Exapting exaptation.

The term exaptation was introduced to encourage biologists to consider alternatives to adaptation to explain the origins of traits. Here, we discuss why exaptation has proved more successful in technological than biological contexts, and propose a revised definition of exaptation applicable to both genetic and cultural evolution.

Enhanced immunogenicity, mortality protection, and reduced viral brain invasion by alum adjuvant with an H5N1 split-virion vaccine in the ferret.

BACKGROUND: Pre-pandemic development of an inactivated, split-virion avian influenza vaccine is challenged by the lack of pre-existing immunity and the reduced immunogenicity of some H5 hemagglutinins compared to that of seasonal influenza vaccines. Identification of an acceptable effective adjuvant is needed to improve immunogenicity of a split-virion avian influenza vaccine. METHODS AND FINDINGS: Ferrets (N = 118) were vaccinated twice with a split-virion vaccine preparation of A/Vietnam/1203/2004 or saline either 21 days apart (unadjuvanted: 1.9 µg, 7.5 µg, 30 µg, or saline), or 28 days apart (unadjuvanted: 22.5 µg, or alum-adjuvanted: 22.5 or 7.5 µg). Vaccinated animals were challenged intranasally 21 or 28 days later with 10(6) EID(50) of the homologous strain. Immunogenicity was measured by hemagglutination inhibition and neutralization assays. Morbidity was assessed by observed behavior, weight loss, temperature, cytopenias, histopathology, and viral load. No serum antibodies were detected after vaccination with unadjuvanted vaccine, whereas alum-adjuvanted vaccination induced a robust antibody response. Survival after unadjuvanted dose regimens of 30 µg, 7.5 µg and 1.9 µg (21-day intervals) was 64%, 43%, and 43%, respectively, yet survivors experienced weight loss, fever and thrombocytopenia. Survival after unadjuvanted dose regimen of 22.5 µg (28-day intervals) was 0%, suggesting important differences in intervals in this model. In contrast to unadjuvanted survivors, either dose of alum-adjuvanted vaccine resulted in 93% survival with minimal morbidity and without fever or weight loss. The rarity of brain inflammation in alum-adjuvanted survivors, compared to high levels in unadjuvanted vaccine survivors, suggested that improved protection associated with the alum adjuvant was due to markedly reduced early viral invasion of the ferret brain. CONCLUSION: Alum adjuvant significantly improves efficacy of an H5N1 split-virion vaccine in the ferret model as measured by immunogenicity, mortality, morbidity, and brain invasion.

Foraging and farming as niche construction: stable and unstable adaptations.

All forager (or hunter-gatherer) societies construct niches, many of them actively by the concentration of wild plants into useful stands, small-scale cultivation, burning of natural vegetation to encourage useful species, and various forms of hunting, collectively termed 'low-level food production'. Many such niches are stable and can continue indefinitely, because forager populations are usually stable. Some are unstable, but these usually transform into other foraging niches, not geographically expansive farming niches. The Epipalaeolithic (final hunter-gatherer) niche in the Near East was complex but stable, with a relatively high population density, until destabilized by an abrupt climatic change. The niche was unintentionally transformed into an agricultural one, due to chance genetic and behavioural attributes of some wild plant and animal species. The agricultural niche could be exported with modifications over much of the Old World. This was driven by massive population increase and had huge impacts on local people, animals and plants wherever the farming niche was carried. Farming niches in some areas may temporarily come close to stability, but the history of the last 11,000 years does not suggest that agriculture is an effective strategy for achieving demographic and political stability in the world's farming populations.

Levofloxacin cures experimental pneumonic plague in African green monkeys.

BACKGROUND: Yersinia pestis, the agent of plague, is considered a potential bioweapon due to rapid lethality when delivered as an aerosol. Levofloxacin was tested for primary pneumonic plague treatment in a nonhuman primate model mimicking human disease. METHODS AND RESULTS: Twenty-four African Green monkeys (AGMs, Chlorocebus aethiops) were challenged via head-only aerosol inhalation with 3-145 (mean = 65) 50% lethal (LD(50)) doses of Y. pestis strain CO92. Telemetered body temperature >39 °C initiated intravenous infusions to seven 5% dextrose controls or 17 levofloxacin treated animals. Levofloxacin was administered as a "humanized" dose regimen of alternating 8 mg/kg and 2 mg/kg 30-min infusions every 24-h, continuing until animal death or 20 total infusions, followed by 14 days of observation. Fever appeared at 53-165 h and radiographs found multilobar pneumonia in all exposed animals. All control animals died of severe pneumonic plague within five days of aerosol exposure. All 16 animals infused with levofloxacin for 10 days survived. Levofloxacin treatment abolished bacteremia within 24 h in animals with confirmed pre-infusion bacteremia, and reduced tachypnea and leukocytosis but not fever during the first 2 days of infusions. CONCLUSION: Levofloxacin cures established pneumonic plague when treatment is initiated after the onset of fever in the lethal aerosol-challenged AGM nonhuman primate model, and can be considered for treatment of other forms of plague. Levofloxacin may also be considered for primary presumptive-use, multi-agent antibiotic in bioterrorism events prior to identification of the pathogen.

Milestones in progression of primary pneumonic plague in cynomolgus macaques.

Vaccines against primary pneumonic plague, a potential bioweapon, must be tested for efficacy in well-characterized nonhuman primate models. Telemetered cynomolgus macaques (Macaca fascicularis) were challenged by the aerosol route with doses equivalent to approximately 100 50% effective doses of Yersinia pestis strain CO92 and necropsied at 24-h intervals postexposure (p.e.). Data for telemetered heart rates, respiratory rates, and increases in the temperature greater than the diurnal baseline values identified the onset of the systemic response at 55 to 60 h p.e. in all animals observed for at least 70 h p.e. Bacteremia was detected at 72 h p.e. by a Yersinia 16S rRNA-specific quantitative reverse transcription-PCR and was detected later by the culture method at the time of moribund necropsy. By 72 h p.e. multilobar pneumonia with diffuse septal inflammation consistent with early bacteremia was established, and all lung tissues had a high bacterial burden. The levels of cytokines or chemokines in serum were not significantly elevated at any time, and only the interleukin-1beta, CCL2, and CCL3 levels were elevated in lung tissue. Inhalational plague in the cynomolgus macaque inoculated by the aerosol route produces most clinical features of the human disease, and in addition the disease progression mimics the disease progression from the anti-inflammatory phase to the proinflammatory phase described for the murine model. Defined milestones of disease progression, particularly the onset of fever, tachypnea, and bacteremia, should be useful for evaluating the efficacy of candidate vaccines.

Kinship, marriage, and the genetics of past human dispersals.

The extent to which colonizing farmer populations have overwhelmed or "replaced" indigenous forager populations, as opposed to having intermarried with them, has been widely debated. Indigenous-colonist "admixture" is often represented in genetic models as a single parameter that, although parsimonious and simple, is incongruous with the sex-specific nature of mtDNA and Y-chromosome data. To help interpret genetic patterns, we can construct useful null hypotheses about the generalized migration history of females (mtDNA) as opposed to males (Y chromosome), which differ significantly in almost every ethnographically known society. We seek to integrate ethnographic knowledge into models that incorporate new social parameters for predicting geographic patterns in mtDNA and Y-chromosome distributions. We provide an example of a model simulation for the spread of agriculture in which this individual-scale evidence is used to refine the parameters.

Detection of macrocyclic trichothecene mycotoxin in a caprine (goat) tracheal instillation model.

This study demonstrates the detection and dynamics of macrocyclic trichothecene mycotoxin (MTM) tissue loading using a commercially available assay in a goat model. The detection of MTMs has been difficult and complex due to the uncertainty of what tissues to examine and when to sample. Twelve goats (two groups of each) were instilled with Stachybotrys chartarum conidial suspension via the trachea. The first group was challenged repeatedly with fungal conidia containing 1 mg/kg of MTM per instillation whereas the second group was exposed once, to spores with a calculated concentration of 5 microg/kg of mycotoxin. These toxin estimates were generated by the QuantiTox(TM) Kit assay; a conidium of S. chartarum possessed 8.5 pg of MTM. After repeated exposure of 3 days, MTM was detected in one of six animals. This animal and two others from the same group had mycotoxin detected in their serum 24 hours after challenge at a comparable level (1.69 ng/mL) to the six animals challenged with a single dose (2.02 ng/mL) at the same time post-instillation. Results showed that MTMs are detectable in experimental animals soon after challenge and contribute to the understanding of the role of these mycotoxins in the disease process following mold exposure.

Effects of inhaled fine dust on lung tissue changes and antibody response induced by spores of opportunistic fungi in goats.

OBJECTIVE: To investigate the effects of sterile fine dust aerosol inhalation on antibody responses and lung tissue changes induced by Mucor ramosissimus or Trichoderma viride spores following intratracheal inoculation in goats. ANIMALS: 36 weanling Boer-Spanish goats. PROCEDURES: 6 goats were allocated to each of 2 M ramosissimus-inoculated groups, 2 T viride-inoculated groups, and 2 control (tent or pen) groups. One of each pair of sporetreated groups and the tent control group were exposed 7 times to sterilized fine feedyard dust (mean+/-SD particle diameter, <7.72+/-0.69 microm) for 4 hours in a specially constructed tent. Goats in the 4 fungal treatment groups were inoculated intratracheally 5 times with a fungal spore preparation (30 mL), whereas tent control goats were intratracheally inoculated with physiologic saline (0.9% NaCl) solution (30 mL). Pen control goats were not inoculated or exposed to dust. Goats received an IV challenge with equine RBCs to assess antibody responses to foreign antigens. Postmortem examinations were performed at study completion (day 68) to evaluate lung tissue lesions. RESULTS: 5 of 7 deaths occurred between days 18 and 45 and were attributed to fine dust exposures prior to fungal treatments. Fine dust inhalation induced similar lung lesions and precipitating antibodies among spore-treated goats. Following spore inoculations, dust-exposed goats had significantly more spores per gram of consolidated lung tissue than did their nonexposed counterparts. CONCLUSIONS AND CLINICAL RELEVANCE: Fine dust inhalation appeared to decrease the ability of goats to successfully clear fungal spores from the lungs following intratracheal inoculation.

Virulence of fungal spores determined by tracheal inoculation of goats following inhalation of aerosolized sterile feedyard dust.

OBJECTIVE: To compare the virulence of spores of 7 fungi by tracheal inoculation of goats following exposure of goats to an aerosol of sterilized feedyard dust. Animals-54 weanling Boer-Spanish goats. PROCEDURE: A prospective randomized controlled study was conducted. There were 7 fungal treatment groups, a tent control group, and a pen control group (n = 6 goats/group). Goats in the 7 treatment and tent control groups were exposed to autoclaved aerosolized feedyard dust for 4 hours in a specially constructed tent. Goats in the 7 treatment groups were then inoculated intratracheally with 30 mL of a fungal spore preparation, whereas tent control goats were intratracheally inoculated with 30 mL of physiologic saline (0.9% NaCI) solution. These treatments were repeated each week for 6 weeks. RESULTS: Severity of pathologic changes differed significantly among the 7 fungal treatment groups as determined on the basis of gross atelectatic and consolidated lung lesions and histologic lesions of the lungs. Descending order for severity of lesions was Mucor ramosissimus, Trichoderma viride, Chaetomium globosum, Stachybotrys chartarum, Aspergillus fumigatus, Penicillium chrysogenum, and Monotospora lanuginosa. Trichoderma viride spores were the most invasive and were isolated from the bronchial lymph nodes and thoracic fluid of all 6 goats administered this organism. Spores were observed-histologically in lung tissues harvested 72 hours after inoculation from all treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: 4 of 7 fungal spore types induced significantly larger lung lesions, compared with those induced by the other 3 spore types or those evident in control goats.