Protein synthesis is essential for cells to perform life metabolic processes.Pathological alterations of protein content can lead to particular diseases.Cells have an intrinsic array of mechanisms and pathways that ar...Protein synthesis is essential for cells to perform life metabolic processes.Pathological alterations of protein content can lead to particular diseases.Cells have an intrinsic array of mechanisms and pathways that are activated when protein misfolding,accumulation,aggregation or mislocalization occur.Some of them(like the unfolded protein response)represent complex interactions between endoplasmic reticulum sensors and elongation factors that tend to increase expression of chaperone proteins and/or repress translation in order to restore protein homeostasis(also known as proteostasis).This is even more important in neurons,as they are very susceptible to harmful effects associated with protein overload and proteostatic mechanisms are less effective with age.Several neurodegenerative pathologies such as Alzheimer’s,Parkinson’s,and Huntington’s diseases,amyotrophic lateral sclerosis and frontotemporal dementia exhibit a particular molecular signature of distinct,unbalanced protein overload.In amyotrophic lateral sclerosis and frontotemporal dementia,the majority of cases present intracellular inclusions of ubiquitinated transactive response DNA-binding protein of 43 kDa(TDP-43).TDP-43 is an RNA binding protein that participates in RNA metabolism,among other functions.Dysregulation of TDP-43(e.g.aggregation and mislocalization)can dramatically affect neurons,and this has been linked to disease development.Expression of amyotrophic lateral sclerosis/frontotemporal dementia TDP-43-related mutations in cellular and animal models has been shown to recapitulate key features of the amyotrophic lateral sclerosis/frontotemporal dementia disease spectrum.These variants can be causative of degeneration onset and progression.Most neurodegenerative diseases(including amyotrophic lateral sclerosis and frontotemporal dementia)have no cure at the moment;however,modulating translation has recently emerged as an attractive approach that can be performed at several steps(i.e.regulating activation of initiation and elongation factors,inhibiting unfolded protein response activation or inducing chaperone expression and activity).This review focuses on the features of protein imbalance in neurodegenerative disorders and the relevance of developing therapeutical compounds aiming at restoring proteostasis.We strive to highlight the importance of research on drugs that,not only restore protein imbalance without compromising translational activity of cells,but are also as safe as possible for the patients.展开更多
The full-bridge converters usually use transformer leakage inductance and parallel resonant capacitors to achieve smooth current commutation and soft switching functions,which can easily cause problems such as energy ...The full-bridge converters usually use transformer leakage inductance and parallel resonant capacitors to achieve smooth current commutation and soft switching functions,which can easily cause problems such as energy leakage and significant duty cycle loss.This paper designs a novel full-bridge zero-current(FB-ZCS)converter with series resonant capacitors and proposes a frequency and phase-shift synthesis modulation(FPSSM)control strategy based on this topology.Compared with the traditional parallel resonant capacitor circuit,the passive components used are significantly reduced,the structure is simple,and there is only a slight energy loss.By controlling the charging time of the capacitor,it can be achieved without additional switches or auxiliary circuits.The automatic control of capacitor energy based on input current addresses the low efficiency of the traditional control strategies.This paper introduces its principle in detail and verifies it through simulation.Finally,an experimental prototype was built further to demonstrate the feasibility of the theory through experiments.The module can be applied to a photovoltaic DC collection system using input parallel output series(IPOS)cascade to provide a new topology for large-scale,long-distance DC transmission.展开更多
Hollow metal-organic frameworks(MOFs)have attracted increasing attention in the field of catalysis in recent years due to their unique cavity structure with fast mass-diffusion rates and easily accessible active sites...Hollow metal-organic frameworks(MOFs)have attracted increasing attention in the field of catalysis in recent years due to their unique cavity structure with fast mass-diffusion rates and easily accessible active sites.Here,we report the use of dynamic modulators,which are formed by the in-situ imine condensation reaction of 4-aminobenzoic acid and 4-formylbenzoic acid,to regulate the growth of MOFs to synthesize well-defined hollow thioether functionalized UiO-67(denoted as H-UiO-67-S)single crystals.After supporting Pd nanoparticles,the designed catalysts Pd@H-UiO-67-S show excellent conversion(>99.9%),selectivity(>99.9%),and stability(10 cycles)in the selective hydrogenation of nitrobenzenes with other reducible groups.Density functional theory calculations and the experimental results reveal that Pd nanoparticles not only selectively adsorb the nitro-groups on nitrobenzene,but also restrict the adsorption of the aniline product,due to the interaction of thioether with Pd in the confined pores of H-UiO-67-S,finally result in a significant increase in selectivity of nitro-hydrogenation.展开更多
DNA translesion synthesis(TLS)is a DNA damage tolerance mechanism that relies on a series of specialized DNA polymerases able to bypass a lesion on a DNA template strand during replication or post-repair synthesis.TLS...DNA translesion synthesis(TLS)is a DNA damage tolerance mechanism that relies on a series of specialized DNA polymerases able to bypass a lesion on a DNA template strand during replication or post-repair synthesis.TLS DNA polymerases pursue replication by inserting a base opposite this lesion,correctly or incorrectly展开更多
基金supported by research grants to LMI from University of Buenos Aires(UBACyT)the Agencia Nacional de Promoción Científica y Tecnológica(ANPCyT)under grants PICT 2015-0975 and PICT 2017-2140。
文摘Protein synthesis is essential for cells to perform life metabolic processes.Pathological alterations of protein content can lead to particular diseases.Cells have an intrinsic array of mechanisms and pathways that are activated when protein misfolding,accumulation,aggregation or mislocalization occur.Some of them(like the unfolded protein response)represent complex interactions between endoplasmic reticulum sensors and elongation factors that tend to increase expression of chaperone proteins and/or repress translation in order to restore protein homeostasis(also known as proteostasis).This is even more important in neurons,as they are very susceptible to harmful effects associated with protein overload and proteostatic mechanisms are less effective with age.Several neurodegenerative pathologies such as Alzheimer’s,Parkinson’s,and Huntington’s diseases,amyotrophic lateral sclerosis and frontotemporal dementia exhibit a particular molecular signature of distinct,unbalanced protein overload.In amyotrophic lateral sclerosis and frontotemporal dementia,the majority of cases present intracellular inclusions of ubiquitinated transactive response DNA-binding protein of 43 kDa(TDP-43).TDP-43 is an RNA binding protein that participates in RNA metabolism,among other functions.Dysregulation of TDP-43(e.g.aggregation and mislocalization)can dramatically affect neurons,and this has been linked to disease development.Expression of amyotrophic lateral sclerosis/frontotemporal dementia TDP-43-related mutations in cellular and animal models has been shown to recapitulate key features of the amyotrophic lateral sclerosis/frontotemporal dementia disease spectrum.These variants can be causative of degeneration onset and progression.Most neurodegenerative diseases(including amyotrophic lateral sclerosis and frontotemporal dementia)have no cure at the moment;however,modulating translation has recently emerged as an attractive approach that can be performed at several steps(i.e.regulating activation of initiation and elongation factors,inhibiting unfolded protein response activation or inducing chaperone expression and activity).This review focuses on the features of protein imbalance in neurodegenerative disorders and the relevance of developing therapeutical compounds aiming at restoring proteostasis.We strive to highlight the importance of research on drugs that,not only restore protein imbalance without compromising translational activity of cells,but are also as safe as possible for the patients.
基金This work was supported by the Key R&D Program of Tianjin(No.20YFYSGX00060).
文摘The full-bridge converters usually use transformer leakage inductance and parallel resonant capacitors to achieve smooth current commutation and soft switching functions,which can easily cause problems such as energy leakage and significant duty cycle loss.This paper designs a novel full-bridge zero-current(FB-ZCS)converter with series resonant capacitors and proposes a frequency and phase-shift synthesis modulation(FPSSM)control strategy based on this topology.Compared with the traditional parallel resonant capacitor circuit,the passive components used are significantly reduced,the structure is simple,and there is only a slight energy loss.By controlling the charging time of the capacitor,it can be achieved without additional switches or auxiliary circuits.The automatic control of capacitor energy based on input current addresses the low efficiency of the traditional control strategies.This paper introduces its principle in detail and verifies it through simulation.Finally,an experimental prototype was built further to demonstrate the feasibility of the theory through experiments.The module can be applied to a photovoltaic DC collection system using input parallel output series(IPOS)cascade to provide a new topology for large-scale,long-distance DC transmission.
基金The authors acknowledge financial support from the National Natural Science Foundation of China(Nos.21905195,M.T.Z.and 22103055,J.G.)Natural Science Foundation of Tianjin City(No.20JCYBJC00800,M.T.Z.)+1 种基金Science and Technology Plans of Tianjin(No.21ZYJDJC00050,J.G.)PEIYANG Young Scholars Program of Tianjin University(No.2020XRX-0023,M.T.Z.).
文摘Hollow metal-organic frameworks(MOFs)have attracted increasing attention in the field of catalysis in recent years due to their unique cavity structure with fast mass-diffusion rates and easily accessible active sites.Here,we report the use of dynamic modulators,which are formed by the in-situ imine condensation reaction of 4-aminobenzoic acid and 4-formylbenzoic acid,to regulate the growth of MOFs to synthesize well-defined hollow thioether functionalized UiO-67(denoted as H-UiO-67-S)single crystals.After supporting Pd nanoparticles,the designed catalysts Pd@H-UiO-67-S show excellent conversion(>99.9%),selectivity(>99.9%),and stability(10 cycles)in the selective hydrogenation of nitrobenzenes with other reducible groups.Density functional theory calculations and the experimental results reveal that Pd nanoparticles not only selectively adsorb the nitro-groups on nitrobenzene,but also restrict the adsorption of the aniline product,due to the interaction of thioether with Pd in the confined pores of H-UiO-67-S,finally result in a significant increase in selectivity of nitro-hydrogenation.
文摘DNA translesion synthesis(TLS)is a DNA damage tolerance mechanism that relies on a series of specialized DNA polymerases able to bypass a lesion on a DNA template strand during replication or post-repair synthesis.TLS DNA polymerases pursue replication by inserting a base opposite this lesion,correctly or incorrectly
