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排序方式: 共有171条查询结果,搜索用时 15 毫秒
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Nausicaa V Licata Riccardo Cristofani Sally Salomonsson Katherine M Wilson Liam Kempthorne Deniz Vaizoglu Vito G DAgostino Daniele Pollini Rosa Loffredo Michael Pancher Valentina Adami Paola Bellosta Antonia Ratti Gabriella Viero Alessandro Quattrone Adrian M Isaacs Angelo Poletti Alessandro Provenzani 《The EMBO journal》2022,41(1)
Intronic GGGGCC (G4C2) hexanucleotide repeat expansion within the human C9orf72 gene represents the most common cause of familial forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9ALS/FTD). Repeat‐associated non‐AUG (RAN) translation of repeat‐containing C9orf72 RNA results in the production of neurotoxic dipeptide‐repeat proteins (DPRs). Here, we developed a high‐throughput drug screen for the identification of positive and negative modulators of DPR levels. We found that HSP90 inhibitor geldanamycin and aldosterone antagonist spironolactone reduced DPR levels by promoting protein degradation via the proteasome and autophagy pathways respectively. Surprisingly, cAMP‐elevating compounds boosting protein kinase A (PKA) activity increased DPR levels. Inhibition of PKA activity, by both pharmacological and genetic approaches, reduced DPR levels in cells and rescued pathological phenotypes in a Drosophila model of C9ALS/FTD. Moreover, knockdown of PKA‐catalytic subunits correlated with reduced translation efficiency of DPRs, while the PKA inhibitor H89 reduced endogenous DPR levels in C9ALS/FTD patient‐derived iPSC motor neurons. Together, our results suggest new and druggable pathways modulating DPR levels in C9ALS/FTD. 相似文献
93.
Giorgio Adami 《Origins of life and evolution of the biosphere》2006,36(5-6):567-576
The search for traces of past and present life is a complex and multidisciplinary research activity involving several scientific heritages and a specific industrial ability for planetary exploration. Laben was established in 1958 to design and manufacture electronic instruments for research in nuclear physics. In the mid 2004 the company was merged with Alenia Spazio. It is now part of Alcatel Alenia Space, a French Italian joint venture. Alcatel Alenia Space Italia SpA is a Finmeccanica Company. Currently the plant of Vimodrone provides a wide heritage in life science oriented to space application. The experience in Space Life Science is consolidated in the following research areas: (1) Physiology: Mouse models related to studies on human physiology Human neuroscience research and dosimetry (2) Animal Adaptation and Behaviour: mice behaviour related to stabling stress (3) Developmental Biology: aquatic microorganisms cultivation (4) Cell culture & Biotechnology: Protein crystal growth General purpose Multiwell Next Biotechnology studies and development: Bio reactor, mainly oriented to tissue engineering Microsensor for tissue control (organ replacement) Multiwell for adherent cell culture or for automated biosensor based on cell culture Experiment Container for organic systems Experiment Container for small animals Instrumentation based on fluorescent Biosensors Sensors for Life science experiments for Biopan capsule and Space Vehicle Ray Shielding Materials Random Positioning Machine specialisation (Support ground equipment) The biological features of this heritage is at disposal for the exobiology multi science. The involvement of industries, from the beginning of the exobiology projects, allows a cost effective technologies closed loop development between Research Centres, Principal Investigators and industry. 相似文献
94.
Christophe Nemos Rgis Delage-Mourroux Michle Jouvenot Pascale Adami 《Experimental cell research》2004,296(2):2577
In normal endometrial glandular epithelial cells (GEC), 17β-estradiol (E2) enhances proliferation and c-fos expression only in the presence of growth factors. On the contrary, growth factors are not required for the E2 effects in cancerous cells. Thus, a repression of E2 action could exist in normal cells and be turned off in cancerous cells, allowing a direct estrogen-dependent proliferation. To verify this hypothesis, we established immortalized and transformed cell models, then investigated alterations of E2 effects during oncogenesis. SV40 large T-antigen was used to generate immortalized GEC model (IGEC). After observation of telomerase reactivation, IGEC model was transfected by activated c-Ha-ras to obtain transformed cell lines (TGEC1 and TGEC2). The phenotypic, morphological, and genetic characteristics of these models were determined before studying the E2 effects. In IGEC, the E2 action on proliferation and c-fos expression required the presence of growth factors, as observed in GECs. In TGECs, this action arose in the absence of growth factors. After IGEC transformation, the activation of ras pathway would substitute the priming events required for the release of repression in GEC and IGEC and thus permit direct E2 effects. Our cell models are particularly suitable to investigate alterations of gene regulation by E2 during oncogenesis. 相似文献
95.
N Muirhead G R Catto N Edward S Adami R M Manning J L O'Riordan 《BMJ (Clinical research ed.)》1984,288(6412):177-179
A study was conducted evaluating the response of serum parathyroid hormone to acute hypercalcaemia and long term administration of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in patients receiving maintenance haemodialysis. During infusion of elemental calcium 4 mg/kg/h over four hours in 12 patients not receiving vitamin D the concentration of serum amino terminal parathyroid hormone fell by 31-96% (mean 74.8 (SD 17.6)%) while that of carboxy terminal parathyroid hormone changed little. There was a strong inverse correlation between baseline serum calcium concentration and percentage fall in amino terminal parathyroid hormone during infusion (r = 0.88; p less than 0.001). In seven patients who received prolonged treatment with 1,25(OH)2D3 after calcium infusion there was a positive correlation between maximum percentage fall in amino terminal parathyroid hormone during infusion and the percentage fall in amino terminal parathyroid hormone after 1,25(OH)2D3 treatment (r = 0.79; p less than 0.05). The responsiveness of the parathyroid glands to changes in calcium in acute studies may be used to predict the efficacy of long term treatment with 1,25(OH)2D3. Patients in whom calcium infusion does not suppress parathyroid hormone may have true parathyroid autonomy and require early parathyroidectomy. 相似文献
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97.
Background
Much work in systems biology, but also in the analysis of social network and communication and transport infrastructure, involves an in-depth analysis of local and global properties of those networks, and how these properties relate to the function of the network within the integrated system. Most often, systematic controls for such networks are difficult to obtain, because the features of the network under study are thought to be germane to that function. In most such cases, a surrogate network that carries any or all of the features under consideration, while created artificially and in the absence of any selective pressure relating to the function of the network being studied, would be of considerable interest. 相似文献98.
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