Biology subjects

Martin, C.

Publications and source records attributed to Martin, C..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Distributed fMRI patterns coupled to low-frequency cardiorespiratory dynamics provide markers of aging

How aging affects brain-body connections can be investigated through changes in the coupling between functional magnetic resonance imaging (fMRI) signals and bodily autonomic processes across the adult lifespan. Recent studies using univariate approaches have identified age-related changes in the association between fMRI signals from multiple individual brain regions and low-frequency respiratory and cardiac activity. Here, we investigate if whole-brain spatial fMRI patterns associated with low-frequency physiological processes (heart rate and respiratory volume fluctuations) present generalizable changes with age. Data from human participants of both sexes are included in the analysis. We find that chronological age can be predicted statistically beyond chance from patterns of low-frequency fMRI-physiology coupling, even after accounting for individual differences in physiological signal characteristics and brain anatomy. Notably, brain areas implicated in central autonomic regulation, including nodes within salience and ventral attention networks (e.g., insula and middle cingulate cortex), are amongst the strongest contributors to age prediction. Further, we observe that after removing physiological effects from fMRI data, the residual blood oxygen level-dependent (BOLD) signal variability is still a reliable indicator of age. Together, these findings underscore the close integration between brain and body physiology, and highlight this interaction as a potential biomarker of the aging process. Significance StatementThe association between brain activity and respiratory or cardiac activity is often dismissed as "noise" in functional magnetic resonance imaging (fMRI) studies. However, emerging evidence suggests that coupling between fMRI and peripheral physiological signals can provide valuable insight into the brain-body connection. In this study, we show that whole brain patterns of coupling between fMRI signals and low-frequency respiratory and cardiac processes can reliably predict age across the adult lifespan. Brain regions involved in autonomic regulation, such as insula and cingulate cortex, were among the most informative predictors of age. These findings suggest that fMRI-physiology coupling may capture aging-related changes in brain vascular health and autonomic function and may have broader relevance for tracking disease-related disruptions in brain-body interaction.

neuroscience↗

bioRxiv2025

Chromosome-Scale Genome Assembly of Australian Finger Lime and Resequencing Reveal the Hidden Diversity of Oceanian Citrus

Oceanian citrus species, including wild taxa native to Australia and Papua New Guinea, form a genetically distinct clade within the Citrus L. (1753) genus. These species remain largely underexplored, despite their adaptation to diverse environments and relevance for citrus improvement. To support their use in breeding and evolutionary studies, we generated a high-quality, Chromosome-scale genome assembly of an Australian finger lime accession (SRA 1002), a natural interspecific hybrid. The genome was assembled using long-read sequencing, optical mapping, and a high-density genetic map, resulting in nine pseudomolecules covering over 97% of the genome. Using this reference, we analyzed whole-genome resequencing data from 132 accessions representing the diversity of Asian and Oceanian citrus. Variant calling across the dataset produced a high-resolution catalogue of single nucleotide polymorphisms (SNPs) and derived database of SNP fully discriminant of 20 Citrus species (DSNPs), enabling detailed exploration of inter- and intra-specific diversity. The data reveal a strong population structure within the group with clear heterozygosity variation between ancestral species and admixed accessions, reflecting their complex evolutionary history and hybridization patterns. This study provides the first integrated genomic framework for Oceanian citrus diversity, offering essential tools for downstream applications in citrus breeding, conservation, and evolutionary genomics. The resources generated lay the groundwork for future association studies and the targeted introgression of beneficial traits into cultivated citrus.

plant biology↗

bioRxiv2025

Phage N4 uses a SAR endolysin-holin system for host cell lysis

Abstract Bacteriophages (phages) cause active host cell lysis to terminate their infection and release progeny into the environment. However, some phages have systems to delay their lysis, and thereby increase progeny yield, in specific conditions: a phenomenon called lysis inhibition (LIN). Two dissimilar phages of Escherichia coli are known to exhibit LIN: T4 and N4. In T4, a multi-protein mechanism stalls lysis and maintains the LIN state in response to superinfection in a high phage population density. However, the lysis proteins responsible for T4 lysis and LIN are not conserved with phage N4. In this study, we characterize the phage N4 proteins involved in lysis by molecular and genetic means. We define the functions of the minimal gene set required for lysis through heterologous expression and complementation. Furthermore, by sequence comparison with a selected mutant library that does not induce LIN, we have identified genomic regions both within and outside the lysis cassette involved in N4 LIN. We propose a model where N4 lysis proteins that execute rapid N4 lysis can be regulated to induce LIN. Despite the lack of conservation with T4 components, our study suggests that direct modulation of lysis initiation may be common and provides a springboard for identifying similar mechanisms in other phages. Importance Phages are viruses that kill only bacteria. To do so, they use lysis proteins to disrupt the structural components of the bacterial envelope. There are commonalities between the phages that infect bacteria with similar structures, but there are also interesting differences we can exploit to learn more about specific phages or their bacterial hosts. In this study, we characterize the lysis proteins of the E. coli phage N4. Our results suggest that lysis regulation controls phage yield in N4 differently than in well-studied phage T4. Future studies on the relationship between lysis proteins and phage yield could provide handles to use this information for optimal large-scale phage production for clinical or industrial applications.

microbiology↗

bioRxiv2025

The Ligand Preference of LRP1 is Regulated by O-glycans

Low-density lipoprotein receptor (LDLR) and LDLR-related proteins (LRPs) are endocytic receptors serving as essential physiological regulators of multiple processes including cholesterol clearance, protein reabsorption and neuronal protein trafficking. We originally discovered O-glycans in linkers of the ligand-binding domains of LDLR/LRP receptors and showed that these play critical roles for uptake of LDL by LDLR and albumin by LRP2. Remarkably, these linker O-glycans are introduced exclusively by GALNT11, one out of 20 polypeptide GalNAc-transferase isoenzymes. Here, we investigate the role of linker O-glycans on the large ([~]600 kDa) and widely expressed multiligand LRP1 receptor implicated in diseases including neuropathies. In genetically engineered cell models we activated endogenous full-coding LRP1 with and without O-glycans and demonstrate that while the uptake of certain ligands, such as RAP and ApoE, was unaffected by O-glycans, the uptake of the neurotoxic molecules tau and amyloid beta was altered and in opposite directions. This demonstrates that O-glycans in ligand-binding domains can differentially modulate ligand affinity and specificity of LRP1. Our findings highlight an overlooked regulatory mechanism of endocytic receptors and identify the ligand repertoire of LRP1 as being influenced by O-glycans, with potential implications for neurodegenerative disease.

molecular biology↗

bioRxiv2025

Local thalamic interneurons drive spindle termination and enable sleep-dependent learning

The thalamus is central to fundamental brain functions including sensation, attention, and sleep through the precise generation and regulation of neuronal ensemble oscillatory activity. Sensory thalamic circuits are considered feedforward structures, lacking lateral connectivity, while recurrence in the network is mediated by interactions with inhibitory neurons of the thalamic reticular nucleus. Here, we define previously uncharacterized functional roles of local thalamic interneurons, a component of the sensory thalamus whose function has remained unexplored. We demonstrate that local interneuron activation induces rebound oscillations in thalamocortical relay neurons ex vivo and neocortical spindles in vivo, while their inhibition increases spindle occurrence, overall spindle duration and impairs sensory learning. Our findings reveal that local thalamic interneurons have shared and complementary functions to those of thalamic reticular neurons and are required for proper spindle formation and sleep-dependent learning. Together, this work establishes an important neural substrate of thalamocortical circuit function.

neuroscience↗

bioRxiv2025

Optimizing and assessing multichannel TMS focality

BackgroundMultichannel transcranial magnetic stimulation (mTMS) enables electronic steering of induced electric fields across multiple cortical targets without physical coil repositioning, addressing key limitations of conventional single-channel TMS (sTMS). However, determining optimal input currents for focal stimulation remains challenging, and different mTMS systems have not been systematically compared under realistic hardware constraints. ObjectiveTo develop an user-centric framework for optimizing and assessing mTMS focality by introducing a generic optimization algorithm, establishing meaningful quality metrics, and comparing mTMS coil arrays with traditional single-channel TMS across cortical targets. MethodsWe developed a fast optimization framework incorporating target E-field constraints via parametrization of degenerated hyperellipsoids, explicitly integrating current-rate limits, for example from stimulator electronics and coil heating. Using high-resolution finite-element models of nine individual brains, we compared two mTMS designs (5-channel planar and 6/12-channel spherical systems) with standard sTMS figure-of-eight coils through E-field simulations. Three complementary metrics quantified stimulation quality: Focality, Target2Max, and OverstimulatedArea. ResultsDespite using a single optimized placement for all region-of-interest targets, mTMS achieved focality comparable to repositioned single-channel TMS in this in-silico study. For superficial targets, single-channel TMS showed slightly better stimulation, but for deeper cortical targets (>25 mm skin-cortex distance), mTMS performed similarly. More mTMS channels improved focality but required stronger current-rate constraints. The planar design performed better for deeper targets, while spherical designs improved with additional channels. ConclusionmTMS systems demonstrate remarkable performance comparable to standard TMS, enabling efficient multi-target stimulation without repositioning. Our open-source framework provides practical tools for designing and evaluating mTMS systems, supporting goal-directed mTMS development and effective application.

neuroscience↗

bioRxiv2025

Smart Microscopy: Current Implementations and a Roadmap for Interoperability

Smart microscopy is transforming life sciences by automating experimental imaging workflows and enabling real-time adaptation based on feedback from images and other data streams. This shift increases throughput, improves reproducibility, and expands the functional capabilities of microscopes. However, the current landscape is highly fragmented. Academic researchers often develop custom solutions for specific scientific needs, while industry offerings are typically proprietary and tied to specific hardware. This diversity, while fostering innovation, also creates major challenges in interoperability, reproducibility, and standardization, which slows progress and adaption. This article presents a collaborative effort between academic and industry leaders to survey the current state of smart microscopy, highlight representative implementations, and identify common technical and organizational barriers. We propose a framework for greater interoperability based on shared standards, modular software design, and community-driven development. Our goal is to support collaboration across the field and lay the groundwork for a more connected, reusable, and accessible smart microscopy ecosystem. We conclude with a call to action for researchers, hardware developers, and institutions to join in building an open, interoperable foundation that will unlock the full potential of smart microscopy in life science research.

cell biology↗

bioRxiv2025

BCG-induced reprogramming of monocyte/macrophage populations enhances lung antitumor immunity in mice

The tumor microenvironment (TME) significantly influences antitumor immunity, with monocytes and macrophages playing pivotal roles both in pro- and anti-tumoral functions. Tumor-associated macrophages (TAMs) often adopt immunosuppressive phenotypes that promote tumor progression by inhibiting cytotoxic T and NK cells. This study investigates the antitumor mechanisms of intravenous (IV) Bacillus Calmette-Guerin (BCG) in a B16-F10 lung melanoma mouse model, focusing on its impact on monocyte/macrophage populations. Single-cell RNA sequencing revealed that IV BCG reprograms tumor-associated monocyte-derived macrophages (mo-macs), shifting them from immunosuppressive to pro-inflammatory phenotypes enriched in interferon-response signatures. BCG treatment increased the recruitment of classical (Mon Iigp1) and non-classical (Mon Fcgr4) monocytes, which exhibited enhanced antigen presentation and pro-inflammatory cytokine production, while reducing immunosuppressive subsets prevalent in untreated controls. These BCG-induced mo-macs established robust interactions with NK and T cells, promoting their activation and enhancing cytotoxic function, as validated by functional assays. Notably, transfer of BCG reprogrammed bone marrow progenitors into naive recipients elicited a sustained generation of immunostimulatory mo-macs that enhanced NK and T cell responses upon tumor challenge, These findings highlight IV BCGs potential as a cancer immunotherapy that targets the myeloid compartment to foster a pro-inflammatory TME, offering durable antitumor immunity by engaging both innate and adaptive immune responses.

immunology↗

bioRxiv2025

What are all these soil fungi doing? Complex carbon use ability as a predictive trait for fungal community functions

Fungal communities in soil play important roles in decomposition processes and soil organic carbon cycling. These communities are tremendously diverse, making it challenging to assign relevant functions to individual species. Fungal communities may be differentiated at the level of functional guilds; beyond such broad classification we have little delimitation, especially in fungal taxa common in grassland and agricultural soils. To resolve the level of functional similarity in fungal communities and define traits predictive of soil carbon cycling, we characterized fungal isolates abundant in agricultural soils to test the hypotheses that (i) the majority of saprobic soil fungi have the ability to use complex carbon sources, (ii) differences in complex carbon use abilities correlate with fungal enzymatic profiles, following principles of the fungal economics spectrum and (iii) carbon use ability is a predictive trait for fungal community functions. Using specialized growth media, we isolated and characterized 105 isolates and developed a novel FungiResp approach that directly tests fungal activity on complex carbon sources. The largest amount of variance between isolates was explained by differential abilities to use cellulose and starch, with only few phylogenetically distinct fungal clades showing high respiratory activity on these biopolymers. A preference for bacterial necromass was another major distinction among taxa. These key traits correlated with soil fungal community shifts in response to carbon substrate availability. By contrast, enzymatic activity was a poor predictor of fungal carbon use ability, except for correlations in lignin use and laccase activity. The newly established functional trait of carbon use ability offers important insights into diverse fungal communities: Many taxa lack the ability to use complex carbon (on their own), while the most common enzymes analyzed in soil showed little correlation with fungal mineralization potential. The discovery of key functional traits is an important step towards predicting the significance of fungal community shifts for soil carbon cycling.

ecology↗

bioRxiv2025

A recurrent pathogenic BRCA2 truncating variant reveals a role for BRCA2-PCAF complex in modulating NF-κB-driven transcription

Germline monoallelic truncating mutations in BRCA2, a critical mediator of homologous recombination (HR), predispose individuals to breast and ovarian cancer. While tumorigenesis is usually attributed to biallelic inactivation, emerging evidence suggests that haploinsufficiency may suffice in certain contexts. To investigate this, we recreated two BRCA2 pathogenic truncating variants in heterozygosis in non-tumorigenic breast epithelial cells. Cells carrying a truncating mutation that was not produced prompted sensitivity to PARP inhibitors (PARPi) and reduced the HR capacity indicating haploinsufficiency. Surprisingly, the other variant was expressed as a truncated product and prompted a transcriptional rewiring. Mechanistically, the truncated BRCA2 product formed abnormal oligomers with full-length BRCA2 and bound to the PCAF acetyltransferase, sequestering it. This led to reduced global histone H4 acetylation and decreased NF-{kappa}B transcriptional activity, ultimately impairing epithelial cell migration--a process also altered in tumors. Our findings uncover a previously unrecognized BRCA2-PCAF axis that modulates NF-{kappa}B-driven transcriptional program, a process that is co-opted by a recurrent BRCA2 pathogenic variant.

cancer biology↗

bioRxiv2025

Discovery of a tRNA-regulatory transcription factor that suppresses breast cancer metastasis

Transfer RNAs (tRNAs), once viewed as static adaptors in translation, are now recognized as dynamic regulators of gene expression. While recent studies have illuminated roles for tRNA stability, the upstream mechanisms governing tRNA transcription remain poorly understood. To address this gap, we generated the EXpression atlas of tRNA (EXTRNA), a high-resolution tRNA expression dataset spanning 24 cell lines across 9 human tissues. EXTRNA revealed both tissue-type-specific expression programs ("tRNAomes") and unexpected intra-tissue heterogeneity across breast cancer samples. Integrating EXTRNA with computational network analysis and data from other publicly available datasets, we identified Zinc Finger ZZ-Type And EF-Hand Domain Containing 1 (ZZEF1) as the first sequence-specific transcription factor of a particular tRNA. ZZEF1 promoted tRNA-LysUUU transcription by partnering with the ATP-dependent chromatin remodeler Chromodomain Helicase DNA Binding Protein 6 (CHD6), enhancing chromatin accessibility at tRNA-Lys-TTT-3 loci. ZZEF1 deficiency reduced tRNA-LysUUU abundance, decreased the translational efficiency of AAR codon-enriched mRNAs--including the tumor suppressor Serine/Threonine Kinase 3 (STK3)--and promoted metastatic progression in breast cancer in vivo. Together, our findings establish a previously unrecognized mechanism for RNA polymerase III-mediated tRNA transcription and define a regulatory circuit linking chromatin remodeling, codon-specific translation, and tumor suppression. More broadly, this work introduces a framework for dissecting the regulatory logic of the tRNAome and highlights tRNA expression control as a promising avenue for therapeutic intervention.

genomics↗

bioRxiv2025

Target-Specificity and Repeatability in Neuro-Cardiac-Guided TMS for Heart-Brain Coupling

The dorsolateral prefrontal cortex (DLPFC) is a principal target for transcranial magnetic stimulation (TMS) in treating major depressive disorder, with therapeutic effects thought to be mediated by its connectivity with the subgenual anterior cingulate cortex. As both regions are involved in autonomic regulation, short-term heart rate changes following DLPFC stimulation may serve as physiological markers to identify stimulation targets. We employed neuro-cardiac guided TMS in a cohort of healthy participants to examine the effects of stimulation intensity and DLPFC target specificity on heart-brain coupling (HBC). We used generalized additive models to assess nonlinear effects of stimulation intensity and target location on HBC, while accounting for pain ratings and other side effects. Intra-subject repeatability across three sessions was evaluated using intraclass correlation coefficients. We observed a non-linear modulation of HBC depending on stimulation intensity and target location, with greater effects at the F3 lateral and F3 posterior targets compared to sham. By evaluating these effects across sessions within participants, we demonstrate the robustness of our results beyond the influence of pain and other side effects on HBC modulation. Exploratory analyses of the directionality show a consistent decrease in HR only at the F3 lateral target with suprathreshold stimulation. These results demonstrate that HBC is modulated in a target- and intensity-specific manner, with particularly consistent effects at F3 lateral sites within the DLPFC. The findings enhance the understanding of TMS-modulated heart-brain interactions, offering a potential framework for optimizing individualized rTMS treatment protocols for depression.

neuroscience↗

bioRxiv2025

Host environment shapes filarial parasites fitness and Wolbachia endosymbionts dynamics

Filarial nematodes, responsible for diseases like lymphatic filariasis and onchocerciasis, depend on symbiotic Wolbachia bacteria for reproduction and development. Using the Litomosoides sigmodontis rodent model, we investigated how host type-2 immunity influences Wolbachia dynamics and parasite development. Type-2 immune environments selectively reduce germline Wolbachia in female filariae from wild-type mice, a change associated with disrupted oogenesis, embryogenesis, and microfilarial production, while somatic Wolbachia remain unaffected. Antibiotic treatments achieving systemic Wolbachia clearance result in similar reproductive impairments. Notably, Wolbachia-free microfilariae are observed shortly after Wolbachia depletion, suggesting that early-stage embryogenesis can proceed temporarily before progressive germline dysfunction ensues. Wolbachia-free microfilariae develop into infective larvae in the vector, but stall beyond the L4 stage in vertebrate hosts, showing arrested growth and reproductive organ maturation defects in both male and female larvae. These findings highlight the variable dependency on Wolbachia across life stages and provide insights into host-parasite-endosymbiont interactions shaped by environmental pressures. Graphical abstract. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=136 SRC="FIGDIR/small/632327v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@98e008org.highwire.dtl.DTLVardef@9c32a7org.highwire.dtl.DTLVardef@c19000org.highwire.dtl.DTLVardef@1d523ad_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2024

Ecological associations of the coastal marsh periwinkle snail Littoraria irrorata: field and laboratory evidence of vegetation habitat preferences

Coastal salt marshes serve as the margin between terrestrial and marine biomes, provide a variety of important services, and are dynamic ecosystems characterized by keystone species that shape trophic networks. In coastal salt marshes of the Eastern Atlantic and Gulf of Mexico, marsh periwinkle snails (Littoraria irrorata) exhibit high abundance and form critical trophic pathways as important herbivores and detritivores. Specifically, snails forage on Spartina alterniflora and associated fungal growth, for which L. irrorata may act as a top-down control on plant growth. Yet, L. irrorata occupies other salt marsh plants, suggesting its habitat niche may be broader than previously reported. Here, we documented snail densities and size distributions in a Louisiana (USA) salt marsh composed of multiple marsh graminoids and report the results of behavioral choice experiments designed to test snail habitat preferences as a potential mechanism underlying their field distribution. We observed higher snail densities on S. alterniflora stalks (283.0 snails m-2) than other plant species, however, snails were highly abundant on S. patens (115.6 snails m-2), Juncus roemerianus (94.8 snails m-2), and Distichlis spicata (56.9 nails m-2) with densities comparable or higher on all species than reported on S. alterniflora in other studies along the U.S. Atlantic and Gulf coasts. Snails found on S. alterniflora and J. roemerianus, both plants with tall and rigid stalks, were also larger than snails found on other plant species. In species preference experiments, snails preferred S. alterniflora over S. patens and D. spicata, but no clear preferences were observed between S. alterniflora and J. roemerianus, nor between any combinations of S. patens, D. spicata, and J. roemerianus. Finally, we found that snails preferred senescing and dead S. alterniflora tissue over fresh S. alterniflora. Interpreting these results in tandem, this study suggests L. irrorata snails have consistent patterns of field distributions that match their habitat preferences, and future studies should test potential processes driving snail habitat selection, such as dietary habits and predator refugia (i.e., climbing sturdy stalks to avoid aquatic predators). Considering the abundance and trophic role of L. irrorata in coastal salt marshes, snail behavior may be a key modulator for salt marsh trophic networks.

ecology↗

bioRxiv2024

Three cytochrome P450 enzymes catalyse the formation of furanoclerodane precursors in Salvia spp.

Salvia species native to the Americas are rich in valuable bioactive furanoclerodanes, like the psychoactive salvinorin A found in Salvia divinorum, which is used in treatment of opioid addiction. However, there is relatively little known about their biosynthesis. To address this, we investigated the biosynthesis of salviarin, the simplest furanoclerodane structure in the ornamental sage Salvia splendens. Using a self-organizing map and mutual rank analysis of RNA-seq co-expression data, we identified three cytochrome P450 enzymes responsible for converting kolavenol into salviarin precursors, consecutively: annonene, hardwickiic acid and hautriwaic acid. As annonene and hardwickiic acid have also been proposed as intermediates in the biosynthesis of salvinorin A, and to examine our hypothesis for common evolutionary origin of the furanoclerodane pathway between the two Salvia species, we searched for homologous genes in available data for S. divinorum. The enzymes encoded by orthologous genes from S. divinorum displayed kolavenol synthase (SdKLS), annonene synthase (SdANS), and hardwickiic acid synthase (SdHDAS) activity respectively, supporting the view that these are intermediate steps in the biosynthesis of salvinorin A. We investigated the origin of annonene synthase and the role of gene duplication in the evolution of this specific activity. Our work shows how S. splendens can serve as a model species for studying furanoclerodanes biosynthesis in Salvia species, contributes to understanding the evolution of specialized metabolism in plants, and provides new tools to produce salvinorin A in biotechnological chassis.

plant biology↗

bioRxiv2024

NK cells mediate preventive efficacy of intravenous BCG against lung metastasis in mice

Lung metastases frequently arise from primary tumors, including bladder cancer, and represent a critical negative prognostic factor. Natural Killer (NK) cells have shown to play a vital role in controlling metastasis. Consequently, tumor cells have evolved specific mechanisms to evade NK cell-mediated immune surveillance, promoting metastasis and resistance to immunotherapy. In this study, we investigated the prophylactic and therapeutic potential of intravenous Bacillus Calmette-Guerin (BCG) in preventing lung metastases from bladder cancer cells using a murine model. We demonstrated that prophylactic BCG administration significantly reduced tumor burden and prolonged survival, largely through NK cell activation. However, BCG treatment was ineffective when administered over established tumors, likely due to tumor-driven immune evasion mechanisms. Our results revealed the contribution of interferon-gamma (IFN-{gamma}) to tumor resistance. Tumor cells exposed to IFN-{gamma} upregulated were more resistant to BCG in vivo, which correlated with the overexpression of immune checkpoint molecules, whereas disruption of the IFN-{gamma} signaling pathway in tumor cells partially restored the therapeutic efficacy of BCG. Our findings highlight the importance of understanding tumor immune escape mechanisms and suggest that BCG could be a promising treatment for preventing lung metastases in bladder cancer.

immunology↗

bioRxiv2024

EPHA2 Regulates SOX2 during Esophageal Development

The human esophagus, derived from the anterior foregut endoderm, requires proper dorsal-ventral patterning for development. The transcription factor SOX2, crucial in this process, when dysregulated, leads to congenital esophageal abnormalities. EPHA2, a receptor tyrosine kinase, is vital in various developmental processes and cancer models, where it activates SOX2. This study demonstrates that EPHA2 regulates SOX2 expression during esophageal development using human iPSCs and iPSC-derived human esophageal organoids (HEO). Inhibition of EPHA2 decreased iPSC-derived HEO formation and SOX2 expression. These findings provide evidence of EPHA2 as being a key regulator of SOX2 signaling in early esophageal development. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC="FIGDIR/small/617209v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@16b8a8aorg.highwire.dtl.DTLVardef@1548672org.highwire.dtl.DTLVardef@46e28corg.highwire.dtl.DTLVardef@1c35578_HPS_FORMAT_FIGEXP M_FIG SFD: Serum-Free Differentiation media; EPC: esophageal progenitor cells; HEO: human esophageal organoids Created with BioRender.com C_FIG HighlightsO_LISOX2 is crucial for proper esophageal development. C_LIO_LIEPHA2 is a receptor tyrosine kinase involved in various developmental processes. C_LIO_LIEPHA2 activates SOX2. C_LIO_LIInhibition of EPHA2 decreased SOX2 expression and human esophageal organoid formation. C_LI

developmental biology↗

bioRxiv2024

The Roboscope: Smart and Fast Microscopy for Generic Event-Driven Acquisition

Automation of fluorescence microscopy is a challenge for capturing rare or transient events in biology and medicine. It relies on smart devices that integrate and interpret the observed data, and react to the targeted biological event. We report on the Roboscope, a novel autonomous microscope combining sequence interruption and deep learning integration, allowing generic event-driven acquisitions. This system distinguishes itself by its adaptability to various experiments, quick capture of dynamic events, and minimal data greediness - training with less than 100 images per class. The Roboscopes capability is demonstrated in non-synchronized cells by capturing the metaphase, a 20-minute event happening once per day or less. Conversely, double thymidine-block synchronisation, despite occurring during DNA replication, may perturb mitotic-spindle mechanics. The Roboscopes versatility and efficiency offer significant advancements to tackle the current challenges of cell biology, spreading out advanced microscopy methods to fundamental research as well as high content screening and precision medicine.

bioengineering↗