Hypoxia Upregulates Estrogen Receptor β in Pulmonary Artery Endothelial Cells in a HIF-1α-Dependent Manner

17β-Estradiol (E2) attenuates hypoxia-induced pulmonary hypertension (HPH) through estrogen receptor (ER)-dependent effects, including inhibition of hypoxia-induced endothelial cell proliferation; however, the mechanisms responsible for this remain unknown. We hypothesized that the protective effects of E2 in HPH are mediated through hypoxia-inducible factor 1α (HIF-1α)-dependent increases in ERβ expression. Sprague-Dawley rats and ERα or ERβ knockout mice were exposed to hypobaric hypoxia for 2-3 weeks. The effects of hypoxia were also studied in primary rat or human pulmonary artery endothelial cells (PAECs). Hypoxia increased expression of ERβ, but not ERα, in lungs from HPH rats as well as in rat and human PAECs. ERβ mRNA time dependently increased in PAECs exposed to hypoxia. Normoxic HIF-1α/HIF-2α stabilization increased PAEC ERβ, whereas HIF-1α knockdown decreased ERβ abundance in hypoxic PAECs. In turn, ERβ knockdown in hypoxic PAECs increased HIF-2α expression, suggesting a hypoxia-sensitive feedback mechanism. ERβ knockdown in hypoxic PAECs also decreased expression of the HIF inhibitor prolyl hydroxylase 2 (PHD2), whereas ERβ activation increased PHD2 and decreased both HIF-1α and HIF-2α, suggesting that ERβ regulates the PHD2/HIF-1α/HIF-2α axis during hypoxia. Whereas hypoxic wild-type or ERα knockout mice treated with E2 demonstrated less pulmonary vascular remodeling and decreased HIF-1α after hypoxia compared with untreated hypoxic mice, ERβ knockout mice exhibited increased HIF-2α and an attenuated response to E2 during hypoxia. Taken together, our results demonstrate a novel and potentially therapeutically targetable mechanism whereby hypoxia, via HIF-1α, increases ERβ expression and the E2-ERβ axis targets PHD2, HIF-1α, and HIF-2α to attenuate HPH development

Representations of (2,n)(2,n)-semigroups by multiplace functions

We describe the representations of $(2,n)$-semigroups, i.e. groupoids with $n$ binary associative operations, by partial $n$-place functions and prove that any such representation is a union of some family of representations induced by Schein's determining pairs.Comment: 17 page

Spatial focus for UWB signals

Method of focus in the time domain and its analogue, a method of radiowave tomosynthesis in the frequency domain by the criterion of level artifacts in the reconstructed radio images of the test object are compared. To verify the advantages of focus in the time domain method numerical model of clocked nonequidistant flat antenna array has been developed at the Department of Radio Physics at Tomsk State University

Electron Clusters in Inert Gases

The paper addresses counterintuitive behavior of electrons injected into dense cryogenic media with negative scattering length $a_0$. Instead of expected polaronic effect (formation of density enhancement clusters) which should substantially reduce the electron mobility, an opposite picture is observed: with increasing $|a_0|$ (the trend taking place for inert gases with the growth of atomic number) and the medium density, the electrons remain practically free. An explanation of this behaviour is provided based on consistent accounting for the non-linearity of electron interaction with the gaseous medium in the gas atom number density

Policy, toxicology and physicochemical considerations on the inhalation of high concentrations of food flavour

Food flavour ingredients are required by law to obtain prior approval from regulatory bodies, such as the U.S. Food and Drug Administration (FDA) or the European Food Safety Authority (EFSA) in terms of toxicological data and intended use levels. However, there are no regulations for labelling the type and concentration of flavour additives on the product, primarily due to their low concentration in food and generally recognised as safe (GRAS) status determined by the flavour and extract manufacturers’ association (FEMA). Their status for use in e-cigarettes and other vaping products challenges these fundamental assumptions, because their concentration can be over ten-thousand times higher than in food, and the method of administration is through inhalation, which is currently not evaluated by the FEMA expert panel. This work provides a review of some common flavour ingredients used in food and vaping products, their product concentrations, inhalation toxicity and aroma interactions reported with different biological substrates. We have identified several studies, which suggest that the high concentrations of flavour through inhalation may pose a serious health threat, especially in terms of their cytotoxicity. As a result of the wide range of possible protein-aroma interactions reported in our diet and metabolism, including links to several non-communicable diseases, we suggest that it is instrumental to update current flavour- labelling regulations, and support new strategies of understanding the effects of flavour uptake on the digestive and respiratory systems, in order to prevent the onset of future non-communicable diseases. © 2020, The Author(s)

Representations of Menger (2,n)(2,n)-semigroups by multiplace functions

Investigation of partial multiplace functions by algebraic methods plays an important role in modern mathematics were we consider various operations on sets of functions, which are naturally defined. The basic operation for $n$-place functions is an $(n+1)$-ary superposition $[ ]$, but there are some other naturally defined operations, which are also worth of consideration. In this paper we consider binary Mann's compositions \op{1},...,\op{n} for partial $n$-place functions, which have many important applications for the study of binary and $n$-ary operations. We present methods of representations of such algebras by $n$-place functions and find an abstract characterization of the set of $n$-place functions closed with respect to the set-theoretic inclusion