Acidic Nonsteroidal Anti-inflammatory Drugs Inhibit Rat Brain Fatty Acid Amide Hydrolase in a pH-dependent Manner

Previous studies have demonstrated that fatty acid amide hydrolase, the enzyme responsible for the metabolism of anandamide, is inhibited by the acidic non-steroidal anti-inflammatory drug (NSAID) ibuprofen with a potency that increases as the assay pH is reduced. Here we show that (R) -, (S) - and (R, S) -flurbiprofen, indomethacin and niflumic acid show similar pH-dependent shifts in potency to that seen with ibuprofen. Thus, (S) -flurbiprofen inhibited 2 μM [3 H]anandamide metabolism with IC 50 values of 13 and 50 μM at assay pH values of 6 and 8, respectively. In contrast, the neutral compound celecoxib was a weak fatty acid amide hydrolase inhibitor and showed no pH dependency (IC 50 values ~300 μM at both assay pH). The cyclooxygenase-2-selective inhibitors nimesulide and SC-58125 did not inhibit fatty acid amide hydrolase activity at either pH. The data are consistent with the conclusion that the non-ionised forms of the acidic NSAIDs are responsible for the inhibition of fatty acid amide hydrolase.     

Theoretical models of species' borders: single species approaches

The range of potential mechanisms limiting species' distributions in space is nearly as varied and complex as the diversity of life itself. Yet viewed abstractly, a species' border is a geographic manifestation of a species' demographic responses to a spatially and temporally varying world. Population dynamic models provide insight into the different routes by which range limits can arise owing to gradients in demographic rates. In a metapopulation context, for example, range limits may be caused by gradients in extinction rates, colonization rates or habitat availability. We have consider invasion models in uniform and heterogeneous environments as a framework for understanding non-equilibrium range limits, and explore conditions under which invasions may cease to spread leaving behind a stationary range limit. We conclude that non-equilibrial range dynamics need further theoretical and empirical attention.     

Intestinal proteases of free-living and parasitic astigmatid mites

Among arthropod pests, mites are responsible for considerable damage to crops, humans and other animals. However, detailed physiological data on these organisms remain sparse, mainly because of their small size but possibly also because of their extreme diversity. Focusing on intestinal proteases, we draw together information from three distinct mite species that all feed on skin but have separately adapted to a free-living, a strictly ecto-parasitic and a parasitic lifestyle. A wide range of studies involving immunohistology, molecular biology, X-ray crystallography and enzyme biochemistry of mite gut proteases suggests that these creatures have diverged considerably as house dust mites, sheep scab mites and scabies mites. Each species has evolved a particular variation of a presumably ancestral repertoire of digestive enzymes that have become specifically adapted to their individual environmental requirements.     

Unfolded phosphopolypeptides enable soft and hard tissues to coexist in the same organism with relative ease

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Highlights? Some unfolded phosphoproteins form stable complexes with amorphous calcium phosphate. ? Stable complexes require ≥3 phosphorylated residues within a short sub-sequence. ? Soft and hard tissues can co-exist in the same organism because of these complexes.     

Introducing a new staircase design to quantify healthy knee function during stair ascent and descent

The design, manufacture and validation of a new free standing staircase for motion analysis measurements are described in this paper. The errors in vertical force measurements introduced when the stairs interface with a force plate (FP) are less than 0.6%. The centre of pressure error introduced is less than 0.7 mm compared to the error from the FP. The challenges of introducing stair gait into a clinical trial with a limited number of FPs and time limitations for assessment sessions are addressed by introducing this cost effective solution.

The staircase was used in a study to measure non-pathological knee function of 10 subjects performing stair ascent and descent. The resulting knee kinematics and knee joint moments are in agreement with previous studies. The kinematic and joint moment profiles provide a normative range, which will be useful in future studies for identifying alterations in joint function associated with pathology and intervention.