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11.
Background
Apoptosis is an essential cell death process throughout the entire life span of all metazoans and its deregulation in humans has been implicated in many proliferative and degenerative diseases. Mitochondrial outer membrane permeabilisation (MOMP) and activation of effector caspases are key processes during apoptosis signalling. MOMP can be subject to spatial coordination in human cancer cells, resulting in intracellular waves of cytochrome-c release. To investigate the consequences of these spatial anisotropies in mitochondrial permeabilisation on subsequent effector caspase activation, we devised a mathematical reaction-diffusion model building on a set of partial differential equations. 相似文献12.
Anjali Prabhu Qin Xu Michaele B. Manigrasso Moumita Biswas Elizabeth Flynn Radu Iliescu Edwin D. Lephart Christine Maric 《Steroids》2010,75(11):779-787
Our previous studies have shown that diabetes in the male streptozotocin (STZ)-induced diabetic rat is characterized by a decrease in circulating testosterone and concomitant increase in estradiol levels. Interestingly, this increase in estradiol levels persists even after castration, suggesting extra-testicular origins of estradiol in diabetes. The aim of the present study was to examine whether other target organs of diabetes may be sources of estradiol. The study was performed in male Sprague–Dawley non-diabetic (ND), STZ-induced diabetic (D) and STZ-induced diabetic castrated (Dcas) rats (n = 8–9/group). 14 weeks of diabetes was associated with decreased testicular (ND, 26.3 ± 4.19; D, 18.4 ± 1.54; P < 0.05), but increased renal (ND, 1.83 ± 0.92; D, 7.85 ± 1.38; P < 0.05) and ocular (D, 23.4 ± 3.66; D, 87.1 ± 28.1; P < 0.05) aromatase activity. This increase in renal (Dcas, 6.30 ± 1.25) and ocular (Dcas, 62.7 ± 11.9) aromatase activity persisted after castration. The diabetic kidney also had increased levels of tissue estrogen (ND, 0.31 ± 0.01; D, 0.51 ± 0.11; Dcas, 0.45 ± 0.08) as well as estrogen receptor alpha protein expression (ND, 0.63 ± 0.09; D, 1.62 ± 0.28; Dcas, 1.38 ± 0.20). These data suggest that in male STZ-induced diabetic rats, tissues other than the testis may become sources of estradiol. In particular, the diabetic kidney appears to produce estradiol following castration, a state that is associated with a high degree or renal injury. Overall, our data provides evidence for the extra-testicular source of estradiol that in males, through an intracrine mechanism, may contribute to the development and/or progression of end-organ damage associated with diabetes. 相似文献
13.
Jessica AB van Nies Rute B Marques Stella Trompet Zuzana de Jong Fina AS Kurreeman Rene EM Toes J Wouter Jukema Tom WJ Huizinga Annette HM van der Helm-van Mil 《Arthritis research & therapy》2010,12(2):R38
Introduction
Recently an association between a genetic variation in TRAF1/C5 and mortality from sepsis or cancer was found in rheumatoid arthritis (RA). The most prevalent cause of death, cardiovascular disease, may have been missed in that study, since patients were enrolled at an advanced disease stage. Therefore, we used an inception cohort of RA patients to investigate the association between TRAF1/C5 and cardiovascular mortality, and replicate the findings on all-cause mortality. As TRAF1/C5 associated mortality may not be restricted to RA, we also studied a large cohort of non-RA patients. 相似文献14.
Sylvia Kamphuis Kolbrún Hrafnkelsdóttir Mark R Klein Wilco de Jager Margje H Haverkamp Jolanda HM van Bilsen Salvatore Albani Wietse Kuis Marca HM Wauben Berent J Prakken 《Arthritis research & therapy》2007,8(6):R178
Juvenile idiopathic arthritis (JIA) is a heterogeneous autoimmune disease characterized by chronic joint inflammation. Knowing
which antigens drive the autoreactive T-cell response in JIA is crucial for the understanding of disease pathogenesis and
additionally may provide targets for antigen-specific immune therapy. In this study, we tested 9 self-peptides derived from
joint-related autoantigens for T-cell recognition (T-cell proliferative responses and cytokine production) in 36 JIA patients
and 15 healthy controls. Positive T-cell proliferative responses (stimulation index ≥2) to one or more peptides were detected
in peripheral blood mononuclear cells (PBMC) of 69% of JIA patients irrespective of major histocompatibility complex (MHC)
genotype. The peptides derived from aggrecan, fibrillin, and matrix metalloproteinase (MMP)-3 yielded the highest frequency
of T-cell proliferative responses in JIA patients. In both the oligoarticular and polyarticular subtypes of JIA, the aggrecan
peptide induced T-cell proliferative responses that were inversely related with disease duration. The fibrillin peptide, to
our knowledge, is the first identified autoantigen that is primarily recognized in polyarticular JIA patients. Finally, the
epitope derived from MMP-3 elicited immune responses in both subtypes of JIA and in healthy controls. Cytokine production
in short-term peptide-specific T-cell lines revealed production of interferon-γ (aggrecan/MMP-3) and interleukin (IL)-17 (aggrecan)
and inhibition of IL-10 production (aggrecan). Here, we have identified a triplet of self-epitopes, each with distinct patterns
of T-cell recognition in JIA patients. Additional experiments need to be performed to explore their qualities and role in
disease pathogenesis in further detail. 相似文献
15.
Wuchty S Arjona D Li A Kotliarov Y Walling J Ahn S Zhang A Maric D Anolik R Zenklusen JC Fine HA 《PloS one》2011,6(2):e14681
Despite progress in the determination of miR interactions, their regulatory role in cancer is only beginning to be unraveled. Utilizing gene expression data from 27 glioblastoma samples we found that the mere knowledge of physical interactions between specific mRNAs and miRs can be used to determine associated regulatory interactions, allowing us to identify 626 associated interactions, involving 128 miRs that putatively modulate the expression of 246 mRNAs. Experimentally determining the expression of miRs, we found an over-representation of over(under)-expressed miRs with various predicted mRNA target sequences. Such significantly associated miRs that putatively bind over-expressed genes strongly tend to have binding sites nearby the 3'UTR of the corresponding mRNAs, suggesting that the presence of the miRs near the translation stop site may be a factor in their regulatory ability. Our analysis predicted a significant association between miR-128 and the protein kinase WEE1, which we subsequently validated experimentally by showing that the over-expression of the naturally under-expressed miR-128 in glioma cells resulted in the inhibition of WEE1 in glioblastoma cells. 相似文献
16.
Nexø BA Christensen T Frederiksen J Møller-Larsen A Oturai AB Villesen P Hansen B Nissen KK Laska MJ Petersen TS Bonnesen S Hedemand A Wu T Wang X Zhang X Brudek T Maric R Søndergaard HB Sellebjerg F Brusgaard K Kjeldbjerg AL Rasmussen HB Nielsen AL Nyegaard M Petersen T Børglum AD Pedersen FS 《PloS one》2011,6(2):e16652
We have investigated the role of human endogenous retroviruses in multiple sclerosis by analyzing the DNA of patients and controls in 4 cohorts for associations between multiple sclerosis and polymorphisms near viral restriction genes or near endogenous retroviral loci with one or more intact or almost-intact genes. We found that SNPs in the gene TRIM5 were inversely correlated with disease. Conversely, SNPs around one retroviral locus, HERV-Fc1, showed a highly significant association with disease. The latter association was limited to a narrow region that contains no other known genes. We conclude that HERV-Fc1 and TRIM5 play a role in the etiology of multiple sclerosis. If these results are confirmed, they point to new modes of treatment for multiple sclerosis. 相似文献
17.
The growth of surplus brewers' yeast in a fed-batch process was studied with the aim of increasing the fermentation activity of the yeast cells and of optimizing the growth conditions: 20 h cultivation at 30° C and pH 5.0–5.5 using beet molasses as substrate, with a regulated feeding rate, showed satisfactory results. Under the chosen conditions, the final amount of biomass increased more than fivefold, achieving a specific growth rate of 0.1 h–1 and substrate yield coefficient of 0.54 g·g–1. The increase in fermentation activity of yeast cells during cultivation correlated very well with the concentration of reduced glutathione, which increased from 1.2 to 2.7 mg·g–1 (dry matter). At the same time the fermentation activity increased fivefold, which related to the nitrogen content of the yeast cells. Ethanol formation throughout the cultivation did not exceed 0.5 g·l–1.
Correspondence to: B. Strel 相似文献
18.
Le Loir Y Azevedo V Oliveira SC Freitas DA Miyoshi A Bermúdez-Humarán LG Nouaille S Ribeiro LA Leclercq S Gabriel JE Guimaraes VD Oliveira MN Charlier C Gautier M Langella P 《Microbial cell factories》2005,4(1):2-13
Lactococcus lactis, the model lactic acid bacterium (LAB), is a food grade and well-characterized Gram positive bacterium. It is a good candidate for heterologous protein delivery in foodstuff or in the digestive tract. L. lactis can also be used as a protein producer in fermentor. Many heterologous proteins have already been produced in L. lactis but only few reports allow comparing production yields for a given protein either produced intracellularly or secreted in the medium. Here, we review several works evaluating the influence of the localization on the production yields of several heterologous proteins produced in L. lactis. The questions of size limits, conformation, and proteolysis are addressed and discussed with regard to protein yields. These data show that i) secretion is preferable to cytoplasmic production; ii) secretion enhancement (by signal peptide and propeptide optimization) results in increased production yield; iii) protein conformation rather than protein size can impair secretion and thus alter production yields; and iv) fusion of a stable protein can stabilize labile proteins. The role of intracellular proteolysis on heterologous cytoplasmic proteins and precursors is discussed. The new challenges now are the development of food grade systems and the identification and optimization of host factors affecting heterologous protein production not only in L. lactis, but also in other LAB species. 相似文献
19.
20.
Suzanne V Frankfort Valerie D Doodeman Remco Bakker Linda R Tulner Jos PCM van Campen Paul HM Smits Jos H Beijnen 《Molecular neurodegeneration》2006,1(1):1-5
Amyloid β is an in vitro substrate for P-glycoprotein (P-gp), an efflux pump at the blood brain barrier (BBB). The Multi Drug Resistance (ABCB1) gene, encoding for P-gp, is highly polymorphic and this may result in a changed function of P-gp and may possibly interfere with the pathogenesis of Alzheimer's disease. This study investigates to what extent ABCB1 Single Nucleotide Polymorphisms (SNPs; C1236T in exon 12, G2677T/A in exon 21 and C3435T in exon 26) and inferred haplotypes exist in an elderly population and if these SNPs and haplotypes differ between patients with dementia and age-matched non-demented control patients. ABCB1 genotype, allele and haplotype frequencies were neither significantly different between patients with dementia and age-matched controls, nor between subgroups of different types of dementia nor age-matched controls. This study shows ABCB1 genotype frequencies to be comparable with described younger populations. To our knowledge this is the first study on ABCB1 genotypes in dementia. ABCB1 genotypes are presently not useful as a biomarker for dementia, as they were not significantly different between demented patients and age-matched control subjects. 相似文献