Search results for "Mouse"

ERK1/2 activation in human taste bud cells regulates fatty acid signaling and gustatory perception of fat in mice and humans

2016

Obesity is a major public health problem. An in-depth knowledge of the molecular mechanisms of oro-sensory detection of dietary lipids may help fight it. Humans and rodents can detect fatty acids via lipido-receptors, such as CD36 and GPR120. We studied the implication of the MAPK pathways, in particular, ERK1/2, in the gustatory detection of fatty acids. Linoleic acid, a dietary fatty acid, induced via CD36 the phosphorylation of MEK1/2-ERK1/2-ETS-like transcription factor-1 cascade, which requires Fyn-Src kinase and lipid rafts in human taste bud cells (TBCs). ERK1/2 cascade was activated by Ca2+ signaling via opening of the calcium-homeostasis modulator-1 (CALHM1) channel. Furthermore, f…

Characterization of the first-in-class T-cell-engaging bispecific single-chain antibody for targeted immunotherapy of solid tumors expressing the onc…

2015

abstract The fetal tight junction molecule claudin 6 (CLDN6) is virtually absent from any normal tissue, whereas it is aberrantly and frequently expressed in various cancers of high medical need. We engineered 6PHU3, a T-cell-engaging bispecific single chain molecule (bi-(scFv)2) with anti-CD3/anti-CLDN6 specificities, and characterized its pharmacodynamic properties. Our data show that upon engagement by 6PHU3, T cells strongly upregulate cytotoxicity and activation markers, proliferate and acquire an effector phenotype. 6PHU3 exerts potent killing of cancer cells in vitro with EC50 values in the pg/mL range. Subcutaneous xenograft tumors in NSG mice engrafted with human PBMCs are eradicat…

Bronchial inflammation and bacterial load in stable COPD is associated with TLR4 overexpression.

2017

Toll-like receptors (TLRs) and nucleotide-binding oligomerisation domain (NOD)-like receptors (NLRs) are two major forms of innate immune sensors but their role in the immunopathology of stable chronic obstructive pulmonary disease (COPD) is incompletely studied. Our objective here was to investigate TLR and NLR signalling pathways in the bronchial mucosa in stable COPD.Using immunohistochemistry, the expression levels of TLR2, TLR4, TLR9, NOD1, NOD2, CD14, myeloid differentiation primary response gene 88 (MyD88), Toll-interleukin-1 receptor domain-containing adaptor protein (TIRAP), and the interleukin-1 receptor-associated kinases phospho-IRAK1 and IRAK4 were measured in the bronchial muc…

Alternative Splice Forms of CYLD Mediate Ubiquitination of SMAD7 to Prevent TGFB Signaling and Promote Colitis

2018

Background & Aims The CYLD lysine 63 deubiquitinase gene (CYLD) encodes tumor suppressor protein that is mutated in familial cylindromatosus, and variants have been associated with Crohn disease (CD). Splice forms of CYLD that lack exons 7 and 8 regulate transcription factors and functions of immune cells. We examined the expression of splice forms of CYLD in colon tissues from patients with CD and their effects in mice. Methods We performed immunohistochemical analyses of colon tissues from patients with untreated CD and patients without inflammatory bowel diseases (controls). We obtained mice that expressed splice forms of CYLD (sCYLD mice) without or with SMAD7 (sCYLD/SMAD7 mice) from tr…

Mouse models of multiple myeloma: technologic platforms and perspectives.

2018

Murine models of human multiple myeloma (MM) are key tools for the study of disease biology as well as for investigation and selection of novel candidate therapeutics for clinical translation. In the last years, a variety of pre-clinical models have been generated to recapitulate a wide spectrum of biological features of MM. These systems range from spontaneous or transgenic models of murine MM, to subcutaneous or orthothopic xenografts of human MM cell lines in immune compromised animals, to platform allowing the engraftment of primary/bone marrow-dependent MM cells within a human bone marrow milieu to fully recapitulate human disease. Selecting the right model for specific pre-clinical re…

Identification and Characterization of the Dermal Panniculus Carnosus Muscle Stem Cells

2016

Summary The dermal Panniculus carnosus (PC) muscle is important for wound contraction in lower mammals and represents an interesting model of muscle regeneration due to its high cell turnover. The resident satellite cells (the bona fide muscle stem cells) remain poorly characterized. Here we analyzed PC satellite cells with regard to developmental origin and purported function. Lineage tracing shows that they originate in Myf5+, Pax3/Pax7+ cell populations. Skin and muscle wounding increased PC myofiber turnover, with the satellite cell progeny being involved in muscle regeneration but with no detectable contribution to the wound-bed myofibroblasts. Since hematopoietic stem cells fuse to PC…

Negative transfer effects between reference memory and working memory training in the water maze in C57BL/6 mice

2017

The water maze is one of the most widely employed spatial learning paradigms in the cognitive profiling of genetically modified mice. Oftentimes, tests of reference memory (RM) and working memory (WM) in the water maze are sequentially evaluated in the same animals. However, critical difference in the rules governing efficient escape from the water between WM and RM tests is expected to promote the adoption of incompatible mnemonic or navigational strategies. Hence, performance in a given test is likely poorer if it follows the other test instead of being conducted first. Yet, the presence of such negative transfer effects (or proactive interference) between WM and RM training in the water …

Effects of muscular dystrophy, exercise and blocking activin receptor IIB ligands on the unfolded protein response and oxidative stress

2016

Protein homeostasis in cells, proteostasis, is maintained through several integrated processes and pathways and its dysregulation may mediate pathology in many diseases including Duchenne muscular dystrophy (DMD). Oxidative stress, heat shock proteins, endoplasmic reticulum (ER) stress and its response, i.e. unfolded protein response (UPR), play key roles in proteostasis but their involvement in the pathology of DMD are largely unknown. Moreover, exercise and activin receptor IIB blocking are two strategies that may be beneficial to DMD muscle, but studies to examine their effects on these proteostasis pathways are lacking. Therefore, these pathways were examined in the muscle of mdx mice, …

Unusual multiparasitism causes overweight in a wood mouse,Apodemus sylvaticus(Rodentia: Muridae), from a post-fire regeneration area

2016

Multiparasitism is a common ecological phenomenon, being the norm rather than the exception, in the wild. This article describes the case of a wood mouse, Apodemus sylvaticus, originating from a post-fire regeneration area, infected with multiple helminth species and remarkable overweight. The mouse analyzed was captured at a post-fire regeneration site in the Serra Calderona Natural Park (Comunitat Valenciana, Spain). The rodent was captured and marked for the first time in the spring of 2011, weighing 22.5 g. When it was recaptured in the winter of 2012, it weighed 44.0 g. The mouse was parasitized by a total of 31 helminths belonging to seven species, including six Taenia parva metacesto…

2017

Allogeneic hematopoietic stem cell transplantation is the only curative treatment option for several hematological malignancies and immune deficiency syndromes. Nevertheless, the development of a graft-versus-host disease (GvHD) after transplantation is a high risk and a severe complication with high morbidity and mortality causing therapeutic challenges. Current pharmacological therapies of GvHD lead to generalized immunosuppression followed by severe adverse side effects including infections and relapse of leukemia. Several novel cell-based immunomodulatory strategies for treatment or prevention of GvHD have been developed. Herein, thymus-derived regulatory T cells (tTreg), essential for …