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Fatigue from voluntary muscular effort is a complex phenomenon involving the central nervous system (CNS) and muscle. An understanding of the mechanisms within muscle that cause fatigue has led to the development of nutritional strategies to enhance performance. Until recently, little was known about CNS mechanisms of fatigue, even though the inability or unwillingness to generate and maintain central activation of muscle is the most likely explanation of fatigue for most people during normal daily activities. A possible role of nutrition in central fatigue is receiving more attention with the development of theories that provide a clue to its biological mechanisms. The focus is on the neurotransmitter serotonin [5-hydroxytryptamine (5-HT)] because of its role in depression, sensory perception, sleepiness, and mood. Nutritional strategies have been designed to alter the metabolism of brain 5-HT by affecting the availability of its amino acid precursor. Increases in brain 5-HT concentration and overall activity have been associated with increased physical and perhaps mental fatigue during endurance exercise. Carbohydrate (CHO) or branched-chain amino acid (BCAA) feedings may attenuate increases in 5-HT and improve performance. However, it is difficult to distinguish between the effects of CHO on the brain and those on the muscles themselves, and most studies involving BCAA show no performance benefits. It appears that important relations exist between brain 5-HT and central fatigue. Good theoretical rationale and data exist to support a beneficial role of CHO and BCAA on brain 5-HT and central fatigue, but the strength of evidence is presently weak.

Phosphopeptides (PPs) isolated from highly purified calf thymus DNA (N-DNA) and extracted from calf thymus nuclei were fractionated, and the effect of one PP fraction on DNA replication has been examined. In the absence of inhibitors, the increasing PP concentration caused a linear decrease of 3H-thymidine uptake in L5178Y cells. If PP fraction was mildly hydrolysed with 1NHCl, the decrease in uptake was much steeper. The studies in which the inhibitors were used revealed that by the addition of the unhydrolysed PP fraction the inhibition of 3H-thymidine uptake by alpha-amanitin could be completely overcome, and that the inhibition by puromycin was reduced to 65-77% of the control. With puromycin, there was a gradual decrease of 3H-thymidine uptake with PP concentration above 3 mg/ml. The PPs gave an increase in incorporation of 3H-thymidine even after removal of alpha-amanitin and puromycin; thus, it is suggested that there is no direct interaction of either inhibitor with PP in the cell. Data on the utilization of 3H-cytidine for the synthesise of new DNA suggest that PP fraction might cause an acceleration of DNA replication.

1. Aqueous solutions of tobacco mosaic virus were found to undergo a number of spontaneous changes on standing in the cold. The results of pH measurements, acid and base titrations, intrinsic viscosity determinations, studies on the irreversible binding of methylene blue with the virus, ultraviolet absorption, and the extent of nucleic acid splitting by heat denaturation indicated the occurrence of two successive reactions, the first one causing the release of hydrogen ions and a greater lability of the nucleic acid, and the second one, which involved end-to-end dimerization and which took place after 8 days of standing, requiring hydrogen ions. 2. The first over-all reaction was found to be a mixture of various types of reversible disaggregation and aggregation reactions, the nature of which depended on the pretreatment, the TMV concentration, the time of standing, and the phosphate concentration. For longer times of standing at high protein concentration a sudden drop in ultraviolet absorption is noted after dilution; also the drops in viscosity and pH are largest with a steep rise following, indicating the greatest breakup of end-to-end aggregates with formation of the side-to-side type. For concentrated solutions of TMV in water which have not stood long no drop in ultraviolet absorption is noted on dilution; the decrease in the other quantities is less, indicating that only a less extensive breakdown of end-to-end aggregates occurs. Addition of phosphate to concentrated solutions of TMV causes formation of side-to-side aggregates which break up on dilution. 3. Using the results for the pH increase and the viscosity increase in a given time interval for a given TMV preparation and also the slope of the corresponding titration curve at the pH mean, a value for the number of hydrogen ions taken up per TMV monomer in the formation of the end-to-end dimer was finally calculated. The average result obtained for two preparations was 3300. 4. Methylene blue, in the polymeric form, was demonstrated to cause complete irreversible conversion of TMV monomers to end-to-end dimers. At dye concentrations above 10(-4)M, higher TMV polymers are formed, but these are broken down to dimers on removal of free dye by dialysis. The irreversible binding ratios were shown to be decreased in accordance with the extent of the end-to-end aggregation of the preparation at the time of the experiment, which is in agreement with the concept that the irreversibly bound dye polymers go into the junction formed between two interacting TMV monomers. On the basis that only the monomers initially present in solution can react, maximum binding ratios corresponding to complete conversion of monomers to dimers were calculated from the observed irreversible binding ratios and from the fraction of dimers initially present which was obtained from viscosity data. The average result for three preparations in different states of aggregation was calculated to be 6565 for tetrameric binding or 3230 for dimeric binding, which agrees closely with the result obtained for the uptake of hydrogen ions per TMV monomer in the spontaneous dimerization.