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Here, the authors solve a series of cryo-EM structures of the Swi2/Snf2 family transcription regulator Mot1 to show how this remodeler uses energy to displace the transcription initiation factor TBP from its gene promoters.

The flagellum is a beautiful structure and a fascinating model system for understanding how genes are regulated to ensure the correct assembly of a complex structure. Chevance and Hughes discuss the regulation of flagellar gene transcription and how it is intimately coupled to the assembly of this exquisite bacterial nanomachine.

Growth of a flagellum outside the bacterial cell proceeds by successive subunit acquisition from the cell export machinery to form a chain that is pulled to the flagellum tip, where subunit crystallization provides the entropic force to drive the process.

Cellular membranes have specific lipidic compositions that influence their biophysical properties. PtdIns4P accumulates in the plasma membrane and modifies its inner surface charge, which controls the localization and function of signalling proteins.

The cryo-electron microscopy structure of C9orf72–SMCR8–WDR41 suggests that this complex is a GTPase-activating protein for ARF-family small GTPases, which sheds light on the role of C9orf72 mutations in neuronal dysfunction.

Birds have an excellent ability to learn to discriminate harmless insects from those that they mimic on the basis of subtle differences in appearance.

Understanding the cellular target of hit compounds from phenotypic screens presents a major challenge yet is essential in the development of chemical probes. Here, the authors reveal the target of Hedgehog Pathway Inhibitor-1, by converting it to a bifunctional degrader, to be BET bromodomains.

A global dataset of the satellite-tracked movements of pelagic sharks and fishing fleets show that sharks—and, in particular, commercially important species—have limited spatial refuge from fishing effort.

Targeted protein degradation of cell-surface glycoproteins suppresses cancer in mice.

tag-Targeted Protein Degrader (tTPD) systems are powerful tools for preclinical target validation. Here the authors extend the tTPD platform by developing NanoTACs that degrade NanoLuc tagged substrates and benchmark each tTPD system using an interchangeable tag reporter system.

Mitesh Dongre et al. have identified a novel bacterial cytotoxin from Vibrio chloerae, whose virulence depends on flagella-mediated secretion. This suggests that the flagella’s role in cytotoxin export could improve survival and proliferation of bacteria when exposed to environmental stress.

Excavation in Island New Guinea reveals features associated with the Pacific Lapita cultural complex as well as sustained local cultural traditions from 3,480–3,060 years ago, contemporary with the earliest known Lapita settlements 700 km away. This supports New Guinea as a springboard for Lapita dispersal throughout the Pacific and illuminates their origins.

Autoimmune diabetes in mice is averted by electrically stimulating the nerve projecting to the pancreas.

The study describes the molecular structure of the human histamine 2 receptor in active conformation and in complex with G_s heterotrimer, synthesized in a cell-free system and co-translationally inserted into preformed nanodiscs.

Mutations within subunits of the tRNA splicing endonuclease complex (TSEN) are associated with pontocerebellar hypoplasia (PCH). Here the authors show that tRNA intron excision is catalyzed by tetrameric TSEN assembled from inactive heterodimers, and provide evidence that modulation of TSEN stability may contribute to PCH phenotypes.

The valve-like trichomes of the desert plant Tillandsia landbeckii allow water acquisition from fog while minimising transpiration. Here, Raux et al. show that a hygroscopic cell-wall adjacent to a semi-permeable plasma membrane at the base of the trichome confers this asymmetry in water conductance.

Protein degraders are an emerging drug modality; however, their properties lie beyond typical drug-like space. Here the authors report optimisation via structure-based exit vector and linker design towards the VHL-recruiting PROTAC ACBI2, an orally bioavailable and selective degrader of SMARCA2.

The study provides a comprehensive transcriptomic atlas of the human gastrointestinal tract across the lifespan, highlighting inflammation-induced changes in epithelial stem cells that alter mucosal architecture and promote further inflammation.

Flexible electronic platforms would enable the integration of functional electronic circuitry with many everyday objects; here, a low-cost and fully flexible 32-bit microprocessor is produced.

Hemochromatosis is a metabolic disorder caused by mutations in the HFE gene. Here, the authors show that a single administration of AAV8 vectors expressing an Adenine Base Editor facilitates efficient in vivo gene correction in hepatocytes and leads to improvement of iron-specific parameters in the liver and the blood in mouse models of the disease.

Human infections with Campylobacter fetus are often assumed to be derived from livestock. Here, Iraola et al. provide evidence that healthy humans may act as carriers and dispersers, and C. fetus may have originated in humans as an intestinal pathobiont and then adapted as a livestock pathogen.

Using asteroseismology to analyse 7,000 helium-burning red giants observed by NASA’s Kepler mission results in the separation of two classes of stars that must have undergone considerable mass loss, presumably due to stripping in binary interactions.

The Endocrine Society's recent Scientific Statement on postmenopausal hormone therapy highlights the dangers of calculating risks and benefits associated with hormone therapy for women in early menopause on the basis of evidence from previous studies. But does it provide a quantum shift in the clinician's perception of risk versus benefit from hormone therapy?

The Sequencing Quality Control (SEQC) consortium shows that junction discovery and differential gene expression profiling with RNA-seq can be robust but transcript-level and absolute measurements remain challenging.

The role of actin/tropomyosin filaments in the assembly of cell–substrate adhesions has been investigated and it is now shown by cryo-electron tomography that they are essential for adhesion assembly and also regulate mechanosensing, matrix remodelling and transformation of cells towards a cancer phenotype.

Understanding the factors that contribute to the evolution and maintenance of virulence is crucial for a full understanding of infectious disease biology. Focusing onStaphylococcus aureus and Staphylococcus epidermidis, the authors argue that host-to-host transmission is a key factor in determining the level of bacterial virulence.

AMPK acts as an intracellular energy sensor, as its activity is tuned by the relative levels of ATP, ADP and AMP. Therefore, it has a central role in the regulation of cellular metabolic pathways and in the control of whole-body energy balance.