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1.
Nat Commun ; 15(1): 4906, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38851803

ABSTRACT

Various low-density lipoprotein receptors (LPRs) have been identified as entry factors for alphaviruses, and structures of the corresponding virion-receptor complexes have been determined. Here, we analyze the similarities and differences in the receptor binding modes of multiple alphaviruses to understand their ability to infect a wide range of hosts. We further discuss the challenges associated with the development of broad-spectrum treatment strategies against a diverse range of alphaviruses.


Subject(s)
Alphavirus , Antiviral Agents , Receptors, LDL , Virus Internalization , Animals , Humans , Alphavirus/drug effects , Alphavirus/physiology , Alphavirus/genetics , Alphavirus Infections/drug therapy , Alphavirus Infections/virology , Antiviral Agents/therapeutic use , Antiviral Agents/pharmacology , Protein Binding , Receptors, LDL/metabolism , Receptors, LDL/genetics , Receptors, Virus/metabolism , Receptors, Virus/chemistry , Virion/metabolism , Virus Internalization/drug effects
2.
Science ; 382(6667): 223-230, 2023 10 13.
Article in English | MEDLINE | ID: mdl-37824668

ABSTRACT

Neurons relay information via specialized presynaptic compartments for neurotransmission. Unlike conventional organelles, the specialized apparatus characterizing the neuronal presynapse must form de novo. How the components for presynaptic neurotransmission are transported and assembled is poorly understood. Our results show that the rare late endosomal signaling lipid phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] directs the axonal cotransport of synaptic vesicle and active zone proteins in precursor vesicles in human neurons. Precursor vesicles are distinct from conventional secretory organelles, endosomes, and degradative lysosomes and are transported by coincident detection of PI(3,5)P2 and active ARL8 via kinesin KIF1A to the presynaptic compartment. Our findings identify a crucial mechanism that mediates the delivery of synaptic vesicle and active zone proteins to developing synapses.


Subject(s)
Axonal Transport , Neurons , Phosphatidylinositol Phosphates , Synaptic Vesicles , Humans , Axonal Transport/physiology , Kinesins/metabolism , Neurons/metabolism , Synaptic Vesicles/metabolism , Phosphatidylinositol Phosphates/metabolism
3.
Materials (Basel) ; 16(16)2023 Aug 17.
Article in English | MEDLINE | ID: mdl-37629961

ABSTRACT

The gas diffusion layer (GDL), as a key component of proton exchange membrane fuel cells (PEMFCs), plays a crucial role in PEMFC's polarization performance, particularly in mass transport properties at high current densities. To elucidate the correlation between GDLs' structure and their mass transport properties, a limiting current test with the H2 molecular probe was established and employed to investigate three representative GDLs with and without the microporous layer (MPL). By varying humidity and back pressure, the mass transport resistance of three GDLs was measured in an operating fuel cell, and an elaborate analysis of H2 transport was conducted. The results showed that the transport resistance (RDM) of GDLs was affected by the thickness and pore size distribution of the macroporous substrate (MPS) and the MPL. In the process of gas transport, the smaller pore size and thicker MPL increase the force of gas on the pore wall, resulting in an increase in transmission resistance. Through further calculation and analysis, the total transport resistance can be divided into pressure-related resistance (RP) and pressure-independent resistance (RNP). RP mainly originates from the transport resistance in both MPLs and the substrate layers of GDLs, exhibiting a linear relationship to the pressure; RNP mainly originates from the transport resistance in the MPLs. 29BC with thick MPL shows the largest RNP, and T060 without MPL shows the RNP = 0. This methodology enables in situ measurements of mass transport resistances for gas diffusion media, which can be easily applied for developing and deploying PEMFCs.

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