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蛋白质序列和结构的保守性与其功能的关系

Zoological Research 1999年第1期20卷 21-25页

作者：黄京飞 tom l.blundell 中国科学院昆明动物研究所细胞与分子进化开放研究实验室剑桥大学生物化学系

以蛋白质酪氨酸磷酸酶为模型，通过序列和结构的比较，对蛋白质序列、结构的保守性与其功能和进化的关系问题进行了研究。结果显示，虽然在酪氨酸磷酸酶超家族分子的序列中，仅有３个与其催化功能密切相关的残基是高度保守的，但它们功... 详细信息

以蛋白质酪氨酸磷酸酶为模型，通过序列和结构的比较，对蛋白质序列、结构的保守性与其功能和进化的关系问题进行了研究。结果显示，虽然在酪氨酸磷酸酶超家族分子的序列中，仅有３个与其催化功能密切相关的残基是高度保守的，但它们功能结构域的核心拓扑结构却明显类似，其中存在着βαβ和βαβα２个保守的结构单元；此外，它们活性位点的拓扑结构也极其相似。因此，在保持蛋白质功能方面具有重要作用的残基是高度保守的，而具维持蛋白质结构作用的残基则是相对保守的。在进化过程中，蛋白质三维拓扑结构的保守性，似乎主要是体现在保持某些共同的特有二级结构单元和共同的折叠方式上。

关键词：酪氨酸磷酸酶保守性功能进化蛋白质结构

Crystal structure,biochemical and biophysical characterisation of NHR1 domain of E3 Ubiquitin ligase neutralized

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Advances in Enzyme Research 2013年第3期1卷 61-75页

作者： Deepti Gupta Sylvie Beaufils Veronique Vie Gilles Paboeuf Bill Broadhurst Francois Schweisguth tom l.blundell Victor M.Bolanos-Garcia Department of Biochemistry University of CambridgeCambridgeUnited Kingdom UMR-CNRS 6251 IPRUniversite de RennesCampus de BeaulieuFrance Institut Pasteur CNRS URA2578ParisFrance Department of Biological and Medical Sciences Oxford Brookes UniversityOxfordEngland

Notch signaling controls diverse developmental decisions of central importance to cell activity. One of the conserved positive regulators of Notch signaling is Neuralized, the E3 Ubiquitin ligase enzyme that regulates signaling activity by endocytosis. Neuralized has two novel repeats, NHR1 and NHR2, with a RING finger motif at the C-terminus. Both endocytosis of the Notch ligand, Delta, and inhibition of Notch signaling by tom, a bearded family member, require the NHR1 domain. Here we describe the first crystal structure of NHR1 domain from Drosophila melanogaster, solved to 2.1 A resolution by X-ray analysis. Using NMR and other biophysical techniques we define a minimal binding region of tom, consisting of 12 residues, which interacts with NHR1 and show by interfacial analysis of protein monolayers that NHR1 binds PI4P. Taken together, the studies provide insight into molecular interactions that are important for Notch signaling.

关键词： Notch Signaling Neuralized NHR1 Bearded tom Endocytosis Neurogenesis

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酪氨酸磷酸酶超家族序列与结构的比较研究

酪氨酸磷酸酶超家族序列与结构的比较研究

Remaking a connection:molecular players involved in post-injury synapse formation

“科技增强国力，青年开创未来——携手走向辉煌的新世纪”中国科协第三届青年学术年会

作者：黄京飞 tom l.blundell 中国科学院昆明动物研究所 Department of Biochemistry University of CambridgeUK

本文在对酪氨酸磷酸酶三维结构进行重叠和序列联配的基础上,就其序列与结构进行了比较研究。结果显示,虽然蛋白质磷酸酶Ⅰ与Ⅱ之间的序列一致性较低,但它们的三维结构、活性位点的构象却明显相似,且共同具有一个保守的特征序列片段。因... 详细信息

本文在对酪氨酸磷酸酶三维结构进行重叠和序列联配的基础上,就其序列与结构进行了比较研究。结果显示,虽然蛋白质磷酸酶Ⅰ与Ⅱ之间的序列一致性较低,但它们的三维结构、活性位点的构象却明显相似,且共同具有一个保守的特征序列片段。因此作者建议,磷酸酶Ⅰ与Ⅱ应属于同一超家族的蛋白质,而不是分属于两个超家族。基于研究结果,本文还就蛋白质序列与结构的关系问题进行了初步探讨。

关键词：磷酸酶超家族联配

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Neural Regeneration Research 2025年第6期20卷 1719-1720页

作者： Diogo tomé Ramiro D.Almeida iBiMED-Institute of Biomedicine Department of Medical SciencesUniversity of AveiroAveiroPortugal CNC-Center for Neuroscience and Cell Biology University of CoimbraCoimbraPortugal

Functional recovery from central nervous system(CNS)trauma depends not only on axon regeneration or compensatory sprouting of uninjured fibers but also on the ability of newly grown axons to establish functional synapses with appropriate *** several studies have successfully promoted long-distance axonal regeneration in distinct CNS injury models,none of them have resulted in a viable therapeutic approach for patient recovery.A possible reason may be the lack of new synaptogenesis for reestablishing the circuitry lost after ***,we discuss how our understanding of the mechanisms that instruct synapse formation in the injured nervous system may contribute to the design of new strategies to promote functional restoration in traumatic CNS disorders.

关键词： viable injury instru

Brain-derived neurotrophic factor signaling in the neuromuscular junction during developmental axonal competition and synapse elimination

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Neural Regeneration Research 2025年第2期20卷 394-401页

作者： Josep tomàs Víctor Cilleros-Mañé laia Just-Borràs Marta Balanyà-Segura Aleksandra Polishchuk laura Nadal Marta tomàs Carolina Silvera-Simón Manel M.Santafé Maria A.lanuza Unitat d’Histologia i Neurobiologia(UHNeurob) Facultat de Medicina i Ciències de la SalutUniversitat Rovira i VirgiliReusSpain

During the development of the nervous system,there is an overproduction of neurons and *** competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or *** have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse *** purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this *** particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental *** dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific *** describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon *** downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary ***,calcium entry through l-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to red

关键词： acetylcholine release adenosine receptors axonal competition brain-derived neurotrophic factor calcium channels motor end-plate muscarinic acetylcholine receptors postnatal synapse elimination serine kinases tropomyosin-related kinase receptorB

Importance of the Development of Veterinary Toxicology in Argentina

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Biomedical and Environmental Sciences 1989年第1期2卷 7-16页

作者： tomáS A.lóPEZ Instituto

The different types of toxic substances that affect farm animals in Argentina are described. These substances include (a) toxic plants, such as Solanum glaucophyllum. Baccharis coridifolia, Festuca arundinacea; (b) mycotoxins, such as zearalenone, tremorgenic mycotoxins, and ergoalkaloid; (c) trace elements, such as fluorine, copper, molybdenum, and arsenic; and (d) others, such as toxic algae and pesticides. The direct and indirect economic loss of farm animals associated with these toxic substances in Argentina is roughly estimated at 50 million dollars a year. A number of recommendations are made to ameliorate the situation. 1989 Academic Press, Inc.

关键词： In Importance of the Development of Veterinary Toxicology in Argentina

An ultrafast reconfigurable nanophotonic switch using wavefront shaping of light in a nonlinear nanomaterial

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light(Science & Applications) 2014年第1期3卷 78-84页

作者： tom Strudley Roman Bruck Ben Mills Otto l Muskens Physics and Astronomy Faculty of Physical Sciences and EngineeringUniversity of SouthamptonHighfieldSouthampton SO171BJUK Optoelectronics Research Centre Faculty of Physical Sciences and EngineeringUniversity of SouthamptonHighfieldSouthampton SO171BJUK

We demonstrate a new concept for reconfigurable nanophotonic devices exploiting ultrafast nonlinear control of shaped wavefronts in a multimode nanomaterial consisting of semiconductor *** pulsed laser excitation of the nanowire mat is shown to provide an efficient nonlinear mechanism to control both destructive and constructive interference in a shaped *** of up to 63%are induced by optical pumping,due to a combination of multimode dephasing and induced transient *** show that part of the nonlinear phase dynamics can be inverted to provide a dynamical revival of the wavefront into an optimized spot with up to 18%increase of the peak to background ratio caused by pulsed laser *** concepts of multimode nonlinear switching demonstrated here are generally extendable to other photonic and plasmonic systems and enable new avenues for ultrafast and reconfigurable nanophotonic devices.

关键词： nanophotonics nanowires nonlinear optics reconfigurable ultrafast wavefront shaping

Redundancy in Biology and Robotics:Potential of Kinematic Redundancy and its Interplay with Elasticity

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Journal of Bionic Engineering 2020年第4期17卷 695-707页

作者： tom Verstraten Christian Schumacher Rapha(e)l Furnémont Andre Seyfarth Philipp Beckerle Robotics and Multibody Mechanics Research Group(R&MM) Vrije Universiteit Brussel and Flanders MakePleinlaan 21050 ElseneBelgium Institute of Sports Science TU DarmstadtMagdalenenstraβe 2764289 DarmstadtGermany Elastic lightweight Robotics Group Robotics Research InstituteTU DortmundOtto-Hahn-Straβe 844227 DortmundGermany Institüt fur Mechatronische Systeme im Maschinenbau TU DarmstadtOtto-Berndt-Straβe 264287 DarmstadtGermany

Redundancy facilitates some of the most remarkable capabilities of humans,and is therefore omni-present in our *** relationship between redundancy in robotics and biology is investigated in detail on the Series Elastic Dual-Motor Actuator(SEDMA),an actuator inspired by the kinematic redundancy exhibited by *** actuator consists of two motors coupled to a single spring at the *** a system has a redundant degree of freedom,which can be exploited to optimize aspects such as accuracy,impedance,fault-tolerance and energy *** test its potential for human-like motions,the SEDMA actuator is implemented in a hopping *** on a physical demonstrator show that the robot's movement patterns resemble human squat *** conclude that robots with bio-inspired actuator designs facilitate human-like movement,although current technical limitations may prevent them from reaching the same dynamic and energetic performance.

关键词： bioinspired redundant actuation series elastic actuation hopping robots energy efficiency human physiology

Rock joint coefficients and their computerized classification

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International Journal of Mining Science and Technology 2019年第5期29卷 701-709页

作者： tomás Ficker Faculty of Civil Engineering Brno University of Technology60200 BrnoCzech Republic

A computerized method for determining rock joint coefficients is *** relative similarity indicators are introduced to classify surface morphology of rock *** classification enables to compare investigated and database rock *** a comparison aims at finding the couple of surfaces that are distinguished by the highest dynamical *** first absolute indicator results from the Fourier matrix and evaluates wavy shapes of *** second absolute indicator quantifies the heights of surface reliefs and is defined as the root mean square height of the surface *** reliability of these indicators is tested within the surface analysis of a series of limestone *** the computerized assessment,25 people have performed visual assessment of these limestone *** results of visual assessments have been statistically processed and compared to the results received from the computerized *** newly introduced absolute indicators have proved to be prospective numerical tools for evaluating joint rock coefficients.

关键词： Rock joints Shear strength Joint rock coefficients Numerical indicators Computerized assessment