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The anterior cingulate cortex encodes affective pain behaviours modulated by opioids; targeting opioid-sensitive neurons through a new chemogenetic gene therapy replicates the analgesic effects of morphine, providing precise chronic pain relief without affecting sensory detection.

Here Jaster et al., show a single psilocybin dose produce sex-specific post-acute changes in opioid reward and withdrawal via 5-HT2A receptors in frontal cortex-to–nucleus accumbens circuits, with epigenetic and synaptic changes shaping therapeutic potential.

μ-opioid signalling has a known role in the response to various rewarding stimuli, including pleasant foods. Here, Nummenmaa et al. show using PET and fMRI that individual differences in brain μ-opioid receptor density predict the strength of the neural response to highly palatable foods in humans

μ-opioid receptor (MOR) was previously shown to be necessary for opiate reward, analgesia and dependence. To better understand the specific anatomical and cell type loci of MOR action in opiate reward and reinforcement learning, the authors use cell-specific rescue expression of MOR in subtypes of neurons in the mouse brain that lack MOR globally and show that MOR in the striatal direct-pathway medium spiny neurons is sufficient to rescue the reward action of opioids without affecting opioid analgesia or withdrawal in MOR knockout mice.

Mass-wasting deposits that accumulated against mid-ocean ridge faults have high porosity in which calcium carbonate precipitated, storing seawater carbon dioxide, as revealed by cores of a 61-million-year-old seafloor talus deposit.

CRISPR/Cas9 knock-out of GRKs combined with mutagenesis and phospho-specific antibodies reveal the sites of the mu-opioid receptor that underlie the differences in regulation of this receptor by morphine and fentanyl.

Tools for gaining long-term genetic access to mu-opioid receptor (MOR) neural cell types are limited. Here, the authors develop a suite of adeno-associated viral tools allowing selective genetic access to MOR cell types, and showcase their use across species.

Opioids are potent analgesics but also have addiction risk. Here a lateral preoptic area to lateral habenula connection is identified by which opioids relieve ongoing pain but do not produce reward in animals that do not have ongoing pain.

Carbon–carbon bonds are ubiquitous in lignin, limiting monomer yields from current depolymerization strategies mainly targeting C–O bonds. Now, a bifunctional hydrocracking approach uses a Pt/zeolite catalyst to break C–C bonds in lignin waste, achieving monocyclic hydrocarbon yields up to 54 C%.

μ opioid receptors (MORs) expressed on primary afferent nociceptor neurons are responsible for two maladaptive side-effects of chronic opioid use: opioid tolerance and opioid-induced hyperalgesia (pain). A combination therapy of opioid receptor agonism plus peripheral-restricted MOR antagonism abrogates these side-effects while preserving opioid analgesia in rodent models of peri-operative and chronic pain.

Copper-exchanged zeolites with mordenite structure can mimic the active sites in particulate methane monooxygenase. Here, the authors show that mordenite micropores can stabilize trinuclear copper-oxo clusters that exhibit a high reactivity towards activation of carbon–hydrogen bonds in methane.

Cryo-EM has facilitated structural studies of membrane proteins, but inactive GPCRs have remained inaccessible due to their small size. Robertson et al. demonstrate a common nanobody-based approach to streamline the determination of such structures.

Despite advances in GPCR structures and peptide design, creating high-affinity ligands remains a challenge. Here the authors develop a computational method, successfully identifying peptide-based molecules for KOR: their platform shows promise for streamlined GPCR ligand discovery.

A monospecific aggregation of multituberculate mammals from the Late Cretaceous of Montana suggests an early origin for multigenerational group living and burrowing behaviour among mammals.

Tectonic plate and lower-mantle motions are often considered independent. Plate tectonic reconstructions reveal long-lived interactions between mantle plumes and mid-ocean ridges that imply feedback between plate boundaries and the deep mantle.

A suite of generally applicable methods and tools, developed to enable single-molecule FRET-based studies of transmembrane proteins diffusing in the cell membrane of living cells, was used to study the oligomerization and dynamics of GPCRs.

Interstellar magnetic fields determined from pulsar polarimetry in the GHz-band may be biased by mechanical-optical rotation in pulsars’ magnetospheres. Here the authors show how observations at sub-GHz frequencies can be used to resolve such a bias and determine pulsar rotation directions.

Direct methanol fuel cells offer high energy densities but face challenges including catalyst degradation and surface fouling, which reduce performance over time. Here the authors introduce a control system inspired by reinforcement learning to optimize the power output and mitigate degradation of direct methanol fuel cells by dynamically adjusting the voltage.

Orphan GPCRs represent a pool of unexploited potential pharmacological targets. Here, authors introduce G_zESTY, a sensitive cell-based assay that can detect receptor activation and revealed the presence of endogenous ligands in raw tissue extracts.

Many neurotransmitters act on receptors coupled to GTP-binding G proteins. Here authors report the structure and activity of a mutant that locks the nucleotide-free and receptor-bound state of the G protein, leading to a rare neurological disorder.

PtRu nanoparticles are the state-of-the-art catalysts for methanol electrooxidation—the anodic reaction in direct methanol fuel cells. Now, a method of dispersing single Pt atoms over Ru nanoparticles is presented and monitored in situ, thereby boosting the catalytic performance in the methanol oxidation reaction.

Denervation of muscle fibres induces muscle atrophy, via mechanisms that remain unclear. Here, the authors show that binding of acetylcoline to its receptor at the neuromuscular junction represses the expression of connexins 43 and 45, which promote atrophy, and is sufficient to prevent denervation-induced loss of myofibre mass.

Solvent-mediated interaction networks control a wide range of protein functions, but their design has been neglected owing to a lack of accurate computational tools. Now it is shown that allosteric signalling membrane proteins can be engineered through such networks, revealing a broader space of designable protein interactions and functions.

Biased signaling in κ-opiod receptors (KOR) offer an attractive strategy for pain management. Here the authors identify determinants of KOR signaling bias using structural methods in combination with molecular dynamics simulations.

Capturing radioactive organic iodides from nuclear waste is important for safe nuclear energy usage, but remains a significant challenge. Here, Li and co-workers fabricate a stable metal–organic framework functionalized with tertiary amine groups that exhibits high capacities for radioactive organic iodides uptake.

Enhanced chemical weathering following continental breakup may have driven a succession of Mesozoic oceanic anoxic events, according to tectonic and biogeochemical modelling.

Breathing is controlled automatically but is also conditionally integrated with behavior and emotion in awake animals. Here, authors identify brainstem neurons that are important for controlling awake-state-dependent breathing patterns in mice.

Martínez Corrales et al. show that the activation of the conserved pro-longevity transcription factor FOXO solely in youth promotes subsequent health and survival in female fruit flies, via chromatin remodeling and induction of Xbp1.

The timescale for segregation and transport of basaltic melts, which are ultimately responsible for formation of the Earth's crust, is critically dependent on the permeability of the partly molten asthenospheric mantle, yet this permeability is known mainly from semi-empirical and analogue models. A high-pressure, high-temperature centrifuge is now used to measure the rate of basalt melt flow in olivine aggregates; the resulting permeabilities are one to two orders of magnitude larger than predicted by current parameterizations.

The yeast Saccharomyces cerevisiae is powerful for studying human G protein-coupled receptors as they can be coupled to its mating pathway. Here the authors engineer baker’s yeast to produce human sterols and show that vertebrate G protein coupled receptors are more sensitive in this membrane environment.