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Jinsong Liu - One of the best experts on this subject based on the ideXlab platform.
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unique conformation in a natural Interruption sequence of type xix collagen revealed by its high resolution crystal structure
Biochemistry, 2018Co-Authors: Congzhao Zhou, Jianxi Xiao, Jinsong LiuAbstract:Naturally occurring Interruptions in nonfibrillar collagen play key roles in molecular flexibility, collagen degradation, and ligand binding. The structural feature of the Interruption sequences and the molecular basis for their functions have not been well studied. Here, we focused on a G5G type natural Interruption sequence G-POALO-G from human type XIX collagen, a homotrimer collagen, as this sequence possesses distinct properties compared with those of a pathological similar Gly mutation sequence in collagen mimic peptides. We determined the crystal structures of the host–guest peptide (GPO)3-GPOALO-(GPO)4 to 1.03 A resolution in two crystal forms. In these structures, the Interruption zone brings localized disruptions to the triple helix and introduces a light 6–8° bend with the same directional preference to the whole molecule, which may correspond structurally to the first physiological kink site in type XIX collagen. Furthermore, at the G5G Interruption site, the presence of Ala and Leu residues, ...
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Unique Conformation in a Natural Interruption Sequence of Type XIX Collagen Revealed by Its High-Resolution Crystal Structure
2018Co-Authors: Congzhao Zhou, Jianxi Xiao, Jinsong LiuAbstract:Naturally occurring Interruptions in nonfibrillar collagen play key roles in molecular flexibility, collagen degradation, and ligand binding. The structural feature of the Interruption sequences and the molecular basis for their functions have not been well studied. Here, we focused on a G5G type natural Interruption sequence G-POALO-G from human type XIX collagen, a homotrimer collagen, as this sequence possesses distinct properties compared with those of a pathological similar Gly mutation sequence in collagen mimic peptides. We determined the crystal structures of the host–guest peptide (GPO)3-GPOALO-(GPO)4 to 1.03 Å resolution in two crystal forms. In these structures, the Interruption zone brings localized disruptions to the triple helix and introduces a light 6–8° bend with the same directional preference to the whole molecule, which may correspond structurally to the first physiological kink site in type XIX collagen. Furthermore, at the G5G Interruption site, the presence of Ala and Leu residues, both with free N–H groups, allows the formation of more direct and water-mediated interchain hydrogen bonds than in the related Gly → Ala structure. These could partly explain the difference in thermal stability between the different Interruptions. In addition, our structures provide a detailed view of the dynamic property of such an interrupted zone with respect to hydrogen bonding topology, torsion angles, and helical parameters. Our results, for the first time, also identified the binding of zinc to the end of the triple helix. These findings will shed light on how the Interruption sequence influences the conformation of the collagen molecule and provide a structural basis for further functional studies
Jianxi Xiao - One of the best experts on this subject based on the ideXlab platform.
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unique conformation in a natural Interruption sequence of type xix collagen revealed by its high resolution crystal structure
Biochemistry, 2018Co-Authors: Congzhao Zhou, Jianxi Xiao, Jinsong LiuAbstract:Naturally occurring Interruptions in nonfibrillar collagen play key roles in molecular flexibility, collagen degradation, and ligand binding. The structural feature of the Interruption sequences and the molecular basis for their functions have not been well studied. Here, we focused on a G5G type natural Interruption sequence G-POALO-G from human type XIX collagen, a homotrimer collagen, as this sequence possesses distinct properties compared with those of a pathological similar Gly mutation sequence in collagen mimic peptides. We determined the crystal structures of the host–guest peptide (GPO)3-GPOALO-(GPO)4 to 1.03 A resolution in two crystal forms. In these structures, the Interruption zone brings localized disruptions to the triple helix and introduces a light 6–8° bend with the same directional preference to the whole molecule, which may correspond structurally to the first physiological kink site in type XIX collagen. Furthermore, at the G5G Interruption site, the presence of Ala and Leu residues, ...
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Unique Conformation in a Natural Interruption Sequence of Type XIX Collagen Revealed by Its High-Resolution Crystal Structure
2018Co-Authors: Congzhao Zhou, Jianxi Xiao, Jinsong LiuAbstract:Naturally occurring Interruptions in nonfibrillar collagen play key roles in molecular flexibility, collagen degradation, and ligand binding. The structural feature of the Interruption sequences and the molecular basis for their functions have not been well studied. Here, we focused on a G5G type natural Interruption sequence G-POALO-G from human type XIX collagen, a homotrimer collagen, as this sequence possesses distinct properties compared with those of a pathological similar Gly mutation sequence in collagen mimic peptides. We determined the crystal structures of the host–guest peptide (GPO)3-GPOALO-(GPO)4 to 1.03 Å resolution in two crystal forms. In these structures, the Interruption zone brings localized disruptions to the triple helix and introduces a light 6–8° bend with the same directional preference to the whole molecule, which may correspond structurally to the first physiological kink site in type XIX collagen. Furthermore, at the G5G Interruption site, the presence of Ala and Leu residues, both with free N–H groups, allows the formation of more direct and water-mediated interchain hydrogen bonds than in the related Gly → Ala structure. These could partly explain the difference in thermal stability between the different Interruptions. In addition, our structures provide a detailed view of the dynamic property of such an interrupted zone with respect to hydrogen bonding topology, torsion angles, and helical parameters. Our results, for the first time, also identified the binding of zinc to the end of the triple helix. These findings will shed light on how the Interruption sequence influences the conformation of the collagen molecule and provide a structural basis for further functional studies
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nmr studies demonstrate a unique aab composition and chain register for a heterotrimeric type iv collagen model peptide containing a natural Interruption site
Journal of Biological Chemistry, 2015Co-Authors: Jianxi Xiao, Barbara Brodsky, Xiuxia Sun, Balaraman Madhan, Jean BaumAbstract:All non-fibrillar collagens contain Interruptions in the (Gly-X-Y)n repeating sequence, such as the more than 20 Interruptions found in chains of basement membrane type IV collagen. Two selectively doubly labeled peptides are designed to model a site in type IV collagen with a GVG Interruption in the α1(IV) and a corresponding GISLK sequence within the α2(IV) chain. CD and NMR studies on a 2:1 mixture of these two peptides support the formation of a single-component heterotrimer that maintains the one-residue staggering in the triple-helix, has a unique chain register, and contains hydrogen bonds at the Interruption site. Formation of hydrogen bonds at Interruption sites may provide a driving force for self-assembly and chain register in type IV and other non-fibrillar collagens. This study illustrates the potential role of Interruptions in the structure, dynamics, and folding of natural collagen heterotrimers and forms a basis for understanding their biological role.
Congzhao Zhou - One of the best experts on this subject based on the ideXlab platform.
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unique conformation in a natural Interruption sequence of type xix collagen revealed by its high resolution crystal structure
Biochemistry, 2018Co-Authors: Congzhao Zhou, Jianxi Xiao, Jinsong LiuAbstract:Naturally occurring Interruptions in nonfibrillar collagen play key roles in molecular flexibility, collagen degradation, and ligand binding. The structural feature of the Interruption sequences and the molecular basis for their functions have not been well studied. Here, we focused on a G5G type natural Interruption sequence G-POALO-G from human type XIX collagen, a homotrimer collagen, as this sequence possesses distinct properties compared with those of a pathological similar Gly mutation sequence in collagen mimic peptides. We determined the crystal structures of the host–guest peptide (GPO)3-GPOALO-(GPO)4 to 1.03 A resolution in two crystal forms. In these structures, the Interruption zone brings localized disruptions to the triple helix and introduces a light 6–8° bend with the same directional preference to the whole molecule, which may correspond structurally to the first physiological kink site in type XIX collagen. Furthermore, at the G5G Interruption site, the presence of Ala and Leu residues, ...
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Unique Conformation in a Natural Interruption Sequence of Type XIX Collagen Revealed by Its High-Resolution Crystal Structure
2018Co-Authors: Congzhao Zhou, Jianxi Xiao, Jinsong LiuAbstract:Naturally occurring Interruptions in nonfibrillar collagen play key roles in molecular flexibility, collagen degradation, and ligand binding. The structural feature of the Interruption sequences and the molecular basis for their functions have not been well studied. Here, we focused on a G5G type natural Interruption sequence G-POALO-G from human type XIX collagen, a homotrimer collagen, as this sequence possesses distinct properties compared with those of a pathological similar Gly mutation sequence in collagen mimic peptides. We determined the crystal structures of the host–guest peptide (GPO)3-GPOALO-(GPO)4 to 1.03 Å resolution in two crystal forms. In these structures, the Interruption zone brings localized disruptions to the triple helix and introduces a light 6–8° bend with the same directional preference to the whole molecule, which may correspond structurally to the first physiological kink site in type XIX collagen. Furthermore, at the G5G Interruption site, the presence of Ala and Leu residues, both with free N–H groups, allows the formation of more direct and water-mediated interchain hydrogen bonds than in the related Gly → Ala structure. These could partly explain the difference in thermal stability between the different Interruptions. In addition, our structures provide a detailed view of the dynamic property of such an interrupted zone with respect to hydrogen bonding topology, torsion angles, and helical parameters. Our results, for the first time, also identified the binding of zinc to the end of the triple helix. These findings will shed light on how the Interruption sequence influences the conformation of the collagen molecule and provide a structural basis for further functional studies
Eric D Peterson - One of the best experts on this subject based on the ideXlab platform.
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effect of temporary Interruption of warfarin due to an intervention on downstream time in therapeutic range in patients with atrial fibrillation from orbit af
American Journal of Cardiology, 2020Co-Authors: Malini Madhavan, Gregg C Fonarow, Peter R Kowey, Kenneth W Mahaffey, Dajuanicia N Holmes, Jonathan P Piccini, James V Freeman, Elaine M Hylek, Karen S Pieper, Eric D PetersonAbstract:The aim of this study was to quantify time in therapeutic range (TTR) before and after a temporary Interruption of warfarin due to an intervention in the Outcomes Registry for Better Informed Treatment of atrial fibrillation (AF). AF patients on warfarin who had a temporary Interruption followed by resumption were identified. A nonparametric method for estimating survival functions for interval censored data was used to examine the first therapeutic International Normalized Ratio (INR) after Interruption. TTR was compared using Wilcoxon signed rank test. Cox proportional hazards model was used to investigate the association between TTR in the first 3 months after Interruption and subsequent outcomes at 3 to 9 months. Of 9,749 AF patients, 71% were on warfarin. Over a median (IQR) follow-up of 2.6 (1.8 to 3.1) y, 33% of patients had a total of 3,022 temporary Interruptions. The first therapeutic INR was recorded within 1 week in 35.0% (95% confidence interval 32.6% to 37.4%), 2 weeks in 54.6% (52.2% to 57.0%), 30 days in 70.0% (67.9% to 72.1%) and 90 days in 91.3% (90.0% to 92.5%) of patients. Compared with pre-Interruption, TTR 3 months after Interruption was significantly lower (61.1% [36.6% to 85.0%] vs 67.6% [50.0% to 81.3%], p
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use and outcomes associated with bridging during anticoagulation Interruptions in patients with atrial fibrillation findings from the outcomes registry for better informed treatment of atrial fibrillation orbit af
Circulation, 2015Co-Authors: Benjamin A Steinberg, Gregg C Fonarow, Eric D Peterson, Sunghee Kim, Laine Thomas, Bernard J Gersh, Peter R Kowey, Kenneth W Mahaffey, Matthew W Sherwood, Paul ChangAbstract:Background—Temporary Interruption of oral anticoagulation for procedures is often required, and some propose using bridging anticoagulation. However, the use and outcomes of bridging during oral anticoagulation Interruptions in clinical practice are unknown. Methods and Results—The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry is a prospective, observational registry study of US outpatients with atrial fibrillation. We recorded incident temporary Interruptions of oral anticoagulation for a procedure, including the use and type of bridging therapy. Outcomes included multivariable-adjusted rates of myocardial infarction, stroke or systemic embolism, major bleeding, cause-specific hospitalization, and death within 30 days. Of 7372 patients treated with oral anticoagulation, 2803 overall Interruption events occurred in 2200 patients (30%) at a median follow-up of 2 years. Bridging anticoagulants were used in 24% (n=665), predominantly low-molecular-weight heparin (...
J. Gregory Trafton - One of the best experts on this subject based on the ideXlab platform.
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An Eye Movement Analysis of the Effect of Interruption Modality on Primary Task Resumption
Human factors, 2010Co-Authors: Raj M. Ratwani, J. Gregory TraftonAbstract:Objective: We examined the effect of Interruption modality (visual or auditory) on primary task (visual) resumption to determine which modality was the least disruptive. Background: Theories examining Interruption modality have focused on specific periods of the Interruption timeline. Preemption theory has focused on the switch from the primary task to the interrupting task. Multiple resource theory has focused on interrupting tasks that are to be performed concurrently with the primary task. Our focus was on examining how Interruption modality influences task resumption. We leverage the memory-for-goals theory, which suggests that maintaining an associative link between environmental cues and the suspended primary task goal is important for resumption. Method: Three Interruption modality conditions were examined: auditory Interruption with the primary task visible, auditory Interruption with a blank screen occluding the primary task, and a visual Interruption occluding the primary task. Reaction time and eye movement data were collected. Results: The auditory condition with the primary task visible was the least disruptive. Eye movement data suggest that participants in this condition were actively maintaining an associative link between relevant environmental cues on the primary task interface and the suspended primary task goal during the Interruption. Conclusion: These data suggest that maintaining cue association is the important factor for reducing the disruptiveness of Interruptions, not Interruption modality. Application: Interruption-prone computing environments should be designed to allow for the user to have access to relevant primary task cues during an Interruption to minimize disruptiveness.
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Mitigating Disruptions: Can Resuming an Interrupted Task Be Trained?
Proceedings of the Human Factors and Ergonomics Society Annual Meeting, 2006Co-Authors: David M. Cades, J. Gregory Trafton, Deborah A. Boehm-davisAbstract:Research has shown that with practice people improve on most tasks. It has also been made clear that over time Interruptions become less disruptive. It is unclear whether the reduction in Interruption disruptiveness is due to a general practice effect or specific to the Interruption/resumption process. In this experiment, participants performed three sessions of a task with one, two, or three of the sessions containing Interruptions. We found that in addition to all participants showing primary task improvement, those with more exposure to Interruptions also showed improvement in dealing with the Interruptions. Specifically, participants with practice on only the primary task did not show improvement with the Interruptions. These results suggest that the mitigations of the disruptions are directly related to people getting better at handling the Interruptions.
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Recovering from Interruptions: implications for driver distraction research.
Human factors, 2004Co-Authors: Christopher A Monk, Deborah A. Boehm-davis, J. Gregory TraftonAbstract:This research adopted a model of goal activation to study the mechanisms underlying interrupted task performance. The effects of Interruption timing, type of Interruption, and age on task time and primary task resumption time were explored under conditions in which attention was switched back and forth between two tasks, much as when drivers shift attention between attending to the road and to an in-vehicle task. The timing of Interruptions had a significant impact on task resumption times, indicating that the most costly time to interrupt task performance is during the middle of a task. However, this effect was overshadowed by age-related performance decrements for older participants. Interruptions that prevented strategic rehearsal of goals resulted in longer resumption times as compared with Interruptions that allowed rehearsal. Actual or potential applications of this research include the design of in-vehicle device user interfaces, the timing of in-vehicle messages, and current metrics for assessing driver distraction.
