Studies showed that complexation of polyphenols with milk allergens reduced their immunogenic potential.However,the relationship between structures of polyphenols and their hypoallergenic effects on milk allergens in ...Studies showed that complexation of polyphenols with milk allergens reduced their immunogenic potential.However,the relationship between structures of polyphenols and their hypoallergenic effects on milk allergens in association with physiological and conformational changes of the complexes remain unclear.In this study,polyphenols from eight botanical sources were extracted to prepare non-covalent complexes withβ-lactoglobulin(β-LG),a major allergen in milk.The dominant phenolic compounds bound toβ-LG with a diminished allergenicity were identified to investigate their respective role on the structural and allergenic properties ofβ-LG.Extracts from Vaccinium fruits and black soybeans were found to have great inhibitory effects on the IgE-and IgG-binding abilities ofβ-LG.Among the fourteen structure-related phenolic compounds,flavonoids and tannins with larger MWs and multi-hydroxyl substituents,notably rutin,EGCG,and ellagitannins were more potent to elicit changes on the conformational structures ofβ-LG to decrease the allergenicity of complexedβ-LG.Correlation analysis further demonstrated that a destabilized secondary structure and protein depolymerization caused by polyphenol-binding were closely related to the allergenicity property of formed complexes.This study provides insights into the understanding of structure-allergenicity relationship ofβ-LG-polyphenol interactions and would benefit the development of polyphenol-fortified matrices with hypoallergenic potential.展开更多
γ-Secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the ...γ-Secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface receptors.Mutations inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-Secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as well.However,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-secretase.In this review,we focus on recent studies of structural dynamic mechanisms ofγ-secretase.Different mechanisms,including the“Fit-Stay-Trim,”“Sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics simulations.While an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental findings.The approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-secretase.In addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is discussed.Finally,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations of theγ-secretase-substrate complexes.Comprehensive understanding of the functional mechanisms ofγ-secretase will greatly facilitate the rational design of effective drug molecules for treating familial Alzheimer’s disease and perhaps Alzheimer’s disease in general.展开更多
Here, using the Scale-Symmetric Theory (SST) we explain the cosmological tension and the origin of the largest cosmic structures. We show that a change in value of strong coupling constant for cold baryonic matter lea...Here, using the Scale-Symmetric Theory (SST) we explain the cosmological tension and the origin of the largest cosmic structures. We show that a change in value of strong coupling constant for cold baryonic matter leads to the disagreement in the galaxy clustering amplitude, quantified by the parameter S8. Within the same model we described the Hubble tension. We described also the mechanism that transforms the gravitational collapse into an explosion—it concerns the dynamics of virtual fields that lead to dark energy. Our calculations concern the Type Ia supernovae and the core-collapse supernovae. We calculated the quantized masses of the progenitors of supernovae, emitted total energy during explosion, and we calculated how much of the released energy was transferred to neutrinos. Value of the speed of sound in the strongly interacting matter measured at the LHC confirms that presented here model is correct. Our calculations show that the Universe is cyclic.展开更多
Plankton size structure is crucial for understanding marine ecosystem dynamics and the associated biogeochemical processes.A fixation step by acid Lugol’s solution has been commonly employed to preserve plankton samp...Plankton size structure is crucial for understanding marine ecosystem dynamics and the associated biogeochemical processes.A fixation step by acid Lugol’s solution has been commonly employed to preserve plankton samples in the field.However,the acid Lugol’s solution can bias the estimation of size structure and the preserved plankton size structure can vary with time.Here,we explore the impact of sample storage time on the size-structure of the plankton community preserved by Lugol’s solution.Two short-term experiments and one long-term experiment were conducted to explore the change of plankton community size structure with the storage time:covering from a week to a month,and to nearly seven months based on particle-size data obtained by continuous Flow Cytometer and Microscope(FlowCAM)measurements.We found a linear change of plankton size with the storage time in short-term periods(less than 3 months)with a decrease of the slope but an increase of the intercept for the normalized biomass size spectrum(NBS S).However,there were opposite trends for NBSS with increasing slope but decreasing intercept after3 months.The potential causes of the distinct patterns of the NBSS parameters are addressed in terms of the interplay between particle aggregation and fragmentation.We found large changes in plankton biovolume and abundance among different size classes,which may indicate a distinct effect of acid Lugol’s solution on various plankton size classes.The mechanism driving temporal change in the size-structure of the Lugolfixed plankton community was further discussed in terms of particle aggregation and fragmentation.Finally,we emphasize that the effect of storage time should be taken into account when interpreting or comparing data of plankton community acquired from samples with various storage durations.展开更多
On December 18,2023,an M_(s)6.2 earthquake occurred in Jishishan,Gansu Province,China.This earthquake happened in the eastern region of the Qilian Orogenic Belt,which is situated at the forefront of the NE margin of t...On December 18,2023,an M_(s)6.2 earthquake occurred in Jishishan,Gansu Province,China.This earthquake happened in the eastern region of the Qilian Orogenic Belt,which is situated at the forefront of the NE margin of the Tibetan Plateau(i.e.,Qinghai-Tibet Plateau),encompassing a rhombic-shaped area that intersects the Qilian-Qaidam Basin,Alxa Block,Ordos Block,and South China Block.In this study,we analyzed the deep tectonic pattern of the Jishishan earthquake by incorporating data on the crustal thickness,velocity structure,global navigation satellite system(GNSS)strain field,and anisotropy.We discovered that the location of the earthquake was related to changes in the crustal structure.The results showed that the Jishishan M_(s)6.2 earthquake occurred in a unique position,with rapid changes in the crustal thickness,Vp/Vs,phase velocity,and S-wave velocity.The epicenter of the earthquake was situated at the transition zone between high and low velocities and was in proximity to a low-velocity region.Additionally,the source area is flanked by two high-velocity anomalies from the east and west.The principal compressive strain orientation near the Lajishan Fault is primarily in the NNE and NE directions,which align with the principal compressive stress direction in this region.In some areas of the Lajishan Fault,the principal compressive strain orientations show the NNW direction,consistent with the direction of the upper crustal fast-wave polarization from local earthquakes and the phase velocity azimuthal anisotropy.These features underscore the relationship between the occurrence of the Jishishan M_(s)6.2 earthquake and the deep inhomogeneous structure and deep tectonic characteristics.The NE margin of the Tibetan Plateau was thickened by crustal extension in the process of northeastward expansion,and the middle and lower crustal materials underwent structural deformation and may have been filled with salt-containing fluids during the extension process.The presence of this weak layer makes it easier for strong earthquakes to occur through the release of overlying rigid crustal stresses.However,it is unlikely that an earthquake of comparable or larger magnitude would occur in the short term(e.g.,in one year)at the Jishishan east margin fault.展开更多
基金supported by the Zhejiang Provincial Natural Science Foundation of China(LGN22C200027 and LZ23C200001).
文摘Studies showed that complexation of polyphenols with milk allergens reduced their immunogenic potential.However,the relationship between structures of polyphenols and their hypoallergenic effects on milk allergens in association with physiological and conformational changes of the complexes remain unclear.In this study,polyphenols from eight botanical sources were extracted to prepare non-covalent complexes withβ-lactoglobulin(β-LG),a major allergen in milk.The dominant phenolic compounds bound toβ-LG with a diminished allergenicity were identified to investigate their respective role on the structural and allergenic properties ofβ-LG.Extracts from Vaccinium fruits and black soybeans were found to have great inhibitory effects on the IgE-and IgG-binding abilities ofβ-LG.Among the fourteen structure-related phenolic compounds,flavonoids and tannins with larger MWs and multi-hydroxyl substituents,notably rutin,EGCG,and ellagitannins were more potent to elicit changes on the conformational structures ofβ-LG to decrease the allergenicity of complexedβ-LG.Correlation analysis further demonstrated that a destabilized secondary structure and protein depolymerization caused by polyphenol-binding were closely related to the allergenicity property of formed complexes.This study provides insights into the understanding of structure-allergenicity relationship ofβ-LG-polyphenol interactions and would benefit the development of polyphenol-fortified matrices with hypoallergenic potential.
基金supported in part by Award 2121063 from National Science Foundation(to YM)AG66986 from the National Institutes of Health(to MSW).
文摘γ-Secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface receptors.Mutations inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-Secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as well.However,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-secretase.In this review,we focus on recent studies of structural dynamic mechanisms ofγ-secretase.Different mechanisms,including the“Fit-Stay-Trim,”“Sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics simulations.While an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental findings.The approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-secretase.In addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is discussed.Finally,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations of theγ-secretase-substrate complexes.Comprehensive understanding of the functional mechanisms ofγ-secretase will greatly facilitate the rational design of effective drug molecules for treating familial Alzheimer’s disease and perhaps Alzheimer’s disease in general.
文摘Here, using the Scale-Symmetric Theory (SST) we explain the cosmological tension and the origin of the largest cosmic structures. We show that a change in value of strong coupling constant for cold baryonic matter leads to the disagreement in the galaxy clustering amplitude, quantified by the parameter S8. Within the same model we described the Hubble tension. We described also the mechanism that transforms the gravitational collapse into an explosion—it concerns the dynamics of virtual fields that lead to dark energy. Our calculations concern the Type Ia supernovae and the core-collapse supernovae. We calculated the quantized masses of the progenitors of supernovae, emitted total energy during explosion, and we calculated how much of the released energy was transferred to neutrinos. Value of the speed of sound in the strongly interacting matter measured at the LHC confirms that presented here model is correct. Our calculations show that the Universe is cyclic.
基金Supported by the Guangdong Province Special Support Plan for Leading Talents(No.2019TX05H216)the Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou)(No.GML2019ZD0305)+1 种基金the National Natural Science Foundation of China(No.41906132)the Science and Technology Program of Guangzhou(No.202102021229)。
文摘Plankton size structure is crucial for understanding marine ecosystem dynamics and the associated biogeochemical processes.A fixation step by acid Lugol’s solution has been commonly employed to preserve plankton samples in the field.However,the acid Lugol’s solution can bias the estimation of size structure and the preserved plankton size structure can vary with time.Here,we explore the impact of sample storage time on the size-structure of the plankton community preserved by Lugol’s solution.Two short-term experiments and one long-term experiment were conducted to explore the change of plankton community size structure with the storage time:covering from a week to a month,and to nearly seven months based on particle-size data obtained by continuous Flow Cytometer and Microscope(FlowCAM)measurements.We found a linear change of plankton size with the storage time in short-term periods(less than 3 months)with a decrease of the slope but an increase of the intercept for the normalized biomass size spectrum(NBS S).However,there were opposite trends for NBSS with increasing slope but decreasing intercept after3 months.The potential causes of the distinct patterns of the NBSS parameters are addressed in terms of the interplay between particle aggregation and fragmentation.We found large changes in plankton biovolume and abundance among different size classes,which may indicate a distinct effect of acid Lugol’s solution on various plankton size classes.The mechanism driving temporal change in the size-structure of the Lugolfixed plankton community was further discussed in terms of particle aggregation and fragmentation.Finally,we emphasize that the effect of storage time should be taken into account when interpreting or comparing data of plankton community acquired from samples with various storage durations.
基金the National Natural Science Foundation of China(Project Nos.41804046 and 41974050)the Special Fund of the Key Laboratory of Earthquake Prediction,China Earthquake Administration(No.CEAIEF2022010100).
文摘On December 18,2023,an M_(s)6.2 earthquake occurred in Jishishan,Gansu Province,China.This earthquake happened in the eastern region of the Qilian Orogenic Belt,which is situated at the forefront of the NE margin of the Tibetan Plateau(i.e.,Qinghai-Tibet Plateau),encompassing a rhombic-shaped area that intersects the Qilian-Qaidam Basin,Alxa Block,Ordos Block,and South China Block.In this study,we analyzed the deep tectonic pattern of the Jishishan earthquake by incorporating data on the crustal thickness,velocity structure,global navigation satellite system(GNSS)strain field,and anisotropy.We discovered that the location of the earthquake was related to changes in the crustal structure.The results showed that the Jishishan M_(s)6.2 earthquake occurred in a unique position,with rapid changes in the crustal thickness,Vp/Vs,phase velocity,and S-wave velocity.The epicenter of the earthquake was situated at the transition zone between high and low velocities and was in proximity to a low-velocity region.Additionally,the source area is flanked by two high-velocity anomalies from the east and west.The principal compressive strain orientation near the Lajishan Fault is primarily in the NNE and NE directions,which align with the principal compressive stress direction in this region.In some areas of the Lajishan Fault,the principal compressive strain orientations show the NNW direction,consistent with the direction of the upper crustal fast-wave polarization from local earthquakes and the phase velocity azimuthal anisotropy.These features underscore the relationship between the occurrence of the Jishishan M_(s)6.2 earthquake and the deep inhomogeneous structure and deep tectonic characteristics.The NE margin of the Tibetan Plateau was thickened by crustal extension in the process of northeastward expansion,and the middle and lower crustal materials underwent structural deformation and may have been filled with salt-containing fluids during the extension process.The presence of this weak layer makes it easier for strong earthquakes to occur through the release of overlying rigid crustal stresses.However,it is unlikely that an earthquake of comparable or larger magnitude would occur in the short term(e.g.,in one year)at the Jishishan east margin fault.
