Comparison of Two Detailed Models of Aedes aegypti Population Dynamics

The success of control programs for mosquito-­borne diseases can be enhanced by crucial information provided by models of the mosquito populations. Models, however, can differ in their structure, complexity, and biological assumptions, and these differences impact their predictions. Unfortunately, it is typically difficult to determine why two complex models make different predictions because we lack structured side-­by-­side comparisons of models using comparable parameterization. Here, we present a detailed comparison of two complex, spatially explicit, stochastic models of the population dynamics of Aedes aegypti, the main vector of dengue, yellow fever, chikungunya, and Zika viruses. Both models describe the mosquito?s biological and ecological characteristics, but differ in complexity and specific assumptions. We compare the predictions of these models in two selected climatic settings: a tropical and weakly seasonal climate in Iquitos, Peru, and a temperate and strongly seasonal climate in Buenos Aires, Argentina. Both models were calibrated to operate at identical average densities in unperturbedconditions in both settings, by adjusting parameters regulating densities in each model (number of larval development sites and amount of nutritional resources). We show that the models differ in their sensitivityto environmental conditions (temperature and rainfall) and trace differences to specific model assumptions.Temporal dynamics of the Ae. aegypti populations predicted by the two models differ more markedly under strongly seasonal Buenos Aires conditions. We use both models to simulate killing of larvae and/or adults with insecticides in selected areas. We show that predictions of population recovery by the models differ substantially, an effect likely related to model assumptions regarding larval development and (director delayed) density dependence. Our methodical comparison provides important guidance for model improvement by identifying key areas of Ae. aegypti ecology that substantially affect model predictions, and revealing the impact of model assumptions on population dynamics predictions in unperturbed and perturbed conditions.Fil: Legros, Mathieu. University of North Carolina; Estados UnidosFil: Otero, Marcelo Javier. Universidad de Buenos Aires; ArgentinaFil: Romeo Aznar, Victoria Teresa. Universidad de Buenos Aires; ArgentinaFil: Solari, Hernan Gustavo. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Gould, Fred. National Institutes of Health; Estados UnidosFil: Lloyd, Alun L.. National Institutes of Health; Estados Unido

Currents associated with Saturn's intra-D ring azimuthal field perturbations

During the final 22 full revolutions of the Cassini mission in 2017, the spacecraft passed at periapsis near the noon meridian through the gap between the inner edge of Saturn’s D ring and the denser layers of the planet’s atmosphere, revealing the presence of an unanticipated low-latitude current system via the associated azimuthal perturbation field peaking typically at ~10-30 nT. Assuming approximate axisymmetry, here we use the field data to calculate the associated horizontal meridional currents flowing in the ionosphere at the feet of the field lines traversed, together with the exterior field-aligned currents required by current continuity. We show that the ionospheric currents are typically~0.5–1.5 MA per radian of azimuth, similar to auroral region currents, while the field-aligned current densities above the ionosphere are typically ~5-10 nA m-2 , more than an order less than auroral values. The principal factor involved in this difference is the ionospheric areas into which the currents map. While around a third of passes exhibit unidirectional currents flowing northward in the ionosphere closing southward along exterior field lines, many passes also display layers of reversed northward field-aligned current of comparable or larger magnitude in the region interior to the D ring, which may reverse sign again on the innermost field lines traversed. Overall, however, the currents generally show a high degree of north-south conjugacy indicative of an interhemispheric system, certainly on the larger overall spatial scales involved, if less so for the smaller-scale structures, possibly due to rapid temporal or local time variations

Life table analysis of Diaphorina citri (Hemiptera: Psyllidae) infesting sweet orange (Citrus sinensis) in São Paulo

An ecological life table for eggs and nymphs of Diaphorina citri Kuwayama (Hemiptera: Psyllidae) was constructed with data obtained from orange orchards (Citrus sinensis Osbeck) in 2 regions of the State of São Paulo, over 4 generations in the period from XI-2006 to V-2007, comprising spring, summer, and fall seasons. Young growing shoots with D. citri eggs present were identifed, and live individuals were counted until adult emergence. No predatory arthropods were observed in association with D. citri eggs and nymphs during the study. The mean parasitism of fourth- and ffth-instar nymphs by Tamarixia radiata Waterston (Hymenoptera: Eulophidae) was 2.3%. The durations of the egg–adult period were similar among the 4 generations, ranging from 18.0 to 24.7 d (at mean temperatures ranging from 21.6 to 26.0 °C) and followed the temperature requirement models obtained in the laboratory for D. citri. However, survival from the egg to the adult stage for the same period varied considerably from 1.7 to 21.4%; the highest mortalities were observed in the egg and small nymphal (frst- to thirdinstar) stages, which were considered to be key phases for population growth of the pest.Uma tabela de vida ecológica foi construída para ovos e ninfas de Diaphorina citri Kuwayama (Hemiptera: Psyllidae) com dados obtidos em pomares de laranja (Citrus sinensis Osbeck) em 2 regiões do estado de São Paulo, com 4 gerações, no período de novembro de 2006 a maio de 2007, compreendendo as estações de primavera, verão e outono. Ramos jovens em crescimento com a presença de ovos de D. citri foram identificados e os indivíduos vivos foram contados até a emergência dos adultos. Nenhum predador foi observado associado a ovos e ninfas de D. citri durante o estudo. A taxa média de parasitismo de ninfas de quarto e quinto ínstares por Tamarixia radiata Waterson (Hymenoptera: Eulophidae) foi de 2.3%. A duração do período de ovo a adulto foi semelhante entre as quatro gerações, variando de 18.0 a 24.7 dias (com temperaturas médias de 21.6 a 26.0 °C) e seguiram os modelos de exigencias térmicas obtidas em laboratório para D. citri. Todavia, a sobrevivencia de ovo até o estágio adulto variou consideravelmente para o mesmo período, de 1.7 a 21.4%, sendo que as maiores mortalidades foram observadas nos estágios de ovos e ninfas pequenas (de primeiro a terceiro ínstares), as quais foram consideradas fases chaves para o crescimento populacional desta praga.info:eu-repo/semantics/publishedVersio

Targeting HIF2α-ARNT hetero-dimerisation as a novel therapeutic strategy for pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a destructive disease of the pulmonary vasculature often leading to right heart failure and death. Current therapeutic intervention strategies only slow disease progression. The role of aberrant hypoxia-inducible factor (HIF)2α stability and function in the initiation and development of pulmonary hypertension (PH) has been an area of intense interest for nearly two decades. Here we determine the effect of a novel HIF2α inhibitor (PT2567) on PH disease initiation and progression, using two pre-clinical models of PH. Haemodynamic measurements were performed, followed by collection of heart, lung and blood for pathological, gene expression and biochemical analysis. Blood outgrowth endothelial cells from idiopathic PAH patients were used to determine the impact of HIF2α-inhibition on endothelial function. Global inhibition of HIF2a reduced pulmonary vascular haemodynamics and pulmonary vascular remodelling in both su5416/hypoxia prevention and intervention models. PT2567 intervention reduced the expression of PH-associated target genes in both lung and cardiac tissues and restored plasma nitrite concentration. Treatment of monocrotaline-exposed rodents with PT2567 reduced the impact on cardiovascular haemodynamics and promoted a survival advantage. In vitro, loss of HIF2α signalling in human pulmonary arterial endothelial cells suppresses target genes associated with inflammation, and PT2567 reduced the hyperproliferative phenotype and overactive arginase activity in blood outgrowth endothelial cells from idiopathic PAH patients. These data suggest that targeting HIF2α hetero-dimerisation with an orally bioavailable compound could offer a new therapeutic approach for PAH. Future studies are required to determine the role of HIF in the heterogeneous PAH population

Midday auroral breakup events and related energy and momentum transfer from the magnetosheath

Combined observations by meridian-scanning photometers, all-sky auroral TV camera and the EISCAT radar permitted a detailed analysis of the temporal and spatial development of the midday auroral breakup phenomenon and the related ionospheric ion flow pattern within the 71°–75° invariant latitude radar field of view. The radar data revealed dominating northward and westward ion drifts, of magnitudes close to the corresponding velocities of the discrete, transient auroral forms, during the two different events reported here, characterized by IMF |BY/BZ| 2, respectively (IMF BZ between −8 and −3 nT and BY > 0). The spatial scales of the discrete optical events were ∼50 km in latitude by ∼500 km in longitude, and their lifetimes were less than 10 min. Electric potential enhancements with peak values in the 30–50 kV range are inferred along the discrete arc in the IMF |BY/BZ| 2 case. Joule heat dissipation rates in the maximum phase of the discrete structures of ∼ 100 ergs cm−2 s−1 (0.1 W m−2) are estimated from the photometer intensities and the ion drift data. These observations combined with the additional characteristics of the events, documented here and in several recent studies (i.e., their quasi-periodic nature, their motion pattern relative to the persistent cusp or cleft auroral arc, the strong relationship with the interplanetary magnetic field and the associated ion drift/E field events and ground magnetic signatures), are considered to be strong evidence in favour of a transient, intermittent reconnection process at the dayside magnetopause and associated energy and momentum transfer to the ionosphere in the polar cusp and cleft regions. The filamentary spatial structure and the spectral characteristics of the optical signature indicate associated localized ˜1-kV potential drops between the magnetopause and the ionosphere during the most intense auroral events. The duration of the events compares well with the predicted characteristic times of momentum transfer to the ionosphere associated with the flux transfer event-related current tubes. It is suggested that, after this 2–10 min interval, the sheath particles can no longer reach the ionosphere down the open flux tube, due to the subsequent super-Alfvénic flow along the magnetopause, conductivities are lower and much less momentum is extracted from the solar wind by the ionosphere. The recurrence time (3–15 min) and the local time distribution (∼0900–1500 MLT) of the dayside auroral breakup events, combined with the above information, indicate the important roles of transient magnetopause reconnection and the polar cusp and cleft regions in the transfer of momentum and energy between the solar wind and the magnetosphere

Saturn's Auroral Field-Aligned Currents: Observations from the Northern Hemisphere Dawn Sector During Cassini's Proximal Orbits

We examine the azimuthal magnetic field signatures associated with Saturn's northern hemisphere auroral field‐aligned currents observed in the dawn sector during Cassini's Proximal orbits (April 2017 and September 2017). We compare these currents with observations of the auroral currents from near noon taken during the F‐ring orbits prior to the Proximal orbits. First, we show that the position of the main auroral upward current is displaced poleward between the two local times (LTs). This is consistent with the statistical position of the ultraviolet auroral oval for the same time interval. Second, we show the overall average ionospheric meridional current profile differs significantly on the equatorward boundary of the upward current with a swept‐forward configuration with respect to planetary rotation present at dawn. We separate the planetary period oscillation (PPO) currents from the PPO‐independent currents and show their positional relationship is maintained as the latitude of the current shifts in LT implying an intrinsic link between the two systems. Focusing on the individual upward current sheets pass‐by‐pass, we find that the main upward current at dawn is stronger compared to near noon. This results in the current density being ~1.4 times higher in the dawn sector. We determine a proxy for the precipitating electron power and show that the dawn PPO‐independent upward current electron power is ~1.9 times higher than at noon. These new observations of the dawn auroral region from the Proximal orbits may show evidence of an additional upward current at dawn likely associated with strong flows in the outer magnetosphere

Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire

Idiosyncratic adverse drug reactions are unpredictable, dose independent and potentially life threatening; this makes them a major factor contributing to the cost and uncertainty of drug development. Clinical data suggest that many such reactions involve immune mechanisms, and genetic association studies have identified strong linkage between drug hypersensitivity reactions to several drugs and specific HLA alleles. One of the strongest such genetic associations found has been for the antiviral drug abacavir, which causes severe adverse reactions exclusively in patients expressing the HLA molecular variant B*57:01. Abacavir adverse reactions were recently shown to be driven by drug-specific activation of cytokine-producing, cytotoxic CD8+ T cells that required HLA-B*57:01 molecules for their function. However, the mechanism by which abacavir induces this pathologic T cell response remains unclear. Here we show that abacavir can bind within the F-pocket of the peptide-binding groove of HLA-B*57:01 thereby altering its specificity. This supports a novel explanation for HLA-linked idiosyncratic adverse drug reactions; namely that drugs can alter the repertoire of self-peptides presented to T cells thus causing the equivalent of an alloreactive T cell response. Indeed, we identified specific self-peptides that are presented only in the presence of abacavir, and that were recognized by T cells of hypersensitive patients. The assays we have established can be applied to test additional compounds with suspected HLA linked hypersensitivities in vitro. Where successful, these assays could speed up the discovery and mechanistic understanding of HLA linked hypersensitivities as well as guide the development of safer drugs

Partial pathogen protection by tick-bite sensitization and epitope recognition in peptide-immunized HLA DR3 transgenic mice

Ticks are notorious vectors of disease for humans, and many species of ticks transmit multiple pathogens, sometimes in the same tick bite. Accordingly, a broad-spectrum vaccine that targets vector ticks and pathogen transmission at the tick/host interface, rather than multiple vaccines against every possible tickborne pathogen, could become an important tool for resolving an emerging public health crisis. The concept for such a tick protective vaccine comes from observations of an acquired tick resistance (ATR) that can develop in non-natural hosts of ticks following sensitization to tick salivary components. Mice are commonly used as models to study immune responses to human pathogens but normal mice are natural hosts for many species of ticks and fail to develop ATR. We evaluated HLA DR3 transgenic (tg) “humanized” mice as a potential model of ATR and assessed the possibility of using this animal model for tick protective vaccine discovery studies. Serial tick infestations with pathogen-free Ixodes scapularis ticks were used to tick-bite sensitize HLA DR3 tg mice. Sensitization resulted in a cytokine skew favoring a Th2 bias as well as partial (57%) protection to infection with Lyme disease spirochetes (Borrelia burgdorferi) following infected tick challenge when compared to tick naïve counterparts. I. scapularis salivary gland homogenate (SGH) and a group of immunoinformatic-predicted T cell epitopes identified from the I. scapularis salivary transcriptome were used separately to vaccinate HLA DR3 tg mice, and these mice also were assessed for both pathogen protection and epitope recognition. Reduced pathogen transmission along with a Th2 skew resulted from SGH vaccination, while no significant protection and a possible T regulatory bias was seen in epitope-vaccinated mice. This study provides the first proof-of-concept for using HLA DR tg “humanized” mice for studying the potential tick protective effects of immunoinformatic- or otherwise-derived tick salivary components as tickborne disease vaccines