Epilepsy is a chronic neurological disorder affecting~65 million individuals worldwide.Abnormal synaptic plasticity is one of the most important pathological features of this condition.We investigated how ubiquitin-sp...Epilepsy is a chronic neurological disorder affecting~65 million individuals worldwide.Abnormal synaptic plasticity is one of the most important pathological features of this condition.We investigated how ubiquitin-specific peptidase 47(USP47)influences synaptic plasticity and its link to epilepsy.We found that USP47 enhanced excitatory postsynaptic transmission and increased the density of total dendritic spines and the proportion of mature dendritic spines.Furthermore,USP47 inhibited the degradation of the ubiquitinatedα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor(AMPAR)subunit glutamate receptor 1(GluR1),which is associated with synaptic plasticity.In addition,elevated levels of USP47 were found in epileptic mice,and USP47 knockdown reduced the frequency and duration of seizure-like events and alleviated epileptic seizures.To summarize,we present a new mechanism whereby USP47 regulates excitatory postsynaptic plasticity through the inhibition of ubiquitinated GluR1 degradation.Modulating USP47 may offer a potential approach for controlling seizures and modifying disease progression in future therapeutic strategies.展开更多
Noninvasive tomographic imaging of cellular processes in vivo may provide valuable cytological and histological information for disease diagnosis.However,such strategies are usually hampered by optical aberrations cau...Noninvasive tomographic imaging of cellular processes in vivo may provide valuable cytological and histological information for disease diagnosis.However,such strategies are usually hampered by optical aberrations caused by the imaging system and tissue turbidity.State-of-the-art aberration correction methods require that the light signal be phase stable over the full-field data acquisition period,which is difficult to maintain during dynamic cellular processes in vivo.Here we show that any optical aberrations in the path length difference(OPD)domain can be corrected without the phase stability requirement based on maximum intensity assumption.Specifically,we demonstrate a novel optical tomographic technique,termed amplitude division aperture synthesis optical coherence tomography(ADAS-OCT),which corrects aberrations induced by turbid tissues by physical aperture synthesis and simultaneously data acquisition from sub-apertures.Even with just two subapertures,ADAS-OCT enabled in vivo visualization of red blood cells in human labial mucosa.We further demonstrated that adding sub-apertures could significantly scale up the aberration correction capability.This technology has the potential to impact a number of clinical areas where noninvasive examinations are preferred,such as blood count and cancers detection.展开更多
基金supported by grants from the National Natural Science Foundation of China(82071458 and 32160190)the United Foundation of Zunyi Municipality(Zunshikehe HZ Zi(2021)14)+3 种基金the Science and Technology Project of Guizhou Provincial Health Commission(gzwkj2021-020)the Guizhou Epilepsy Basic and Clinical Research Scientific,Technological Innovation Talent Team Project(CXTD[2022]013)the Excellent Young Talents Training Program of the Affiliated Hospital of Zunyi Medical University(rc220220906)the Guizhou Provincial Hundred Level Innovative Talents Funds(GCC-2022-038-1).
文摘Epilepsy is a chronic neurological disorder affecting~65 million individuals worldwide.Abnormal synaptic plasticity is one of the most important pathological features of this condition.We investigated how ubiquitin-specific peptidase 47(USP47)influences synaptic plasticity and its link to epilepsy.We found that USP47 enhanced excitatory postsynaptic transmission and increased the density of total dendritic spines and the proportion of mature dendritic spines.Furthermore,USP47 inhibited the degradation of the ubiquitinatedα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor(AMPAR)subunit glutamate receptor 1(GluR1),which is associated with synaptic plasticity.In addition,elevated levels of USP47 were found in epileptic mice,and USP47 knockdown reduced the frequency and duration of seizure-like events and alleviated epileptic seizures.To summarize,we present a new mechanism whereby USP47 regulates excitatory postsynaptic plasticity through the inhibition of ubiquitinated GluR1 degradation.Modulating USP47 may offer a potential approach for controlling seizures and modifying disease progression in future therapeutic strategies.
基金supported by National Research Foundation Singapore under its Competitive Research Program(NRF-CRP13–2014-05)Ministry of Education Singapore under its Academic Research Fund Tier 1(2018-T1–001-144)Agency for Science,Technology and Research(A*STAR)under its Industrial Alignment Fund(Pre-positioning)(H17/01/a0/008).
文摘Noninvasive tomographic imaging of cellular processes in vivo may provide valuable cytological and histological information for disease diagnosis.However,such strategies are usually hampered by optical aberrations caused by the imaging system and tissue turbidity.State-of-the-art aberration correction methods require that the light signal be phase stable over the full-field data acquisition period,which is difficult to maintain during dynamic cellular processes in vivo.Here we show that any optical aberrations in the path length difference(OPD)domain can be corrected without the phase stability requirement based on maximum intensity assumption.Specifically,we demonstrate a novel optical tomographic technique,termed amplitude division aperture synthesis optical coherence tomography(ADAS-OCT),which corrects aberrations induced by turbid tissues by physical aperture synthesis and simultaneously data acquisition from sub-apertures.Even with just two subapertures,ADAS-OCT enabled in vivo visualization of red blood cells in human labial mucosa.We further demonstrated that adding sub-apertures could significantly scale up the aberration correction capability.This technology has the potential to impact a number of clinical areas where noninvasive examinations are preferred,such as blood count and cancers detection.
