A new look at an old virus: patterns of mutation accumulation in the human H1N1 influenza virus since 1918

BACKGROUND: The H1N1 influenza A virus has been circulating in the human population for over 95 years, first manifesting itself in the pandemic of 1917–1918. Initial mortality was extremely high, but dropped exponentially over time. Influenza viruses have high mutation rates, and H1N1 has undergone significant genetic changes since 1918. The exact nature of H1N1 mutation accumulation over time has not been fully explored. METHODS: We have made a comprehensive historical analysis of mutational changes within H1N1 by examining over 4100 fully-sequenced H1N1 genomes. This has allowed us to examine the genetic changes arising within H1N1 from 1918 to the present. RESULTS: We document multiple extinction events, including the previously known extinction of the human H1N1 lineage in the 1950s, and an apparent second extinction of the human H1N1 lineage in 2009. These extinctions appear to be due to a continuous accumulation of mutations. At the time of its disappearance in 2009, the human H1N1 lineage had accumulated over 1400 point mutations (more than 10% of the genome), including approximately 330 non-synonymous changes (7.4% of all codons). The accumulation of both point mutations and non-synonymous amino acid changes occurred at constant rates (μ = 14.4 and 2.4 new mutations/year, respectively), and mutations accumulated uniformly across the entire influenza genome. We observed a continuous erosion over time of codon-specificity in H1N1, including a shift away from host (human, swine, and bird [duck]) codon preference patterns. CONCLUSIONS: While there have been numerous adaptations within the H1N1 genome, most of the genetic changes we document here appear to be non-adaptive, and much of the change appears to be degenerative. We suggest H1N1 has been undergoing natural genetic attenuation, and that significant attenuation may even occur during a single pandemic. This process may play a role in natural pandemic cessation and has apparently contributed to the exponential decline in mortality rates over time, as seen in all major human influenza strains. These findings may be relevant to the development of strategies for managing influenza pandemics and strain evolution

Hanging drop crystal growth apparatus

This invention relates generally to control systems for controlling crystal growth, and more particularly to such a system which uses a beam of light refracted by the fluid in which crystals are growing to detect concentration of solutes in the liquid. In a hanging drop apparatus, a laser beam is directed onto drop which refracts the laser light into primary and secondary bows, respectively, which in turn fall upon linear diode detector arrays. As concentration of solutes in drop increases due to solvent removal, these bows move farther apart on the arrays, with the relative separation being detected by arrays and used by a computer to adjust solvent vapor transport from the drop. A forward scattering detector is used to detect crystal nucleation in drop, and a humidity detector is used, in one embodiment, to detect relative humidity in the enclosure wherein drop is suspended. The novelty of this invention lies in utilizing angular variance of light refracted from drop to infer, by a computer algorithm, concentration of solutes therein. Additional novelty is believed to lie in using a forward scattering detector to detect nucleating crystallites in drop

An Overview of the Independent Histories of the Human Y Chromosome and the Human Mitochondrial chromosome

Our paper will report an analysis of the history of the human Y chromosome. Thousands of full-length Y chromosome sequences from multiple world populations have recently become available for the first time. This data gives us an unprecedented opportunity to look backwards into human history. The Y chromosome is ideal for such analysis because it combines direct paternal inheritance with no recombination along most of its length. Any newly arising mutation that first appears in any male child will be directly inherited by every descendant of that male. This means that every branch on a phylogenetic tree of the Y chromosome reveals a historical individual, who lived at a specific time, and who is the founder (patriarch) of a unique lineage. We use a technique called ancestral reconstruction to calculate the sequences of the major haplogroup and macrohaplogroup founders. We then compare the Y chromosome sequence of each founder to their descendants, and also to the other founders. We report three basic findings. First, we report the sequence of each founder patriarch. We will show that three of the earliest patriarchs were very closely related. It is clear that most human male lineages trace back to just a few men who were separated by a surprisingly few number of mutations. This is remarkably consistent with the biblical account of how all males were derived from three brothers (Shem, Ham, and Japheth). Second, we report that different lineages appear to have mutated at a different rates, suggesting that the molecular clock is not reliable. This directly contradicts one of the major assumptions behind the out-of-Africa hypothesis. Third, we approximate the sequence of the common ancestor of the three primary patriarchs. It is possible this common ancestor is the Biblical Noah, sitting at the center of our Y chromosome phylogenetic tree. The sequence of this person, in turn, may represent a reasonable approximation of Adam’s Y chromosomal sequence. Lastly, we will attempt to put a time interval between Noah/Adam and his living descendants using published y-chromosome mutation rates, while allowing for divergent mutation rates among various lineages

A conceptual design study of the reusable reentry satellite

Experimentation leading to an understanding of life processes under reduced and extremely low gravitational forces will profoundly contribute to the success of future space missions involving humans. In addition to research on gravitational biology, research on the effects of cosmic radiation and the interruption and change of circadian rhythms on life systems is also of prime importance. Research in space, however, is currently viewed by biological scientists as an arena that is essential, yet largely inaccessible to them for their experimentation. To fulfill this need, a project and spacecraft system described as the Reusuable Reentry Satellite or Lifesat has been proposed by NASA

The Effect of Pressures up to 16000 Atmospheres Upon the E.M.F. of the Weston Standard Cell

A variety of types of Weston standard cells were constructed and the electromotive force was found to increase with the pressure. The shape of the curve being effected somewhat by the material of which the cell case was constructed

Antioxidative Properties of Bitter Gourd (Momordica charantia) and Zucchini (Cucurbita pepo)

The enzymatic and non-enzymatic antioxidative capacities of bitter gourd (Momordica charantia) and zucchini (Cucurbita pepo) were investigated in water extracts and chemical buffer extracts. Bitter gourd and zucchini fruits were purchased from a farmer’s market and homogenized separately in water and in a native enzyme extraction buffer. Total phenolic compounds, free radical DPPH scavenging activity, SOD activity and β- glucosidase activity were assayed in the extracts. The average total phenolic compounds recorded in bitter gourd were 13.28 GAE/g fresh weights while in zucchini, the average was 8.67GAE/g fresh weight. This study also found that bitter gourd was 82.05% as effective as ascorbic acid in inhibiting the free radical DPPH while zucchini was 12.19% as effective. The results indicated that bitter gourd was significantly higher in antioxidant content and in β-glucosidase activities than zucchini (P\u3c0.05). On the other hand, significantly higher SOD activities were recorded in zucchini than in bitter gourd extracts