Biology subjects

Long, F.

Publications and source records attributed to Long, F..

At least 19 recordsLinked to original sources

bioRxiv2026

Tunable Magnetorheological Elastomer Substrates for Studying Mechano-Genetic Interactions in Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease. While sarcomeric genomic variants drive HCM, a role for mechanical stress in disease pathogenesis is increasingly appreciated. However, existing in vitro models of HCM rely on model systems (e.g., hydrogels) with static mechanical properties, precluding investigation of how dynamic mechanical loading interacts with genetic susceptibility during disease initiation. Here, we leveraged a dynamically tunable magnetorheological elastomer (MRE) platform to model progressive mechanical stiffening in order to study mechano-genetic interactions in human induced pluripotent stem cell (hiPSC) derived cardiomyocytes harboring an HCM-associated MYBPC3 frameshift (MYBPC3fs) loss-of-function variant. Dynamic stiffening selectively unmasked pathological structural remodeling in MYBPC3fs cardiomyocytes while producing only modest changes in isogenic controls, suggesting that MYBPC3fs confers heightened mechanosensitivity. In MYBPC3fs cardiomyocytes, mechanical stiffening drove hypertrophic remodeling, sarcomere disorganization, nuclear remodeling, dysregulated NFAT3 signaling, and aberrant cell-cycle activity. MRE stiffening also drove fibroblast-to-myofibroblast transition in primary cardiac fibroblasts, recapitulating early fibrotic remodeling. Together, these findings position dynamically tunable MRE substrates as a human-relevant platform for dissecting mechano-genetic disease mechanisms and evaluating therapies targeting mechanotransduction pathways in HCM.

bioengineering↗

bioRxiv2026

Impaired glycolysis in bone underlies age-related bone loss in mice

Bone loss and metabolic dysregulation often coexist in older adults, yet the relationship between age-related changes in bone cell metabolism and bone-forming activity remains unclear. By modeling both conditions in aged mice and using in vivo stable-isotope tracing, we demonstrated that age-related decline in bone formation was coupled with an intrinsic impairment of glycolysis within bone tissue. Impaired glycolysis was associated with reduced protein levels of key glycolysis enzymes, and transcriptomics analyses revealed compensatory upregulation of glycolysis genes in aged bone. Metabolic intervention through long-term caloric restriction prevented age-related trabecular bone loss. Furthermore, osteoblast-specific genetic enhancement of glycolysis, via overexpression of HIF1 or the rate-limiting enzyme PFKFB3, significantly improved osteoblast function and increased bone mass in aged mice. Together, the study identifies glycolytic decline as a cell-autonomous driver of osteoblast deficiency and provides proof of principle that reactivating glycolysis can promote bone accrual in aging.

physiology↗

bioRxiv2026

Strigolactone signaling regulates corm development through SPL15-mediated hormonal crosstalk in banana

Strigolactones (SLs) are an important class of plant hormones that play crucial roles in regulating plant branching, root architecture, and organ development. However, the regulatory mechanisms underlying the crosstalk between SLs and other plant hormones remain largely unclear, particularly regarding the key regulatory genes that integrate and coordinate multiple hormonal signaling pathways. In this study, secondary cup seedlings of the Pisang Awak banana cultivar Yufen 6 at the eight-leaf stage were used as experimental materials. The roots were treated with a nutrient solution containing 30 mol/L exogenous SLs, while a nutrient solution supplemented with water served as the control. Tissues near the corm growth point were collected at 0, 15, 30, 60, 90, and 120 days after treatment to measure corm weight, height, and diameter, and transcriptome sequencing was performed using the collected tissues. Differentially expressed genes (DEGs) at different treatment stages were identified, followed by Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to systematically investigate the crosstalk between SLs and endogenous hormone metabolism and signaling during corm development in Pisang Awak banana. The results showed that SL treatment significantly inhibited the weight, height, and diameter of the corm. The regulatory effect of SLs on Pisang Awak banana corm development exhibited a clear temporal dynamic pattern, representing a gradual accumulation process that ultimately triggers key developmental transitions. The highest number of DEGs was detected at 15 days after treatment, including 3943 upregulated genes and 3704 downregulated genes, indicating that this stage represents a critical phase for SL response initiation. GO enrichment analysis revealed that the DEGs were mainly involved in metabolic processes, biological regulation, response to stimulus, and regulation of biological processes. KEGG pathway analysis indicated that these DEGs were significantly enriched in pathways related to plant hormone signal transduction, starch and sucrose metabolism, and secondary metabolite biosynthesis. Further analysis revealed that the crosstalk between SLs and multiple hormone metabolic and signaling pathways is mediated by the SPL15 gene, involving auxin (IAA), cytokinin (CTK), abscisic acid (ABA), brassinosteroids (BRs), gibberellins (GA), and jasmonic acid (JA) pathways. This study reveals the molecular mechanism by which SLs regulate Pisang Awak banana corm development through SPL15-mediated integration of multiple hormonal signals, providing new insights into the role of SLs in regulating the development of underground organs in banana.

bioinformatics↗

bioRxiv2026

A single cell atlas defines perinatal factors that drive murine bone marrow development

Processes that direct initial colonization and maturation of the bone marrow remain elusive, despite lifelong importance to hematopoiesis. Bone marrow mesenchymal and stromal cell (BMSC) maturation establishes supportive niches prior to hematopoietic stem cell (HSC) recruitment. We define mouse BMSC progenitor identities and temporal emergence in a developmental single cell atlas spanning fetal life through 18 months of age. We clarify Cxcl12-abundant reticular (CAR) cell and osteoblast development, including temporal emergence of signaling modalities that direct HSC quiescence and regenerative capacity. CAR cells are absent until birth, with a developmental block during fetal maturation related to transcriptional changes during perinatal life. Temporal changes in Early B Cell Factor (Ebf) 1-3 expression and activity correlate with CAR formation and niche establishment, including Ebf2 repression and induction of Ebf3 activities that direct metabolic changes. Changes in systemic physiology underlie these transcriptional changes, including perinatal induction of lipid metabolism, inflammation, and hypoxic signaling. These systemic factors direct CAR cell emergence after birth, providing temporal and developmental resolution underlying the colonization and maturation of the bone marrow environment.

developmental biology↗

bioRxiv2026

Brain-wide Organization of Post-Synaptic Sites: Three Principles

Synapses are fundamental units of neural computation and structural plasticity in the brain, yet their brain-wide spatial organization in mammals remains largely unknown. Building on our previous mapping and modeling of dendritic spines and axonal boutons, we developed a statistical approach to generate over 17.99 million predicted post-synaptic sites based on the potential arbor contacts (PPSSPAC) across the dendritic arbors of 155,743 neurons spanning the entire mouse brain. By analyzing the topological features of these sites, we identified three key organizational principles. First, PPSSPAC exhibits a distinct region-specific spatial pattern at the dendritic branch level, preferentially enriching near the distal ends of dendritic segments, in contrast to the valley-like distribution of pre-synaptic sites along axonal branches. Cross-species validation against independent electron microscopy datasets from mouse and human brains, revealed a conserved and previously unquantified pattern of synaptic organization. Second, the spatial distribution of PPSSPAC effectively captures variations across cell types in the hippocampus, enabling neuron classification based on synaptic architecture. This serves as a complementary mesoscale descriptor to existing classifications based on global neuronal connectivity (source-target relationships) or local dendritic microenvironments. Third, the spatial distribution of PPSSPAC, rather than synapse density, shows remarkable correlation with independent whole-brain electrophysiological activity. The spatial organization of PPSSPAC also correlates with several gene expression datasets. These results suggest the post-synaptic pattern could be mediator linking molecular signatures, neural dynamics, and connectivity types of cells. Our study reveals, for the first time, a structural substrate for hierarchical information processing in the brain, providing new insights into neural computation and a foundation for brain digital twin models to support next-generation AI infrastructure.

neuroscience↗

bioRxiv2025

HapBridge: A Methylation-Guided Approach for Correcting Switch Errors and Bridging Phased Blocks in Long-Read Phasing

Long-read sequencing has substantially advanced haplotype phasing yet continues to face challenges in low-heterozygosity regions and switch errors caused by read noise. DNA methylation exhibits haplotype-specific patterns, providing complementary linkage information, but existing phasing algorithms have not fully leveraged these signals owing to their variability. Here, we present Hap-Bridge, a methylation-guided phasing framework that enhances single-nucleotide variant (SNV)-based phasing by detecting and correcting switch errors and bridging adjacent phased blocks. Evaluations on Oxford Nanopore R9/R10 and PacBio HiFi datasets show that HapBridge reduces switch errors by 3.07-18.72% and improves N50 length by 5.84-68.61% compared with Meth-Phaser, achieving higher phasing accuracy and contiguity. These results demonstrate that integrating methylation with sequence variation can provide a robust and intrinsic linkage signal that effectively improves haplotype continuity in long-read sequencing. HapBridge is publicly available at GitHub https://github.com/Humonex/HapBridge.

bioinformatics↗

bioRxiv2025

IGF-1 from bone marrow Adipoq-lineage cells stimulates endocortical bone formation in mature female mice

Insulin-like growth factor 1 (IGF-1) is an anabolic signal promoting growth, differentiation and function of both embryonic and postnatal tissues. Both endocrine and paracrine functions of IGF-1 have been documented to regulate bone growth and bone marrow hematopoiesis. Local production of IGF-1 from various cell types may contribute differently to the overall bioactivity of IGF-1 in bone, but relevant sources and mechanisms are yet to be fully elucidated. Here we report that the Adipoq+ stromal cells are a notable source of IGF-1 in the bone marrow of postnatal mice. Deletion of IGF-1 with Adipoq-Cre diminished endocortical bone formation and cortical bone mass in mature female mice. On the other hand, the trabecular bone parameters or hematopoietic properties were not affected in mutant mice of either sex. The study uncovers a local source of IGF-1 in the bone marrow microenvironment that contributes to bone anabolic regulation in a site-specific manner. Lay SummaryThe insulin-like growth factor 1 (IGF-1) is known to play important roles in promoting bone growth and in regulating blood stem or progenitor cells. The factor is available both through the blood circulation and from the local production by cells in the bone tissue, but the functional contribution of each source is not well understood. Here we discover the non-blood cells in the bone marrow (bone marrow stromal cells) as a notable source of IGF-1 which specifically stimulates bone formation in the bone shaft of the long bone.

developmental biology↗

bioRxiv2025

Mechanistic insights and in vivo HIV suppression by the BRD4-targeting small molecule ZL0580

Epigenetic suppression and durable silencing of HIV represent a promising strategy to achieve ART-free remission, consistent with the "block and lock" HIV cure paradigm. BRD4 is a host epigenetic reader and plays a critical role in HIV transcriptional regulation. We previously identified ZL0580, a first-in-class BRD4-selective small molecule distinct from the pan-BET inhibitor JQ1, which induces HIV epigenetic suppression. However, detailed molecular mechanisms, pharmacokinetics (PK), and in vivo HIV-suppressive efficacy of ZL0580 remain undefined. Here, we show that ZL0580 selectively targets BRD4 bromodomain 1 (BD1) through interaction with a key glutamic acid residue (E151), as determined by structural modeling and mutagenesis. Transcriptomic profiling by RNA-seq reveals that ZL0580 and JQ1 induce opposing gene expression programs, consistent with their distinct effects on HIV proviral transcription and latency. In a humanized mouse model of HIV infection, ZL0580 monotherapy, or in combination with ART, potently suppressed active HIV replication, reducing the plasma viremia to nearly undetectable levels, and delayed viral rebound following treatment interruption. Collectively, these findings establish ZL0580 as an epigenetic suppressor of HIV in vivo and provide proof-of-concept for its potential as a "block and lock" HIV cure candidate, warranting further optimization and development.

microbiology↗

bioRxiv2024

How do gepotidacin and zoliflodacin stabilize DNA-cleavage complexes with bacterial type IIA topoisomerases? 1. Experimental definition of metal binding sites

One of the challenges for experimental structural biology in the 21st century is to see chemical reactions happen. Staphylococcus aureus (S. aureus) DNA gyrase is a type IIA topoisomerase that can create temporary double-stranded DNA breaks to regulate DNA topology. Drugs, such as gepotidacin, zoliflodacin and the quinolone moxifloxacin, can stabilize these normally transient DNA-strand breaks and kill bacteria. Crystal structures of uncleaved DNA with a gepotidacin precursor (2.1[A] GSK2999423) or with doubly cleaved DNA and zoliflodacin (or with its progenitor QPT-1) have been solved in the same P61 space-group (a=b{approx}93[A], c{approx}412[A]). This suggests it may be possible to observe the two DNA-cleavage steps (and two DNA-religation steps) in this P61 space-group. Here a 2.58[A] anomalous manganese dataset in this crystal form is solved, and four previous crystal structures (1.98[A], 2.1[A], 2.5[A] and 2.65[A]) in this crystal form are re-refined to clarify crystal contacts. The structures clearly suggest a single moving metal mechanism - presented in an accompanying (2nd) paper. A previously published 2.98[A] structure of a yeast topoisomerase II, which has static disorder around a crystallographic twofold axis, was published as containing two metals at one active site. Re-refined coordinates of this 2.98[A] yeast structure are consistent with other type IIA topoisomerase structures in only having one metal ion at each of the two different active sites.

biophysics↗

bioRxiv2024

How do gepotidacin and zolifodacin stabilize DNA-cleavage complexes with bacterial type IIA topoisomerases? 2. A Single Moving Metal Mechanism.

DNA gyrase is a type IIA topoisomerase that can create temporary double-stranded DNA breaks to regulate DNA topology and an archetypical target of antibiotics. The widely used quinolone class of drugs use a water-metal ion bridge in interacting with the GyrA subunit of DNA gyrase. Zoliflodacin sits in the same pocket as quinolones but interacts with the GyrB subunit and also stabilizes lethal double-stranded DNA-breaks. Gepotidacin had been observed to sit on the twofold axis of the complex, midway between the two four base-pair separated DNA-cleavage sites and has been observed to stabilize singe-stranded DNA-breaks. Here we use information from three crystal structures of complexes of Staphlococcus aureus DNA gyrase (one with a precursor of gepotidacin and one with the progenitor of zoliflodacin) to propose a simple single moving metal-ion catalyzed DNA-cleavage mechanism. Our model explains why the catalytic tyrosine is in the tyrosinate (negatively charged) form for DNA-cleavage. Movement of a single catalytic metal-ion (Mg2+ or Mn2+) guides water mediated protonation and cleavage of the scissile phosphate which is then accepted by the catalytic tyrosinate. Type IIA topoisomerases need to be able to rapidly cut the DNA when it becomes positively supercoiled (in front of replication forks and transcription bubbles) and we propose that the original purpose of the small Greek Key domain, common to all type IIA topoisomerases, was to allow access of the catalytic metal to the DNA-cleavage site. Although the proposed mechanism is consistent with published data, it is not proven and other mechanisms have been proposed. Finally how such mechanisms can be experimentally distinguished is considered.

biophysics↗

bioRxiv2024

Hepatic GCGR is required for the superior weight loss effects of a structurally related analogue of the dual GCGR/GLP1R agonist survodutide

The dual glucagon/glucagon-like peptide 1 receptor (GCGR/GLP1R) agonists have superior efficacy in promoting weight loss and metabolic improvements in obesity and metabolic dysfunction-associated steatohepatitis (MASH) than current available mono-agonists. However, the mechanisms underlying these benefits are not fully understood. While the effects on appetite regulation and glucose control through GLP1R agonism are well established, the role of GCGR agonism in promoting weight loss and metabolic changes is less defined. Using a dual GCGR/GLP1R agonist BI 456908 and a selective GLP1R agonist semaglutide, we could show that the dual agonist achieved superior weight loss efficacy by engaging hepatic GCGR without adversely affecting glucose control. Furthermore, we could demonstrate that hepatic GCGR is critical for facilitating plasma and liver lipid clearance stimulated by the dual agonist. Overall, these findings highlight the crucial metabolic contributions of hepatic GCGR to the efficacy of combined GCGR/GL1R activation.

physiology↗

bioRxiv2023

Neutron crystallographic refinement with REFMAC5 of the CCP4 suite

Hydrogen (H) atoms are abundant in macromolecules and often play critical roles in enzyme catalysis, ligand recognition processes, and protein-protein interactions. However, their direct visualisation by diffraction techniques is challenging. Macromolecular X-ray crystallography affords the localisation of the most ordered H atoms at (sub-)atomic resolution (around 1.2 [A] or higher), that is not often attainable. Differently, neutron diffraction methods enable the visualisation of most H atoms, typically in the form of deuterium (D) atoms at much more common resolution values (better than 2.5 [A]). Thus, neutron crystallography, although technically demanding, is often the method of choice when direct information on protonation states is sought. REFMAC5 of the Collaborative Computational Project No. 4 (CCP4) is a program for the refinement of macromolecular models against X-ray crystallographic and cryo-EM data. This contribution describes its extension to include the refinement of structural models obtained from neutron crystallographic data. Stereochemical restraints with accurate bond distances between H atoms and their parent atom nuclei are now part of the CCP4 Monomer Library, the source of prior chemical information used in refinement. One new feature for neutron data analysis in REFMAC5 is the refinement of the protium/deuterium (1H/D) fraction. This parameter describes the relative 1H/D contribution to neutron scattering for H atoms. The newly developed REFMAC5 algorithms were tested by performing the (re-)refinement of several entries available in the PDB and of one novel structure (FutA) by using either (i) neutron data-only or (ii) neutron data supplemented by external restraints to a reference X-ray crystallographic structure. Re-refinement with REFMAC5 afforded models characterised by R-factor values that are consistent with, and in some cases better than, the originally deposited values. The use of external reference structure restraints during refinement has been observed to be a valuable strategy especially for structures at medium-low resolution. SynopsisThe macromolecular refinement package REFMAC5 of the CCP4 suite has been extended with the incorporation of algorithms for neutron crystallography.

bioinformatics↗

bioRxiv2023

Osteoblast-intrinsic defect in glucose metabolism impairs bone formation in type II diabetic mice

Skeletal fragility is associated with type 2 diabetes mellitus (T2D), but the underlying mechanism is not well understood. Here, in a mouse model for youth-onset T2D, we show that both trabecular and cortical bone mass are reduced due to diminished osteoblast activity. Stable isotope tracing in vivo with 13C-glucose demonstrates that both glycolysis and glucose fueling of the TCA cycle are impaired in diabetic bones. Similarly, Seahorse assays show suppression of both glycolysis and oxidative phosphorylation by diabetes in bone marrow mesenchymal cells as a whole, whereas single-cell RNA sequencing reveals distinct modes of metabolic dysregulation among the subpopulations. Metformin not only promotes glycolysis and osteoblast differentiation in vitro, but also improves bone mass in diabetic mice. Finally, targeted overexpression of Hif1a or Pfkfb3 in osteoblasts of T2D mice averts bone loss. The study identifies osteoblast-intrinsic defects in glucose metabolism as an underlying cause of diabetic osteopenia, which may be targeted therapeutically.

physiology↗

bioRxiv2022

Shear and hydrostatic stress regulate fetal heart valve remodeling through YAP-mediated mechanotransduction

Clinically serious congenital heart valve defects arise from improper growth and remodeling of endocardial cushions into leaflets. Genetic mutations have been extensively studied but explain less than 20% of cases. Mechanical forces generated by beating hearts drive valve development, but how these forces collectively determine valve growth and remodeling remains incompletely understood. Here we decouple the influence of those forces on valve size and shape, and study the role of YAP pathway in determining the size and shape. The low oscillatory shear stress promotes YAP nuclear translocation in valvular endothelial cells (VEC), while the high unidirectional shear stress restricts YAP in cytoplasm. The hydrostatic compressive stress activated YAP in valvular interstitial cells (VIC), whereas the tensile stress deactivated YAP. YAP activation by small molecules promoted VIC proliferation and increased valve size. YAP inhibition suppressed the VIC proliferation and reduced valve size, but enhanced cell-cell adhesions between VEC thus maintaining an elongated shape. Finally, left atrial ligation was performed in chick embryonic hearts to manipulate the shear and hydrostatic stress in-vivo. The restricted flow in the left ventricle induced a globular and hypoplastic left atrioventricular (AV) valves with an inhibited YAP expression. By contrast, the right AV valves with sustained YAP expression grew and elongated normally. This study establishes a simple yet elegant mechanobiological system by which transduction of local stresses regulates valve growth and remodeling. This system guides leaflets to grow into proper sizes and shapes with the ventricular development, without the need of a genetically prescribed timing mechanism. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=143 SRC="FIGDIR/small/517814v1_ufig1.gif" ALT="Figure 1"> View larger version (73K): org.highwire.dtl.DTLVardef@167b319org.highwire.dtl.DTLVardef@11f2f07org.highwire.dtl.DTLVardef@4894f1org.highwire.dtl.DTLVardef@12a66ab_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2022

Super resolution ultrasound imaging using deep learning based micro-bubbles localization

Super resolution ultrasound imaging has shown its potential to detect minor structures of tissues beyond the limit of diffraction and achieve sub-wavelength resolution through localizing and tracking the ultrasound contrast agents, such as micro-bubbles. Normally, one important step of super resolution ultrasound imaging, micro-bubbles localization is implemented through conventional computer vision techniques, such as local maxima detection etc. However, these classical techniques are generally time consuming and need fine-tuning multiple parameters to achieve the optimal results. Hence, in the manuscript, a deep learning based micro-bubbles localization is proposed, trying to replace or simplify the complex operations of classical methods. The efficiency of our proposed models is preliminarily proved through 2022 ultra-SR challenge.

biophysics↗

bioRxiv2020

Identification of Gli1 as a progenitor cell marker for meniscus development and injury repair

Meniscal tears are associated with a high risk of osteoarthritis but currently have no disease-modifying therapies. Using Gli1-CreER tdTomato mice, we found that Gli1+ cells contribute to the development of meniscus horns from 2 weeks of age. In adult mice, Gli1+ cells resided at the superficial layer of meniscus and expressed known mesenchymal progenitor markers. In culture, meniscal Gli1+ cells possessed high progenitor activities under the control of Hh signal. Meniscus injury at the anterior horn induced a quick expansion of Gli1+ cells. Normally, the tissue healed slowly, leading to cartilage degeneration. Ablation of Gli1+ cells further hindered this repair process. Strikingly, intra-articular injection of Gli1+ meniscal cells or an Hh activator right after injury accelerated the bridging of the interrupted ends and attenuated signs of osteoarthritis. Taken together, our work identified a novel progenitor population in meniscus and proposes a new treatment for repairing injured meniscus and preventing osteoarthritis.

developmental biology↗

bioRxiv2020

Deep learning model for ultrafast quantification of blood flow in diffuse correlation spectroscopy

Diffuse correlation spectroscopy (DCS) is increasingly used in the optical imaging field to assess blood flow in humans due to its non-invasive, real-time characteristics and its ability to provide label-free, bedside monitoring of blood flow changes. Previous DCS studies have utilized a traditional curve fitting of the analytical or Monte Carlo models to extract the blood flow changes, which are computationally demanding and less accurate when the signal to noise ratio decreases. Here, we present a deep learning model that eliminates this bottleneck by solving the inverse problem more than 2300% faster, with equivalent or improved accuracy compared to the nonlinear fitting with an analytical method. The proposed deep learning inverse model will enable real-time and accurate tissue blood flow quantification with the DCS technique.

bioengineering↗

bioRxiv2020

A variant in SMOC2, inhibiting BMP signaling by competitively binding to BMPR1B, causes multiple epiphyseal dysplasia

Previously study showed that SMOC, a matricellular protein, inhibits BMP signaling downstream of its receptor via activation of mitogen-activated protein kinase (MAPK) signaling. In our study, exome sequencing revealed a missense mutation (c.1076T>G, p.Leu359Arg) in EC domain of SMOC2 in a Chinese family with multiple epiphyseal disease (MED). The pathogenicity of this SMOC2 variant was verified by Smoc2L359R/L359R knock-in mice. Of note, decreasing phosphorylation of SMAD1/5/9 was detected in growth plates and primary chondrocytes from Smoc2L359R/L359R mice. Furthermore, binding affinity of mutant SMOC2 with collagen IX and HSPG in the extracellular matrix of cartilage were reduced while binding affinity with BMPRIB was intact. In addition, in contrast to previously results, that SMOC2 cannot antagonize BMP activity in the presence of a constitutively activated BMP receptor. These results support that SMOC2 with p.Leu359Arg variant act as an antagonist of canonical BMP pathway by competitively binding with BMP receptors.

genomics↗