Muscle performance depends on the supply of metabolic fuels and disposal of end-products. Using circulating metabolite concentrations to infer changes in fluxes is highly unreliable because the relationship between these parameters varies greatly with physiological state. Quantifying fuel kinetics directly is therefore crucial to the understanding of muscle metabolism. This review focuses on how carbohydrates, lipids and amino acids are provided to fish muscles during hypoxia and swimming. Both stresses force white muscle to produce lactate at higher rates than it can be processed by aerobic tissues. However, lactate accumulation is minimized because disposal is also strongly stimulated. Exogenous supply shows that trout have a much higher capacity to metabolize lactate than observed during hypoxia or intense swimming. The low density of monocarboxylate transporters and their lack of upregulation with exercise explain the phenomenon of white muscle lactate retention. This tissue operates as a quasi-closed system, where glycogen stores act as an 'energy spring' that alternates between explosive power release during swimming and slow recoil from lactate in situ during recovery. To cope with exogenous glucose, trout can completely suppress hepatic production and boost glucose disposal. Without these responses, glycemia would increase four times faster and reach dangerous levels. The capacity of salmonids for glucoregulation is therefore much better than presently described in the literature. Instead of albumin-bound fatty acids, fish use lipoproteins to shuttle energy from adipose tissue to working muscles during prolonged exercise. Proteins may play an important role in fueling muscle work in fish, but their exact contribution is yet to be established. The membrane pacemaker theory of metabolism accurately predicts general properties of muscle membranes such as unsaturation, but it does not explain allometric patterns of specific fatty acids. Investigations of metabolic fuel kinetics carried out in fish to date have demonstrated that these ectotherms use several unique strategies to orchestrate energy supply to working muscles and to survive hypoxia.

SUMMARY

Hepatitis C virus (HCV) establishes persistent infection in the majority of infected individuals. The currently accepted hypothesis of immune evasion by antigenic variation in hypervariable region 1 (HVR1) of glycoprotein E2 does not however, explain the lack of subsequent immune recognition. Here, we show that the N-terminal region of E2 is antigenically and structurally similar to human immunoglobulin (Ig) variable domains. E2 is recognized by anti-human IgG antibodies and also possesses common amino acid (aa) sequence features of the conserved v-gene framework regions of human Ig light chains in particular but also heavy chains and T cell receptors. Using a position specific scoring system, the degree of similarity of HVR1 to Ig types correlated with immune escape and persistence in humans and experimentally infected chimpanzees. We propose a unique role for threshold levels of Ig molecular mimicry in HCV biology that not only advances our concept of viral immune escape and persistent infection but also provides insight into host-dependent disease patterns.

, with a trivial mismatch between R a and R d that only affects blood concentration minimally. Results also show that the catheterizations and blood sampling needed to measure metabolite kinetics in exercising fish have no significant impact on Ṁ O2 or TCOT. However, these experimental procedures affect locomotion energetics by increasing NCOT at high speeds and by decreasing U crit .

Intense swimming causes circulatory lactate accumulation in rainbow trout because lactate disposal (Rd) is not stimulated as strongly as lactate appearance (Ra). This mismatch suggests that maximal Rd is limited by tissue capacity to metabolize lactate. This study uses exogenous lactate to investigate what constrains maximal Rd and minimal Ra. Our goals were to determine how exogenous lactate affects: 1) Ra and Rd of lactate under baseline conditions or during graded swimming, and 2) exercise performance (critical swimming speed, Ucrit) and energetics (cost of transport, COT). Results show that exogenous lactate allows swimming trout to boost maximal Rd lactate by 40% and reach impressive rates of 56 μmol·kg(-1)·min(-1). This shows that the metabolic capacity of tissues for lactate disposal is not responsible for setting the highest Rd normally observed after intense swimming. Baseline endogenous Ra (resting in normoxic water) is not significantly reduced by exogenous lactate supply. Therefore, trout have an obligatory need to produce lactate, either as a fuel for oxidative tissues and/or from organs relying on glycolysis. Exogenous lactate does not affect Ucrit or COT, probably because it acts as a substitute for glucose and lipids rather than extra fuel. We conclude that the observed 40% increase in Rd lactate is made possible by accelerating lactate entry into oxidative tissues via monocarboxylate transporters (MCTs). This observation together with the weak expression of MCTs and the phenomenon of white muscle lactate retention show that lactate metabolism of rainbow trout is significantly constrained by transmembrane transport.