Zhang Z, Yao J, Lin Z
… +3 more, Tang Y, Liu J, Li L
J Photochem Photobiol B
· 2026 Jun · PMID 42330774
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The development of microscale biocompatible systems for precise regulation of biological processes presents considerable challenges, particularly in achieving spatiotemporal control over gaseous signaling molecules. In t...The development of microscale biocompatible systems for precise regulation of biological processes presents considerable challenges, particularly in achieving spatiotemporal control over gaseous signaling molecules. In this work, we engineered coacervate microspheres through a self-assembly approach to co-encapsulate a hydrogen sulfide (H₂S) donor, histidine dithiocarbamate (His-DTC), together with near-infrared (NIR)-responsive gold-silver alloy nanoparticles (Au@Au/Ag NPs). These microspheres, with an average diameter of 13.6 ± 3.5 μm, exhibited strong photothermal conversion under 780 nm NIR irradiation, triggering the thermal decomposition of His-DTC and enabling controlled H₂S release. The optimized coacervate microdroplets enabled efficient, NIR-triggered release of physiologically significant amounts of H₂S, as quantified by fluorescence spectroscopy. In co-culture experiments with CEM cells, this release effectively elevated intracellular H₂S levels and activated the NRF2-HO-1-NQO1 pathway to exert potent anti-inflammatory effects. This remote-controlled and on-demand platform provides a novel strategy for the intelligent modulation of H₂S, offering broad potential for studying gasotransmitter-mediated cellular responses.
The human endocrine system orchestrates critical physiological processes, yet a systematic quantitative synthesis of clinically relevant circulating hormones has been lacking. Here, we present a comprehensive, integrativ...The human endocrine system orchestrates critical physiological processes, yet a systematic quantitative synthesis of clinically relevant circulating hormones has been lacking. Here, we present a comprehensive, integrative analysis of circulating human hormones, leveraging clinically validated reference intervals across major endocrine subsystems. We use clinically validated reference intervals that we further validate using published datasets. Our analysis reveals that the total mass of circulating hormones is approximately 40 ± 2 mg. We find that this mass in healthy young adults is dominated by Adiponectin and DHEAS, which constitute over 90% of both total hormone weight and copy number. We show there are on the order of a million hormone molecules per cell in the human body. Females have about half the number of circulating hormone molecules compared to males. Across 56 hormones with curated affinity data, free (receptor-available) concentration correlates with receptor binding affinity, with class-specific scaling. Bioavailability mechanisms segregate by chemical class, consistent with chemical structure constraining available buffering strategies. Together, these data provide a quantitative reference for the human endocrine system and highlight relationships linking receptor affinity, bioavailability, and chemical class.
The ability of Mycobacterium tuberculosis (Mtb) to dynamically adjust its growth behavior in response to host environments is critical for survival under immune and drug stress, but how these behaviors shift at the singl...The ability of Mycobacterium tuberculosis (Mtb) to dynamically adjust its growth behavior in response to host environments is critical for survival under immune and drug stress, but how these behaviors shift at the single-cell level remains poorly understood. Here, using high-resolution single-cell analysis, we show that Mtb adapts to acidic conditions by increasing the proportion of bacteria in a growth-arrested state, rather than uniformly slowing the growth rate of the entire population. This nongrowing subpopulation exhibits enhanced tolerance to ethambutol, highlighting its role in drug survival. Clinical strains displayed higher proportions of growth-arrested cells under both neutral and acidic conditions, suggesting that growth arrest may serve as one of the strategies for persistence during infection. While the PhoPR two-component system partially regulates this state, our RNA sequencing analysis revealed additional transcriptional regulators that are upregulated following acidic adaptation and may contribute to entry into the growth-arrested state and increased tolerance to ethambutol. Our study demonstrates that increasing the proportion of nongrowing subpopulations is an active adaptive strategy that can influence antibiotic susceptibility under acidic conditions, offering new perspectives for targeting bacterial heterogeneity in tuberculosis therapy.
Fluctuations in single-neuron activity in the sensory cortex often correlate with perceptual decisions. This kind of correlation is often hypothesized to reflect a causal influence of sensory signals on decisions, but it...Fluctuations in single-neuron activity in the sensory cortex often correlate with perceptual decisions. This kind of correlation is often hypothesized to reflect a causal influence of sensory signals on decisions, but it can be attributed to various noncausal factors as well. To disentangle these different possibilities, we have examined local field potentials (LFPs) recorded from the middle temporal (MT) area and area V4 of nonhuman primates (Macaca mulatta) while they performed two different perceptual decision-making tasks. Compared to single-neuron spiking, LFPs have the advantage of being decomposable into frequency bands that are associated with different anatomical sources of input. More importantly, they persist when spiking activity is inactivated, which precludes a causal influence of the corresponding neural activity on behavior. We found that high-gamma frequency (70-150 Hz) LFP power was correlated with perceptual decisions and that this correlation disappeared when spikes were inactivated, consistent with a causal role for this frequency band in decision-making. These signals overlapped in time with decision signals in the lower gamma band (30-70 Hz), which persisted after spiking inactivation, suggesting a noncausal input. Interestingly, lower-frequency LFP signals (5-30 Hz) reflected both impending perceptual decisions and the outcome of preceding trials, suggesting a modulatory influence of recent experience on neural dynamics. Our results, therefore, reveal that neural activity multiplexes different sources of information about perceptual decisions and that these types of information can be estimated reliably from different LFP frequencies.
Prada F, Marchini C, Montagna P
… +11 more, Taviani M, Maestrini G, Mancuso A, Di Fazio V, Ghiroldi C, Simoni A, Polishchuk I, Pokroy B, Gattelli R, Falini G, Goffredo S
BACKGROUND: Cold-water corals (CWCs) are key ecosystem engineers that create complex three-dimensional habitats much like tropical reefs, but in deep, cold seas. However, like other reef-building systems, they are increa...BACKGROUND: Cold-water corals (CWCs) are key ecosystem engineers that create complex three-dimensional habitats much like tropical reefs, but in deep, cold seas. However, like other reef-building systems, they are increasingly threatened by climate change and ocean acidification. CWC communities in the Mediterranean Sea may be especially vulnerable because these waters absorb more atmospheric CO than the global ocean, making it a mesocosm that mirrors broader global trends affecting marine life. Since calcification is energetically costly and likely becomes even more demanding as pH and carbonate ion availability decline, understanding how the decrease in aragonite saturation state (Ω) affects biomineralization is essential for predicting the future of these corals. RESULTS: Here, we investigated skeletal structural and compositional changes of the scleractinian CWC Desmophyllum dianthus along an Ω gradient in the Mediterranean Sea using specimens collected between 400 and 1200 m depth. Our findings indicate that skeletal porosity increases at the macro-scale with decreasing Ω, while micro- and nano-scale structural and compositional features remained unaffected. CONCLUSIONS: The persistence of micro- and nano-scale skeletal features across an 800 m depth gradient suggests that D. dianthus maintains tight biological control over mineralization at these scales, even as Ω declines. This control does not extend to the macro-scale, where increasing porosity alters the skeleton's overall architecture under lower Ω. D. dianthus thus appears to preserve the fundamental "building blocks" of its skeleton while changing its larger-scale structure, a decoupling that may make macro-scale porosity an early marker of acidification stress in CWCs.
BACKGROUND: Understanding what shapes variation in organisms' capacity to utilize novel resources is essential to predicting how species will respond to environmental change. For herbivores, exposure to toxic phytochemic...BACKGROUND: Understanding what shapes variation in organisms' capacity to utilize novel resources is essential to predicting how species will respond to environmental change. For herbivores, exposure to toxic phytochemicals in novel plants may limit persistence in new habitats. We investigated the behavioral, physiological, genetic, and microbial consequences of diet switching in two closely related species of rodent herbivores that each consume differentially toxic plants in their native habitat, and that maintain different dietary strategies (i.e., relative dietary specialist versus relative generalist). RESULTS: In reciprocal laboratory feeding trials, we exposed wild-caught woodrats (genus Neotoma) to toxins characteristic of either familiar or novel plant secondary compounds. We measured changes in food and water intake, locomotor activity, gut microbial composition, and gene expression across the digestive tract following feeding trials. The dietary generalist responded minimally, but the specialist responded strongly when exposed to the novel diet. This response included behavioral and genetic components including increased water intake, reduction in locomotor activity, increased differential expression of detoxification genes, and a greater shift in gut microbial composition. CONCLUSIONS: The dietary specialist exhibited a strong response to diet switching that corresponded with ecologically relevant shifts in behavior and physiology that would have negative fitness consequences. Although the dietary specialist had a strong genetic and microbial response to novel plant secondary compounds, this response would likely be insufficient to overcome the immediate challenge of exposure to novel dietary toxins in the wild. Our results underscore the link between feeding strategy and the capacity to shift to novel dietary resources in response to environmental change.
Infectious diseases and autoimmunity are leading causes of mortality worldwide. The lack of vaccines and resistance to current treatments by microbes highlight the importance of developing novel therapeutics. Similarly,...Infectious diseases and autoimmunity are leading causes of mortality worldwide. The lack of vaccines and resistance to current treatments by microbes highlight the importance of developing novel therapeutics. Similarly, treatments for autoimmune diseases are limited and require improved approaches. Identifying relevant proteins involved in host defense and tolerance to self-antigens is key to designing novel therapeutic strategies. Thrombospondin-1 (TSP-1) is a host glycoprotein involved in host defense and inflammation. Here, we analyze how TSP-1 interacts with different ligands involved in immunity. Then, we discuss the roles of TSP-1 in infection and autoimmunity to finally examine the therapeutic potential of TSP-1.
BACKGROUND: Food ingestion is fundamental for animal survival and growth, with the cessation of feeding upon nutrient fulfillment being tightly regulated by a variety of satiety factors. Notably, sulfakinin/cholecystokin...BACKGROUND: Food ingestion is fundamental for animal survival and growth, with the cessation of feeding upon nutrient fulfillment being tightly regulated by a variety of satiety factors. Notably, sulfakinin/cholecystokinin (SK/CCK)-type neuropeptide signaling has been identified as an inhibitory regulator of food intake across the animal kingdom. However, its regulatory mechanism in feeding in deuterostome invertebrates remains unclear. Here, we characterized SK/CCK-type signaling in a deuterostome invertebrate, the sea cucumber Apostichopus japonicus (phylum Echinodermata). RESULTS: A single SK/CCK-type precursor in A. japonicus generates two mature peptides (AjSK/CCK1, AjSK/CCK2) that activate a shared receptor (AjSK/CCKR), triggering Ca mobilization via the Gαq-dependent pathway and extracellular signal regulated kinase 1/2 (ERK1/2) phosphorylation. Both peptides induce dose-dependent contraction of longitudinal muscles, while AjSK/CCK2 additionally elicits sustained contraction of the posterior intestine, an effect absent in other gut regions. Long-term injection of both peptides reduces food intake and significantly downregulates orexin-type neuropeptide genes (AjOrexin1P, AjOrexin2P) in the circumoral nerve ring (CNR) and intestine. CONCLUSIONS: Unlike mammals, where CCK inhibits feeding by contracting the pyloric sphincter to delay gastric emptying, SK/CCK-type peptides in sea cucumbers exert their anorexic effect in part by selectively contracting the posterior intestine, thereby inhibiting intestinal emptying. This divergence in action sites highlights the evolutionary adaptability of SK/CCK-type signaling as a conserved inhibitory regulator of feeding across bilaterian animals. Elucidating these mechanisms in the economically important A. japonicus may inform development of appetite-promoting agents for sustainable aquaculture.
Kinoshita-Terauchi N, Terauchi M, Shiba K
… +4 more, Bellgrove A, Nagasato C, Noguchi H, Inaba K
J Photochem Photobiol B
· 2026 Jun · PMID 42314526
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Phototaxis in brown algal gametes is a key behavioral response that enables successful fertilization and dispersal, yet the molecular basis underlying this process remains largely unexplored. Here, we applied an integrat...Phototaxis in brown algal gametes is a key behavioral response that enables successful fertilization and dispersal, yet the molecular basis underlying this process remains largely unexplored. Here, we applied an integrative multi-omics framework to identify candidate genes potentially involved in phototaxis. The framework revealed 20 orthogroups uniquely conserved in phototactic species but absent from non-phototactic lineages. Among these, only two orthogroups were previously characterized flagellar proteins: the blue-light photoreceptor Helmchrome, localized to the posterior flagellum, and the calcium-binding protein CABAF1, enriched in the anterior flagellum, indicating that these candidate genes may include previously unrecognized flagellar proteins functionally associated with Helmchrome and potentially involved in phototaxis. We further examined an ABC1-like kinase that emerged as a strong phototaxis-associated candidate and found that it localized to the electron-dense region of the paraflagellar body (PFB) in the posterior flagellum. This represents the first molecular component identified only at the PFB, a structure long recognized but lacking molecular characterization. Our findings provide a systematic framework for exploring the molecular mechanism of phototaxis in brown algae.
Deng Z, Zhang M, Zhu S
… +7 more, Zhang Y, Liao H, Li J, Yan P, Zhang Q, Liu R, Ma B
J Photochem Photobiol B
· 2026 Jun · PMID 42314525
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Osteosarcoma (OS), a highly aggressive bone cancer with a dismal prognosis in the metastatic setting, urgently demands novel therapeutic modalities. While phototherapy offers a promising, minimally invasive strategy, its...Osteosarcoma (OS), a highly aggressive bone cancer with a dismal prognosis in the metastatic setting, urgently demands novel therapeutic modalities. While phototherapy offers a promising, minimally invasive strategy, its clinical efficacy is often hampered by the poor aqueous solubility of photosensitizers and the development of multidrug resistance. In response, we constructed the dual-modal nanoplatform BDP-NPs by leveraging a multifunctional F127/TPGS mixed micelle to encapsulate a cationic BODIPY photosensitizer, thereby creating a system engineered for enhanced tumor accumulation and to overcome multidrug resistance. Benefiting from their uniform size, colloidal stability, and hypoxia-responsive properties, the BDP-NPs demonstrate potent reactive oxygen species generation and high photothermal conversion efficiency under 525 nm laser irradiation. This dual-modal action induces severe mitochondrial dysfunction, thereby triggering apoptosis in both 3D tumor spheroids and tumor tissues. The synergistic phototherapy elicited profound mitochondrial-targeted cytotoxicity, inhibited clonogenic survival, and significantly suppressed tumor growth in human osteosarcoma models, all while maintaining a favorable biosafety profile. Mechanistic analyses revealed that this synergistic phototherapy plays a pivotal role in suppressing the YAP1/β-catenin axis, thereby reversing the epithelial-mesenchymal transition (EMT) program and consequently inhibiting OS cell proliferation, migration and invasion. This study not only establishes BDP-NPs as a potent and biocompatible nanotherapeutic for OS but also presents a groundbreaking phototherapeutic strategy to disrupt the YAP1/β-catenin axis-a key signaling network driving tumorigenesis and malignant progression. This approach provides a robust conceptual foundation for devising next-generation phototherapeutics that precisely target oncogenic signaling in aggressive cancers.
Structural neuroplasticity supports learning, development, and shapes vulnerability to brain disorders, making it a central priority in neuroscience research. However, progress in humans has remained limited by the inabi...Structural neuroplasticity supports learning, development, and shapes vulnerability to brain disorders, making it a central priority in neuroscience research. However, progress in humans has remained limited by the inability to probe cellular processes in vivo, leaving mechanistic insight largely dependent on animal models. To address this gap, here we combined the sub-voxel sensitivity of ultra-high-gradient diffusion MRI with the cell-compartment specificity of the Soma and Neurite Density Imaging (SANDI) model to probe structural plasticity directly in the living human brain. By tracking how learning modulates the temporal dynamics of cell bodies and cell processes, we aimed to distinguish plastic from nonplastic biological processes driving changes in microstructure. We found that learning a motor skill triggered two distinct temporal responses: a transient expansion of cell bodies across all brain regions engaged by the task, consistent with a short-lived homeostatic mechanism, and a sustained increase in cell-process density restricted to key motor regions, consistent with structural plasticity. Our approach provides a mechanistic window into human neuroplasticity and marks a significant step toward bridging the gap between animal and human neuroscience.
Anobile DP, Barbar L, Maucotel E
… +15 more, Cornec A, Manriquez V, Richer W, Denizeau J, Sedlik C, Bories C, Couderc E, Leclere R, Sobas J, Papillon E, Mena Osuna R, Tosello-Boari J, Burbage M, Piaggio E, Poirier EZ
One of the first-line treatments for advanced non-small cell lung cancer (NSCLC) are immune checkpoint inhibitors (ICI), which activate the antitumor immune response. Despite their success, ICI remain ineffective in many...One of the first-line treatments for advanced non-small cell lung cancer (NSCLC) are immune checkpoint inhibitors (ICI), which activate the antitumor immune response. Despite their success, ICI remain ineffective in many patients, highlighting the need for strategies to overcome resistance. Most efforts have focused on promoting immune cell infiltration into refractory tumors to improve ICI efficacy. In this work, we mobilize this approach by focusing on Argonaute 2 (Ago2), a pivotal member of the RNA interference pathway. Using two murine models of immunorefractory NSCLC, we demonstrate that tumoral Ago2 suppresses interferon signaling, leading to poor immunogenicity and failure of ICI therapy. Genetic deletion of Ago2 in cancer cells restores interferon signaling and supports immune infiltration of the tumor. Consequently, whereas wild-type tumors are resistant to ICI, tumors devoid of Ago2 become sensitive to treatment. In NSCLC patients treated with ICI, high Ago2 expression and a low interferon signature in tumors correlate with reduced survival. Ago2 is thus a driver of the immunorefractory phenotype observed in NSCLC and may represent a therapeutic target when aiming to sensitize patients to ICI.
Docampo-Seara A, Cosacak MI, Heilemann K
… +11 more, Kessel F, Oprişoreanu AM, Westphal M, Çark Ö, Zöller D, Arnold J, Bretschneider A, Hnatiuk A, Ninov N, Becker CG, Becker T
Zebrafish, in contrast to mammals, regenerate neurons after spinal cord injury, but little is known about the control mechanisms of this process. Here we use scRNA-seq and in vivo experiments to show that sema4ab, mainly...Zebrafish, in contrast to mammals, regenerate neurons after spinal cord injury, but little is known about the control mechanisms of this process. Here we use scRNA-seq and in vivo experiments to show that sema4ab, mainly expressed by lesion-reactive microglia, attenuates regenerative neurogenesis by changing the complex lesion environment. After spinal injury, disruption of sema4ab doubles the number of newly generated progenitor cells and neurons but attenuates axon regrowth and recovery of swimming function. Disruption of the plxnb1a/b receptors, selectively expressed by neural progenitor cells, increases regenerative neurogenesis. In addition, disruption of sema4ab alters activation state and cytokine expression of microglia, such that fibroblasts increase expression of the cytokine tgfb3, which strongly promotes regenerative neurogenesis. Hence, we propose that sema4ab expression in microglia attenuates regenerative neurogenesis in multiple ways, likely directly through plxnb1a/b receptors and indirectly, by controlling the inflammatory milieu and tgfb3 levels. Targeting Sema4A-dependent signaling in non-regenerating vertebrates may be a future strategy to improve regenerative outcomes.
Adiponectin is the most abundant hormone in the circulation. Plasma adiponectin decreases in obesity but increases in leanness, including during caloric restriction (CR) in animals and humans. In obesity, adiponectin def...Adiponectin is the most abundant hormone in the circulation. Plasma adiponectin decreases in obesity but increases in leanness, including during caloric restriction (CR) in animals and humans. In obesity, adiponectin deficiency promotes cardiometabolic dysfunction. In contrast, the roles of adiponectin in CR, when it is at its highest, are largely unknown. To address this, we studied global adiponectin knockout (KO) in male and female mice fed either ad libitum (AL) or a 30% CR diet from 9-13 weeks of age. We show that adiponectin KO did not alter CR effects on body mass, body composition, or energy expenditure. However, KO unexpectedly decreased blood glucose levels during CR, both with fasting and following an oral glucose challenge. This is opposite to the effects of adiponectin deficiency during AL feeding or obesity and occurred without changes in insulin concentrations or sensitivity. Moreover, adiponectin KO augmented CR-induced increases in plasma fatty acids in both sexes and, in males only, impaired systemic triglyceride clearance on both AL and CR diets. These effects on lipid metabolism were associated with sex- and diet-specific KO effects on white adipose tissue, including altered adipocyte size and expression of key regulators of adipocyte lipid metabolism. Indirect calorimetry further revealed that adiponectin KO alters the shifts between carbohydrate and lipid utilization that occur during transitions between fed and fasted states. To determine potential molecular mechanisms, we investigated effects of adiponectin KO on the liver, a major adiponectin target that plays key roles entraining metabolism to nutritional state. Hepatic transcriptomics revealed that, in both sexes, adiponectin KO upregulates sterol and fatty acid synthesis genes under AL while increasing amino acid catabolic genes during CR. However, the latter occurred without altering plasma or hepatic amino acid concentrations. Together, our findings suggest that adiponectin exerts sexually dimorphic effects on glucose, lipid, and amino acid metabolism during CR, in whole or in part through effects on the liver. Thus, the roles adiponectin in CR differ markedly from its widely reported functions in obesity, insulin resistance, and other pathological states.
A population's ability to adapt is determined by its levels of additive genetic variance (VA), and while it is agreed that most organisms have genetic variation for most traits, the extent to which it varies between spec...A population's ability to adapt is determined by its levels of additive genetic variance (VA), and while it is agreed that most organisms have genetic variation for most traits, the extent to which it varies between species is poorly characterized. Here, we investigate this question by compiling 3,209 and 1,852 estimates of heritability and evolvability (the additive genetic variance divided by the square of the mean), respectively, for a variety of traits from 220 and 172 multicellular eukaryotic species. Using phylogenetic generalized linear mixed models, we find substantial and highly significant interspecific variation in evolvability. Much of the variation is explained by phylogenetic relatedness, with plants in our data having substantially higher evolvability than animals. While heritability also varies between species, the differences are more subtle, and plants are not exceptional. We investigate whether the variation in evolvability and heritability between species is due to variation in the mutation rate, effective population size, genome size, ploidy, and recombination rate, but find little evidence of any factor being important. However, the confidence intervals are large suggesting that we have little power to detect any associations between these factors and our estimates of VA.
Marine fungi were assumed to have a minor role in carbon cycling, unable to compete with bacteria. A new PLOS Biology study challenges this dogma, showing fungi can dominate labile dissolved organic matter assimilation,...Marine fungi were assumed to have a minor role in carbon cycling, unable to compete with bacteria. A new PLOS Biology study challenges this dogma, showing fungi can dominate labile dissolved organic matter assimilation, reshaping our understanding of ocean carbon retention and storage.
Crossover (CO) formation ensures accurate segregation of homologous chromosomes during the first meiotic division. The pro-crossover proteins are essential for crossover formation and undergo dynamic changes during meiot...Crossover (CO) formation ensures accurate segregation of homologous chromosomes during the first meiotic division. The pro-crossover proteins are essential for crossover formation and undergo dynamic changes during meiotic prophase I, although the underlying regulatory mechanism is largely unknown. Here, we found that the ubiquitin-proteasome system (UPS) plays a pivotal role in orchestrating pro-crossover protein dynamics and crossover patterning during meiosis in Caenorhabditis elegans. Knockdown of either the ubiquitin-activating enzyme E1 or the proteasome resulted in elevated pro-crossover protein levels and crossover designation. Impairing ubiquitination, but not proteasome activity, led to persistent association of pro-crossover proteins on meiotic chromosomes, a process mediated by the CDC-48UFD-1/NPL-4 segregase. Utilizing a hypomorphic allele of cosa-1, a well-characterized pro-crossover protein-encoding gene, we further demonstrate that the UPS restricts crossover formation. Collectively, our findings reveal a multilayered UPS-mediated regulatory network that maintains proper pro-crossover protein dynamics, thereby coordinating crossover formation with meiotic chromosome segregation.
Fungi serve as critical biological carbon storage reservoirs in soil ecosystems, but whether this fungal trait is also important for marine sediment carbon storage processes is poorly understood. Here, we quantify for th...Fungi serve as critical biological carbon storage reservoirs in soil ecosystems, but whether this fungal trait is also important for marine sediment carbon storage processes is poorly understood. Here, we quantify for the first time assimilation of dissolved free amino acids by fungi in marine sediments from a high Arctic fjord and show that a distinct community of marine fungi promoted the stabilization of assimilated carbon via a relatively high metabolic efficiency. This corresponded to higher in situ ratios of fungi:prokaryote biomass in the fjord benthos, indicating efficient fungal metabolism promotes increased retention of microbial biomass at the seafloor. Quantitative stable isotope probing linked this efficient assimilation of amino acids to more than 80 fungal taxa in the fjord sediments, primarily associated with aquatic hyphomycetes. An efficient assimilation of amino acids is shown here to be a trait of marine fungi that plays a role in retaining labile dissolved organic matter as microbial biomass in Arctic fjord benthic ecosystems, hotspots for carbon sequestration that are currently experiencing rapid change due to climate warming. Our results indicate that fungal metabolism and biomass in marine sediment should be considered as an important contributor to seafloor carbon storage.
BACKGROUND: Endometriosis is a chronic inflammatory disorder affecting ~ 10% of reproductive-age women, often causing pelvic pain and infertility. Despite its prevalence, diagnosis remains delayed due to non-specific sym...BACKGROUND: Endometriosis is a chronic inflammatory disorder affecting ~ 10% of reproductive-age women, often causing pelvic pain and infertility. Despite its prevalence, diagnosis remains delayed due to non-specific symptoms and lack of reliable non-invasive biomarkers. Emerging evidence implicates the microbiome in disease pathogenesis. RESULTS: We analyzed uterine microbiomes from 266 tissue samples collected during either the proliferative or secretory phase, using 16S rRNA gene sequencing. Genus-level analysis revealed variable Lactobacillus abundance among all individuals. Prevotella showed borderline enrichment in proliferative-phase patients. Sub-genus analyses identified a small number of differentially abundant taxa, though none remained significant after FDR correction. To capture subtle microbial shifts, we developed a feature set combining weakly differential taxa, algorithmically selected taxa via machine learning, and a functional dysbiosis score. A supervised classifier trained on proliferative-phase data achieved moderate predictive performance (AUC = 0.70), while secretory-phase models performed more poorly (AUC = 0.58). CONCLUSIONS: The uterine microbiome shows phase-dependent differences in its potential to inform endometriosis status. Although no robust individual microbial biomarkers were identified, machine learning models incorporating subtle community features from the proliferative phase yielded modest diagnostic potential. These results highlight the importance of menstrual cycle-aware sampling and support further development of microbiome-informed diagnostic tools for endometriosis.
BACKGROUND: The domestication of transposable elements is a key source of evolutionary innovation, yet the pathways by which their functional modules are repurposed by the host remain poorly understood. The Tc1/mariner s...BACKGROUND: The domestication of transposable elements is a key source of evolutionary innovation, yet the pathways by which their functional modules are repurposed by the host remain poorly understood. The Tc1/mariner superfamily is a widespread group of DNA transposons, but the prevalence and patterns of their domestication are underexplored. RESULTS: We performed a systematic genomic screen across 43 drosophilid species using stringent criteria for molecular domestication. This analysis identified five high-confidence, evolutionarily conserved genes derived from Tc1/mariner transposases. Phylogenetic and structural analyses suggest domestication via two distinct molecular pathways: co-option of the DNA-binding module and co-option of the catalytic domain. The DNA-binding module pathway includes CG4570, the previously known genes cag and toy (the latter fused with a homeodomain), and a lineage-restricted gene in the Drosophila obscura group that exhibits signatures of recent domestication. In contrast, the catalytic domain pathway is represented solely by CG14478. Structural modeling reveals that CG14478 protein preserves a canonical DDE endonuclease fold. Co-expression network analysis suggests potential cellular roles of these genes: CG14478 is linked to RNA/chromatin-related processes, CG4570 to cell cycle/chromosome functions, cag to ciliary and nuclear functions, and toy to neuronal development. CONCLUSIONS: This study establishes a stringent framework for identifying domesticated TEs, demonstrating that Tc1/mariner elements are co-opted via two distinct pathways: retention of either catalytic or DNA-binding modules. Our findings suggest that domestication is a dynamic continuum, ranging from recent, lineage-specific events to ancient, conserved genes, and underscore how genomic conflict with TEs can drive eukaryotic evolution and regulatory complexity.