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991.
Yurong Wen Ester Behiels Jan Felix Jonathan Elegheert Bjorn Vergauwen Bart Devreese Savvas N. Savvides 《Nucleic acids research》2014,42(15):10134-10147
Nearly all bacteria exhibit a type of phenotypic growth described as persistence that is thought to underlie antibiotic tolerance and recalcitrant chronic infections. The chromosomally encoded high-persistence (Hip) toxin–antitoxin proteins HipASO and HipBSO from Shewanella oneidensis, a proteobacterium with unusual respiratory capacities, constitute a type II toxin–antitoxin protein module. Here we show that phosphorylated HipASO can engage in an unexpected ternary complex with HipBSO and double-stranded operator DNA that is distinct from the prototypical counterpart complex from Escherichia coli. The structure of HipBSO in complex with operator DNA reveals a flexible C-terminus that is sequestered by HipASO in the ternary complex, indicative of its role in binding HipASO to abolish its function in persistence. The structure of HipASO in complex with a non-hydrolyzable ATP analogue shows that HipASO autophosphorylation is coupled to an unusual conformational change of its phosphorylation loop. However, HipASO is unable to phosphorylate the translation factor Elongation factor Tu, contrary to previous reports, but in agreement with more recent findings. Our studies suggest that the phosphorylation state of HipA is an important factor in persistence and that the structural and mechanistic diversity of HipAB modules as regulatory factors in bacterial persistence is broader than previously thought. 相似文献
992.
Peggy J. de Vos van Steenwijk Mariette I. E. van Poelgeest Tamara H. Ramwadhdoebe Margriet J. G. Löwik Dorien M. A. Berends-van der Meer Caroline E. van der Minne Nikki M. Loof Linda F. M. Stynenbosch Lorraine M. Fathers A. Rob P. M. Valentijn Jaap Oostendorp Elisabeth M. Osse Gert Jan Fleuren Linda Nooij Marjolein J. Kagie Bart W. J. Hellebrekers Cornelis J. M. Melief Marij J. P. Welters Sjoerd H. van der Burg Gemma G. Kenter 《Cancer immunology, immunotherapy : CII》2014,63(2):147-160
The capacity of a low-dose HPV16 synthetic long-peptide vaccine (HPV16-SLP) to induce an HPV16-specific T-cell response as well as to establish long-term immunologic memory in patients with low-grade abnormalities of the cervix was determined in a placebo-controlled, double-blinded phase II study. In addition, the effect of a booster vaccination after 1 year was evaluated. Patients received either the HPV16-SLP or a placebo at the start of the study. After 1 year, the vaccinated patients were again randomized to receive the HPV16-SLP or a placebo. Patients were followed for 2 years. HPV16-specific T-cell responses were determined in pre- and post-vaccination blood samples by ELISPOT, proliferation assay and cytokine assays. We show that the HPV16-specific T-cell responses detected after vaccination are clearly due to vaccination and that reactivity was maintained for at least 2 years. Interestingly, a booster vaccination after 1 year especially augmented the HPV16-specific Th2 response. Furthermore, pre-existing immunity to HPV16 was associated with a stronger response to vaccination and with more side effects, reflected by flu-like symptoms. We conclude that two low-dose injections of HPV16-SLP can induce a strong and stable HPV16-specific T-cell response that lasts for at least 1 year. If booster vaccination is required, then polarizing adjuvant should be added to maintain the Th1 focus of the vaccine-induced T-cell response. 相似文献
993.
Sandra Van Lint Sofie Wilgenhof Carlo Heirman Jurgen Corthals Karine Breckpot Aude Bonehill Bart Neyns Kris Thielemans 《Cancer immunology, immunotherapy : CII》2014,63(9):959-967
Since decades, the main goal of tumor immunologists has been to increase the capacity of the immune system to mediate tumor regression. In this regard, one of the major focuses of cancer immunotherapy has been the design of vaccines promoting strong tumor-specific cytotoxic T lymphocyte responses in cancer patients. Here, dendritic cells (DCs) play a pivotal role as they are regarded as nature’s adjuvant and as such have become the natural agents for antigen delivery in order to finally elicit strong T cell responses (Villadangos and Schnorrer in Nat Rev Immunol 7:543–555, 2007; Melief in Immunity 29:372–383, 2008; Palucka and Banchereau in Nat Rev Cancer 12:265–277, 2012; Vacchelli et al. in Oncoimmunology 2:e25771, 2013; Galluzzi et al. in Oncoimmunology 1:1111–1134, 2012). Therefore, many investigators are actively pursuing the use of DCs as an efficient way of inducing anticancer immune responses. Nowadays, DCs can be generated at a large scale in closed systems, yielding sufficient numbers of cells for clinical application. In addition, with the identification of tumor-associated antigens, which are either selectively or preferentially expressed by tumors, a whole range of strategies using DCs for immunotherapy have been designed and tested in clinical studies. Despite the evidence that DCs loaded with tumor-associated antigens can elicit immune responses in vivo, clinical responses remained disappointingly low. Therefore, optimization of the cellular product and route of administration was urgently needed. Here, we review the path we have followed in the development of TriMixDC-MEL, a potent DC-based cellular therapy, discussing its development as well as further modifications and applications. 相似文献
994.
Rascha J. M. Nuijten Andrea Kölzsch Jan A. van Gils Bethany J. Hoye Kees Oosterbeek Peter P. de Vries Marcel Klaassen Bart A. Nolet 《Journal of avian biology》2014,45(2):113-122
In the vast majority of migratory bird species studied so far, spring migration has been found to proceed faster than autumn migration. In spring, selection pressures for rapid migration are purportedly higher, and migratory conditions such as food supply, daylength, and/or wind support may be better than in autumn. In swans, however, spring migration appears to be slower than autumn migration. Based on a comparison of tundra swan Cygnus columbianus tracking data with long‐term temperature data from wheather stations, it has previously been suggested that this was due to a capital breeding strategy (gathering resources for breeding during spring migration) and/or to ice cover constraining spring but not autumn migration. Here we directly test the hypothesis that Bewick's swans Cygnus columbianus bewickii follow the ice front in spring, but not in autumn, by comparing three years of GPS tracking data from individual swans with concurrent ice cover data at five important migratory stop‐over sites. In general, ice constrained the swans in the middle part of spring migration, but not in the first (no ice cover was present in the first part) nor in the last part. In autumn, the swans migrated far ahead of ice formation, possibly in order to prevent being trapped by an early onset of winter. We conclude that spring migration in swans is slower than autumn migration because spring migration speed is constrained by ice cover. This restriction to spring migration speed may be more common in northerly migrating birds that rely on freshwater resources. 相似文献
995.
Pieter Vandermeeren Steffi Herrmann Danuta Cichocka Pieter Busschaert Bart Lievens Hans-Hermann Richnow Dirk Springael 《Biodegradation》2014,25(5):757-776
Anaerobic reductive dechlorination of hexachlorobenzene (HCB) and three isomers of tetrachlorobenzene (TeCB) (1,2,3,4-, 1,2,3,5- and 1,2,4,5-TeCB) was investigated in microcosms containing chloroaromatic contaminated river sediment. All chlorobenzenes were dechlorinated to dichlorobenzene (DCB) or monochlorobenzene. From the sediment, a methanogenic sediment-free culture was obtained which dechlorinated HCB, pentachlorobenzene, three TeCB isomers, three trichlorobenzene (TCB) isomers (1,2,3-, 1,2,4- and 1,3,5-TCB) and 1,2-DCB. Dechlorination involved multiple pathways including the removal of doubly flanked, singly flanked and isolated chlorine substituents. 454-pyrosequencing of partial bacterial 16S rRNA genes amplified from selected chlorobenzene dechlorinating sediment-free enrichment cultures revealed the presence of a variety of bacterial species, including Dehalobacter and Dehalococcoides mccartyi, that were previously documented as organohalide respiring bacteria. A genus with apparent close relationship to Desulfitobacterium that also has been associated with organohalide respiration, composed the major fraction of the operational taxonomic units (OTUs). Another major OTU was linked with Sedimentibacter sp., a genus that was previously identified in strict co-cultures of consortia reductively dehalogenating chlorinated compounds. Our data point towards the existence of multiple interactions within highly chlorinated benzene dechlorinating communities. 相似文献
996.
The trefoil factor (TFF) family, which comprises TFF1, TFF2 and TFF3, plays an essential role in epithelial regeneration within the gastrointestinal tract. All three TFFs are present in human saliva; TFF3 is the predominant trefoil peptide. Little is known about the expression and tissue distribution of TFFs in rats, which are commonly used as a model system for human studies. We investigated the localization of the TFF genes that encode secretory peptides in rat submandibular glands (SMG). All three TFFs were expressed in rat SMG, although their location varied. Substantial amounts of TFF1 were detected only in the cytoplasm of epithelial cells in the SMG granular convoluted tubules (GCT), while TFF2 and TFF3 were widely distributed in the cytoplasm of epithelial cells of intercalated ducts (ID), striated ducts (SD) and interlobular ducts (ILD). The three TFFs also were detected especially in the lumens of the SD and ILD. Semi-quantitative RT-PCR and in situ hybridization experiments confirmed TFF1, TFF2 and TFF3 mRNA expressions in the SMG. Greater expression of TFF peptides and mRNA was observed in male rats than in females. The broad expression of TFFs in rat SMG cells and lumens suggests that TFFs function in this organ by their secretion into the duct lumens. We also found differences in TFF expression profiles between rat and human SMG; therefore, caution should be exercised when using rats as a model for human TFF studies. 相似文献
997.
Trichieurina haladai
sp. n. (Diptera, Chloropidae), is described from Zambia. All known Trichieurina species are keyed and main differential characters are illustrated. 相似文献
998.
Jonathan Somme Bart Van Laer Martine Roovers Jan Steyaert Wim Versées Louis Droogmans 《RNA (New York, N.Y.)》2014,20(8):1257-1271
The 2′-O-methylation of the nucleoside at position 32 of tRNA is found in organisms belonging to the three domains of life. Unrelated enzymes catalyzing this modification in Bacteria (TrmJ) and Eukarya (Trm7) have already been identified, but until now, no information is available for the archaeal enzyme. In this work we have identified the methyltransferase of the archaeon Sulfolobus acidocaldarius responsible for the 2′-O-methylation at position 32. This enzyme is a homolog of the bacterial TrmJ. Remarkably, both enzymes have different specificities for the nature of the nucleoside at position 32. While the four canonical nucleosides are substrates of the Escherichia coli enzyme, the archaeal TrmJ can only methylate the ribose of a cytidine. Moreover, the two enzymes recognize their tRNA substrates in a different way. We have solved the crystal structure of the catalytic domain of both enzymes to gain better understanding of these differences at a molecular level. 相似文献
999.
Shrub encroachment can follow grazing or burning release in páramo grasslands. While encroachment decreases herbaceous species richness in some grassland systems, the effects of this process on the herbaceous community in páramo grasslands are currently unknown. We collected data on shrub cover, herbaceous‐species cover and species composition in a páramo grassland 12 years after release from burning and cattle grazing near Zuleta, Ecuador. Topographic and soil measures were also included as predictor variables of differences in community composition. Contrary to studies in other systems, shrub cover did not have a significant effect on herbaceous‐species richness, whereas shrub‐species richness significantly increased with shrub cover. However, shrub cover was associated with significant shifts in herbaceous–community composition. Most notably, there was an increase in some shade‐tolerant forbs and tall‐statured wetland grasses with increasing shrub cover, and a corresponding decrease in some short‐statured grasses and early successional forbs. These results could indicate that the ameliorative effects of shrubs (e.g. frost and wind protection) in harsh alpine environments may partially compensate for the expected competitive effect of shrubs due to shading. 相似文献
1000.
Viktorian Miok Saskia M Wilting Mark A van de Wiel Annelieke Jaspers Paula I van Noort Ruud H Brakenhoff Peter JF Snijders Renske DM Steenbergen Wessel N van Wieringen 《BMC bioinformatics》2014,15(1)