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Small molecule machine learning aims to predict properties from molecular structures. Here, the authors introduce the myopic MCES distance and show that frequently used datasets fail to uniformly cover biomolecular structures, limiting resulting models.

The aggregation of the neuronal protein α-Synuclein is associated with the onset of Parkinson’s disease. Here the authors report a two-dimensional Fragment Assisted Structure-based technique to find antagonists of α-Synuclein aggregation and show its promise for identifying lead therapeutics for Parkinson’s disease.

Combining conformal prediction machine learning with molecular docking, a method to efficiently screen multi-billion-scale libraries is developed, enabling the discovery of a dual-target ligand modulating the A_2A adenosine and D₂ dopamine receptors.

Changes in terrestrial runoff into the Bay of Bengal during both extremely weak and strong Indian summer monsoon phases since the Last Glacial Maximum caused a collapse in marine primary production linked to increased stratification, according to proxy records from a marine sediment core.

Realizing large area magnetoreceptive electronic skin with spatially continuous sensing is difficult. Here, the authors integrate the giant magnetoresistance effect and electrical resistance tomography to achieve continuous sensing of magnetic fields across an area of 120 × 120 mm2 with a resolution of 1 mm.

This protocol provides a set of seven customizable example procedures for using microcontroller boards (MCBs) and single-board computers (SBCs) for applications in chemical and biochemical research.

The mechanisms regulating protein lactylation, a post-translational modification, are not fully understood. Here, the authors discover that Histone deacetylase 6 (HDAC6) acts as the primary lactyltransferase for α-tubulin, regulating microtubule dynamics.

The orbital-scale timing of South Asian monsoon precipitation is poorly understood. Here the authors show that the long held view that precession drove changes in monsoon strength is wrong, and that obliquity and eccentricity played a stronger role.

An adequate immune response is necessary to promote heart regeneration. Here, the authors identified a link between antigen presentation, immune cells, and endocardial cells during the regenerative response to cardiac injury in the adult zebrafish.

Aedes aegypti is the main vector of several major pathogens including dengue, Zika and chikungunya viruses. Here the authors find that a CRISPR/Cas9 based split gene drive in Aedes aegypti could successfully bias inheritance up to 89% over successive generations in a multi-cage trial with further deep sequencing suggesting that the multiplexing design could mitigate resistance allele formation.

CRISPR/Cas gene drives can bias transgene inheritance through different mechanisms. Here the authors use gene linkage to show that in males inheritance bias of wGDe did not occur by homing, rather through increased propagation of the donor drive element.

Mammalian orthoreovirus causes serotype-specific disease in the brain. Here, Shang et al. identify and characterise the role of paired immunoglobulin-like receptor B in reovirus attachment, entry and infectivity in the brain.

Psychedelic alkaloids served as lead structures for the development of tabernanthalog, a non-hallucinogenic and non-toxic analogue that reduces alcohol- and heroin-seeking behaviour and produces antidepressant-like effects in rodents.

Sessile communities may support high species richness, despite competition for space. Here, the authors use fungal competition assays to show that intransitive competition can overwhelm pairwise competitive exclusion to facilitate biodiversity.

CRISPR/Cas9-based homing gene drives have emerged as a potential new approach to mosquito control. Here the authors use transgenic lines with germline-specific regulatory elements to express Cas9 and achieve up to 94% inheritance bias, closing the gap between A. aegyptidrives and the highly efficient drives observed in Anopheles species.

Generating diverse structures with a minimum amount of synthetic effort is an important goal for drug discovery. Here, the authors report a two-phase synthesis for the generation of skeletally diverse small molecules—forming molecular scaffolds and subsequently diversifying each into multiple structures.

The paleoseawater temperature record from the oxygen isotope compositions of fossil foraminifera tests may be biased by up to about 1 °C due to grain-boundary diffusion alone, according to isotope exchange experiments on foraminifera tests.

A new way to virtually screen HIV-1 TAR RNA using dynamic ensembles better identifies small molecules targeting RNA secondary structures for development.

An atomic force microscope and confocal microscope set-up that allows nanomechanical mapping of virus binding under cell culture conditions shows that the first binding steps of a virus to a cell surface receptor are specific and weak, but affinity increases as more bonds are formed between the virus and cell surface receptors.

We identify that the larval zebrafish unpaired pre-anal fin fold is derived from the lateral plate mesoderm, can be readily duplicated, and thus may represent a developmental intermediate between median and paired fins.

VVD-133214, a clinical-stage, covalent allosteric inhibitor of the helicase WRN, was well tolerated in mice and led to robust tumour regression in multiple microsatellite-instability-high colorectal cancer cell lines and patient-derived xenograft models.

Complex clinical samples can be imaged with 25 nm resolution using a light-emitting-diode-based wide-field microscope.

This work describes the identification and characterization of novel small molecule activators of SIRT1, an NAD⁺-dependent deacetylase that mediates the beneficial effects of caloric restriction. These small molecules are structurally unrelated to, and much more potent than, resveratrol, and improve metabolic function in animal models of diabetes and obesity.

Direct carbonization of zeolitic imidazolate framework-type metal-organic frameworks, as described in this protocol, results in nanoporous carbons that can be used for diverse electrochemical applications.

The authors describe the fabrication, assembly and long-term implantation of ultraflexible neural probes for the simultaneous recording of neural activity and neuromodulation in rodents.

Cardinal v.3 is an open-source software for reproducible analysis of mass spectrometry imaging experiments, and includes data processing features such as mass recalibration, statistical analyses such as single-ion segmentation and rough annotation-based classification, and analyses of large-scale multitissue experiments.

Tumor-reactive T cells are generated by coculturing tumor organoids and autologous peripheral blood lymphocytes and are evaluated for their capacity to carry out effector functions after recognition of tumor cells and whether they kill tumor organoids.

Mirkin and colleagues outline the synthesis of protein spherical nucleic acids (ProSNAs), which constitute a versatile plug-and-play platform that uses protein functionalization with a dense nucleic acid corona to enable intracellular delivery both in vitro and in vivo.

Sarah De Baets et al. investigate the effect of root hair abundance on root-substrate cohesion and experimental soil erosion in Arabidopsis. They find that plants with root hairs are more difficult to detach from soil and are better able to prevent soil erosion than root hairless plants and present a model to predict the impact of root hairs on soil erosion resistance.