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Zhu et al show that LRRK2 kinase promotes invagination of the plasma membrane to create ‘reservoirs’, which dynamically store or release excess membrane. Salmonella can exploit these membrane reservoirs during invasion of host cells by controlling the activity of LRRK2.

 In fish, water motion is detected by mechanosensitive hair cells located in the lateral line. Here the authors show that the molecular machinery for mechanotransduction, including transmembrane channel-like 2b (Tmc2b), varies depending on both hair cell location and hair bundle orientation.

Locus coeruleus (LC) activation enhanced thalamic feature selectivity & perceptual performance. Electrophysiology and modeling suggest this improvement is due to reduction in Ca²⁺ T-channel activity by LC regulation of intrathalamic circuit dynamics.

Sorption modeling treating soil as a homogenous medium misrepresents PFAS mobility in the subsurface. Exploring minerals reveals the role of aluminum-oxide electrostatics for short PFAS and organic matter and air-water interface for long-chains.

A specialized technology can restore and preserve microcirculation and cellular functions hours post-mortem in an isolated pig brain.

How synaptic plasticity rules lead to diverse neural responses in a spiking neural network model remains poorly understood. Here, the authors show how a diversity of response types contributes to network function and task performance.

Innate defense behaviours in animals in response to approaching threats are mostly studied in response to visual stimuli. Here, the authors show that looming sounds elicit stereotypical sequential defensive reactions that require the auditory cortex, superior colliculus and the striatum.

Efficient transmission of SARS-CoV-2 among infected ferrets requires a functional furin cleavage site in the SARS-CoV-2 spike protein.

Perivascular and leptomeningeal macrophages, collectively termed here parenchymal border macrophages, are shown to regulate flow dynamics of cerebrospinal fluid, implicating this cell population as new therapeutic targets in neurological diseases such as Alzheimer’s.

Humans adapt decision strategies in response to environmental demands. Here the authors show that decisions in a virtual foraging task can be modelled based on perceived patch value, which includes reward, competition and threat, and is associated with activity in ventromedial prefrontal and medial cingulate cortices.

Combinations of single-stranded DNA repair templates and small molecules markedly enhance genome editing.

Alterations in lipid metabolism and circulating lipid species have been reported in patients with acute critical illness. Here the authors show that selective rise in systemic phosphatidylethanolamine levels is a common feature of critical illness that associates with worse clinical outcomes.

We show that gain-of-function cancer mutations in the KBTBD4 E3 ligase promote neodegradation of substrates via a shape-complementarity-based mechanism, which converges with the mechanism of action of the UM171 molecular glue degrader and can be blocked by HDAC1/2 inhibitors.

The activity of G-protein-coupled receptors is regulated by their interaction with arrestins. Here the authors show that loops located on C-edge of arrestin-1 serve as a membrane anchor during the multi-step binding process that leads to a stable receptor–arrestin complex.

Soft mechanism driven robots, made via multi-material 3D printing, combine soft and rigid components for robust, adaptable locomotion. This framework balances flexibility and strength, enabling effective operation across varied terrains.

White matter in the human brain is known to change its properties during an individual's lifespan. Here, Yeatman et al. use quantitative imaging measurements of the living human brain to model changes in white mater structure based on tissue development and decline between the ages of 7–85 years.

Targeted mass spectrometry enables reproducible and accurate lipid quantification but dedicated software tools to develop targeted lipidomics assays are lacking. Here, the authors develop a targeted lipidomics workbench and lipid knowledgebase for the streamlined generation of targeted assays.

This Protocol Extension describes Zebrafish targeting of Reactive Electrophiles and oXidants (Z-REX), an extension of a Protocol on the targetable reactive electrophiles and oxidants, adapted for on-demand redox targeting in live zebrafish embryos. The protocol details how to generate transgenic fish and run Z-REX, as well as its downstream validation.

Irisin is shown to mediate beneficial effects on cognitive function associated with exercise and to improve cognitive function in mouse models of Alzheimer’s disease, probably through its direct action in the brain.

Interferon (IFN) is an important component of antiviral immunity, but can also be exploited by bacteria for immune evasion. Here the authors show that Listeria monocytogenes (Lm) induces type I IFN to suppress the degradation of Lm virulence proteins, ActA and LLO, and promote Lm infection in an IFITM3-dependent manner, thereby hinting at a potential target for antimicrobial therapy.

Protein expression from circular RNAs is enhanced several hundred-fold by optimizing vector design.

Tirofiban is an inhibitor of platelet αIIbβ3 which may contribute to venous thrombosis. Here the authors developed a non-agonizing modified tirofiban, defined by its cryo-EM structure bound to platelet αIIbβ3 and elucidated the pathogenic role of αIIbβ3 in venous thrombogenesis.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

The genomic features of precursor conditions of multiple myeloma provide multiple biological insights into disease origins and evolution, together with opportunities to identify those at highest risk of progression.

Using multiple datasets from real-world evidence and completed trials, a machine learning model using routine blood and clinical data is shown to be predictive of patient response to immune checkpoint inhibitor therapy, across cancer types and outperforming standard biomarkers.

The authors find that structural economic inequality is linked to reduced brain volume and connectivity in middle-aged and older adults across the Americas, more so in Alzheimer’s disease than in frontotemporal dementia. The findings emphasize the biological embedding of inequality in aging and dementia.

There are currently no treatment options for infection with Rift Valley fever virus (RVFV). Here, Chapman et al., show that a combination of human monoclonal antibodies targeting two different steps in early virus cell entry enhances protection in a mouse model and is effective at low doses.

Whether Alzheimer’s disease originates in basal forebrain or entorhinal cortex remains highly debated. Here the authors use structural magnetic resonance data from a longitudinal sample of participants stratified by cerebrospinal biomarker and clinical diagnosis to show that tissue volume changes appear earlier in the basal forebrain than in the entorhinal cortex.

The Cancer Genome Atlas Research Network report integrated genomic and molecular analyses of 164 squamous cell carcinomas and adenocarcinomas of the oesophagus; they find genomic and molecular features that differentiate squamous and adenocarcinomas of the oesophagus, and strong similarities between oesophageal adenocarcinomas and the chromosomally unstable variant of gastric adenocarcinoma, suggesting that gastroesophageal adenocarcinoma is a single disease entity.

Zona incerta (ZI) is an inhibitory subthalamic nucleus with diverse connectivity yet its functional importance has not been extensively studied. Here the authors report that ZI receives mPFC input and can modulate both innate and learned defensive behaviors via its inhibitory projection to the PAG.

The yeast NuA3 complex regulates gene transcription and the cell cycle. Nguyen et al. show that intersubunit interactions involving the Taf14, Yng1 and Sas3 subunits are essential in biological activities of the NuA3 complex.

Extracellular vesicles have been exploited as potential therapeutic agents. Here, the authors apply a nanovial technology to select sub-populations of cells that secrete high levels of extracellular vesicles, leading to improved therapeutic efficacy when delivered in vivo.

[¹⁸F]OXD-2314 is a brain penetrant positron emission tomography radiotracer with high affinity for tau aggregates in Alzheimer’s disease (AD) and non-AD tauopathies based on in vitro and in vivo studies, and is suitable for first-in-human use.

Prov-GigaPath, a whole-slide pathology foundation model pretrained on a large dataset containing around 1.3 billion pathology images, attains state-of-the-art performance in cancer classification and pathomics tasks.

The structure of the GABA_B receptor in an inactive state reveals, amongst other features, a latch between the two subunits that locks the transmembrane domain interface, and the presence of large phospholipids that may modulate receptor function.

Large-scale phylogenetic analysis of coral reef fish species shows that functional traits evolve fastest in those at high and low trophic levels with narrow diet breadth.

A fluorescence-based sensor of PKA activity has increased brightness, dynamic range and signal-to-noise ratio over related sensors and is useful for visualizing kinase activity in HeLa cells, primary neurons and the cortex of awake mice.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

Antigenic variation of influenza A viruses necessitates the annual reformulation of vaccines. Kanekiyo et al. develop a mosaic nanoparticle vaccine against influenza virus that is able to elicit neutralizing antibodies that span nearly 100 years of variation of influenza A virus.

Understanding the human antibody response to influenza A virus strains is important for vaccine development. Here, Creanga et al. generate a panel of 55 replication-deficient reporter viruses representing diversity of human H1N1 and H3N2, and pandemic subtypes and characterize the neutralization profile of 24 antibodies and polyclonal sera.

The role of type I interferon signalling in the control of myeloid derived suppressor cells (MDSC) activity remains controversial. Here the authors show that downregulation of type I interferon receptor is observed in MDSC from cancer patients and tumor-bearing mice and is required for the activation of their immune suppressive properties.

The translation of upstream open reading frames in skin tumour models protects some cancer-related mRNAs from global reductions in protein synthesis during the early stages of tumour initiation, suggesting that unconventional translation has a crucial role in tumorigenesis.

Junior researchers need to engage with policymakers, institutions, funders and media outlets to argue against planned budget cut-backs, warn Brian Cahill and Marco Masia.

Of 12 serology assays tested, four detect antibodies in more than 80% of patients with COVID-19.

Studies on the essentiality of Ku in human cells reveal that Ku interacts with diverse double-stranded RNA molecules, including antisense Alu, and enables tolerance of Alu sequence expansion in primates.

A negative allosteric modulator of the G-protein-coupled receptor β₂-adrenergic receptor binds to a membrane-facing surface adjacent to a molecular switch for receptor activation, and its binding disrupts a water-mediated polar network stabilizing an inactive switch conformation.

This manuscript describes the structure of an endocannabinoid analog-bound CB1 complex and reveals the structural determinants of ligand efficacy. The activation mechanism, unique to CB1, that is exploited by allosteric modulators is also outlined.