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Abstract: As global tree‐growing efforts have escalated in the past decade, copious failures and unintended consequences have prompted many reforestation best practices guidelines. The extent to which organizations have integrated these ecological and socioeconomic recommendations, however, remains uncertain. We reviewed websites of 99 intermediary organizations that promote and fund tree‐growing projects to determine how well they report following best practices. Nearly half the organizations stated tree or area planting targets, but only 25% had measurable, time‐bound objectives. Most organizations discussed the benefits local communities would receive from trees, but only 38% reported measures of these outcomes. Nonprofit organizations with greater prior experience converged more closely on best practices, and their level of scientific expertise was positively associated with clearer project selection standards. Although many tree‐growing organizations acknowledge the importance of clear goals, local community involvement, and monitoring, our results raise questions regarding whether long‐term benefits are being achieved and emphasize the need for stronger public accountability standards.

Abstract Next-generation risk assessment relies on mechanistic data from new approach methods, including transcriptome data. Various technologies, such as high-throughput targeted sequencing methods and microarray technologies based on hybridization with complementary probes, are used to determine differentially expressed genes (DEGs). The integration of data from different technologies requires a good understanding of the differences arising from the use of various technologies. To better understand the differences between the TempO-Seq platform and Affymetrix chip technology, whole-genome data for the volatile compound dimethylamine were compared. Selected DEGs were also confirmed using RTqPCR validation. Although the overlap of DEGs between TempO-Seq and Affymetrix was no higher than 37%, a comparison of the gene regulation in terms of log2fold changes revealed a very high concordance. RTqPCR confirmed the majority of DEGs from either platform in the examined dataset. Only a few conflicts were found (11%), while 22% were not confirmed, and 3% were not detected. Despite the observed differences between the two platforms, both can be validated using RTqPCR. Here we highlight some of the differences between the two platforms and discuss their applications in toxicology.

Selectivity profiling is key for assessing the pharmacological properties of multi-target drugs. We have developed a cell-based and barcoded assay encompassing ten druggable targets, including G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs), nuclear receptors, a protease as well as their key downstream pathways and profiled 17 drugs in living cells for efficacy, potency, and side effects. Notably, this multiplex assay, termed safetyProfiler assay, enabled the simultaneous assessment of multiple target and pathway activities, shedding light on the polypharmacological profile of compounds. For example, the neuroleptics clozapine, paliperidone, and risperidone potently inhibited primary targets DRD2 and HTR2A as well as cAMP and calcium pathways. However, while paliperidone and risperidone also potently inhibited the secondary target ADRA1A and mitogen-activated protein kinase (MAPK) downstream pathways, clozapine only exhibited mild antagonistic effects on ADRA1A and lacked MAPK inhibition downstream of DRD2 and HTR2A. Furthermore, we present data on the selectivity for bazedoxifene, an estrogen receptor antagonist currently undergoing clinical phase 2 trials for breast cancer, on MAPK signaling. Additionally, precise potency data for LY2452473, an androgen receptor antagonist, that completed a phase 2 clinical trial for prostate cancer, are presented. The non-selective kinase inhibitor staurosporine was observed to potently inactivate the two RTKs EGFR and ERBB4 as well as MAPK signaling, while eliciting stress-related cAMP responses. Our findings underscore the value of comprehensive profiling in elucidating the pharmacological properties of established and novel therapeutics, thereby facilitating the development of novel multi-target drugs with enhanced efficacy and selectivity.

The Gorini-Kossakowski-Sudarshan-Lindblad master equation (ME) governs the density matrix of open quantum systems (OQSs). When an OQS is subjected to weak continuous measurement, its state evolves as a stochastic quantum trajectory, whose statistical average solves the ME. The ensemble of such trajectories is termed an unraveling of the ME. We propose a method to operationally distinguish unravelings produced by the same ME in different measurement scenarios, using nonlinear averages of observables over trajectories. We apply the method to the paradigmatic quantum nonlinear system of resonance fluorescence in a two-level atom. We compare the Poisson-type unraveling, induced by direct detection of photons scattered from the two-level emitter, and the Wiener-type unraveling, induced by phase-sensitive detection of the emitted field. We show that a quantum-trajectory-averaged variance is able to distinguish these measurement scenarios. We evaluate the performance of the method, which can be readily extended to more complex OQSs, under a range of realistic experimental conditions.

Abstract Background Prey are more vulnerable during migration due to decreased familiarity with their surroundings and spatially concentrated movements. Predators may respond to increased prey vulnerability by shifting their ranges to match prey. Moose (Alces alces) and white-tailed deer (Odocoileus virginianus) are primary gray wolf (Canis lupus) prey and important subsistence species for Indigenous communities. We hypothesized wolves would increase use of ungulate migration corridors during migrations and predicted wolf distributions would overlap primary available prey. Methods We examined seasonal gray wolf, moose, and white-tailed deer movements on and near the Grand Portage Indian Reservation, Minnesota, USA. We analyzed GPS collar data during 2012–2021 using Brownian bridge movement models (BBMM) in Migration Mapper and mechanistic range shift analysis (MRSA) to estimate individual- and population-level occurrence distributions and determine the status and timing of range shifts. We estimated proportional overlap of wolf distributions with moose and deer distributions and tested for differences among seasons, prey populations, and wolf sex and pack affiliations. Results We identified a single migration corridor through which white-tailed deer synchronously departed in April and returned in October–November. Gray wolf distributions overlapped the deer migration corridor similarly year-round, but wolves altered within-range distributions seasonally corresponding to prey distributions. Seasonal wolf distributions had the greatest overlap with deer during fall migration (10 October–28 November) and greatest overlap with moose during summer (3 May–9 October). Conclusions Gray wolves did not increase their use of the white-tailed deer migration corridor but altered distributions within their territories in response to seasonal prey distributions. Greater overlap of wolves and white-tailed deer in fall may be due to greater predation success facilitated by asynchronous deer migration movements. Greater summer overlap between wolves and moose may be linked to moose calf vulnerability, American beaver (Castor canadensis) co-occurrence, and reduced deer abundance associated with migration. Our results suggest increases in predation pressure on deer in fall and moose in summer, which can inform Indigenous conservation efforts. We observed seasonal plasticity of wolf distributions suggestive of prey switching; that wolves did not exhibit migratory coupling was likely due to spatial constraints resulting from territoriality.

Groundwater extracted from coal seams may be a resource for irrigation of land in areas with low rainfall, but the effect of this water on soil properties needs to be established. A lysimeter study was conducted using intact soil cores (0.75 m diameter, 1.4 m deep) of four different soil types (Sodic Vertisol, Calcic Solonetz, Haplic Solonetz and Xanthic Lixisol) from southern Queensland, Australia, to study changes in soil physical and chemical properties under accelerated rates of irrigation with coal seam (CS) water (electrical conductivity (ECw) of 3 dS/m, pH of 8.8, and a sodium adsorption ratio (SAR) of 100). Cores were also alternately irrigated with deionised water to simulate rainfall, and either lucerne (Medicago sativa L) or Rhodes grass (Chloris gayana Kunth.) where grown in the lysimeters. The soil surface was treated with stoichiometric rates of elemental sulfur (1.4 t/ha) and gypsum (2.5 t/ha) prior to every 450 mm CS water irrigation to minimise changes in SAR and pH. Three of the soils (Vertisol, both Solonetz) had low leaching fractions (≤ 0.1 %) due to their clay texture and were initially saline in the subsoil (ECse 1.4–4.4 dS/m). Irrigation with CS water resulted in a gradual increase in salt content (EC) and SAR throughout the soil profile, but pH was not increased due to surface-applied elemental sulfur. The Lixisol had a higher hydraulic conductivity and leaching fraction (6.7 %) due to is loamy texture – in this soil, accumulated salts could be leached and no increase in salinity or pH were measured. Despite an increase in SAR for this loamy soil, no structural degradation was observed, and it could be sustainably irrigated with up to 3200 mm CS water (with cumulative irrigation volume of 5400 mm). Hence, leaching fractions rather than soil chemistry are good indicators to identify soils suitable for irrigation with CS water that is saline, alkaline, and sodic.

Learning management systems (LMSs) are ubiquitous in higher education, yet few studies have examined changes in student engagement online with year level. Using data mining of LMSs, we examined the frequency and timing with which first, second, and third year science students accessed the various LMS resources. We compared online access with both attendance and performance. The findings demonstrated that students of all year levels showed a preference for lecture slides over recordings, although there was a marked increase in engagement with year level. For all students, the pattern of engagement with online resources was largely a function of motivation and exam anxiety—students accessed the LMS most frequently in the final three weeks of semester. Finally, attendance was predictive of performance only for first year students, with this demonstrating that approaches are required especially for these students to increase engagement. This study has shown that engagement can vary across year levels and should be considered when designing teaching and learning activities.

Background OX40 has been widely studied as a target for immunotherapy with agonist antibodies taken forward into clinical trials for cancer where they are yet to show substantial efficacy. Here, we investigated potential mechanisms of action of anti-mouse (m) OX40 and anti-human (h) OX40 antibodies, including a clinically relevant monoclonal antibody (mAb) (GSK3174998) and evaluated how isotype can alter those mechanisms with the aim to develop improved antibodies for use in rational combination treatments for cancer.Methods Anti-mOX40 and anti-hOX40 mAbs were evaluated in a number of in vivo models, including an OT-I adoptive transfer immunization model in hOX40 knock-in (KI) mice and syngeneic tumor models. The impact of FcγR engagement was evaluated in hOX40 KI mice deficient for Fc gamma receptors (FcγR). Additionally, combination studies using anti-mouse programmed cell death protein-1 (mPD-1) were assessed. In vitro experiments using peripheral blood mononuclear cells (PBMCs) examining possible anti-hOX40 mAb mechanisms of action were also performed.Results Isotype variants of the clinically relevant mAb GSK3174998 showed immunomodulatory effects that differed in mechanism; mIgG1 mediated direct T-cell agonism while mIgG2a acted indirectly, likely through depletion of regulatory T cells (Tregs) via activating FcγRs. In both the OT-I and EG.7-OVA models, hIgG1 was the most effective human isotype, capable of acting both directly and through Treg depletion. The anti-hOX40 hIgG1 synergized with anti-mPD-1 to improve therapeutic outcomes in the EG.7-OVA model. Finally, in vitro assays with human peripheral blood mononuclear cells (hPBMCs), anti-hOX40 hIgG1 also showed the potential for T-cell stimulation and Treg depletion.Conclusions These findings underline the importance of understanding the role of isotype in the mechanism of action of therapeutic mAbs. As an hIgG1, the anti-hOX40 mAb can elicit multiple mechanisms of action that could aid or hinder therapeutic outcomes, dependent on the microenvironment. This should be considered when designing potential combinatorial partners and their FcγR requirements to achieve maximal benefit and improvement of patient outcomes.

The Earth Cloud Aerosol and Radiation Explorer (EarthCARE) is a satellite mission implemented by the European Space Agency (ESA) in cooperation with the Japan Aerospace Exploration Agency (JAXA) to measure vertical profiles of aerosols, clouds, and precipitation properties together with radiative fluxes and derived heating rates. The data will be used in particular to evaluate the representation of clouds, aerosols, precipitation, and associated radiative fluxes in weather forecasting and climate models. The satellite embarks four instruments: the ATmospheric LIDar (ATLID), the Cloud Profiling Radar (CPR), the Multi-Spectral Imager (MSI), and the Broadband Radiometer (BBR). The science data acquired by the four satellite instruments are processed on ground. Calibrated instrument data – level 1 data products – and retrieved geophysical data products – level 2 data products – are produced in the ESA and JAXA ground segments. This paper provides an overview of the data processing chains of ESA and JAXA and explains the instrument level 1 data products and main aspects of the calibration algorithms. Furthermore, an overview of the level 2 data products, with references to the respective dedicated papers, is provided.

Abstract Patients with corticosteroid-refractory acute graft-versus-host disease (aGVHD) have a low one-year survival rate. Identification and validation of novel targetable kinases in patients who experience corticosteroid-refractory-aGVHD may help improve outcomes. Kinase-specific proteomics of leukocytes from patients with corticosteroid-refractory-GVHD identified rho kinase type 1 (ROCK1) as the most significantly upregulated kinase. ROCK1/2 inhibition improved survival and histological GVHD severity in mice and was synergistic with JAK1/2 inhibition, without compromising graft-versus-leukemia-effects. ROCK1/2-inhibition in macrophages or dendritic cells prior to transfer reduced GVHD severity. Mechanistically, ROCK1/2 inhibition or ROCK1 knockdown interfered with CD80, CD86, MHC-II expression and IL-6, IL-1β, iNOS and TNF production in myeloid cells. This was accompanied by impaired T cell activation by dendritic cells and inhibition of cytoskeletal rearrangements, thereby reducing macrophage and DC migration. NF-κB signaling was reduced in myeloid cells following ROCK1/2 inhibition. In conclusion, ROCK1/2 inhibition interferes with immune activation at multiple levels and reduces acute GVHD while maintaining GVL-effects, including in corticosteroid-refractory settings.