Environmental and geographical factors influence the occurrence and abundance of the southern house mosquito, Culex quinquefasciatus, in Hawai'i.

Hawaiian honeycreepers, a group of endemic Hawaiian forest birds, are being threatened by avian malaria, a non-native disease that is driving honeycreepers populations to extinction. Avian malaria is caused by the parasite Plasmodium relictum, which is transmitted by the invasive mosquito Culex quinquefasciatus. Environmental and geographical factors play an important role in shaping mosquito-borne disease transmission dynamics through their influence on the distribution and abundance of mosquitoes. We assessed the effects of environmental (temperature, precipitation), geographic (site, elevation, distance to anthropogenic features), and trap type (CDC light trap, CDC gravid trap) factors on mosquito occurrence and abundance. Occurrence was analyzed using classification and regression tree models (CART) and generalized linear models (GLM); abundance (count data) was analyzed using generalized linear mixed models (GLMMs). Models predicted highest mosquito occurrence at mid-elevation sites and between July and November. Occurrence increased with temperature and precipitation up to 580 mm. For abundance, the best model was a zero-inflated negative-binomial model that indicated higher abundance of mosquitoes at mid-elevation sites and peak abundance between August and October. Estimation of occurrence and abundance as well as understanding the factors that influence them are key for mosquito control, which may reduce the risk of forest bird extinction.

Accounting for spatial habitat and management boundaries when estimating forest bird population distribution and density: inferences from a soap film smoother.

Birds are often obligate to specific habitats which can result in study areas with complex boundaries due to sudden changes in vegetation or other features. This can result in study areas with concave arcs or that include holes of unsuitable habitat such as lakes or agricultural fields. Spatial models used to produce species' distribution and density estimates need to respect such boundaries to make informed decisions for species conservation and management. The soap film smoother is one model for complex study regions which controls the boundary behaviour, ensuring realistic values at the edges of the region. We apply the soap film smoother to account for boundary effects and compare it with thin plate regression spline (TPRS) smooth and design-based conventional distance sampling methods to produce abundance estimates from point-transect distance sampling collected data on Hawai'i 'Akepa Loxops coccineus in the Hakalau Forest Unit of the Big Island National Wildlife Refuge Complex, Hawai'i Island, USA. The soap film smoother predicted zero or near zero densities in the northern part of the domain and two hotspots (in the southern and central parts of the domain). Along the boundary the soap film model predicted relatively high densities where 'Akepa occur in the adjacent forest and near zero elsewhere. The design-based and soap film abundance estimates were nearly identical. The width of the soap film confidence interval was 16.5% and 0.8% wider than the width of the TPRS smooth and design-based confidence intervals, respectively. The peaks in predicted densities along the boundary indicates leakage by the TPRS smooth. We provide a discussion of the statistical methods, biological findings and management implications of applying soap film smoothers to estimate forest bird population status.

No evidence of critical slowing down in two endangered Hawaiian honeycreepers.

There is debate about the current population trends and predicted short-term fates of the endangered forest birds, Hawai`i Creeper (Loxops mana) and Hawai`i `Akepa (L. coccineus). Using long-term population size estimates, some studies report forest bird populations as stable or increasing, while other studies report signs of population decline or impending extinction associated with introduced Japanese White-eye (Zosterops japonicus) increase. Reliable predictors of impending population collapse, well before the collapse begins, have been reported in simulations and microcosm experiments. In these studies, statistical indicators of critical slowing down, a phenomenon characterized by longer recovery rates after population size perturbation, are reported to be early warning signals of an impending regime shift observable prior to the tipping point. While the conservation applications of these metrics are commonly discussed, early warning signal detection methods are rarely applied to population size data from natural populations, so their efficacy and utility in species management remain unclear. We evaluated two time series of state-space abundance estimates (1987-2012) from Hakalau Forest National Wildlife Refuge, Hawai`i to test for evidence of early warning signals of impending population collapse for the Hawai`i Creeper and Hawai`i `Akepa. We looked for signals throughout the time series, and prior to 2000, when white-eye abundance began increasing. We found no evidence for either species of increasing variance, autocorrelation, or skewness, which are commonly reported early warning signals. We calculated linear rather than ordinary skewness because the latter is biased, particularly for small sample sizes. Furthermore, we identified break-points in trends over time for both endangered species, indicating shifts in slopes away from strongly increasing trends, but they were only weakly supported by Bayesian change-point analyses (i.e., no step-wise changes in abundance). The break-point and change-point test results, in addition to the early warning signal analyses, support that the two populations do not appear to show signs of critical slowing down or decline.

Collapsing avian community on a Hawaiian island.

The viability of many species has been jeopardized by numerous negative factors over the centuries, but climate change is predicted to accelerate and increase the pressure of many of these threats, leading to extinctions. The Hawaiian honeycreepers, famous for their spectacular adaptive radiation, are predicted to experience negative responses to climate change, given their susceptibility to introduced disease, the strong linkage of disease distribution to climatic conditions, and their current distribution. We document the rapid collapse of the native avifauna on the island of Kaua'i that corresponds to changes in climate and disease prevalence. Although multiple factors may be pressuring the community, we suggest that a tipping point has been crossed in which temperatures in forest habitats at high elevations have reached a threshold that facilitates the development of avian malaria and its vector throughout these species' ranges. Continued incursion of invasive weeds and non-native avian competitors may be facilitated by climate change and could also contribute to declines. If current rates of decline continue, we predict multiple extinctions in the coming decades. Kaua'i represents an early warning for the forest bird communities on the Maui and Hawai'i islands, as well as other species around the world that are trapped within a climatic space that is rapidly disappearing.

Changing climate and the altitudinal range of avian malaria in the Hawaiian Islands - an ongoing conservation crisis on the island of Kaua'i.

Transmission of avian malaria in the Hawaiian Islands varies across altitudinal gradients and is greatest at elevations below 1500 m where both temperature and moisture are favorable for the sole mosquito vector, Culex quinquefasciatus, and extrinsic sporogonic development of the parasite, Plasmodium relictum. Potential consequences of global warming on this system have been recognized for over a decade with concerns that increases in mean temperatures could lead to expansion of malaria into habitats where cool temperatures currently limit transmission to highly susceptible endemic forest birds. Recent declines in two endangered species on the island of Kaua'i, the 'Akikiki (Oreomystis bairdi) and 'Akeke'e (Loxops caeruleirostris), and retreat of more common native honeycreepers to the last remaining high elevation habitat on the Alaka'i Plateau suggest that predicted changes in disease transmission may be occurring. We compared prevalence of malarial infections in forest birds that were sampled at three locations on the Plateau during 1994-1997 and again during 2007-2013, and also evaluated changes in the occurrence of mosquito larvae in available aquatic habitats during the same time periods. Prevalence of infection increased significantly at the lower (1100 m, 10.3% to 28.2%), middle (1250 m, 8.4% to 12.2%), and upper ends of the Plateau (1350 m, 2.0% to 19.3%). A concurrent increase in detections of Culex larvae in aquatic habitats associated with stream margins indicates that populations of the vector are also increasing. These increases are at least in part due to local transmission because overall prevalence in Kaua'i 'Elepaio (Chasiempis sclateri), a sedentary native species, has increased from 17.2% to 27.0%. Increasing mean air temperatures, declining precipitation, and changes in streamflow that have taken place over the past 20 years are creating environmental conditions throughout major portions of the Alaka'i Plateau that support increased transmission of avian malaria.

Dynamics of Cl + propane, butanes revisited: a crossed beam slice imaging study.

We report velocity-flux contour maps for H-D abstraction in selected Cl + alkane reactions measured by means of crossed beam scattering combined with universal DC slice imaging. The studied hydrocarbons are propane and its two selectively deuterated isotopologues, namely 1,1,1,3,3,3-propane-d6 and 2,2-propane-d2, n-butane and isobutane (2-methyl-propane), with detection of the hydrocarbon radical product by 157 nm single photon ionization. Data are obtained at collision energies of 12-13 kcal mol(-1) using a high-density atomic chlorine radical source combining Cl2 photolysis with ablation. All presented scattering distributions involving secondary and tertiary abstractions show distinct differences. Their comparisons allow for revisiting the dynamical picture of these reactions in terms of the nature of the abstraction sites, radical product energy disposal, and H vs. D abstraction. Results are discussed in the light of previous work and ab initio thermochemical calculations, along with proposals to future directions for investigation.

Crossed-beam slice imaging of Cl reaction dynamics with butene isomers.

We present a crossed-beam imaging study of the reaction of chlorine atoms with several butene isomers. A high-intensity pulsed ablation Cl source is used with DC slice imaging and single-photon ionization detection at 157 nm to record the velocity-flux contour maps for these reactions. The target unsaturated hydrocarbons are 1-butene, trans-2-butene, cis-2-butene, and isobutene (2-methylpropene). Data are obtained at collision energies of ~13.0 kcal·mol(-1). Distinct differences in the scattering distributions and in particular the coupling of angular and translational energy release provide insight into the dynamics of this little-studied class of reactions. We find that these distributions reflect the energetics for competition between addition/elimination and direct abstraction in line with ab initio thermochemical data. A possible role for Cl atom roaming mediating the addition/elimination pathway is suggested.

Humoral autoimmune responses to the squamous cell carcinoma antigen protein family in psoriasis.

Substantial evidence indicates that psoriasis is a T-lymphocyte-mediated autoimmune disease. However, longstanding data also indicate IgG and complement deposition in upper epidermis of psoriasis plaques. This led us to propose that autoantigen-autoantibody interactions in the skin may also be of pathogenic importance. Here, we have confirmed the presence of IgG in upper lesional epidermis and used high-resolution two-dimensional immunoblotting of extracts from this tissue, and laser desorption mass spectrometry of tryptic peptides, to define a series of epidermal proteins that bind IgG from psoriatic serum. The most prominent of these autoantigens are homologues of the serpin, squamous cell carcinoma antigen (SCCA), the other autoantigens identified including arginase 1, enolase 1, and keratin 10. Blood levels of IgG autoantibodies that bind to SCCA proteins were significantly higher in psoriasis than healthy controls (P=0.005), but were not detectable in sera from patients with active atopic dermatitis. To our knowledge, SCCA proteins have not previously been described as autoantigenic in animals or humans and form complexes with IgG that are associated with complement deposition. These findings expose potentially pathogenic humoral immunologic events and thus possible therapeutic targets in psoriasis.

Increased blood levels of IgG reactive with secreted Streptococcus pyogenes proteins in chronic plaque psoriasis.

A pathogenic role for Streptococcus (S) pyogenes infections in chronic plaque psoriasis is suspected but poorly defined. We separated cellular and supernatant proteins from S. pyogenes cultures by high-resolution two-dimensional gel electrophoresis, and used immunoblotting to demonstrate the diversity of serum or plasma IgGs that react with elements of the proteome of this bacterium. We have shown that a substantial proportion of IgG-reactive proteins from cultured S. pyogenes are secreted. The total secreted protein fraction, including diverse IgG-binding elements, was subsequently used in an ELISA to measure blood titers of reactive IgG. This ELISA showed that blood samples from patients with chronic plaque psoriasis contained significantly higher titers of reactive IgG than samples from age- and sex-matched healthy controls (P=0.0009). In contrast, neither a standard assay measuring antistreptolysin O titers nor ELISAs measuring titers of IgG reactive with protein fractions from Staphylococcus aureus and Staphylococcus epidermidis, were able to distinguish between blood samples from the two groups. These findings justify the hypothesis that S. pyogenes infections are more important in the pathogenesis of chronic plaque psoriasis than has previously been recognized, and indicate the need for further controlled therapeutic trials of antibacterial measures in this common skin disease.

IgE-dependent activation of T cells by allergen in atopic dermatitis: pathophysiologic relevance.

The importance of interactions between allergen and IgE in allergen-mediated activation of T lymphocytes from patients with atopic dermatitis (AD) is unclear. A role for this interaction is implied by past evidence for IgE-facilitated presentation of allergen to T cells, but this phenomenon has only been demonstrated in specific in vitro systems biased to maximize the effect. It is therefore not known whether the process is relevant in patients. We now show that the responses to allergen of unmodified peripheral blood mononuclear cells (PBMC) from individual AD patients are significantly greater in the presence of fresh, unheated, IgE-containing autologous serum than the same serum heated under IgE-denaturing conditions or specifically depleted of IgE by immunoprecipitation. In six independent experiments, 59%-67% of the maximal in vitro PBMC response to allergen was found to be dependent upon the presence of IgE in autologous serum used at 5% final concentration. These data provide the first evidence that sufficient amounts of allergen-specific IgE and allergen-reactive T cells occur concomitantly in the blood of individual AD patients to allow IgE-enhanced T cell responses to allergen. We conclude that IgE-enhanced T cell responses are pathophysiologically relevant and a therapeutic target in AD.

Novel cyclic and linear oligopeptides that bind to integrin beta1 chain and either inhibit or costimulate T lymphocytes.

There is a redundancy of cellular beta1 integrin (very late antigen or VLA) receptors that mediate interactions between different extracellular matrix proteins (ECMP) and T lymphocytes. This suggests that antagonists targeted at individual VLA receptors may be of limited therapeutic efficacy in T cell-mediated diseases and that agents such as monoclonal antibody 4B4, which bind to the common integrin beta1 chain and inhibit interactions between effector T cells and a range of ECMP, may be of greater therapeutic interest if toxicity can be avoided. We have therefore sought proof of principle as to whether small molecules that interact with the integrin beta1 chain at or near the 4B4 binding site can modulate T cell costimulation and adhesion in the presence of type I collagen or fibronectin (FN). Two phage display libraries, each expressing more than 10(9) independent cyclic or linear 7-mer peptides, were used to identify molecules of interest by an enrichment process involving specific recovery of phage bound to a human T cell line by elution with a large excess of 4B4 antibody. Novel cyclic and linear peptides have thus been identified and found to inhibit interactions between T cells and both type I collagen and fibronectin. A separate cyclic peptide was found to costimulate T cells in a beta1 integrin-dependent manner. These findings form a basis for the development of small molecules that interact in inhibitory or stimulatory capacities with the common integrin beta1 chain, and may be of interest as therapeutic antagonists or immunologic adjuvants.

Recognition of pathogenically relevant house dust mite hypersensitivity in adults with atopic dermatitis: a new approach?

BACKGROUND: The pathogenic importance of the ubiquitous house dust mite, Dermatophagoides pteronyssinus (Dp), in atopic dermatitis is unclear. OBJECTIVE: We aimed to explore the relevance of Dp hypersensitivity in adult patients with atopic dermatitis by using an in vivo topical challenge method and in vitro assays for T-cell reactivity. METHODS: Dp and control skin prick test solutions were applied to the cubital fossae of 20 patients twice daily for 4 days; the severity of dermatitis and pruritus in the challenge sites were determined before and after testing. The same solutions were used in PBMC proliferation assays that included 10% fresh, autologous serum, the latter aimed at maximizing IgE facilitated allergen presentation. RESULTS: Although most patients had markedly elevated Dp-specific serum IgE levels, only 6 of 20 patients developed increases in cubital fossa dermatitis severity and pruritus scores that were greater at sites of application of Dp solution than at control sites. In addition, PBMC proliferation in response to Dp solution in the presence of autologous serum was significantly greater in the in vivo challenge-positive patients than in those who did not respond to challenge. A subgroup of patients (7/20) also developed transient but pronounced contact urticaria at sites of Dp application. CONCLUSION: These findings suggest that hypersensitivity to Dp might be clinically relevant in approximately one third of the adult atopic dermatitis population studied. They also point to methods of identifying patients who might respond to house dust avoidance measures.