Subtropical-temperate forested wetlands of coastal south-eastern Australia – an analysis of vegetation data to support ecosystem risk assessment at regional, national and global scales

Forested wetlands occurring on fluvial sediments are among the most threatened ecosystems in south-east Australia. The first quantitative diagnosis of forested wetland types in NSW was completed in 2005. Since then, there has been a three-fold increase in survey data on coastal floodplains, vegetation classification systems have been developed in New South Wales, Queensland and Victoria, and methods for the assessment of ecosystem conservation risks have been adopted by the International Union for the Conservation of Nature (IUCN). Aims. To ensure an evidence base that can support conservation decisions and national conservation assessments, there is a need to review and update the classification of forested wetlands and integrate classification schemes across jurisdictions. Methods. We evaluated the efficacy of a multi-stage clustering strategy, applied to data from different sources with largely unknown methodological idiosyncrasies, to retrieve ecologically meaningful clusters. We assessed the veracity and robustness of the 2005 classification of forest wetlands as a framework for national risk assessments over an expanded range. Key results. We derived a quantitative, cross- jurisdictional classification of forested wetlands based on a synthesis of 5173 plot samples drawn from three states and identified the status of our units in relation to IUCN's Global Ecosystem Typology. Conclusions. Our analyses support the retention of the five legacy types which are the basis for threatened ecosystem listings under the NSW Biodiversity Conservation Act 2016 and Commonwealth Environment Protection and Biodiversity Conservation Act 1999. Implications. Our results will support revised assessments of current listings and facilitate their integration at state, national and global scale

Nitric Oxide Synthase Inhibition Enhances the Antitumor Effect of Radiation in the Treatment of Squamous Carcinoma Xenografts

This study tests whether the nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine (L-NNA), combines favorably with ionizing radiation (IR) in controlling squamous carcinoma tumor growth. Animals bearing FaDu and A431 xenografts were treated with L-NNA in the drinking water. IR exposure was 10 Gy for tumor growth and survival studies and 4 Gy for ex vivo clonogenic assays. Cryosections were examined immunohistochemically for markers of apoptosis and hypoxia. Blood flow was assayed by fluorescent microscopy of tissue cryosections after i.v. injection of fluorospheres. Orally administered L-NNA for 24 hrs reduces tumor blood flow by 80% (p<0.01). Within 24 hrs L-NNA treatment stopped tumor growth for at least 10 days before tumor growth again ensued. The growth arrest was in part due to increased cell killing since a combination of L-NNA and a single 4 Gy IR caused 82% tumor cell killing measured by an ex vivo clonogenic assay compared to 49% by L-NNA or 29% by IR alone. A Kaplan-Meyer analysis of animal survival revealed a distinct survival advantage for the combined treatment. Combining L-NNA and IR was also found to be at least as effective as a single i.p. dose of cisplatin plus IR. In contrast to the in vivo studies, exposure of cells to L-NNA in vitro was without effect on clonogenicity with or without IR. Western and immunochemical analysis of expression of a number of proteins involved in NO signaling indicated that L-NNA treatment enhanced arginase-2 expression and that this may represent vasculature remodeling and escape from NOS inhibition. For tumors such as head and neck squamous carcinomas that show only modest responses to inhibitors of specific angiogenic pathways, targeting NO-dependent pro-survival and angiogenic mechanisms in both tumor and supporting stromal cells may present a potential new strategy for tumor control

Pharmacologically directed strategies in academic anticancer drug discovery based on the European NCI compounds initiative

Background: The European NCI compounds programme, a joint initiative of the EORTC Research Branch, Cancer Research Campaign and the US National Cancer Institute, was initiated in 1993. The objective was to help the NCI in reducing the backlog of in vivo testing of potential anticancer compounds, synthesised in Europe that emerged from the NCI in vitro 60-cell screen. Methods: Over a period of more than twenty years the EORTC—Cancer Research Campaign panel reviewed ~2000 compounds of which 95 were selected for further evaluation. Selected compounds were stepwise developed with clear go/no go decision points using a pharmacologically directed programme. Results: This approach eliminated quickly compounds with unsuitable pharmacological properties. A few compounds went into Phase I clinical evaluation. The lessons learned and many of the principles outlined in the paper can easily be applied to current and future drug discovery and development programmes. Conclusions: Changes in the review panel, restrictions regarding numbers and types of compounds tested in the NCI in vitro screen and the appearance of targeted agents led to the discontinuation of the European NCI programme in 2017 and its transformation into an academic platform of excellence for anticancer drug discovery and development within the EORTC-PAMM group. This group remains open for advice and collaboration with interested parties in the field of cancer pharmacology

Functional and Structural Characteristics of Tumor Angiogenesis in Lung Cancers Overexpressing Different VEGF Isoforms Assessed by DCE- and SSCE-MRI

The expressions of different vascular endothelial growth factor (VEGF) isoforms are associated with the degree of tumor invasiveness and the patient's prognosis in human cancers. We hypothesized that different VEGF isoforms can exert different effects on the functional and structural characteristics of tumor angiogenesis. We used dynamic contrast-enhanced MRI (DCE-MRI) and steady-state contrast-enhanced MRI (SSCE-MRI) to evaluate in vivo vascular functions (e.g., perfusion and permeability) and structural characteristics (e.g., vascular size and vessel density) of the tumor angiogenesis induced by different VEGF isoforms (VEGF121, VEGF165, and VEGF189) in a murine xenograft model of human lung cancer. Tumors overexpressing VEGF189 were larger than those overexpressing the other two VEGF isoforms. The Ktrans map obtained from DCE-MRI revealed that the perfusion and permeability functions of tumor microvessels was highest in both the rim and core regions of VEGF189-overexpressing tumors (p<0.001 for both tumor rim and core). The relative vessel density and relative vessel size indexes derived from SSCE-MRI revealed that VEGF189-overexpressing tumors had the smallest (p<0.05) and the most-dense (p<0.01) microvessels, which penetrated deeply from the tumor rim into the core, followed by the VEGF165-overepxressing tumor, whose microvessels were located mainly in the tumor rim. The lowest-density microvessels were found in the VEGF121-overexpressing tumor; these microvessels had a relatively large lumen and were found mainly in the tumor rim. We conclude that among the three VEGF isoforms evaluated, VEGF189 induces the most densely sprouting and smallest tumor microvessels with the highest in vivo perfusion and permeability functions. These characteristics of tumor microvessels may contribute to the reported adverse effects of VEGF189 overexpression on tumor progression, metastasis, and patient survival in several human cancers, including non-small cell lung cancer, and suggest that applying aggressive therapy may be necessary in human cancers in which VEGF189 is overexpressed

Functional tissue engineering of ligament healing

Ligaments and tendons are dense connective tissues that are important in transmitting forces and facilitate joint articulation in the musculoskeletal system. Their injury frequency is high especially for those that are functional important, like the anterior cruciate ligament (ACL) and medial collateral ligament (MCL) of the knee as well as the glenohumeral ligaments and the rotator cuff tendons of the shoulder. Because the healing responses are different in these ligaments and tendons after injury, the consequences and treatments are tissue- and site-specific. In this review, we will elaborate on the injuries of the knee ligaments as well as using functional tissue engineering (FTE) approaches to improve their healing. Specifically, the ACL of knee has limited capability to heal, and results of non-surgical management of its midsubstance rupture have been poor. Consequently, surgical reconstruction of the ACL is regularly performed to gain knee stability. However, the long-term results are not satisfactory besides the numerous complications accompanied with the surgeries. With the rapid development of FTE, there is a renewed interest in revisiting ACL healing. Approaches such as using growth factors, stem cells and scaffolds have been widely investigated. In this article, the biology of normal and healing ligaments is first reviewed, followed by a discussion on the issues related to the treatment of ACL injuries. Afterwards, current promising FTE methods are presented for the treatment of ligament injuries, including the use of growth factors, gene delivery, and cell therapy with a particular emphasis on the use of ECM bioscaffolds. The challenging areas are listed in the future direction that suggests where collection of energy could be placed in order to restore the injured ligaments and tendons structurally and functionally

A function-based typology for Earth's ecosystems

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: Descriptions, images and interactive maps for the typology are updated periodically at https://global-ecosystems.org/. The spatial data for this study are available at Zenodo (https://doi.org/10.5281/zenodo.3546513).As the United Nations develops a post-2020 global biodiversity framework for the Convention on Biological Diversity, attention is focusing on how new goals and targets for ecosystem conservation might serve its vision of 'living in harmony with nature'1,2. Advancing dual imperatives to conserve biodiversity and sustain ecosystem services requires reliable and resilient generalizations and predictions about ecosystem responses to environmental change and management3. Ecosystems vary in their biota4, service provision5 and relative exposure to risks6, yet there is no globally consistent classification of ecosystems that reflects functional responses to change and management. This hampers progress on developing conservation targets and sustainability goals. Here we present the International Union for Conservation of Nature (IUCN) Global Ecosystem Typology, a conceptually robust, scalable, spatially explicit approach for generalizations and predictions about functions, biota, risks and management remedies across the entire biosphere. The outcome of a major cross-disciplinary collaboration, this novel framework places all of Earth's ecosystems into a unifying theoretical context to guide the transformation of ecosystem policy and management from global to local scales. This new information infrastructure will support knowledge transfer for ecosystem-specific management and restoration, globally standardized ecosystem risk assessments, natural capital accounting and progress on the post-2020 global biodiversity framework.Natural Environment Research Council (NERC

The persistence niche: what makes it and what breaks it for two fire-prone plant species

Persistence niches are expected to favour qualitatively different plant life histories compared with regeneration niches. In fire-prone habitats, for example, resprouting plants may be expected to exploit persistence niches, whereas obligate-seeders by definition exploit regeneration niches. Resprouter life histories should be typified by high rates of survival, which may be offset by relatively low rates of growth and reproduction. This combination of characters is expected to result from trade-offs in resource allocation and because the longevity of individual plants should buffer their populations against the effects of recruitment failure. We asked whether two resprouting perennial shrubs, Epacris barbata Melville and Xanthorrhoea resinifera (Sol. Ex Kite) E.C.Nelson & D.J.Bedford, exhibited the life-history character combinations that are expected for species exploiting a persistence niche. We also investigated how a change in habitat suitability caused by the invasion of a root pathogen may limit the ability of these species to occupy persistence niches. Demographic censuses of several years' duration in two populations of each species yielded estimates of vital rates that were consistent with the life-history profile expected for a persistence niche. Rates of background survival were high and rates of fire-related mortality were low in both species. As expected, these were associated with low rates of growth and seedling establishment, although rates of seed production and viability were relatively high in both species. The importance of survival was confirmed by stochastic population models, which showed that population viability was more sensitive to decreases in survival of mature plants and increases in fire mortality of established plants than to changes in other vital rates. Seedling growth rates were also relatively important in E. barbata. Populations of both species that had been infected by root rot disease, Phytophthora cinnamomi, had substantially reduced survival rates and, consequently, reduced population viability. These effects were more extreme in E. barbata than in X. resinifera. We conclude that processes that reduce survival, such as disease infection and habitat loss, rather than processes that impede seed production and recruitment mediate the persistence niche. However, we discuss the possibility that this dependency might be mitigated by high fecundity if infrequent conditions that permit large recruitment events have so far eluded detection