A group contribution method for the estimation of equilibrium constants for biochemical reactions

Using Gibbs Energies of compounds, as well as Gibbs Energy changes and equilibrium constants of biochemical reactions, the contributions of functional groups to the Gibbs Energy (in aqueous solution, temperature 25°C, and pH=7) have been estimated. These contributions allow the estimation of the Gibbs Free Energy and the equilibrium constant of a biochemical reaction, given the structure of the reactants and products.     

Oxidative Damage to DNA and Deoxyribose by β-Lactam Antibiotics in the Presence of Iron and Copper Salts

β-lactam antibiotics in the presence of certain metal ions damage deoxyribose and DNA with the release of thiobarbituric acid-reactive material. This damage can be substantially prevented by catalase, metal chelators and some scavengers of the hydroxyl radical. Ferric salts in the presence of certain β-lactam antibiotics were effective in degrading deoxyribose but they did not appear to damage DNA. In contrast copper salts and p-lactam antibiotics were extremely effective in damaging both DNA and deoxyribose.     

Biological responses to overload training in endurance sports

Five subjects undertook 10 days of twice daily interval training sessions on a treadmill followed by 5 days of active recovery. On days 1, 6, 11, and 16 the subjects were required to undertake a test of submaximal and maximal work capacity on a treadmill combined with a performance test consisting of a run to exhaustion with the treadmill set at 18 km.h-1 and 1% gradient. Also on these days a pre-exercise blood sample was collected and analysed for a range of haematological, biochemical and immunological parameters. The subjects experienced a significant fall in performance on day 11 which had returned to pretraining levels on day 16. Serum ferritin concentrations were depressed significantly from pretraining concentrations at the conclusion of the recovery period while the expression of lymphocyte activation antigens (CD25+ and HLA-DR+) was increased both after the training phase and the recovery phase. The number of CD56+ cells in the peripheral circulation was depressed at the conclusion of the recovery period. Several parameters previously reported to change in association with overload training failing to reflect the decrease in performance experienced by subjects in this study, suggesting that overtraining may best be diagnosed through a multifactorial approach to the recognition of symptoms. The most important factor to consider may be a decrease in the level of performance following a regeneration period. The magnitude of this decreased performance necessary for the diagnosis of overtraining and the nature of an "appropriate" regeneration period are, however, difficult to define and may vary depending upon the training background of the subjects and the nature of the preceding training. It may or may not be associated with biochemical, haematological, physiological and immunological indicators. Individual cases may present a different range of symptoms and diagnosis of overtraining should not be excluded based on the failure of blood parameters to demonstrate variation. However, blood parameters may be useful to identify possible aetiology in each separate case report of over-training. An outstanding factor to emerge from this study was the difficulty associated with an objective diagnosis of overtraining and this is a possible reason why there have been new accounts of overtraining research in the literature.     

Somatic embryogenesis and plant regeneration from zygotic embryo explants in mexican weeping bamboo,Otatea acuminata aztecorum

An efficient protocol has been developed for the in vitro propagation of Mexican Weeping Bamboo through somatic embryogenesis from zygotic embryo explants. Mature seeds and excised embryos were cultured in the light or in the dark on both Murashige and Skoog's and Gamborg's B5 basal media with various supplements. Optimal somatic embryogenesis and plant regeneration were obtained by culture in the dark on Murashige and Skoog's basal medium supplemented with 3 mg/1 2,4-dichlorophenoxyacetic acid, 0.5 mg/1 6-benzylaminopurine and 2.0% sucrose. More than 95% of the germinating somatic embryos developed shoots and roots, and were transferred to soil with 85% success.     

Nucleoside triphosphates are required to open the CFTR chloride channel.

The CFTR Cl- channel contains two predicted nucleotide-binding domains (NBD1 and NBD2); therefore, we examined the effect of ATP on channel activity. Once phosphorylated by cAMP-dependent protein kinase (PKA), channels required cytosolic ATP to open. Activation occurred by a PKA-independent mechanism. ATP gamma S substituted for ATP in PKA phosphorylation, but it did not open the channel. Several hydrolyzable nucleotides (ATP greater than GTP greater than ITP approximately UTP greater than CTP) reversibly activated phosphorylated channels, but nonhydrolyzable analogs and Mg(2+)-free ATP did not. Studies of CFTR mutants indicated that ATP controls channel activity independent of the R domain and suggested that hydrolysis of ATP by NBD1 may be sufficient for channel opening. The finding that nucleoside triphosphates regulate CFTR begins to explain why CF-associated mutations in the NBDs block Cl- channel function.     

Decision making in critically ill patients with hematologic malignancy.

Hematologic neoplasms that were previously considered fatal are now potentially curable with techniques such as bone marrow transplantation. Such therapies also carry significant morbidity and mortality. With the increasing application of these therapies, a growing number of physicians are using medical decision making regarding critical care for these patients. The process by which ethical decisions are reached for these critically ill patients may be baffling because of several factors: rapidly evolving treatments, uncertain probabilities of the cure of the malignant disorder, the relatively young age of many of these patients, and the poor prognosis with critical illness. I discuss a process to reach acceptable decisions, providing a case example of the application of the process. This process is derived from the ethical principles that drive decision making in general medicine and attempts to maximize patients'' autonomy. It involves a consideration of accurate information regarding the disease process and the prognosis, a clear delineation of the goals of the medical care, and communication with patients. Appropriate, ethical, and consistent decisions regarding the critical care of patients with hematologic malignancy can be reached when these considerations are addressed.     

On the interpretation of host-parasite ecology: Heligmosomoides polygyrus (Nematoda) in wild wood mouse (Apodemus sylvaticus) populations

This paper describes epidemiological and seasonal patterns in the interaction between wood mice, Apodemus sylvaticus and Heligmosomoides polygyrus. Data used in the analysis were collected by C. S. Elton and co-workers at Bagley Wood, Oxfordshire in the late 1920s. Heligmosomoides polygyrus was by far the most common helminth parasite with 70% of all wood mice infected and average intensity around 12 worms per mouse. Male and female mice were shown to harbour similar parasite burdens. Parasite numbers per host were highly overdispersed and were well described by the negative binomial distribution. There was little evidence for convexity in age (= weight)-intensity curves, either within or across sexes.
Host and parasite numbers showed predictable seasonal patterns, with mouse populations at their largest at the end of the breeding season, in August and September, and parasite populations at their largest in the late spring, around May. Results are discussed in relation to the ecology of H. polygyrus in wood and laboratory mice, and tentative comparison is made with human helminth infection. The interpretation of epidemiological patterns in these data was problematic. Of particular importance was the statistical distribution of parasites within the host population, and possible differences between mouse sexes in relation to growth, survival and trapping. Such difficulties are relevant to a range of similar field data.     

Somatic recombination rather than uniparental disomy suggested as another mechanism by which genetic imprinting may play a role in the etiology of Prader-Willi syndrome

Summary Six Prader-Willi syndrome (PWS) patients with normal karyotypes and their parents were analyzed to determine the nature of the molecular aberrations present in the proximal region of 15q and to determine the parental origin of the aberrant chromosome 15. In addition, the likehood that uniparental disomy plays a significant role in the etiology of PWS patients with normal karyotypes was studied. Restriction fragment length polymorphisms (RFLPs) recognized by seven probes [pML34 (D15S9), pTD3-21, pCGS0.9, pCGS1.1 (D15S10), IR4.3 (D15S11), IR10.1 (DS15S12), p189-1 (D15S13), IR39 (D15S18), and CMW-1 (D15S24)] mapping to the Prader-Willi chromosome region (PWCR) and an additional two probes [pMS1-14 (D15S1); the cDNA of neuromedin B] mapping elsewhere on chromosome 15 were analyzed in the six PWS patients and their parents. Copy number of each locus within the PWCR was determined by densitometry. Molecular rearrangements of the proximal region of 15q were observed in all of the six probands and the origin of the aberrant chromosome 15 when determined was consistently paternal in origin. While data obtained from our six patients does not support the mechanism of disomy, results obtained from three of the six patients show more complex rearrangements hypothesized to have resulted from somatic recombination. These rearrangements have resulted in acquired homozygosity and the lack of a paternal allele at various loci within the PWCR. The presence of only a maternal contribution at certain loci as the result of somatic recombination may be another mechanism by which genetic imprinting plays a role in the presentation of the PWS phenotype.     

Population structure,spite, and the iterated Prisoner's Dilemma

Evolutionary stability (sensu Maynard Smith: Evolution and the Theory of Games, Cambridge: Cambridge University Press, 1982) of TIT FOR TAT (TFT) under the social ecology of the iterated Prisoner's Dilemma is a function of the number of pure TFT groups (dyads) in the population, relative to the social position of a focal invading defector. Defecting against TFT always raises the defector's relative intragroup fitness; when Axelrod's (Am. Polit. Sci. Rev. 75:306–318, 1981; The Evolution of Cooperation. New York: Basic Books, 1984) Evolutionary stable strategy (ESS) conditions are met, defection also lowers the absolute fitness of the defector. Here the retaliatory (punishing) character of TFT converts defection into spite, permitting pure TFT groups to sufficiently outproduce the defector for the latter's evolutionary suppression. Increasing the relative impact of spiteful defection on a population lowers the range of evolutionary stability for TFT. When individuals participate in multiple dyads, those participating in the greatest number of dyads are most likely to provide a vehicle for the successful invasion of defection. Within social networks, ESS conditions for TFT are thus individual specific. This logic is generalized to the context of an interated n-person Prisoner's Dilemma, providing a cooperative solution conceptually identical with TFT in the two-person game.