PPM1D modulates hematopoietic cell fitness and response to DNA damage and is a therapeutic target in myeloid malignancy.

PPM1D encodes a phosphatase that is recurrently activated across cancer, most notably in therapy-related myeloid neoplasms. However, the function of PPM1D in hematopoiesis and its contribution to tumor cell growth remain incompletely understood. Using conditional mouse models, we uncover a central role for Ppm1d in hematopoiesis and validate its potential as a therapeutic target. We find that Ppm1d regulates the competitive fitness and self-renewal of hematopoietic stem cells (HSCs) with and without exogenous genotoxic stresses. We also show that although Ppm1d activation confers cellular resistance to cytotoxic therapy, it does so to a lesser degree than p53 loss, informing the clonal competition phenotypes often observed in human studies. Notably, loss of Ppm1d sensitizes leukemias to cytotoxic therapies in vitro and in vivo, even in the absence of a Ppm1d mutation. Vulnerability to PPM1D inhibition is observed across many cancer types and dependent on p53 activity. Importantly, organism-wide loss of Ppm1d in adult mice is well tolerated, supporting the tolerability of pharmacologically targeting PPM1D. Our data link PPM1D gain-of-function mutations to the clonal expansion of HSCs, inform human genetic observations, and support the therapeutic targeting of PPM1D in cancer.

Life cycle complexity and body mass drive erratic changes in climate vulnerability across ontogeny in a seasonally migrating butterfly.

Physiological traits are often used for vulnerability assessments of organismal responses to climate change. Trait values can change dramatically over the life cycle of organisms but are typically assessed at a single developmental stage. Reconciling ontogenetic changes in physiological traits with vulnerability assessments often reveals early life-stage vulnerabilities. The degree to which ontogenetic changes in physiological traits are due to changes in body mass over development versus stage-specific responses determines the degree to which mass can be used as a proxy for vulnerability. Here, we use the painted lady butterfly, Vanessa cardui, to test ontogenetic changes in two physiological traits, the acute thermal sensitivity of routine metabolic rate (RMR Q10) and the critical thermal maximum (CTmax). RMR Q10 generally followed ontogenetic changes in body mass, with stages characterized by smaller body mass exhibiting lower acute thermal sensitivity. However, CTmax was largely decoupled from ontogenetic changes in body mass. In contrast with trends from other studies showing increasing vulnerability among progressively earlier developmental stages, our study revealed highly erratic patterns of vulnerability across ontogeny. Specifically, we found the lowest joint-trait vulnerability (both RMR Q10 and CTmax) in the earliest developmental stage we tested (3rd instar larvae), the highest vulnerabilities in the next two developmental stages (4th and 5th instar larvae), and reduced vulnerability into the pupal and adult stages. Our study supports growing evidence of mechanistic decoupling of physiology across developmental stages and suggests that body mass is not a universal proxy for all physiological trait indicators of climate vulnerability.

The final frontier: ecological and evolutionary dynamics of a global parasite invasion.

Studying rapid biological changes accompanying the introduction of alien organisms into native ecosystems can provide insights into fundamental ecological and evolutionary theory. While powerful, this quasi-experimental approach is difficult to implement because the timing of invasions and their consequences are hard to predict, meaning that baseline pre-invasion data are often missing. Exceptionally, the eventual arrival of Varroa destructor (hereafter Varroa) in Australia has been predicted for decades. Varroa is a major driver of honeybee declines worldwide, particularly as vectors of diverse RNA viruses. The detection of Varroa in 2022 at over a hundred sites poses a risk of further spread across the continent. At the same time, careful study of Varroa's spread, if it does become established, can provide a wealth of information that can fill knowledge gaps about its effects worldwide. This includes how Varroa affects honeybee populations and pollination. Even more generally, Varroa invasion can serve as a model for evolution, virology and ecological interactions between the parasite, the host and other organisms.

Vulnerability to climate change increases with trophic level in terrestrial organisms.

The resilience of ecosystem function under global climate change is governed by individual species vulnerabilities and the functional groups they contribute to (e.g. decomposition, primary production, pollination, primary, secondary and tertiary consumption). Yet it remains unclear whether species that contribute to different functional groups, which underpin ecosystem function, differ in their vulnerability to climate change. We used existing upper thermal limit data across a range of terrestrial species (N = 1701) to calculate species warming margins (degrees distance between a species upper thermal limit and the maximum environmental temperature they inhabit), as a metric of climate change vulnerability. We examined whether species that comprise different functional groups exhibit differential vulnerability to climate change, and if vulnerability trends change across geographic space while considering evolutionary history. Primary producers had the broadest warming margins across the globe (µ = 18.72 °C) and tertiary consumers had the narrowest warming margins (µ = 9.64 °C), where vulnerability tended to increase with trophic level. Warming margins had a nonlinear relationship (second-degree polynomial) with absolute latitude, where warming margins were narrowest at about 33°, and were broader at lower and higher absolute latitudes. Evolutionary history explained significant variation in species warming margins, as did the methodology used to estimate species upper thermal limits. We investigated if variation in body mass across the trophic levels could explain why higher trophic level organisms had narrower warming margins than lower trophic level organisms, however, we did not find support for this hypothesis. This study provides a critical first step in linking individual species vulnerabilities with whole ecosystem responses to climate change.

Climate change and invasive species: a physiological performance comparison of invasive and endemic bees in Fiji.

Anthropogenic climate change and invasive species are two of the greatest threats to biodiversity, affecting the survival, fitness and distribution of many species around the globe. Invasive species are often expected to have broad thermal tolerance, be highly plastic, or have high adaptive potential when faced with novel environments. Tropical island ectotherms are expected to be vulnerable to climate change as they often have narrow thermal tolerance and limited plasticity. In Fiji, only one species of endemic bee, Homalictus fijiensis, is commonly found in the lowland regions, but two invasive bee species, Braunsapis puangensis and Ceratina dentipes, have recently been introduced into Fiji. These introduced species pollinate invasive plants and might compete with H. fijiensis and other native pollinators for resources. To test whether certain performance traits promote invasiveness of some species, and to determine which species are the most vulnerable to climate change, we compared the thermal tolerance, desiccation resistance, metabolic rate and seasonal performance adjustments of endemic and invasive bees in Fiji. The two invasive species tended to be more resistant to thermal and desiccation stress than H. fijiensis, while H. fijiensis had greater capacity to adjust their CTmax with season, and H. fijiensis females tended to have higher metabolic rates than B. puangensis females. These findings provide mixed support for current hypotheses for the functional basis of the success of invasive species; however, we expect the invasive bees in Fiji to be more resilient to climate change because of their increased thermal tolerance and desiccation resistance.

Intertidal gobies acclimate rate of luminance change for background matching with shifts in seasonal temperature.

Rate of colour change and background matching capacity are important functional traits for avoiding predation and hiding from prey. Acute changes in environmental temperature are known to impact the rate at which animals change colour, and therefore may affect their survival. Many ectotherms have the ability to acclimate performance traits such as locomotion, metabolic rate and growth rate with changes in seasonal temperature. However, it remains unclear how other functional traits that are directly linked to behaviour and survival respond to long-term changes in temperature (within an individual's lifetime). We assessed whether the rate of colour change is altered by long-term changes in temperature (seasonal variation) and if rate of colour change can acclimate to seasonal thermal conditions. We used an intertidal rock-pool goby Bathygobius cocosensis, to test this and exposed individuals to representative seasonal mean temperatures (16 or 31°C, herein referred to cold- and warm-exposed fish respectively) for 9 weeks and then tested their rate of luminance change when placed on white and black backgrounds at acute test temperatures 16 and 31°C. We modelled rate of luminance change using the visual sensitives of a coral trout Plectropmus leopardus to determine how well gobies matched their backgrounds in terms of luminance contrast to a potential predator. After exposure to long-term seasonal conditions, the warm-exposed fish had faster rates of luminance change and matched their background more closely when tested at 31 than at 16°C. Similarly, the cold-exposed fish had faster rates of luminance change and matched their backgrounds more closely at 16°C than at 31°C. This demonstrates that rate of luminance change can be adjusted to compensate for long-term changes in seasonal temperature. This is the first study to show that animals can acclimate rate of colour change for background matching to seasonal thermal conditions. We also show that rapid changes in acute temperature reduce background matching capabilities. Stochastic changes in climate are likely to affect the frequency of predator-prey interactions which may have substantial knock-on effects throughout ecosystems.

Oxygen Limitation Does Not Drive the Decreasing Heat Tolerance of Grasshoppers during Development.

Thermal physiology changes as organisms grow and develop, but we do not understand what causes these ontogenetic shifts. According to the theory of oxygen- and capacity-limited thermal tolerance, an organism's heat tolerance should change throughout ontogeny as its ability to deliver oxygen varies. As insects grow during an instar, their metabolic demand increases without a proportional increase in the size of tracheae that supply oxygen to the tissues. If oxygen delivery limits heat tolerance, the mismatch between supply and demand should make insects more susceptible to heat and hypoxia as they progress through an instar. We tested this hypothesis by measuring the heat tolerance of grasshoppers (Schistocerca americana) on the second and seventh days of the sixth instar, in either a normoxic or a hypoxic atmosphere (21% or 10% O2, respectively). As expected, heat tolerance decreased as grasshoppers grew larger. Yet contrary to expectation, hypoxia had no effect on heat tolerance across all stages and sizes. Although heat tolerance declines as grasshoppers grow, this pattern must stem from a mechanism other than oxygen limitation.

An intertidal fish shows thermal acclimation despite living in a rapidly fluctuating environment.

The co-evolution of acclimation capacity and thermal performance breadth has been a contentious issue for decades, and little is known regarding the extent to which acclimation alters the shape of acute thermal performance curves. Current acclimation theory suggests that when daily variation is large and unpredictable ectotherms should not acclimate but should evolve wide performance breadths, allowing maintenance of performance across a wide thermal range. The subtropical intertidal zone, however, experiences a large amount of daily thermal variation, but daily means and ranges shift in predictable ways with season, where daily and seasonal variation is roughly equal. We predicted that animals in this habitat would maintain their capacity to acclimate and that performance breadth would not be altered by acclimation to maintain function with rapidly fluctuating daily temperatures. We tested our prediction using a subtropical goby, Bathygobius cocosensis, which lives in tide pools that vary widely, over days and seasons. We exposed B. cocosensis to winter (12-17 °C) and summer (30-35 °C) thermal conditions for six weeks and then measured the thermal dependence of burst swimming speed, routine and maximum metabolic rate, and ventilation rate between 12 and 36 °C. B. cocosensis exhibited an acclimation response for burst swimming speed, maximum metabolic rate and metabolic scope, but acclimation did not alter the shape of acute thermal performance curves. These results indicate that thermal acclimation can occur when short-term thermal variability is large and equal to seasonal variation, and wide performance breadths can be maintained with acclimation in heterogeneous environments.

[Integrating teaching nursing work and citizenship]. / Integração ensino-trabalho-cidadania na formação de enfermeiros.

This study aims to identify the conflicts found daily throughout the development of the specialization course Process of Change in Superior Education and Health Services. This descriptive qualitative study is a case study carried out at a private University Center in the State of Rio de Janeiro, Brazil. The subjects were 18 students from the specialization course, who spontaneously decided to participate in the study The data was collected in April 2009 and analyzed and described in five thematic units that describe the focus of conflicts in the world of the work: Integration among Education, Work and Citizenship; Team work; Permanent education, Social responsibility; Establishment of the care line. The intersection between the academic field and health services produces tensions and conflicts which are latent most of the time, but are never evident.