Gender Violence

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Distinct effects of folate pathway genes MTHFR and MTHFD1L on ruminative response style: a potential risk mechanism for depression

Alterations in the folate pathway have been related to both major depression and cognitive inflexibility; however, they have not been investigated in the genetic background of ruminative response style, which is a form of perseverative cognition and a risk factor for depression. In the present study, we explored the association of rumination (measured by the Ruminative Responses Scale) with polymorphisms of two distinct folate pathway genes, MTHFR rs1801133 (C677T) and MTHFD1L rs11754661, in a combined European white sample from Budapest, Hungary (n=895) and Manchester, United Kingdom (n=1309). Post hoc analysis investigated whether the association could be replicated in each of the two samples, and the relationship between folate pathway genes, rumination, lifetime depression and Brief Symptom Inventory depression score. Despite its functional effect on folate metabolism, the MTHFR rs1801133 showed no effect on rumination. However, the A allele of MTHFD1L rs11754661 was significantly associated with greater rumination, and this effect was replicated in both the Budapest and Manchester samples. In addition, rumination completely mediated the effects of MTHFD1L rs11754661 on depression phenotypes. These findings suggest that the MTHFD1L gene, and thus the C1-THF synthase enzyme of the folate pathway localized in mitochondria, has an important effect on the pathophysiology of depression through rumination, and maybe via this cognitive intermediate phenotype on other mental and physical disorders. Further research should unravel whether the reversible metabolic effect of MTHFD1L is responsible for increased rumination or other long-term effects on brain development

Evaluation of SARS-CoV-2 genomic architecture and its alteration pattern through ORF analysis/ Avaliação da arquitetura genômica do SARS-CoV-2 e seu padrão de alteração por meio de análise de ORF

Members of the Coronaviridae family comprise four genera Alphacoronavirus and Betacoronavirus, which infect only mammals, and Gammacoronavirus and Deltacoronavirus infect birds and mammals. Since the end of 2019, humanity has witnessed the emergence of a new pandemic caused by a line of beta-coronavirus (SARS-CoV-2) responsible for causing a novel severe acute respiratory syndrome named coronavirus disease (COVID-19) affecting countries worldwide. In this context, this work aimed to investigate the main changes in SARS-CoV-2 genomic architecture through the time since the beginning of the infection using in silico analysis. A genomic database was built using complete and revised genomes from NCBI as well as analyzed through sequencing alignment and phylogenetic softwares. This study was able to show a change in the organizational pattern of the genome of the new coronavirus for the different regions studied, in addition to showing specific changes in the genomic sequence requiring further analysis of the collected genomes and may provide new evidence for the key protein changes like Spike protein

Regional default mode network connectivity in major depressive disorder

The relationship between altered default mode network (DMN) connectivity and abnormal serotonin function in major depressive disorder (MDD) has not been investigated. Using intravenous citalopram and resting-state fMRI, we investigated DMN intra-network connectivity and serotonin function in 77 healthy controls and patients with MDD. There were no significant main effects of MDD or citalopram on DMN intra-network connectivity; however, significant interactions indicated that group differences under saline were modified by citalopram. In MDD patients during saline infusion, in contrast with controls, the DMN (i) did not include the precuneus that was instead part of an anti-correlated network but (ii) did include amygdala that was part of the anti-correlated network in controls. Citalopram infusion in MDD patients restored the pattern seen in controls under saline. In healthy controls, citalopram infusion disengaged the precuneus from the DMN and engaged the amygdala, partially reproducing the abnormalities seen under saline in MDD. In exploratory analyses within the MDD group, greater rumination self-ratings were associated with greater intra-network connectivity of the anterior cingulate cortex with the DMN. We hypothesise that, in MDD, disengagement of the precuneus from the DMN relates to overgeneral memory bias in rumination. The opposite effect, with greater engagement of the amygdala in the DMN, reflects the negative valence of rumination. Reversal of these abnormalities by citalopram suggests that they may be related to impaired serotonin function. That citalopram engaged the amygdala in the DMN in controls may relate to the paradoxical effects on aversive processing seen with acute SSRIs in healthy subjects

Variants in the CNR1 gene predispose to headache with nausea in the presence of life stress

One of the main effects of the endocannabinoid system in the brain is stress adaptation with presynaptic endocannabinoid receptor 1 (CB1 receptors) playing a major role. In the present study, we investigated whether the effect of the CB1 receptor coding CNR1 gene on migraine and its symptoms is conditional on life stress. In a cross-sectional European population (n = 2426), recruited from Manchester and Budapest, we used the ID-Migraine questionnaire for migraine screening, the Life Threatening Experiences questionnaire to measure recent negative life events (RLE), and covered the CNR1 gene with 11 SNPs. The main genetic effects and the CNR1 × RLE interaction with age and sex as covariates were tested. None of the SNPs showed main genetic effects on possible migraine or its symptoms, but 5 SNPs showed nominally significant interaction with RLE on headache with nausea using logistic regression models. The effect of rs806366 remained significant after correction for multiple testing and replicated in the subpopulations. This effect was independent from depression- and anxiety-related phenotypes. In addition, a Bayesian systems-based analysis demonstrated that in the development of headache with nausea all SNPs were more relevant with higher a posteriori probability in those who experienced recent life stress. In summary, the CNR1 gene in interaction with life stress increased the risk of headache with nausea suggesting a specific pathological mechanism to develop migraine, and indicating that a subgroup of migraine patients, who suffer from life stress triggered migraine with frequent nausea, may benefit from therapies that increase the endocannabinoid tone

Reversed Frontotemporal Connectivity During Emotional Face Processing in Remitted Depression

BackgroundVulnerability to relapse persists after remission of an acute episode of major depressive disorder. This has been attributed to abnormal biases in the processing of emotional stimuli in limbic circuits. However, neuroimaging studies have not so far revealed consistent evidence of abnormal responses to emotional stimuli in limbic structures, such as the amygdala, in remitted depression. This suggests the problem might lie in the integrated functioning of emotion processing circuits.MethodsWe recruited 22 unmedicated patients in remission from major depressive disorder (rMDD) and 21 age-matched healthy control subjects. Functional magnetic resonance imaging was performed during a face emotion processing task. Dynamic causal modeling was used with Bayesian model selection to determine the most likely brain networks and valence-specific modulation of connectivity in healthy control subjects and rMDD.ResultsIn healthy volunteers, sad faces modulated bi-directional connections between amygdala and orbitofrontal cortex and between fusiform gyrus and orbitofrontal cortex. Happy faces modulated unidirectional connections from fusiform gyrus to orbitofrontal cortex. In rMDD, the opposite pattern was observed, with evidence of happy faces modulating bidirectional frontotemporal connections and sad faces modulating unidirectional fusiform–orbitofrontal connections.ConclusionsParticipants with rMDD have abnormal modulation of frontotemporal effective connectivity in response to happy and sad face emotions, despite normal activations within each region. Specifically, processing of mood incongruent happy information was associated with a more richly modulated frontotemporal brain network, whereas mood congruent sad information was associated with less network modulation. This supports a hypothesis of dysfunction within cortico–limbic connections in individuals vulnerable to depression

The ethical implications of HCI’s turn to the cultural

We explore the ethical implications of HCI’s turn to the ‘cultural’. This is motivated by an awareness of how cultural applications, in our case interactive performances, raise ethical issues that may challenge established research ethics processes. We review research ethics, HCI’s engagement with ethics and the ethics of theatrical performance. Following an approach grounded in Responsible Research Innovation, we present the findings from a workshop in which artists, curators, commissioners, and researchers explored ethical challenges revealed by four case studies. We identify six ethical challenges for HCI’s engagement with cultural applications: transgression, boundaries, consent, withdrawal, data, and integrity. We discuss two broader implications of these: managing tensions between multiple overlapping ethical frames; and the importance of managing ethical challenges during and after an experience as well as beforehand. Finally, we discuss how our findings extend previous discussions of Value Sensitive Design in HCI

International perceptions of an integrated, multi-sectoral, ecosystem approach to management:Editor’s Choice

Abstract The Ecosystem Approach to Management (EAM) has emerged over the past decades, largely to promote biodiversity conservation, and more recently sectoral tradeoffs in the management of marine ecosystems. To ascertain the state of practice of EAM operationalization, a workshop was held, which included a pre-workshop online survey. The survey gauged international participants’ perspectives regarding capacity, knowledge, and application of EAM. When asked about the subject, most survey respondents had a general understanding of EAM, and provided a clear definition. Major perceived challenges to EAM objectives by those surveyed included limited knowledge, conflicting interests, insufficient communication, and limited organizational legal frameworks or governance structures. Of those directly involved in an ecosystem approach, the majority responded that processes were in place or developed for application of integrated knowledge toward assessing key issues within their respective sectors (i.e. fisheries, conservation, energy), and that capacity was generally high. Our results show that most respondents, irrespective of sector or geography, see value in considering an integrated, broader ecosystem approach as they manage their sector. Although many participants were from the North Atlantic region, our results suggest that much of the international community is converging toward continued understanding of broad-scale, integrated approaches to marine resource management.</jats:p

Catalytic asymmetric synthesis of the alkaloid (+)-myrtine

A new protocol for the asymmetric synthesis of trans-2,6-disubstituted-4-piperidones has been developed using a catalytic enantioselective conjugate addition reaction in combination with a diastereoselective lithiation–substitution sequence; an efficient synthesis of (+)-myrtine has been achieved via this route.