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61.
Tiziano Tuccinardi Simone Bertini Carlotta Granchi Gabriella Ortore Marco Macchia Filippo Minutolo Adriano Martinelli Claudiu T. Supuran 《Bioorganic & medicinal chemistry》2013,21(6):1511-1515
New compounds containing a novel zinc binding group (salicylaldoxime system) were identified as effective inhibitors of carbonic anhydrases (CAs). This structural motif seems to bind the catalytic zinc ion of CAs, revealing itself as a new valid alternative to the sulfonamide group. Computational procedures were used to investigate the binding mode of this class of compounds, within the active site of CAII. This study suggests that the salicylaldoxime moiety binds the zinc ion through the oxime oxygen atom that also forms an H-bond with T199. The results herein obtained will allow the development of new CA-inhibitors bearing the salicylaldoxime moiety. 相似文献
62.
Daniela Valenti Lidia de Bari Gabriella Arcangela Manente Leonardo Rossi Luciano Mutti Laura Moro Rosa Anna Vacca 《生物化学与生物物理学报:疾病的分子基础》2013,1832(12):2085-2096
Increasing evidence reveals a large dependency of epithelial cancer cells on oxidative phosphorylation (OXPHOS) for energy production. In this study we tested the potential of epigallocatechin-3-gallate (EGCG), a natural polyphenol known to target mitochondria, in inducing OXPHOS impairment and cell energy deficit in human epitheliod (REN cells) and biphasic (MSTO-211H cells) malignant pleural mesothelioma (MMe), a rare but highly aggressive tumor with high unmet need for treatment. Due to EGCG instability that causes H2O2 formation in culture medium, the drug was added to MMe cells in the presence of exogenous superoxide dismutase and catalase, already proved to stabilize the EGCG molecule and prevent EGCG-dependent reactive oxygen species formation. We show that under these experimental conditions, EGCG causes the selective arrest of MMe cell growth with respect to normal mesothelial cells and the induction of mitochondria-mediated apoptosis, as revealed by early mitochondrial ultrastructure modification, swelling and cytochrome c release. We disclose a novel mechanism by which EGCG induces apoptosis through the impairment of mitochondrial respiratory chain complexes, particularly of complex I, II and ATP synthase. This induces a strong reduction in ATP production by OXPHOS, that is not adequately counterbalanced by glycolytic shift, resulting in cell energy deficit, cell cycle arrest and apoptosis. The EGCG-dependent negative modulation of mitochondrial energy metabolism, selective for cancer cells, gives an important input for the development of novel pharmacological strategies for MMe. 相似文献
63.
64.
Phuti E. Makgotlho Gabriella Marincola Daniel Sch?fer Qian Liu Taeok Bae Tobias Geiger Elizabeth Wasserman Christiane Wolz Wilma Ziebuhr Bhanu Sinha 《PloS one》2013,8(8)
The Staphylococcus aureus regulatory saePQRS system controls the expression of numerous virulence factors, including extracellular adherence protein (Eap), which amongst others facilitates invasion of host cells. The saePQRS operon codes for 4 proteins: the histidine kinase SaeS, the response regulator SaeR, the lipoprotein SaeP and the transmembrane protein SaeQ. S. aureus strain Newman has a single amino acid substitution in the transmembrane domain of SaeS (L18P) which results in constitutive kinase activity. SDS was shown to be one of the signals interfering with SaeS activity leading to inhibition of the sae target gene eap in strains with SaeSL but causing activation in strains containing SaeSP. Here, we analyzed the possible involvement of the SaeP protein and saePQ region in SDS-mediated sae/eap expression. We found that SaePQ is not needed for SDS-mediated SaeS signaling. Furthermore, we could show that SaeS activity is closely linked to the expression of Eap and the capacity to invade host cells in a number of clinical isolates. This suggests that SaeS activity might be directly modulated by structurally non-complex environmental signals, as SDS, which possibly altering its kinase/phosphatase activity. 相似文献
65.
Pauline Scherdel Jean-Fran?ois Salaün Marie-No?lle Robberecht-Riquet Laura Reali Gabriella Páll Elke J?ger-Roman Manuel Praena Crespo Marilena Moretto Margareta Seher-Zupan?i? Sigurlaug Agustsson the European Confederation of Primary Care Paediatricians research group Martin Chalumeau 《PloS one》2013,8(8)
Objective
We aimed to study current practices in growth monitoring by European primary care paediatricians and to explore their perceived needs in this field.Methods
We developed a cross-sectional, anonymous on-line survey and contacted primary care paediatricians listed in national directories in the 18 European countries with a confederation of primary care paediatricians. Paediatricians participated in the survey between April and September 2011.Results
Of the 1,198 paediatricians from 11 European countries (response rate 13%) who participated, 29% used the 2006 World Health Organization Multicentre Growth Reference Study growth charts, 69% used national growth charts; 61% used software to draw growth charts and 79% did not use a formal algorithm to detect abnormal growth on growth charts. Among the 21% of paediatricians who used algorithms, many used non-algorithmic simple thresholds for height and weight and none used the algorithms published in the international literature. In all, 69% of paediatricians declared that a validated algorithm to monitor growth would be useful in daily practice. We found important between-country variations.Conclusion
The varied growth-monitoring practices declared by primary care paediatricians reveals the need for standardization and evidence-based algorithms to define abnormal growth and the development of software that would use such algorithms. 相似文献66.
Gabriella M. Anic Vernon K. Sondak Jane L. Messina Neil A. Fenske Jonathan S. Zager Basil S. Cherpelis Ji-Hyun Lee William J. Fulp Pearlie K. Epling-Burnette Jong Y. Park Dana E. Rollison 《Cancer epidemiology》2013,37(4):434-439
Background: Telomeres help maintain chromosomal structure and may influence tumorigenesis. We examined the association between telomere length and skin cancer in a clinic-based case-control study of 198 melanoma cases, 136 squamous cell carcinoma (SCC) cases, 185 basal cell carcinoma (BCC) cases, and 372 healthy controls. Methods: Cases were histologically confirmed patients treated at the Moffitt Cancer Center and University of South Florida Dermatology Clinic in Tampa, FL. Controls self-reported no history of cancer and underwent a skin cancer screening exam at study enrollment to rule out the presence of skin cancer. Quantitative real time PCR was used to measure telomere length in peripheral blood samples. Results: Melanoma patients had longer telomeres than controls (odds ratio (OR) = 3.75; 95% confidence interval (CI): 2.02–6.94 for highest versus lowest tertile) (P for trend = <0.0001). In contrast, longer telomere length was significantly inversely associated with SCC (OR = 0.01; 95% CI: 0.00–0.05 for highest versus lowest tertile) (P for trend = <0.0001) and BCC (OR = 0.10; 95% CI: 0.06–0.19 for highest versus lowest tertile) (P for trend = <0.0001). Conclusion: Telomere length may be involved in the development of skin cancer, although the effect on cancer risk differs for melanoma and non-melanoma carcinomas. Our findings suggest that long telomere length is positively associated with melanoma while inversely associated with SCC and BCC. 相似文献
67.
Giovanni Benelli Elisa Donati Donato Romano Giacomo Ragni Gabriella Bonsignori Cesare Stefanini Angelo Canale 《Insect Science》2016,23(6):869-880
Variations in male body size are known to affect inter‐ and intrasexual selection outcomes in a wide range of animals. In mating systems involving sexual signaling before mating, body size often acts as a key factor affecting signal strength and mate choice. We evaluated the effect of male size on courtship displays and mating success of the olive fruit fly, Bactrocera oleae (Diptera: Tephritidae). Wing vibrations performed during successful and unsuccessful courtships by large and small males were recorded by high‐speed videos and analyzed through frame‐by‐frame analysis. Mating success of large and small males was investigated. The effect of male–male competition on mating success was evaluated. Male body size affected both male courtship signals and mating outcomes. Successful males showed wing‐borne signals with high frequencies and short interpulse intervals. Wing vibrations displayed by successful large males during copulation attempt had higher frequencies over smaller males and unsuccessful large males. In no‐competition conditions, large males achieved higher mating success with respect to smaller ones. Allowing large and small males to compete for a female, large males achieve more mating success over smaller ones. Mate choice by females may be based on selection of the larger males, able to produce high‐frequency wing vibrations. Such traits may be indicative of “good genes,” which under sexual selection could means good social‐interaction genes, or a good competitive manipulator of conspecifics. 相似文献
68.
Prospective study of pregnancy and newborn outcomes in mothers with West nile illness during pregnancy 下载免费PDF全文
69.
Cell proliferation, metabolism, migration and survival are coordinated through the tight control of two target of rapamycin (TOR) kinase complexes: TORC1 and TORC2. Here, we show that a novel phosphorylation of fission yeast Gad8 (AGC kinase) on the evolutionarily conserved threonine 6 (Thr6) prevents the physical association between Gad8 and TORC2. Accordingly, this block to protein interactions by Gad8 Thr6 phosphorylation decreases TORC2-controlled activation of Gad8. Likewise, phosphorylation of Gad8 Thr6, possibly by PKC, prevents the association of Gad8 with TORC2 thereby increasing TORC2 activity, because it reduces Gad8-mediated feedback inhibition of TORC2. Consistently, the introduction of a Gad8 T6D mutant, that mimics phosphorylation, increased TORC2 activity. Increased PKCPck2 expression prevented Gad8–TORC2 binding and so reduced the TORC2-mediated phosphorylation of Gad8 serine 546 that activates Gad8. Interestingly, independent of the Ser546 phosphorylation status, Gad8 Thr6 phosphorylation is important for remodelling the actin cytoskeleton and survival upon potassium ion and heat stresses. In contrast, Ser546 phosphorylation is required for the control of G1 arrest, mating, cell length at division and vascular size. Finally, these findings reveal a novel mode of TORC2 activation that is essential for cell survival following stress. 相似文献