[{"citation":{"apa":"Geurts, F., Timmermans, J., Shigemoto, R., & De Schutter, E. (2001). Morphological and neurochemical differentiation of large granular layer interneurons in the adult rat cerebellum. Neuroscience. Elsevier. https://doi.org/10.1016/S0306-4522(01)00058-6","ieee":"F. Geurts, J. Timmermans, R. Shigemoto, and E. De Schutter, “Morphological and neurochemical differentiation of large granular layer interneurons in the adult rat cerebellum,” Neuroscience, vol. 104, no. 2. Elsevier, pp. 499–512, 2001.","chicago":"Geurts, Frederik, Jean Timmermans, Ryuichi Shigemoto, and Erik De Schutter. “Morphological and Neurochemical Differentiation of Large Granular Layer Interneurons in the Adult Rat Cerebellum.” Neuroscience. Elsevier, 2001. https://doi.org/10.1016/S0306-4522(01)00058-6.","ista":"Geurts F, Timmermans J, Shigemoto R, De Schutter E. 2001. Morphological and neurochemical differentiation of large granular layer interneurons in the adult rat cerebellum. Neuroscience. 104(2), 499–512.","mla":"Geurts, Frederik, et al. “Morphological and Neurochemical Differentiation of Large Granular Layer Interneurons in the Adult Rat Cerebellum.” Neuroscience, vol. 104, no. 2, Elsevier, 2001, pp. 499–512, doi:10.1016/S0306-4522(01)00058-6.","short":"F. Geurts, J. Timmermans, R. Shigemoto, E. De Schutter, Neuroscience 104 (2001) 499–512.","ama":"Geurts F, Timmermans J, Shigemoto R, De Schutter E. Morphological and neurochemical differentiation of large granular layer interneurons in the adult rat cerebellum. Neuroscience. 2001;104(2):499-512. doi:10.1016/S0306-4522(01)00058-6"},"issue":"2","user_id":"ea97e931-d5af-11eb-85d4-e6957dddbf17","type":"journal_article","volume":104,"date_updated":"2023-05-24T12:45:30Z","abstract":[{"text":"The granular layer of the cerebellar cortex consists of densely packed neuronal cells, classified into granule cells and large interneurons. In this study, we provide a comparative survey of large granular layer interneurons in the adult rat cerebellum based on both morphological and neurochemical criteria. To this end, double immunofluorescence histochemistry was performed by combining antibodies against the cytoplasmic antigen Rat-303, calretinin, the metabotropic glutamate receptor mGluR2 and somatostatin. Based on Rat-303/calretinin double immunohistochemistry, three distinct populations of large granular layer interneurons could be discerned: cells immunopositive for Rat-303, calretinin or both. Rat-303 or calretinin single-labeled cells represented Golgi cells and unipolar brush cells, respectively. Rat-303/calretinin double-labeled cells located just underneath the Purkinje cell layer represented Lugaro cells. Morphometrical analysis distinguished two populations of Rat-303-positive Golgi cells according to their location: vermis versus hemisphere. Immunostaining for the metabotropic glutamate receptor mGluR2 combined with Rat-303 or calretinin revealed that the majority of Golgi cells (about 90%) appeared to be mGluR2 positive. Lugaro cells were mGluR2 negative. In addition, a limited population of large polymorphous interneurons in the depth of the granular layer with morphological features resembling Golgi cells also displayed Rat-303/calretinin immunoreactivity and were mGluR2 negative. Double immunohistochemistry for Rat-303 and somatostatin revealed three populations of labeled cells in the depth of the granular layer. Besides double-labeled Golgi cells, Rat-303 or somatostatin single-labeled cells were present. Based on mGluR2/somatostatin and calretinin/somatostatin double immunostainings, Rat-303 single-labeled cells were found to correspond to Rat-303/calretinin-positive, mGluR2-negative Golgi-like cells, while the identity of somatostatin single-labeled cells remained unclear. The data presented in this article elaborate previous reports on the morphological and neurochemical differentiation of large interneurons in the rat cerebellar granular layer. In addition, they indicate that the current classification of these cells into Golgi cells, Lugaro cells and unipolar brush cells does not describe the observed neurochemical heterogeneity.","lang":"eng"}],"language":[{"iso":"eng"}],"page":"499 - 512","article_type":"original","_id":"2605","day":"10","publisher":"Elsevier","extern":"1","doi":"10.1016/S0306-4522(01)00058-6","external_id":{"pmid":["11377850"]},"oa_version":"None","scopus_import":"1","title":"Morphological and neurochemical differentiation of large granular layer interneurons in the adult rat cerebellum","quality_controlled":"1","article_processing_charge":"No","publication":"Neuroscience","pmid":1,"publication_status":"published","date_published":"2001-05-10T00:00:00Z","year":"2001","status":"public","month":"05","date_created":"2018-12-11T11:58:38Z","author":[{"full_name":"Geurts, Frederik","last_name":"Geurts","first_name":"Frederik"},{"last_name":"Timmermans","first_name":"Jean","full_name":"Timmermans, Jean"},{"first_name":"Ryuichi","last_name":"Shigemoto","orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Erik","last_name":"De Schutter","full_name":"De Schutter, Erik"}],"intvolume":" 104","publication_identifier":{"issn":["0306-4522"]},"publist_id":"4292"},{"issue":"6","citation":{"ieee":"G. Martínez, G. López Bendito, R. Luján, R. Shigemoto, A. Fairén, and M. Valdeolmillos, “Cajal-Retzius cells in early postnatal mouse cortex selectively express functional metabotropic glutamate receptors,” European Journal of Neuroscience, vol. 13, no. 6. Wiley-Blackwell, pp. 1147–1154, 2001.","chicago":"Martínez, Galán, Guillermina López Bendito, Rafael Luján, Ryuichi Shigemoto, Alfonso Fairén, and Miguel Valdeolmillos. “Cajal-Retzius Cells in Early Postnatal Mouse Cortex Selectively Express Functional Metabotropic Glutamate Receptors.” European Journal of Neuroscience. Wiley-Blackwell, 2001. https://doi.org/10.1046/j.0953-816X.2001.01494.x.","apa":"Martínez, G., López Bendito, G., Luján, R., Shigemoto, R., Fairén, A., & Valdeolmillos, M. (2001). Cajal-Retzius cells in early postnatal mouse cortex selectively express functional metabotropic glutamate receptors. European Journal of Neuroscience. Wiley-Blackwell. https://doi.org/10.1046/j.0953-816X.2001.01494.x","ista":"Martínez G, López Bendito G, Luján R, Shigemoto R, Fairén A, Valdeolmillos M. 2001. Cajal-Retzius cells in early postnatal mouse cortex selectively express functional metabotropic glutamate receptors. European Journal of Neuroscience. 13(6), 1147–1154.","mla":"Martínez, Galán, et al. “Cajal-Retzius Cells in Early Postnatal Mouse Cortex Selectively Express Functional Metabotropic Glutamate Receptors.” European Journal of Neuroscience, vol. 13, no. 6, Wiley-Blackwell, 2001, pp. 1147–54, doi:10.1046/j.0953-816X.2001.01494.x.","ama":"Martínez G, López Bendito G, Luján R, Shigemoto R, Fairén A, Valdeolmillos M. Cajal-Retzius cells in early postnatal mouse cortex selectively express functional metabotropic glutamate receptors. European Journal of Neuroscience. 2001;13(6):1147-1154. doi:10.1046/j.0953-816X.2001.01494.x","short":"G. Martínez, G. López Bendito, R. Luján, R. Shigemoto, A. Fairén, M. Valdeolmillos, European Journal of Neuroscience 13 (2001) 1147–1154."},"date_updated":"2023-05-24T12:53:46Z","language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"Glutamate receptors have been linked to the regulation of several developmental events in the CNS. By using cortical slices of early postnatal mice, we show that in layer I cells, glutamate produces intracellular calcium ([Ca2+]i) elevations mediated by ionotropic and metabotropic glutamate receptors (mGluRs). The contribution of mGluRs to these responses was demonstrated by application of tACPD, an agonist to groups I and II mGluRs, which evoked [Ca2+]i increases that could be reversibly blocked by MCPG, an antagonist to groups I and II mGluRs. In the absence of extracellular Ca2+, repetitive applications of tACPD or quisqualate, an agonist to group I mGluRs, elicited decreasing [Ca2+]i responses that were restored by refilling a thapsigargin-sensitive Ca2+ store. The use of specific group I mGluR agonists CHPG and DHPG indicated that the functional mGluR in layer I was of the mGluR1 subtype. Subtype specific antibodies confirmed the presence of mGlur1α, but not mGluR5, in Cajal-Retzius (Reelin-immunoreactive) neurons."}],"user_id":"ea97e931-d5af-11eb-85d4-e6957dddbf17","volume":13,"type":"journal_article","page":"1147 - 1154","day":"01","publisher":"Wiley-Blackwell","extern":"1","_id":"2606","article_type":"original","scopus_import":"1","quality_controlled":"1","title":"Cajal-Retzius cells in early postnatal mouse cortex selectively express functional metabotropic glutamate receptors","doi":"10.1046/j.0953-816X.2001.01494.x","oa_version":"None","external_id":{"pmid":["11285012"]},"acknowledgement":"MV and AF are senior coauthors of this work, which was supported by Ministerio de Educacion y Cultura, grants SAF97/0195 and SAF 2000-0152-C02-02 to M.V; PB94-0219-CO2-01 and PB97-0582-CO2-01 to A.F., Accio Especial de R+D AE98-18 from Generalitat Valenciana, and a Fellowship from Bancaixa-C.S.I.C. to J.R.M.-G. We wish to thank Andre M. Goffinet for his G10 antireelin antibody and Roberto Gallego, Juan M. Luque and Felix Viana for their constructive criticisms on previous versions of the manuscript.","publication":"European Journal of Neuroscience","pmid":1,"article_processing_charge":"No","date_published":"2001-03-01T00:00:00Z","publication_status":"published","date_created":"2018-12-11T11:58:38Z","publication_identifier":{"issn":["0953-816X"]},"intvolume":" 13","publist_id":"4293","author":[{"full_name":"Martínez, Galán","first_name":"Galán","last_name":"Martínez"},{"full_name":"López Bendito, Guillermina","first_name":"Guillermina","last_name":"López Bendito"},{"full_name":"Luján, Rafael","last_name":"Luján","first_name":"Rafael"},{"orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","first_name":"Ryuichi","last_name":"Shigemoto"},{"full_name":"Fairén, Alfonso","first_name":"Alfonso","last_name":"Fairén"},{"last_name":"Valdeolmillos","first_name":"Miguel","full_name":"Valdeolmillos, Miguel"}],"year":"2001","month":"03","status":"public"},{"publication_status":"published","date_published":"2001-06-01T00:00:00Z","year":"2001","month":"06","status":"public","date_created":"2018-12-11T11:58:38Z","intvolume":" 17","publication_identifier":{"issn":["1044-7431"]},"publist_id":"4291","author":[{"full_name":"Mion, Silvia","last_name":"Mion","first_name":"Silvia"},{"full_name":"Corti, Corrado","last_name":"Corti","first_name":"Corrado"},{"first_name":"Akio","last_name":"Neki","full_name":"Neki, Akio"},{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444","last_name":"Shigemoto","first_name":"Ryuichi"},{"first_name":"Mauro","last_name":"Corsi","full_name":"Corsi, Mauro"},{"full_name":"Fumagalli, Guido","first_name":"Guido","last_name":"Fumagalli"},{"first_name":"Francesco","last_name":"Ferraguti","full_name":"Ferraguti, Francesco"}],"external_id":{"pmid":["11414786"]},"oa_version":"None","doi":"10.1006/mcne.2001.0993","scopus_import":"1","quality_controlled":"1","title":"Bidirectional regulation of neurite elaboration by alternatively spliced metabotropic glutamate receptor 5 (mGluR5) isoforms","article_processing_charge":"No","acknowledgement":"The authors thank: Dr. J. M. Rimland and M. T. Scupoli for their technical help with X. oocytes recordings and FAC sorting, respectively; Dr. Y. Dalezios for helping with the statistical analyses; and Dr. G. Varani for helping with the analyses of mRNA and genomic sequences. We are also grateful to Professor F. Benfenati, Dr. F. Conquet, Dr. Rafael Lujan, Dr. J. McIlhinney, Professor P. Somogyi, Dr. J. H. Xuereb, and Dr. M. Zoli for careful reading of the manuscript\r\nand helpful suggestions. R.S. is supported by the Laboratory of Cerebral Structure, National Institute for Physiological Sciences, Myodaiji, Okazaki 444-8585, CREST Japan Science and Technology Corporation, Japan.","publication":"Molecular and Cellular Neuroscience","pmid":1,"page":"957 - 972","article_type":"original","_id":"2607","day":"01","publisher":"Academic Press","extern":"1","citation":{"ama":"Mion S, Corti C, Neki A, et al. Bidirectional regulation of neurite elaboration by alternatively spliced metabotropic glutamate receptor 5 (mGluR5) isoforms. Molecular and Cellular Neuroscience. 2001;17(6):957-972. doi:10.1006/mcne.2001.0993","short":"S. Mion, C. Corti, A. Neki, R. Shigemoto, M. Corsi, G. Fumagalli, F. Ferraguti, Molecular and Cellular Neuroscience 17 (2001) 957–972.","mla":"Mion, Silvia, et al. “Bidirectional Regulation of Neurite Elaboration by Alternatively Spliced Metabotropic Glutamate Receptor 5 (MGluR5) Isoforms.” Molecular and Cellular Neuroscience, vol. 17, no. 6, Academic Press, 2001, pp. 957–72, doi:10.1006/mcne.2001.0993.","ista":"Mion S, Corti C, Neki A, Shigemoto R, Corsi M, Fumagalli G, Ferraguti F. 2001. Bidirectional regulation of neurite elaboration by alternatively spliced metabotropic glutamate receptor 5 (mGluR5) isoforms. Molecular and Cellular Neuroscience. 17(6), 957–972.","chicago":"Mion, Silvia, Corrado Corti, Akio Neki, Ryuichi Shigemoto, Mauro Corsi, Guido Fumagalli, and Francesco Ferraguti. “Bidirectional Regulation of Neurite Elaboration by Alternatively Spliced Metabotropic Glutamate Receptor 5 (MGluR5) Isoforms.” Molecular and Cellular Neuroscience. Academic Press, 2001. https://doi.org/10.1006/mcne.2001.0993.","ieee":"S. Mion et al., “Bidirectional regulation of neurite elaboration by alternatively spliced metabotropic glutamate receptor 5 (mGluR5) isoforms,” Molecular and Cellular Neuroscience, vol. 17, no. 6. Academic Press, pp. 957–972, 2001.","apa":"Mion, S., Corti, C., Neki, A., Shigemoto, R., Corsi, M., Fumagalli, G., & Ferraguti, F. (2001). Bidirectional regulation of neurite elaboration by alternatively spliced metabotropic glutamate receptor 5 (mGluR5) isoforms. Molecular and Cellular Neuroscience. Academic Press. https://doi.org/10.1006/mcne.2001.0993"},"issue":"6","user_id":"ea97e931-d5af-11eb-85d4-e6957dddbf17","type":"journal_article","volume":17,"date_updated":"2023-05-24T09:34:13Z","language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"Alternative splicing in the mGluR5 gene generates two different receptor isoforms, of which expression is developmentally regulated. However, little is known about the functional significance of mGluR5 splice variants. We have examined the functional coupling, subcellular targeting, and effect on neuronal differentiation of epitope-tagged mGluR5 isoforms by expression in neuroblastoma NG108-15 cells. We found that both mGluR5 splice variants give rise to comparable [Ca2+]i transients and have similar pharmacological profile. Tagged receptors were shown by immunofluorescence to be inserted in the plasma membrane. In undifferentiated cells the subcellular localization of the two mGluR5 isoforms was partially segregated, whereas in differentiated cells the labeling largely redistributed to the newly formed neurites. Interestingly, we demonstrate that mGluR5 splice variants dramatically influence the formation and maturation of neurites; mGluR5a hinders the acquisition of mature neuronal traits and mGluR5b fosters the elaboration and extension of neurites. These effects are partly inhibited by MPEP."}]},{"extern":"1","publisher":"Elsevier","day":"27","article_type":"original","_id":"2608","page":"413 - 429","abstract":[{"lang":"eng","text":"The regulation of neurotransmitter receptors during synapse formation has been studied extensively at the neuromuscular junction, but little is known about the development of excitatory neurotransmitter receptors during synaptogenesis in central synapses. In this study we show qualitatively and quantitatively that a receptor undergoes changes in localisation on the surface of rat Purkinje cells during development in association with its excitatory synapses. The presence of mGluR1α at parallel and climbing fibre synapses on developing Purkinje cells was studied using high-resolution immunoelectron microscopy. Immunoreactivity for mGluR1α was detected from embryonic day 18 in Purkinje cells, and showed dramatic changes in its localisation with age. At early postnatal ages (P0 and P3), mGluR1α was found both in somata and stem dendrites but was not usually associated with synaptic contacts. At P7, mGluR1α became concentrated in somatic spines associated with climbing fibres and in the growing dendritic arborisation even before innervation by parallel fibres. During the second and third postnatal week, when spines and parallel fibre synapses were generated, mGluR1α became progressively concentrated in the molecular layer, particularly in the synaptic specialisations. As a result, during the fourth postnatal week, the pattern and level of mGluR1α expression became similar to the adult and mGluR1α appeared in high density in perisynaptic sites. Our results indicate that mGluR1α is present in the developing Purkinje cells prior to their innervation by climbing and parallel fibres and demonstrate that this receptor undergoes a dynamic and specific regulation during postnatal development in association with the establishment of synaptic inputs to Purkinje cell."}],"language":[{"iso":"eng"}],"date_updated":"2023-05-24T09:31:48Z","type":"journal_article","volume":105,"user_id":"ea97e931-d5af-11eb-85d4-e6957dddbf17","issue":"2","citation":{"mla":"López Bendito, Guillermina, et al. “Developmental Changes in the Localisation of the MGluR1α Subtype of Metabotropic Glutamate Receptors in Purkinje Cells.” Neuroscience, vol. 105, no. 2, Elsevier, 2001, pp. 413–29, doi:10.1016/S0306-4522(01)00188-9.","short":"G. López Bendito, R. Shigemoto, R. Luján, J. Juíz, Neuroscience 105 (2001) 413–429.","ama":"López Bendito G, Shigemoto R, Luján R, Juíz J. Developmental changes in the localisation of the mGluR1α subtype of metabotropic glutamate receptors in Purkinje cells. Neuroscience. 2001;105(2):413-429. doi:10.1016/S0306-4522(01)00188-9","apa":"López Bendito, G., Shigemoto, R., Luján, R., & Juíz, J. (2001). Developmental changes in the localisation of the mGluR1α subtype of metabotropic glutamate receptors in Purkinje cells. Neuroscience. Elsevier. https://doi.org/10.1016/S0306-4522(01)00188-9","ieee":"G. López Bendito, R. Shigemoto, R. Luján, and J. Juíz, “Developmental changes in the localisation of the mGluR1α subtype of metabotropic glutamate receptors in Purkinje cells,” Neuroscience, vol. 105, no. 2. Elsevier, pp. 413–429, 2001.","chicago":"López Bendito, Guillermina, Ryuichi Shigemoto, Rafael Luján, and José Juíz. “Developmental Changes in the Localisation of the MGluR1α Subtype of Metabotropic Glutamate Receptors in Purkinje Cells.” Neuroscience. Elsevier, 2001. https://doi.org/10.1016/S0306-4522(01)00188-9.","ista":"López Bendito G, Shigemoto R, Luján R, Juíz J. 2001. Developmental changes in the localisation of the mGluR1α subtype of metabotropic glutamate receptors in Purkinje cells. Neuroscience. 105(2), 413–429."},"author":[{"last_name":"López Bendito","first_name":"Guillermina","full_name":"López Bendito, Guillermina"},{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444","last_name":"Shigemoto","first_name":"Ryuichi"},{"first_name":"Rafael","last_name":"Luján","full_name":"Luján, Rafael"},{"full_name":"Juíz, José","first_name":"José","last_name":"Juíz"}],"publist_id":"4290","intvolume":" 105","publication_identifier":{"issn":["0306-4522"]},"date_created":"2018-12-11T11:58:39Z","status":"public","month":"07","year":"2001","date_published":"2001-07-27T00:00:00Z","publication_status":"published","pmid":1,"publication":"Neuroscience","acknowledgement":"öWe thank Drs. Paul Bolam, Ole Paulsen, Je¡ McIlhinney, Alfonso Faire¨n and Francisco Ciruela for reviewing a previous version of this manuscript and Mrs Alexandra Salewski for the English revision of the manuscript. We also want to thank Dr. Peter Somogyi for offering the facilities of the MRC Anatomical Neuropharmacology Unit to carry out part of this study. This work was supported by a Grant from the European Community (QLG3-CT-1999-00192 to R.L.) and the Spanish Ministry of Education (DGES PM 97-0082 to J.M.J.).","article_processing_charge":"No","title":"Developmental changes in the localisation of the mGluR1α subtype of metabotropic glutamate receptors in Purkinje cells","quality_controlled":"1","scopus_import":"1","external_id":{"pmid":["11672608 "]},"doi":"10.1016/S0306-4522(01)00188-9","oa_version":"None"},{"page":"481 - 503","article_type":"original","_id":"2609","extern":"1","day":"27","publisher":"Elsevier","citation":{"apa":"Tamaru, Y., Nomura, S., Mizuno, N., & Shigemoto, R. (2001). Distribution of metabotropic glutamate receptor mGluR3 in the mouse CNS: Differential location relative to pre- and postsynaptic sites. Neuroscience. Elsevier. https://doi.org/10.1016/S0306-4522(01)00305-0","chicago":"Tamaru, Y, Sakashi Nomura, Noboru Mizuno, and Ryuichi Shigemoto. “Distribution of Metabotropic Glutamate Receptor MGluR3 in the Mouse CNS: Differential Location Relative to Pre- and Postsynaptic Sites.” Neuroscience. Elsevier, 2001. https://doi.org/10.1016/S0306-4522(01)00305-0.","ieee":"Y. Tamaru, S. Nomura, N. Mizuno, and R. Shigemoto, “Distribution of metabotropic glutamate receptor mGluR3 in the mouse CNS: Differential location relative to pre- and postsynaptic sites,” Neuroscience, vol. 106, no. 3. Elsevier, pp. 481–503, 2001.","ista":"Tamaru Y, Nomura S, Mizuno N, Shigemoto R. 2001. Distribution of metabotropic glutamate receptor mGluR3 in the mouse CNS: Differential location relative to pre- and postsynaptic sites. Neuroscience. 106(3), 481–503.","mla":"Tamaru, Y., et al. “Distribution of Metabotropic Glutamate Receptor MGluR3 in the Mouse CNS: Differential Location Relative to Pre- and Postsynaptic Sites.” Neuroscience, vol. 106, no. 3, Elsevier, 2001, pp. 481–503, doi:10.1016/S0306-4522(01)00305-0.","short":"Y. Tamaru, S. Nomura, N. Mizuno, R. Shigemoto, Neuroscience 106 (2001) 481–503.","ama":"Tamaru Y, Nomura S, Mizuno N, Shigemoto R. Distribution of metabotropic glutamate receptor mGluR3 in the mouse CNS: Differential location relative to pre- and postsynaptic sites. Neuroscience. 2001;106(3):481-503. doi:10.1016/S0306-4522(01)00305-0"},"issue":"3","volume":106,"type":"journal_article","user_id":"ea97e931-d5af-11eb-85d4-e6957dddbf17","abstract":[{"lang":"eng","text":"The metabotropic glutamate receptors (mGluRs) have distinct distribution patterns in the CNS but subtypes within group I or group III mGluRs share similar ultrastructural localization relative to neurotransmitter release sites: group I mGluRs are concentrated in an annulus surrounding the edge of the postsynaptic density, whereas group III mGluRs are concentrated in the presynaptic active zone. One of the group II subtypes, mGluR2, is expressed in both pre- and postsynaptic elements, having no close association with synapses. In order to determine if such a distribution is common to another group II subtype, mGluR3, an antibody was raised against a carboxy-terminus of mGluR3 and used for light and electron microscopic immunohistochemistry in the mouse CNS. The antibody reacted strongly with mGluR3, but it also reacted, though only weakly, with mGluR2. Therefore, to examine mGluR3-selective distribution, we used mGluR2-deficient mice as well as wild-type mice. Strong immunoreactivity for mGluR3 was found in the cerebral cortex, striatum, dentate gyrus of the hippocampus, olfactory tubercle, lateral septal nucleus, lateral and basolateral amygdaloid nuclei, and nucleus of the lateral olfactory tract. Pre-embedding immunoperoxidase and immunogold methods revealed mGluR3 labeling in both presynaptic and postsynaptic elements, and also in glial profiles. Double labeling revealed that the vast majority of mGluR3 in presynaptic elements is not closely associated with glutamate and GABA release sites in the striatum and thalamus, respectively. However, in the spines of the dentate granule cells, the highest receptor density was found in perisynaptic sites (20% of immunogold particles within 60 nm from the edge of postsynaptic membrane specialization) followed by a decreasing receptor density away from the synapses (to ∼5% of particles per 60 nm). Furthermore, 19% of immunogold particles were located in asymmetrical postsynaptic specialization, indicating an association of mGluR3 to glutamatergic synapses. The present results indicate that the localization of mGluR3 is rather similar to that of group I mGluRs in the postsynaptic elements, suggesting a unique functional role of mGluR3 in glutamatergic neurotransmission in the CNS."}],"language":[{"iso":"eng"}],"date_updated":"2023-05-24T08:51:17Z","publication_status":"published","date_published":"2001-09-27T00:00:00Z","status":"public","month":"09","year":"2001","author":[{"full_name":"Tamaru, Y","first_name":"Y","last_name":"Tamaru"},{"last_name":"Nomura","first_name":"Sakashi","full_name":"Nomura, Sakashi"},{"full_name":"Mizuno, Noboru","last_name":"Mizuno","first_name":"Noboru"},{"orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","first_name":"Ryuichi","last_name":"Shigemoto"}],"publication_identifier":{"issn":["0306-4522"]},"intvolume":" 106","publist_id":"4289","date_created":"2018-12-11T11:58:39Z","doi":"10.1016/S0306-4522(01)00305-0","oa_version":"None","external_id":{"pmid":["11591452"]},"title":"Distribution of metabotropic glutamate receptor mGluR3 in the mouse CNS: Differential location relative to pre- and postsynaptic sites","quality_controlled":"1","scopus_import":"1","article_processing_charge":"No","pmid":1,"publication":"Neuroscience","acknowledgement":"We are grateful to M. Yokoi and S. Nakanishi for kindly providing us with the mGluR2-de¢cient mice and F. Ferraguti for mGluR8b cDNA. The technical assistance of S. Doi and the photographic assistance of A. Uesugi are acknowledged. This work has been supported by research grants from the Ministry of Education, Sports, Culture, Science, and Technology of Japan."},{"extern":"1","day":"15","publisher":"Society for Neuroscience","article_type":"original","_id":"2610","page":"8734 - 8745","abstract":[{"lang":"eng","text":"To study the role of mGlu7 receptors (mGluR7), we used homologous recombination to generate mice lacking this metabotropic receptor subtype (mGluR7 -/-). After the serendipitous discovery of a sensory stimulus-evoked epileptic phenotype, we tested two convulsant drugs, pentylenetetrazole (PTZ) and bicuculline. In animals aged 12 weeks and older, subthreshold doses of these drugs induced seizures in mGluR7 -/-, but not in mGluR7 +/-, mice. PTZ-induced seizures were inhibited by three standard anticonvulsant drugs, but not by the group III selective mGluR agonist (R,S)-4-phosphonophenylglycine (PPG). Consistent with the lack of signs of epileptic activity in the absence of specific stimuli, mGluR7 -/- mice showed no major changes in synaptic properties in two slice preparations. However, slightly increased excitability was evident in hippocampal slices. In addition, there was slower recovery from frequency facilitation in cortical slices, suggesting a role for mGluR7 as a frequency-dependent regulator in presynaptic terminals. Our findings suggest that mGluR7 receptors have a unique role in regulating neuronal excitability and that these receptors may be a novel target for the development of anticonvulsant drugs."}],"language":[{"iso":"eng"}],"date_updated":"2023-05-24T08:47:53Z","type":"journal_article","volume":21,"oa":1,"user_id":"ea97e931-d5af-11eb-85d4-e6957dddbf17","issue":"22","citation":{"mla":"Sansig, Gilles, et al. “Increased Seizure Susceptibility in Mice Lacking Metabotropic Glutamate Receptor 7.” Journal of Neuroscience, vol. 21, no. 22, Society for Neuroscience, 2001, pp. 8734–45, doi:10.1523/JNEUROSCI.21-22-08734.2001.","short":"G. Sansig, T. Bushell, V. Clarke, A. Rozov, N. Burnashev, C. Portet, F. Gasparini, M. Schmutz, K. Klebs, R. Shigemoto, P. Flor, R. Kühn, T. Knoepfel, M. Schroeder, D. Hampson, V. Collett, C. Zhang, R. Duvoisin, G. Collingridge, H. Van Der Putten, Journal of Neuroscience 21 (2001) 8734–8745.","ama":"Sansig G, Bushell T, Clarke V, et al. Increased seizure susceptibility in mice lacking metabotropic glutamate receptor 7. Journal of Neuroscience. 2001;21(22):8734-8745. doi:10.1523/JNEUROSCI.21-22-08734.2001","apa":"Sansig, G., Bushell, T., Clarke, V., Rozov, A., Burnashev, N., Portet, C., … Van Der Putten, H. (2001). Increased seizure susceptibility in mice lacking metabotropic glutamate receptor 7. Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.21-22-08734.2001","ieee":"G. Sansig et al., “Increased seizure susceptibility in mice lacking metabotropic glutamate receptor 7,” Journal of Neuroscience, vol. 21, no. 22. Society for Neuroscience, pp. 8734–8745, 2001.","chicago":"Sansig, Gilles, Trevor Bushell, Vernon Clarke, Andrei Rozov, Nail Burnashev, Chantal Portet, Fabrizio Gasparini, et al. “Increased Seizure Susceptibility in Mice Lacking Metabotropic Glutamate Receptor 7.” Journal of Neuroscience. Society for Neuroscience, 2001. https://doi.org/10.1523/JNEUROSCI.21-22-08734.2001.","ista":"Sansig G, Bushell T, Clarke V, Rozov A, Burnashev N, Portet C, Gasparini F, Schmutz M, Klebs K, Shigemoto R, Flor P, Kühn R, Knoepfel T, Schroeder M, Hampson D, Collett V, Zhang C, Duvoisin R, Collingridge G, Van Der Putten H. 2001. Increased seizure susceptibility in mice lacking metabotropic glutamate receptor 7. Journal of Neuroscience. 21(22), 8734–8745."},"author":[{"full_name":"Sansig, Gilles","first_name":"Gilles","last_name":"Sansig"},{"first_name":"Trevor","last_name":"Bushell","full_name":"Bushell, Trevor"},{"last_name":"Clarke","first_name":"Vernon","full_name":"Clarke, Vernon"},{"full_name":"Rozov, Andrei","last_name":"Rozov","first_name":"Andrei"},{"full_name":"Burnashev, Nail","last_name":"Burnashev","first_name":"Nail"},{"last_name":"Portet","first_name":"Chantal","full_name":"Portet, Chantal"},{"full_name":"Gasparini, Fabrizio","first_name":"Fabrizio","last_name":"Gasparini"},{"full_name":"Schmutz, Markus","last_name":"Schmutz","first_name":"Markus"},{"last_name":"Klebs","first_name":"Klaus","full_name":"Klebs, Klaus"},{"last_name":"Shigemoto","first_name":"Ryuichi","full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444"},{"full_name":"Flor, Peter","last_name":"Flor","first_name":"Peter"},{"first_name":"Rainer","last_name":"Kühn","full_name":"Kühn, Rainer"},{"first_name":"Thomas","last_name":"Knoepfel","full_name":"Knoepfel, Thomas"},{"last_name":"Schroeder","first_name":"Markus","full_name":"Schroeder, Markus"},{"last_name":"Hampson","first_name":"David","full_name":"Hampson, David"},{"full_name":"Collett, Valerie","first_name":"Valerie","last_name":"Collett"},{"first_name":"Congxiao","last_name":"Zhang","full_name":"Zhang, Congxiao"},{"last_name":"Duvoisin","first_name":"Robert","full_name":"Duvoisin, Robert"},{"full_name":"Collingridge, Graham","last_name":"Collingridge","first_name":"Graham"},{"first_name":"Herman","last_name":"Van Der Putten","full_name":"Van Der Putten, Herman"}],"intvolume":" 21","publist_id":"4288","publication_identifier":{"issn":["0270-6474"]},"date_created":"2018-12-11T11:58:39Z","status":"public","month":"11","year":"2001","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762269/","open_access":"1"}],"date_published":"2001-11-15T00:00:00Z","publication_status":"published","pmid":1,"publication":"Journal of Neuroscience","acknowledgement":"This work was supported in part by the Biotechnology and Biological Sciences Research Council and Medical Research Council (UK). We thank Doris Ruegg for sequencing, Gemma Texido and Klaus Rajewsky for pTV-0 DNA, J.-F. Pin for mGluR8 cDNA, K. von Figura for E14 ES cells, Pedro Grandes for histological examination of brain sections, Christoph Wiessner for help with plots and statistics, Valerie Schuler for help with Western blots, and the team of the Novartis special strain breeding facility for their support.","article_processing_charge":"No","title":"Increased seizure susceptibility in mice lacking metabotropic glutamate receptor 7","quality_controlled":"1","scopus_import":"1","oa_version":"Published Version","external_id":{"pmid":["11698585"]},"doi":"10.1523/JNEUROSCI.21-22-08734.2001"},{"external_id":{"pmid":["11738139"]},"doi":"10.1016/S0306-4522(01)00158-0","oa_version":"None","quality_controlled":"1","title":"Sympathectomies lead to transient substance P-immunoreactive sensory fibre plasticity in the rat skin","scopus_import":"1","article_processing_charge":"No","publication":"Neuroscience","pmid":1,"acknowledgement":"The work contained in this manuscript was sponsored by the Canadian MRC, Grants # MT-12170 and MoP-38093. The authors would like to thank Sylvain Cote for technical assistance and Sid Parkinson for editorial assistance.","publication_status":"published","date_published":"2001-12-05T00:00:00Z","month":"12","status":"public","year":"2001","publist_id":"4286","publication_identifier":{"issn":["0306-4522"]},"intvolume":" 108","author":[{"full_name":"Ruocco, Isabella","last_name":"Ruocco","first_name":"Isabella"},{"first_name":"Augusto","last_name":"Cuello","full_name":"Cuello, Augusto"},{"first_name":"Ryuichi","last_name":"Shigemoto","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi"},{"last_name":"Ribeiro Da Silva","first_name":"Alfredo","full_name":"Ribeiro Da Silva, Alfredo"}],"date_created":"2018-12-11T11:58:40Z","citation":{"mla":"Ruocco, Isabella, et al. “Sympathectomies Lead to Transient Substance P-Immunoreactive Sensory Fibre Plasticity in the Rat Skin.” Neuroscience, vol. 108, no. 1, Elsevier, 2001, pp. 157–66, doi:10.1016/S0306-4522(01)00158-0.","ama":"Ruocco I, Cuello A, Shigemoto R, Ribeiro Da Silva A. Sympathectomies lead to transient substance P-immunoreactive sensory fibre plasticity in the rat skin. Neuroscience. 2001;108(1):157-166. doi:10.1016/S0306-4522(01)00158-0","short":"I. Ruocco, A. Cuello, R. Shigemoto, A. Ribeiro Da Silva, Neuroscience 108 (2001) 157–166.","chicago":"Ruocco, Isabella, Augusto Cuello, Ryuichi Shigemoto, and Alfredo Ribeiro Da Silva. “Sympathectomies Lead to Transient Substance P-Immunoreactive Sensory Fibre Plasticity in the Rat Skin.” Neuroscience. Elsevier, 2001. https://doi.org/10.1016/S0306-4522(01)00158-0.","ieee":"I. Ruocco, A. Cuello, R. Shigemoto, and A. Ribeiro Da Silva, “Sympathectomies lead to transient substance P-immunoreactive sensory fibre plasticity in the rat skin,” Neuroscience, vol. 108, no. 1. Elsevier, pp. 157–166, 2001.","apa":"Ruocco, I., Cuello, A., Shigemoto, R., & Ribeiro Da Silva, A. (2001). Sympathectomies lead to transient substance P-immunoreactive sensory fibre plasticity in the rat skin. Neuroscience. Elsevier. https://doi.org/10.1016/S0306-4522(01)00158-0","ista":"Ruocco I, Cuello A, Shigemoto R, Ribeiro Da Silva A. 2001. Sympathectomies lead to transient substance P-immunoreactive sensory fibre plasticity in the rat skin. Neuroscience. 108(1), 157–166."},"issue":"1","type":"journal_article","volume":108,"user_id":"ea97e931-d5af-11eb-85d4-e6957dddbf17","language":[{"iso":"eng"}],"abstract":[{"text":"Research using animal models of neuropathic pain has revealed sympathetic sprouting onto dorsal root ganglion cells. More recently, sensory fibre sprouting onto dorsal root ganglion cells has also been observed. Previous work in our laboratory demonstrated persistent sympathetic fibre sprouting in the skin of the rat lower lip following sensory denervation of this region. Therefore, we applied immunocytochemistry to determine the effects of sympathectomies on the terminal fields of sensory fibres. The superior cervical ganglia were removed bilaterally and the effects on the innervation of the skin of the rat lower lip were observed 1, 2, 3, 4, 6 and 8 weeks post-surgery. Substance P and dopamine-β-hydroxylase immunoreactivities were used to identify a subset of sensory and sympathetic fibres, respectively. We also assessed neurokinin-1 receptor immunoreactivity. Quantitative data was obtained with the aid of an image analysis system. In controls, the epidermis and upper dermis were innervated by substance P-immunoreactive fibres only and upper dermal blood vessels possessed the highest density of neurokinin-1 receptor immunoreactivity. Blood vessels in the lower dermis were innervated by both substance P- and dopamine-β-hydroxylase-immunoreactive fibres. Following sympathectomies, substance P-immunoreactive fibres in the epidermis and upper dermis were more intensely labelled only 1 and 2 weeks post-surgery when compared to sham controls. The length of substance P-immunoreactive fibres in this region was also increased only on the second week. Neurokinin-1 receptor immunoreactivity in the upper dermis was slightly decreased 1 and 2 weeks post-surgery. In the lower dermis, substance P-immunoreactive fibres associated with blood vessels were more intensely labelled only 1 and 2 weeks post-surgery, and at all post-surgical time points studied, blood vessels in this region were devoid of dopamine-β-hydroxylase-immunoreactive fibres. The length of substance P-immunoreactive fibres was increased from the first to the third week post-surgery in the lower dermis. These results indicate that sympathectomies lead to transient changes in substance P-immunoreactive fibre innervation and neurokinin-1 receptor expression in rat lower lip skin. The effects are most prominent in the lower dermis probably due to a greater local concentration of nerve growth factor in this region. The plasticity of the interactions between sensory and sympathetic fibres may prove important in the regulation of skin microcirculation and in the generation of painful sensations under normal conditions or following peripheral nerve injuries.","lang":"eng"}],"date_updated":"2023-05-22T12:15:44Z","page":"157 - 166","article_type":"original","_id":"2611","extern":"1","day":"05","publisher":"Elsevier"},{"citation":{"ama":"Li J, Shigemoto R, Kulik Á, et al. Immunocytochemical localization of GABAB receptors in mesencephalic trigeminal nucleus neurons in the rat. Neuroscience Letters. 2001;315(1-2):93-97. doi:10.1016/S0304-3940(01)02321-7","short":"J. Li, R. Shigemoto, Á. Kulik, P. Chen, S. Nomura, T. Kaneko, N. Mizuno, Neuroscience Letters 315 (2001) 93–97.","mla":"Li, Jin, et al. “Immunocytochemical Localization of GABAB Receptors in Mesencephalic Trigeminal Nucleus Neurons in the Rat.” Neuroscience Letters, vol. 315, no. 1–2, Elsevier, 2001, pp. 93–97, doi:10.1016/S0304-3940(01)02321-7.","ista":"Li J, Shigemoto R, Kulik Á, Chen P, Nomura S, Kaneko T, Mizuno N. 2001. Immunocytochemical localization of GABAB receptors in mesencephalic trigeminal nucleus neurons in the rat. Neuroscience Letters. 315(1–2), 93–97.","ieee":"J. Li et al., “Immunocytochemical localization of GABAB receptors in mesencephalic trigeminal nucleus neurons in the rat,” Neuroscience Letters, vol. 315, no. 1–2. Elsevier, pp. 93–97, 2001.","chicago":"Li, Jin, Ryuichi Shigemoto, Ákos Kulik, Peng Chen, Sakashi Nomura, Takeshi Kaneko, and Noboru Mizuno. “Immunocytochemical Localization of GABAB Receptors in Mesencephalic Trigeminal Nucleus Neurons in the Rat.” Neuroscience Letters. Elsevier, 2001. https://doi.org/10.1016/S0304-3940(01)02321-7.","apa":"Li, J., Shigemoto, R., Kulik, Á., Chen, P., Nomura, S., Kaneko, T., & Mizuno, N. (2001). Immunocytochemical localization of GABAB receptors in mesencephalic trigeminal nucleus neurons in the rat. Neuroscience Letters. Elsevier. https://doi.org/10.1016/S0304-3940(01)02321-7"},"issue":"1-2","user_id":"ea97e931-d5af-11eb-85d4-e6957dddbf17","type":"journal_article","volume":315,"date_updated":"2023-05-22T12:30:05Z","language":[{"iso":"eng"}],"abstract":[{"text":"We examined immunoreactivities for γ-aminobutyric acidB-receptor (GABABR) subtypes, GABABR1 and GABABR2, in the mesencephalic trigeminal nucleus neurons (MTN neurons) of the rat. Immunoreactivity for GABABR1 was prominent in cell bodies of MTN, whereas that for GABABR2 was very weak, if existed. For electron microscopy, the immunogold-silver method for GABABR1 was combined with the immunoperoxidase method for glutamic acid decarboxylase (GAD: the synthetic enzyme of GABA). Immunogold-silver particles indicating GABABR1 immunoreactivity were distributed widely in the cytoplasm of the cell bodies postsynaptic to GAD-immunoreactive axon terminals, but were rarely associated with synaptic membrane specialization or extrasynaptic sites of plasma membrane. It has been indicated that GABABR1 may not be transported to plasma membrane when no GABABR2 exists. Thus, it was presumed that GABABR1 in the cell body of the rat MTN neurons might not be involved in the synaptic transmission.","lang":"eng"}],"page":"93 - 97","_id":"2612","article_type":"original","day":"23","publisher":"Elsevier","extern":"1","doi":"10.1016/S0304-3940(01)02321-7","external_id":{"pmid":["11711223"]},"oa_version":"None","scopus_import":"1","quality_controlled":"1","title":"Immunocytochemical localization of GABAB receptors in mesencephalic trigeminal nucleus neurons in the rat","article_processing_charge":"No","acknowledgement":"This work was supported in part by Grants-in-Aid from the National Natural Science Foundation of China (39870262, 39970239), from the Foundation for University Key Teacher of the Ministry of Education of China, and from the Ministry of Education, Science, Sports, Culture and Technology of Japan (12308039, 12680743).","publication":"Neuroscience Letters","pmid":1,"publication_status":"published","date_published":"2001-11-23T00:00:00Z","year":"2001","month":"11","status":"public","date_created":"2018-12-11T11:58:40Z","intvolume":" 315","publication_identifier":{"issn":["0304-3940"]},"publist_id":"4287","author":[{"full_name":"Li, Jin","first_name":"Jin","last_name":"Li"},{"orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi","first_name":"Ryuichi","last_name":"Shigemoto"},{"first_name":"Ákos","last_name":"Kulik","full_name":"Kulik, Ákos"},{"first_name":"Peng","last_name":"Chen","full_name":"Chen, Peng"},{"last_name":"Nomura","first_name":"Sakashi","full_name":"Nomura, Sakashi"},{"full_name":"Kaneko, Takeshi","last_name":"Kaneko","first_name":"Takeshi"},{"last_name":"Mizuno","first_name":"Noboru","full_name":"Mizuno, Noboru"}]},{"date_updated":"2023-06-02T09:38:37Z","language":[{"iso":"eng"}],"user_id":"ea97e931-d5af-11eb-85d4-e6957dddbf17","volume":17,"type":"journal_article","issue":"9","citation":{"ama":"Wolf Y, Kondrashov F, Koonin E. Footprints of primordial introns on the eukaryotic genome: still no clear traces . Trends in Genetics. 2001;17(9):499-501. doi:10.1016/S0168-9525(01)02376-9","short":"Y. Wolf, F. Kondrashov, E. Koonin, Trends in Genetics 17 (2001) 499–501.","mla":"Wolf, Yuri, et al. “Footprints of Primordial Introns on the Eukaryotic Genome: Still No Clear Traces .” Trends in Genetics, vol. 17, no. 9, Elsevier, 2001, pp. 499–501, doi:10.1016/S0168-9525(01)02376-9.","ista":"Wolf Y, Kondrashov F, Koonin E. 2001. Footprints of primordial introns on the eukaryotic genome: still no clear traces . Trends in Genetics. 17(9), 499–501.","chicago":"Wolf, Yuri, Fyodor Kondrashov, and Eugene Koonin. “Footprints of Primordial Introns on the Eukaryotic Genome: Still No Clear Traces .” Trends in Genetics. Elsevier, 2001. https://doi.org/10.1016/S0168-9525(01)02376-9.","ieee":"Y. Wolf, F. Kondrashov, and E. Koonin, “Footprints of primordial introns on the eukaryotic genome: still no clear traces ,” Trends in Genetics, vol. 17, no. 9. Elsevier, pp. 499–501, 2001.","apa":"Wolf, Y., Kondrashov, F., & Koonin, E. (2001). Footprints of primordial introns on the eukaryotic genome: still no clear traces . Trends in Genetics. Elsevier. https://doi.org/10.1016/S0168-9525(01)02376-9"},"day":"01","publisher":"Elsevier","extern":"1","_id":"841","article_type":"original","page":"499 - 501","pmid":1,"publication":"Trends in Genetics","article_processing_charge":"No","scopus_import":"1","title":"Footprints of primordial introns on the eukaryotic genome: still no clear traces ","quality_controlled":"1","doi":"10.1016/S0168-9525(01)02376-9","oa_version":"None","external_id":{"pmid":["11721681"]},"date_created":"2018-12-11T11:48:47Z","author":[{"full_name":"Wolf, Yuri","last_name":"Wolf","first_name":"Yuri"},{"last_name":"Kondrashov","first_name":"Fyodor","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","full_name":"Kondrashov, Fyodor","orcid":"0000-0001-8243-4694"},{"full_name":"Koonin, Eugene","last_name":"Koonin","first_name":"Eugene"}],"publication_identifier":{"issn":["0168-9479"]},"intvolume":" 17","publist_id":"6805","year":"2001","status":"public","month":"09","date_published":"2001-09-01T00:00:00Z","publication_status":"published"},{"acknowledgement":"Russian Fund of Fundamental Research. Grant Number: 99-04-49535. NIH. Grant Number: GM 20293. NASA. Grant Number: NCC2-1057","pmid":1,"publication":"Human Mutation","article_processing_charge":"No","scopus_import":"1","quality_controlled":"1","title":"Use of mutation spectra analysis software","external_id":{"pmid":["11180592"]},"oa_version":"None","doi":"10.1002/1098-1004(200102)17:2<83::AID-HUMU1>3.0.CO;2-E","date_created":"2018-12-11T11:48:50Z","publist_id":"6796","publication_identifier":{"issn":["1059-7794"]},"intvolume":" 17","author":[{"first_name":"Igor","last_name":"Rogozin","full_name":"Rogozin, Igor"},{"orcid":"0000-0001-8243-4694","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","full_name":"Kondrashov, Fyodor","first_name":"Fyodor","last_name":"Kondrashov"},{"full_name":"Glazko, Galina","first_name":"Galina","last_name":"Glazko"}],"year":"2001","month":"01","status":"public","date_published":"2001-01-01T00:00:00Z","publication_status":"published","date_updated":"2023-06-02T09:22:17Z","language":[{"iso":"eng"}],"abstract":[{"text":"The study and comparison of mutation(al) spectra is an important problem in molecular biology, because these spectra often reflect on important features of mutations and their fixation. Such features include the interaction of DNA with various mutagens, the function of repair/replication enzymes, and properties of target proteins. It is known that mutability varies significantly along nucleotide sequences, such that mutations often concentrate at certain positions, called "hotspots," in a sequence. In this paper, we discuss in detail two approaches for mutation spectra analysis: the comparison of mutation spectra with a HG-PUBL program, (FTP: sunsite.unc.edu/pub/academic/ biology/dna-mutations/hyperg) and hotspot prediction with the CLUSTERM program (www.itba.mi.cnr.it/webmutation; ftp.bionet.nsc.ru/pub/biology/dbms/clusterm.zip). Several other approaches for mutational spectra analysis, such as the analysis of a target protein structure, hotspot context revealing, multiple spectra comparisons, as well as a number of mutation databases are briefly described. Mutation spectra in the lacI gene of E. coli and the human p53 gene are used for illustration of various difficulties of such analysis.","lang":"eng"}],"user_id":"ea97e931-d5af-11eb-85d4-e6957dddbf17","type":"journal_article","volume":17,"issue":"2","citation":{"ista":"Rogozin I, Kondrashov F, Glazko G. 2001. Use of mutation spectra analysis software. Human Mutation. 17(2), 83–102.","ieee":"I. Rogozin, F. Kondrashov, and G. Glazko, “Use of mutation spectra analysis software,” Human Mutation, vol. 17, no. 2. Wiley-Blackwell, pp. 83–102, 2001.","chicago":"Rogozin, Igor, Fyodor Kondrashov, and Galina Glazko. “Use of Mutation Spectra Analysis Software.” Human Mutation. Wiley-Blackwell, 2001. https://doi.org/10.1002/1098-1004(200102)17:2<83::AID-HUMU1>3.0.CO;2-E.","apa":"Rogozin, I., Kondrashov, F., & Glazko, G. (2001). Use of mutation spectra analysis software. Human Mutation. Wiley-Blackwell. https://doi.org/10.1002/1098-1004(200102)17:2<83::AID-HUMU1>3.0.CO;2-E","ama":"Rogozin I, Kondrashov F, Glazko G. Use of mutation spectra analysis software. Human Mutation. 2001;17(2):83-102. doi:10.1002/1098-1004(200102)17:2<83::AID-HUMU1>3.0.CO;2-E","short":"I. Rogozin, F. Kondrashov, G. Glazko, Human Mutation 17 (2001) 83–102.","mla":"Rogozin, Igor, et al. “Use of Mutation Spectra Analysis Software.” Human Mutation, vol. 17, no. 2, Wiley-Blackwell, 2001, pp. 83–102, doi:10.1002/1098-1004(200102)17:2<83::AID-HUMU1>3.0.CO;2-E."},"publisher":"Wiley-Blackwell","day":"01","extern":"1","_id":"851","article_type":"original","page":"83 - 102"},{"doi":"10.1090/s1079-6762-01-00091-9","citation":{"ista":"Kaloshin V, Hunt BR. 2001. A stretched exponential bound on the rate of growth of the number of periodic points for prevalent diffeomorphisms II. Electronic Research Announcements of the American Mathematical Society. 7(5), 28–36.","chicago":"Kaloshin, Vadim, and Brian R. Hunt. “A Stretched Exponential Bound on the Rate of Growth of the Number of Periodic Points for Prevalent Diffeomorphisms II.” Electronic Research Announcements of the American Mathematical Society. American Mathematical Society, 2001. https://doi.org/10.1090/s1079-6762-01-00091-9.","ieee":"V. Kaloshin and B. R. Hunt, “A stretched exponential bound on the rate of growth of the number of periodic points for prevalent diffeomorphisms II,” Electronic Research Announcements of the American Mathematical Society, vol. 7, no. 5. American Mathematical Society, pp. 28–36, 2001.","apa":"Kaloshin, V., & Hunt, B. R. (2001). A stretched exponential bound on the rate of growth of the number of periodic points for prevalent diffeomorphisms II. Electronic Research Announcements of the American Mathematical Society. American Mathematical Society. https://doi.org/10.1090/s1079-6762-01-00091-9","ama":"Kaloshin V, Hunt BR. A stretched exponential bound on the rate of growth of the number of periodic points for prevalent diffeomorphisms II. Electronic Research Announcements of the American Mathematical Society. 2001;7(5):28-36. doi:10.1090/s1079-6762-01-00091-9","short":"V. Kaloshin, B.R. Hunt, Electronic Research Announcements of the American Mathematical Society 7 (2001) 28–36.","mla":"Kaloshin, Vadim, and Brian R. Hunt. “A Stretched Exponential Bound on the Rate of Growth of the Number of Periodic Points for Prevalent Diffeomorphisms II.” Electronic Research Announcements of the American Mathematical Society, vol. 7, no. 5, American Mathematical Society, 2001, pp. 28–36, doi:10.1090/s1079-6762-01-00091-9."},"oa_version":"None","issue":"5","quality_controlled":"1","title":"A stretched exponential bound on the rate of growth of the number of periodic points for prevalent diffeomorphisms II","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"No","volume":7,"type":"journal_article","keyword":["General Mathematics"],"date_updated":"2021-01-12T08:19:51Z","language":[{"iso":"eng"}],"publication":"Electronic Research Announcements of the American Mathematical Society","abstract":[{"text":"We continue the previous article's discussion of bounds, for prevalent diffeomorphisms of smooth compact manifolds, on the growth of the number of periodic points and the decay of their hyperbolicity as a function of their period $n$. In that article we reduced the main results to a problem, for certain families of diffeomorphisms, of bounding the measure of parameter values for which the diffeomorphism has (for a given period $n$) an almost periodic point that is almost nonhyperbolic. We also formulated our results for $1$-dimensional endomorphisms on a compact interval. In this article we describe some of the main techniques involved and outline the rest of the proof. To simplify notation, we concentrate primarily on the $1$-dimensional case.","lang":"eng"}],"page":"28-36","publication_status":"published","date_published":"2001-04-24T00:00:00Z","year":"2001","_id":"8521","month":"04","article_type":"original","status":"public","publisher":"American Mathematical Society","day":"24","date_created":"2020-09-18T10:49:43Z","publication_identifier":{"issn":["1079-6762"]},"intvolume":" 7","author":[{"orcid":"0000-0002-6051-2628","full_name":"Kaloshin, Vadim","id":"FE553552-CDE8-11E9-B324-C0EBE5697425","first_name":"Vadim","last_name":"Kaloshin"},{"full_name":"Hunt, Brian R.","last_name":"Hunt","first_name":"Brian R."}],"extern":"1"},{"date_created":"2020-09-18T10:49:56Z","publisher":"American Mathematical Society","day":"18","author":[{"full_name":"Kaloshin, Vadim","id":"FE553552-CDE8-11E9-B324-C0EBE5697425","orcid":"0000-0002-6051-2628","last_name":"Kaloshin","first_name":"Vadim"},{"first_name":"Brian R.","last_name":"Hunt","full_name":"Hunt, Brian R."}],"extern":"1","publication_identifier":{"issn":["1079-6762"]},"intvolume":" 7","year":"2001","status":"public","month":"04","_id":"8522","article_type":"original","date_published":"2001-04-18T00:00:00Z","page":"17-27","publication_status":"published","date_updated":"2021-01-12T08:19:51Z","abstract":[{"lang":"eng","text":"For diffeomorphisms of smooth compact manifolds, we consider the problem of how fast the number of periodic points with period $n$grows as a function of $n$. In many familiar cases (e.g., Anosov systems) the growth is exponential, but arbitrarily fast growth is possible; in fact, the first author has shown that arbitrarily fast growth is topologically (Baire) generic for $C^2$ or smoother diffeomorphisms. In the present work we show that, by contrast, for a measure-theoretic notion of genericity we call ``prevalence'', the growth is not much faster than exponential. Specifically, we show that for each $\\delta > 0$, there is a prevalent set of ( $C^{1+\\rho}$ or smoother) diffeomorphisms for which the number of period $n$ points is bounded above by $\\operatorname{exp}(C n^{1+\\delta})$ for some $C$ independent of $n$. We also obtain a related bound on the decay of the hyperbolicity of the periodic points as a function of $n$. The contrast between topologically generic and measure-theoretically generic behavior for the growth of the number of periodic points and the decay of their hyperbolicity shows this to be a subtle and complex phenomenon, reminiscent of KAM theory."}],"publication":"Electronic Research Announcements of the American Mathematical Society","language":[{"iso":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","keyword":["General Mathematics"],"article_processing_charge":"No","type":"journal_article","volume":7,"issue":"4","title":"A stretched exponential bound on the rate of growth of the number of periodic points for prevalent diffeomorphisms I","quality_controlled":"1","doi":"10.1090/s1079-6762-01-00090-7","oa_version":"None","citation":{"mla":"Kaloshin, Vadim, and Brian R. Hunt. “A Stretched Exponential Bound on the Rate of Growth of the Number of Periodic Points for Prevalent Diffeomorphisms I.” Electronic Research Announcements of the American Mathematical Society, vol. 7, no. 4, American Mathematical Society, 2001, pp. 17–27, doi:10.1090/s1079-6762-01-00090-7.","short":"V. Kaloshin, B.R. Hunt, Electronic Research Announcements of the American Mathematical Society 7 (2001) 17–27.","ama":"Kaloshin V, Hunt BR. A stretched exponential bound on the rate of growth of the number of periodic points for prevalent diffeomorphisms I. Electronic Research Announcements of the American Mathematical Society. 2001;7(4):17-27. doi:10.1090/s1079-6762-01-00090-7","apa":"Kaloshin, V., & Hunt, B. R. (2001). A stretched exponential bound on the rate of growth of the number of periodic points for prevalent diffeomorphisms I. Electronic Research Announcements of the American Mathematical Society. American Mathematical Society. https://doi.org/10.1090/s1079-6762-01-00090-7","chicago":"Kaloshin, Vadim, and Brian R. Hunt. “A Stretched Exponential Bound on the Rate of Growth of the Number of Periodic Points for Prevalent Diffeomorphisms I.” Electronic Research Announcements of the American Mathematical Society. American Mathematical Society, 2001. https://doi.org/10.1090/s1079-6762-01-00090-7.","ieee":"V. Kaloshin and B. R. Hunt, “A stretched exponential bound on the rate of growth of the number of periodic points for prevalent diffeomorphisms I,” Electronic Research Announcements of the American Mathematical Society, vol. 7, no. 4. American Mathematical Society, pp. 17–27, 2001.","ista":"Kaloshin V, Hunt BR. 2001. A stretched exponential bound on the rate of growth of the number of periodic points for prevalent diffeomorphisms I. Electronic Research Announcements of the American Mathematical Society. 7(4), 17–27."}},{"page":"953-970","publication_status":"published","date_published":"2001-12-01T00:00:00Z","_id":"8524","month":"12","article_type":"original","status":"public","year":"2001","intvolume":" 11","publication_identifier":{"issn":["1016-443X","1420-8970"]},"author":[{"full_name":"Kaloshin, Vadim","id":"FE553552-CDE8-11E9-B324-C0EBE5697425","orcid":"0000-0002-6051-2628","last_name":"Kaloshin","first_name":"Vadim"},{"full_name":"Rodnianski, I.","first_name":"I.","last_name":"Rodnianski"}],"extern":"1","day":"01","publisher":"Springer Nature","date_created":"2020-09-18T10:50:11Z","doi":"10.1007/s00039-001-8222-8","citation":{"short":"V. Kaloshin, I. Rodnianski, Geometric And Functional Analysis 11 (2001) 953–970.","ama":"Kaloshin V, Rodnianski I. Diophantine properties of elements of SO(3). Geometric And Functional Analysis. 2001;11(5):953-970. doi:10.1007/s00039-001-8222-8","mla":"Kaloshin, Vadim, and I. Rodnianski. “Diophantine Properties of Elements of SO(3).” Geometric And Functional Analysis, vol. 11, no. 5, Springer Nature, 2001, pp. 953–70, doi:10.1007/s00039-001-8222-8.","ista":"Kaloshin V, Rodnianski I. 2001. Diophantine properties of elements of SO(3). Geometric And Functional Analysis. 11(5), 953–970.","apa":"Kaloshin, V., & Rodnianski, I. (2001). Diophantine properties of elements of SO(3). Geometric And Functional Analysis. Springer Nature. https://doi.org/10.1007/s00039-001-8222-8","chicago":"Kaloshin, Vadim, and I. Rodnianski. “Diophantine Properties of Elements of SO(3).” Geometric And Functional Analysis. Springer Nature, 2001. https://doi.org/10.1007/s00039-001-8222-8.","ieee":"V. Kaloshin and I. Rodnianski, “Diophantine properties of elements of SO(3),” Geometric And Functional Analysis, vol. 11, no. 5. Springer Nature, pp. 953–970, 2001."},"oa_version":"None","quality_controlled":"1","title":"Diophantine properties of elements of SO(3)","issue":"5","volume":11,"article_processing_charge":"No","type":"journal_article","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"A number α∈R is diophantine if it is not well approximable by rationals, i.e. for some C,ε>0 and any relatively prime p,q∈Z we have |αq−p|>Cq−1−ε. It is well-known and is easy to prove that almost every α in R is diophantine. In this paper we address a noncommutative version of the diophantine properties. Consider a pair A,B∈SO(3) and for each n∈Z+ take all possible words in A, A -1, B, and B - 1 of length n, i.e. for a multiindex I=(i1,i1,…,im,jm) define |I|=∑mk=1(|ik|+|jk|)=n and \\( W_n(A,B ) = \\{W_{\\cal I}(A,B) = A^{i_1} B^{j_1} \\dots A^{i_m} B^{j_m}\\}_{|{\\cal I|}=n \\).¶Gamburd—Jakobson—Sarnak [GJS] raised the problem: prove that for Haar almost every pair A,B∈SO(3) the closest distance of words of length n to the identity, i.e. sA,B(n)=min|I|=n∥WI(A,B)−E∥, is bounded from below by an exponential function in n. This is the analog of the diophantine property for elements of SO(3). In this paper we prove that s A,B (n) is bounded from below by an exponential function in n 2. We also exhibit obstructions to a “simple” proof of the exponential estimate in n."}],"publication":"Geometric And Functional Analysis","date_updated":"2021-01-12T08:19:52Z"},{"page":"890 - 900","article_type":"original","_id":"855","day":"01","publisher":"Oxford University Press","extern":"1","citation":{"apa":"Rogozin, I., Kochetov, A., Kondrashov, F., Koonin, E., & Milanesi, L. (2001). Presence of ATG triplets in 5′ untranslated regions of eukaryotic cDNAs correlates with a ’weak’context of the start codon. Bioinformatics. Oxford University Press. https://doi.org/10.1093/bioinformatics/17.10.890","ieee":"I. Rogozin, A. Kochetov, F. Kondrashov, E. Koonin, and L. Milanesi, “Presence of ATG triplets in 5′ untranslated regions of eukaryotic cDNAs correlates with a ’weak’context of the start codon,” Bioinformatics, vol. 17, no. 10. Oxford University Press, pp. 890–900, 2001.","chicago":"Rogozin, Igor, Alex Kochetov, Fyodor Kondrashov, Eugene Koonin, and Luciano Milanesi. “Presence of ATG Triplets in 5′ Untranslated Regions of Eukaryotic CDNAs Correlates with a ’weak’context of the Start Codon.” Bioinformatics. Oxford University Press, 2001. https://doi.org/10.1093/bioinformatics/17.10.890.","ista":"Rogozin I, Kochetov A, Kondrashov F, Koonin E, Milanesi L. 2001. Presence of ATG triplets in 5′ untranslated regions of eukaryotic cDNAs correlates with a ’weak’context of the start codon. Bioinformatics. 17(10), 890–900.","mla":"Rogozin, Igor, et al. “Presence of ATG Triplets in 5′ Untranslated Regions of Eukaryotic CDNAs Correlates with a ’weak’context of the Start Codon.” Bioinformatics, vol. 17, no. 10, Oxford University Press, 2001, pp. 890–900, doi:10.1093/bioinformatics/17.10.890.","short":"I. Rogozin, A. Kochetov, F. Kondrashov, E. Koonin, L. Milanesi, Bioinformatics 17 (2001) 890–900.","ama":"Rogozin I, Kochetov A, Kondrashov F, Koonin E, Milanesi L. Presence of ATG triplets in 5′ untranslated regions of eukaryotic cDNAs correlates with a ’weak’context of the start codon. Bioinformatics. 2001;17(10):890-900. doi:10.1093/bioinformatics/17.10.890"},"issue":"10","user_id":"ea97e931-d5af-11eb-85d4-e6957dddbf17","volume":17,"type":"journal_article","date_updated":"2023-06-02T09:08:25Z","language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"Motivation: The context of the start codon (typically, AUG) and the features of the 5′ Untranslated Regions (5′ UTRs) are important for understanding translation regulation in eukaryotic mRNAs and for accurate prediction of the coding region in genomic and cDNA sequences. The presence of AUG triplets in 5′ UTRs (upstream AUGs) might effect the initiation rate and, in the context of gene prediction, could reduce the accuracy of the identification of the authentic start. To reveal potential connections between the presence of upstream AUGs and other features of 5′ UTRs, such as their length and the start codon context, we undertook a systematic analysis of the available eukaryotic 5′ UTR sequences. Results: We show that a large fraction of 5′ UTRs in the available cDNA sequences, 15-53% depending on the organism, contain upstream ATGs. A negative correlation was observed between the information content of the translation start signal and the length of the 5′ UTR. Similarly, a negative correlation exists between the 'strength' of the start context and the number of upstream ATGs. Typically, cDNAs containing long 5′ UTRs with multiple upstream ATGs have a 'weak' start context, and in contrast, cDNAs containing short 5′ UTRs without ATGs have 'strong' starts. These counter-intuitive results may be interpreted in terms of upstream AUGs having an important role in the regulation of translation efficiency by ensuring low basal translation level via double negative control and creating the potential for additional regulatory mechanisms. One of such mechanisms, supported by experimental studies of some mRNAs, includes removal of the AUG-containing portion of the 5′ UTR by alternative splicing."}],"publication_status":"published","date_published":"2001-10-01T00:00:00Z","year":"2001","month":"10","status":"public","date_created":"2018-12-11T11:48:52Z","intvolume":" 17","publication_identifier":{"issn":["1367-4803"]},"publist_id":"6795","author":[{"first_name":"Igor","last_name":"Rogozin","full_name":"Rogozin, Igor"},{"last_name":"Kochetov","first_name":"Alex","full_name":"Kochetov, Alex"},{"id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","full_name":"Kondrashov, Fyodor","orcid":"0000-0001-8243-4694","last_name":"Kondrashov","first_name":"Fyodor"},{"full_name":"Koonin, Eugene","first_name":"Eugene","last_name":"Koonin"},{"first_name":"Luciano","last_name":"Milanesi","full_name":"Milanesi, Luciano"}],"external_id":{"pmid":["11673233"]},"oa_version":"None","doi":"10.1093/bioinformatics/17.10.890","scopus_import":"1","quality_controlled":"1","title":"Presence of ATG triplets in 5′ untranslated regions of eukaryotic cDNAs correlates with a 'weak'context of the start codon","article_processing_charge":"No","acknowledgement":"This work has been partially supported by EU 'TRADAT' project and by CNR Genetic Engineering (Italy), the RFBR grant for support of scientific schools (00-15-97968) and SD RAS grant for young scientists (AVK). The authors wish to thank J.Lyons-Weiler for helpful comments and A. Sorokin for help with the ATG_EVALUATOR program.","publication":"Bioinformatics","pmid":1},{"month":"11","status":"public","year":"2001","intvolume":" 10","publist_id":"6777","publication_identifier":{"issn":["0964-6906"]},"author":[{"full_name":"Kondrashov, Fyodor","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8243-4694","last_name":"Kondrashov","first_name":"Fyodor"},{"last_name":"Koonin","first_name":"Eugene","full_name":"Koonin, Eugene"}],"date_created":"2018-12-11T11:48:55Z","publication_status":"published","date_published":"2001-11-01T00:00:00Z","article_processing_charge":"No","publication":"Human Molecular Genetics","pmid":1,"external_id":{"pmid":["11726553"]},"doi":"10.1093/hmg/10.23.2661","oa_version":"Published Version","quality_controlled":"1","title":"Origin of alternative splicing by tandem exon duplication","scopus_import":"1","_id":"867","article_type":"original","extern":"1","publisher":"Oxford University Press","day":"01","page":"2661 - 2669","volume":10,"type":"journal_article","user_id":"ea97e931-d5af-11eb-85d4-e6957dddbf17","language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"Genes with new functions often evolve by gene duplication. Alternative splicing is another means of evolutionary innovation in eukaryotes, which allows a single gene to encode functionally diverse proteins. We investigate a connection between these two evolutionary phenomena. For ∼10% of the described cases of substitution alternative splicing, such that either one or another amino acid sequence is included into the protein, evidence of origin by tandem exon duplication was found. This is a conservative estimate because alternative exons are typically short and, on many occasions, duplicates may have diverged beyond recognition. Dating exon duplications through a combination of the available experimental data on alternative splicing in orthologous genes from different species and computational analysis indicates that most of the duplications antedate at least the radiation of mammalian orders or even the radiation of vertebrate classes. At present, tandem exon duplication is the only mechanism of evolution of substitution alternative splicing that can be specifically demonstrated. Along with gene duplication, this could be a major route for generating functional diversity during evolution of multicellular eukaryotes."}],"date_updated":"2023-06-02T08:39:47Z","citation":{"short":"F. Kondrashov, E. Koonin, Human Molecular Genetics 10 (2001) 2661–2669.","ama":"Kondrashov F, Koonin E. Origin of alternative splicing by tandem exon duplication. Human Molecular Genetics. 2001;10(23):2661-2669. doi:10.1093/hmg/10.23.2661","mla":"Kondrashov, Fyodor, and Eugene Koonin. “Origin of Alternative Splicing by Tandem Exon Duplication.” Human Molecular Genetics, vol. 10, no. 23, Oxford University Press, 2001, pp. 2661–69, doi:10.1093/hmg/10.23.2661.","ista":"Kondrashov F, Koonin E. 2001. Origin of alternative splicing by tandem exon duplication. Human Molecular Genetics. 10(23), 2661–2669.","apa":"Kondrashov, F., & Koonin, E. (2001). Origin of alternative splicing by tandem exon duplication. Human Molecular Genetics. Oxford University Press. https://doi.org/10.1093/hmg/10.23.2661","chicago":"Kondrashov, Fyodor, and Eugene Koonin. “Origin of Alternative Splicing by Tandem Exon Duplication.” Human Molecular Genetics. Oxford University Press, 2001. https://doi.org/10.1093/hmg/10.23.2661.","ieee":"F. Kondrashov and E. Koonin, “Origin of alternative splicing by tandem exon duplication,” Human Molecular Genetics, vol. 10, no. 23. Oxford University Press, pp. 2661–2669, 2001."},"issue":"23"},{"issue":"21","citation":{"ama":"Kondrashov F, Kondrashov A. Multidimensional epistasis and the disadvantage of sex. PNAS. 2001;98(21):12089-12092. doi:10.1073/pnas.211214298","short":"F. Kondrashov, A. Kondrashov, PNAS 98 (2001) 12089–12092.","mla":"Kondrashov, Fyodor, and Alexey Kondrashov. “Multidimensional Epistasis and the Disadvantage of Sex.” PNAS, vol. 98, no. 21, National Academy of Sciences, 2001, pp. 12089–92, doi:10.1073/pnas.211214298.","ista":"Kondrashov F, Kondrashov A. 2001. Multidimensional epistasis and the disadvantage of sex. PNAS. 98(21), 12089–12092.","chicago":"Kondrashov, Fyodor, and Alexey Kondrashov. “Multidimensional Epistasis and the Disadvantage of Sex.” PNAS. National Academy of Sciences, 2001. https://doi.org/10.1073/pnas.211214298.","ieee":"F. Kondrashov and A. Kondrashov, “Multidimensional epistasis and the disadvantage of sex,” PNAS, vol. 98, no. 21. National Academy of Sciences, pp. 12089–12092, 2001.","apa":"Kondrashov, F., & Kondrashov, A. (2001). Multidimensional epistasis and the disadvantage of sex. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.211214298"},"language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"Sex is thought to facilitate accumulation of initially rare beneficial mutations by allowing simultaneous allele replacements at many loci. However, this advantage of sex depends on a restrictive assumption that the fitness of a genotype is determined by fitness potential, a single intermediate variable to which all loci contribute additively, so that new alleles can accumulate in any order. Individual-based simulations of sexual and asexual populations reveal that under generic selection, sex often retards adaptive evolution. When new alleles are beneficial only if they accumulate in a prescribed order, a sexual population may evolve two or more times slower than an asexual population because only asexual reproduction allows some overlap of successive allele replacements. Many other fitness surfaces lead to an even greater disadvantage of sex. Thus, either sex exists in spite of its impact on the rate of adaptive allele replacements, or natural fitness surfaces have rather specific properties, at least at the scale of intrapopulation genetic variability."}],"date_updated":"2023-06-02T08:18:22Z","type":"journal_article","volume":98,"user_id":"ea97e931-d5af-11eb-85d4-e6957dddbf17","oa":1,"page":"12089 - 12092","extern":"1","publisher":"National Academy of Sciences","day":"09","_id":"874","article_type":"original","quality_controlled":"1","title":"Multidimensional epistasis and the disadvantage of sex","scopus_import":"1","external_id":{"pmid":["11593020"]},"doi":"10.1073/pnas.211214298","oa_version":"Published Version","pmid":1,"publication":"PNAS","article_processing_charge":"No","date_published":"2001-10-09T00:00:00Z","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC59772/","open_access":"1"}],"publication_status":"published","publication_identifier":{"issn":["0027-8424"]},"intvolume":" 98","publist_id":"6774","author":[{"id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","full_name":"Kondrashov, Fyodor","orcid":"0000-0001-8243-4694","last_name":"Kondrashov","first_name":"Fyodor"},{"full_name":"Kondrashov, Alexey","first_name":"Alexey","last_name":"Kondrashov"}],"date_created":"2018-12-11T11:48:58Z","month":"10","status":"public","year":"2001"},{"issue":"12","article_number":"research0053.1","citation":{"apa":"Jordan, I., Kondrashov, F., Rogozin, I., Tatusov, R., Wolf, Y., & Koonin, E. (2001). Constant relative rate of protein evolution and detection of functional diversification among bacterial, archaeal and eukaryotic proteins . Genome Biology. BioMed Central. https://doi.org/10.1186/gb-2001-2-12-research0053","chicago":"Jordan, Ingo, Fyodor Kondrashov, Igor Rogozin, Roman Tatusov, Yuri Wolf, and Eugene Koonin. “Constant Relative Rate of Protein Evolution and Detection of Functional Diversification among Bacterial, Archaeal and Eukaryotic Proteins .” Genome Biology. BioMed Central, 2001. https://doi.org/10.1186/gb-2001-2-12-research0053.","ieee":"I. Jordan, F. Kondrashov, I. Rogozin, R. Tatusov, Y. Wolf, and E. Koonin, “Constant relative rate of protein evolution and detection of functional diversification among bacterial, archaeal and eukaryotic proteins ,” Genome Biology, vol. 2, no. 12. BioMed Central, 2001.","ista":"Jordan I, Kondrashov F, Rogozin I, Tatusov R, Wolf Y, Koonin E. 2001. Constant relative rate of protein evolution and detection of functional diversification among bacterial, archaeal and eukaryotic proteins . Genome Biology. 2(12), research0053.1.","mla":"Jordan, Ingo, et al. “Constant Relative Rate of Protein Evolution and Detection of Functional Diversification among Bacterial, Archaeal and Eukaryotic Proteins .” Genome Biology, vol. 2, no. 12, research0053.1, BioMed Central, 2001, doi:10.1186/gb-2001-2-12-research0053.","short":"I. Jordan, F. Kondrashov, I. Rogozin, R. Tatusov, Y. Wolf, E. Koonin, Genome Biology 2 (2001).","ama":"Jordan I, Kondrashov F, Rogozin I, Tatusov R, Wolf Y, Koonin E. Constant relative rate of protein evolution and detection of functional diversification among bacterial, archaeal and eukaryotic proteins . Genome Biology. 2001;2(12). doi:10.1186/gb-2001-2-12-research0053"},"date_updated":"2023-05-31T12:15:37Z","abstract":[{"text":"BACKGROUND: Detection of changes in a protein's evolutionary rate may reveal cases of change in that protein's function. We developed and implemented a simple relative rates test in an attempt to assess the rate constancy of protein evolution and to detect cases of functional diversification between orthologous proteins. The test was performed on clusters of orthologous protein sequences from complete bacterial genomes (Chlamydia trachomatis, C. muridarum and Chlamydophila pneumoniae), complete archaeal genomes (Pyrococcus horikoshii, P. abyssi and P. furiosus) and partially sequenced mammalian genomes (human, mouse and rat). RESULTS: Amino-acid sequence evolution rates are significantly correlated on different branches of phylogenetic trees representing the great majority of analyzed orthologous protein sets from all three domains of life. However, approximately 1% of the proteins from each group of species deviates from this pattern and instead shows variation that is consistent with an acceleration of the rate of amino-acid substitution, which may be due to functional diversification. Most of the putative functionally diversified proteins from all three species groups are predicted to function at the periphery of the cells and mediate their interaction with the environment. CONCLUSIONS: Relative rates of protein evolution are remarkably constant for the three species groups analyzed here. Deviations from this rate constancy are probably due to changes in selective constraints associated with diversification between orthologs. Functional diversification between orthologs is thought to be a relatively rare event. However, the resolution afforded by the test designed specifically for genomic-scale datasets allowed us to identify numerous cases of possible functional diversification between orthologous proteins.","lang":"eng"}],"language":[{"iso":"eng"}],"oa":1,"user_id":"ea97e931-d5af-11eb-85d4-e6957dddbf17","volume":2,"type":"journal_article","day":"01","publisher":"BioMed Central","extern":"1","article_type":"original","_id":"888","scopus_import":"1","title":"Constant relative rate of protein evolution and detection of functional diversification among bacterial, archaeal and eukaryotic proteins ","quality_controlled":"1","oa_version":"Published Version","doi":"10.1186/gb-2001-2-12-research0053","external_id":{"pmid":["11790256"]},"acknowledgement":"We thank Alexey Kondrashov for many helpful discussions and constructive criticisms, Charles DeLisi, David Landsman, Detlef Leipe, Wojciech Makalowski and Itai Yanai for critical reading of the manuscript and constructive comments and L. Aravind for advice on protein function prediction. The release of the unpublished P. furiosus genome sequence by the Utah Genome Center at the University of Utah is acknowledged and appreciated.","publication":"Genome Biology","pmid":1,"article_processing_charge":"No","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC64838/","open_access":"1"}],"date_published":"2001-01-01T00:00:00Z","publication_status":"published","date_created":"2018-12-11T11:49:02Z","author":[{"full_name":"Jordan, Ingo","first_name":"Ingo","last_name":"Jordan"},{"first_name":"Fyodor","last_name":"Kondrashov","orcid":"0000-0001-8243-4694","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","full_name":"Kondrashov, Fyodor"},{"full_name":"Rogozin, Igor","last_name":"Rogozin","first_name":"Igor"},{"full_name":"Tatusov, Roman","first_name":"Roman","last_name":"Tatusov"},{"first_name":"Yuri","last_name":"Wolf","full_name":"Wolf, Yuri"},{"first_name":"Eugene","last_name":"Koonin","full_name":"Koonin, Eugene"}],"intvolume":" 2","publist_id":"6758","publication_identifier":{"issn":["1465-6906"]},"year":"2001","status":"public","month":"01"},{"page":"2077-2080","_id":"9444","article_type":"original","publisher":"American Association for the Advancement of Science","day":"15","extern":"1","citation":{"mla":"Lindroth, A. M., et al. “Requirement of CHROMOMETHYLASE3 for Maintenance of CpXpG Methylation.” Science, vol. 292, no. 5524, American Association for the Advancement of Science, 2001, pp. 2077–80, doi:10.1126/science.1059745.","short":"A.M. Lindroth, X. Cao, J.P. Jackson, D. Zilberman, C.M. McCallum, S. Henikoff, S.E. Jacobsen, Science 292 (2001) 2077–2080.","ama":"Lindroth AM, Cao X, Jackson JP, et al. Requirement of CHROMOMETHYLASE3 for maintenance of CpXpG methylation. Science. 2001;292(5524):2077-2080. doi:10.1126/science.1059745","apa":"Lindroth, A. M., Cao, X., Jackson, J. P., Zilberman, D., McCallum, C. M., Henikoff, S., & Jacobsen, S. E. (2001). Requirement of CHROMOMETHYLASE3 for maintenance of CpXpG methylation. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.1059745","chicago":"Lindroth, A. M., Xiaofeng Cao, James P. Jackson, Daniel Zilberman, Claire M. McCallum, Steven Henikoff, and Steven E. Jacobsen. “Requirement of CHROMOMETHYLASE3 for Maintenance of CpXpG Methylation.” Science. American Association for the Advancement of Science, 2001. https://doi.org/10.1126/science.1059745.","ieee":"A. M. Lindroth et al., “Requirement of CHROMOMETHYLASE3 for maintenance of CpXpG methylation,” Science, vol. 292, no. 5524. American Association for the Advancement of Science, pp. 2077–2080, 2001.","ista":"Lindroth AM, Cao X, Jackson JP, Zilberman D, McCallum CM, Henikoff S, Jacobsen SE. 2001. Requirement of CHROMOMETHYLASE3 for maintenance of CpXpG methylation. Science. 292(5524), 2077–2080."},"issue":"5524","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","type":"journal_article","volume":292,"keyword":["Multidisciplinary"],"date_updated":"2021-12-14T08:40:32Z","language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"Epigenetic silenced alleles of the Arabidopsis SUPERMANlocus (the clark kent alleles) are associated with dense hypermethylation at noncanonical cytosines (CpXpG and asymmetric sites, where X = A, T, C, or G). A genetic screen for suppressors of a hypermethylated clark kent mutant identified nine loss-of-function alleles of CHROMOMETHYLASE3(CMT3), a novel cytosine methyltransferase homolog. These cmt3 mutants display a wild-type morphology but exhibit decreased CpXpG methylation of the SUP gene and of other sequences throughout the genome. They also show reactivated expression of endogenous retrotransposon sequences. These results show that a non-CpG DNA methyltransferase is responsible for maintaining epigenetic gene silencing."}],"publication_status":"published","department":[{"_id":"DaZi"}],"date_published":"2001-06-15T00:00:00Z","year":"2001","month":"06","status":"public","date_created":"2021-06-02T13:35:16Z","intvolume":" 292","publication_identifier":{"eissn":["1095-9203"],"issn":["0036-8075"]},"author":[{"full_name":"Lindroth, A. M.","first_name":"A. M.","last_name":"Lindroth"},{"last_name":"Cao","first_name":"Xiaofeng","full_name":"Cao, Xiaofeng"},{"full_name":"Jackson, James P.","first_name":"James P.","last_name":"Jackson"},{"last_name":"Zilberman","first_name":"Daniel","full_name":"Zilberman, Daniel","id":"6973db13-dd5f-11ea-814e-b3e5455e9ed1","orcid":"0000-0002-0123-8649"},{"first_name":"Claire M.","last_name":"McCallum","full_name":"McCallum, Claire M."},{"full_name":"Henikoff, Steven","first_name":"Steven","last_name":"Henikoff"},{"first_name":"Steven E.","last_name":"Jacobsen","full_name":"Jacobsen, Steven E."}],"doi":"10.1126/science.1059745","external_id":{"pmid":["11349138"]},"oa_version":"None","scopus_import":"1","quality_controlled":"1","title":"Requirement of CHROMOMETHYLASE3 for maintenance of CpXpG methylation","article_processing_charge":"No","publication":"Science","pmid":1},{"user_id":"ea97e931-d5af-11eb-85d4-e6957dddbf17","volume":18,"type":"journal_article","date_updated":"2023-05-08T12:22:38Z","abstract":[{"lang":"eng","text":"State-space explosion is a fundamental obstacle in the formal verification of designs and protocols. Several techniques for combating this problem have emerged in the past few years, among which two are significant: partial-order reduction and symbolic state-space search. In asynchronous systems, interleavings of independent concurrent events are equivalent, and only a representative interleaving needs to be explored to verify local properties. Partial-order methods exploit this redundancy and visit only a subset of the reachable states. Symbolic techniques, on the other hand, capture the transition relation of a system and the set of reachable states as boolean functions. In many cases, these functions can be represented compactly using binary decision diagrams (BDDs). Traditionally, the two techniques have been practiced by two different schools—partial-order methods with enumerative depth-first search for the analysis of asynchronous network protocols, and symbolic breadth-first search for the analysis of synchronous hardware designs. We combine both approaches and develop a method for using partial-order reduction techniques in symbolic BDD-based invariant checking. We present theoretical results to prove the correctness of the method, and experimental results to demonstrate its efficacy."}],"language":[{"iso":"eng"}],"citation":{"mla":"Alur, Rajeev, et al. “Partial-Order Reduction in Symbolic State-Space Exploration.” Formal Methods in System Design, vol. 18, no. 2, Springer, 2001, pp. 97–116, doi:10.1023/A:1008767206905.","ama":"Alur R, Brayton R, Henzinger TA, Qadeer S, Rajamani S. Partial-order reduction in symbolic state-space exploration. Formal Methods in System Design. 2001;18(2):97-116. doi:10.1023/A:1008767206905","short":"R. Alur, R. Brayton, T.A. Henzinger, S. Qadeer, S. Rajamani, Formal Methods in System Design 18 (2001) 97–116.","chicago":"Alur, Rajeev, Robert Brayton, Thomas A Henzinger, Shaz Qadeer, and Sriram Rajamani. “Partial-Order Reduction in Symbolic State-Space Exploration.” Formal Methods in System Design. Springer, 2001. https://doi.org/10.1023/A:1008767206905.","ieee":"R. Alur, R. Brayton, T. A. Henzinger, S. Qadeer, and S. Rajamani, “Partial-order reduction in symbolic state-space exploration,” Formal Methods in System Design, vol. 18, no. 2. Springer, pp. 97–116, 2001.","apa":"Alur, R., Brayton, R., Henzinger, T. A., Qadeer, S., & Rajamani, S. (2001). Partial-order reduction in symbolic state-space exploration. Formal Methods in System Design. Springer. https://doi.org/10.1023/A:1008767206905","ista":"Alur R, Brayton R, Henzinger TA, Qadeer S, Rajamani S. 2001. Partial-order reduction in symbolic state-space exploration. Formal Methods in System Design. 18(2), 97–116."},"issue":"2","article_type":"original","_id":"4599","publisher":"Springer","day":"01","extern":"1","page":"97 - 116","article_processing_charge":"No","acknowledgement":"Gerard Holzmann provided us with information on SPIN. Ken McMillan and Doron Peled contributed through discussions. The VIS group at UC Berkeley and Rajeev Ranjan in particular helped with the experiments.","publication":"Formal Methods in System Design","oa_version":"None","doi":"10.1023/A:1008767206905","scopus_import":"1","title":"Partial-order reduction in symbolic state-space exploration","quality_controlled":"1","year":"2001","status":"public","month":"03","date_created":"2018-12-11T12:09:41Z","author":[{"first_name":"Rajeev","last_name":"Alur","full_name":"Alur, Rajeev"},{"last_name":"Brayton","first_name":"Robert","full_name":"Brayton, Robert"},{"last_name":"Henzinger","first_name":"Thomas A","id":"40876CD8-F248-11E8-B48F-1D18A9856A87","full_name":"Henzinger, Thomas A","orcid":"0000−0002−2985−7724"},{"last_name":"Qadeer","first_name":"Shaz","full_name":"Qadeer, Shaz"},{"first_name":"Sriram","last_name":"Rajamani","full_name":"Rajamani, Sriram"}],"publist_id":"108","intvolume":" 18","publication_identifier":{"issn":["0925-9856"]},"publication_status":"published","date_published":"2001-03-01T00:00:00Z"},{"title":"jMocha: A model-checking tool that exploits design structure","quality_controlled":"1","conference":{"name":"ICSE: Software Engineering"},"doi":"10.1109/ICSE.2001.919196","citation":{"ista":"Alur R, De Alfaro L, Grosu R, Henzinger TA, Kang M, Kirsch C, Majumdar R, Mang F, Wang B. 2001. jMocha: A model-checking tool that exploits design structure. Proceedings of the 23rd International Conference on Software Engineering. ICSE: Software Engineering, 835–836.","apa":"Alur, R., De Alfaro, L., Grosu, R., Henzinger, T. A., Kang, M., Kirsch, C., … Wang, B. (2001). jMocha: A model-checking tool that exploits design structure. In Proceedings of the 23rd International Conference on Software Engineering (pp. 835–836). IEEE. https://doi.org/10.1109/ICSE.2001.919196","chicago":"Alur, Rajeev, Luca De Alfaro, Radu Grosu, Thomas A Henzinger, Myong Kang, Christoph Kirsch, Ritankar Majumdar, Freddy Mang, and Bow Wang. “JMocha: A Model-Checking Tool That Exploits Design Structure.” In Proceedings of the 23rd International Conference on Software Engineering, 835–36. IEEE, 2001. https://doi.org/10.1109/ICSE.2001.919196.","ieee":"R. Alur et al., “jMocha: A model-checking tool that exploits design structure,” in Proceedings of the 23rd International Conference on Software Engineering, 2001, pp. 835–836.","short":"R. Alur, L. De Alfaro, R. Grosu, T.A. Henzinger, M. Kang, C. Kirsch, R. Majumdar, F. Mang, B. Wang, in:, Proceedings of the 23rd International Conference on Software Engineering, IEEE, 2001, pp. 835–836.","ama":"Alur R, De Alfaro L, Grosu R, et al. jMocha: A model-checking tool that exploits design structure. In: Proceedings of the 23rd International Conference on Software Engineering. IEEE; 2001:835-836. doi:10.1109/ICSE.2001.919196","mla":"Alur, Rajeev, et al. “JMocha: A Model-Checking Tool That Exploits Design Structure.” Proceedings of the 23rd International Conference on Software Engineering, IEEE, 2001, pp. 835–36, doi:10.1109/ICSE.2001.919196."},"oa_version":"None","publication":"Proceedings of the 23rd International Conference on Software Engineering","abstract":[{"lang":"eng","text":"Model checking is a practical tool for automated debugging of embedded software. In model checking, a high-level description of a system is compared against a logical correctness requirement to discover inconsistencies. Since model checking is based on exhaustive state-space exploration and the size of the state space of a design grows exponentially with the size of the description, scalability remains a challenge. We have thus developed techniques for exploiting modular design structure during model checking, and the model checker jMocha (Java MOdel-CHecking Algorithm) is based on this theme. Instead of manipulating unstructured state-transition graphs, it supports the hierarchical modeling framework of reactive modules. jMocha is a growing interactive software environment for specification, simulation and verification, and is intended as a vehicle for the development of new verification algorithms and approaches. It is written in Java and uses native C-code BDD libraries from VIS. jMocha offers: (1) a GUI that looks familiar to Windows/Java users; (2) a simulator that displays traces in a message sequence chart fashion; (3) requirements verification both by symbolic and enumerative model checking; (4) implementation verification by checking trace containment; (5) a proof manager that aids compositional and assume-guarantee reasoning; and (6) SLANG (Scripting LANGuage) for the rapid and structured development of new verification algorithms. jMocha is available publicly at ; it is a successor and extension of the original Mocha tool that was entirely written in C."}],"language":[{"iso":"eng"}],"date_updated":"2023-05-08T14:06:55Z","acknowledgement":"We thank Himyanshu Anand, Ben Horowitz, Franjo Ivancic, Michael McDougall, Marius Minea, Oliver Moeller. Shaz Qadeer, Sriram Rajamani, and Jean-Francois Raskin for their assistance in the development of JMOCHA. The MOCHA project is funded in part by the DARPA grant NAG2-1214, the NSF CAREER awards CCR95-01708 and CCR97-34115, the NSF grant CCR99-70925, the NSF ITR grant CCR0085949, the MARC0 grant 98-DT-660, and the SRC contracts 99-TJ-683.003 and 99-TJ-688. ","article_processing_charge":"No","type":"conference","user_id":"ea97e931-d5af-11eb-85d4-e6957dddbf17","date_published":"2001-08-07T00:00:00Z","page":"835 - 836","publication_status":"published","author":[{"full_name":"Alur, Rajeev","last_name":"Alur","first_name":"Rajeev"},{"full_name":"De Alfaro, Luca","first_name":"Luca","last_name":"De Alfaro"},{"last_name":"Grosu","first_name":"Radu","full_name":"Grosu, Radu"},{"full_name":"Henzinger, Thomas A","id":"40876CD8-F248-11E8-B48F-1D18A9856A87","orcid":"0000−0002−2985−7724","last_name":"Henzinger","first_name":"Thomas A"},{"full_name":"Kang, Myong","last_name":"Kang","first_name":"Myong"},{"full_name":"Kirsch, Christoph","last_name":"Kirsch","first_name":"Christoph"},{"full_name":"Majumdar, Ritankar","last_name":"Majumdar","first_name":"Ritankar"},{"first_name":"Freddy","last_name":"Mang","full_name":"Mang, Freddy"},{"last_name":"Wang","first_name":"Bow","full_name":"Wang, Bow"}],"extern":"1","publication_identifier":{"isbn":["0769510507"]},"publist_id":"109","date_created":"2018-12-11T12:09:41Z","publisher":"IEEE","day":"07","status":"public","_id":"4600","month":"08","year":"2001"}]