TY  - JOUR
A1  - Brunet, Frédéric G.
A1  - Volff, Jean-Nicolas
A1  - Schartl, Manfred
T1  - Whole Genome Duplications Shaped the Receptor Tyrosine Kinase Repertoire of Jawed Vertebrates
JF  - Genome Biology Evolution
N2  - The receptor tyrosine kinase (RTK) gene family, involved primarily in cell growth and differentiation, comprises proteins with a common enzymatic tyrosine kinase intracellular domain adjacent to a transmembrane region. The amino-terminal portion of RTKs is extracellular and made of different domains, the combination of which characterizes each of the 20 RTK subfamilies among mammals. We analyzed a total of 7,376 RTK sequences among 143 vertebrate species to provide here the first comprehensive census of the jawed vertebrate repertoire. We ascertained the 58 genes previously described in the human and mouse genomes and established their phylogenetic relationships. We also identified five additional RTKs amounting to a total of 63 genes in jawed vertebrates. We found that the vertebrate RTK gene family has been shaped by the two successive rounds of whole genome duplications (WGD) called 1R and 2R (1R/2R) that occurred at the base of the vertebrates. In addition, the Vegfr and Ephrin receptor subfamilies were expanded by single gene duplications. In teleost fish, 23 additional RTK genes have been retained after another expansion through the fish-specific third round (3R) of WGD. Several lineage-specific gene losses were observed. For instance, birds have lost three RTKs, and different genes are missing in several fish sublineages. The RTK gene family presents an unusual high gene retention rate from the vertebrate WGDs (58.75% after 1R/2R, 64.4% after 3R), resulting in an expansion that might be correlated with the evolution of complexity of vertebrate cellular communication and intracellular signaling.
KW  - receptor tyrosine kinase
KW  - vertebrates
KW  - deuterostomes
KW  - whole genome duplications
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146988
VL  - 8
IS  - 15
ER  - 
TY  - JOUR
A1  - Giordano, Rosaria
A1  - Canesi, Margherita
A1  - Isalberti, Maurizio
A1  - Isaias, Ioannis Ugo
A1  - Montemurro, Tiziana
A1  - Viganò, Mariele
A1  - Montelatici, Elisa
A1  - Boldrin, Valentina
A1  - Benti, Riccardo
A1  - Cortelezzi, Agostino
A1  - Fracchiolla, Nicola
A1  - Lazzari, Lorenza
A1  - Pezzoli, Gianni
T1  - Autologous mesenchymal stem cell therapy for progressive supranuclear palsy: translation into a phase I controlled, randomized clinical study
JF  - Journal of Translational Medicine
N2  - Background: Progressive Supranuclear Palsy (PSP) is a sporadic and progressive neurodegenerative disease which belongs to the family of tauopathies and involves both cortical and subcortical structures. No effective therapy is to date available. 
Methods/design: Autologous bone marrow (BM) mesenchymal stem cells (MSC) from patients affected by different type of parkinsonisms have shown their ability to improve the dopaminergic function in preclinical and clinical models. It is also possible to isolate and expand MSC from the BM of PSP patients with the same proliferation rate and immuphenotypic profile as MSC from healthy donors. BM MSC can be efficiently delivered to the affected brain regions of PSP patients where they can exert their beneficial effects through different mechanisms including the secretion of neurotrophic factors. Here we propose a randomized, placebo-controlled, double-blind phase I clinical trial in patients affected by PSP with MSC delivered via intra-arterial injection. 
Discussion: To our knowledge, this is the first clinical trial to be applied in a no-option parkinsonism that aims to test the safety and to exploit the properties of autologous mesenchymal stem cells in reducing disease progression. The study has been designed to test the safety of this " first-in-man" approach and to preliminarily explore its efficacy by excluding the placebo effect. 
Trial registration: NCT01824121
KW  - Parkinson's disease
KW  - cellular therapy
KW  - deep brain-stimulation
KW  - bone-marrow
KW  - transplantation
KW  - receptor tyrosine kinase
KW  - Richardson-Olszewski-Syndrome
KW  - multiple system atrophy
KW  - advanced therapy medicinal products
KW  - mesenchymal stem and stromal cells
KW  - progressive supranuclear palsy
KW  - treatment options
KW  - adrenal medulla
KW  - stromal cells
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117594
VL  - 12
IS  - 14
ER  -