The role of adenosine in chondrocyte death in murine osteoarthritis and in a murine chondrocyte cell line

SummaryObjectiveTo investigate the role of adenosine in chondrocyte death in murine osteoarthritis (OA).Methods5′-Nucleotidase (5′NT) generates adenosine. Enzyme activity was measured histochemically in normal murine and osteoarthritic STR/ort strain tibial cartilage. Adenosine-mediated cell death was investigated in MC615 chondrocyte cultures. Adenosine receptors (ARs) were assessed by reverse transcriptase polymerase chain reaction (RT-PCR). Cellular uptake of [3H] adenosine was measured with or without the inhibitor, nitrobenzylthioinosine (NBTI). Cell death was assessed by cell counting and DNA laddering following selective receptor stimulation, or after modulating adenosine metabolism with adenosine deaminase (ADA) or adenosine kinase (AK) inhibitors [erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and Iodotubericidin (Itub)], or with homocysteine (HC). Markers of apoptosis were assessed by Western blotting. Cell studies were validated by incubating normal murine knee joints in a medium containing adenosine and metabolic inhibitors. Apoptotic chondrocytes were identified with the TUNEL reaction.Results5′NT activity in STR/ort tibial cartilage increased with development of OA, especially close to OA lesions. Adenosine induced MC615 cell death in the presence of ADA inhibition (100μM EHNA), or 1mM HC, or both. Adenosine uptake, mediated by NBTI-sensitive adenosine transporters, was required for cell death. ARs were expressed (A2b>A2a>A1) but were not involved in mediating cell death. Cell death involved the activation of caspase-3 and DNA fragmentation and was prevented by inhibiting caspase activity. However, neither caspase-8 nor caspase-9 was detected. Adenosine+EHNA induced chondrocyte apoptosis in normal murine knee joints.ConclusionIncreased adenosine production may induce chondrocyte apoptosis and play a role in OA in STR/ort mice

ASAP progress and expenditure report for the month of February 1--29, 1996

This is the ASAP progress and expenditure report for the month of February, 1996. The individual projects` report includes the sponsoring organization, the project identification, the principal investigator, long term objectives, short term objectives, accomplishments this reporting period, identification of issues or concerns, project budget estimate for the fiscal year, and monthly actual and year to date expenditures. The research project concerns a joint US/UK program to develop a high-priority radar system based on real aperture and synthetic aperature radar. Topics being researched include airborne RAR/SAR; radar data processor; ground-based SAR signal processing workstation; static airborne radar; radar field experiments; data analysis and detection theory; program management; modeling and analysis; UCSB wave tank; stratified wave tank; and experiments in a thermo-stratified tank at the Institute of Applied Physics, Russia

The New Political History

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66569/2/10.1177_000276427702100204.pd

Search for supersymmetry with a dominant R-parity violating LQDbar couplings in e+e- collisions at centre-of-mass energies of 130GeV to 172 GeV

A search for pair-production of supersymmetric particles under the assumption that R-parity is violated via a dominant LQDbar coupling has been performed using the data collected by ALEPH at centre-of-mass energies of 130-172 GeV. The observed candidate events in the data are in agreement with the Standard Model expectation. This result is translated into lower limits on the masses of charginos, neutralinos, sleptons, sneutrinos and squarks. For instance, for m_0=500 GeV/c^2 and tan(beta)=sqrt(2) charginos with masses smaller than 81 GeV/c^2 and neutralinos with masses smaller than 29 GeV/c^2 are excluded at the 95% confidence level for any generation structure of the LQDbar coupling.Comment: 32 pages, 30 figure

Climatic significance of the marginalization of Scots pine (Pinus sylvestris L.) c. 2500 BC at White Moss, south Cheshire, UK

Subfossil wood from White Moss, south Cheshire, has become the focus of palaeoenvironmental research employing not only conventional coring, pollen analysis, radiocarbon dating and dendrochronology on pine and oak, but also the exhumation of in situ peat areas and dendroecology of the pine ring-width records. Initial dendrochronological research at the site yielded five pine chronologies dating from 3520 to 2462 cal. BC. These and other data indicate three episodes of pine colonization of the mire in the period between 3643 and 1740 cal. BC. Comparison of the pollen and spore records suggest that pine became marginalized at the site c. 2500 cal. BC after successive episodes of increased wetness, and this may represent a staged response to climatic deterioration. Two oak chronologies were dated by reference to the Belfast and to English oak master chronologies to 3228-2898 BC and 2190-1891 BC, respectively, showing the possible co-existence of pine and oak on the mire for part of the time. Further dendrochronological work on subfossil pine at the site resulted in a chronology (WM4) that was cross-matched with pine from elsewhere in England, and subsequently dated absolutely to 2881-2559 BC. Detailed dendroecological information, such as fire episodes and periods of environmental stress indicated in the tree-ring records, have been assigned, precisely and accurately, to calendar years in prehistory. The detailed data show the potential for both dendroecological and wider palaeoclimatic and palaeoenvironmental information that may become available from prehistoric bog-pine chronologies, which might then permit precise correlation and comparisons of proxy-climate data between sites

Best practices for managing large CryoEM facilities

Microscopic imaging and technolog

The size of juxtaluminal hypoechoic area in ultrasound images of asymptomatic carotid plaques predicts the occurrence of stroke

Objective: To test the hypothesis that the size of a juxtaluminal black (hypoechoic) area (JBA) in ultrasound images of asymptomatic carotid artery plaques predicts future ipsilateral ischemic stroke. Methods: A JBA was defined as an area of pixels with a grayscale value <25 adjacent to the lumen without a visible echogenic cap after image normalization. The size of a JBA was measured in the carotid plaque images of 1121 patients with asymptomatic carotid stenosis 50% to 99% in relation to the bulb (Asymptomatic Carotid Stenosis and Risk of Stroke study); the patients were followed for up to 8 years. Results: The JBA had a linear association with future stroke rate. The area under the receiver-operating characteristic curve was 0.816. Using Kaplan-Meier curves, the mean annual stroke rate was 0.4% in 706 patients with a JBA <4 mm 2, 1.4% in 171 patients with a JBA 4 to 8 mm2, 3.2% in 46 patients with a JBA 8 to 10 mm2, and 5% in 198 patients with a JBA >10 mm2 (P <.001). In a Cox model with ipsilateral ischemic events (amaurosis fugax, transient ischemic attack [TIA], or stroke) as the dependent variable, the JBA (<4 mm2, 4-8 mm2, >8 mm2) was still significant after adjusting for other plaque features known to be associated with increased risk, including stenosis, grayscale median, presence of discrete white areas without acoustic shadowing indicating neovascularization, plaque area, and history of contralateral TIA or stroke. Plaque area and grayscale median were not significant. Using the significant variables (stenosis, discrete white areas without acoustic shadowing, JBA, and history of contralateral TIA or stroke), this model predicted the annual risk of stroke for each patient (range, 0.1%-10.0%). The average annual stroke risk was <1% in 734 patients, 1% to 1.9% in 94 patients, 2% to 3.9% in 134 patients, 4% to 5.9% in 125 patients, and 6% to 10% in 34 patients. Conclusions: The size of a JBA is linearly related to the risk of stroke and can be used in risk stratification models. These findings need to be confirmed in future prospective studies or in the medical arm of randomized controlled studies in the presence of optimal medical therapy. In the meantime, the JBA may be used to select asymptomatic patients at high stroke risk for carotid endarterectomy and spare patients at low risk from an unnecessary operation