XIST directly regulates X-linked and autosomal genes in naive human pluripotent cells.

X chromosome inactivation (XCI) serves as a paradigm for RNA-mediated regulation of gene expression, wherein the long non-coding RNA XIST spreads across the X chromosome in cis to mediate gene silencing chromosome-wide. In female naive human pluripotent stem cells (hPSCs), XIST is in a dispersed configuration, and XCI does not occur, raising questions about XIST's function. We found that XIST spreads across the X chromosome and induces dampening of X-linked gene expression in naive hPSCs. Surprisingly, XIST also targets specific autosomal regions, where it induces repressive chromatin changes and gene expression dampening. Thereby, XIST equalizes X-linked gene dosage between male and female cells while inducing differences in autosomes. The dispersed Xist configuration and autosomal localization also occur transiently during XCI initiation in mouse PSCs. Together, our study identifies XIST as the regulator of X chromosome dampening, uncovers an evolutionarily conserved trans-acting role of XIST/Xist, and reveals a correlation between XIST/Xist dispersal and autosomal targeting.

The Srs2 helicase dampens DNA damage checkpoint by recycling RPA from chromatin.

The DNA damage checkpoint induces many cellular changes to cope with genotoxic stress. However, persistent checkpoint signaling can be detrimental to growth partly due to blockage of cell cycle resumption. Checkpoint dampening is essential to counter such harmful effects, but its mechanisms remain to be understood. Here, we show that the DNA helicase Srs2 removes a key checkpoint sensor complex, RPA, from chromatin to down-regulate checkpoint signaling in budding yeast. The Srs2 and RPA antagonism is supported by their numerous suppressive genetic interactions. Importantly, moderate reduction of RPA binding to single-strand DNA (ssDNA) rescues hypercheckpoint signaling caused by the loss of Srs2 or its helicase activity. This rescue correlates with a reduction in the accumulated RPA and the associated checkpoint kinase on chromatin in srs2 mutants. Moreover, our data suggest that Srs2 regulation of RPA is separable from its roles in recombinational repair and critically contributes to genotoxin resistance. We conclude that dampening checkpoint by Srs2-mediated RPA recycling from chromatin aids cellular survival of genotoxic stress and has potential implications in other types of DNA transactions.

Relieving the Gambling Itch Through Alcohol Consumption: The Impact of COVID-19 Restrictions on Australian Casino Patrons.

This paper extends our understanding of how casino patrons are affected by COVID-19 restrictions and how they cope by substituting gambling with alcohol consumption. We conducted two studies using a nationwide survey sample collected in Australia during the pandemic lockdown. Study 1 compares the casino patrons with two reference groups (other gambling patrons and non-gambling individuals) and investigates the lockdown restrictions on respondents' relational strength, and their potential impact on mental health and future prospects. Study 2 applies the stress-response dampening model (SRD) and tests how respondents used alcohol consumption to cope with the lack of access to casinos during the lockdown. The results from Study 1 suggest that lockdown restrictions on respondents' relational strength have significant negative impacts on anxiety, life satisfaction and post-pandemic outlook. Study 2 finds that casino patrons substituted gambling with alcohol consumption during the lockdown, with increased alcohol consumption negatively related to life satisfaction. Paradoxically, Australian gambling venue owners may not be adversely affected as many also run liquor retail operations.

Behavioural approach-avoidance tendencies among individuals with elevated blood pressure.

Emotional dampening (blunted responses to affective stimuli or experiences) has been reported in individuals with clinical and subclinical levels of elevated blood pressure (BP). Our aim in the present study was to explore how the basic motivational systems of approach and avoidance to positively- and negatively-valenced stimuli are affected in elevated BP. High BP (n = 27) and Low BP (n = 29) participants completed an approach-avoidance task. In this task, participants pulled the joystick towards them when viewing a happy face (approach) and pushing it away when viewing an angry face (avoid) in the congruent condition, and reversed these action-to-emotion pairings in the incongruent condition. A mixed-design ANOVA revealed a significant main effect of condition, such that overall participants were faster across trials in the congruent than trials of the incongruent condition. There was also an emotion x BP interaction. Among the Low BP group, there were no RT differences to happy and angry expressions (across congruent and incongruent conditions) but those with High BP were quicker to respond to actions paired with angry than happy facial expressions (across conditions). Findings suggest that valence-specific motivational reactions are not dampened with an increase in BP, and are rather sensitized for the negative emotion of anger. Supplementary information: The online version contains supplementary material available at 10.1007/s12144-023-04337-2.

Mechanisms of energy dissipation and relationship with tissue composition in human meniscus.

OBJECTIVE: The human meniscus is essential in maintaining proper knee joint function. The meniscus absorbs shock, distributes loads, and stabilizes the knee joint to prevent the onset of osteoarthritis. The extent of its shock-absorbing role can be estimated by measuring the energy dissipated by the meniscus during cyclic mechanical loading. METHODS: Samples were prepared from the central and horn regions of medial and lateral human menisci from 8 donors (both knees for total of 16 samples). Cyclic compression tests at several compression strains and frequencies yielded the energy dissipated per tissue volume. A GEE regression model was used to investigate the effects of compression, meniscal side and region, and water content on energy dissipation in order to account for repeated measures within samples. RESULTS: Energy dissipation by the meniscus increased with compressive strain from ∼0.1 kJ/m3 (at 10% strain) to ∼10 kJ/m3 (at 20% strain) and decreased with loading frequency. Samples from the anterior region provided the largest energy dissipation when compared to central and posterior samples (P < 0.05). Water content for the 16 meniscal tissues was 77.9 (C.I. 72.0-83.8%) of the total tissue mass. A negative correlation was found between energy dissipation and water content (P < 0.05). CONCLUSION: The extent of energy dissipated by the meniscus is inversely related to loading frequency and meniscal water content.

Resting (Tonic) Blood Pressure Is Associated With Sensitivity to Imagined and Acute Experiences of Social Pain: Evidence From Three Studies.

Social pain is a common experience that has potent implications for health. However, individuals differ in their sensitivity to social pain. Recent evidence suggests that sensitivity to social pain varies according to a biological factor that modulates sensitivity to physical pain: resting (tonic) blood pressure. The current studies extended this evidence by testing whether blood pressure relates to sensitivity to imagined (Study 1: N = 762, 51% female adults) and acute (Study 2, preregistered: N = 204, 57% female adults) experiences of social pain and whether associations extend to general emotional responding (Studies 1-3; Study 3: N = 162, 59% female adults). In line with prior evidence, results showed that higher resting blood pressure was associated with lower sensitivity to social pain. Moreover, associations regarding blood pressure and sensitivity to social pain did not appear to be explained by individual differences in general emotional responding. Findings appear to be compatible with the interpretation that social and physical pain share similar cardiovascular correlates and may be modulated by convergent interoceptive pathways.

Transcutaneous and percutaneous bone conduction sound propagation in single-sided deaf patients and cadaveric heads.

OBJECTIVE: To investigate transcranial transmission (TT) and the dampening effect of the skin in patients and cadaver heads. DESIGN: In patients a pure tone bone conduction audiogram for ipsilateral and contralateral stimulation was performed. The TT was defined as the difference between ipsilateral and contralateral hearing thresholds. In cadaver heads ipsilateral and contralateral promontory motion was measured using a three-dimensional Laser Doppler Vibrometer system. STUDY SAMPLE: Seven single-sided deaf patients fitted with a Baha® Connect, fifteen single-sided deaf patients without a bone conduction hearing aid and five Thiel-embalmed cadaver heads were included. RESULTS: The TT decreased with increasing frequency in patients and cadaver heads. No significant difference was seen between patients and cadaver heads. Measurements on patients and cadaver heads showed increasing skin attenuation with increasing frequency. However, the dampening effect was 3-12 dB higher in patients than in cadavers at all frequencies. CONCLUSION: The TT was not significantly different for patients compared to cadaver heads. The value of promontory motion to estimate TT in patients need to be further evaluated. The skin attenuates a BC stimulus by 10-20 dB in patients and by a smaller amount in cadaver heads, probably due to changes in the properties of the Thiel-conserved skin.

Dampened X-chromosomes in human pluripotent stem cells: dampening or erasure of X-upregulation?

The recent report of X-chromosome dampening in human preimplantation embryos remains controversial. Subsequently, Sahakyan et al. found evidence of X-chromosome dampening in human naïve pluripotent stem cells (hPSCs) as well. Here, we discuss whether X-dampening reported in hPSCs truly reflects the dampening of X-chromosomes or it is a consequence of the erasure of X-chromosome upregulation.

Chlamydia trachomatis Oligopeptide Transporter Performs Dual Functions of Oligopeptide Transport and Peptidoglycan Recycling.

Peptidoglycan, the sugar-amino acid polymer that composes the bacterial cell wall, requires a significant expenditure of energy to synthesize and is highly immunogenic. To minimize the loss of an energetically expensive metabolite and avoid host detection, bacteria often recycle their peptidoglycan, transporting its components back into the cytoplasm, where they can be used for subsequent rounds of new synthesis. The peptidoglycan-recycling substrate binding protein (SBP) MppA, which is responsible for recycling peptidoglycan fragments in Escherichia coli, has not been annotated for most intracellular pathogens. One such pathogen, Chlamydia trachomatis, has a limited capacity to synthesize amino acids de novo and therefore must obtain oligopeptides from its host cell for growth. Bioinformatics analysis suggests that the putative C. trachomatis oligopeptide transporter OppABCDF (OppABCDF Ct ) encodes multiple SBPs (OppA1 Ct , OppA2 Ct , and OppA3 Ct ). Intracellular pathogens often encode multiple SBPs, while only one, OppA, is encoded in the E. coliopp operon. We hypothesized that the putative OppABCDF transporter of C. trachomatis functions in both oligopeptide transport and peptidoglycan recycling. We coexpressed the putative SBP genes (oppA1Ct , oppA2Ct , oppA3Ct ) along with oppBCDFCt in an E. coli mutant lacking the Opp transporter and determined that all three chlamydial OppA subunits supported oligopeptide transport. We also demonstrated the in vivo functionality of the chlamydial Opp transporter in C. trachomatis Importantly, we found that one chlamydial SBP, OppA3 Ct , possessed dual substrate recognition properties and is capable of transporting peptidoglycan fragments (tri-diaminopimelic acid) in E. coli and in C. trachomatis These findings suggest that Chlamydia evolved an oligopeptide transporter to facilitate the acquisition of oligopeptides for growth while simultaneously reducing the accumulation of immunostimulatory peptidoglycan fragments in the host cell cytosol. The latter property reflects bacterial pathoadaptation that dampens the host innate immune response to Chlamydia infection.

Suppressed Sensory Response to Predictable Object Stimuli throughout the Ventral Visual Stream.

Prediction plays a crucial role in perception, as prominently suggested by predictive coding theories. However, the exact form and mechanism of predictive modulations of sensory processing remain unclear, with some studies reporting a downregulation of the sensory response for predictable input whereas others observed an enhanced response. In a similar vein, downregulation of the sensory response for predictable input has been linked to either sharpening or dampening of the sensory representation, which are opposite in nature. In the present study, we set out to investigate the neural consequences of perceptual expectation of object stimuli throughout the visual hierarchy, using fMRI in human volunteers. Participants of both sexes were exposed to pairs of sequentially presented object images in a statistical learning paradigm, in which the first object predicted the identity of the second object. Image transitions were not task relevant; thus, all learning of statistical regularities was incidental. We found strong suppression of neural responses to expected compared with unexpected stimuli throughout the ventral visual stream, including primary visual cortex, lateral occipital complex, and anterior ventral visual areas. Expectation suppression in lateral occipital complex scaled positively with image preference and voxel selectivity, lending support to the dampening account of expectation suppression in object perception.SIGNIFICANCE STATEMENT It has been suggested that the brain fundamentally relies on predictions and constructs models of the world to make sense of sensory information. Previous research on the neural basis of prediction has documented suppressed neural responses to expected compared with unexpected stimuli. In the present study, we demonstrate robust expectation suppression throughout the entire ventral visual stream, and underlying this suppression a dampening of the sensory representation in object-selective visual cortex, but not in primary visual cortex. Together, our results provide novel evidence in support of theories conceptualizing perception as an active inference process, which selectively dampens cortical representations of predictable objects. This dampening may support our ability to automatically filter out irrelevant, predictable objects.

Struggling with Happiness: A Pathway Leading Depression to Gambling Disorder.

A number of studies have suggested that depressive mood might lead to the development and/or maintenance of a gambling disorder (GD). The pathways by which such relationships are fostered may involve deficits in emotional regulation capacity and dysfunctional coping styles. This study aims to explore the role played by depressive symptomatology and the regulation of positive emotion in GD. We administered the South Oaks Gambling Inventory (SOGS, Lesieur and Blume in Am J Psychiatry 144(9):1184-1188, 1987), the 21-item Depression Anxiety Stress Scale (DASS-21, Lovibond and Lovibond in Manual for the depression anxiety stress scales. Psychology Foundation, Sydney, 1995) and the Kill-joy Thinking subscale of the Ways of Savouring Checklist (WOSC, Bryant and Veroff in Savoring: a new model of positive experience. Lawrence Erlbaum, Mahwah, 2007) to a sample of pathological gamblers (n = 91) and a sample of community participants (n = 105). The pathological gamblers scored higher on the DASS-21 subscales and obtained higher scores on the Kill-joy Thinking subscale of the WOSC compared to the controls. Moreover, the SOGS scores positively correlate with the DASS-21 subscales, and with the Kill-Joy Thinking measure. Finally, it is evident that Kill-joy Thinking fully mediates the relationship between depressive symptomatology and GD severity. Our results further confirm the roles of depression, anxiety and stress in GD. Moreover, this is the first study to explore the mediating role of dampening processes in the relationship between depression and GD. Future lines of research are also discussed.

Psychometric properties and utility of the Responses to Positive Affect questionnaire (RPA) in a sample of people with bipolar disorder.

OBJECTIVES: To evaluate the psychometric properties of the Responses to Positive Affect (RPA) questionnaire in a sample of persons with bipolar disorder (BD). METHOD: Cross-sectional survey study with 107 persons with BD. The original 3-factor model of the RPA was compared with a 2-factor model. Construct validity was determined with measures of well-being, personal recovery, social role participation, and psychopathology and incremental validity was evaluated. RESULTS: The fit of the 3-factor model was acceptable for most fit indices. Subscores of the RPA revealed a significant relationship with aspects of well-being, personal recovery, and psychopathology. Dampening and self-focused positive rumination explained additional variance in personal recovery above and beyond well-being. CONCLUSIONS: The RPA is an internally consistent and valid tool to assess positive emotion regulation processes in persons with BD. Specifically, the processes of dampening and emotion-focused positive rumination seem to play an important role in BD.

Emotion regulation strategies in mania risk: A systematic review.

OBJECTIVES: Difficulties in emotion regulation may contribute to the development of mania. This review aimed to assess how emotion regulation strategies reported by individuals at risk of mania compare with clinical and nonclinical controls. METHODS: Search terms relating to mania risk and emotion regulation were entered into three databases. Sixteen studies were included. RESULTS: Mania risk was typically associated with overall endorsement of emotion regulation strategies, particularly dampening, and positive and negative rumination. CONCLUSIONS: Findings were limited by overall lack of evidence for individual strategies, lack of consideration of key mediating factors and reliance upon self-report designs.

Assessing emotional processing difficulties in normotensive individuals with high and isolated blood pressure elevations.

This study examined the effect of sense modality (auditory/visual) on emotional dampening (reduced responsiveness to emotions with elevation in blood pressure). Fifty-six normotensive participants were assessed on tasks requiring labelling and matching of emotions in faces and voices. Based on median split of systolic and diastolic blood pressures (SBP and DBP, respectively), participants were divided into low BP, high BP and isolated BP groups. On emotion-labelling tasks, analysis revealed reduced emotion recognition in the high BP than the low BP group. On emotion-matching tasks, reduced emotion recognition was noted in high and also isolated BP group as compared to low BP group for the task that required matching a visual target with one of the four auditory distractors. Our findings show for the first time that even isolated elevations in either SBP or DBP may result in emotional dampening. Furthermore, the study highlights that the emotional dampening effect generalises to explicit processing (labelling) of emotional information in both faces and voices-and that these effects tentatively occur during more pragmatic and covert (matching) emotion recognition processes too. These findings require replication in clinical hypertensives.

Ruminative and dampening responses to positive affect in bipolar disorder and major depressive disorder.

BACKGROUND: Although previous research has focused on distinguishing cognitive styles between Bipolar Disorder (BD) and Major Depressive Disorder (MDD), little is known about differences in positive affect regulation between these affective groups. The aim of the present study was to extend previous research by investigating such differences between BD and MDD, and between the bipolar subtypes (BD-I vs. BD-II and predominant polarities), using large, clinical, outpatient samples. METHODS: In total, 298 participants (96 BD-I, 27 BD-II, and 175 MDD) were included. All completed the Responses to Positive Affect (RPA) questionnaire. Mood symptoms in BD patients were clinically assessed by means of the Clinical Global Impression for Bipolar Disorders (CGI-BP), while depressive symptom severity in MDD patients were assessed by means of the Inventory of Depressive Symptomatology (IDS-SR). RESULTS: Results showed differences between affective groups and bipolar subtypes. The most salient finding was that both BD-I and BD-II patients were more likely to ruminate about positive affect than MDD patients, while MDD patients were more likely to engage in dampening responses to positive affect. CONCLUSIONS: Differentiation of responses to positive affect between BD and MDD may have relevant clinical implications in terms of symptomatology, course, and treatment.

When Do Good Things Lift You Up? Dampening, Enhancing, and Uplifts in Relation To Depressive and Anhedonic Symptoms in Early Adolescence.

Longitudinal studies examining the role of response styles to positive affect (i.e., dampening and enhancing) for depressive symptoms have yielded inconsistent results. We examined concurrent and prospective relations of dampening and enhancing with depressive and anhedonic symptoms, and whether these relations depend on the frequency of uplifts. Early adolescents (N = 674, 51.6% girls, Mage = 12.7 years, range 11.3-14.9) completed questionnaires three times (one-year intervals). Dampening interacted with daily uplifts predicting concurrent depressive symptoms. Dampening was unrelated to depressive and anhedonic symptoms one year later. High dampening and low enhancing predicted relative increases in anhedonia over two years. Relationships did not differ for girls and boys. Therapeutic interventions designed to promote adaptive responding to positive affect may, thus, reduce anhedonia in adolescence.

A two-year longitudinal study of gender differences in responses to positive affect and depressive symptoms during middle adolescence.

This study aimed to analyze the prospective associations during adolescence between depressive symptoms and response styles to positive affect and to examine gender differences. A longitudinal study was conducted with three waves separated by 1 year each to assess a non-clinical sample of 622 Spanish adolescents who were 13 and 14 years old (50.2% boys, 49.8% girls). The participants completed self-report measures of depressive symptoms and responses to positive affect (emotion-focused positive rumination, self-focused positive rumination and dampening of positive emotion). The results showed that the increase in depressive symptoms was associated with an increase in dampening and decreases in emotion-focused and self-focused positive rumination. Furthermore, girls presented more depressive symptoms, as well as higher dampening and lower self-focused positive rumination, than boys. The conclusions highlight the need to consider responses to positive affect in explaining gender differences in depressive symptoms during mid-adolescence, as well as in designing prevention programs.

Attentional bias in euthymic bipolar I disorder.

Little is known about the nature of the relation between information-processing biases and affective traits in bipolar disorder. The present study was designed to investigate whether attentional biases are evident in persons diagnosed with bipolar disorder when they are in a positive mood state, and whether biases are related to indices of emotion regulation and to prior history of mood episodes. Ninety adults diagnosed with bipolar I disorder and 81 controls with no lifetime mood disorder underwent a positive mood induction and then completed an emotion face dot-probe task; participants in the bipolar disorder group also completed a self-report measure of responses to positive affect. Attentional bias was not related to a diagnosis of bipolar disorder or to symptom severity. Consistent with hypotheses, analyses within the bipolar group indicated that greater dampening of positive affect related to significantly less attention paid to the positively valenced faces. Discussion focuses on the potential role of affective traits in shaping attentional bias in bipolar disorder.

Conditioned frequency-dependent hearing sensitivity reduction in the bottlenose dolphin (Tursiops truncatus).

The frequency specificity of conditioned dampening of hearing, when a loud sound is preceded by a warning sound, was investigated in a bottlenose dolphin. The loud sounds were 5 s tones of 16, 22.5 or 32 kHz, sound pressure level of 165 dB root mean square (RMS) re. 1 µPa. Hearing sensitivity was tested at the same three frequencies. Hearing sensitivity was measured using pip-train test stimuli and auditory evoked potential recording. The test sound stimuli served also as warning sounds. The durations of the warning sounds were varied randomly to avoid locking a conditioning effect to the timing immediately before the loud sound. Hearing thresholds before the loud sound increased, relative to the baseline, at test frequencies equal to or higher than the loud sound frequency. The highest threshold increase appeared at test frequencies of 0.5 octaves above the loud sound frequencies.

Mothers' attachment styles and their children's self-reported security, as related to maternal socialization of children's positive affect regulation.

This study investigated how mothers' attachment was related to their responses to their own and their children's positive events and positive affect (PA). Ninety-seven mothers reported on their attachment and their responses to their own and their 7-12-year-old children's positive events and emotions. Children reported on their mothers' responses to the children's positive events and their attachment security with their mothers. The results indicated that more avoidant mothers reported less intense PA in response to their own and their children's positive events. More avoidant mothers also were less likely to encourage their children to savor positive events (through expressing PA, reflecting on PA or themselves, giving rewards, and affectionate responses). Mothers higher on anxiety reported greater likelihood of dampening (e.g., minimizing the event's importance) their own positive events and reported being more likely to feel discomfort and to reprimand their children for expressing PA. Children's security was predicted by mothers' lower likelihood of encouraging children's dampening and of reprimanding children for PA displays. This study advances the literature on how mothers' attachment is related to the ways in which they regulate their own and their children's PA, which may have implications for children's attachment and developing PA regulation.