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The molecular mechanisms underlying drug resistance in relapsed or refractory (rr) acute myeloid leukemia (AML) remain to be explored. Here, the use of bulk and single cell multi-omics and ex vivo drug profiling for 21 rrAML patients reveals mechanisms of resistance to the Bcl-2 inhibitor venetoclax and treatment vulnerabilities.

Many island plant species share a syndrome of characteristic phenotype and life history. Cerca et al. find the genomic basis of the plant island syndrome in one of Darwin’s giant daisies, while separating ancestral genomes in a chromosome-resolved polyploid assembly.

Plasma turbulence is the main driver to deteriorate the performance of fusion power plants. This work presents an unprecedented comparison of plasma turbulence between experiment and simulation, proving that the gyrokinetic model GENE reached a high level of maturity to predict core turbulence.

Androgen response elements (AREs) regulation produce opposite effects in normal and cancer prostate cells. Here, authors engineer a modifier of ARE-containing chromatin (MACC) to define the elements responsible for a normal growth-suppressive program, which can be reengaged in prostate cancer cells.

An experimental economics approach finds that punishment increases the frequency of cooperation, but not the average payoff. Thus, the option of costly punishment does not confer an advantage to the group. Moreover, players who end up with the highest total payoff ('winners') do not use punishment, whereas players who end up with the lowest payoff ('losers') use punishment most frequently.

Lobinska et al. explore the evolutionary dynamics of COVID-19. Their results suggest that even with fast vaccination, social distancing (or contact reduction) must be maintained to minimize the risk of selecting for vaccine-resistant variants.

Tumours frequently metastasize to multiple anatomical sites and understanding how these different metastases evolve may be important for therapy. Here, the authors develop a method—Treeomics—that can construct phylogenies from multiple metastases from next-generation sequencing data.

Schmid et al. present a unified framework for direct and indirect reciprocity, exploring how people choose to cooperate on the basis of either their direct experience with others (direct reciprocity) or the others’ general reputation (indirect reciprocity).

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

Prosocial behaviours are ubiquitous in nature. These building blocks of cooperative societies can come in many forms, depending on how the underlying social good is produced and distributed. In this study, the authors show that heterogeneous populations can strongly promote the evolution of prosocial behaviours. However, this efficient evolution reveals a thorny side of prosocial behaviours: they generate the possibility of widespread wealth inequality, even to the point of being a detriment to the poorest in the population. The authors provide a general framework that can be used to understand when this harmful prosociality will emerge in a population. These findings suggest that institutional interventions are often essential for maintaining equitable outcomes in heterogeneous societies.

Master of games and equations.

Highly active antiretroviral therapy is crucial to controlling the progression of HIV infection. Therapy failure is often—but not always—attributed to resistance mutations in the HIV-1–encoded protein targets. Here Rosenbloom et al. use mathematical modeling to explain the distinct patterns of resistance found with different classes of antiretroviral drugs and predict specific single-pill combination therapies that might prevent resistance even in the setting of poor patient adherence.

Linking structural variants to gene expression information identifies aberrant signaling pathways.

Confining plasma and managing disruptions in tokamak devices is a challenge. Here the authors demonstrate a method predicting and possibly preventing disruptions and macroscopic instabilities in tokamak plasma using data from JET.

During language evolution, rules emerge and exceptions decline. A quantitative study measures the rate at which a human language becomes more regular over time. Specifically, the regularization of English verbs over the last 1200 years was studied, and it was found that half-life of a verb scales as the square root of its frequency, meaning that irregular verbs that are 100 times as rare regularize ten times faster.

This work on colorectal cancer shows that secondary mutations in KRAS that confer resistance to panitumumab, an anti-EGFR monoclonal antibody, are already present when antibody treatment begins; the apparent inevitability of resistance suggests that combinations of drugs targeting at least two different oncogenic pathway will be needed for treatment.

In many instances of reciprocity, individuals cooperate in turns. Here, the authors analyze the equilibria and the dynamics of such alternating games, and in particular describe all strategies with one-round memory that maintain cooperation.

Long-read single-cell RNA sequencing is capable of detecting isoform-level gene expression and genomic alterations such as mutations and gene fusions, thereby providing cell-specific genotype-phenotype information. Here, the authors use long-read scRNA-seq on metastatic ovarian cancer samples and detect cell-type specific isoforms and gene fusions that may otherwise be misclassified in short-read data.

Chromodomain Helicase DNA-binding (CHD) proteins have been implicated in neurodevelopmental processes. Here, the authors identify missense variants in CHD3 that disturb its chromatin remodeling activities and cause a neurodevelopmental disorder with macrocephaly and speech and language impairment.

The suppression of edge-localized modes in tokamak plasmas is crucial to prevent them from damaging the walls of the chamber. Now experiments confirm the role that magnetic islands play in suppressing these detrimental modes.

Genome wide association studies in cancer are used to understand the heritable genetic contribution to disease risk. Here, the authors perform a genome wide association study in European patients with acute myeloid leukemia and identify loci associated with risk of developing the disease.

Everybody knows that overconfidence can be foolhardy. But a study reveals that having an overly positive self-image might confer an evolutionary advantage if the rewards outweigh the risks. See Letter p.317

The spatial structure of a population is often critical for the evolution of cooperation. Here, Allen and colleagues show that when spatial structure is represented by an isothermal graph, the effective number of neighbors per individual determines whether or not cooperation can evolve.

It has been postulated that there is a threshold temperature above which permafrost will reach a global tipping point, causing accelerated thaw and global collapse. Here it is argued that permafrost-thaw feedbacks are dominated by local- to regional-scale processes, but this also means there is no safety margin.

Comparison of multiple lesions from individual pancreases sheds light on how ancestral clones can spread through the ductal system and give rise to precursor lesions, with acquisition of further mutations leading to pancreatic cancer.

Models of the origin of life generally require a mechanism to structure emerging populations. Here, Krieger et al. develop spatial models showing that coherent structures arising in turbulent flows in aquatic environments could have provided compartments that facilitated the origin of life.

Analysis of growth dynamics in a dataset from 107 patients with chronic lymphocytic leukaemia (CLL) reveals both exponential and logistic patterns of growth, which are associated with differences in genetic attributes and clinical outcomes.

Most evolutionary game theory focuses on isolated games. Here, Donahue et al. present a general framework for ‘multichannel games’ in which individuals engage in a set of parallel games with a partner, and show that such parallel interactions favor the evolution of reciprocity across games.

It is generally assumed that a person’s cooperative behaviour is consistent, but direct evidence is lacking. Here, the authors show consistent patterns of an individual’s behaviour both in different cooperation games and through time, suggesting that an individual's cooperative behaviour is general and stable.

Cancer patients often respond well to primary treatment but then develop resistance. Here, Misale et al. show that dual treatment with EGFR and MEK inhibitors block resistance in mice containing patient-derived xenografts and provide a mathematical model that describes the temporal development of resistant tumour clones.

Quantum electrodynamics predicts a rare process in which light is scattered by light. The ATLAS Collaboration reports signs of this elusive effect in the collisions of ultra-relativistic lead ions.

Economic games are used to investigate the cognitive mechanisms underlying cooperative behaviour, and show that intuition supports cooperation in social dilemmas, whereas reflection can undermine these cooperative impulses.

An intergenerational cooperation game has been developed to study decision-making regarding resource use: when decisions about resource extraction were made individually the resource was rapidly depleted by a minority of defectors; the resource was sustainably maintained across generations, however, when decisions were made democratically by voting.

In human societies, altruistic behaviour can evolve because those who fail to co-operate are lumbered with a bad reputation. This study explores the circumstances under which punishment is favoured using a game theory model in which all individuals observe the interactions between others and assess their reputation under various social norms. It is shown that punishment is only a successful strategy under a narrow set of parameters, including the relative costs of punishment and cooperation, the reliability of reputations and the spread of gossip.