Alzheimer's disease(AD)is closely linked to the accumulation of amyloid-beta peptides(Aβ),which impair synaptic plasticity and contribute to cognitive decline.Among the fragments of Aβ,the CT16 peptide(the equiv...Alzheimer's disease(AD)is closely linked to the accumulation of amyloid-beta peptides(Aβ),which impair synaptic plasticity and contribute to cognitive decline.Among the fragments of Aβ,the CT16 peptide(the equivalent of Aβ16,derived from soluble amyloid precursor proteinα,s APPα)has been shown to interact with theα7 nicotinic acetylcholine receptor(α7nAChR),potentially enhancing synaptic plasticity.However,the concentrationdependent modulation of CT16 onα7nAChR and its underlying mechanisms remain poorly understood.We employ molecular dynamics simulations to investigate how varying concentrations of CT16 affect the conformation and function of theα7nAChR,and establishes the proportional relationship between CT16 concentration andα7nAChR receptor function regulation at the molecular level,finding a stoichiometric ratio of 1:3 for maximum activation ofα7nAChR by CT16,and establishing the first demonstration that the constriction geometry of the pore within extracellular domain(specifically its minimal cross-sectional area)serves as the dominant structural determinant for ion permeation pathways at stoichiometric CT16:α7nAChR binding(1:1 ratio),a phenomenon contrasting sharply with scenarios at higher ratios(CT16:α7nAChR>1:1).The presence of CT16 not only induces significant conformational changes,stabilizes specific receptor regions,but also modulates the ion channel's pore geometry in a concentration-dependent manner.These findings shed light on the potential role of CT16 in regulating synaptic plasticity and offer theoretical insights into its dual role as a positive allosteric modulator at low concentrations and an inhibitor at higher concentrations,which may have implications for therapeutic strategies targetingα7nAChR in AD and other neurodegenerative diseases.展开更多
Dose estimation and quality control in computed tomography (CT) scanners are useful in controlling the dose of radiation given to patients while tests are carried out. The study was performed in a 16-slice Computed To...Dose estimation and quality control in computed tomography (CT) scanners are useful in controlling the dose of radiation given to patients while tests are carried out. The study was performed in a 16-slice Computed Tomography (CT) system of LightSpeed RT16 Xtra CT scanner. Quality control was done using a vendor-provided QA Phantom, and the six aspects of image quality were measured. For CT dosimetry, Computed Tomography Dose index volume (CTDIvol) was performed using Computed Tomography Dose Index (CTDI) Phantom. CTDI Phantom consists of three parts: Pediatric Head, Adult Head, and Adult Body Phantom. A 10 cm long pencil ion chamber DCT-10 was used to measure the dose at different positions inside the CTDI Phantom. Data were collected using MagicMax Universal software. For dose estimation of the CTDIvol Report of AAPM Task Group, 96 and 111 formalisms were used. For Pediatric Head, Adult Head, and Adult Body Phantom the measured CIDIvol was 61.04 mGy, 48.11 mGy, and 18.08 mGy respectively. The study has shown deviations of 7%, 15%, and 19% between estimated and console-displayed doses for Pediatric Head, Adult Head, and Adult Body scan techniques respectively. The six aspects of image quality measured by QA Phantom were found to be compatible with the specifications of the machine and CTDIvol measured by CTDI Phantom were found within a tolerance limit of ±20%. Hence, the QC and dosimetry of the mentioned machine are within the limit.展开更多
基金supported by the Shandong Provincial Natural Science Foundation(ZR2022MB073)of China。
文摘Alzheimer's disease(AD)is closely linked to the accumulation of amyloid-beta peptides(Aβ),which impair synaptic plasticity and contribute to cognitive decline.Among the fragments of Aβ,the CT16 peptide(the equivalent of Aβ16,derived from soluble amyloid precursor proteinα,s APPα)has been shown to interact with theα7 nicotinic acetylcholine receptor(α7nAChR),potentially enhancing synaptic plasticity.However,the concentrationdependent modulation of CT16 onα7nAChR and its underlying mechanisms remain poorly understood.We employ molecular dynamics simulations to investigate how varying concentrations of CT16 affect the conformation and function of theα7nAChR,and establishes the proportional relationship between CT16 concentration andα7nAChR receptor function regulation at the molecular level,finding a stoichiometric ratio of 1:3 for maximum activation ofα7nAChR by CT16,and establishing the first demonstration that the constriction geometry of the pore within extracellular domain(specifically its minimal cross-sectional area)serves as the dominant structural determinant for ion permeation pathways at stoichiometric CT16:α7nAChR binding(1:1 ratio),a phenomenon contrasting sharply with scenarios at higher ratios(CT16:α7nAChR>1:1).The presence of CT16 not only induces significant conformational changes,stabilizes specific receptor regions,but also modulates the ion channel's pore geometry in a concentration-dependent manner.These findings shed light on the potential role of CT16 in regulating synaptic plasticity and offer theoretical insights into its dual role as a positive allosteric modulator at low concentrations and an inhibitor at higher concentrations,which may have implications for therapeutic strategies targetingα7nAChR in AD and other neurodegenerative diseases.
文摘Dose estimation and quality control in computed tomography (CT) scanners are useful in controlling the dose of radiation given to patients while tests are carried out. The study was performed in a 16-slice Computed Tomography (CT) system of LightSpeed RT16 Xtra CT scanner. Quality control was done using a vendor-provided QA Phantom, and the six aspects of image quality were measured. For CT dosimetry, Computed Tomography Dose index volume (CTDIvol) was performed using Computed Tomography Dose Index (CTDI) Phantom. CTDI Phantom consists of three parts: Pediatric Head, Adult Head, and Adult Body Phantom. A 10 cm long pencil ion chamber DCT-10 was used to measure the dose at different positions inside the CTDI Phantom. Data were collected using MagicMax Universal software. For dose estimation of the CTDIvol Report of AAPM Task Group, 96 and 111 formalisms were used. For Pediatric Head, Adult Head, and Adult Body Phantom the measured CIDIvol was 61.04 mGy, 48.11 mGy, and 18.08 mGy respectively. The study has shown deviations of 7%, 15%, and 19% between estimated and console-displayed doses for Pediatric Head, Adult Head, and Adult Body scan techniques respectively. The six aspects of image quality measured by QA Phantom were found to be compatible with the specifications of the machine and CTDIvol measured by CTDI Phantom were found within a tolerance limit of ±20%. Hence, the QC and dosimetry of the mentioned machine are within the limit.
