UK PubMed Central (United Kingdom)

Studies on alcoholic liver injury mechanisms show a significant inhibition of the proteasome activity. To investigate this phenomenon, we isolated proteasome complexes from the liver of rats...Full Text Available

UK PubMed Central (United Kingdom)

The ubiquitin–proteasome pathway is the principal system for extralysosomal protein degradation in eukaryotic cells, and is essential for the regulation and maintenance of basic cellular processes,...Full Text Available

UK PubMed Central (United Kingdom)

Human myeloid-lineage cells are refractory to HIV-1 infection. The Vpx proteins from HIV-2 and sooty mangabey SIV render these cells permissive to HIV-1 infection through proteasomal degradation of...Full Text Available

British Library Electronic Table of Contents (United Kingdom)

Abstract Epstein-Barr virus (EBV), which infects not only B cells, but also T cells and natural killer (NK) cells, is associated with multiple lymphoid malignancies. Recently, the proteasome inhibitor bortezomib was reported to induce apoptosis of EBV-transformed B cells. We evaluated the killing effect of this proteasome inhibitor on EBV-associated T lymphoma cells and NK lymphoma cells. First, we found that bortezomib treatment decreased the viability of multiple T and NK cell lines. No significant difference was observed between EBV-positive and EBV-negative cell lines. The decreased viability in response to bortezomib treatment was abrogated by a pan-caspase inhibitor. The induction of apoptosis was confirmed by flow cytometric assessment of annexin V staining. Additionally, cleavage o...

UK PubMed Central (United Kingdom)

Environmental and occupational exposures to heavy metals such as methylmercury (MeHg) and cadmium (Cd) pose significant health risks to humans, including neurotoxicity. The underlying mechanisms of...Full Text Available

Science.gov (United States)

1,3-Dienes derived from steroidal D-ring C17-ketones undergo Ni(II)-catalyzed hydrovinylation to give 1,2- or 1,4-addition of ethylene. Using finely tuned phosphoramidite ligands it is possible to synthesize either the C20 (R)- or the C20 (S)-derivatives without mutual contamination. The proportion of the 1,4-adduct, which is also formed stereoselectively, can be minimized by optimizing the reaction conditions. Since the two alkenes in the resultant dienes have differing steric demands for many potential reactions, and are ideally juxtaposed for further D-ring functionalization, these intermediates could be useful for the preparation of biologically important compounds such as vitamin D analogs and various antitumor steroidal glycosides.

Science.gov (United States)

Autoreactive cytotoxic CD8 T-cells (CTLs) play a key pathogenic role in the destruction of insulin-producing beta-cells resulting in type 1 diabetes. However, knowledge regarding their targets is limited, restricting the ability to monitor the course of the disease and immune interventions. In a multi-step discovery process to identify novel CTL epitopes in human preproinsulin (PPI), PPI was digested with purified human proteasomes, and resulting COOH-fragments aligned with algorithm-predicted HLA-binding peptides to yield nine potential HLA-A1, -A2, -A3 or -B7-restricted candidates. An UV-exchange method allowed the generation of a repertoire of multimers including low-affinity HLA-binding peptides. These were labeled with quantum dot-fluorochromes and encoded in a combinatorial fashion, allowing parallel and sensitive detection of specific, low-avidity T-cells. Significantly increased frequencies of T-cells against four novel PPI epitopes (PPI(4-13)/B7, ...

British Library Electronic Table of Contents (United Kingdom)

Abstract Objective: The aim of this investigation was to compare the healing of laser-irradiated and non-irradiated wounds covered by an occlusive dressing in mice. Background data: Many previous studies of the effects of laser irradiation of experimental wounds in mice and rats did not cover the wounds so that healing occurred mainly by contraction. Healing of covered wounds is slower and mimics more closely wound healing in humans. Materials and Methods: Forty-seven diabetic and twenty non-diabetic mice were used. A single wound (5?mm diameter) was created on the left flank of each animal and covered by Tegaderm HP dressing (Day 1). Wounds were irradiated (660?nm) for 20?s using a lower power (18?mW) or higher power (80?mW) laser starting immediately post-wounding for seven consecutive d...

Energy Technology Data Exchange (ETDEWEB)

A suspension of bone marrow cells from femurs of female (CBA . C57B1)F1 mice was exposed to 2450 MHz CW microwaves in a specially designed waveguide exposure system. The temperature of the suspension rose, during exposure to microwaves, from 20/sup 0/C to 45/sup 0/C, and at an interval within 20/sup 0/C to 45/sup 0/C the number of haemopoietic stem cells (CFUs) was determined by the spleen exocolony method. The time of exposure of bone marrow cells to each temperature studied was 20 s. Control suspensions of bone marrow cells were exposed to a water bath temperature. There were no significant effects of the CFUs with the water bath temperature, while after exposure to microwaves the number of spleen colonies was elevated with a nadir at the temperature of 37/sup 0/C. With a microwave-induced increase of the temperature above 41/sup 0/C the number of CFUs in the bone marrow suspension decreased. The increase in the number of colonies was related ...

International Nuclear Information System (INIS)

Thermal fatigue is one of the key factors governing the lifetime of the divertor plate. Tungsten is a promising candidate to cover the surface of the divertor plate in the design of the international thermonuclear experimental reactor (ITER). The W/Cr-bronze divertor small scale mock-ups were manufactured by hot isostatic pressing (HIPing) technique. Thermal fatigue tests of W/Cr-bronze divertor mock-ups have been carried out by an electron beam facility. The mock-ups were tested under a cyclic surface heat flux of 9 MW m"-"2 for 1000 cycles. The electron beam was loaded on the mock-up surface for 20 s and unloaded for 20 s, alternately. The flow rate of water coolant was 0.1 L s"-"1. The 0.3 mm diameter NiCr-NiSi thermocouples were used to monitor the temperature distribution of the mock-up. It was found that the maximum temperature of the tungsten surface was about 400 degree sign C. The saturated temperature at the joint of tungsten and ...

Energy Technology Data Exchange (ETDEWEB)

In the investigations reported here, a helium-jet/tape-transport system was used for the rapid transfer of fission products to a low-background environment where their aggregate beta and gamma-ray spectra were measured as a function of delay time after neutron induced fission of {sup 235}U, {sup 238}U and {sup 239}Pu. Beta and gamma-ray energy distributions have been deduced for delay times as short as 0.2 s and extending out to 100,000s. Instrumentation development during the initial phase of the project included: (1) assembly and characterization of a NaI(Tl) spectrometer for determining aggregate gamma-ray energy distributions, (2) development and characterization of a beta spectrometer (having excellent gamma-ray rejection) for measuring aggregate beta-particle energy distributions, (3) assembly and characterization of a Compton-suppressed HPGe spectrometer for determining gamma-ray intensities of individual fission products to deduce fission-product yields. Spectral decomposition ...