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Monoecious species provide an excellent system to study the specific determinants that underlie male and female flower development. Quercus suber is a monoecious species with unisexual flowers at inception. Despite the overall importance of this and other tree species with a similar reproductive habit, little is known regarding the mechanisms involved in the development of their male and female flowers. Here, we have characterised members of the ABCDE MADS-box gene family of Q. suber . The temporal expression of these genes was found to be sex-biased. The B-class genes, in particular, are predominantly, or exclusively (in the case of QsPISTILLATA ), expressed in the male flowers. Functional analysis in Arabidopsis suggests that the B-class genes have their function conserved. The identification of sex-biased gene expression plus the identification of unusual protein-protein interactions suggest that the floral organ identity of Q. suber may be under control of specific changes in the dynamics of the ABCDE model. This study constitutes a major step towards the characterisation of the mechanisms involved in reproductive organ identity in a monoecious tree with a potential contribution towards the knowledge of conserved developmental mechanisms in other species with a similar sex habit.

Facial width to height ratio (fWHR) is a morphological cue that correlates with sexual dimorphism and social traits. Currently, it is unclear how vertical and horizontal components of fWHR, distinctly capture faces' social information. Using a new methodology, we orthogonally manipulated the upper facial height and the bizygomatic width to test their selective effect in the formation of impressions. Subjects (n = 90) saw pair of faces and had to select the face expressing better different social traits (trustworthiness, aggressiveness and femininity). We further investigated how sex and fWHR components interact in the formation of these judgements. Across experiments, changes along the vertical component better predicted participants' ratings rather than the horizontal component. Faces with smaller height were perceived as less trustworthy, less feminine and more aggressive. By dissociating fWHR and testing the contribution of its components independently, we obtained a powerful and discriminative measure of how facial morphology guides social judgements.

The first genome of Vitis vinifera vinifera (PN40024), published in 2007, boosted grapevine related studies. While this reference genome is a suitable tool for the overall studies in the field, it lacks the ability to unveil changes accumulated during V. v. vinifera domestication. The subspecies V. v. sylvestris preserves wild characteristics, making it a good material to provide insights into V. v. vinifera domestication. The difference in the reproductive strategy between both subspecies is one of the characteristics that set them apart. While V. v. vinifera flowers are hermaphrodite, V. v. sylvestris is mostly dioecious. In this paper, we compare the re-sequencing of the genomes from a male and a female individual of the wild sylvestris , against the reference vinifera genome (PN40024). Variant analysis reveals a low number but with high impact modifications in coding regions, essentially non-synonymous single nucleotide polymorphisms and frame shifts caused by insertions and deletions. The sex-locus was manually inspected, and the results obtained are in line with the most recent works related with wild grapevine sex. In this paper we also describe for the first time RNA editing in transcripts of 14 genes in the sex-determining region, including VviYABBY and VviPLATZ .

Emotional memories require coordinated activity of the amygdala and hippocampus. Human intracranial recordings have shown that formation of aversive memories involves an amygdala theta-hippocampal gamma phase code. Yet, the mechanisms engaged during translation of aversive experiences into memories and subsequent retrieval remain unclear. Directly recording from human amygdala and hippocampus, here we show that hippocampal gamma activity increases for correctly remembered aversive scenes. Crucially, patterns of amygdala high amplitude gamma activity at encoding are reactivated in the hippocampus, but not amygdala, during both aversive encoding and retrieval. Trial-specific hippocampal gamma patterns showing highest representational similarity with amygdala activity at encoding are reactivated in the hippocampus during aversive retrieval. This reactivation process occurs against a background of gamma activity that is otherwise decorrelated between encoding and retrieval. Thus, phasic hippocampal gamma responses track the retrieval of aversive memories, with activity patterns apparently entrained by the amygdala during encoding. Human intracranial recordings reveal that during aversive memory retrieval, memory-specific gamma activity patterns, shaped by the amygdala during encoding, are reactivated in hippocampus.

Background: Early-onset dementia (EOD) is defined as dementia with symptom onset before 65 years. The role of environmental risk factors in the etiology of EOD is still undefined. We aimed at assessing the role of environmental risk factors in EOD etiology, taking into account its different clinical types. Methods: Using a case-control study, we recruited all EOD cases referred to Modena hospitals from 2016 to 2019, while the referent population was drawn from cases’ caregivers. We investigated residential history, occupational and environmental exposures to chemicals and lifestyle behaviors through a self-administered questionnaire. We computed the odds ratios of EOD risk (overall and restricting to the Alzheimer’s dementia (AD) or frontotemporal dementia (FTD) diagnoses) and the corresponding 95% confidence intervals using an unconditional logistic regression model. Results: Fifty-eight EOD patients (19 FTD and 32 AD) and 54 controls agreed to participate. Most of the investigated exposures, such as occupational exposure to aluminum, pesticides, dyes, paints or thinners, were associated with an increased odds ratio (OR) for FTD but not for AD. Long-term use of selenium-containing dietary supplements was associated with increased OR for EOD and, particularly, for FTD. For both EOD forms, smoking and playing football showed an increased odds ratio, while cycling was associated with increased risk only in FTD. Overall sports practice appeared to be a protective factor for both types. Conclusions: Our results suggest a role of environmental and behavioral risk factors such as some chemical exposures and professional sports in EOD etiology, in particular with reference to FTD. Overall sports practice may be associated with a reduced EOD risk.

The study aimed to evaluate Zolpidem and Benzodiazepines prescription and dispensing data in private pharmacies in Brazil from 2014 to 2021. Methods: This retrospective cohort study was carried out with retrospective open data from the Brazilian Federal Government from January 2014 to August 2021 containing medicines registered in the National Controlled Products Management System (SNGPC). Between January 2014 and August 2021, a total of 32,441,392 sales of thirteen drugs from the z-drug and benzodiazepine classes used to treat sleep disorders were recorded in Brazil. Throughout the entire period, clonazepam emerged as the most popular drug, accounting for 29.8% of total sales. Alprazolam followed in second place with 20.6% of sales, while zolpidem came in third with 14.4%. The normal-release form of zolpidem was consistently the highest-selling variant during the evaluation period. However, the fast-acting-release form exhibited the most significant growth, indicated by a noticeable upward trend in sales since 2020. In contrast, the extended-release form of zolpidem remained stable over the years. The increased sales of zolpidem in Brazilian private pharmacies raise concerns about potential misuse and dependence on this drug mainly for the treatment of insomnia. The epidemic of sleeping pills arises in a scenario of expectancy of short-term amelioration of symptoms, with no correspondence in best clinical practice. Education and counseling for both healthcare professionals and the general population are essential to address this growing health concern and ensure the safe and appropriate use of medications for sleep disorders.

Memory for aversive events is central to survival but can become maladaptive in psychiatric disorders. Memory enhancement for emotional events is thought to depend on amygdala modulation of hippocampal activity. However, the neural dynamics of amygdala-hippocampal communication during emotional memory encoding remain unknown. Using simultaneous intracranial recordings from both structures in human patients, here we show that successful emotional memory encoding depends on the amygdala theta phase to which hippocampal gamma activity and neuronal firing couple. The phase difference between subsequently remembered vs. not-remembered emotional stimuli translates to a time period that enables lagged coherence between amygdala and downstream hippocampal gamma. These results reveal a mechanism whereby amygdala theta phase coordinates transient amygdala -hippocampal gamma coherence to facilitate aversive memory encoding. Pacing of lagged gamma coherence via amygdala theta phase may represent a general mechanism through which the amygdala relays emotional content to distant brain regions to modulate other aspects of cognition, such as attention and decision-making. The amygdala facilitates memory encoding in the hippocampus. Here the authors show, using simultaneous intracranial recordings from these regions, that emotional memory encoding is mediated by the amygdala theta phase to which hippocampal gamma activity and neuronal firing is coupled.

The establishment of new interactions between transcriptional regulators increases the regulatory diversity that drives phenotypic novelty. To understand how such interactions evolve, we have studied a regulatory module (DDR) composed by three MYB-like proteins: DIVARICATA (DIV), RADIALIS (RAD), and DIV-and-RAD-Interacting Factor (DRIF). The DIV and DRIF proteins form a transcriptional complex that is disrupted in the presence of RAD, a small interfering peptide, due to the formation of RAD–DRIF dimers. This dynamic interaction result in a molecular switch mechanism responsible for the control of distinct developmental processes in plants. Here, we have determined how the DDR regulatory module was established by analyzing the origin and evolution of the DIV, DRIF, and RAD protein families and the evolutionary history of their interactions. We show that duplications of a pre-existing MYB domain originated the DIV and DRIF protein families in the ancestral lineage of green algae, and, later, the RAD family in seed plants. Intraspecies interactions between the MYB domains of DIV and DRIF proteins are detected in green algae, whereas the earliest evidence of an interaction between DRIF and RAD proteins occurs in the gymnosperms, coincident with the establishment of the RAD family. Therefore, the DDR module evolved in a stepwise progression with the DIV–DRIF transcription complex evolving prior to the antagonistic RAD–DRIF interaction that established the molecular switch mechanism. Our results suggest that the successive rearrangement and divergence of a single protein domain can be an effective evolutionary mechanism driving new protein interactions and the establishment of novel regulatory modules.

Risk of early-onset dementia (EOD) might be modified by environmental factors and lifestyles, including diet. The aim of this study is to evaluate the association between dietary habits and EOD risk. We recruited 54 newly-diagnosed EOD patients in Modena (Northern Italy) and 54 caregivers as controls. We investigated dietary habits through a food frequency questionnaire, assessing both food intake and adherence to dietary patterns, namely the Greek-Mediterranean, the Dietary Approaches to Stop Hypertension (DASH), and the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets. We modeled the relation between dietary factors and risk using the restricted cubic spline regression analysis. Cereal intake showed a U-shaped relation with EOD, with risk increasing above 350 g/day. A high intake (>400 g/day) of dairy products was also associated with excess risk. Although overall fish and seafood consumption showed no association with EOD risk, we found a U-shaped relation with preserved/tinned fish, and an inverse relation with other fish. Similarly, vegetables (especially leafy) showed a strong inverse association above 100 g/day, as did citrus and dry fruits. Overall, sweet consumption was not associated with EOD risk, while dry cake and ice-cream showed a positive relation and chocolate products an inverse one. For beverages, we found no relation with EOD risk apart from a U-shaped relation for coffee consumption. Concerning dietary patterns, EOD risk linearly decreased with the increasing adherence to the MIND pattern. On the other hand, an inverse association for the Greek-Mediterranean and DASH diets emerged only at very high adherence levels. To the best of our knowledge, this is the first study that explores the association between dietary factors and EOD risk, and suggests that adherence to the MIND dietary pattern may decrease such risk.

•First study to quantify QALY loss due to varicella in hospitalised children.•First study to describe QALY loss in the carers of children with varicella.•High QALY loss in the family units of children admitted to hospital with varicella.•Significant impact on HRQoL of varicella infection in family units. Although usually benign, varicella can lead to serious complications and sometimes long-term sequelae. Vaccines are safe and effective but not yet included in immunisation programmes in many countries. We aimed to quantify the impact on health-related quality of life (HRQoL) in terms of quality-adjusted life years (QALY) in children with varicella and their families, key to assessing cost-utility in countries with low mortality due to this infection. Children with varicella in the community and admitted to hospitals in Portugal were included over 18 months from January 2019. Children's and carers’ HRQoL losses were assessed prospectively using standard multi-attribute utility instruments for measuring HRQoL (EQ-5D and CHU9D), from presentation to recovery, allowing the calculation of QALYs. Among 109 families with children with varicella recruited from attendees at a pediatric emergency service (community arm), the mean HRQoL loss/child was 2.0 days (95 % CI 1.9–2.2, n = 101) (mean 5.4 QALYs/1000 children (95 % CI 5.3–6.1) and 1.3 days/primary carer (95 % CI 1.2–1.6, n = 103) (mean 3.6 QALYs /1000 carers (95 % CI 3.4–4.4). Among 114 families with children admitted to hospital because of severe varicella or a complication (hospital arm), the mean HRQoL loss/child was 9.8 days (95 % CI 9.4–10.6, n = 114) (mean 26.8 QALYs /1000 children (95 % CI 25.8–29.0) and 8.5 days/primary carer (95 % CI 7.4–9.6, n = 114) (mean 23.4 QALYs/1000 carers (95 % CI 20.3–26.2). Mean QALY losses/1000 patients were particularly high for bone and joint infections [67.5 (95 % CI 43.9–97.6)]. Estimates for children’s QALYs lost using the CHU9D tool were well correlated with those obtained using EQ-5D, but substantially lower. The impact of varicella on HRQoL is substantial. We report the first measurements of QALYs lost in hospitalised children and in the families of children both in the community and admitted to hospital, providing important information to guide vaccination policy recommendations.