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In this work, fragments identified by 19F-NMR are optimized into submicromolar binders of the MITF transcription factor. These results support direct targeting of bHLH-LZ DNA binding domains and provide a foundation for the development of new melanoma therapies.

Plastic crystals like neopentyl glycol show strong barocaloric effects but struggle with suitable operating temperatures and low-pressure performance. Here, the authors improved this by blending neopentyl glycol with pentaglycerine and adding 2% pentaerythritol for tunable, reversible phase transitions.

A detailed and systematic neutron scattering study uncovers a spiral spin-liquid state in the quantum magnet MnSc₂S₄.

Echinocandins inhibit the biosynthesis of β−1,3-glucan, an essential component of the fungal cell wall, but their efficacy against the pathogen Aspergillus fumigatus is limited. Here, Dickwella Widanage et al. show that A. fumigatus responds to echinocandin treatment by remodelling various cell wall polymers, thus maintaining cell wall integrity and modulating the permeability and circulation of the drug in the cell wall.

Combining molecular dynamic simulations with in vivo functional assays, Gagelin et al. identified unique molecular features of the mitochondrial carrier uncoupling protein 1 that are crucial to its inhibition by nucleotides

Mechanical signals regulate tissue differentiation but how this triggers downstream biochemical signals is unclear. Here, the authors place micro-magnets in theDrosophilaembryonic epithelia and show this triggers apical pulsations, in turn stabilizing Myosin-II, resulting in mesoderm invagination.

Charge and thermal transport in low-dimensional and mesoscopic systems exhibit significant deviation from classical behaviour. Here the authors study quantitatively how heat flow in a quantum circuit is affected by thermal shot noise and Coulomb interactions.

Characterization of the interaction between PTH and its G-protein-coupled receptor, PTHR, shows conformational changes coupled to residues interacting with His9, which helps position the PTH N terminus at the PTHR transmembrane domain to facilitate β-arrestin coupling.

BaFe₂As₂ is a parent compound for iron based superconductors, and this has motivated extensive study of its magnetic and electronics properties. Here, using neutron polarisation analysis, the authors demonstrate the critical importance of spin-orbit coupling to properties of BaFe₂As₂.

High entropy alloys are multi-element random alloys with a strong short range disorder. Here, the authors show that their heat carrying lattice waves, while strongly attenuated by the force-constant disorder, propagate until high energy.

Using the site-specific incorporation of isotopically labeled glutamines and NMR, Elena-Real et al. identified helical stability of pathogenic huntingtin exon 1 as a key feature defining the aggregation propensity that triggers Huntington’s disease.

While it is widely believed that high-temperature superconductivity in cuprate materials arises from an intertwined interplay between charge and spin fluctuations, the microscopic coupling between charge and spin degrees of freedom still remains a mystery in these materials. Here, the authors profit from neutron scattering with superior beam focusing to probe the subtle spin-density wave order under uniaxial pressure, and demonstrate that charge and spin orders respond to the external tuning parameter in the same manner.

How synaptic vesicles (SVs) are clustered at the presynapse is suggestive of anchoring processes counteracting their diffusion. Here, the authors co-track recycling and reserve SVs in live neurons to find that Synapsin 2a tetramerization dynamically immobilizes reserve SVs at the presynapse.

Phonon lifetime is a fundamental parameter of thermal transport however its determination is challenging. Using inelastic neutron scattering and the neutron resonant spin-echo technique, Lory et al. determine the acoustic phonon lifetime in a single crystal of clathrate Ba7.81Ge40.67Au5.33.

Myosin X is a molecular motor unique in its ability to generate filopodia, but the mechanism explaining this behaviour is not known. Here, through a combination of structure, single-molecule assays and modelling the authors show that myosin X is optimized for transport along actin bundles.

Pentameric ligand-gated ion channels (pLGICs) mediate fast synaptic signaling in response to neurotransmitter binding, but the conformational changes induced by neurotransmitter binding are unknown. The crystal structures of mutated GLIC, a bacterial pLGIC homolog, reveal a novel, locally closed channel conformation that provides insight into pLGIC allosteric transitions.

The Fanconi anemia (FA) DNA-repair pathway is important in processing of DNA interstrand cross-links and in resistance to exogenously added aldehyde. Genetic analyses now reveal the synthetic lethality of deficiencies in the FA pathway and formaldehyde catabolism, indicting that this pathway repairs lesions caused by endogenous formaldehyde.

The pseudogap state in high-T_c superconducting copper oxides in one of the most mysterious quantum states of matter whose understanding remains a challenge for condensed matter physicists. The authors report a hidden magnetic texture deep in the pseudogap state highlighting another piece of the puzzle.

An environmentally safe means of mosquito control is the application of Bacillus thuringiensis israelensis, which produces a cocktail of four naturally crystalline proteins exclusively toxic to mosquito. Here the authors report the atomic-resolution structures of Bti Cry11Aa and related Btj Cry11Ba solved de novo through Serial Femtosecond Crystallography on naturally-occurring nanocrystals.

2M1510 is an approximately 45-million-year-old triple system of brown dwarfs, two of which form a close binary in a 20-day orbit and have almost the same mass (3.82% and 3.75% of the mass of the Sun, respectively). Their physical parameters are in good agreement with evolutionary models except for luminosity, suggesting that we might be underestimating the masses of brown dwarfs and massive exoplanets by about 30%.

The authors report a particle-particle correlation and velocity-difference profile method to measure nuclear lifetime. The results obtained for excited states of 23Mg are used to constrain the production of 22Na in the astrophysical novae explosions.

Endogenous and alcohol-derived acetaldehyde causes a specific pattern of DNA damage in haemopoietic stem cells; the effects are mitigated by detoxification, specific DNA repair mechanisms and a p53 response.

Bacillus thuringiensis israelensis (Bti) produces the naturally-crystalline proteinaceous toxin Cyt1Aa that is toxic to mosquito larvae. Here the authors grow recombinant nanocrystals of the Cyt1Aa protoxin in vivo and use serial femtosecond crystallography to determine its structure at different redox and pH conditions and by combining their structural data with further biochemical, toxicological and biophysical analyses provide mechanistic insights into the Cyt1Aa bioactivation cascade.

Ketan Patel and colleagues report a new mouse model of Fanconi anemia. The authors show that mice deficient in Btbd12, the mouse ortholog of SLX4 (a new Fanconi anemia gene), phenocopy the human disease.

The function of haematopoietic stem and progenitor cells is impaired by damaged DNA; here, endogenously generated aldehydes are found to be one source of such damage, which is repaired by the Fanconi anaemia pathway.

Long-term swarm-type seismic activity combined with rainfall can cause instability of volcanic structures like flanks and crater walls, according to statistical analyses of 10 years of observations at the Piton de la Fournaise volcano and lab experiments