Connexin-Mediated Signaling in Nonsensory Cells Is Crucial for the Development of Sensory Inner Hair Cells in the Mouse Cochlea

Mutations in the genes encoding for gap junction proteins connexin 26 (Cx26) and connexin 30 (Cx30) have been linked to syndromic and nonsyndromic hearing loss in mice and humans. The release of ATP from connexin hemichannels in cochlear nonsensory cells has been proposed to be the main trigger for action potential activity in immature sensory inner hair cells (IHCs), which is crucial for the refinement of the developing auditory circuitry. Using connexin knock-out mice, we show that IHCs fire spontaneous action potentials even in the absence of ATP-dependent intercellular Ca(2+) signaling in the nonsensory cells. However, this signaling from nonsensory cells was able to increase the intrinsic IHC firing frequency. We also found that connexin expression is key to IHC functional maturation. In Cx26 conditional knock-out mice (Cx26(Sox10-Cre)), the maturation of IHCs, which normally occurs at approximately postnatal day 12, was partially prevented. Although Cx30 has been shown not to be required for hearing in young adult mice, IHCs from Cx30 knock-out mice exhibited a comprehensive brake in their development, such that their basolateral membrane currents and synaptic machinery retain a prehearing phenotype. We propose that IHC functional differentiation into mature sensory receptors is initiated in the prehearing cochlea provided that the expression of either connexin reaches a threshold level. As such, connexins regulate one of the most crucial functional refinements in the mammalian cochlea, the disruption of which contributes to the deafness phenotype observed in mice and DFNB1 patients. SIGNIFICANCE STATEMENT: The correct development and function of the mammalian cochlea relies not only on the sensory hair cells, but also on the surrounding nonsensory cells. Although the nonsensory cells have been largely implicated in the general homeostasis in the mature cochlea, their involvement in the initial functional differentiation of the sensory inner hair cells is less clear. Using mutant mouse models for the most common form of congenital deafness in humans, which are knock-outs for the gap-junction channels connexin 26 and connexin 30 genes, we show that defects in nonsensory cells prevented the functional maturation of inner hair cells. In connexin knock-outs, inner hair cells remained stuck at a prehearing stage of development and, as such, are unable to process sound information

Study of the functional product’s protein compounds digestion features

The aim of the study was to investigate the transformation of meat product’s proteins from pig hearts and aortas during enzymatic hydrolysis in an in vitro model of the gastrointestinal tract. The model consisted of three phases simulating digestion processes: “oral cavity” phase (a-amylase, pH 7.0; 2 min), “stomach” phase (pork pepsin, pH 3.0; 120 min), “intestine” phase (pork pancreatin, pH 7.0; 130 min). The product was sequentially subjected to hydrolysis, at the end of each phase, samples were taken to determine the protein concentration (biuret method) and visualize the protein fractions (one-dimensional electrophoresis). A significant increase in protein concentration at the “stomach” phase was revealed by 3.2 times, and the absolute content by 4.6 times. At the “intestine” phase, a decrease in the number of peptide complexes with copper ions by 1.8 times, the absolute protein content by 8.5% was re‑ vealed. The noted tendency was confirmed by electrophoretic studies — at the stage, simulating digestion in the stomach, the prod‑ ucts of meat product’s proteins hydrolysis were visualized; at the “intestine” phase, a low expression of protein fractions in the range of more than 10 kDa is shown. The maximum hydrolysis of protein compounds at the “stomach” phase to poly- and oligopeptides was confirmed, continuing at the “intestine” stage with the accumulation of free amino acids. This methodology makes it possible to visualize the products of hydrolysis of proteins in a meat product at all stages of the model and to monitor changes in protein concentration in the system

On the idea of true philosophy

Background: Discussions on the actual role and status of philosophy continuously arise, especially at the time of crises, abrupt changes to habitual ways of life and patterns of thought and behavior. Throughout the 20th century philosophical thought, both in the West and in Russia, has undergone a number of major reconsiderations, with controversial outcomes. Philosophy was, in fact, transformed into ideology, i.e. a system of beliefs that ultimately serves the interests of the ruling elite and has a definite apologetic aim – to justify the existing social arrangements and foster the required unanimity of opinions in the society. Liberal arts students and anyone pursuing philosophical studies are taught that the true philosophy is philosophy of science, while philosophy per se does not deserve serious attention because such philosophy is a relic of the past.Objective: The article aims to reveal the causes of the decline of philosophy, to reclaim the status and meaning of true philosophy, and to forecast its perspective development in the modern world. To meet these objectives the authors make use of the analytical, historical, cultural, comparative and hermeneutical methods of research.Results: The article gives substantial evidence to the fact that the inability of modern philosophy to address urgent political, social, etc. issues in Russia is the result of its deliberate three-stage transformation into ideology throughout the 20th century.It is demonstrated that the philosophy of culture is the modern way of philosophizing and the true philosophy of our time. The article highlights some unresolved issues connected with this approach: the essence of culture; the principles, laws and the purpose of cultural development; the correlation between culture and life.The article also argues that the ultimate goal of unraveling the meaning of modern philosophy is to go from the philosophy “about something” to the philosophy of the person generated by his/her independent thought. This kind of further development is only possible in the situation of academic freedom and the person’s independence in finding and absorbing knowledge.Conclusion: The contribution of this study to the contemporary philosophical discourse is threefold: firstly, it demonstrates that the role and status of modern philosophy are different from and surpass those of narrower fields of knowledge; secondly, it defines modern philosophy as the philosophy of culture; thirdly, it envisions the future of modern philosophy as the philosophy generated by the person capable of independent thinking.This study can be applied to interpreting and evaluating current and past social issues from a cultural and philosophical standpoint.Keywords: philosophy, true philosophy, modern philosophy, culture, philosophy of cultur