940 resultados para enchancesprotective immunity
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C-type lectins are calcium-dependent carbohydrate-binding proteins that play Important roles in innate immunity In this study, a C-type lectin homologue (SmLec1) was identified from turbot (Scophthalmus maximus) and analyzed at expression and functional levels. The open reading frame of SmLec1 is 504 bp, with a 5'-untranslated region (UTR) of 101 bp and a 3'-UTR of 164 bp The deduced amino acid sequence of SmLec1 shares 34%-38% overall identities with the C-type lectins of several fish species In silico analysis identified in SmLec1 conserved C-type lectin features, including a carbohydrate-recognition domain, four disulfide bond-forming cysteine residues, and the mannose-type carbohydrate-binding motif In addition, SmLec1 possesses a putative signal peptide sequence and is predicted to be localized in the extracellular. Expression of SmLec1 was highest in liver and responded positively to experimental challenges with fish pathogens Recombinant SmLec1 (rSmLec1) purified from yeast was able to agglutinate the Gram-negative fish pathogen Listonella anguillarum but not the Gram-positive pathogen Streptococcus uncle The agglutinating ability of rSmLec1 was abolished in the presence of mannose and ethylenediaminetetraacetic acid and by elevated temperature (65 degrees C) Further analysis showed that rSmLec1 could stimulate kidney lymphocyte proliferation and enhance the killing of bacterial pathogen by macrophages Taken together, these results suggest that SmLec1 is a unique mannose-binding C-type lectin that possesses apparent immunomodulating property and is likely to be involved in host defense against bacterial infection (C) 2010 Elsevier Ltd. All rights reserved
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针对目前刺参养殖过程中亟需解决的种质、环境和产品品质之间日益突出的矛盾,本论文从刺参的自身防御和内分泌机制入手,比较系统地研究了环境胁迫与细胞免疫和应激激素之间的作用机理;并从生理和分子的角度对刺参的夏眠机理进行了初步研究,主要研究成果如下: 1. 查阅国内外大量文献资料,较为系统地综述了海参的免疫体系、生态免疫学研究进展、当前夏眠机理的研究状况和刺参夏眠的基础研究。对刺参生态免疫及其夏眠机理研究提出了新的见解和思路。 2. 研究了温度(0、8、16、24、32℃)和盐度(20、25、35)的急性胁迫(72h)作用对刺参免疫指标的影响。刺参体腔液内几种免疫酶类活性受升温胁迫影响显著;而降温胁迫的影响并不显著。高盐胁迫可使刺参体腔液细胞吞噬活性、超氧化物歧化酶和过氧化氢酶活性显著变化,而对髓过氧化物酶和溶菌酶活性都没有显著影响。从这几种免疫指标变化情况来看,温度胁迫对刺参的影响要强于盐度胁迫,且高温胁迫的影响要强于低温胁迫。 3. 研究了温度(8、16、24℃)、盐度(20、25、35)和露空等急性胁迫(24h)作用对刺参体腔液儿茶酚胺类激素含量的影响。急性温度胁迫能够显著影响刺参体腔液内肾上腺素、去甲肾上腺素和多巴胺的含量;而盐度和露空胁迫对刺参体腔液肾上腺素含量、去甲肾上腺素含量以及多巴胺含量都没有产生显著影响。 4. 完成了刺参体腔液几种酶类变化的周年测定(2006年7月到2007年6月)。一年内刺参体腔液内几种酶类变化的转折点为9月份,10月份,1月份,2月份,4月份和5月份。刺参体腔液内几种酶类活性变化与温度和盐度等环境因素并不存在简单的相关关系,因此推测这些显著变化并不是单一温度、盐度等因素作用的结果,还可能与刺参生长、繁殖及其它环境因素的作用有关。 5. 开展了夏眠期间刺参免疫指标的现场研究(2006年7月到11月)。在此期间刺参体腔液细胞总数显著下降;刺参体腔液内免疫相关酶类均在8月份、9月份达到最高值;肾上腺素和去甲肾上腺素的含量均在8月下旬和11月下旬显著升高,而多巴胺含量则没有显著变化。刺参完全进入夏眠的8、9月份,体腔液内各项免疫指标也都具有显著变化,说明夏眠对刺参机体的免疫状态产生影响。 6. 探讨了刺参夏眠前后肠道基因表达的差异(2007年7月至12月)。抑制消减杂交实验结果表明接头连接效率大于50%,说明连接效率较高。消减效率分析结果表明,消减后进行cDNA保守序列扩增比未消减落后约10个循环才能明显看到扩增产物,说明对共同序列的消减效率比较高。利用抑制消减杂交技术成功构建了符合技术要求的夏眠刺参与未夏眠刺参肠道抑制消减杂交基因文库。
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针对目前栉孔扇贝Chlamys farreri养殖亟待解决的种质、病害、环境和产品质量等日趋严重的问题,从栉孔扇贝本身的防御机制和神经内分泌机制入手,较为系统地研究了环境胁迫,应激激素与血细胞免疫功能之间的相互作用机制;从生态免疫学角度,探讨了栉孔扇贝大规模死亡的原因,为栉孔扇贝病害防治和种质优化提供了一些理论依据。主要研究结果如下: 1.较为系统地综述了贝类生态免疫机制的研究进展。分析了应激激素对贝类细胞免疫活性的抑制作用,以及生态免疫过程中免疫成本的投入与其他生态因子之间的内在联系,分析了病原体与宿主之间的相互作用机制,提出了贝类生态免疫机制研究新见解和新思路。 2.筛选出一种较适用的抗凝剂配方:Glucose 20.8 gL-1,EDTA 20mM, Sodium chloride 20 gL-1,Tris-HCl 0.05M,pH=7.4。 3.模拟研究了栉孔扇贝养殖过程中的主要环境胁迫因子,包括露空胁迫(5°C,17°C和25°C露空最长持续24小时),急性温度胁迫(从17°C分别直接升至23°C和28°C或降至11°C),急性盐度胁迫(从盐度31直接升至盐度35或降至盐度25和20),饥饿胁迫(持续40天)和密度胁迫(分为低、中和高密度),对栉孔扇贝血细胞免疫功能的影响,养殖过程中的露空胁迫对栉孔扇贝的血细胞免疫功能具有抑制作用,从而削弱了扇贝胁迫后恢复的最初24小时中抗击病原体的能力。高温下(25°C)的露空胁迫能够显著地降低扇贝的成活率。急性升温胁迫(从17°C突变至28°C)会严重的破坏栉孔扇贝的内稳态,损伤其血细胞免疫功能,从而增加了扇贝对病原体的易感性。而扇贝对快速的降温胁迫(从17°C突变至11°C)则具有较高的耐受性。盐度20的低盐胁迫能够显著抑制栉孔扇贝的血细胞防御功能,同时低盐有利于许多病原体的繁殖,两方面的协同作用,将大大增加扇贝大规模死亡的几率。饥饿胁迫(40天)能够显著地抑制血细胞的免疫活性,然而在实验室饵料充足的条件下,养殖密度除了对血细胞的吞噬活性有一定的抑制作用外,对血细胞其他的免疫活性影响不明显。 4.揭示了环境胁迫因子,包括露空胁迫(17°C 露空24小时),温度胁迫(从17°C分别直接升至28°C或降至11°C持续7天),低盐胁迫(从盐度31直接降至盐度20持续7天)和饥饿40天胁迫,对栉孔扇贝血细胞超微结构的影响,露空胁迫(17°C 露空24小时),低盐胁迫(盐度20持续7天)和饥饿40天胁迫严重损伤了血细胞的膜系统及各种细胞器的结构。 5.利用酶联免疫法测定了栉孔扇贝血淋巴中应激激素(肾上腺素,去甲肾上腺素和多巴胺)的基础浓度,分别为0.088±0.11, 18.63±1.96 和 2.59±0.46ng/ml。研究了血淋巴中应激激素对环境胁迫(包括露空,急性升温和急性降盐)的响应水平,急性露空,升温和降盐能够显著提高血淋巴中肾上腺素和去甲肾上腺素的浓度,而多巴胺浓度变化却呈现出完全相反的趋势。 6.肾上腺素和去甲肾上腺素体外诱导栉孔扇贝血细胞研究结果表明:浓度为30ng/ml或50ng/ml的去甲肾上腺素能够显著抑制血细胞的吞噬活性,浓度为50ng/ml的去甲肾上腺素能够显著抑制血细胞的活性氧产物,而肾上腺素对血细胞免疫功能的影响则不显著。
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We examined the growth, survival and immune response of the scallop, Chlamys farreri, during a 1-year period in deep water of Haizhou Bay. Scallops were cultured using two methods: (1) in lantern nets at a 5 m depth and (2) in a bottom culture system (sleeves) on the seabed at about a 25 m depth. Shell heights, meat dry weight and immune activities in the haemolymph (superoxide dismutase and myeloperoxidase) were measured bimonthly or quarterly from July 2007 to June 2008. Survival was measured at the end of the study and environmental parameters in the experimental layers were monitored during the experiment. The growth and immune activities of scallops were lower when the water temperature was high, which was consistent with the main mortality occurring in summer. The growth and immunity of scallops were higher in the suspended culture than in the bottom culture during the experiment, with the exception of shell growth during the last study period. Survival of scallops in the suspended culture (54.6 +/- 12.3%) was significantly lower than that in the bottom culture (86.8 +/- 3.5%) at the end of this study. We conclude from our results that the high mortality of C. farreri can be prevented by culturing them in a bottom culture system before November of the first year, and then transferring them to a suspended culture to improve scallop production.
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Invertebrates are increasingly raised in mariculture, where it is important to monitor immune function and to minimize stresses that could suppress immunity. The activities of phagocytosis, superoxide dismutase (SOD), catalase (CAT), myeloperoxiclase (MPO), and lysozyme (LSZ) were measured to evaluate the immune capacities of the sea cucumber, Apostichopus japonicus, to acute temperature changes (from 12 degrees C to 0 degrees C, 8 degrees C, 16 degrees C, 24 degrees C, and 32 degrees C for 72 h) and salinity changes (from 30 parts per thousand to 20 parts per thousand, 25 parts per thousand, and 35 parts per thousand for 72 h) in the laboratory. Phagocytosis was significantly affected by temperature increases in 3 h, and by salinity (25 parts per thousand and 35 parts per thousand) changes in 1 h. SOD activities decreased significantly in 0.5 h to 6 h samples at 24 degrees C. At 32 degrees C, SOD activities decreased significantly in 0.5 h and 1 h exposures, and obviously increased for 12 h exposure. CAT activities decreased significantly at 24 degrees C for 0.5 h exposure, and increased significantly at 32 degrees C in 3 h to 12 h exposures. Activities of MPO increased significantly at 0 degrees C in 0.5 h to 6 In exposures and at 8 degrees C for 1 h. By contrast, activities of MPO decreased significantly in 24 degrees C and 32 degrees C treatments. In elevated-temperature treatments, activities of LSZ increased significantly except at 32 degrees C for 6 h to 12 h exposures. SOD activity was significantly affected by salinity change. CAT activity decreased significantly after only 1 h exposure to salinity of 20 parts per thousand.. Activities of MPO and LSZ showed that A. japonicus tolerates limited salinity stress. High-temperature stress had a much greater effect on the immune capacities of A. japonicus than did low-temperature and salinity stresses. Crown Copyright (C) 2008 Published by Elsevier Inc. All rights reserved.
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A comparative investigation of hot dip Zn-25Al alloy, Zn-55Al-Si and Zn coatings on steel was performed with attention to their corrosion performance in seawater. The results of 2-year exposure testing of these at Zhoushan test site are reported here. In tidal and immersion environments, Zn-25Al alloy coating is several times more durable than zinc coating of double thickness. At long exposure times, corrosion rate for the Zn-25Al alloy coating remains indistinguishable from that for the Zn-55Al-Si coating of similar thickness in tidal zone, and is two to three times lower than the latter in immersion zone. The decrease in tensile strength suggested that galvanized and Zn-55Al-Si coated steel suffer intense pitting corrosion in immersion zone. The electrochemical tests showed that all these coatings provide cathodic protection to the substrate metal; the galvanic potentials are equal to - 1,050, - 1,025 and - 880 mV (SCE) for zinc, Zn-25Al alloy and Zn-55Al-Si coating, respectively, which are adequate to keep the steel inside the immunity region. It is believed that the superior performance of the Zn-25Al alloy coating is due to its optimal combination of the uniform corrosion resistance and pitting corrosion resistance. The inferior corrosion performance by comparison of the Zn coating mainly results from its larger dissolution rate, while the failure of the Zn-55Al-Si coating is probably related to its higher susceptibility to pitting corrosion in seawater.
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To extend the cross-hole seismic 2D data to outside 3D seismic data, reconstructing the low frequency data to high frequency data is necessary. Blind deconvolution method is a key technology. In this paper, an implementation of Blind deconvolution is introduced. And optimized precondition conjugate gradient method is used to improve the stability of the algorithm and reduce the computation. Then high-frequency retrieved Seismic data and the cross-hole seismic data is combined for constraint inversion. Real data processing proved the method is effective. To solve the problem that the seismic data resolution can’t meet the request of reservoir prediction in the river face thin-layers in Chinese eastern oil fields, a high frequency data reconstruction method is proposed. The extrema of the seismic data are used to get the modulation function which operated with the original seismic data to get the high frequency part of the reconstruction data to rebuild the wide band data. This method greatly saves the computation, and easy to adjust the parameters. In the output profile, the original features of the seismic events are kept, the common feint that breaking the events and adding new zeros to produce alias is avoided. And the interbeded details are enhanced compared to the original profiles. The effective band of seismic data is expended and the method is approved by the processing of the field data. Aim to the problem in the exploration and development of Chinese eastern oil field that the high frequency log data and the relative low frequency seismic data can’t be merged, a workflow of log data extrapolation constrained by time-phase model based on local wave decomposition is raised. The seismic instantaneous phase is resolved by local wave decomposition to build time-phase model, the layers beside the well is matched to build the relation of log and seismic data, multiple log info is extrapolated constrained by seismic equiphase map, high precision attributes inverse sections are produced. In the course of resolve the instantaneous phase, a new method of local wave decomposition --Hilbert transform mean mode decomposition(HMMD) is raised to improve the computation speed and noise immunity. The method is applied in the high resolution reservoir prediction in Mao2 survey of Daqing oil field, Multiple attributes profiles of wave impedance, gamma-ray, electrical resistivity, sand membership degree are produced, of which the resolution is high and the horizontal continuous is good. It’s proved to be a effective method for reservoir prediction and estimation.
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Objective:Developing a generalized psychological intervention program, and explore its influence on the emotion, subjective health, and immunity function of the perioperation patients with breast cancer. Method:Sixty patients with breast cancer were randomly divided into intervention and control groups. The clinical psychological intervention was performed on patients in the intervention group for 20 days, in addition to the routine therapy and care. Levels of emotion (SAS & SDS), subjective health (SF-36), and immunity function (t lymphocyte subsets) of the patients were tested. Results: 1.There was no significant difference between the age, income, educational level, and type of prefession of the two groups. There was no significant difference between SAS, SDS, SF-36 and lymphocyte subsets(CD3+, CD4+, CD8+, CD4+/CD8+, NK) of the two groups. 2. Scores of SAS and SDS decreased significantly after intervention in experimental group, while the score of SF-36, the average value of CD4+, CD4+/CD8+, and NK increased significantly. For the control group, the score of depression decreased significantly after intervention, while the score of PF, GH, VT, SF, RE, and MH increased significantly. 3. In comparison of the intervention and control group, the intervention effect of SAS, SDS, SF-36 scores (except SF), CD3+, CD4+, CD4+/CD8+, and NK differed significantly, with the priority of experimental group. 4. SDS, SAS, and CD3+, CD4+, NK correlated in negative respectively, while SDS, SAS, and CD8+ correlated in positive. PF, RP, GH, SF, and MH of subjective health correlated in positive with every index of immunity function in positive, except negative correlation with CD4+/CD8+. BP, RE correlated with CD3+,CD4+,CD8+, and NK in positive. VT correlated in positive with CD3+, CD8+, and NK, in negative with CD4+/CD8+. Conclusions: 1. Anxiety, depression, and subjective health, correlated with immunity function in perioperation patients with breast cancer. 2. Psychological intervention can improve the emotional status, subjective health, and immune function of patients with breast cancer to the optimum in perioperative period.
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Depression is one of the most important psychological diseases to threaten human health. “Cytokine theory of depression” suggests that cytokines may play an important role in depression, which provided a new perspective in the study the mechanism and the therapy of depressive symptoms. This view is supported by various findings. Administration of pro-inflammatory cytokine or lipoposaccharide in animal induces depressive-like behavior such as anhedonia and low locomotion, which is very similar to the behavioral symptoms of depression in humans. However, the earlier researches may only pay attention to the short-time behavior effects; the effects of long-time behavior changes have not been clearly reported. In addition, there are few reports about the effects of pro-inflammatory cytokine or anti-inflammatory cytokine on the depressive-like behavior induced by chronic stressors. To further understand the role of cytokines in depression, the purpose of the present study is to investigate the dose and time effects of pro-inflammatory cytokines induced by lipoposaccharide on depressive-like behavior, sensitization effect of pro-inflammatory and blockage effect of anti-inflammatory on depressive-like behavior induced by chronic cold swimming stress. The behavioral observation was carried out using sacharin preference test, open field test and elevated-plus maze. The results indicated that: 1) The activated immunity induced by LPS i.p administration could induce significant depressive-like behavior, but these behaviors had no long-term effect; 2)The depressive-like behaviors induced by stress could be elicited earlier and kept longer by the activated immunity induced by LPS ip ; 4) The chronic activated immunity induced by LPS icv administration could provoke significant depressive-like behavior, and the depressive-like behaviors induced by stress could be enhanced by icv LPS, LPS and stress had certain interact-sensitization effect on depressive-like behavior; 5) Anti-inflammatory cytokines IL-10 icv reversed the depressive-like behaviors induced by the stress. In conclusion, cytokines play an important role in the depressive-like behavior. Both peripheral and central administration of LPS induced a certain depressive-like behavior and enhanced stress-induced depressive behavior. The anti-inflammatory cytokine IL-10 icv could reverse the depressive-like behaviors induced by the stress. Keywords: lipoposaccharide, depressive-like behavior, anhedonia, locomotion, chronic cold swimming stress
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This study was undertaken to investigate the effect of emotional stress on humoral immunoactivity and to examine whether the sympathetic nervous system was involved in the immunomodulation. In the present study, two types of emotional stressors were used. One was footshock apparatus used to cause the rats which were given footshock before, emotional stressed; the other was an empty water bottle used to cause the rats which were trained to drink water at two set times each day, emotional stressed. The effect of emotional stress on the primary immune function (anti-ovallum antibody level and spleen index), the endocrine response (corticosterone level, epinephrine and norepinephrine level), the behavioral changes (freezing, defecation, grooming and attacking behavior) were investigated. The main results were: 1. Two types of emotional stress significantly increased the level of plasma corticosterone, norepinephrine and epinephrine, as well as freezing, defecation and attacking behavior. 2. Two types of emotional stress significantly decreased the level of anti-ovallum antibody. A negative correlation between catecholamine level (epinephrine and norepinephrine) and antibody level or spleen index was found. 3. β-adrenergic receptor antagonist propranolol could reverse the immunomodulation induced by emotional stress. 4. After two types of emotional stress, c-fos expression was observed in the following brain areas or nucleus; arcuate nucleus, anterior commissure nucleus, diffuse part of dorsalmedial nucleus hypothalamus, lateral dorsal nucleus thalamus, medial nucleus amygdala, solitary nucleus, frontal cortex and cingulum. These brain areas and nucleus are involved in the central modulation of the autonomic nervous system. Taken together, these findings demonstrate that emotional stress can suppress humoral immunity and the activation of the sympathetic nervous system is involved in the humoral immunomodulation induced by emotional stress.
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Ebolaviruses (EBOVs) are among the most virulent and deadly pathogens ever known, causing fulminant haemorrhagic fevers in humans and non-human primates. The 2014 outbreak of Ebola virus disease (EVD) in West Africa has claimed more lives than all previous EVD outbreaks combined. The EBOV high mortality rates have been related to the virus-induced impairment of the host innate immunity reaction due to two virus-coded proteins, VP24 and VP35. EBOV VP35 is a multifunctional protein, it is essential for viral replication as a component of the viral RNA polymerase and it also participates in nucleocapsid assembly. Early during EBOV infection, alpha-beta interferon (IFN-α/β) production would be triggered upon recognition of viral dsRNA products by cytoplasmic retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs). However, this recognition is efficiently prevented by the double-stranded RNA (dsRNA) binding activity of the EBOV VP35 protein, which hides RLRs binding sites on the dsRNA phosphate backbone as well the 5’-triphosphate (5’-ppp) dsRNA ends to RIG-I recognition. In addition to dsRNA binding and sequestration, EBOV VP35 inhibits IFN-α/β production preventing the activation of the IFN regulatory factor 3 (IRF-3) by direct interaction with cellular proteins. Previous studies demonstrated that single amino acid changes in the VP35 dsRNA binding domain reduce EBOV virulence, indicating that VP35 is an attractive target for antiviral drugs development. Within this context, here we report the establishment of a novel method to characterize the EBOV VP35 inhibitory function of the dsRNA-dependent RIG-I-mediated IFN-β signaling pathway in a BLS2 cell culture setting. In such system, a plasmid containing the promoter region of IFN-β gene linked with a luciferase reporter gene was transfected, together with a EBOV VP35 mammalian expression plasmid, into the IFN-sensitive A549 cell line, and the IFN-induction was stimulated through dsRNA transfection. Through alanine scanning mutational studies with biochemical, cellular and computational methods we highlighted the importance of some VP35 residues involved in dsRNA end-capping binding, such as R312, K282 and R322, that may serve as target for the development of small-molecule inhibitors against EBOV. Furthermore, we identified a synthetic compound that increased IFN-induction only under antiviral response stimulation and subverted VP35 inhibition, proving to be very attractive for the development of an antiviral drug. In conclusion, our results provide the establishment of a new assay as a straightforward tool for the screening of antiviral compounds that target i) dsRNA-VP35 or cellular protein-VP35 interaction and ii) dsRNA-dependent RIG-I-mediated IFN signaling pathway, in order to potentiate the IFN response against VP35 inhibition, setting the bases for further drug development.
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Chronic graft-versus-host disease (cGVHD) is a frequent cause of morbimortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and severely compromises patients' physical capacity. Despite the aggressive nature of the disease, aerobic exercise training can positively impact survival as well as clinical and functional parameters. We analyzed potential mechanisms underlying the recently reported cardiac function improvement in an exercise-trained cGVHD murine model receiving lethal total body irradiation and immunosuppressant treatment (Fiuza-Luces et al., 2013. Med Sci Sports Exerc 45, 1703-1711). We hypothesized that a cellular quality-control mechanism that is receiving growing attention in biomedicine, autophagy, was involved in such improvement. Our results suggest that exercise training elicits a positive autophagic adaptation in the myocardium that may help preserve cardiac function even at the end-stage of a devastating disease like cGVHD. These preliminary findings might provide new insights into the cardiac exercise benefits in chronic/debilitating conditions.
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Wheeler, Nicholas, 'Dying for `Enduring Freedom': Accepting Responsibility for Civilian Casualties in the War against Terrorism', International Relations (2002) 16(2) pp.205-225 RAE2008
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The Extradomain A from fibronectin (EDA) has an immunomodulatory role as fusion protein with viral and tumor antigens, but its effect when administered with bacteria has not been assessed. Here, we investigated the adjuvant effect of EDA in mice immunizations against Salmonella enterica subspecies enterica serovar Enteritidis (Salmonella Enteritidis). Since lipopolysaccharide (LPS) is a major virulence factor and the LPS O-polysaccharide (O-PS) is the immunodominant antigen in serological diagnostic tests, Salmonella mutants lacking O-PS (rough mutants) represent an interesting approach for developing new vaccines and diagnostic tests to differentiate infected and vaccinated animals (DIVA tests). Here, antigenic preparations (hot-saline extracts and formalin-inactivated bacterins) from two Salmonella Enteritidis rough mutants, carrying either intact (SE Delta waaL) or deep-defective (SE Delta gal) LPS-Core, were used in combination with EDA. Biotinylated bacterins, in particular SE Delta waaL bacterin, decorated with EDAvidin (EDA and streptavidin fusion protein) improved the protection conferred by hot-saline or bacterins alone and prevented significantly the virulent infection at least to the levels of live attenuated rough mutants. These findings demonstrate the adjuvant effect of EDAvidin when administered with biotinylated bacterins from Salmonella Enteritidis lacking O-PS and the usefulness of BEDA-SE Delta waaL as non-live vaccine in the mouse model.
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Wydział Biologii: Instytut Biologii Molekularnej i Biotechnologii Zakład Genetyki Molekularnej Człowieka