Growth regulation by GTP. Regulation of nucleotide pools in Neurospora by nitrogen and sulfur control systems.

Purine nucleotide pools in the fungus Neurospora crassa decline in response to carbon, nitrogen, or sulfur deprivation. There is, in addition, a decline in GTP/ATP ratios on nitrogen or sulfur deprivation in wild type. The GTP/ATP decline is missing on nitrogen deprivation of the nitrogen control mutant, nit-2, and on sulfur deprivation of the sulfur control mutant, cys-3. The nit-2 mutant also shows elevated UTP pools on nitrogen deprivation when compared with similarly treated wild type. Six-hour sulfur-deprived cys-3 shows multiple aberrations in nucleotide pools when compared with similarly treated wild type. These include very low energy charge and depletion of pools of most nucleotides. ATP in sulfur-deprived cys-3 drops by about 88%. Sulfur-deprived cys-3 is also greatly impaired in comparison with wild type in its ability to resume growth when restored to nutritional sufficiency after a period of sulfur deprivation. These results clearly demonstrate that the nitrogen (nit-2) and sulfur (cys-3 regulatory systems are not limited to control of catabolism of exogenous nitrogen and sulfur sources, respectively, but rather influence, a broader range of cellular properties than has been previously thought. The pattern of GTP pool control is consistent with a positive role for GTP in growth control. Evidence in other systems supporting such a growth-regulating role for GTP is discussed.

Regulation of lactate/pyruvate ratios by cyclic AMP in Neurospora crassa.

Cyclic AMP is thought to have a general role in stimulating the breakdown of carbohydrate reserves and subsequent glycolytic activity. This would be expected to increase the availability of reducing equivalents in the form of cytoplasmic NADH. The current study examines another potential reaction controlling cytoplasmic NADH in the fungus Neurospora crassa, that of lactate dehydrogenase, to determine whether it is also regulated by cyclic AMP. The cr-1, adenylate cyclase and cyclic AMP-deficient mutant, grown with and without exogenous cyclic AMP was compared with an isogenic wild type. The results show that cyclic AMP raises pyruvic acid pools and lowers both lactic acid pools and lactate/pyruvate ratios. It does that, in part or in whole, by lowering lactate dehydrogenase activity. The possibility that cytoplasmic NAD+/NADH is a major target of cyclic AMP control is discussed. The high performance liquid chromatography procedures used in these studies are applicable to the measurement of intracellular pools of tricarboxylic acid cycle and other organic acids.

Experimental evaluation of an interactive information processing aid for an emergency poison center.

In the recent literature, many studies have addressed the evaluation of the user interface in interactive systems. However, there are few theoretically based methodologies for this purpose. This study is an attempt to develop a methodology for examining the complex division of information processing labor between user and computer. A special concern was the computer-naive user searching for information using a self-teaching system. Our test bed was an emergency poison information center whose functioning depended on fast, accurate processing of patient and antidote data by a nurse. We augmented the nurses' traditional information support--a manual card file and reference books--with an interactive software system which summarized and suggested inferences from data on past successful treatment of patients. Analysis of recordings of user comments and user-system interactions showed that: (1) the support system should be more robust and have more "reasoning" power; and (2) the users' expressed information needs changed after the new support was introduced. From the results, we abstracted elements of an effective naive user-support system division of labor: (1) the support system should "actively" help the user's error recovery; (2) the system should have a sufficient knowledge base to allow "intelligent" conversation about the problem domain; and (3) the support system should allow the user to reconceptualize his information problem as his environment changes. Our method of recording user-system interactions and verbal protocols was time consuming, but did yield significant insight into the user-system division of labor. Also, considering the poison center as a living system, analysis of processing by the nurse and the traditional, the new, or an envisioned information support system showed that a highly dispersed associator and effective internal transducer promoted the functioning of the entire group.