806 research outputs found
Viral expression and molecular profiling in liver tissue versus microdissected hepatocytes in hepatitis B virus - associated hepatocellular carcinoma.
Background: The molecular mechanisms whereby hepatitis B virus (HBV) induces hepatocellular carcinoma (HCC)
remain elusive. We used genomic and molecular techniques to investigate host-virus interactions by studying multiple areas of the same liver from patients with HCC.
Methods: We compared the gene signature of whole liver tissue (WLT) versus laser capture-microdissected (LCM)
hepatocytes along with the intrahepatic expression of HBV. Gene expression profiling was performed on up to 17 WLT specimens obtained at various distances from the tumor center from individual livers of 11 patients with HCC and on selected LCM samples. HBV markers in liver and serum were determined by real-time polymerase chain reaction (PCR)and confocal immunofluorescence.
Results: Analysis of 5 areas of the liver showed a sharp change in gene expression between the immediate perilesional area and tumor periphery that correlated with a significant decrease in the intrahepatic expression of HB surface antigen (HBsAg). The tumor was characterized by a large preponderance of down-regulated genes, mostly involved in the
metabolism of lipids and fatty acids, glucose, amino acids and drugs, with down-regulation of pathways involved in the activation of PXR/RXR and PPARα/RXRα nuclear receptors, comprising PGC-1α and FOXO1, two key regulators
critically involved not only in the metabolic functions of the liver but also in the life cycle of HBV, acting as essential transcription factors for viral gene expression. These findings were confirmed by gene expression of microdissected
hepatocytes. Moreover, LCM of malignant hepatocytes also revealed up-regulation of unique genes associated with
cancer and signaling Pathways, including two novel HCC-associated cancer testis antigen genes, NUF2 and TTK.
Conclusions: Integrated gene expression profiling of whole liver tissue with that of microdissected hepatocytes
demonstrated that HBV-associated HCC is characterized by a metabolism switch-off and by a significant reduction in
HBsAg. LCM proved to be a critical tool to validate gene signatures associated with HCC and to identify genes that may play a role in hepatocarcinogenesis, opening new perspectives for the discovery of novel diagnostic markers and therapeutic targets
Multiscale analysis of human tissue engineered matrices for heart valve tissue engineering applications
Human tissue-engineered matrices (hTEMs) have been proposed as a promising approach for in-situ tissue engineered heart valves (TEHVs). However, there is still a limited understanding on how ECM composition in hTEMs develops over tissue culture time. Therefore, we performed a longitudinal hTEM assessment by 1) multiscale evaluation of hTEM composition during culture time (2, 4, 6-weeks), using (immuno)histology, biochemical assays, and mass spectrometry (LC-MS/MS); 2) analysis of protein pathways involved in ECM development using gene set enrichment analysis (GSEA); and 3) assessment of hTEM mechanical characterization using uniaxial tensile testing. Finally, as proof-of-concept, TEHVs manufactured using 6-weeks hTEM samples were tested in a pulse duplicator. LC-MS/MS confirmed the tissue culture time-dependent increase in ECM proteins observed in histology and biochemical assays, revealing the most abundant collagens (COL6,COL12), proteoglycans (HSPG2,VCAN), and glycoproteins (FN,TNC). GSEA identified the most represented protein pathways in the hTEM at 2-weeks (mRNA metabolic processes), 4-weeks (ECM production), and 6-weeks (ECM organization and maturation). Uniaxial mechanical testing showed increased stiffness and stress at failure, and reduction in strain over tissue culture time. hTEM-based TEHVs demonstrated promising in vitro performance at both pulmonary and aortic pressure conditions, with symmetric leaflet coaptation and no stenosis. In conclusion, ECM protein abundance and maturation increased over tissue culture time, with consequent improvement of hTEM mechanical characterics. These findings suggest that longer tissue culture impacts tissue organization, leading to an hTEM that may be suitable for high-pressure applications. STATEMENT OF SIGNIFICANCE: : It is believed that the composition of the extracellular matrix (ECM) in the human tissue engineered matrices (hTEM) may favor tissue engineered heart valve (TEHV) remodeling upon implantation. However, the exact protein composition of the hTEM, and how this impacts tissue mechanical properties, remains unclear. Hence, we developed a reproducible rotation-based tissue culture method to produce hTEM samples. We performed a longitudinal assessment using different analytical techniques and mass spectrometry. Our data provided an in-depth characterization of the hTEM proteome with focus on ECM components, their development, and how they may impact the mechanical properties. Based on these results, we manufactured functional hTEM-based TEHVs at aortic-like condition in vitro. These outcomes pose an important step in translating hTEM-based TEHVs into clinics and in predicting their remodeling potential upon implantation
Transapical aortic implantation of autologous marrow stromal cell-based tissue-engineered heart valves: first experiences in the systemic circulation
Photodetection of propagating quantum microwaves in circuit QED
We develop the theory of a metamaterial composed of an array of discrete
quantum absorbers inside a one-dimensional waveguide that implements a
high-efficiency microwave photon detector. A basic design consists of a few
metastable superconducting nanocircuits spread inside and coupled to a
one-dimensional waveguide in a circuit QED setup. The arrival of a {\it
propagating} quantum microwave field induces an irreversible change in the
population of the internal levels of the absorbers, due to a selective
absorption of photon excitations. This design is studied using a formal but
simple quantum field theory, which allows us to evaluate the single-photon
absorption efficiency for one and many absorber setups. As an example, we
consider a particular design that combines a coplanar coaxial waveguide with
superconducting phase qubits, a natural but not exclusive playground for
experimental implementations. This work and a possible experimental realization
may stimulate the possible arrival of "all-optical" quantum information
processing with propagating quantum microwaves, where a microwave photodetector
could play a key role.Comment: 27 pages, submitted to Physica Scripta for Nobel Symposium on "Qubits
for Quantum Information", 200
Bose-Einstein condensation on a superconducting atom chip
We have produced a Bose-Einstein condensate (BEC) on an atom chip using only
superconducting wires in a cryogenic environment. We observe the onset of
condensation for 10^4 atoms at a temperature of 100 nK. This result opens the
way for studies of atom losses and decoherence in a BEC interacting with a
superconducting surface. Studies of dipole-blockade with long-lived Rydberg
atoms in a small and dense atomic sample are underway.Comment: 4 pages, 4 figures. Accepted for publication in Europhysics Letter
NRLMSIS 2.1: An Empirical Model of Nitric Oxide Incorporated Into MSIS
We have developed an empirical model of nitric oxide (NO) number density at altitudes from similar to 73 km to the exobase, as a function of altitude, latitude, day of year, solar zenith angle, solar activity, and geomagnetic activity. The model is part of the NRLMSIS (R) 2.1 empirical model of atmospheric temperature and species densities; this upgrade to NRLMSIS 2.0 consists solely of the addition of NO. MSIS 2.1 assimilates observations from six space-based instruments: UARS/HALOE, SNOE, Envisat/MIPAS, ACE/FTS, Odin/SMR, and AIM/SOFIE. We additionally evaluated the new model against independent extant NO data sets. In this paper, we describe the formulation and fitting of the model, examine biases between the data sets and model and among the data sets, compare with another empirical NO model (NOEM), and discuss scientific aspects of our analysis
NRLMSIS 2.1: An Empirical Model of Nitric Oxide Incorporated Into MSIS
We have developed an empirical model of nitric oxide (NO) number density at altitudes from ∼73 km to the exobase, as a function of altitude, latitude, day of year, solar zenith angle, solar activity, and geomagnetic activity. The model is part of the NRLMSIS® 2.1 empirical model of atmospheric temperature and species densities; this upgrade to NRLMSIS 2.0 consists solely of the addition of NO. MSIS 2.1 assimilates observations from six space-based instruments: UARS/HALOE, SNOE, Envisat/MIPAS, ACE/FTS, Odin/SMR, and AIM/SOFIE. We additionally evaluated the new model against independent extant NO data sets. In this paper, we describe the formulation and fitting of the model, examine biases between the data sets and model and among the data sets, compare with another empirical NO model (NOEM), and discuss scientific aspects of our analysis
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