Biology subjects

Hahn, A.

Publications and source records attributed to Hahn, A..

47 records · Page 3Linked to original sources

bioRxiv2020

DNA methyltransferase 1 (DNMT1) function is implicated in the age-related loss of cortical interneurons

Increased life expectancy in modern society comes at the cost of age-associated disabilities and diseases. Aged brains not only show reduced excitability and plasticity, but also a decline in inhibition. Age-associated defects in inhibitory circuits likely contribute to cognitive decline and age-related disorders. Molecular mechanisms that exert epigenetic control of gene expression, contribute to age-associated neuronal impairments. Both DNA methylation, mediated by DNA methyltransferases (DNMTs), and histone modifications maintain neuronal function throughout lifespan. Here we provide evidence that DNMT1 function is implicated in the age-related loss of cortical inhibitory interneurons. Deletion of Dnmt1 in parvalbumin-positive interneurons attenuates their age-related decline in the cerebral cortex. Moreover, DNMT1-deficient mice show improved somatomotor performance and reduced aging-associated transcriptional changes. A decline in the proteostasis network, responsible for the proper degradation and removal of defective proteins, is suggested to be essentially implicated in age- and disease-related neurodegeneration. Our data suggest that DNMT1 acts indirectly on interneuron survival in aged mice by modulating the proteostasis network during life-time.

neuroscience↗

bioRxiv2019

Sex differences in monetary reward and punishment processing are associated with fast dynamics of dopamine synthesis

PurposeIn the human brain endogenous dopamine release is commonly assessed by the PET competition model. Although thoroughly validated, cognitive processing yields low signal changes and the assessment of several task conditions requires repeated scanning. Using the framework of functional PET imaging we introduce a novel approach which leverages the incorporation of the radioligand 6-[18F]FDOPA into the dynamic fast-acting regulation of the corresponding enzyme activities by neuronal firing and neurotransmitter release. We demonstrate the feasibility of the approach by the assessment of widely described sex differences in dopamine neurotransmission. MethodsReward and punishment processing was behaviorally investigated in 36 healthy participants, where 16 underwent fPET and fMRI while performing the monetary incentive delay task. 6-[18F]FDOPA was applied as bolus+infusion during a single 50 min PET acquisition. Task-specific changes in dopamine synthesis were identified with the general linear model and quantified with the Gjedde-Patlak plot. ResultsMonetary gain induced 78% increase in nucleus accumbens dopamine synthesis vs. 49% for loss in men. Interestingly, the opposite was discovered in women (gain: 51%, loss: 78%). Behavioral modeling revealed direct associations of task-specific dopamine synthesis with reward sensitivity in men (rho = -0.7) and with punishment sensitivity in women (rho = 0.89). As expected, fMRI showed robust task-specific neuronal activation but no sex difference. ConclusionsOur findings provide a dopaminergic basis for well-known behavioral differences in reward and punishment processing between women and men. This has important implications in psychiatric conditions showing sex-specific prevalence rates, altered reward processing and dopamine signaling. The high temporal resolution and pronounced magnitude of task-specific changes make fPET a promising tool to investigate functional neurotransmitter dynamics during cognitive or emotional processing in various brain disorders.

neuroscience↗

bioRxiv2019

Context-specific effects of facial dominance and trustworthiness on hypothetical leadership decisions

Social judgments of faces predict important social outcomes, including leadership decisions. Previous work suggests that facial cues associated with perceptions of dominance and trustworthiness have context-specific effects on leadership decisions. Facial cues linked to perceived dominance have been found to be preferred in leaders for hypothetical wartime contexts and facial cues linked to perceived trustworthiness have been found to be preferred in leaders for hypothetical peacetime contexts. Here we sought to replicate these effects using images of womens faces. Consistent with previous work, a linear mixed effects model demonstrated that more trustworthy-looking faces were preferred in leaders during times of peace and more dominant-looking faces were preferred in leaders during times of war. These results provide converging evidence for context-specific effects of facial cues on hypothetical leadership judgments.

animal behavior and cognition↗

bioRxiv2018

Facial masculinity is only weakly correlated with handgrip strength in young adult women

ObjectivesAncestrally, strength is likely to have played a critical role in determining the ability to obtain and retain resources and the allocation of social status among humans. Responses to facial cues of strength are therefore thought to play an important role in human social interaction. Although many researchers have proposed that sexually dimorphic facial morphology is reliably correlated with physical strength, evidence for this hypothesis is somewhat mixed. Moreover, to date, only one study has investigated the putative relationship between facial masculinity and physical strength in women. Consequently, we tested for correlations between handgrip strength and objective measures of face-shape masculinity.\n\nMethods531 women took part in the study. We measured each participants handgrip strength (dominant hand). Sexual dimorphism of face shape was objectively measured from each face photograph using two methods: discriminant analysis and vector analysis. These methods use shape components derived from principal component analyses of facial landmarks to measure the probability of the face being classified as male (discriminant analysis method) or to locate the face on a female-male continuum (vector analysis method).\n\nResultsOur analyses revealed that handgrip strength is, at best, only weakly correlated with facial masculinity in women. There was a weak significant association between handgrip strength and one measure of womens facial masculinity. The relationship between handgrip strength and our other measure of womens facial masculinity was not significant.\n\nDiscussionTogether, these results do not support the hypothesis that face-shape masculinity is an important cue of physical strength, at least in women.

animal behavior and cognition↗

bioRxiv2018

Does the strength of women’s attraction to male vocal masculinity track changes in steroid hormones?

Recent studies that either used luteinizing hormone tests to confirm the timing of ovulation or measured steroid hormones from saliva have found little evidence that womens preferences for facial or body masculinity track within-subject changes in womens fertility or hormonal status. Fewer studies using these methods have examined womens preferences for vocal masculinity, however, and those that did report mixed results. Consequently, we used a longitudinal design and measured steroid hormones from saliva to test for evidence of hormonal regulation of womens (N=351) preferences for two aspects of male vocal masculinity (low pitch and low formants). Analyses suggested that preferences for masculine pitch, but not masculine formants, may track within-woman changes in estradiol. Although these results present some evidence for the hypothesis that within-subject hormones regulate womens attraction to masculine men, we do not discount the possibility that the effect of estradiol on pitch preferences in the current study is a false positive.

animal behavior and cognition↗

bioRxiv2018

Does the interaction between partnership status and average progesterone level reliably predict women’s preferences for facial masculinity? Comment on Marcinkowska et al. (2018)

Many studies have attempted to identify biological factors that reliably predict individual differences in womens preferences for masculine male faces. Marcinkowska et al. (2018, Hormones & Behavior) recently reported that womens (N=102) preferences for facial masculinity were predicted by the interaction between their relationship status (partnered versus unpartnered) and average progesterone level. Because previous findings for between-women differences in masculinity preferences have often not replicated well, we attempted to replicate Marcinkowska et als result in an open data set from another recent study that had not tested this hypothesis (Jones et al., 2018 Psychological Science). In this sample of 316 women, we found that facial masculinity preferences were predicted by the interaction between womens relationship status and average progesterone level, consistent with Marcinkowska et als results. Together, these findings suggest that the combined effects of relationship status and average progesterone level may predict facial masculinity preferences relatively reliably.

animal behavior and cognition↗

bioRxiv2017

No evidence for correlations between handgrip strength and sexually dimorphic acoustic properties of voices

ObjectivesRecent research on the signal value of masculine physical characteristics in men has focused on the possibility that such characteristics are valid cues of physical strength. However, evidence that sexually dimorphic vocal characteristics are correlated with physical strength is equivocal. Consequently, we undertook a further test for possible relationships between physical strength and masculine vocal characteristics.\n\nMethodsWe tested the putative relationships between White UK (N=115) and Chinese (N=106) participants handgrip strength (a widely used proxy for general upper-body strength) and five sexually dimorphic acoustic properties of voices: fundamental frequency (F0), fundamental frequencys standard deviation (F0-SD), formant dispersion (Df), formant position (Pf), and estimated vocal-tract length (VTL).\n\nResultsAnalyses revealed no clear evidence that stronger individuals had more masculine voices.\n\nConclusionsOur results do not support the hypothesis that masculine vocal characteristics are a valid cue of physical strength.

evolutionary biology↗

bioRxiv2017

A longitudinal analysis of men’s intrasexual competitiveness, state anxiety, salivary testosterone, and salivary cortisol

Many previous studies have investigated relationships between mens competitiveness and testosterone. For example, the extent of changes in mens testosterone levels following a competitive task predicts the likelihood of them choosing to compete again. Recent work investigating whether individual differences in mens testosterone levels predict individual differences in their competitiveness have produced mixed results. Consequently, we investigated whether mens (N=59) scores on the Intrasexual Competitiveness Scale were related to either within-subject changes or between-subject differences in mens testosterone levels. Mens responses on the Intrasexual Competitiveness Scale did not appear to track within-subject changes in testosterone. By contrast with one recent study, mens Intrasexual Competitiveness Scale also did not appear to be related to between-individual differences in testosterone. Thus, our results present no evidence for associations between mens testosterone and their responses on the Intrasexual Competitiveness Scale.

animal behavior and cognition↗

bioRxiv2017

Pan-cancer analysis reveals complex tumor-specific alternative polyadenylation

Alternative polyadenylation (APA) of 3 untranslated regions (3 UTRs) has been implicated in cancer development. Earlier reports on APA in cancer primarily focused on 3 UTR length modifications, and the conventional wisdom is that tumor cells preferentially express transcripts with shorter 3 UTRs. Here, we analyzed the APA patterns of 114 genes, a select list of oncogenes and tumor suppressors, in 9,939 tumor and 729 normal tissue samples across 33 cancer types using RNA-Seq data from The Cancer Genome Atlas, and we found that the APA regulation machinery is much more complicated than what was previously thought. We report 77 cases (gene-cancer type pairs) of differential 3 UTR cleavage patterns between normal and tumor tissues, involving 33 genes in 13 cancer types. For 15 genes, the tumor-specific cleavage patterns are recurrent across multiple cancer types. While the cleavage patterns in certain genes indicate apparent trends of 3 UTR shortening in tumor samples, over half of the 77 cases imply 3 UTR length change trends in cancer that are more complex than simple shortening or lengthening. This work extends the current understanding of APA regulation in cancer, and demonstrates how large volumes of RNA-seq data generated for characterizing cancer cohorts can be mined to investigate this process.

genomics↗

bioRxiv2017

Hormonal correlates of pathogen disgust: Testing the Compensatory Prophylaxis Hypothesis

Raised progesterone during the menstrual cycle is associated with suppressed physiological immune responses, reducing the probability that the immune system will compromise the blastocysts development. The Compensatory Prophylaxis Hypothesis proposes that this progesterone-linked immunosuppression triggers increased disgust responses to pathogen cues, compensating for the reduction in physiological immune responses by minimizing contact with pathogens. Although a popular and influential hypothesis, there is no direct, within-woman evidence for correlated changes in progesterone and pathogen disgust. To address this issue, we used a longitudinal design to test for correlated changes in salivary progesterone and pathogen disgust (measured using the pathogen disgust subscale of the Three Domain Disgust Scale) in a large sample of women (N=375). Our analyses showed no evidence that pathogen disgust tracked changes in progesterone, estradiol, testosterone, or cortisol. Thus, our results provide no support for the Compensatory Prophylaxis Hypothesis of variation in pathogen disgust.

animal behavior and cognition↗

bioRxiv2017

General sexual desire, but not desire for uncommitted sexual relationships, tracks changes in women’s hormonal status

Several recent longitudinal studies have investigated the hormonal correlates of both young adult womens general sexual desire and, more specifically, their desire for uncommitted sexual relationships. Findings across these studies have been mixed, potentially because each study tested only small samples of women (Ns = 43, 33, and 14). Here we report results from a much larger (N = 375) longitudinal study of hormonal correlates of young adult womens general sexual desire and their desire for uncommitted sexual relationships. Our analyses suggest that within-woman changes in general sexual desire are negatively related to progesterone, but are not related to testosterone or cortisol. We observed some positive relationships for estradiol, but these were generally only significant for solitary sexual desire. By contrast with our results for general sexual desire, analyses showed no evidence that changes in womens desire for uncommitted sexual relationships are related to their hormonal status. Together, these results suggest that changes in hormonal status contribute to changes in womens general sexual desire, but do not influence womens desire for uncommitted sexual relationships.

animal behavior and cognition↗