DIFFERENCES IN GROWTH AND PHYSIOLOGY OF MARINE SYNECHOCOCCUS (CYANOBACTERIA) ON NITRATE VERSUS AMMONIUM ARE NOT DETERMINED SOLELY BY NITROGEN SOURCE REDOX STATE(1).

The preference of phytoplankton for ammonium over nitrate has traditionally been explained by the greater metabolic cost of reducing oxidized forms of nitrogen. This "metabolic cost hypothesis" implies that there should be a growth disadvantage on nitrate compared to ammonium or other forms of reduced nitrogen such as urea, especially when light limits growth, but in a variety of phytoplankton taxa, this predicted difference has not been observed. Our experiments with three strains of marine Synechococcus (WH7803, WH7805, and WH8112) did not reveal consistently faster growth (cell division) on ammonium or urea as compared to nitrate. Urease and glutamine synthetase (GS) activities varied with nitrogen source in a manner consistent with regulation by cellular nitrogen status via NtcA (rather than by external availability of nitrogen) in all three strains and indicated that each strain experienced some degree of nitrogen insufficiency during growth on nitrate. At light intensities that strongly limited growth, the composition (carbon, nitrogen, and pigment quotas) of WH7805 cells using nitrate was indistinguishable from that of cells using ammonium, but at saturating light intensities, cellular carbon, nitrogen, and pigment quotas were significantly lower in cells using nitrate than ammonium. These and similar results from other phytoplankton taxa suggest that a limitation in some step of nitrate uptake or assimilation, rather than the extra cost of reducing nitrate per se, may be the cause of differences in growth and physiology between cells using nitrate and ammonium.

First-in-class pan caspase inhibitor developed for the treatment of liver disease.

A series of oxamyl dipeptides were optimized for pan caspase inhibition, anti-apoptotic cellular activity and in vivo efficacy. This structure-activity relationship study focused on the P4 oxamides and warhead moieties. Primarily on the basis of in vitro data, inhibitors were selected for study in a murine model of alpha-Fas-induced liver injury. IDN-6556 (1) was further profiled in additional in vivo models and pharmacokinetic studies. This first-in-class caspase inhibitor is now the subject of two Phase II clinical trials, evaluating its safety and efficacy for use in liver disease.

On the quantitative theory of reproductive effort in clonal plants: Refinements of theory, with evidence from goldenrods and mayapples.

Recently I proposed a quantitative theory which predicts the partition of resources between vegetative growth and seed production in highly rhizomatous clonal plants (Armstrong 1982, 1983). My basic premise was that this partition should be controlled by basic geometric properties of clonal growth. My conclusions were that the ratio of resources expended on seeds and rhizomes should be relatively constant in time and space, and that the value of this ratio should be predictable from a knowledge of the allometric relationships among certain morphological characters.In the present paper I first refine this theory to yield explicit ramet-level predictions directly applicable to clonal species with densely-packed canopies. These predictions are then tested using observations on goldenrods (Solidago altissima) and mayapples (Podophyllum peltatum). In the Solidago studies, the ratio of infructescence weight to total rhizome weight was found to be asymptotically constant for the larger ramets in a clone, confirming an important prediction of the theory. A second prediction of the theory, that the ratio of infructescence weight to total rhizome weight should be constant across clones, was not confirmed using the goldenrod data. This observation may simply be due to measurement biases. An alternative hypothesis is that the prediction of this theory constitute an r-limit strategy, and so are applicable only in the limit of density independent growth. Data from Sohn and Policansky (1977) on mayapples support this latter interpretation.