37 research outputs found
Expression Profiling of Mammalian Micrornas Uncovers a Subset of Brain-Expressed Micrornas with Possible Roles in Murine and Human Neuronal Differentiation
No full textBackground: The microRNAs (miRNAs) are an extensive class of small noncoding RNAs (18 to 25 nucleotides) with probable roles in the regulation of gene expression. In Caenorhabditis elegans , lin-4 and let-7 miRNAs control the timing of fate specification of neuronal and hypodermal cells during larval development. lin-4 , let-7 and other miRNA genes are conserved in mammals, and their potential functions in mammalian development are under active study. Results: In order to identify mammalian miRNAs that might function in development, we characterized the expression of 119 previously reported miRN As in adult organs from mouse and human using northern blot analysis. Of these, 30 miRNAs were specifically expressed or greatly enriched in a particular organ (brain, lung, liver or skeletal muscle). This suggests organ- or tissue- specific functions for miRNAs. To test if any of the 66 brain-expressed miRNAs were present in neurons, embryonal carcinoma cells were treated with all-trans-retinoic acid to promote neuronal differentiation. A total of 19 brain-expressed miRNAs (including lin-4 and let-7 orthologs) were coordinately upregulated in both human and mo use embryonal carcinoma cells during neuronal differentiation. The mammalian ortholog of C. elegans lin-28 , which is downregulated by lin-4 in worms via 3\u27 untranslated region binding, was also repressed during neuronal differentiation of mammalian embryonal carcinoma cells. Mammalian lin-28 messenger RNAs contain conserved predicted binding sites in their 3\u27 untranslated regions for neuron-expressed miR-125b (a lin-4 ortholog), let-7a, and miR-218. Conclusions: The identification of a subset of brain-expressed miRNAs whose expression behavior is conserved in both mouse and human differentiating neurons implicates these miRNAs in mammalian neuronal development or function
The added value of ordinal analysis in clinical trials: an example in traumatic brain injury.
No full textINTRODUCTION: In clinical trials, ordinal outcome measures are often dichotomized into two categories. In traumatic brain injury (TBI) the 5-point Glasgow outcome scale (GOS) is collapsed into unfavourable versus favourable outcome. Simulation studies have shown that exploiting the ordinal nature of the GOS increases chances of detecting treatment effects. The objective of this study is to quantify the benefits of ordinal analysis in the real-life situation of a large TBI trial. METHODS: We used data from the CRASH trial that investigated the efficacy of corticosteroids in TBI patients (n = 9,554). We applied two techniques for ordinal analysis: proportional odds analysis and the sliding dichotomy approach, where the GOS is dichotomized at different cut-offs according to baseline prognostic risk. These approaches were compared to dichotomous analysis. The information density in each analysis was indicated by a Wald statistic. All analyses were adjusted for baseline characteristics. RESULTS: Dichotomous analysis of the six-month GOS showed a non-significant treatment effect (OR = 1.09, 95% CI 0.98 to 1.21, P = 0.096). Ordinal analysis with proportional odds regression or sliding dichotomy showed highly statistically significant treatment effects (OR 1.15, 95% CI 1.06 to 1.25, P = 0.0007 and 1.19, 95% CI 1.08 to 1.30, P = 0.0002), with 2.05-fold and 2.56-fold higher information density compared to the dichotomous approach respectively. CONCLUSIONS: Analysis of the CRASH trial data confirmed that ordinal analysis of outcome substantially increases statistical power. We expect these results to hold for other fields of critical care medicine that use ordinal outcome measures and recommend that future trials adopt ordinal analyses. This will permit detection of smaller treatment effects
A novel bilayered expanded polytetrafluoroethylene glaucoma implant creates a permeable thin capsule independent of aqueous humor exposure
No full textWhite matter differences between healthy young ApoE4 carriers and non-carriers identified with tractography and support vector machines.
No full textThe apolipoprotein E4 (ApoE4) is an established risk factor for Alzheimer's disease (AD). Previous work has shown that this allele is associated with functional (fMRI) changes as well structural grey matter (GM) changes in healthy young, middle-aged and older subjects. Here, we assess the diffusion characteristics and the white matter (WM) tracts of healthy young (20-38 years) ApoE4 carriers and non-carriers. No significant differences in diffusion indices were found between young carriers (ApoE4+) and non-carriers (ApoE4-). There were also no significant differences between the groups in terms of normalised GM or WM volume. A feature selection algorithm (ReliefF) was used to select the most salient voxels from the diffusion data for subsequent classification with support vector machines (SVMs). SVMs were capable of classifying ApoE4 carrier and non-carrier groups with an extremely high level of accuracy. The top 500 voxels selected by ReliefF were then used as seeds for tractography which identified a WM network that included regions of the parietal lobe, the cingulum bundle and the dorsolateral frontal lobe. There was a non-significant decrease in volume of this WM network in the ApoE4 carrier group. Our results indicate that there are subtle WM differences between healthy young ApoE4 carriers and non-carriers and that the WM network identified may be particularly vulnerable to further degeneration in ApoE4 carriers as they enter middle and old age
‘He Sang the Story’ Narrative and Poetic Identity in Keats’s Work
No full textStory-telling is a mode central to the practice and achievement of John Keats. In ‘Sleep and Poetry’, he refers to life as ‘The reading of an ever-changing tale’. This line suggests his sense of the centrality of narrative to human experiences. Yet the Keatsian narrative is as a medium for Keats to investigate the nature and development of his poetic identity. His idea of poetry and of the poet, and his narrative figuring of himself as a poet are my subject, as they are his, when in the phrase the thesis takes for its title Keats writes of a poet in Endymion, ‘He sang the story up into the air’ (II, 838).
Recent scholarship has interpreted Keats’s narrative techniques in different ways. Critical approaches have modified the Bloomian concept of the anxiety of influence by using a reader response approach, or have taken on board or swerved from a McGannian New Historicist perspective. In the process Keats’s formal achievement, once celebrated by critics such as Walter Jackson Bate and Helen Vendler, has received comparatively little attention. This thesis, adopting ideas and approaches associated with narratology (including its application to lyric poetry), analyses Keats’s poetic career, focusing on the poetry’s narrative techniques and its treatment of the narrator’s role. My approach might be described as aiming to accomplish a ‘poetics of attention’.
This thesis consists of eight chapters. Chapter one discusses ‘I stood tip-toe upon a little hill’ and ‘Sleep and Poetry’, poems that are crucial in understanding Keats’s use of narrative to explore his poetic identity. In chapter two, concentrating on Endymion’s enactment of imaginative struggle, I attempt to show the purposeful function of the poem’s ‘wandering’ and complex narrative structure, which allows Keats space to develop and examine his beliefs about mythology, beauty, and visionary quest. Chapters three and four examine narrative techniques and the narrator’s role in ‘Isabella; or, The Pot of Basil’ and ‘The Eve of St. Agnes’ as Keats questions the nature and function of ‘old Romance’, even as he employs it, thus bringing a modern self-consciousness to bear on his task. Chapters five and six are devoted to the narrativity shown in the odes. Such an exploration of the ‘lyric narrative’ seeks to shed new light on our understanding of Keats’s odes. Chapter seven considers the ambivalence that Keats creates in ‘Lamia’. Lamia’s enigmatic identity as a woman and a serpent makes the narrative complex and the narrator perplexed. Chapter eight analyses ‘Hyperion: A Fragment’ and ‘The Fall of Hyperion: A Dream’, arguing that Keats uses these two poems as narratives to explore his idea of poetry and of the poet.
In his short creative life, Keats demonstrates different and various narrative skills. These narrative skills shape his ideas and ideals of poetry as well as of the poet. Via his use of narrative, we are able to see the evolution of his poetic identity. He presents himself as what he recommended a poet should be, a shape-changing figure, who might be best described as a ‘camelion Poet’
Surfactant protein D inhibits HIV-1 infection of target cells via interference with gp120-CD4 interaction and modulates pro-inflammatory cytokine production
No full text© 2014 Pandit et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Surfactant Protein SP-D, a member of the collectin family, is a pattern recognition protein, secreted by mucosal epithelial cells and has an important role in innate immunity against various pathogens. In this study, we confirm that native human SP-D and a recombinant fragment of human SP-D (rhSP-D) bind to gp120 of HIV-1 and significantly inhibit viral replication in vitro in a calcium and dose-dependent manner. We show, for the first time, that SP-D and rhSP-D act as potent inhibitors of HIV-1 entry in to target cells and block the interaction between CD4 and gp120 in a dose-dependent manner. The rhSP-D-mediated inhibition of viral replication was examined using three clinical isolates of HIV-1 and three target cells: Jurkat T cells, U937 monocytic cells and PBMCs. HIV-1 induced cytokine storm in the three target cells was significantly suppressed by rhSP-D. Phosphorylation of key kinases p38, Erk1/2 and AKT, which contribute to HIV-1 induced immune activation, was significantly reduced in vitro in the presence of rhSP-D. Notably, anti-HIV-1 activity of rhSP-D was retained in the presence of biological fluids such as cervico-vaginal lavage and seminal plasma. Our study illustrates the multi-faceted role of human SPD against HIV-1 and potential of rhSP-D for immunotherapy to inhibit viral entry and immune activation in acute HIV infection. © 2014 Pandit et al.The work (Project no. 2011-16850) was supported by Medical Innovation Fund of Indian Council of Medical Research, New Delhi, India (www.icmr.nic.in/)
Synthesis, cyclopolymerization and cyclo-copolymerization of 9-(2-Diallylaminoethyl)adenine and Its Hydrochloride Salt
No full textWe report herein the synthesis and characterization of 9-(2- diallylaminoethyl) adenine. We evaluated two different synthetic routes starting with adenine where the optimal route was achieved through coupling of 9-(2-chloroethyl)adenine with diallylamine. The cyclopolymerization and cyclo-copolymerization of 9-(2-diallylaminoethyl)adenine hydrochloride salt resulted in low molecular weight oligomers in low yields. In contrast, 9-(2-diallylaminoethyl)adenine failed to cyclopolymerize, however, it formed a copolymer with SO 2 in relatively good yields. The molecular weights of the cyclopolymers were around 1,700-6,000 g-mol, as estimated by SEC. The cyclo-copolymer was stable up to 226 °C. To the best of our knowledge, this is the first example of a free-radical cyclo-copolymerization of a neutral alkyldiallylamine derivative with SO 2. These polymers represent a novel class of carbocyclic polynucleotides. © 2012 by the authors.Agrawal S, 1999, BBA-GENE STRUCT EXPR, V1489, P53, DOI 10.1016-S0167-4781(99)00141-4; Ai H, 2002, BIOMACROMOLECULES, V3, P560, DOI 10.1021-bm015659r; AKASHI M, 1977, MAKROMOL CHEM, V178, P353; Ali SA, 1998, J APPL POLYM SCI, V69, P1329, DOI 10.1002-(SICI)1097-4628(19980815)69:71329::AID-APP73.0.CO;2-G; Ali SA, 2001, POLYMER, V42, P2785, DOI 10.1016-S0032-3861(00)00665-0; Al-Muallem HA, 2002, POLYMER, V43, P4285, DOI 10.1016-S0032-3861(02)00251-3; Armentrout RS, 2000, MACROMOLECULES, V33, P2944, DOI 10.1021-ma991531e; BUTLER GB, 1982, ACCOUNTS CHEM RES, V15, P370, DOI 10.1021-ar00083a005; Chen JC, 2003, J APPL POLYM SCI, V90, P1662, DOI 10.1002-app.12834; Gorbunova M, 2009, POLYM ADVAN TECHNOL, V20, P209, DOI 10.1002-pat.1253; Gorbunova M, 2009, INT J POLYM ANAL CH, V14, P575, DOI 10.1080-10236660903225445; Han MJ, 2000, ADV POLYM SCI, V153, P1; HARADA S, 1966, MAKROMOLEKUL CHEM, V90, P177; LITT M, 1960, J POLYM SCI, V45, P379, DOI 10.1002-pol.1960.1204514608; Miller KJ, 1998, PHARM SCI TECHNOL TO, V1, P377, DOI 10.1016-S1461-5347(98)00098-4; Hamma T, 1999, BIOCHEMISTRY-US, V38, P15333, DOI 10.1021-bi991962p; MILLIGAN JF, 1993, J MED CHEM, V36, P1923, DOI 10.1021-jm00066a001; Odian G, 2004, PRINCIPLES POLYM, P144; OTTENBRITE RM, 1980, IND ENG CHEM PROD RD, V19, P528, DOI 10.1021-i360076a009; Pei RJ, 2001, BIOMACROMOLECULES, V2, P463, DOI 10.1021-bm0001289; PITHA J, 1968, J ORG CHEM, V33, P1341, DOI 10.1021-jo01268a006; Rullens F, 2006, CHEM MATER, V18, P3078, DOI 10.1021-cm060209x; Sawada H, 1997, J FLUORINE CHEM, V84, P141, DOI 10.1016-S0022-1139(97)00050-X; Schuller W.H., 1959, J CHEM ENG DATA, V4, P273, DOI 10.1021-je60003a021; Shatila RS, 2006, TETRAHEDRON LETT, V47, P1767, DOI 10.1016-j.tetlet.2006.01.035; SOLOMON DH, 1976, J MACROMOL SCI R M C, VC 15, P143; Timofeeva L.M., 2005, POLYM SCI SER A, V47, P273; Timofeeva LM, 2006, DOKL PHYS CHEM, V406, P53, DOI 10.1134-S0012501606020072; Timofeeva LM, 2009, BIOMACROMOLECULES, V10, P2976, DOI 10.1021-bm900435v; Tsai JY, 2003, J ORG CHEM, V68, P1235, DOI 10.1021-jo026379k; Tuzun NS, 2007, INT J QUANTUM CHEM, V107, P894, DOI 10.1002-qua.21227; Tuzun NS, 2003, J ORG CHEM, V68, P6369, DOI 10.1021-jo034033j; UEDA N, 1968, MAKROMOL CHEM, V120, P13; UHLMANN E, 1990, CHEM REV, V90, P543, DOI 10.1021-cr00102a001; Ustyuzhanin G.E., 1978, CHEM HETEROCYCL COMP, V14, P562, DOI 10.1007-BF00673345; Vasilieva YA, 2000, RUSS CHEM B+, V49, P431, DOI 10.1007-BF02494771; Vivekanandam TS, 2005, J APPL POLYM SCI, V98, P1548, DOI 10.1002-app.22073; Vivekanandam TS, 2000, EUR POLYM J, V36, P385, DOI 10.1016-S0014-3057(99)00071-3; Wang GJ, 1998, J PHYS ORG CHEM, V11, P305, DOI 10.1002-(SICI)1099-1395(199805)11:5305::AID-POC83.0.CO;2-K; Weber W, 2004, J BIOTECHNOL, V114, P315, DOI 10.1016-j.jbiotec.2004.07.014; Zhou JL, 1997, SYNTHETIC COMMUN, V27, P3591, DOI 10.1080-003979197080070810
