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91.
Francesca Tatini Anna Maria Pugliese Chiara Traini Sandra Niccoli Giovanna Maraula Teresa Ed Dami Benedetta Mannini Tania Scartabelli Felicita Pedata Fiorella Casamenti Fabrizio Chiti 《Neurobiology of aging》2013
Protein misfolded oligomers are thought to be the primary pathogenic species in many protein deposition diseases. Oligomers by the amyloid-β peptide play a central role in Alzheimer's disease pathogenesis, being implicated in synaptic dysfunction. Here we show that the oligomers formed by a protein that has no link with human disease, namely the N-terminal domain of HypF from Escherichia coli (HypF-N), are also synaptotoxic. HypF-N oligomers were found to (i) colocalize with post-synaptic densities in primary rat hippocampal neurons; (ii) induce impairment of long-term potentiation in rat hippocampal slices; and (iii) impair spatial learning of rats in the Morris Water Maze test. By contrast, the native protein and control nontoxic oligomers had none of such effects. These results raise the importance of using HypF-N oligomers as a valid tool to investigate the pathogenesis of Alzheimer's disease, with advantages over other systems for their stability, reproducibility, and costs. The results also suggest that, in the context of a compromised protein homeostasis resulting from aggregation of the amyloid β peptide, a number of oligomeric species sharing common synaptotoxic activity can arise and cooperate in the pathogenesis of the disease. 相似文献
92.
Romagnolo Alberto Balestrino Roberta Imbalzano Gabriele Ciccone Giovannino Riccardini Franco Artusi Carlo Alberto Bozzali Marco Ferrero Bruno Montalenti Elisa Montanaro Elisa Rizzone Mario Giorgio Vaula Giovanna Zibetti Maurizio Lopiano Leonardo 《Journal of neurology》2021,268(3):762-769
Journal of Neurology - Neurological symptoms of COVID-19 patients have been recently described. However, no comprehensive data have been reported on pre-existing neurological comorbidities and... 相似文献
93.
Bucello Sebastiano Annovazzi Pietro Ragonese Paolo Altieri Marta Barcella Valeria Bergamaschi Roberto Bianchi Alessia Borriello Giovanna Buscarinu Maria Chiara Callari Graziella Capobianco Marco Capone Fioravante Cavalla Paola Cavarretta Rosella Cortese Antonio De Luca Giovanna Di Filippo Massimiliano Dattola Vincenzo Fantozzi Roberta Ferraro Elisabetta Filippi Maria Maddalena Gasperini Claudio Grimaldi Luigi Maria Edoardo Landi Doriana Re Marianna Lo Mallucci Giulia Manganotti Paolo Marfia Girolama Alessandra Mirabella Massimiliano Perini Paola Pisa Marco Realmuto Sabrina Russo Margherita Tomassini Valentina Torri-Clerici Valentina Liliana Adriana Zaffaroni Mauro Zuliani Cristina Zywicki Sofia Filippi Massimo Prosperini Luca 《Journal of neurology》2021,268(8):2922-2932
Journal of Neurology - To identify baseline factors associated with disease activity in patients with relapsing–remitting multiple sclerosis (RRMS) under teriflunomide treatment. This was an... 相似文献
94.
Thomas Klopstock MD Aleksandar Videnovic MD Almut Turid Bischoff MD Cecilia Bonnet MD Laura Cif MD Cynthia Comella MD Marta Correa-Vela MD Maria L. Escolar MD Jamie L. Fraser MD Victoria Gonzalez MD Neal Hermanowicz MD Robert Jech MD Hyder A. Jinnah MD Tomasz Kmiec MD Anthony Lang MD Maria J. Martí MD Saadet Mercimek-Andrews MD Migvis Monduy MD Graeme A.M. Nimmo MBBS Belen Perez-Dueñas MD Helle Cecilie Viekilde Pfeiffer MD Lluis Planellas MD Emmanuel Roze MD Nivedita Thakur MD Laura Tochen MD Nora Vanegas-Arroyave MD Giovanna Zorzi MD Colleen Burns PhD Feriandas Greblikas MD 《Movement disorders》2021,36(6):1342-1352
95.
Marco Romano Monica Sen Cristiano Scottà Rowa Y. Alhabbab Andres Rico-Armada Robert I. Lechler Michael Burch Giovanna Lombardi 《European journal of immunology》2021,51(8):2086-2092
Regulatory T-cells (Tregs) are a subset of T cells generated in the thymus with intrinsic immunosuppressive properties. Phase I clinical trials have shown safety and feasibility of Treg infusion to promote immune tolerance and new studies are ongoing to evaluate their efficacy. During heart transplantation, thymic tissue is routinely discarded providing an attractive source of Tregs. In this study, we developed a GMP-compatible protocol for expanding sorted thymus-derived CD3+CD4+CD25+CD127– (Tregs) as well as CD3+CD4+CD25+CD127–CD45RA+ (RA+Tregs) cells. We aimed to understand whether thymic RA+Tregs can be isolated and expanded offering an advantage in terms of stability as it has been previously shown for circulating adult CD45RA+ Tregs. We show that both Tregs and RA+Tregs could be expanded in large numbers and the presence of rapamycin is essential to inhibit the growth of IFN-γ producing cells. High levels of FOXP3, CTLA4, and CD25 expression, demethylation of the FOXP3 promoter, and high suppressive ability were found with no differences between Tregs and RA+Tregs. After freezing and thawing, all Treg preparations maintained their suppressive ability, stability, as well as CD25 and FOXP3 expression. The number of thymic Tregs that could be isolated with our protocol, their fold expansion, and functional characteristics allow the clinical application of this cell population to promote tolerance in pediatric heart transplant patients. 相似文献
96.
97.
Hector Caballero-Flores Cleber Keiti Nabeshima Giovanna Sarra Maria Stella Moreira Victor Elias Arana-Chavez Márcia Martins Marques Manoel Eduardo de Lima Machado 《Dental materials》2021,37(7):e414-e425
ObjectiveAn ideal scaffold for endodontic regeneration should allow the predictableness of the new tissue organization and limit the negative impact of residual bacteria. Therefore, composition and functionalization of the scaffold play an important role in tissue bioengineering. The objective of this study was to assess the morphological, physicochemical, biological and antimicrobial properties of a new solid chitosan-based scaffold associated with gelatin, microparticulate dentin and genipin.MethodsScaffolds based on chitosan (Ch); chitosan associated with gelatin and genipin (ChGG); and chitosan associated with gelatin, microparticulate dentin and genipin (ChGDG) were prepared by using the freeze-drying method. The morphology of the scaffolds was analyzed by scanning electron microscopy (SEM). The physicochemical properties were assessed for biodegradation, swelling and total released proteins. The biological aspects of the scaffolds were assessed using human cells from the apical papilla (hCAPs). Cell morphology and adhesion to the scaffolds were evaluated by SEM, cytotoxicity and cell proliferation by MTT reduction-assay. Cell differentiation in scaffolds was assessed by using alizarin red assay. The antimicrobial effect of the scaffolds was evaluated by using the bacterial culture method, and bacterial adhesion to the scaffolds was observed by SEM.ResultsAll the scaffolds presented porous structures. The ChCDG had more protein release, adhesion, proliferation and differentiation of hCAPs, and bacteriostatic effect on Enterococcus faecalis than Ch and ChGG (p < 0.05).SignificanceThe chitosan associated with gelatin, microparticulate dentin and genipin has morphological, physicochemical, biological and antibacterial characteristics suitable for their potential use as scaffold in regenerative endodontics. 相似文献
98.
Roberta Roncarati Chiara Viviani Anselmi Peter Krawitz Giovanna Lattanzi Yskert von Kodolitsch Andreas Perrot Elisa di Pasquale Laura Papa Paola Portararo Marta Columbaro Alberto Forni Giuseppe Faggian Gianluigi Condorelli Peter N Robinson 《European journal of human genetics : EJHG》2013,21(10):1105-1111
Familial dilated cardiomyopathy (DCM) is a heterogeneous disease; although 30 disease genes have been discovered, they explain only no more than half of all cases; in addition, the causes of intra-familial variability in DCM have remained largely unknown. In this study, we exploited the use of whole-exome sequencing (WES) to investigate the causes of clinical variability in an extended family with 14 affected subjects, four of whom showed particular severe manifestations of cardiomyopathy requiring heart transplantation in early adulthood. This analysis, followed by confirmative conventional sequencing, identified the mutation p.K219T in the lamin A/C gene in all 14 affected patients. An additional variant in the gene for titin, p.L4855F, was identified in the severely affected patients. The age for heart transplantation was substantially less for LMNA:p.K219T/TTN:p.L4855F double heterozygotes than that for LMNA:p.K219T single heterozygotes. Myocardial specimens of doubly heterozygote individuals showed increased nuclear length, sarcomeric disorganization, and myonuclear clustering compared with samples from single heterozygotes. In conclusion, our results show that WES can be used for the identification of causal and modifier variants in families with variable manifestations of DCM. In addition, they not only indicate that LMNA and TTN mutational status may be useful in this family for risk stratification in individuals at risk for DCM but also suggest titin as a modifier for DCM. 相似文献
99.
100.
Laura Kropp Anish Baswanth Chakka Svetlana Yatsenko Eleonora Di Gregorio Daniela Lacerenza Giovanna Vaula Flavia Talarico Paola Mandich Camilo Toro Eleonore Eymard Pierre Pierre Labauge Sabina Capellari Pietro Cortelli Filippo Pinto Vairo Diego Miguel Danielle Stubbolo Lourenco Charles Marques William Gahl Odile Boespflug‐Tanguy Atle Melberg Sharon Hassin‐Baer Oren S. Cohen Rastislav Pjontek Armin Grau Thomas Klopstock Brent Fogel Inge Meijer Guy Rouleau Jean‐Pierre L. Bouchard Madhavi Ganapathiraju Adeline Vanderver Niklas Dahl Grace Hobson Alfredo Brusco Quasar Saleem Padiath 《Human mutation》2013,34(8):1160-1171
Autosomal dominant leukodystrophy (ADLD) is an adult onset demyelinating disorder that is caused by duplications of the lamin B1 (LMNB1) gene. However, as only a few cases have been analyzed in detail, the mechanisms underlying LMNB1 duplications are unclear. We report the detailed molecular analysis of the largest collection of ADLD families studied, to date. We have identified the minimal duplicated region necessary for the disease, defined all the duplication junctions at the nucleotide level and identified the first inverted LMNB1 duplication. We have demonstrated that the duplications are not recurrent; patients with identical duplications share the same haplotype, likely inherited from a common founder and that the duplications originated from intrachromosomal events. The duplication junction sequences indicated that nonhomologous end joining or replication‐based mechanisms such fork stalling and template switching or microhomology‐mediated break induced repair are likely to be involved. LMNB1 expression was increased in patients’ fibroblasts both at mRNA and protein levels and the three LMNB1 alleles in ADLD patients show equal expression, suggesting that regulatory regions are maintained within the rearranged segment. These results have allowed us to elucidate duplication mechanisms and provide insights into allele‐specific LMNB1 expression levels. 相似文献