The M2 proteins of influenza A and B virus,AM2 and BM2,respectively,are transmembrane proteins that oligomerize in the viral membrane to form proton-selective channels.Proton conductance of the M2 proteins is required...The M2 proteins of influenza A and B virus,AM2 and BM2,respectively,are transmembrane proteins that oligomerize in the viral membrane to form proton-selective channels.Proton conductance of the M2 proteins is required for viral replication;it is believed to equilibrate pH across the viral membrane during cell entry and across the trans-Golgi membrane of infected cells during viral maturation.In addition to the role of M2 in proton conductance,recent mutagenesis and structural studies suggest that the cytoplasmic domains of the M2 proteins also play a role in recruiting the matrix proteins to the cell surface during virus budding.As viral ion channels of minimalist architecture,the membrane-embedded channel domain of M2 has been a model system for investigating the mechanism of proton conduction.Moreover,as a proven drug target for the treatment of influenza A infection,M2 has been the subject of intense research for developing new anti-flu therapeutics.AM2 is the target of two anti-influenza A drugs,amantadine and rimantadine,both belonging to the adamantane class of compounds.However,resistance of influenza A to adamantane is now widespread due to mutations in the channel domain of AM2.This review summarizes the structure and function of both AM2 and BM2 channels,the mechanism of drug inhibition and drug resistance of AM2,as well as the development of new M2 inhibitors as potential anti-flu drugs.展开更多
Precise,quantitative in vivo monitoring of hydration levels in the near surface regions of the skin can be useful in preventing skinbased pathologies,and regulating external appearance.Here we introduce multimodal sen...Precise,quantitative in vivo monitoring of hydration levels in the near surface regions of the skin can be useful in preventing skinbased pathologies,and regulating external appearance.Here we introduce multimodal sensors with important capabilities in this context,rendered in soft,ultrathin,‘skin-like’formats with numerous advantages over alternative technologies,including the ability to establish intimate,conformal contact without applied pressure,and to provide spatiotemporally resolved data on both electrical and thermal transport properties from sensitive regions of the skin.Systematic in vitro studies and computational models establish the underlying measurement principles and associated approaches for determination of temperature,thermal conductivity,thermal diffusivity,volumetric heat capacity,and electrical impedance using simple analysis algorithms.Clinical studies on 20 patients subjected to a variety of external stimuli validate the device operation and allow quantitative comparisons of measurement capabilities to those of existing state-of-the-art tools.展开更多
基金We thank Matthew Call for insightful discussion and critical reading of the manuscript.This work was supported by the NIH grant AI054520(to JJC).
文摘The M2 proteins of influenza A and B virus,AM2 and BM2,respectively,are transmembrane proteins that oligomerize in the viral membrane to form proton-selective channels.Proton conductance of the M2 proteins is required for viral replication;it is believed to equilibrate pH across the viral membrane during cell entry and across the trans-Golgi membrane of infected cells during viral maturation.In addition to the role of M2 in proton conductance,recent mutagenesis and structural studies suggest that the cytoplasmic domains of the M2 proteins also play a role in recruiting the matrix proteins to the cell surface during virus budding.As viral ion channels of minimalist architecture,the membrane-embedded channel domain of M2 has been a model system for investigating the mechanism of proton conduction.Moreover,as a proven drug target for the treatment of influenza A infection,M2 has been the subject of intense research for developing new anti-flu therapeutics.AM2 is the target of two anti-influenza A drugs,amantadine and rimantadine,both belonging to the adamantane class of compounds.However,resistance of influenza A to adamantane is now widespread due to mutations in the channel domain of AM2.This review summarizes the structure and function of both AM2 and BM2 channels,the mechanism of drug inhibition and drug resistance of AM2,as well as the development of new M2 inhibitors as potential anti-flu drugs.
基金YM and XF acknowledge the support from the National Basic Research Program of China(Grant No.2015CB351900)National Natural Science Foundation of China(Grant Nos.11402135,11320101001)+2 种基金YH acknowledges the support from NSF(Grant Nos.DMR1121262,CMMI1300846,CMMI1400169,and CMMI1534120)the NIH(Grant No.R01EB019337)RCW acknowledges support from the National Science Foundation under grant no.DGE-1144245.
文摘Precise,quantitative in vivo monitoring of hydration levels in the near surface regions of the skin can be useful in preventing skinbased pathologies,and regulating external appearance.Here we introduce multimodal sensors with important capabilities in this context,rendered in soft,ultrathin,‘skin-like’formats with numerous advantages over alternative technologies,including the ability to establish intimate,conformal contact without applied pressure,and to provide spatiotemporally resolved data on both electrical and thermal transport properties from sensitive regions of the skin.Systematic in vitro studies and computational models establish the underlying measurement principles and associated approaches for determination of temperature,thermal conductivity,thermal diffusivity,volumetric heat capacity,and electrical impedance using simple analysis algorithms.Clinical studies on 20 patients subjected to a variety of external stimuli validate the device operation and allow quantitative comparisons of measurement capabilities to those of existing state-of-the-art tools.
