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排序方式: 共有480条查询结果,搜索用时 15 毫秒
61.
Chromatin-remodelling mechanisms in cancer 总被引:1,自引:0,他引:1
Chromatin-remodelling mechanisms include DNA methylation, histone-tail acetylation, poly-ADP-ribosylation, and ATP-dependent chromatin-remodelling processes. Some epigenetic modifications among others have been observed in cancer cells, namely (1) local DNA hypermethylation and global hypomethylation, (2) alteration in histone acetylation/deacetylation balance, (3) increased or decreased poly-ADP-ribosylation, and (4) failures in ATP-dependent chromatin-remodelling mechanisms. Moreover, these alterations can influence the response to classical anti-tumour treatments. Drugs targeting epigenetic alterations are under development. Currently, DNA methylation and histone deacetylase inhibitors are in use in cancer therapy, and poly-ADP-ribosylation inhibitors are undergoing clinical trials. Epigenetic therapy is gaining in importance in pharmacology as a new tool to improve anti-cancer therapies. 相似文献
62.
Guaragna A Amoresano A Pinto V Monti G Mastrobuoni G Marino G Palumbo G 《Bioconjugate chemistry》2008,19(5):1095-1104
During recent years, quantitative proteome profiling has taken advantage of incorporating the traditional stable isotope dilution analysis into global scale or discovery-based proteomic experiments that use mass spectrometers as detectors to allow the pairwise study of differently expressed proteins. Quantitative protein analysis by means of the isotope-coded affinity tag (ICAT) method and tandem mass spectrometry (MS) enables the pairwise comparison of protein expression levels in biological samples. Herein, a modified ICAT reagent, named BAA-ICAT (beta-alanine-arm-ICAT) in which the polyether linker is replaced by a more water-soluble polyamide one, was investigated. 相似文献
63.
Marini M Falcieri E Margonato V Treré D Lapalombella R di Tullio S Marchionni C Burattini S Samaja M Esposito F Veicsteinas A 《Histochemistry and cell biology》2008,129(4):479-487
Enhanced angiogenesis, or capillary growth, has a prominent role among the various beneficial effects of exercise training
on the myocardium. The aim of the present study is to assess if training-induced increases in capillarity and vascularization
persist after 4 weeks of detraining. Adult male rats were trained to run on a treadmill for 10 weeks at ∼60% VO2max, which did not induce cardiac hypertrophy, but increased (P < 0.05) the soleus/body weight ratio, left ventricle capillarity and von Willebrand-positive cell density (n = 6). In another group of animals (n = 6) subjected to training followed by 4-week detraining, the soleus/body weight ratio returned to normal, with only partial
reversal of left ventricle capillarity and von Willebrand-positive cell density. Markers of angiogenesis (VEGF, KDR/VEGF-R2
and HIF-1α mRNA, studied by real-time RT-PCR) were upregulated at the end of training, and returned to baseline value after
detraining. Electron microscopy highlighted some morphological features in trained hearts (endothelial cell sprouting and
bridges and pericyte detachment), suggestive of endothelial cell proliferation and capillary growth that were absent in untrained
and detrained hearts. We conclude that the training-induced increase in cardiac capillarity and vascularization are retained
for some time upon cessation of the training program even in the absence of angiogenic stimuli. 相似文献
64.
65.
Tenai Eguen Jorge Gomez Ariza Vittoria Brambilla Bin Sun Kaushal Kumar Bhati Fabio Fornara Stephan Wenkel 《植物学报(英文版)》2020,62(6):730-736
Photoperiod‐dependent flowering in rice is regulated by HEADING DATE 1 (Hd1), which acts as both an activator and repressor of flowering in a daylength‐dependent manner. To investigate the use of microProteins as a tool to modify rice sensitivity to the photoperiod, we designed a synthetic Hd1 microProtein (Hd1miP) capable of interacting with Hd1 protein, and overexpressed it in rice. Transgenic OX‐Hd1miP plants flowered significantly earlier than wild type plants when grown in non‐inductive long day conditions. Our results show the potential of microProteins to serve as powerful tools for modulating crop traits and unraveling protein function. 相似文献
66.
67.
Flavia Varano Daniela Catarzi Matteo Falsini Fabrizio Vincenzi Silvia Pasquini Katia Varani Vittoria Colotta 《Bioorganic & medicinal chemistry》2018,26(12):3688-3695
In this study a new set of thiazolo[5,4-d]pyrimidine derivatives was synthesized. These derivatives bear different substituents at positions 2 and 5 of the thiazolopyrimidine core while maintaining a free amino group at position-7. The new compounds were tested for their affinity and potency at human (h) A1, A2A, A2B and A3 adenosine receptors expressed in CHO cells. The results reveal that the higher affinity of these new set of thiazolopyrimidines is toward the hA1 and hA2A adenosine receptors subtypes and is tuned by the substitution pattern at both the 2 and 5 positions of the thiazolopyrimidine nucleus. Functional studies evidenced that the compounds behaved as dual A1/A2A antagonists/inverse agonists. Compound 3, bearing a 5-((2-methoxyphenyl) methylamino) group and a phenyl moiety at position 2, displayed the highest affinity (hA1 Ki?=?10.2?nM; hA2A Ki?=?4.72?nM) and behaved as a potent A1/A2A antagonist/inverse agonist (hA1 IC50?=?13.4?nM; hA2A IC50?=?5.34?nM). 相似文献
68.
Camilla Cenni Tim W. Fawcett 《Ethology : formerly Zeitschrift fur Tierpsychologie》2018,124(5):290-301
Although play–fighting is widespread among juvenile mammals, its adaptive significance remains unclear. It has been proposed that play is beneficial for developing skills to improve success in adult contests (motor‐training hypothesis), but the links between juvenile play–fighting and adult aggression are complex and not well understood. In this theoretical study, we investigate the coevolution between juvenile play–fighting and adult aggression using evolutionary computer simulations. We consider a simple life history with two sequential stages: a juvenile phase in which individuals play–fight with other juveniles to develop their fighting skills; and an adult phase in which individuals engage in potentially aggressive contests over access to resources and ultimately mating opportunities, leading to reproductive success. The simulations track genetic evolution in key traits affecting adult contests, such as the level of aggression, as well as juvenile investment in play–fighting, capturing the coevolutionary feedbacks between juvenile and adult decisions. We find that coevolution leads to one of two outcomes: a high‐play, high‐aggression situation with highly aggressive adult contests preceded by a prolonged period of juvenile play–fighting to improve fighting ability, or a low‐play, low‐aggression situation in which adult contests are resolved without fighting and there is minimal investment in play–fighting before individuals mature. Which of these outcomes is favoured depends on the mortality costs and on the type of societal structure: societies with strong reproductive skew, favouring monopolization of resources, show high levels of adult aggression and high investment in juvenile play–fighting, whereas societies with low reproductive skew have both low adult aggression and low levels of play–fighting. A review of empirical evidence, particularly in the primate genus Macaca, highlights some limitations of our model and suggests that other, complementary functional explanations are needed to account for the full range of competitive and cooperative forms of play–fighting. Our study illustrates the power of evolutionary simulations to shed light on the long‐standing puzzle of animal play. 相似文献
69.
Irene Zubiri Vittoria Lombardi Michael Bremang Vikram Mitra Giovanni Nardo Rocco Adiutori Ching-Hua Lu Emanuela Leoni Ping Yip Ozlem Yildiz Malcolm Ward Linda Greensmith Caterina Bendotti Ian Pike Andrea Malaspina 《Molecular neurodegeneration》2018,13(1):60
Background
It is unclear to what extent pre-clinical studies in genetically homogeneous animal models of amyotrophic lateral sclerosis (ALS), an invariably fatal neurodegenerative disorder, can be informative of human pathology. The disease modifying effects in animal models of most therapeutic compounds have not been reproduced in patients. To advance therapeutics in ALS, we need easily accessible disease biomarkers which can discriminate across the phenotypic variants observed in ALS patients and can bridge animal and human pathology. Peripheral blood mononuclear cells alterations reflect the rate of progression of the disease representing an ideal biological substrate for biomarkers discovery.Methods
We have applied TMTcalibrator?, a novel tissue-enhanced bio fluid mass spectrometry technique, to study the plasma proteome in ALS, using peripheral blood mononuclear cells as tissue calibrator. We have tested slow and fast progressing SOD1G93A mouse models of ALS at a pre-symptomatic and symptomatic stage in parallel with fast and slow progressing ALS patients at an early and late stage of the disease. Immunoassays were used to retest the expression of relevant protein candidates.Results
The biological features differentiating fast from slow progressing mouse model plasma proteomes were different from those identified in human pathology, with only processes encompassing membrane trafficking with translocation of GLUT4, innate immunity, acute phase response and cytoskeleton organization showing enrichment in both species. Biological processes associated with senescence, RNA processing, cell stress and metabolism, major histocompatibility complex-II linked immune-reactivity and apoptosis (early stage) were enriched specifically in fast progressing ALS patients. Immunodetection confirmed regulation of the immunosenescence markers Galectin-3, Integrin beta 3 and Transforming growth factor beta-1 in plasma from pre-symptomatic and symptomatic transgenic animals while Apolipoprotein E differential plasma expression provided a good separation between fast and slow progressing ALS patients.Conclusions
These findings implicate immunosenescence and metabolism as novel targets for biomarkers and therapeutic discovery and suggest immunomodulation as an early intervention. The variance observed in the plasma proteomes may depend on different biological patterns of disease progression in human and animal model.70.
Andrea Bolognesi Letizia Polito Fabiola Olivieri Paola Valbonesi Luigi Barbieri M. Giulia Battelli M. Vittoria Carusi Eugenio Benvenuto Francesca Del Vecchio Blanco Antimo Di Maro Augusto Parente Mario Di Loreto Fiorenzo Stirpe 《Planta》1997,203(4):422-429
New single-chain (type 1) ribosome-inactivating proteins (RIPs) were isolated from the seeds of Basella rubra L. (two proteins) and from the leaves of Bougainvillea spectabilis Willd. (one protein). These RIPs inhibit protein synthesis both in a cell-free system, with an IC50 (concentration causing 50% inhibition) in the 10−10 M range, and by various cell lines, with IC50s in the 10−8–10−6 M range. All three RIPs released adenine not only from rat liver ribosomes but also from Escherichia coli rRNA, polyadenylic acid, herring sperm DNA, and artichoke mottled crinkle virus (AMCV) genomic RNA, thus being polynucleotide:adenosine
glycosidases. The proteins from Basella rubra had toxicity to mice similar to that of most type 1 RIPs (Barbieri et al., 1993, Biochim Biophys Acta 1154: 237–282) with
an LD50 (concentration that is 50% lethal) ≤ 8 mg · kg−1 body weight, whilst the RIP from Bougainvillea spectabilis had an LD50 >32 mg · kg−1. The N-terminal sequence of the two RIPs from Basella rubra had 80–93% identity, whereas it differed from the sequence of the RIP from Bougainvillea spectabilis. When tested with antibodies against various RIPs, the RIPs from Basella gave some cross-reactivity with sera against dianthin 32, and weak cross-reactivity with momordin I and momorcochin-S, whilst
the RIP from Bougainvillea did not cross-react with any antiserum tested. An RIP from Basella rubra and one from Bougainvillea spectabilis were tested for antiviral activity, and both inhibited infection of Nicotiana benthamiana by AMCV.
Received: 5 March 1997 / Accepted: 27 May 1997 相似文献