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Molecular and Translational Classifications of DAMPs in Immunogenic Cell Death
2015
The immunogenicity of malignant cells has recently been acknowledged as a critical determinant of efficacy in cancer therapy. Thus, besides developing direct immunostimulatory regimens, including dendritic cell-based vaccines, checkpoint-blocking therapies, and adoptive T-cell transfer, researchers have started to focus on the overall immunobiology of neoplastic cells. It is now clear that cancer cells can succumb to some anticancer therapies by undergoing a peculiar form of cell death that is characterized by an increased immunogenic potential, owing to the emission of the so-called "damage-associated molecular patterns" (DAMPs). The emission of DAMPs and other immunostimulatory factors by…
P258 Combining tDCS with prismatic adaptation for non invasive neuromodulation of the motor cortex
2017
Introduction Prismatic adaptation (PA) shifts visual field laterally and induces lateralized deviations of spatial attention. Recently, it has been suggested that prismatic goggles are also able to modulate brain excitability ( Magnani, 2014 ), with cognitive after-effects documented even in tasks not necessarily spatial in nature ( Oliveri, 2013 ). Objectives The aim of the present study was to test whether prisms can modulate motor cortical excitability similarly as anodal transcranial direct current stimulation (tDCS) does; to test whether neuromodulatory effects obtained from tDCS and prismatic goggles could interact and induce homeostatic changes in brain excitability. Materials and me…
Gene expression centroids that link with low intrinsic aerobic exercise capacity and complex disease risk
2010
A strong link exists between low aerobic exercise capacity and complex metabolic diseases. To probe this linkage, we utilized rat models of low and high intrinsic aerobic endurance running capacity that differ also in the risk for metabolic syndrome. We investigated in skeletal muscle gene-phenotype relationships that connect aerobic endurance capacity with metabolic disease risk factors. The study compared 12 high capacity runners (HCRs) and 12 low capacity runners (LCRs) from generation 18 of selection that differed by 615% for maximal treadmill endurance running capacity. On average, LCRs were heavier and had increased blood glucose, insulin, and triglycerides compared with HCRs. HCRs we…
Use of a three-factor interpretive optimisation strategy in the development of an isocratic chromatographic procedure for the screening of diuretics …
2000
Screening of diuretics in urine is feasible through direct injection of the samples into the chromatographic system and isocratic reversed-phase liquid chromatography (RPLC) with micellar-organic mobile phases of sodium dodecyl sulfate (SDS) and 1-propanol. The surfactant coverage of the chromatographic column makes the addition of organic competing amines less necessary than in conventional aqueous-organic RPLC to achieve well-shaped peaks. Also, the range of elution strengths of micellar mobile phases required to elute mixtures of hydrophobic and hydrophilic diuretics is smaller. This allows the isocratic separation of the diuretics within adequate analysis times. An interpretive methodol…
Metalloprotease meprin beta generates nontoxic N-terminal amyloid precursor protein fragments in vivo.
2011
Identification of physiologically relevant substrates is still the most challenging part in protease research for understanding the biological activity of these enzymes. The zinc-dependent metalloprotease meprin β is known to be expressed in many tissues with functions in health and disease. Here, we demonstrate unique interactions between meprin β and the amyloid precursor protein (APP). Although APP is intensively studied as a ubiquitously expressed cell surface protein, which is involved in Alzheimer disease, its precise physiological role and relevance remain elusive. Based on a novel proteomics technique termed terminal amine isotopic labeling of substrates (TAILS), APP was identified …
Heat shock protein expression and anti-heat shock protein reactivity in renal cell carcinoma.
2002
Heat shock proteins (HSP) are families of highly conserved proteins which are induced in cells and tissues upon exposure to extreme conditions causing acute or chronic stress. They exhibit distinct functions and have been implicated in the pathogenesis of a number of diseases, including cancer. A causal relationship between HSP expression and immunogenicity has been demonstrated in murine and human tumors and is also associated with the immune response. In order to investigate the correlation of HSP expression and their immunogenic potential in renal cell carcinoma (RCC), we here analyzed (i) the protein expression profile of various members of the HSP family in untreated and interferon (IF…
Comparison of adjuvant and adjuvant-free murine experimental asthma models
2009
Introduction The most widely used protocol for the induction of experimental allergic airway inflammation in mice involves sensitization by intraperitoneal (i.p.) injections of the antigen ovalbumin (OVA) used in conjunction with the adjuvant aluminium hydroxide (alum). Although adjuvants are frequently used, there are questions regarding the necessity of alum for murine asthma studies due to the non-physiological nature of this chemical. Objective The objective of this study was to compare experimental asthma phenotypes between adjuvant and adjuvant-free protocols of murine allergic airway inflammation in an attempt to develop a standardized alternative to adjuvant use. Method An adjuvant-…
Induction of Type-Specific Neutralizing Antibodies by Capsomeres of Human Papillomavirus Type 33
2001
Abstract The immunogenicity of capsomeres of human papillomavirus type 33 was evaluated in a dose–response analysis. Capsomeres were obtained free of capsids by expression of L1 carrying the single point mutation C427S. Neutralizing antibodies were detected using an in vitro pseudoinfection assay. Capsomeres induced type-specific, neutralizing antibodies in mice even in the absence of adjuvant. The neutralization titers of immune sera raised without adjuvant were 10- to 20-fold lower than those of antisera to virus-like particles, but virtually identical using Freund's adjuvant. These data indicate that capsomeres may substitute for virus-like particles in future vaccines when used with an …
Generating p53-specific cytotoxic T lymphocytes by recombinant adenoviral vector-based vaccination in mice, but not man.
2002
Mutations and aberrant expression of the p53 tumor suppressor protein are the most frequent molecular alterations in human malignancy. Peptides derived from the wild-type (wt) p53 protein and presented by major histocompatibility complex (MHC) molecules for T lymphocyte recognition are believed to serve as universal tumor-associated antigens for cancer immunotherapy. We studied the immunogeneicity of a recombinant replication-defective adenoviral vector encoding human full-length wt p53 (rAd/hup53) in human leukocyte antigen (HLA)-A2K(b)-transgenic (Tg) mice and man. The generation of p53 epitope-specific cytotoxic T lymphocytes (CTLs) in p53-proficient and p53-deficient A2K(b)-Tg mice was …
P 96. Prismatic lenses as a novel tool to directionally manipulate motor cortex excitability: Evidence from paired-pulse TMS
2013
Introduction Prismatic adaptation (PA) is a visuo-motor procedure requiring participants to adapt to prismatic lenses shifting the visual scene horizontally. Such an adaptation produces a phenomenon called “after-effect”, opposite to the side of lenses deviation. The after-effect has been frequently associated with a shift of spatial attention in the same direction and with a restoration of hemispatial neglect symptoms. PA has captured the interest of neuroscientists in the last decades, since it affects high-order spatial cognition even thought consisting of low-level visuo-motor processes. Objectives Despite a huge literature on this procedure, the basic neural processes related to PA and…