Search results for "genetics [Transcriptome]"

Release of choline in the isolated heart, an indicator of ischemic phospholipid degradation and its protection by ischemic preconditioning: No eviden…

2003

Abstract The release of choline as a water-soluble product of phospholipid hydrolysis was measured in the perfusate of rat hearts to monitor ischemic membrane degradation and its protection by ischemic preconditioning (IPC). Hearts were subjected to global ischemia (GI; 30 min of no-flow) followed by 60 min of reperfusion. To induce IPC, GI was preceded by four no-flow episodes of 5 min each. Deleterious consequences of GI and reperfusion, namely coronary flow reduction, incidence of arrhythmias and release of cardiac troponin T, were significantly attenuated by IPC. The release of choline increased during reperfusion in a biphasic manner: a first phase peaked immediately after GI and was f…

Cavity optomechanics mediated by a quantum two-level system

2015

Coupling electromagnetic waves in a cavity and mechanical vibrations via the radiation pressure of photons is a promising platform for investigations of quantum–mechanical properties of motion. A drawback is that the effect of one photon tends to be tiny, and hence one of the pressing challenges is to substantially increase the interaction strength. A novel scenario is to introduce into the setup a quantum two-level system (qubit), which, besides strengthening the coupling, allows for rich physics via strongly enhanced nonlinearities. Here we present a design of cavity optomechanics in the microwave frequency regime involving a Josephson junction qubit. We demonstrate boosting of the radiat…

Induced unconventional superconductivity on the surface states of Bi2Te3 topological insulator

2017

Topological superconductivity is central to a variety of novel phenomena involving the interplay between topologically ordered phases and broken-symmetry states. The key ingredient is an unconventional order parameter, with an orbital component containing a chiral $p_x$ + i$p_y$ wave term. Here we present phase-sensitive measurements, based on the quantum interference in nanoscale Josephson junctions, realized by using Bi$_2$Te$_3$ topological insulator. We demonstrate that the induced superconductivity is unconventional and consistent with a sign-changing order parameter, such as a chiral $p_x$ + i$p_y$ component. The magnetic field pattern of the junctions shows a dip at zero externally a…

Regulation of X Chromosome-Linked Inhibitor of Apoptosis Protein (XIAP) in Kainic Acid Induced Neuronal Cell Death in the Rat Hippocampus

2001

INTRODUCTION. Inhibitor of apoptosis protein (IAP) family consists of several antiapoptotic proteins conserved among species. The IAPs have a well-conserved motif of approximately 65 residues, called the baculovirus inhibitory repeat (BIR) (1). Baculovirus and drosophila IAPs have two, but most IAPs contain three BIR domains. Most of the IAPs also have a C-terminal RING domain which consists of conserved amino acids with zinc binding capacity. XIAP is one of the five known human IAPs and it binds directly and inhibits the activity of caspases (2). The BIR2 domain in XIAP is sufficient to mediate this inhibition (3). However little is known about the presence and function of XIAP in the nerv…

2018

Oncogenic human papillomaviruses (HPV) are small DNA viruses that infect keratinocytes. After HPV binding to cell surface receptors, a cascade of molecular interactions mediates the infectious cellular internalization of virus particles. Aside from the virus itself, important molecular players involved in virus entry include the tetraspanin CD151 and the epidermal growth factor receptor (EGFR). To date, it is unknown how these components are coordinated in space and time. Here, we studied plasma membrane dynamics of CD151 and EGFR and the HPV16 capsid during the early phase of infection. We find that the proteinase ADAM17 activates the extracellular signal-regulated kinases (ERK1/2) pathway…

Langerhans Cells Prevent Autoimmunity via Expansion of Keratinocyte Antigen-Specific Regulatory T Cells

2017

Langerhans cells (LCs) are antigen-presenting cells in the epidermis whose roles in antigen-specific immune regulation remain incompletely understood. Desmoglein 3 (Dsg3) is a keratinocyte cell-cell adhesion molecule critical for epidermal integrity and an autoantigen in the autoimmune blistering disease pemphigus. Although antibody-mediated disease mechanisms in pemphigus are extensively characterized, the T cell aspect of this autoimmune disease still remains poorly understood. Herein, we utilized a mouse model of CD4+ T cell-mediated autoimmunity against Dsg3 to show that acquisition of Dsg3 and subsequent presentation to T cells by LCs depended on the C-type lectin langerin. The lack of…

Telomerase Reverse Transcriptase Delays Aging in Cancer-Resistant Mice

2008

Summary Telomerase confers limitless proliferative potential to most human cells through its ability to elongate telomeres, the natural ends of chromosomes, which otherwise would undergo progressive attrition and eventually compromise cell viability. However, the role of telomerase in organismal aging has remained unaddressed, in part because of the cancer-promoting activity of telomerase. To circumvent this problem, we have constitutively expressed telomerase reverse transcriptase (TERT), one of the components of telomerase, in mice engineered to be cancer resistant by means of enhanced expression of the tumor suppressors p53, p16, and p19ARF. In this context, TERT overexpression improves …

Identification of avarol derivatives as potential antipsoriatic drugs using an in vitro model for keratinocyte growth and differentiation.

2006

Contains fulltext : 49512schalkwijk.pdf (Publisher’s version ) (Closed access) Avarol, a marine sesquiterpenoid hydroquinone, and 14 avarol derivatives have shown interesting anti-inflammatory properties in previous studies. In this study, avarol and derivatives were evaluated in high-throughput keratinocyte culture models using cytokeratin 10 and SKALP/Elafin expression as markers for respectively normal and psoriatic differentiation. Avarol and five of its derivatives (5, 10, 13, 14 and 15) were selected for further study. Only 10, 13, 14 and 15 were able to inhibit keratinocyte cell growth. Changes in expression levels of 22 genes were assessed by quantitative real time PCR (qPCR). From …

Epigenetic control of IL-23 expression in keratinocytes is important for chronic skin inflammation

2018

The chronic skin inflammation psoriasis is crucially dependent on the IL-23/IL-17 cytokine axis. Although IL-23 is expressed by psoriatic keratinocytes and immune cells, only the immune cell-derived IL-23 is believed to be disease relevant. Here we use a genetic mouse model to show that keratinocyte-produced IL-23 is sufficient to cause a chronic skin inflammation with an IL-17 profile. Furthermore, we reveal a cell-autonomous nuclear function for the actin polymerizing molecule N-WASP, which controls IL-23 expression in keratinocytes by regulating the degradation of the histone methyltransferases G9a and GLP, and H3K9 dimethylation of the IL-23 promoter. This mechanism mediates the inducti…

Exosomes released by keratinocytes modulate melanocyte pigmentation

2015

Cells secrete extracellular vesicles (EVs), exosomes and microvesicles, which transfer proteins, lipids and RNAs to regulate recipient cell functions. Skin pigmentation relies on a tight dialogue between keratinocytes and melanocytes in the epidermis. Here we report that exosomes secreted by keratinocytes enhance melanin synthesis by increasing both the expression and activity of melanosomal proteins. Furthermore, we show that the function of keratinocyte-derived exosomes is phototype-dependent and is modulated by ultraviolet B. In sum, this study uncovers an important physiological function for exosomes in human pigmentation and opens new avenues in our understanding of how pigmentation is…