Effects of passage history and sampling bias on phylogenetic reconstruction of human influenza A evolution

In this paper we determine the extent to which host-mediated mutations and a known sampling bias affect evolutionary studies of human influenza A. Previous phylogenetic reconstruction of influenza A (H3N2) evolution using the hemagglutinin gene revealed an excess of nonsilent substitutions assigned to the terminal branches of the tree. We investigate two hypotheses to explain this observation. The first hypothesis is that the excess reflects mutations that were either not present or were at low frequency in the viral sample isolated from its human host, and that these mutations increased in frequency during passage of the virus in embryonated eggs. A set of 22 codons known to undergo such “host-mediated” mutations showed a significant excess of mutations assigned to branches attaching sequences from egg-cultured (as opposed to cell-cultured) isolates to the tree. Our second hypothesis is that the remaining excess results from sampling bias. Influenza surveillance is purposefully biased toward sequencing antigenically dissimilar strains in an effort to identify new variants that may signal the need to update the vaccine. This bias produces an excess of mutations assigned to terminal branches simply because an isolate with no close relatives is by definition attached to the tree by a relatively long branch. Simulations show that the magnitude of excess mutations we observed in the hemagglutinin tree is consistent with expectations based on our sampling protocol. Sampling bias does not affect inferences about evolution drawn from phylogenetic analyses. However, if possible, the excess caused by host-mediated mutations should be removed from studies of the evolution of influenza viruses as they replicate in their human hosts.

Clues to epidermal cancer proneness revealed by reconstruction of DNA repair-deficient xeroderma pigmentosum skin in vitro

Sun exposure has been clearly implicated in premature skin aging and neoplastic development. These features are exacerbated in patients with xeroderma pigmentosum (XP), a hereditary disease, the biochemical hallmark of which is a severe deficiency in the nucleotide excision repair of UV-induced DNA lesions. To develop an organotypic model of DNA repair deficiency, we have cultured several strains of primary XP keratinocytes and XP fibroblasts from skin biopsies of XP patients. XP skin comprising both a full-thickness epidermis and a dermal equivalent was succesfully reconstructed in vitro. Satisfactory features of stratification were obtained, but the expression of epidermal differentiation products, such as keratin K10 and loricrin, was delayed and reduced. In addition, the proliferation of XP keratinocytes was more rapid than that of normal keratinocytes. Moreover, increased deposition of cell attachment proteins, α-6 and β-1 integrins, was observed in the basement membrane zone, and β-1 integrin subunit, the expression of which is normally confined to basal keratinocytes, extended into several suprabasal cell layers. Most strikingly, the in vitro reconstructed XP skin displayed numerous proliferative epidermal invasions within dermal equivalents. Epidermal invasion and higher proliferation rate are reminiscent of early steps of neoplasia. Compared with normal skin, the DNA repair deficiency of in vitro reconstructed XP skin was documented by long-lasting persistence of UVB-induced DNA damage in all epidermal layers, including the basal layer from which carcinoma develops. The availability of in vitro reconstructed XP skin provides opportunities for research in the fields of photoaging, photocarcinogenesis, and tissue therapy.

Age determination and Sea surface temperature reconstruction for sediment core H214

We present sea surface temperature (SST) records with centennial-scale resolution from the Bay of Plenty, north of New Zealand. Foraminiferal assemblage-based paleo-SST estimates provide a deglacial record of SST since 16.5 14C ka. Average Holocene SSTs are 15.6°C for winter and 20.3°C for summer, whereas average glacial values were 14.2°C for winter and 19.5°C for summer. Compared to modern time, cooling of SSTs at the Last Glacial Maximum (LGM) was ~0.9°C in winter and ~1.5°C in summer. The shift from glacial to Holocene temperatures began at 14.25 14C ka, warming by ~2°C until 12.85 14C ka when temperatures dipped back to glacial values at 11.65 14C ka. The timing of this return to glacial-like SST correlates well with the Antarctic Cold Reversal (ACR) rather than the Younger Dryas and documents that the influence of the ACR extended into the subtropics of the Southern Hemisphere, at least in this region of the southwest Pacific. By 10.55 14C ka an SST maximum in summer SSTs of up to 3°C warmer than modern occurred (?24°C), after which SST dropped, remaining at present-day temperatures since 9.3 14C ka. This early Holocene climatic optimum has been widely noted in the Southern Ocean, and this record indicates that this phenomenon also extended into the subtropics to the north of New Zealand.

Analytical pedestrian accident reconstruction using computer simulation. Final report.

Mode of access: Internet.

Peoples of the Near East without a national future.

"Prepared by William L. Westermann."

Training program for accident investigation and coding in the National Crash Severity Study. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

National Crash Severity Study - quality control. Task V: analysis to refine spinout aspects of CRASH. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Volume one (1) - staged collision and damage data report for accident reconstruction of twenty five (25) test vehicles (1980 model year). Final report.

National Highway Traffic Safety Administration, Accident Investigation Division, Washington, D.C.

Volume two (2) - staged collision and damage data report for accident reconstruction of twenty five (25) test vehicles (1980 model year). Final report.

National Highway Traffic Safety Administration, Accident Investigation Division, Washington, D.C.

Volume one (1) - staged collision and damage data report for accident reconstruction of thirty (30) test vehicles. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Volume three (3) - staged collision and damage data report for accident reconstruction of thirty (30) test vehicles. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Volume two (2) - staged collision and damage data report for accident reconstruction of thirty (30) test vehicles. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Mathematical reconstruction of highway accidents - further extensions and refinements of the CRASH computer program. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Experimental child pedestrian accident reconstruction: thoracic impact. Final report.

Mode of access: Internet.

Development of reconstruction procedure for pole accidents. Final report.

National Highway Traffic Safety Administration, Washington, D.C.