Biology subjects

Yang, J.

Publications and source records attributed to Yang, J..

At least 433 records · Page 24Linked to original sources

bioRxiv2024

CLCC1 Governs Bilayer Equilibration at the Endoplasmic Reticulum to Maintain Cellular and Systemic Lipid Homeostasis

The intricate orchestration of lipid production, storage, and mobilization is vital for cellular and systemic homeostasis1,2. Dysfunctional plasma lipid control represents the major risk factor for cardio-metabolic diseases, the leading cause of human mortality3,4. Within the cellular landscape, the endoplasmic reticulum (ER) is the central hub of lipid synthesis and secretion, particularly in metabolically active hepatocytes in the liver or enterocytes in the gut5,6. Initially assembled in the ER lumen, lipid-ferrying lipoproteins necessitate the cross-membrane transfer of both neutral and phospho-lipids onto the lumenal apolipoprotein B (APOB), in a poorly-defined process7-10. Here we show that trans-bilayer equilibration of phospholipids, regulated by the ER protein CLCC1, determines lipid partition across the ER membrane and consequently systemic lipid homeostasis. CLCC1 partners with the phospholipid scramblase TMEM41B11,12 to recognize imbalanced bilayers and promote lipid scrambling, thereby licensing lipoprotein biogenesis and the subsequent bulk lipid transport. Strikingly, loss of CLCC1 or TMEM41B leads to the emergence of giant lumenal lipid droplets enclosed by extensively imbalanced ER bilayers, and consequently drastically accelerated pathogenesis of metabolic-dysfunction-associated liver steatohepatitis (MASH). The above results establish phospholipid scrambling at the ER as the lynchpin to maintain a dynamic equilibrium. Considering the requirement of trans-bilayer phospholipid equilibration in numerous biological processes, ranging from catabolic autophagy to viral infection13-16, our study may enable further elucidation of a previously under-appreciated homeostatic control mechanism intrinsic to the ER function in lipid biogenesis and distribution.

cell biology↗

bioRxiv2024

Functional imaging of whole mouse embryonic development in utero

Despite significant advances in structural and genetic studies, investigations of early embryonic functions, such as brain activity, have long been constrained by technical challenges. Functional ultrasound (fUS) has emerged as a breakthrough modality, enabling real-time monitoring of brain activity with exceptional spatial and temporal resolution and offering unprecedented opportunities for studying functional embryonic development. In this study, we used fUS to monitor whole-embryo activity in mice from embryonic days E8.5 to E18.5, revealing patterns of neural activity throughout embryogenesis. This approach provides new opportunities to explore brain development dynamically as it unfolds. Moreover, we observed embryo responses to external stimuli, including sound, in both mice and cynomolgus macaques, offering insights into early sensory processing and neural maturation. In summary, our study establishes fUS as a powerful tool for studying embryonic brain functional development, with significant implications for scientific research, especially in non- human primate models, and clinical applications.

developmental biology↗

bioRxiv2024

Exosomal miRNA-124 is involved in the immune regulation of cervical cancer by regulating CD45 alternative splicing

ObjectiveTo investigate the regulatory mechanism of miRNA-124 in tumor immune regulation of cervical cancer. MethodsPeripheral blood samples of cervical cancer patients and transient infection controls were collected to extract exosomal miR-124 and Stem-loop Q-PCR to detect the expression level of miR-124. QPCR, WB, and flow cytometry were used to detect the mRNA and protein expression of Th cell differentiation and function-related genes. Transfection, QPCR, and flow cytometry were used to detect the effects of miR-124 overexpression and silencing on the differentiation of Th immune memory cells. In vitro, cell-killing experiments were performed to detect the tumor-killing activity of TH immune memory cells co-cultured with the Hela cell line, and the downstream target genes of miR-124 were predicted and verified by luciferase. Multiplex PCR was used to detect the genotype of miR-124 SNP in peripheral blood DNA. QPCR and WB were used to detect the mRNA and protein expression and phosphorylation of miR-124 target gene GSK3-PSF-CD45 pathway, and GSK3 inhibitor was used to block the pathway. ResultsWe found that exosomal miRNA-124 was significantly downregulated in cervical cancer tissues and affected Th cell immune function and memory cell generation. The overexpression of miRNA-124 can directly target GSK3, phosphorylate the target gene, and inhibit the expression of GSK3, thereby increasing the expression of CD45, increasing the ability of Th immune cells to recognize and kill the HPV virus, and significantly inhibiting the proliferation and migration of cervical cancer cells.

molecular biology↗

bioRxiv2024

Cortex Folding by Combined Progenitor Expansion and Adhesion-Controlled Neuronal Migration

Folding of the mammalian cerebral cortex into sulcal fissures and gyral peaks is the result of complex processes that are incompletely understood. Previously we showed that genetic deletion of Flrt1/3 adhesion molecules causes folding of the smooth mouse cortex into sulci resulting from increased lateral dispersion and faster neuron migration, without progenitor expansion. Here, we find that combining the Flrt1/3 double knockout with an additional genetic deletion that causes progenitor expansion, greatly enhances cortex folding. Expansion of intermediate progenitors by deletion of Cep83 results in enhanced formation of sulci. Expansion of apical progenitors by deletion of Fgf10 results in enhanced formation of gyri. Single cell transcriptomics and simulations suggest that changes in adhesive properties of cortical neurons, their proportions and densities in the cortical plate, combined with lateral dispersion during their radial migration are important folding parameters. These results identify key developmental mechanisms that cooperate to promote cortical gyrification. HIGHLIGHTSO_LICortex folding is enhanced by combining progenitor expansion and divergent migration. C_LIO_LIConcomitant expansion of intermediate progenitors results in the formation of sulci C_LIO_LIConcomitant expansion of apical progenitors results in the formation of gyri C_LIO_LIProgenitors differentially affect cortical neurons with distinct adhesive properties C_LI

neuroscience↗

bioRxiv2024

Precise Generation of Conformational Ensembles for Intrinsically Disordered Proteins Using Fine-tuned Diffusion Models

Intrinsically disordered proteins (IDPs) play pivotal roles in various biological functions and are closely linked to many human diseases including cancer, diabetes and Alzheimer disease. Structural investigations of IDPs typically involve a combination of molecular dynamics (MD) simulations and experimental data to correct for intrinsic biases in simulation methods. However, these simulations are hindered by their high computational cost and a scarcity of experimental data, severely limiting their applicability. Despite the recent advancements in structure prediction for structured proteins, understanding the conformational properties of IDPs remains challenging partly due to the poor conservation of disordered protein sequences and limited experimental characterization. Here, we introduce IDPFold, a method capable of generating conformational ensembles for IDPs directly from their sequences using fine-tuned diffusion models. IDPFold bypasses the need for Multiple Sequence Alignments (MSA) or experimental data, achieving accurate predictions of ensemble properties across numerous IDPs. By sampling conformations at the backbone level, IDPFold provides more detailed structural features and more precise property estimation compared to other state-of-the-art methods. IDPFold is ready to be used in the elucidate the sequence-disorder-function paradigm of IDPs.

bioinformatics↗

bioRxiv2024

In vitro heterochronic parabiosis identifies pigment epithelium-derived factor as a systemic mediator of rejuvenation by young blood

Several decades of heterochronic parabiosis (HCPB) studies have demonstrated the restorative impact of young blood, and deleterious influence of aged blood, on physiological function and homeostasis across tissues, although few of the factors responsible for these observations have been identified. Here we develop an in vitro HCPB system to identify these circulating factors, using replicative lifespan (RLS) of primary human fibroblasts as an endpoint of cellular health. We find that RLS is inversely correlated with serum donor age and sensitive to the presence or absence of specific serum components. Through in vitro HCPB, we identify the secreted protein pigment epithelium-derived factor (PEDF) as a circulating factor that extends RLS of primary human fibroblasts and declines with age in mammals. Systemic administration of PEDF to aged mice reverses age-related functional decline and pathology across several tissues, improving cognitive function and reducing hepatic fibrosis and renal lipid accumulation. Together, our data supports PEDF as a systemic mediator of the effect of young blood on organismal health and homeostasis and establishes our in vitro HCPB system as a valuable screening platform for the identification of candidate circulating factors involved in aging and rejuvenation.

cell biology↗

bioRxiv2024

Cryo-EM Reveals the Mechanochemical Cycle of Reactive Full-length Human Dynein-1

Dynein-driven cargo transport plays pivotal roles in diverse cellular activities, central to which is dyneins mechanochemical cycle. Here, we performed a systematic cryo-electron microscopic investigation of the conformational landscape of full-length human dynein-1 in reaction, under various nucleotide conditions, on and off microtubules. Our approach reveals over 40 high-resolution structures, categorized into eight states, providing a dynamic and comprehensive view of dynein throughout its mechanochemical cycle. The novel intermediate states reveal important mechanistic insights into dynein function, including a backdoor phosphate release model that coordinates linker straightening, how microtubule binding enhances ATPase activity through a two-way communication mechanism, and the crosstalk mechanism between AAA1 and the regulatory AAA3 site. Our findings also lead to a substantially revised model for the force-generating powerstroke and reveal a means by which dynein exhibits unidirectional stepping. These results substantially improve our understanding of dynein and provide a more complete model of its mechanochemical cycle.

biochemistry↗

bioRxiv2024

Megabarcoding reveals a tale of two very different dark taxa along the same elevational gradient

AbstractOur planet is entering the sixth mass extinction without detailed spatio-temporal distribution and abundance information for most insect species. Particularly lacking is this information for dark taxa although they contain most animal species. This problem can be addressed with high-throughput single specimen barcoding (megabarcoding), but it remain unknown to what extent one dark taxon can be used as a proxy for another because of similar biodiversity patterns. This is here tested and we show that two Diptera taxa (Phoridae, Mycetophilidae) have very different spatio-temporal distributions across the same elevational gradient. We applied COI megabarcoding to samples collected every 14 days over three seasons at six elevations (800 to 1,800 m) in a temperate forest ecosystem in Northern China (Baihua Mountain Reserve). Elevation, precipitation, and temperature were used as environmental variables to understand the data obtained for 17,179 specimens representing 492 mOTUs of Phoridae and 2,281 specimens of 148 mOTUs of Mycetophilidae. Congruent is that the alpha diversity for both taxa increased in the summer and there is evidence for a mid-domain effect and phylogenetic clustering in high elevations. However, the extent and pattern of seasonal variation differed considerably. Phorid communities exhibited shifts between spring, summer and autumn seasons, but surprisingly little difference between elevations. In contrast, mycetophilid communities were structured along the elevational gradient and dependent on precipitation. Our study highlights the urgent need for obtaining detailed spatio-temporal information for the most diverse dark taxa, but also illustrates that these data can be readily obtained with megabarcoding.

ecology↗

bioRxiv2024

Linkage: an interactive shiny app and R package for linking of DNA regulatory peaks to genes

SummaryExisting studies have demonstrated that the integration analysis of transcriptomic and epigenomic data can be used to better understand the onset and progression of many diseases, as well as identify new diagnostic and prognostic biomarkers. However, such investigations on large-scale sequencing data remain challenging for researchers or clinicians with limited bioinformatics knowledge. To facilitate the interpretation of gene regulatory landscape, we developed an R Shiny application and R package [Linking of atac-seq to gene expression data (Linkage)] for exploring and visualizing potential cis-regulatory elements (CREs) of genes based on ATAC-seq and RNA-seq data. Linkage offers six modules to systematically identify, annotate, and interpret potential gene regulatory elements from the whole genome step by step. Linkage can provide interactive visualization for the correlation between chromatin accessibility and gene expression. More than that, Linkage identifies transcription factors (TFs) that potentially drive the chromatin changes through identifying TF binding motifs within the CREs and constructing trans-regulatory networks of the target gene set. This powerful tool enables researchers to conduct extensive multiomics integration analysis and generate visually appealing visualizations that effectively highlight the relationship between genes and corresponding regulatory elements. With Linkage, users can obtain publishable results and gain deeper insights into the gene regulatory landscape. Availability and implementation Linkage is freely available as a Shiny web application (https://xulabgdpu.org.cn/linkage) and an R package (https://github.com/XuLab-GDPU/Linkage). The documentation is available at (https://aicplane.github.io/Linkage-tutorial/).

bioinformatics↗

bioRxiv2024

Specific oncogene activation of the cell of origin in mucosal melanoma

Mucosal melanoma (MM) is a deadly cancer derived from mucosal melanocytes. To test the consequences of MM genetics, we developed a zebrafish model in which all melanocytes experienced CCND1 expression and loss of PTEN and TP53. Surprisingly, melanoma only developed from melanocytes lining internal organs, analogous to the location of patient MM. We found that zebrafish MMs had a unique chromatin landscape from cutaneous melanoma. Internal melanocytes could be labeled using a MM-specific transcriptional enhancer. Normal zebrafish internal melanocytes shared a gene expression signature with MMs. Patient and zebrafish MMs have increased migratory neural crest gene and decreased antigen presentation gene expression, consistent with the increased metastatic behavior and decreased immunotherapy sensitivity of MM. Our work suggests the cell state of the originating melanocyte influences the behavior of derived melanomas. Our animal model phenotypically and transcriptionally mimics patient tumors, allowing this model to be used for MM therapeutic discovery.

cancer biology↗

bioRxiv2024

Exploring differences between depression and bipolar disorder through the urinary proteome

How to differentiate the diagnosis of depression and bipolar disorder has always been an important problem that needs to be solved urgently in clinical practice. In this study, from the perspective of urine proteomics, urine samples of similar age were collected from two hospitals to investigate the candidate biomarkers for differentiating the diagnosis of depression and bipolar disorder using both group analysis and one-to-many analysis(1 patient: many control samples). The experimental results of the paired group analysis showed that 108 differential proteins were identified in the depressed group compared to the bipolar group under strict screening conditions with screening criteria of FC [≥] 2 or [≤] 0.5 and a two-tailed unpaired t-test of P < 0.01, with an average of 3.7 randomly generated differential proteins, and a confidence level of 96.6 % for the correlation between these proteins and the disease difference. In the one-to-many analysis, 24 differential proteins were co-identified by the samples of 13 depressed patients, 16 of which showed a completely consistent trend of expression changes in all depressed patients studied, and 6 of which were associated with immunoglobulins; 41 differential proteins were co-identified by the samples of 12 depressed patients out of 13, and 19 of which showed a completely consistent trend of expression change in the These results reflect the strong consistency of differential proteins between the two groups of patients. 12 or more samples from depressed patients were enriched for differential proteins related to multiple biological processes and signaling pathways associated with the immune system, which is consistent with previous studies: immune mechanisms may be one of the pathogenetic mechanisms of major depression and that drugs with major immune targets can improve depressive symptoms. In the future, it may be possible to observe the immune status of patients with depression to provide direction and basis for the precise treatment of depression. The results of this paper show that urine proteomics can differentiate between depression and bipolar disorder, suggest possible mechanisms and potential targets for the treatment of depression and bipolar disorder, and provide a tool for future differential diagnosis and precision treatment of the diseases.

biochemistry↗

bioRxiv2024

Dzip1 is dynamically expressed in the vertebrate germline and regulates the development of Xenopus primordial germ cells.

Primordial germ cells (PGCs) are the precursors of sperms and oocytes. Proper development of PGCs is crucial for the survival of the species. In many organisms, factors responsible for PGC development are synthesized during early oogenesis and assembled into the germ plasm. During early embryonic development, germ plasm is inherited by a few cells, leading to the formation of PGCs. While germline development has been extensively studied, how components of the germ plasm regulate PGC development is not fully understood. Here, we report that Dzip1 is dynamically expressed in vertebrate germline and is a novel component of the germ plasm in Xenopus and zebrafish. Knockdown of Dzip1 impairs PGC development in Xenopus embryos. At the molecular level, Dzip1 physically interacts with Dazl, an evolutionarily conserved RNA-binding protein that plays a multifaced role during germline development. We further showed that the sequence between amino acid residues 282 and 550 of Dzip1 is responsible for binding to Dazl. Disruption of the binding between Dzip1 and Dazl leads to defective PGC development. Taken together, our results presented here demonstrate that Dzip1 is dynamically expressed in the vertebrate germline and plays a novel function during Xenopus PGC development.

developmental biology↗

bioRxiv2024

Nanocluster-antibody-drug conjugates (NADC) as an intravesical precision theranostic agent for interstitial cystitis

Interstitial cystitis (IC) is a chronic inflammatory bladder disorder with recurring severe pain, lacking timely diagnostic and therapeutic options. Here, we propose a unitary theranostic nanocluster-antibody-drug conjugate (NADC) by covalently placing dihydroorotate dehydrogenase inhibitors (DHODHi) and ultrasmall gold quantum clusters (AuQCs) on a nerve growth factor (NGF) antagonistic antibody with simultaneous X-ray computed tomographic and near-infrared fluorescence imaging contrasts. Combining anti-inflammatory effects from all individual components, intravesical NADC specifically homed to mucosal lesions with NGF overexpression in voided bladder and capably alleviated inflammation in chronic, acute, and prophylactic IC models of rats, as revealed by behavioral and pathological evaluations. Transcriptomics unveiled cytokine modulation and concomitant inhibition of perturbed IL-17, NF-{kappa}B, TNF, and JAK-STAT signaling pathways. Notably, NADC indirectly remodeled the host bladder microbiota by differentially varying anti-inflammatory and pro-inflammatory bacteria diversities. Distinct from conventional nanoparticles conjugated with antibodies and drugs, NADC relies on the antibody framework, outperforms clinical standard-of-care agents, and represents an emerging category of precision theranostic agents with translational potential for IC theranostics in clinical practice.

microbiology↗

bioRxiv2024

MOL-AE: Auto-Encoder Based Molecular Representation Learning With 3D Cloze Test Objective

3D molecular representation learning has gained tremendous interest and achieved promising performance in various downstream tasks. A series of recent approaches follow a prevalent framework: an encoder-only model coupled with a coordinate denoising objective. However, through a series of analytical experiments, we prove that the encoderonly model with coordinate denoising objective exhibits inconsistency between pre-training and downstream objectives, as well as issues with disrupted atomic identifiers. To address these two issues, we propose MO_SCPLOWOLC_SCPLOW-AE for molecular representation learning, an auto-encoder model using positional encoding as atomic identifiers. We also propose a new training objective named 3D Cloze Test to make the model learn better atom spatial relationships from real molecular substructures. Empirical results demonstrate that MO_SCPLOWOLC_SCPLOW-AE achieves a large margin performance gain compared to the current state-of-the-art 3D molecular modeling approach. The source codes of MO_SCPLOWOLC_SCPLOW-AE are publicly available at https://github.com/yjwtheonly/MolAE.

bioinformatics↗

bioRxiv2024

scPanel: A tool for automatic identification of sparse gene panels for generalizable patient classification using scRNA-seq datasets

Single-cell RNA sequencing (scRNA-seq) technologies can generate transcriptomic profiles at a single-cell resolution in large patient cohorts, facilitating discovery of gene and cellular biomarkers for disease. Yet, when the number of biomarker genes is large the translation to clinical applications is challenging due to prohibitive sequencing costs. Here we introduce scPanel, a computational framework designed to bridge the gap between biomarker discovery and clinical application by identifying a minimal gene panel for patient classification from the cell population(s) most responsive to perturbations (e.g., diseases/drugs). scPanel incorporates a data-driven way to automatically determine the number of selected genes. Patient-level classification is achieved by aggregating the prediction probabilities of cells associated with a patient using the area under the curve score. Application of scPanel on scleroderma and COVID-19 datasets resulted in high patient classification accuracy using a small number (<20) of genes automatically selected from the entire transcriptome. We demonstrate 100% cross-dataset accuracy to predict COVID-19 disease state on an external dataset, illustrating the generalizability of the predicted genes. scPanel outperforms other state-of-the-art gene selection methods for patient classification and can be used to identify small sets of reliable biomarker candidates for clinical translation.

bioinformatics↗

bioRxiv2024

MGPfactXMBD: A Model-Based Factorization Method for scRNA Data Unveils Bifurcating Transcriptional Modules Underlying Cell Fate Determination

Manifold-learning is particularly useful to resolve the complex cellular state space from single-cell RNA sequences. While current manifold-learning methods provide insights into cell fate by inferring graph-based trajectory at cell level, challenges remain to retrieve interpretable biology underlying the diverse cellular states. Here, we described MGPfactXMBD, a model-based manifold-learning framework and capable to factorize complex development trajectories into independent bifurcation processes of gene sets, and thus enables trajectory inference based on relevant features. MGPfactXMBD offers more nuanced understanding of the biological processes underlying cellular trajectories with potential determinants. When bench-tested across 239 datasets, MGPfactXMBD showed advantages in major quantity-control metrics, such as branch division accuracy and trajectory topology, outperforming most established methods. In real datasets, MGPfactXMBD recovered the critical pathways and cell types in microglia development with experimentally valid regulons and markers. Furthermore, MGPfactXMBD discovered evolutionary trajectories of tumor-associated CD8+ T cells and yielded new subtypes of CD8+ T cells with gene expression signatures significantly predictive of the responses to immune checkpoint inhibitor in independent cohorts. In summary, MGPfactXMBD offers a manifold-learning framework in scRNA-seq data which enables feature selection for specific biological processes and contributing to advance our understanding of biological determination of cell fate.

bioinformatics↗

bioRxiv2024

Quinoline-based compounds can inhibit diverse enzymes that act on DNA

DNA methylation, as exemplified by cytosine-C5 methylation in mammals and adenine-N6 methylation in bacteria, is a crucial epigenetic mechanism driving numerous vital biological processes. Developing non-nucleoside inhibitors to cause DNA hypomethylation is a high priority, in order to treat a variety of significant medical conditions without the toxicities associated with existing cytidine-based hypomethylating agents. In this study, we have characterized fifteen quinoline-based analogs. Notably, compounds with additions like a methylamine (9) or methylpiperazine (11) demonstrate similar low micromolar inhibitory potency against both human DNMT1 (which generates C5-methylcytosine) and Clostridioides difficile CamA (which generates N6-methyladenine). Structurally, compounds 9 and 11 specifically intercalate into CamA-bound DNA via the minor groove, adjacent to the target adenine, leading to a substantial conformational shift that moves the catalytic domain away from the DNA. This study adds to the limited examples of DNA methyltransferases being inhibited by non-nucleotide compounds through DNA intercalation, following the discovery of dicyanopyridine-based inhibitors for DNMT1. Furthermore, our study shows that some of these quinoline-based analogs inhibit other enzymes that act on DNA, such as polymerases and base excision repair glycosylases. Finally, in cancer cells compound 11 elicits DNA damage response via p53 activation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/587980v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@da2e94org.highwire.dtl.DTLVardef@27f909org.highwire.dtl.DTLVardef@4ec628org.highwire.dtl.DTLVardef@1b384df_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LISix of fifteen quinoline-based derivatives demonstrated comparable low micromolar inhibitory effects on human cytosine methyltransferase DNMT1, and the bacterial adenine methyltransferases Clostridioides difficile CamA and Caulobacter crescentus CcrM. C_LIO_LICompounds 9 and 11 were found to intercalate into a DNA substrate bound by CamA. C_LIO_LIThese quinoline-based derivatives also showed inhibitory activity against various base excision repair DNA glycosylases, and DNA and RNA polymerases. C_LIO_LICompound 11 provokes DNA damage response via p53 activation in cancer cells. C_LI

molecular biology↗

bioRxiv2024

Mechano-regulation of GLP-1 production by Piezo1 in intestinal L cells

Glucagon-like peptide 1 (GLP-1) is a gut-derived hormone secreted by intestinal L cells and vital for postprandial glycemic control. As open-type enteroendocrine cells, whether L cells can sense mechanical stimuli caused by chyme and thus regulate GLP-1 synthesis and secretion is unexplored. Our study showed expression of Piezo1 in intestinal L cells. Its level varied in different energy status and correlates with blood glucose and GLP-1 levels. Mice with L cell-specific loss of Piezo1 (IntL-Piezo1-/-) exhibited impaired glucose tolerance, increased body weight, reduced GLP-1 production and decreased CaMKK{beta}/CaMKIV-mTORC1 signaling pathway under normal chow diet or high fed diet. Activation of the intestinal Piezo1 by its agonist Yoda1 or intestinal bead implantation increased the synthesis and secretion of GLP-1, thus alleviated glucose intolerance in diet-induced-diabetic mice. Overexpression of Piezo1, Yoda1 treatment or stretching stimulated GLP-1 production and CaMKK{beta}/CaMKIV-mTORC1 signaling pathway, which could be abolished by knockdown or blockage of Piezo1 in primary cultured mouse L cells and STC-1 cells. These findings suggest a previously undiscovered mechano-regulation of GLP-1 production in L cells, which may shed new light on the treatments of diabetes.

physiology↗