Planktos: An Agent-Based Modeling Framework for Small Organism Movement and Dispersal in a Fluid Environment with Immersed Structures.

Multiscale modeling of marine and aerial plankton has traditionally been difficult to address holistically due to the challenge of resolving individual locomotion dynamics while being carried with larger-scale flows. However, such problems are of paramount importance, e.g., dispersal of marine larval plankton is critical for the health of coral reefs, and aerial plankton (tiny arthropods) can be used as effective agricultural biocontrol agents. Here we introduce the open-source, agent-based modeling software Planktos targeted at 2D and 3D fluid environments in Python. Agents in this modeling framework are relatively tiny organisms in sufficiently low densities that their effect on the surrounding fluid motion can be considered negligible. This library can be used for scientific exploration and quantification of collective and emergent behavior, including interaction with immersed structures. In this paper, we detail the implementation and functionality of the library along with some illustrative examples. Functionality includes arbitrary agent behavior obeying either ordinary differential equations, stochastic differential equations, or coded movement algorithms, all under the influence of time-dependent fluid velocity fields generated by computational fluid dynamics, experiments, or analytical models in domains with static immersed mesh structures with sliding or sticky collisions. In addition, data visualization tools provide images or animations with kernel density estimation and velocity field analysis with respect to deterministic agent behavior via the finite-time Lyapunov exponent.

Effect of vaccination with a novel GnRH-based immunocontraceptive on immune responses and fertility in rats.

1. As human-wildlife conflicts increase worldwide, novel methods are required for mitigating these conflicts. Fertility control, based on immunocontraceptives, has emerged as an alternative option to lethal methods for managing wildlife. 2. Immunocontraceptives are vaccines that generate an immune response to key components of an animal's reproductive system. Some of these vaccines target the gonadotropin-releasing hormone (GnRH) and have been used successfully as contraceptives for many wildlife species. However, the need to capture animals for treatment limits the field applications of injectable vaccines. The availability of orally delivered immunocontraceptives would increase the breadth of applications of fertility control for wildlife management. 3. This study explored a new approach to developing an oral immunocontraceptive, exploiting the bioadhesive and immunologically active properties of killed Mycobacterium avium cell wall fragments (MAF). The MAF was conjugated to a GnRH recombinant protein called IMX294, used as a GnRH-specific immunogen. 4. An initial trial using the MAF-IMX294 conjugate provided the first evidence that an orally delivered immunocontraceptive vaccine could generate anti-GnRH antibody titres in laboratory rats. 5. Increasing the dose and frequency of vaccine administered to rats, in a second trial, enhanced the immune response, eliciting titres that reduced the proportion of females giving birth. This provided the first evidence of the contraceptive effect of an oral anti-GnRH vaccine. 6. Future work is required to further increase the immunogenic effect of the oral vaccine and to establish a dosing schedule that is effective for practical field applications.

Antiferromagnetic Correlations in Two-Dimensional Fermionic Mott-Insulating and Metallic Phases.

We experimentally study the emergence of antiferromagnetic correlations between ultracold fermionic atoms in a two-dimensional optical lattice with decreasing temperature. We determine the uniform magnetic susceptibility of the two-dimensional Hubbard model from simultaneous measurements of the in situ density distribution of both spin components. At half filling and strong interactions our data approach the Heisenberg model of localized spins with antiferromagnetic correlations. Moreover, we observe a fast decay of magnetic correlations when doping the system away from half filling.

Analysis of MIC and Disk Diffusion Testing Variables for Gepotidacin and Comparator Agents against Select Bacterial Pathogens.

This study was conducted to determine the effect of testing parameters on the in vitro activity of gepotidacin, a new triazaacenaphthylene antibacterial agent for the treatment of conventional and biothreat pathogens. CLSI methods, and variations of those methods, were used to test 10 Staphylococcus aureus, 10 Streptococcus pneumoniae, 10 Haemophilus influenzae, and 5 Escherichia coli isolates by MIC and 30 S. aureus, 15 S. pneumoniae, and 15 S. pyogenes isolates by disk diffusion (DD) methods. Levofloxacin and linezolid were tested as comparator agents for MIC and DD methods, respectively. Broth microdilution (BMD), macrodilution (MD), and agar dilution (AD) methods were compared. Variations in media, temperature, incubation time, CO2 level, and inoculum concentration were tested by all methods, and variations in pH, calcium, magnesium, zinc, potassium, thymidine, and polysorbate 80 levels were tested by BMD and DD. The addition of albumin, serum, and lung surfactant was studied by BMD. The variables that impacted the results the most were high inoculum and pH 5.5 (no growth of H. influenzae and S. pneumoniae by BMD). Gepotidacin AD MIC levels were increased and disk zone diameters were decreased for all species in 10% CO2 incubation. The following variables had a minimal effect on gepotidacin results: pH, agar method, atmospheric condition, temperature, and addition of serum and albumin for broth methods. There were also some slight differences in gepotidacin disk results between disk manufacturers and some agar types and also with potassium and thymidine for S. pneumoniae For all other variations, gepotidacin MIC and disk results were considered comparable to reference results.

Thermodynamics versus Local Density Fluctuations in the Metal-Mott-Insulator Crossover.

The crossover between a metal and a Mott insulator leads to a localization of fermions from delocalized Bloch states to localized states. We experimentally study this crossover using fermionic atoms in an optical lattice by measuring thermodynamic and local (on-site) density correlations. In the metallic phase at incommensurable filling we observe the violation of the local fluctuation-dissipation theorem indicating that the thermodynamics of the system cannot be characterized by local observables alone. In contrast, in the Mott insulator we observe the convergence of local and thermodynamic fluctuations indicating the absence of long-range density-density correlations.

In Vitro Activity of Gepotidacin, a Novel Triazaacenaphthylene Bacterial Topoisomerase Inhibitor, against a Broad Spectrum of Bacterial Pathogens.

Gepotidacin inhibits bacterial DNA replication through a mode different from that of fluoroquinolones. Gepotidacin and comparators were tested by broth and agar dilution against clinical isolates. The in vitro activities of gepotidacin were comparable against methicillin-susceptible and -resistant Staphylococcus aureus (MSSA and MRSA, respectively) isolates (MIC90, 0.5 µg/ml). The gepotidacin MIC90s were as follows (in micrograms per milliliter) for the indicated bacteria: Streptococcus pyogenes, 0.25; Escherichia coli, 2; Moraxella catarrhalis, ≤ 0.06; Streptococcus pneumoniae (0.25), Haemophilus influenzae, 1; Clostridium perfringens, 0.5; and Shigella spp., 1, including levofloxacin-resistant subsets. Gepotidacin warrants further investigation for clinical development.

Lift vs. drag based mechanisms for vertical force production in the smallest flying insects.

We used computational fluid dynamics to determine whether lift- or drag-based mechanisms generate the most vertical force in the flight of the smallest insects. These insects fly at Re on the order of 4-60 where viscous effects are significant. Detailed quantitative data on the wing kinematics of the smallest insects is not available, and as a result both drag- and lift-based strategies have been suggested as the mechanisms by which these insects stay aloft. We used the immersed boundary method to solve the fully-coupled fluid-structure interaction problem of a flexible wing immersed in a two-dimensional viscous fluid to compare three idealized hovering kinematics: a drag-based stroke in the vertical plane, a lift-based stroke in the horizontal plane, and a hybrid stroke on a tilted plane. Our results suggest that at higher Re, a lift-based strategy produces more vertical force than a drag-based strategy. At the Re pertinent to small insect hovering, however, there is little difference in performance between the two strategies. A drag-based mechanism of flight could produce more vertical force than a lift-based mechanism for insects at Re<5; however, we are unaware of active fliers at this scale.

Sevoflurane for analgesia-testing a modified vaporiser for delivery.

The Diamedica Sevoflurane Inhaler (Diamedica UK Ltd, Bratton Fleming, UK) (DSI) is a breathing system which includes a modification of an existing vaporiser (Diamedica Draw-over Vaporiser, Diamedica UK Ltd, Bratton Fleming, UK), to enable the delivery of 0.8% sevoflurane. Previous studies have suggested that self-administered sevoflurane at sub-anaesthetic concentration can provide useful pain relief during the first stage of labour and that it may be more effective than Entonox. Further research and potential clinical use have been impeded by the lack of a practical delivery system. In this study, the performance of two versions of the DSI (DSI-1 and DSI-2) was investigated. DSI-1 was tested over a range of minute volumes (1 to 30 l/min) and ambient temperatures (10°C to 40°C). The sevoflurane output increased unacceptably with rising ambient temperature, therefore the design was modified to create the DSI-2. The results from testing this revised version are also described. Mean sevoflurane output from the DSI-2 was found to be within a clinically acceptable range at the minute volumes tested (0.78% to 0.88%) and ambient temperatures tested (0.69% to 0.9%). Based upon these results, the authors propose to undertake further studies of sevoflurane analgesia using the DSI-2.

Early life exposure to allergen and ozone results in altered development in adolescent rhesus macaque lungs.

In rhesus macaques, previous studies have shown that episodic exposure to allergen alone or combined with ozone inhalation during the first 6 months of life results in a condition with many of the hallmarks of asthma. This exposure regimen results in altered development of the distal airways and parenchyma (Avdalovic et al., 2012). We hypothesized that the observed alterations in the lung parenchyma would be permanent following a long-term recovery in filtered air (FA) housing. Forty-eight infant rhesus macaques (30 days old) sensitized to house dust mite (HDM) were treated with two week cycles of FA, house dust mite allergen (HDMA), ozone (O3) or HDMA/ozone (HDMA+O3) for five months. At the end of the five months, six animals from each group were necropsied. The other six animals in each group were allowed to recover in FA for 30 more months at which time they were necropsied. Design-based stereology was used to estimate volumes of lung components, number of alveoli, size of alveoli, distribution of alveolar volumes, interalveolar capillary density. After 30 months of recovery, monkeys exposed to HDMA, in either group, had significantly more alveoli than filtered air. These alveoli also had higher capillary densities as compared with FA controls. These results indicate that early life exposure to HDMA alone or HDMA+O3 alters the development process in the lung alveoli.

Relaxation dynamics of a Fermi gas in an optical superlattice.

This Letter comprises an experimental and theoretical investigation of the time evolution of a Fermi gas following fast and slow quenches of a one-dimensional optical double-well superlattice potential. We investigate both the local tunneling in the connected double wells and the global dynamics towards a steady state, i.e., a time-independent state. The local observables in the steady state resemble those of a thermal equilibrium state, whereas the global properties indicate a strong nonequilibrium situation.

Lung effects of inhaled corticosteroids in a rhesus monkey model of childhood asthma.

BACKGROUND: The risks for infants and young children receiving inhaled corticosteroid (ICS) therapy are largely unknown. Recent clinical studies indicate that ICS therapy in pre-school children with symptoms of asthma result in decreased symptoms without influencing the clinical disease course, but potentially affect postnatal growth and development. The current study employs a primate experimental model to identify the risks posed by ICS therapy. OBJECTIVE: To (1) establish whether ICS therapy in developing primate lungs reverses pulmonary pathobiology associated with allergic airway disease (AAD) and (2) define the impact of ICS on postnatal lung growth and development in primates. METHODS: Infant rhesus monkeys were exposed, from 1 through 6 months, to filtered air (FA) with house dust mite allergen and ozone using a protocol that produces AAD (AAD monkeys), or to FA alone (Control monkeys). From three through 6 months, the monkeys were treated daily with ICS (budesonide) or saline. RESULTS: Several AAD manifestations (airflow restrictions, lavage eosinophilia, basement membrane zone thickening, epithelial mucin composition) were reduced with ICS treatment, without adverse effects on body growth or adrenal function; however, airway branching abnormalities and intraepithelial innervation were not reduced. In addition, several indicators of postnatal lung growth and differentiation: vital capacity, inspiratory capacity, compliance, non-parenchymal lung volume and alveolarization, were increased in both AAD and Control monkeys that received ICS treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Incomplete prevention of pathobiological changes in the airways and disruption of postnatal growth and differentiation of airways and lung parenchyma in response to ICS pose risks for developing primate lungs. These responses also represent two mechanisms that could compromise ICS therapy's ability to alter clinical disease course in young children.

Shipboard measurements of the hearing of the white-beaked dolphin Lagenorhynchus albirostris.

This is the first report of an underwater audiogram from a dolphin in a capture-and-release scenario. Two bow-riding white-beaked dolphins Lagenorhynchus albirostris (a female and a male) were captured using the hoop-net technique in Faxaflói Bay, Iceland. The dolphins were transferred to a stretcher and hoisted into a plastic research tank on board a small fishing vessel. Two underwater transducers were used to cover the frequency range from 16 to 215 kHz. Two human EEG electrodes mounted in suction cups, one placed near the blow hole and the other on the dorsal fin, picked up bioelectrical responses to acoustic stimuli. Responses to about 1000 sinusoidal amplitude modulated stimuli for each amplitude/frequency combination were averaged and analyzed using a fast Fourier transform to obtain an evoked auditory response. Threshold was defined as the zero crossing of the response using linear regression. Two threshold frequencies at 50 kHz and 64 kHz were obtained from the female. An audiogram ranging from 16 to 181 kHz was obtained from an adult male and showed the typical ;U' shaped curve for odontocetes. The thresholds for both white-beaks were comparable and demonstrated the most sensitive high frequency hearing of any known dolphin and were as sensitive as the harbor porpoise.

Potato aucuba mosaic virus in Potato in New York State.

Solanum tuberosum cv. Elmer's Blue is one of a number of heritage potato accessions maintained at Cornell University that exhibit virus-like symptoms of stunting and a leaf yellowing or a mottle mosaic. Testing of this cultivar by double-antibody sandwich (DAS)-ELISA revealed that it was infected with Potato virus S (PVS) but none of the other common potato viruses screened for in North American potato certification programs (3). Mechanical inoculation of sap from potato cv. Elmer's Blue onto Nicotiana debneyii, N. megalosiphon, N. occidentalis, and N. tabacum produced a range of yellowing and mosaic symptoms (symptomless on N. tabacum), indicating the presence of a transmissible agent, but all these hosts tested negative for PVS. To identify possible viruses, reverse transcription (RT)-PCR assays involving generic primers for different groups of viruses were performed on the potato and the Nicotiana spp. Degenerate primers specific to members of the genus Potexvirus (4) amplified a 600-bp region from the symptomatic potato and N. debneyii. Nucleotide sequencing of the RT-PCR amplified product from potato cv. Elmer's Blue (Genbank Accession No. EF609120) and comparisons with GenBank sequences revealed the amplified sequence as having 91% identity with the genomic sequence of Potato aucuba mosaic virus (PAMV; Accession No. S73580). The presence of this virus in potato cv. Elmer's Blue and N. debneyii was confirmed by PAMV-specific antibodies (Agdia, Inc., Elkhart, IN) in a DAS-ELISA format. PAMV is reported to occur worldwide, but uncommonly, with most descriptive work from Europe (2). While this virus has been studied in North America (1,2), these reports employed virus stocks from Europe under experimental conditions or virus in tubers obtained directly from Europe; to our knowledge, there are no unambiguous reports of PAMV in naturally infected North American potato cultivars. By contrast, the PAMV-infected cultivar in this report is a selection originally from a Canadian grower, and although not grown commercially, it is maintained in garden and field plots in New York and other states. References: (1) R. H. Bagnall. Phytopathology 50:460, 1960. (2) G. F. Kollmer and R. H. Larson. Res. Bull. Agric. Exp. Stn. Univ. Wis. 223:1, 1960. (3) S. A. Slack. Page 61 in: Potato Health Management. The American Phytopathological Society. St. Paul, MN, 1993. (4) R. A. A. van der Vlugt and M. Berendsen. Eur. J. Plant Pathol. 108:367, 2002.

Effect of method of delivering nicarbazin to mallards on plasma 4,4'-dinitrocarbanilide levels and reproduction.

Nicarbazin (NCZ), a coccidiostat used in the poultry industry, has been developed as a contraceptive for resident Canada geese. We tested the efficacy of NCZ as a contraceptive using mallards (Anas platyrhynchos) as a model for Canada geese. Nicarbazin-treated corn was fed ad libitum for 14 d at 0, 750, 1,000, or 1,500 ppm. Plasma and egg levels of 4,4'-dinitrocarbanilide (DNC), the active anticoccidial component of NCZ, differed among treatment groups in a dose-response relationship, but plasma levels did not differ between sexes. Nicarbazin caused a decrease in egg weight, but there was no effect of NCZ on the numbers of eggs laid per female per day. Nicarbazin did not significantly impact bird health. An additional trial tested the effect of the method of NCZ delivery on plasma DNC levels. Mallards were given NCZ daily for 12 d either by gavage with a corn oil suspension, gavage with a water suspension, peroral administration of a capsule, or feeding 500 mg of NCZ/kg of pelleted feed ad libitum. The method of delivery significantly affected plasma DNC levels, with the highest levels in the corn oil suspension group and the lowest levels in the pelleted feed group. This is likely due to decreased availability of NCZ in a pellet compared with gavage with a suspension or capsule. Mallards receiving 34.2 mg of NCZ/kg of BW when fed cracked corn coated with NCZ daily for 14 d had higher plasma DNC levels than those obtained by liquid gavage, capsule, or pelleted NCZ feed. For maximum effect in the field, NCZ should be coated onto corn. A higher concentration of NCZ is needed in pelleted feed to obtain comparable plasma DNC levels to allow for the decreased absorption of DNC.

Source levels and harmonic content of whistles in white-beaked dolphins (Lagenorhynchus albirostris).

Recordings of white-beaked dolphin whistles were made in Faxafl6i Bay (Iceland) using a three-hydrophone towed linear array. Signals from the hydrophones were routed through an amplifier to a lunch box computer on board the boat and digitized using a sample rate of 125 kHz per channel. Using this method more than 5000 whistles were recorded. All recordings were made in sea states 0-1 (Beaufort scale). Dolphins were located in a 2D horizontal plane by using the difference of arrival time to the three hydrophones, and source levels were estimated from these positions using two different methods (I and II). Forty-three whistles gave a reliable location for the vocalizing dolphin when using method II and of these 12 when using method I. Source level estimates on the center hydrophone were higher using method I [average source level 148 (rms) +/- 12 dB, n = 36] than for method II [average source level 139 (rms) +/- 12 dB, n = 36]. Using these rms values the maximum possible communication range for whistling dolphins given the local ambient noise conditions was then estimated. The maximum range was 10.5 km for a dolphin whistle with the highest source level (167 dB) and about 140 m for a whistle with the lowest source level (118 dB). Only two of the 43 whistles contained an unequal number of harmonics recorded at the three hydrophones judging from the spectrograms. Such signals could be used to calculate the directionality of whistles, but more recordings are necessary to describe the directionality of white-beaked dolphin whistles.

Molecular effects of nicarbazin on avian reproduction.

Nicarbazin (NCZ) is an anticoccidial drug routinely used in the poultry industry that can negatively affect reproduction by reducing egg production, egg weight, and egg hatchability. The molecular mechanisms by which NCZ affects reproduction are unknown. Lipoprotein lipase, vitellogenin, transglutaminase, and calcium are all involved in egg formation and embryogenesis. Therefore, in vitro assays were used to evaluate 4 potential mechanisms of action of NCZ on egg formation and embryogenesis. First, a lipoprotein lipase assay was conducted to determine if NCZ increases lipoprotein lipase activity. Second, vitellogenin phosphorylation was evaluated to determine if NCZ acts as a vitellogenin phosphatase. Third, transglutaminase activity was measured to determine if NCZ inhibits transglutaminase activity. Finally, bull sperm was used as a model to determine if specific channel-mediated calcium uptake can be blocked by NCZ. Nicarbazin increased the activity of lipoprotein lipase in vitro at 3.9 and 7.8 microg of NCZ/mL. Nicarbazin increased intracellular calcium levels in bull sperm, suggesting it also acts as a calcium ionophore. The portion of the NCZ molecule responsible for the increase in intracellular calcium is 2-hydroxy-4,6-dimethylpyrimidine. Nicarbazin affected vitellogenin phosphorylation but only at a concentration many times higher than expected plasma values. Nicarbazin also inhibited transglutaminase activity in vitro. Whereas the 4,4'-dinitrocarbanilide portion of the NCZ molecule inhibited transglutaminase activity, the 2-hydroxy-4,6-dimethylpyrimidine portion increased transglutaminase activity. All of these assays were conducted in vitro; therefore these results should be viewed as preliminary findings to aid in directing further research on the effect of NCZ on reproduction in vivo. Because NCZ increases lipoprotein lipase activity and acts as a calcium ionophore, future experiments should investigate these effects in particular.

Evaluation of nicarbazin as a potential waterfowl contraceptive using mallards as a model.

Contraception may provide a useful nonlethal management tool to reduce wild bird populations. We tested the efficacy of nicarbazin (NCZ) as a contraceptive for waterfowl and assessed health effects of NCZ, using domestic mallards (Anas platyrhynchos) as a model for Canada geese (Branta canadensis). Mallards were given gelatin capsules containing 0, 8.5, 17.0, or 33.75 mg of NCZ/kg of BW perorally once daily for 14 d. Fecal 4,4'-dinitrocarbanilide (DNC) and fluorescein were evaluated as potential markers of plasma and egg DNC levels. Plasma, egg, and fecal DNC levels differed among treatment groups in a dose response relationship. There were no significant effects on the numbers of eggs laid per female per day, proportion of fertile eggs, proportion of eggs hatching, or egg yolk mottling. Hatchability was 0.55 +/- 0.1 in the control group compared with 0.26 +/- 0.1 in the 33.75 mg/kg of BW group. Degeneration of the vitelline membrane was evident at all treatment levels; severity was dose-related and greater in the outer vitelline membrane than the inner vitelline membrane. No significant health effects were observed for birds treated with NCZ. The heterophil:lymphocyte ratio was elevated during the treatment and posttreatment periods in all groups, indicating birds were experiencing stress due to handling. Fecal DNC levels did not correlate well with plasma DNC levels, likely due to NCZ being administered as a bolus dose rather than being fed ad libitum. Fluorescein correlated well with plasma DNC levels during the treatment period and can therefore be used successfully as a noninvasive marker to determine the approximate amount of NCZ a bird is consuming. As a contraceptive, NCZ likely would have minimal adverse health effects on the target animal, although field studies with the species of interest need to be conducted. Further research using higher NCZ levels needs to be conducted to determine whether NCZ can inhibit reproduction in waterfowl.

Patients' understanding of disease status and treatment plan at initial hematopoietic stem cell transplantation consultation.

Patients referred for hematopoietic stem cell transplantation (HSCT) often have knowledge deficits about their disease and overestimate their prognosis making it difficult initially to discuss potentially life-threatening transplant options. To determine patients' understanding of their disease and the adequacy of a 3-h consultation at our center, we developed a survey that measured perceived knowledge deficits of disease, prognosis, and emotional status before and after their initial consultation. Ninety nine consecutive eligible patients completed the survey. Although 76.7% claimed adequate information about their disease pre-HCST visit, 51.5 and 41.4% respectively lacked knowledge about their 1-year prognosis with and without any therapy. After the visit, 66.7% of the patients had obtained enough information to make an informed decision regarding HSCT versus 23.2% pre-visit, and a significant reduction in the need for further information was reported by 53.5% of patients (P<0.001). Patients were not overwhelmed or confused by the visit and there was a small but significant decrease in negative affect. Measures to increase patients understanding of their disease and its prognosis pre-HSCT consultation visit are warranted; however, a 3-h consultation visit provides the majority of patients with sufficient information to make an informed decision about the risk/benefit ratio of HSCT.

Comparison of nicarbazin absorption in chickens, mallards, and Canada geese.

Nicarbazin (NCZ), a coccidiostat commonly used in the poultry industry, causes reduced hatchability and egg quality in layer hens at a concentration of 125 ppm (8.4 mg/kg) in the feed. Although this effect is undesirable in the poultry industry, NCZ could provide a useful wildlife contraception tool for waterfowl, particularly urban geese. We tested the absorption of NCZ in chickens (Gallus gallus), mallards (Anas platyrhynchos), and Canada geese (Branta canadensis) gavaged with 8.4 mg of NCZ/kg per bird each day for 8 d. Plasma levels of 4,4'-dinitrocarbanilide (DNC) differed significantly among species. Peak plasma DNC levels were 2.87 +/- 0.15 microg/mL, 2.39 +/- 0.15 microg/mL, and 1.53 +/- 0.15 microg/ mL in chickens, mallards, and Canada geese respectively. It took 6 d to obtain peak DNC levels in chickens as opposed to 8 d in mallards and Canada geese. The half life of DNC in plasma was 1.43 d in chickens, 0.72 d in mallards, and 1.26 d in Canada geese. Mallards eliminated 100% of plasma DNC 4 d post-treatment, whereas Canada geese eliminated 100% of plasma DNC 8 d post-treatment. Chickens had only eliminated 99% of plasma DNC 8 d post-treatment. Mallard plasma DNC levels were highly correlated with Canada goose plasma DNC levels. This research showed mallards are an ideal model species for the Canada goose for future reproductive studies on NCZ in a laboratory setting. However, levels higher than 8.4 mg/kg must be fed to waterfowl in order to obtain a plasma level comparable to chickens.

Airway generation-specific differences in the spatial distribution of immune cells and cytokines in allergen-challenged rhesus monkeys.

BACKGROUND: Accumulation of immune cell populations and their cytokine products within tracheobronchial airways contributes to the pathogenesis of allergic asthma. It has been postulated that peripheral regions of the lung play a more significant role than proximal airways with regard to inflammatory events and airflow obstruction. OBJECTIVE: To determine whether immune cell populations and associated cytokines are uniformly distributed throughout the conducting airway tree in a non-human primate model of allergic asthma. METHODS: We used a stereologic approach with a stratified sampling scheme to measure the volume density of immune cells within the epithelium and interstitium of trachea and 4-5 intrapulmonary airway generations from house dust mite (HDM) (Dermatophagoides farinae)-challenged adult monkeys. In conjunction with immune cell distribution profiles, mRNA levels for 21 cytokines/chemokines and three chemokine receptors were evaluated at four different airway generations from microdissected lungs. RESULTS: In HDM-challenged monkeys, the volume of CD1a+ dendritic cells, CD4+ T helper lymphocytes, CD25+ cells, IgE+ cells, eosinophils, and proliferating cells were significantly increased within airways. All five immune cell types accumulated within airways in unique patterns of distribution, suggesting compartmentalized responses with regard to trafficking. Although cytokine mRNA levels were elevated throughout the conducting airway tree of HDM-challenged animals, the distal airways (terminal and respiratory bronchioles) exhibited the most pronounced up-regulation. CONCLUSION: These findings demonstrate that key effector immune cell populations and cytokines associated with asthma differentially accumulate within distinct regions and compartments of tracheobronchial airways from allergen-challenged primates.