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51.
Gloria Omosa-Manyonyi Juliet Mpendo Eugene Ruzagira William Kilembe Elwyn Chomba Fran?ois Roman Patricia Bourguignon Marguerite Koutsoukos Alix Collard Gerald Voss Dagna Laufer Gwynn Stevens Peter Hayes Lorna Clark Emmanuel Cormier Len Dally Burc Barin Jim Ackland Kristen Syvertsen Devika Zachariah Kamaal Anas Eddy Sayeed Angela Lombardo Jill Gilmour Josephine Cox Patricia Fast Frances Priddy 《PloS one》2015,10(5)
Background
Sequential prime-boost or co-administration of HIV vaccine candidates based on an adjuvanted clade B p24, RT, Nef, p17 fusion protein (F4/AS01) plus a non-replicating adenovirus 35 expressing clade A Gag, RT, Int and Nef (Ad35-GRIN) may lead to a unique immune profile, inducing both strong T-cell and antibody responses.Methods
In a phase 1, double-blind, placebo-controlled trial, 146 healthy adult volunteers were randomized to one of four regimens: heterologous prime-boost with two doses of F4/AS01E or F4/AS01B followed by Ad35-GRIN; Ad35-GRIN followed by two doses of F4/AS01B; or three co-administrations of Ad35-GRIN and F4/AS01B. T cell and antibody responses were measured.Results
The vaccines were generally well-tolerated, and did not cause serious adverse events. The response rate, by IFN-γ ELISPOT, was greater when Ad35-GRIN was the priming vaccine and in the co-administration groups. F4/AS01 induced CD4+ T-cells expressing primarily CD40L and IL2 +/- TNF-α, while Ad35-GRIN induced predominantly CD8+ T-cells expressing IFN-γ +/- IL2 or TNF-α. Viral inhibition was induced after Ad35-GRIN vaccination, regardless of the regimen. Strong F4-specific antibody responses were induced. Immune responses persisted at least a year after the last vaccination. The complementary response profiles, characteristic of each vaccine, were both expressed after co-administration.Conclusion
Co-administration of an adjuvanted protein and an adenovirus vector showed an acceptable safety and reactogenicity profile and resulted in strong, multifunctional and complementary HIV-specific immune responses.Trial Registration
ClinicalTrials.gov NCT01264445 相似文献52.
Yohana de Oliveira Fernanda Pinto André Luís Lopes da Silva Ivan Guedes Luiz Antonio Biasi Marguerite Quoirin 《In vitro cellular & developmental biology. Plant》2010,46(2):192-197
Melaleuca alternifolia is cultivated for the production of an essential oil useful in the cosmetic and pharmaceutical industries. Despite the economic
importance of this species, there is little knowledge about its in vitro propagation. The aim of this study was to establish an efficient protocol for micropropagation of M. alternifolia. With the goal of in vitro multiplication by axillary shoot proliferation, both solid and liquid MS and WPM media were tested with supplementation with
BA at 0, 0.55, 1.11, 2.22, 3.33, and 4.44 μM. The best result for shoot multiplication was obtained when either 0.55 μM BA
was added into solid MS medium or 1.11 μM BA was added into liquid MS medium, with 5.6 and 11.8 shoots per explant generated,
respectively. On solid or liquid WPM medium supplemented with 0.55 μM BA, the proliferation rates were 5.5 and 4.7, respectively.
Three auxins (NAA, IAA, and IBA) were tested at 0.53 and 2.64 μM during the rooting stage. Several sucrose concentrations
(15, 30, and 45 g L−1) were compared to a sucrose-free medium. Rooting performances on four culture media were then compared: MS, half-strength
MS (MS/2), MS + activated charcoal (AC), and MS/2 + AC. The results showed that auxin addition to culture medium is not necessary
for in vitro rooting. Rooted microcuttings from different culture media were acclimatized in a greenhouse, and the survival percentage was evaluated.
All shoots cultured in an auxin-free MS medium supplemented with sucrose (30 g L−1) produced roots, and all plants survived during acclimatization. Activated charcoal added in rooting medium reduced rooting
rates. 相似文献
53.
Rho GTPase-activating bacterial toxins: from bacterial virulence regulation to eukaryotic cell biology 总被引:1,自引:0,他引:1
Studies on the interactions of bacterial pathogens with their host have provided an invaluable source of information on the major functions of eukaryotic and prokaryotic cell biology. In addition, this expanding field of research, known as cellular microbiology, has revealed fascinating examples of trans-kingdom functional interplay. Bacterial factors actually exploit eukaryotic cell machineries using refined molecular strategies to promote invasion and proliferation within their host. Here, we review a family of bacterial toxins that modulate their activity in eukaryotic cells by activating Rho GTPases and exploiting the ubiquitin/proteasome machineries. This family, found in human and animal pathogenic Gram-negative bacteria, encompasses the cytotoxic necrotizing factors (CNFs) from Escherichia coli and Yersinia species as well as dermonecrotic toxins from Bordetella species. We survey the genetics, biochemistry, molecular and cellular biology of these bacterial factors from the standpoint of the CNF1 toxin, the paradigm of Rho GTPase-activating toxins produced by urinary tract infections causing pathogenic Escherichia coli. Because it reveals important connections between bacterial invasion and the host inflammatory response, the mode of action of CNF1 and its related Rho GTPase-targetting toxins addresses major issues of basic and medical research and constitutes a privileged experimental model for host-pathogen interaction. 相似文献
54.
IgE-antibody-dependent immunotherapy of solid tumors: cytotoxic and phagocytic mechanisms of eradication of ovarian cancer cells 总被引:1,自引:0,他引:1
Karagiannis SN Bracher MG Hunt J McCloskey N Beavil RL Beavil AJ Fear DJ Thompson RG East N Burke F Moore RJ Dombrowicz DD Balkwill FR Gould HJ 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(5):2832-2843
Abs have a paramount place in the treatment of certain, mainly lymphoid, malignancies, although tumors of nonhemopoietic origin have proved more refractory ones. We have previously shown that the efficacy of immunotherapy of solid tumors, in particular ovarian carcinoma, may be improved by the use of IgE Abs in place of the conventional IgG. An IgE Ab (MOv18 IgE) against an ovarian-tumor-specific Ag (folate binding protein), in combination with human PBMC, introduced into ovarian cancer xenograft-bearing mice, greatly exceeded the analogous IgG1 in promoting survival. In this study, we analyzed the mechanisms by which MOv18 IgE may exert its antitumor activities. Monocytes were essential IgE receptor-expressing effector cells that mediated the enhanced survival of tumor-bearing mice by MOv18 IgE and human PBMC. Monocytes mediated MOv18 IgE-dependent ovarian tumor cell killing in vitro by two distinct pathways, cytotoxicity and phagocytosis, acting respectively through the IgE receptors FcepsilonRI and CD23. We also show that human eosinophils were potent effector cells in MOv18 IgE Ab-dependent ovarian tumor cell cytotoxicity in vitro. These results demonstrate that IgE Abs can engage cell surface IgE receptors and activate effector cells against ovarian tumor cells. Our findings offer a framework for an improved immunotherapeutic strategy for combating solid tumors. 相似文献
55.
Laurent A Wright M Laayoun A Meunier B Tissot L Pitie M 《Nucleosides, nucleotides & nucleic acids》2007,26(8-9):927-930
For the first time Clip-Phen (1) was conjugated to oligonucleotides to provide very efficient tools for the cleavage of nucleic acids at specific positions. The synthesis of the conjugates as well as the cleavage experiments are reported. 相似文献
56.
The conformational behavior of hyaluronan (HA) polysaccharide chains in aqueous NaCl solution was characterized directly at the single-molecule level. This communication reports on one of the first single-chain atomic force microscopy (AFM) experiments performed at variable temperatures, investigating the influence of the temperature on the stability of the HA single-chain conformation. Through AFM single-molecule force spectroscopy, the temperature destabilization of a local structure was proven. This structure involved a hydrogen-bonded network along the polymeric chain, with hydrogen bonds between the polar groups of HA and possibly water, and a change from a nonrandom coil to a random coil behavior was observed when increasing the temperature from 29 +/- 1 to 46 +/- 1 degrees C. As a result of the applied force, this superstructure was found to break progressively at room temperature. The use of a hydrogen-bonding breaker solvent demonstrated the hydrogen-bonded water-bridged nature of the network structure of HA single chains in aqueous NaCl solution. 相似文献
57.
Dimitra Gkika Loic Lemonnier George Shapovalov Dmitri Gordienko Céline Poux Michela Bernardini Alexandre Bokhobza Gabriel Bidaux Cindy Degerny Kathye Verreman Basma Guarmit Mohamed Benahmed Yvan de Launoit Rene J.M. Bindels Alessandra Fiorio Pla Natalia Prevarskaya 《The Journal of cell biology》2015,208(1):89-107
TRPM8 is a cold sensor that is highly expressed in the prostate as well as in other non-temperature-sensing organs, and is regulated by downstream receptor–activated signaling pathways. However, little is known about the intracellular proteins necessary for channel function. Here, we identify two previously unknown proteins, which we have named “TRP channel–associated factors” (TCAFs), as new TRPM8 partner proteins, and we demonstrate that they are necessary for channel function. TCAF1 and TCAF2 both bind to the TRPM8 channel and promote its trafficking to the cell surface. However, they exert opposing effects on TRPM8 gating properties. Functional interaction of TCAF1/TRPM8 also leads to a reduction in both the speed and directionality of migration of prostate cancer cells, which is consistent with an observed loss of expression of TCAF1 in metastatic human specimens, whereas TCAF2 promotes migration. The identification of TCAFs introduces a novel mechanism for modulation of TRPM8 channel activity. 相似文献
58.
59.
Genetic variants modify the effect of age on APOE methylation in the Genetics of Lipid Lowering Drugs and Diet Network study
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Yiyi Ma Caren E. Smith Chao‐Qiang Lai Marguerite R. Irvin Laurence D. Parnell Yu‐Chi Lee Lucia Pham Stella Aslibekyan Steven A. Claas Michael Y. Tsai Ingrid B. Borecki Edmond K. Kabagambe Silvia Berciano José M. Ordovás Devin M. Absher Donna K. Arnett 《Aging cell》2015,14(1):49-59
Although apolipoprotein E (APOE) variants are associated with age-related diseases, the underlying mechanism is unknown and DNA methylation may be a potential one. With methylation data, measured by the Infinium Human Methylation 450 array, from 993 participants (age ranging from 18 to 87 years) in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study, and from Encyclopedia of DNA Elements (ENCODE) consortium, combined with published methylation datasets, we described the methylation pattern of 13 CpG sites within APOE locus, their correlations with gene expression across cell types, and their relationships with age, plasma lipids, and sequence variants. Based on methylation levels and the genetic regions, we categorized the 13 APOE CpG sites into three groups: Group 1 showed hypermethylation (> 50%) and were located in the promoter region, Group 2 exhibited hypomethylation (< 50%) and were located in the first two exons and introns, and Group 3 showed hypermethylation (> 50%) and were located in the exon 4. APOE methylation was negatively correlated with gene expression (minimum r = −0.66, P = 0.004). APOE methylation was significantly associated with age (minimum P = 2.06E-08) and plasma total cholesterol (minimum P = 3.53E-03). Finally, APOE methylation patterns differed across APOE ε variants (minimum P = 3.51E-05) and the promoter variant rs405509 (minimum P = 0.01), which further showed a significant interaction with age (P = 0.03). These findings suggest that methylation may be a potential mechanistic explanation for APOE functions related to aging and call for further molecular mechanistic studies. 相似文献
60.
The genome sequence of the leaf-cutter ant Atta cephalotes reveals insights into its obligate symbiotic lifestyle 总被引:1,自引:0,他引:1
Suen G Teiling C Li L Holt C Abouheif E Bornberg-Bauer E Bouffard P Caldera EJ Cash E Cavanaugh A Denas O Elhaik E Favé MJ Gadau J Gibson JD Graur D Grubbs KJ Hagen DE Harkins TT Helmkampf M Hu H Johnson BR Kim J Marsh SE Moeller JA Muñoz-Torres MC Murphy MC Naughton MC Nigam S Overson R Rajakumar R Reese JT Scott JJ Smith CR Tao S Tsutsui ND Viljakainen L Wissler L Yandell MD Zimmer F Taylor J Slater SC Clifton SW Warren WC Elsik CG Smith CD Weinstock GM Gerardo NM Currie CR 《PLoS genetics》2011,7(2):e1002007
Leaf-cutter ants are one of the most important herbivorous insects in the Neotropics, harvesting vast quantities of fresh leaf material. The ants use leaves to cultivate a fungus that serves as the colony's primary food source. This obligate ant-fungus mutualism is one of the few occurrences of farming by non-humans and likely facilitated the formation of their massive colonies. Mature leaf-cutter ant colonies contain millions of workers ranging in size from small garden tenders to large soldiers, resulting in one of the most complex polymorphic caste systems within ants. To begin uncovering the genomic underpinnings of this system, we sequenced the genome of Atta cephalotes using 454 pyrosequencing. One prediction from this ant's lifestyle is that it has undergone genetic modifications that reflect its obligate dependence on the fungus for nutrients. Analysis of this genome sequence is consistent with this hypothesis, as we find evidence for reductions in genes related to nutrient acquisition. These include extensive reductions in serine proteases (which are likely unnecessary because proteolysis is not a primary mechanism used to process nutrients obtained from the fungus), a loss of genes involved in arginine biosynthesis (suggesting that this amino acid is obtained from the fungus), and the absence of a hexamerin (which sequesters amino acids during larval development in other insects). Following recent reports of genome sequences from other insects that engage in symbioses with beneficial microbes, the A. cephalotes genome provides new insights into the symbiotic lifestyle of this ant and advances our understanding of host-microbe symbioses. 相似文献