检索结果-内蒙古大学图书馆

A novel 3D bilayer hydrogel tri-culture system for studying functional motor units

CELL AND BIOSCIENCE 2023年第1期13卷 1页

作者： Lin, Yu-Lung Nhieu, Jennifer Lerdall, Thomas Milbauer, Liming Wei, Chin-Wen Lee, Dong Jun Oh, Sang-Hyun Thayer, Stanley Wei, Li-Na Univ Minnesota Med Sch Dept Pharmacol Minneapolis MN 55455 USA Univ Minnesota Dept Elect & Comp Engn Minneapolis MN 55455 USA Taipei Med Univ Coll Med Sci & Technol PhD Program Translat Med Taipei Taiwan Taipei Med Univ Coll Med Sci & Technol Int PhD Program Translat Sci Taipei Taiwan

BackgroundA motor unit (MU) is formed by a single alpha motor neuron (MN) and the muscle fibers it innervates. The MU is essential for all voluntary movements. Functional deficits in the MU result in neuromuscular disorders (NMDs). The pathological mechanisms underlying most NMDs remain poorly understood, in part due to the lack of in vitro models that can comprehensively recapitulate multistage intercellular interactions and physiological function of the *** have designed a novel three-dimensional (3D) bilayer hydrogel tri-culture system where architecturally organized MUs can form in vitro. A sequential co-culture procedure using the three cell types of a MU, MN, myoblast, and Schwann cell was designed to construct a co-differentiating tri-culture on a bilayer hydrogel matrix. We utilized a & mu;-molded hydrogel with an additional Matrigel layer to form the bilayer hydrogel device. The & mu;-molded hydrogel layer provides the topological cues for myoblast differentiation. The Matrigel layer, with embedded Schwann cells, not only separates the MNs from myoblasts but also provides a proper micro-environment for MU development. The completed model shows key MU features including an organized MU structure, myelinated nerves, aligned myotubes innervated on clustered neuromuscular junctions (NMJs), MN-driven myotube contractions, and increases in cytosolic Ca2+ upon *** organized and functional in vitro MU model provides an opportunity to study pathological events involved in NMDs and peripheral neuropathies, and can serve as a platform for physiological and pharmacological studies such as modeling and drug screening. Technically, the rational of this 3D bilayer hydrogel co-culture system exploits multiple distinct properties of hydrogels, facilitating effective and efficient co-culturing of diverse cell types for tissue engineering.

关键词： Motor unit Motor neuron Muscle Schwann cell Neuromuscular Hydrogel Co-culture Motor neuron disorders

来源：评论

学校读者我要写书评

暂无评论

Evolutionary graph theory beyond pairwise interactions: Higher-order network motifs shape times to fixation in structured populations

引用

PLOS COMPUTATIONAL BIOLOGY 2024年第3期20卷 e1011905页

作者： Kuo, Yang Ping Carja, Oana Carnegie Mellon Univ Sch Comp Sci Computat Biol Dept Pittsburgh PA 15213 USA Carnegie Mellon Univ Joint Carnegie Mellon Univ Univ Pittsburgh PhD Program Computat Biol Pittsburgh PA USA

To design population topologies that can accelerate rates of solution discovery in directed evolution problems or for evolutionary optimization applications, we must first systematically understand how population structure shapes evolutionary outcome. Using the mathematical formalism of evolutionary graph theory, recent studies have shown how to topologically build networks of population interaction that increase probabilities of fixation of beneficial mutations, at the expense, however, of longer fixation times, which can slow down rates of evolution, under elevated mutation rate. Here we find that moving beyond dyadic interactions in population graphs is fundamental to explain the trade-offs between probabilities and times to fixation of new mutants in the population. We show that higher-order motifs, and in particular three-node structures, allow the tuning of times to fixation, without changes in probabilities of fixation. This gives a near-continuous control over achieving solutions that allow for a wide range of times to fixation. We apply our algorithms and analytic results to two evolutionary optimization problems and show that the rate of solution discovery can be tuned near continuously by adjusting the higher-order topology of the population. We show that the effects of population structure on the rate of evolution critically depend on the optimization landscape and find that decelerators, with longer times to fixation of new mutants, are able to reach the optimal solutions faster than accelerators in complex solution spaces. Our results highlight that no one population topology fits all optimization applications, and we provide analytic and computational tools that allow for the design of networks suitable for each specific task. Accelerating the rate of solution discovery has been a long-standing goal in directed evolution and evolutionary optimization problems. One way to accelerate evolutionary search is to design population structures that control th

关键词： Network motifs Optimization Evolutionary rate Evolutionary systematics Monte Carlo method Topology Approximation methods Natural selection

来源：评论

学校读者我要写书评

暂无评论

Identifying and Overcoming the Sampling Challenges in Relative Binding Free Energy Calculations of a Model Protein:Protein Complex

引用

JOURNAL OF CHEMICAL THEORY AND COMPUTATION 2023年第15期19卷 4863-4882页

作者： Zhang, Ivy Rufa, Dominic A. Pulido, Ivan Henry, Michael M. Rosen, Laura E. Hauser, Kevin Singh, Sukrit Chodera, John D. Mem Sloan Kettering Canc Ctr Sloan Kettering Inst Computat & Syst Biol Program New York NY 10065 USA Cornell Univ Weill Cornell Med Coll Triinst PhD Program Computat Biol & Med New York NY 10065 USA Cornell Univ Weill Cornell Med Coll Triinst PhD Program Chem Biol New York NY 10065 USA Vir Biotechnol San Francisco CA 94158 USA

Relativealchemical binding free energy calculations are routinelyused in drug discovery projects to optimize the affinity of smallmolecules for their drug targets. Alchemical methods can also be usedto estimate the impact of amino acid mutations on protein:proteinbinding affinities, but these calculations can involve sampling challengesdue to the complex networks of protein and water interactions frequentlypresent in protein:protein interfaces. We investigate these challengesby extending a graphics processing unit (GPU)-accelerated open-sourcerelative free energy calculation package (Perses) to predict the impactof amino acid mutations on protein:protein binding. Using the well-characterizedmodel system barnase:barstar, we describe analyses for identifyingand characterizing sampling problems in protein:protein relative freeenergy calculations. We find that mutations with sampling problemsoften involve charge-changes, and inadequate sampling can be attributedto slow degrees of freedom that are mutation-specific. We also explorethe accuracy and efficiency of current state-of-the-art approaches alchemicalreplica exchange and alchemical replica exchange with solute tempering forovercoming relevant sampling problems. By employing sufficiently longsimulations, we achieve accurate predictions (RMSE 1.61, 95% CI: [1.12,2.11] kcal/mol), with 86% of estimates within 1 kcal/mol of the experimentallydetermined relative binding free energies and 100% of predictionscorrectly classifying the sign of the changes in binding free ***, we provide a model workflow for applying protein mutationfree energy calculations to protein:protein complexes, and importantly,catalog the sampling challenges associated with these types of alchemicaltransformations. Our free open-source package (Perses) is based onOpenMM and is available at https://***/choderalab/perses.

关键词：

来源：评论

学校读者我要写书评

暂无评论

Enabled geographic information system technology toward non-revenue water reduction

引用

DESALINATION AND WATER TREATMENT 2023年 292卷 233-246页

作者： AbuEltayef, Hatem AbuAlhin, Khaldoun Alastal, Khalil Islamic Univ Gaza Joint PhD Program Water Technol Gaza Palestine Al Azhar Univ Gaza Gaza Palestine Islamic Univ Gaza Gaza Palestine

In recent years, advances in information communications technology have proven their role in reducing water losses in water distribution systems. The geographic information system is a spe-cialized set of Information Communication and Technology, which provides effective methods in the management of the water sector, in particular, non-revenue water. The Palestinian national strategic plan reported that reducing the non-revenue water from 38% to 35% will increase the revenue by US$40 million within 10 y. Similarly, the water sector regulatory council estimates that the non-revenue water rate is 33%. Surprisingly, water utilities have yet to implement extensive water loss management. Approximately 95% of the urban population in Khan Younis is served by a municipal water supply network. A high level of non-revenue water was recorded in Khan Younis in 2012 (about 40%). Many actions have been implemented to reduce the non-revenue water to 30% by 2020. This study aimed to quantify the non-revenue water of each water distribution zone and to classify the non-revenue water loss for distribution zone 20 (DZ20) per house con-nection. It was concluded that the adaptation of geographic information system made it possible to classify the highest loss rate of non-revenue water between 3% and 5% for DZ23. However, the distribution zone DZ20 showed a very high level of water loss (58.78%). The filed investigations illustrate that the developed map accuracy was presented as 83% accurate, whilst a strong posi-tive correlation was revealed between non-revenue water and the age of the water meter and the number of populations occupying the house connection.

关键词： None revenue water Water loss Information Communication and Technology Geographic information system

来源：评论

学校读者我要写书评

暂无评论

Optimized M24B Aminopeptidase Inhibitors for CARD8 Inflammasome Activation

引用

JOURNAL OF MEDICINAL CHEMISTRY 2023年第4期66卷 2589-2607页

作者： Chen, Qifeng Wang, Alvin Covelli, Dominic J. Bhattacharjee, Abir Wang, Qinghui Orth-He, Elizabeth L. Rao, Sahana D. Huang, Hsin-Che Ball, Daniel P. Hsiao, Jeffrey C. Bachovchin, Daniel A. Mem Sloan Kettering Canc Ctr Chem Biol Program New York NY 10065 USA Mem Sloan Kettering Canc Ctr Triinst PhD Program Chem Biol New York NY 10065 USA Mem Sloan Kettering Canc Ctr Weill Cornell Grad Sch Med Sci Pharmacol Program New York NY 10065 USA Mem Sloan Kettering Canc Ctr Weill Cornell Grad Sch Med Sci Triinst PhD Program Chem Biol New York NY 10065 USA

Inflammasomes are innate immune signaling platforms that trigger pyroptotic cell death. NLRP1 and CARD8 are related human inflammasomes that detect similar danger signals, but NLRP1 has a higher activation threshold and triggers a more inflammatory form of pyroptosis. Both sense the accumulation of intracellular peptides with Xaa-Pro N-termini, but Xaa-Pro peptides on their own without a second danger signal only activate the CARD8 inflammasome. We recently reported that a dual inhibitor of the Xaa-Pro-cleaving M24B aminopeptidases PEPD and XPNPEP1 called CQ31 selectively activates the CARD8 inflammasome by inducing the build-up of Xaa-Pro peptides. Here, we performed structure-activity relationship studies on CQ31 to develop the optimized dual PEPD/XPNPEP1 inhibitor CQ80 that more effectively induces CARD8 inflammasome activation. We anticipate that CQ80 will become a valuable tool to study the basic biology and therapeutic potential of selective CARD8 inflammasome activation.

关键词： Alkyls Inflammation Inhibitors Nuclear magnetic resonance spectroscopy Peptides and proteins

来源：评论

学校读者我要写书评

暂无评论

Periostin in the relation between periodontal disease and atherosclerotic coronary artery disease: A pilot randomized clinical study

引用

JOURNAL OF PERIODONTAL RESEARCH 2024年第3期59卷 446-457页

作者： Padial-Molina, Miguel Gonzalez-Perez, Gloria Martin-Morales, Natividad Sanchez-Fernandez, Elena O'Valle, Francisco Galindo-Moreno, Pablo Univ Granada Sch Dent Dept Oral Surg & Implant Dent Campus Univ Cartuja s-n Granada 18071 Spain Inst Invest Biosanit Ibs GRANADA Granada Spain Univ Granada PhD Program Clin Med & Publ Hlth Granada Spain Univ Granada PhD Program Biomed Granada Spain Univ Granada Sch Med Dept Pathol Granada Spain Univ Granada Inst Biopathol & Regenerat Med IBIMER CIBM Granada Spain

ObjectiveThe aim of this study was to analyze the effects of periodontal treatment on markers of atherosclerotic coronary artery disease and circulating levels of *** is necessary for periodontal stability, but it is highly present in atherosclerotic plaques. Treatment of periodontal disease, with low levels of local periostin, is thought to reduce systemic levels of periostin. Thus, this may contribute to cardiovascular *** pilot randomized controlled clinical trial was designed to include patients with severe periodontal disease and history of atherosclerotic coronary artery disease. Samples of gingival crevicular fluid (GCF) and serum were collected before and after periodontal treatment by periodontal surgery or non-surgical therapy. The levels of several markers of inflammation and cardiovascular damage were evaluated including CRP, IFN-gamma, IL-1ss, IL-10, MIP-1 alpha, periostin, and TNF-alpha in GCF and CRP, Fibrinogen, IFN-gamma, IL-1ss, IL-6, IL-10, L-Selectin, MIP-1 alpha, Periostin, TNF-alpha, and vWF in *** total of 22 patients with an average of 56 years old were recruited for participating in this study. Twenty of them were male. Most of them (82%) had suffered an acute myocardial event and underwent surgery for placing 1, 2, or 3 stents in the coronary arteries more than 6 months ago but less than 1 year. The treatment of periodontal disease resulted in an overall improvement of all periodontal parameters. Regarding the evaluation of GCF and serum, a significant increase of periostin in the GCF was observed after periodontal surgery. In contrast, although other markers in GCF and serum improved, no significant correlations were *** of periodontal disease through periodontal surgery induces a local and transient increase in the levels of periostin in the gingival crevicular fluid. The effects on systemic markers of inflammation and cardiovascular function have not been confirmed.

关键词： atherosclerosis coronary heart disease extracellular matrix periodontal disease periodontal therapy periostin

来源：评论

学校读者我要写书评

暂无评论

SMAD4: A critical regulator of cardiac neural crest cell fate and vascular smooth muscle development

引用

DEVELOPMENTAL DYNAMICS 2024年第1期253卷 119-143页

作者： Alexander, Brianna E. Zhao, Huaning Astrof, Sophie Univ Med & Dent New Jersey Rutgers Biomed & Hlth Sci Dept Cell Biol & Mol Med Newark NJ 07103 USA Univ Med & Dent New Jersey Multidisciplinary PhD Program Biomed Sci Cell Biol Rutgers Biomed & Hlth Sci Newark NJ 07103 USA Univ Med & Dent New Jersey Multidisciplinary PhD Program Biomed Sci Mol Biol Rutgers Biomed & Hlth Sci Newark NJ 07103 USA

Background: During embryogenesis, cardiac neural crest-derived cells (NCs) migrate into the pharyngeal arches and give rise to the vascular smooth muscle cells (vSMCs) of the pharyngeal arch arteries (PAAs). vSMCs are critical for the remodeling of the PAAs into their final adult configuration, giving rise to the aortic arch and its arteries (AAAs).Results: We investigated the role of SMAD4 in NC-to-vSMC differentiation using lineage-specific inducible mouse strains. We found that the expression of SMAD4 in the NC is indelible for regulating the survival of cardiac NCs. Although the ablation of SMAD4 at E9.5 in the NC lineage led to a near-complete absence of NCs in the pharyngeal arches, PAAs became invested with vSMCs derived from a compensatory source. Analysis of AAA development at E16.5 showed that the alternative vSMC source compensated for the lack of NC-derived vSMCs and rescued AAA ***: Our studies uncovered the requisite role of SMAD4 in the contribution of the NC to the pharyngeal arch mesenchyme. We found that in the absence of SMAD4+ NCs, vSMCs around the PAAs arose from a different progenitor source, rescuing AAA morphogenesis. These findings shed light on the remarkable plasticity of developmental mechanisms governing AAA development.

关键词： aortic arch aortic arch arteries cardiac neural crest pharyngeal arch arteries SMAD4 vascular smooth muscle cells

来源：评论

学校读者我要写书评

暂无评论

PEO-b-PBD Diblock Copolymers Induce Packing Defects in Lipid/Hybrid Membranes and Improve Insertion Rates of Natively Folded Peptides

引用

BIOMACROMOLECULES 2022年第11期23卷 4756-4765页

作者： Steinkuhler, Jan Jacobs, Miranda L. Boyd, Margrethe A. Villasenor, Citlayi G. Loverde, Sharon M. Kamat, Neha P. Northwestern Univ Dept Biomed Engn Evanston IL 60208 USA CUNY Dept Chem Coll Staten Isl Staten Isl NY 10314 USA Northwestern Univ Ctr Synthet Biol Evanston IL 60657 USA CUNY Grad Ctr PhD Program Biochem New York NY 10016 USA CUNY Grad Ctr PhD Program Chem New York NY 10016 USA CUNY Grad Ctr PhD Program Phys New York NY 10016 USA

Hybrid membranes assembled from biological lipids and synthetic polymers are a promising scaffold for the reconstitution and utilization of membrane proteins. Recent observations indicate that inclusion of small fractions of polymer in lipid membranes can improve protein folding and function, but the exact structural and physical changes a given polymer sequence imparts on a membrane often remain unclear. Here, we use all-atom molecular dynamics simulations to study the structure of hybrid membranes assembled from DOPC phospholipids and PEO-b-PBD diblock copolymers. We verified our computational model using new and existing experimental data and obtained a detailed picture of the polymer conformations in the lipid membrane that we can relate to changes in membrane elastic properties. We find that inclusion of low polymer fractions induces transient packing defects into the membrane. These packing defects act as insertion sites for two model peptides, and in this way, small amounts of polymer content in lipid membranes can lead to large increases in peptide insertion rates. Additionally, we report the peptide conformational space in both pure lipid and hybrid membranes. Both membranes support similar alpha helical peptide structures, exemplifying the biocompatibi l i t y of hybrid membranes.

关键词： Defects Membranes Peptides and proteins Polymers Vesicles

来源：评论

学校读者我要写书评

暂无评论

Harnessing Split-Inteins as a Tool for the Selective Modification of Surface Receptors in Live Cells

引用

CHEMBIOCHEM 2023年第3期24卷 e202200487-e202200487页

作者： Ray, Devin M. Flood, Julia R. David, Yael Triinst PhD Program Chem Biol New York NY 10065 USA Mem Sloan Kettering Canc Ctr Chem Biol Program New York NY 10065 USA Triinst MD PhD Program New York NY 10065 USA Weill Cornell Med Coll Dept Pharmacol New York NY 10065 USA Weill Cornell Med Coll Dept Physiol Biophys & Syst Biol New York NY 10065 USA

Biochemical studies of integral membrane proteins are often hampered by low purification yields and technical limitations such as aggregation causing in vitro manipulations to be challenging. The ability of controlling proteins in live cells bypasses these limitations while broadening the scope of accessible questions owing to the proteins being in their native environment. Here we take advantage of the intein biorthogonality to mammalian systems, site specificity, fast kinetics, and auto-processing nature as an attractive option for modifying surface proteins. Using EGFR as a model, we demonstrate that the split-intein pair Ava(N)/Npu(C) can be used to efficiently and specifically modify target membrane proteins with a synthetic adduct for downstream live cell application.

关键词： EGFR membrane proteins protein engineering protein modifications split intein

来源：评论

学校读者我要写书评

暂无评论

Reducing alcohol and cannabis use risk in South American young adults: is behavioral economics an effective approach? Results from a randomized controlled pilot trial

引用

CURRENT PSYCHOLOGY 2024年第44期43卷 34254-34271页

作者： Pereira-Morales, Angela J. Cortazar, Felipe Ramirez Mayorga, Maria Fernanda Redondo Eslava-Schmalbach, Javier Hernando Univ Nacl Colombia Sch Med PhD Program Publ Hlth Cra 30 45?-?03 Bogota Colombia Univ Nacl Colombia Sch Human Sci Bogota Colombia Univ Nacl Colombia Sch Human Sci PhD Program Psychol Bogota Colombia Univ Nacl Colombia Hosp Univ Nacl Colombia Sch Med Bogota Colombia

The UN Saludable Trial was a randomized controlled pilot trial of a behavioral economics (BE) intervention designed to reduce the risk of hazardous alcohol and cannabis use among young university students from a large public Colombian university. The trial aimed to determine the feasibility of delivering a BE intervention and to explore its preliminary efficacy compared with a personalized normative feedback (PNF) intervention. A total of 709 young Colombian adults were recruited, and 470 were randomly assigned to receive either the BE intervention or the PNF comparison intervention. Changes in outcomes were assessed at 1-month and 6-month follow-up. The BE intervention resulted in a statistically significant decrease in the amount of alcohol and cannabis consumed per week, as well as a significant reduction in the time spent using these substances compared to the PNF intervention. However, we observed a significant dropout rate, with approximately 10% of the participants who were initially randomized completing the entire follow-up period. To our knowledge, BE approach has never been applied before in South American countries to address and prevent hazardous alcohol and cannabis use in young adults. Overall, the current findings suggest that an intervention combining monetary incentives with decision-making tools may be a promising approach to prevent the progression towards high-risk use in young South American adults. Schools and universities should promote a safe and healthy learning environment for all students by implementing effective drug prevention programs. Further research is needed to replicate these results and explore suitable ways to reduce the dropout rates.

关键词： Behavioral economics Decision making Alcohol Cannabis Young adults Substance use harm reduction

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：