Essential role of TNF receptor superfamily 25 (TNFRSF25) in the development of allergic lung inflammation

We identify the tumor necrosis factor receptor superfamily 25 (TNFRSF25)/TNFSF15 pair as critical trigger for allergic lung inflammation, which is a cardinal feature of asthma. TNFRSF25 (TNFR25) signals are required to exert T helper cell 2 (Th2) effector function in Th2-polarized CD4 cells and co-stimulate interleukin (IL)-13 production by glycosphingolipid-activated NKT cells. In vivo, antibody blockade of TNFSF15 (TL1A), which is the ligand for TNFR25, inhibits lung inflammation and production of Th2 cytokines such as IL-13, even when administered days after airway antigen exposure. Similarly, blockade of TNFR25 by a dominant-negative (DN) transgene, DN TNFR25, confers resistance to lung inflammation in mice. Allergic lung inflammation–resistant, NKT-deficient mice become susceptible upon adoptive transfer of wild-type NKT cells, but not after transfer of DN TNFR25 transgenic NKT cells. The TNFR25/TL1A pair appears to provide an early signal for Th2 cytokine production in the lung, and therefore may be a drug target in attempts to attenuate lung inflammation in asthmatics

Bases legais como fator condicionante subjacente à exploracão do agroturismo e do ecoturismo: uma análise das condições atuais na Rússia e na Bielorrússia

This paper considers various possibilities and prospects for the development of agricultural and ecotourism in Russia. In the context of financial and logistical constraints on the Russian business, the closure of many traditional tourist destinations necessitates a reorientation of tourist flows both in terms of location and in terms of tourist interest. Currently, travelers are inclined to choose new types of tourism, including agrotourism and ecotourism. Agrotourism and ecotourism can become a significant economic component for several agricultural and natural areas. The study demonstrates that the closure of traditional tourist destinations for Russian tourists creates unique conditions for the redirection of tourist flows and the qualitative reorientation of tourism. The main tasks of regulation in this area are streamlining relations in the following combination "agricultural and natural territories – tourism business – a consumer of a tourism product (tourist)", as well as observing the legitimate interests of all participants in such relations. The authors of the article study positive global experience in the organization and regulation of agrotourism and ecotourism. They also propose some legal formulations for the formation of legal concepts aimed at supporting the development of the tourism business in both agricultural and environmental areas.Este artículo examina diversas posibilidades y perspectivas de desarrollo del turismo agrícola y ecológico en Rusia. En el contexto de las limitaciones financieras y logísticas del negocio ruso, el cierre de muchos destinos turísticos tradicionales hace necesaria una reorientación de los flujos turísticos tanto en términos de localización como de interés turístico. Actualmente, los viajeros se inclinan por nuevos tipos de turismo, entre ellos el agrícola y el ecoturismo. El agroturismo y el ecoturismo pueden convertirse en un componente económico importante para varias zonas agrícolas y naturales. El estudio demuestra que el cierre de los destinos turísticos tradicionales para los turistas rusos crea condiciones únicas para la reorientación de los flujos turísticos y la reorientación cualitativa del turismo. Las principales tareas de regulación en este ámbito son la racionalización de las relaciones en la siguiente combinación "territorios agrícolas y naturales - empresa turística - consumidor de un producto turístico (turista)", así como la observación de los intereses legítimos de todos los participantes en dichas relaciones. Los autores del artículo estudian la experiencia global positiva en la organización y regulación del agroturismo y el ecoturismo. También proponen algunas formulaciones jurídicas para la formación de conceptos legales destinados a apoyar el desarrollo del negocio del turismo tanto en el ámbito agrícola como en el medioambiental.Este artigo considera várias possibilidades e perspectivas para o desenvolvimento da agricultura e do ecoturismo na Rússia. No contexto de constrangimentos financeiros e logísticos do negócio russo, o fechamento de muitos destinos turísticos tradicionais exige uma reorientação dos fluxos turísticos, tanto em termos de localização como em termos de interesse turístico. Atualmente, os viajantes estão inclinados a escolher novos tipos de turismo, incluindo o turismo agrícola e o ecoturismo. O agroturismo e o ecoturismo podem tornar-se uma componente económica significativa para várias áreas agrícolas e naturais. O estudo demonstra que o encerramento de destinos turísticos tradicionais para turistas russos cria condições únicas para a reorientação dos fluxos turísticos e para a reorientação qualitativa do turismo. As principais tarefas de regulamentação nesta área são a racionalização das relações na seguinte combinação "territórios agrícolas e naturais - negócio turístico - consumidor de um produto turístico (turista)", bem como a observação dos legítimos interesses de todos os participantes em tais relações. Os autores do artigo estudam a experiência global positiva na organização e regulamentação da agricultura e do ecoturismo. Propõem também algumas formulações legais para a formação de conceitos jurídicos destinados a apoiar o desenvolvimento do negócio turístico, tanto na área agrícola como na ambiental

PUBLIC HEALTH AND BIOPOLITICS STRATEGY UNDER THE COVID-19 PANDEMIC

The purpose of the presented study is the complex analysis of competence and sufficiency of public safety measures implemented by the authorities in the early stages of the coronavirus pandemic. The article reveals the need for governmental involvement in solving the issues of essential services and maintaining public healthcare. The article also integrated the results of studies of governmental approaches to the development of compensatory policies in different countries while considering the population as a specific object of national biopolitics. A comparative description of examples of national biopolitics as a reaction to the development of an epidemiological threat (cholera, smallpox, Ebola, coronavirus) is presented. A comprehensive strategic approach to developing state biopolitics is recommended, which includes a system of necessary measures, analyzes factors and threats affecting the mechanism of biological security, and summarizes international experience in preventing the spread of dangerous infectious diseases. The conclusion is drawn about the necessity of phased implementation of a complex of proactive preventive measures capable of ensuring the protection of the interests of all participants in the process of socio-economic development of society and the state

Topological Darkness: How to Design a Metamaterial for Optical Biosensing with Virtually Unlimited Sensitivity

Due to the absence of labels and fast analyses, optical biosensors promise major advances in biomedical diagnostics, security, environmental and food safety applications. However, sensitivity of the most advanced plasmonic biosensor implementations has a fundamental limitation caused by losses in the system and or geometry of biochips. Here, we report a scissor effect in topologically dark metamaterials which is capable of providing virtually unlimited bona fide sensitivity to biosensing thus solving the bottleneck sensitivity limitation problem. We explain how the scissor effect can be realized via a proper design of topologically dark metamaterials and describe strategies for their fabrication. To validate the applicability of this effect in biosensing, we demonstrate the detection of folic acid (vitamin important for human health) in the wide 3-log linear dynamic range with the limit of detection of 0.125 nM, which is orders of magnitude better than previously reported for all optical counterparts. Our work opens possibilities for designing and realising plasmonic, semiconductor and dielectric metamaterials with ultra-sensitivity to binding events.Comment: 22 pages, 4 figure

Selective staining and eradication of cancer cells by protein-carrying DARPin-functionalized liposomes

Since their discovery, liposomes have been widely employed in biomedical research. These nano-size spherical vesicles consisting one or few phospholipid bilayers surrounding an aqueous core are capable of carrying a wide variety of bioactive compounds, including drugs, peptides, nucleic acids, proteins and others. Despite considerable success achieved in synthesis of liposome constructs containing bioactive compounds, preparation of ligand-targeted liposomes comprising large quantities of encapsulated proteins that are capable of affecting pathological cells still remains a big challenge. Here we described a novel method for preparation of small (80\u201390 nm in diameter) unilamellar liposomes containing very large quantities (thousands of protein molecules per liposome) of heme-containing cytochrome c, highly fluorescent mCherry and highly toxic PE40 (Pseudomonas aeruginosa Exotoxin A domain). Efficient encapsulation of the proteins was achieved through electrostatic interaction between positively charged proteins (at pH lower than pI) and negatively charged liposome membrane. The proteoliposomes containing large quantities of mCherry or PE40 and functionalized with designed ankyrin repeat protein (DARPin)_9-29, which targets human epidermal growth factor receptor 2 (HER2) were shown to specifically stain and kill in sub-nanomolar concentrations HER2-positive cells, overexpressing HER2, respectively. Specific staining and eradication of the receptor-positive cells demonstrated here makes the DARPin-functionalized liposomes carrying large quantities of fluorescent and/or toxic proteins a promising candidate for tumor detection and therapy

Submicron polyacrolein particles in situ embedded with upconversion nanoparticles for bioassay

We report a new surface modification approach of upconversion nanoparticles (UCNPs) structured as inorganic hosts NaYF4 codoped with Yb3+ and Er3+ based on their encapsulation in a two-stage process of precipitation polymerization of acrolein under alkaline conditions in the presence of UCNPs. The use of tetramethylammonium hydroxide both as an initiator of acrolein polymerization and as an agent for UCNP hydrophilization made it possible to increase the polyacrolein yield up to 90%. This approach enabled the facile, lossless embedment of UCNPs into the polymer particles suitable for bioassay. These particles are readily dispersible in aqueous and physiological buffers, exhibiting excellent photoluminescence properties, chemical stability, and also allow the control of particle diameters. The feasibility of the as-produced photoluminescent polymer particles mean-sized 260 nm for in vivo optical whole-animal imaging was also demonstrated using a home-built epi-luminescence imaging system

Cytotoxicity and non-specific cellular uptake of bare and surface-modified upconversion nanoparticles in human skin cells

The cytotoxicity and non-specific cellular uptake of the most popular composition of upconversion nanoparticle (UCNP), NaYF4:Yb3+:Er3+, is reported using normal human skin cells, including dermal fibroblasts and immortalized human epidermal linear keratinocytes (HaCaT). A new hydrophilization reaction of as-synthesized UCNPs based on tetramethylammonium hydroxide (TMAH) enabled evaluation of the intrinsic cytotoxicity of bare UCNPs. The cytotoxicity effects of the UCNP surface-coating and polystyrene host were investigated over the concentration range 62.5–125 μg/mL with 24-h incubation, using a MTT test and optical microscopy. The fibroblast viability was not compromised by UCNPs, whereas the viability of keratinocytes varied from 52% ± 4% to 100% ± 10% than the control group, depending on the surface modification. Bare UCNPs reduced the keratinocyte viability to 76% ± 3%, while exhibiting profound non-specific cellular uptake. Hydrophilic poly(D,L-lactide)- and poly(maleic anhydride-alt-1-octadecene)-coated UCNPs were found to be least cytotoxic among the polymer-coated UCNPs, and were readily internalized by human skin cells. Polystyrene microbeads impregnated with UCNPs remained nontoxic. Surprisingly, no correlation was found between UCNP cytotoxicity and the internalization level in cells, although the latter ranged broadly from 0.03% to 59%, benchmarked against 100% uptake level of TMAH-UCNPs. [Figure not available: see fulltext.