Development and Characterisation of a New Patient-Derived Xenograft Model of AR-Negative Metastatic Castration-Resistant Prostate Cancer.

As the treatment landscape for prostate cancer gradually evolves, the frequency of treatment-induced neuroendocrine prostate cancer (NEPC) and double-negative prostate cancer (DNPC) that is deficient for androgen receptor (AR) and neuroendocrine (NE) markers has increased. These prostate cancer subtypes are typically refractory to AR-directed therapies and exhibit poor clinical outcomes. Only a small range of NEPC/DNPC models exist, limiting our molecular understanding of this disease and hindering our ability to perform preclinical trials exploring novel therapies to treat NEPC/DNPC that are urgently needed in the clinic. Here, we report the development of the CU-PC01 PDX model that represents AR-negative mCRPC with PTEN/RB/PSMA loss and CTNN1B/TP53/BRCA2 genetic variants. The CU-PC01 model lacks classic NE markers, with only focal and/or weak expression of chromogranin A, INSM1 and CD56. Collectively, these findings are most consistent with a DNPC phenotype. Ex vivo and in vivo preclinical studies revealed that CU-PC01 PDX tumours are resistant to mCRPC standard-of-care treatments enzalutamide and docetaxel, mirroring the donor patient's treatment response. Furthermore, short-term CU-PC01 tumour explant cultures indicate this model is initially sensitive to PARP inhibition with olaparib. Thus, the CU-PC01 PDX model provides a valuable opportunity to study AR-negative mCRPC biology and to discover new treatment avenues for this hard-to-treat disease.

A globally relevant change taxonomy and evidence-based change framework for land monitoring.

A globally relevant and standardized taxonomy and framework for consistently describing land cover change based on evidence is presented, which makes use of structured land cover taxonomies and is underpinned by the Driver-Pressure-State-Impact-Response (DPSIR) framework. The Global Change Taxonomy currently lists 246 classes based on the notation 'impact (pressure)', with this encompassing the consequence of observed change and associated reason(s), and uses scale-independent terms that factor in time. Evidence for different impacts is gathered through temporal comparison (e.g., days, decades apart) of land cover classes constructed and described from Environmental Descriptors (EDs; state indicators) with pre-defined measurement units (e.g., m, %) or categories (e.g., species type). Evidence for pressures, whether abiotic, biotic or human-influenced, is similarly accumulated, but EDs often differ from those used to determine impacts. Each impact and pressure term is defined separately, allowing flexible combination into 'impact (pressure)' categories, and all are listed in an openly accessible glossary to ensure consistent use and common understanding. The taxonomy and framework are globally relevant and can reference EDs quantified on the ground, retrieved/classified remotely (from ground-based, airborne or spaceborne sensors) or predicted through modelling. By providing capacity to more consistently describe change processes-including land degradation, desertification and ecosystem restoration-the overall framework addresses a wide and diverse range of local to international needs including those relevant to policy, socioeconomics and land management. Actions in response to impacts and pressures and monitoring towards targets are also supported to assist future planning, including impact mitigation actions.

Does rapid utilization of elevated nutrient availability allow eucalypts to dominate in the tropical savannas of Australia?

Northern Australia's savannas are among the most fire-prone biomes on Earth and are dominated by eucalypts (Eucalyptus and Corymbia spp.). It is not clear what processes allow this group to dominate under such extreme fire frequencies and whether a superior ability to compete for nutrients and water might play a role. There is evidence that eucalypts are adapted to frequent fires; juvenile eucalypts escape the fire trap by growing rapidly in height between fires. However, non-eucalypts are less able to escape the fire trap and tend to have stand structures strongly skewed toward suppressed juveniles. The mechanisms that drive these contrasting fire responses are not well understood. Here, we describe the results of a controlled glasshouse seedling experiment that evaluated the relative importance of nutrient and water availability in determining height growth and biomass growth of two eucalypt and one noneucalypt tree species, common in northern Australian savannas. We demonstrate that growth of eucalypt seedlings is particularly responsive to nutrient addition. Eucalypt seedlings are able to rapidly utilize soil nutrients and accumulate biomass at a much greater rate than noneucalypt seedlings. We suggest that a seasonal spike in nutrient availability creates a nutrient-rich microsite that allows eucalypt seedlings to rapidly gain height and biomass, increasing their likelihood of establishing successfully and reaching a fire-resistant size. Our results extend our understanding of how eucalypts dominate northern Australian savannas under extremely high fire frequencies.

Facultative and Obligate Trees in a Mesic Savanna: Fire Effects on Savanna Structure Imply Contrasting Strategies of Eco-Taxonomic Groups.

Fire is a major determinant of savanna tree communities and, as such, manipulation of fire frequency is an important management tool. Resolving the effects of fire management on tree size class distributions can help managers predict and plan for short-term ecological and economic outcomes, reveal different strategies by which woody plants cope with frequent fire, and help us predict vegetation changes under future fire scenarios. Savanna structure and size class distribution are strongly influenced by the ability of suppressed tree resprouts to escape stem death by frequent fire. A widespread assumption is that resprouts have an imperative to escape fire to reach sexual maturity in the canopy and thereby ensure long-term species viability. We use a census of Australian mesic savanna tree communities subjected to annual, triennial, and fire exclusion (unburnt) fire treatments to ask how fire frequency affects size class distributions within and between eco-taxonomic groups of species. Total tree densities did not significantly differ, but were highest in the triennial (7,610 ± se 1,162 trees ha-1) and unburnt fire treatments (7,051 ± se 578 trees ha-1) and lowest in the annual fire treatment (6,168 ± se 523 trees ha-1). This was caused by increased sapling densities in the triennial and unburnt fire treatments, predominantly of Acacia and pantropical genera. Eucalypts (Eucalyptus and Corymbia spp.) dominated the canopy across all fire treatments indicating relatively greater success in recruiting to larger sizes than other species groups. However, in the sub-canopy size classes eucalypts co-dominated with, and in some size classes were outnumbered by, pantropicals and Acacia, regardless of fire treatment. We hypothesize that such results are caused by fundamental differences in woody plant strategies, in particular sexual reproduction, that have not been widely recognized in Australian savannas.

Natural abundance (δ¹5N) indicates shifts in nitrogen relations of woody taxa along a savanna-woodland continental rainfall gradient.

Water and nitrogen (N) interact to influence soil N cycling and plant N acquisition. We studied indices of soil N availability and acquisition by woody plant taxa with distinct nutritional specialisations along a north Australian rainfall gradient from monsoonal savanna (1,600-1,300 mm annual rainfall) to semi-arid woodland (600-250 mm). Aridity resulted in increased 'openness' of N cycling, indicated by increasing δ(15)N(soil) and nitrate:ammonium ratios, as plant communities transitioned from N to water limitation. In this context, we tested the hypothesis that δ(15)N(root) xylem sap provides a more direct measure of plant N acquisition than δ(15)N(foliage). We found highly variable offsets between δ(15)N(foliage) and δ(15)N(root) xylem sap, both between taxa at a single site (1.3-3.4 ‰) and within taxa across sites (0.8-3.4 ‰). As a result, δ(15)N(foliage) overlapped between N-fixing Acacia and non-fixing Eucalyptus/Corymbia and could not be used to reliably identify biological N fixation (BNF). However, Acacia δ(15)N(root) xylem sap indicated a decline in BNF with aridity corroborated by absence of root nodules and increasing xylem sap nitrate concentrations and consistent with shifting resource limitation. Acacia dominance at arid sites may be attributed to flexibility in N acquisition rather than BNF capacity. δ(15)N(root) xylem sap showed no evidence of shifting N acquisition in non-mycorrhizal Hakea/Grevillea and indicated only minor shifts in Eucalyptus/Corymbia consistent with enrichment of δ(15)N(soil) and/or decreasing mycorrhizal colonisation with aridity. We propose that δ(15)N(root) xylem sap is a more direct indicator of N source than δ(15)N(foliage), with calibration required before it could be applied to quantify BNF.

The development of seasonal tree water deficit in Callitris intratropica.

The tropical conifer Callitris intratropica (Cupressaceae) produces clear annual growth rings, and has been shown to be potentially useful for understanding past climate variability in northern Australia. As climate patterns in this region become less predictable, an understanding of plant responses to different weather patterns is of importance. In this paper, we examine tree water relations using a parameter here called tree water deficit (ΔD), determined from de-trended stem size variability in densely grown ('grove') and isolated trees. This parameter provides an integrated measure of the trees' response to water supply and demand under constantly changing environmental conditions. The work, conducted over 12 months, found that daily variation in tree water deficit was determined mainly by soil water availability, but temperature and relative humidity contributed more to the variability over some periods. Isolated and grove trees exhibited quite distinct patterns of ΔD development during the year, but particularly during the transition between the dry and wet seasons. The results of this work suggest that the dendrochronological interpretation of tree rings in the context of strongly seasonal water availability should incorporate an understanding of the development of seasonal drought in isolated trees compared with trees experiencing strong intra-specific competition. Different responses based on the ecological situations of the trees will affect their patterns of stem growth, and ultimately the climatic information that is incorporated in ring width variability.

Complementary resource use by tree species in a rain forest tree plantation.

Mixed-species tree plantations, composed of high-value native rain forest timbers, are potential forestry systems for the subtropics and tropics that can provide ecological and production benefits. Choices of rain forest tree species for mixtures are generally based on the concept that assemblages of fast-growing and light-demanding species are less productive than assemblages of species with different shade tolerances. We examined the hypothesis that mixtures of two fast-growing species compete for resources, while mixtures of shade-tolerant and shade-intolerant species are complementary. Ecophysiological characteristics of young trees were determined and analyzed with a physiology-based canopy model (MAESTRA) to test species interactions. Contrary to predictions, there was evidence for complementary interactions between two fast-growing species with respect to nutrient uptake, nutrient use efficiency, and nutrient cycling. Fast-growing Elaeocarpus angustifolius had maximum demand for soil nutrients in summer, the most efficient internal recycling of N, and low P use efficiency at the leaf and whole-plant level and produced a large amount of nutrient-rich litter. In contrast, fast-growing Grevillea robusta had maximum demand for soil nutrients in spring and highest leaf nutrient use efficiency for N and P and produced low-nutrient litter. Thus, mixtures of fast-growing G. robusta and E. angustifolius or G. robusta and slow-growing, shade-tolerant Castanospermum australe may have similar or even greater productivity than monocultures, as light requirement is just one of several factors affecting performance of mixed-species plantations. We conclude that the knowledge gained here will be useful for designing large-scale experimental mixtures and commercial forestry systems in subtropical Australia and elsewhere.

The influence of mixed tree plantations on the nutrition of individual species: a review.

Productivity of tree plantations is a function of the supply, capture and efficiency of use of resources, as outlined in the Production Ecology Equation. Species interactions in mixed-species stands can influence each of these variables. The importance of resource-use efficiency in determining forest productivity has been clearly demonstrated in monocultures; however, substantial knowledge gaps remain for mixtures. This review examines how the physiology and morphology of a given species can vary depending on whether it grows in a mixture or monoculture. We outline how physiological and morphological shifts within species, resulting from interactions in mixtures, may influence the three variables of the Production Ecology Equation, with an emphasis on nutrient resources [nitrogen (N) and phosphorus (P)]. These include (i) resource availability, including soil nutrient mineralization, N2 fixation and litter decomposition; (ii) proportion of resources captured, resulting from shifts in spatial, temporal and chemical patterns of root dynamics; (iii) resource-use efficiency. We found that more than 50% of mixed-species studies report a shift to greater above-ground nutrient content of species grown in mixtures compared to monocultures, indicating an increase in the proportion of resources captured from a site. Secondly, a meta-analysis showed that foliar N concentrations significantly increased for a given species in a mixture containing N2-fixing species, compared to a monoculture, suggesting higher rates of photosynthesis and greater resource-use efficiency. Significant shifts in N- and P-use efficiencies of a given species, when grown in a mixture compared to a monoculture, occurred in over 65% of studies where resource-use efficiency could be calculated. Such shifts can result from changes in canopy photosynthetic capacities, changes in carbon allocation or changes to foliar nutrient residence times of species in a mixture. We recommend that future research focus on individual species' changes, particularly with respect to resource-use efficiency (including nutrients, water and light), when trees are grown in mixtures compared to monocultures. A better understanding of processes responsible for changes to tree productivity in mixed-species tree plantations can improve species, and within-species, selection so that the long-term outcome of mixtures is more predictable.

The relationship between stem biomechanics and wood density is modified by rainfall in 32 Australian woody plant species.

*Stem mechanical properties are critically linked to foliage deployment and growth strategy, yet variation in stem mechanics across species and habitats is poorly understood. *Here, we compared 32 plant species growing across four sites of contrasting rainfall and soil nutrient availability in Australia. *The modulus of elasticity (MOE) and modulus of rupture (MOR) were tightly correlated with dry sapwood density within sites, but species from low-rainfall environments had higher wood density for a given MOE and MOR compared with species growing in high-rainfall environments. The ratio of MOE to MOR was slightly lower for species at low-rainfall sites, suggesting that wood was stronger for a given elasticity. Most species had thick bark, but the mechanical contribution of bark to stem MOE was small. *Our results suggest that arid-adapted species would need to deploy more dry mass to support stems. Our results also highlight the importance of understanding how the biomechanics-wood density relationship evolves under different environmental conditions to better understand plant growth across diverse habitats.