Biology subjects

Hudson, M.

Publications and source records attributed to Hudson, M..

At least 19 recordsLinked to original sources

bioRxiv2026

Metabolic and transcriptional responses reveal co-option of symbiotic processes during early soybean-soybean cyst nematode interaction

The biochemical mechanisms by which virulent populations of soybean cyst nematode (Heterodera glycines, SCN) overcome host resistance are critical to understanding this economically important pathogen. Here, we deployed metabolic and transcriptome profiling of soybean roots during the SCN infection and establishment process to investigate the molecular and biochemical mechanisms of pathogen establishment. Across samples from a time series spanning nematode invasion to syncytium maturation, we demonstrate that compatible SCN infection does not bypass host immunity but systematically remodels it. In a compatible interaction between soybean carrying the high-copy Rhg1 resistance locus challenged with HG Type 2.5.7 SCN virulent on this host, we identify a 72-metabolite defense signature spanning isoflavonoids, triterpenoid saponins, and phenylpropanoids that persist across all infection stages. Despite activation of this metabolic defense signature by the pathogen on infection, defense transcription is near silence by 3 days post-infection, while defense metabolites persist, revealing a critical decoupling of transcriptional and metabolic defense programs at the precise window of syncytium initiation. Suppression of phenylpropanoid accumulation occurs downstream of PAL transcription, indicating a block at the metabolic level invisible to transcriptomics alone. By 5 days post-infection, cytokinin accumulation coincides with nodulin gene induction and phospholipid remodeling consistent with activation of the legume symbiosis program during syncytium maturation. Together, these findings establish that compatibility arises not from failed recognition but from progressive immune dismantling, including suppression of defense chemistry and co-option of the legume-rhizobium symbiosis machinery.

plant biology↗

bioRxiv2026

Detecting DNA methylation patterns suggestive of variable escape from X-chromosome inactivation

The X chromosome is often excluded from studies analyzing associations between traits and DNA methylation. In females, one copy of most genes on the X is inactivated (X-chromosome inactivation; XCI) through DNA methylation of the gene promoter on the inactive X. This leads to challenges in analyzing and interpreting DNA methylation data patterns. Particularly for sex-biased diseases and traits, there may be many loci of interest on the X chromosome, which contains about 5% of the genome. To address the need for appropriate analysis of DNA methylation data on the X chromosome, we develop a statistical approach to infer locus-specific escape from XCI sensitive to phenotype or covariate values. Performance of this method is illustrated by analysis of data from two sex-biased traits: rheumatoid arthritis which is 3-fold more common in females, and recurrent venous thromboembolism which occurs 2.5 times more often in males. Analyses of these two datasets identify new trait-associated loci on the X chromosome, demonstrate the capabilities of the new method for both bisulfite sequencing data and Illumina EPIC data, suggest at least one locus where variable escape may explain a sex-specific disease association, and rule out variable escape as a potential explanation at other loci. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=176 HEIGHT=200 SRC="FIGDIR/small/732395v1_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@108c23aorg.highwire.dtl.DTLVardef@77dc0org.highwire.dtl.DTLVardef@1d105d0org.highwire.dtl.DTLVardef@1d4b543_HPS_FORMAT_FIGEXP M_FIG C_FIG Created with BioRender (bioRender.com)

genomics↗

bioRxiv2026

Neurometabolic correlates of accelerated aging and neurocognitive late effects in long-term survivors of pediatric hodgkin lymphoma and acute lymphoblastic leukemia

Adult survivors of pediatric cancers are at elevated risk for neurocognitive late effects, but how these effects relate to metabolic perturbations in the brain remains unclear. To address this knowledge gap, the present study explored associations between neurometabolite levels and neurocognitive function in adult survivors of Hodgkin lymphoma (HL) and acute lymphocytic leukemia (ALL). Data were collected from a single-center observational study conducted at St. Jude Childrens Research Hospital (SJCRH) between October 2022 and November 2024. Adult survivors of HL (N=11 [5 females]; [≥]5 years post-diagnosis; mean [SD] current age 34 [9.5] years) and ALL (N=24 [16 females]; [≥]5 years post-diagnosis; current age 40 [12.6] years) and community controls (N=35 [17 females]; current age 40 [11] years) completed standardized neurocognitive tests of memory, attention, executive function, and processing speed. Participants also underwent proton magnetic resonance spectroscopy (1H MRS) to quantify neurometabolite levels in the left dorsolateral prefrontal cortex (dlPFC), left hippocampus, and left cerebellum. Analyses used regression models to examine differences in the slope of the relationship between neurometabolite and neurocognitive function or between neurometabolite and age. When comparing HL survivors vs controls, significant interactions were identified for group x age on the ratio of myo-inositol to N-Acetyl aspartic acid (mI/NAA; p=0.007) and group x Gamma-Aminobutyric Acid (GABA) on processing speed (p=0.04) in the left dlPFC. When comparing ALL survivors vs controls, significant interactions were identified for group x myo-inositol on verbal fluency in the left hippocampus (p=0.01) and group x GABA on cognitive flexibility in the left cerebellum (p=0.01). These preliminary findings suggest that neuroinflammation may be a mechanistic underpinning of age-associated neurocognitive impairment in pediatric cancer survivors.

neuroscience↗

bioRxiv2025

Intracellular aggregation of the transthyretin protein is limited by Hsp70 chaperones

Extracellular amyloid deposits are a hallmark feature of systemic protein aggregation diseases such as transthyretin amyloidosis (ATTR). However, emerging evidence suggests that extracellular transthyretin (TTR) aggregates are internalized and result in an intracellular stress response, including elevated Hsp70 levels. While ATTR research has predominantly focused on extracellular TTR amyloid, our understanding of TTR aggregation inside the cell is poorly explored. To better understand how intracellular chaperones impact intracellular TTR, we used a yeast model that expresses TTR fused eGFP (TTR-eGFP) within the cytoplasm. Since the Hsp70 chaperone family, and co-chaperones the J-domain proteins (JDPs) and Hsp110, act as a disaggregase in vitro, we asked how these molecular chaperones impact TTR aggregation intracellularly in vivo. TTR-eGFP forms detergent-soluble high molecular weight (HMW) aggregates in yeast that have biochemistry profiles similar to human patient TTR. While knockdown of the JDP, Sis1, and deletion of the Hsp110, Sse1, appear to slightly increase TTR-eGFP aggregation, the loss of two major yeast Hsp70s, Ssa1 and Ssa2, lead to a significant increase in the size of HMW species. Taken together, our data suggest that Hsp70s limit the formation of HMW TTR aggregates in the intracellular environment. Based on our results, it is possible that the age-related decline of protein homeostasis, including Hsp70s, may promote the intracellular aggregation of TTR.

biochemistry↗

bioRxiv2025

Attentional reconfiguration during acute and sustained fear

BACKGROUNDFear is a fundamental survival mechanism that both enhances the chances of survival by rapid detection and adaptive responses to potential threat and by optimizing sensory input and cognitive processing. Here we used naturalistic design with eye tracking to map the spatiotemporal dynamics of attention and arousal during fearful events with slow and fast temporal dynamics. METHODS21 participants watched a full-length horror movie while their eye-movements were recoded with eye tracker. Moment-to-moment intensity of sustained fear as well as the onsets of the jump scares (acute fear) were annotated and used to predict gaze parameters (fixation duration & counts, blink frequency, saccade amplitude, pupil size and intersubject synchronization of gaze position). RESULTSAcute fear events led to shortening of fixation duration, suppression of blinking, as well as increase of fixation count, saccade amplitude, and pupil size. Sustained fear was in turn associated with increased pupil size and decrease in blinking and saccade amplitude. These effects remained significant when controlling for luminosity. CONCLUSIONSDuring natural vision both acute and sustained fear cause rapid reconfiguration, state dependent and individual changes in visual attention prioritizing that is accompanied by increased affective arousal.

neuroscience↗

bioRxiv2025

HCN channels reveal conserved and divergent physiology in supragranular pyramidal neurons in primate species

The physiological properties of human and rodent neurons differ, yet the extent to which these differences reflect human specializations is often unclear. Compared with their rodent counterparts, human supragranular pyramidal neurons possess enriched HCN-channel-dependent intrinsic membrane properties and a related sensitivity to synaptic inputs containing delta/theta band frequencies. We tested whether other primate species possess enriched HCN-channel dependent membrane properties. We found ubiquitous HCN1 subunit gene expression in supragranular glutamatergic neurons across New World Monkeys, Old-World Monkeys, and great apes in single nucleus RNA-sequencing datasets. Using Patch-seq recordings from acute and cultured brain slices, we found robust HCN-dependent physiological properties in supragranular pyramidal neurons in a species of New-World monkey (Saimiri sciureus) and two species of Old-World Monkey (Macaca mulatta, Macaca nemestrina). In both human and macaque neocortex, HCN-related intrinsic properties increased in magnitude with increasing laminar depth, especially in one transcriptomic cell type. Within this type, HCN dependent properties were more pronounced in macaque than human neurons. These findings indicate that HCN-governed membrane properties and sensitivity to delta/theta band frequencies are roughly conserved in supragranular pyramidal neurons across at least 36 million years of primate evolution.

neuroscience↗

bioRxiv2025

Developing future resilience from signatures of adaptation across the sorghum pangenome

While the green revolution adapted a handful of crops to homogenous and high-input industrialized agriculture, much of the global population still relies on local food production from low-input smallholder farms that grow highly variable crop cultivars. The high diversity of the grain and bioenergy crop sorghum 1-4, and many other crops that were not homogenized during the green revolution 5, not only provides the raw materials for breeders to make substantial gains in cultivar improvement, but also constrains breeding efforts due to highly specialized locally adapted plant phenotypes 6. Here, we construct a 33-member pangenome and identify trait-associated variants in 1,988 cultivars and landraces. We then apply these resources to explore the complex interplay between historical contingency, ongoing adaptation, and the potential for future gains through climate-aware genome-enabled breeding. Specifically, our analyses conclusively demonstrate that multiple nested, deeply diverged, and previously uncharacterized structural variants in the domestication gene SHATTERING1 distinguish the previously established multicentric origin of sorghum. We then apply landscape genomics tests to reveal how gene flow, adaptation, and secondary contact created the complex genetic mosaic in current global breeding networks. Further analysis of climate-gene associations highlights candidate loci underlying adaptation, including the biosynthetic gene cluster for the cyanogenic glucoside dhurrin. Combined, the pangenome-informed variants developed here will enable both trait discovery and subsequent marker assays to accelerate breeding and provide a framework for similar applications in other diverse and non-model crops.

genomics↗

bioRxiv2025

Retroelement expansions underlie genome evolution in stingless bees

Stingless bees are essential pollinators and emerging models for studying behavioral and genomic evolution. In the genus Melipona, a major difference in heterochromatin organization defines two groups: Group I species (e.g., M. quadrifasciata) with <50% of pericentromeric heterochromatin and Group II species (e.g., M. scutellaris) containing >50% heterochromatin across their chromosomes. These differences are thought to correlate with genome size and transposable element (TE) content, offering a unique opportunity to explore how heterochromatin variation, TE dynamics, and chromosomal evolution interact in a phylogenetic context. We present pseudo-chromosome-level genome assemblies for M. quadrifasciata and M. scutellaris obtained by long-read sequencing and Hi-C scaffolding. Comparative analyses reveal conserved synteny but marked divergence in structural variants and TEs. M. scutellaris shows an expansion of retrotransposons, particularly Gypsy/DIRS1 elements, concentrated in TE hotspots linked to chromosomal rearrangements and structural variants. This coincides with distinct methylation entropy and an expansion of histone deacetylase orthologs, potentially affecting heterochromatin organization. The increased ratio of retrotransposons in M. scutellaris is counterbalanced by more DNA transposons in M. quadrifasciata, resulting in genomes of similar overall sizes but of distinct heterochromatin distribution. Advancing our understanding of genome evolution in eusocial insects, we provide high-resolution genomic resources for two Melipona species that differ in heterochromatin content. Our results highlight the complex role of TEs in shaping genomes and underscore their influence on chromosomal and epigenetic innovation, providing strong evidence that TE dynamics underly the striking heterochromatic differences observed in Melipona.

genomics↗

bioRxiv2025

Low Dose Methotrexate has Divergent Effects on Cycling and Resting Human Hematopoietic Stem and Progenitor Cells

Low dose methotrexate (LD-MTX) remains the gold standard in rheumatoid arthritis (RA) therapy. Multiple mechanisms on a variety of immune cells contribute to the anti-inflammatory effects of LD-MTX. Inflammatory signaling is deeply implicated in hematopoiesis by regulating hematopoietic stem and progenitor cell (HSPC) fate decisions; raising the question of whether HSPC are also modulated by LD-MTX. This is the first study to characterize the effects of LD-MTX on HSPC. CD34+ HSPC were isolated from healthy donors non-mobilized peripheral blood. Resting and/or cycling HSPCs were treated with LD-MTX [dose equivalent to that used in RA patients]. Flow cytometry was performed to assess HSPC viability, cell cycle, surface abundance of reduced folate carrier 1 (RFC1), proliferation, reactive oxygen species (ROS) levels, DNA double-strand breaks, p38 activation, and CD34+ subpopulations. HSPC clonogenicity was tested in colony-forming cell assays. Our results indicate that in cycling HSPC, membrane RFC1 is upregulated and, following LD-MTX treatment, they accumulate more intracellular MTX than resting HSPC. In cycling HSPC, LD-MTX inhibits HSPC expansion by promoting S-phase cell-cycle arrest, increases intracellular HSPC ROS levels and DNA damage, and reduces HSPC viability. Those effects involve the activation of the p38 MAPK pathway and are rescued by folinic acid. The effects of LD-MTX are more evident in CD34+CD38High progenitors. In non-cycling HSPC, LD-MTX also reduces the proliferative response while preserving their clonogenicity. In summary, HSPC uptake LD-MTX differentially according to their cycling state. In turn, LD-MTX results in reduced proliferation and the preservation of HSPC clonogenicity. Study Highlight QuestionsO_ST_ABSWhat is the current knowledge on the topic?C_ST_ABSO_LILow dose-methotrexate (LD-MTX) regulates the function of key cells involved in rheumatoid arthritis (RA) pathogenesis (e.g. T cells, macrophages, neutrophils, endothelial cells and fibroblast-like synoviocytes) and through the activation of multiple pathways contribute to the suppression of inflammation in RA. C_LIO_LIInflammatory signaling impacts hematopoiesis by regulating hematopoietic stem and progenitor cells (i.e. HSPC, CD34+ cells). C_LI What question did this study address?O_LIDoes LD-MTX modulate key functional properties of HSPC subpopulations (i.e. resting and/or cycling HSPCs) C_LI What does this study add to our knowledge?O_LIHSPC uptake LD-MTX differentially according to their cycling state. C_LIO_LICycling HSPC upregulate membrane RFC1 and uptake more MTX than resting HSPC with activation of the p38 MAPK pathway. This leads to inhibition of HSPC expansion, increased intracellular ROS levels and DNA damage, and reduced HSPC viability. C_LIO_LILD-MTX preserves the clonogenicity of non-cycling HSPC. C_LI How might this change clinical pharmacology or translational science?O_LIWe describe a novel mechanism of action of LD-MTX that extends its therapeutic effects from mature immune cells to the modulation of hematopoiesis. C_LI

immunology↗

bioRxiv2024

Reward responses to vicarious feeding depend on BMI

Eating is inherently social for humans. Yet, most neuroimaging studies of appetite and food-induced reward have focused on studying brain responses to food intake or viewing pictures of food alone. Here we used functional magnetic resonance imaging (fMRI) to measure haemodynamic responses to "vicarious" feeding. The subjects (n=97) viewed series of short videos representing naturalistic episodes of social eating intermixed with videos without feeding / appetite related content. Viewing the vicarious feeding (versus control) videos activated motor and premotor cortices, thalamus, and dorsolateral prefrontal cortices, consistent with somatomotor and affective engagement. Responses to the feeding videos were also downregulated as a function of the participants BMI. Altogether these results suggest that seeing others eating engages the corresponding motor and affective programs in the viewers brain, potentially increasing appetite and promoting mutual feeding.

neuroscience↗

bioRxiv2024

Enhancing lipid production in plant cells through high-throughput genome editing and phenotyping via a scalable automated pipeline

Plant bioengineering is a time-consuming and labor-intensive process, with no guarantee of achieving the desired trait. Here we report a fast, automated, scalable, high-throughput pipeline for plant bioengineering (FAST-PB). FAST-PB achieves gene cloning, genome editing, and product characterization by integrating automated biofoundry engineering of callus and protoplast cells with single cell matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). We first demonstrate that FAST-PB can streamline the Golden Gate cloning process, with the capacity to construct 96 vectors in parallel. To prove the concept, using FAST-PB, we first found that PEG2050 significantly increases transfection efficiency by over 45%. To validate the pipeline, we established a reporter-gene-free method for CRISPR editing via mutation of HCF136, affecting cellular chlorophyll fluorescence. Next, we applied this pipeline for lipid production and found that diverse lipids were significantly enhanced up to sixfold through introducing multi-gene cassettes via CRISPR activation, and regenerated plant using this platform. Lastly, we harnessed FAST-PB to achieve high-throughput single-cell lipid profiling through the integration of MALDI-MS with the biofoundry, and differentiated engineered and unengineered cells using the single-cell lipidomics. These innovations massively increase the throughput of synthetic biology, genome editing, and metabolic engineering, and change what is possibly using single-cell metabolomics in plants.

synthetic biology↗

bioRxiv2023

Age, sex, and cell type-resolved hypothalamic gene expression across the pubertal transition in mice

Although the hypothalamus plays a critical role in the regulation of puberty, more research is needed to identify the gene regulatory networks that control pubertal timing. Here, we investigate the age-, sex- and cell-type-specific gene regulation in the hypothalamus across the pubertal transition. We used RNA-seq to profile hypothalamic gene expression in male and female mice at five time points spanning the onset of puberty (postnatal days (PD) 12, 22, 27, 32, and 37). By combining this data with hypothalamic scRNA-seq data of pre- and post-pubertal mice, we were able to assign gene expression changes to their cell types of origin. In our colony, pubertal onset occurs earlier in male mice allowing us to focus on genes whose expression is dynamic across ages and offset between sexes and to explore bases of sex effects. Our age-by- sex pattern of expression enriched for biological pathways involved hormone production, neuronal activation, and glial maturation. Additionally, we found a dramatic expansion of oligodendrocytes precursor cells into mature oligodendrocytes spanning the pre-pubertal (PD12) to peri-pubertal (PD27) timepoints, and that genes driving this expansion enrich for genes involved in pubertal regulation. Together, by incorporating multiple biological timepoints with male and female mice simultaneously, our work furthers the understanding of gene and cell-type changes that accompany the development of secondary sex characteristics in both sexes.

genomics↗

bioRxiv2022

Decoding brain basis of laughter and crying in natural scenes.

Laughter and crying are universal signals of prosociality and distress, respectively. Here we investigated the functional brain basis of perceiving laughter and crying using naturalistic functional magnetic resonance imaging (fMRI) approach. We measured haemodynamic brain activity evoked by laughter and crying in three experiments with 100 subjects in each. The subjects i) viewed a 20-minute medley of short video clips, and ii) 30 minutes of a full-length feature film, and iii) listened to 15 minutes of a radio play that all contained bursts of laughter and crying. Intensity of laughing and crying in the videos and radio play was annotated by independent observes, and the resulting time series were used to predict hemodynamic activity to laughter and crying episodes. Multivariate pattern analysis (MVPA) was used to test for regional selectivity in laughter and crying evoked activations. Laughter induced widespread activity in ventral visual cortex and superior and middle temporal and motor cortices. Crying activated thalamus, cingulate cortex along the anterior-posterior axis, insula and orbitofrontal cortex. Both laughter and crying could be decoded accurately (66-77% depending on the experiment) from the BOLD signal, and the voxels contributing most significantly to classification were in superior temporal cortex. These results suggest that perceiving laughter and crying engage distinct neural networks, whose activity suppresses each other to manage appropriate behavioral responses to others bonding and distress signals. Significance statementLaughter and crying are universal signals of prosociality and distress, respectively. They occur in complex, dynamic social settings with variable and dynamically evolving time courses. Here we used functional magnetic resonance imaging experiments and statistical pattern recognition for disentangling the neural systems that encode laughter and crying signals from dynamic and highly naturalistic scenes. These results show that separable neural circuits are engaged in processing distinct types of social attachment cues, and that pattern recognition during dynamic scene perception allows reliable separation of laughter and crying evoked activation patterns. Coordinated activity of these networks allows managing appropriate behavioral responses to others bonding and distress signals.

neuroscience↗

bioRxiv2022

Triangulation reduces the polygon of error for the history of Transeurasian

In a recent study we used an interdisciplinary approach combining linguistics, archaeology and genetics to analyse the Transeurasian languages1. Our analysis concluded that the early dispersals of these languages were driven by agriculture. A preprint published on this server presents objections to the Transeurasian hypothesis and its association with farming dispersals2. However, close inspection of that text reveals numerous misinterpretations and inconsistencies. In the interest of furthering scientific debate over Transeurasian language and population history, we address the critiques, revising datasets and fine-tuning approaches. The linguistic critique questions the quantity and quality of our datasets. Here we show that the number of surviving cognate sets for Transeurasian is in line with that for well-established language families. In addition, we find that Tian et al.s failure to reject a core of regularly corresponding cognates in the basic vocabulary creates ground for a consensus about the genealogical relatability of the Transeurasian languages. The archaeological critique attempts a re-analysis of one Bayesian test using re-scored data only for northern China. Over half of the suggested re-scorings contain inconsistencies and it is not explained why the re-analysis retains the original data for sites outside northern China, comprising almost 60% of the total. More importantly, the sweeping claim that there is no evidence supporting the prehistoric migrations analysed in our study is not backed by any discussion of the archaeological record. With respect to genetics, the preprint claims a re-analysis showing that the data do not conclusively support the farming-driven dispersal of Turkic, Mongolian, and Tungusic, nor the two-wave spread of farming to Korea. In fact, the only genetic re-analysis presented is limited to samples from Korea and Japan and does not contradict our original conservative modelling of Neolithic individuals with Hongshan and our Bronze Age ones with Upper Xiajiadian. In sum, in bringing multiple lines of evidence together through triangulation, we gained a more balanced and richer understanding of Transeurasian dispersals than each discipline could provide individually. Our research doubtless leaves room for improvement but we remain confident that triangulation did not fail, but rather brought us a step closer to understanding the history of the Transeurasian languages.

evolutionary biology↗

bioRxiv2022

Neural responses to biological motion distinguish autistic and schizotypal traits in the general population

Difficulties in social interactions are common to both autism and schizophrenia, and contribute to correlated autistic and schizotypal traits in the neurotypical population. It remains unresolved whether this represents a shared etiology or a superficial phenotypic overlap. Both conditions are associated with atypical neural activity in response to the perception of social stimuli, and also decreased neural synchronization between individuals that may prohibit establishing shared experiences. This study sought to establish if neural activity and neural synchronization associated with biological motion perception are differentially associated with autistic and schizotypal traits in the neurotypical population. Participants watched an audiovisual montage of naturalistic social interactions whilst hemodynamic brain activity was measured with fMRI. A separate sample of participants provided a continuous measure of the extent of biological motion, which was used to predict hemodynamic activity. General Linear Model analysis revealed that biological motion perception was associated with neural activity across the action-observation network. However, inter-subject phase synchronization analysis revealed that neural activity synchronized between individuals in occipital and parietal areas, but de-synchronized in temporal and frontal regions. Autistic traits were associated with a decrease in neural activity (precuneus, middle cingulate gyrus) and schizotypal traits were associated with a decrease in neural synchronization (middle and inferior frontal gyri). Biological motion perception elicits convergent and divergent patterns of neural activity and neural synchronization, and are differentially associated with shared traits related with autism and schizophrenia in the general population, suggesting that they originate from different neural mechanisms.

neuroscience↗

bioRxiv2022

Mice regulate their attentional intensity and arousal to exploit increases in task utility

Changes in autonomic arousal, such as mounting sleep pressure, and changes in motivation, such as fluctuating environmental reward statistics, both profoundly influence behavior. Our experience tells us that we have some capacity to control our arousal when doing so is important, such as staying awake while driving a motor vehicle. However, little is known about how decision computations are jointly influenced by arousal and motivation, including whether animals, such as rodents, can adapt their arousal state to their needs. Here, we developed and show results from an auditory feature-based sustained-attention task with intermittently shifting task utility. We use pupil size to estimate arousal across a wide range of states and apply novel signal detection theoretic and accumulation-to-bound modeling approaches in a large behavioral cohort. We find that both pupil-linked arousal and task utility have major impacts on multiple aspects of performance. Although substantial arousal fluctuations persist across utility conditions, mice partially stabilize their arousal near an intermediate, and optimal, level when task utility is high. Behavioral analyses show that multiple elements of behavior improve during high task utility and that arousal influences some, but not all, of them. Specifically, arousal influences the likelihood and timescale of sensory evidence accumulation, but not the quantity of evidence accumulated per time step while attending. In sum, the results establish specific decision-computational signatures of arousal, motivation, and their interaction, in attention. So doing, we provide an experimental and analysis framework for studying arousal self-regulation in neurotypical brains and diseases such as attention-deficit/hyperactivity disorder.

neuroscience↗

bioRxiv2022

Accurate sex classification from neural responses to sexual stimuli

Sex differences in brain activity evoked by sexual stimuli remain elusive despite robust evidence for stronger enjoyment of and interest towards sexual stimuli in men than in women. To test whether visual sexual stimuli evoke different brain activity patterns in men and women, we measured haemodynamic brain activity induced by visual sexual stimuli in two experiments in 91 subjects (46 males). In one experiment, the subjects viewed sexual and non-sexual film clips and dynamic annotations for nudity in the clips was used to predict their hemodynamic activity. In the second experiment, the subjects viewed sexual and non-sexual pictures in an event-related design. Males showed stronger activation than females in the visual and prefrontal cortices and dorsal attention network in both experiments. Furthermore, using multivariate pattern classification we could accurately predict the sex of the subject on the basis of the brain activity elicited by the sexual stimuli. The classification generalized across the experiments indicating that the sex differences were consistent. Eye tracking data obtained from an independent sample of subjects (N = 110) showed that men looked longer than women at the chest area of the nude female actors in the film clips. These results indicate that visual sexual stimuli evoke discernible brain activity patterns in men and women which may reflect stronger attentional engagement with sexual stimuli in men than women.

neuroscience↗

bioRxiv2022

Postnatal developmental trajectory of sex-biased gene expression in the mouse pituitary gland

The pituitary gland regulates essential physiological processes such as growth, pubertal onset, stress response, metabolism, reproduction, and lactation. While sex biases in these functions and hormone production have been described, the underlying identity, temporal deployment, and cell-type specificity of sex-biased pituitary gene regulatory networks are not fully understood. To capture sex differences in pituitary gene regulation dynamics during postnatal development, we performed 3 untranslated region sequencing and small RNA sequencing to ascertain gene and microRNA expression respectively across five postnatal ages (postnatal days 12, 22, 27, 32, 37) that span the pubertal transition in female and male C57BL/6J mouse pituitaries (n=5-6 biological replicates for each sex at each age). We observed over 900 instances of sex-biased gene expression and 17 sex-biased microRNAs, with the majority of sex differences occurring with puberty. Using miRNA-gene target interaction databases, we identified 18 sex-biased genes that were putative targets of 5 sex-biased microRNAs. In addition, by combining our bulk RNA-seq with publicly available male and female mouse pituitary single-nuclei RNA-seq data, we obtained evidence that cell-type proportion sex differences exist prior to puberty and persist post-puberty for three major hormone-producing cell types: somatotropes, lactotropes, and gonadotropes. Finally, we predicted sex-biased genes in these three pituitary cell types after accounting for cell-type proportion differences between sexes. Our study reveals the identity and postnatal developmental trajectory of sex-biased gene expression in the mouse pituitary. This work also highlights the importance of considering sex biases in cell-type composition when understanding sex differences in the processes regulated by the pituitary gland. HighlightsO_LIMale and female mouse pituitary gland gene and miRNA expression was profiled across five postnatal ages spanning pubertal development C_LIO_LIAbundant sex differences in pituitary gene expression exist prior to puberty and become more prominent upon puberty C_LIO_LICombining expression data from genes and miRNAs revealed 18 putative sex-biased gene targets of 5 sex-biased miRNAs C_LIO_LISex differences in the proportions of somatotropes, lactotropes, and gonadotropes are predicted to occur prior to puberty C_LI

genomics↗