Expression of E-cadherin by CD8+ T cells promotes their invasion into biliary epithelial cells.

The presence of CD8+ T cells in the cytoplasm of biliary epithelial cells (BEC) has been correlated with biliary damage associated with primary biliary cholangitis (PBC). Here, we characterise the mechanism of CD8+ T cell invasion into BEC. CD8+ T cells observed within BEC were large, eccentric, and expressed E-cadherin, CD103 and CD69. They were also not contained within secondary vesicles. Internalisation required cytoskeletal rearrangements which facilitated contact with BEC. Internalised CD8+ T cells were observed in both non-cirrhotic and cirrhotic diseased liver tissues but enriched in PBC patients, both during active disease and at the time of transplantation. E-cadherin expression by CD8+ T cells correlated with frequency of internalisation of these cells into BEC. E-cadherin+ CD8+ T cells formed ß-catenin-associated interactions with BEC, were larger than E-cadherin- CD8+ T cells and invaded into BEC more frequently. Overall, we unveil a distinct cell-in-cell structure process in the liver detailing the invasion of E-cadherin+ CD103+ CD69+ CD8+ T cells into BEC.

Building capacity for estimating fire emissions from tropical peatlands; a worked example from Indonesia.

Tropical peatlands are globally significant in the terrestrial carbon cycle as they are comprised of a large forest carbon sink and a large peat carbon store-both of which can potentially be exchanged with the atmosphere on decadal time frames. Greenhouse gas emissions from fire-disturbance and development of tropical peatlands over the last few decades, and the potential for ongoing emissions, highlights the need for policy to slow or halt emissions and to activate mechanisms to sequester carbon through restoration of degraded peatlands. The UN REDD + scheme provides a means for developing countries to receive payments for avoided deforestation and forest degradation, but the steps to achieve REDD+ compliance are rigorous and the details required can be a barrier to activating benefits-especially for peatlands where repeated cycles of fire interrupt forest recovery and create a range of recovery classes. Therefore, to improve estimates of peat fire emissions and of carbon balance of tropical peatlands, the biomass and combustion factor parameters need to be developed and applied according to forest recovery stage. In this study we use published activity data from the extensive 1997 fires in the peatlands of Indonesian Borneo to detail a transparent and accountable way to estimate and report emissions from tropical peatland fires. This example for estimating and reporting emissions is provided to assist REDD+ countries to efficiently develop their capacity for improving emissions estimates from fire-impacted tropical peatlands.

CCL24 regulates biliary inflammation and fibrosis in primary sclerosing cholangitis.

ˆCCL24 is a pro-fibrotic, pro-inflammatory chemokine expressed in several chronic fibrotic diseases. In the liver, CCL24 plays a role in fibrosis and inflammation, and blocking CCL24 led to reduced liver injury in experimental models. We studied the role of CCL24 in primary sclerosing cholangitis (PSC) and evaluated the potential therapeutic effect of blocking CCL24 in this disease. Multidrug resistance gene 2-knockout (Mdr2-/-) mice demonstrated CCL24 expression in liver macrophages and were used as a relevant experimental PSC model. CCL24-neutralizing monoclonal antibody, CM-101, significantly improved inflammation, fibrosis, and cholestasis-related markers in the biliary area. Moreover, using spatial transcriptomics, we observed reduced proliferation and senescence of cholangiocytes following CCL24 neutralization. Next, we demonstrated that CCL24 expression was elevated under pro-fibrotic conditions in primary human cholangiocytes and macrophages, and it induced proliferation of primary human hepatic stellate cells and cholangiocytes, which was attenuated following CCL24 inhibition. Correspondingly, CCL24 was found to be highly expressed in liver biopsies of patients with PSC. CCL24 serum levels correlated with Enhanced Liver Fibrosis score, most notably in patients with high alkaline phosphatase levels. These results suggest that blocking CCL24 may have a therapeutic effect in patients with PSC by reducing liver inflammation, fibrosis, and cholestasis.

Tree mortality and carbon emission as a function of wildfire severity in south-eastern Australian temperate forests.

Disturbance trends over recent decades indicate that climate change is resulting in increased fire severity and extent in Australia's temperate Eucalyptus forests. As disturbance cycles become shorter and more severe, empirical measurements are required to identify potential change in forest carbon (C) stock and emissions. However, such estimates are rare in the literature. The 2019-2020 wildfires burnt through 6 to 7 million ha of mainly temperate open Eucalyptus forest in south-east Australia, with top down emission estimates ranging from 97 to 130 tonnes CO2 ha-1. Study sites that had been assessed for all aboveground C pools prior to the wildfires, were burnt in January 2020 by wildfire that varied in severity. Here we quantify the impact of high and low/moderate fire severities on tree mortality, C loss and C redistribution and assess implications for future C storage in these temperate Eucalyptus forests. Higher fire severity resulted in greater overstorey tree mortality but not understorey or loss of dead standing trees than in low/moderate severity fires. High severity fires combusted almost twice as much C from live trees (42 Mg C ha-1) as low/moderate severity fires (25 Mg C ha-1), while C loss from dead standing trees was similar among fire severity classes (average 17 Mg C ha-1). Total aboveground C lost across study sites was 42 Mg C ha-1 for high and 47 Mg C ha-1 for low/moderate severity, with an average of 45 Mg C ha-1 equivalent to 15 % (high severity) and 14 % (low/moderate severity) of AGC. Extrapolating our findings to other tall to medium open Eucalyptus forests across Victoria revealed that 37.33 ± 12.25 Tg C (mean ± s.e.) or 152 ± 50 Mg CO2 ha-1 was lost to the atmosphere from the 0.9 million ha of these productive forests, equating to about 20 % of Australia's total net annual emissions.

Effects of prescribed fire frequency on wildfire emissions and carbon sequestration in a fire adapted ecosystem using a comprehensive carbon model.

Prescribed fire to reduce forest fuels has been routinely applied to reduce wildfire risk in many parts of the world. It has also been proposed that prescribed fire can be used to mitigate greenhouse gas (GHG) emissions. Although prescribed fire creates emissions, if the treatment also decreases the incidence of subsequent wildfires, it is possible for the net outcome to be an emissions decline. Previous studies have suggested prescribed fire, at the frequencies required to materially impact wildfire occurrence, generally leads to net emissions increases. A focus on emissions means any change in carbon storage within the ecosystem remains unaccounted for; because living, dead, and soil carbon pools are characterized by different residence times, a re-distribution of carbon amongst these pools may either reduce or increase long-term ecosystem carbon stores. A full ecosystem carbon model has been developed to investigate the implications of prescribed fire management on total Net Ecosystem Carbon Balance (NECB), inclusive of both emissions and carbon storage. Consistent with previous work, the results suggested limited potential for reducing net GHG emissions through applying prescribed fire, with higher emissions from prescribed fire approximately offset by lower emissions and avoided carbon losses from the subsequent reduction in wildfire frequency. For example, shortening the prescribed fire interval from 25 to 10 years resulted in a NECB sequestration that was typically less than ±0.4 Mg C ha-1 yr-1, or less than approximately 0.1% of the total ecosystem carbon storage. Hence, whilst there was limited opportunity for achieving emission abatement outcomes from changing prescribed fire management, there were no significant emission penalties for doing so. These results suggest land managers should be free to adopt prescribed fire regimes to target specific management outcomes, without significantly impacting net emissions or total ecosystem carbon storage over the long term.

Carbon balance of tropical peat forests at different fire history and implications for carbon emissions.

Accurate assessment of tropical peat forest carbon stocks and impact of fires on carbon pools is required to determine the magnitude of emissions to the atmosphere and to support emissions reduction policies. We assessed total aboveground carbon (AGC) in biomass pools including trees, shrubs, deadwood, litter and char, and peat carbon to develop empirical estimates of peat swamp forest carbon stocks in response to fire and disturbance. In contrast to the common assumption that peat fires combust all AGC, we observed that about half of undisturbed forest AGC, equivalent to about 70 Mg C ha-1, remains after one or two recent fires - mainly in dead trees, woody debris and pyrogenic carbon. Both recently burnt and repeatedly burnt peat forests store similar amounts of carbon in the top 10 cm of peat when compared with undisturbed forests (70 Mg C ha-1), mainly due to increased peat bulk density after fires that compensates for their lower peat C%. The proportion of fuel mass consumed in fire, or combustion factor (CF), is required to make accurate estimates of peat fire emissions for both AGC and peat carbon. This study estimated a CF for AGC (CFAGC) of 0.56, comparable to the default value of the Intergovernmental Panel on Climate Change (IPCC). This study estimated a varying CF for peat (CFPEAT) that ranged from 0.4 to 0.68 as depth of burn increased. This revised CFPEAT is one third to one half of the IPCC default value of 1.0. The current assumption of complete combustion of peat (CF = 1.0) is widely acknowledged in the literature as oversimplification and is not supported by our field observations or data. This study provides novel empirical data to improve estimates of peat forests carbon stocks and emissions from tropical peat fires.

The Contribution of Liver Sinusoidal Endothelial Cells to Clearance of Therapeutic Antibody.

Many chronic inflammatory diseases are treated by administration of "biological" therapies in terms of fully human and humanized monoclonal antibodies or Fc fusion proteins. These tools have widespread efficacy and are favored because they generally exhibit high specificity for target with a low toxicity. However, the design of clinically applicable humanized antibodies is complicated by the need to circumvent normal antibody clearance mechanisms to maintain therapeutic dosing, whilst avoiding development of off target antibody dependent cellular toxicity. Classically, professional phagocytic immune cells are responsible for scavenging and clearance of antibody via interactions with the Fc portion. Immune cells such as macrophages, monocytes, and neutrophils express Fc receptor subsets, such as the FcγR that can then clear immune complexes. Another, the neonatal Fc receptor (FcRn) is key to clearance of IgG in vivo and serum half-life of antibody is explicitly linked to function of this receptor. The liver is a site of significant expression of FcRn and indeed several hepatic cell populations including Kupffer cells and liver sinusoidal endothelial cells (LSEC), play key roles in antibody clearance. This combined with the fact that the liver is a highly perfused organ with a relatively permissive microcirculation means that hepatic binding of antibody has a significant effect on pharmacokinetics of clearance. Liver disease can alter systemic distribution or pharmacokinetics of antibody-based therapies and impact on clinical effectiveness, however, few studies document the changes in key membrane receptors involved in antibody clearance across the spectrum of liver disease. Similarly, the individual contribution of LSEC scavenger receptors to antibody clearance in a healthy or chronically diseased organ is not well characterized. This is an important omission since pharmacokinetic studies of antibody distribution are often based on studies in healthy individuals and thus may not reflect the picture in an aging or chronically diseased population. Therefore, in this review we consider the expression and function of key antibody-binding receptors on LSEC, and the features of therapeutic antibodies which may accentuate clearance by the liver. We then discuss the implications of this for the design and utility of monoclonal antibody-based therapies.

Identifying and addressing knowledge gaps for improving greenhouse gas emissions estimates from tropical peat forest fires.

Tropical peatlands are areas of high carbon density that are important in biosphere-atmosphere interactions. Drainage and burning of tropical peatlands releases about 5% of global greenhouse gas (GHG) emissions, yet there is great uncertainty in these estimates. Our comprehensive literature review of parameters required to calculate GHG emissions from burnt peat forests, following the international guidelines, revealed many gaps in knowledge of carbon pools and few recent supporting studies. To improve future estimates of the total ecosystem carbon balance and peatfire emissions this study aimed to account for all carbon pools: aboveground, deadwood, pyrogenic carbon (PyC) and peat of single and repeatedly burnt peat forests. A further aim was to identify the minimum sampling intensity required to detect with 80% power significant differences in these carbon pools among long unburnt, recently burnt and repeatedly burnt peat swamp forests. About 90 Mg C ha-1 remains aboveground as deadwood after a single fire and half of this remains after a second fire. One fire produces 4.5 ± 0.6 Mg C ha-1 of PyC, with a second fire increasing this to 7.1 ± 0.8 Mg C ha-1. For peat swamp forests these aboveground carbon pools are rarely accounted in estimates of emissions following multiple fires, while PyC has not been included in the total peat carbon mass balance. Peat bulk density and peat carbon content change with fire frequency, yet these parameters often remain constant in the published emission estimates following a single and multiple fires. Our power analysis indicated that as few as 12 plots are required to detect meaningful differences between fire treatments for the major carbon pools. Further field studies directed at improving the parameters for calculating carbon balance of disturbed peat forest ecosystems are required to better constrain peatfire GHG emission estimates.

Defining Myocardial Abnormalities Across the Stages of Chronic Kidney Disease: A Cardiac Magnetic Resonance Imaging Study.

OBJECTIVES: A proof of concept cross-sectional study investigating changes in myocardial abnormalities across stages of chronic kidney disease (CKD). Characterizing noninvasive markers of myocardial fibrosis on cardiac magnetic resonance, echocardiography, and correlating with biomarkers of fibrosis, myocardial injury, and functional correlates including exercise tolerance. BACKGROUND: CKD is associated with an increased risk of cardiovascular death. Much of the excess mortality is attributed to uremic cardiomyopathy, defined by increased left ventricular hypertrophy, myocardial dysfunction, and fibrosis. The prevalence of these abnormalities across stages of CKD and their impact on cardiovascular performance is unknown. METHODS: A total of 134 nondiabetic, pre-dialysis subjects with CKD stages 2 to 5 without myocardial ischemia underwent cardiac magnetic resonance (1.5-T) including; T1 mapping (biomarker of diffuse fibrosis), T2 mapping (edema), late gadolinium enhancement, and assessment of aortic distensibility. Serum biomarkers including collagen turnover (P1NP, P3NP), troponin T, and N-terminal pro-B-type natriuretic peptide were measured. Cardiovascular performance was quantified by bicycle cardiopulmonary exercise testing and echocardiography. RESULTS: Native myocardial T1 times increased incrementally from stage 2 to 5 (966 ± 21 ms vs. 994 ± 33 ms; p < 0.001), independent of hypertension and aortic distensibility. Left atrial volume, E/e', N-terminal pro-B-type natriuretic peptide, P1NP, and P3NP increased with CKD stage (p < 0.05), while effort tolerance (% predicted VO2Peak, %VO2VT) decreased (p < 0.001). In multivariable linear regression models, estimated glomerular filtration rate was the strongest predictor of native myocardial T1 time (p < 0.001). Native myocardial T1 time, left atrial dilatation, and high-sensitivity troponin T were independent predictors of % predicted VO2Peak (p < 0.001). CONCLUSIONS: Imaging and serum biomarkers of myocardial fibrosis increase with advancing CKD independent of effects of left ventricular afterload and might be a key intermediary in the development of uremic cardiomyopathy. Further studies are needed to determine whether these changes lead to the increased rates of heart failure and death in CKD. (Left Ventricular Fibrosis in Chronic Kidney Disease [FibroCKD]; NCT03176862).

The platelet receptor CLEC-2 blocks neutrophil mediated hepatic recovery in acetaminophen induced acute liver failure.

Acetaminophen (APAP) is the main cause of acute liver failure in the West. Specific efficacious therapies for acute liver failure (ALF) are limited and time-dependent. The mechanisms that drive irreversible acute liver failure remain poorly characterized. Here we report that the recently discovered platelet receptor CLEC-2 (C-type lectin-like receptor) perpetuates and worsens liver damage after toxic liver injury. Our data demonstrate that blocking platelet CLEC-2 signalling enhances liver recovery from acute toxic liver injuries (APAP and carbon tetrachloride) by increasing tumour necrosis factor-α (TNF-α) production which then enhances reparative hepatic neutrophil recruitment. We provide data from humans and mice demonstrating that platelet CLEC-2 influences the hepatic sterile inflammatory response and that this can be manipulated for therapeutic benefit in acute liver injury. Since CLEC-2 mediated platelet activation is independent of major haemostatic pathways, blocking this pathway represents a coagulopathy-sparing, specific and novel therapy in acute liver failure.

Vascular Adhesion Protein-1 Determines the Cellular Properties of Endometrial Pericytes.

Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible adhesion molecule and a primary amine oxidase involved in immune cell trafficking. Leukocyte extravasation into tissues is mediated by adhesion molecules expressed on endothelial cells and pericytes. Pericytes play a major role in the angiogenesis and vascularization of cycling endometrium. However, the functional properties of pericytes in the human endometrium are not known. Here we show that pericytes surrounding the spiral arterioles in midluteal human endometrium constitutively express VAP-1. We first characterize these pericytes and demonstrate that knockdown of VAP-1 perturbed their biophysical properties and compromised their contractile, migratory, adhesive and clonogenic capacities. Furthermore, we show that loss of VAP-1 disrupts pericyte-uterine natural killer cell interactions in vitro. Taken together, the data not only reveal that endometrial pericytes represent a cell population with distinct biophysical and functional properties but also suggest a pivotal role for VAP-1 in regulating the recruitment of innate immune cells in human endometrium. We posit that VAP-1 could serve as a potential biomarker for pregnancy pathologies caused by a compromised perivascular environment prior to conception.

Expression of AXL receptor tyrosine kinase relates to monocyte dysfunction and severity of cirrhosis.

Infectious complications in patients with cirrhosis frequently initiate episodes of decompensation and substantially contribute to the high mortality. Mechanisms of the underlying immuneparesis remain underexplored. TAM receptors (TYRO3/AXL/MERTK) are important inhibitors of innate immune responses. To understand the pathophysiology of immuneparesis in cirrhosis, we detailed TAM receptor expression in relation to monocyte function and disease severity prior to the onset of acute decompensation. TNF-α/IL-6 responses to lipopolysaccharide were attenuated in monocytes from patients with cirrhosis (n = 96) compared with controls (n = 27) and decreased in parallel with disease severity. Concurrently, an AXL-expressing (AXL+) monocyte population expanded. AXL+ cells (CD14+CD16highHLA-DRhigh) were characterised by attenuated TNF-α/IL-6 responses and T cell activation but enhanced efferocytosis and preserved phagocytosis of Escherichia coli Their expansion correlated with disease severity, complications, infection, and 1-yr mortality. AXL+ monocytes were generated in response to microbial products and efferocytosis in vitro. AXL kinase inhibition and down-regulation reversed attenuated monocyte inflammatory responses in cirrhosis ex vivo. AXL may thus serve as prognostic marker and deserves evaluation as immunotherapeutic target in cirrhosis.

Effect of thinning and burning fuel reduction treatments on forest carbon and bushfire fuel hazard in Eucalyptus sieberi forests of South-Eastern Australia.

More frequent hot and windy weather in fire prone forested landscapes requires that a full suite of fuel reduction measures be investigated for effectiveness in fuel hazard reduction, environmental impact and carbon (C) outcomes. Although prescribed fire and thinning are routinely applied in forests of North America to reduce fuel loads, there are few detailed studies from Australia. We report the impacts of fuel reduction treatments including burning, mechanical thinning and the combination of both on forest C and fuel hazard in open forests dominated by Eucalyptus sieberi in south-eastern Australia. Carbon losses to the atmosphere and redistribution within the forest were calculated from stocks within each fuel category before and after treatment. Mechanical thinning + burning was the most effective treatment for reducing aboveground C and fuel hazard, with major reductions in dead trees, stumps and understorey, as well as stems removed for sale as pulpwood. However forest floor fuel loads increased in thinned treatments relative to control forests. The overall fuel hazard rating in the burn only treatment was significantly reduced from extreme to low immediately following burning. In thinned only stands, the overall fuel hazard rating did not change from the pre-treatment rating of extreme, due to high surface and forest floor fuel loads and loose and flammable bark on the retained overstorey trees. This result suggests the current fuel hazard guide in use in Australia should be revised to enable it to better describe the benefits of thinning for fuel reduction - in this case the removal of about 50% of aboveground C mostly as overstorey trees, and a significant reduction in understorey, dead trees and stumps.

Platelet GPIbα is a mediator and potential interventional target for NASH and subsequent liver cancer.

Non-alcoholic fatty liver disease ranges from steatosis to non-alcoholic steatohepatitis (NASH), potentially progressing to cirrhosis and hepatocellular carcinoma (HCC). Here, we show that platelet number, platelet activation and platelet aggregation are increased in NASH but not in steatosis or insulin resistance. Antiplatelet therapy (APT; aspirin/clopidogrel, ticagrelor) but not nonsteroidal anti-inflammatory drug (NSAID) treatment with sulindac prevented NASH and subsequent HCC development. Intravital microscopy showed that liver colonization by platelets depended primarily on Kupffer cells at early and late stages of NASH, involving hyaluronan-CD44 binding. APT reduced intrahepatic platelet accumulation and the frequency of platelet-immune cell interaction, thereby limiting hepatic immune cell trafficking. Consequently, intrahepatic cytokine and chemokine release, macrovesicular steatosis and liver damage were attenuated. Platelet cargo, platelet adhesion and platelet activation but not platelet aggregation were identified as pivotal for NASH and subsequent hepatocarcinogenesis. In particular, platelet-derived GPIbα proved critical for development of NASH and subsequent HCC, independent of its reported cognate ligands vWF, P-selectin or Mac-1, offering a potential target against NASH.

Aboveground carbon of community-managed Chirpine (Pinus roxburghii Sarg.) forests of Nepal based on stand types and geographic aspects.

On a global scale, about 15.5% of forests are administered through community-based forestry programs that offer the opportunity for enhanced carbon sequestration while maintaining the supply of more traditional goods and services such as cooking fuels, animal fodder and bedding. A challenge in community forest (CF) management is to realize their carbon value without compromising their role in the provision of these traditional goods and services. In this study of CF dominated by Pinus roxburghii in the Phalebas region of Nepal, the impacts of stand composition and geographic aspect on aboveground forest carbon is investigated as a means to optimize CF management for both traditional values and for emerging carbon market values. The aboveground carbon of mixed and monospecific stands of Pinus roxburghii was estimated using a combination of destructive sampling and species-specific allometric equations. On average, monospecific stands contained 106.2 Mg C ha-1 in aboveground tree biomass, significantly more than mixed stands at 73.1 Mg C ha-1 (p = 0.022). Similarly, stands growing on northern aspects (northeast 124.8 Mg C ha-1, northwest 100.9 Mg C ha-1) stored significantly more carbon (p = 0.002) than southern aspects (southeast 75.3 Mg C ha-1, southwest 57.6 Mg C ha-1), reflecting the more favorable growing conditions of northern aspects. These results suggest monospecific stands planted on northern aspects may be best suited for management to achieve carbon benefits, whilst mixed-species stands on southern aspects may be better suited for biodiversity conservation and supporting livelihoods. To maintain and increase carbon value, community forestry may need to implement nutrient return practices to limit the impact of sustained nutrient removals on stand productivity.

Novel Targets in the Immune Microenvironment of the Hepatic Sinusoids for Treating Liver Diseases.

Immune dysregulation and accumulation of leukocytes is a hallmark of adult chronic liver diseases. Progressive hepatic inflammation can lead to fibrosis and cirrhosis with a high risk of liver failure or hepatocellular cancer (HCC). Recent advances have been made in the treatment of liver disease including the development of highly effective antiviral therapy for hepatitis C and the potential of immunotherapy for HCC. Despite this, the majority of other chronic liver diseases including alcoholic liver disease, fatty liver disease, and cholestatic diseases do not respond to conventional anti-inflammatory therapies. Recent studies defining the organ-specific properties that contribute to resident immune activation and immune cell recruitment from the circulation in these conditions have identified novel hepatic inflammatory pathways, which are now being targeted in clinical trials. Further understanding of how the immune microenvironment is regulated within the liver and how disease-specific mechanisms alter this process will hopefully lead to combination therapies to prevent aberrant inflammation and also promote fibrosis resolution. In this review, we focus on the advances that have been made in identifying key components of the inflammatory pathway including the recognition of danger signals, the recruitment and retention of lymphocytes from the circulation, and the pathways that promote resolution.

Fire intensity effects on post-fire fuel recovery in Eucalyptus open forests of south-eastern Australia.

This is a study of the re-accumulation of bushfire fuels following both prescribed fire of low fireline intensity (<700 kW m-1) and wildfire of high intensity (>10,000 kW m-1) in Australian Eucalyptus open forests of differing annual rainfall. Repeated measurements over 5 to 7 years of litter, elevated fuels, coarse woody debris, and bark revealed more rapid fuel recovery in higher rainfall forests compared with lower rainfall forests, following prescribed fire. In prescribed-burnt forests with mean annual rainfall 900-950 mm all fuel categories recovered to very high within seven years, with elevated fuels exceeding pre-fire loads by up to 200%. No fuels in prescribed-burnt forests with mean annual rainfall 600-650 mm recovered to pre-fire loads after six years suggesting that rainfall is an important driver of the rate of fuels recovery. High intensity wildfire in lower rainfall forests (600-650 mm) stimulated the rapid recovery of elevated fuels to over 600% of pre-fire loads - effectively transforming open forest formations into shrublands over the 6 years after fire. The recovery of elevated fuels following both prescribed fire in high rainfall forests and wildfire in low rainfall forests did not follow a gradual negative exponential increase often approximated by an Olson curve, but peaked early after fires. This suggests that the Olson recovery function, the default for predicting loads for these fuels in the operational fire behaviour models in use in south-eastern Australia, may not be appropriate in all cases. Fire simulations were run for forests burnt in wildfires using default (forest) and observed (shrubland) vegetation types. Under weather conditions similar to the previous wildfire, predictions for fireline intensities and the rate of spread would be at least 50% greater in transitional shrubland than forest, emphasizing the importance of accounting for vegetation dynamics for safe response management.

The Reactive Oxygen Species-Mitophagy Signaling Pathway Regulates Liver Endothelial Cell Survival During Ischemia/Reperfusion Injury.

Ischemia/reperfusion injury (IRI) is the main cause of complications following liver transplantation. Reactive oxygen species (ROS) were thought to be the main regulators of IRI. However, recent studies demonstrate that ROS activate the cytoprotective mechanism of autophagy promoting cell survival. Liver IRI initially damages the liver endothelial cells (LEC), but whether ROS-autophagy promotes cell survival in LEC during IRI is not known. Primary human LEC were isolated from human liver tissue and exposed to an in vitro model of IRI to assess the role of autophagy in LEC. The role of autophagy during liver IRI in vivo was assessed using a murine model of partial liver IRI. During IRI, ROS specifically activate autophagy-related protein (ATG) 7 promoting autophagic flux and the formation of LC3B-positive puncta around mitochondria in primary human LEC. Inhibition of ROS reduces autophagic flux in LEC during IRI inducing necrosis. In addition, small interfering RNA knockdown of ATG7 sensitized LEC to necrosis during IRI. In vivo murine livers in uninjured liver lobes demonstrate autophagy within LEC that is reduced following IRI with concomitant reduction in autophagic flux and increased cell death. In conclusion, these findings demonstrate that during liver IRI ROS-dependent autophagy promotes the survival of LEC, and therapeutic targeting of this signaling pathway may reduce liver IRI following transplantation.

A data - Model fusion methodology for mapping bushfire fuels for smoke emissions forecasting in forested landscapes of south-eastern Australia.

The increasing regional and global impact of wildfires on the environment, and particularly on the human population, is becoming a focus of the research community. Both fire behaviour and smoke dispersion models are now underpinning strategic and tactical fire management by many government agencies and therefore model accuracy at regional and local scales is increasingly important. This demands accuracy of all the components of the model systems, biomass fuel loads being among the more significant. Validation of spatial fuels maps at a regional scale is uncommon; in part due to the limited availability of independent observations of fuel loads, and in part due to a focus on the impact of model outputs. In this study we evaluate two approaches for estimating fuel loads at a regional scale and test their accuracy against an extensive set of field observations for the State of Victoria, Australia. The first approach, which assumes that fuel accumulation is an attribute of the vegetation class, was developed for the fire behaviour model Phoenix Rapid-Fire, with apparent success; the second approach applies the Community Atmosphere Biosphere Land Exchange (CABLE) process-based terrestrial biosphere model, implemented at high resolution across the Australian continent. We show that while neither model is accurate over the full range of fine and coarse fuel loads, CABLE biases can be corrected for the full regional domain with a single linear correction, however the classification based Phoenix requires a matrix of factors to correct its bias. We conclude that these examples illustrate that the benefits of simplicity and resolution inherent in classification-based models do not compensate for their lack of accuracy, and that lower resolution but inherently more accurate carbon-cycle models may be preferable for estimating fuel loads for input into smoke dispersion models.