Purinerge und cholinerge Aktivierung enterischer Gliazellen im entzündlichen Geschehen

Die enterischen Gliazellen (EGZ) rückten in den letzten Jahren in den Fokus der Forschung entzündlicher Vorgänge des Gastrointestinaltraktes. Ihnen werden in der Literatur als „aktivierte EGZ“ sowohl anti- als auch proinflammatorische Einflüsse zugeschrieben. Sie schützen einerseits den Darm vor schädigenden Einflüssen, indem sie das Immunsystem aktivieren. Andererseits tragen sie auch zur Inhibition der auf die Dauer schädigenden Einflüsse des Immunsystems bei. Zudem haben sie einen großen Anteil in der Aufrechterhaltung der intestinalen epithelialen Barriere. Purinerge (P1- und P2-Rezeptoren) und cholinerge Rezeptoren (muskarinerg und nikotinerg, m/nAChR) sind bekannt dafür, auf EGZ exprimiert zu werden und ebenfalls an der Regulation von entzündlichen Prozessen im enterischen Gewebe beteiligt zu sein. Während den P1-Rezeptoren sowohl pro- als auch antiinflammatorische Wirkungen zugesprochen werden, werden die P2-Rezeptoren hauptsächlich als antiinflammatorisch beschrieben. Die AChR, vor allem die nAChR, haben bei inflammatorischen Prozessen im GI-Trakt eine überwiegend inhibitorische Funktion inne. In der vorliegenden Arbeit sollte untersucht werden, inwiefern purinerge und cholinerge Rezeptoren auf EGZ am entzündlichen Geschehen des Darms beteiligt sind. Zunächst stellten wir die Hypothese eines negativen Feedback-Mechanismus auf, in dem ATP über die P2-Rezeptoren auf den EGZ die IL-6-Sekretion erhöht und sein Abbauprodukt Adenosin diesen Effekt über die P1-Rezeptoren wieder hemmt. Zusätzlich erwarteten wir eine Hemmung der IL-6-Sekretion durch Stimulation cholinerger Rezeptoren. Die Hypothese der antiinflammatorischen Wirkung von ACh konnte in Hinblick auf die ATP-vermittelte IL-6-Sekretion nicht bestätigt werden. Daneben zeigte diese Arbeit eine erhöhte IL-6-Sekretion durch die kultivierten EGZ nach Stimulation mit ATP, wobei die Wirkung über den P2-Rezeptor vermittelt wurde. Der P2X7-Rezeptor konnte als verantwortlicher Rezeptor ausgeschlossen werden. Der vermutete negative Feedback-Mechanismus zeigte sich durch Hemmung der ATP-vermittelten IL-6-Sekretion über Stimulation des A2A-Rezeptors. Weitere Forschungen sind notwendig, um die vielseitige und essentielle Rolle der aktivierte EGZ innerhalb intestinaler Entzündungsgeschehen zu ermitteln und so gezielte Therapien zu entwickeln

The Intersection of Autism and Transgender and Nonbinary Identities:Community and Academic Dialogue on Research and Advocacy

Many transgender people are autistic. Community expressions of the autism transgender intersection abound. Some commentators have questioned the proportional overrepresentation of autism among gender-diverse people, suggesting these individuals may not be truly autistic or truly transgender. However, increasing evidence challenges assertions that deny the authenticity of co-occurring autistic and transgender identities. Specifically, research by authors of this article indicates autistic transgender people show neurophenotypes generally consistent with cisgender autistic people and implicit gender phenotypes consistent with nonautistic transgender people. This article features a dialogue between eight leading experts in the field of intersectional autism and gender diversity, including clinicians, researchers, community advocates, and experts who are themselves autistic transgender. Key topics of discussion included: how research findings on autism and gender diversity inform respectful and supportive responses to autistic transgender people; the benefits and harms of increased societal attention toward the autism transgender intersection; and research and advocacy priorities. The expert panel concluded the following: (1) it is important to respect transgender autistic people’s wellness and resilience, while also acknowledging the pathologization and stigmatization they face; (2) autistic gender-diverse people are experts of their own identity and should be involved in all aspects of research and clinical care; (3) research is needed to understand the disparities autistic transgender people face; (4) attempts to restrict autistic transgender people’s access to gender care are unsupported by existing research; (5) adult gender care may benefit from incorporating universal design principles and neurodiversity-affirming strategies to reduce barriers to care and improve clinician–client communication in treatment delivery and the informed consent process; (6) cross-cultural and cross-societal research will improve best care practices in diverse contexts; (7) research and advocacy must be inclusive across ethnoracial identities, including in leadership and perspectives represented; and (8) a life span developmental framework is needed for adult research in this field.</p

Improved reference genome of the arboviral vector Aedes albopictus

Background: The Asian tiger mosquito Aedes albopictus is globally expanding and has become the main vector for human arboviruses in Europe. With limited antiviral drugs and vaccines available, vector control is the primary approach to prevent mosquito-borne diseases. A reliable and accurate DNA sequence of the Ae. albopictus genome is essential to develop new approaches that involve genetic manipulation of mosquitoes. Results: We use long-read sequencing methods and modern scaffolding techniques (PacBio, 10X, and Hi-C) to produce AalbF2, a dramatically improved assembly of the Ae. albopictus genome. AalbF2 reveals widespread viral insertions, novel microRNAs and piRNA clusters, the sex-determining locus, and new immunity genes, and enables genome-wide studies of geographically diverse Ae. albopictus populations and analyses of the developmental and stage-dependent network of expression data. Additionally, we build the first physical map for this species with 75% of the assembled genome anchored to the chromosomes. Conclusion: The AalbF2 genome assembly represents the most up-to-date collective knowledge of the Ae. albopictus genome. These resources represent a foundation to improve understanding of the adaptation potential and the epidemiological relevance of this species and foster the development of innovative control measures

Recommendations for a better understanding of sex and gender in neuroscience of mental health

There are prominent sex/gender differences in the prevalence, expression and lifespan course of mental health and neurodiverse conditions. Yet the underlying sex and gender related mechanisms and their interactions are still not fully understood. This lack of knowledge has harmful consequences for those suffering from mental health problems. Hence, we set up a co-creation session in a one week workshop with a multidisciplinary team of 25 researchers, clinicians and policy makers, to identify the main barriers in sex and gender research in neuroscience of mental health. Based on this work, we here provide recommendations for methodologies, translational research and stakeholder involvement. These include guidelines for recording, reporting, analysis beyond binary groups, and open science. Improved understanding of sex and gender related mechanisms in neuroscience may benefit public health as this is an important step towards precision medicine and may function as an archetype for studying diversity

The Toronto Adolescent and Youth Cohort Study:Study Design and Early Data Related to Psychosis Spectrum Symptoms, Functioning, and Suicidality

BACKGROUND: Psychosis spectrum symptoms (PSSs) occur in a sizable percentage of youth and are associated with poorer cognitive performance, poorer functioning, and suicidality (i.e., suicidal thoughts and behaviors). PSSs may occur more frequently in youths already experiencing another mental illness, but the antecedents are not well known. The Toronto Adolescent and Youth (TAY) Cohort Study aims to characterize developmental trajectories in youths with mental illness and understand associations with PSSs, functioning, and suicidality.METHODS: The TAY Cohort Study is a longitudinal cohort study that aims to assess 1500 youths (age 11-24 years) presenting to tertiary care. In this article, we describe the extensive diagnostic and clinical characterization of psychopathology, substance use, functioning, suicidality, and health service utilization in these youths, with follow-up every 6 months over 5 years, including early baseline data.RESULTS: A total of 417 participants were enrolled between May 4, 2021, and February 2, 2023. Participants met diagnostic criteria for an average of 3.5 psychiatric diagnoses, most frequently anxiety and depressive disorders. Forty-nine percent of participants met a pre-established threshold for PSSs and exhibited higher rates of functional impairment, internalizing and externalizing symptoms, and suicidality than participants without PSSs.CONCLUSIONS: Initial findings from the TAY Cohort Study demonstrate the feasibility of extensive clinical phenotyping in youths who are seeking help for mental health problems. PSS prevalence is much higher than in community-based studies. Our early data support the critical need to better understand longitudinal trajectories of clinical youth cohorts in relation to psychosis risk, functioning, and suicidality.</p

INSAR Special Interest Group Report: Stakeholder Perspectives on Priorities for Future Research on Autism, Sexuality, and Intimate Relationships

The number of empirical studies on sexuality and intimate relationships in autistic people has grown over the last years with the increasing awareness that sexuality and intimate relationships are an important part of life and well-being for autistic people. Further, expression and enjoyment of sexuality is a fundamental, basic human right. This paper reports on needs for future research in this area based on the input of autistic adults, researchers, and other stakeholders (e.g., parents and professionals). Utilizing the nominal group technique, 65 individuals participated in eight groups in which they brainstormed on research questions they deemed most important. Responses were categorized into themes and ranked according to importance based on the level of priority attributed by participants. Findings suggest that future research should focus on developing ways to support sexual and relationship well-being and getting a better understanding of sexuality and relationships in autistic people. Also, attention was drawn to the need for studying the influence of stereotypical societal views, and stigma. Finally, the importance of participatory research to include perspectives of autistic people in research and practice was stressed. Lay Summary: Sexuality and romantic relationships are part of daily life for most people, including autistic people. For this study, groups of autistic people, professionals, and autism researchers discussed which research on autism, sexuality, and relationships is needed and can help autistic adolescents and adults. The group discussions revealed that more research is needed on how to support well-being relating to romantic relationships and sexuality in autistic people and how the people around them can contribute to this. Therefore, we also need to learn more about how autistic people of all ages and throughout their lives experience sexuality and relationships. Finally, the need for attention to the role of stereotypical ideas and stigma about autism, sexuality, and relationships was pointed out. Attention to the experiences of autistic people can help professionals, researchers, and policy makers to offer and organize attuned support and do relevant research. Autism Res 2020, 13: 1248–1257

Gender dysphoria and autism spectrum disorder: A narrative review

The current literature shows growing evidence of a link between gender dysphoria (GD) and autism spectrum disorder (ASD). This study reviews the available clinical and empirical data. A systematic search of the literature was conducted using the following databases: PubMed, Web of Science, PsycINFO and Scopus; utilizing different combinations of the following search terms: autism, autism spectrum disorder (ASD), Aspergers disorder (AD), co-morbidity, gender dysphoria (GD), gender identity disorder (GID), transgenderism and transsexualism. In total, 25 articles and reports were selected and discussed. Information was grouped by found co-occurrence rates, underlying hypotheses and implications for diagnosis and treatment. GD and ASD were found to co-occur frequently - sometimes characterized by atypical presentation of GD, which makes a correct diagnosis and determination of treatment options for GD difficult. Despite these challenges there are several case reports describing gender affirming treatment of co-occurring GD in adolescents and adults with ASD. Various underlying hypotheses for the link between GD and ASD were suggested, but almost all of them lack evidence. 201

Is There a Link Between Gender Dysphoria and Autism Spectrum Disorder?

In their Translations article in the January issue of the Journal, Turban and van Schalkwyk provide a critical evaluation of the recently published literature on co-occurring gender dysphoria (GD) and autism spectrum disorder (ASD).1 In addition, they refer to this flux in interest as part of a larger increase in publications on transgender people, which are mostly reviews and do not contain new data. Given the low-grade evidence in this field for most clinical recommendations,2 good-quality research is of great relevance. We support the debate on the GD-ASD literature and acknowledge that translations of the findings to the lay press such as “Do transgender children just have autism?” are not helpful. Also, we agree with many of the limitations brought forward by the authors and acknowledge that, at present, sound underlying evidence for a GD−ASD link is lacking. However, we believe that some nuance in argumentation could help forward the debate of this clinically important topic