187,277 research outputs found
Mutations upstream of fabI in triclosan resistant Staphylococcus aureus strains are associated with elevated fabI gene expression
No full textBackground
The enoyl-acyl carrier protein (ACP) reductase enzyme (FabI) is the target for a series of antimicrobial agents including novel compounds in clinical trial and the biocide triclosan. Mutations in fabI and heterodiploidy for fabI have been shown to confer resistance in S. aureus strains in a previous study. Here we further determined the fabI upstream sequence of a selection of these strains and the gene expression levels in strains with promoter region mutations.
Results
Mutations in the fabI promoter were found in 18% of triclosan resistant clinical isolates, regardless the previously identified molecular mechanism conferring resistance. Although not significant, a higher rate of promoter mutations were found in strains without previously described mechanisms of resistance. Some of the mutations identified in the clinical isolates were also detected in a series of laboratory mutants. Microarray analysis of selected laboratory mutants with fabI promoter region mutations, grown in the absence of triclosan, revealed increased fabI expression in three out of four tested strains. In two of these strains, only few genes other than fabI were upregulated. Consistently with these data, whole genome sequencing of in vitro selected mutants identified only few mutations except the upstream and coding regions of fabI, with the promoter mutation as the most probable cause of fabI overexpression. Importantly the gene expression profiling of clinical isolates containing similar mutations in the fabI promoter also showed, when compared to unrelated non-mutated isolates, a significant up-regulation of fabI.
Conclusions
In conclusion, we have demonstrated the presence of C34T, T109G, and A101C mutations in the fabI promoter region of strains with fabI up-regulation, both in clinical isolates and/or laboratory mutants. These data provide further observations linking mutations upstream fabI with up-regulated expression of the fabI gene
Study of Techniques For Reliable Data Transmission In Wireless Sensor Networks
No full textThis thesis addresses the problem of traffic transfer in wireless sensor networks (WSN). In such networks, the foremost challenge in the design of data communication techniques is that the sensor's transceiver circuitry consumes the major portion of the available power. Thus, due to stringent limitations on the nodes' hardware and power resources in WSN, data transmission must be power-efficient in order to reduce the nodes' power consumption, and hence to maximize the network lifetime while satisfying the required data rate. The transmit power is itself under the influence of data rate and source-destination distance. Thanks to the dense deployment of nodes in WSN, multi-hop communication can be applied to mitigate the transmit power for sending bits of information, i.e., gathered data by the sensor nodes to the destination node (gateway) compared to single-hop scenarios. In our approach, we achieve a reasonable trade-off between power-efficiency and transmission data rate by devising cooperative communication strategies through which the network traffic (i.e. nodes' gathered information) is relayed hop-by-hop to the gateway. In such strategies, the sensor nodes serve as data originator as well as data router, and assist the data transfer from the sensors to the gateway. We develop several data transmission schemes, and we prove their capability in transmitting the data from the sensor nodes at the highest possible rates allowed by the network limitations. In particular, we consider that (i) network has linear or quasi-linear topology, (ii) nodes are equipped with half-duplex radios, implying that they cannot transmit and receive simultaneously, (iii) nodes transmit their traffic at the same average rate. We compute the average data rate corresponding to each proposed strategy. Next, we take an information-theoretic approach and derive an upper bound to the achievable rate of traffic transfer in the networks under consideration, and analyze its tightness. We show that our proposed strategies outperform the conventional multi-hop scheme, and their average achievable rate approaches the upper bound at low levels of signal to noise ratio
"To Fashion the Wonderful Garment:" W.E.B. Du Bois’s The Quest of the Silver Fleece and Nella Larsen’s Quicksand
No full textThe essay argues that Nella Larsen’s first novel, Quicksand (1928), is an intertextual revision of W.E.B. Du Bois’s The Quest of the Silver Fleece (1911). In Quicksand Larsen registers the clothing and color symbolism running through Du Bois’s novel to articulate her critique of the gender politics such symbolism enshrines. Exploring this previously neglected intertextual relationship enables a deeper appreciation and revises traditional scholarly assessments of both novels, foregrounding the political significance of Larsen’s fiction and illuminating the critically underestimated literariness of The Quest of the Silver Fleece
Book Review: _Activist Sentiments: Reading Black Women in the Nineteenth Century_, P. Gabrielle Foreman, University of Illinois Press, Urbana and Chicago, 2009; _Eroticism, Spirituality, and Resistance in Black Women's Writings_, Donna Aza Weir-Soley, University Press of Florida, Gainesville, 2009.
No full textReview of _Activist Sentiments: Reading Black Women in the Nineteenth Century_, by P. Gabrielle Foreman, and _Eroticism, Spirituality, and Resistance in Black Women's Writings_, by Donna Aza Weir-Soley
Una proposta di Meta-Analisi basata sulla combinazione di classificatory per il problema del riconoscimento del parlatore
No full text
Corrigendum to ‘Eribulin in combination with bevacizumab as second-line treatment for HER2-negative metastatic breast cancer progressing after first-line therapy with paclitaxel and bevacizumab: a multicenter, phase II, single arm trial (GIM11-BERGI)’: (ESMO Open (2021) 6(2), (S2059702921000089), (10.1016/j.esmoop.2021.100054))
No full textThe authors regret that at the time the article was published the following two authors were missing from the author list: R. Caputo and D. Cianniello. Both authors affiliation is the Breast Oncology Department, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy. The updated author list is as follows: C. De Angelis, D. Bruzzese, A. Bernardo, E. Baldini, L. Leo, A. Fabi, T. Gamucci, P. De Placido, F. Poggio, S. Russo, V. Forestieri, R. Lauria, I. De Santo, R. Caputo, D. Cianniello, A. Michelotti, L. Del Mastro, M. De Laurentiis, M. Giuliano, S. De Placido, G. Arpino. The authors would like to apologise for any inconvenience caused
Inhibiting enoyl-ACP reductase (FabI) across pathogenic microorganisms by linear sesquiterpene lactones from Anthemis auriculata
No full textEnoyl-ACP reductase (FabI) is a key enzyme of the type II fatty acid biosynthesis (FAS-II) pathway and a validated antimicrobial target. In the current study, three linear sesquiterpene lactones obtained from Anthemis auriculata, namely anthecotulide (1), 4-hydroxyanthecotulide (2) and 4-acetoxyanthecotulide (3) were evaluated for specific inhibitory effects against the FabI enzyme from three pathogenic microorganisms, Plasmodium falciparum (PfFabI), Mycobacterium tuberculosis (MtFabI) and Escherichia coli (EcFabI). In addition, the compounds were also tested against two elongation enzymes from the plasmodial FAS-II system, β-ketoacyl-ACP reductase (PfFabG) and β-hydroxyacyl-ACP deydratase (PfFabZ). The compounds showed clear differentiation in inhibition of FabI enzymes from different microorganisms. Anthecotulide (1) was most active against MtFabI (IC50 4.5 μg/ml), whereas the oxygenated derivatives thereof (compounds 2 and 3) specifically inhibited plasmodial FAS-II enzymes, PfFabI and PfFabG (IC50 values 20-75 μg/ml). All compounds were inactive towards EcFabI. In whole cell assays, all three compounds exhibited antimalarial and antibacterial activities. © 2008 Elsevier GmbH. All rights reserved
First-line therapy in HER2 positive metastatic breast cancer: is the mosaic fully completed or are we missing additional pieces?
No full textThe discovery of human epidermal growth factor receptor 2 (HER2) and its role in the biology of breast cancer and the subsequent development of HER2-targeted therapies, have dramatically improved clinical outcomes for women with early-stage and advanced HER2-positive breast cancer (BC). HER-2 targeted therapies represent a major step forward in achieving the goal of delivering individualized targeted therapy for BC, and trastuzumab was the first anti-HER-2 strategy to be approved for treatment of HER-2 positive BC. This review discusses the treatment of metastatic HER2-positive BC and describes efficacy and safety of novel anti-HER2 target therapies in first-line metastatic settings and the future challenges include refining such treatments, reducing toxicity and simultaneously developing innovative therapies. Furthermore, combinations of trastuzumab and drugs targeting the downstream pathway are described. In the next future will be possible to use an ample armamentarium of combination therapies directed against HER2 and key signaling components integrated in the HER network. This approach will allow clinicians to tailor the management of the individual patient on the basis of tumor- specific biomarker profiles. There is an urgent need for prospective biomarker-driven trials to identify patients for whom targeting is cost-effective
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