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71.
72.
Fabrizio?FerrèEmail author Gabriele?Ausiello Andreas?Zanzoni Manuela?Helmer-Citterich 《BMC bioinformatics》2005,6(1):194
Background
Protein function is often dependent on subsets of solvent-exposed residues that may exist in a similar three-dimensional configuration in non homologous proteins thus having different order and/or spacing in the sequence. Hence, functional annotation by means of sequence or fold similarity is not adequate for such cases. 相似文献73.
Federica Prati Manuela Bartolini Elena Simoni Angela De Simone Antonella Pinto Vincenza Andrisano Maria Laura Bolognesi 《Bioorganic & medicinal chemistry letters》2013,23(23):6254-6258
The anti-amyloid properties shared by several quinones inspired the design of a new series of hybrids derived from the multi-target drug candidate memoquin (1). The hybrids consist of a central benzoquinone core and a fragment taken from non-steroidal anti-inflammatory drugs, connected through polyamine linkers. The new hybrids retain the potent anti-aggregating activity of the parent 1, while exhibiting micromolar AChE inhibitory activities. Remarkably, 2, 4, (R)-6 and (S)-6 were Aβ aggregation inhibitors even more potent than 1. The balanced amyloid/cholinesterase inhibitory profile is an added value that makes the present series of compounds promising leads against Alzheimer’s disease. 相似文献
74.
Pierre-David Petit Manuela Pensini Joël Tessaro Claude Desnuelle Patrick Legros Serge S. Colson 《Journal of electromyography and kinesiology》2010,20(6):1186-1195
This study compared the effects of 6-week whole-body vibration (WBV) training programs with different frequency and peak-to-peak displacement settings on knee extensor muscle strength and power. The underlying mechanisms of the expected gains were also investigated. Thirty-two physically active male subjects were randomly assigned to a high-frequency/high peak-to-peak displacement group (HH; n = 12), a low-frequency/low peak-to-peak displacement group (LL; n = 10) or a sham training group (SHAM; n = 10). Maximal voluntary isometric, concentric and eccentric torque of the knee extensors, maximal voluntary isometric torque of the knee flexors, jump performance, voluntary muscle activation, and contractile properties of the knee extensors were assessed before and after the training period. Significant improvement in knee extensor eccentric voluntary torque (P < 0.01), knee flexor isometric voluntary torque (P < 0.05), and jump performance (P < 0.05) was observed only for HH group. Regardless of the group, knee extensor muscle contractile properties (P < 0.05) were enhanced. No modification was observed for voluntary muscle activation or electrical activity of agonist and antagonist muscles. We concluded that high-frequency/high peak-to-peak displacement was the most effective vibration setting to enhance knee extensor muscle strength and jump performance during a 6-week WBV training program and that these improvements were not mediated by central neural adaptations. 相似文献
75.
Manuela La Montagna Lei Shi Peter Magee Sudhakar Sahoo Matteo Fassan Michela Garofalo 《Cell death and differentiation》2021,28(9):2673
AMP-activated protein kinase (AMPK) is a critical sensor of energy status that coordinates cell growth with energy balance. In non-small cell lung cancer (NSCLC) the role of AMPKα is controversial and its contribution to lung carcinogenesis is not well-defined. Furthermore, it remains largely unknown whether long non-coding RNAs (lncRNAs) are involved in the regulation of AMPK-mediated pathways. Here, we found that loss of AMPKα in combination with activation of mutant KRASG12D increased lung tumour burden and reduced survival in KrasLSLG12D/+/AMPKαfl/fl mice. In agreement, functional in vitro studies revealed that AMPKα silencing increased growth and migration of NSCLC cells. In addition, we identified an AMPKα-modulated lncRNA, KIMAT1 (ENSG00000228709), which in turn regulates AMPKα activation by stabilizing the lactate dehydrogenase B (LDHB). Collectively, our study indicates that AMPKα loss promotes KRAS-mediated lung tumorigenesis and proposes a novel KRAS/KIMAT1/LDHB/AMPKα axis that could be exploited for therapeutic purposes.Subject terms: Cancer models, Non-small-cell lung cancer 相似文献
76.
FOXM1 Transcription Factor: A New Component of Chronic Myeloid Leukemia Stem Cell Proliferation Advantage 下载免费PDF全文
Manuela Mancini Fausto Castagnetti Simona Soverini Elisa Leo Caterina De Benedittis Gabriele Gugliotta Gianantonio Rosti Luana Bavaro Sara De Santis Cecilia Monaldi Margherita Martelli Maria Alessandra Santucci Michele Cavo Giovanni Martinelli 《Journal of cellular biochemistry》2017,118(11):3968-3975
77.
Edna Grünblatt Camelia Maria Monoranu† Manuela Apfelbacher† Daniela Keller Tanja M. Michel‡ Irina Alafuzoff§§§§ Isidro Ferrer¶ Safa Al-Saraj Kathy Keyvani†† rea Schmitt‡‡ Peter Falkai‡‡ Jens Schittenhelm§§ Catriona McLean¶¶ Glenda M. Halliday††† Clive Harper‡‡‡ Jürgen Deckert Wolfgang Roggendorf† Peter Riederer 《Journal of neurochemistry》2009,110(5):1400-1408
Postmortem human brain tissue is widely used in neuroscience research, but use of tissue originating from different brain bank centers is considered inaccurate because of possible heterogeneity in sample quality. There is thus a need for well-characterized markers to assess the quality of postmortem brain tissue. Toward this aim, we determined tryptophan (TRP) concentrations, phosphofructokinase-1 and glutamate decarboxylase activities in 119 brain tissue samples. These neurochemical parameters were tested in samples from autopsied individuals, including control and pathological cases provided by 10 different brain bank centers. Parameters were assessed for correlation with agonal state, postmortem interval, age and gender, brain region, preservation and freezing methods, storage conditions and storage time, RNA integrity, and tissue pH value. TRP concentrations were elevated significantly ( p = 0.045) with increased postmortem interval; which might indicate increased protein degradation. Therefore, TRP concentration might be one useful and convenient marker for estimating the quality of human postmortem brain tissue. 相似文献
78.
Capone S Zampaglione I Vitelli A Pezzanera M Kierstead L Burns J Ruggeri L Arcuri M Cappelletti M Meola A Ercole BB Tafi R Santini C Luzzago A Fu TM Colloca S Ciliberto G Cortese R Nicosia A Fattori E Folgori A 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(10):7462-7471
Induction of multispecific, functional CD4+ and CD8+ T cells is the immunological hallmark of acute self-limiting hepatitis C virus (HCV) infection in humans. In the present study, we showed that gene electrotransfer (GET) of a novel candidate DNA vaccine encoding an optimized version of the nonstructural region of HCV (from NS3 to NS5B) induced substantially more potent, broad, and long-lasting CD4+ and CD8+ cellular immunity than naked DNA injection in mice and in rhesus macaques as measured by a combination of assays, including IFN-gamma ELISPOT, intracellular cytokine staining, and cytotoxic T cell assays. A protocol based on three injections of DNA with GET induced a substantially higher CD4+ T cell response than an adenovirus 6-based viral vector encoding the same Ag. To better evaluate the immunological potency and probability of success of this vaccine, we have immunized two chimpanzees and have compared vaccine-induced cell-mediated immunity to that measured in acute self-limiting infection in humans. GET of the candidate HCV vaccine led to vigorous, multispecific IFN-gamma+CD8+ and CD4+ T lymphocyte responses in chimpanzees, which were comparable to those measured in five individuals that cleared spontaneously HCV infection. These data support the hypothesis that T cell responses elicited by the present strategy could be beneficial in prophylactic vaccine approaches against HCV. 相似文献
79.
80.
Dorothee Dormann Anja Capell Aaron M. Carlson Sunita S. Shankaran† Ramona Rodde Manuela Neumann‡ Elisabeth Kremmer§ Takashi Matsuwaki¶ Keitaro Yamanouchi¶ Masugi Nishihara¶ Christian Haass 《Journal of neurochemistry》2009,110(3):1082-1094
Neuronal and glial deposition of misfolded, proteolytically processed, polyubiquitinated and abnormally phosphorylated C-terminal fragments (CTFs) of the TAR DNA binding protein-43 (TDP-43) is a pathological hallmark of frontotemporal lobar degeneration with ubiquitin positive inclusions (FTLD-U) and certain cases of amyotrophic lateral sclerosis. We demonstrate that TDP-43 can be proteolytically processed by caspases upon induction of apoptosis to a major 35 kDa and a minor 25 kDa CTF. These fragments are initially soluble, but over time they accumulate as insoluble and pathologically phosphorylated derivatives. However, proteolytic processing appears not to be absolutely required for the deposition of insoluble TDP-43 species, since a caspase resistant mutant of TDP-43 is also converted into insoluble species. Phosphorylation at S409/410 apparently occurs late during the conversion of soluble to insoluble TDP-43, suggesting that phosphorylation is not a prerequisite for aggregation. Loss of function of the progranulin (PGRN) gene causes FTLD-U with TDP-43 positive inclusions and has been suggested to lead to caspase activation and subsequent TDP-43 processing. However, siRNA-mediated knockdown of PGRN in cell culture as well as a PGRN gene knockout in mice failed to cause the formation of the disease characterizing CTFs of TDP-43. Our findings therefore suggest that caspase-mediated processing generates CTFs of similar biochemical properties as those occurring in nuclear and cytoplasmic deposits of FTLD-U patients independent of PGRN levels. 相似文献