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Understanding how carnivores impact ecological communities is essential for guiding effective management actions and conserving biodiversity. Quantifying predators' diets, including prey selectivity, allows for the assessment of the relative effects native and invasive predators may have on prey populations. In Australia, populations of a native, terrestrial apex predator, the dingo Canis dingo/C. familiaris , and introduced and invasive subordinate mesopredators, the European red fox Vulpes vulpes and feral cat Felis catus , co‐occur, but there is limited understanding of their relative impacts on native and invasive prey in different ecosystems. To assess the possible effects of dingoes, foxes and cats on prey, we examined their diet and prey selectivity across a ~10,000 km 2 semi‐arid mallee ecosystem. Using macroscopic scat analysis, we identified strong dietary niche separation. Larger‐bodied dingoes primarily consumed large marsupial herbivores, whereas foxes and cats primarily consumed smaller prey, including introduced and native rodents and birds. Foxes had the broadest diet, and the greatest dietary overlap with cats ( = 0.81), compared with dingoes ( = 0.50) or between dingoes and cats ( = 0.36). Livestock were identified in 2% of dingo and 7% of fox scats. Cats and foxes consumed more than 15 times the volume of small native mammals compared with dingoes, including threatened species such as fat‐tailed dunnarts Sminthopsis crassicaudata . Cats and foxes also selectively consumed small mammals relative to their estimated availability and consumed fewer large mammals. In contrast, dingoes consumed fewer birds and more echidnas relative to their availability. Our results suggest limited intraguild competition within this semi‐arid ecosystem, as dingoes are primarily exerting top‐down pressure on large herbivores, whereas invasive mesopredators are disproportionately impacting smaller prey, including threatened native mammals. Practical implication . Our findings suggest that ongoing conservation management of dingoes, red foxes and feral cats must consider the variation in diets, impacts on prey and ecological roles of these different predator species, and avoid indiscriminate lethal control methods. Quantifying actual, rather than assumed, impacts of predators on threatened native species, large herbivores and livestock is essential to achieve effective and integrated ecosystem management.

Environmental contamination by pharmaceuticals is global, substantially altering crucial behaviours in animals and impacting on their reproduction and survival. A key question is whether the consequences of these pollutants extend beyond mean behavioural changes, restraining differences in behaviour between individuals. In a controlled, two-year, multigenerational experiment with independent mesocosm populations, we exposed guppies ( Poecilia reticulata ) to environmentally realistic levels of the ubiquitous pollutant fluoxetine (Prozac). Fish (unexposed: n = 59, low fluoxetine: n = 57, high fluoxetine: n = 58) were repeatedly assayed on four separate occasions for activity and risk-taking behaviour. Fluoxetine homogenized individuals' activity, with individual variation in populations exposed to even low concentrations falling to less than half that in unexposed populations. To understand the proximate mechanism underlying these changes, we tested the relative contribution of variation within and between individuals to the overall decline in individual variation. We found strong evidence that fluoxetine erodes variation in activity between but not within individuals, revealing the hidden consequences of a ubiquitous contaminant on phenotypic variation in fish—likely to impair adaptive potential to environmental change.

Biological invasions are a prominent example of human-induced environmental change that pose a significant threat to worldwide biodiversity. Recent evidence suggests that behavioural traits play a key role in mediating invasion success. However, little research has investigated how rapidly behavioural traits can change during the initial stages of invasion. We investigated the influence of invasion on behaviour in a recent aquatic invader, the Siamese fighting fish (Betta splendens), in northern Australia. These fish represent a recent introduction (ca. 2010) and are thought to be descended from ornamental varieties released into the wild from the aquarium trade. Using fish reared under captive conditions, we measured differences in three ecologically relevant behaviours (activity, foraging, and aggression) across invasive and domestic fighting fish. We found that fish descended from the recent invasive population were more active and consumed fewer food items than their domestic counterparts. Furthermore, foraging latency was repeatable in invasive, but not domestic fish, and this seemed to be driven by an increase in among-individual variation in the invasive population. Finally, while we detected a positive relationship between activity and number of food items eaten in domestic fish, this relationship was absent in the invasive population, suggesting that invasion may have disrupted this behavioural syndrome. Our results highlight that invasion can alter ecologically important behavioural traits and behavioural syndromes, even during the initial stages of invasion, and emphasise the importance of incorporating behaviour into our understanding of invasion biology.

Environmental contamination by pharmaceuticals is global, substantially altering crucial behaviours in animals and impacting on their reproduction and survival. A key question is whether the consequences of these pollutants extend beyond mean behavioural changes, restraining differences in behaviour between individuals. In a controlled, two-year, multigenerational experiment with independent mesocosm populations, we exposed guppies (Poecilia reticulata) to environmentally realistic levels of the ubiquitous pollutant fluoxetine (Prozac). Fish (unexposed: n = 59, low fluoxetine: n = 57, high fluoxetine: n = 58) were repeatedly assayed on four separate occasions for activity and risk-taking behaviour. Fluoxetine homogenized individuals’ activity, with individual variation in populations exposed to even low concentrations falling to less than half that in unexposed populations. To understand the proximate mechanism underlying these changes, we tested the relative contribution of variation within and between individuals to the overall decline in individual variation.We found strong evidence that fluoxetine erodes variation in activity between but not within individuals, revealing the hidden consequences of a ubiquitous contaminant on phenotypic variation in fish—likely to impair adaptive potential to environmental change.

Cancer cells characteristically consume glucose through Warburg metabolism 1 , a process that forms the basis of tumour imaging by positron emission tomography (PET). Tumour-infiltrating immune cells also rely on glucose, and impaired immune cell metabolism in the tumour microenvironment (TME) contributes to immune evasion by tumour cells 2 – 4 . However, whether the metabolism of immune cells is dysregulated in the TME by cell-intrinsic programs or by competition with cancer cells for limited nutrients remains unclear. Here we used PET tracers to measure the access to and uptake of glucose and glutamine by specific cell subsets in the TME. Notably, myeloid cells had the greatest capacity to take up intratumoral glucose, followed by T cells and cancer cells, across a range of cancer models. By contrast, cancer cells showed the highest uptake of glutamine. This distinct nutrient partitioning was programmed in a cell-intrinsic manner through mTORC1 signalling and the expression of genes related to the metabolism of glucose and glutamine. Inhibiting glutamine uptake enhanced glucose uptake across tumour-resident cell types, showing that glutamine metabolism suppresses glucose uptake without glucose being a limiting factor in the TME. Thus, cell-intrinsic programs drive the preferential acquisition of glucose and glutamine by immune and cancer cells, respectively. Cell-selective partitioning of these nutrients could be exploited to develop therapies and imaging strategies to enhance or monitor the metabolic programs and activities of specific cell populations in the TME. Positron emission tomography measurements of nutrient uptake in cells of the tumour microenvironment reveal cell-intrinsic partitioning in which glucose uptake is higher in myeloid cells, whereas glutamine is preferentially acquired by cancer cells.

Immune-mediated anti-tumoral responses, elicited by oncolytic viruses and augmented with checkpoint inhibition, may be an effective treatment approach for glioblastoma. Here in this multicenter phase 1/2 study we evaluated the combination of intratumoral delivery of oncolytic virus DNX-2401 followed by intravenous anti-PD-1 antibody pembrolizumab in recurrent glioblastoma, first in a dose-escalation and then in a dose-expansion phase, in 49 patients. The primary endpoints were overall safety and objective response rate. The primary safety endpoint was met, whereas the primary efficacy endpoint was not met. There were no dose-limiting toxicities, and full dose combined treatment was well tolerated. The objective response rate was 10.4% (90% confidence interval (CI) 4.2–20.7%), which was not statistically greater than the prespecified control rate of 5%. The secondary endpoint of overall survival at 12 months was 52.7% (95% CI 40.1–69.2%), which was statistically greater than the prespecified control rate of 20%. Median overall survival was 12.5 months (10.7–13.5 months). Objective responses led to longer survival (hazard ratio 0.20, 95% CI 0.05–0.87). A total of 56.2% (95% CI 41.1–70.5%) of patients had a clinical benefit defined as stable disease or better. Three patients completed treatment with durable responses and remain alive at 45, 48 and 60 months. Exploratory mutational, gene-expression and immunophenotypic analyses revealed that the balance between immune cell infiltration and expression of checkpoint inhibitors may potentially inform on response to treatment and mechanisms of resistance. Overall, the combination of intratumoral DNX-2401 followed by pembrolizumab was safe with notable survival benefit in select patients (ClinicalTrials.gov registration: NCT02798406). A safety and efficacy trial of a single intratumoral dose of the oncolytic adenovirus DNX-2401 followed by intravenous anti-PD-1 pembrolizumab in patients with recurrent glioblastoma shows an encouraging clinical benefit rate and 12 months overall survival.

Mindfulness meditation may improve well-being at work; however, effects on food cravings and metabolic health are not well known. We tested effects of digital meditation, alone or in combination with a healthy eating program, on perceived stress, cravings, and adiposity. We randomized 161 participants with overweight and moderate stress to digital meditation (‘MED,’ n = 38), digital meditation + healthy eating (‘MED+HE,’ n = 40), active control (‘HE,’ n = 41), or waitlist control (‘WL,’ n = 42) for 8 weeks. Participants ( n = 145; M(SD) BMI: 30.8 (5.4) kg/m 2 ) completed baseline and 8-week measures of stress (Perceived Stress Scale), cravings (Food Acceptance and Awareness Questionnaire) and adiposity (sagittal diameter and BMI). ANCOVAs revealed that those randomized to MED or MED+HE (vs. HE or WL) showed decreases in perceived stress ( F = 15.19, p < .001, η 2 = .10) and sagittal diameter ( F = 4.59, p = .03, η 2 = .04), with no differences in cravings or BMI. Those high in binge eating who received MED or MED+HE showed decreases in sagittal diameter ( p = .03). Those with greater adherence to MED or MED+HE had greater reductions in stress, cravings, and adiposity ( ps < .05). A brief digital mindfulness-based program is a low-cost method for reducing perceptions of stress and improving abdominal fat distribution patterns among adults with overweight and moderate stress. Future work should seek to clarify mechanisms by which such interventions contribute to improvements in health. Trial registration: Clinical trial registration http://www.ClinicalTrials.gov : identifier NCT03945214 .

Insulin resistance predisposes to cardiometabolic disorders, which are commonly comorbid with schizophrenia and are key contributors to the significant excess mortality in schizophrenia. Mechanisms for the comorbidity remain unclear, but observational studies have implicated inflammation in both schizophrenia and cardiometabolic disorders separately. We aimed to examine whether there is genetic evidence that insulin resistance and 7 related cardiometabolic traits may be causally associated with schizophrenia, and whether evidence supports inflammation as a common mechanism for cardiometabolic disorders and schizophrenia. We used summary data from genome-wide association studies of mostly European adults from large consortia (Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) featuring up to 108,557 participants; Diabetes Genetics Replication And Meta-analysis (DIAGRAM) featuring up to 435,387 participants; Global Lipids Genetics Consortium (GLGC) featuring up to 173,082 participants; Genetic Investigation of Anthropometric Traits (GIANT) featuring up to 339,224 participants; Psychiatric Genomics Consortium (PGC) featuring up to 105,318 participants; and Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium featuring up to 204,402 participants). We conducted two-sample uni- and multivariable mendelian randomization (MR) analysis to test whether (i) 10 cardiometabolic traits (fasting insulin, high-density lipoprotein and triglycerides representing an insulin resistance phenotype, and 7 related cardiometabolic traits: low-density lipoprotein, fasting plasma glucose, glycated haemoglobin, leptin, body mass index, glucose tolerance, and type 2 diabetes) could be causally associated with schizophrenia; and (ii) inflammation could be a shared mechanism for these phenotypes. We conducted a detailed set of sensitivity analyses to test the assumptions for a valid MR analysis. We did not find statistically significant evidence in support of a causal relationship between cardiometabolic traits and schizophrenia, or vice versa. However, we report that a genetically predicted inflammation-related insulin resistance phenotype (raised fasting insulin (raised fasting insulin (Wald ratio OR = 2.95, 95% C.I, 1.38-6.34, Holm-Bonferroni corrected p-value (p) = 0.035) and lower high-density lipoprotein (Wald ratio OR = 0.55, 95% C.I., 0.36-0.84; p = 0.035)) was associated with schizophrenia. Evidence for these associations attenuated to the null in multivariable MR analyses after adjusting for C-reactive protein, an archetypal inflammatory marker: (fasting insulin Wald ratio OR = 1.02, 95% C.I, 0.37-2.78, p = 0.975), high-density lipoprotein (Wald ratio OR = 1.00, 95% C.I., 0.85-1.16; p = 0.849), suggesting that the associations could be fully explained by inflammation. One potential limitation of the study is that the full range of gene products from the genetic variants we used as proxies for the exposures is unknown, and so we are unable to comment on potential biological mechanisms of association other than inflammation, which may also be relevant. Our findings support a role for inflammation as a common cause for insulin resistance and schizophrenia, which may at least partly explain why the traits commonly co-occur in clinical practice. Inflammation and immune pathways may represent novel therapeutic targets for the prevention or treatment of schizophrenia and comorbid insulin resistance. Future work is needed to understand how inflammation may contribute to the risk of schizophrenia and insulin resistance.

Study of SARS-CoV-2 Dynamics in the NBAA SARS-CoV-2 surveillance program conducted by the National Basketball Association identified 173 newly infected persons. The viral kinetics were systematically studied and are described.

Arginine-rich cell-penetrating peptides do not enter cells by directly passing through a lipid membrane; they instead passively enter vesicles and live cells by inducing membrane multilamellarity and fusion. The molecular picture of this penetration mode, which differs qualitatively from the previously proposed direct mechanism, is provided by molecular dynamics simulations. The kinetics of vesicle agglomeration and fusion by an iconic cellpenetrating peptide—nonaarginine—are documented via real-time fluorescence techniques, while the induction of multilamellar phases in vesicles and live cells is demonstrated by a combination of electron and fluorescence microscopies. This concert of experiments and simulations reveals that the identified passive cell penetration mechanism bears analogy to vesicle fusion induced by calcium ions, indicating that the two processes may share a common mechanistic origin.