Selective Estrogen Receptor Modulators: A Potential Option For Non-Binary Gender-Affirming Hormonal Care?

Gender dysphoria describes the distress associated with having a gender identity that differs from one’s birth-assigned sex. To relieve this distress, transgender, and gender diverse (henceforth, trans) individuals commonly undergo medical transition involving hormonal treatments. Current hormonal treatment guidelines cater almost exclusively for those who wish to transition from male to female or vice versa. In contrast, there is a dearth of hormonal options for those trans individuals who identify as non-binary and seek an androgynous appearance that is neither overtly male nor female. Though prolonged puberty suppression with gonadotrophin releasing hormone agonists (GnRHa) could in theory be gender-affirming by preventing the development of unwanted secondary sex characteristics, this treatment option would be limited to pre- or peri-pubertal adolescents and likely have harmful effects. Here, we discuss the theoretical use of Selective Estrogen Receptor Modulators (SERMs) for non-binary people assigned male at birth (AMAB) who are seeking an androgynous appearance through partial feminization without breast growth. Given their unique range of pharmacodynamic effects, SERMs may represent a potential gender-affirming treatment for this population, but there is a lack of knowledge regarding their use and potentially adverse effects in this context

Conserved transcriptomic profiles underpin monogamy across vertebrates

Social monogamy, typically characterized by the formation of a pair bond, increased territorial defense, and often biparental care, has independently evolved multiple times in animals. Despite its independent origins, several homologous brain regions, neuropeptides and their receptors have been shown to play a conserved role in regulating social affiliation and parental care, but little is known is known about the neuromolecular mechanisms underlying monogamy on a genomic scale. Here, we compare neural transcriptomes of reproductive males in monogamous and nonmonogamous species pairs of Peromyscus mice, Microtus voles, parid songbirds, dendrobatid frogs, and Xenotilapia species of cichlid fishes. We find that while evolutionary divergence time between species or clades did not explain gene expression similarity, characteristics of mating system correlated with neural gene expression patterns and neural gene expression varies concordantly across vertebrates when species transition to monogamy. Our study provides evidence of a universal transcriptomic mechanism underlying the evolution of monogamy in vertebrates

Social odors conveying dominance and reproductive information induce rapid physiological and neuromolecular changes in a cichlid fish

Background: Social plasticity is a pervasive feature of animal behavior. Animals adjust the expression of their social behavior to the daily changes in social life and to transitions between life-history stages, and this ability has an impact in their Darwinian fitness. This behavioral plasticity may be achieved either by rewiring or by biochemically switching nodes of the neural network underlying social behavior in response to perceived social information. Independent of the proximate mechanisms, at the neuromolecular level social plasticity relies on the regulation of gene expression, such that different neurogenomic states emerge in response to different social stimuli and the switches between states are orchestrated by signaling pathways that interface the social environment and the genotype. Here, we test this hypothesis by characterizing the changes in the brain profile of gene expression in response to social odors in the Mozambique Tilapia, Oreochromis mossambicus. This species has a rich repertoire of social behaviors during which both visual and chemical information are conveyed to conspecifics. Specifically, dominant males increase their urination frequency during agonist encounters and during courtship to convey chemical information reflecting their dominance status. Results: We recorded electro-olfactograms to test the extent to which the olfactory epithelium can discriminate between olfactory information from dominant and subordinate males as well as from pre- and post-spawning females. We then performed a genome-scale gene expression analysis of the olfactory bulb and the olfactory cortex homolog in order to identify the neuromolecular systems involved in processing these social stimuli. Conclusions: Our results show that different olfactory stimuli from conspecifics' have a major impact in the brain transcriptome, with different chemical social cues eliciting specific patterns of gene expression in the brain. These results confirm the role of rapid changes in gene expression in the brain as a genomic mechanism underlying behavioral plasticity and reinforce the idea of an extensive transcriptional plasticity of cichlid genomes, especially in response to rapid changes in their social environment.Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) [EXCL/BIA-ANM/0549/2012, Pest-OE/MAR/UI0331/2011]; Dwight W. and Blanche Faye Reeder Centennial Fellowship in Systematic and Evolutionary Biology; Institute for Cellular and Molecular Biology Fellowship; FCTinfo:eu-repo/semantics/publishedVersio

Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans

Antibody responses to SARS-CoV-2 can be detected in most infected individuals 10–15 d after the onset of COVID-19 symptoms. However, due to the recent emergence of SARS-CoV-2 in the human population, it is not known how long antibody responses will be maintained or whether they will provide protection from reinfection. Using sequential serum samples collected up to 94 d post onset of symptoms (POS) from 65 individuals with real-time quantitative PCR-confirmed SARS-CoV-2 infection, we show seroconversion (immunoglobulin (Ig)M, IgA, IgG) in >95% of cases and neutralizing antibody responses when sampled beyond 8 d POS. We show that the kinetics of the neutralizing antibody response is typical of an acute viral infection, with declining neutralizing antibody titres observed after an initial peak, and that the magnitude of this peak is dependent on disease severity. Although some individuals with high peak infective dose (ID50 > 10,000) maintained neutralizing antibody titres >1,000 at >60 d POS, some with lower peak ID50 had neutralizing antibody titres approaching baseline within the follow-up period. A similar decline in neutralizing antibody titres was observed in a cohort of 31 seropositive healthcare workers. The present study has important implications when considering widespread serological testing and antibody protection against reinfection with SARS-CoV-2, and may suggest that vaccine boosters are required to provide long-lasting protection

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Speciation and secondary contact in a fossorial island endemic, the São Tomé caecilian

A period of isolation in allopatry typically precedes local adaptation and subsequent divergence among lineages. Alternatively, locally adapted phenotypes may arise and persist in the face of gene flow, resulting in strong correlations between ecologically- relevant phenotypic variation and corresponding environmental gradients. Quantifying genetic, ecological, and phenotypic divergence in such lineages can provide insights into the abiotic and biotic mechanisms that structure populations and drive the accumulation of phenotypic and taxonomic diversity. Low- vagility organisms whose distributions span ephemeral geographic barriers present the ideal evolutionary context within which to address these questions. Here, we combine genetic (mtDNA and genome- wide SNPs) and phenotypic data to investigate the divergence history of caecilians (Amphibia: Gymnophiona) endemic to the oceanic island of São Tomé in the Gulf of Guinea archipelago. Consistent with a previous mtDNA study, we find two phenotypically and genetically distinct lineages that occur along a north- to- south axis with extensive admixture in the centre of the island. Demographic modelling supports divergence in allopatry (~300 kya) followed by secondary contact (~95 kya). Consequently, in contrast to a morphological study that interpreted latitudinal phenotypic variation in these caecilians as a cline within a single widespread species, our analyses suggest a history of allopatric lineage divergence and subsequent hybridization that may have blurred species boundaries. We propose that late Pleistocene volcanic activity favoured allopatric divergence between these lineages with local adaptation to climate maintaining a stable hybrid zone in the centre of São Tomé Island. Our study joins a growing number of systems demonstrating lineage divergence on volcanic islands with stark environmental transitions across small geographic distances.ResumoUm período de isolamento em alopatria geralmente precede adaptação local e divergência subsequente entre linhagens evolutivas. Alternativamente, fenótipos adaptados localmente podem surgir e persistir apesar de fluxo gênico, resultando em fortes correlações entre variação fenotípica ecologicamente relevante e os gradientes ambientais correspondentes. Quantificar divergência genética, ecológica e fenotípica em tais linhagens pode ajudar a clarificar os mecanismos abióticos e bióticos que estruturam as populações e levam ao acúmulo de diversidade fenotípica e taxonômica. Organismos de baixa vagilidade, cujas áreas de distribuição incluem barreiras geográficas efêmeras, representam um contexto evolutivo ideal para abordar essas questões. Neste estudo, combinamos dados genéticos (mtDNA e SNPs genômicos) e fenotípicos para investigar a história de divergência de cecílias endêmicas da ilha oceânica de São Tomé, no arquipélago do Golfo da Guiné. Consistentemente com um estudo anterior de mtDNA, encontramos duas linhagens fenotipicamente e geneticamente distintas que ocorrem ao longo de um eixo norte- sul, com extensa mistura genética no centro da ilha. Modelagem demográfica suportou um cenário de divergência em alopatria (~ 300 mil anos atrás) seguida de contato secundário (~ 95 mil anos atrás). Ao contrário de um estudo morfológico que interpretou a variação fenotípica latitudinal nessas cecílias como uma clina dentro de uma única espécie amplamente difundida, nossas análises sugerem uma história de divergência de linhagens em alopatria e subsequente hibridização que pode ter confundido os limites das espécies. Propomos que atividade vulcânica durante o Pleistoceno tardio favoreceu divergência alopátrica entre essas linhagens, com adaptação local ao clima mantendo uma zona híbrida estável no centro da Ilha de São Tomé. Nosso estudo se une a um número crescente de sistemas que demonstram divergência entre linhagens em ilhas vulcânicas com transições ambientais marcantes ao longo de distâncias geográficas curtas.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/168310/1/mec15928-sup-0002-FigS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168310/2/mec15928-sup-0003-FigS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168310/3/mec15928-sup-0005-FigS4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168310/4/mec15928-sup-0004-FigS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168310/5/mec15928_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168310/6/mec15928.pd

Step-by-step protocol, also available on protocols.io.

Step-by-step protocol, also available on protocols.io.</p

Tadpole mortality and GFP expression in brain cells.

(A) Tadpole mortality increased with pulse number during brain electroporation. Smaller circles show tadpoles that survived (0) or died (1), larger circles and error bars show the mean ± 95% CI of the proportion of tadpoles that died (estimated from a binomial GLMM). (B) The proportional area of transfected brain cells increased with pulse number across all species. However, the magnitude of treatment effects varied by species. Smaller circles show the proportional area of individual brains with GFP-positive cells, larger circles and error bars show the mean ± 95% CI (estimated from a beta-binomial GLMM). In both plots, data points are jittered to show stacked points. (C) Images of dissected brains (top row) and live tadpoles (bottom row) showing GFP-positive brain cells (green; from fluorescence microscopy). (D) An image from two-photon microscopy showing GFP-labeled cells in vivo within the hindbrain of an R. imitator tadpole.</p

Species relationships and phenotypes of the study species.

(A) The African clawed frog Xenopus laevis (Pipidae) is a model organism for laboratory studies and for developing in vivo techniques for testing gene function. Images by JD, the adult was photographed near Hluhluwe, KwaZulu-Natal, South Africa. (B) The glassfrog Hyalinobatrachium fleischmanni (Centrolenidae) exhibits transparent tissues, through which many organs are visible during embryonic, tadpole and adult life-stages. Fathers provide parental care to developing eggs and embryos can time hatching in response to parenting [28–31]. Images by JD, the adult was photographed near San Gabriel Mixtepec, Oaxaca, Mexico. (C) Allobates femoralis is a cryptic poison frog (Aromobatidae) whose adult behavior is well studied in the context of spatial cognition and parental behavior [32–35]. Images by DS (tadpole) and Andrius Pašukonis (adult from Nouragues Nature Reserve, French Guiana). (D) Poison frogs of the Dendrobatidae are well known for their aposematic coloration, chemical defenses, and diverse social behaviors [25–27, 36]. Images are of Dendrobates tinctorius by DS (captive animals) and Ranitomeya imitator, by DS (tadpole) and Evan Twomey (adult from near San Jose, San Martin, Peru).</p