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1. Sex differences in DNA methylation in bats

   https://doi.org/10.1101/2025.05.13.653776  

   Rayner, Jack G; Bock, Samantha L; Lonski, Andrew J; Riddle, Nicole C; Wilkinson, Gerald S (May 2025, bioRxiv)

   Sex-biased longevity is observed across a wide range of animal taxa, including bats, for reasons not well understood. Patterns of cytosine methylation vary predictably with age in many organisms, offering a valuable means to investigate differences in patterns of aging at the molecular level. We tested sex differences in cytosine methylation across 14 bat species and compared patterns of age-associated variation. Sex differences were overrepresented on the X chromosome, showing a strong pattern of female hypermethylation within promoter regions. Sex and age-associated differences in methylation were non-randomly distributed with respect to proximity to putative sex hormone receptor binding sites, with sites hypermethylated in males and females tending to be underrepresented near androgen and estrogen receptor binding sites, respectively. Across species, we observed the relative steepness of male versus female slopes of age-associated variation was associated with the strength of precopulatory sexual selection, with especially strong trends towards male-biased age-associated slopes in two harem-polygynous species that exhibit female-biased longevity. Our results offer insights into how patterns of methylation differ across sexes and ages, and raise intriguing questions for future research, such as whether sex differences in molecular aging reflect sex-biased longevity, for which records in bats are sparse. 

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2. Clonality, local population structure and gametophyte sex ratios in cryptic species of the Sphagnum magellanicum complex

   https://doi.org/10.1093/aob/mcad077  

   Shaw, A. Jonathan; Duffy, Aaron M.; Nieto-Lugilde, Marta; Aguero, Blanka; Schuette, Scott; Robinson, Sean; Loveland, James; Hicks, Karen A.; Weston, David; Piatkowski, Bryan; et al (July 2023, Annals of Botany)

   Abstract Background and AimsSphagnum (peatmoss) comprises a moss (Bryophyta) clade with ~300–500 species. The genus has unparalleled ecological importance because Sphagnum-dominated peatlands store almost a third of the terrestrial carbon pool and peatmosses engineer the formation and microtopography of peatlands. Genomic resources for Sphagnum are being actively expanded, but many aspects of their biology are still poorly known. Among these are the degree to which Sphagnum species reproduce asexually, and the relative frequencies of male and female gametophytes in these haploid-dominant plants. We assess clonality and gametophyte sex ratios and test hypotheses about the local-scale distribution of clones and sexes in four North American species of the S. magellanicum complex. These four species are difficult to distinguish morphologically and are very closely related. We also assess microbial communities associated with Sphagnum host plant clones and sexes at two sites. MethodsFour hundred and five samples of the four species, representing 57 populations, were subjected to restriction site-associated DNA sequencing (RADseq). Analyses of population structure and clonality based on the molecular data utilized both phylogenetic and phenetic approaches. Multi-locus genotypes (genets) were identified using the RADseq data. Sexes of sampled ramets were determined using a molecular approach that utilized coverage of loci on the sex chromosomes after the method was validated using a sample of plants that expressed sex phenotypically. Sex ratios were estimated for each species, and populations within species. Difference in fitness between genets was estimated as the numbers of ramets each genet comprised. Degrees of clonality [numbers of genets/numbers of ramets (samples)] within species, among sites, and between gametophyte sexes were estimated. Sex ratios were estimated for each species, and populations within species. Sphagnum-associated microbial communities were assessed at two sites in relation to Sphagnum clonality and sex. Key ResultsAll four species appear to engage in a mixture of sexual and asexual (clonal) reproduction. A single ramet represents most genets but two to eight ramets were dsumbers ansd text etected for some genets. Only one genet is represented by ramets in multiple populations; all other genets are restricted to a single population. Within populations ramets of individual genets are spatially clustered, suggesting limited dispersal even within peatlands. Sex ratios are male-biased in S. diabolicum but female-biased in the other three species, although significantly so only in S. divinum. Neither species nor males/females differ in levels of clonal propagation. At St Regis Lake (NY) and Franklin Bog (VT), microbial community composition is strongly differentiated between the sites, but differences between species, genets and sexes were not detected. Within S. divinum, however, female gametophytes harboured two to three times the number of microbial taxa as males. ConclusionsThese four Sphagnum species all exhibit similar reproductive patterns that result from a mixture of sexual and asexual reproduction. The spatial patterns of clonally replicated ramets of genets suggest that these species fall between the so-called phalanx patterns, where genets abut one another but do not extensively mix because of limited ramet fragmentation, and the guerrilla patterns, where extensive genet fragmentation and dispersal result in greater mixing of different genets. Although sex ratios in bryophytes are most often female-biased, both male and female biases occur in this complex of closely related species. The association of far greater microbial diversity for female gametophytes in S. divinum, which has a female-biased sex ratio, suggests additional research to determine if levels of microbial diversity are consistently correlated with differing patterns of sex ratio biases. 

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3. Mathematical Modeling Suggests That Monocyte Activity May Drive Sex Disparities during Influenza Infection

   https://doi.org/10.3390/v16060837  

   Liparulo, Tatum S; Shoemaker, Jason E (May 2024, Viruses)

   In humans, females of reproductive age often experience a more severe disease during influenza A virus infection, which may be due to differences in their innate immune response. Sex-specific outcomes to influenza infection have been recapitulated in mice, enabling researchers to study viral and immune dynamics in vivo in order to identify immune mechanisms that are differently regulated between the sexes. This study is based on the hypothesis that sex-specific outcomes emerge due to differences in the rates/speeds that select immune components respond. Using publicly available sex-specific murine data, we utilized dynamic mathematical models of the innate immune response to identify candidate mechanisms that may lead to increased disease severity in female mice. We implemented a large computational screen using the Bayesian information criterion (BIC), wherein the goodness of fit of the competing model scenarios is balanced against complexity (i.e., the number of parameters). Our results suggest that having sex-specific rates for proinflammatory monocyte induction by interferon and monocyte inhibition of virus replication provides the simplest (lowest BIC) explanation for the difference observed in the male and female immune responses. Markov-chain Monte Carlo (MCMC) analysis and global sensitivity analysis of the top performing scenario were performed to provide rigorous estimates of the sex-specific parameter distributions and to provide insight into which parameters most affect innate immune responses. Simulations using the top-performing model suggest that monocyte activity could be a key target to reduce influenza disease severity in females. Overall, our Bayesian statistical and dynamic modeling approach suggests that monocyte activity and induction parameters are sex-specific and may explain sex-differences in influenza disease immune dynamics. 

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4. Comprehensive study of sex-based anatomical variations of human brain and development of sex-specific brain templates

   https://doi.org/10.1016/j.brain.2023.100077  

   Ramzanpour, Mohammadreza; Jafari, Bahram; Smith, Jeremy; Allen, Jason; Hajiaghamemar, Marzieh (January 2023, Brain Multiphysics)

   he sex-based human brain structural variations alongside the necessity and development process for sex-specific brain templates were investigated in this study. Comparing magnetic resonance images of 500 female and 500 male subjects, no significant sex-based difference was observed for average cortical thickness, however, all the volumetric values, including the total brain volume (TBV) and major 19 brain regions, were found to be significantly different between females and males. Moreover, analyzing the fractional volume of the regions showed that these sex variations were not proportional to TBV for all regions. These findings underscore the importance of distinguishing the sex-based differences in human brain studies. While brain templates have been developed for general population and cohorts with the same characteristics such as race or age, there is a lack of sex-specific brain templates. To fill this gap and find a representative reference brain image for each sex, nonlinear templates were developed for female, male, and mixed population subjects. Next, a separate set of 109 female and 109 male brain images were used to evaluate the sex-specificity of the brain templates. It was observed that the female and male test subjects were registered to their sex-specific templates with the lowest amount of deformation/warping confirming better representativeness of the sex-specific templates for their target population. The findings of this study including the templates and the reported variations can be used in research involving sex dimorphic brain disorders, diseases, and/or injuries such as traumatic brain injury that is affected by the sex-based brain anatomical differences. Statement of significance: Human brain exhibits sex-based variation both in size and volumetric composition of different regions. Despite these differences, there is a paucity of sex-specific brain templates. Addressing this gap marks the significance of our study as briefly explained here. We have shown that differences in male and female brain go beyond simple scaling and the observation of regional differences that are not proportional to the sex-based total brain volume variations has motivated us to develop sex-specific templates. The representativeness and difference of these sex-specific templates were assessed by measuring the amount of required warping in nonlinear registration of test subjects to them. It was shown that registration of female and male subjects to their corresponding sex-specific template involved lower level of warping compared to their registration to their opposite sex or mixed population brain template. 

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5. Sex differences in early transcriptomic responses to oxidative stress in the copepod Tigriopus californicus

   https://doi.org/10.1186/s12864-020-07179-5  

   Li, Ning; Flanagan, Ben A.; Partridge, MacKenzie; Huang, Elaine J.; Edmands, Suzanne (December 2020, BMC Genomics)

   null (Ed.)

   Abstract Background Patterns of gene expression can be dramatically different between males and females of the same species, in part due to genes on sex chromosomes. Here we test for sex differences in early transcriptomic response to oxidative stress in a species which lacks heteromorphic sex chromosomes, the copepod Tigriopus californicus . Results Male and female individuals were separately exposed to control conditions and pro-oxidant conditions (hydrogen peroxide and paraquat) for periods of 3 hours and 6 hours. Variance partitioning showed the greatest expression variance among individuals, highlighting the important information that can be obscured by the common practice of pooling individuals. Gene expression variance between sexes was greater than that among treatments, showing the profound effect of sex even when males and females share the same genome. Males exhibited a larger response to both pro-oxidants, differentially expressing more than four times as many genes, including up-regulation of more antioxidant genes, heat shock proteins and protease genes. While females differentially expressed fewer genes, the magnitudes of fold change were generally greater, indicating a more targeted response. Although females shared a smaller fraction of differentially expressed genes between stressors and time points, expression patterns of antioxidant and protease genes were more similar between stressors and more GO terms were shared between time points. Conclusions Early transcriptomic responses to the pro-oxidants H 2 O 2 and paraquat in copepods revealed substantial variation among individuals and between sexes. The finding of such profound sex differences in oxidative stress response, even in the absence of sex chromosomes, highlights the importance of studying both sexes and the potential for developing sex-specific strategies to promote optimal health and aging in humans. 

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