ALBERT

Description: Intratumour heterogeneity is increasingly recognized as a frequent problem for cancer treatment as it allows for the evolution of resistance against treatment. While cancer genotyping becomes more and more established and allows to determine the genetic heterogeneity, less is known about the phenotypic heterogeneity among cancer cells. We investigate how phenotypic differences can impact the efficiency of therapy options that select on this diversity, compared to therapy options that are independent of the phenotype. We employ the ecological concept of trait distributions and characterize the cancer cell population as a collection of subpopulations that differ in their growth rate. We show in a deterministic model that growth rate-dependent treatment types alter the trait distribution of the cell population, resulting in a delayed relapse compared to a growth rate-independent treatment. Whether the cancer cell population goes extinct or relapse occurs is determined by stochastic dynamics, which we investigate using a stochastic model. Again, we find that relapse is delayed for the growth rate-dependent treatment type, albeit an increased relapse probability, suggesting that slowly growing subpopulations are shielded from extinction. Sequential application of growth rate-dependent and growth rate-independent treatment types can largely increase treatment efficiency and delay relapse. Interestingly, even longer intervals between decisions to change the treatment type may achieve close-to-optimal efficiencies and relapse times. Monitoring patients at regular check-ups may thus provide the temporally resolved guidance to tailor treatments to the changing cancer cell trait distribution and allow clinicians to cope with this dynamic heterogeneity.

Description: Predicting the implications of ongoing ocean climate warming demands a better understanding of how short-term thermal variability impacts marine ectotherms, particularly at beyond-optimal average conditions during summer heatwaves. Using a globally important model species, the blue mussel Mytilus, in a 5-week-long experiment, we (a) assessed growth performance traits under 12 scenarios, consisting of four thermal averages (18.5, 21, 23.5 and 26℃) imposed as constant or daily fluctuating regimes with amplitudes of 2 or 4℃. Additionally, we conducted a short-term assay using different mussel individuals to (b) test for the species capacity for suppression and recovery of metabolic performance traits (feeding and aerobic respiration) when exposed to a 1-day thermal fluctuation regime (16.8–30.5℃). Using this high-resolution data, we (c) generated short-term thermal metabolic performance curves to predict and explain growth responses observed in the long-term experiment. We found that daily high-amplitude thermal cycles (4℃) improved mussel growth when fluctuations were imposed around an extreme average temperature of 26℃, representing end-of-century heatwaves. In contrast, thermal cycles negatively affected mussel growth at a less extreme average temperature of 23.5℃, resembling current peak summer temperature scenarios. These results suggest that fluctuations ameliorate heat stress impacts only at critically high average temperatures. The short-term assay demonstrated that during the warming phase, animals stopped feeding between 24 and 30℃ while gradually suppressing respiration. In the subsequent cooling phase, feeding and respiration partially and fully recovered to pre-heating rates respectively. Furthermore, nonlinear averaging of short-term feeding responses (upscaling) well-predicted longer term growth responses to fluctuations. Our findings suggest that fluctuations can be beneficial to or detrimental for the long-term performance of ectothermic animals, depending on the fluctuations' average and amplitude. Furthermore, the observed effects can be linked to fluctuation-mediated metabolic suppression and recovery. In a general framework, we propose various hypothetical scenarios of fluctuation impacts on ectotherm performance considering inter- or intra-species variability in heat sensitivity. Our research highlights the need for studying metabolic performance in relation to cyclic abiotic fluctuations to advance the understanding of climate change impacts on aquatic systems. A free Plain Language Summary can be found within the Supporting Information of this article

Description: Climate change imposes unusual long‐term trends in environmental conditions, plus some tremendous shifts in short‐term environmental variability, exerting additional stress on marine ecosystems. This paper describes an empirical method that aims to improve our understanding of the performance of benthic filter feeders experiencing changes in environmental conditions, such as temperature, on time scales of minutes to hours, especially during daily cycles or extreme events such as marine heatwaves or hypoxic upwelling. We describe the Fluorometer and Oximeter equipped Flow‐through Setup (FOFS), experimental design, and methodological protocols to evaluate the flood of data, enabling researchers to monitor important energy budget traits, including filtration and respiration of benthic filter‐feeders in response to fine‐tuned environmental variability. FOFS allows online recording of deviations in chlorophyll and dissolved oxygen concentrations induced by the study organism. Transparent data processing through Python scripts provides the possibility to adjust procedures to needs when working in different environmental contexts (e.g., temperature vs. pH, salinity, oxygen, biological cues) and with different filter‐feeding species. We successfully demonstrate the functionality of the method through recording responses of Baltic Sea blue mussels (Mytilus) during one‐day thermal cycles. This method practically provides a tool to help researchers exposing organisms to environmental variability for some weeks or months, to relate the observed long‐term performance responses to short‐term energy budget responses, and to explain their findings with the potential to generalize patterns. The method, therefore, allows a more detailed description of stress‐response relationships and the detection of species' tolerance limits.

Description: 1. Predicting the implications of ongoing ocean climate warming demands a better understanding of how short-term thermal variability impacts marine ectotherms, particularly at beyond-optimal average conditions during summer heatwaves. 2. Using a globally important model species, the blue mussel Mytilus, in a 5-week-long experiment, we (a) assessed growth performance traits under 12 scenarios, consisting of four thermal averages (18.5, 21, 23.5 and 26℃) imposed as constant or daily fluctuating regimes with amplitudes of 2 or 4℃. Additionally, we conducted a short-term assay using different mussel individuals to (b) test for the species capacity for suppression and recovery of metabolic performance traits (feeding and aerobic respiration) when exposed to a 1-day thermal fluctuation regime (16.8–30.5℃). Using this high-resolution data, we (c) generated short-term thermal metabolic performance curves to predict and explain growth responses observed in the long-term experiment. 3. We found that daily high-amplitude thermal cycles (4℃) improved mussel growth when fluctuations were imposed around an extreme average temperature of 26℃, representing end-of-century heatwaves. In contrast, thermal cycles negatively affected mussel growth at a less extreme average temperature of 23.5℃, resembling current peak summer temperature scenarios. These results suggest that fluctuations ameliorate heat stress impacts only at critically high average temperatures. The short-term assay demonstrated that during the warming phase, animals stopped feeding between 24 and 30℃ while gradually suppressing respiration. In the subsequent cooling phase, feeding and respiration partially and fully recovered to pre-heating rates respectively. Furthermore, nonlinear averaging of short-term feeding responses (upscaling) well-predicted longer term growth responses to fluctuations. 4. Our findings suggest that fluctuations can be beneficial to or detrimental for the long-term performance of ectothermic animals, depending on the fluctuations' average and amplitude. Furthermore, the observed effects can be linked to fluctuation-mediated metabolic suppression and recovery. In a general framework, we propose various hypothetical scenarios of fluctuation impacts on ectotherm performance considering inter- or intra-species variability in heat sensitivity. Our research highlights the need for studying metabolic performance in relation to cyclic abiotic fluctuations to advance the understanding of climate change impacts on aquatic systems.

Description: The relevance of considering environmental variability for understanding and predicting biological responses to environmental changes has resulted in a recent surge in variability-focused ecological research. However, integration of findings that emerge across studies and identification of remaining knowledge gaps in aquatic ecosystems remain critical. Here, we address these aspects by: (1) summarizing relevant terms of variability research including the components (characteristics) of variability and key interactions when considering multiple environmental factors; (2) identifying conceptual frameworks for understanding the consequences of environmental variability in single and multifactorial scenarios; (3) highlighting challenges for bridging theoretical and experimental studies involving transitioning from simple to more complex scenarios; (4) proposing improved approaches to overcome current mismatches between theoretical predictions and experimental observations; and (5) providing a guide for designing integrated experiments across multiple scales, degrees of control, and complexity in light of their specific strengths and limitations.

Description: Data sets are outputs of two experiments (each experiment includes two or more temporally replicated trials - named by date) that were conducted using a newly developed Fluorometer and Oximeter equipped Flow-through Setup (FOFS). The corresponding method paper is titled 'Simultaneous recording of filtration and respiration in marine organisms in response to short-term environmental variability'. The paper is under review by Limnology and Oceanography: Methods. The main directory of experimental data (e.g., FOFS_test/blank_trials) contain subdirectories termed raw_data_temperature (including °C-temperature .xlsx files), raw_data_Chl, and raw_data_Oxygen, the two latter contains folders named after the starting dates of the trials (e.g., 04_nov). Each of these folders has three subfolders named after the three stages of the trial (i.e., pre, main, and post). Each subfolder includes data sheets of mV-Chl (.CSV) or %air-saturation (.xlxs, which are outputs of the DO calulator.py) that were collected in the corresponding stage and trial. The data can be processed through the Python scripts accompanying the method paper, providing time-series of filtration, respiration, and scope for growth along daily thermal cycles for the studied blue mussel Mytilus spp. specimens (see the paper for details).