Biology subjects

Dong, C.

Publications and source records attributed to Dong, C..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Cross-Molecular Active Learning for the Discovery of Antimicrobial Polyacrylamides

Antimicrobial resistance poses an urgent and increasing threat to global health. The development of new antimicrobials is crucial. Synthetic copolymers are attractive as a potential solution, because they can be produced at scale and designed to mimic antimicrobial peptides and act as broad-spectrum antimicrobials capable of evading resistance mechanisms. This work leverages a cross-molecular machine learning pipeline, trained on antimicrobial peptides, to develop potent antimicrobial polymers to combat Escherichia coli, which were then synthesized and validated experimentally. One candidate copolymer was further characterized and shown to permeabilize the bacterial membrane, which is associated with decreased resistance. Furthermore, this copolymer demonstrated remarkable synergy in eradicating biofilm-associated E. coli when combined with a first-line clinical drug regimen, reducing the amount needed to eradicate bacteria in biofilms by three orders of magnitude. These results demonstrate promise for potentiating antibacterial activity of currently available antibiotics, treating serious and complicated infections, and combatting antimicrobial resistance.

microbiology↗

bioRxiv2025

Environmental Novelty Modulates Rapid Cortical Plasticity During Navigation

In novel environments, animals quickly learn to navigate, and position-correlated spatial representations rapidly emerge in both the retrosplenial cortex (RSC) and primary visual cortex (V1). However, the role of plasticity in building these spatial representations, and how experience modulates this process, are not well understood. Here, we investigated the plasticity of spatial representations with real-time, cellular-resolution read and write control of neural activity using two-photon calcium imaging combined with holographic optogenetic stimulation in mice navigating virtual reality environments. Targeted stimulation of individual layer 2/3 neurons rapidly biased neural activity towards stimulation-paired locations in novel, but not familiar, environments. In contrast, RSC layer 5 neurons exhibited stimulation-induced plasticity regardless of environmental familiarity. These findings reveal a layer-specific, experience-dependent modulation of plasticity and offer a framework for how neocortical spatial representations strike a balance between stability of familiar environments with flexibility for continuous updates of relevant context information. HighlightsO_LIAll optical read-write approach reveals experience-dependent plasticity in cortex C_LIO_LIStimulating layer 2/3 neurons biases activity in novel but not familiar environments C_LIO_LILayer 5 neurons exhibit plasticity regardless of environmental familiarity C_LI

neuroscience↗

bioRxiv2025

Measuring Transcranial Magnetic Stimulation-Induced Electric Fields in Anatomically and Conductively Accurate Rat Head Phantoms

The efficacy of neuromodulation techniques like transcranial magnetic stimulation (TMS), are highly dependent on the geometry and conductivity of the stimulated target of the brain. Although anatomically accurate head models are routinely used for computational simulations of TMS-induced electric (E) felds, there is still a need for realistic phantoms that mimic the anatomy and electrical conductivity of the head. Here, we present a realistic rat brain phantom constructed using advanced 3-d printing technologies. Our phantom allows validation of TMS-induced E-fields using embedded mutually orthogonal triaxial dipole probes (TDP) that can measure induced E-fields along three axes. We tested the TDP probes in the constructed phantom using four TMS coils with different core materials and core geometry. These measurements were then compared to computational simulations using the finite element method (FEM). The rat brain phantoms had a conductivity of roughly 0.5 S/m, which was mimicked in the FEM simulations. When the measured induced e-fields in the phantoms were compared to the simulated results, the measured results were in the same expected range and fairly close to one another with an average error of 5.1%. The peak E-fields (measured vs. simulated) close to the surface of the grey matter were: permender v-tip core (115.3 V/m - 110V/m), permender flat tip core (91.9V/m - 85 V/m), AISI 1010 v-tip core (94.7 V/m - 100 V/m), and AISI 1010 flat-tip core (85.9 V/m - 84 V/m) respectively.

bioengineering↗

bioRxiv2025

PI-FC: Pre-training Individual-specific Functional Connectome through State-invariant Contrastive Learning

Functional MRI enables non-invasive mapping of brain connectivity, yet its clinical translation remains hindered by uncontrolled state-dependent variability that obscures individual-specific signatures during routine scanning. Here we introduce PI-FC -- a deep learning framework leveraging state-invariant contrastive learning to extract stable individual brain signatures across diverse arousal levels, cognitive states, and temporal scales spanning tens of seconds to hours. PI-FC achieves equivalent phenotypic prediction accuracy using substantially reduced scanning time, and eliminates state-dependent effects varying task demands and brain states. Trained on 36,119 subjects across 8 independent datasets, our model demonstrates superior cross-site generalization and outperforms traditional functional connectome (FC) in predicting neuropsychiatric conditions including schizophrenia, autism, depression, and anxiety. Furthermore, PI-FC enables zero-shot inference of brain age, biological sex, and cognitive ability without site-specific retraining. Overall, PI-FC represents a robust, clinically scalable framework that overcomes fundamental barriers to real-world deployment of precision functional neuroimaging.

neuroscience↗

bioRxiv2025

Clonal analysis of SepSecS-specific CD4 T cells reveals a new HLA-DPA102:01/HLA-DPB101:01-restricted immunodominant epitope in autoimmune hepatitis

Autoreactive CD4 T cells, recognizing liver-self-antigens such as SepSecS, are main drivers of the chronic inflammatory response during autoimmune hepatitis (AIH). Previous studies have uncovered immunodominant SepSecS epitopes often associated with HLA-DRB1*03 or HLA-DRB1*04 restriction, two alleles enriched in AIH population. However, HLA restriction of numerous SepSecS epitopes remains incomplete and it is still unclear if immunodominant epitopes could be presented by non-HLA-DR molecules. Here, we investigated epitope recognition of SepSecS-specific TCRs isolated from AIH patients, and their HLA restriction by generating TCR hybridoma cell lines. Seventeen TCRs recognized eight SepSecS epitopes with four distinct HLA restrictions, including a novel HLA-DPA1*02:01/DPB1*01:01-restricted SepSecS epitope. TCR clustering analysis using GLIPH2 algorithm suggested that this epitope is recognized by multiple distinct TCRs in HLA-DPA1*02:01[~]HLA-DPB1*01:01 patients. Our study provides new insights into liver-self-antigen T cell reactivity during AIH, which could offer potential therapeutic strategies by targeting autoreactive CD4 T cells.

immunology↗

bioRxiv2025

The Role of Primate-Specific Genes and Network Dynamics in Cancer Evolution

The atavistic evolutionary theory of cancer evolution highlights the role of ancient and unicell-originated genes, and comprehensive research demonstrated the evolutionary inference. Comparably, very few reports linked young genes with cancer development and maintenance. Here, we found that in cancer cell lines a higher proportion of core essential genes was present among primate-specific genes (PSG) than early metazoan-originated genes (Wilcoxon rank-sum test, p-value = 4.67e-12) and mammal-originated genes (Wilcoxon rank-sum test, p-value = 1.22e-16). Additionally, we found that the loss of many co-expression gene pairs in pan-cancer leads to their network becoming looser compared with normal tissue. However, PSGs particularly those being essential, exhibit a dynamic increase in co-expression, explaining their enhanced role in maintaining cancers. Furthermore, clustering of the gene co-expressions brings a cancer-exclusive module, which contains a large number of PSG connections. We also demonstrate the divergence between essential genes in healthy individuals and those in cancer cells. Our findings complement the atavistic theory in elucidating the evolutionary process of cancer.

evolutionary biology↗

bioRxiv2025

Long-acting hydrogel-based depot formulations of tirzepatide and semaglutide for the management of type 2 diabetes and weight

Several incretin hormone therapies have been clinically approved and have revolutionized the treatment of diabetes and obesity. Promising therapeutics include semaglutide (Ozempic(R) and Wegovy(R)), an agonist for glucagon-like peptide-1 (GLP-1) receptor, and tirzepatide (Mounjaro(R)), a dual agonist for GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors. These molecules help to regulate blood glucose levels, enhance insulin secretion and sensitivity, and reduce appetite. Currently, these treatments require weekly injections, which can be challenging for patients to adhere to. We recently reported the development of an injectable hydrogel depot technology enabling months-long release of semaglutide (Sema). Here, we further develop this technology for improved prolonged release of both Sema and tirzepatide (TZP). In a rat model of diabetes, we show a single administration of hydrogel-based formulations of either Sema or TZP maintained relevant drug levels for over 6 weeks. In these studies, single administrations of long-acting hydrogel-based therapies of Sema or TZP were similarly effective at regulating blood glucose and weight compared to daily injections of either Sema or TZP in standard aqueous vehicles. This hydrogel depot technology is easy to manufacture, injectable, and exhibits excellent biocompatibility, enabling months-long-acting treatments with the potential to improve management of diabetes and weight.

bioengineering↗

bioRxiv2025

Engineering Sustained-Release Broadly Neutralizing Antibody Formulations

Sustained serum levels of broadly neutralizing antibodies (bnAbs) are crucial for effective passive immunization against infectious diseases as protection persists only while these bnAbs remain at adequate concentrations within the body. Current obstacles, such as poor pharmacokinetics (PK) and burdensome administration, must be overcome to make bnAbs a viable option for pre- and post-exposure prophylaxis. In this work, we explore how a polymer-nanoparticle (PNP) hydrogel depot technology can be engineered to prolong protein delivery. In-vivo studies in mice and rats demonstrate prolonged protein release, and modeling efforts predict the impact of both the elimination half-life of the active pharmaceutical ingredient and hydrogel depot volume on overall pharmacokinetics. Moreover, flow cytometry characterization reveals that immune cell infiltration into the hydrogel depot can result in faster-than-expected release of antibody cargo on account of active transport via cellular uptake. We then demonstrate that co-formulation of antibodies with an anti-inflammatory agent reduces cellular infiltration and resulting active transport, further extending delivery and pharmacokinetics. Finally, multicompartmental modeling predicts the human PK profiles of clinically relevant HIV bnAbs delivered via subcutaneous hydrogel injection. These findings aid in the development of next generation hydrogel materials that stabilize and slowly release bnAbs for long-term pre-exposure immunoprophylaxis.

bioengineering↗

bioRxiv2025

Host adaptation and genome evolution of the broad host range fungal rust pathogen, Austropuccinia psidii

Rust diseases on plants are caused by fungi in the order Pucciniales. Typically, rust fungi have narrow host specificity however the pandemic biotype of Austropuccinia psidii has an unusually broad host range causing disease on over 480 myrtaceous species globally. We assembled and analysed a fully phased chromosome-level genome for the pandemic A. psidii and addressed key outstanding questions of its infection biology. Our research revealed a conserved rust fungal karyotype of 18 haploid chromosomes, in line with fungi for distantly related cereal rusts. We observed chromosomal re-assortment between the two nuclei, with one nucleus carrying 19 and the other 17 chromosomes. The synteny of universal single-copy orthologs is mostly maintained with the distantly related rust fungus Puccinia graminis f. sp. tritici. In contrast, nucleotide composition and methylation profiles of A. psidii are distinct compared to rust fungi with smaller genome sizes that have not undergone massive transposable element expansions. Our analysis of mating type loci supports a tetrapolar mating system for A. psidii with a novel finding of expanded numbers of pheromone peptide precursors. We show that infection dynamics of A. psidii are consistent on four different susceptible host species separated by 65 mya of evolution and that transcriptional regulation during infection reveals two distinct waves of gene expression in early and late infection, including allele-specific expression of candidate effectors. Together, these findings enhance the understanding of the genome biology and pathology of A. psidii, while also providing a valuable resource for future research on this serious rust pathogen.

microbiology↗

bioRxiv2025

IL-17A-driven Macrophage Disorder Promotes Plaque Instability in Psoriatic Atherosclerosis

Psoriasis is a common chronic inflammatory skin disease that predisposes individuals to cardiovascular diseases such as atherosclerosis. However, the underlying mechanisms linking these conditions have not yet been fully elucidated. Recent studies have indicated that the inflammatory cytokine IL-17A plays a significant role in both diseases. The aim of this study was to investigate how psoriasis affects the stability of atherosclerotic plaques via the IL-17A/IL-17RA pathway. We performed single-cell sequencing on patients with both psoriasis and atherosclerosis to analyze changes in the immune microenvironment within their carotid plaques and psoriatic lesions. We found that IL-17A significantly upregulated the expression of pro-inflammatory factors (e.g., CXCL8) in macrophages of psoriatic atherosclerosis patients, leading to weakening of the fibrous cap structure of plaques. Additionally, IL-17A further exacerbated plaque instability by interfering with macrophage lipid metabolism, particularly sphingolipid metabolism. Finally, using in vitro experiments and animal models, we demonstrated that IL-17A enhances pro-inflammatory and metabolic abnormalities in macrophages by downregulating PPAR{gamma}. Therapeutic strategies targeting IL-17A may contribute to the simultaneous mitigation of psoriasis and atherosclerosis-associated cardiovascular risk, providing new directions for clinical intervention.

cell biology↗

bioRxiv2025

Scalable Culture of Mammalian Cells in RGD Peptide-Modified Alginate Hydrogel Microtubes

Traditional livestock farming is resource-intensive and environmentally unsustainable, necessitating alternative methods for meat production. Cell cultured meat, produced by expanding and differentiating animal cells, offers great potential for substituting for conventional animal meat. Nevertheless, it is still limited by the scalability and efficiency of current cell culture technologies. In this study, we developed an RGD peptide-modified alginate hydrogel microtube microbioreactor (AlgTubes) to support the scalable culture of anchor-dependent cells, such as myoblasts and adipocytes, for cell-cultured meat production. AlgTubes provide a cell-friendly 3D microenvironment that enhances cell viability, growth, and yield while overcoming limitations of conventional bioreactors, such as shear stress, aggregation, and diffusion constraints. We successfully expanded mouse (C2C12) and quail (QM7) myoblasts in AlgTubes, achieving cell densities exceeding 1.0 x 10 cells/mL, far surpassing traditional stirred-tank bioreactors. Differentiation resulted in the formation of mature myotubes. Co-culturing myoblasts with mesenchymal stem cells or fibroblasts further improved yield and viability, particularly under differentiation conditions. By significantly increasing cell culture density, AlgTubes can substantially reduce culture volume, lowering labor requirements, reagent costs, equipment needs, facility space, and manufacturing expenses.

bioengineering↗

bioRxiv2025

Collagen Nanofiber Reinforced Alginate Hydrogel Tube Microbioreactors for Cell Culture

The large-scale production of mammalian cells is pivotal for various applications; however, current bioreactor technologies encounter significant technical and economic challenges. Scaling up cell cultures remains problematic due to excessive cell aggregation, shear stress-induced cell death, batch-to-batch inconsistencies, and limited scalability. We propose that engineering a cell-friendly microenvironment can enhance culture efficiency. Previously, we developed alginate hydrogel microtubes (AlgTubes) that significantly improved cell density and growth rates. Nevertheless, AlgTubes lack adhesion sites essential for anchorage-dependent cells and frequently break, causing cell leakage and production inconsistencies. To address these limitations, this study reinforced AlgTubes with collagen nanofibers, creating collagen-alginate hybrid hydrogel microtubes (ColAlgTubes). Utilizing a novel micro-extruder, we efficiently produced cell-loaded ColAlgTubes. Collagen formed a dense nanofiber network interwoven with the alginate mesh, enhancing the hydrogels mechanical properties while providing cell adhesion sites. ColAlgTubes protected cells from hydrodynamic stress and maintained cell mass within a 400 m diameter, ensuring efficient nutrient exchange and waste removal. This optimized microenvironment resulted in high cell viability, rapid proliferation, and exceptional yields of 5x108 cells/mL - 200 times higher than conventional culture methods. With their scalability, cost-effectiveness, and efficiency, ColAlgTubes offers a transformative solution for large-scale cell production with broad applications in biotechnology, regenerative medicine, and therapeutic manufacturing.

bioengineering↗

bioRxiv2025

Transferrin receptor 1 (TfR1) functions as an entry receptor for scale drop disease virus to invade host cell via clathrin-mediated endocytosis

Scale drop disease virus (SDDV), a distinct member of the genus Megalocytivirus within the Iridoviridae family, has emerged as a novel threat to global teleost aquaculture. Despite its importance, the pathogenic mechanism of SDDV remains largely elusive. In this study, we identified mandarin fish transferrin receptor 1 (mfTfR1) as an entry receptor for SDDV to invade host cells. Firstly, mfTfR1 was detected in high abundance in purified SDDV virions and exhibited dynamic responses to SDDV infection, showing distinct regulatory patterns both in vivo and in vitro. Overexpression of mfTfR1 in low-permissive fathead minnow (FHM) cells significantly enhanced SDDV replication, particularly during the early stages of viral binding and entry. Conversely, antibody-blocking experiments and treatment with the TfR1 inhibitor ferristatin II significantly suppressed SDDV entry. Further investigation revealed that mfTfR1 directly interacted with the major capsid protein (MCP) of SDDV, and the helical domain of mfTfR1 was identified as the crucial docking site. The binding site within the helical domain was determined, and disrupting this interaction significantly reduced viral entry and host mortality. Finally, we demonstrated that SDDV could activate Src kinase-mediated tyrosine phosphorylation of mfTfR1. This phosphorylation event enhanced the internalization of mfTfR1 and facilitated clathrin-mediated endocytosis. Collectively, our study provides compelling evidence to confirm that mfTfR1 functions as an entry receptor that mediates SDDV entry into host cells via clathrin-mediated endocytosis, leading to a lethal infection outcome. Our work lays the ground work for the development of targeted therapeutic strategies to mitigate the impact of SDDV in aquaculture. IMPORTANCETfR1, a dimeric glycoprotein classified as a type II transmembrane receptor, facilitates the cellular internalization of holo-transferrin. In several mammalian and avian RNA viruses, TfR1 serves as a crucial receptor to mediate the entry of viruses into host cells. As an emerging large DNA virus, SDDV poses an emerging threat to teleosts globally, however, its underlying pathogenic mechanisms remain poorly understood. In this study, we are the first to identify mfTfR1 as a crucial receptor for SDDV entry. We demonstrated a specific interaction between mfTfR1 and the major capsid protein (MCP) of SDDV, with the helical domain of mfTfR1 acting as the binding site. Moreover, we confirmed that SDDV enters cells through mfTfR1-mediated clathrin-dependent endocytosis. This work highlights the essential role of TfR1 in aquatic DNA viral infections and establishes the theoretical foundation for developing targeted therapeutic strategies against SDDV.

microbiology↗

bioRxiv2025

Biosynthesis of modular signaling molecules requires functional diversification of carboxylesterases in Pristionchus pacificus

The model nematode Pristionchus pacificus produces four types of complex ascaroside pheromones named UBAS, DASC, NPAR, and PASC. However, the exact biosynthetic pathways of these modular signaling molecules remain enigmatic. We have previously identified a carboxylesterase Ppa-UAR-1 for the biosynthesis of UBAS, enabling the attachment of ureidoisobutyric acid at the 4-position of simple ascarosides. Here, we report three new carboxylesterases Ppa-UAR-5, Ppa-UAR-6 and Ppa-UAR-12 from P. pacificus. Ppa-UAR-5 functions downstream of Ppa-UAR-1 to furnish the biosynthesis of ubas#1 and ubas#2, whereas Ppa-UAR-12 specifically links two ascr#1 at the 4-position to synthesize dasc#1. Finally, Ppa-UAR-6 is essential for the biosynthesis of npar#1-3 and part#9. The expression patterns of Ppa-uar-6 and Ppa-uar-12 in the intestinal and epidermal cells suggest pheromone biosynthesis to be restricted to specific tissues. These findings indicate that the expansion and functional diversification of carboxylesterases plays a crucial role in the evolution of complex pheromones in nematodes. SIGNIFICANCEOur study identified three new carboxylesterase genes (Ppa-uar-5, Ppa-uar-12 and Ppa-uar-6) from P. pacificus. The encoded enzymes separately regulated the biosynthesis of three types of modular pheromones (UBAS, DASC, and NPAR-types) in worms intestinal cells and exhibited extremely high substrate-specificity. For example, we verified that Ppa-UAR-12 specifically linked one ascr#1 to the 4-position of another ascr#1 to finally furnish the biosynthesis of ascaroside dimer dasc#1. These new discoveries largely clarify the delicate biosynthetic mechanisms of how diversification of carboxylesterases functions in P. pacificus to build up enormous complexity of modular signaling molecules. Such a biosynthetic mechanism of nematode pheromones might be widely conserved in the phylum Nematoda.

biochemistry↗

bioRxiv2025

Scale drop disease virus (SDDV) triggering ferroptosis both in vivo and in vitro facilitates virus infection via targeting transferrin receptor 1 (TfR1)

Scale drop disease virus (SDDV) is a distinct member in genus Megalocytivirus of family Iridoviridae, garnering increasing attention due to its significant threat to teleost. Ferroptosis is a new type of cell death discovered recently and involved in various viral infections. Knowledges on SDDV induced ferroptosis remains unclear. Here, we demonstrated that SDDV infection triggers ferroptosis, as evidenced by hallmark features such as iron overload, massive lipid peroxides accumulation, glutathione depletion and glutathione peroxidase 4 downregulation. SDDV-infected MFF-1 cells exhibited increased reactive oxygen species production and mitochondrial shrinkage. Treatment with Ferrostatin-1, a potent ferroptosis inhibitor, significantly attenuated SDDV replication in MFF-1 cells and could improve the survival of mandarin fish upon SDDV challenge. Treatment with an iron chelator mitigated ferroptosis and reduced the mortality of mandarin fish following SDDV infection, suggesting that SDDV-induced ferroptosis is iron-dependent. Finally, we demonstrated that SDDV infection could upregulate the expression of transferrin receptor protein 1 (TfR1), a critical iron transporter, to disrupt cellular iron homeostasis, induce ferroptosis, and then facilitate viral infection. Collectively, our findings provide compelling evidence that SDDV infection induces ferroptosis by targeting TfR1 to facilitate virus infection. Inhibiting ferroptosis represents a promising immunotherapeutic strategy for combating SDDV infection in aquaculture.

microbiology↗

bioRxiv2025

Spatial and molecular insights into microglial roles in cerebellar aging

Aging induces region-specific functional decline across the brain. The cerebellum, critical for motor coordination and cognitive function, undergoes significant structural and functional changes with age. The molecular mechanisms driving cerebellar aging--particularly the role of cerebellar glia, including microglia--remain poorly understood. Here, we used single-nuclei RNA sequencing (snRNA-seq), microglial bulk RNA-seq, and multiplexed error-robust fluorescence in situ hybridization (MERFISH) to characterize transcriptional changes associated with cellular aging in the mouse cerebellum. We discovered that microglia exhibited the most pronounced age-related changes of all cell types and that their transcriptional signatures pointed to enhanced neuroprotective immune activation and reduced lipid-droplet accumulation compared to hippocampal microglia. Furthermore, cerebellar microglia in aged mice, compared to young mice, were found in closer proximity to granule cells. This relationship was characterized using the newly defined neuron-associated microglia score, which captures proximity-dependent transcriptional changes and suggests a novel microglial responsiveness. These findings underscore the unique adaptations of the cerebellum during aging and its potential resilience to Alzheimers disease (AD) related pathology, providing crucial insight into region-specific mechanisms that may shape disease susceptibility.

neuroscience↗

bioRxiv2025

Biplanar nulling coil system for OPM-MEG using printed circuit boards

Optically pumped magnetometers (OPMs) are a promising sensor technology for non-invasive measurement of human electrophysiological signals, in particular the magnetoencephalogram (MEG). OPMs do not need cryogenic cooling and can be placed conformal to the subjects scalp, thus greatly reducing the sensor-to-source distance and improving signal sensitivity. OPMs, however, require near-zero background magnetic field to achieve linearity and minimize signal distortion. Prior work has proposed the use of biplanar field nulling coils to remove the uniform and gradient components of the background magnetic field. Biplanar coils have been expensive to construct, involving tedious error-prone manual winding of over 1000 m of copper wire. In this work, we designed and fabricated background field nulling coils (three uniform and three gradient components) on two-layer Printed Circuit Boards (PCBs). We used an open-source software (bfieldtools) to determine the current loops needed to produce the target magnetic field in a 50-cm-diameter spherical volume. We developed a software-based approach to connect the discrete current loops into a continuous conducting path traversing the two layers of the PCB. For ease of manufacture, the designed (1.5 x 1.5 m2) coils were cut along the symmetry axis and printed as pairs of 1.5 x 0.75 m2 PCBs (2 oz Cu), soldered together and mounted on a sliding aluminum frame. The efficiency of the coils (1.3 - 7.1 nT/mA) was similar or higher than previously reported in the literature. We mapped the field inside the target region after field nulling inside our single-layer shielded room and were able to reduce the largest component of the background field from 21 to 2 nT. Using our nulling coil system, we were able to operate OPMs in a lightly shielded room (background field varying from 6.5 to 108 nT in the floor-to-ceiling direction) to record somatosensory evoked fields (SEFs) comparable to those measured using SQUID-based MEG in a 3-layer shielded room. We disseminate the software and hardware as an open-source package opmcoils. This work will facilitate access to more affordable field nulling coils for OPM-MEG and help to realize the potential of OPM-MEG as an accessible sensor technology for use in human neuroscience.

neuroscience↗

bioRxiv2025

Top-down control of the descending pain modulatory system drives placebo analgesia

In placebo analgesia, prior experience and expectations lead to pain suppression by the administration of an inert substance, but causal evidence for its neural basis is lacking. To identify the underlying neural circuits, we reverse-translated a conditioned placebo protocol from humans to mice. Surprisingly, the placebo effect suppresses both nociception and unconditioned emotional-motivational pain-related behavior. Descending pain modulatory neurons in the periaqueductal gray (PAG) are critical for both morphine and placebo antinociception. The placebo effect depends on input to the PAG from the medial prefrontal and anterior cingulate cortices, but not anterior insular cortex. Conditioning enhances noxious stimulus-evoked endogenous opioid release in the PAG to produce analgesia. Our results suggest that cortical control of the descending pain modulatory system (DPMS) is gated by rapid endogenous opioid signaling in the PAG during placebo trials. This study bridges clinical and preclinical research, establishing a central role for the DPMS in placebo analgesia.

neuroscience↗