Freshwater mussels are declining globally, and effective conservation requires prioritizing research and actions to identify and mitigate threats impacting mussel species. Conservation priorities vary widely, ranging from preventing imminent extinction to maintaining abundant populations. Here, we develop a portfolio of priority research topics for freshwater mussel conservation assessment. To address these topics, we group research priorities into two categories: intrinsic or extrinsic factors. Intrinsic factors are indicators of organismal or population status, while extrinsic factors encompass environmental variables and threats. An understanding of intrinsic factors is useful in monitoring, and of extrinsic factors are important to understand ongoing and potential impacts on conservation status. This dual approach can guide conservation status assessments prior to the establishment of priority species and implementation of conservation management actions.

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The pharmacokinetics and pharmacodynamics of oral S-1, a dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine, were compared with those of protracted venous infusion (PVI) of 5-fluorouracil (5-FU). In all, 10 patients with gastric cancer received PVI of 5-FU at a dose of 250 mg m À2 day À1 for 5 days. After a washout period of 9 days, the patients received two divided doses daily for 28 days. S-1 was administered orally at about 0900 and 1900 hours. The daily dose of S-1 in terms of tegafur was 80 mg day À1 in patients with a body surface area (BSA) of o1.25 m 2 , 100 mg day À1 in those with a BSA of X1.25 m 2 to o1.5 m 2 , and 120 mg day Continuous protracted intravenous infusion (PVI) of 5-fluorouracil (5-FU) has a higher response rate, less frequent haematologic toxicity (mainly neutropenia), and more frequent hand -foot syndrome (HFS) than bolus injection of 5-FU in patients with metastatic colorectal cancer (The Meta-Analysis Group in Cancer, 1998). Hand -foot syndrome and stomatitis each occur in about 23% of patients given 5-FU by PVI, whereas grade 3 leukopenia develops in only 1%. Most patients who receive 5-FU by PVI have no severe toxicity; the dose-limiting toxicity (DLT) is HFS (Lokich et al, 1989). Previous clinical trials have shown that PVI of 5-FU is one of the most effective and safest regimens. However, PVI requires a central venous catheter as well as an ambulatory pump, which is expensive and may lead to complications, and adversely affect patients' quality of life. Oral fluoropyrimidine derivatives have been developed to circumvent the problems associated with PVI of 5-FU. S-1 is one such derivative that combines tegafur with two modulators of 5-FU metabolism, 5-chloro-2,4-dihydroxypyridine (CDHP), a reversible inhibitor of dihydropyrimidine dehydrogenase (DPD), and potassium oxonate, in a molar ratio of 1 : 0.4 : 1. Tegafur, an oral prodrug of 5-FU, is gradually converted to 5-FU and rapidly metabolised by DPD in the liver. The DPD-inhibitory activity of CDHP is 180-fold higher than that of uracil, confirmed to be an effective DPD inhibitor in the form of uracil/tegafur (UFT) in vitro. Potassium oxonate is an orotate phosphoribosyl transferase inhibitor that is distributed primarily to the gastrointestinal tract. This component of S-1 decreases the incorporation of 5-fluorouridine triphosphate into RNA in the gastrointestinal mucosa and reduces the incidence of diarrhoea.F-b-alanine (FBAL) is a main metabolite of 5-FU. F-b-alanine and fluorocitrate are thought to cause the cardiotoxic and neurotoxic effects of 5-FU by inhibiting the tricarboxylic acid cycle (Koenig and Patel, 1970;Okeda et al, 1990;Robben et al, 1993;Diasio, 1998;Kuwata et al, 2000;Kato et al, 2001). The CDHP component of S-1 inhibits DPD, the rate-limiting enzyme in the catabolic pathway of 5-FU. Consequently, the plasma FBAL concentration after oral administration of S-1 is significantly lower than that after PVI of 5-FU. However, information on plasma FBAL concentrations in patients given 5-FU remains scant...

AaSTRACT Sea urchin spermatozoa demembranated with Triton X-100 in the presence of EGTA, termed potentially asymmetric, generate asymmetric bending waves in reactivation solutions containing EGTA. After they are converted to the potentially symmetric condition by extraction with Triton and millimolar Ca ++, they generate symmetric bending waves in reactivation solutions containing EGTA. In the presence of EGTA, their asymmetry can be restored by addition of brain calmodulin or the concentrated supernatant obtained from extraction with Triton and millimolar Ca ++. These extracts contain calmodulin, as assayed by gel electrophoresis, radioimmunassay, activation of brain phosphodiesterase, and Ca++-dependent binding of asymmetry-restoring activity to a trifluorophenothiazine-affinity resin. Conversion to the potentially symmetric condition can also be achieved with trifluoperazine substituted for Triton during the exposure to millimolar Ca ++, which suggests that the calmodulin-binding activity of Triton is important for this conversion.These observations suggest that the conversion to the potentially symmetric condition is the result of removal of some of the axonemal calmodulin and provide additional evidence for axonemal calmodulin as a mediator of the effect of Ca +÷ on the asymmetry of flagellar bending.Extensive evidence that ciliary and flagellar bending is regulated by intracellular calcium concentrations has been obtained, especially from experiments that use demembranated or membrane-permeabilized cilia or flagella to demonstrate the modulation of motility by changing the calcium concentration of the reactivation medium. A role for calmodulin in these responses to calcium has been suggested, principally based on evidence for the presence of calmodulin or calmodulin-like proteins in cilia and flagella (18,20,26,31,33,41,44). Experiments with calmodulin-binding drugs such as trifluoperazine (TFP) j have provided supporting evidence in some systems (37,38,49), but in other systems, these agents appeared to have little or no effect at the micromolar concentrations at which they bind to calmodulin (41). In addition, Verdugo et al. (45) reported an increased effect of calcium on the beat frequency of demembranated cilia of tracheal cells by adding exogenous calmodulin.With sea urchin sperm flagella, the situation is complicated by the observation that the response of demembranated flageUa to calcium depends on the previous exposure of the flagella to calcium (7). Sea urchin spermatozoa demembranated with Triton X-100 in the presence of EGTA have "potentially asymmetric" flagella (15). They swim in circular Abbreviation used in this paper. TFP, trifluoperazine.

To provide river managers and researchers with practical knowledge about fish rehabilitation, various studies of fish habitat rehabilitation that used wood were reviewed. The review focuses on fish responses, wood installation methods, and geomorphic features of the rehabilitation sites. Most studies were conducted in moderately sized (small and medium) streams with relatively high bed gradients and aimed to improve the habitats of salmonid species. In this stream type, structures spanning the full (log dam) and partial (log deflector) width of the river were most common, and wood structures that created pools and covers were successful in improving fish habitat. Some projects were conducted in moderately sized lowgradient streams, in which wooden devices used to create instream cover were effective for fish assemblages. There were few studies in other aquatic ecosystems. However, well-designed large wood structures, known as engineered log jams, were used in rehabilitation projects for large rivers. In slack-water or lentic systems such as sidechannels, estuaries, and reservoirs, small and large wood structures that created cover were used to improve habitat for many fish species. For successful fish habitat rehabilitation projects, the hydrogeomorphic conditions of rehabilitation sites should be carefully examined to avoid physical failure of wood structures. Although artificial wood structures can be used to improve fish habitat in various aquatic ecosystems, they should be considered to be a complementary or interim habitat enhancement technique. The recovery of natural dynamic processes at the watershed scale is the ultimate target of restoration programs.