Characterization of orexin input to dopamine neurons of the ventral tegmental area projecting to the medial prefrontal cortex and shell of nucleus accumbens

Orexin neurons are involved in homeostatic regulatory processes, including arousal and feeding, and provide a major input from the hypothalamus to the ventral tegmental area (VTA) of the midbrain. VTA neurons are a central hub processing reward and motivation and target the medial prefrontal cortex (mPFC) and the shell part of nucleus accumbens (NAcs). We investigated whether subpopulations of dopamine (DA) neurons in the VTA projecting either to the mPFC or the medial division of shell part of nucleus accumbens (mNAcs) receive differential input from orexin neurons and whether orexin exerts differential electrophysiological effects upon these cells. VTA neurons projecting to the mPFC or the mNAcs were traced retrogradely by Cav2-Cre virus and identified by expression of yellow fluorescent protein (YFP). Immunocytochemical analysis showed that a higher proportion of all orexin-innervated DA neurons projected to the mNAcs (34.5%) than to the mPFC (5.2%). Of all sampled VTA neurons projecting either to the mPFC or mNAcs, the dopaminergic (68.3 vs. 79.6%) and orexin-innervated DA neurons (68.9 vs. 64.4%) represented the major phenotype. Whole-cell current clamp recordings were obtained from fluorescently labeled neurons in slices during baseline periods and bath application of orexin A. Orexin similarly increased the firing rate of VTA dopamine neurons projecting to mNAcs (1.99 ± 0.61 Hz to 2.53 ± 0.72 Hz) and mPFC (0.40 ± 0.22 Hz to 1.45 ± 0.56 Hz). Thus, the hypothalamic orexin system targets mNAcs and to a lesser extent mPFC-projecting dopaminergic neurons of the VTA and exerts facilitatory effects on both clusters of dopamine neurons.

CCT3-LINC00326 axis regulates hepatocarcinogenic lipid metabolism

ObjectiveTo better comprehend transcriptional phenotypes of cancer cells, we globally characterised RNA-binding proteins (RBPs) to identify altered RNAs, including long non-coding RNAs (lncRNAs).DesignTo unravel RBP-lncRNA interactions in cancer, we curated a list of ~2300 highly expressed RBPs in human cells, tested effects of RBPs and lncRNAs on patient survival in multiple cohorts, altered expression levels, integrated various sequencing, molecular and cell-based data.ResultsHigh expression of RBPs negatively affected patient survival in 21 cancer types, especially hepatocellular carcinoma (HCC). After knockdown of the top 10 upregulated RBPs and subsequent transcriptome analysis, we identified 88 differentially expressed lncRNAs, including 34 novel transcripts. CRISPRa-mediated overexpression of four lncRNAs had major effects on the HCC cell phenotype and transcriptome. Further investigation of four RBP-lncRNA pairs revealed involvement in distinct regulatory processes. The most noticeable RBP-lncRNA connection affected lipid metabolism, whereby the non-canonical RBP CCT3 regulated LINC00326 in a chaperonin-independent manner. Perturbation of the CCT3-LINC00326 regulatory network led to decreased lipid accumulation and increased lipid degradation in cellulo as well as diminished tumour growth in vivo.ConclusionsWe revealed that RBP gene expression is perturbed in HCC and identified that RBPs exerted additional functions beyond their tasks under normal physiological conditions, which can be stimulated or intensified via lncRNAs and affected tumour growth.

The Influence of the Western Diet on Microbiota and Gastrointestinal Immunity

Diet exerts a major influence upon host immune function and the gastrointestinal microbiota. Although components of the human diet (including carbohydrates, fats, and proteins) are essential sources of nutrition for the host, they also influence immune function directly through interaction with innate and cell-mediated immune regulatory mechanisms. Regulation of the microbiota community structure also provides a mechanism by which food components influence host immune regulatory processes. Here, we consider the complex interplay between components of the modern (Western) diet, the microbiota, and host immunity in the context of obesity and metabolic disease, inflammatory bowel disease, and infection. Expected final online publication date for the Annual Review of Food Science and Technology, Volume 13 is March 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Metabolic Adaptions/Reprogramming in Islet Beta-Cells in Response to Physiological Stimulators—What Are the Consequences

Irreversible pancreatic β-cell damage may be a result of chronic exposure to supraphysiological glucose or lipid concentrations or chronic exposure to therapeutic anti-diabetic drugs. The β-cells are able to respond to blood glucose in a narrow concentration range and release insulin in response, following activation of metabolic pathways such as glycolysis and the TCA cycle. The β-cell cannot protect itself from glucose toxicity by blocking glucose uptake, but indeed relies on alternative metabolic protection mechanisms to avoid dysfunction and death. Alteration of normal metabolic pathway function occurs as a counter regulatory response to high nutrient, inflammatory factor, hormone or therapeutic drug concentrations. Metabolic reprogramming is a term widely used to describe a change in regulation of various metabolic enzymes and transporters, usually associated with cell growth and proliferation and may involve reshaping epigenetic responses, in particular the acetylation and methylation of histone proteins and DNA. Other metabolic modifications such as Malonylation, Succinylation, Hydroxybutyrylation, ADP-ribosylation, and Lactylation, may impact regulatory processes, many of which need to be investigated in detail to contribute to current advances in metabolism. By describing multiple mechanisms of metabolic adaption that are available to the β-cell across its lifespan, we hope to identify sites for metabolic reprogramming mechanisms, most of which are incompletely described or understood. Many of these mechanisms are related to prominent antioxidant responses. Here, we have attempted to describe the key β-cell metabolic adaptions and changes which are required for survival and function in various physiological, pathological and pharmacological conditions.

Can Digital Therapeutics Open a New Era of Sleep Medicine?

Digital therapeutics (DTx) are products that provide evidence-based interventions driven by high-quality software programs to prevent, manage, or treat a medical disease. DTx are receiving increasing attention as a new therapeutic approach. Several DTx for insomnia are on the market, some of which have received approval by national regulatory agencies. DTx for insomnia are usually based on cognitive behavioral therapy for insomnia. No DTx for other sleep disorders, such as narcolepsy or sleep-related breathing disorders, have received regulatory authority approval as a medical device. DTx have the substantial benefits of being accessible and relatively low-cost. However, several issues related to DTx have not yet been fully resolved, and discussions regarding DTx are still in the early stages. To use DTx for sleep disorders as an effective treatment option in the future, considering the current status of DTx is necessary. This review discusses definitions and background of DTx; specific DTx for insomnia that have been developed; use of DTx for sleep and related psychiatric comorbid symptoms; global regulatory processes for DTx, including prescribing and medical billing issues; and remaining challenges regarding the use of DTx.

Productive behavior in relation to the personal and regulatory characteristics of students in the educational process

В интенсивно развивающемся обществе и введении в обучение специальных автоматизированных технологий используемых при проведении занятий значительно облегчает учебный процесс. Цель статьи заключается в нахождении взаимосвязи личностных и регуляторных характеристик выявленных при построении обратной связи в учебном процессе для актуализации продуктивного поведения. Для нахождения вдохновляющего триггера продуктивного поведения авторами выявлен принцип обратной связи, определяющий форму информационного взаимодействия, контроль которого осуществляется системой приемов, направленных на его участников для оценки результатов и последующей их коррекции. Раскрыта сущность проявления саморегуляции заключающейся в функционировании регуляторных процессов планирования, программирования, моделирования и оценки результатов, а также регуляторно-личностными свойствами в установлении взаимосвязи между волевой саморегуляцией и склонностью к продуктивному поведению. Предложено рассмотрение построения обратной связи в формате сильно-структурированной среды (ФГОС, информационные платформы, удаленные формы обучения во время пандемии) оказывающей влияние на проявление стабильных и регуляторных характеристик обучающихся. Доказано, что введение дистанционного образования в вузе в постоянном формате приводит к повышению уровня нейротизма у 30% обучающихся и у 70% проявление отношения к дистанционному обучению как к трудной ситуации. Статья предназначена для исследователей в области автоматизированных технологий, педагогам, педагогам-психологам и аспирантам. In an intensively developing society and the introduction of special automated technologies used in teaching classes, it greatly facilitates the educational process. The purpose of the article is to find the relationship between personal and regulatory characteristics identified when building feedback in the educational process to actualize productive behavior. To find an inspiring trigger of productive behavior, the authors identified the principle of feedback, which determines the form of information interaction, which is controlled by a system of techniques aimed at its participants to assess the results and their subsequent correction. The essence of the manifestation of self-regulation is revealed, which consists in the functioning of regulatory processes of planning, programming, modeling and evaluation of results, as well as regulatory and personal properties in establishing the relationship between volitional self-regulation and the propensity for productive behavior. It is proposed to consider the construction of feedback in the format of a highly structured environment (FSES, information platforms, remote forms of education during a pandemic) that influences the manifestation of stable and regulatory characteristics of students. It has been proven that the introduction of distance education in a university in a permanent format leads to an increase in the level of neuroticism in 30% of students and in 70% of the manifestation of an attitude towards distance learning as a difficult situation. The article is intended for researchers in the field of automated technologies, educators, educational psychologists and graduate students.

Developing connections for engagement in stroke rehabilitation

Background and Aims: Engagement is increasingly recognised as important for maximising rehabilitation outcome following stroke. However, engagement can be challenging when neurological impairment impacts a persons’ ability to activate the regulatory processes necessary for engagement and in the context of a changed self. We explored engagement in stroke rehabilitation from the perspective of people with stroke with a primary focus on identifying key processes that appeared important to engagement in stroke rehabilitation. Design and Methods: This study drew on Interpretive Description methodology. Maximum variation and theoretical sampling were used to capture diversity in the sample and access a depth and breadth of perspectives. Data collection included semi-structured interviews with people with stroke (n = 19). Data were analysed through a collaborative and iterative process drawing on range of analytical tools including coding, memoing, diagramming and group discussions. Findings: Our findings highlight that engagement is a complex, nuanced, responsive, flexible and inherently two-way process. Developing connections appeared central to engagement with connections taking various forms. The most fundamental was the therapeutic connection between the person with stroke and their practitioner as it provided the foundation on which to build other connections. Connection was made possible through five collaborative processes: Knowing, Entrusting, Adapting, Investing and Reciprocating. Conclusions: Engagement is a social and relational process enabled through an inherently person-centred approach and active and ongoing reflexivity – highlighting the importance of a humanising approach to care where aspects of self, care and emotion are evident, for both the person with stroke and their practitioner.

9. European Union agencies:

The institutional development of EU agencies is striking. Over the past decades, forty-six EU agencies have been established to support the European Commission and member states in their regulatory and executive tasks. Today, EU agencies are a vital part of the EU’s administrative capacity. EU agencies have received considerable scholarly attention that used a myriad of theoretical approaches—ranging from institutional, organizational, and bureaucratic reputation to interest-group theories—to explain why EU agencies have been created; how they develop over time; whether they are wielders of supranational or intergovernmental power; how they legitimize themselves and cultivate a positive bureaucratic reputation; and how they form alliances or insulate themselves from specific stakeholders. This chapter reviews the rise of EU agencies and introduces a selection of theoretical perspectives that have been used by EU agency scholars to study EU-level agencification and EU agency behaviour, regulatory processes, and outputs.

Career Goal Discrepancy, Career Distress, and Goal Adjustment: Testing a Dual Moderated Process Model in Young Adults

Identifying a large discrepancy in young people’s career goal progress can lead to distress, activating meaning-making, self-regulatory mechanisms aimed at resolving the uncomfortable situation. We assessed these important career-regulatory processes in a theoretical model by testing the indirect effects of career goal discrepancy on goal adjustment (assimilation and accommodation) via career distress, and assessed the conditionality of these effects based on two moderators (career calling and negative career feedback). In a cross-sectional study, we recruited 287 young adults with a mean age of 23.79 years ( SD = 3.35), and tested complex dual moderated process model (OLS regression). Greater career goal discrepancy was associated with more career distress, and, in turn, less assimilative and more accommodative tendencies. These indirect effects depended on the level of career calling and negative career feedback. The findings can be used to tailor interventions to optimise the consequences of identified gaps in young people’s career progress.

Black and Latino Adolescents’ Self-Regulation: Placing College Preparedness in Context

Students from minoritized backgrounds, who disproportionately face higher poverty rates, are more likely to encounter risk factors, which tend to undermine individuals’ broader well-being by compromising self-regulatory processes. Yet, sociocultural theory highlights the presence of minoritized families’ cultural wealth. Consistent with a focus on assets, it is notable that college enrollment rates have increased among Black and Latino students in the U.S. Using a mixed methods approach, the current study integrated asset and risk frameworks, in order to advance knowledge on the context of minoritized teens’ college preparedness, defined here as making decisions and taking action steps toward college. Participants included low-income, predominantly Black and Latino families with adolescents ( n = 344). First, drawing from the voices of families, we examined responses to open-ended questions about aspirations, supports, and challenges. Salient themes included social-emotional and social-cultural factors. Indicators of cumulative contextual risk and cumulative individual risk were based on the qualitative data. Second, we tested whether the linkage from cumulative risk indices to teens’ college preparedness occurred via various dimensions of self-regulation (i.e., lower impulsivity, more cognitive control, and better organization skills), net of background characteristics. Adolescents’ organization skills were a significant mediator. Possible next steps for research are discussed.