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61.
Lee CY Kam YW Fric J Malleret B Koh EG Prakash C Huang W Lee WW Lin C Lin RT Renia L Wang CI Ng LF Warter L 《PLoS pathogens》2011,7(12):e1002390
Chikungunya virus (CHIKV) is an alphavirus responsible for numerous epidemics throughout Africa and Asia, causing infectious arthritis and reportedly linked with fatal infections in newborns and elderly. Previous studies in animal models indicate that humoral immunity can protect against CHIKV infection, but despite the potential efficacy of B-cell-driven intervention strategies, there are no virus-specific vaccines or therapies currently available. In addition, CHIKV has been reported to elicit long-lasting virus-specific IgM in humans, and to establish long-term persistence in non-human primates, suggesting that the virus might evade immune defenses to establish chronic infections in man. However, the mechanisms of immune evasion potentially employed by CHIKV remain uncharacterized. We previously described two human monoclonal antibodies that potently neutralize CHIKV infection. In the current report, we have characterized CHIKV mutants that escape antibody-dependent neutralization to identify the CHIKV E2 domain B and fusion loop "groove" as the primary determinants of CHIKV interaction with these antibodies. Furthermore, for the first time, we have also demonstrated direct CHIKV cell-to-cell transmission, as a mechanism that involves the E2 domain A and that is associated with viral resistance to antibody-dependent neutralization. Identification of CHIKV sub-domains that are associated with human protective immunity, will pave the way for the development of CHIKV-specific sub-domain vaccination strategies. Moreover, the clear demonstration of CHIKV cell-to-cell transmission and its possible role in the establishment of CHIKV persistence, will also inform the development of future anti-viral interventions. These data shed new light on CHIKV-host interactions that will help to combat human CHIKV infection and inform future studies of CHIKV pathogenesis. 相似文献
62.
Induction of antitumor immunity by indomethacin 总被引:4,自引:0,他引:4
Morecki S Yacovlev E Gelfand Y Trembovler V Shohami E Slavin S 《Cancer immunology, immunotherapy : CII》2000,48(11):613-620
Irradiated tumor cells given, together with indomethacin, to syngeneic mice induced an antitumor response and conferred protection
against a challenge of a lethal dose of murine mammary (4T1) and lung (3LL) carcinoma cells. Continuous administration of
indomethacin was crucial throughout the entire period of immunization and challenge, as no protection was achieved when the
drug was given during only one of these procedures. Antitumor immunity was long-lasting and, when tested in the 4T1 model,
48% of mice were resistant to a second challenge of lethal tumor cells. Tumor-free immune mice that were given indomethacin
for more than 300 days remained healthy with normal white blood cell counts and normal spleen size. Cells isolated from immune
mice were able to kill tumor cells in culture after in vitro activation by interleukin-2, in a manner similar to cells from
naive normal control mice. In addition, the mitogenic response of their T cells was as high as that of the control naive mice.
While indomethacin was able to induce antitumor immunity to 4T1 and 3LL murine carcinoma cells, both of which contain a high
concentration of endogenic prostaglandin E2 (PGE2), no such immunity was achieved to murine tumor cells with a low concentration of endogenic PGE2. These results suggest
a correlation between PGE2 concentration and the ability of indomethacin to induce antitumor immunity. We therefore suggest
that an immunotherapy protocol with long-term dispensation of a tolerable dose of an immunomodulator, given together with
irradiated autologous tumor cells, may stimulate antitumor responses to tumors containing high concentrations of endogenic
PGE2.
Received: 12 August 1999 / Accepted: 21 September 1999 相似文献
63.
Marcel Dreischarf Laia Albiol Antonius Rohlmann Esther Pries Maxim Bashkuev Thomas Zander Georg Duda Claudia Druschel Patrick Strube Michael Putzier Hendrik Schmidt 《PloS one》2014,9(12)
Background
The understanding of the individual shape and mobility of the lumbar spine are key factors for the prevention and treatment of low back pain. The influence of age and sex on the total lumbar lordosis and the range of motion as well as on different lumbar sub-regions (lower, middle and upper lordosis) in asymptomatic subjects still merits discussion, since it is essential for patient-specific treatment and evidence-based distinction between painful degenerative pathologies and asymptomatic aging.Methods and Findings
A novel non-invasive measuring system was used to assess the total and local lumbar shape and its mobility of 323 asymptomatic volunteers (age: 20–75 yrs; BMI <26.0 kg/m2; males/females: 139/184). The lumbar lordosis for standing and the range of motion for maximal upper body flexion (RoF) and extension (RoE) were determined. The total lordosis was significantly reduced by approximately 20%, the RoF by 12% and the RoE by 31% in the oldest (>50 yrs) compared to the youngest age cohort (20–29 yrs). Locally, these decreases mostly occurred in the middle part of the lordosis and less towards the lumbo-sacral and thoraco-lumbar transitions. The sex only affected the RoE.Conclusions
During aging, the lower lumbar spine retains its lordosis and mobility, whereas the middle part flattens and becomes less mobile. These findings lay the ground for a better understanding of the incidence of level- and age-dependent spinal disorders, and may have important implications for the clinical long-term success of different surgical interventions. 相似文献64.
Richardson RT Alekseev OM Grossman G Widgren EE Thresher R Wagner EJ Sullivan KD Marzluff WF O'Rand MG 《The Journal of biological chemistry》2006,281(30):21526-21534
A multichaperone nucleosome-remodeling complex that contains the H1 linker histone chaperone nuclear autoantigenic sperm protein (NASP) has recently been described. Linker histones (H1) are required for the proper completion of normal development, and NASP transports H1 histones into nuclei and exchanges H1 histones with DNA. Consequently, we investigated whether NASP is required for normal cell cycle progression and development. We now report that without sufficient NASP, HeLa cells and U2OS cells are unable to replicate their DNA and progress through the cell cycle and that the NASP(-/-) null mutation causes embryonic lethality. Although the null mutation NASP(-/-) caused embryonic lethality, null embryos survive until the blastocyst stage, which may be explained by the presence of stored NASP protein in the cytoplasm of oocytes. We conclude from this study that NASP and therefore the linker histones are key players in the assembly of chromatin after DNA replication. 相似文献
65.
Rendal Vázquez ME Rodríguez Cabarcos M Martinez Santos MV Fernández Mallo RO Sánchez Ibáñez J Segura Iglesias R Matheu Capó G Filgueira Fernández P Pértega Díaz S Bermúdez González T Andión Núñez C 《Cell and tissue banking》2004,5(2):111-118
Several in vitro studies have demonstrated diminished post-thaw functional activity. Therefore, the aim of this study was to investigate the consequences of thawing and storage method used on the post-thaw functional activity of cryopreserved pig aortas with the aim of adjusting the freezing and thawing protocol so that the vascular segments are preserved in the best possible state, maintaining structure and functionality so that they can later be transplanted with success. In vitro responses of frozen, thawed pig aortas were used to investigate the functional activity after thawing at 15 degrees C and 100 degrees C/min and after storage in gas or liquid phase of liquid nitrogen. Cryopreservation was performed in RPMI 1640 medium + 10% dimethylsulfoxide and the rate of cooling was -1 degrees C/min, until -150 degrees C was reached.After thawing the maximal contractile responses to all the contracting agonists tested (KCl, noradrenaline) were in the ranges of 13-27% compared with the responses in unfrozen pig aortas. Contractile responses were slightly better when thawing was performed at 15 degrees C/min compared with 100 degrees C/min. The endothelium independent relaxant responses to sodium nitroprusside were reduced ( P < 0.05). Cryostorage of pig arteries also resulted in a loss of the endothelium-dependent relaxant response to acetylcholine. The cryopreservation method used provided a limited preservation of pig aorta contractibility, a reduction of the endothelium independent relaxant responses, and no apparent preservation of the endothelium-dependent relaxation. It is possible that further refinements of the cryopreservation protocol might allow better post-thaw functional recovery of pig aortas. 相似文献
66.
Pura Díaz-Veiga Mayte Sancho Álvaro García Esther Rivas Elixabet Abad Nerea Suárez Gabriela Mondragón Cristina Buiza Ana Orbegozo Javier Yanguas 《Revista espa?ola de geriatría y gerontología》2014
Introduction
The Model of Person Centered Care has attracted increasing interest for use in gerontology centers. Therefore, the contributions about its impact are scarce in our context. The objective of this paper is to establish the impact that the interventions associated with the Model of Person Centered Care in the «Etxean Ondo» Project have on the quality of life of residents with cognitive impairment.Material and methods
One hundred and ninetten residents with cognitive impairment were selected: 59 in the control group and 60 in the experimental group. Subjects in each group were sorted by cognitive impairment: mild or severe. Changes were implemented in the physical and organizational environments for the promotion of autonomy and wellbeing. Quality of life was assessed before and 6 months after intervention using the Fumat Scales (mild cognitive impairment) and Qualid (severe cognitive impairment). The t-Student test was used for comparison of means.Results
In intergroup comparisons, significant differences in the Fumat Scale for the control group with mild cognitive impairment were initially identified. These differences were not recorded in the post assessment. The experimental group with severe cognitive impairment was significantly improved in the Qualid Scale post assessment. In intragroup comparisons, significant improvements were evident in the quality of life of experimental subjects, both with severe cognitive impairment (Qualid) and mild (Fumat).Conclusions
The findings support the effectiveness of the interventions and identify methodological and conceptual issues that have been considered to analyze the Model of Person Centered Care efects. 相似文献67.
The AtRbx1 protein is part of plant SCF complexes,and its down-regulation causes severe growth and developmental defects 总被引:8,自引:0,他引:8
Lechner E Xie D Grava S Pigaglio E Planchais S Murray JA Parmentier Y Mutterer J Dubreucq B Shen WH Genschik P 《The Journal of biological chemistry》2002,277(51):50069-50080
Recently in yeast and animal cells, one particular class of ubiquitin ligase (E3), called the SCF, was demonstrated to regulate diverse processes including cell cycle and development. In plants SCF-dependent proteolysis is also involved in different developmental and hormonal regulations. To further investigate the function of SCF, we characterized at the molecular level the Arabidopsis RING-H2 finger protein AtRbx1. We demonstrated that the plant gene is able to functionally complement a yeast knockout mutant strain and showed that AtRbx1 protein interacts physically with at least two members of the Arabidopsis cullin family (AtCul1 and AtCul4). AtRbx1 also associates with AtCul1 and the Arabidopsis SKP1-related proteins in planta, indicating that it is part of plant SCF complexes. AtRbx1 mRNAs accumulate in various tissues of the plant, but at higher levels in tissues containing actively dividing cells. Finally to study the function of the gene in planta, we either overexpressed AtRbx1 or reduced its expression by a dsRNA strategy. Down-regulation of AtRbx1 impaired seedling growth and development, indicating that the gene is essential in plants. Furthermore, the AtRbx1-silenced plants showed a reduced level of AtCul1 protein, but accumulated higher level of cyclin D3. 相似文献
68.
69.
Rajendra Prasad Jason G. Williams Esther W. Hou Samuel H. Wilson 《Nucleic acids research》2012,40(22):11571-11582
During mammalian base excision repair (BER) of lesion-containing DNA, it is proposed that toxic strand-break intermediates generated throughout the pathway are sequestered and passed from one step to the next until repair is complete. This stepwise process is termed substrate channeling. A working model evaluated here is that a complex of BER factors may facilitate the BER process. FLAG-tagged DNA polymerase (pol) β was expressed in mouse fibroblasts carrying a deletion in the endogenous pol β gene, and the cell extract was subjected to an ‘affinity-capture’ procedure using anti-FLAG antibody. The pol β affinity-capture fraction (ACF) was found to contain several BER factors including polymerase-1, X-ray cross-complementing factor1-DNA ligase III and enzymes involved in processing 3′-blocked ends of BER intermediates, e.g. polynucleotide kinase and tyrosyl-DNA phosphodiesterase 1. In contrast, DNA glycosylases, apurinic/aprymidinic endonuclease 1 and flap endonuclease 1 and several other factors involved in BER were not present. Some of the BER factors in the pol β ACF were in a multi-protein complex as observed by sucrose gradient centrifugation. The pol β ACF was capable of substrate channeling for steps in vitro BER and was proficient in in vitro repair of substrates mimicking a 3′-blocked topoisomerase I covalent intermediate or an oxidative stress-induced 3′-blocked intermediate. 相似文献
70.
Ramírez-Lázaro MJ Lario S Casalots A Sanfeliu E Boix L García-Iglesias P Sánchez-Delgado J Montserrat A Bella-Cueto MR Gallach M Sanfeliu I Segura F Calvet X 《PloS one》2011,6(5):e20009