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71.
Lang KS Hegazy AN Lang PA Eschli B Löhning M Hengartner H Zinkernagel RM Recher M 《PloS one》2007,2(11):e1162
Background
Cooperation of CD4+ T helper cells with specific B cells is crucial for protective vaccination against pathogens by inducing long-lived neutralizing antibody responses. During infection with persistence-prone viruses, prolonged virus replication correlates with low neutralizing antibody responses. We recently described that a viral mutant of lymphocytic choriomeningitis virus (LCMV), which lacks a T helper epitope, counterintuitively induced an enhanced protective antibody response. Likewise, partial depletion of the CD4+ T cell compartment by using anti-CD4 antibodies enhanced protective antibodies.Principal Findings
Here we have developed a protocol to selectively reduce the CD4+ T cell response against viral CD4+ T cell epitopes. We demonstrate that in vivo treatment with LCMV-derived MHC-II peptides induced non-responsiveness of specific CD4+ T cells without affecting CD4+ T cell reactivity towards other antigens. This was associated with accelerated virus-specific neutralizing IgG-antibody responses. In contrast to a complete absence of CD4+ T cell help, tolerisation did not impair CD8+ T cell responses.Conclusions
This result reveals a novel “negative vaccination” strategy where specific CD4+ T cell unresponsiveness may be used to enhance the delayed protective antibody responses in chronic virus infections. 相似文献72.
Mohamed H. Abd El-Razek Ibrahim A. Saleh Sally Abdel-Halim Shaymaa M. Bata Ahmed F. Essa Taha A. Hussien Ahmed A. El-Beih Tarik A. Mohamed Mohamed-Elamir F. Hegazy 《化学与生物多样性》2023,20(8):e202201249
In the current study, both the essential oil composition and biological activity of Saussurea lappa and Ligusticum sinensis were investigated by means of microwave-assisted hydrodistillation (MAHD) and characterized by Gas chromatography/mass spectrometry (GC/MS), whereas the antimicrobial efficiency of MAHD essential oils was examined against four pathogens: Staphylococcus aureus, Escherichia coli, Aspergillus niger, and Candida albicans responsible for microbial infections. The goal was to spot synergy and a favorable method that gives essential oils to possibly use as alternatives to common antimicrobial agents for the treatment of bacterial infections using a microdilution assay. S. lappa's 21 compounds were characterized by MAHD extraction. Sesquiterpene lactones (39.7 % MAHD) represented the major components, followed by sesquiterpene dialdehyde (25.50 % MAHD), while L. sinensis's 14 compounds were identified by MAHD extraction. Tetrahydroisobenzofurans (72.94 % MAHD) was the predominant compound class. S. lappa essential oil collection showed the strongest antimicrobial activity with MIC values of 16 μg/ml against all pathogens tested, while L. sinensis showed strong antibacterial activity and moderate antifungal activity with MIC values of 32 μg/ml and 500 μg/ml, respectively. The principal components of both oils, (velleral, eremanthin and neocnidilide), were docked into the bacterial histidine kinase (HK) and the fungal heat shock protein 90 (Hsp90). 相似文献
73.
Transgene-mediated and elicitor-induced perturbation of metabolic channeling at the entry point into the phenylpropanoid pathway 总被引:12,自引:0,他引:12 下载免费PDF全文
3H-l-Phenylalanine is incorporated into a range of phenylpropanoid compounds when fed to tobacco cell cultures. A significant proportion of (3)H-trans-cinnamic acid formed from (3)H-l-phenylalanine did not equilibrate with exogenous trans-cinnamic acid and therefore may be rapidly channeled through the cinnamate 4-hydroxylase (C4H) reaction to 4-coumaric acid. Such compartmentalization of trans-cinnamic acid was not observed after elicitation or in cell cultures constitutively expressing a bean phenylalanine ammonia-lyase (PAL) transgene. Channeling between PAL and C4H was confirmed in vitro in isolated microsomes from tobacco stems or cell suspension cultures. This channeling was strongly reduced in microsomes from stems or cell cultures of transgenic PAL-overexpressing plants or after elicitation of wild-type cell cultures. Protein gel blot analysis showed that tobacco PAL1 and bean PAL were localized in both soluble and microsomal fractions, whereas tobacco PAL2 was found only in the soluble fraction. We propose that metabolic channeling of trans-cinnamic acid requires the close association of specific forms of PAL with C4H on microsomal membranes. 相似文献
74.
Phylogenetic analyses of the rbcL sequences from haptophytes and heterokont algae suggest their chloroplasts are unrelated 总被引:2,自引:0,他引:2
Using the large subunit of RuBisCo (rbcL) sequences from cyanobacteria,
proteobacteria, and diverse groups of algae and green plants, we evaluated
the plastid relationship between haptophytes and heterokont algae. The rbcL
sequences were determined from three taxa of heterokont algae
(Bumilleriopsis filiformis, Pelagomonas calceolata, and Pseudopedinella
elastica) and added to 25 published sequences to obtain a data set
comprising 1,434 unambiguously aligned sites (approximately 98% of the
total rbcL gene). Higher levels of mutational saturation in third codon
positions were observed by plotting the pairwise substitutions with and
without corrections for multiple substitutions at the same site for first
and second codon positions only and for third positions only. In accordance
with this finding phylogeny reconstructions were completed by omitting
third codon positions, thus using 956 bp in weighted-parsimony and
maximum-likelihood analyses. The midpoint-rooted phylogenies showed two
major clusters, one containing cyanobacteria, glaucocystophytes, a
phototrophic euglenoid, chlorophytes, and embryophytes (the green lineage),
the other containing proteobacteria, haptophytes, red algae, a cryptophyte,
and heterokont algae (the non-green lineage). In the nongreen lineage, the
haptophytes formed a sister group to the clade containing heterokont algae,
red algae, and the cryptophyte Guillardia theta. This branching pattern was
well supported in terms of bootstrap values in weighted- parsimony and
maximum-likelihood analyses (100% and 92%, respectively). However, the
phylogenetic relationship among red algae, heterokonts, and a cryptophyte
taxon was not especially well resolved. A four- cluster analysis was
performed to further explore the statistical significance of the
relationship between proteobacteria, red algae (including and excluding
Guillardia theta), haptophytes, and heterokont algae. This test strongly
favored the hypothesis that the heterokonts and red algae are more closely
related to each other than either is to proteobacteria or haptophytes.
Hence, this molecular study based on a plastid-encoded gene provides
additional evidence for a distant relationship between haptophytes and the
heterokont algae. It suggests an evolutionary scenario in which the
ancestor of the haptophyte lineage engulfed a phototrophic eukaryote and,
more recently, the heterokont lineage became phototrophic by engulfing a
red alga.
相似文献
75.
Because of the important role that oxidative stress is thought to play in the aging process, antioxidants could be candidates for preventing its related pathologies. We investigated the ameliorative effects of two antioxidant supplements, ginger and alpha lipoic acid (ALA), on hepatic ultrastructural alterations in old rats. Livers of young (4 months) and old (24 months) Wistar rats were studied using transmission electron microscopy. Livers of old rats showed sinusoidal collapse and congestion, endothelial thickening and defenestration, and inconsistent perisinusoidal extracellular matrix deposition. Aged hepatocytes were characterized by hypertrophy, cytoplasmic vacuolization and a significant increase in the volume densities of the nuclei, mitochondria and dense bodies. Lipofuscin accumulation and decreased microvilli in bile canaliculi and space of Disse also were observed. The adverse alterations were ameliorated significantly by both ginger and ALA supplementation; ALA was more effective than ginger. Ginger and ALA appear to be promising anti-aging agents based on their amelioration of ultrastructural alterations in livers of old rats. 相似文献
76.
Hexavalent chromium (CrVI) is a heavy metal widely used in more than 50 industries. Nephrotoxicity is a major adverse effect of chromium poisoning. The present study investigated the potential renoprotective effect of lactoferrin (Lf) against potassium dichromate (PDC)-induced acute kidney injury (AKI) in rats. Beside, because previous studies suggest that interlukin-18 (IL-18) and insulin-like growth factor-1 (IGF-1) play important roles in promoting kidney damage, the present work aimed to evaluate the involvement of these two cytokines in PDC model of AKI and in the potential renoprotective effect of lactoferrin. Adult male albino Wistar rats were pretreated with Lf (200mg/kg/day, p.o.) or (300mg/kg/day, p.o.); the doses that are usually used in the experiment studies, for 14 days followed by a single dose of PDC (15mg/kg, s.c.). PDC caused significant increase in serum urea, creatinine, and total protein levels. This was accompanied with decreased renal glutathione content, and increased renal malondialdehyde, IL-18, IL-4, nuclear factor kappa B (NFκB), IGF-1, and the phosphorylated form of forkhead box protein O1 (FoxO1) levels. Moreover, normal expression IFN-γ mRNA and enhanced expression of TNF-α mRNA was demonstrated in renal tissues. Histopathological investigations provoked deleterious changes in the renal tissues. Tubular epithelial hyperplasia and apoptosis were demonstrated immunohistochemically by positive proliferating cell nuclear antigen (PCNA), Bax, and Caspase-3 expression, respectively. Pretreatment of rats with Lf in both doses significantly corrected all previously mentioned PDC-induced changes with no significant difference between both doses. In conclusion, the findings of the present study demonstrated the involvement of oxidative stress, inflammatory reactions, tubular hyperplasia and apoptosis in PDC-induced AKI. It suggested a role of IL-18 through stimulation of IL-4-induced inflammatory pathway, and IGF-1 through triggering FoxO1-induced cell proliferation. Moreover, the study revealed that Lf protected the kidney against Cr-induced AKI in rats and significantly showed antioxidant, anti-inflammatory, and anti-proliferative properties with down-regulation of IL-18 and IGF-1. 相似文献
77.
The loop following helix α2 in glutathione transferase P1-1 has two conserved residues, Cys48 and Tyr50, important for glutathione (GSH) binding and catalytic activity. Chemical modification of Cys48 thwarts the catalytic activity of the enzyme, and mutation of Tyr50 generally decreases the kcat value and the affinity for GSH in a differential manner. Cys48 and Tyr50 were targeted by site-specific mutations and chemical modifications in order to investigate how the α2 loop modulates GSH binding and catalysis. Mutation of Cys48 into Ala increased KMGSH 24-fold and decreased the binding energy of GSH by 1.5 kcal/mol. Furthermore, the protein stability against thermal inactivation and chemical denaturation decreased. The crystal structure of the Cys-free variant was determined, and its similarity to the wild-type structure suggests that the mutation of Cys48 increases the flexibility of the α2 loop rather than dislocating the GSH-interacting residues. On the other hand, replacement of Tyr50 with Cys, producing mutant Y50C, increased the Gibbs free energy of the catalyzed reaction by 4.8 kcal/mol, lowered the affinity for S-hexyl glutathione by 2.2 kcal/mol, and decreased the thermal stability. The targeted alkylation of Cys50 in Y50C increased the affinity for GSH and protein stability. Characterization of the most active alkylated variants, S-n-butyl-, S-n-pentyl-, and S-cyclobutylmethyl-Y50C, indicated that the affinity for GSH is restored by stabilizing the α2 loop through positioning of the key residue into the lock structure of the neighboring subunit. In addition, kcat can be further modulated by varying the structure of the key residue side chain, which impinges on the rate-limiting step of catalysis. 相似文献
78.
BACKGROUND AND AIMS: Unlike the dispersal mechanisms of many desert plants, the whole dead skeleton of Anastatica hierochuntica is involved in seed dispersal and preservation. This process depends on the hygrochastic nature of the lignified conducting tissue that bends when dry and straightens under wet conditions. An anatomical interpretation of this mechanical movement was investigated. METHODS: An anatomical study of the stem was conducted on the juvenile plants raised under different water treatments and on the branch-orders of adult A. hierochuntica size-classes. KEY RESULTS: In the juvenile stem of A. hierochuntica, the area of cortex, conducting tissue and pith increased with water availability. However, the hydraulic conductance decreased, resulting in a better withdrawal of water in water-stressed plants. The anatomical investigation of the hygrochastic mechanism revealed an asymmetric distribution of the cortical tissues, with the conducting tissues of the stem of juvenile and adult plants being larger in the lower side. The hydraulic conductance was better in the basal and middle branch-orders than the terminal ones, permitting better conductance of water to the subsequent branch-orders. CONCLUSIONS: The lignified conducting tissue of the whole stem, having a hygrochastic nature, controls the movement of the branches. The greater amount of conducting tissue associated with a higher density of wide xylem vessels was observed in the lower side of the stem as compared with the upper side. Consequently, the conducting tissue in the lower side of the stem was suggested to be more effective in the opening process of the curled dry branches through better and more rapid conductance of water. Alternatively, due to the few narrow xylem vessels in the upper side of the stem, it was likely that the conducting tissue in the upper side is more effective in the closing process by providing more rapid drying. The mechanical rise of water and the related hygrochastic efficiency were maximized in the basal and middle branch-orders that are mostly involved in the mechanical movement. 相似文献
79.
Haridy MS Hegazy ME Mohamed Ael-H Paré PW Hirata T 《Zeitschrift für Naturforschung. C, Journal of biosciences》2010,65(9-10):599-602
Cell suspensions of Marchantia polymorpha hydrogenate progesterone to 5alpha-pregnane-3,20-dione. Structure elucidation of the product was achieved by comprehensive NMR analyses. 相似文献
80.
Protein phosphatase 2A (PP2A) is a heterotrimeric complex comprising a catalytic, scaffolding, and regulatory subunit. The regulatory subunits are essential for substrate specificity and localization of the complex and are classified into B/B55, B'', and B” non-related families in higher plants. In Arabidopsis thaliana, the close paralogs B''η, B''θ, B''γ, and B''ζ were further classified into a subfamily of B'' called B''η. Here we present results that consolidate the evidence for a role of the B''η subfamily in regulation of innate immunity, energy metabolism and flowering time. Proliferation of the virulent Pseudomonas syringae in B''θ knockout mutant decreased in comparison with wild type plants. Additionally, B''θ knockout plants were delayed in flowering, and this phenotype was supported by high expression of FLC (FLOWERING LOCUS C). B''ζ knockout seedlings showed growth retardation on sucrose-free medium, indicating a role for B''ζ in energy metabolism. This work provides insight into functions of the B''η subfamily members, highlighting their regulation of shared physiological traits while localizing to distinct cellular compartments. 相似文献