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At least 37 records · Page 2

ZW sex chromosome structure in Amborella trichopoda

Sex chromosomes have evolved hundreds of times across the flowering plant tree of life; their recent origins in some members of this clade can shed light on the early consequences of suppressed recombination, a crucial step in sex chromosome evolution. Amborella trichopoda, the sole species of a lineage that is sister to all other extant flowering plants, is dioecious with a young ZW sex determination system. Here we present a haplotype-resolved genome assembly, including highly contiguous assemblies of the Z and W chromosomes. We identify a ~3-megabase sex-determination region (SDR) captured in two strata that includes a ~300-kilobase inversion that is enriched with repetitive sequences and contains a homologue of the Arabidopsis METHYLTHIOADENOSINE NUCLEOSIDASE (MTN1-2) genes, which are known to be involved in fertility. However, the remainder of the SDR does not show patterns typically found in non-recombining SDRs, such as repeat accumulation and gene loss. These findings are consistent with the hypothesis that dioecy is derived in Amborella and the sex chromosome pair has not significantly degenerated.

59 BASIC BIOLOGICAL SCIENCES↗

In-depth quantitative proteomic characterization of organotypic hippocampal slice culture reveals sex-specific differences in biochemical pathways

Sex differences in the brain of mammals range from neuroarchitecture through cognition to cellular metabolism. The hippocampus, a structure mostly associated with learning and memory, presents high vulnerability to neurodegeneration and aging. Therefore, we explored basal sex-related differences in the proteome of organotypic hippocampal slice culture, a major in vitro model for studying the cellular and molecular mechanisms related to neurodegenerative disorders. Results suggest a greater prevalence of astrocytic metabolism in females and significant neuronal metabolism in males. The preference for glucose use in glycolysis, pentose phosphate pathway and glycogen metabolism in females and high abundance of mitochondrial respiration subunits in males support this idea. An overall upregulation of lipid metabolism was observed in females. Upregulation of proteins responsible for neuronal glutamate and GABA synthesis, along with synaptic associated proteins, were observed in males. In general, the significant spectrum of pathways known to predominate in neurons or astrocytes, together with the well-known neuronal and glial markers observed, revealed sex-specific metabolic differences in the hippocampus. TEM qualitative analysis might indicate a greater presence of mitochondria at CA1 synapses in females. These findings are crucial to a better understanding of how sex chromosomes can influence the physiology of cultured hippocampal slices and allow us to gain insights into distinct responses of males and females on neurological diseases that present a sex-biased incidence.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Benefits of colorectal cancer screening using fecal immunochemical testing with varying positivity thresholds by age and sex

Background Fecal immunochemical test (FIT) performance for colorectal cancer screening varies by age and sex, yet most FIT-based screening programs use uniform positivity thresholds. This study assessed the potential benefits of stratifying FIT thresholds based on age and sex. Methods We conducted a meta-analysis of FIT sensitivity and specificity at various positivity thresholds by age and sex. We then used these estimates in 2 microsimulation models of colorectal cancer and projected lifetime clinical outcomes, incremental costs, and quality-adjusted life-years (QALYs) gained from age- and sex-stratified FIT strategies. FIT thresholds ranged from 10 to 50 µg hemoglobin per gram of feces. Results For current uniform FIT screening (20 µg hemoglobin/gram of feces), models projected 85.67 to 122.15 QALYs gained at incremental costs of ‒$982 to $504 per 1000 individuals compared with no screening. At equivalent costs to current uniform screening, only 1 model found stratified FIT approaches cost-effective, yielding a marginal increase of 1.04 and 1.10 QALYs gained/1000 female and male individuals, respectively. At a willingness-to-pay threshold of $100 000/QALYs gained, both models found stratified FIT cutoffs to be the best strategy, with cutoffs being equal to or higher for males and lowest at older ages (70-75 years). Uniform strategies showed comparable effectiveness, falling within 1 quality-adjusted life-day per person of efficient strategies at up to $112 more per person. Results were sensitive to FIT test performance characteristics and 1-time setup costs. Conclusion Stratifying FIT thresholds by age and sex may be cost-effective compared to current screening. The gain in expected health benefits with stratified FIT screening, however, is likely small.

Harlass, Matthias↗

Incubation temperature alters stripe formation and head colouration in American alligator hatchlings and is unaffected by estradiol-induced sex reversal

ABSTRACT Considerations of the impact climate change has on reptiles are typically focused on habitat change or loss, range shifts and skewed sex ratios in species with temperature-dependent sex determination. Here, we show that incubation temperature alters stripe number and head colouration of hatchling American alligators (Alligator mississippiensis). Animals incubated at higher temperatures (33.5°C) had, on average, one more stripe than those at lower temperatures (29.5°C), and also had significantly lighter heads. These patterns were not affected by estradiol-induced sex reversal, suggesting independence from hatchling sex. Therefore, increases in nest temperatures as a result of climate change have the potential to alter pigmentation patterning, which may have implications for offspring fitness.

60 APPLIED LIFE SCIENCES↗

Let’s talk about sex: A biological variable in immune response against melanoma

As science culture gravitates toward a more holistic inclusion of both males and females in research design, the outlining of sex differences and their respective intersections with disease physiology and pathophysiology should see reciprocal expansion. Melanoma skin cancer, for example, has observed a female advantage in incidence, mortality, and overall survival since the early 1970s. The exact biological mechanism of this trend, however, is unclear and further complicated by a layering of clinical variables such as skin phototype, age, and body mass index. In this perspective, we highlight epidemiological evidence of sex differences in melanoma and summarize the landscape of their potential origin. Among several biological hallmarks, we make a note of sex-specific immune profiles—along with divergent hormonal regulation, social practices, DNA damage and oxidative stress responses, body composition, genetic variants, and X-chromosome expression—as probable drivers of disparity in melanoma initiation and progression. This review further focuses the conversation of sex as an influencing factor in melanoma development and its potential implication for disease management and treatment strategies.

59 BASIC BIOLOGICAL SCIENCES↗

The Frequency of Sex: Population Genomics Reveals Differences in Recombination and Population Structure of the Aflatoxin-Producing Fungus Aspergillus flavus

The apparent rarity of sex in many fungal species has raised questions about how much sex is needed to purge deleterious mutations and how differences in frequency of sex impact fungal evolution. We sought to determine how differences in the extent of recombination between populations of Aspergillus flavus impact the evolution of genes associated with the synthesis of aflatoxin, a notoriously potent carcinogen. We sequenced the genomes of, and quantified aflatoxin production in, 94 isolates of A. flavus sampled from seven states in eastern and central latitudinal transects of the United States. The overall population is subdivided into three genetically differentiated populations (A, B, and C) that differ greatly in their extent of recombination, diversity, and aflatoxin-producing ability. Estimates of the number of recombination events and linkage disequilibrium decay suggest relatively frequent sex only in population A. Population B is sympatric with population A but produces significantly less aflatoxin and is the only population where the inability of nonaflatoxigenic isolates to produce aflatoxin was explained by multiple gene deletions. Population expansion evident in population B suggests a recent introduction or range expansion. Population C is largely nonaflatoxigenic and restricted mainly to northern sampling locations through restricted migration and/or selection. Despite differences in the number and type of mutations in the aflatoxin gene cluster, codon optimization and site frequency differences in synonymous and nonsynonymous mutations suggest that low levels of recombination in some A. flavus populations are sufficient to purge deleterious mutations.

59 BASIC BIOLOGICAL SCIENCES↗

Systemic immunological responses are dependent on sex and ovarian hormone presence following acute inhaled woodsmoke exposure

Background: Rural regions of the western United States have experienced a noticeable surge in both the frequency and severity of acute wildfire events, which brings significant challenges to both public safety and environmental conservation efforts, with impacts felt globally. Identifying factors contributing to immune dysfunction, including endocrinological phenotypes, is essential to understanding how hormones may influence toxicological susceptibility. Methods: This exploratory study utilized male and female C57BL/6 mice as in vivo models to investigate distinct responses to acute woodsmoke (WS) exposure with a focus on sex-based differences. In a second set of investigations, two groups were established within the female mouse cohort. In one group, mice experienced ovariectomy (OVX) to simulate an ovarian hormone-deficient state similar to surgical menopause, while the other group received Sham surgery as controls, to investigate the mechanistic role of ovarian hormone presence in driving immune dysregulation following acute WS exposure. Each experimental cohort followed a consecutive 2-day protocol with daily 4-h exposure intervals under two conditions: control HEPA-filtered air (FA) and acute WS to simulate an acute wildfire episode. Results: Metals analysis of WS particulate matter (PM) revealed significantly increased levels of 63 Cu, 182 W, 208 Pb, and 238 U, compared to filtered air (FA) controls, providing insights into the specific metal components most impacted by the changing dynamics of wildfire occurrences in the region. Male and female mice exhibited diverse patterns in lung mRNA cytokine expression following WS exposure, with males showing downregulation and females displaying upregulation, notably for IL-1β, TNF-α, CXCL-1, CCL-5, TGF-β, and IL-6. After acute WS exposure, there were notable differences in the responses of macrophages, neutrophils, and bronchoalveolar lavage (BAL) cytokines IL-10, IL-6, IL-1β, and TNF-α. Significant diverse alterations were observed in BAL cytokines, specifically IL-1β, IL-10, IL-6, and TNF-α, as well as in the populations of immune cells, such as macrophages and polymorphonuclear leukocytes, in both Sham and OVX mice, following acute WS exposure. These findings elucidated the profound influence of hormonal changes on inflammatory outcomes, delineating substantial sex-related differences in immune activation and revealing altered immune responses in OVX mice due to ovarian hormone deficiency. In addition, the flow cytometry analysis highlighted the complex interaction between OVX surgery, acute WS exposure, and their collective impact on immune cell populations within the hematopoietic bone marrow niche. Conclusions: In summary, both male and female mice, alongside females subjected to OVX and those who had sham surgery, exhibit significant variations in the expression of proinflammatory cytokines, chemokines, lung mRNA gene expression, and related functional networks linked to signaling pathways. These differences potentially act as mediators of sex-specific and hormonal influences in the systemic inflammatory response to acute WS exposure during a wildfire event. Understanding the regulatory roles of genes expressed differentially under environmental stressors holds considerable implications, aiding in identifying sex-specific therapeutic targets for addressing acute lung inflammation and injury.

59 BASIC BIOLOGICAL SCIENCES↗

Sequencing and Analysis of the Sex Determination Region of Populus trichocarpa

The ages and sizes of a sex-determination region (SDR) are difficult to determine in non-model species. Due to the lack of recombination and enrichment of repetitive elements in SDRs, the quality of assembly with short sequencing reads is universally low. Unique features present in the SDRs help provide clues about how SDRs are established and how they evolve in the absence of recombination. Several Populus species have been reported with a male heterogametic configuration of sex (XX/XY system) mapped on chromosome 19, but the exact location of the SDR has been inconsistent among species, and thus far, none of these SDRs has been fully assembled in a genomic context. Here we identify the Y-SDR from a Y-linked contig directly from a long-read PacBio assembly of a Populus trichocarpa male individual. We also identified homologous gene sequences in the SDR of P. trichocarpa and the SDR of the W chromosome in Salix purpurea. We show that inverted repeats (IRs) found in the Y-SDR and the W-SDR are lineage-specific. We hypothesize that, although the two IRs are derived from the same orthologous gene within each species, they likely have independent evolutionary histories. Furthermore, the truncated inverted repeats in P. trichocarpa may code for small RNAs that target the homologous gene for RNA-directed DNA methylation. These findings support the hypothesis that diverse sex-determining systems may be achieved through similar evolutionary pathways, thereby providing a possible mechanism to explain the lability of sex-determination systems in plants in general.

59 BASIC BIOLOGICAL SCIENCES↗

De Novo Assembly and Annotation of 11 Diverse Shrub Willow (Salix) Genomes Reveals Novel Gene Organization in Sex-Linked Regions

Poplar and willow species in the Salicaceae are dioecious, yet have been shown to use different sex determination systems located on different chromosomes. Willows in the subgenus Vetrix are interesting for comparative studies of sex determination systems, yet genomic resources for these species are still quite limited. Only a few annotated reference genome assemblies are available, despite many species in use in breeding programs. Here we present de novo assemblies and annotations of 11 shrub willow genomes from six species. Copy number variation of candidate sex determination genes within each genome was characterized and revealed remarkable differences in putative master regulator gene duplication and deletion. We also analyzed copy number and expression of candidate genes involved in floral secondary metabolism, and identified substantial variation across genotypes, which can be used for parental selection in breeding programs. Lastly, we report on a genotype that produces only female descendants and identified gene presence/absence variation in the mitochondrial genome that may be responsible for this unusual inheritance.

59 BASIC BIOLOGICAL SCIENCES↗

Determination and analysis of sex ratios in heme oxygenase 1 gene targeted mouse embryos

Abstract Heme oxygenase 1 or Hmox1 enzyme is involved in catalyzing the first and rate‐limiting step in heme breakdown reactions. Many studies have reported a partial lethality of Hmox1 knockout mice obtained from heterozygous breeding pairs. Similar results were obtained in our transgenic mice colony and a sex specific bias was observed in the favor of males in the adult mice. Hmox1 independent factors which could have caused this bias were initially analyzed and it was found that those factors were not a reason behind this anomaly. Certain studies involving gene knockout hinted toward a prenatal or neonatal lethality of female knockout mice embryos or pups, respectively. In order to check if this bias was occurring in embryonic stages, that is, either if mutant female embryos were dying or if heterozygous mothers were not carrying embryos to term, we analyzed the sex‐ratios in mid‐ and late‐gestational ages (9.5–13.5 dpc and 14.5–18.5 dpc, respectively). Our results did not indicate any significant difference in the sex ratios in embryonic stages; hence, it was concluded that females are not dying in embryonic stages. It can be speculated that these deaths were probably occurring at neonatal age. More studies are required to confirm that the lack of Hmox1 gene products is the sole reason for this female lethality.

Jain, Sidhant↗

Newly identified sex chromosomes in the Sphagnum (peat moss) genome alter carbon sequestration and ecosystem dynamics

Peatlands are crucial sinks for atmospheric carbon but are critically threatened due to warming climates. Sphagnum (peat moss) species are keystone members of peatland communities where they actively engineer hyperacidic conditions, which improves their competitive advantage and accelerates ecosystem-level carbon sequestration. To dissect the molecular and physiological sources of this unique biology, we generated chromosome-scale genomes of two Sphagnum species: S. divinum and S. angustifolium. Sphagnum genomes show no gene colinearity with any other reference genome to date, demonstrating that Sphagnum represents an unsampled lineage of land plant evolution. The genomes also revealed an average recombination rate an order of magnitude higher than vascular land plants and short putative U/V sex chromosomes. These newly described sex chromosomes interact with autosomal loci that significantly impact growth across diverse pH conditions. This discovery demonstrates that the ability of Sphagnum to sequester carbon in acidic peat bogs is mediated by interactions between sex, autosomes and environment.

59 BASIC BIOLOGICAL SCIENCES↗

Low thermal conductivity in Bi 8 CsO 8 SeX 7 (X = Cl, Br) by combining different structural motifs

Understanding the structure–property relationships of materials in order to supress thermal conductivity is crucial for developing efficient thermoelectric generators and thermal barrier coatings. Low thermal conductivity materials can often contain a single dominant phonon scattering mechanism. Here, we highlight how combining different structural features into one material can aid in the design and identification of new materials with low thermal conductivities. We synthesise two new mixed-anion materials, Bi 8 CsO 8 SeX 7 (X = Cl and Br), with low thermal conductivities of 0.27(2) and 0.22(2) W m -1 K -1 respectively, measured along their c-axes at room temperature. The Bi 8 CsO 8 SeX 7 materials possess a combination of bond strength hierarchies, Cs + vacancies, and low frequency Cs + rattling. These different features significantly inhibit phonon transport along different crystallographic directions. Due to sharp bond strength contrast between the van der Waals gaps and [Bi 2 O 2 ] 2+ layers, the Bi 8 CsO 8 SeX 7 materials exhibit thermal conductivities <50% of the theoretical minimum when measured along the stacking direction. Conversely, the thermal conductivity associated with the ab-plane is reduced by Cs + rattling when compared to the structurally and compositionally related BiOCl.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Rates of Seasonal Fuel Loading Do Not Differ by Sex or Overwintering Strategy in Three Species of Bats

For temperate-zone mammals, seasonal changes in weather and food availability often govern energy allocation. In addition, energy allocation strategies usually differ between males and females. Bats are an interesting group in which to evaluate energetic trade-offs as they are highly mobile and lead energetically demanding lives in habitats across a variety of seasonally variable climates. We evaluated year-round changes in body mass and fuel load for three species of bats in northern California: Silver-haired Bat (Lasionycteris noctivagans), California Myotis (Myotis californicus), and Yuma Myotis (Myotis yumanensis). Silver-haired bats are considered migratory species with females likely migrating farther than males. The two species of myotis are considered residents. Body mass of all species peaked in late autumn and was at a minimum during spring. We calculated a fuel load index to normalize size difference between species and sexes. We used sex- and season-specific multiple linear regression models to evaluate rates of change in seasonal fuel loading. Rates of change in fuel load did not differ among species or sexes except for male silver-haired bats that increased fuel loads rapidly during summer. Interspecific comparisons provided valuable insights into the energy allocation and overwintering strategies of these species and are an important initial step toward understanding their ecology over the full annual cycle.

body condition↗

DNA methylation–based age prediction and sex-specific epigenetic aging in a lizard with female-biased longevity

Sex differences in life span are widespread across animal taxa, but their causes remain unresolved. Alterations to the epigenome are hypothesized to contribute to vertebrate aging, and DNA methylation–based aging clocks allow for quantitative estimation of biological aging trajectories. Here, we investigate the influence of age, sex, and their interaction on genome-wide DNA methylation patterns in the brown anole (Anolis sagrei), a lizard with pronounced female-biased survival and longevity. We develop a series of age predictor models and find that, contrary to our predictions, rates of epigenetic aging were not slower in female lizards. However, methylation states at loci acquiring age-associated changes appear to be more “youthful” in young females, suggesting that female DNA methylomes are preemptively fortified in early life in opposition to the direction of age-related drift. Collectively, our findings provide insights into epigenetic aging in reptiles and suggest that early-life epigenetic profiles may be more informative than rates of change for predicting sex biases in longevity.

59 BASIC BIOLOGICAL SCIENCES↗

Age at release affects developmental physiology and sex-specific phenotypic diversity of hatchery steelhead trout (Oncorhynchus mykiss)

Most steelhead trout hatcheries increase growth rate during rearing to produce and release yearling smolts for harvest augmentation, but natural steelhead exhibit variable age of smoltification, so this common rearing practice may not be ideal for programs focused on recovering imperiled wild stocks; therefore, it is important to investigate and compare alternative hatchery rearing methods that promote life history diversity. Over six consecutive years, the Winthrop National Fish Hatchery on the Methow River, WA reared and released paired groups of age-1 (S1) and age-2 (S2) steelhead smolts. To understand how the two rearing methods affected developmental ontogeny and life-history, fish were sampled prior to hatchery release for factors associated with smoltification (size, gill Na+/K+ ATPase activity, and a qualitative smolt phenotype) and sexual maturation (sex, pituitary and testis mRNA transcripts, gonadosomatic index, and plasma 11-ketotestosterone). Our objectives were to quantify levels of smoltification and male maturation during hatchery rearing, combine metrics to estimate residualism (failure to migrate upon release), and compare the treatments by sex. Overall, S2 rearing produced 7.8% more smolts and 44-fold (4.4 vs. 0.1%) more precociously mature males than S1 rearing. Conversely, S1 rearing produced 31.6% more residuals than S2 rearing. While the proportion of total male residuals was comparable between treatments, the S1 treatment produced approximately five-fold more female residuals (20.6 vs. 4.2%). Because residuals contribute minimally to adult returns and the number of returning adult females is critical to the success of salmonid supplementation efforts, developing rearing techniques that maximize migration in females is a management priority. Physiological assessments are useful for characterizing and quantifying the effects and risks of different hatchery rearing regimes on steelhead life-history, in addition to providing sex-specific guidance to inform and optimize conservation management goals in supplementation programs.

Middleton, Mollie A. (ORCID:0009000905577865)↗

Neuroinflammation is dependent on sex and ovarian hormone presence following acute woodsmoke exposure

Woodsmoke (WS) exposure is associated with significant health-related sequelae. Different populations can potentially exhibit varying susceptibility, based on endocrine phenotypes, to WS and investigating neurological impacts following inhaled WS is a growing area of research. In this study, a whole-body inhalation chamber was used to expose both male and female C57BL/6 mice (n = 8 per group) to either control filtered air (FA) or acute WS (0.861 ± 0.210 mg/m 3 ) for 4 h/d for 2 days. Neuroinflammatory and lipid-based biological markers were then assessed. In a second set of studies, female mice were divided into two groups: one group was ovariectomized (OVX) to simulate an ovarian hormone-deficient state (surgical menopause), and the other underwent Sham surgery as controls, to mechanistically assess the impact of ovarian hormone presence on neuroinflammation following FA and acute WS exposure to simulate an acute wildfire episode. There was a statistically significant impact of sex (P ≤ 0.05) and statistically significant interactions between sex and treatment in IL-1β, CXCL-1, TGF-β, and IL-6 brain relative gene expression. Hippocampal and cortex genes also exhibited significant changes in acute WS-exposed Sham and OVX mice, particularly in TGF-β (hippocampus) and CCL-2 and CXCL-1 (cortex). Cortex GFAP optical density (OD) showed a notable elevation in male mice exposed to acute WS, compared to the control FA. Sham and OVX females demonstrated differential GFAP expression, depending on brain region. Overall, targeted lipidomics in phosphatidylcholine (PC) and phosphatidylethanolamine (PE) serum and brain lipids demonstrated more significant changes between control FA and acute WS exposure in female mice, compared to males. In summary, male and female mice show distinct neuroinflammatory markers in response to acute WS exposure. Furthermore, ovarian hormone deficiency may impact the neuroinflammatory response following an acute WS event.

59 BASIC BIOLOGICAL SCIENCES↗

The architecture of resilience: a genome assembly of Myrothamnus flabellifolia sheds light on desiccation tolerance and sex determination

Myrothamnus flabellifolia is a dioecious resurrection plant endemic to southern Africa that has become an important model for understanding desiccation tolerance. Despite its ecological and medicinal significance, genomic and transcriptomic resources for the species are limited. We generated a chromosome-level, haplotype-resolved reference genome assembly and annotation for M. flabellifolia and conducted transcriptomic profiling across a natural dehydration–rehydration time course in the field. Genome architecture and sex determination were characterized, and co-expression network and cis-regulatory element (CRE) enrichment analyses were used to investigate dynamic responses to desiccation. The 1.28-Gb genome exhibits unusually consistent chromatin architecture with unique chromosome organization across highly divergent haplotypes. We identified an XY sexual system with a small sex-determining region on Chromosome 8. Transcriptomic responses varied with dehydration severity, pointing to early suppression of growth, progressive activation of protective mechanisms, and subsequent return to homeostasis upon rehydration. Late embryogenesis abundant and early light-induced protein transcripts were dynamically regulated and showed enrichment of abscisic acid and stress-responsive CREs pointing toward conserved responses. Together, this study provides foundational resources for understanding the genomic architecture and reproductive biology of M. flabellifolia and offers new insights into the mechanisms of desiccation tolerance.

chromosome structure↗

Sex Determination and Ovarian Development in Reptiles and Amphibians: From Genetic Pathways to Environmental Influences

Background: Reptiles and amphibians provide untapped potential for discovering how a diversity of genetic pathways and environmental conditions are incorporated into developmental processes that can lead to similar functional outcomes. These groups display a multitude of reproductive strategies, and whereas many attributes are conserved within groups and even across vertebrates, several aspects of sexual development show considerable variation. Summary: Here, in this review, we focus our attention on the development of the reptilian and amphibian ovary. First, we review and describe the events leading to ovarian development, including sex determination and ovarian maturation, through a comparative lens. We then describe how these events are influenced by environmental factors, focusing on temperature and exposure to anthropogenic chemicals. Lastly, we identify critical knowledge gaps and future research directions that will be crucial to moving forward in our understanding of ovarian development and the influences of the environment in reptiles and amphibians. Key Messages: Reptiles and amphibians provide excellent models for understanding the diversity of sex determination strategies and reproductive development. However, a greater understanding of the basic biology of these systems is necessary for deciphering the adaptive and potentially disruptive implications of embryo-by-environment interactions in a rapidly changing world.

59 BASIC BIOLOGICAL SCIENCES↗