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1.
The phosphorylation of at least five proteins with Mr of about 160,000; 93,000; 85,000; 45,000; and 29,000 respectively was demonstrated in crude extracts from the facultative chemolithotrophThiobacillus novellus. The incorporation of [-32P]phosphate from ATP into these proteins was dependent on the presence of magnesium ion. The phosphorylation reactions were found to be reversible and required 12.5 mM NaF for maximal activity, indicating the action of phosphatases. In addition, 3,5-cAMP had little effect on protein kinase activity, whereas Ca2+ alone was weakly stimulatory. This activation was enhanced by the addition of 3,5-cAMP. Ca2+ with calmodulin had a strong stimulatory effect on phosphate incorporation into the proteins. A highly purified preparation containing only the 160, 93, and 85 kDa proteins phosphorylated histone, whereas the uptake of32P by the three proteins was inhibited. Rabbit muscle phosphorylase b prevented incorporation of radiolabel only into the 160 and 93 kDa proteins. 相似文献
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Alphonse Ouédraogo Alfred B. Tiono Désiré Kargougou Jean Baptiste Yaro Esperance Ouédraogo Youssouf Kaboré David Kangoye Edith C. Bougouma Adama Gansane Noelie Henri Amidou Diarra Souleymane Sanon Issiaka Soulama Amadou T. Konate Nora L. Watson Valerie Brown Jenny Hendriks Maria Grazia Pau Isabella Versteege Edison Wiesken Jerald Sadoff Issa Nebie Sodiomon B. Sirima 《PloS one》2013,8(11)
Background
Ad35.CS.01 is a pre-erythrocytic malaria candidate vaccine. It is a codon optimized nucleotide sequence representing the P. falciparum circumsporozoite (CS) surface antigen inserted in a replication deficient Adenovirus 35 backbone. A Phase 1a trial has been conducted in the USA in naïve adults and showed that the vaccine was safe. The aim of this study is to assess the safety and immunogenicity of ascending dosages in sub Saharan Africa.Methods
A double blind, randomized, controlled, dose escalation, phase Ib trial was conducted in a rural area of Balonghin, the Saponé health district (Burkina Faso). Forty-eight healthy adults aged 18-45 years were randomized into 4 cohorts of 12 to receive three vaccine doses (day 0, 28 and 84) of 109, 1010, 5X1010, 1011 vp of Ad35.CS.01 or normal saline by intra muscular injection. Subjects were monitored carefully during the 14 days following each vaccination for non serious adverse events. Severe and serious adverse events were collected throughout the participant study duration (12 months from the first vaccination). Humoral and cellular immune responses were measured on study days 0, 28, 56, 84, 112 and 140.Results
Of the forty-eight subjects enrolled, forty-four (91.7%) received all three scheduled vaccine doses. Local reactions, all of mild severity, occurred in thirteen (27.1%) subjects. Severe (grade 3) laboratory abnormalities occurred in five (10.4%) subjects. One serious adverse event was reported and attributed to infection judged unrelated to vaccine. The vaccine induced both antibody titers and CD8 T cells producing IFNγ and TNFα with specificity to CS while eliciting modest neutralizing antibody responses against Ad35.Conclusion
Study vaccine Ad35.CS.01 at four different dose levels was well-tolerated and modestly immunogenic in this population. These results suggest that Ad35.CS.01 should be further investigated for preliminary efficacy in human challenge models and as part of heterologous prime-boost vaccination strategies.Trial Registration
ClinicalTrials.gov NCT01018459 http://clinicaltrials.gov/ct2/show/NCT01018459 相似文献4.
Amina Amadou Alban Fabre Gabriela Torres-Mejía Carolina Ortega-Olvera Angélica Angeles-Llerenas Fiona McKenzie Carine Biessy Pierre Hainaut Isabelle Romieu 《PloS one》2013,8(11)
The use of hormonal therapies, including hormonal contraceptives (HC) and postmenopausal hormone replacement therapy (HRT) have been shown to influence breast cancer (BC) risk. However, the variations of these effects among populations and ethnic groups are not completely documented, especially among Hispanic women. We evaluated the association between HC and premenopausal BC risk, and between HRT and postmenopausal BC risk in Mexican women. Data from a Mexican multi-center population-based case–control study ofwomen aged 35 to 69 years were analysed. A total of 1000 cases and 1074 matched controls were recruited between 2004 and 2007. Information on hormonal therapy was collected through a structured questionnaire. Results were analysed using conditional logistic regression models. Overall, HC were used by 422/891 (47.3%) premenopausal women and HRT was used by 220/1117 (19.7%) postmenopausal women. For HC, odds ratios (ORs) for BC were 1.11 (95% confidence interval (CI): 0.82, 1.49) for current users and 1.68 (95% CI: 0.67, 4.21) for ever-users. No clear effect of duration of use was observed. For HRT, the OR for BC was significantly increased in ever users (OR: 1.45; 95% CI: 1.01, 2.08). A non-significant increased risk was observed for combined estrogen/progestin, (OR = 1.85; 95% CI: 0.84, 4.07) whereas no effect was observed for the use of estrogen alone (OR = 1.14; 95% CI: 0.68, 1.91). Our results indicate that, HC had a non-significant effect on the risk of pre-menopausal BC, but suggested that injected contraceptives may slightly increase the risk, whereas HRT had a significant effect on post-menopausal BC in this population. This study provides new information about the effects of HC and HRT on BC risk in a Mexican population, which may be of relevance for the population of Latin America as a whole. 相似文献
5.
Paul S Marley Aboubacar Toure Jay Shebayan DA Aba AO Toure AG Diallo 《Archives Of Phytopathology And Plant Protection》2013,46(1):29-34
Fourteen elite sorghum lines were evaluated for their resistance to Striga hermonthica at three locations in Nigeria and Mali. Results showed that many of the lines especially MALISOR 84-1, SAMSORG 41, 97-SB-F5DT-64 (Keninkédié) and the check SRN 39 remained resistant to Striga in all locations with low emerged Striga counts, while SAMSORG 14 had the highest Striga infestation in all locations. Considerable variation in reaction to Striga infestation was observed on Séguètana, 97-SB-F5DT-63 (Wasa), 97-SB-F5DT-65, CMDT 38, CMDT 39 and CMDT 45 which were susceptible to Striga at Samaru, Nigeria but were resistant to Striga at both locations in Mali. Based on low Striga resistance and high grain yield, lines MALISOR 84-1, SAMSORG 41, 97-SB-F5DT-64, 97-SB-F5DT-65, CMDT 39 and SAMSORT 14 have been nominated for wider evaluation across more West African countries. 相似文献
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Dynamic microtubules produce an asymmetric E-cadherin–Bazooka complex to maintain segment boundaries
Natalia A. Bulgakova Ilya Grigoriev Alpha S. Yap Anna Akhmanova Nicholas H. Brown 《The Journal of cell biology》2013,201(6):887-901
Distributing junctional components around the cell periphery is key for epithelial tissue morphogenesis and homeostasis. We discovered that positioning of dynamic microtubules controls the asymmetric accumulation of E-cadherin. Microtubules are oriented preferentially along the dorso-ventral axis in Drosophila melanogaster embryonic epidermal cells, and thus more frequently contact E-cadherin at dorso-ventral cell–cell borders. This inhibits RhoGEF2, reducing membrane recruitment of Rho-kinase, and increasing a specific E-cadherin pool that is mobile when assayed by fluorescence recovery after photobleaching. This mobile E-cadherin is complexed with Bazooka/Par-3, which in turn is required for normal levels of mobile E-cadherin. Mobile E-cadherin–Bazooka prevents formation of multicellular rosette structures and cell motility across the segment border in Drosophila embryos. Altogether, the combined action of dynamic microtubules and Rho signaling determines the level and asymmetric distribution of a mobile E-cadherin–Bazooka complex, which regulates cell behavior during the generation of a patterned epithelium. 相似文献
8.
Alfred N. Fonteh Jiarong Chiang Matthew Cipolla Jack Hale Fatimatou Diallo Alejandra Chirino Xianghong Arakaki Michael G. Harrington 《Journal of lipid research》2013,54(10):2884-2897
Our aim is to study selected cerebrospinal fluid (CSF) glycerophospholipids (GP) that are important in brain pathophysiology. We recruited cognitively healthy (CH), minimally cognitively impaired (MCI), and late onset Alzheimer''s disease (LOAD) study participants and collected their CSF. After fractionation into nanometer particles (NP) and supernatant fluids (SF), we studied the lipid composition of these compartments. LC-MS/MS studies reveal that both CSF fractions from CH subjects have N-acyl phosphatidylethanolamine, 1-radyl-2-acyl-sn-glycerophosphoethanolamine (PE), 1-radyl-2-acyl-sn-glycerophosphocholine (PC), 1,2-diacyl-sn-glycerophosphoserine (PS), platelet-activating factor-like lipids, and lysophosphatidylcholine (LPC). In the NP fraction, GPs are enriched with a mixture of saturated, monounsaturated, and polyunsaturated fatty acid species, while PE and PS in the SF fractions are enriched with PUFA-containing molecular species. PC, PE, and PS levels in CSF fractions decrease progressively in participants from CH to MCI, and then to LOAD. Whereas most PC species decrease equally in LOAD, plasmalogen species account for most of the decrease in PE. A significant increase in the LPC-to-PC ratio and PLA2 activity accompanies the GP decrease in LOAD. These studies reveal that CSF supernatant fluid and nanometer particles have different GP composition, and that PLA2 activity accounts for altered GPs in these fractions as neurodegeneration progresses. 相似文献
9.
David F. Stowe Ashish K. Gadicherla Yifan Zhou Mohammed Aldakkak Qunli Cheng Wai-Meng Kwok Ming Tao Jiang James S. Heisner MeiYing Yang Amadou K.S. Camara 《生物化学与生物物理学报:生物膜》2013,1828(2):427-442
We tested if small conductance, Ca2 +‐sensitive K+ channels (SKCa) precondition hearts against ischemia reperfusion (IR) injury by improving mitochondrial (m) bioenergetics, if O2‐derived free radicals are required to initiate protection via SKCa channels, and, importantly, if SKCa channels are present in cardiac cell inner mitochondrial membrane (IMM). NADH and FAD, superoxide (O2?), and m[Ca2 +] were measured in guinea pig isolated hearts by fluorescence spectrophotometry. SKCa and IKCa channel opener DCEBIO (DCEB) was given for 10 min and ended 20 min before IR. Either TBAP, a dismutator of O2?, NS8593, an antagonist of SKCa isoforms, or other KCa and KATP channel antagonists, were given before DCEB and before ischemia. DCEB treatment resulted in a 2-fold increase in LV pressure on reperfusion and a 2.5 fold decrease in infarct size vs. non-treated hearts associated with reduced O2? and m[Ca2 +], and more normalized NADH and FAD during IR. Only NS8593 and TBAP antagonized protection by DCEB. Localization of SKCa channels to mitochondria and IMM was evidenced by a) identification of purified mSKCa protein by Western blotting, immuno-histochemical staining, confocal microscopy, and immuno-gold electron microscopy, b) 2-D gel electrophoresis and mass spectroscopy of IMM protein, c) [Ca2 +]‐dependence of mSKCa channels in planar lipid bilayers, and d) matrix K+ influx induced by DCEB and blocked by SKCa antagonist UCL1684. This study shows that 1) SKCa channels are located and functional in IMM, 2) mSKCa channel opening by DCEB leads to protection that is O2? dependent, and 3) protection by DCEB is evident beginning during ischemia. 相似文献
10.
The proliferation of biomedical applications, which rely on different knowledge organization systems, such as ontologies and thesauri raises the issue of the automated identification of the correspondences between these models, in particular for the data integration need. A significant effort has been conducted for tackling this issue of ontology alignment. However, few systems are able to deal with ontologies containing tens of thousands of entities, as it may be the case in the biomedical domain where resources such as SNOMED-CT, the FMA or the NCI thesaurus are commonly used. We present in this paper ServOMap, an efficient system for large-scale ontology alignment. It relies on an Ontology Server (ServO) and uses Information Retrieval techniques for computing similarity between entities. The system participated with two configurations in the 2012 Ontology Alignment Evaluation Initiative campaign. We report the very promising results obtained by the system for large biomedical ontologies alignment. ServOMap is freely available for download at http://code.google.com/p/servo/. 相似文献