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A conifer metabolite corrects episodic ataxia type 1 by voltage sensor-mediated ligand activation of Kv1.1.
Proc Natl Acad Sci U S A
January 2025
Bioelectricity Laboratory, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA 92697.
Loss-of-function sequence variants in , which encodes the voltage-gated potassium channel Kv1.1, cause Episodic Ataxia Type 1 (EA1) and epilepsy. Due to a paucity of drugs that directly rescue mutant Kv1.
View Article and Find Full Text PDFMetabolic enhancement contributed by horizontal gene transfer is essential for dietary specialization in leaf beetles.
Proc Natl Acad Sci U S A
January 2025
State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan 430062, China.
Horizontal gene transfer (HGT) from bacteria to insects is widely reported and often associated with the adaptation and diversification of insects. However, compelling evidence demonstrating how HGT-conferred metabolic adjustments enable species to adapt to surrounding environment remains scarce. Dietary specialization is an important ecological strategy adopted by animals to reduce inter- and intraspecific competition for limited resources.
View Article and Find Full Text PDFGeometrically modulated contact forces enable hula hoop levitation.
Proc Natl Acad Sci U S A
January 2025
Applied Mathematics Laboratory, Courant Institute of Mathematical Sciences, Department of Mathematics, New York University, New York, NY 10012.
Mechanical systems with moving points of contact-including rolling, sliding, and impacts-are common in engineering applications and everyday experiences. The challenges in analyzing such systems are compounded when an object dynamically explores the complex surface shape of a moving structure, as arises in familiar but poorly understood contexts such as hula hooping. We study this activity as a unique form of mechanical levitation against gravity and identify the conditions required for the stable suspension of an object rolling around a gyrating body.
View Article and Find Full Text PDFLiquid-nano-liquid interface-oriented anisotropic encapsulation.
Proc Natl Acad Sci U S A
January 2025
Department of Chemistry, State Key Laboratory of Molecular Engineering of Polymers, College of Chemistry and Materials, iChem (Collaborative Innovation Center of Chemistry for Energy Materials), Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai 200433, China.
Emulsion interface engineering has been widely employed for the synthesis of nanomaterials with various morphologies. However, the instability of the liquid-liquid interface and uncertain interfacial interactions impose significant limitations on controllable fabrications. Here, we developed a liquid-nano-liquid interface-oriented anisotropic encapsulation strategy for fabricating asymmetric nanohybrids.
View Article and Find Full Text PDFComputational-aided rational mutation design of pertuzumab to overcome active HER2 mutation S310F through antibody-drug conjugates.
Proc Natl Acad Sci U S A
January 2025
Laboratory of Precision Medicine and Biopharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Recurrent missense mutations in the human epidermal growth factor receptor 2 (HER2) have been identified across various human cancers. Among these mutations, the active S310F mutation in the HER2 extracellular domain stands out as not only oncogenic but also confers resistance to pertuzumab, an antibody drug widely used in clinical cancer therapy, by impeding its binding. In this study, we have successfully employed computational-aided rational design to undertake directed evolution of pertuzumab, resulting in the creation of an evolved pertuzumab variant named Ptz-SA.
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