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31.
Himoudi N Yan M Papanastasiou A Anderson J 《Cancer immunology, immunotherapy : CII》2008,57(5):693-700
MYCN is a potential target for cancer immunotherapy by virtue of its overexpression in numerous human malignancies and its
functional role in tumour progression. Here we show limited expression of MYCN in normal human tissues indicating that anti-MYCN
immune responses are unlikely to cross react with self tissues. An HLA-A2 restricted ten amino acid peptide epitope from MYCN,
VILKKATEYV, was used to stimulate cytotoxic T cell lines from the peripheral blood of normal blood donors, and from a patient
with MYCN amplified neuroblastoma. Strong and specific activity was seen against each MYCN overexpressing cell line and against
autologous tumour cells. We generated two CTL clones capable of killing cells pulsed with as low as 0.5 nM of VIL peptide.
Therefore strong and specific immune responses against MYCN expressing tumours are possible in patients with the most common
HLA class 1 type in the Caucasian population. 相似文献
32.
Mycobacteria exploit nitric oxide‐induced transformation of macrophages into permissive giant cells 下载免费PDF全文
Kourosh Gharun Julia Senges Maximilian Seidl Anne Lösslein Julia Kolter Florens Lohrmann Manfred Fliegauf Magdeldin Elgizouli Martina Vavra Kristina Schachtrup Anna L Illert Martine Gilleron Carsten J Kirschning Antigoni Triantafyllopoulou Philipp Henneke 《EMBO reports》2017,18(12):2144-2159
Immunity to mycobacteria involves the formation of granulomas, characterized by a unique macrophage (MΦ) species, so‐called multinucleated giant cells (MGC). It remains unresolved whether MGC are beneficial to the host, that is, by prevention of bacterial spread, or whether they promote mycobacterial persistence. Here, we show that the prototypical antimycobacterial molecule nitric oxide (NO), which is produced by MGC in excessive amounts, is a double‐edged sword. Next to its antibacterial capacity, NO propagates the transformation of MΦ into MGC, which are relatively permissive for mycobacterial persistence. The mechanism underlying MGC formation involves NO‐induced DNA damage and impairment of p53 function. Moreover, MGC have an unsurpassed potential to engulf mycobacteria‐infected apoptotic cells, which adds a further burden to their antimycobacterial capacity. Accordingly, mycobacteria take paradoxical advantage of antimicrobial cellular efforts by driving effector MΦ into a permissive MGC state. 相似文献
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Aristos J. Alexandrou Adam R. Brown Mark L. Chapman Mark Estacion Jamie Turner Malgorzata A. Mis Anna Wilbrey Elizabeth C. Payne Alex Gutteridge Peter J. Cox Rachel Doyle David Printzenhoff Zhixin Lin Brian E. Marron Christopher West Nigel A. Swain R. Ian Storer Paul A. Stupple Neil A. Castle James A. Hounshell Mirko Rivara Andrew Randall Sulayman D. Dib-Hajj Douglas Krafte Stephen G. Waxman Manoj K. Patel Richard P. Butt Edward B. Stevens 《PloS one》2016,11(4)
Human genetic studies show that the voltage gated sodium channel 1.7 (Nav1.7) is a key molecular determinant of pain sensation. However, defining the Nav1.7 contribution to nociceptive signalling has been hampered by a lack of selective inhibitors. Here we report two potent and selective arylsulfonamide Nav1.7 inhibitors; PF-05198007 and PF-05089771, which we have used to directly interrogate Nav1.7’s role in nociceptor physiology. We report that Nav1.7 is the predominant functional TTX-sensitive Nav in mouse and human nociceptors and contributes to the initiation and the upstroke phase of the nociceptor action potential. Moreover, we confirm a role for Nav1.7 in influencing synaptic transmission in the dorsal horn of the spinal cord as well as peripheral neuropeptide release in the skin. These findings demonstrate multiple contributions of Nav1.7 to nociceptor signalling and shed new light on the relative functional contribution of this channel to peripheral and central noxious signal transmission. 相似文献
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C. Sismani J. Donoghue A Alexandrou M. Karkaletsi S. Christopoulou A.E. Konstantinidou P. Livanos P.C. Patsalis V. Velissariou 《Gene》2013
Duplications of the X chromosome are rare cytogenetic findings, and have been associated with an abnormal phenotype in the male offspring of apparently normal or near normal female carriers. We report on the prenatal diagnosis of a duplication on the long arm of chromosome X from chromosomal band Xq13.2 to q21.31 in a male fetus with increased nuchal translucency in the first trimester and polyhydramnios at 22 weeks of gestation. Amniocentesis was undertaken and cytogenetic analysis revealed additional chromosomal material in the long arm of chromosome X at position Xq13. Analysis with high resolution array CGH revealed the additional material is in fact a duplication of the region Xq13.2–q21.13. The duplication is 14.8 Mb in size and includes fourteen genes: SLC16A2, KIAA2022, ABCB7, ZDHHC15, ATRX, MAGT1, ATP7A, PGK1, TBX22, BRWD3, POU3F4, ZNF711, POF1B and CHM. Analysis of the parents revealed the mother to be a carrier of the same duplication. After elected termination of the pregnancy at 28 weeks a detailed autopsy of the fetus allowed for genotype–phenotype correlations. 相似文献
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Tatiane C. Mariguela Markos A. Alexandrou Fausto Foresti Claudio Oliveira 《Journal of Zoological Systematics and Evolutionary Research》2013,51(4):308-315
The family Callichthyidae, divided into the subfamilies Corydoradinae and Callichthyinae, contains more than 200 species of armoured catfishes distributed throughout the Neotropics, as well as fossil species dating from the Palaeocene. Both subfamilies are very widely distributed throughout the continent, with some species ranges extending across multiple hypothesized biogeographical barriers. Species with such vast geographical ranges could be made up of multiple cryptic populations that are genetically distinct and have diverged over time. Although relationships among Callichthyinae genera have been thoroughly investigated, the historical biogeography of the Callichthyinae and the presence of species complexes have yet to be examined. Furthermore, there is a lack of fossil‐calibrated molecular phylogenies providing a time frame for the evolution of the Callichthyinae. Here, we present a novel molecular data set for all Callichthyinae genera composed of partial sequences of mitochondrial and nuclear markers. These data were used to construct a fossil‐calibrated tree for the Callichthyinae and to reconstruct patterns of spatiotemporal evolution. All phylogenetic analyses [Bayesian, maximum likelihood and maximum parsimony (MP)] resulted in a single fully resolved and well‐supported hypothesis for the Callichthyinae, where Dianema is the sister group of all the remaining genera. Results suggest that the ancestry of most Callichthyinae genera originated in the Amazonas basin, with a number of subsequent ancestral dispersal events between adjacent basins. High divergences in sequences and time were observed for several samples of Hoplosternum littorale, Megalechis picta and Callichthys callichthys, suggesting that these species may contain cryptic diversity. The results highlight the need for a taxonomic revision of species complexes within the Callichthyinae, which may reveal more diversity within this relatively species‐poor lineage. 相似文献
38.
Kouyianou K De Bock PJ Müller SA Nikolaki A Rizos A Krzyžánek V Aktoudianaki A Vandekerckhove J Engel A Gevaert K Tsiotis G 《Proteomics》2011,11(14):2867-2880
Chlorosomes, the antenna complexes of green bacteria, are unique antenna systems in which pigments are organized in aggregates. Studies on isolated chlorosomes from Chlorobaculum tepidum based on SDS-PAGE, immunoblotting and molecular biology have revealed that they contain ten chlorosomal proteins, but no comprehensive information is available about the protein composition of the entire organelle. To extend these studies, chlorosomes were isolated from C. tepidum using three related and one independent isolation protocol and characterized by absorption spectroscopy, tricine SDS-PAGE, dynamic light scattering (DLS) and electron microscopy. Tricine SDS-PAGE showed the presence of more than 20 proteins with molecular weights ranging between 6 and 70 kDa. The chlorosomes varied in size. Their hydrodynamic radius (R(h) ) ranged from 51 to 75 nm and electron microscopy indicated that they were on average 140 nm wide and 170 nm long. Furthermore, the mass of 184 whole chlorosome organelles determined by scanning transmission electron microscopy ranged from 27 to 237 MDa being on average 88 (±28) MDa. In contrast their mass-per-area was independent of their size, indicating that there is a strict limit to chlorosome thickness. The average protein composition of the C. tepidum chlorosome organelles was obtained by MS/MS-driven proteomics and for the first time a detailed protein catalogue of the isolated chlorosomal proteome is presented. Based on the proteomics results for chlorosomes isolated by different protocols, four proteins that are involved in the electron or ion transport are proposed to be tightly associated with or incorporated into C. tepidum chlorosomes as well as the ten Csm proteins known to date. 相似文献
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Pliatsika P Antoniou A Alexandrou A Panoulis C Kouskouni E Augoulea A Dendrinos S Aravantinos L Creatsa M Lambrinoudaki I 《Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology》2012,28(8):655-660
Contradictory results have been reported regarding a relationship between serum lipid levels and bone mineral density. The purpose of this study was to further investigate a possible relationship between those parameters in Greek postmenopausal women. A total of 591 patients followed at a tertiary hospital were examined for seven different lipid factors in relation to dual-emission X-ray absorptiometry measurements at the lumbar spine. Lipoprotein-a was the only lipid measurement that univariately showed an almost significant trend of association with bone mass category (analysis of variance [ANOVA] p value 0.062 for Ln(Lipoprotein-a)). In multiple regression, it was noted that a non-significant negative trend of association of high density lipoprotein (HDL) cholesterol and Apolipoprotein AI with lumbar T-score (p value 0.058 and 0.075, respectively). In age subgroup analysis, Lipoprotein-a and Ln(Lipoprotein-a) presented a negative correlation with lumbar T-score for women with age ≥ 53 years (p value 0.043 and 0.070, respectively), while a negative correlation of HDL and Apolipoprotein AI levels with lumbar T-score remained in women with age < 53 years (p value 0.039 and 0.052, respectively). The findings do not support a strong relationship between lipid levels and bone mass measurements. 相似文献
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Antigoni L Elefsinioti Pantelis G Bagos Ioannis C Spyropoulos Stavros J Hamodrakas 《BMC bioinformatics》2004,5(1):208