ADAM Metalloproteinase Domain 17 Regulates Cholestasis-Associated Liver Injury and Sickness Behavior Development in Mice

Disintegrin and metalloproteinase domain-containing protein 17 (ADAM17) is a ubiquitously expressed membrane-bound enzyme that mediates shedding of a wide variety of important regulators in inflammation including cytokines and adhesion molecules. Hepatic expression of numerous cytokines and adhesion molecules are increased in cholestatic liver diseases including primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), however, the pathophysiological role of ADAM17 in regulating these conditions remains unknown. Therefore, we evaluated the role of ADAM17 in a mouse model of cholestatic liver injury due to bile duct ligation (BDL). We found that BDL enhanced hepatic ADAM17 protein expression, paralleled by increased ADAM17 bioactivity. Moreover, inhibition of ADAM17 bioactivity with the specific inhibitor DPC 333 significantly improved both biochemical and histological evidence of liver damage in BDL mice. Patients with cholestatic liver disease commonly experience adverse behavioral symptoms, termed sickness behaviors. Similarly, BDL in mice induces reproducible sickness behavior development, driven by the upregulated expression of cytokines and adhesion molecules that are in turn regulated by ADAM17 activity. Indeed, inhibition of ADAM17 activity significantly ameliorated BDL-associated sickness behavior development. In translational studies, we evaluated changes in ADAM17 protein expression in liver biopsies obtained from patients with PBC and PSC, compared to normal control livers. PSC and PBC patients demonstrated increased hepatic ADAM17 expression in hepatocytes, cholangiocytes and in association with liver-infiltrating immune cells compared to normal controls. In summary, cholestatic liver injury in mice and humans is associated with increased hepatic ADAM17 expression. Furthermore, inhibition of ADAM17 activity improves both cholestatic liver injury and associated sickness behavior development, suggesting that ADAM17 inhibition may represent a novel therapeutic approach for treating patients with PBC/PSC.

„Jutro należy do kotów”. Problemy (eco) science fiction w powieści Bernarda Werbera

Why tomorrow should not belong to humans, but to another species? Science fiction seems to answer this question with alarmingly accurate arguments. SF texts often seem like prophecies that predict the future. We most willingly accept visions in which man is the author of innovative technologies as well as cultural and economic progress. What if this development is not ascribed to the human race, but for example: to monkeys or cats? The classic repertoire of science fiction heroes, apart from humans, includes robots, cyborgs, androids or newcomers from another planet (aliens). Their humanoid character — anthropomorphic features of appearance, behavior, development of the species in the form of created (or mid creation) civilization and culture — is designed to break the anthropocentric view of man. The function of the Other in science fiction can, however, be taken over by a creature much closer and longer known to man than a newcomer from a foreign planet or a creature of highly developed technology — an animal. The essay is an attempt to analyze Bernard Werber’s novel Tomorrow the cats from the perspective of general science fiction and ecofiction issues. At the same time, the issue of species chauvinism and the ways in which it manifests itself in literature are discussed.

THE ESSENCE AND STRUCTURE OF EDUCATIONAL ENVIRONMENT IN THE CONTEXT OF THE FORMATION OF PARTNERSHIPS OF ADOLESCENTS

The successful formation of partnerships of adolescents is conditioned by certain factors and elements of educational environment, contributing to the formation of motivational-value, cognitive and operational-activity components of personality development of children of this age category. The peculiarities of the influence of this environment have a certain specificity associated with the conditions of formation of its structural components. Due to the action of these elements of the educational environment, certain age characteristics of adolescents are formed, which are necessary to ensure the effective principles of partnership, which will affect personal development and further development of academic achievement. Taking into account the importance of considering the theoretical aspects of determining the characteristics of the educational environment of adolescents, which determines the formation of their partnership, the study of this issue is considered relevant and will ensure the development of scientific thought. The purpose of the article is to systematize the approaches to defining the essence of the concept and structure of the educational environment of adolescents as a sphere of development of their partnership. Research methods applied: a systematic approach, which is used to systematize the provisions of scientific views related to the evaluated issues; comparative method used to compare the approaches of scientists. The study presents a systematization of approaches to defining the essence of the concept and structure of the educational environment of adolescents, which contributes to the development of their partnerships. It is proved that the main essential features of the concept of educational environment of adolescents, which contributes to the development of their partnerships include: structural feature (in the interpretations of the authors, mainly determined by reference to certain components of this phenomenon), performance feature (emphasis on areas of influence - behavior, development of value beliefs, etc.), organizational feature (indication that the subjects of the environment provide active assistance in the development of certain skills, qualities of adolescents), subject-oriented feature, which involves the formation and development of the educational environment of adolescents in the context of subject-subject direction (humanistic approach ). The composition of the conditions for the formation of this phenomenon is determined, which include general categories, in particular: objective, specially (artificially) created, static, dynamic. The interpretation of the studied concept is formulated, which is based on taking into account the list of basic essential features and categories of conditions of formation of the educational environment, which promotes the development of their partnership.

A brain atlas of synapse protein lifetime across the mouse lifespan.

Protein turnover is required for synapse maintenance and remodelling and may impact memory duration. We quantified the lifetime of postsynaptic protein PSD95 in individual excitatory synapses across the mouse brain and lifespan, generating the Protein Lifetime Synaptome Atlas. Excitatory synapses have a wide range of protein lifetimes that may extend from a few hours to several months, with distinct spatial distributions in dendrites, neuron types and brain regions. Short protein lifetime (SPL) synapses are enriched in developing animals and in regions controlling innate behaviors, whereas long protein lifetime (LPL) synapses accumulate during development, are enriched in the cortex and CA1 where memories are stored, and are preferentially preserved in old age. The protein lifetime synaptome architecture is disrupted in an autism model, with synapse protein lifetime increased throughout the brain. These findings add a further layer to synapse diversity in the brain and enrich prevailing concepts in behavior, development, ageing and brain repair.

Law genesis: problems of methodology

The subject is related to the insufficient investigation of a general theoretical conception of the law genesis. The conception prevailing in Russian legal literature and proceeding from the inseparable connection between state and law genesis is weak in some aspects As a theoretical basis of this investigation the author uses the concept that regards a law genesis in the context of a world evolution. With this approach, the social factors of the emergence of law are preceded by natural factors of the same dimension, and the thesis about the emergence of law simultaneously with human society becomes the starting point in the study. As a result, the subject of the research acquires an interdisciplinary approach and includes the issues of nonlegal scientific disciplines, not only humanitarian (anthropology, ethnology, etc.), but also natural sciences (psychology, genetics of a behavior, etc.). The conclusion that the patterns of behavior development and the mechanisms of its regulation are formed at the natural stage of world evolution is of paramount importance. They arise in the form of reflexes and are then perceived by the merged norms of the custom-mononorm. The latter become a kind of connecting link in the transition from the natural mechanism of regulation of behavior to the social and from the preclass to the early class society regulation mechanism. Law genesis is considered in the article as a contradictory, multiaspect and multistage process with a natural and social content. Sociocultural differences between the countries of the West and the East led to the dissimilarity of the process of law genesis in both. In the first of them, with the victory of capitalism, law overcomes the phenomenon of fusion and appears in a pure form, while in the second, even today there are traditional relations and understanding of law, adequate to the preclass and early class era.

FOREIGN MODELS OF STATE REGULATION OF CONSUMER BEHAVIOR: RESEARCH BY COMPARISON

The paper highlights the main elements of foreign models of consumer behavior development, which can be used in the practice of improving the institutions and mechanisms that influence its content in the modern national economy of the Russian Federation. The possibilities of transformation in the current economic conditions of individual elements of the Soviet model of the development of consumer behavior are considered.

Effects of Low Temperature on Shrimp and Crab Physiology, Behavior, and Growth: A Review

As important aquaculture species worldwide, shrimps and crabs are thermophilic animals with a feeble thermoregulation ability. Changes in environmental factors are the main reason for the decrease in the immunity and disease resistance ability of cultured organisms. Water temperature is one of the most common abiotic stress factors for aquatic ectotherms. It influences nearly all biochemical and physiological processes in crustaceans, resulting in an imbalance in ion and water homeostasis, neuromuscular function loss, cellular dehydration, and altered metabolic pathways. The present review summarizes the current knowledge on the effects of low temperature on the physiological response, and the behavior, development, and growth of shrimp and crab. We suggest a deeper research to understand the physiological processes involved in thermoregulation; this knowledge could be used to reduce the adverse effects in the shrimps and crabs during the culture.

Origin of an evolutionary novelty: the worker phenotype of eusocial wasps

Complex problems in evolutionary biology can be approached in two ways, top down using theoretical constructs and bottom up using empirical studies . Theoretical concepts predominate evolutionary interpretations of eusociality in a literature that is small relative to an enormous literature of natural history and basic research that is not synthesized into a conceptual whole. Here, I draw insights from this literature to show how paper wasps’ allomaternal non-reproductive worker phenotype originates in every colony cycle via confluence of multiple factors of paper wasp biology. These include behavior, development, nutrient dynamics, indirect genetic effects, sex ratio, and demography. A novel perspective on the colony cycle, based on individuals’ reproductive physiology, serves as context to examine of each of these. It will be shown that the allomaternal non-reproductive worker phenotype does not require relatedness among colony members to originate. Allomaternal care of non-relatives is frequent and can occur in at least twelve contexts. Life histories of living species as they will be presented here show that relatedness among colony members is not the target of selection in simple eusociality. However, the novel allomaternal non-reproductive worker phenotype had to be present at the ancestral origins of complex eusociality in which relatedness among colony members is essential.