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Surprisingly, motor cortex becomes less involved in performing skilled motor behaviors as they are practiced. This is addressed by a model of two descending pathways featuring different types of learning: fast learning in a cortical pathway to maximize rewards and slow learning in a subcortical pathway to reinforce behaviors through repetition.
Dihydrobenzofurans and indolines are common substructures in medicines and natural products. Herein, the authors report a palladium-catalyzed [3 + 2] (hetero)annulation proceeding in an anti-selective fashion and enabling direct access to these valuable heterocycles with broad reaction scope.
β-tryptases are responsible for most of the proteolytic activity during mast cell activation. Here, the authors develop β-tryptase-inhibiting antibodies and provide structural and biochemical evidence that the bivalency of the antibodies is a prerequisite for their inhibitory activity.
The navigation of catheters through blood vessels requires flexible guiding wires that are pushable and tractable at the same time. Pancaldi et al. rely on hydrodynamic forces and magnetic torque in order to access even rather small capillaries with an ultraflexible magnetomechanical probe.
In vivo mutagenesis systems can often show restricted capabilities and deleterious off-site mutations. Here the authors fuse base deaminases to T7 RNA polymerase to mutate a target sequence and use dCas9 to define the boundaries of the diversified DNA.
The dopamine D2 receptor (D2R) is a GPCR and an important drug target for schizophrenia treatment. Here, the authors present the crystal structure of human D2R in complex with the antipsychotic drug spiperone, which is of interest for designing antipsychotics with improved receptor selectivity.
A group of long non-coding RNAs (lncRNAs), Mammary Tumor Associated RNAs1-30 (MaTARs1-30), are differentially expressed between mammary tumor cells and normal mammary epithelial cells. Here the authors report that MaTAR25 plays a role in breast cancer cell proliferation, migration and invasion by regulating the expression of the Tensin1 gene in trans.
Design and discovery of catalysts to make clean energy and mitigate the harmful effect of greenhouse gases remains a massive challenge. Here the authors report a combustion-synthesised iron-based catalyst of high activity and selectivity for directly converting CO2 to aviation jet fuel.
Chlamydia trachomatis does not possess TrpL-mediated transcription attenuation of its trp operon. Here, the authors show that an iron-dependent regulator, YtgR, acts as a tryptophan-dependent attenuator of the trp operon in this organism, due to translational regulation of YtgR levels via a triple tryptophan motif.
Designing efficient blue perovskite LEDs by using mixed halides perovskite is still a challenge, limited mainly by the phase segregation issue. Here, the authors demonstrate in situ fabrication of quasi-2D CsPbClBr2 nanocrystal films with mixed ligands to overcome the constraint.
Using Chang’E data, the authors here identify more than 109,000 previously unrecognized lunar craters and date almost 19,000 craters based on transfer learning with deep neural networks. A new lunar crater database is derived and distributed to the planetary community.
The vertebrate TATA-binding protein (TBP) paralogue (TBPL2) is only expressed in growing oocytes, where TBP is absent. Here the authors highlight a unique role for the TBPL2/TFIIA complex in the establishment of the oocyte transcriptome by using a specific TSS recognition code.
The actin-related protein (Arp)2/3 complex nucleates branched actin filament networks pivotal for cell migration, endocytosis and pathogen infection. Here, authors report a 9.0 Å resolution structure of the actin filament Arp2/3 complex branch junction in cells using cryo-electron tomography and subtomogram averaging.
IL-2/anti-IL-2 complexes have been proposed to curtail the severe adverse effects associated with IL-2 immunotherapy. Here, the authors, by integrating unmutated human IL-2 in the antigen binding groove of an anti-IL-2 monoclonal antibody, generate a CD122-biased fusion protein that prevents binding of IL-2 to CD25 and promotes anti-tumor immune response in several preclinical metastatic cancer models.
Molecular profiling of breast cancer in non-Caucasian populations remains underexplored. Here the authors report a high prevalence of HER2-subtypes and enriched immune score with improved survival and higher rates of TP53 somatic mutations with poorer survival in ER+ tumours in a Malaysian cohort.
The fungal pathogen Candida auris is resistant to multiple drugs including the common antifungal fluconazole. Here, Iyer et al. identify a compound that potentiates fluconazole activity against C. auris in vitro and in vivo by inhibiting a major efflux pump and thus increasing intracellular fluconazole accumulation.
Pre conditioning injury or environmental enrichment have been shown to promote axon regeneration. Here the authors show that environmental enrichment, combined with preconditioning injury promotes regeneration via a redox signalling dependent mechanism.
Arrays of ordered metal atoms on bulk insulating materials are promising for future applications, such as optoelectronics and data storage. Here, the authors demonstrate a strategy to create an ordered metal array based on tailored anchoring and hard-sphere repulsion of metal-complexing molecules.
The causes and consequences of social intelligence are challenging to establish. A study on wild cleaner fish reports that large forebrains enable individuals to score higher in a social competence test, suggesting forebrain size is important for complex social decision-making.
Intestinal cancer stem cells (CSC) are associated with colon cancer. Here, the authors show that Wnt/beta-catenin signalling in CSC requires the epigenetic regulator Mll1 to promote stemness and tumourigenesis in murine and human colon cancer models.