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Central giant cell lesion of the jaws: study of CCND1 gene amplification and p16INK4a protein levels
Renato Luiz Maia Nogueira Mário Henrique Girão Faria Rafael Lima Verde Osterne Roberta Barroso Cavalcante Ronaldo Albuquerque Ribeiro Cassiano Francisco Weege Nonaka Silvia Helena Barem Rabenhorst 《Journal of molecular histology》2013,44(5):527-534
Central giant cell lesions (CGCLs) are uncommon benign jaw lesions with uncertain etiology and a variable clinical behavior. In neoplasms, alterations in molecules involved in the G1/S checkpoint are frequently found. Loss of p16INK4a expression or overexpression of cyclin D1 may stimulate cell proliferation. The purpose of this study was to analyze CCND1 gene amplification and the expression of p16INK4a in CGCLs. Structural analysis of the CCND1 was performed using chromogenic in situ hybridization. Immmunohistochemistry was used to identify p16INK4a protein levels. Statistical analysis correlated the two biomarkers with clinical behavior and between each other. Twenty-four lesions were included, being 11 aggressive and 13 non-aggressive. Moderate/high-level CCND1 amplification was found in 12 lesions. Also, immunoreactivity for p16INK4a was present in 12 cases, mainly in mononuclear cells. There was a significantly higher level of p16INK4a expression in mononuclear cells of non-aggressive lesions and lesions with moderate/high-level CCND1 amplification in mononuclear cells. It could be speculated that some CGCLs may develop as a true benign neoplasm. The higher expression of p16INK4a in non-aggressive lesions and in cases with moderate/high-level CCND1 amplification may show that these molecules have a role in CGCLs. 相似文献
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New records of Cynipid gall wasps and inquilines for the Italian peninsula and Sicily and their new host plants for the Palaearctic Region are listed and commented on. Among them we find: Cerroneuroterus cerrifloralis (Müllner 1901) as new for Italy and new for the Palaearctic region as host on Quercus suber; Andricus multiplicatus Giraud 1859 on Q. suber, as new host for the Palaearctic region; Aylax papaveris (Perris 1839), reported in Italy over a century ago, but later overlooked; Cerroneuroterus minutulus (Giraud 1859), also reported more than a century ago from Sicily, but later overlooked. Among the inquilines are here listed: Synergus variabilis Mayr 1872, emerged from Janetia cerris (Kollar 1850) galls (Diptera Cecidomyiidae), and found for the first time in the Palaearctic Region as host on Q. suber; Saphonecrus haimi (Mayr 1872) and Saphonecrus barbotini Pujade-Villar & Nieves-Aldrey 1986, are new records for Italy. 相似文献
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Annalisa Vilasi Silvia Vilasi Rocco Romano Fausto Acernese Fabrizio Barone Maria Luisa Balestrieri Rosa Maritato Gaetano Irace Ivana Sirangelo 《Journal of cellular physiology》2013,228(6):1359-1367
A range of debilitating human diseases is known to be associated with the formation of stable highly organized protein aggregates known as amyloid fibrils. The early prefibrillar aggregates behave as cytotoxic agents and their toxicity appears to result from an intrinsic ability to impair fundamental cellular processes by interacting with cellular membranes, causing oxidative stress and increase in free Ca2+ that lead to apoptotic or necrotic cell death. However, specific signaling pathways that underlie amyloid pathogenicity remain still unclear. This work aimed to clarify cell impairment induced by amyloid aggregated. To this end, we used a combined proteomic and one‐dimensional 1H‐NMR approach on NIH‐3T3 cells exposed to prefibrillar aggregates from the amyloidogenic apomyoglobin mutant W7FW14F. The results indicated that cell exposure to prefibrillar aggregates induces changes of the expression level of proteins and metabolites involved in stress response. The majority of the proteins and metabolites detected are reported to be related to oxidative stress, perturbation of calcium homeostasis, apoptotic and survival pathways, and membrane damage. In conclusion, the combined proteomic and 1H‐NMR metabonomic approach, described in this study, contributes to unveil novel proteins and metabolites that could take part to the general framework of the toxicity induced by amyloid aggregates. These findings offer new insights in therapeutic and diagnostic opportunities. J. Cell. Physiol. 228: 1359–1367, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
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Erik Procko Rickard Hedman Keith Hamilton Jayaraman Seetharaman Sarel J. Fleishman Min Su James Aramini Gregory Kornhaber John F. Hunt Liang Tong Gaetano T. Montelione David Baker 《Journal of molecular biology》2013
While there has been considerable progress in designing protein–protein interactions, the design of proteins that bind polar surfaces is an unmet challenge. We describe the computational design of a protein that binds the acidic active site of hen egg lysozyme and inhibits the enzyme. The design process starts with two polar amino acids that fit deep into the enzyme active site, identifies a protein scaffold that supports these residues and is complementary in shape to the lysozyme active-site region, and finally optimizes the surrounding contact surface for high-affinity binding. Following affinity maturation, a protein designed using this method bound lysozyme with low nanomolar affinity, and a combination of NMR studies, crystallography, and knockout mutagenesis confirmed the designed binding surface and orientation. Saturation mutagenesis with selection and deep sequencing demonstrated that specific designed interactions extending well beyond the centrally grafted polar residues are critical for high-affinity binding. 相似文献
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Luciano Pirone Luigi Vitagliano Sonia Di Gaetano Emilia Pedone 《Journal of molecular recognition : JMR》2013,26(10):488-495
Recent investigations have shown that members of the KCTD family play important roles in fundamental biological processes. Despite their roles, very limited information is available on their structures and molecular organization. By combining different experimental and theoretical techniques, we have here characterized the two folded domains of KCTD12, an integral component and modulator of the GABAB2 receptor. Secondary prediction methods and CD spectroscopy have shown that the N‐terminal domain KCTD12BTB assumes an α/β structure, whereas the C‐terminal domain KCTD12H1 is predominantly characterized by a β‐structure. Binding assays indicate that the two domains independently expressed show a good affinity for each other. This suggests that the overall protein is likely endowed with a rather compact structure with two interacting structured domains joint by a long disordered region. Notably, both KCTD12BTB and KCTD12H1 are tetrameric when individually expressed. This finding could modify the traditional view that ascribes only to POZ/BTB domain a specific oligomerization role. The first quantification of the affinity of KCTD12POZ/BTB for the C‐terminal region of GABAB2 shows that it falls in the low micromolar range. Interestingly, we also demonstrate that a GABAB2‐related peptide is able to bind KCTD12BTB with a very high affinity. This peptide may represent a useful tool for modulating KCTD12/GABAB2 interaction in vitro and may also constitute the starting point for the development of peptidomimetic compounds with a potential for therapeutic applications. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
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Sihem Dabbou Samia Dabbou Guido Flamini Gaetano Pandino Laura Gasco Ahmed Noureddine Helal 《化学与生物多样性》2016,13(11):1475-1483
The phytochemical composition in two Tunisian globe artichoke cultivars (bracts, leaves, and floral stems) was evaluated in the plant byproducts. The results indicated that the bracts contain the highest levels of total phenols, o‐diphenols, and flavonoids, whereas tannins seem to be more abundant in the leaves. Bracts from the ‘Violet d'Hyères’ cultivar possessed more total phenols (160.8 mg/g DW), flavonoids (64.9 mg/g DW), and anthocyanins (15.3 μg/g DW) than the ‘Blanc d'Oran’ bracts (134.5 mg/g DW, 51.2 mg/g DW, and 8.3 μg/g DW, resp.). Sixty‐four volatile compounds were identified in the headspace of globe artichoke material, particularly in the bracts. The volatile profile showed that sesquiterpene hydrocarbons and non‐terpene derivatives were the main volatiles emitted by the bracts in both cultivars. These results suggest that globe artichoke byproducts might represent a potential source of natural compounds, which could be used as nutraceuticals or as ingredients in the design of functional foods. 相似文献