Browse Articles

Mutant glycosidases for labeling sialoglycans with high specificity and affinity

Author Correction: Specialized contact sites regulate the fusion of chlamydial inclusion membranes

Mélange dehydration and melting beneath South Sandwich Islands arc

Biological age model using explainable automated CT-based cardiometabolic biomarkers for phenotypic prediction of longevity

Tissue shear as a cue for aligning planar polarity in the developing Drosophila wing

Abstract Planar polarity establishment in epithelia requires interpretation of directional tissue-level information at cellular and molecular levels. Mechanical forces exerted during tissue morphogenesis are emerging as crucial tissue-level directional cues, yet the mechanisms by which they regulate planar polarity are poorly understood. Using the Drosophila pupal wing, we confirm that tissue stress promotes proximal-distal (PD) planar polarity alignment. Moreover, high tissue stress anisotropy can reduce the rate of accumulation and lower the stability on cell junctions of the core planar polarity protein Frizzled (Fz). Notably, under high tissue stress anisotropy, we see an increased gradient of cell flow, characterised by differential velocities across adjacent cell rows. This promotes core protein turnover at cell-cell contacts parallel to the flow direction, possibly via dissociation of transmembrane complexes by shear forces. We propose that gradients of cell flow play a critical role in establishing and maintaining PD-oriented polarity alignment in the developing pupal wing.

Deterministic multi-phonon entanglement between two mechanical resonators on separate substrates

The anti-PD-L1/CTLA-4 bispecific antibody KN046 plus lenvatinib in advanced unresectable or metastatic hepatocellular carcinoma: a phase II trial

P-block element modulated 1 T phase MoS2 with Ru lattice grafting for high-performance Li | |O2 batteries

Periodic splay Fréedericksz transitions in a ferroelectric nematic

Abstract Electric field-induced splay of molecular orientation, called the Fréedericksz transition, is a fundamental electro-optic phenomenon in nonpolar nematic liquid crystals. In a ferroelectric nematic NF with a spontaneous electric polarization $${{\bf{P}}}$$ P , the splay is suppressed since it produces bound electric charges. Here, we demonstrate that an alternating current (ac) electric field causes three patterns of NF polarization. At low voltages, $${{\bf{P}}}$$ P oscillates around the field-free orientation with no stationary deformations. As the voltage increases, the polarization acquires stationary distortions, first splay and twist in a stripe pattern and then splay and bend in a square lattice of +1 and -1 defects. In all patterns, $${{\bf{P}}}$$ P oscillates around the stationary orientations. The stationary bound charge is reduced by a geometrical “splay cancellation” mechanism that does not require free ions: the charge created by splay in one plane is reduced by splay of an opposite sign in the orthogonal plane.

Anti-Markovnikov hydroallylation reaction of alkenes via scandium-catalyzed allylic C‒H activation

Author Correction: Targeting chondrocytes for arresting bony fusion in ankylosing spondylitis

Retrotrans-genomics identifies aberrant THE1B endogenous retrovirus fusion transcripts in the pathogenesis of sarcoidosis

Deep reinforcement learning for active flow control in a turbulent separation bubble

Abstract The control efficacy of deep reinforcement learning (DRL) compared with classical periodic forcing is numerically assessed for a turbulent separation bubble (TSB). We show that a control strategy learned on a coarse grid works on a fine grid as long as the coarse grid captures main flow features. This allows to significantly reduce the computational cost of DRL training in a turbulent-flow environment. On the fine grid, the periodic control is able to reduce the TSB area by 6.8%, while the DRL-based control achieves 9.0% reduction. Furthermore, the DRL agent provides a smoother control strategy while conserving momentum instantaneously. The physical analysis of the DRL control strategy reveals the production of large-scale counter-rotating vortices by adjacent actuator pairs. It is shown that the DRL agent acts on a wide range of frequencies to sustain these vortices in time. Last, we also introduce our computational fluid dynamics and DRL open-source framework suited for the next generation of exascale computing machines.

Ni-catalysed acceptorless dehydrogenative aromatisation of cyclohexanones enabled by concerted catalysis specific to supported nanoparticles

A synthetic chronogenetic gene circuit for programmed circadian drug delivery

A framework for soft mechanism driven robots

Observation of anomalously large Nernst effects in conducting polymers

A multistage drug delivery approach for colorectal primary tumors and lymph node metastases

Orphan G protein-coupled receptor GPRC5B controls macrophage function by facilitating prostaglandin E receptor 2 signaling

Abstract Macrophages express numerous G protein-coupled receptors (GPCRs) that regulate adhesion, migration, and activation, but the function of orphan receptor GPRC5B in macrophages is unknown. Both resident peritoneal and bone marrow-derived macrophages from myeloid-specific GPRC5B-deficient mice show increased migration and phagocytosis, resulting in improved bacterial clearance in a peritonitis model. In other models such as myocardial infarction, increased myeloid cell recruitment has adverse effects. Mechanistically, we found that GPRC5B physically interacts with GPCRs of the prostanoid receptor family, resulting in enhanced signaling through the prostaglandin E receptor 2 (EP2). In GPRC5B-deficient macrophages, EP2-mediated anti-inflammatory effects are diminished, resulting in hyperactivity. Using in silico modelling and docking, we identify residues potentially mediating GPRC5B/EP2 dimerization and show that their mutation results in loss of GPRC5B-mediated facilitation of EP2 signaling. Finally, we demonstrate that decoy peptides mimicking the interacting sequence are able to reduce GPRC5B-mediated facilitation of EP2-induced cAMP signaling in macrophages.

Targeting eEF1A reprograms translation and uncovers broad-spectrum antivirals against cap or m6A protein synthesis routes