Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Functions of Positive Emotions: Gratitude as a Motivator of Self-Improvement and Positive Change

Positive emotions are highly valued and frequently sought. Beyond just being pleasant, however, positive emotions may also lead to long-term benefits in important domains, including work, physical health, and interpersonal relationships. Research thus far has focused on the broader functions of positive emotions. According to the broaden-and-build theory, positive emotions expand people’s thought–action repertoires and allow them to build psychological, intellectual, and social resources. New evidence suggests that positive emotions—particularly gratitude—may also play a role in motivating individuals to engage in positive behaviors leading to self-improvement. We propose and offer supportive evidence that expressing gratitude leads people to muster effort to improve themselves via increases in connectedness, elevation, humility, and specific negative states including indebtedness

Functions of Positive Emotions: Gratitude as a Motivator of Self-Improvement and Positive Change

Positive emotions are highly valued and frequently sought. Beyond just being pleasant, however, positive emotions may also lead to long-term benefits in important domains, including work, physical health, and interpersonal relationships. Research thus far has focused on the broader functions of positive emotions. According to the broaden-and-build theory, positive emotions expand people’s thought–action repertoires and allow them to build psychological, intellectual, and social resources. New evidence suggests that positive emotions—particularly gratitude—may also play a role in motivating individuals to engage in positive behaviors leading to self-improvement. We propose and offer supportive evidence that expressing gratitude leads people to muster effort to improve themselves via increases in connectedness, elevation, humility, and specific negative states including indebtedness

Satisfied yet striving: Gratitude fosters life satisfaction and improvement motivation in youth.

Could 10 min of gratitude per week have the potential to change the trajectories of young students' lives? With over 1,000 ninth- and tenth-grade students, we tested whether a simple 4-week classroom-based gratitude intervention would prompt increases in well-being and motivate students to become better people and attain better grades. Over the course of 1 month, students were assigned to spend 10 min each week writing gratitude letters to their parents, teachers, coaches, or friends and completing additional gratitude-related reflection activities or to try to become more organized each week by listing their daily activities and reflecting on the obstacles and benefits (control). Importantly, relative to controls, students in the gratitude conditions reported greater LS and motivation to improve themselves and maintained these levels throughout the semester. This sustained self-improvement motivation and LS were partially mediated by increases in feelings of connectedness, elevation, and indebtedness. Interestingly, negative affect partially mediated the effect of gratitude on LS, but not on improvement motivation. No group differences emerged in academic performance over time. This study provides evidence that expressing gratitude and reflecting on their benefactors' actions may help keep high school students motivated and satisfied with their lives over the course of a semester. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

More than Merely Positive: The Immediate Affective and Motivational Consequences of Gratitude

Although gratitude is typically conceptualized as a positive emotion, it may also induce socially oriented negative feelings, such as indebtedness and guilt. Given its mixed emotional experience, we argue that gratitude motivates people to improve themselves in important life domains. Two single-timepoint studies tested the immediate emotional and motivational effects of expressing gratitude. We recruited employees (n = 224) from French companies in Study 1 and students (n = 1026) from U.S. high schools in Study 2. Participants in both studies were randomly assigned to either write gratitude letters to benefactors or outline their weekly activities (control condition). Expressing gratitude led to mixed emotional experiences (e.g., greater elevation and indebtedness) for employees and students as compared with the control group. Students also felt more motivated and capable of improving themselves, as well as conveyed stronger intentions to muster effort towards self-improvement endeavors

The proximal experience of gratitude

Although a great deal of research has tested the longitudinal effects of regularly practicing gratitude, much less attention has been paid to the emotional landscape directly following engagement in gratitude exercises. In three studies, we explored the array of discrete emotions people experience after being prompted to express or recall gratitude. In Studies 1 and 2, two different gratitude exercises produced not only greater feelings of gratitude relative to two positive emotion control conditions (i.e., recalling relief), but also higher levels of other socially relevant states like elevation, connectedness, and indebtedness. In a third study, conducted in both the U.S. and S. Korea, we compared a gratitude exercise to another positive emotion elicitation (i.e., recalling a kind act) and to a neutral task, and again found that the gratitude exercise prompted greater gratitude, elevation, indebtedness, and guilt, but no more embarrassment or shame, than the two comparison conditions. Additionally, in all three studies, emodiversity and cluster analyses revealed that gratitude exercises led to the simultaneous experience of both pleasant and unpleasant socially-relevant states. In sum, although it may seem obvious that gratitude exercises would evoke grateful, positive states, a meta-analysis of our three studies revealed that gratitude exercises actually elicit a mixed emotional experience-one that simultaneously leads individuals to feel uplifted and indebted