Bone mineral measurement from Apollo experiment M-078

Loss of mineral from bone during periods of immobilization, recumbency, or weightlessness is examined. This report describes the instrumentation, technique, and bone mineral changes observed preflight and postflight for the Apollo 14, 15, and 16 missions. The bone mineral changes documented during the Apollo Program are reviewed, and their relevance to future missions is discussed

Circadian, endocrine, and metabolic effects of prolonged bedrest: Two 56-day bedrest studies

Two bedrest studies of 56 days each have been conducted to evaluate the effects of prolonged bedrest on circadian synchrony and endocrine and metabolic function. Measurements included the pituitary-adrenal, thyroid, parathyroid, insulin-glucose-growth hormones, catecholamine excretion, body temperature, and heart rate. The results indicated that a rigorous regimen of exercise did not prevent the endocrine and metabolic effects of prolonged bedrest. Changes in circadian, endocrine, and metabolic functions in bedrest appear to be due to changes in hydrostatic pressure and lack of postural cues rather than to inactivity, confinement, or the bleeding schedule. Prolonged bedrest, particularly beyond 24 days, resulted in rhythm desynchronization in spite of well regulated light/dark cycles, temperature, humidity, activity, and meal times and meal composition and in increased lability of all endocrine parameter measured. It also resulted in an apparent insensitivity of the glucose response to insulin, of cortisol secretion to ACTH, and of growth hormone secretion to hypoglycemia

Apollo experience report: Food systems

Development, delivery, and use of food systems in support of the Apollo 7 to 14 missions are discussed. Changes in design criteria for this unique program as mission requirements varied are traced from the baseline system that was established before the completion of the Gemini Program. Problems and progress in subsystem management, material selection, food packaging, development of new food items, menu design, and food-consumption methods under zero-gravity conditions are described. The effectiveness of various approaches in meeting food system objectives of providing flight crews with safe, nutritious, easy to prepare, and highly acceptable foods is considered. Nutritional quality and adequacy in maintaining crew health are discussed in relation to the establishment of nutritional criteria for future missions. Technological advances that have resulted from the design of separate food systems for the command module, the lunar module, The Mobile Quarantine Facility, and the Lunar Receiving Laboratory are presented for application to future manned spacecraft and to unique populations in earthbound situations

Molecular footprint of drug-selective pressure in a human immunodeficiency virus transmission chain

Known human immunodeficiency virus (HIV) transmission histories are invaluable models for investigating the evolutionary and transmission dynamics of the virus and to assess the accuracy of phylogenetic reconstructions. Here we have characterized an HIV-1 transmission chain consisting of nine infected patients, almost all of whom were treated with antiviral drugs at later stages of infection. Partial pol and env gp41 regions of the HIV genome were directly sequenced from plasma viral RNA for at least one sample from each patient. Phylogenetic analyses in pol using likelihood methods inferred an evolutionary history not fully compatible with the known transmission history. This could be attributed to parallel evolution of drug resistance mutations resulting in the incorrect clustering of multidrug-resistant virus. On the other hand, a fully compatible phylogenetic tree was reconstructed from the env sequences. We were able to identify and quantify the molecular footprint of drug-selective pressure in pol using maximum likelihood inference under different codon substitution models. An increased fixation rate of mutations in the HIV population of the multidrug-resistant patient was demonstrated using molecular clock modeling. We show that molecular evolutionary analyses, guided by a known transmission history, can reveal the presence of confounding factors like natural selection and caution should be taken when accurate descriptions of HIV evolution are required.status: publishe

A Novel Sequence-Based Antigenic Distance Measure for H1N1, with Application to Vaccine Effectiveness and the Selection of Vaccine Strains

H1N1 influenza causes substantial seasonal illness and was the subtype of the 2009 influenza pandemic. Precise measures of antigenic distance between the vaccine and circulating virus strains help researchers design influenza vaccines with high vaccine effectiveness. We here introduce a sequence-based method to predict vaccine effectiveness in humans. Historical epidemiological data show that this sequence-based method is as predictive of vaccine effectiveness as hemagglutination inhibition (HI) assay data from ferret animal model studies. Interestingly, the expected vaccine effectiveness is greater against H1N1 than H3N2, suggesting a stronger immune response against H1N1 than H3N2. The evolution rate of hemagglutinin in H1N1 is also shown to be greater than that in H3N2, presumably due to greater immune selection pressure.Comment: 26 pages, 7 figures, 2 tables, supplemen

Hidden breakpoints in genome alignments

During the course of evolution, an organism's genome can undergo changes that affect the large-scale structure of the genome. These changes include gene gain, loss, duplication, chromosome fusion, fission, and rearrangement. When gene gain and loss occurs in addition to other types of rearrangement, breakpoints of rearrangement can exist that are only detectable by comparison of three or more genomes. An arbitrarily large number of these "hidden" breakpoints can exist among genomes that exhibit no rearrangements in pairwise comparisons. We present an extension of the multichromosomal breakpoint median problem to genomes that have undergone gene gain and loss. We then demonstrate that the median distance among three genomes can be used to calculate a lower bound on the number of hidden breakpoints present. We provide an implementation of this calculation including the median distance, along with some practical improvements on the time complexity of the underlying algorithm. We apply our approach to measure the abundance of hidden breakpoints in simulated data sets under a wide range of evolutionary scenarios. We demonstrate that in simulations the hidden breakpoint counts depend strongly on relative rates of inversion and gene gain/loss. Finally we apply current multiple genome aligners to the simulated genomes, and show that all aligners introduce a high degree of error in hidden breakpoint counts, and that this error grows with evolutionary distance in the simulation. Our results suggest that hidden breakpoint error may be pervasive in genome alignments.Comment: 13 pages, 4 figure

Genesis and pathogenesis of the 1918 pandemic H1N1 influenza A virus

The source, timing, and geographical origin of the 1918–1920 pandemic influenza A virus have remained tenaciously obscure for nearly a century, as have the reasons for its unusual severity among young adults. Here, we reconstruct the origins of the pandemic virus and the classic swine influenza and (postpandemic) seasonal H1N1 lineages using a host-specific molecular clock approach that is demonstrably more accurate than previous methods. Our results suggest that the 1918 pandemic virus originated shortly before 1918 when a human H1 virus, which we infer emerged before ∼1907, acquired avian N1 neuraminidase and internal protein genes. We find that the resulting pandemic virus jumped directly to swine but was likely displaced in humans by ∼1922 by a reassortant with an antigenically distinct H1 HA. Hence, although the swine lineage was a direct descendent of the pandemic virus, the post-1918 seasonal H1N1 lineage evidently was not, at least for HA. These findings help resolve several seemingly disparate observations from 20th century influenza epidemiology, seroarcheology, and immunology. The phylogenetic results, combined with these other lines of evidence, suggest that the highmortality in 1918 among adults aged ∼20 to ∼40 y may have been due primarily to their childhood exposure to a doubly heterosubtypic putative H3N8 virus, which we estimate circulated from ∼1889–1900. All other age groups (except immunologically naive infants) were likely partially protected by childhood exposure to N1 and/or H1-related antigens. Similar processes may underlie age-specific mortality differences between seasonal H1N1 vs. H3N2 and human H5N1 vs. H7N9 infections

Choosing among Partition Models in Bayesian Phylogenetics

Bayesian phylogenetic analyses often depend on Bayes factors (BFs) to determine the optimal way to partition the data. The marginal likelihoods used to compute BFs, in turn, are most commonly estimated using the harmonic mean (HM) method, which has been shown to be inaccurate. We describe a new more accurate method for estimating the marginal likelihood of a model and compare it with the HM method on both simulated and empirical data. The new method generalizes our previously described stepping-stone (SS) approach by making use of a reference distribution parameterized using samples from the posterior distribution. This avoids one challenging aspect of the original SS method, namely the need to sample from distributions that are close (in the Kullback–Leibler sense) to the prior. We specifically address the choice of partition models and find that using the HM method can lead to a strong preference for an overpartitioned model. In contrast to the HM method and the original SS method, we show using simulated data that the generalized SS method is strikingly more precise (repeatable BF values of the same data and partition model) and yields BF values that are much more reasonable than those produced by the HM method. Comparisons of HM and generalized SS methods on an empirical data set demonstrate that the generalized SS method tends to choose simpler partition schemes that are more in line with expectation based on inferred patterns of molecular evolution. The generalized SS method shares with thermodynamic integration the need to sample from a series of distributions in addition to the posterior. Such dedicated path-based Markov chain Monte Carlo analyses appear to be a cost of estimating marginal likelihoods accurately