Biology subjects

Kumar, C.

Publications and source records attributed to Kumar, C..

17 recordsLinked to original sources

bioRxiv2026

Dual Recognition Drives Site-Directed G-Quadruplex Stabilization: Exploring Oligonucleotide Design in G4 Ligand-Oligonucleotide Conjugates

G-quadruplex (G4) DNA structures are increasingly recognized for their roles in key cellular processes, including transcriptional regulation and genome stability, making them attractive therapeutic targets. Selective recognition of individual G4s remains challenging due to the high structural similarity among human G4 motifs. The G4 Ligand-conjugated Oligonucleotide strategy addresses this need by combining the G4-binding capabilities of small-molecule G4-ligands with the sequence specificity of an oligonucleotide complementary to the flanking region of the target G4. Here, we systematically explore how the oligonucleotide component governs G4 binding and stabilization by varying its length, backbone composition, and sequence complementarity. This revealed that efficient G4 recognition depends on a strong interdependence between hybridization and G4-ligand binding, such that both elements cooperatively reinforce complex stability and site specificity. Central mismatches disrupt this dual recognition and reduce selectivity. While longer oligonucleotides hybridize more slowly, they form more stable complexes and show stronger G4 stabilization in thermal melting and polymerase stop assays. Replacing the DNA oligonucleotide with peptide nucleic acid enhances binding strength, thermal stability, and metabolic stability, but selective G4 stabilization is achieved only upon ligand conjugation. Together, these results show how rational oligonucleotide design enables selective and potent recognition of G4 structures using GL-Os.

molecular biology↗

bioRxiv2026

Computational predictions and evolutionary analysis of LrK10 kinase-related putative PSTOL1 gene homeologs in wheat and orthologs of its wild relatives.

Phosphorus Starvation Tolerance 1 in rice (OsPSTOL1, known as Phosphorus uptake 1, Pup1) is a receptor-like cytoplasmic protein kinase that confers tolerance to phosphorus deficiency. The OsPSTOL1 gene possesses a Ser/Thr kinase and shows high amino-acid sequence similarity with the leaf rust receptor-like kinase (OsLrK10). We hypothesize that the putative wheat TaPSTOL1 and TaLrK10 have a common ancestral origin and that putative TaPSTOL1 diverged recently acquiring new structural modifications and biological functions in the process. In this study, we identified all putative TaPSTOL1 homeologs and examine the evolutionary relationship between TaPSTOL1 and TaLrK10 in Triticum species. Our results indicate that the putative TaPSTOL1 diverged recently without possessing the amino-terminal domain, which is a typical characteristic of TaLrK10. We observed numerous conversions tracts between these two genes and the substitution pattern of randomly selected amino acids indicates that dynamic selection pressures acted on both genes. The putative TaPSTOL1 shows high nucleotide diversity compared to TaLrK10 within Triticum species. Further, a multiple-sequence analysis reveals that the third exon of TaLrK10 appears to have been duplicated and diverged as a putative single-exon based TaPSTOL1 in bread wheat. Overall, our comparative analysis indicates that both TaPSTOL1 and TaLrK10 appears to have diverged from a common ancestor, acquiring distinct structural organizations and biological functions.

genomics↗

bioRxiv2025

3-Dimensional Piezoelectric Fibrous Constructs for Muscle Regeneration

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), a biocompatible and biodegradable polymer with inherent piezoelectricity, holds promise for developing biomimetic scaffolds for tissue regeneration. Its ability to generate electrical charges in response to mechanical stimulation, mimicking the electromechanical environment in native tissues like muscle, makes it attractive. This study focuses on harnessing PHBV properties to engineer electrospun fibrous scaffolds for muscle regeneration. We investigated processing parameters, such as solvent combinations, polymer concentrations, and tip-to-collector distances on fiber morphology, porosity, and piezoelectric properties. We observed a 25-fold increase in the quasi-static piezoelectric coefficient (d33 from 0.117 to 2.9 pC/N) for scaffolds with controlled porosity. This piezoelectric activity was corroborated by dynamic Vector Network Analyzer (VNA) measurements, which identified an electromechanical coupling factor (kt) of 13.86%. This enhanced electromechanical response highlights their potential for stimulating cellular responses for tissue regeneration. The mechanical properties of these scaffolds demonstrated their ability to undergo strain up to 40%, within the optimal range for muscle tissue engineering and compatibility with muscle functionality. Cytocompatibility of PHBV scaffolds was confirmed, and preliminary studies suggest their potential to support myogenic differentiation. This research highlights PHBV-based biomimetic scaffolds potential for muscle regeneration and sets groundwork for developing advanced therapies addressing muscle injury and disease.

bioengineering↗

bioRxiv2024

Sporophyte Directed Gametogenesis via the Ubiquitin Proteasome System

Plants alternate between diploid sporophyte and haploid gametophyte generations. In mosses which retain features of ancestral land plants, the gametophyte is dominant and has an independent existence. However, in flowering plants the gametophyte has undergone evolutionary reduction to just a few cells enclosed within the sporophyte. The gametophyte is thought to retain genetic control of its development even after reduction. Here we demonstrate that male gametophyte development in Arabidopsis, long considered to be autonomous, is also under genetic control of the sporophyte via a repressive mechanism involving large-scale regulation of protein turnover. We identify an Arabidopsis gene SHUKR as an inhibitor of male gametogenesis. SHUKR is unrelated to proteins of known function and acts sporophytically in meiosis to control gametophyte development by negatively regulating expression of a large set of ubiquitination genes specific to post-meiotic gametogenesis. This control is late-emerging as SHUKR homologs are found only in eudicots. We show that SHUKR is rapidly evolving under positive selection suggesting that variation in control of protein turnover during male gametogenesis has played an important role in evolution within eudicots.

plant biology↗

bioRxiv2024

Cryo-EM structures of G4-stalled CMG reveal inchworm mechanism of DNA translocation

DNA G-quadruplexes (G4s) are non-B-form DNA secondary structures that threaten genome stability by impeding DNA replication. To elucidate how G4s induce replication fork arrest, we have characterized fork collisions with preformed G4s in the parental DNA using fully reconstituted yeast and human replisomes. We demonstrate that a single G4 in the leading strand template is sufficient to stall replisomes by blocking the CMG helicase. An ensemble of high-resolution cryo-EM structures of stalled yeast and human CMG complexes reveals that the G4 is fully folded and lodged inside the CMG central channel. The stalled CMG is conformationally constrained and arrests in the transition between translocation states. Unexpectedly, our analysis suggests that CMG employs an unprecedented inchworm mechanism to translocate on DNA. These findings illuminate the eukaryotic replication fork mechanism under both normal and perturbed conditions.

biochemistry↗

bioRxiv2024

Dbf4-Dependent Kinase Finetunes INO80 Function at Chromosome Replication Origins

The highly conserved Dbf4-Dependent Kinase (DDK) plays a pivotal role in the nucleus during S phase, where it directly phosphorylates the replicative helicase, the minichromosome maintenance (MCM) complex. This leads to the initiation of chromosome replication. However, aside from the MCM complex, few other targets have been identified to date, leaving DDK an understudied kinase. Here, we describe a two-pronged mass spectrometry-based approach and define the nuclear DDK-dependent phosphoproteome, which consists of approximately 400 phosphorylation events. Within this network, we found that DDK directly phosphorylates the Arp8 subunit of the multi-subunit chromatin remodeler complex INO80. Arp8 phosphorylation stabilises INO80s intramolecular complex integrity, which finetunes its nucleosome spacing activity at replication origins. This adjustment of origin chromatin architecture stimulates replication and is important for the response to replication stress. Our results represent a significant advance in our understanding of the molecular mechanisms underlying the regulation of replication origins.

biochemistry↗

bioRxiv2023

Engineered dsRNA-protein nanoparticles for effective long-distance transport, delivery and gene silencing in plants

Long-distance transport of exogenous biologically active RNA molecules in higher plants has not been reported. Here, we report that cationized bovine serum albumin (cBSA) avidly binds double-stranded beta-glucuronidase RNA (dsGUS RNA) to form nucleic acid-protein nanocomplexes. Using tobacco and poplar plants, we have shown effective uptake and long-distance transport of cBSA/dsGUS RNA nanocomplexes from basal ends of leaf petioles to leaf blades as well as from basal ends of shoots to their apexes and apical leaves. We have further demonstrated that the cBSA/dsGUS RNA nanocomplexes are highly effective in silencing both conditionally inducible DR5-GUS gene and constitutively active 35S-GUS gene in leaf, shoot and shoot meristem tissues. This cBSA/dsRNA delivery technology may provide a convenient, fast, and inexpensive tool for characterizing gene functions in plants, and potentially for in planta gene-editing.

molecular biology↗

bioRxiv2023

Human complement Factor H and Properdin act as soluble pattern recognition receptors and differentially modulate SARS-CoV-2 Infection

Severe cases of SARS-CoV-2 infection are characterised by an imbalanced immune response, excessive inflammation, and the development of acute respiratory distress syndrome, which can lead to multiorgan failure and death. Several studies have demonstrated dysregulated complement activity as an indicator of immunopathogenesis in the SARS-CoV-2 infection. Notably, the complement alternative pathway has been implicated in driving the excessive inflammation during severe SARS-CoV-2 infection. Reduced levels of factor H (FH), a down-regulator of the alternative pathway, and increased levels of properdin (Factor P/FP), the only known up-regulator of the alternative pathway, have been observed in individuals with severe COVID-19 infection. The present study investigated the complement activation-independent, and a more direct role of FH and FP against SARS-CoV-2 infection. Using direct ELISA, the interactions of FH and FP with the SARS-CoV-2 spike (S) and receptor binding domain (RBD) were assessed. Using S protein expressing lentiviral pseudotypes, the cell binding and luciferase-based virus entry assays were employed to assess the potential modulatory effects of FH, FP, and recombinant thrombospondin repeats 4 and 5 (TSR4+5) on SARS-CoV-2 cell entry. We also evaluated the immunomodulatory functions of FH and FP in the cytokine response triggered by SARS-CoV-2 pseudotypes via RT-qPCR. SARS-CoV-2 S and RBD proteins were found to bind both FH and FP. Treatment of A549 cells expressing human ACE2 and TMPRSS2 with FP or TSR4+5 resulted in increased cell entry and binding of SARS-CoV-2 pseudotypes. In silico studies revealed that FP increases affinity between SARS-CoV-2 and host ACE2. The impact of FP on viral cell entry and binding was reversed by anti-FP antibody treatment in A549-hACE2+TMPRSS2 cells. However, FH treatment reduced the cell entry and binding of SARS-CoV-2 lentiviral pseudotypes. Furthermore, the A549-hACE2+TMPRSS2 cells challenged with SARS-CoV-2 spike, envelope, nucleoprotein, and membrane protein expressing alphaviral pseudotypes pre-treated with FP or TSR4+5, exhibited upregulation of the transcripts of pro-inflammatory cytokines, such as IL-1{beta}, IL-8, IL-6, TNF-, IFN- and RANTES (as well as NF-{kappa}B). Conversely, FH pre-treatment downregulated the expression of these pro-inflammatory cytokines. Treatment of A549-hACE2+TMPRSS2 cells with FP increased S protein-mediated NF-{kappa}B activation, while FH treatment reduced it. These findings suggest that FH may act as an inhibitor of SARS-CoV-2 cell entry and binding, thereby attenuating the infection-associated inflammatory response in a complement activation-independent manner. FP may contribute to viral cell entry, binding, and exacerbating the immune response. That may result in potentially influencing the severity of the infection.

immunology↗

bioRxiv2023

From gonadogenesis to testicular cancer: Unravelling the novel regulators and identification of drug candidates against FGF9 and PTGDS

Sex determination is the preliminary step toward gonadogenesis in mammals. Antagonistic interactions of key regulators have been only fragmentarily mentioned so far. Therefore, exploring regulators underlying the phenomena is required to solve questions, especially regarding female gonad development and gonadal disorders in congenital or adults. Inhibiting discrepancies in PPI pathways and combating related disorders are of urgent necessity, for which novel drugs are constantly required. Here, we performed in silico analysis using robust bioinformatics methods, which is unprecedented work in sex determination studies, providing large-scale analysis without exorbitant wet lab procedures. Analyzed regulators were overlapped with our RNA-seq data for authentication, to obtain differentially expressed elements. Additionally, CADD approach was used to discover inhibitors for FGF9 and PTGDS to search for potential drugs combating gonadal disorders in adults. Along with druggable properties, only FGF9 and PTGDS had full-length protein structures available, among 25 key genes under investigation. Our large-scale analysis of PPIN, produced highly interacting hub-bottleneck nodes as novel genes. Further, functional enrichment analysis revealed importance of these regulators in gonadogenesis. We identified sex-specific novel genes, miRNAs-target pairs, and lncRNAs-target pairs, which appear to play an important role in regulation of ovary development. CADD with molecular docking, MD simulations, and molecular mechanics confirmed stability of two novel compounds, DB12884 and DB12412 that could potentially inhibit FGF9 and PTGDS respectively. Taken together our study provides valuable information regarding involvement of crucial regulators in antagonistic mechanism of gonadogenesis and their related disorders, which will further assist in refining wet lab experiments.

bioinformatics↗

bioRxiv2022

Msh2-Msh3 interferes with DNA metabolism in vivo

Mismatch repair (MMR) is a highly conserved DNA repair pathway that safeguards the genome from errors in DNA replication. In Saccharomyces cerevisiae, two MutS homolog (Msh) complexes, Msh2-Msh3 or Msh2-Msh6, initiate MMR. Msh2-Msh3, the focus of this study, recognizes and directs repair of insertion/deletion loops (IDLs) up to ~17 nucleotides. Msh2-Msh3 also recognizes and binds distinct looped and branched DNA structures with varying affinities, thereby contributing to genome stability outside post-replicative MMR through homologous recombination, double-strand break repair (DSBR), and the DNA damage response. Msh2-Msh3 also promotes genome instability through trinucleotide repeat (TNR) expansions. This non-canonical activity is likely an unfortunate consequence of Msh2-Msh3s intrinsic ability to bind a wide range of DNA structures, including those formed with single-stranded (ss) TNR sequences. We previously demonstrated that Msh2-Msh3 binding to 5 ssDNA flap structures interfered with the in vitro binding and cleavage activities of the flap endonuclease Rad27 (Fen1 in mammals), which promotes 5 ssDNA flap processing during Okazaki fragment maturation (OFM) and long-patch base excision repair (LP-BER). Here we demonstrate that elevated Msh2-Msh3 levels interfere with DNA replication and LP-BER in vivo, consistent with the hypothesis that protein abundance and Msh3 ATPase activities are key drivers of Msh2-Msh3-mediated genomic instability.

genetics↗

bioRxiv2022

Human Surfactant Protein D Facilitates SARS-CoV-2 Pseudotype Binding and Entry in DC-SIGN Expressing Cells, and Downregulates Spike protein Induced Inflammation

Pattern recognition receptors are crucial for innate anti-viral immunity, including C-type lectin receptors. Two such examples are Lung surfactant protein D (SP-D) and Dendritic cell-specific intercellular adhesion molecules-3 grabbing non-integrin (DC-SIGN) which are soluble and membrane-bound C-type lectin receptors, respectively. SP-D has a crucial immune function in detecting and clearing pulmonary pathogens; DC-SIGN is involved in facilitating dendritic cell interaction as an antigen-presenting cell with naive T cells to mount an anti-viral immune response. Both SP-D and DC-SIGN have been shown to interact with various viruses, including HIV-1, Influenza A virus and SARS-CoV-2. SARS-CoV-2 is an enveloped RNA virus that causes COVID-19. A recombinant fragment of human SP-D (rfhSP-D) comprising of -helical neck region, carbohydrate recognition domain, and eight N-terminal Gly-X-Y repeats has been shown to bind SARS-CoV-2 Spike protein and inhibit SARS-CoV-2 replication by preventing viral entry in Vero cells and HEK293T cells expressing ACE2. DC-SIGN has also been shown to act as a cell surface receptor for SARS-CoV-2 independent of ACE2. Since rfhSP-D is known to interact with SARS-CoV-2 Spike protein and DC-SIGN, this study was aimed at investigating the potential of rfhSP-D in modulating SARS-CoV-2 infection. Coincubation of rfhSP-D with Spike protein improved the Spike Protein: DC-SIGN interaction. Molecular dynamic studies revealed that rfhSP-D stabilised the interaction between DC-SIGN and Spike protein. Cell binding analysis with DC-SIGN expressing HEK 293T and THP-1 cells and rfhSP-D treated SARS-CoV-2 Spike pseudotypes confirmed the increased binding. Furthermore, infection assays using the pseudotypes revealed their increased uptake by DC-SIGN expressing cells. The immunomodulatory effect of rfhSP-D on the DC-SIGN: Spike protein interaction on DC-SIGN expressing epithelial and macrophage-like cell lines was also assessed by measuring the mRNA expression of cytokines and chemokines. The RT-qPCR analysis showed that rfhSP-D treatment downregulated the mRNA expression levels of pro-inflammatory cytokines and chemokines such as TNF-, IFN-, IL-1{beta}, IL-6, IL-8, and RANTES (as well as NF-{kappa}B) in DC-SIGN expressing cells challenged by Spike protein. Furthermore, rfhSP-D treatment was found to downregulate the mRNA levels of MHC class II in DC expressing THP-1 when compared to the untreated controls. We conclude that rfhSP-D helps stabilise the interaction of SARS-CoV-2 Spike protein and DC-SIGN and increases viral uptake by macrophages via DC-SIGN, suggesting an additional role for rfhSP-D in SARS-CoV-2 infection.

immunology↗

bioRxiv2022

Quantitative crosslinking and mass spectrometry determine binding interfaces and affinities mediating kinetochore stabilization

Crosslinking and mass spectrometry (XLMS) are used in integrative structural biology to acquire spatial restraints. We found a dependency between crosslink distances and intensities and developed a quantitative workflow to simultaneously estimate apparent dissociation constants (KD) of contacts within multi-subunit complexes and to aid interface prediction. Quantitative XLMS was applied to study the assembly of the macromolecular kinetochore complex, which is built on centromeric chromatin and establishes a stable link to spindle microtubules in order to segregate chromosomes during cell division. Inter-protein crosslink intensities facilitated determination of phosphorylation-induced binding interfaces and affinity changes. Phosphorylation of outer and inner kinetochore proteins mediated cooperative kinetochore stabilization and decreased the KD values of its interactions to the centromeric nucleosome by ~200-fold, which was essential for cell viability. This work demonstrates the potential of quantitative XLMS for characterizing mechanistic effects on protein assemblies upon post-translational modifications or cofactor interaction and for biological modeling.

biochemistry↗

bioRxiv2022

Multistep loading of PCNA onto DNA by RFC

The DNA sliding clamp proliferating cell nuclear antigen (PCNA) is an essential co-factor for many eukaryotic DNA metabolic enzymes. PCNA is loaded around DNA by the ATP-dependent clamp loader replication factor C (RFC), which acts at single-stranded/double-stranded DNA junctions harboring a recessed 3 end (3 ss/dsDNA junctions) and at DNA nicks. To illuminate the loading mechanism we have investigated the structure of RFC:PCNA bound to ATP{gamma}S and 3 ss/dsDNA junctions or nicked DNA using cryogenic electron microscopy. Unexpectedly, we observe open and closed PCNA conformations in the RFC:PCNA:DNA complex, revealing that PCNA can adopt an open, planar conformation that allows direct insertion of dsDNA, and indicating that PCNA ring-closure is not mechanistically coupled to ATP-hydrolysis. By resolving multiple DNA-bound states of RFC:PCNA we observe that partial melting facilitates lateral insertion into the central channel formed by RFC:PCNA. We also resolve the Rfc1 N-terminal domain and demonstrate that its single BRCT domain participates in coordinating DNA prior to insertion into the central RFC channel, which promotes PCNA loading on the lagging strand of replication forks in vitro. Combined, our data suggest a comprehensive and fundamentally revised model for the RFC-catalyzed loading of PCNA onto DNA.

molecular biology↗

bioRxiv2021

The interplay of RNA:DNA hybrid structure and G-quadruplexes determines the outcome of R-loop-replisome collisions

R-loops are a major source of genome instability associated with transcription-induced replication stress. However, how R-loops inherently impact replication fork progression is not understood. Here, we characterize R-loop-replisome collisions using a fully reconstituted eukaryotic DNA replication system. We find that RNA:DNA hybrids and G-quadruplexes at both co-directional and head-on R-loops can impact fork progression by inducing fork stalling, uncoupling of leading strand synthesis from replisome progression, and nascent strand gaps. RNase H1 and Pif1 suppress replication defects by resolving RNA:DNA hybrids and G-quadruplexes, respectively. We also identify an intrinsic capacity of replisomes to maintain fork progression at certain R-loops by unwinding RNA:DNA hybrids, repriming leading strand synthesis downstream of G-quadruplexes, or utilizing R-loop transcripts to prime leading strand restart during co-directional R-loop-replisome collisions. Collectively, the data demonstrates that the outcome of R-loop-replisome collisions is modulated by R-loop structure, providing a mechanistic basis for the distinction of deleterious from non-deleterious R-loops.

biochemistry↗

bioRxiv2021

A bacterial derived plant- mimicking cytokinin hormone regulates social behaviour in a rice pathogen

Many plant-associated bacteria produce plant- mimicking hormones which are involved in modulating host physiology. However, their function in modulating bacterial physiology has not been reported. Here we show that the XopQ protein, a type-III effector of the rice pathogen, Xanthomonas oryzae pv. oryzae (Xoo), is involved in cytokinin biosynthesis. Xoo produces and secretes an active form of cytokinin which enables the bacterium to maintain a planktonic lifestyle and promotes virulence. RNA-seq analysis indicates that the cytokinin produced by Xoo is required for the regulation of several genes which are involved in biofilm formation. We have also identified the Xoo isopentenyl transferase gene, which is involved in the cytokinin biosynthesis pathway and is required for maintaining planktonic behaviour and virulence. Furthermore, mutations in the predicted cytokinin receptor kinase (PcrK) and the downstream response regulator (PcrR) of Xoo phenocopy the cytokinin biosynthetic mutants, but are not complemented by supplementation with exogenous cytokinin. Cytokinin biosynthetic functions are encoded in a number of diverse bacterial genomes suggesting that cytokinin may be a widespread signalling molecule in the bacterial kingdom.

microbiology↗

bioRxiv2021

Organ-specific metabolic pathways distinguish prediabetes, type 2 diabetes and normal tissues

Defects in pancreatic islets and the progression of multi-tissue insulin resistance in combination with environmental factors are the main causes of type 2 diabetes (T2D). Mass spectrometry-based proteomics of five key-metabolic tissues on a cohort of 42 multi-organ donors provided deep coverage of the proteomes of pancreatic islets, visceral adipose tissue (VAT), liver, skeletal muscle and serum. Enrichment analysis of gene ontology (GO) terms built a tissue-specific map of the chronological order of altered biological processes across healthy controls (CTRL), pre-diabetes (PD) and T2D subjects. This unique dataset allowed us to explore alterations of entire biological pathways and individual proteins in multiple tissues. We confirmed the significant decrease of the citric acid cycle and the respiratory electron transport in VAT and muscle of T2D and we provided a thorough visual representation of the complete set of downregulated proteins. Importantly, we found widespread novel alterations in relevant biological pathways including the increase in hemostasis in pancreatic islets of PD, the increase in the complement cascade in liver and pancreatic islets of PD and the elevation in cholesterol biosynthesis in liver of T2D. Overall, our findings suggest inflammatory, immune and vascular impairments in pancreatic islets as potentially causal factors of insufficient insulin production and increased glucagon levels in the early stages of T2D. In contrast alterations in lipid metabolism and mitochondrial function in the liver and VAT/muscle, respectively, became evident later in manifest T2D. This first multi-tissue proteomic map indicates the temporal order of tissue-specific metabolic dysregulation in T2D development.

cell biology↗

bioRxiv2018

Intra- and inter-individual metabolic profiling highlights carnitine and lysophosphatidylcholine pathways as key molecular defects in type-2 diabetes

Type-2 diabetes (T2D) mellitus is a complex metabolic disease commonly caused by insulin resistance in several tissues. We performed a matched two-dimensional metabolic screening in tissue samples from a cohort of 43 multi-organ donors. The intra-individual analysis was assessed across five key-metabolic tissues (serum, adipose tissue, liver, pancreatic islets and muscle), and the inter-individual across three different groups reflecting T2D progression. We identified 92 metabolites differing significantly between non-diabetes and T2D subjects. Carnitines were significantly higher in liver, while lysophosphatidylcholines significantly lower in muscle and serum. An investigation of the progression to overt T2D showed that deoxycholic acid glycine conjugate was significantly higher in liver of pre-diabetes samples while additional increase in T2D was insignificant. A subset of lysophosphatidylcholines were significantly lower in the muscle of pre-diabetes subjects. Overall, the analysis of this unique dataset can increase the understanding of the metabolic interplay between organs in the development of T2D.

physiology↗