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Genotype-environment interaction is pervasive in forest genetics. Delineation of spatial breeding zones (BZs) is fundamental for accommodating genotype-environment interaction. Here we developed a BZ classification pipeline for the forest tree Eucalyptus globulus in 2 Australian regions based on phenotypic, genomic, and pedigree data, as well on a detailed environmental characterization (“envirotyping”) and spatial mapping of BZs. First, the factor analytic method was used to model additive genetic variance and site–site genetic correlations (rB) in stem volume across 48 trials of 126,467 full-sib progeny from 2 separate breeding programs. Thirty-three trials were envirotyped using 145 environmental variables (EVs), involving soil and landscape (71), climate (73), and management (1) EVs. Next, sparse partial least squares-discriminant analysis was used to identify EVs that were required to predict classification of sites into 5 non-exclusive BZ classes based on rB. Finally, these BZs were spatially mapped across the West Australian and “Green Triangle” commercial estates by enviromic prediction using EVs for 80 locations and 15 sets of observed climate data to represent temporal variation. The factor analytic model explained 85.9% of estimated additive variance. Our environmental classification system produced within-zone mean rB between 0.76 and 0.84, which improves upon the existing values of 0.62 for Western Australia and 0.67 for Green Triangle as regional BZs. The delineation of 5 BZ classes provides a powerful framework for increasing genetic gain by matching genotypes to current and predicted future environments.

Madangamine alkaloids have attracted considerable interest in the scientific community due to their complex polycyclic structures and potent biological activities. The six members identified to date have exhibited diverse and significant cytotoxic activities against various cancer cell lines. Despite their structural complexity, seven total syntheses—covering five of the six members—have been reported to date. These syntheses, involving 28 to 36 steps and global yields ranging from 0.006% to 0.029%, highlight the formidable challenge these compounds present. This review summarizes the key synthetic strategies developed to access critical fragments, including the construction of the ABC diazatricyclic core and the ACE ring systems. Approaches to assembling the ABCD and ABCE tetracyclic frameworks are also discussed. Finally, we highlight the completed total syntheses of madangamines A–E, with a focus on pivotal transformations and strategic innovations that have enabled progress in this field.

This study aimed to determine the in vitro cytotoxicity and understand possible cytotoxic mechanisms via an in silico study of eleven chalcones synthesized from two acetophenones. Five were synthesized from a prenylacetophenone isolated from a plant that grows in the Andean region of the Atacama Desert. The cytotoxic activity of all the synthesized chalcones was tested against breast cancer cell lines using an MTT cell proliferation assay. The results suggest that the prenyl group in the A-ring of the methoxy and hydroxyl substituents of the B-ring appear to be crucial for the cytotoxicity of these compounds. The chalcones 12 and 13 showed significant inhibitory effects against growth in MCF-7 cells (IC50 4.19 ± 1.04 µM and IC50 3.30 ± 0.92 µM), ZR-75-1 cells (IC50 9.40 ± 1.74 µM and IC50 8.75 ± 2.01µM), and MDA-MB-231 cells (IC50 6.12 ± 0.84 µM and IC50 18.10 ± 1.65 µM). Moreover, these chalcones showed differential activity between MCF-10F (IC50 95.76 ± 1.52 µM and IC50 95.11 ± 1.97 µM, respectively) and the tumor lines. The in vitro results agree with molecular coupling results, whose affinity energies and binding mode agree with the most active compounds. Thus, compounds 12 and 13 can be considered for further studies and are candidates for developing new antitumor agents. In conclusion, these observations give rise to a new hypothesis for designing chalcones with potential cytotoxicity with high potential for the pharmaceutical industry.

Single-step GBLUP (HBLUP) efficiently combines genomic, pedigree, and phenotypic information for holistic genetic analyses of disjunct breeding populations. We combined data from two independent multigenerational Eucalyptus globulus breeding populations to provide direct comparisons across the programs and indirect predictions in environments where pedigreed families had not been evaluated. Despite few known pedigree connections between the programs, genomic relationships provided the connectivity required to create a unified relationship matrix, H, which was used to compare pedigree-based and HBLUP models. Stem volume data from 48 sites spread across three regions of southern Australia and wood quality data across 20 sites provided comparisons of model accuracy. Genotyping proved valuable for correcting pedigree errors and HBLUP more precisely defines relationships within and among populations, with relationships among the genotyped individuals used to connect the pedigrees of the two programs. Cryptic relationships among the native range populations provided evidence of population structure and evidence of the origin of landrace populations. HBLUP across programs improved the prediction accuracy of parents and genotyped individuals and enabled breeding value predictions to be directly compared and inferred in regions where little to no testing has been undertaken. The impact of incorporating genetic groups in the estimation of H will further align traditional genetic evaluation pipelines with approaches that incorporate marker-derived relationships into prediction models.

Genetic groups have been widely adopted in tree breeding to account for provenance effects within pedigree-derived relationship matrices. However, provenances or genetic groups have not yet been incorporated into single-step genomic BLUP (“HBLUP”) analyses of tree populations. To quantify the impact of accounting for population structure in Eucalyptus globulus, we used HBLUP to compare breeding value predictions from models excluding base population effects and models including either fixed genetic groups or the marker-derived proxies, also known as metafounders. Full-sib families from 2 separate breeding populations were evaluated across 13 sites in the “Green Triangle” region of Australia. Gamma matrices (Γ) describing similarities among metafounders reflected the geographic distribution of populations and the origins of 2 land races were identified. Diagonal elements of Γ provided population diversity or allelic covariation estimates between 0.24 and 0.56. Genetic group solutions were strongly correlated with metafounder solutions across models and metafounder effects influenced the genetic solutions of base population parents. The accuracy, stability, dispersion, and bias of model solutions were compared using the linear regression method. Addition of genomic information increased accuracy from 0.41 to 0.47 and stability from 0.68 to 0.71, while increasing bias slightly. Dispersion was within 0.10 of the ideal value (1.0) for all models. Although inclusion of metafounders did not strongly affect accuracy or stability and had mixed effects on bias, we nevertheless recommend the incorporation of metafounders in prediction models to represent the hierarchical genetic population structure of recently domesticated populations.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder in which cholinergic dysfunction and oxidative stress act as synergistic contributors to cognitive decline and neuronal damage. Multitarget-directed ligands (MTDLs) capable of modulating both acetylcholinesterase (AChE) activity and oxidative stress pathways are promising candidates for disease-modifying therapies. A series of conformationally locked 7-aryl tetrahydroisoquinoline derivatives was synthesized via a tandem cross-metathesis/Michael/annulation strategy. These compounds feature a stable intramolecular O-H···O=C hydrogen bond that enforces a quasi-planar geometry and modulates the electronic properties of the aryl substituent. The compounds were evaluated for their AChE inhibitory activity using Ellman's assay and for antioxidant capacity using the oxygen radical absorbance capacity (ORAC) assay. Molecular docking studies were performed to analyze binding modes within AChE's aromatic gorge, while density functional theory (DFT) calculations were conducted to assess the thermodynamics of hydrogen atom transfer (HAT) and ionization potential (IP) related to antioxidant behavior. All derivatives exhibited micromolar AChE inhibition (IC = 33-54 µM), with structure-activity relationships driven by the electronic nature and π-polarizability of the 7-aryl ring. Docking results revealed a conserved, π-dominated binding pose within the enzyme's active site. ORAC measurements showed substituent-dependent radical-scavenging activity consistent with the electronic trends observed in enzyme inhibition. DFT calculations indicated a thermodynamic preference for hydrogen atom transfer (HAT) from benzylic C-H over phenolic O-H cleavage, supporting the observed antioxidant profile. This study identifies 7-aryl tetrahydroisoquinolines as a novel, mechanistically coherent scaffold for the development of dual-acting neuroprotective agents targeting both cholinergic dysfunction and oxidative stress in Alzheimer's disease. Their tunable electronic properties and preorganized geometry offer a promising foundation for further optimization within the multitarget therapeutic framework.

This work proposes the design of β-keto esters as antibacterial compounds. The design was based on the structure of the autoinducer of bacterial quorum sensing, N-(3-oxo-hexanoyl)-l-homoserine lactone (3-oxo-C6-HSL). Eight β-keto ester analogues were synthesised with good yields and were spectroscopically characterised, showing that the compounds were only present in their β-keto ester tautomer form. We carried out a computational analysis of the reactivity and ADME (absorption, distribution, metabolism, and excretion) properties of the compounds as well as molecular docking and molecular dynamics calculations with the LasR and LuxS quorum-sensing (QS) proteins, which are involved in bacterial resistance to antibiotics. The results show that all the compounds exhibit reliable ADME properties and that only compound 7 can present electrophile toxicity. The theoretical reactivity study shows that compounds 6 and 8 present a differential local reactivity regarding the rest of the series. Compound 8 presents the most promising potential in terms of its ability to interact with the LasR and LuxS QS proteins efficiently according to its molecular docking and molecular dynamics calculations. An initial in vitro antimicrobial screening was performed against the human pathogenic bacteria Pseudomonas aeruginosa and Staphylococcus aureus as well as the phytopathogenic bacteria Pseudomonas syringae and Agrobacterium tumefaciens. Compounds 6 and 8 exhibit the most promising results in the in vitro antimicrobial screening against the panel of bacteria studied.

This paper reviews and critiques a potential innovation in resource and environmental management as a means of stimulating further research and refinement. Given the perceived limitations of top‐down, centralized management of natural resources, calls for the devolution of authority for local resources to local communities have increasingly been expressed. Proponents of community‐based resource management argue that, situating decision‐making closer to the place of resource use and subjecting decision‐makers to the repercussions of their decisions creates the potential for more flexible and prudent resource management. Further, by empowering communities to develop their own strategies for local economic development, greater community stability may be achieved. However, neither of these potentials will be realized if the credibility and capacity of communities are assumed rather than interrogated. These hypothesized contingent conditions of effective community‐based resource management are described and illustrated based on two examples in western Canada in which communities have been empowered to determine the use of local resources: the siting of a hazardous‐waste treatment facility near the town of Swan Hills, Alberta; and the development of the Community Forest Pilot Project in British Columbia. These examples raise a series of concerns and questions that suggest a need for further, in‐depth investigation. Ultimately, by identifying barriers to effective community‐based resource management, a more refined model of this potentially innovative approach can be fostered. Cette dissertation étudie et critique une innovation potentielle quant à la gestion de l’environnement et des ressources dans le but de stimuler des recherches plus approfondies et d’affiner les résultats. Étant donné les limitations perçues d’une gestion centralisée et descendante des ressources naturelles, on demande de plus en plus fréquemment que les collectivités locales soient responsables de la gestion des ressources locales. Les partisans d’une gestion des ressources par les collectivités avancent qu’en rapprochant la prise de décision du lieu d’utilisation des ressources et en soumettant les décideurs aux répercussions de leurs décisions, on favorise potentiellement une gestion plus souple et plus prudente des ressources. De plus, en habilitant les collectivités à déterminer leurs propres stratégies de développement économique local, une plus grande stabilité des collectivités est possible. Toutefois, ni l’un ni l’autre de ces potentiels ne seront réalisés si l’on admet sans les mettre en question la crédibilité et la capacité de gestion de ces collectivités. Ces conditions contingentes d’une gestion efficace des ressources par les collectivités sont décrites et illustrées par deux exemples provenant de l’Ouest du Canada, où les communautés ont toute discrétion quant à l’utilisation des ressources locales : l’implantation d’un centre de traitement des déchets dangereux près de la ville de Swan Hills, dans l’Alberta, et l’exécution du Community Forest Pilot Project (projet pilote de forêt domaniale) en Colombie britannique. Ces exemples soulèvent une série de questions et de préoccupations qui suggèrent le besoin de nouvelles recherches plus approfondies. En fin de compte, en identifiant ce qui s’oppose à une gestion efficace des ressources par les collectivités, on pourra stimuler l’élaboration d’un modèle plus perfectionné de cette démarche potentiellement innovante.

Forest plantations can access water from some unconfined aquifers that also contain nitrate at concentrations that could support hydroponic culture, but the separate effects of such additional water and nitrogen availability on tree growth have not hitherto been quantified. We demonstrate these effects using simulation modelling at two contrasting sites supporting Eucalyptus globulus Labill. or Pinus radiata D.Don plantations. The APSIM Eucalyptus and Pinus models simulated plantation growth within 2% of observed growth where the water table was at 4 m depth for eucalypts (height 28 m, MAI 32 m3 ha−1 year−1) and at 23 m for pines (height 37 m, MAI 20 m3 ha−1 year−1). In simulations without an aquifer, observed growth could only be matched using unrealistically high surface soil nitrogen (N) supply, suggesting this is an unlikely mechanism. Simulated aquifer N concentrations, evapotranspiration, and net N mineralization and leaching (emergent properties of modelling) were similar to measured values. These results strengthen the plausibility that aquifer N uptake by plantations could be contributing to tree growth. This hypothesis warrants further research that quantifies these processes at multiple sites. Simulations included growth of herbaceous and tree weed species, and pasture, which demonstrated the utility of the process-based APSIM modelling framework for dynamically simulating carbon, water and N of plantations and other mixed-species systems.

A straightforward synthetic entry to functionalized hydrindane compounds based on a rapid assembly of the core nucleus by a Danheiser cycloaddition is reported. Valuable bicyclic building blocks containing the fused five and six-membered carbocyclic ring system can be achieved in only four steps from a simple acyclic β-keto ester.