scholarly journals Toxicological and anti-tumoral effects of a Linden extract (Tilia platyphyllos Scop.) in HPV16-transgenic mouse model

2021 ◽  
Author(s):  
TIAGO FERREIRA ◽  
Elisabete Nascimento-Gonçalves ◽  
Sara Macedo ◽  
Inês Sá Borges ◽  
Adelina Gama ◽  
...  
Keyword(s):  
Phenolic Compounds ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Transgenic Mouse Model ◽  
Southern Europe ◽  
Tilia Platyphyllos ◽  
Anti Inflammatory

Tilia platyphyllos Scop., is a popular broad-leave tree, native to central and southern Europe. Hydroethanolic extracts rich in phenolic compounds obtained from T. platyphyllos Scop. showed in vitro antioxidant, anti-inflammatory...

P1-312: Blocking interleukin-1 function attenuates Alzheimer's pathology via reducing anti-inflammatory responses in a transgenic mouse model

2010 ◽  
Vol 6 ◽  
pp. S264-S264
Author(s):  
Masashi Kitazawa ◽  
David Cheng ◽  
Michelle Tsukamoto ◽  
Vitaly Vasilevko ◽  
David C. Cribbs ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Inflammatory Responses ◽  
Interleukin 1 ◽  
Transgenic Mouse Model ◽  
Anti Inflammatory ◽  
Alzheimer’S Pathology

scholarly journals Conserved Asp-137 Is Important for both Structure and Regulatory Functions of Cardiac α-Tropomyosin (α-TM) in a Novel Transgenic Mouse Model Expressing α-TM-D137L

2013 ◽  
Vol 288 (23) ◽  
pp. 16235-16246 ◽  
Author(s):  
Sumeyye Yar ◽  
Shamim A. K. Chowdhury ◽  
Robert T. Davis ◽  
Minae Kobayashi ◽  
Michelle M. Monasky ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Coiled Coil ◽  
Transgenic Mouse Model ◽  
Hydrophobic Core ◽  
Scanning Calorimetry ◽  
Physiological Importance ◽  
Cardiomyocyte Contractility ◽  
Regulatory Functions

α-Tropomyosin (α-TM) has a conserved, charged Asp-137 residue located in the hydrophobic core of its coiled-coil structure, which is unusual in that the residue is found at a position typically occupied by a hydrophobic residue. Asp-137 is thought to destabilize the coiled-coil and so impart structural flexibility to the molecule, which is believed to be crucial for its function in the heart. A previous in vitro study indicated that the conversion of Asp-137 to a more typical canonical Leu alters flexibility of TM and affects its in vitro regulatory functions. However, the physiological importance of the residue Asp-137 and altered TM flexibility is unknown. In this study, we further analyzed structural properties of the α-TM-D137L variant and addressed the physiological importance of TM flexibility in cardiac function in studies with a novel transgenic mouse model expressing α-TM-D137L in the heart. Our NMR spectroscopy data indicated that the presence of D137L introduced long range rearrangements in TM structure. Differential scanning calorimetry measurements demonstrated that α-TM-D137L has higher thermal stability compared with α-TM, which correlated with decreased flexibility. Hearts of transgenic mice expressing α-TM-D137L showed systolic and diastolic dysfunction with decreased myofilament Ca2+ sensitivity and cardiomyocyte contractility without changes in intracellular Ca2+ transients or post-translational modifications of major myofilament proteins. We conclude that conversion of the highly conserved Asp-137 to Leu results in loss of flexibility of TM that is important for its regulatory functions in mouse hearts. Thus, our results provide insight into the link between flexibility of TM and its function in ejecting hearts.

scholarly journals Optogenetic Modulation of Cortical Neurons Using Organic Light Emitting Diodes (OLEDs)

2019 ◽  
Author(s):  
Arati Sridharan ◽  
Ankur Shah ◽  
Swathy Sampath Kumar ◽  
James Kyeh ◽  
Joseph Smith ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Cortical Neurons ◽  
Microelectrode Array ◽  
Light Emitting Diodes ◽  
Green Light ◽  
Transgenic Mouse Model ◽  
Light Emitting

ABSTRACTObjectiveThere is a need for low power, scalable photoelectronic devices and systems for emerging optogenetic needs in neuromodulation. Conventional light emitting diodes (LEDs) are constrained by power and lead-counts necessary for scalability. Organic LEDs (OLEDs) offer an exciting approach to decrease power and lead-counts while achieving high channel counts on thin, flexible substrates that conform to brain surfaces or peripheral neuronal fibers. In this study, we investigate the potential for using OLEDs to modulate neuronal networks cultured in vitro on a transparent microelectrode array (MEA) and subsequently validate neurostimulation in vivo in a transgenic mouse model.ApproachCultured mouse cortical neurons were transfected with light-sensitive opsins such as blue-light sensitive channel-rhodopsin (ChR2) and green-light sensitive chimeric channel-rhodopsin (C1V1tt) and stimulated using blue and green OLEDs (with 455 and 520 nm peak emission spectra respectively) at a power of 1 mW/mm2 under pulsed conditions.Main resultsWe demonstrate neuromodulation and optostimulus-locked, single unit-neuronal activity in neurons expressing stimulating and inhibiting opsins (n=4 MEAs, each with 16 recordable channels). We also validated the optostimulus-locked response in a channel-rhodopsin expressing transgenic mouse model, where at least three isolatable single neuronal cortical units respond to OLED stimulation.SignificanceThe above results indicate the feasibility of generating sufficient luminance from OLEDs to perform neuromodulation both in vitro and in vivo. This opens up the possibility of developing thin, flexible OLED films with multiple stimulation sites that can conform to the shape of the neuronal targets in the brain or the peripheral nervous system. However, stability of these OLEDs under chronic conditions still needs to be carefully assessed with appropriate packaging approaches.

scholarly journals Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice

2017 ◽  
Vol 114 (40) ◽  
pp. 10719-10724 ◽  
Author(s):  
Kerstin Berer ◽  
Lisa Ann Gerdes ◽  
Egle Cekanaviciute ◽  
Xiaoming Jia ◽  
Liang Xiao ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Autoimmune Disease ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Immune Cells ◽  
Disease Incidence ◽  
Transgenic Mouse Model ◽  
Microbial Composition ◽  
Multiple Sclerosis Patients

There is emerging evidence that the commensal microbiota has a role in the pathogenesis of multiple sclerosis (MS), a putative autoimmune disease of the CNS. Here, we compared the gut microbial composition of 34 monozygotic twin pairs discordant for MS. While there were no major differences in the overall microbial profiles, we found a significant increase in some taxa such as Akkermansia in untreated MS twins. Furthermore, most notably, when transplanted to a transgenic mouse model of spontaneous brain autoimmunity, MS twin-derived microbiota induced a significantly higher incidence of autoimmunity than the healthy twin-derived microbiota. The microbial profiles of the colonized mice showed a high intraindividual and remarkable temporal stability with several differences, including Sutterella, an organism shown to induce a protective immunoregulatory profile in vitro. Immune cells from mouse recipients of MS-twin samples produced less IL-10 than immune cells from mice colonized with healthy-twin samples. IL-10 may have a regulatory role in spontaneous CNS autoimmunity, as neutralization of the cytokine in mice colonized with healthy-twin fecal samples increased disease incidence. These findings provide evidence that MS-derived microbiota contain factors that precipitate an MS-like autoimmune disease in a transgenic mouse model. They hence encourage the detailed search for protective and pathogenic microbial components in human MS.

scholarly journals The CRE luc Bioluminescence Transgenic Mouse Model for Detecting Ligand Activation of GPCRs

2013 ◽  
Vol 19 (2) ◽  
pp. 232-241 ◽  
Author(s):  
Holly Dressler ◽  
Kyriakos Economides ◽  
Sarah Favara ◽  
Nancy N. Wu ◽  
Zhen Pang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Expression Profiles ◽  
Tissue Expression ◽  
Transgenic Mouse Model ◽  
Luciferase Reporter ◽  
Primary Cells ◽  
Compound Libraries ◽  
Cellular Environment

Numerous assays have been developed to investigate the interactions between G-protein–coupled receptors (GPCRs) and their ligands since GPCRs are key therapeutic targets. Reporter-based assays using the cAMP response element (CRE) coupled with bioluminescence from a luciferase reporter have been used extensively in vitro with high-throughput screens (HTS) of large chemical compound libraries. We have generated a transgenic mouse model (CRE luc) with a luciferase reporter under the control of a synthetic promoter that contains several CREs, which supports real-time bioimaging of GPCR ligand activity in whole animals, tissues, or primary cells. In the CRE luc model, GPCR signaling through the cAMP pathway can be detected from the target GPCR that is in a native cellular environment with a full complement of associated receptors and membrane constituents. Multiple independent lines have been produced by random integration of the transgene, resulting in tissue expression profiles covering the major organs. The goal of the CRE luc model is to accelerate the transition from HTS to profiling of GPCR small-molecule leads in preclinical animal disease models, as well as define the mechanism of action of GPCR drugs in three experimental formats: primary cells, tissue homogenates, and whole animals.

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