibrotic efficacy. Administration of NPs dramatically inhibited the proliferation of HCC cells and fibroblasts in vitro. Animal experiments revealed that MMF-LA@DSPE-PEG achieved significantly higher anti-HCC efficacy than free MMF and MMF-LA@PEG-PLA both in C57BL/6 HCC model and highly-fibrotic HCC models. Immunohistochemistry further confirmed that MMF-LA@DSPE-PEG dramatically reduced cancer-associated fibroblast (CAF) density in tumours, as the expression levels of alpha-smooth muscle actin (α-SMA), fibroblast activation protein (FAP) and collagen IV were significantly downregulated. In addition, we found the presence of CAF strongly correlated with increased HCC recurrence risk after liver transplantation. MMF-LA@DSPE-PEG might act as a rational therapeutic strategy in treating HCC and preventing post-transplant HCC recurrence.     

Effect of host plant on cornucopia of mango fruit flies (Diptera: Tephritidae) and their triumphant management in context of climate change

A study was performed to assess the preference of fourteen mango cultivars for fruit flies and their management by bagging. So the choice of Tephritid flies to mango cultivars during fruiting phase is crucial. Fourteen different cultivars of mango viz., ‘Dusehri’, ‘Malda’, ‘Langra’ early cultivars, ‘Chaunsa’, ‘Fajri Klan’, ‘Sensation’ medium whereas ‘Sanglakhi’, ‘Retaul-12’, ‘Mehmood Khan’, ‘Tukhmi’, ‘Kala Chaunsa’, ‘Chitta Chaunsa’, ‘Dai Wala’ and ‘Sobey De Ting’ late cultivars were assessed for their suitability for fruit flies. The results indicate that the population density of fruit flies was higher on late cultivars like ‘Sanglakhi’ (20.61 percent), ‘Mehmood Khan’ (20.22 percent) and ‘Reutal-12’ (19.92 percent) were proved to be highly susceptible to fruit flies. Among these the cultivar ‘Reutal-12’ was selected being commercial and future cultivar for the management of fruit flies through bagging. The results reported that the attack of tephritid fruit flies and other insect pests were zero in bagged fruits as compared with control. It was further recorded that the bagged fruits has maximum average fruit weight i.e. 203.50 and 197.83 g per fruit was noted in those treatments where butter paper bag and brown paper bag was wrapped with better coloration as compared with un-bagged fruit with 159.5 g per fruit. Similarly, on an average fruit length were more i.e. 90.17, 91.33 mm in bagged fruit and 85.33 in un-bagged fruits. Furthermore, bagged fruits have zero incidence of disease with reduced fruit crack, fruit sunburn, mechanical damage, bird damage, fruit blemished and agrochemical residues on the fruit. So, it is concluded that the special attention should be given on ‘Reutal-12’ for the management of fruit flies when devising an IPM program for the control of fruit flies. Further, bagging has proved to be the good agricultural practices for the production of quality mango.     

Direct response of tree growth to soil water and its implications for terrestrial carbon cycle modelling

Wood growth constitutes the main process for long‐term atmospheric carbon sequestration in vegetation. However, our understanding of the process of wood growth and its response to environmental drivers is limited. Current dynamic global vegetation models (DGVMs) are mainly photosynthesis‐driven and thus do not explicitly include a direct environmental effect on tree growth. However, physiological evidence suggests that, to realistically model vegetation carbon allocation under increased climatic stressors, it is crucial to treat growth responses independently from photosynthesis. A plausible growth response function suitable for global simulations in DGVMs has been lacking. Here, we present the first soil water‐growth response function and parameter range for deciduous and evergreen conifers. The response curve was calibrated against European larch and Norway spruce in a dry temperate forest in the Swiss Alps. We present a new data‐driven approach based on a combination of tree ring width (TRW) records, growing season length and simulated subdaily soil hydrology to parameterize ring width increment simulations. We found that a simple linear response function, with an intercept at zero moisture stress, used in growth simulations reproduced 62.3% and 59.4% of observed TRW variability for larch and spruce respectively and, importantly, the response function slope was much steeper than literature values for soil moisture effects on photosynthesis and stomatal conductance. Specifically, we found stem growth stops at soil moisture potentials of ?0.47 MPa for larch and ?0.66 MPa for spruce, whereas photosynthesis in trees continues down to ?1.2 MPa or lower, depending on species and measurement method. These results are strong evidence that the response functions of source and sink processes are indeed very different in trees, and need to be considered separately to correctly assess vegetation responses to environmental change. The results provide a parameterization for the explicit representation of growth responses to soil water in vegetation models.     

Sixteen hundred years of increasing tree cover prior to modern deforestation in Southern Amazon and Central Brazilian savannas

Tropical ecosystems are under increasing pressure from land‐use change and deforestation. Changes in tropical forest cover are expected to affect carbon and water cycling with important implications for climatic stability at global scales. A major roadblock for predicting how tropical deforestation affects climate is the lack of baseline conditions (i.e., prior to human disturbance) of forest–savanna dynamics. To address this limitation, we developed a long‐term analysis of forest and savanna distribution across the Amazon–Cerrado transition of central Brazil. We used soil organic carbon isotope ratios as a proxy for changes in woody vegetation cover over time in response to fluctuations in precipitation inferred from speleothem oxygen and strontium stable isotope records. Based on stable isotope signatures and radiocarbon activity of organic matter in soil profiles, we quantified the magnitude and direction of changes in forest and savanna ecosystem cover. Using changes in tree cover measured in 83 different locations for forests and savannas, we developed interpolation maps to assess the coherence of regional changes in vegetation. Our analysis reveals a broad pattern of woody vegetation expansion into savannas and densification within forests and savannas for at least the past ~1,600 years. The rates of vegetation change varied significantly among sampling locations possibly due to variation in local environmental factors that constrain primary productivity. The few instances in which tree cover declined (7.7% of all sampled profiles) were associated with savannas under dry conditions. Our results suggest a regional increase in moisture and expansion of woody vegetation prior to modern deforestation, which could help inform conservation and management efforts for climate change mitigation. We discuss the possible mechanisms driving forest expansion and densification of savannas directly (i.e., increasing precipitation) and indirectly (e.g., decreasing disturbance) and suggest future research directions that have the potential to improve climate and ecosystem models.     

966. CLAVIJA DOMINGENSIS

Clavija domingensis Urb. & Ekman was one of the many Haitian endemics that were described based on collections made by the great Swedish botanist Leonard Ekman between 1924 and 1928. The species is Critically Endangered sensu IUCN (criteria c2a(i); D) and it is currently the focus of conservation initiatives in Jardin Botanique des Cayes (Haiti), Jardín Botánico Nacional Dr. Rafael M. Moscoso (Dominican Republic), and Fairchild Tropical Botanic Garden (U.S.A.). Now known from only six localities from southern Haiti, each locality only represents a single individual. The species is illustrated based on plants grown in Fairchild Tropical Botanic Garden.     

Advances in approaches to seagrass restoration in Australia

Three case studies involving two temperate Australian seagrass species – Pondweed (Ruppia tuberosa) and Ribbon Weed (Posidonia australis) – highlight different approaches to their restoration. Seeds and rhizomes were used in three collaborative programmes to promote new approaches to scale up restoration outcomes.     

Spatial co‐localisation of extreme weather events: a clear and present danger

Extreme weather events have become a dominant feature of the narrative surrounding changes in global climate with large impacts on ecosystem stability, functioning and resilience; however, understanding of their risk of co‐occurrence at the regional scale is lacking. Based on the UK Met Office’s long‐term temperature and rainfall records, we present the first evidence demonstrating significant increases in the magnitude, direction of change and spatial co‐localisation of extreme weather events since 1961. Combining this new understanding with land‐use data sets allowed us to assess the likely consequences on future agricultural production and conservation priority areas. All land‐uses are impacted by the increasing risk of at least one extreme event and conservation areas were identified as the hotspots of risk for the co‐occurrence of multiple event types. Our findings provide a basis to regionally guide land‐use optimisation, land management practices and regulatory actions preserving ecosystem services against multiple climate threats.