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Oral poly(ADP)-ribose polymerase (PARP) inhibitors have been shown to have great promise in the treatment of cancer inBRCA mutation carriers. This case provides evidence that these agents are efficacious in patients with PTEN deficiency but no BRCAmutations, opening up a new patient cohort for this treatment.

The Hsp90 chaperone is responsible for the stabilization of a large variety of regulatory proteins. By labeling the subunits in the Hsp90 homodimer with different dyes and in different positions, the kinetics of Hsp90 conformational changes along the ATPase cycle was characterized, revealing different intermediate states and the different roles of cochaperones.

The allosteric binding of MSI-1436 to the intrinsically disordered C-terminal region of PTP1B promotes a conformational change to generate a compact inactive structure, validating the use of MSI-1436 to inhibit HER2-mediated tumorigenesis.

Mechanical forces play a crucial role during morphogenesis, but how these are sensed and transduced in vivo is not fully understood. Here the authors apply a FRET tension sensor to live zebrafish and study changes in VE-cadherin tension at endothelial cell-cell junctions during arterial maturation.

Excitation transfer between nitrogen–vacancy centres and graphene can be used to detect the spin of the electron in the nitrogen–vacancy centre through electrical measurements.

Brain tumours are difficult to treat because of their propensity to infiltrate brain tissue; here long processes, or tumour microtubes, extended by astrocytomas are shown to promote brain infiltration and to create an interconnected network that enables multicellular communication and that protects the tumours from radiotherapy-induced cell death, suggesting that disruption of the network could be a new therapeutic approach.

Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.

Coupling limited proteolysis and a proteomics workflow enables measurement of both subtle and wholesale protein conformational changes in a eukaryotic proteome.

Functionalisation of conjugated polymers is essential for performance in many applications, yet there are limited approaches to achieve this. Here the authors developed a method for the direct postpolymerisation modification of the aromatic backbone of conjugated polymers and used them to create multifunctional semiconducting nanoparticles.

This protocol describes a nondestructive FRET-based assay for measuring protein interactions in cultured cells. The correlation between FRET efficiencies and relative protein concentration can be used to determine relative binding affinities.

Brakemann et al. present a reversibly photoswitchable fluorescent protein, called Dreiklang, that can be turned on and off at wavelengths distinct from those used for imaging. They show that the protein is advantageous for studying protein dynamics in living cells and for super-resolution imaging.

A method for producing multiprotein complexes engineered with site–specifically introduced noncanonical amino acids is described, enabling applications in biochemical and biophysical analysis, as well as in biotechnology.

The relative importance of the mechanisms underlying species radiation remains unclear. Here, the authors combine reference genome assembly and population genetics analyses to show that neutral forces have contributed to the radiation of the most species-rich tree genus Syzygium.

Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.

The dependence of the afterglow in millisecond time scale and light yield (in the inset) on the Gd content in the Gd_xLu_1-xAlO₃ single crystal scintillator.

Microtubule-associated protein 6 (MAP6) is known to be important for synaptic plasticity and cognition, supposedly via interaction with microtubules. Here, the authors found that MAP6 is crucial for the stabilisation of enlarged synapses through its association with a different cytoskeletal element, actin.

Here the authors evaluate the burden of 144 health conditions in adult cancer survivors, and show that the magnitude of late morbidities experienced by survivors varies according to the type of cancer and treatment, highlighting opportunities for optimising patient care

xProphet, a tool using a target-decoy strategy, determines false discovery rate in mass-spectrometry data of chemically cross-linked peptides.

How is acetyl-CoA produced in the context of the endogenous, eukaryotic pyruvate dehydrogenase complex metabolon? Here the authors dissect the embedded transacetylase reaction through biochemical, cryo-EM, HADDOCKing and molecular dynamics methods.

The bright, photostable fluorescent protein StayGold is converted into a monomer.

Covalent inhibitors are a successful class of drugs, however, the optimization of targeted covalent inhibitors has challenges due to the need to increase non-covalent interactions and modulate reactivity. Here, the authors study the structure-reactivity-activity relationships of analogues of the EGFR inhibitor poziotinib, showing practical methods to characterize structure-activity relationships, providing insights into the origins of potency and highlighting the effect of chirality on covalent binding.

Giaume et al. describe the function of a rice florigen-like protein expressed at the shoot apical meristem, required to promote phase transition and shape panicle architecture.

While many treatments for prostate cancer suppress the androgen receptor it becomes reactivated during disease progression. Here, the authors show that a KLF5 transcriptional programme is also activated during treatment and promotes migration and the appearance of a basal cell phenotype.

Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.

Results of the TRACERx study shed new light into the association between body composition and body weight with survival in individuals with non-small cell lung cancer, and delineate potential biological processes and mediators contributing to the development of cancer-associated cachexia.

Current outcomes are reported from the ongoing National Lung Matrix Trial, an umbrella trial for the treatment of non-small-cell lung cancer in which patients are triaged according to their tumour genotype and matched with targeted therapeutic agents.

The adipokine leptin modulates intestinal inflammation in mice. Here the authors describe a patient with inflammatory bowel disease and lipodystrophy, providing evidence that leptin aggravates intestinal inflammation with proinflammatory effects on leukocytes that are reversible by TNFα blockade.

Two EEG studies in healthy human adults suggest that choice history and stimulus probability-induced biases in somatosensory perception are reflected in distinct prestimulus beta power modulations across distinct cortical regions.

The Tyrolean Iceman is 5,300 years old and his mitochondrial genome has been previously sequenced. This study reports the full genome sequence of the Iceman and reveals that he probably had brown eyes, was at risk for coronary disease and may have been infected with the pathogen Lyme borreliosis.

Quasicrystals are perfectly ordered crystals lacking translational symmetry. Here the authors unravel the formation mechanism of two-dimensional dodecagonal quasicrystals that arise from systematic modifications of a hexagonal honeycomb structure.

Results are presented from the first Critical Assessment of protein Intrinsic Disorder prediction (CAID) experiment, a community-based blind test to determine the state of the art in predicting intrinsically disordered regions in proteins.

The observation of a flare of radiation from the centre of an inactive galaxy fits a model of the tidal disruption of a helium-rich stellar core and its accretion onto a black hole of about three million solar masses.

The structure of the nuclear pore complexes in intact nuclei is studied by cryoelectron tomography. The trajectory of cargo molecules was traced used gold-labelled proteins fused to a nuclear localization signal. Superimposition of multiple tomograms has yielded a map outlining the pathway of cargo molecules during import into the nucleus.

AlphaFold predicts protein structures with an accuracy competitive with experimental structures in the majority of cases using a novel deep learning architecture.

Hubble Space Telescope, Keck telescope and Spitzer satellite data reveal the formation of the dense stellar core of a massive galaxy occurring three billion years after the Big Bang.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

A near-infrared-light-sensitive photovoltaic subretinal prosthesis triggers behavioural responses in awake macaques, even two years after device implantation.

Measurements of subclonal expansion of ctDNA in the plasma before surgery may enable the prediction of future metastatic subclones, offering the possibility for early intervention in patients with non-small-cell lung cancer.

Whole-genome sequencing of chronic lymphocytic leukemia from 485 patients identifies putative coding and noncoding drivers of disease. Genomically defined subgroups show distinct clinical and biological characteristics.