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91.
Endoplasmic reticulum (ER) stress is increasingly recognized as an important mechanism in a wide range of diseases including
cystic fibrosis, alpha-1 antitrypsin deficiency, Parkinson's and Alzheimer's disease. Therefore, there is an increased need
for reliable and quantitative markers for detection of ER stress in human tissues and cells. Accumulation of unfolded or misfolded
proteins in the endoplasmic reticulum can cause ER stress, which leads to the activation of the unfolded protein response
(UPR). UPR signaling involves splicing of X-box binding protein-1 (XBP1) mRNA, which is frequently used as a marker for ER
stress. In most studies, the splicing of the XBP1 mRNA is visualized by gel electrophoresis which is laborious and difficult
to quantify. In the present study, we have developed and validated a quantitative real-time RT-PCR method to detect the spliced
form of XBP1 mRNA. 相似文献
92.
Rebecca J Garlock Shishir PS Chundawat Venkatesh Balan Bruce E Dale 《Biotechnology for biofuels》2009,2(1):29-14
Background
Corn stover composition changes considerably throughout the growing season and also varies between the various fractions of the plant. These differences can impact optimal pretreatment conditions, enzymatic digestibility and maximum achievable sugar yields in the process of converting lignocellulosics to ethanol. The goal of this project was to determine which combination of corn stover fractions provides the most benefit to the biorefinery in terms of sugar yields and to determine the preferential order in which fractions should be harvested. Ammonia fiber expansion (AFEX) pretreatment, followed by enzymatic hydrolysis, was performed on early and late harvest corn stover fractions (stem, leaf, husk and cob). Sugar yields were used to optimize scenarios for the selective harvest of corn stover assuming 70% or 30% collection of the total available stover. 相似文献93.
Nell MJ Tjabringa GS Wafelman AR Verrijk R Hiemstra PS Drijfhout JW Grote JJ 《Peptides》2006,27(4):649-660
New peptides for lipopolysaccharide (LPS) and lipoteichoic acid (LTA) neutralization in upper respiratory tract infections were developed and evaluated in terms of efficacy and safety for application in humans. Based on the sequence of the human antimicrobial peptide LL-37 we developed and investigated length variants, substitution analogues and modifications to stabilize the peptides to prevent enzymatic degradation and to improve efficacy. The most promising peptide appears P60.4, a 24 amino acid peptide with similar efficacy as LL-37 in terms of LPS and LTA neutralization and lower pro-inflammatory activity. In addition, the acetylated and amidated version of this peptide shows no toxicity and displays higher or equal antimicrobial activity compared to LL-37. 相似文献
94.
Ediriweera PS Chandana Yasuhiro Maeda Akihiko Ueda Hiroshi Kiyonari Naoko Oshima Mako Yamamoto Shunya Kondo Junseo Oh Rei Takahashi Yoko Yoshida Satoshi Kawashima David B Alexander Hitoshi Kitayama Chiaki Takahashi Yasuhiko Tabata Tomoko Matsuzaki Makoto Noda 《BMC developmental biology》2010,10(1):1-13
Background
The accessibility of the developing zebrafish pharyngeal dentition makes it an advantageous system in which to study many aspects of tooth development from early initiation to late morphogenesis. In mammals, hedgehog signaling is known to be essential for multiple stages of odontogenesis; however, potential roles for the pathway during initiation of tooth development or in later morphogenesis are incompletely understood.Results
We have identified mRNA expression of the hedgehog ligands shha and the receptors ptc1 and ptc2 during zebrafish pharyngeal tooth development. We looked for, but did not detect, tooth germ expression of the other known zebrafish hedgehog ligands shhb, dhh, ihha, or ihhb, suggesting that as in mammals, only Shh participates in zebrafish tooth development. Supporting this idea, we found that morphological and gene expression evidence of tooth initiation is eliminated in shha mutant embryos, and that morpholino antisense oligonucleotide knockdown of shha, but not shhb, function prevents mature tooth formation. Hedgehog pathway inhibition with the antagonist compound cyclopamine affected tooth formation at each stage in which we applied it: arresting development at early stages and disrupting mature tooth morphology when applied later. These results suggest that hedgehog signaling is required continuously during odontogenesis. In contrast, over-expression of shha had no effect on the developing dentition, possibly because shha is normally extensively expressed in the zebrafish pharyngeal region.Conclusion
We have identified previously unknown requirements for hedgehog signaling for early tooth initiation and later morphogenesis. The similarity of our results with data from mouse and other vertebrates suggests that despite gene duplication and changes in the location of where teeth form, the roles of hedgehog signaling in tooth development have been largely conserved during evolution. 相似文献95.
Gerry T. M. Wagenaar Pavel Uhrin Klara Weipoltshammer Marlene Almeder Pieter S. Hiemstra Margarethe Geiger Joost C. M. Meijers Christian Schöfer 《Journal of molecular histology》2010,41(1):27-37
Proteolysis of extracellular matrix is an important requirement for embryonic development and is instrumental in processes
such as morphogenesis, angiogenesis, and cell migration. Efficient remodeling requires controlled spatio-temporal expression
of both the proteases and their inhibitors. Protein C inhibitor (PCI) effectively blocks a range of serine proteases, and
recently has been suggested to play a role in cell differentiation and angiogenesis. In this study, we mapped the expression
pattern of PCI throughout mouse development using in situ hybridization and immunohistochemistry. We detected a wide-spread,
yet distinct expression pattern with prominent PCI levels in skin including vibrissae, and in fore- and hindgut. Further sites
of PCI expression were choroid plexus of brain ventricles, heart, skeletal muscles, urogenital tract, and cartilages. A strong
and stage-dependent PCI expression was observed in the developing lung. In the pseudoglandular stage, PCI expression was present
in distal branching tubules whereas proximal tubules did not express PCI. Later in development, in the saccular stage, PCI
expression was restricted to distal bronchioli whereas sacculi did not express PCI. PCI expression declined in postnatal stages
and was not detected in adult lungs. In general, embryonic PCI expression indicates multifunctional roles of PCI during mouse
development. The expression pattern of PCI during lung development suggests its possible involvement in lung morphogenesis
and angiogenesis. 相似文献
96.
Zeeuwen PL de Jongh GJ Rodijk-Olthuis D Kamsteeg M Verhoosel RM van Rossum MM Hiemstra PS Schalkwijk J 《PloS one》2008,3(6):e2301
In the past decades, chronic inflammatory diseases such as psoriasis, atopic dermatitis, asthma, Crohn's disease and celiac disease were generally regarded as immune-mediated conditions involving activated T-cells and proinflammatory cytokines produced by these cells. This paradigm has recently been challenged by the finding that mutations and polymorphisms in epithelium-expressed genes involved in physical barrier function or innate immunity, are risk factors of these conditions. We used a functional genomics approach to analyze cultured keratinocytes from patients with psoriasis or atopic dermatitis and healthy controls. First passage primary cells derived from non-lesional skin were stimulated with pro-inflammatory cytokines, and expression of a panel of 55 genes associated with epidermal differentiation and cutaneous inflammation was measured by quantitative PCR. A subset of these genes was analyzed at the protein level. Using cluster analysis and multivariate analysis of variance we identified groups of genes that were differentially expressed, and could, depending on the stimulus, provide a disease-specific gene expression signature. We found particularly large differences in expression levels of innate immunity genes between keratinocytes from psoriasis patients and atopic dermatitis patients. Our findings indicate that cell-autonomous differences exist between cultured keratinocytes of psoriasis and atopic dermatitis patients, which we interpret to be genetically determined. We hypothesize that polymorphisms of innate immunity genes both with signaling and effector functions are coadapted, each with balancing advantages and disadvantages. In the case of psoriasis, high expression levels of antimicrobial proteins genes putatively confer increased protection against microbial infection, but the biological cost could be a beneficial system gone awry, leading to overt inflammatory disease. 相似文献
97.
Duits LA Rademaker M Ravensbergen B van Sterkenburg MA van Strijen E Hiemstra PS Nibbering PH 《Biochemical and biophysical research communications》2001,280(2):522-525
Intensive use of corticosteroids may be accompanied by increased susceptibility to infections; hence, we investigated the effects of dexamethasone on the expression of antimicrobial peptides, termed human beta-defensins (hBD), by cultured bronchial epithelial cells and mononuclear phagocytes. The results revealed that dexamethasone inhibited the (stimulated) expression of mRNA for hBD-3, but not hBD-1 and hBD-2 by these epithelial cells. Dexamethasone did not affect the (stimulated) mRNA expression of hBD-1 and hBD-2 by mononuclear phagocytes, whereas these cells did not express hBD-3 mRNA. 相似文献
98.
Nell MJ Tjabringa GS Vonk MJ Hiemstra PS Grote JJ 《FEMS immunology and medical microbiology》2004,42(2):225-231
The respiratory epithelium plays a major role in the primary defense of the airways against infection. It has been demonstrated that bacterial products are involved in the induction of inflammatory reactions of the upper airways. Little is known about the effects of bacterial products on expression of the antimicrobial peptide hCAP-18/LL-37, the only human cathelicidin identified so far. The aim of this study was to investigate the effects of bacterial products from both gram-positive and gram-negative bacteria on the expression of hCAP-18/LL-37 by sinus epithelial cells using an air-exposed tissue culture model. Lipopolysaccharide and lipoteichoic acid both increased hCAP-18/LL-37 expression in cultured sinus epithelium as assessed by immunohistochemistry, where maximal stimulation occurred at 100 ng ml(-1) lipopolysaccharide or 10 microg ml(-1) lipoteichoic acid. The stimulatory effect of lipopolysaccharide and lipoteichoic acid was not restricted to expression of hCAP-18/LL-37, since also mucin expression and IL-8 release from cultured sinus epithelium cells were increased by lipopolysaccharide and lipoteichoic acid. This suggests that bacterial products may stimulate innate immunity in the upper airways. 相似文献
99.
Tjabringa GS Vos JB Olthuis D Ninaber DK Rabe KF Schalkwijk J Hiemstra PS Zeeuwen PL 《FEMS immunology and medical microbiology》2005,45(2):151-158
Mucosal secretions contain a range of defense effector molecules including antimicrobial peptides and proteinase inhibitors. These molecules play a central role in host defense against infection, and in a variety of immune and inflammatory reactions. The aim of this study was to analyze the levels of neutrophil defensins, the cathelicidin hCAP-18/LL-37, and the proteinase inhibitors secretory leukocyte proteinase inhibitor, SKALP/elafin and cystatin M/E in various mucosal secretions and urine. We show here that especially seminal plasma is characterized by high concentrations of hCAP-18/LL-37, SLPI, SKALP/elafin and cystatin M/E. The results of this study demonstrate that each mucosal secretion is characterized by a unique profile of effector molecules, which may supply individual mucosal secretions with specific properties related to the control of local infection and inflammation. 相似文献
100.
Stimulation of bacterial adherence by neutrophil defensins varies among bacterial species but not among host cell types 总被引:2,自引:0,他引:2
Gorter AD Hiemstra PS de Bentzmann S van Wetering S Dankert J van Alphen L 《FEMS immunology and medical microbiology》2000,28(2):105-111
Adherence of Haemophilus influenzae to bronchial epithelial cells is enhanced by neutrophil defensins, which are released from activated neutrophils during inflammation [Gorter et al. (1998) J. Infect. Dis. 178, 1067-1078]. In this study, we showed that the adherence of H. influenzae to various epithelial, fibroblast-like and endothelial cell types was significantly enhanced by defensins (20 microg ml(-1)). Defensins stimulated also the adherence of Moraxella catarrhalis, Neisseria meningitidis and nonencapsulated Streptococcus pneumoniae to the NCI-H292 cell line. In contrast, defensins did not affect the adherence of Pseudomonas aeruginosa, encapsulated S. pneumoniae, Escherichia coli and Staphylococcus epidermidis. These results suggest that the defensin-enhanced adherence might support the adherence and possibly persistence of the selected bacterial species using the respiratory tract as port of entry. 相似文献