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71.
Cervantes-Barragán L Firner S Bechmann I Waisman A Lahl K Sparwasser T Thiel V Ludewig B 《Journal of immunology (Baltimore, Md. : 1950)》2012,188(8):3678-3685
Regulatory T cells (Tregs) are important for the attenuation of immune reactions. During viral CNS infections, however, an indiscriminate maintenance of CNS immune privilege through Treg-mediated negative regulation could prevent autoimmune sequelae but impair the control of viral replication. We analyzed in this study the impact of Tregs on the development of acute viral encephalomyelitis, T cell-mediated antiviral protection, and prevention of CNS autoimmunity following intranasal infection with the gliatropic mouse hepatitis virus strain A59. To assess the contribution of Tregs in vivo, we specifically depleted CD4(+)Foxp3(+) T cells in a diphtheria toxin-dependent manner. We found that depletion of Tregs had no impact on viral distribution and clearance and did not significantly alter virus-specific CD4(+) and CD8(+) T cell responses. However, Treg depletion led to a more severe CNS inflammation associated with neuronal damage. Dissection of the underlying immunopathological mechanisms revealed the elaborate Treg-dependent regulation of self-reactive CD4(+) T cell proliferation within the CNS-draining lymph node and downtuning of CXCR3 expression on T cells. Taken together, these results suggest that Tregs preserve CNS immune privilege through selective control of CNS-specific Th cells while keeping protective antiviral immunity fully operative. 相似文献
72.
Tiberio L Tiberio GA Bardella L Cervi E Cerea K Dreano M Garotta G Fra A Montani N Ferrari-Bravo A Callea F Grigolato P Giulini SM Schiaffonati L 《Cytokine》2006,34(3-4):131-142
Numerous animal studies simulating liver injury have demonstrated that interleukin-6 (IL-6) exerts a protective effect. This study was designed to further analyze the molecular mechanisms underlying the protective role of IL-6 in a rat model of liver ischemia/reperfusion injury. We show that IL-6: (i) at high doses reduces cell damage which occurs in ischemic-reperfused liver, while at low doses displays only a limited protective capacity, (ii) anticipates and enhances hepatocyte compensatory proliferation seen in ischemic-reperfused liver also at a low, more pharmacologically acceptable dose, (iii) sustains the acute phase response which is dampened in ischemic-reperfused liver, (iv) strengthens the heat shock-stress response shown by ischemic-reperfused liver and (v) overcomes the dysfunctions of the unfolding protein response found in ischemic-reperfused liver. We also show that IL-6-enhanced STAT3 activation probably plays a crucial role in the potentiation of the different protective pathways activated in ischemic-reperfused liver. Our data confirm that IL-6 is a potential therapeutic in liver injury of different etiologies and reveal novel mechanisms by which IL-6 sustains liver function after ischemia/reperfusion injury. 相似文献
73.
Luisa S. Serafim Paulo C. Lemos Maria G. E. Albuquerque Maria A. M. Reis 《Applied microbiology and biotechnology》2008,81(4):615-628
Production of polyhydroxyalkanoates (PHA) by mixed cultures has been widely studied in the last decade. Storage of PHA by
mixed microbial cultures occurs under transient conditions of carbon or oxygen availability, known respectively as aerobic
dynamic feeding and anaerobic/aerobic process. In these processes, PHA-accumulating organisms, which are quite diverse in
terms of phenotype, are selected by the dynamic operating conditions imposed to the reactor. The stability of these processes
during long-time operation and the similarity of the polymer physical/chemical properties to the one produced by pure cultures
were demonstrated. This process could be implemented at industrial scale, providing that some technological aspects are solved.
This review summarizes the relevant research carried out with mixed cultures for PHA production, with main focus on the use
of wastes or industrial surplus as feedstocks. Basic concepts, regarding the metabolism and microbiology, and technological
approaches, with emphasis on the kind of feedstock and reactor operating conditions for culture selection and PHA accumulation,
are described. Challenges for the process optimization are also discussed. 相似文献
74.
Corona-Rivera A Urbina-Cano P Bobadilla-Morales L Vargas-Lares Jde J Ramirez-Herrera MA Mendoza-Magaua ML Troyo-Sanroman R Diaz-Esquivel P Corona-Rivera JR 《Journal of applied genetics》2007,48(4):389-396
Curcumin is a phytochemical with antiinflammatory, antioxidant and anticarcinogenic activities. Apparently, curcumin is not genotoxic in vivo, but in vitro copper and curcumin interactions induce genetic damage. The aim of this study was to test if in vivo copper excess induces DNA damage measured by comet and micronucleus assays in the presence of curcumin. We tested 0.2% curcumin in Balb-C mice at normal (13 ppm) and high (65, 130 and 390 ppm) copper ion concentrations. The comet and micronucleus assays were performed 48 hr after chemical application. Comet tail length in animals treated with 0.2% curcumin was not significantly different from the control. Animals exposed to copper cations (up to 390 ppm) exhibited higher oxidative DNA damage. Curcumin reduced the DNA damage induced by 390 ppm copper. We observed statistically significant increase in damage in individuals exposed to 390 ppm copper versus the control or curcumin groups, which was lowered by the presence of curcumin. Qualitative data on comets evidenced that cells from individuals exposed to 390 ppm copper had longer tails (categories 3 and 4) than in 390 ppm copper + curcumin. A statistically significant increase in frequency of micronucleated erythrocytes (MNE/10000TE) was observed only in 390 ppm copper versus the control and curcumin alone. Also cytotoxicity measured as the frequency of polychromatic erythrocytes (PE/1000TE) was attributable to 390 ppm copper. The lowest cytotoxic effect observed was attributed to curcumin. In vivo exposure to 0.2% curcumin for 48 hr did not cause genomic damage, while 390 ppm copper was genotoxic, but DNA damage induced by 390 ppm copper was diminished by curcumin. Curcumin seems to exert a genoprotective effect against DNA damage induced by high concentrations of copper cations. The comet and micronucleus assays prove to be suitable tools to detect DNA damage by copper in the presence of curcumin. 相似文献
75.
Murciano C Villamón E Yáñez A Murciano J Mir A O'Connor JE Gozalbo D Gil ML 《FEMS immunology and medical microbiology》2007,51(2):327-335
Invasive infections with opportunistic fungi, such as Candida albicans, have become an increasing problem in aged adults in recent years. This work investigates the influence of human ageing on C. albicans recognition by toll-like receptors (TLRs), essential components of the innate immune system, using a cohort of 96 young (15-42 years) and aged (>70 years) human volunteers. No significant differences between aged and young donors were observed on (1) cell surface TLR2, TLR6 and TLR4 expression on lymphocytes, monocytes and granulocytes, (2) production of cytokines [IL-8, IL-1beta, IL-6, IL-10, tumour necrosis factor (TNF)-alpha and IL-12p70] and prostaglandin E(2) (PGE(2)) by whole human blood in response to C. albicans and (3) fungicidal activity of whole blood. A statistically significant higher titre of natural anti-C. albicans antibodies was found in plasma of volunteers between 80 and 95 years old when compared with other age groups, probably as a consequence of the increased levels of serum Ig that has been described in elderly subjects. Therefore, the results indicate that the increased susceptibility to C. albicans infections in the elderly is not a consequence of defects in TLRs expression or signalling, nor of an impaired fungicidal activity of blood. 相似文献
76.
The TRIM (tripartite motif) family of proteins is characterized by the presence of the tripartite motif module, composed of a RING domain, one or two B-box domains and a coiled-coil region. TRIM proteins are involved in many cellular processes and represent the largest subfamily of RING-containing putative ubiquitin E3 ligases. Whereas their role as E3 ubiquitin ligases has been presumed, and in several cases established, little is known about their specific interactions with the ubiquitin-conjugating E2 enzymes or UBE2s. In the present paper, we report a thorough screening of interactions between the TRIM and UBE2 families. We found a general preference of the TRIM proteins for the D and E classes of UBE2 enzymes, but we also revealed very specific interactions between TRIM9 and UBE2G2, and TRIM32 and UBE2V1/2. Furthermore, we demonstrated that the TRIM E3 activity is only manifest with the UBE2 with which they interact. For most specific interactions, we could also observe subcellular co-localization of the TRIM involved and its cognate UBE2 enzyme, suggesting that the specific selection of TRIM-UBE2 pairs has physiological relevance. Our findings represent the basis for future studies on the specific reactions catalysed by the TRIM E3 ligases to determine the fate of their targets. 相似文献
77.
Domínguez-Escobar J Beltrán Y Bergman B Díez B Ininbergs K Souza V Falcón LI 《FEMS microbiology letters》2011,316(2):90-99
Heterocyst-forming cyanobacteria are important players at both evolutionary and ecological scales, but to date it has been difficult to establish their phylogenetic affiliations. We present data from a phylogenetic and molecular clock analysis of heterocystous cyanobacteria within the family Rivulariaceae, including the genera Calothrix, Rivularia, Gloeotrichia and Tolypothrix. The strains were isolated from distant geographic regions including fresh and brackish water bodies, microbial mats from beach rock, microbialites, pebble beaches, plus PCC strains 7103 and 7504. Phylogenetic inferences (distance, likelihood and Bayesian) suggested the monophyly of genera Calothrix and Rivularia. Molecular clock estimates indicate that Calothrix and Rivularia originated ~1500 million years ago (MYA) ago and species date back to 400-300 MYA while Tolypothrix and Gloeotrichia are younger genera (600-400 MYA). 相似文献
78.
79.
Behar DM Metspalu E Kivisild T Achilli A Hadid Y Tzur S Pereira L Amorim A Quintana-Murci L Majamaa K Herrnstadt C Howell N Balanovsky O Kutuev I Pshenichnov A Gurwitz D Bonne-Tamir B Torroni A Villems R Skorecki K 《American journal of human genetics》2006,78(3):487-497
Both the extent and location of the maternal ancestral deme from which the Ashkenazi Jewry arose remain obscure. Here, using complete sequences of the maternally inherited mitochondrial DNA (mtDNA), we show that close to one-half of Ashkenazi Jews, estimated at 8,000,000 people, can be traced back to only 4 women carrying distinct mtDNAs that are virtually absent in other populations, with the important exception of low frequencies among non-Ashkenazi Jews. We conclude that four founding mtDNAs, likely of Near Eastern ancestry, underwent major expansion(s) in Europe within the past millennium. 相似文献
80.
Gabriella Tamasi Agnese Magnani Luisa Chiasserini Chiara Gabbiani Michael A. Jakupec Michael B. Hursthouse 《Journal of inorganic biochemistry》2010,104(8):799-313
The reaction of aqueous cis-[Pt(NH3)2(H2O)2](NO3)2 with Na+HMEL− (H2MEL, meloxicam, 4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide), and Na+HISO− (H2ISO, isoxicam, 4-hydroxy-2-methyl-N-(5-methylisoxazol-3-yl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide) at pH 7 produced micro-crystalline cis-[Pt(NH3)2(N1′-HMEL)2], 5 and cis-[Pt(NH3)2(N1′-HISO)2], 6. The X-ray diffraction structure of 5 shows two HMEL− anions donating through the thiazole nitrogen atoms and adopting a head-to-tail (HT) conformation. The 1H NMR spectrum for 5 from DMSO-d6 shows inertness of the complex up to at least 24 h. Delivery studies for 5 and 6 from vinyl hydrogel based on l-phenylalanine (pH 6.5, 25 °C) show that concentrations of complexes ranging between 2.5 and 5 μM can be reached after a day. Compounds 5 and 6 show strong anti-proliferative effects on CH1 cells (ovarian carcinoma, human) in vitro, IC50 values being 0.60 and 0.37 μM, respectively (0.16 μM for reference, cis-diamminodichloridoplatinum(II), cisplatin). ESI-MS measurements clearly documented that both 5 and 6 form adducts with the three model proteins ubiquitin (UBI), cytochrome c (CYT C) and superoxide dismutase (SOD), the HISO− complex being significantly more effective than the HMEL− one. Density functional methods help in finding rationale for the easiest dissociation of Pt-H2ISO/HISO bonds when compared to the Pt-N1′-H2MEL/N1′-HMEL linkages. 相似文献