RESUMO
Estimating connectivity among fragmented habitat patches is crucial for evaluating the functionality of ecological networks. However, current estimates of landscape resistance to animal movement and dispersal lack landscape-level data on local habitat structure. Here, we used a landscape genetics approach to show that high-fidelity habitat structure maps derived from Light Detection and Ranging (LiDAR) data critically improve functional connectivity estimates compared to conventional land cover data. We related pairwise genetic distances of 128 Capercaillie (Tetrao urogallus) genotypes to least-cost path distances at multiple scales derived from land cover data. Resulting ß values of linear mixed effects models ranged from 0.372 to 0.495, while those derived from LiDAR ranged from 0.558 to 0.758. The identification and conservation of functional ecological networks suffering from habitat fragmentation and homogenization will thus benefit from the growing availability of detailed and contiguous data on three-dimensional habitat structure and associated habitat quality.
Assuntos
Ecossistema , Genética Populacional , AnimaisRESUMO
BACKGROUND: Binding of allergen-specific IgE to its high-affinity receptor FcεRI on basophils and mast cells is a central event in the development of allergies. Exposure of these cells to allergens induces the release of soluble mediators causing allergic symptoms. The inhibitory low-affinity IgG Fc-receptor FcγRIIB is co-expressed on allergic effector cells and has been implicated in negative regulation of immediate hypersensitivity responses. In order to harvest the inhibitory function of this receptor, we aimed to select specific binders against FcγRIIB and to generate a bispecific molecule simultaneously targeting FcγRIIB and FcεRI-bound IgE on the surface of allergic effector cells. METHODS: We selected FcγRIIB-specific binding molecules from a library of designed ankyrin repeat proteins using ribosome display technology. The bispecific binding modality was generated by molecular cloning and recombinant protein expression. We determined binding characteristics on molecular and cellular levels using SPR, ELISA, and flow cytometry. The inhibitory potential of the newly described molecules was assessed in different cellular degranulation assays ex vivo and in a mouse model of passive systemic anaphylaxis. RESULTS: We demonstrate that the selected DARPin® proteins recognize FcγRIIB with high affinity. Furthermore, the bispecific binding protein successfully interferes with allergen-induced cell degranulation and efficiently inhibits systemic anaphylaxis in vivo. Mechanistically, we report that FcγRIIB-mediated inhibition of effector cell activation requires direct ligation to an activating FcεRI receptor. CONCLUSION: The described bispecific DARPin protein has the ability to co-ligate FcγRIIB with FcεRI-bound IgE on allergic effector cells and represents an efficient dual-modality to interfere with allergic hypersensitivity reactions.
Assuntos
Hipersensibilidade/imunologia , Hipersensibilidade/metabolismo , Imunoglobulina E/imunologia , Imunoglobulina E/metabolismo , Receptores de IgE/metabolismo , Receptores de IgG/metabolismo , Proteínas Recombinantes de Fusão/farmacologia , Animais , Basófilos/efeitos dos fármacos , Basófilos/imunologia , Basófilos/metabolismo , Degranulação Celular/efeitos dos fármacos , Degranulação Celular/imunologia , Reações Cruzadas/imunologia , Modelos Animais de Doenças , Humanos , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Camundongos , Camundongos Transgênicos , Ligação Proteica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
IgE-associated allergic diseases belong to the most common inflammatory conditions. Their clinical manifestation ranges from mild symptoms to life-threatening episodes. Often patients experience a reduction in physical and psychologic well-being and suffer from a decreased quality of life due to disease activity. The continuously rising number of people that are affected by an allergic condition indicates an urgent need for better diagnostics and more efficient treatment options. Recent progress in the understanding of pathophysiologic mechanisms underlying IgE-associated allergic disorders has led to the identification of novel therapeutic targets and the development of drug candidates that are currently under evaluation. In this review, we highlight studies and clinical trials, which have helped to gain further insight in the etiology of IgE-associated allergic conditions as well as advances in the development of diagnostic tools and therapeutic approaches recently published in Allergy (European Journal of Allergy and Clinical Immunology).
Assuntos
Hipersensibilidade Imediata/diagnóstico , Hipersensibilidade Imediata/etiologia , Hipersensibilidade Imediata/terapia , Ensaios Clínicos como Assunto , Gerenciamento Clínico , Humanos , Imunoglobulina E/imunologiaRESUMO
3D-imaging technologies provide measurements of terrestrial and aquatic ecosystems' structure, key for biodiversity studies. However, the practical use of these observations globally faces practical challenges. First, available 3D data are geographically biased, with significant gaps in the tropics. Second, no data source provides, by itself, global coverage at a suitable temporal recurrence. Thus, global monitoring initiatives, such as assessment of essential biodiversity variables (EBVs), will necessarily have to involve the combination of disparate data sets. We propose a standardized framework of ecosystem morphological traits - height, cover, and structural complexity - that could enable monitoring of globally consistent EBVs at regional scales, by flexibly integrating different information sources - satellites, aircrafts, drones, or ground data - allowing global biodiversity targets relating to ecosystem structure to be monitored and regularly reported.