Stem Cell Rev Rep. 2021 Apr 6. doi: 10.1007/s12015-021-10158-2. Online ahead of print.

NO ABSTRACT

PMID:33825111 | DOI:10.1007/s12015-021-10158-2

Int J Nanomedicine. 2021 Mar 29;16:2487-2499. doi: 10.2147/IJN.S294279. eCollection 2021.

ABSTRACT

PURPOSE: Due to the shortcomings of nanocarriers, the development of carrier-free nanodelivery systems has attracted more and more attention in cancer treatment. However, there are few studies on carrier-free nanosystems that can simultaneously achieve monitoring functions. Here a multifunctional carrier-free nanosystem loaded with curcumin and irinotecan hydrochloride was established for the treatment and monitoring of gastric cancer.

METHODS: In this study, an irinotecan hydrochloride-curcumin nanosystem in the early stage (the system is named SICN) was prepared. Based on the fluorescence of curcumin, flow cytometry, laser confocal microscopy, and zebrafish fluorescence imaging were used to study the monitoring function of SICN in vivo and in vitro. In addition, HGC-27 human gastric cancer cells were used to study SICN cytotoxicity.

RESULTS: Flow cytometry and zebrafish fluorescence imaging monitoring results showed that the uptake of SICN was significantly higher than free curcumin, and the excretion rate was lower. SICN had higher accumulation and retention in cells and zebrafish. Laser confocal microscopy monitoring results showed that SICN was internalized into HGC-27 cells through multiple pathways, including macropinocytosis, caveolin, and clathrin-mediated and clathrin -independent endocytosis, and distributed intracellularly throughout the whole cytoplasm, including lysosomes and Golgi apparatus. In vitro cell experiments showed that SICN nanoparticles were more toxic than single components, and HGC-27 cells had more absorption and higher toxicity to nanoparticles under slightly acidic conditions.

CONCLUSION: SICN is a promising carrier-free nanoparticle, and the combination of two single-component therapies can exert a synergistic antitumor effect. When exposed to a tumor acidic environment, SICN showed stronger cytotoxicity due to charge conversion. More importantly, the nanoparticles' self-monitoring function has been developed, opening up new ideas for combined tumor therapy.

PMID:33824587 | PMC:PMC8018427 | DOI:10.2147/IJN.S294279

Nat Rev Drug Discov. 2021 Apr 6. doi: 10.1038/s41573-021-00163-y. Online ahead of print.

ABSTRACT

Adjuvants are vaccine components that enhance the magnitude, breadth and durability of the immune response. Following its introduction in the 1920s, alum remained the only adjuvant licensed for human use for the next 70 years. Since the 1990s, a further five adjuvants have been included in licensed vaccines, but the molecular mechanisms by which these adjuvants work remain only partially understood. However, a revolution in our understanding of the activation of the innate immune system through pattern recognition receptors (PRRs) is improving the mechanistic understanding of adjuvants, and recent conceptual advances highlight the notion that tissue damage, different forms of cell death, and metabolic and nutrient sensors can all modulate the innate immune system to activate adaptive immunity. Furthermore, recent advances in the use of systems biology to probe the molecular networks driving immune response to vaccines ('systems vaccinology') are revealing mechanistic insights and providing a new paradigm for the vaccine discovery and development process. Here, we review the 'known knowns' and 'known unknowns' of adjuvants, discuss these emerging concepts and highlight how our expanding knowledge about innate immunity and systems vaccinology are revitalizing the science and development of novel adjuvants for use in vaccines against COVID-19 and future pandemics.

PMID:33824489 | DOI:10.1038/s41573-021-00163-y

Commun Biol. 2021 Apr 6;4(1):440. doi: 10.1038/s42003-021-01964-y.

ABSTRACT

Hydrogen to deuterium isotopic substitution has only a minor effect on physical and chemical properties of water and, as such, is not supposed to influence its neutral taste. Here we conclusively demonstrate that humans are, nevertheless, able to distinguish D2O from H2O by taste. Indeed, highly purified heavy water has a distinctly sweeter taste than same-purity normal water and can add to perceived sweetness of sweeteners. In contrast, mice do not prefer D2O over H2O, indicating that they are not likely to perceive heavy water as sweet. HEK 293T cells transfected with the TAS1R2/TAS1R3 heterodimer and chimeric G-proteins are activated by D2O but not by H2O. Lactisole, which is a known sweetness inhibitor acting via the TAS1R3 monomer of the TAS1R2/TAS1R3, suppresses the sweetness of D2O in human sensory tests, as well as the calcium release elicited by D2O in sweet taste receptor-expressing cells. The present multifaceted experimental study, complemented by homology modelling and molecular dynamics simulations, resolves a long-standing controversy about the taste of heavy water, shows that its sweet taste is mediated by the human TAS1R2/TAS1R3 taste receptor, and opens way to future studies of the detailed mechanism of action.

PMID:33824405 | DOI:10.1038/s42003-021-01964-y

Commun Biol. 2021 Apr 6;4(1):459. doi: 10.1038/s42003-021-02005-4.

NO ABSTRACT

PMID:33824400 | DOI:10.1038/s42003-021-02005-4

Commun Biol. 2021 Apr 6;4(1):442. doi: 10.1038/s42003-021-01970-0.

ABSTRACT

Cranial Neural Crest Cells (CNCC) originate at the cephalic region from forebrain, midbrain and hindbrain, migrate into the developing craniofacial region, and subsequently differentiate into multiple cell types. The entire specification, delamination, migration, and differentiation process is highly regulated and abnormalities during this craniofacial development cause birth defects. To better understand the molecular networks underlying CNCC, we integrate paired gene expression & chromatin accessibility data and reconstruct the genome-wide human Regulatory network of CNCC (hReg-CNCC). Consensus optimization predicts high-quality regulations and reveals the architecture of upstream, core, and downstream transcription factors that are associated with functions of neural plate border, specification, and migration. hReg-CNCC allows us to annotate genetic variants of human facial GWAS and disease traits with associated cis-regulatory modules, transcription factors, and target genes. For example, we reveal the distal and combinatorial regulation of multiple SNPs to core TF ALX1 and associations to facial distances and cranial rare disease. In addition, hReg-CNCC connects the DNA sequence differences in evolution, such as ultra-conserved elements and human accelerated regions, with gene expression and phenotype. hReg-CNCC provides a valuable resource to interpret genetic variants as early as gastrulation during embryonic development. The network resources are available at https://github.com/AMSSwanglab/hReg-CNCC .

PMID:33824393 | DOI:10.1038/s42003-021-01970-0

NPJ Vaccines. 2021 Apr 6;6(1):48. doi: 10.1038/s41541-021-00310-x.

ABSTRACT

Despite the importance of immunity against neuraminidase (NA), NA content and immunogenicity are neglected in current influenza vaccines. To address this, a recombinant N1/N2 NA vaccine (NAV) was developed. Stability assays were used to determine optimal temperature and buffer conditions for vaccine storage. The effect of divalent cation-related enhancement of NA stability and activity on N1 and N2 immunogenicity and efficacy against viral challenge was assessed. Differences in activity between N1 and N2 and cation-related activity enhancement did not translate into differences in immunogenicity or efficacy. NAV-vaccinated mice showed robust antibody titers against N1 and N2, and after challenge with influenza A (H1N1) virus, decreased viral titers and decreased antiviral and inflammatory responses by transcriptomic analysis. These findings provide guidance for optimal storage and assessment of NA-based vaccines and confirm the importance of NA in influenza vaccination strategies in attenuating viral replication and limiting inflammatory responses necessary to clear infection.

PMID:33824333 | DOI:10.1038/s41541-021-00310-x

mBio. 2021 Apr 6;12(2):e03438-20. doi: 10.1128/mBio.03438-20.

ABSTRACT

The redox cofactor NADPH is required as a reducing equivalent in about 100 anabolic reactions throughout metabolism. To ensure fitness under all conditions, the demand is fulfilled by a few dehydrogenases in central carbon metabolism that reduce NADP+ with electrons derived from the catabolism of nutrients. In the case of Bacillus subtilis growing on glucose, quantitative flux analyses indicate that NADPH production largely exceeds biosynthetic needs, suggesting a hitherto unknown mechanism for NADPH balancing. We investigated the role of the four malic enzymes present in B. subtilis that could bring about a metabolic cycle for transhydrogenation of NADPH into NADH. Using quantitative 13C metabolic flux analysis, we found that isoform YtsJ alone contributes to NADPH balancing in vivo and demonstrated relevant NADPH-oxidizing activity by YtsJ in vitro To our surprise, we discovered that depending on NADPH, YtsJ switches activity from a pyruvate-producing malic enzyme to a lactate-generating malolactic enzyme. This switch in activity allows YtsJ to adaptively compensate for cellular NADPH over- and underproduction upon demand. Finally, NADPH-dependent bifunctional activity was also detected in the YtsJ homolog in Escherichia coli MaeB. Overall, our study extends the known redox cofactor balancing mechanisms by providing first-time evidence that the type of catalyzed reaction by an enzyme depends on metabolite abundance.IMPORTANCE A new mechanism for NADPH balancing was discovered in Bacillus subtilis It pivots on the bifunctional enzyme YtsJ, which is known to catalyze NADP-dependent malate decarboxylation. We found that in the presence of excessive NADPH, the same enzyme switches to malolactic activity and creates a transhydrogenation cycle that ultimately converts NADPH to NADH. This provides a regulated mechanism to immediately adjust NADPH/NADP+ in response to instantaneous needs.

PMID:33824210 | DOI:10.1128/mBio.03438-20

BMC Plant Biol. 2021 Apr 6;21(1):166. doi: 10.1186/s12870-021-02944-4.

ABSTRACT

BACKGROUND: Pollination accelerate sepal development that enhances plant fitness by protecting seeds in female spinach. This response requires pollination signals that result in the remodeling within the sepal cells for retention and development, but the regulatory mechanism for this response is still unclear. To investigate the early pollination-induced metabolic changes in sepal, we utilize the high-throughput RNA-seq approach.

RESULTS: Spinach variety 'Cornel 9' was used for differentially expressed gene analysis followed by experiments of auxin analog and auxin inhibitor treatments. We first compared the candidate transcripts expressed differentially at different time points (12H, 48H, and 96H) after pollination and detected significant difference in Trp-dependent auxin biosynthesis and auxin modulation and transduction process. Furthermore, several auxin regulatory pathways i.e. cell division, cell wall expansion, and biogenesis were activated from pollination to early developmental symptoms in sepals following pollination. To further confirm the role auxin genes play in the sepal development, auxin analog (2, 4-D; IAA) and auxin transport inhibitor (NPA) with different concentrations gradient were sprayed to the spinach unpollinated and pollinated flowers, respectively. NPA treatment resulted in auxin transport weakening that led to inhibition of sepal development at concentration 0.1 and 1 mM after pollination. 2, 4-D and IAA treatment to unpollinated flowers resulted in sepal development at lower concentration but wilting at higher concentration.

CONCLUSION: We hypothesized that sepal retention and development might have associated with auxin homeostasis that regulates the sepal size by modulating associated pathways. These findings advanced the understanding of this unusual phenomenon of sepal growth instead of abscission after pollination in spinach.

PMID:33823793 | DOI:10.1186/s12870-021-02944-4

Nucleic Acids Res. 2021 Apr 6:gkab180. doi: 10.1093/nar/gkab180. Online ahead of print.

ABSTRACT

The lysine specific demethylase 1 (LSD1) plays a pivotal role in cellular differentiation by regulating the expression of key developmental genes in concert with different coregulatory proteins. This process is impaired in different cancer types and incompletely understood. To comprehensively identify functional coregulators of LSD1, we established a novel tractable fluorescent reporter system to monitor LSD1 activity in living cells. Combining this reporter system with a state-of-the-art multiplexed RNAi screen, we identify the DEAD-box helicase 19A (DDX19A) as a novel coregulator and demonstrate that suppression of Ddx19a results in an increase of R-loops and reduced LSD1-mediated gene silencing. We further show that DDX19A binds to tri-methylated lysine 27 of histone 3 (H3K27me3) and it regulates gene expression through the removal of transcription promoting R-loops. Our results uncover a novel transcriptional regulatory cascade where the downregulation of genes is dependent on the LSD1 mediated demethylation of histone H3 lysine 4 (H3K4). This allows the polycomb repressive complex 2 (PRC2) to methylate H3K27, which serves as a binding site for DDX19A. Finally, the binding of DDX19A leads to the efficient removal of R-loops at active promoters, which further de-represses LSD1 and PRC2, establishing a positive feedback loop leading to a robust repression of the target gene.

PMID:33823549 | DOI:10.1093/nar/gkab180

Mol Hum Reprod. 2021 Apr 6:gaab024. doi: 10.1093/molehr/gaab024. Online ahead of print.

ABSTRACT

The onset of labour is a culmination of a series of highly coordinated and preparatory physiological events that take place throughout the gestational period. In order to produce the associated contractions needed for fetal delivery, smooth muscle cells in the muscular layer of the uterus (i.e. myometrium) undergo a transition from quiescent to contractile phenotypes. Here, we present the current understanding of the roles transcription factors play in critical labour-associated gene expression changes as part of the molecular mechanistic basis for this transition. Consideration is given to both transcription factors that have been well-studied in a myometrial context, i.e. activator protein 1 (AP-1), progesterone receptors (PRs), estrogen receptors (ERs), and nuclear factor kappa B (NF-κB), as well as additional transcription factors whose gestational event-driving contributions have been demonstrated more recently. These transcription factors may form pregnancy- and labour- associated transcriptional regulatory networks in the myometrium to modulate the timing of labour onset. A more thorough understanding of the transcription factor-mediated, labour-promoting regulatory pathways holds promise for the development of new therapeutic treatments that can be used for the prevention of preterm labour in at-risk women.

PMID:33823545 | DOI:10.1093/molehr/gaab024

Environ Pollut. 2021 Mar 24;282:117014. doi: 10.1016/j.envpol.2021.117014. Online ahead of print.

ABSTRACT

Summer intensive air measurements of alkylated polycyclic aromatic compounds (Alk-PACs), nitrated polycyclic aromatic hydrocarbons (NPAHs), and oxygenated polycyclic aromatic hydrocarbons (OPAHs) was conducted during the summer of 2013 at an air monitoring site near the community of Fort McKay in the Athabasca oil sands region (AOSR). This study uses the ambient air measurements in conjunction with supplementary meteorological and air quality data from coordinated ground- and aircraft-based sampling over the same period to characterize diurnal variations and changes in the organic air pollutant profiles associated with the plume episodes. Principal component analysis showed a distinct PAC profile during plume episodes, driven mainly by higher fluorenone (FLO) and 9,10-anthraquinone (ANQ) concentrations. During the plume episodes (August 23-24), means of NPAHs and OPAHs concentrations were 120 and 2020 pg/m3, respectively, which were 2.7 and 2.5 times higher than those measured on the other days, while Alk-PACs did not reach maxima. The relative constancy of Alk-PACs during the plume episodes and baseline air quality periods likely reflects a continuous and broad emission of Alk-PACs from the oil sands mining activities. Only four OPAHs, including FLO, ANQ, benzo(a)fluorenone, and benzanthrone, exhibited higher average daytime than nighttime concentrations (p-value < 0.05). Categorizing air samples into clean and polluted conditions demonstrated that the polluted condition air samples were characterized by higher percent composition of alkylated fluorenes, FLO, MANQ, and photochemically-derived 1M4NN. A comparison of PAC profiles in air samples and oil sand ore samples suggests that the NPAHs were likely influenced by atmospheric formation while the OPAHs were impacted by a combination of primary sources and atmospheric formation. The strong correlations found between a number of NPAHs and OPAHs, and PM2.5 and NOx in this study could support the modelling of ambient air burdens of these compounds across the region.

PMID:33823311 | DOI:10.1016/j.envpol.2021.117014

Biotechnol Adv. 2021 Apr 3:107748. doi: 10.1016/j.biotechadv.2021.107748. Online ahead of print.

ABSTRACT

Rhodococcus spp. are a group of non-model gram-positive bacteria with diverse catabolic activities and strong adaptive capabilities, which enable their wide application in whole-cell biocatalysis, environmental bioremediation, and lignocellulosic biomass conversion. Compared with model microorganisms, the engineering of Rhodococcus is challenging because of the lack of universal molecular tools, high genome GC content (61% ~ 71%), and low transformation and recombination efficiencies. Nevertheless, because of the high interest in Rhodococcus species for bioproduction, various genetic elements and engineering tools have been recently developed for Rhodococcus spp., including R. opacus, R. jostii, R. ruber, and R. erythropolis, leading to the expansion of the genetic toolkits for Rhodococcus engineering. In this article, we provide a comprehensive review of the important developed genetic elements for Rhodococcus, including shuttle vectors, promoters, antibiotic markers, ribosome binding sites, and reporter genes. In addition, we also summarize gene transfer techniques and strategies to improve transformation efficiency, as well as random and precise genome editing tools available for Rhodococcus, including transposition, homologous recombination, recombineering, and CRISPR/Cas9. We conclude by discussing future trends in Rhodococcus engineering. We expect that more synthetic and systems biology tools (such as multiplex genome editing, dynamic regulation, and genome-scale metabolic models) will be adapted and optimized for Rhodococcus.

PMID:33823269 | DOI:10.1016/j.biotechadv.2021.107748

Plant Cell. 2021 Apr 5:koab099. doi: 10.1093/plcell/koab099. Online ahead of print.

ABSTRACT

CRISPR-Cas systems have revolutionized genome engineering by facilitating a wide range of targeted DNA perturbations. These systems have resulted in the development of powerful new screens to test gene functions at the genomic scale. While there is tremendous potential to map and interrogate gene regulatory networks at unprecedented speed and scale using CRISPR screens, their implementation in plants remains in its infancy. Here we discuss the general concepts, tools, and workflows for establishing CRISPR screens in plants and analyze the handful of recent reports describing the use of this strategy to generate mutant knockout collections or to diversify DNA sequences. In addition, we provide insight into how to design CRISPR knockout screens in plants given the current challenges and limitations and examine multiple design options. Finally, we discuss the unique multiplexing capabilities of CRISPR screens to investigate redundant gene function in highly duplicated plant genomes. Combinatorial mutant screens have the potential to routinely generate higher-order mutant collections and facilitate the characterization of gene networks. By integrating this approach with the numerous genomic profiles that have been generated over the past two decades, the implementation of CRISPR screens offers new opportunities to analyze plant genomes at deeper resolution and will lead to great advances in functional and synthetic biology.

PMID:33823021 | DOI:10.1093/plcell/koab099

Plant Cell. 2020 Aug 3;32(8):2457-2473. doi: 10.1105/tpc.19.00716.

ABSTRACT

Deep sequencing of DNase-I treated chromatin (DNase-seq) can be used to identify DNase I-hypersensitive sites (DHSs) and facilitates genome-scale mining of de novo cis-regulatory DNA elements. Here, we adapted DNase-seq to generate genome-wide maps of DHSs using control and cold-treated leaf, stem, and root tissues of three widely studied grass species: Brachypodium distachyon, foxtail millet (Setaria italica), and sorghum (Sorghum bicolor). Functional validation demonstrated that 12 of 15 DHSs drove reporter gene expression in transiently transgenic B. distachyon protoplasts. DHSs under both normal and cold treatment substantially differed among tissues and species. Intriguingly, the putative DHS-derived transcription factors (TFs) are largely colocated among tissues and species and include 17 ubiquitous motifs covering all grass taxa and all tissues examined in this study. This feature allowed us to reconstruct a regulatory network that responds to cold stress. Ethylene-responsive TFs SHINE3, ERF2, and ERF9 occurred frequently in cold feedback loops in the tissues examined, pointing to their possible roles in the regulatory network. Overall, we provide experimental annotation of 322,713 DHSs and 93 derived cold-response TF binding motifs in multiple grasses, which could serve as a valuable resource for elucidating the transcriptional networks that function in the cold-stress response and other physiological processes.

PMID:33822993 | DOI:10.1105/tpc.19.00716

Bioinformatics. 2021 Apr 5:btab187. doi: 10.1093/bioinformatics/btab187. Online ahead of print.

ABSTRACT

SUMMARY: ProDy, an integrated API developed for modelling and analysing protein dynamics, has significantly evolved in recent years in response to the growing data and needs of computational biology community. We present major developments that led to ProDy 2.0: (i) improved interfacing with databases and parsing new file formats, (ii) SignDy for signature dynamics of protein families, (iii) CryoDy for collective dynamics of supramolecular systems using cryo-EM density maps, and (v) essential site scanning analysis (ESSA) for identifying sites essential to modulating global dynamics.

AVAILABILITY AND IMPLEMENTATION: ProDy is open-source and freely available under MIT License from https://github.com/prody/ProDy.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online, and tutorials at http://prody.csb.pitt.edu/.

PMID:33822884 | DOI:10.1093/bioinformatics/btab187

Bioinformatics. 2021 Apr 2:btab227. doi: 10.1093/bioinformatics/btab227. Online ahead of print.

ABSTRACT

SUMMARY: Ordinary differential equation models facilitate the understanding of cellular signal transduction and other biological processes. However, for large and comprehensive models, the computational cost of simulating or calibrating can be limiting. AMICI is a modular toolbox implemented in C ++/Python/MATLAB that provides efficient simulation and sensitivity analysis routines tailored for scalable, gradient-based parameter estimation and uncertainty quantification.

AVAILABILITY: AMICI is published under the permissive BSD-3-Clause license with source code publicly available on https://github.com/AMICI-dev/AMICI. Citeable releases are archived on Zenodo.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:33821950 | DOI:10.1093/bioinformatics/btab227

Elife. 2021 Apr 6;10:e62236. doi: 10.7554/eLife.62236.

ABSTRACT

BACKGROUND: Glucocorticoids are among the most commonly prescribed drugs, but there is no biomarker that can quantify their action. The aim of the study was to identify and validate circulating biomarkers of glucocorticoid action.

METHODS: In a randomized, crossover, single-blind, discovery study, 10 subjects with primary adrenal insufficiency (and no other endocrinopathies) were admitted at the in-patient clinic and studied during physiological glucocorticoid exposure and withdrawal. A randomization plan before the first intervention was used. Besides mild physical and/or mental fatigue and salt craving, no serious adverse events were observed. The transcriptome in peripheral blood mononuclear cells and adipose tissue, plasma miRNAomic, and serum metabolomics were compared between the interventions using integrated multi-omic analysis.

RESULTS: We identified a transcriptomic profile derived from two tissues and a multi-omic cluster, both predictive of glucocorticoid exposure. A microRNA (miR-122-5p) that was correlated with genes and metabolites regulated by glucocorticoid exposure was identified (p=0.009) and replicated in independent studies with varying glucocorticoid exposure (0.01 ≤ p≤0.05).

CONCLUSIONS: We have generated results that construct the basis for successful discovery of biomarker(s) to measure effects of glucocorticoids, allowing strategies to individualize and optimize glucocorticoid therapy, and shedding light on disease etiology related to unphysiological glucocorticoid exposure, such as in cardiovascular disease and obesity.

FUNDING: The Swedish Research Council (Grant 2015-02561 and 2019-01112); The Swedish federal government under the LUA/ALF agreement (Grant ALFGBG-719531); The Swedish Endocrinology Association; The Gothenburg Medical Society; Wellcome Trust; The Medical Research Council, UK; The Chief Scientist Office, UK; The Eva Madura's Foundation; The Research Foundation of Copenhagen University Hospital; and The Danish Rheumatism Association.

CLINICAL TRIAL NUMBER: NCT02152553.

PMID:33821793 | DOI:10.7554/eLife.62236

Elife. 2021 Apr 6;10:e57012. doi: 10.7554/eLife.57012.

ABSTRACT

How do we choose when confronted with many alternatives? There is surprisingly little decision modelling work with large choice sets, despite their prevalence in everyday life. Even further, there is an apparent disconnect between research in small choice sets, supporting a process of gaze-driven evidence accumulation, and research in larger choice sets, arguing for models of optimal choice, satisficing, and hybrids of the two. Here, we bridge this divide by developing and comparing different versions of these models in a many-alternative value-based choice experiment with 9, 16, 25, or 36 alternatives. We find that human choices are best explained by models incorporating an active effect of gaze on subjective value. A gaze-driven, probabilistic version of satisficing generally provides slightly better fits to choices and response times, while the gaze-driven evidence accumulation and comparison model provides the best overall account of the data when also considering the empirical relation between gaze allocation and choice.

PMID:33821787 | DOI:10.7554/eLife.57012

J Sex Res. 2021 Apr 6:1-9. doi: 10.1080/00224499.2021.1903378. Online ahead of print.

ABSTRACT

Male androphilia (i.e., male sexual attraction to adult males) is considered an evolutionary paradox because it is partially influenced by genes and associated with decreased reproduction. Traits associated with attachment to genetic relatives (i.e., kin) could prompt increased kin-directed altruism, thereby offsetting decreased reproduction by helping kin reproduce. These traits include childhood separation anxiety and adulthood neuroticism, which have been associated with feminine gender expression. In prior research, gay men with a receptive (Bottom or Versatile) anal sex role (ASR) reported greater childhood gender nonconformity (GNC) than those with an insertive (Top) ASR. We examined whether ASR groups also differed on recalled childhood separation anxiety and adulthood neuroticism. The Separation Anxiety Scale-Revised and Big-Five Personality Inventory - short form were completed by 350 gay and 146 heterosexual men. For neuroticism, ASR preference groups differed from heterosexual men but not from one another. Gay men who preferred a Bottom or Versatile ASR reported higher recalled childhood separation anxiety than Tops and heterosexual men. Recalled childhood GNC mediated ASR group differences with heterosexual men on childhood separation anxiety. These results indicate that subgroups of gay men delineated by ASR differ on an evolutionarily relevant developmental trait, childhood separation anxiety.

PMID:33821703 | DOI:10.1080/00224499.2021.1903378