Maximal indirect development, set-aside cells, and levels of selection

The evolution of metazoan development as described by Davidson et al. (1995. Science 270:1319-1325) is readily interpretable in terms of levels-of-selection conflicts, for instance, as recently modeled by Michod (1999. Darwinian Dynamics, Princeton, NJ: Princeton University Press). Davidson et al. propose certain features of early bilaterians including small size, a small and fixed number of cell divisions during and subsequent to cleavage, and specification of cell fates prior to cell movement. These features suggest constraints on certain parameters of Michod's model, specifically t (the time available for cell division) and b (the benefit to cells of not cooperating in terms of their rate of replication). Such constraints clearly enhance between-cell cooperation and allow multicellularity to more easily evolve and be maintained. Nevertheless, these constraints are completely abrogated by the phenomenon of "set-aside cells," that is, undifferentiated cells that retain indefinite division potential. Levels-of-selection theory predicts that the evolution of these set-aside cells must be accompanied by features which alleviate cell-cell competition, and indeed the results of Ransick et al. (1996. Proc Natl Acad Sci USA 93:6759-6763) support this prediction: the evolution of "set-aside cells" in metazoans was accompanied by the evolution of the sequestration of the germ line.     

Maximal dismounts from high bar

In men's artistic gymnastics the triple straight somersault dismount from the high bar has yet to be performed in competition. The present study used a simulation model of a gymnast and the high bar apparatus (J. Appl. Biomech. 19(2003a) 119) to determine whether a gymnast could produce the required angular momentum and flight to complete a triple straight somersault dismount. Optimisations were carried out to maximise the margin for error in timing the bar release for a given number of straight somersaults in flight. The amount of rotation potential (number of straight somersaults) the model could produce whilst maintaining a realistic margin for error was determined. A simulation model of aerial movement (J. Biomech.23 (1990) 85) was used to find what would be possible with this amount of rotation potential. The model was able to produce sufficient angular momentum and time in the air to complete a triple straight somersault dismount. The margin for error when releasing the bar using the optimum technique was 28 ms, which is small when compared with the mean margin for error determined for high bar finalists at the 2000 Sydney Olympic Games (55 ms). Although the triple straight somersault dismount is theoretically possible, it would require close to maximum effort and precise timing of the release from the bar. However, when the model was required to have a realistic margin for error, it was able to produce sufficient angular momentum for a double twisting triple somersault dismount.     

Digital PCR Modeling for Maximal Sensitivity,Dynamic Range and Measurement Precision

The great promise of digital PCR is the potential for unparalleled precision enabling accurate measurements for genetic quantification. A challenge associated with digital PCR experiments, when testing unknown samples, is to perform experiments at dilutions allowing the detection of one or more targets of interest at a desired level of precision. While theory states that optimal precision (P_o) is achieved by targeting ~1.59 mean copies per partition (λ), and that dynamic range (R) includes the space spanning one positive (λ_L) to one negative (λ_U) result from the total number of partitions (n), these results are tempered for the practitioner seeking to construct digital PCR experiments in the laboratory. A mathematical framework is presented elucidating the relationships between precision, dynamic range, number of partitions, interrogated volume, and sensitivity in digital PCR. The impact that false reaction calls and volumetric variation have on sensitivity and precision is next considered. The resultant effects on sensitivity and precision are established via Monte Carlo simulations reflecting the real-world likelihood of encountering such scenarios in the laboratory. The simulations provide insight to the practitioner on how to adapt experimental loading concentrations to counteract any one of these conditions. The framework is augmented with a method of extending the dynamic range of digital PCR, with and without increasing n, via the use of dilutions. An example experiment demonstrating the capabilities of the framework is presented enabling detection across 3.33 logs of starting copy concentration.     

RNA Virus Population Diversity,an Optimum for Maximal Fitness and Virulence

The ability of an RNA virus to exist as a population of genetically distinct variants permits the virus to overcome events during infections that would otherwise limit virus multiplication or drive the population to extinction. Viral genetic diversity is created by the ribonucleotide misincorporation frequency of the viral RNA-dependent RNA polymerase (RdRp). We have identified a poliovirus (PV) RdRp derivative (H273R) possessing a mutator phenotype. GMP misincorporation efficiency for H273R RdRp in vitro was increased by 2–3-fold that manifested in a 2–3-fold increase in the diversity of the H273R PV population in cells. Circular sequencing analysis indicated that some mutations were RdRp-independent. Consistent with the population genetics theory, H273R PV was driven to extinction more easily than WT in cell culture. Furthermore, we observed a substantial reduction in H273R PV virulence, measured as the ability to cause paralysis in the cPVR mouse model. Reduced virulence correlated with the inability of H273R PV to sustain replication in tissues/organs in which WT persists. Despite the attenuated phenotype, H273R PV was capable of replicating in mice to levels sufficient to induce a protective immune response, even when the infecting dose used was insufficient to elicit any visual signs of infection. We conclude that optimal RdRp fidelity is a virulence determinant that can be targeted for viral attenuation or antiviral therapies, and we suggest that the RdRp may not be the only source of mutations in a RNA virus genome.     

Maximal oxygen uptake,sweating and tolerance to exercise in the heat

The purpose of this experiment was to determine if tolerance to exercise in the heat is related to maximal oxygen uptake (max ₀₂) and sweating. Seven men with max ₀₂ between 42 and 66 ml/(min·kg) underwent one 2-hr exposure at 24°C T_q while working on a bicycle ergometer at rel ₀₂ of 28% ( ₀₂ = 1.23 1/min). In the hot exposures the high capacity subjects had maximal sweat rates of 800 to 1,000 g/(hr·m²) while the lower capacity men sweated 300 to 400 g/(hr·m²). These differences in sweating were not related to neuromuscular stimuli, ₀₂ (metabolic rate), T_re, T_re, _s, _s or tolerance time. Tolerance to exercise in the heat was not related to maximal ₀₂ capacity when the subjects worked at the same relative load in spite of large differences in sweating. These results question the importance of the rate of sweating for predicting work performance in hot environments.

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Zusammenfassung Das Ziel dieser Untersuchung war, zu prüfen, ob die Toleranz bei Arbeit in der Hitze in einer Beziehung steht zur maximalen O₂-Aufnahme und Schwitzen. Sieben Männer mit V₀₂ zwischen 42 – 66 ml/(min·kg) wurden belastet während 2 Stunden bei T_a 24°C und 3 × 2 Stunden bei 47°C mit Arbeit auf dem Fahrrad-Ergometer bei im Mittel von 28% V₀₂ = 1.23 1/min. Während der Hitzebelastung zeigten die leistungsfähigen Personen Schweissekretionsraten von 800 – 1000 g/(hr·m²) und die wenig leistungsfähigen 300 – 400 g/(hr·m²). Diese Unterschiede waren ohne Beziehung zu neuromuskulären Stimuli, Stoffwechselrate, T_re, T_re, _s, _s oder der Toleranzzeit. Ausdauer bei Arbeit in der Hitze war ohne Beziehung zur maximalen V₀₂-Kapazität, wenn die Personen bei der gleichen relativen Belastung arbeiteten tro grosser Unterschiede im Schwitzen. Die Ergebnisse stellen den Wert der Schweissekretionsrate zur Voraussage der Arbeitsleistung in der Hitze in Frage.

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Resume Dans cette étude, on a cherché à voir si la tolérance au travail sous contrainte de chaleur était en relation avec la possibilité maximum d'absorption de O₂ ( ₀₂) d'une part, de transpirer d'autre part. 7 hommes présentant des ₀₂ compris entre 42 et 66 ml/(min · kg) ont pédalé sur un ergomètre pendant 2 heures par une T_a de 24°C et 3 × 2 heures par 47°C et cela par une ₀₂ relative de 28% ( ₀₂ = 1,25 1/min). Durant l'effort sous contrainte de chaleur, les plus actifs ont eu des sécrétions de sueur de 800 à 1.000 g h^–1 m^–2 et les moins actifs de 300 à 400 g/h · m². Ces différences étaient sans rapport avec les stimulus neuro-musculaires, le taux de métabolisme, T_re, T_re, T_s et T_s ou la durée de tolérance. L'endurance au travail sous contrainte de chaleur n'a pas été fonction de la capacité maximum de ₀₂, lorsque les personnes travaillaient dans des conditions analogues, même si l'on a noté de grandes différences dans la transpiration. Ces résultats mettent en doute la représentativité du taux de sécrétion de sueur comme indicatif des possibilités de travailler en atmosphère chaude.

     

Maximal strength testing in healthy children

Strength training has become an accepted method of conditioning in children. However, there is concern among some observers that maximal strength testing may be inappropriate or potentially injurious to children. The purpose of this study was to evaluate the safety and efficacy of 1 repetition maximum (1RM) strength testing in healthy children. Thirty-two girls and 64 boys between 6.2 and 12.3 years of age (mean age 9.3 +/- 1.6 years) volunteered to participate in this study. All subjects were screened for medical conditions that could worsen during maximal strength testing. Under close supervision by qualified professionals, each subject performed a 1RM test on 1 upper-body (standing chest press or seated chest press) and 1 lower-body (leg press or leg extension) exercise using child-size weight training machines. No injuries occurred during the study period, and the testing protocol was well tolerated by the subjects. No gender differences were found for any upper- or lower-body strength test. These findings demonstrate that healthy children can safely perform 1RM strength tests, provided that appropriate procedures are followed.     

Maximal stabilities of reversible two-state proteins

The hydrophobic effect is the major force driving protein folding. Around room temperature, small organic solutes and hydrophobic amino acids have low solubilities in water and the hydrophobic effect is the strongest. These facts suggest that globular proteins should be maximally stable around room temperature. While this fundamental paradigm has been expected, it has not actually been shown to hold. Toward this goal, we have collected and analyzed experimental thermodynamic data for 31 proteins that show reversible two-state folding <--> unfolding transitions at or near neutral pH. Twenty-six of these are unique, and 20 of the 26 are maximally stable around room temperature irrespective of their structural properties, the melting temperature, or the living temperatures of their source organisms. Their average temperature of maximal stability is 293 +/- 8 K (20 +/- 8 degrees C). These proteins differ in size, fold, and number of domains, hydrophobic folding units, and oligomeric states. They derive from the cold-loving psychrophiles, from mesophiles, and from thermophiles. Analysis of the single-domain proteins present in this set shows that the variations in their thermodynamic parameters are correlated in a way which may explain the adaptation of the proteins to the living temperatures of the organisms from which they derive. The average energetic contribution of the individual amino acids toward protein stability decreases with an increase in protein size, suggesting that there may be an upper limit for protein maximal thermodynamic stability. For the remaining proteins, deviation of the maximal stability temperatures from room temperature may be due to greater uncertainties in their heat capacity change (DeltaC(p)) values, a weaker hydrophobic effect, and/or a stronger electrostatic contribution.     

Maximal activities of hexokinase, 6-phosphofructokinase,oxoglutarate dehydrogenase,and carnitine palmitoyltransferase in rat and avian muscles

The maximum activities of 6-phosphofructokinase and oxoglutarate dehydrogenase in muscle provide quantitative indices of the maximum capacities of anaerobic glycolysis and the Krebs cycle (i.e. the aerobic capacity) respectively. These activities were measured in red, white, and cardiac muscle of birds and the rat. The activities in the white pectoral muscle of the domestic fowl suggest that the Krebs cycle plus electron transfer could provide only about 1% of the rate of ATP production provided by anaerobic glycolysis whereas in pigeon pectoral muscle the predicted maximal rates from the two processes are similar. In contrast to domestic-fowl pectoral muscle, the white rat muscle, epitrochlearis, contains a significant activity of oxoglutarate dehydrogenase, which indicates that the Krebs cycle could provide about 12% of the maximum rate of ATP formation. This may be explained by a higher proportion of type-I and -IIA fibres in the rat muscle compared to the avian muscle. In the aerobic muscles of the rat the maximum activities of carnitine palmitoyl transferase indicate that fatty-acid oxidation could provide a high rate of ATP formation.