Different ecological conditions support individual specialization in closely related,ecologically similar species

Individual generalist predators often have more specialized diets than their populations do. Individual specialization (IS) is influenced by ecological opportunity, intraspecific competition, and interspecific competition, although the effects of these parameters are inconsistent across studies. We investigated IS in five species of frogs and toads, Anaxyrus americanus, A. fowleri, Lithobates catesbeianus, L. clamitans, and L. sphenocephalus. We used the natural history and ecology of each species to predict which parameters would influence IS. Our predictions were supported for some species but not others. We predicted IS would be positively influenced by resource diversity in all species, but this prediction held for only three species, with the relationship significant in A. fowleri and L. catesbeianus and marginally significant in A. americanus. We also predicted that interspecific competition would have a negative relationship with IS in L. clamitans because L. catesbeianus is competitively superior to L. clamitans and likely to suppress its foraging options. This prediction was upheld. Finally, we predicted that IS in A. americanus, A. fowleri, and L. clamitans would be influenced by intraspecific competition. However, IS was not influenced by intraspecific competition in any species, a surprising result given that intraspecific competition has traditionally been assumed to be the ecological parameter with the strongest effects on IS. Many previous studies did not simultaneously consider all three ecological parameters, which may have increased the apparent importance of intraspecific competition for IS. Our results revealed that the ecological parameters affected IS differently even across closely related and ecologically similar species, and demonstrated that these differences are sometimes predictable based on natural history. This study also suggests that sympatric ecological speciation based on IS may be rare because the ecological parameters driving IS are inconsistent across species, and the strength of their effects on intraspecific diet variation varies in space.     

Electrophysiology of the marine diatom Coscinodiscus wailesii IV: types of non-linear current-voltage-time relationships recorded with single saw-tooth voltage-clamp experiments

Electrophysiological states of the marine diatom Coscinodiscus wailesii are known to change spontaneously in the temporal range of seconds. In order to assess the genuine current-voltage-time relationships of individual states in less than a second, voltage-clamp experiments have been carried out using single sweeps of saw-tooth shaped command voltages. This method is introduced with model calculations. Plotting the results in current-voltage coordinates provides convenient access to several electrophysiological entities, such as absence of drift (smoothly closed IV loops), membrane capacitance (by I jump at sign reversal of dV/dt), and ohmic conductances (in linear regions of the current-voltage relationship), as well as equilibrium voltage (internal intersection of capacitance-corrected, 8-shaped tracings) and coarse gating kinetics (rise or fall of capacitance-corrected I at sign reversal of dV/dt) of a voltage-sensitive ion conductance. From electrophysiological measurements with double-barreled glass-microelectrodes on C. wailesii, several distinct types of current-voltage loops are presented. Most of the data, including recordings from electrical excitation, can be interpreted as temporal relaxations of voltage-sensitive conductances for K⁺ and Cl⁻. A more detailed analysis of the effect of tetraethylammonium (TEA⁺) shows that 10 and 20 mM TEA⁺ inhibit the K⁺ conductance in C. wailesii only by up to about 20% but predominantly via a K⁺ outward rectifier. Received: 23 December 1998 / Revised version: 1 June 1999 / Accepted: 1 June 1999     

The discovery of rofecoxib, [MK 966, Vioxx, 4-(4'-methylsulfonylphenyl)-3-phenyl-2(5H)-furanone], an orally active cyclooxygenase-2-inhibitor.

The development of a COX-2 inhibitor rofecoxib (MK 966, Vioxx) is described. It is essentially equipotent to indomethacin both in vitro and in vivo but without the ulcerogenic side effect due to COX-1 inhibition.     

Biologic Response to Peripheral and Central Administration of Recombinant Human Leptin in Dogs

LEBEL, CARL, AMY BOURDEAU, DAVID LAU, AND PAMELA HUNT. Biologic response to peripheral and central administration of recombinant human leptin in dogs. Obes Res. Objective: Because leptin is believed to act within the central nervous system, the objective of this study was to test that presumption by comparing the biologic responses to recombinant human leptin (rHuLeptin) when delivered either subcutaneously or intrathecally in a large animal species, the beagle dog. Methods and Procedures: Adult beagle dogs were used for all studies (n = 3 to 14). Treatment with rHuLeptin was either as daily subcutaneous or intermittent intrathecal injections. Results: Subcutaneously administered rHuLeptin was absorbed with peak concentrations appearing at 2 to 4 hours. After intrathecal administration, cerebral spinal fluid concentrations declined in a bi-phasic manner with a terminal half-life of ?6 to 8 hours. When lean beagles were given leptin subcutaneously, at 0. 05 to 5 gkglday for up to 6 months, reductions in body weight (up to 30%) and food intake (up to 75%) were observed. Body fat loss was observed in both lean and obese dogs, and confirmed by dual energy X-ray absorptiometry and histology of adipose tissue. When rHuleptin was delivered intrathecally at 4 to 1000 μg/dose for up to 3 months, the primary effects observed were reductions in body weight and food intake. In general all findings reported in the intrathecal studies were consistent with those noted in the subcutaneous studies; however, the required intrathecal dose was substantially lower than that for subcutaneous delivery. Discussion: These studies demonstrate that both subcutaneous and intrathecal treatment of rHuLeptin was associated with effects on body weight, food intake, and body fat in dogs. These results support the concept that the central nervous system is the probable primary site of action for leptin and suggest that rHuLeptin has similar physiologic activities that influence body weight, body fat, and metabolism in large animals to those reported previously in rodents.     

Expansion of Bacteriophages Is Linked to Aggravated Intestinal Inflammation and Colitis

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Rational design, synthesis and structure-activity relationships of a cyclic succinate series of TNF-alpha converting enzyme inhibitors. Part 2: lead optimization

Modifications of the lead TACE inhibitor 1 (N-hydroxy-trans-2-[[4-(4-quinolinyloxymethyl)anilinyl]carbonyl]-1-cyclohexanecarboxamide) at the cyclohexyl ring and the quinoline moiety led to the identification of a series of piperidine containing TACE inhibitors with potent activity in the inhibition of TNF-alpha release in the whole blood assay (WBA). The most potent analogue IM491 [N-hydroxy-(5S,6S)-1-methyl-6-[[4-(2-methyl-4-quinolinylmethoxy)anilinyl]carbonyl]-5-piperidinecarboxamide] exhibited an IC(50) value of 20 nM in WBA with excellent selectivity over MMP-1, -2 and -9 and is orally bioavailable with an F value of 43% in beagle dogs.