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1.
Cell ; 187(6): 1327-1334, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38490174

RESUMEN

To build a just, equitable, and diverse academy, scientists and institutions must address systemic barriers that sex and gender minorities face. This Commentary summarizes (1) critical context informing the contemporary oppression of transgender people, (2) how this shapes extant research on sex and gender, and (3) actions to build an inclusive and rigorous academy for all.


Asunto(s)
Minorías Sexuales y de Género , Personas Transgénero , Masculino , Femenino , Humanos , Identidad de Género
2.
Horm Behav ; 157: 105445, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37979209

RESUMEN

Sex is ubiquitous and variable throughout the animal kingdom. Historically, scientists have used reductionist methodologies that rely on a priori sex categorizations, in which two discrete sexes are inextricably linked with gamete type. However, this binarized operationalization does not adequately reflect the diversity of sex observed in nature. This is due, in part, to the fact that sex exists across many levels of biological analysis, including genetic, molecular, cellular, morphological, behavioral, and population levels. Furthermore, the biological mechanisms governing sex are embedded in complex networks that dynamically interact with other systems. To produce the most accurate and scientifically rigorous work examining sex in neuroendocrinology and to capture the full range of sex variability and diversity present in animal systems, we must critically assess the frameworks, experimental designs, and analytical methods used in our research. In this perspective piece, we first propose a new conceptual framework to guide the integrative study of sex. Then, we provide practical guidance on research approaches for studying sex-associated variables, including factors to consider in study design, selection of model organisms, experimental methodologies, and statistical analyses. We invite fellow scientists to conscientiously apply these modernized approaches to advance our biological understanding of sex and to encourage academically and socially responsible outcomes of our work. By expanding our conceptual frameworks and methodological approaches to the study of sex, we will gain insight into the unique ways that sex exists across levels of biological organization to produce the vast array of variability and diversity observed in nature.


Asunto(s)
Neuroendocrinología , Sexo , Animales , Neuroendocrinología/métodos
3.
Horm Behav ; 156: 105441, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37862978

RESUMEN

The scientific community widely recognizes that "sex" is a complex category composed of multiple physiologies. Yet in practice, basic scientific research often treats "sex" as a single, internally consistent, and often binary variable. This practice occludes important physiological factors and processes, and thus limits the scientific value of our findings. In human-oriented biomedical research, the use of simplistic (and often binary) models of sex ignores the existence of intersex, trans, non-binary, and gender non-conforming people and contributes to a medical paradigm that neglects their needs and interests. More broadly, our collective reliance on these models legitimizes a false paradigm of human biology that undergirds harmful medical practices and anti-trans political movements. Herein, we continue the conversations begun at the SBN 2022 Symposium on Hormones and Trans Health, providing guiding questions to help scientists deconstruct and rethink the use of "sex" across the stages of the scientific method. We offer these as a step toward a scientific paradigm that more accurately recognizes and represents sexed physiologies as multiple, interacting, variable, and unbounded by gendered preconceptions. We hope this paper will serve as a useful resource for scientists who seek a new paradigm for researching and understanding sexed physiologies that improves our science, widens the applicability of our findings, and deters the misuse of our research against marginalized groups.


Asunto(s)
Investigación Biomédica , Transexualidad , Humanos , Neuroendocrinología , Identidad de Género , Comunicación
4.
bioRxiv ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39314438

RESUMEN

Basal synaptic strength can vary greatly between synapses formed by an individual neuron because of diverse probabilities of action potential (AP) evoked transmitter release ( Pr ). Optical quantal analysis on large numbers of identified Drosophila larval glutamatergic synapses shows that short-term plasticity (STP) also varies greatly between synapses made by an individual type I motor neuron (MN) onto a single body wall muscle. Synapses with high and low P r and different forms and level of STP have a random spatial distribution in the MN nerve terminal, and ones with very different properties can be located within 200 nm of one other. While synapses start off with widely diverse basal P r at low MN AP firing frequency and change P r differentially when MN firing frequency increases, the overall distribution of P r remains remarkably constant due to a balance between the numbers of synapses that facilitate and depress as well as their degree of change and basal synaptic weights. This constancy in transmitter release can ensure robustness across changing behavioral conditions.

5.
J Endocr Soc ; 8(1): bvad144, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38090229

RESUMEN

We have recently proposed experimental design guidelines and areas of study for preclinical rodent models of gender-affirming hormone therapy in neuroscience. These guidelines also apply to any field subject to the influences of gonadal steroid hormones, including metabolism and growth, cancer, and physiology. This perspective briefly describes our suggestions for these fields. Studying the effects of exogenous steroid hormones will have translational benefits for the community. We also discuss the need for equitable practices for cisgender scientists who wish to implement these guidelines and engage with the community. It is necessary that community-informed practices are implemented in preclinical research to maximize the benefit to transgender, nonbinary, and/or gender diverse (TNG) healthcare, which is currently in jeopardy in the United States, Europe, and across the globe.

6.
Neuropsychopharmacology ; 48(6): 852-856, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36928352

RESUMEN

Research regarding the mental health of the Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, Asexual, 2 Spirit (LGBTQIA2S+) community has been historically biased by individual and structural homophobia, biphobia, and transphobia, resulting in research that does not represent the best quality science. Furthermore, much of this research does not serve the best interests or priorities of LGBTQIA2S + communities, despite significant mental health disparities and great need for quality mental health research and treatments in these populations. Here, we will highlight how bias has resulted in missed opportunities for advancing understanding of mental health within LGBTQIA2S + communities. We cite up-to-date research on mental health disparities facing the LGBTQIA2S + community and targeted treatment strategies, as well as guidance from health care professionals. Importantly, research is discussed from both preclinical and clinical perspectives, providing common language and research priorities from a translational perspective. Given the rising tide of anti-transgender sentiment among certain political factions, we further emphasize and discuss the impact of historical and present day ciscentrism and structural transphobia in transgender mental health research, from both clinical and translational perspectives, with suggestions for future directions to improve the quality of this field. Finally, we address current best practices for treatment of mental health issues in this community. This approach provides an opportunity to dispel myths regarding the LGBTQIA2S + community as well as inform the scientific community of best practices to work with this community in an equitable manner. Thus, our approach ties preclinical and clinical research within the LGBTQIA2S + community.


Asunto(s)
Minorías Sexuales y de Género , Personas Transgénero , Transexualidad , Femenino , Humanos , Personas Transgénero/psicología , Conducta Sexual , Identidad de Género
7.
Artículo en Inglés | MEDLINE | ID: mdl-35863692

RESUMEN

Most studies attempting to address the health care needs of the millions of transgender, nonbinary, and/or gender-diverse (TNG) individuals rely on human subjects, overlooking the benefits of translational research in animal models. Researchers have identified many ways in which gonadal steroid hormones regulate neuronal gene expression, connectivity, activity, and function across the brain to control behavior. However, these discoveries primarily benefit cisgender populations. Research into the effects of exogenous hormones such as estradiol, testosterone, and progesterone has a direct translational benefit for TNG individuals on gender-affirming hormone therapies (GAHTs). Despite this potential, endocrinological health care for TNG individuals remains largely unimproved. Here, we outline important areas of translational research that could address the unique health care needs of TNG individuals on GAHT. We highlight key biomedical questions regarding GAHT that can be investigated using animal models. We discuss how contemporary research fails to address the needs of GAHT users and identify equitable practices for cisgender scientists engaging with this work. We conclude that if necessary and important steps are taken to address these issues, translational research on GAHTs will greatly benefit the health care outcomes of TNG people.


Asunto(s)
Hormonas , Investigación Biomédica Traslacional , Humanos
8.
Nat Commun ; 13(1): 229, 2022 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-35017509

RESUMEN

Neural circuit function depends on the pattern of synaptic connections between neurons and the strength of those connections. Synaptic strength is determined by both postsynaptic sensitivity to neurotransmitter and the presynaptic probability of action potential evoked transmitter release (Pr). Whereas morphology and neurotransmitter receptor number indicate postsynaptic sensitivity, presynaptic indicators and the mechanism that sets Pr remain to be defined. To address this, we developed QuaSOR, a super-resolution method for determining Pr from quantal synaptic transmission imaging at hundreds of glutamatergic synapses at a time. We mapped the Pr onto super-resolution 3D molecular reconstructions of the presynaptic active zones (AZs) of the same synapses at the Drosophila larval neuromuscular junction (NMJ). We find that Pr varies greatly between synapses made by a single axon, quantify the contribution of key AZ proteins to Pr diversity and find that one of these, Complexin, suppresses spontaneous and evoked transmission differentially, thereby generating a spatial and quantitative mismatch between release modes. Transmission is thus regulated by the balance and nanoscale distribution of release-enhancing and suppressing presynaptic proteins to generate high signal-to-noise evoked transmission.


Asunto(s)
Diagnóstico por Imagen , Neurotransmisores/fisiología , Sinapsis/fisiología , Transmisión Sináptica/fisiología , Animales , Drosophila , Femenino , Unión Neuromuscular/metabolismo , Imagen Óptica , Terminales Presinápticos
9.
Nat Commun ; 10(1): 1221, 2019 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-30874546

RESUMEN

Inherited and age-related retinal degenerative diseases cause progressive loss of rod and cone photoreceptors, leading to blindness, but spare downstream retinal neurons, which can be targeted for optogenetic therapy. However, optogenetic approaches have been limited by either low light sensitivity or slow kinetics, and lack adaptation to changes in ambient light, and not been shown to restore object vision. We find that the vertebrate medium wavelength cone opsin (MW-opsin) overcomes these limitations and supports vision in dim light. MW-opsin enables an otherwise blind retinitis pigmenotosa mouse to discriminate temporal and spatial light patterns displayed on a standard LCD computer tablet, displays adaption to changes in ambient light, and restores open-field novel object exploration under incidental room light. By contrast, rhodopsin, which is similar in sensitivity but slower in light response and has greater rundown, fails these tests. Thus, MW-opsin provides the speed, sensitivity and adaptation needed to restore patterned vision.


Asunto(s)
Ceguera/prevención & control , Opsinas de los Conos/genética , Terapia Genética/métodos , Optogenética/métodos , Degeneración Retiniana/terapia , Animales , Ceguera/etiología , Línea Celular , Dependovirus/genética , Modelos Animales de Enfermedad , Vectores Genéticos/administración & dosificación , Vectores Genéticos/genética , Humanos , Inyecciones Intravítreas , Queratinocitos , Ratones , Ratones Endogámicos C57BL , Técnicas de Placa-Clamp , Retina/patología , Células Fotorreceptoras Retinianas Conos/patología , Degeneración Retiniana/complicaciones , Degeneración Retiniana/patología , Rodopsina/genética , Resultado del Tratamiento
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