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The relevance of studying the features of the meaning regulation of a person is due to the need to describe the mechanisms of the formation of meanings under the influence of cultural, social, historical and ideological aspects of his life. The authors present a theoretical analysis of the features of the formation of the system of personal meanings of people belonging to Western and Eastern Christianity. The purpose of the article is to identify the cultural and confessional factors of psychological differences in adaptive and preadaptive meaning regulation that exist among representatives of the Catholic and Orthodox branches of the Christian world. The paper analyzes the influence of various cultural and confessional factors on the meaning regulation of representatives of Catholicism and Orthodoxy. Catholicism and Orthodoxy, as the western and eastern branches of Christianity, have corresponding differences in the field of religious priorities: God's descent to earth at Christmas and likening to man against the divine Resurrection as a sacrifice for man; worldview: anthropocentrism against сhristocentrism; epistemological views: logical analysis and materialistic rationalism of the intellect and against the sacred unity of the relationship between man and nature; value attitudes: acceptance of one's imperfection against the desire for a divine prototype; cultural priorities: welfare versus sanctity; ethical beliefs: primacy of individual rights versus duties to the soul's conscience; social identities: self-affirmation based on law versus religious humility before spiritual precepts; political preferences: individual freedom versus the common good; legal concepts: legal contract versus moral union. Based on the analysis of the scientific works presented in this study, it is proposed to consider the cultural and confessional features of Catholicism as correlating mainly with the adaptive orientation of meaning-forming strategies, and Orthodoxy as correlating mainly with the preadaptive orientation of meaning-forming strategies.

The monograph includes studies of the last decades by a group of scientists engaged in solving problems of theoretical and methodological study of the problem of psychological manifestations of modern generations. The authors reflected the versatility of definitions of the concept of "generation" and revealed the multidimensional phenomenon of generations. The author's approach to the succession of generations deserves attention, which opens up prospects in the study of intergenerational relations. A level model of value-semantic mediation of intergenerational relations is presented, which allows a comprehensive look at the manifestations of generations. Reviews of generational studies are presented and empirical cross-sections are presented in the value-semantic perspective of the formation of generations. The problem of perception of generations by each other in age and gender aspects is considered in a special way. Attention is paid to the problems of spreading the belief in conspiracies in the modern youth environment and the harmful consequences of this. The empirical model of the conspirativist mentality is the beginning of research in this regard. It is addressed to philosophers, cultural scientists, sociologists, psychologists of various schools and anyone interested in new and recurring trends in human development in the world.

In the course of acmeological development, transition of an individual from adaptation to preadaptive activity takes place. Thanks to preadaptivity, a person has new opportunities for the development of such features of his personality that help to overcome various crisis and uncertain situations. In such conditions, the system of personal senses becomes an integral regulator of life activity. The state of integrity of this system shows the possible ways of raising a person above self-actualization as a result of self realization in reality. Self-transcendence follows self-actualization and means going beyond the present self to fulfill the highest purpose. Self-transcendence is based on the process of overcoming the existential crisis of finiteness of one's being, as a result of which the system of personal senses gets restarted and shifts to creating cultural benefits for other people. Self-transcendence contains such existential attributes as experience of creative insights, preservation of subjectivity, ability to overcome existential crises in a positive way, tolerance to uncertainty, creative thinking, freedom in taking responsibility in search for one's own destiny

While studying sense-making regulation, we have previously elaborated on a basic personological model based on dual relations of personal traits. Their representation in the form of an ensemble of bipolar semantic scales' shows two strategies for organization of the notional sphere – positive development or degradation of the personality (Godunov, 2017). This approach reduces all the variety of options for personal development to a pair of oppositions. The purpose of this article is to theoretically substantiate the transition from the dual to trinal model of sense-making strategies and their description. The genesis of personal traits and meanings that determine them is examined from trialectic viewpoint on the basis of the three-fold sense-making strategies. This methodological approach allows carrying out multifactor diagnostics and qualitative interpretation of various states of personal value-semantic sphere which simulates behavior patterns in various life situations. This helps one to realize the peculiarities of one’s being and otherness as conditions of spiritual self-improvement in the way of self-transcendence

Life-purpose orientations and self-reflection are important factors in person-al meaning regulation. Anyone living in the transitive society of today does not exercise full control over his or her life activity due to various factors of indefiniteness. The coronavirus (COVID-19) pandemic, starting at the beginning of 2020, swept the world and is now considered to be a global indefiniteness factor. Life indefiniteness that grew with the pandemic is a supplementary stress factor, the one that can be treated as either distress or eustress. This article is aimed at showing the results of an empirical study of differences in the life-purpose orientations and self-reflection in young unmarried females being trained in psychology in the city of Rostov-on-Don in March 2017 (n=53) and in October 2020 (n=43), that is prior to and during the pan-demic, which may be considered as different indefiniteness effects in life. D.A. Leontyev's "life-purpose orientations"test and I.A. Stetsenko's self-reflection questionnaire were implied in the study. Growth of all mean indicators in both tests during the pandemic against the same indicators prior to the pandemic, was revealed. Differences in all parameters are statistically veratious, which was stated by the Mann-Whitney test. The empirical study established that the pandemic may be viewed in respect of the examined acmeologically homogenous category as eustress, i.e. an overcomable indefiniteness factor. The above eustress resulted in a positive reconstruction of meaning regulation processes and in psychological adaptation, which lead to the growth of the level of life orientation meaningfulness and self-reflection among the respondents. © The Authors, published by EDP Sciences, 2021.

The article is aimed at analyzing the features of life style and meaningfulness of life among students depending on different attitudes to time. The analysis of modern studies of time perspective as a category of psychology is presented; the main components of meaning-life orientations, locus-control of the Ego are described. The object of the study was university students from 18 to 21 years old in the number of 294 people. The following methods were used: F. Zimbardo's time perspective questionnaire; D.A. Leontiev's "Life Orientations" test; Kellerman-Plutchik Lifestyle Index questionnaire, Mann-Whitney U statistical criterion; Spearman rank correlation. It is proved that depending on the respondents' attitude to the time perspective, both the level of meaningfulness of life and the strategy of behavior in stressful situations change. It is concluded that respondents with a focus on the future have a greater meaningfulness of life, they also are more tend to setting life goals. Moreover, the leading types of life styles statistically differ, depending on the the responders’ attitude to time.

This paragraph is devoted to the peculiarities of creating value-based and meaningful choice situations for students in the conditions of digital pedagogy. As part of the study, a didactic model was developed in the pedagogical process, aimed at increasing the motivation of students by creating situations of sense choice using information and communication technologies (ICT). The proposed model of value-based and meaningful choice situations for students includes: purpose, principles, content, technologies, methods and teaching techniques. These components in the complex regulate emotional and sensitive as well as motivational and value-based manifestations of students in situations of choice. The diverse content is integrated into students’ personal sense, and technologies and methods directly “incorporate” the student’s sense development process.

This study looks into psychotechnics used in education and contributing to initiating logic among students, their personal growth and characterizes psychological features of “sense-deducting”. Here you will find a review of the sense-making techniques considering as one of the categories of psychotechnics. The described techniques are based on the human psychology, they improve the quality of instruction, create a favorable and unique system of values, take into account the individual characteristics of all types of education, and influence the sense-making process development among children. Sense-making techniques are stated in the author's classification and extended by practical methods. The study of psychological features of influence of sense-making techniques on the personality of a student lets us see new patterns in personal, subjective and “meta-subjective” results of acquiring of the school program via transformation and development of value/logic consciousness of a child. The work emphasizes that the use of sense-making techniques is effective in the educational and after-school activities of the educational organization. The achieved results make it possible to understand, to substantiate the naturalness and relevance of the sense-technical approach according to personal and academic indicators of students. In the process of competent and correct use of the semantic techniques, we see the possibility of conveying the best, productive and quality pedagogical experience, as well as the perspective of innovative developments in the psychological and pedagogical sciences. For children and adolescents, information, thanks to sense-techniques, starts to be personal in nature, knowledge is objectified, learning activity becomes an individual need.

The article presents an analysis of using distance learning technology in university education in the context of the COVID-19 pandemic and the attitude of students to this format of education The authors justify the urgency of the problem under study for modern education and update the basic requirements for education in the situation of growing uncertainty The paper describe the methodological foundations and genesis of the development of distance learning, distinguishes the concepts of "distance education" and "distance learning" The authors determine the features of distance learning in modern conditions and highlight the main problems and contradictions that were provoked by the COVID-19 pandemic and the social isolation The aim of this study is to evaluate emotional attitude of university students of the humanities and natural sciences to distance learning, implemented in the pandemic situation The presented results of an empirical study reveal the pros and cons of distance learning, the active use of Internet resources by students in learning, and the willingness to rebuild in a changing environment © The Authors, published by EDP Sciences, 2020

Dynamism in culture and personal value orientations leave their mark on such a socio-cultural phenomenon as success. It is classified as one of those concepts, the life meaning of which is clearly understood by everyday consciousness, but its psychological essence is sometimes not obvious due to the multifaceted nature of its meanings and relationships, expressed in its semantics. It was proved that codependent relationships affect the value-semantic sphere of the codependent, the content characteristics of the value-semantic sphere of the codependent change. Among other things, ideas about one's own life, one's future may change, the image of the I and the image of the world, the idea of success, change. The study involved 167 participants - women in codependent relationships. Research methods: methodology "Research of ideas about successful professional activity" (O. Yu. Klochkova); methodology "Motivation for success and fear of failure" (A. A. Rean); methodology "Self-assessment of manifestations of fear of success" (G.V. Turetskaya); scale of measuring codependency in relationships (L. Spann-D. Fisher, adapted by V.D. Moskalenko). Statistical analysis and data processing were performed using the «Microsoft Excel 7.0» и «SPSS» (22.0). Our comparative analysis of the data made it possible to reveal that there are significant differences in the indicators of ideas about success among women with a high and normal level of codependency, and there is also a relationship between the level of codependency and ideas about success.

In the digital age of a transitive society, interaction between people is undergoing significant changes. Many researchers talk about the virtualization of modern society, in which visual communication comes to the fore. However, despite the prevalence of the above-mentioned processes, questions remain about strategies for presenting themselves to society using social networks, and how people position themselves when publicly presenting themselves in an online environment. As part of the empirical study, the object was 30 boys and 30 girls, representatives of modern youth who actively use social networks. The age of the subjects is from 14 to 17 years. We used four test methods: the "Who am I" Method of Kuhn and McPortland; the "Scale of self-presentation tactics" by S.J. Li in the adaptation of Pikuleva O.A.; "Scale of perfectionist self-presentation" By P. Hewitt in the adaptation of Zolotareva A.A.; "Test of self-confidence" by V.G. Romek. The theoretical and practical significance of the research lies in the development of ideas about the specifics of self-presentation of modern youth who actively use social networks. The results of the study can be used in the practice of family and individual counseling of parents and adolescents, as well as in teachers and psychologists of various educational institutions.

In any branch of the agro-industrial complex, a special role is played by the management team. The success of an agro-industrial enterprise depends largely on the level of motivation of its head, as he forms and directs the work of subordinate personnel. Despite extensive theoretical and practical research in the field of labor motivation, these studies lack an industry-specific approach that takes into account the specifics of the labor activity of managers of the agro-industrial sector of production. The object of the study was 30 managers of various experimental production farms in the Rostov region. During the empirical study, two test methods were used: “career Anchors” (E. Shane) and “Motivational profile” (S. Ritchie and P. Martin), as well as the author’s projective questionnaire. The practical significance of the work consists in scientifically-based recommendations developed based on the analysis of the results of the study. These recommendations can be taken into account by managers and employees of personnel services of enterprises in the agro-industrial area when forming systems of motivation and development of higher needs for employees who hold senior positions in modern market conditions.

Insights into meaning regulation expand, thus making possible to forecast human behavior with greater accuracy. This is of special importance in overcoming crisis situations in a fast-changing society. A meaning-making strategy defines the direction and content of generated meanings, which control human behavior and attitude to what is happening. To develop a meaning psychology, one should improve the well-known simple schemata of dual interpretation of meaning-making strategies. The next, more complex, yet more adequate level of meaning-making interpretation, is the trialectic approach. The authors of this article propose a theoretical justification to the trialectic model of meaning-making strategies. This theoretical model grounds the following triad of meaning-making strategies: hypoadaptivity strategy, hyperadaptivity strategy and preadaptivity strategy. It permits to better detect the actual human meanings and simulate development of man in today’s world. Determination of such peculiarities enables to carry out multi-variant empirical diagnostic of deeds, attitudes, and behavioral responses.

The authors conducted a study aimed at studying the characteristics of students with different models of information behavior in connection with the changes in psychological boundaries when using Internet technologies. The article reveals the role of information technologies and technical means, which become an important component of the life of a modern person and change his living space. The authors show the influence of information technologies on mental processes and relationships of people and consider the features of information behavior in connection with possible violation of psychological boundaries when using technical means The article analyses the problem of diagnosing information behavior and contains an overview of diagnostic methods of studying Internet addiction. It’s shown that in modern world information behavior is needed to be studied outside the context of addictive behavior. In the empirical part of the study authors distinguish the models of information behavior: entertaining, informational, communicative, productive and pragmatic. The empirical study defines the main behavioral characteristics of the presented information behavior models and investigate the changes in psychological boundaries when using the Internet among students with different models of information behavior. The results of the study allow to reveal the subjective attitude of students to the possibilities and availability of Internet resources in connection with differences in the severity of the expansion of psychological boundaries in communication, in the reflection of violation of boundaries, in changing needs.

The study of the meaning-forming strategies of students studying the specialty "Psychology". The features of resource capacity, styles of self-regulation of behavior, emotional tone and mental activation of students with various semantic strategies during the session in a remote format were studied. In conclusion, conclusions and recommendations are presented with suggestions for using the results in the training of future psychologists.

The research in question investigates the technologies of initiating independent activity within the framework of distance learning and their psychological aspects. The authors' classification of educational technologies of initiating students into independent cognitive activity is presented. Such technologies utilize various psychological mechanisms of exciting students' cognitive interest, intensifying cognitive processes, developing independent activity skills, and, as a result, increase motivation for independent activity and learning on the whole. These include such types of technologies as devel­opmental technologies, interactive technologies, technologies of information transfer, technologies of meaning-making initiation. The research of the attitude of distance learning educators to independent activity of students and the con­tent of the academic courses were done at Moodle-based education programs. The findings show the differences in retention rate among distance learning educators whose competence in terms of initiating students into independent (self-guided) activity varies. It's emphasized that interactive lectures, video­conferences, audio-visual aids, interactive seminars, glossaries, interactive tests are considered the most efficient technologies in initiating students into independent (self-guided) activity. The obtained results have made it possible to stress the developmental effect of distance learning technologies and the technologies of initiating students into independent (self-guided) activity in various psychic spheres of students: cognitive, individual, emotional. We men­tion the changes in motivational sphere of students and their meaning-making activity. In the course of correct development of distance learning we notice the development of voluntary and nonvoluntary cognitive activity. A student starts actively participating in educational process, he becomes the creator of his own world.

Summary Hydrogen peroxide (H2O2) is central to mitochondrial oxidative damage and redox signaling, but its roles are poorly understood due to the difficulty of measuring mitochondrial H2O2 in vivo. Here we report a ratiometric mass spectrometry probe approach to assess mitochondrial matrix H2O2 levels in vivo. The probe, MitoB, comprises a triphenylphosphonium (TPP) cation driving its accumulation within mitochondria, conjugated to an arylboronic acid that reacts with H2O2 to form a phenol, MitoP. Quantifying the MitoP/MitoB ratio by liquid chromatography-tandem mass spectrometry enabled measurement of a weighted average of mitochondrial H2O2 that predominantly reports on thoracic muscle mitochondria within living flies. There was an increase in mitochondrial H2O2 with age in flies, which was not coordinately altered by interventions that modulated life span. Our findings provide approaches to investigate mitochondrial ROS in vivo and suggest that while an increase in overall mitochondrial H2O2 correlates with aging, it may not be causative., Highlights ► A mitochondria-targeted mass spectrometry probe measures mitochondrial H2O2 in vivo ► Overall mitochondrial H2O2 increases with age but can be independent of life span ► Increased physical activity leads to a decrease in mitochondrial H2O2 ► Hypotheses dependent on overall mitochondrial ROS can now be assessed in vivo

The article presents the results of an empirical study on models of Internet behavior of humanitarian students, taking into account their gender characteristics. The relevance of this study is determined by the active inclusion of modern students in the Internet space. The lack of studies on the problem of Internet behavior in the student community led to the need for empirical research. As an empirical object of research, we choose humanities faculties students of universities in Rostov-on-Don and the Rostov region in the amount of 60 people, including 28 young men and 32 young women. The psychological profiles of students’ Internet behavior were studied, differences in the used models of Internet behavior in male and female samples were revealed. The features of Internet behavior are shown, indicating the fact that the student environment is dominated by entertainment and leisure activities in the use of Internet resources. It was revealed that the behavior of girls is predominant, defined as information surfing with a longer stay in the Internet space, boys have a shorter stay («Quickies» and «Single Missions») aimed at solving a specific problem.

Epidemiological, clinical, and experimental animal studies suggest a strong correlation between insulin resistance and Alzheimer's disease. In fact, type-2 diabetes is considered an important risk factor of developing Alzheimer's disease. In addition, impaired insulin signaling in the Alzheimer's disease brain may promote Aβ production, impair Aβ clearance and induce tau hyperphosphorylation, thereby leading to deterioration of the disease. The pathological prion protein, PrPSc, deposits in the form of extracellular aggregates and leads to dementia, raising the question as to whether prion pathogenesis may also be affected by insulin resistance. We therefore established high-fat diet-induced insulin resistance in tga20 mice, which overexpress the prion protein. We then inoculated the insulin-resistant mice with prions. We found that insulin resistance in tga20 mice did not affect prion disease progression, PrPSc deposition, astrogliosis or microglial activation, and had no effect on survival. Our study demonstrates that in a mouse model, insulin resistance does not significantly contribute to prion pathogenesis.

Calcifications in the basal ganglia are a common incidental finding and are sometimes inherited as an autosomal dominant trait (idiopathic basal ganglia calcification (IBGC)). Recently, mutations in the PDGFRB gene coding for the platelet-derived growth factor receptor β (PDGF-Rβ) were linked to IBGC. Here we identify six families of different ancestry with nonsense and missense mutations in the gene encoding PDGF-B, the main ligand for PDGF-Rβ. We also show that mice carrying hypomorphic Pdgfb alleles develop brain calcifications that show age-related expansion. The occurrence of these calcium depositions depends on the loss of endothelial PDGF-B and correlates with the degree of pericyte and blood-brain barrier deficiency. Thus, our data present a clear link between Pdgfb mutations and brain calcifications in mice, as well as between PDGFB mutations and IBGC in humans.

Reactive oxygen species are byproducts of mitochondrial respiration and thus potential regulators of mitochondrial function. Pyruvate dehydrogenase kinase 2 (PDHK2) inhibits the pyruvate dehydrogenase complex, thereby regulating entry of carbohydrates into the tricarboxylic acid (TCA) cycle. Here we show that PDHK2 activity is inhibited by low levels of hydrogen peroxide (H(2)O(2)) generated by the respiratory chain. This occurs via reversible oxidation of cysteine residues 45 and 392 on PDHK2 and results in increased pyruvate dehydrogenase complex activity. H(2)O(2) derives from superoxide (O(2)(.)), and we show that conditions that inhibit PDHK2 also inactivate the TCA cycle enzyme, aconitase. These findings suggest that under conditions of high mitochondrial O(2)(.) production, such as may occur under nutrient excess and low ATP demand, the increase in O(2)() and H(2)O(2) may provide feedback signals to modulate mitochondrial metabolism.

The role of hydrogen peroxide (H(2)O(2)) in mitochondrial oxidative damage and redox signaling is poorly understood, because it is difficult to measure H(2)O(2) in vivo. Here we describe a method for assessing changes in H(2)O(2) within the mitochondrial matrix of living Drosophila. We use a ratiometric mass spectrometry probe, MitoB ((3-hydroxybenzyl)triphenylphosphonium bromide), which contains a triphenylphosphonium cation component that drives its accumulation within mitochondria. The arylboronic moiety of MitoB reacts with H(2)O(2) to form a phenol product, MitoP. On injection into the fly, MitoB is rapidly taken up by mitochondria and the extent of its conversion to MitoP enables the quantification of H(2)O(2). To assess MitoB conversion to MitoP, the compounds are extracted and the MitoP/MitoB ratio is quantified by liquid chromatography-tandem mass spectrometry relative to deuterated internal standards. This method facilitates the investigation of mitochondrial H(2)O(2) in fly models of pathology and metabolic alteration, and it can also be extended to assess mitochondrial H(2)O(2) production in mouse and cell culture studies.

The mitochondria-targeted quinone MitoQ protects mitochondria in animal studies of pathologies in vivo and is being developed as a therapy for humans. However, it is unclear whether the protective action of MitoQ is entirely due to its antioxidant properties, because long-term MitoQ administration may alter whole-body metabolism and gene expression. To address this point, we administered high levels of MitoQ orally to wild-type C57BL/6 mice for up to 28 weeks and investigated the effects on whole-body physiology, metabolism, and gene expression, finding no measurable deleterious effects. In addition, because antioxidants can act as pro-oxidants under certain conditions in vitro, we examined the effects of MitoQ administration on markers of oxidative damage. There were no changes in the expression of mitochondrial or antioxidant genes as assessed by DNA microarray analysis. There were also no increases in oxidative damage to mitochondrial protein, DNA, or cardiolipin, and the activities of mitochondrial enzymes were unchanged. Therefore, MitoQ does not act as a pro-oxidant in vivo. These findings indicate that mitochondria-targeted antioxidants can be safely administered long-term to wild-type mice.

Nitric oxide (NO • ) competitively inhibits oxygen consumption by mitochondria at cytochrome c oxidase and S -nitrosates thiol proteins. We developed mitochondria-targeted S -nitrosothiols (MitoSNOs) that selectively modulate and protect mitochondrial function. The exemplar MitoSNO1, produced by covalently linking an S -nitrosothiol to the lipophilic triphenylphosphonium cation, was rapidly and extensively accumulated within mitochondria, driven by the membrane potential, where it generated NO • and S -nitrosated thiol proteins. MitoSNO1-induced NO • production reversibly inhibited respiration at cytochrome c oxidase and increased extracellular oxygen concentration under hypoxic conditions. MitoSNO1 also caused vasorelaxation due to its NO • generation. Infusion of MitoSNO1 during reperfusion was protective against heart ischemia-reperfusion injury, consistent with a functional modification of mitochondrial proteins, such as complex I, following S -nitrosation. These results support the idea that selectively targeting NO • donors to mitochondria is an effective strategy to reversibly modulate respiration and to protect mitochondria against ischemia-reperfusion injury.

Mitochondrial oxidative damage is thought to contribute to a wide range of human diseases; therefore, the development of approaches to decrease this damage may have therapeutic potential. Mitochondria-targeted antioxidants that selectively block mitochondrial oxidative damage and prevent some types of cell death have been developed. These compounds contain antioxidant moieties, such as ubiquinone, tocopherol, or nitroxide, that are targeted to mitochondria by covalent attachment to a lipophilic triphenylphosphonium cation. Because of the large mitochondrial membrane potential, the cations are accumulated within the mitochondria inside cells. There, the conjugated antioxidant moiety protects mitochondria from oxidative damage. Here, we outline some of the work done to date on these compounds and how they may be developed as therapies.

Mitochondria-targeted molecules comprising the lipophilic TPP (triphenylphosphonium) cation covalently linked to a hydrophobic bioactive moiety are used to modify and probe mitochondria in cells and in vivo. However, it is unclear how hydrophobicity affects the rate and extent of their uptake into mitochondria within cells, making it difficult to interpret experiments because their intracellular concentration in different compartments is uncertain. To address this issue, we compared the uptake into both isolated mitochondria and mitochondria within cells of two hydrophobic TPP derivatives, [3H]MitoQ (mitoquinone) and [3H]DecylTPP, with the more hydrophilic TPP cation [3H]TPMP (methyltriphenylphosphonium). Uptake of MitoQ by mitochondria and cells was described by the Nernst equation and was approximately 5-fold greater than that for TPMP, as a result of its greater binding within the mitochondrial matrix. DecylTPP was also taken up extensively by cells, indicating that increased hydrophobicity enhanced uptake. Both MitoQ and DecylTPP were taken up very rapidly into cells, reaching a steady state within 15 min, compared with approximately 8 h for TPMP. This far faster uptake was the result of the increased rate of passage of hydrophobic TPP molecules through the plasma membrane. Within cells MitoQ was predominantly located within mitochondria, where it was rapidly reduced to the ubiquinol form, consistent with its protective effects in cells and in vivo being due to the ubiquinol antioxidant. The strong influence of hydrophobicity on TPP cation uptake into mitochondria within cells facilitates the rational design of mitochondria-targeted compounds to report on and modify mitochondrial function in vivo.

Stimulant addiction is often linked to excessive risk taking, sensation seeking, and impulsivity, but in ways that are poorly understood. We report here that a form of impulsivity in rats predicts high rates of intravenous cocaine self-administration and is associated with changes in dopamine (DA) function before drug exposure. Using positron emission tomography, we demonstrated that D2/3 receptor availability is significantly reduced in the nucleus accumbens of impulsive rats that were never exposed to cocaine and that such effects are independent of DA release. These data demonstrate that trait impulsivity predicts cocaine reinforcement and that D2 receptor dysfunction in abstinent cocaine addicts may, in part, be determined by premorbid influences.

Microglial activation is a hallmark of most neurodegenerative disorders, yet it is not clear if it plays beneficial or deleterious roles. Zhu et al. provide evidence for a general protective role of microglia in the pathogenesis of prion diseases., Microglial activation is a hallmark of most neurodegenerative disorders, and is particularly conspicuous in prion diseases. However, the role of microglia, which function as both primary immune effector cells and professional phagocytes in the central nervous system, remains contentious in the context of neurodegeneration. Here, we evaluated the effect of microglial depletion/deficiency on prion pathogenesis. We found that ganciclovir-mediated microglial ablation on tga20/CD11b-thymidine kinase of Herpes simplex virus (HSVTK) cerebellar organotypic cultured slices markedly aggravated prion-induced neurotoxicity. A similar deterioration of disease was recapitulated in in vivo microglial depletion in prion-infected tga20/CD11b-HSVTK mice. Additionally, deficiency of microglia in interleukin 34 knockout (IL34−/−) mice again resulted in significantly augmented proteinase K–resistant prion protein deposition and accelerated prion disease progression. These results provide unambiguous evidence for a general protective role of microglia in prion pathogenesis.