The effect of oxygen tension on calcium homeostasis in bovine articular chondrocytes.

BACKGROUND: Articular chondrocytes normally experience a lower O2 tension compared to that seen by many other tissues. This level may fall further in joint disease. Ionic homeostasis is essential for chondrocyte function but, at least in the case of H+ ions, it is sensitive to changes in O2 levels. Ca2+ homeostasis is also critical but the effect of changes in O2 tension has not been investigated on this parameter. Here we define the effect of hypoxia on Ca2+ homeostasis in bovine articular chondrocytes. METHODS: Chondrocytes from articular cartilage slices were isolated enzymatically using collagenase. Cytoplasmic Ca2+ levels ([Ca2+]i) were followed fluorimetrically using Fura-2 to determine the effect of changes in O2 tension. The effects of ion substitution (replacing extracellular Na+ with NMDG+ and chelating Ca2+ with EGTA) were tested. Levels of reactive oxygen species (ROS) and the mitochondrial membrane potential were measured and correlated with [Ca2+]i. RESULTS: A reduction in O2 tension from 20% to 1% for 16-18 h caused [Ca2+]i to approximately double, reaching 105 +/- 23 nM (p < 0.001). Ion substitutions indicated that Na+/Ca2+ exchange activity was not inhibited at low O2 levels. At 1% O2, ROS levels fell and mitochondria depolarised. Restoring ROS levels (with an oxidant H2O2, a non-specific ROS generator Co2+ or the mitochondrial complex II inhibitor antimycin A) concomitantly reduced [Ca2+]i. CONCLUSIONS: O2 tension exerts a significant effect on [Ca2+]i. The proposed mechanism involves ROS from mitochondria. Findings emphasise the importance of using realistic O2 tensions when studying the physiology and pathology of articular cartilage and the potential interactions between O2, ROS and Ca2+.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

How benign is sickle cell trait?

This is the final version of the article. It first appeared from Elsevier at http://dx.doi.org/10.1016/j.ebiom.2016.08.023

Lipid metabolism in terminal erythropoiesis.

In this issue of Blood, Huang et al have provided evidence that altered lipid metabolism is critical for terminal erythropoiesis. A key role is proposed for the PHOSPHO1 gene product, a phosphocholine phosphatase. PHOSPHO1 knockouts (KOs) showed reduced erythroblast proliferation and enucleation in both mice and human erythroid tissues, apparently through energy depletion mediated via inhibition of oxidative phosphorylation of fatty acids and reduced adenosine triphosphate (ATP) production in late glycolysis. This work emphasizes that altered expression of genes involving lipid metabolism are important during late red cell maturation

A Class of Predictive Adaptive Controls

A new class of control systems termed predictive adaptive controls is developed and the performance characteristics are investigated analytically and experimentally. The concepts of signal prediction, interval control, and synthesis of the control variable by a sum of orthonormal polynomials in t are introduced and developed in relation to adaptive control. A modified least squares integral index of performance is formulated and used as the criterion for system optimization. Control of dynamic processes is subdivided into intervals of a specified length T and prediction is used to obtain estimates of future values of system error. Minimization of the index of performance leads to a family of control laws which specify the structure of the controller. The resulting control configuration is optimum in a specific mathematical sense and is readily realizable with available physical components. The adaptive capability is achieved through time-varying gains which are specific functions of the unit impulse response of the dynamic process being controlled. Predictor design is presented in terms of the classical Wiener-Lee theory, and a relationship for control interval length as a function of prediction accuracy is developed. Preliminary design of the controller is considered from the viewpoints of relative weighting of system error and control effort, control interval length T, and the number of terms needed In the orthonormal polynomial sum approximation of the control variable. A method of obtaining an engineering estimate of the latter quantity is developed and 11 lustrated by three examples, two of which are investigated experimentally. Two applications of predictive adaptive control are investigated on an analog computer. The two dynamic processes used are a first-order process whose parameter varies over a range of ten to one and a second-order process whose parameter varies in such a manner that the process is unstable at one extremum and heavily damped at the other. The results of three basic experiments which evaluate the steady-state adaptability transient response, and statistical signal response of the two systems are reported. It is found that all three aspects of system performance improve with decreasing control interval length, but that the minimum value of the interval length which can be used is limited by the accuracy of the time-varying gain and controller circuitry. Improved performance which can be achieved by increasing the relative weighting of System error and control effort, is limited by saturation considerations. Theoretical, results that .point to the need., for keeping the control interval length short to preserve stability, prediction accuracy, and loss of control doe to process parameter drift are substantiated by the experimental results. For the two systems investigated it is found that satisfactory control Is achieved If the interval length is chosen so that process parameter drift Is no more than 4% per control interval, A figure of 5% was estimated originally, : A one-term approximation of the control variable is used to control .the first-order process- and Is found to give satisfactory performance. A four-term approximation Is found to give adequate control of the second- order process whereas the three-term approximation does not. These results bear out the predictions made in the-theoretical analyses

The Enrichment History of Hot Gas in Poor Galaxy Groups

We have analyzed the ASCA SIS and GIS data for seventeen groups and determined the average temperature and abundance of the hot x-ray emitting gas. For groups with gas temperatures less than 1.5 keV we find that the abundance is correlated with the gas temperature and luminosity. We have also determined the abundance of the alpha-elements and iron independently for those groups with sufficient counts. We find that for the cool groups (i.e. kT <1.5 keV) the ratio of alpha-elements to iron is ~1, about half that seen in clusters. Spectral fits with the S, Si and Fe abundances allowed to vary separately suggest the S/Fe ratio is similar to that seen in clusters while the Si/Fe ratio in groups is half the value determined for richer systems. The mass of metals per unit blue luminosity drops rapidly in groups as the temperature drops. There are two possible explanations for this decrease. One is that the star formation in groups is very different from that in rich clusters. The other explanation is that groups lose much of their enriched material via winds during the early evolution of ellipticals. If the latter is true, we find that poor groups will have contributed significantly (roughly 1/3 of the metals) to the enrichment of the intergalactic medium.Comment: 19 Pages with 2 figures, Accepted for publication in the Astrophysical Journa

The Spectroscopic Age of 47 Tuc

High signal-to-noise integrated spectra of the metal-rich globular cluster 47 Tuc, spanning the H-gamma(HR) and Fe4668 line indices, have been obtained. The combination of these indices has been suggested (Jones & Worthey 1995, ApJ, 446, L31) as the best available mechanism for cleanly separating the age-metallicity degeneracy which hampers the dating of distant, unresolved, elliptical galaxies. For the first time, we apply this technique to a nearby spheroidal system, 47 Tuc, for which independent ages, based upon more established methods, exist. Such an independent test of the technique's suitability has not been attempted before, but is an essential one before its application to more distant, unresolved, stellar populations can be considered valid. Because of its weak series of Balmer lines, relative to model spectra, our results imply a spectroscopic ``age'' for 47 Tuc well in excess of 20 Gyr, at odds with the colour-magnitude diagram age of 14+/-1 Gyr. The derived metal abundance, however, is consistent with the known value. Emission ``fill-in'' of the H-gamma line as the source of the discrepancy cannot be entirely excluded by existing data, although the observational constraints are restrictive.Comment: 17 pages, 4 figures, LaTeX, accepted for publication in The Astronomical Journal, also available at http://casa.colorado.edu/~bgibson/publications.htm

Priorities and Principles for Investment in Aquaculture Research by NSW Department of Primary Industries

This review examined the characteristics of the main aquaculture industries in NSW with respect to current impediments to growth, market development and future opportunities. Within this context, it examined the nature, funding and impacts of the NSW Department of Primary Industries’ current and proposed investments in aquaculture R&D and industry development, as well as its alignment with DPI and industry priorities.aquaculture, research evaluation, public good, Agribusiness, Livestock Production/Industries, Research and Development/Tech Change/Emerging Technologies, Q160,

The evolution of the natural killer complex; a comparison between mammals using new high-quality genome assemblies and targeted annotation.

Natural killer (NK) cells are a diverse population of lymphocytes with a range of biological roles including essential immune functions. NK cell diversity is in part created by the differential expression of cell surface receptors which modulate activation and function, including multiple subfamilies of C-type lectin receptors encoded within the NK complex (NKC). Little is known about the gene content of the NKC beyond rodent and primate lineages, other than it appears to be extremely variable between mammalian groups. We compared the NKC structure between mammalian species using new high-quality draft genome assemblies for cattle and goat; re-annotated sheep, pig, and horse genome assemblies; and the published human, rat, and mouse lemur NKC. The major NKC genes are largely in the equivalent positions in all eight species, with significant independent expansions and deletions between species, allowing us to propose a model for NKC evolution during mammalian radiation. The ruminant species, cattle and goats, have independently evolved a second KLRC locus flanked by KLRA and KLRJ, and a novel KLRH-like gene has acquired an activating tail. This novel gene has duplicated several times within cattle, while other activating receptor genes have been selectively disrupted. Targeted genome enrichment in cattle identified varying levels of allelic polymorphism between the NKC genes concentrated in the predicted extracellular ligand-binding domains. This novel recombination and allelic polymorphism is consistent with NKC evolution under balancing selection, suggesting that this diversity influences individual immune responses and may impact on differential outcomes of pathogen infection and vaccination