Biology subjects

Watanabe, A.

Publications and source records attributed to Watanabe, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Apoptotic Quality Control of Cellular Competence Limits Cryptic Germinal Center B Cell States

Germinal center (GC) B cells undergo extensive apoptosis, but how this process shapes evolving GC populations remains unclear. Using mice lacking intrinsic apoptotic effectors BAK and BAX in B cells, we found that mitochondrial apoptosis was dispensable for affinity maturation but critical for controlling GC size and cellular composition, showing that GC population dynamics and affinity maturation can be uncoupled. BAK/BAX-deficient mice mounted enlarged and prolonged GC responses, largely due to the accumulation of non-proliferating Ki-67loCD71lo dark zone (DZ) B cells. CD71hi and CD71lo DZ cells exhibited similar B-cell receptor (BCR) avidity, retained potential for proliferation and plasmacytic differentiation, and shared clonal lineages, indicating recurrent emergence of non-proliferating DZ populations. A subset also carried Somatic-hypermutation-derived defects that abolished antibody expression despite apparently productive V(D)J sequences; reversion of a single amino acid substitution often restored expression. Mitochondrial apoptosis thus enforces cellular quality control in the GC by limiting the persistence of non-proliferating and expression-defective states while remaining dispensable for affinity maturation.

immunology↗

bioRxiv2026

Collagen Rope Trick: Cell-Laden Fibre Assembly at 1 Liquid Interfaces

Summary ParagraphTissues and organs in living organisms represent centimeter-scale hierarchical architectures comprising nano-to microscale, uniaxially aligned extracellular matrix (ECM) fibres with high mechanical strength, integrated with cellular components, as exemplified in tendon, skin, cartilage, bone, and blood vessels1. Here, we present a liquid-liquid interfacial spinning method to produce highly uniaxially aligned, centimeter-scale collagen fibres. The dried fibres exhibit exceptional mechanical properties, with fracture strength of 280 MPa, Youngs modulus of 6 GPa, and toughness of 17 MJ m-3, comparable to spider silk and tendon collagen, and exceeding supramolecular and double-network hydrogels1. Incorporating living cells into the collagen solution yielded centimeter-scale, cell-laden aligned fibres, with densely adherent, uniaxially aligned cells and over 80% viability. Myoblast-laden fibres recapitulate biological features of fibrotic muscle tissues, as observed in type II diabetes2. Interfacial collagen assembly further enables fabrication of dimension-controlled constructs, like 2D sheets, 0D capsules, and 1D tubes, thus providing modular building blocks for centimeter-scale 3D tissues and organ-like structures. This approach offers a versatile platform to engineer mechanically robust, cell-laden tissues with controlled hierarchical architecture.

bioengineering↗

bioRxiv2026

Layer-5 Pyramidal Cell tLTD Requires Astrocytic Ca2+ and CB1 Receptor Signaling

Timing-dependent long-term depression (tLTD) is a form of spike timing-dependent plasticity (STDP) that has been attributed to presynaptic NMDA and CB1 receptors at synapses between layer 5 (L5) pyramidal cells (PCs) in visual cortex. Here, we asked whether astrocytes, known for gliotransmission and tripartite synapse formation, are also required. Using quadruple whole-cell recordings in acute slices from C57BL/6 mice, we found that L5 PC [->] PC tLTD was abolished by the glial metabolic inhibitor sodium fluoroacetate. Disrupting astrocyte Ca2+ signaling through loss-of-function approaches such as AAV-mediated expression of CalEx and BAPTA loading of astrocyte networks consistently prevented tLTD. Optogenetic activation of astrocyte Gq signaling during tLTD induction abolished tLTD and led to potentiation. Since tLTD relies on endocannabinoid (eCB) signaling and astrocytes express CB1 receptors, we conditionally deleted CB1 receptors from astrocytes and found that this manipulation abolished tLTD. Taken together, our results show that L5 PC [->] PC tLTD requires astrocyte Ca2+ signaling and CB1 receptor activation. These findings suggest that astrocyte-dependent control of STDP may represent a general principle across circuit and synapse types. Significance StatementSpike timing-dependent plasticity (STDP) enables neural circuits to adapt based on the precise timing of activity, with timing-dependent long-term depression (tLTD) promoting competition and stabilization. While tLTD is often considered a two-factor process involving pre- and postsynaptic neurons, we show that astrocytes form a key third element. Using targeted loss-of-function approaches, we demonstrate that tLTD at layer-5 pyramidal cell synapses in visual cortex requires astrocyte Ca2+ signaling and CB1 receptors. Unexpectedly, optogenetic stimulation of astrocyte Gq signaling during induction blocked depression and instead triggered potentiation. These findings call for a revision of existing models of STDP and suggest that astrocyte-dependent plasticity may reflect a general regulatory principle across cortical circuits.

neuroscience↗

bioRxiv2026

Cotton fabrics functionalized with hydroxyl-rich graphene derivatives and silver nanowires: washing resistance and preliminary antibacterial activity against Escherichia coli

Cotton-based antimicrobial textiles are attractive for applications requiring improved microbiological control, but their performance depends on effective surface functionalization and retention of the active materials after use and washing. In this work, cotton fabrics were functionalized with hydroxyl-rich graphene oxide (HGO), hydroxyl-rich reduced graphene oxide (H-rGO), and silver nanowires (AgNWs), either individually or in combined treatments, to investigate their deposition onto the textile surface, washing resistance, and preliminary antibacterial activity. The treated fabrics were prepared by immersion-based coating procedures, and the persistence of the deposited materials after repeated washing was evaluated by UV-Vis analysis of the residual wash solutions. Surface morphology before and after washing was examined by scanning electron microscopy. The results showed that graphene-based coatings, particularly HGO, exhibited stronger retention on cotton fibers, while AgNWs were partially retained after repeated washing cycles. SEM images confirmed the deposition of AgNWs on the cotton surface and showed that part of the coating remained associated with the fibers after washing. A preliminary antibacterial assay against Escherichia coli indicated that nanomaterial-treated fabrics inhibited bacterial growth relative to untreated controls, with the combined HGO/AgNWs treatment showing the most promising inhibitory trend under the tested conditions. These findings demonstrate the feasibility of producing cotton fabrics functionalized with hydroxyl-rich graphene derivatives and silver nanowires, supporting their potential as proof-of-concept antibacterial textiles with partial washing resistance.

microbiology↗

bioRxiv2026

Functional Convergence of Genetically Diverse B-Cell Receptors in Simian-HIV Infected Rhesus Macaques

Germline-targeting or lineage-design vaccine strategies are being used to induce HIV broadly neutralizing antibody (bnAb) responses. These strategies assume that genetically diverse individuals respond similarly to the same immunogen by mobilizing comparable germline precursors, although outcomes vary across bnAb epitopes. Here we explored this premise using a simian-HIV infection model in rhesus macaques. Antigen-unbiased Env- reactive B-cell populations were profiled, followed by systematic analysis of antibody function and B-cell receptor (BCR) genetics. We find that while global Env-reactive B-cell response profiles and antibody functional properties are similar across individuals, underlying BCR genetics are diverse, particularly among non-bnAbs. These results indicate that functional convergence of Env-reactive antibody responses does not necessarily require genetic convergence and suggest that specific germline-targeting may not be an absolute prerequisite for successful vaccine design. These findings support an epitope-focused framework in which bnAb epitopes are engineered to enhance population-level immunogenicity, with potential applicability to other challenging pathogens.

immunology↗

bioRxiv2025

Iterative immunogen optimization to focus elicited responses on a conserved, subdominant influenza hemagglutinin epitope

Designing effective vaccination strategies against genetically diverse viruses, such as HIV or influenza, is hindered by the ability of these pathogens to mutate and readily evade immune responses. While these viruses contain conserved regions that cannot easily mutate without affecting viral fitness, these sites are subdominant, meaning that they are not the primary target of antibodies elicited by natural infection or current vaccines. Here, we integrated recent advances in machine learning methods for protein structure prediction and design to engineer protein immunogens that focus immune responses on a conserved, subdominant HA epitope targeted by broadly cross-reactive influenza antibodies. Iterating between computation-guided optimization and in vivo analyses generated immunogens that faithfully displayed the target epitope and redirected humoral responses toward it upon vaccination. These results provide a blueprint for applying recent protein engineering approaches to immunogen design and may inform the development of broadly protective influenza vaccines.

immunology↗

bioRxiv2025

Ion transport peptide regulates body water balance via a receptor guanylyl cyclase in the Drosophila hindgut

Maintaining internal water balance, including ionic and osmotic balance, is critical for animal development and survival. In insects, internal water balance is regulated through the Malpighian tubules and the hindgut, which transport water and ions across their epithelia under the regulation of multiple peptide hormones. One of these, ion transport peptide (ITP), a member of the highly conserved crustacean hyperglycemic hormone superfamily among ecdysozoans, is an anti-diuretic hormone in insects, but its mechanism of action remains largely unclear. Here, we show that the short amidated isoform of ITP (saITP), secreted from brain neurosecretory cells, regulates water absorption via the receptor guanylyl cyclase (rGC) Gyc76C in the hindgut of the fruit fly Drosophila melanogaster. Both ITP and Gyc76C are evolutionarily conserved and are essential for larval survival in D. melanogaster, as mutation or knockdown of either gene results in early larval lethality. In Drosophila S2 cells, synthetic saITP increases intracellular cyclic GMP (cGMP) in a Gyc76C-dependent manner, an effect abolished by deletion of its putative ligand-binding domain. Using the fluorescent cGMP biosensor RedcGull in ex vivo-cultured hindguts, we found that saITP increases epithelial cGMP levels, and this response requires Gyc76C. Consistently, saITP promotes hindgut water reabsorption via Gyc76C. Thus, saITP acts via Gyc76C in a brain-hindgut neuroendocrine axis that regulates internal water balance during development. Our study provides new insight into the neuroendocrine control of osmoregulation in ecdysozoans and supports a broader role for rGCs in peptide-hormone signaling.

physiology↗

bioRxiv2025

Development of a sandwich ELISA for the detection of bovine A1 beta-casein

The genetic variant A2 beta-casein is associated with fewer digestive and absorption issues compared to A1 beta-casein, leading to increased global demand for A2 milk. However, contamination with the A1 variant during collection, transportation, or sterilization of A2 milk poses a risk, necessitating a verification test to ensure A2 milk does not contain A1 beta-casein. We developed an A1-specific monoclonal antibody (mAb) and a general mAb that reacts with both A1 and A2 variants using the iliac lymph node method. A sandwich ELISA was created using the general mAb as the capture antibody and the A1-specific mAb as the detection antibody to identify A1 beta-casein in milk. This ELISA successfully detected A1 beta-casein in raw and pasteurized A2 milk, including ultra-high temperature treated milk. The test identified A1 beta-casein when the A1 spike in A2 milk exceeded 1% in volume, indicating its capability to detect contamination from one A1A1 cow in a herd of one hundred A2A2 cows. The developed A1 beta-casein ELISA is suitable for high-throughput analysis and can be valuable for monitoring A1 beta-casein contamination in commercially produced A2 milk.

zoology↗

bioRxiv2025

Detailed shape characterization reveals complementary ecomorphological patterns in brain shape and size evolution across the avian radiation

Like mammals, birds have exceptionally large brains for their body sizes, which is thought to have facilitated their diversification through environmental change, and has been associated with many ecological adaptations. Although size metrics are informative and well-studied, they are limited in their ability to characterize localized neuroanatomical variation. Size and shape together can holistically capture the diversification of avian brain form, and how these changes relate to function and ecology. We employ high-density geometric morphometric (GM) shape data across 300 avian species to capture shape variation in whole brain endocasts, and compare how evolutionary patterns differ between shape and size. While ecomorphological signal is mixed across brain regions, we find that the majority of shape variation falls along an elongated-globular spectrum, where terrestrial and aquatic birds generally have anteroposteriorly elongated brains, while aerial bird brains are typically more globular. The supermajority (>90%) of endocranial shape variation is independent of evolutionary allometry, demonstrating that shape characterizes key aspects of avian neuroanatomy that are missing from volumetric data. Our results suggest that neuroanatomical diversity in birds is not driven by the dominance of any particular factors, but rather through clade-specific divergence in localized brain structures from the avian-wide allometric and ecomorphological patterns.

evolutionary biology↗

bioRxiv2025

Bone and cartilage staining protocol for large avian specimens: late-stage embryonic emu (Dromaius novaehollandiae) and adult chickens (Gallus gallus)

The ability to consistently and clearly visualize discrete anatomical parts of a specimen is crucial for biological research. For skeletal tissues, a classic and widely adopted technique uses a combination of Alizarin red for bone and Alcian or toluidine blue stains for cartilage. Published protocols for these stains have generally been optimized for small or prenatal specimens; thus, leaving out applications to relatively large specimens including somatically mature specimens and embryos of large-bodied taxa. Here, we present a newly refined, detailed protocol, accompanied with photographs, for clearing extraneous tissue and staining bone and cartilaginous structures optimized for larger avian specimens, including adult domestic chicken (Gallus gallus domesticus) and late-stage, embryonic emu (Dromaius novaehollandiae). The latter exhibit relatively mature soft tissue, including skeletal muscles, compared to those of late-stage embryos of small vertebrate taxa such as domestic chicken and mice. We found through our experiments that the combined Alcian blue and Alizarin red staining works best on freshly frozen specimens compared to those fixed in formalin and effective clearing and staining was possible without the use of tissue digestion reagents, such as trypsin and pancretin. The central aim of our work is to offer a step-by-step guide that provides researchers to consistently and effectively stain skeletal tissues in larger vertebrate specimens, allowing investigation of skeletal tissues at broader developmental and taxonomic scales.

zoology↗

bioRxiv2025

Aggregation of HAPLN2, a component of the perinodal extracellular matrix, is a hallmark of physiological brain aging in mice

Protein aggregation is a hallmark of neurodegenerative diseases and is also observed in the brains of elderly individuals without such conditions, suggesting that aging drives the accumulation of protein aggregates. However, the comprehensive understanding of age-dependent protein aggregates involved in brain aging remains unclear. Here, we investigated proteins that become sarkosyl-insoluble with age and identified hyaluronan and proteoglycan link protein 2 (HAPLN2), a hyaluronic acid-binding protein of the extracellular matrix at the nodes of Ranvier, as an age-dependent aggregating protein in mouse brains. Elevated hyaluronic acid levels and impaired microglial function reduced the clearance of HAPLN2, leading to its accumulation. HAPLN2 oligomers induced microglial inflammatory responses both in vitro and in vivo. Furthermore, age-associated HAPLN2 aggregation was also observed in the human cerebellum. These findings suggest that HAPLN2 aggregation results from age-related decline in brain homeostasis and may exacerbate the brain environment by activating microglia. This study provides new insights into the mechanisms underlying cerebellar aging and highlights the role of HAPLN2 in age-associated changes in the brain. Author SummaryTo identify age-dependent protein aggregates unrelated to disease, we analyzed the sarkosyl-insoluble proteome of young and aged mouse brains. We discovered that hyaluronan and proteoglycan link protein 2 (HAPLN2), a hyaluronic acid-binding protein existing in the nodal extracellular matrix, accumulated with age. Age-dependently accumulated HAPLN2 formed large protein aggregates that cannot be solubilized by the anionic detergent sarkosyl or by hyaluronidase digestion. In addition, HAPLN2 formed irregularly shaped puncta that were mislocalized from the nodes of Ranvier in the cerebellar white matter of not only aged mice but also aged human brains. Oligomers of full-length HAPLN2 specifically induced microglial activation in vitro and in vivo. Our findings suggest that the accumulation of HAPLN2 aggregates is a new hallmark of brain aging and a possible factor contributing to brain inflammation.

biochemistry↗

bioRxiv2025

Fluorescence-barcoded cell lines stably expressing membrane-anchored influenza neuraminidases

The discovery of broadly protective antibodies to the influenza virus neuraminidase (NA) has raised interest in NA as a vaccine target. However, recombinant, solubilized tetrameric NA ectodomains are often challenging to express and isolate, hindering the study of anti-NA humoral responses. To address this obstacle, we established a panel of 22 non-adherent cell lines stably expressing native, historical N1, N2, N3, N9, and NB NAs anchored on the cell surface. The cell lines are barcoded with fluorescent proteins, enabling high-throughput, 16-plex analyses of antibody binding with commonly available flow cytometers. The cell lines were at least as efficient as a Luminex multiplex binding assay at identifying NA antibodies from a library of unselected clonal IgGs derived from human memory B cells. The cell lines were also useful for measuring the magnitude and breadth of the serum antibody response elicited by experimental infection of rhesus macaques with influenza virus. The membrane-anchored NAs are catalytically active and are compatible with established sialidase activity assays. NA-expressing K530 cell lines therefore represent a useful tool for studying NA immunity and evaluating influenza vaccine efficacy.

immunology↗

bioRxiv2024

Enhanced Subjective Performance Achievement in Wind Instrument Playing through Positive Memory Recall: Effects of Sympathetic Activation and Emotional Valence

Controlling physiological and psychological states before a performance is essential for professional musicians to realize their full potential. However, the characteristics of the optimal pre-performance state remain unclear. While an increase in sympathetic nervous system activity is typically observed before performance, when associated with anxiety, it can degrade the performance quality. This study examined whether recalling positive autobiographical performance memories enhances subjective performance achievement, accompanied by increased emotional arousal, valence, and autonomic nervous system activity. Thirty-six professional wind instrument players participated in the study. Prior to performing musical pieces, participants engaged in one of three conditions: (1) recalling positive autobiographical memories, (2) recalling negative autobiographical memories, or (3) imagining routine pre-performance activities (no-memory condition). During the memory recall phase, heart rate was measured. After each performance, participants rated their subjective arousal, valence, and performance achievement. We calculated the heart rate variability indices, specifically SD1 (reflecting parasympathetic nervous system activity) and SD2/SD1 (reflecting sympathetic nervous system activity). The results showed that performance achievement, arousal, and valence were significantly higher in the positive than in the negative condition. Our path analysis further revealed that an increase in SD2/SD1 did not directly predict performance achievement; instead, it was associated with an increase in emotional valence, which in turn led to improved performance. These findings suggest that recalling positive performance memories activates sympathetic nervous system activity and fosters positive emotions, thereby enhancing the performance achievement of professional musicians.

neuroscience↗

bioRxiv2024

Discovery of allodiploid hybrid species Aspergillus latus in Japan

Allodiploid hybrid species, Aspergillus latus, belonging to section Nidulantes, is a hybrid of A. spinulosporus and unknown species closely related to A. quadrilineatus and A. subltus. This hybrid has often been misidentified as the species in section Nidulantes, such as A. nidulans, A. spinulosporus, A. sublatus, or other cryptic species. A. latus has not been reported in Japan as well as Asia so far. In this study, we screened 23 clinical strains identified as A. spinulosporus isolated in Japan from 2012 to 2023 and found seven A. latus strains. To characterize the A. latus strains, we conducted comprehensive phenotyping including morphological observation, whole genome sequences and phylogenetic analysis based on calmodulin (CaM) gene. In addition, we conducted antifungal susceptibility testing for A. latus strains. As a result, the morphological characters of A. latus were more similar to those of A. spinulosporus compared to A. sublatus. However, the ascospore of A. latus differed from that of A. spinulosporus. A. latus phylogenetically clustered with A. spinulosporus and A. sublatus. Furthermore, A. latus strains showed reduced susceptibility to caspofungin and amphotericin B compared to A. spinulosporus, while they were susceptible to azoles. Our results suggest that A. latus has been a causative pathogen of aspergillosis in Japan since 2013.

microbiology↗

bioRxiv2023

A broad antibody class engages the influenza virus hemagglutinin head at its stem interface

Influenza infection and vaccination impart strain-specific immunity that protects against neither seasonal antigenic variants nor the next pandemic. However, antibodies directed to conserved sites can confer broad protection. Here we identify and characterize a class of human antibodies that engage a previously undescribed, conserved epitope on the influenza hemagglutinin (HA) protein. Prototype antibody S8V1-157 binds at the normally occluded interface between the HA head and stem. Antibodies to this HA head-stem interface epitope are non-neutralizing in vitro but protect against lethal influenza infection in mice. Antibody isotypes that direct clearance of infected cells enhance this protection. Head-stem interface antibodies bind to most influenza A serotypes and seasonal human variants, and are present at low frequencies in the memory B cell populations of multiple human donors. Vaccines designed to elicit these antibodies might contribute to "universal" influenza immunity.

microbiology↗

bioRxiv2023

Analysis of chronic host-aspergilloma interactions using a novel mouse model

An aspergilloma is a fungus ball caused by chronic infection of Aspergillus species in a pre- existing cavity, such as a destroyed lung or the sinuses. Patients with pulmonary aspergilloma are at risk of sudden life-threatening hemoptysis. Antifungal therapy is administered to aspergilloma patients who are ineligible for surgery, but its efficacy is limited. Understanding the pathophysiology of aspergilloma is crucial for developing further treatment strategies. The mechanism behind the long-term host response to aspergilloma is poorly understood. We created a novel mouse model to analyze the host response to aspergilloma by implanting a fungus ball of Aspergillus fumigatus into an air-filled subcutaneous cavity. Our findings indicate that a live fungus ball led to tissue invasion, even in immunized mice. When a fungus ball consisting of dead hyphae was implanted, it persisted for over three months and induced pathological findings simulating human aspergilloma, including an inflammatory cell infiltration into the fungus ball and angiogenesis in the cavity wall. Dead fungus ball induced Th1 and Th17 inflammatory cytokines and vascular endothelial growth factor. Neutrophils infiltrated the inside of the fungus ball immediately after implantation, and macrophages surrounded it after a one-week delay. The macrophages around the fungus ball were swollen with phagocytosed fragments of dead hyphae and transformed into foam cells containing fat droplets. We also confirmed in vitro that macrophages were damaged and transformed into foam cells by direct contact with dead hyphae. This model holds promise to provide new insights into the fungal-host interaction during aspergillomas. NOTATION OF PRIOR ABSTRACT PUBLICATION/PRESENTATIONNone IMPORTANCEChronic aspergillosis, which affects over 3 million people worldwide with a 5-year survival rate of 50%, is understudied compared to other forms. Our study focuses on aspergilloma, a key aspect of chronic aspergillosis, using a groundbreaking mouse model that mirrors clinical features over three months. By studying host-fungal interactions within aspergillomas, we discovered Th1 and Th17 inflammatory responses to dead fungal hyphae. Initially, neutrophils dominate, later giving way to macrophages with a lipid-accumulating foamy phenotype. This transition may impede aspergilloma clearance. In addition, even dead hyphae induce vascular endothelial growth factor and promote angiogenesis. Our findings, which are critical for the prevention of fatal hemoptysis, highlight the need for innovative treatments that target fungal clearance and challenge the limited efficacy of antifungal agents against dead fungal bodies. This research represents a significant step forward in the understanding of chronic aspergillosis.

microbiology↗

bioRxiv2023

Lipopolysaccharides derived from Porphyromonas gingivalis and Escherichia coli: differential and interactive effects on novelty-induced hyperlocomotion, blood cytokine levels and TRL4-related processes

Lipopolysaccharide (LPS), a component of the Gram-negative bacterial cell wall, activates Toll-like receptors (TLRs). Porphyromonas gingivalis (Pg) may be involved in the progression of periodontal disease. Mice exposed to a novel environment show hyperlocomotion that is inhibited by systemic administration of LPS derived from Escherichia coli (Ec-LPS). However, whether Pg-LPS influences novelty-induced locomotion is unknown. Accordingly, we carried out an open field test to analyse the effects of Pg-LPS. For comparison, effects of Ec-LPS were also studied. We also investigated the influence of systemic administration of Pg-LPS or Ec-LPS on IL-6, TNF-alpha, and IL-10 levels in blood, as they could be involved in the changes in locomotion. The TLR4 receptor antagonist TAK-242 was used to study the involvement of TLR4. Since Pg-LPS may block TLR4 in vitro, we analysed the effects of Pg-LPS on Ec-LPS-induced changes in behavioural and biochemical parameters. Male ddY mice were used. Compounds were administered intraperitoneally. Ec-LPS (840 {micro}g/kg), but not Pg-LPS (100, 500 and 840 {micro}g/kg), inhibited novelty-induced locomotion, which was reversed by TAK-242 (3.0 mg/kg). Ec-LPS (840 {micro}g/kg) increased blood levels of IL-6 and IL-10, which was antagonized by TAK-242 (3.0 mg/kg). However, TAK-242 did not inhibit Ec-LPS-induced increases in TNF-alpha levels in blood. Pg-LPS (100, 500, and 840 {micro}g/kg) did not alter blood IL-6, TNF-alpha, or IL-10 levels. The Ec-LPS-induced increase in blood IL-10, but not IL-6 and TNF-alpha, levels was inhibited by Pg-LPS (500 {micro}g/kg). These results suggest that TLR4 stimulation mediates the inhibition of novel environment-induced locomotion in mice following systemic administration of Ec-LPS, while also increasing blood IL-6 and IL-10 levels. In contrast, Pg-LPS did not exhibit these effects. The present study also provides in vivo evidence that Pg-LPS can inhibit TLR4-mediated increases in blood IL-10 levels, which is thought to prevent the development of periodontal disease.

microbiology↗

bioRxiv2023

AI in Paleontology

Accumulating data have led to the emergence of data-driven paleontological studies, which reveal an unprecedented picture of evolutionary history. However, the fast-growing quantity and complication of data modalities make data processing laborious and inconsistent, while also lacking clear benchmarks to evaluate data collection and generation, and the performances of different methods on similar tasks. Recently, Artificial Intelligence (AI) is widely practiced across scientific disciplines, but has not become mainstream in paleontology where manual workflows are still typical. In this study, we review more than 70 paleontological AI studies since the 1980s, covering major tasks including micro-and macrofossil classification, image segmentation, and prediction. These studies feature a wide range of techniques such as Knowledge Based Systems (KBS), neural networks, transfer learning, and many other machine learning methods to automate a variety of paleontological research workflows. Here, we discuss their methods, datasets, and performance and compare them with more conventional AI studies. We attribute the recent increase in paleontological AI studies to the lowering bar in training and deployment of AI models rather than real progress. We also present recently developed AI implementations such as diffusion model content generation and Large Language Models (LLMs) to speculate how these approaches may interface with paleontological research. Even though AI has not yet flourished in paleontological research, successful implementation of AI is growing and show promise for transformative effect on the workflow in paleontological research in the years to come. HighlightsO_LIFirst systematic review of AI applications in paleontology. C_LIO_LIThere is a 10 to 20-year gap between AI in paleontology and mainstream studies. C_LIO_LIRecent progress in paleontological AI studies is likely a result of lowering bar in training and deployment. C_LIO_LIFuture direction discussed for interactions between paleontology and AI. C_LI

paleontology↗