197 research outputs found

    Diffusivities and kinetics of short-range and long-range orderings in Ni-Fe permalloys

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    The microscopic model of atomic diffusion is considered to describe the short-range order relaxation kinetics within the f.c.c.-Ni-Fe Permalloys. The model takes into account both the discrete and anisotropic characters of atomic jumps within the long-range field of concentration heterogeneities of the interacting atoms. The diffusion coefficients and activation energies for the disordered Ni-Fe permalloy are estimated with the evaluated probabilities of atomic jumps. As shown, the increasing of a temperature with a fixed composition influences on the 'potential' field of interatomic interaction ambiguously: the field 'potential' increases for defined coordination shells and decreases for some of other ones. Although the temperature increasing promotes the increasing of any atomic-probabilities jumps generally, but decreasing of the action of 'potential' field generated by the atoms of defined element and caused by its concentration heterogeneities onto the distant sites results in increasing of the atomic-jumps' probabilities of just this element, first of all, into the sites, which are more distant from the 'source' of heterogeneity. Within the framework of the static concentration waves' method along with the self-consistent field approximation, the Onsager-type kinetics equation is obtained to describe the long-range order relaxation by the L12-type superstructure. To calculate diffusivities for the ordered Ni3Fe permalloy, the independent, diffraction experimental data of the long-range order parameter relaxation are used. Theoretical curves of the long-range order time evolution for the non-stoichiometric f.c.c.-Ni-Fe permalloys are plotted. Decreasing of the concentration of alloying element results in decelerating of the long-range order parameter change and in increasing of its relaxation time

    Superconducting joining of melt-textured Y-Ba-Cu-O bulk material

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    The Tm-Ba-Cu-O solder can be successfully used to produce a superconductive joint between MT-YBCO parts. The peculiarities of solidification, phase formation, structure transformations and electromagnetic properties of MT-YBCO soldered with TmBa2Cu3O7-d are discussed.Comment: PS of 6 pages text and 5 figures, presented at ICMC'2000, Brasi

    АНАЛІЗ ΠŸΠ ΠžΠ‘Π›Π•Πœ ВА ΠœΠžΠ–Π›Π˜Π’ΠžΠ‘Π’Π•Π™ Π’Π†Π”Π’Π’ΠžΠ Π•ΠΠΠ― ΠΠ Π’Π˜ΠšΠ£Π›Π―Π¦Π†ΠΠ˜Π₯ Π Π£Π₯Π†Π’ Π©Π•Π›Π•ΠŸΠ˜ Π£ Π¦Π˜Π€Π ΠžΠ’ΠžΠœΠ£ Π‘Π•Π Π•Π”ΠžΠ’Π˜Π©Π†

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    Introduction. The use of virtual articulators, which are essentially software, greatly enhances the effectiveness of planning and implementing stages of complex dental rehabilitation with the ability to completely translate patient data (not only anatomical but also functional) into a digital format.The aim of study. Carry out an analysis of design and simulation systems for jaw kinematic parameters reproduction, basic principles of the architecture of existing software aimed at reproducing articulation components and constructing individualized occlusion patterns during patient-oriented prosthetic treatment.Materials and methods. The search for publications in electronic databases (PubMedCentral (PMC), BioMed Central, InTech, MEDLINE / PubMed, the Public Library of Science One (PloS)) was carried out in accordance with the Medical Subject Headings (MeSH) descriptors, which are peculiar headings categorized by the hierarchy system. Additionally, the analysis of references in already pre-made system reviews related to the objectives of this study and other review publications adjacent to them was provided.Results. The systematic review of the principles of digital modeling of articulation schemes with different initial conditions confirmed the possibility of their practical application during the manufacture of prosthetic elements with individualized occlusive surfaces, thus ensuring the achievement of the best results of dental rehabilitation.Conclusions. A systematic review of the main possibilities for reproduction jaw articulation movements in the digital environment is the primary stage in the development of an own model of a digital atticulator to address specific clinical problems associated with prosthetic retreatment of patients with present occlusive dysfunctions.Π’Π²Π΅Π΄Π΅Π½ΠΈΠ΅. ИспользованиС Π²ΠΈΡ€Ρ‚ΡƒΠ°Π»ΡŒΠ½Ρ‹Ρ… артикуляторов, ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Π΅ ΠΏΠΎ сути ΠΏΡ€Π΅Π΄ΡΡ‚Π°Π²Π»ΡΡŽΡ‚ собой ΠΏΡ€ΠΎΠ³Ρ€Π°ΠΌΠΌΠ½ΠΎΠ΅ обСспСчСниС, Π·Π½Π°Ρ‡ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎ ΠΏΠΎΠ²Ρ‹ΡˆΠ°Π΅Ρ‚ ΡΡ„Ρ„Π΅ΠΊΡ‚ΠΈΠ²Π½ΠΎΡΡ‚ΡŒ планирования ΠΈ рСализация этапов комплСксной стоматологичСской Ρ€Π΅Π°Π±ΠΈΠ»ΠΈΡ‚Π°Ρ†ΠΈΠΈ с Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡ‚ΡŒΡŽ ΠΏΠΎΠ»Π½ΠΎΠ³ΠΎ ΠΏΠ΅Ρ€Π΅Π²ΠΎΠ΄Π° Π΄Π°Π½Π½Ρ‹Ρ… ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚Π° (Π½Π΅ Ρ‚ΠΎΠ»ΡŒΠΊΠΎ анатомичСских, Π½ΠΎ ΠΈ Ρ„ΡƒΠ½ΠΊΡ†ΠΈΠΎΠ½Π°Π»ΡŒΠ½Ρ‹Ρ…) Π² Ρ†ΠΈΡ„Ρ€ΠΎΠ²ΠΎΠΉ Ρ„ΠΎΡ€ΠΌΠ°Ρ‚.ЦСль исслСдования. ΠŸΡ€ΠΎΠ²Π΅ΡΡ‚ΠΈ Π°Π½Π°Π»ΠΈΠ· систСм Π΄ΠΈΠ·Π°ΠΉΠ½Π° ΠΈ ΠΈΠΌΠΈΡ‚Π°Ρ†ΠΈΠΈ кинСматичСских ΠΏΠ°Ρ€Π°ΠΌΠ΅Ρ‚Ρ€ΠΎΠ² Ρ‡Π΅Π»ΡŽΡΡ‚ΠΈ, основных ΠΏΡ€ΠΈΠ½Ρ†ΠΈΠΏΠΎΠ² Π°Ρ€Ρ…ΠΈΡ‚Π΅ΠΊΡ‚ΡƒΡ€Ρ‹ ΠΈΠΌΠ΅ΡŽΡ‰Π΅Π³ΠΎΡΡ ΠΏΡ€ΠΎΠ³Ρ€Π°ΠΌΠΌΠ½ΠΎΠ³ΠΎ обСспСчСния Π½Π°ΠΏΡ€Π°Π²Π»Π΅Π½Π½ΠΎΠ³ΠΎ Π½Π° воспроизводство артикуляционных ΡΠΎΡΡ‚Π°Π²Π»ΡΡŽΡ‰ΠΈΡ… ΠΈ построСниС ΠΈΠ½Π΄ΠΈΠ²ΠΈΠ΄ΡƒΠ°Π»ΠΈΠ·ΠΈΡ€ΠΎΠ²Π°Π½Π½Ρ‹Ρ… ΠΎΠΊΠΊΠ»ΡŽΠ·ΠΈΠΎΠ½Π½Ρ‹Ρ… схСм Π² Ρ…ΠΎΠ΄Π΅ ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚-ΠΎΡ€ΠΈΠ΅Π½Ρ‚ΠΈΡ€ΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ ортопСдичСского лСчСния.ΠœΠ°Ρ‚Π΅Ρ€ΠΈΠ°Π»Ρ‹ ΠΈ ΠΌΠ΅Ρ‚ΠΎΠ΄Ρ‹. Поиск ΠΏΡƒΠ±Π»ΠΈΠΊΠ°Ρ†ΠΈΠΉ Π² элСктронных Π±Π°Π·Π°Ρ… Π΄Π°Π½Π½Ρ‹Ρ… (PubMedCentral (PMC), BioMed Central, InTech, MEDLINE / PubMed, Public Library of Science One (PloS)) осущСствлялся согласно дСскрипторов Medical Subject Headings (MeSH), ΠΏΡ€Π΅Π΄ΡΡ‚Π°Π²Π»ΡΡŽΡ‰ΠΈΡ… собой своСобразныС Π·Π°Π³ΠΎΠ»ΠΎΠ²ΠΊΠΈ, ΠΊΠ°Ρ‚Π΅Π³ΠΎΡ€ΠΈΠ·ΠΈΡ€ΠΎΠ²Π°Π½Π½Ρ‹Ρ… ΠΏΠΎ систСмС ΠΈΠ΅Ρ€Π°Ρ€Ρ…ΠΈΠΈ. Π”ΠΎΠΏΠΎΠ»Π½ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎ проводился Π°Π½Π°Π»ΠΈΠ· ссылок Π² ΡƒΠΆΠ΅ ΠΏΡ€Π΅Π΄Π²Π°Ρ€ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎ ΠΏΡ€ΠΎΠ²Π΅Π΄Π΅Π½Π½Ρ‹Ρ… систСмных ΠΎΠ±Π·ΠΎΡ€Π°Ρ…, ΠΊΠ°ΡΠ°ΡŽΡ‰ΠΈΡ…ΡΡ Ρ†Π΅Π»ΠΈ Π΄Π°Π½Π½ΠΎΠ³ΠΎ исслСдования, ΠΈ Π΄Ρ€ΡƒΠ³ΠΈΡ… ΠΎΠ±Π·ΠΎΡ€Π½Ρ‹Ρ… публикациях, смСТных с Π½ΠΈΠΌΠΈ.Π Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Ρ‹ исслСдования. ΠŸΡ€ΠΎΠ²Π΅Π΄Π΅Π½Π½Ρ‹ΠΉ систСмный ΠΎΠ±Π·ΠΎΡ€ ΠΏΡ€ΠΈΠ½Ρ†ΠΈΠΏΠΎΠ² Ρ†ΠΈΡ„Ρ€ΠΎΠ²ΠΎΠ³ΠΎ модСлирования артикуляционных схСм с Ρ€Π°Π·Π»ΠΈΡ‡Π½Ρ‹ΠΌΠΈ исходными условиями ΠΏΠΎΠ΄Ρ‚Π²Π΅Ρ€Π΄ΠΈΠ» Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡ‚ΡŒ ΠΈΡ… практичСского примСнСния ΠΏΡ€ΠΈ ΠΈΠ·Π³ΠΎΡ‚ΠΎΠ²Π»Π΅Π½ΠΈΠΈ протСтичСских элСмСнтов с ΠΈΠ½Π΄ΠΈΠ²ΠΈΠ΄ΡƒΠ°Π»ΠΈΠ·ΠΈΡ€ΠΎΠ²Π°Π½Π½Ρ‹ΠΌΠΈ ΠΎΠΊΠΊΠ»ΡŽΠ·ΠΈΠΎΠ½Π½Ρ‹ΠΌΠΈ повСрхностями, обСспСчивая Ρ‚Π°ΠΊΠΈΠΌ ΠΎΠ±Ρ€Π°Π·ΠΎΠΌ достиТСниС Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ ΠΎΠΏΡ‚ΠΈΠΌΠ°Π»ΡŒΠ½Ρ‹Ρ… Ρ€Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚ΠΎΠ² стоматологичСской Ρ€Π΅Π°Π±ΠΈΠ»ΠΈΡ‚Π°Ρ†ΠΈΠΈ.Π’Ρ‹Π²ΠΎΠ΄Ρ‹. БистСмный ΠΎΠ±Π·ΠΎΡ€ основных возмоТностСй воспроизвСдСния артикуляционных Π΄Π²ΠΈΠΆΠ΅Π½ΠΈΠΉ Ρ‡Π΅Π»ΡŽΡΡ‚ΠΈ Π² Ρ†ΠΈΡ„Ρ€ΠΎΠ²ΠΎΠΉ срСдС являСтся ΠΏΠ΅Ρ€Π²ΠΈΡ‡Π½Ρ‹ΠΌ этапом Ρ€Π°Π·Ρ€Π°Π±ΠΎΡ‚ΠΊΠΈ собствСнной ΠΌΠΎΠ΄Π΅Π»ΠΈ Ρ†ΠΈΡ„Ρ€ΠΎΠ²ΠΎΠ³ΠΎ атикулятора для Ρ€Π΅ΡˆΠ΅Π½ΠΈΡ ΠΊΠΎΠ½ΠΊΡ€Π΅Ρ‚Π½Ρ‹Ρ… клиничСских ΠΏΡ€ΠΎΠ±Π»Π΅ΠΌ, связанных с ΠΏΠΎΠ²Ρ‚ΠΎΡ€Π½Ρ‹ΠΌ ΠΏΡ€ΠΎΡ‚Π΅Π·ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚ΠΎΠ² с ΠΈΠΌΠ΅ΡŽΡ‰ΠΈΠΌΠΈΡΡ ΠΎΠΊΠΊΠ»ΡŽΠ·ΠΈΠΎΠ½Π½Ρ‹ΠΌΠΈ дисфункциями.Вступ. Використання Π²Ρ–Ρ€Ρ‚ΡƒΠ°Π»ΡŒΠ½ΠΈΡ… артикуляторів, Ρ‰ΠΎ ΠΏΠΎ суті ΠΏΡ€Π΅Π΄ΡΡ‚Π°Π²Π»ΡΡŽΡ‚ΡŒ собою ΠΏΡ€ΠΎΠ³Ρ€Π°ΠΌΠ½Π΅ забСзпСчСння, Π·Π½Π°Ρ‡Π½ΠΎ ΠΏΡ–Π΄Π²ΠΈΡ‰ΡƒΡ” Π΅Ρ„Π΅ΠΊΡ‚ΠΈΠ²Π½Ρ–ΡΡ‚ΡŒ планування Ρ‚Π° рСалізація Π΅Ρ‚Π°ΠΏΡ–Π² комплСксної стоматологічної Ρ€Π΅Π°Π±Ρ–Π»Ρ–Ρ‚Π°Ρ†Ρ–Ρ— Π· ΠΌΠΎΠΆΠ»ΠΈΠ²Ρ–ΡΡ‚ΡŽ ΠΏΠΎΠ²Π½ΠΎΠ³ΠΎ пСрСвСдСння Π΄Π°Π½ΠΈΡ… ΠΏΠ°Ρ†Ρ–Ρ”Π½Ρ‚Π° (Π½Π΅ Ρ‚Ρ–Π»ΡŒΠΊΠΈ Π°Π½Π°Ρ‚ΠΎΠΌΡ–Ρ‡Π½ΠΈΡ…, Π° ΠΉ Ρ„ΡƒΠ½ΠΊΡ†Ρ–ΠΎΠ½Π°Π»ΡŒΠ½ΠΈΡ…) Ρƒ Ρ†ΠΈΡ„Ρ€ΠΎΠ²ΠΈΠΉ Ρ„ΠΎΡ€ΠΌΠ°Ρ‚.ΠœΠ΅Ρ‚Π° дослідТСння. ΠŸΡ€ΠΎΠ²Π΅ΡΡ‚ΠΈ Π°Π½Π°Π»Ρ–Π· систСм Π΄ΠΈΠ·Π°ΠΉΠ½Ρƒ Ρ‚Π° Ρ–ΠΌΡ–Ρ‚Π°Ρ†Ρ–Ρ— ΠΊΡ–Π½Π΅ΠΌΠ°Ρ‚ΠΈΡ‡Π½ΠΈΡ… ΠΏΠ°Ρ€Π°ΠΌΠ΅Ρ‚Ρ€Ρ–Π² Ρ‰Π΅Π»Π΅ΠΏΠΈ, основних ΠΏΡ€ΠΈΠ½Ρ†ΠΈΠΏΡ–Π² Π°Ρ€Ρ…Ρ–Ρ‚Π΅ΠΊΡ‚ΡƒΡ€ΠΈ наявного ΠΏΡ€ΠΎΠ³Ρ€Π°ΠΌΠ½ΠΎΠ³ΠΎ забСзпСчСння спрямованого Π½Π° відтворСння артикуляційних складових Ρ‚Π° ΠΏΠΎΠ±ΡƒΠ΄ΠΎΠ²Ρƒ Ρ–Π½Π΄ΠΈΠ²Ρ–Π΄ΡƒΠ°Π»Ρ–Π·ΠΎΠ²Π°Π½ΠΈΡ… ΠΎΠΊΠ»ΡŽΠ·Ρ–ΠΉΠ½ΠΈΡ… схСм Π² Ρ…ΠΎΠ΄Ρ– ΠΏΠ°Ρ†Ρ–Ρ”Π½Ρ‚-ΠΎΡ€Ρ–Ρ”Π½Ρ‚ΠΎΠ²Π°Π½ΠΎΠ³ΠΎ ΠΎΡ€Ρ‚ΠΎΠΏΠ΅Π΄ΠΈΡ‡Π½ΠΎΠ³ΠΎ лікування.ΠœΠ°Ρ‚Π΅Ρ€Ρ–Π°Π»ΠΈ Ρ‚Π° ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΈ. ΠŸΠΎΡˆΡƒΠΊ ΠΏΡƒΠ±Π»Ρ–ΠΊΠ°Ρ†Ρ–ΠΉ Ρƒ Π΅Π»Π΅ΠΊΡ‚Ρ€ΠΎΠ½Π½ΠΈΡ… Π±Π°Π·Π°Ρ… Π΄Π°Π½ΠΈΡ… (PubMedCentral (PMC), BioMed Central, InTech, MEDLINE/ PubMed, Public Library of Science One (PloS)) Π·Π΄Ρ–ΠΉΡΠ½ΡŽΠ²Π°Π²ΡΡ Π·Π³Ρ–Π΄Π½ΠΎ дСскрипторів Medical Subject Headings (MeSH), Ρ‰ΠΎ ΡΡ‚Π°Π½ΠΎΠ²Π»ΡΡ‚ΡŒ собою своєрідні Π·Π°Π³ΠΎΠ»ΠΎΠ²ΠΊΠΈ, ΠΊΠ°Ρ‚Π΅Π³ΠΎΡ€ΠΈΠ·ΠΎΠ²Π°Π½Ρ– Π·Π° ΡΠΈΡΡ‚Π΅ΠΌΠΎΡŽ Ρ–Ρ”Ρ€Π°Ρ€Ρ…Ρ–Ρ—. Π”ΠΎΠ΄Π°Ρ‚ΠΊΠΎΠ²ΠΎ проводився Π°Π½Π°Π»Ρ–Π· посилань Π² ΡƒΠΆΠ΅ ΠΏΠΎΠΏΠ΅Ρ€Π΅Π΄Π½ΡŒΠΎ ΠΏΡ€ΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ… систСмних оглядах, Ρ‰ΠΎ стосувалися ΠΌΠ΅Ρ‚ΠΈ Π΄Π°Π½ΠΎΠ³ΠΎ дослідТСння, Ρ‚Π° Ρ–Π½ΡˆΠΈΡ… оглядових публікаціях, суміТних Ρ–Π· Π½ΠΈΠΌΠΈ.Π Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚ΠΈ дослідТСння. ΠŸΡ€ΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠΉ систСмний огляд ΠΏΡ€ΠΈΠ½Ρ†ΠΈΠΏΡ–Π² Ρ†ΠΈΡ„Ρ€ΠΎΠ²ΠΎΠ³ΠΎ модСлювання артикуляційних схСм Π· Ρ€Ρ–Π·Π½ΠΈΠΌΠΈ Π²ΠΈΡ…Ρ–Π΄Π½ΠΈΠΌΠΈ ΡƒΠΌΠΎΠ²Π°ΠΌΠΈ ΠΏΡ–Π΄Ρ‚Π²Π΅Ρ€Π΄ΠΈΠ² ΠΌΠΎΠΆΠ»ΠΈΠ²Ρ–ΡΡ‚ΡŒ Ρ—Ρ… ΠΏΡ€Π°ΠΊΡ‚ΠΈΡ‡Π½ΠΎΠ³ΠΎ застосування ΠΏΡ–Π΄ час виготовлСння ΠΏΡ€ΠΎΡ‚Π΅Ρ‚ΠΈΡ‡Π½ΠΈΡ… Π΅Π»Π΅ΠΌΠ΅Π½Ρ‚Ρ–Π² Π· Ρ–Π½Π΄ΠΈΠ²Ρ–Π΄ΡƒΠ°Π»Ρ–Π·ΠΎΠ²Π°Π½ΠΈΠΌΠΈ ΠΎΠΊΠ»ΡŽΠ·Ρ–ΠΉΠ½ΠΈΠΌΠΈ повСрхнями, Π·Π°Π±Π΅Π·ΠΏΠ΅Ρ‡ΡƒΡŽΡ‡ΠΈ Ρ‚Π°ΠΊΠΈΠΌ Ρ‡ΠΈΠ½ΠΎΠΌ досягнСння Π½Π°ΠΉΠ±Ρ–Π»ΡŒΡˆ ΠΎΠΏΡ‚ΠΈΠΌΠ°Π»ΡŒΠ½ΠΈΡ… Ρ€Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Ρ–Π² стоматологічної Ρ€Π΅Π°Π±Ρ–Π»Ρ–Ρ‚Π°Ρ†Ρ–Ρ—.Висновки. БистСмний огляд основних моТливостСй відтворСння артикуляційних Ρ€ΡƒΡ…Ρ–Π² Ρ‰Π΅Π»Π΅ΠΏΠΈ Π² Ρ†ΠΈΡ„Ρ€ΠΎΠ²ΠΎΠΌΡƒ сСрСдовищі Ρ” ΠΏΠ΅Ρ€Π²ΠΈΠ½Π½ΠΈΠΌ Π΅Ρ‚Π°ΠΏΠΎΠΌ Ρ€ΠΎΠ·Ρ€ΠΎΠ±ΠΊΠΈ власної ΠΌΠΎΠ΄Π΅Π»Ρ– Ρ†ΠΈΡ„Ρ€ΠΎΠ²ΠΎΠ³ΠΎ атикулятора для Π²ΠΈΡ€Ρ–ΡˆΠ΅Π½Π½Ρ ΠΊΠΎΠ½ΠΊΡ€Π΅Ρ‚Π½ΠΈΡ… ΠΊΠ»Ρ–Π½Ρ–Ρ‡Π½ΠΈΡ… ΠΏΡ€ΠΎΠ±Π»Π΅ΠΌ пов’язаних Ρ–Π· ΠΏΠΎΠ²Ρ‚ΠΎΡ€Π½ΠΈΠΌ протСзуванням ΠΏΠ°Ρ†Ρ–Ρ”Π½Ρ‚Ρ–Π² Ρ–Π· наявними ΠΎΠΊΠ»ΡŽΠ·Ρ–ΠΉΠ½ΠΈΠΌΠΈ дисфункціями

    Sodium Phenylbutyrate Controls Neuroinflammatory and Antioxidant Activities and Protects Dopaminergic Neurons in Mouse Models of Parkinson’s Disease

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    Neuroinflammation and oxidative stress underlie the pathogenesis of various neurodegenerative disorders. Here we demonstrate that sodium phenylbutyrate (NaPB), an FDA-approved therapy for reducing plasma ammonia and glutamine in urea cycle disorders, can suppress both proinflammatory molecules and reactive oxygen species (ROS) in activated glial cells. Interestingly, NaPB also decreased the level of cholesterol but involved only intermediates, not the end product of cholesterol biosynthesis pathway for these functions. While inhibitors of both geranylgeranyl transferase (GGTI) and farnesyl transferase (FTI) inhibited the activation of NF-ΞΊB, inhibitor of GGTI, but not FTI, suppressed the production of ROS. Accordingly, a dominant-negative mutant of p21rac, but not p21ras, attenuated the production of ROS from activated microglia. Inhibition of both p21ras and p21rac activation by NaPB in microglial cells suggests that NaPB exerts anti-inflammatory and antioxidative effects via inhibition of these small G proteins. Consistently, we found activation of both p21ras and p21rac in vivo in the substantia nigra of acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. Oral administration of NaPB reduced nigral activation of p21ras and p21rac, protected nigral reduced glutathione, attenuated nigral activation of NF-ΞΊB, inhibited nigral expression of proinflammatory molecules, and suppressed nigral activation of glial cells. These findings paralleled dopaminergic neuronal protection, normalized striatal neurotransmitters, and improved motor functions in MPTP-intoxicated mice. Consistently, FTI and GGTI also protected nigrostriata in MPTP-intoxicated mice. Furthermore, NaPB also halted the disease progression in a chronic MPTP mouse model. These results identify novel mode of action of NaPB and suggest that NaPB may be of therapeutic benefit for neurodegenerative disorders

    Nck adapter proteins: functional versatility in T cells

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    Nck is a ubiquitously expressed adapter protein that is almost exclusively built of one SH2 domain and three SH3 domains. The two isoproteins of Nck are functionally redundant in many aspects and differ in only few amino acids that are mostly located in the linker regions between the interaction modules. Nck proteins connect receptor and non-receptor tyrosine kinases to the machinery of actin reorganisation. Thereby, Nck regulates activation-dependent processes during cell polarisation and migration and plays a crucial role in the signal transduction of a variety of receptors including for instance PDGF-, HGF-, VEGF- and Ephrin receptors. In most cases, the SH2 domain mediates binding to the phosphorylated receptor or associated phosphoproteins, while SH3 domain interactions lead to the formation of larger protein complexes. In T lymphocytes, Nck plays a pivotal role in the T cell receptor (TCR)-induced reorganisation of the actin cytoskeleton and the formation of the immunological synapse. However, in this context, two different mechanisms and adapter complexes are discussed. In the first scenario, dependent on an activation-induced conformational change in the CD3Ξ΅ subunits, a direct binding of Nck to components of the TCR/CD3 complex was shown. In the second scenario, Nck is recruited to the TCR complex via phosphorylated Slp76, another central constituent of the membrane proximal activation complex. Over the past years, a large number of putative Nck interactors have been identified in different cellular systems that point to diverse additional functions of the adapter protein, e.g. in the control of gene expression and proliferation

    Molecular Evolution of the Neuropeptide S Receptor

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    The neuropeptide S receptor (NPSR) is a recently deorphanized member of the G protein-coupled receptor (GPCR) superfamily and is activated by the neuropeptide S (NPS). NPSR and NPS are widely expressed in central nervous system and are known to have crucial roles in asthma pathogenesis, locomotor activity, wakefulness, anxiety and food intake. The NPS-NPSR system was previously thought to have first evolved in the tetrapods. Here we examine the origin and the molecular evolution of the NPSR using in-silico comparative analyses and document the molecular basis of divergence of the NPSR from its closest vertebrate paralogs. In this study, NPSR-like sequences have been identified in a hemichordate and a cephalochordate, suggesting an earlier emergence of a NPSR-like sequence in the metazoan lineage. Phylogenetic analyses revealed that the NPSR is most closely related to the invertebrate cardioacceleratory peptide receptor (CCAPR) and the group of vasopressin-like receptors. Gene structure features were congruent with the phylogenetic clustering and supported the orthology of NPSR to the invertebrate NPSR-like and CCAPR. A site-specific analysis between the vertebrate NPSR and the well studied paralogous vasopressin-like receptor subtypes revealed several putative amino acid sites that may account for the observed functional divergence between them. The data can facilitate experimental studies aiming at deciphering the common features as well as those related to ligand binding and signal transduction processes specific to the NPSR
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