检索结果-南通市图书馆

Emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

Neural Regeneration Research 2025年第1期20卷 174-180页

作者： Yinglong Miao Michael S.Wolfe Computational Medicine Program and Department of Pharmacology University of North Carolina–Chapel HillChapel HillNCUSA Department of Medicinal Chemistry University of KansasLawrenceKSUSA

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 *** 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 ***,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-*** this review,we focus on recent studies of structural dynamic mechanisms ofγ-*** 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 *** 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 *** approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-*** addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is ***,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

关键词： Alzheimer’s disease amyloid precursor protein cryo-EM structures drug design intramembrane proteolysis molecular dynamics Notch

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Semi-transparent,flexible,and electrically conductive silicon mesh by capillarity-driven welding of vapor-liquid-solid-grown nanowires over large areas

引用

Nano Research 2020年第5期13卷 1465-1471页

作者： Thomas A.Celano Seokhyoung Kim David J.hill James F.Cahoon Department of Chemistry University of North Carolina at Chapel HillChapel HillNC 27599-3290USA

Bottom-up synthesis of semiconductor nanowires(NWs)by the vapor-liquid-solid(VLS)mechanism has enabled diverse technological applications for these *** metallic NWs,however,it has been challenging to form large-area interconnected NW ***,we generate centimeter-scale meshes of mechanically and electrically interconnected Si NWs by sequentially growing,collapsing,and joining the NWs using a capillarity-driven welding *** fabricate meshes from VLS-grown NWs ranging in diameter from 20 to 100 nm and find that the meshes are three-dimensional with a thickness ranging from^1 to^10 microns depending on the NW *** extinction measurements reveal that the networks are semi-transparent with a color that depends on the absorption and scattering characteristics of individual ***,active voltage contrast imaging of both centimeter-and micron-scale meshes reveals widespread electrical *** a sacrificial layer,we demonstrate that the mesh can be liberated from the growth substrate,yielding a highly flexible and transparent *** transport measurements both on the growth substrate and on liberated,flexible films reveal electrical conduction across a centimeter scale with a sheet resistance of^160-180 kΩ/square that does not change significantly upon *** the ability to encode complex functionality in semiconductor NWs through the VLS process,we believe these meshes of networked NWs could find application as neuromorphic memory,electrode scaffolds,and bioelectronic interfaces.

关键词： semiconductor nanowire conductive network flexible electronics welding thermal annealing active-voltage contrast

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

High-throughput discovery of fluoride-ion conductors via a decoupled,dynamic,and iterative(DDI)framework

引用

npj Computational Materials 2022年第1期8卷 983-991页

作者： Jack D.Sundberg Daniel L.Druffel Lauren M.McRae Matthew G.Lanetti Jacob T.Pawlik Scott C.Warren Department of Chemistry The University of North Carolina at Chapel HillChapel HillNC27599United States

Fluoride–ion batteries are a promising alternative to lithium–ion batteries with higher theoretical capacities and working voltages,but they have experienced limited success due to the poor ionic conductivities of known electrolytes and ***,we report a high-throughput computational screening of 9747 fluoride-containing materials in search of fluoride-ion *** a combination of empirical,lightweight DFT,and nudged elastic band(NEB)calculations,we identified>10 crystal systems with high fluoride *** applied a search strategy where calculations are performed in any order(decoupled),computational resources are reassigned based on need(dynamic),and predictive models are repeatedly updated(iterative).Unlike hierarchical searches,our decoupled,dynamic,and iterative framework(DDI)began by calculating high-quality barrier heights for fluoride-ion mobility in a large and diverse group of *** high-quality dataset provided a benchmark against which a rapid calculation method could be *** accurate method was then used to measure the barrier heights for 6797 fluoride–ion *** final dataset has allowed us to discover many fascinating,high-performance conductors and to derive the design rules that govern their *** materials will accelerate experimental research into fluoride–ion batteries,while the design rules will provide an improved foundation for understanding ionic conduction.

关键词： fluoride dynamic repeatedly

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Cytosolic DNA sensing by cGAS:regulation,function,and human diseases

引用

Signal Transduction and Targeted Therapy 2021年第5期6卷 1483-1497页

作者： Le Yu Pengda Liu Lineberger Comprehensive Cancer Center The University of North Carolina at Chapel HillChapel HillNCUSA Department of Biochemistry and Biophysics The University of North Carolina at Chapel HillChapel HillNCUSA

Sensing invasive cytosolic DNA is an integral component of innate *** was identified in 2013 as the major cytosolic DNA sensor that binds dsDNA to catalyze the synthesis of a special asymmetric cyclic-dinucleotide,2/3/-cGAMP,as the secondary messenger to bind and activate STING for subsequent production of type I interferons and other immune-modulatory *** of cGAS signaling contributes to autoimmune diseases but serves as an adjuvant for anticancer immune *** the other hand,inactivation of cGAS signaling causes deficiency to sense and clear the viral and bacterial infection and creates a tumor-prone immune microenvironment to facilitate tumor evasion of immune ***,cGAS activation is tightly *** this review,we summarize up-to-date multilayers of regulatory mechanisms governing cGAS activation,including cGAS pre-and post-translational regulations,cGAS-binding proteins,and additional cGAS regulators such as ions and small *** will also reveal the pathophysiological function of cGAS and its product cGAMP in human *** hope to provide an up-to-date review for recent research advances of cGAS biology and cGAS-targeted therapies for human diseases.

关键词： diseases function cGAS

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Adrenomedullin and endocrine control of immune cells during pregnancy

引用

Cellular & Molecular Immunology 2014年第5期11卷 456-459页

作者： Brooke C Matson Kathleen M Caron Departments of Cell Biology & Physiology University of North Carolina at Chapel Hill Chapel Hill NC USA Genetics University of North Carolina at Chapel Hill Chapel Hill NC USA

The immunology of pregnancy is complex and incompletely understood. Aberrant immune activity in the decidua and in the placenta is believed to play a role in diseases of pregnancy, such as infertility, miscarriage, fetal growth restriction and preeclampsia. Here, we briefly review the endocrine control of uterine natural killer cell populations and their functions by the peptide hormone adrenomedullin. Studies in genetic animal models have revealed the critical importance of adrenomedullin dosage at the maternal-fetal interface, with cells from both the maternal and fetal compartments contributing to essential aspects underlying appropriate uterine receptivity, implantation and vascular remodeling of spiral arteries. These basic insights into the crosstalk between the endocrine and immune systems within the maternal- fetal interface may ultimately translate to a better understanding of the functions and consequences of dysregulated adrenomedullin levels in clinically complicated pregnancies.

关键词： adrenomedullin preeclampsia pregnancy spiral artery remodeling uNK cells

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Intricacies of TGF-βsignaling in Treg and Th17 cell biology

引用

Cellular & Molecular Immunology 2023年第9期20卷 1002-1022页

作者： Junying Wang Xingqi Zhao Yisong Y.Wan Lineberger Comprehensive Cancer Center University of North Carolina at Chapel HillChapel HillNC 27599USA Department of Microbiology and Immunology University of North Carolina at Chapel HillChapel HillNC 27599USA

Balanced immunity is pivotal for health and ***4+helper T(Th)cells are central to the balance between immune tolerance and immune *** cells adopt distinct functions to maintain tolerance and clear *** of Th cell function often leads to maladies,including autoimmunity,inflammatory disease,cancer,and *** T(Treg)and Th17 cells are critical Th cell types involved in immune tolerance,homeostasis,pathogenicity,and pathogen *** is therefore critical to understand how Treg and Th17 cells are regulated in health and *** are instrumental in directing Treg and Th17 cell *** evolutionarily conserved TGF-β(transforming growth factor-β)cytokine superfamily is of particular interest because it is central to the biology of both Treg cells that are predominantly immunosuppressive and Th17 cells that can be proinflammatory,pathogenic,and immune *** TGF-βsuperfamily members and their intricate signaling pathways regulate Treg and Th17 cell function is a question that has been intensely investigated for two ***,we introduce the fundamental biology of TGF-βsuperfamily signaling,Treg cells,and Th17 cells and discuss in detail how the TGF-βsuperfamily contributes to Treg and Th17 cell biology through complex yet ordered and cooperative signaling networks.

关键词： TGF-beta regulatory T cell Th17 cell Treg

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Deforming generalized cylinders without self-intersection by means of a parametric center curve

引用

Computational Visual Media 2018年第4期4卷 305-321页

作者： Ruibin Ma Qingyu Zhao Rui Wang James Damon Julian Rosenman Stephen Pizer Computer Science University of North Carolina at Chapel Hill Mathematics University of North Carolina at Chapel Hill Radiation Oncology University of North Carolina at Chapel Hill

Large-scale deformations of a tubular object, or generalized cylinder, are often defined by a target shape for its center curve, typically using a parametric target curve. This task is non-trivial for free-form deformations or direct manipulation methods because it is hard to manually control the centerline by adjusting control points. Most skeleton-based methods are no better, again due to the small number of manually adjusted control points. In this paper, we propose a method to deform a generalized cylinder based on its skeleton composed of a centerline and orthogonal cross sections. Although we are not the first to use such a skeleton, we propose a novel skeletonization method that tries to minimize the number of intersections between neighboring cross sections by means of a relative curvature condition to detect intersections. The mesh deformation is first defined geometrically by deforming the centerline and mapping the cross sections. Rotation minimizing frames are used during mapping to control twisting. Secondly, given displacements on the cross sections, the deformation is decomposed into finely subdivided regions. We limit distortion at these vertices by minimizing an elastic thin shell bending energy,in linear time. Our method can handle complicated generalized cylinders such as the human colon.

关键词： generalized cylinder deformation skeleton self-intersection

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Heterospecific interactions and the proliferation of sexually dimorphic traits

引用

Current Zoology 2012年第3期58卷 453-462页

作者： Karin S. PFENNIG Allen H. HURLBERT Department of Biology University of North Carolina Chapel Hill Chapel Hill NC 27599-3280

Sexual selection is expected to promote speciation by fostering the evolution of sexual traits that minimize reproductive interactions among existing or incipient species. In species that compete for access to, or attention of, females, sexual selec- tion fosters more elaborate traits in males compared to females. If these traits also minimize reproductive interactions with het- erospecifics, then species with enhanced risk of interactions between species might display greater numbers of these sexually di- morphic characters. We tested this prediction in eight families of North American birds. In particular, we evaluated whether the number of sexually dimorphic traits was positively associated with species richness at a given site or with degree of sympatry with congeners. We found no strong evidence of enhanced sexual dimorphism with increasing confamilial species richness at a given site. We also found no overall relationship between the number of sexually dimorphic traits and overlap with congeners across these eight families. However, we found patterns consistent with our prediction within Anatidae （ducks, geese and swans） and, to a lesser degree, Parulidae （New World warblers）. Our results suggest that sexually selected plumage traits in these groups potentially play a role in reproductive isolation [Current Zoology 58 （3）： 453--462, 2012].

关键词： Speciation Reproductive character displacement Sexual selection species recognition Reinforcement

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

More than mimicry？ Evaluating scope for flicker-fusion as a defensive strategy in coral snake mimics

引用

Current Zoology 2014年第1期60卷 123-130页

作者： Georgia C. TITCOMB David W. KIKUCHI David W. PFENNIG Department of Biology University of North Carolina at Chapel Hill Chapel Hill NC 27599-3280

Coral snakes and their mimics often have brightly colored banded patterns, generally associated with warning colora- tion or mimicry. However, such color patterns have also been hypothesized to aid snakes in escaping predators through a ＂flicker-fusion＂ effect. According to this hypothesis, banded color patterns confuse potential predators when a snake transitions from resting to moving because its bands blur together to form a different color. To produce this motion blur, a moving snake＇s bands must transition faster than the critical flicker-fusion rate at which a predator＇s photoreceptors can refresh. It is unknown if coral snakes or their mimics meet this requirement. We tested this hypothesis by measuring the movement speed and color pat- terns of two coral snake mimics, Lampropeltis triangulum campbelli and L. elapsoides, and comparing the frequency of color transitions to the photoreceptor activity of the avian eye. We found that snakes often produced a motion blur, but moving snakes created a blurring effect more often in darker conditions, such as sunrise, sunset, and nighttime when these snakes are often active. Thus, at least two species of coral snake mimics are capable of achieving flicker-fusion, indicating that their color patterns may confer an additional defense aside from mimicry

关键词： Coral snake mimicry Flicker-fusion effect CFF Kingsnake Defensive strategy

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

A Batesian mimic and its model share color production mechanisms

引用

Current Zoology 2012年第4期58卷 658-667页

作者： David W. KIKUCHI David W. PFENNIG Department of Biology University of North Carolina at Chapel Hill Chapel Hill NC 27599-3280 USA

Batesian mimics are harmless prey species that resemble dangerous ones （models）, and thus receive protection from predators. How such adaptive resemblances evolve is a classical problem in evolutionary biology. Mimicry is typically thought to be difficult to evolve, especially if the model and mimic produce the convergent phenotype through different proximate mecha- nisms. However, mimicry may evolve more readily if mimic and model share similar pathways for producing the convergent phenotype. In such cases, these pathways can be co-opted in ancestral mimic populations to produce high-fidelity mimicry with- out the need for major evolutionary innovations. Here, we show that a Batesian mimic, the scarlet kingsnake Larnpropeltis elap-soides, produces its coloration using the same physiological mechanisms as does its model, the eastern coral snake Micrurus fulvius. Therefore, precise color mimicry may have been able to evolve easily in this system. Generally, we know relatively little about the proximate mechanisms underlying mimicry .

关键词： Adaptation Coloration Convergent evolution Pteridine Pigment

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

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

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

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

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

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：