Ventral frontostriatal circuitry mediates the computation of reinforcement from symbolic gains and losses.

Reinforcement learning (RL), particularly in primates, is often driven by symbolic outcomes. However, it is usually studied with primary reinforcers. To examine the neural mechanisms underlying learning from symbolic outcomes, we trained monkeys on a task in which they learned to choose options that led to gains of tokens and avoid choosing options that led to losses of tokens. We then recorded simultaneously from the orbitofrontal cortex (OFC), ventral striatum (VS), amygdala (AMY), and mediodorsal thalamus (MDt). We found that the OFC played a dominant role in coding token outcomes and token prediction errors. The other areas contributed complementary functions, with the VS coding appetitive outcomes and the AMY coding the salience of outcomes. The MDt coded actions and relayed information about tokens between the OFC and VS. Thus, the OFC leads the processing of symbolic RL in the ventral frontostriatal circuitry.

Adult age differences in value-based decision making.

A better understanding of age-related differences in judgment and decision making is important from both theoretical and applied perspectives. In this review, we focus on value-based decisions across adulthood and specifically on how loss aversion (a relatively stronger weight of losses than gains on decisions) and the relative motivational impact of gains and losses may change with aging. In doing so, we will also cover recent findings about the effects of gain or loss incentives on performance in cognitive tasks that involve attention, learning, and remembering. We point out open questions and critical moderating variables for future theorizing and research.

Autorecoding A-to-I RNA editing sites in the Adar gene underwent compensatory gains and losses in major insect clades.

As one of the most prevalent RNA modifications in animals, adenosine-to-inosine (A-to-I) RNA editing facilitates the environmental adaptation of organisms by diversifying the proteome in a temporal-spatial manner. In flies and bees, the editing enzyme Adar has independently gained two different autorecoding sites that form an autofeedback loop, stabilizing the overall editing efficiency. This ensures cellular homeostasis by keeping the normal function of target genes. However, in a broader range of insects, the evolutionary dynamics and significance of this Adar autoregulatory mechanism are unclear. We retrieved the genomes of 377 arthropod species covering the five major insect orders (Hemiptera, Hymenoptera, Coleoptera, Diptera, and Lepidoptera) and aligned the Adar autorecoding sites across all genomes. We found that the two autorecoding sites underwent compensatory gains and losses during the evolution of two orders with the most sequenced species (Diptera and Hymenoptera), and that the two editing sites were mutually exclusive among them: One editable site is significantly linked to another uneditable site. This autorecoding mechanism of Adar could flexibly diversify the proteome and stabilize global editing activity. Many insects independently selected different autorecoding sites to achieve a feedback loop and regulate the global RNA editome, revealing an interesting phenomenon during evolution. Our study reveals the evolutionary force acting on accurate regulation of RNA editing activity in insects and thus deepens our understanding of the functional importance of RNA editing in environmental adaptation and evolution.

Disentangling spatiotemporal dynamics in metacommunities through a species-patch network approach.

Colonization and extinction at local and regional scales, and gains and losses of patches are important processes in the spatiotemporal dynamics of metacommunities. However, analytical challenges remain in quantifying such spatiotemporal dynamics when species extinction-colonization and patch gain and loss processes act simultaneously. Recent advances in network analysis show great potential in disentangling the roles of colonization, extinction, and patch dynamics in metacommunities. Here, we developed a species-patch network approach to quantify metacommunity dynamics including (i) temporal changes in network structure, and (ii) temporal beta diversity of species-patch links and its components that reflect species extinction-colonization and patch gain and loss. Application of the methods to simulated datasets demonstrated that the approach was informative about metacommunity assembly processes. Based on three empirical datasets, our species-patch network approach provided additional information about metacommunity dynamics through distinguishing the effects of species colonization and extinction at different scales from patch gains and losses and how specific environmental factors related to species-patch network structure. In conclusion, our species-patch network framework provides effective methods for monitoring and revealing long-term metacommunity dynamics by quantifying gains and losses of both species and patches under local and global environmental change.

Bidirectional Associations of Awareness of Age-Related Change and Attitudes Toward Own Aging With Social Media Use.

OBJECTIVES: We test whether higher awareness of age-related gains (AARC-gains), lower awareness of age-related losses (AARC-losses), and more positive attitudes toward own aging (ATOA) are cross-sectionally related to more frequent social media use. We also investigate the strength and direction of the associations of AARC-gains, AARC-losses, and ATOA with social media use over 1 year, from before to after the onset of the coronavirus 2019 pandemic. METHODS: We used cross-sectional data from 8,320 individuals (mean age = 65.95 years; standard deviation = 7.01) and longitudinal data from a subsample of 4,454 individuals participating in the UK PROTECT study in 2019 and 2020. We used ordered regression models, linear regression models, and tests of interaction. Models were adjusted for age, sex, education, and employment. RESULTS: Higher AARC-gains and more positive ATOA, but not AARC-losses, were cross-sectionally associated with more frequent social media use. Social media use became more frequent at follow-up. In the longitudinal models controlling for baseline levels of the outcome variable, more frequent baseline social media use predicted increases in AARC-gains, whereas baseline AARC-gains did not significantly predict the frequency of social media use at follow-up. Baseline frequency of social media use did not significantly predict AARC-losses, nor ATOA at follow-up, whereas lower levels of AARC-losses and more positive ATOA predicted more frequent social media use at follow-up. DISCUSSION: Although effect sizes were small, decreasing negative views on aging may help increase the engagement of middle-aged and older people with social media. At the same time, fostering social media use could promote positive self-perceptions of aging.

KaryoCreate: A CRISPR-based technology to study chromosome-specific aneuploidy by targeting human centromeres.

Aneuploidy, the presence of chromosome gains or losses, is a hallmark of cancer. Here, we describe KaryoCreate (karyotype CRISPR-engineered aneuploidy technology), a system that enables the generation of chromosome-specific aneuploidies by co-expression of an sgRNA targeting chromosome-specific CENPA-binding ɑ-satellite repeats together with dCas9 fused to mutant KNL1. We design unique and highly specific sgRNAs for 19 of the 24 chromosomes. Expression of these constructs leads to missegregation and induction of gains or losses of the targeted chromosome in cellular progeny, with an average efficiency of 8% for gains and 12% for losses (up to 20%) validated across 10 chromosomes. Using KaryoCreate in colon epithelial cells, we show that chromosome 18q loss, frequent in gastrointestinal cancers, promotes resistance to TGF-ß, likely due to synergistic hemizygous deletion of multiple genes. Altogether, we describe an innovative technology to create and study chromosome missegregation and aneuploidy in the context of cancer and beyond.

Rumination moderates the longitudinal associations of awareness of age-related change with depressive and anxiety symptoms.

OBJECTIVE: Lower awareness of age-related gains (AARC-gains) and higher awareness of age-related losses (AARC-losses) may be risk factors for depressive and anxiety symptoms. We explored whether: (1) Baseline AARC-gains and AARC-losses predict depressive and anxiety symptoms at one-year follow-up; (2) age and rumination moderate these associations; (3) levels of AARC-gains and AARC-losses differ among individuals with different combinations of current and past depression and/or with different combinations of current and past anxiety. METHODS: In this one-year longitudinal cohort study participants (N = 3386; mean age = 66.0; SD = 6.93) completed measures of AARC-gains, AARC-losses, rumination, depression, anxiety, and lifetime diagnosis of depression and anxiety in 2019 and 2020. Regression models with tests of interaction were used. RESULTS: Higher AARC-losses, but not lower AARC-gains, predicted more depressive and anxiety symptoms. Age did not moderate these associations. Associations of lower AARC-gains and higher AARC-losses with more depressive symptoms and of higher AARC-losses with more anxiety symptoms were stronger in those with higher rumination. Individuals with both current and past depression reported highest AARC-losses and lowest AARC-gains. Those with current, but not past anxiety, reported highest AARC-losses. CONCLUSION: Perceiving many age-related losses may place individuals at risk of depressive and anxiety symptoms, especially those who frequently ruminate.

Pay One or Pay All? The Role of Incentive Schemes in Decision Making Across Adulthood.

OBJECTIVES: This research addresses how younger and older adults' decisions and evaluations of gains and losses are affected by the way in which monetary incentives are provided. We compared 2 common incentive schemes in decision making: pay one (only a single decision is incentivized) and pay all (incentives across all decisions are accumulated). METHOD: Younger adults (18-36 years; n = 147) and older adults (60-89 years; n = 139) participated in either a pay-one or pay-all condition and made binary choices between two-outcome monetary lotteries in gain, loss, and mixed domains. We analyzed participants' decision quality, risk taking, and psychometric test scores. Computational modeling of cumulative prospect theory served to measure sensitivity to outcomes and probabilities, loss aversion, and choice sensitivity. RESULTS: Decision quality and risk aversion were higher in the gain than mixed or loss domain, but unaffected by age. Loss aversion was higher, and choice sensitivity was lower in older than younger adults. In the pay-one condition, the value functions were more strongly curved, and choice sensitivity was higher than in the pay-all condition. DISCUSSION: An opportunity of accumulating incentives has similar portfolio effects on younger and older adults' decisions. In general, people appear to decide less cautiously in pay-all than pay-one scenarios. The impact of different incentive schemes should be carefully considered in aging and decision research.

Symptoms of Post-Traumatic Stress Disorder and the Sense of Gains and Losses during the COVID-19 Pandemic: An International Study.

This study was primarily designed to investigate the perception of changes in selected areas of life experienced by adults of various nationalities in connection to the long-lasting COVID-19 pandemic. The second objective was to identify the factors increasing the risk of perception of negative changes in life during the pandemic. The tools applied in the study include a self-report questionnaire designed to measure sociodemographic data and health status of the subjects, COVID-19 Sense of Life Changes Questionnaire, as well as the Impact of Event Scale: Revised. The study involved over 600 adult subjects. With increased intensity of intrusions, the likelihood of negative perception of the changes emerging as a result of the pandemic was reduced by approximately 7%, whereas a higher intensity of hyperarousal increased that risk. Individuals reporting a sense of negative changes presented a greater degree of hyperarousal compared to those reporting positive changes. In the group of subjects perceiving the changes in a positive way, increasing the intensity of intrusion and/or hyperarousal corresponded to a growing conviction about a negative nature of life changes concerning the relationship with their partner and affecting their work as well as regarding a positive meaning of the changes in relations with their parents and in daily life. Generally, there was a prevailing sense of negative changes; however, there was also a group of subjects that perceived these as positive. Intrusions and hyperarousal in certain individuals may play a role in motivating them to take action in protecting against effects of the pandemic and, in others, may lead to frustration and anxiety.

Adult age differences in remembering gain- and loss-related intentions.

Motivational and emotional changes across adulthood have a profound impact on cognition. In this registered report, we conducted an experimental investigation of motivational influence on remembering intentions after a delay (prospective memory; PM) in younger, middle-aged, and older adults, using gain- and loss-framing manipulations. The present study examined for the first time whether motivational framing in a PM task has different effects on younger and older adults' PM performance (N = 180; age range: 18-85 years) in a controlled laboratory setting. Based on lifespan theories of motivation, we assumed that the prevention of losses becomes more relevant with increasing age: We expected that older adults show relatively higher PM performance in a task with loss-related consequences following PM failure than in a task in which successful PM leads to gains. The opposite pattern of performance was expected for younger adults. The findings suggest that the relevance of reward and positive gain-related consequences for successful remembering appears to decrease with age. As hypothesised, a motivational framing × age interaction indicated that age differences in memory performance were smaller with loss-related than gain-related consequences, supporting a loss-prevention view on motivated cognition.

Double adenomas of the pituitary reveal distinct lineage markers, copy number alterations, and epigenetic profiles.

PURPOSE: Pituitary adenoma (PA) constitutes the third most common intracranial neoplasm. The mostly benign endocrine lesions express no hormone (null cell PA) or the pituitary hormone(s) of the cell lineage of origin. In 0.5-1.5% of surgical specimens and in up to 10% of autopsy cases, two or three seemingly separate PA may coincide. These multiple adenomas may express different hormones, but whether or not expression of lineage-restricted transcription factors and molecular features are distinct within multiple lesions remains unknown. METHODS: Searching the data bank of the German Pituitary Tumor Registry 12 double pituitary adenomas with diverse lineage were identified among 3654 adenomas and 6 hypophyseal carcinomas diagnosed between 2012 and 2020. The double adenomas were investigated immunohistochemically for expression of hormones and lineage markers. In addition, chromosomal gains and losses as well as global DNA methylation profiles were assessed, whenever sufficient material was available (n = 8 PA). RESULTS: In accordance with the literature, combinations of GH/prolactin/TSH-FSH/LH adenoma (4/12), GH/prolactin/TSH-ACTH adenoma (3/12), and ACTH-FSH/LH adenoma (3/12) were observed. Further, two out of 12 cases showed a combination of a GH/prolactin/TSH adenoma with a null-cell adenoma. Different expression pattern of hormones were confirmed by different expression of transcription factors in 11/12 patients. Finally, multiple lesions that were molecularly analysed in 4 patients displayed distinct copy number changes and global methylation pattern. CONCLUSION: Our data confirm and extend the knowledge on multiple PA and suggest that such lesions may origin from distinct cell types.

The Role of the Ventromedial Prefrontal Cortex in Public Good and Public Bad Games: Evidence From a tDCS Study.

Although humans constitute an exceptionally cooperative species that is able to collaborate on large scales for common benefits, cooperation remains a longstanding puzzle in biological and social science. Moreover, cooperation is not always related to resource allocation and gains but is often related to losses. Revealing the neurological mechanisms and brain regions related to cooperation is important for reinforcing cooperation-related gains and losses. Recent neuroscience studies have found that the decision-making process of cooperation is involved in the function of the ventromedial prefrontal cortex (VMPFC). In the present study, we aimed to investigate the causal role of the VMPFC in cooperative behavior concerning gains and losses through the application of transcranial direct current stimulation (tDCS). We integrated cooperation-related gains and losses into a unified paradigm. Based on the paradigm, we researched cooperation behaviors regarding gains in standard public good games and introduced public bad games to investigate cooperative behavior regarding losses. Our study revealed that the VMPFC plays different roles concerning gains and losses in situations requiring cooperation. Anodal stimulation over the VMPFC decreased cooperative behavior in public bad games, whereas stimulation over the VMPFC did not change cooperative behavior in public good games. Moreover, participants' beliefs about others' cooperation were changed in public bad games but not in public good games. Finally, participants' cooperative attitudes were not influenced in the public good or public bad games under the three stimulation conditions.

The economic dimension of directing treated wastewater to the production of green fodder in Saudi Arabia.

This study aimed to identify the economic dimension of directing treated wastewater to the production of green fodder. To achieve its objectives, the study relied on economic equations, the method of using multiple criteria, and a scoring technique for prioritization. The study showed that green fodder is a crop that depletes water, as it consumes about 67.27% of the water used for agricultural purposes. In determining the priority of regions intending to use treated wastewater, the ranking put Riyadh region first, followed by the eastern region, the Qassim region, Hail, Makkah Al-Mukarramah, Tabuk, Asir, Al-Jawf, Jizan, Madinah, Najran, the northern borders, and Al-Baha, in this order. The area that can be cultivated with forage crops is estimated to be about 53.05 thousand hectares, with a production of 953.75 thousand tons. The cost of treating wastewater to make it usable amounts to 2126.22 million riyals, while the value of the benefits gained from its use is 2508.95 million riyals; thus, the Saudi agricultural economy achieves a net gain estimated at about 382.73 million riyals annually. Therefore, this study recommends the use of treated wastewater in the production of green fodder.

Comparative Genomics Provide Insights Into Function and Evolution of Odorant Binding Proteins in Cydia pomonella.

Insect olfaction is vital for foraging, mating, host-seeking, and avoidance of predators/pathogens. In insects, odorant binding proteins (OBPs) are involved in transporting hydrophobic odor molecules from the external environment to receptor neurons. The codling moth, Cydia pomonella, one of the most destructive insect fruit pests, causes enormous economic losses. However, little is known about the number, variety, gains and losses, and evolution of OBP genes in C. pomonella. Here we report the identification of 40 OBPs in C. pomonella, most (75%) of which are classic OBPs, using genomic and transcriptomic analyses. Two OBP genes were lost in C. pomonella relative to possible distant ancestor in Lepidoptera lineage based on an analysis of gene gains and losses. The phylogenetic tree and chromosome location showed that the expansion of OBP genes mainly resulted from tandem duplications, as the CpomGOBP2 gene was duplicated twice along with loss of CpomPBPB. Two positive selection sites of the CpomGOBP1 gene were identified while other OBP genes evolved under purifying selection. Our results provide fundamental knowledge of OBP genes allowing further study of their function in C. pomonella.

From gains to losses: Age-related differences in decisions under risk in a non-monetary gambling task.

Lifespan theory suggests a shift from a primary orientation towards attaining gains in young adulthood to preventing losses in older adulthood. The current research tested if this motivational shift is reflected in behavioural and emotional responses to risks in non-monetary gains and losses. Study 1 established in a sample of N = 168 younger (18-30 years) and older adults (65-79 years) that a non-monetary gambling task was experienced similarly by the age groups with respect to arousal and valence of the task, and the willingness to continue playing. In Study 2 (N = 83), differences between young (18-30 years) and older (64-85 years) adults' risk-taking in this non-monetary gambling task with mixed gambles were tested while assessing physiological responses (event-related heart rate change) to gain and loss feedback. Behavioural - but not physiological - results confirm hypotheses derived from a lifespan motivational framework regarding age-differential effects of gains and losses.

How Do Gain and Loss Incentives Affect Memory for Intentions Across Adulthood?

OBJECTIVES: Changes in motivational orientation across adulthood affect cognitive processes. The purpose of this research was to investigate if and how motivational incentives (gains or losses) affect prospective memory for intended actions in younger, middle-aged, and older adults. METHODS: The consequences of memory hits and misses and the framing of the memory tasks were experimentally manipulated between participants: In a gain-framing condition, participants accumulated rewards, dependent on the proportion of target events to which they responded accurately. In a loss-framing condition, participants received an initial endowment from which losses were deducted, dependent on the proportion of targets they missed. We measured memory accuracy, perceived task importance, and ongoing-task performance. RESULTS: Gains and losses had different effects on memory across age groups: Age × Motivational Valence interactions emerged across two studies. Older adults showed relatively better memory performance to avoid losses than to achieve gains. Moreover, higher age was associated with lower memory performance (Study 1) and slower but more accurate decisions in an ongoing activity (Study 2). DISCUSSION: The findings reveal that motivational incentives and the framing of consequences as gains or losses moderate the relation between age and memory performance. Older adults' memory performance may benefit when messages encourage the avoidance of losses. This may also help to design age-tailored interventions in applied settings (e.g., health-related behavior).

Cultural Similarities and Differences in Social Discounting: The Mediating Role of Harmony-Seeking.

One's generosity to others declines as a function of social distance, which is known as social discounting. We examined cultural similarities and differences in social discounting and the mediating roles of the two aspects of interdependence (self-expression and distinctiveness of the self) as well as the two aspects of independence (harmony-seeking and rejection avoidance). Using the same procedure that previous researchers used to test North Americans, Study 1 showed that compared to North Americans, Japanese discount more steeply a partner's outcomes compared to their own future outcomes, whereas the decrease in the subjective value of the partner's outcomes accelerates less as a function of social distance. To examine the cultural similarities and differences in social discounting in more detail, Study 2 tested Japanese and Germans and found that the hyperbolic with exponent model fitted the participants' discounting behaviors better than the other models, except for the loss condition in Germans where the utility of the q-exponential model was indicated. Moreover, although the social discounting rate was higher in Japanese than in Germans, the cultural difference was limited to the gain frame. However, the decline in a person's generosity accelerated less as a function of social distance in Japanese than in Germans. Furthermore, the cultural difference in the social discounting in gains was mediated by the level of harmony-seeking, which was higher in Germans than in Japanese. Implications for individuals' generosity against the backdrop of cultural characteristics are discussed.

WT1, MSH6, GATA5 and PAX5 as epigenetic oral squamous cell carcinoma biomarkers - a short report.

PURPOSE: Oral squamous cell carcinoma (OSCC) is a frequently occurring aggressive malignancy with a heterogeneous clinical behavior. Based on the paucity of specific early diagnostic and prognostic biomarkers, which hampers the appropriate treatment and, ultimately the development of novel targeted therapies, we aimed at identifying such biomarkers through a genetic and epigenetic analysis of these tumors. METHODS: 93 primary OSCCs were subjected to DNA copy number alteration (CNA) and methylation status analyses using methylation-specific multiplex ligation-dependent probe amplification (MS-MPLA). The genetic and epigenetic OSCC profiles obtained were associated with the patients' clinic-pathological features. RESULTS: We found that WT1 gene promoter methylation is a predictor of a better prognosis and that MSH6 and GATA5 gene promoter methylation serve as predictors of a worse prognosis. GATA5 gene promoter methylation was found to be significantly associated with a shorter survival rate. In addition, we found that PAX5 gene promoter methylation was significantly associated with tongue tumors. To the best of our knowledge, this is the first study that highlights this specific set of genes as epigenetic diagnostic and prognostic biomarkers in OSCC. CONCLUSIONS: Our data highlight the importance of epigenetically assessing OSCCs to identify key genes that may serve as diagnostic and prognostic biomarkers and, potentially, as candidate therapeutic targets.