A5060659614- Immune Response and Inflammation
- Peroxisome Proliferator-Activated Receptors
- Streptococcal Infections and Treatments
- Bacterial Genetics and Biotechnology
- Antimicrobial Resistance in Staphylococcus
- Epigenetics and DNA Methylation
- Neonatal and Maternal Infections
- RNA and protein synthesis mechanisms
- Pharmacogenetics and Drug Metabolism
- Escherichia coli research studies
- Metabolism, Diabetes, and Cancer
- Genetics and Neurodevelopmental Disorders
- Urinary Tract Infections Management
- Autophagy in Disease and Therapy
- Microbial Metabolic Engineering and Bioproduction
- Adipose Tissue and Metabolism
- Immune Cell Function and Interaction
- Cancer, Lipids, and Metabolism
- Inflammatory mediators and NSAID effects
- Enzyme Structure and Function
- NF-κB Signaling Pathways
- Metabolism and Genetic Disorders
- Sphingolipid Metabolism and Signaling
- Complement system in diseases
- Drug Transport and Resistance Mechanisms
Lund University
2001-2015
University of Copenhagen
2011-2013
Ninewells Hospital
2004-2009
University of Dundee
2004-2009
University of Edinburgh
2004
University of Leicester
2004
University of California, Los Angeles
2004
Tufts University
1997
Abstract The nuclear receptor peroxisome proliferator-activated δ [PPARδ/β (NR1C2)] has been implicated in colorectal carcinogenesis by various molecular genetic observations. These observations have recently supported studies of activation PPARδ pharmacological agents. Here we present the first report stimulation breast and prostate cancer cell growth using selective agonists. Activation with compound F stimulated proliferation (T47D, MCF7) (LNCaP, PNT1A) lines, which are responsive to sex...
The cyp102A2 and cyp102A3 genes encoding the two Bacillus subtilis homologues (CYP102A2 CYP102A3) of flavocytochrome P450 BM3 (CYP102A1) from megaterium have been cloned, expressed in Escherichia coli, purified, characterized spectroscopically enzymologically. Both enzymes contain heme, flavin adenine dinucleotide (FAD) mononucleotide (FMN) cofactors bind a variety fatty acid molecules, as demonstrated by conversion low-spin resting form heme iron to high-spin induced substrate-binding....
Mucosal Toll-like receptors (TLRs) respond to pathogens, but remain inert the indigenous flora, suggesting that TLRs can receive pathogen-specific signals. For example, TLR4 signalling is activated in CD14-negative epithelial cells by P-fimbriated, uropathogenic Escherichia coli, not lipopolysaccharide. The fimbriae use glycosphingolipids as recognition and there release of ceramide, which membrane-anchoring domain receptors. In this study, ceramide was identified a agonist putative...
Toll-like receptor (TLR) 4 is essential for the defense against infection with gram-negative pathogens, but reduced TLR4 expression has not been linked to altered disease susceptibility in humans. In mice, Tlr4 controls mucosal response Escherichia coli urinary tract infections. Inactivation of mouse causes an asymptomatic carrier state resembling bacteriuria (ABU). The present study compared neutrophil levels between children ABU (n=17) and age-matched control subjects (n=24), significantly...
BackgroundFor unknown reasons, urinary tract infections (UTIs) are clustered in certain individuals. Here we propose a novel, genetically determined cause of susceptibility to acute pyelonephritis, which is the most severe form UTI. The IL-8 receptor, CXCR1, was identified as candidate gene when mIL-8Rh mutant mice developed pyelonephritis (APN) with tissue damage.Methods and FindingsWe have obtained CXCR1 sequences from two, highly selected APN prone patient groups, detected three unique...
Background Polymorphisms affecting Toll-like receptor (TLR) structure appear to be rare, as would expected due their essential coordinator role in innate immunity. Here, we assess variation TLR4 expression, rather than structure, a mechanism diversify immune responses. Methodology/Principal Findings We sequenced the promoter (4,3 kb) Swedish blood donors. Since plays vital susceptibility urinary tract infection (UTI), sequences were obtained from children with mild or severe disease....
Psoriasis is one of the most frequent skin diseases world-wide. The disease impacts enormously on affected patients and poses a huge financial burden health care providers. Several lines evidence suggest that nuclear hormone receptor peroxisome proliferator activator (PPAR) beta/delta, known to regulate epithelial differentiation wound healing, contributes psoriasis pathogenesis. It unclear, however, whether activation PPARbeta/delta sufficient trigger psoriasis-like changes in vivo.Using...
The azlB locus of Bacillus subtilis was defined previously by a mutation conferring resistance to leucine analog, 4-azaleucine (J. B. Ward, Jr., and S. A. Zahler, J. Bacteriol. 116:727-735, 1973). In this report, is shown be the first gene an operon apparently involved in branched-chain amino acid transport. product Lrp-like protein that negatively regulates expression azlBCDEF operon. Resistance mutants due overproduction AzlC AzlD, two novel hydrophobic proteins.
HAMLET, a complex of partially unfolded alpha-lactalbumin and oleic acid, kills wide range tumor cells. Here we propose that HAMLET causes macroautophagy in cells this contributes to their death. Cell death was accompanied by mitochondrial damage reduction the level active mTOR triggered extensive cytoplasmic vacuolization formation double-membrane-enclosed vesicles typical macroautophagy. In addition, caused change from uniform (LC3-I) granular (LC3-II) staining LC3-GFP-transfected...
Many pathogens express a surface protein that binds the human complement regulator factor H (FH), as first described for Streptococcus pyogenes and antiphagocytic M6 protein. It is commonly assumed FH recruited to an M enhances virulence by protecting bacteria against deposition phagocytosis, but role of FH-binding in S. pathogenesis has remained unclear controversial. Here, we studied seven purified proteins ability bind found M5, M18 not M1, M3, M4 M22 proteins. Extensive immunochemical...
Abstract Histone deacetylase inhibitors (HDIs) and HAMLET (human α-lactalbumin made lethal to tumor cells) interact with histones, modify the structure of chromatin, trigger cell death. This study investigated how combination HDIs influences viability, histone acetylation, DNA integrity. The pretreatment cells was shown enhance effect hyperacetylation response increased even further after treatment. were target different domains as bound tailless core whereas acetylation tail. damage in by...
Abstract The M protein of Streptococcus pyogenes , a major bacterial virulence factor, has an amino‐terminal hypervariable region ( HVR ) that is target for type‐specific protective antibodies. Intriguingly, the elicits weak antibody response, indicating it escapes host immunity by two mechanisms, sequence variability and immunogenicity. However, properties influencing immunogenicity regions in remain poorly understood. Here, we studied response to different classical M1 M5 proteins, which...
Members of the Peroxisome Proliferator Activated Receptor, PPAR, subfamily nuclear receptors display complex opposing and overlapping functions a wide range pharmacological molecular genetic tools have been used to dissect their specific functions. Non-agonist bound PPARdelta has shown repress PPAR Response Element, PPRE, signalling several lines evidence point importance repressive actions in both cardiovascular cancer biology.In this report we employed transient transfections luciferase...
The nuclear receptor, NR1C2 or peroxisome proliferator-activated receptor (PPAR)-δ, is ubiquitously expressed and important for placental development, fatty acid metabolism, wound healing, inflammation, tumour development. PPARδ has been hypothesized to function as both a ligand activated transcription factor repressor of in the absence agonist. In this paper, treatment mice conditionally expressing human with GW501516 resulted marked loss body weight that was not evident nontransgenic...
Recent studies indicate that defective activity of complement factor H (FH) is associated with several human diseases, suggesting pure FH may be used for therapy. Here, we describe a simple method to isolate FH, based on the specific interaction between and hypervariable region (HVR) certain Streptococcus pyogenes M proteins. Special interest was focused polymorphism Y402H, which common eye disease age-related macular degeneration (AMD) has also been implicated in binding protein. Using...
In this work we present evidence for a novel diffusible extracellular factor that modulates gene expression in Bacillus subtilis. The was found when studying the regulation of fatR-cyp102A3 operon. Spo0A(-) mutant operon almost abolished. defect could be overcome either by mutation abrB or substance excreted wild-type, and abrB-spo0A double strains.