Caffeine inhibits hypoxia-induced nuclear accumulation in HIF-1α and promotes neonatal neuronal survival

© 2019 The Authors Apnea of prematurity (AOP) defined as cessation of breathing for 15–20 s, is commonly seen in preterm infants. Caffeine is widely used to treat AOP due to its safety and effectiveness. Caffeine releases respiratory arrest by competing with adenosine for binding to adenosine A 1 and A 2A receptors (A 1 R and A 2A R). Long before its use in treating AOP, caffeine has been used as a psychostimulant in adult brains. However, the effect of caffeine on developing brains remains unclear. We found that A 1 R proteins for caffeine binding were expressed in the brains of neonatal rodents and preterm infants (26–27 weeks). Neonatal A 1 R proteins colocalized with PSD-95, suggesting its synaptic localization. In contrast, our finding on A 2 R expression in neonatal neurons was restricted to the mRNA level as detected by single cell RT/PCR due to the lack of specific A 2A R antibody. Furthermore, caffeine (200 μM) at a dose twice higher than the clinically relevant dose (36–130 μM) had minor or no effects on several basic neuronal functions, such as neurite outgrowth, synapse formation, expression of A 1 R and transcription of CREB-1 and c-Fos, further supporting the safety of caffeine for clinical use. We found that treatment with CoCl 2 (125 μM), a hypoxia mimetic agent, for 24 h triggered neuronal death and nuclear accumulation of HIF-1α in primary neuronal cultures. Subsequent treatment with caffeine at a concentration of 100 μM alleviated CoCl 2 -induced cell death and prevented nuclear accumulation of HIF-1α. Consistently, caffeine treatment in early postnatal life of neonatal mice (P4-P7) also prevented subsequent hypoxia-induced nuclear increase of HIF-1α. Together, our data support the utility of caffeine in alleviating hypoxia-induced damages in developing neurons

Ion distribution dynamics near the Earth's bow shock: first measurements with the 2D ion energy spectrometer CORALL on the INTERBALL/Tail-probe satellite

International audienceThe dynamics of the ion distribution function near the Earth's bow shock is studied on the basis of quasi-3D measurements of ion energy spectra in the range of 30?24200 eV/q with the Russian-Cuban CORALL instrument on the INTERBALL/Tail-probe satellite. The instrument was designed for observations of magnetospheric plasma and measures ions, in an angular range of 36°?144° from the Earth-Sun direction. Ion populations generated by the Earth bow shock are often observed upstream from the bow shock. In the solar-wind stream compressed and heated by the passing of very dense magnetic cloud (CME), two types of these ion populations were measured upstream and before the bow shock crossing on 25 August 1995 at 07:37 UT. Both populations were observed in the energy range above 2 keV. At ~06:20 UT, when the angle between the direction of the interplanetary magnetic field and normal to the bow shock VBn was ? 43° the instrument observed a narrow, fast (~800 km/s) field-aligned beam moving from the Earth. At ~07:30, when Bn ? 28°, the wide ion pitch-angle distribution was observed. A similar suprathermal ion population is observed in the magnetosheath simultaneously with the solar-wind ion population being heated and deflected from the Sun-Earth direction. The similarity of observations during the mentioned time-interval and under usual solar-wind conditions allows us to conclude that types of suprathermal ion populations upstream and downstream from the bow shock do not depend on the solar-wind disturbance generated by magnetic cloud

THE GENDER PRINCIPLE IN LAW AS A GUARANTEE OF EQUALITY IN LEGAL REGULATION

The development of modern Ukraine on the basis of the new forms of social relations between the sexes must be carried out in accordance with world universal standards of human rights and equality between the sexes. The article defines the need for a more specific view of gender equality. Using the historical approach and different theoretical methods, the article attempts to systematize knowledge about feminism, gender, transgender, human rights and opportunities of people. The article contains an analysis of gender discrimination and violence and defines ways of overcoming them. The study focuses on the legal aspects of equal rights and opportunities in both international legal acts and Ukrainian legislation. The paper studied how a gender approach in politics, economics and social spheres was being developed. Measures taken to ensure the equal distribution of family responsibilities, ensuring a reduction in the gender pay gap, were analyzed. The main areas of gender equality guaranteed by international and domestic law were identified as follows: equal access to management positions, access to labor market participation, elimination of occupational segregation, violence and discrimination based on gender, unpaid time off, etc. The priorities of the state gender policy for the last 5 years were investigated.The development of modern Ukraine on the basis of the new forms of social relations between the sexes must be carried out in accordance with world universal standards of human rights and equality between the sexes. Article defines the need for a more specific view of gender equality. Using the historical approach and different theoretical methods, article attempts to systematize knowledge about feminism, gender, transgender, human rights and opportunities of people. The article contains an analysis of gender discrimination and violence and defines ways of overcoming them. The study focuses on the legal aspects of equal rights and opportunities in both international legal acts and Ukrainian legislation. The article studied how a gender approach in politics, economics and social spheres was being developed. Measures taken to ensure the equal distribution of family responsibilities, ensuring a reduction in the gender pay gap, were analyzed. The main areas of gender equality guaranteed by international and domestic law were identified as follows: equal access to management positions, access to labor market participation, elimination of occupational segregation, violence and discrimination based on gender, unpaid time off, etc. The priorities of the state gender policy for the last 5 years were investigated

The gender principle in Law as a guarantee of equality in legal regulation = O princípio de gênero no Direito como garantia de igualdade na regulação legal

Define a necessidade de uma visão mais específica da igualdade de gênero, tanto no contexto internacional quanto no ucraniano. Usa uma abordagem histórica e diferentes métodos teóricos para tentar sistematizar o conhecimento sobre feminismo, gênero, transgeneridade, direitos humanos e oportunidades das pessoas

Synchronisation in networks of delay-coupled type-I excitable systems

We use a generic model for type-I excitability (known as the SNIPER or SNIC model) to describe the local dynamics of nodes within a network in the presence of non-zero coupling delays. Utilising the method of the Master Stability Function, we investigate the stability of the zero-lag synchronised dynamics of the network nodes and its dependence on the two coupling parameters, namely the coupling strength and delay time. Unlike in the FitzHugh-Nagumo model (a model for type-II excitability), there are parameter ranges where the stability of synchronisation depends on the coupling strength and delay time. One important implication of these results is that there exist complex networks for which the adding of inhibitory links in a small-world fashion may not only lead to a loss of stable synchronisation, but may also restabilise synchronisation or introduce multiple transitions between synchronisation and desynchronisation. To underline the scope of our results, we show using the Stuart-Landau model that such multiple transitions do not only occur in excitable systems, but also in oscillatory ones.Comment: 10 pages, 9 figure

Mechanisms explaining transitions between tonic and phasic firing in neuronal populations as predicted by a low dimensional firing rate model

Several firing patterns experimentally observed in neural populations have been successfully correlated to animal behavior. Population bursting, hereby regarded as a period of high firing rate followed by a period of quiescence, is typically observed in groups of neurons during behavior. Biophysical membrane-potential models of single cell bursting involve at least three equations. Extending such models to study the collective behavior of neural populations involves thousands of equations and can be very expensive computationally. For this reason, low dimensional population models that capture biophysical aspects of networks are needed. \noindent The present paper uses a firing-rate model to study mechanisms that trigger and stop transitions between tonic and phasic population firing. These mechanisms are captured through a two-dimensional system, which can potentially be extended to include interactions between different areas of the nervous system with a small number of equations. The typical behavior of midbrain dopaminergic neurons in the rodent is used as an example to illustrate and interpret our results. \noindent The model presented here can be used as a building block to study interactions between networks of neurons. This theoretical approach may help contextualize and understand the factors involved in regulating burst firing in populations and how it may modulate distinct aspects of behavior.Comment: 25 pages (including references and appendices); 12 figures uploaded as separate file

Chimera-like states in modular neural networks

Chimera states, namely the coexistence of coherent and incoherent behavior, were previously analyzed in complex networks. However, they have not been extensively studied in modular networks. Here, we consider a neural network inspired by the connectome of the C. elegans soil worm, organized into six interconnected communities, where neurons obey chaotic bursting dynamics. Neurons are assumed to be connected with electrical synapses within their communities and with chemical synapses across them. As our numerical simulations reveal, the coaction of these two types of coupling can shape the dynamics in such a way that chimera-like states can happen. They consist of a fraction of synchronized neurons which belong to the larger communities, and a fraction of desynchronized neurons which are part of smaller communities. In addition to the Kuramoto order parameter ?, we also employ other measures of coherence, such as the chimera-like ? and metastability ? indices, which quantify the degree of synchronization among communities and along time, respectively. We perform the same analysis for networks that share common features with the C. elegans neural network. Similar results suggest that under certain assumptions, chimera-like states are prominent phenomena in modular networks, and might provide insight for the behavior of more complex modular networks