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Abstract 17β-estradiol, the most biologically active estrogen, exerts wide-ranging effects in brain through its action on estrogen receptors (ERs), influencing higher-order cognitive function and neurobiological aging. However, our knowledge of ER expression and regulation by neuroendocrine aging in the living human brain is limited. This in vivo brain 18F-fluoroestradiol (18F-FES) Positron Emission Tomography (PET) study of healthy midlife women reveals progressively higher ER density over the menopause transition in estrogen-regulated networks. Effects were independent of age, plasma estradiol and sex hormone binding globulin, and were highly consistent, correctly classifying all women as being postmenopausal or premenopausal. Higher ER density in target regions was associated with poorer memory performance for both postmenopausal and perimenopausal groups, and predicted presence of self-reported mood and cognitive symptoms after menopause. These findings provide novel insights on brain ER density modulation by female neuroendocrine aging, with clinical implications for women’s health.

This research is realised in the framework of a project recently funded as part of the PNRR (National Recovery and Resilience Plan) in the Accessibility sector. The working team has been established in the framework of the scientific agreement between the Museum of Villa della Regina in Turin, the Department of Architecture and Design at Politecnico di Torino, and the Department of History, Drawing and Restoration of Architecture at Sapienza Università di Roma, and includes knowledge from art history, digital surveying, 3D modelling, and digital solutions for cultural heritage. The research involves the reconstructive 3D modelling of Piffetti’s Library, once placed in the cabinet toward midnight and west inside the Villa della Regina and today in the Palazzo del Quirinale, and its interactive visualisation through augmented reality (AR) and virtual reality (VR) aimed at accessibility.

Background Cyber dating abuse (CDA) refers to physical, verbal, and psychological violence perpetrated towards a romantic part-ner via technology and social media. Another emerging form of online abuse is ghosting, a silent strategy to dissolve undesired relationships without openly having to break them up. The aims of the current study were (i) to explore the relationship between CDA and ghosting behaviours in romantic relationships and (ii) to investigate the roles of gender and personality traits (conscientiousness, agreeableness, extraversion, emotional stability, openness) in pre-diction of CDA (perpetration and victimization) Material and methods A sample of 409 participants (64.8% females), aged between 18 and 53 years (Mage = 26.40, SD = 6.06), took part in the study. Results CDA and ghosting behaviours are interrelated, and women were more prone than men were to use ghosting strate-gies, such as stopping messages abruptly and punishing the partner through silence. Moreover, gender and personal-ity traits differently predicted direct aggression and control/monitoring perpetration and direct aggression victimiza-tion, but they were not significant predictors of control/monitoring victimization. Conclusions The findings are discussed in light of gender differences to improve our understanding of the psychological factors involved in cyber dating violence.

Healthcare systems contribute significantly to climate change, leading to an increase in global morbidity and mortality. The operating theatre, in particular, is the most polluting area in the hospital environment; fortunately, there are numerous aspects on which action can be taken to reduce surgery-related emissions. [ABSTRACT FROM AUTHOR]

The Nedd4 family contains several structurally related but functionally distinct HECT-type ubiquitin ligases. The members of the Nedd4 family are known to recognize substrates through their multiple WW domains, which recognize PY motifs (PPxY, LPxY) or phospho-threonine or phospho-serine residues. To better understand protein interactor recognition mechanisms across the Nedd4 family, we report the development and implementation of a python-based tool, PxYFinder, to identify PY motifs in the primary sequences of previously identified interactors of Nedd4 and related ligases. Using PxYFinder, we find that, on average, half of Nedd4 family interactions are likely PY-motif mediated. Further, we find that PPxY motifs are more prevalent than LPxY motifs and are more likely to occur in proline-rich regions and that PPxY regions are more disordered on average relative to LPxY-containing regions. Informed by consensus sequences for PY motifs across the Nedd4 interactome, we rationally designed a focused peptide library and employed a computational screen, revealing sequence- and biomolecular interaction-dependent determinants of WW-domain/PY-motif interactions. Cumulatively, our efforts provide a new bioinformatic tool and expand our understanding of sequence and structural factors that contribute to PY-motif mediated interactor recognition across the Nedd4 family.

[This corrects the article DOI: 10.1371/journal.pone.0185926.].

After advanced age, female sex is the major risk factor for Alzheimer's disease (AD). The biological mechanisms underlying the increased AD risk in women remain largely undetermined. Preclinical studies identified the perimenopause to menopause transition, a neuroendocrine transition state unique to the female, as a sex-specific risk factor for AD. In animals, estrogenic regulation of cerebral glucose metabolism (CMRglc) falters during perimenopause. This is evident in glucose hypometabolism and decline in mitochondrial efficiency which is sustained thereafter. This study bridges basic to clinical science to characterize brain bioenergetics in a cohort of forty-three, 40-60 year-old clinically and cognitively normal women at different endocrine transition stages including premenopause (controls, CNT, n = 15), perimenopause (PERI, n = 14) and postmenopause (MENO, n = 14). All participants received clinical, laboratory and neuropsychological examinations, 18F-fluoro-deoxyglucose (FDG)-Positron Emission Tomography (PET) FDG-PET scans to estimate CMRglc, and platelet mitochondrial cytochrome oxidase (COX) activity measures. Statistical parametric mapping and multiple regression models were used to examine clinical, CMRglc and COX data across groups. As expected, the MENO group was older than PERI and controls. Groups were otherwise comparable for clinical measures and distribution of APOE4 genotype. Both MENO and PERI groups exhibited reduced CMRglc in AD-vulnerable regions which was correlated with decline in mitochondrial COX activity compared to CNT (p's