Ubiquitous Function Research Articles

Loss of coordination between basic cellular processes in human aging.

Age-related loss of gene expression coordination has been reported for distinct cell types and may lead to impaired cellular function. Here we propose a method for quantifying age-related changes in transcriptional regulatory relationships between genes, based on a model learned from external data. We used this method to uncover age-related trends in gene-gene relationships across eight human tissues, which demonstrates that reduced co-expression may also result from coordinated transcriptional responses. Our analyses reveal similar numbers of strengthening and weakening gene-gene relationships with age, impacting both tissue-specific (for example, coagulation in blood) and ubiquitous biological functions. Regulatory relationships becoming weaker with age were established mostly between genes operating in distinct cellular processes. As opposed to that, regulatory relationships becoming stronger with age were established both within and between different cellular functions. Our work reveals that, although most transcriptional regulatory gene-gene relationships are maintained during aging, those with declining regulatory coupling result mostly from a loss of coordination between distinct cellular processes.

Negation mitigates rather than inverts the neural representations of adjectives.

Combinatoric linguistic operations underpin human language processes, but how meaning is composed and refined in the mind of the reader is not well understood. We address this puzzle by exploiting the ubiquitous function of negation. We track the online effects of negation ("not") and intensifiers ("really") on the representation of scalar adjectives (e.g., "good") in parametrically designed behavioral and neurophysiological (MEG) experiments. The behavioral data show that participants first interpret negated adjectives as affirmative and later modify their interpretation towards, but never exactly as, the opposite meaning. Decoding analyses of neural activity further reveal significant above chance decoding accuracy for negated adjectives within 600 ms from adjective onset, suggesting that negation does not invert the representation of adjectives (i.e., "not bad" represented as "good"); furthermore, decoding accuracy for negated adjectives is found to be significantly lower than that for affirmative adjectives. Overall, these results suggest that negation mitigates rather than inverts the neural representations of adjectives. This putative suppression mechanism of negation is supported by increased synchronization of beta-band neural activity in sensorimotor areas. The analysis of negation provides a steppingstone to understand how the human brain represents changes of meaning over time.

Ubiquitous filter feeders shape open ocean microbial community structure and function.

The mechanism of mortality plays a large role in how microorganisms in the open ocean contribute to global energy and nutrient cycling. Salps are ubiquitous pelagic tunicates that are a well-known mortality source for large phototrophic microorganisms in coastal and high-latitude systems, but their impact on the immense populations of smaller prokaryotes in the tropical and subtropical open ocean gyres is not well quantified. We used robustly quantitative techniques to measure salp clearance and enrichment of specific microbial functional groups in the North Pacific Subtropical Gyre, one of the largest ecosystems on Earth. We discovered that salps are a previously unknown predator of the globally abundant nitrogen fixer Crocosphaera; thus, salps restrain new nitrogen delivery to the marine ecosystem. We show that the ocean's two numerically dominant cells, Prochlorococcus and SAR11, are not consumed by salps, which offers a new explanation for the dominance of small cells in open ocean systems. We also identified a double bonus for Prochlorococcus, wherein it not only escapes salp predation but the salps also remove one of its major mixotrophic predators, the prymnesiophyte Chrysochromulina. When we modeled the interaction between salp mesh and particles, we found that cell size alone could not account for these prey selection patterns. Instead, the results suggest that alternative mechanisms, such as surface property, shape, nutritional quality, or even prey behavior, determine which microbial cells are consumed by salps. Together, these results identify salps as a major factor in shaping the structure, function, and ecology of open ocean microbial communities.

DNA hypomethylation characterizes genes encoding tissue-dominant functional proteins in liver and skeletal muscle

Each tissue has a dominant set of functional proteins required to mediate tissue-specific functions. Epigenetic modifications, transcription, and translational efficiency control tissue-dominant protein production. However, the coordination of these regulatory mechanisms to achieve such tissue-specific protein production remains unclear. Here, we analyzed the DNA methylome, transcriptome, and proteome in mouse liver and skeletal muscle. We found that DNA hypomethylation at promoter regions is globally associated with liver-dominant or skeletal muscle-dominant functional protein production within each tissue, as well as with genes encoding proteins involved in ubiquitous functions in both tissues. Thus, genes encoding liver-dominant proteins, such as those involved in glycolysis or gluconeogenesis, the urea cycle, complement and coagulation systems, enzymes of tryptophan metabolism, and cytochrome P450-related metabolism, were hypomethylated in the liver, whereas those encoding-skeletal muscle-dominant proteins, such as those involved in sarcomere organization, were hypomethylated in the skeletal muscle. Thus, DNA hypomethylation characterizes genes encoding tissue-dominant functional proteins.

Radiation impacts gene redundancy and biofilm regulation of cryoconite microbiomes in Northern Hemisphere glaciers

BackgroundGlaciers harbor diverse microorganisms adapted to extreme conditions with high radiation, fluctuating temperature, and low nutrient availability. In glacial ecosystems, cryoconite granules are hotspots of microbial metabolic activity and could influences the biogeochemical cycle on glacier surface. Climate change could influence glacier dynamics by changing regional meteorological factors (e.g., radiation, precipitation, temperature, wind, and evaporation). Moreover, meteorological factors not only influence glacier dynamics but also directly or indirectly influence cryoconite microbiomes. However, the relationship of the meteorological factors and cryoconite microbiome are poorly understood.ResultsHere, we collected 88 metagenomes from 26 glaciers distributed in the Northern Hemisphere with corresponding public meteorological data to reveal the relationship between meteorological factors and variation of cryoconite microbiome. Our results showed significant differences in taxonomic and genomic characteristics between cryoconite generalists and specialists. Additionally, we found that the biogeography of both generalists and specialists was influenced by solar radiation. Specialists with smaller genome size and lower gene redundancy were more abundant under high radiation stress, implying that streamlined genomes are more adapted to high radiation conditions. Network analysis revealed that biofilm regulation is a ubiquitous function in response to radiation stress, and hub genes were associated with the formation and dispersion of biofilms.ConclusionThese findings enhance our understanding of glacier cryoconite microbiome variation on a hemispheric scale and indicate the response mechanisms to radiation stress, which will support forecasts of the ecological consequences of future climate change.3hvtG_8RFcL8puNgr6T9zaVideo

Harnessing Oleanolic Acid and Its Derivatives as Modulators of Metabolic Nuclear Receptors.

Nuclear receptors (NRs) constitute a superfamily of ligand-activated transcription factors with a paramount role in ubiquitous physiological functions such as metabolism, growth, and reproduction. Owing to their physiological role and druggability, NRs are deemed attractive and valid targets for medicinal chemists. Pentacyclic triterpenes (PTs) represent one of the most important phytochemical classes present in higher plants, where oleanolic acid (OA) is the most studied PTs representative owing to its multitude of biological activities against cancer, inflammation, diabetes, and liver injury. PTs possess a lipophilic skeleton that imitates the NRs endogenous ligands. Herein, we report a literature overview on the modulation of metabolic NRs by OA and its semi-synthetic derivatives, highlighting their health benefits and potential therapeutic applications. Indeed, OA exhibited varying pharmacological effects on FXR, PPAR, LXR, RXR, PXR, and ROR in a tissue-specific manner. Owing to these NRs modulation, OA showed prominent hepatoprotective properties comparable to ursodeoxycholic acid (UDCA) in a bile duct ligation mice model and antiatherosclerosis effect as simvastatin in a model of New Zealand white (NZW) rabbits. It also demonstrated a great promise in alleviating non-alcoholic steatohepatitis (NASH) and liver fibrosis, attenuated alpha-naphthol isothiocyanate (ANIT)-induced cholestatic liver injury, and controlled blood glucose levels, making it a key player in the therapy of metabolic diseases. We also compiled OA semi-synthetic derivatives and explored their synthetic pathways and pharmacological effects on NRs, showcasing their structure-activity relationship (SAR). To the best of our knowledge, this is the first review article to highlight OA activity in terms of NRs modulation.

JAK3 Y841 Autophosphorylation Is Critical for STAT5B Activation, Kinase Domain Stability and Dimer Formation.

Janus tyrosine kinase 3 (JAK3) is primarily expressed in immune cells and is needed for signaling by the common gamma chain (γc) family of cytokines. Abnormal JAK3 signal transduction can manifest as hematological disorders, e.g., leukemia, severe combined immunodeficiency (SCID) and autoimmune disease states. While regulatory JAK3 phosphosites have been well studied, here a functional proteomics approach coupling a JAK3 autokinase assay to mass spectrometry revealed ten previously unreported autophosphorylation sites (Y105, Y190, Y238, Y399, Y633, Y637, Y738, Y762, Y824, and Y841). Of interest, Y841 was determined to be evolutionarily conserved across multiple species and JAK family members, suggesting a broader role for this residue. Phospho-substitution mutants confirmed that Y841 is also required for STAT5 tyrosine phosphorylation. The homologous JAK1 residue Y894 elicited a similar response to mutagenesis, indicating the shared importance for this site in JAK family members. Phospho-specific Y841-JAK3 antibodies recognized activated kinase from various T-cell lines and transforming JAK3 mutants. Computational biophysics analysis linked Y841 phosphorylation to enhanced JAK3 JH1 domain stability across pH environments, as well as to facilitated complementary electrostatic JH1 dimer formation. Interestingly, Y841 is not limited to tyrosine kinases, suggesting it represents a conserved ubiquitous enzymatic function that may hold therapeutic potential across multiple kinase families.

Non-Canonical Amino Acids as Building Blocks for Peptidomimetics: Structure, Function, and Applications.

This review provides a fresh overview of non-canonical amino acids and their applications in the design of peptidomimetics. Non-canonical amino acids appear widely distributed in nature and are known to enhance the stability of specific secondary structures and/or biological function. Contrary to the ubiquitous DNA-encoded amino acids, the structure and function of these residues are not fully understood. Here, results from experimental and molecular modelling approaches are gathered to classify several classes of non-canonical amino acids according to their ability to induce specific secondary structures yielding different biological functions and improved stability. Regarding side-chain modifications, symmetrical and asymmetrical α,α-dialkyl glycines, Cα to Cα cyclized amino acids, proline analogues, β-substituted amino acids, and α,β-dehydro amino acids are some of the non-canonical representatives addressed. Backbone modifications were also examined, especially those that result in retro-inverso peptidomimetics and depsipeptides. All this knowledge has an important application in the field of peptidomimetics, which is in continuous progress and promises to deliver new biologically active molecules and new materials in the near future.

Steroid receptors in the testis: implications in the physiology of prenatal and postnatal development and translation to clinical application.

The testes are the main source of sex steroids in the male, especially androgens and to a lesser extent estrogens. In target cells, steroid hormones typically signal after binding to intracellular receptors, which act as transcription factors. Androgens and estrogens have ubiquitous functions in peripheral organs, but also have paracrine actions within the gonads where they are far more concentrated. The levels of steroid production by the testes vary throughout fetal and postnatal development: they are high in intrauterine life and in the first months after birth, then they decline and are almost undetectable in childhood and increase again during puberty to attain adult levels. The expression of the androgen and estrogen receptors also depict specific ontogenies in the various testicular cell types. The combination of intratesticular steroid concentration with the pattern of expression of the steroid hormone receptors defines androgen and estrogen action on Sertoli, germ and Leydig cells. Here, we review the ontogeny of expression of the androgen and estrogen receptors in the testis, its impact on testicular physiology during prenatal and postnatal development, as well as its implication on the pathophysiology of different disorders affecting gonadal function throughout life.

The Origin of Persistently Nonthermal Solar Wind Electrons: the Steady Electron Runaway Model's Demonstration of Dreicer Bifurcation using Measured and Ion–Electron Coulomb Drag

The Steady Electron Runaway Model (SERM) develops the hypothesis that the solar wind’s observed ubiquitous nonthermal electron velocity distribution functions (eVDFs) are caused by Dreicer's velocity space bifurcation in the strong dimensionless required by quasi-neutrality. SERM’s predicted partitions for the pressure and density are contrasted with appropriately adapted eVDF properties from the Wind 3DP experiment (1995–1998), based on in situ observations of . The observed number fraction of electrons in runaway, δ 3DP, follows a thousandfold decline of Dreicer’s predicted fraction, δ, across the observed tenfold reduction of , satisfying δ 3DP ≃ δ 0.89. SERM’s predictions are shown to reproduce the observed variations with of the electron partial pressure and excess kurtosis, . and are positively correlated across 4 yr, as expected by the SERM–Dreicer origin of the suprathermals. SERM quantitatively explains the observed 50 yr anticorrelation between δ 3DP and the partition slope temperature ratios. This documentation quantitatively establishes Coulomb runaway physics as the missing determinant of the ubiquitous nonthermal solar wind eVDF. Astrophysical plasmas, like stellar winds, are unavoidably inhomogeneous, requiring to enforce quasi-neutrality. Between the stars is expected to be sufficiently large that measurable runaway density fractions (0.1%–30%) will occur, producing widespread leptokurtic eVDFs. Using inhomogeneous two-fluid information, SERM predicts spatially dependent leptokurtic eVDF profiles consonant with Coulomb collisions and the fluid’s E ∥(r). SERM can also comment on its eVDFs’ consistency with Maxwellians presumed in the Spitzer–Härm closure. The solar wind profile shows the implied strong radial gradient of the plasma eVDF’s transformation from near thermal to strongly leptokurtic across 1.5–6 R ⊙.

Aquaporin-mediated dysregulation of cell migration in disease states.

Dysregulated cell migration and invasion are hallmarks of many disease states. This dysregulated migratory behavior is influenced by the changes in expression of aquaporins (AQPs) that occur during pathogenesis, including conditions such as cancer, endometriosis, and arthritis. The ubiquitous function of AQPs in migration of diseased cells makes them a crucial target for potential therapeutics; this possibility has led to extensive research into the specific mechanisms underlying AQP-mediated diseased cell migration. The functions of AQPs depend on a diverse set of variables including cell type, AQP isoform, disease state, cell microenvironments, and even the subcellular localization of AQPs. To consolidate the considerable work that has been conducted across these numerous variables, here we summarize and review the last decade's research covering the role of AQPs in the migration and invasion of cells in diseased states.

Diagnosis of Extracellular Vesicles in Cardiovascular and Metabolic Diseases.

Early detection and identification of those with or at increased risk for cardiovascular disease (CVD) and metabolic dysfunction is crucial for improving disease management and prognosis. Given the complex, multifactorial nature of the pathogenesis of the CVD and metabolic dysfunction, it is essential to have biomarkers that encompass the multiple facets of disease development. The uniquely ubiquitous nature and functionality of extracellular vesicles (EVs) in various disease pathologies can provide novel insight into both diagnosis and prognosis while further improving assessments used in clinical and research practice. Herein we summarize the use of EV count and content (including miRNA and protein) in diagnosis of CVD, obesity, metabolic syndrome, and type 2 diabetes (T2D), as well as highlight the potential utility for enhancing determination of prognosis and long-term complications in these clinical populations. Although the results are promising, future work is needed in both methodology and in relation to other factors such as sex and medications, in order to apply these findings in clinical practice.

Modular knots, automorphic forms, and the Rademacher symbols for triangle groups.

É. Ghys proved that the linking numbers of modular knots and the "missing" trefoil in coincide with the values of a highly ubiquitous function called the Rademacher symbol for . In this article, we replace by the triangle group for any coprime pair (p,q) of integers with . We invoke the theory of harmonic Maass forms for to introduce the notion of the Rademacher symbol , and provide several characterizations. Among other things, we generalize Ghys's theorem for modular knots around any "missing" torus knot in and in a lens space.

New books & media

A Traveler’s Guide to the StarsSection:ChooseTop of pageA Traveler’s Guide to the... <<Einstein: The Man and His...Engines: The Inner Workin...A Traveler’s Guide to the Stars, Les Johnson, Princeton U. Press, 2022, $27.95Although people have been dreaming of space exploration for decades, visiting and settling other worlds is still the stuff of science fiction. Nevertheless, in A Traveler’s Guide to the Stars, the physicist Les Johnson, a long-time proponent of interstellar travel, discusses what it will take to reach for the stars. After first providing a brief history of spaceflight and pondering potential destinations, Johnson launches into the core of the book: the technology challenges that will need to be met, which include revolutionary advancements in spacecraft propulsion, communications, navigation, and life-support systems. Rather than discourage, however, Johnson aims to encourage readers from all disciplines, not just science and engineering, to “think big.” —ccEinstein: The Man and His MindSection:ChooseTop of pageA Traveler’s Guide to the...Einstein: The Man and His... <<Engines: The Inner Workin...Einstein: The Man and His Mind, Gary S. Berger and Michael DiRuggiero, Damiani, 2022, $70.00Nearing 70 years after Albert Einstein’s death, the mystique surrounding the physicist shows no signs of abating. Probably the first celebrity scientist, his name alone is synonymous with genius. This new coffee-table book published by the Italian art press Damiani reproduces over a hundred Einstein-related items—including photographs, letters, and offprints of his scientific articles—from the private collection of Gary Berger. It distinguishes itself from the realm of kitschy Einsteiniana in how the documents illustrate the physicist’s human side: The letters and the inscriptions on the photos show how even after decades in the US, Einstein’s social circles remained dominated by Germanophone émigrés such as the photographer Lotte Jacobi. —rdEngines: The Inner Workings of Machines That Move the WorldSection:ChooseTop of pageA Traveler’s Guide to the...Einstein: The Man and His...Engines: The Inner Workin... <<Engines: The Inner Workings of Machines That Move the World, Theodore Gray; photographs by Nick Mann, Black Dog & Leventhal, 2022, $32.00This new large-format book by Theodore Gray, an author and chemistry enthusiast, is a tinkerer’s dream. Featuring images, cross sections, and diagrams of engines and motors of all varieties, Engines delves into how those ubiquitous devices function. A particular highlight is Gray’s deep dive into the diesel-powered hydraulic motors used by the Amish, who generally eschew electricity but still need to produce furniture on an industrial scale: They retrofit commercial electric devices to use compressed-air motors. The book mainly focuses on steam engines, internal-combustion engines, and electric motors, and a final chapter examines a grab bag of devices such as linear motors and sewing machines. —rd© 2022 American Institute of Physics.

The Cup Whisperer

The Cup Whisperer

Thermal management for the shear-rate driven flow of Carreau fluid in a ciliated channel

Cilia beating impacts bio-fluid transport, and the channels with ciliated walls are ubiquitous functions. This innovative study investigates the properties of Careau fluid’s heat and mass transport in a ciliated channel. A 2D wavy channel caused by a metachronal wave of cilia beating is taken, and the flow is considered laminar and incompressible. The viscosities of a generalized Newtonian fluid (Carreau fluid) are affected by both infinite and zero shear rates. It is necessary to convert fixed coordinates to moving coordinates. The system is then clarified on the assumption that the half-width of the channel is significantly less than the wavelength of the metachronal wave and Reynolds number Re is lower. Small Reynolds number and wave number hypotheses simplify the constitutive equations. To resolve the simplified system, a perturbation approach using a stream function is employed. In the end, in this work, the relationship between the thermal transfer coefficient and temperature distribution was shown. various physical factors. This research investigates the effects of several boundary layers on fluid flow. Additionally, there are graphs showing the growth in pressure, velocity field, and streamline. The aim is to provide promising outcomes in creating biomaterial and biomedical devices. It is observed that an accelerate in cilia length accelerates horizontal velocity and time mean volume flow rate and that apparent deceleration emerges in the boundary regions.

Gut Microbiome-Wide Search for Bacterial Azoreductases Reveals Potentially Uncharacterized Azoreductases Encoded in the Human Gut Microbiome.

The human gut is home to trillions of microorganisms that are responsible for the modification of many orally administered drugs, leading to a wide range of therapeutic outcomes. Prodrugs bearing an azo bond are designed to treat inflammatory bowel disease and colorectal cancer via microbial azo reduction, allowing for topical application of therapeutic moieties to the diseased tissue in the intestines. Despite the inextricable link between microbial azo reduction and the efficacy of azo prodrugs, the prevalence, abundance, and distribution of azoreductases have not been systematically examined across the gut microbiome. Here, we curated and clustered amino acid sequences of experimentally confirmed bacterial azoreductases and conducted a hidden Markov model-driven homolog search for these enzymes across 4644 genome sequences present in the representative Unified Human Gastrointestinal Genomes collection. We identified 1958 putative azo-reducing species, corroborating previous findings that azo reduction appears to be a ubiquitous function of the gut microbiome. However, through a systematic comparison of predicted and confirmed azo-reducing strains, we hypothesize the presence of uncharacterized azoreductases in 25 prominent strains of the human gut microbiome. Finally, we confirmed the azo reduction of Acid Orange 7 by multiple strains of Fusobacterium nucleatum, Bacteroides fragilis, and Clostridium clostridioforme Together, these results suggest the presence and activity of many uncharacterized azoreductases in the human gut microbiome and motivate future studies aimed at characterizing azoreductase genes in prominent members of the human gut microbiome. SIGNIFICANCE STATEMENT: This work systematically examined the prevalence, abundance, and distribution of azoreductases across the healthy and inflammatory bowel disease human gut microbiome, revealing potentially uncharacterized azoreductase genes. It also confirmed the reduction of Acid Orange 7 by strains of Fusobacterium nucleatum, Bacteroides fragilis, and Clostridium clostridioforme.

Silicon nitride stress-optic microresonator modulator for optical control applications.

Modulation-based control and locking of lasers, filters and other photonic components is a ubiquitous function across many applications that span the visible to infrared (IR), including atomic, molecular and optical (AMO), quantum sciences, fiber communications, metrology, and microwave photonics. Today, modulators used to realize these control functions consist of high-power bulk-optic components for tuning, sideband modulation, and phase and frequency shifting, while providing low optical insertion loss and operation from DC to 10s of MHz. In order to reduce the size, weight and cost of these applications and improve their scalability and reliability, modulation control functions need to be implemented in a low loss, wafer-scale CMOS-compatible photonic integration platform. The silicon nitride integration platform has been successful at realizing extremely low waveguide losses across the visible to infrared and components including high performance lasers, filters, resonators, stabilization cavities, and optical frequency combs. Yet, progress towards implementing low loss, low power modulators in the silicon nitride platform, while maintaining wafer-scale process compatibility has been limited. Here we report a significant advance in integration of a piezo-electric (PZT, lead zirconate titanate) actuated micro-ring modulation in a fully-planar, wafer-scale silicon nitride platform, that maintains low optical loss (0.03 dB/cm in a 625 µm resonator) at 1550 nm, with an order of magnitude increase in bandwidth (DC - 15 MHz 3-dB and DC - 25 MHz 6-dB) and order of magnitude lower power consumption of 20 nW improvement over prior PZT modulators. The modulator provides a >14 dB extinction ratio (ER) and 7.1 million quality-factor (Q) over the entire 4 GHz tuning range, a tuning efficiency of 162 MHz/V, and delivers the linearity required for control applications with 65.1 dB·Hz2/3 and 73.8 dB·Hz2/3 third-order intermodulation distortion (IMD3) spurious free dynamic range (SFDR) at 1 MHz and 10 MHz respectively. We demonstrate two control applications, laser stabilization in a Pound-Drever Hall (PDH) lock loop, reducing laser frequency noise by 40 dB, and as a laser carrier tracking filter. This PZT modulator design can be extended to the visible in the ultra-low loss silicon nitride platform with minor waveguide design changes. This integration of PZT modulation in the ultra-low loss silicon nitride waveguide platform enables modulator control functions in a wide range of visible to IR applications such as atomic and molecular transition locking for cooling, trapping and probing, controllable optical frequency combs, low-power external cavity tunable lasers, quantum computers, sensors and communications, atomic clocks, and tunable ultra-low linewidth lasers and ultra-low phase noise microwave synthesizers.

Heterogeneity of enhancers embodies shared and representative functional groups underlying developmental and cell type-specific gene regulation

While enhancers in a particular tissue coordinately fulfill regulatory functions, these functions are heterogeneous in nature and comprise of multiple enhancer subclasses and the associated regulatory mechanisms. In this work, we used multiple cell lines to identify enhancer subclasses linked to development, differentiation, and cellular identity. We found that enhancer functional heterogeneity during development encompasses subclasses of ubiquitous functions (11%), development specific regulatory activity (62%), and chromatin interactions (12%). In differentiated cell lines, ubiquitous enhancers (10%) stay active across multiple cell lines.They are accompanied by a large enhancer subclass (ranging from 33% to 63%) with functions specific to the corresponding lineage. The remaining enhancers (27–40%) establish regulatory chromatin structure and facilitate interactions of cell type-specific enhancers with their target promoters. In addition to specialized functions of cell type-specific enhancers, we show that proper accounting of enhancer heterogeneity leads to a 10% increase in accuracy of enhancer classification, which significantly improves the modeling of enhancers and identification of underlying regulatory mechanisms. In summary, our observations suggest that although cell type-specific enhancers are heterogeneous and coordinate different regulatory programs, enhancers from different cell lines maintain common categories of functional groups across developmental and differentiation stages, indicating a higher order rule followed by enhancer-gene regulation.

Unravelling the sex-specific diversity and functions of adrenal gland macrophages.

SummaryDespite the ubiquitous function of macrophages across the body, the diversity, origin, and function of adrenal gland macrophages remain largely unknown. We define the heterogeneity of adrenal gland immune cells using single-cell RNA sequencing and use genetic models to explore the developmental mechanisms yielding macrophage diversity. We define populations of monocyte-derived and embryonically seeded adrenal gland macrophages and identify a female-specific subset with low major histocompatibility complex (MHC) class II expression. In adulthood, monocyte recruitment dominates adrenal gland macrophage maintenance in female mice. Adrenal gland macrophage sub-tissular distribution follows a sex-dimorphic pattern, with MHC class IIlow macrophages located at the cortico-medullary junction. Macrophage sex dimorphism depends on the presence of the cortical X-zone. Adrenal gland macrophage depletion results in altered tissue homeostasis, modulated lipid metabolism, and decreased local aldosterone production during stress exposure. Overall, these data reveal the heterogeneity of adrenal gland macrophages and point toward sex-restricted distribution and functions of these cells.