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‘We’re humans — brilliant and a mess’: Wikipedia founder Jimmy Wales on trust and optimism
Excess mortality in Europe estimated by EuroMOMO during the COVID-19 pandemic and previous influenza seasons
Mechanistically guided residual learning for battery state monitoring throughout life
Bioadaptive Ni single atoms unlock high rate microbial electrosynthesis of isopropanol from CO2
4D printing through vat photopolymerization of two-stage UV-curable liquid crystal elastomers
Abstract Liquid crystal elastomers (LCEs) offer significant promise as soft actuator materials, but their potential has not yet been fully explored for 4D printing applications. Most existing studies rely on extrusion-based printing methods, which offer limited resolution and impose constraints on fabricating intricate, free-standing structures. Moreover, it remains a significant challenge to design and spatially control liquid crystal orientation within complex 3D structures to achieve desired shape transformations. To address these challenges, this study introduces a 4D printing strategy that combines two-stage UV-curable LCEs with vat photopolymerization-based 3D printing, such as digital light processing (DLP). The LCE can be initially printed into complex geometries with high precision, followed by a post-printing programming step in which mechanical deformation is applied to the printed structure to define the desired shape. A subsequent thermal treatment forms covalent linkages to lock the programmed configuration. The resulting structures can reversibly transition between the printed and programmed configurations upon temperature change. This 4D printing strategy is shown to overcome key limitations of current approaches and significantly broaden the design space and functional potential of programmable shape-changing structures for various applications, including mechanically active metamaterials, morphing architecture, and soft robotics.
AI models were given four weeks of therapy: the results worried researchers
Structural mechanisms for inhibition and activation of human small-conductance Ca2+-activated potassium channel SK2
HEXIM1 inter-monomer autoinhibition governs 7SK RNA binding specificity and P-TEFb inactivation
Abstract Hexim proteins are key RNA-dependent regulators of eukaryotic transcription through 7SK-dependent sequestration and inactivation of the kinase P-TEFb (Cdk9–CyclinT1/2) in the 7SK RNP. P-TEFb activity drives release of RNA polymerase II from promoter-proximal pausing for eukaryotic and HIV-1 transcription. The molecular mechanism by which 7SK binding overcomes an intrinsic Hexim autoinhibition for subsequent P-TEFb inactivation has remained unresolved. Here, using NMR and biophysical methods we demonstrate that Hexim1 homodimer engages two high-affinity sites on 7SK RNA. This dual-site binding triggers a conformational rearrangement in Hexim1’s disordered central region that unmasks the Cdk9-binding site, which is otherwise sequestered within an inter-monomer dimer interface. These findings reveal how Hexim autoinhibition dictates its specificity for 7SK RNA and prevents premature P-TEFb inhibition in the absence of 7SK, thereby providing a mechanistic understanding of Hexim/P-TEFb assembly into the 7SK RNP and further considerations for understanding Hexim–Tat competition during viral transcription.
Inferring chromatin architecture at a single locus through probabilistic in situ DNA localization
Electrochemical desulfurative borylation of thiols, disulfides, thioethers and thioacetals
Abstract Low-valent sulfur-containing compounds are abundant among natural and synthetic products but remain underutilized as starting materials in desulfurative transformations. Herein, we present thiols, disulfides, thioethers, and thioacetals as precursors in a direct desulfurative electrochemical process for the formation of alkylboronic esters, including late-stage functionalization of pharmaceutically relevant scaffolds and natural products. The electrochemical protocol is simple, user-friendly and scalable, successfully producing gram quantities of borylated product.