Affinage

FST

Follistatin · UniProt P19883

Round 2 corrected
Length
344 aa
Mass
38.0 kDa
Annotated
2026-04-28
130 papers in source corpus 16 papers cited in narrative 16 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Follistatin (FST) is a secreted glycoprotein that functions as a high-affinity antagonist of activin, myostatin, and select TGF-β family ligands, thereby regulating diverse processes including reproductive physiology, erythropoiesis, muscle mass, and metabolic homeostasis. Two FST molecules encircle activin, burying one-third of its surface and blocking both type I and type II receptor binding sites; the FST N-terminal domain adopts a fold that mimics the type I receptor motif to occupy the corresponding activin epitope (PMID:16198295). Three splice isoforms (FST288, FST303, FST315) differ in cell-surface proteoglycan binding affinity, which determines their local versus systemic activin-neutralizing potency, while activin itself induces FST transcription through Smad3 and FoxL2 at an intronic enhancer, forming a negative feedback loop (PMID:16627583, PMID:19106105). The liver is the principal source of circulating FST, regulated by the glucagon-to-insulin ratio via cAMP; excess hepatic FST acts as a pathological hepatokine that impairs glucose homeostasis during insulin resistance (PMID:26652766, PMID:29867232).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1988 High

    Cloning of the FST gene revealed the modular exon-encoded domain architecture and two alternative splice forms, establishing the structural framework for understanding FST's multi-domain binding properties.

    Evidence cDNA and genomic library screening with sequencing and Southern blot in human tissues

    PMID:3380788

    Open questions at the time
    • Post-translational processing (glycosylation, proteolytic maturation) not resolved
    • Binding partners not yet identified
  2. 1991 High

    Demonstration that FST binds both activin and inhibin via their shared β-subunit, with activin providing two FST-binding sites versus one for inhibin, established the stoichiometric basis for FST's preferential activin neutralization.

    Evidence Double-ligand blotting with purified proteins

    PMID:2036994

    Open questions at the time
    • Binding affinities not quantified
    • Structural basis of the 2:1 stoichiometry unknown
  3. 1994 High

    Functional paracrine activity was demonstrated in human placenta, where FST completely reversed activin A-induced hormone secretion, extending FST's role beyond the pituitary-gonadal axis to reproductive tissues.

    Evidence RT-PCR, immunohistochemistry, and functional reversal assays in cultured placental cells

    PMID:8288705

    Open questions at the time
    • In vivo placental relevance not confirmed by genetic models
    • Other tissue-specific paracrine roles unexplored
  4. 2002 High

    Discovery that activin induces FST transcription through Smad proteins established a direct negative feedback loop in which the target (FST) neutralizes its own inducer (activin).

    Evidence Transcriptional reporter assays, RT-PCR, and Western blot with Smad pathway analysis

    PMID:11948405

    Open questions at the time
    • Specific Smad isoform and cis-element mediating the response not mapped
    • Feedback kinetics not quantified
  5. 2005 High

    The crystal structure of the FST:activin A complex resolved the long-standing question of how FST neutralizes activin: two FST molecules wrap around activin, and the N-terminal domain adopts a type I receptor-mimicking fold that occludes the type I binding site.

    Evidence X-ray crystallography of the 2:1 FST:activin complex

    PMID:16198295

    Open questions at the time
    • Dynamics of complex formation in solution not characterized
    • Structural basis for differential BMP versus activin affinity not fully resolved
  6. 2006 High

    Systematic comparison of the three FST isoforms showed that differential cell-surface proteoglycan binding (FST288 > FST303 > FST315) is the primary determinant of their distinct bioactivities, and that FST isoforms bind myostatin and select BMPs whereas the related protein FSTL3 does not.

    Evidence Recombinant protein competitive binding assays, kinetic analysis, and TT cell proliferation bioassay

    PMID:16627583

    Open questions at the time
    • Proteoglycan identity mediating surface retention not defined
    • In vivo isoform-specific functions not dissected genetically
  7. 2007 High

    Engineering of a follistatin-derived myostatin-selective inhibitor (FS I-I) demonstrated that FST's myostatin-binding capacity can be uncoupled from activin binding, and that selective myostatin inhibition increases muscle mass and ameliorates muscular dystrophy in mdx mice.

    Evidence Quantitative in vitro binding assays and transgenic mouse muscle phenotyping including mdx cross

    PMID:17893249

    Open questions at the time
    • Long-term safety and off-target effects of FS I-I in vivo unknown
    • Mechanism of hyperplasia versus hypertrophy contribution not resolved
  8. 2008 High

    Identification of FoxL2 as a Smad3 co-factor at an intronic enhancer of the FST gene refined the transcriptional feedback model, showing that activin-driven FST expression requires cooperative binding of Smad3 and FoxL2.

    Evidence ChIP, co-immunoprecipitation, site-directed mutagenesis, and shRNA knockdown in ovarian granulosa-like cells

    PMID:19106105

    Open questions at the time
    • Whether this enhancer module operates in non-gonadal tissues is unknown
    • Epigenetic regulation of this element not addressed
  9. 2010 High

    Exercise physiology studies identified the liver—not exercising skeletal muscle—as the principal source of the marked rise in circulating FST during exercise, reframing FST as a hepatokine.

    Evidence Arterial-venous difference measurements in exercising humans, hepatic mRNA/protein quantification in exercising mice

    PMID:21068158

    Open questions at the time
    • Hepatic signaling pathway driving exercise-induced FST release not identified
    • Contribution of other organs (e.g., adipose) not excluded
  10. 2015 High

    Splanchnic arteriovenous measurements in humans confirmed the liver as the dominant source of circulating FST, and mechanistic studies showed glucagon stimulates and insulin inhibits hepatic FST secretion via cAMP, linking FST to metabolic regulation.

    Evidence Arteriovenous difference across splanchnic bed in humans, cAMP-pathway analysis in cultured hepatocytes, islet functional assays

    PMID:26652766

    Open questions at the time
    • Direct cAMP-responsive element on FST promoter not mapped in hepatocytes
    • Autocrine/paracrine effects of FST on hepatocytes themselves unclear
  11. 2017 High

    Crystal structure of the GDF11:FST288 complex demonstrated that FST neutralizes GDF11 by a mechanism analogous to activin, broadening the structural understanding of FST's multi-ligand antagonism within the TGF-β family.

    Evidence X-ray crystallography of GDF11:FST288 complex with functional signaling and mutagenesis validation

    PMID:28257634

    Open questions at the time
    • In vivo relevance of FST:GDF11 antagonism versus FST:myostatin antagonism not dissected
    • Affinity hierarchy across all TGF-β ligands not fully quantified
  12. 2018 High

    Gain- and loss-of-function experiments in mouse liver established FST as a pathological hepatokine: elevated hepatic FST during insulin resistance impairs systemic glucose homeostasis and adipose insulin signaling, effects reversed by hepatic FST knockdown.

    Evidence Hepatic shRNA knockdown and overexpression in LDKO and wild-type mice, GTT/ITT, human bariatric surgery cohort correlation

    PMID:29867232

    Open questions at the time
    • Target tissue receptor or signaling mechanism through which circulating FST impairs glucose metabolism is unknown
    • Whether FST's metabolic effect is activin-dependent or involves a distinct receptor pathway is unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The receptor or signaling mechanism by which circulating FST exerts its metabolic (hepatokine) effects on peripheral tissues remains unidentified, and isoform-specific in vivo functions have not been resolved by conditional genetic models.
  • No receptor for FST's metabolic actions identified
  • Conditional isoform-specific knockouts not reported
  • Structural basis for isoform-specific proteoglycan interaction unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0048018 receptor ligand activity 4 GO:0140313 molecular sequestering activity 3
Localization
GO:0005576 extracellular region 6
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1266738 Developmental Biology 3 R-HSA-1430728 Metabolism 2
Partners
BMP2FOXL2GDF11INHBAMSTNSMAD3

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 The human follistatin (FST) gene encodes a single-chain precursor of 344 or 317 amino acids (via alternative splicing). The mature protein contains four contiguous domains encoded by separate exons, three of which are highly similar to each other and to human EGF and pancreatic secretory trypsin inhibitor, suggesting exon shuffling during evolution. cDNA library screening, genomic library analysis, sequencing, Southern blot, structural domain analysis Proceedings of the National Academy of Sciences of the United States of America High 3380788
1991 Follistatin binds to both activin and inhibin through the common beta-subunit. Activin-A has two binding sites for follistatin, whereas inhibin-A has only one binding site, as determined by double-ligand blotting. Double-ligand blotting technique Endocrinology High 2036994
1994 Human placenta, fetal membranes (amnion, chorion), and decidua express follistatin mRNA and protein. Follistatin is localized in syncytial cells and secreted by cultured placental cells. Exogenous follistatin completely reverses activin A-induced hCG and progesterone release from placental cells, demonstrating a functional paracrine role in regulating placental hormone production. RT-PCR, immunohistochemistry, RIA of culture medium, functional cell culture assay with recombinant follistatin The Journal of Clinical Endocrinology and Metabolism High 8288705
1998 The majority of follistatin's biological functions are mediated through its high-affinity binding to activin, neutralizing activin's effects. This activin-follistatin interplay constitutes a powerful regulatory mechanism in multiple tissues including the gonad, pituitary, pregnancy membranes, vasculature, and liver. Biochemical characterization, binding studies, functional assays (review synthesizing experimental work) Frontiers in Neuroendocrinology High 9799587
2002 Activin A induces transcription of both FLRG and follistatin (FST) at the mRNA and protein level through Smad proteins, establishing a negative feedback loop: activin activates Smad-dependent FST transcription, and the secreted follistatin then neutralizes activin signaling. Transcriptional reporter assay, RT-PCR, Western blot, Smad pathway analysis Oncogene High 11948405
2003 Follistatin modulates activin A-induced erythropoiesis in human primary CD34+ cells. Both follistatin and FLRG downmodulate the effects of activin A and BMP2 on erythroid maturation, indicating FST acts as a negative regulator of TGF-beta family member signaling during human erythropoiesis. In vitro erythroid differentiation of CD34+ primary cells, functional assay with follistatin protein Experimental Cell Research Medium 12531697
2005 Crystal structure of the follistatin:activin A complex reveals that two follistatin molecules encircle activin, burying one-third of its residues and blocking both type I and type II receptor binding sites. The follistatin N-terminal domain has an unexpected fold that mimics a universal type I receptor motif, directly occupying the type I receptor binding site on activin. The structure also explains how follistatin:BMP:type I receptor ternary complexes can form. X-ray crystallography (crystal structure determination) Developmental Cell High 16198295
2006 Three FST isoforms (FST288, FST303, FST315) differ in cell-surface binding activity (FST288 > FST303 > FST315), which determines their biological activity in inhibiting endogenous activin. Cell-surface proteoglycan binding is the primary determinant of differential isoform activity: FST288 suppresses whereas FST315 enhances activin-dependent TT cell proliferation. FST isoforms also differ from FSTL3 in ligand specificity: FST isoforms bind myostatin and some BMPs, whereas FSTL3 does not bind BMPs 2 and 4. Membrane anchoring of FSTL3 dramatically increases its endogenous activin inhibitory activity. Recombinant protein production, competitive binding assays, in vitro bioassay (TT cell proliferation), kinetic binding analysis (activin-binding affinities), membrane-anchoring construct experiments Endocrinology High 16627583
2007 A follistatin-derived myostatin inhibitor (FS I-I) selectively inhibits myostatin (Kd ~46.8 nM) with ~1000-fold reduced affinity for activin (Kd ~64.3 μM), compared to full-length follistatin which binds activin with Kd ~1.72 nM and myostatin with Kd ~12.3 nM. Transgenic expression of FS I-I in skeletal muscle increases muscle mass and strength via both hyperplasia and hypertrophy, and ameliorates pathology in mdx dystrophic mice. In vitro binding assays (Kd determination), transgenic mouse generation, muscle morphometry, functional strength testing, mdx mouse crossing FASEB Journal High 17893249
2008 FoxL2 and Smad3 coordinately regulate follistatin gene transcription. Activin induces follistatin transcription primarily through Smad3 at an intronic Smad-binding element (SBE1). FoxL2 binds an adjacent forkhead-binding element (FKHB) and directly associates with Smad3 (via Smad3's MH2 domain and FoxL2's intact forkhead domain) to drive SBE1-mediated transcription. Endogenous FoxL2 and Smad3 are recruited to the intronic enhancer by ChIP assay. Chromatin immunoprecipitation (ChIP), promoter reporter assay, shRNA knockdown, co-immunoprecipitation, site-directed mutagenesis of binding elements, proteomics approach for partner identification The Journal of Biological Chemistry High 19106105
2008 Integrin alpha6beta4 signaling induces demethylation of the FST promoter, leading to upregulation of FST mRNA expression. This epigenetic regulation is confirmed by bisulfite sequencing, and FST upregulation contributes to the motile/invasive phenotype conferred by alpha6beta4 in breast carcinoma cells. Affymetrix GeneChip expression profiling, siRNA, promoter analysis, ChIP, bisulfite sequencing, DNA methyltransferase inhibitor experiments The Journal of Biological Chemistry Medium 19011242
2010 Plasma follistatin increases markedly (~7-fold peak) during exercise and recovery. No net release was detected from the exercising limb (arterial-venous difference). In mice, swimming exercise increased both plasma follistatin and hepatic follistatin mRNA and protein, identifying the liver as the major source of circulating follistatin. IL-6 and epinephrine did not drive hepatic follistatin secretion. Arterial-venous difference measurements in humans, quantitative PCR, Western blotting in mouse tissues, cytokine/epinephrine infusion experiments Endocrinology High 21068158
2014 Overexpressed ERRβ induces FST-mediated apoptosis in breast cancer cells and enhances E-cadherin expression via upregulation of FST. ERRβ drives FST transcription through β-catenin/TCF4 recruitment to the FST promoter (identified by ChIP cloning). ERRβ-mediated BCAS2 upregulation inhibits FST transcription by downregulating β-catenin/TCF4 recruitment, constituting a regulatory circuit. FST overexpression also restricts MMP7 expression. ChIP cloning, gel supershift assay, co-immunoprecipitation, confocal microscopy, Western blotting, quantitative RT-PCR, functional apoptosis assays British Journal of Cancer Medium 24667650
2015 The liver is the major contributor to circulating follistatin in humans, both at rest and during exercise, as demonstrated by arterial-to-venous differences across the splanchnic bed. Glucagon increases and insulin inhibits follistatin secretion from the liver both in vivo and in vitro, mediated via the secondary messenger cAMP in hepatocytes. Short-term follistatin treatment reduced glucagon secretion from islets of Langerhans, and long-term treatment prevented apoptosis and induced proliferation of rat β cells. Arterial-to-venous difference measurements (splanchnic bed), cultured hepatocyte experiments, cAMP pathway analysis, islet of Langerhans functional assays The Journal of Clinical Endocrinology and Metabolism High 26652766
2017 Crystal structures of the GDF11:FS288 complex, apo-GDF8, and apo-GDF11 reveal that despite high similarity, GDF11 has unique structural properties in the type I receptor binding site that confer greater SMAD2/3 signaling potency than GDF8. Follistatin-288 (FST288 isoform) forms a complex with GDF11 analogous to the activin:follistatin complex, neutralizing this TGF-beta ligand. X-ray crystallography (crystal structure determination), SMAD2/3 signaling assays, receptor binding assays, site-directed mutagenesis (GDF8 with GDF11 residues) BMC Biology High 28257634
2018 Follistatin (FST) functions as a pathological hepatokine during hepatic insulin resistance. Hepatic FoxO1 inactivation normalizes elevated FST levels in insulin receptor substrate 1/2 double knockout (LDKO) mice. Knockdown of hepatic FST in LDKO mice restored glucose tolerance, white adipose tissue insulin signaling, and insulin-mediated suppression of hepatic glucose production. Conversely, overexpression of FST in healthy mouse liver impaired glucose homeostasis. Serum FST decreased in parallel with HbA1c in obese diabetic patients following gastric bypass surgery. Hepatic knockdown (shRNA/siRNA), transgenic mouse models (LDKO, LTKO), glucose tolerance tests, insulin signaling assays, hepatokine identification, human clinical correlation Nature Medicine High 29867232

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
1999 Indirect measures of gene flow and migration: FST not equal to 1/(4Nm + 1). Heredity 699 10098262
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
1999 Thirty-seven candidate genes for polycystic ovary syndrome: strongest evidence for linkage is with follistatin. Proceedings of the National Academy of Sciences of the United States of America 360 10411917
2012 Strength training with blood flow restriction diminishes myostatin gene expression. Medicine and science in sports and exercise 319 21900845
2011 Comparison of F(ST) outlier tests for SNP loci under selection. Molecular ecology resources 305 21429174
1991 Follistatin binds to both activin and inhibin through the common subunit. Endocrinology 270 2036994
2011 A directed protein interaction network for investigating intracellular signal transduction. Science signaling 258 21900206
1988 Primary structure of the human follistatin precursor and its genomic organization. Proceedings of the National Academy of Sciences of the United States of America 241 3380788
2005 The structure of the follistatin:activin complex reveals antagonism of both type I and type II receptor binding. Developmental cell 233 16198295
1998 Follistatin: a multifunctional regulatory protein. Frontiers in neuroendocrinology 216 9799587
2009 A genome-wide short hairpin RNA screening of jurkat T-cells for human proteins contributing to productive HIV-1 replication. The Journal of biological chemistry 211 19460752
2002 FLAGdb/FST: a database of mapped flanking insertion sites (FSTs) of Arabidopsis thaliana T-DNA transformants. Nucleic acids research 196 11752264
2006 Biological activity of follistatin isoforms and follistatin-like-3 is dependent on differential cell surface binding and specificity for activin, myostatin, and bone morphogenetic proteins. Endocrinology 181 16627583
2011 G'ST and D do not replace FST. Molecular ecology 175 21375616
2007 Transgenic expression of a myostatin inhibitor derived from follistatin increases skeletal muscle mass and ameliorates dystrophic pathology in mdx mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 156 17893249
2010 Exercise induces a marked increase in plasma follistatin: evidence that follistatin is a contraction-induced hepatokine. Endocrinology 151 21068158
2008 Integrin alpha6beta4 controls the expression of genes associated with cell motility, invasion, and metastasis, including S100A4/metastasin. The Journal of biological chemistry 131 19011242
1978 fs(1)K10, a germline-dependent female sterile mutation causing abnormal chorion morphology inDrosophila melanogaster. Wilhelm Roux's archives of developmental biology 116 28305014
2021 A protein interaction landscape of breast cancer. Science (New York, N.Y.) 111 34591612
2010 A large-scale candidate gene association study of age at menarche and age at natural menopause. Human genetics 106 20734064
2015 Circulating Follistatin Is Liver-Derived and Regulated by the Glucagon-to-Insulin Ratio. The Journal of clinical endocrinology and metabolism 105 26652766
2010 Rapid developmental maturation of neocortical FS cell intrinsic excitability. Cerebral cortex (New York, N.Y. : 1991) 103 20705896
2018 Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei. Molecular & cellular proteomics : MCP 101 30021884
2001 Evidence for association of polycystic ovary syndrome in caucasian women with a marker at the insulin receptor gene locus. The Journal of clinical endocrinology and metabolism 100 11232039
2017 Structural basis for potency differences between GDF8 and GDF11. BMC biology 95 28257634
2008 FoxL2 and Smad3 coordinately regulate follistatin gene transcription. The Journal of biological chemistry 94 19106105
1986 Genetic and molecular analysis of fs(1)h, a maternal effect homeotic gene in Drosophila. Developmental biology 93 3007240
2004 Signal peptide prediction based on analysis of experimentally verified cleavage sites. Protein science : a publication of the Protein Society 92 15340161
2007 Divergent selection as revealed by P(ST) and QTL-based F(ST) in three-spined stickleback (Gasterosteus aculeatus) populations along a coastal-inland gradient. Molecular ecology 91 17284219
2003 Regulation of human erythropoiesis by activin A, BMP2, and BMP4, members of the TGFbeta family. Experimental cell research 90 12531697
2018 Inactivating hepatic follistatin alleviates hyperglycemia. Nature medicine 83 29867232
1991 FST in a hierarchical island model. Genetics 83 2016058
2003 Serum concentrations of activin and follistatin are elevated and run in parallel in patients with septicemia. European journal of endocrinology 82 12720540
1999 Somatic signaling mediated by fs(1)Yb is essential for germline stem cell maintenance during Drosophila oogenesis. Development (Cambridge, England) 80 10101118
2002 Transcription activation of FLRG and follistatin by activin A, through Smad proteins, participates in a negative feedback loop to modulate activin A function. Oncogene 79 11948405
1994 Local production and action of follistatin in human placenta. The Journal of clinical endocrinology and metabolism 70 8288705
2009 Snake venom Vascular Endothelial Growth Factors (VEGF-Fs) exclusively vary their structures and functions among species. The Journal of biological chemistry 69 19208624
2013 Combined analyses of kinship and FST suggest potential drivers of chaotic genetic patchiness in high gene-flow populations. Molecular ecology 66 23802550
1996 AmpliTaq DNA polymerase, FS dye-terminator sequencing: analysis of peak height patterns. BioTechniques 66 8891223
1991 The Drosophila maternal-effect gene fs(1)Ya encodes a cell cycle-dependent nuclear envelope component required for embryonic mitosis. Cell 65 1986869
2016 Population-specific FST values for forensic STR markers: A worldwide survey. Forensic science international. Genetics 64 27082756
2013 A mechanistic and kinetic study on the formation of PBDD/Fs from PBDEs. Environmental science & technology 63 23578223
2003 Validation of the CALUX bioassay for the screening of PCDD/Fs and dioxin-like PCBs in retail fish. The Analyst 53 12790202
2007 Inferring local adaptation from QST-FST comparisons: neutral genetic and quantitative trait variation in European populations of great snipe. Journal of evolutionary biology 49 17584249
2019 Background selection and FST : Consequences for detecting local adaptation. Molecular ecology 48 31349365
2010 Organochlorine pesticides (OCPs), dioxin-like polychlorinated biphenyls (dl-PCBs), polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo furans (PCDD/Fs) in edible fish from Lake Volta, Lake Bosumtwi and Weija Lake in Ghana. Chemosphere 46 20843537
1987 Oocyte-specific transcription of fs(1)K10: a Drosophila gene affecting dorsal-ventral developmental polarity. The EMBO journal 46 16453754
2013 The antidepressant-like effect of inosine in the FST is associated with both adenosine A1 and A 2A receptors. Purinergic signalling 45 23613131
2009 PCDD/Fs and dioxin-like PCBs in home-produced eggs from Belgium: levels, contamination sources and health risks. The Science of the total environment 44 19155055
2019 Generation of deep ultraviolet sub-2-fs pulses. Optics letters 42 30874637
2014 ERRβ signalling through FST and BCAS2 inhibits cellular proliferation in breast cancer cells. British journal of cancer 41 24667650
2016 The bioaccessibility of polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) in cooked plant and animal origin foods. Environment international 40 27203782
2014 Activation of the mTOR signaling pathway in the antidepressant-like activity of the mGlu5 antagonist MTEP and the mGlu7 agonist AMN082 in the FST in rats. Neuropharmacology 40 24631968
2011 If F(ST) does not measure neutral genetic differentiation, then comparing it with Q(ST) is misleading. Or is it? Molecular ecology 40 21410574
2003 Enterococcus faecalis plasmid pAD1-encoded Fst toxin affects membrane permeability and alters cellular responses to lantibiotics. Journal of bacteriology 40 12644486
2021 Few-fs resolution of a photoactive protein traversing a conical intersection. Nature 38 34732893
2011 Formation and mitigation of PCDD/Fs in iron ore sintering. Chemosphere 36 21880347
2007 Increased sensitivity to antidepressants of D3 dopamine receptor-deficient mice in the forced swim test (FST). European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 36 17804207
2013 Correlation between endogenous VWF:Ag and PK parameters and bleeding frequency in severe haemophilia A subjects during three-times-weekly prophylaxis with rFVIII-FS. Haemophilia : the official journal of the World Federation of Hemophilia 35 24252058
1989 Information from e.x.a.f.s. spectroscopy on the structures of different forms of molybdenum in xanthine oxidase and the catalytic mechanism of the enzyme. The Biochemical journal 35 2764889
2008 Coalescence times and FST under a skewed offspring distribution among individuals in a population. Genetics 34 19047415
2020 Polybrominated dibenzo-p-dioxins and furans (PBDD/Fs): Contamination in food, humans and dietary exposure. The Science of the total environment 33 33160676
1998 Establishment and characterization of a porcine kidney cell line, FS-L3, which forms unique multicellular domes in serum-free culture. In vitro cellular & developmental biology. Animal 31 9542636
1995 The role of fs(1)K10 in the localization of the mRNA of the TGF alpha homolog gurken within the Drosophila oocyte. Mechanisms of development 31 7547466
2008 F(ST) and Q(ST) under neutrality. Genetics 30 18780742
1987 Specific bradycardic agents, a new therapeutic modality for anesthesiology: hemodynamic effects of UL-FS 49 and propranolol in conscious and isoflurane-anesthetized dogs. Anesthesiology 30 3674471
2010 Solution structure and membrane binding of the toxin fst of the par addiction module. Biochemistry 29 20677831
2004 Formation of PCDD/Fs and PCBs in the process of production of 1,4-dichlorobenzene. Chemosphere 28 15519376
2001 Drosophila vitelline membrane cross-linking requires the fs(1)Nasrat, fs(1)polehole and chorion genes activities. Development genes and evolution 27 11819114
2019 Mechanochemical degradation of PCDD/Fs in fly ash within different milling systems. Chemosphere 24 30780029
2021 DNA fingerprinting, fixation-index (Fst), and admixture mapping of selected Bambara groundnut (Vigna subterranea [L.] Verdc.) accessions using ISSR markers system. Scientific reports 23 34267249
2017 Examination of Enterococcus faecalis Toxin-Antitoxin System Toxin Fst Function Utilizing a Pheromone-Inducible Expression Vector with Tight Repression and Broad Dynamic Range. Journal of bacteriology 23 28348028
2014 Biophysical effects in off-resonant gold nanoparticle mediated (GNOME) laser transfection of cell lines, primary- and stem cells using fs laser pulses. Journal of biophotonics 23 25302483
2011 Cornea microstructure and mechanical responses measured with nonlinear optical and optical coherence microscopy using sub-10-fs pulses. Biomedical optics express 23 21559126
1999 Among-locus variation in Fst: fish, allozymes and the Lewontin-Krakauer test revisited. Genetics 23 10353907
1995 fs (1) Yb is required for ovary follicle cell differentiation in Drosophila melanogaster and has genetic interactions with the Notch group of neurogenic genes. Genetics 23 7635286
1995 Mutational analyses of fs(1)Ya, an essential, developmentally regulated, nuclear envelope protein in Drosophila. Genetics 23 8601487
2009 Differential induction of cytochrome P450 1A1 and 1B1 mRNA in primary cultured bovine hepatocytes treated with TCDD, PBDD/Fs and feed ingredients. Toxicology letters 22 19167471
2007 Two-body Coulomb explosion and hydrogen migration in methanol induced by intense 7 and 21 fs laser pulses. The Journal of chemical physics 22 17867746
2022 Bisphenols A, F, S and AF trigger apoptosis and/or endoplasmic reticulum stress in human endometrial stromal cells. Toxicology 21 35940389
2012 Characterization of the effects of an rpoC mutation that confers resistance to the Fst peptide toxin-antitoxin system toxin. Journal of bacteriology 21 23104812
1995 General characteristics of the polytene chromosome from ovarian pseudonurse cells of the Drosophila melanogaster otu11 and fs(2)B mutants. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 21 7780663
2020 Fermentation optimization and disease suppression ability of a Streptomyces ma. FS-4 from banana rhizosphere soil. BMC microbiology 20 32005152
2019 Cell migration and osteo/odontogenesis stimulation of iRoot FS as a potential apical barrier material in apexification. International endodontic journal 20 31622505
2018 Metabolomics Identifies Distinctive Metabolite Signatures for Measures of Glucose Homeostasis: The Insulin Resistance Atherosclerosis Family Study (IRAS-FS). The Journal of clinical endocrinology and metabolism 20 29546329
2012 Quantitative analysis of follistatin (FST) promoter methylation in peripheral blood of patients with polycystic ovary syndrome. Reproductive biomedicine online 20 23265961
2021 Thermal cotreatment of municipal solid waste incineration fly ash with sewage sludge for PCDD/Fs decomposition and reformation suppression. Journal of hazardous materials 19 34492973
2019 Rationale, Design, Methodology and Baseline Data of Fushun Diabetic Retinopathy Cohort Study (FS-DIRECT). Ophthalmic epidemiology 19 31722595
2017 Polymorphisms of FST gene and their association with wool quality traits in Chinese Merino sheep. PloS one 19 28384189
2019 Control of excitatory hierarchical circuits by parvalbumin-FS basket cells in layer 5 of the frontal cortex: insights for cortical oscillations. Journal of neurophysiology 18 30995139
2014 Mixed halogenated dioxins/furans (PXDD/Fs) and biphenyls (PXBs) in food: occurrence and toxic equivalent exposure using specific relative potencies. Environment international 17 25108070
2000 Purification of collagenase and specificity of its related enzyme from Bacillus subtilis FS-2. Bioscience, biotechnology, and biochemistry 17 10705465
2021 FS-GBDT: identification multicancer-risk module via a feature selection algorithm by integrating Fisher score and GBDT. Briefings in bioinformatics 16 34020547
2020 Discovery of selection-driven genetic differences of Duroc, Landrace, and Yorkshire pig breeds by EigenGWAS and Fst analyses. Animal genetics 16 32400898
1998 A new assay for classical swine fever virus based on cytopathogenicity in porcine kidney cell line FS-L3. Journal of virological methods 16 9506817
2020 Disagreement in FST estimators: A case study from sex chromosomes. Molecular ecology resources 15 32543001
2019 , Jost's D, and FST are similarly constrained by allele frequencies: A mathematical, simulation, and empirical study. Molecular ecology 15 30589985
2010 Analysis of PCDD/Fs and dioxin-like PCBs in atmospheric deposition samples from the Flemish measurement network: Optimization and validation of a new CALUX bioassay method. Chemosphere 15 21094512
1973 Penetration into host cells of naked, partially injected (post-FST) DNA of bacteriophage T5. Journal of virology 15 4583885
2020 Polybrominated dibenzo-p-dioxins and furans (PBDD/Fs) in Italian food: Occurrence and dietary exposure. The Science of the total environment 14 32585481
2020 The Fst/Ldr Family of Type I TA System Toxins: Potential Roles in Stress Response, Metabolism and Pathogenesis. Toxins 14 32722354
2019 Health risk of childhood exposure to PCDD/Fs emitted from a municipal waste incinerator in Zhejiang, China. The Science of the total environment 14 31280174
2014 Spatial and temporal variation, source profile, and formation mechanisms of PCDD/FS in the atmosphere of an e-waste recycling area, south China. Environmental toxicology and chemistry 14 24249304
2011 Assessment of risk of PCDD/Fs and dioxin-like PCBs in marine and freshwater fish in Pearl River Delta, China. Marine pollution bulletin 14 21392810
2010 A case of CMT 1B due to Val 102/fs null mutation of the MPZ gene presenting as hyperCKemia. Clinical neurology and neurosurgery 14 20537790
2008 The joint effects of selection and dominance on the QST - FST contrast. Genetics 14 18984567
2022 Mathematical constraints on F: multiallelic markers in arbitrarily many populations. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 13 35430885
2018 Cytocompatibility of Biodentine and iRoot FS with human periodontal ligament cells: an in vitro study. International endodontic journal 13 29350756
1977 The use of the FST statistic of Wright for estimating the effects of genetic drift, selection and migration populations, with special reference to Ireland. Human heredity 13 863462
2022 Genome-Wide Association Study and FST Analysis Reveal Four Quantitative Trait Loci and Six Candidate Genes for Meat Color in Pigs. Frontiers in genetics 12 35464836
2020 The Differential Expression of Cytokines and Growth Factors After SMILE Compared With FS-LASIK in Rabbits. Investigative ophthalmology & visual science 12 32460319
2012 Aerosol-water distribution of PCDD/Fs and PCBs in the Baltic Sea region. Environmental science & technology 12 23214413
2023 Fucogalactan Sulfate (FS) from Laminaria japonica Regulates Lipid Metabolism in Diet-Induced Humanized Dyslipidemia Mice via an Intestinal FXR-FGF19-CYP7A1/CYP8B1 Pathway. Journal of agricultural and food chemistry 11 37702045
2022 Formation pathways, gas-solid partitioning, and reaction kinetics of PCDD/Fs associated with baghouse filters operated at high temperatures: A case study. The Science of the total environment 11 36265614
2001 Identification of new X-chromosomal genes required for Drosophila oogenesis and novel roles for fs(1)Yb, brainiac and dunce. Genome research 11 11156616
2012 Analysis of PCDD/Fs and dioxin-like PCBs in atmospheric deposition samples from the Flemish measurement network: correlation between the CALUX bioassay and GC-HRMS. Chemosphere 10 22560702
2011 A pH/enzyme-responsive polymer film consisting of Eudragit FS 30 D and arabinoxylane as a potential material formulation for colon-specific drug delivery system. Pharmaceutical development and technology 10 21222512
1996 Cloning, sequencing and transcriptional regulation of the draT and draG genes of Azospirillum lipoferum FS. Gene 10 8621068
2021 8 fs laser pulses from a compact gas-filled multi-pass cell. Optics express 9 34615123
2020 Femtosecond Plasmonic Laser Nanosurgery (fs-PLN) mediated by molecularly targeted gold nanospheres at ultra-low pulse fluences. Scientific reports 9 32709944
2019 Residue concentrations and profiles of PCDD/Fs in ash samples from multiple thermal industrial processes in Vietnam: Formation, emission levels, and risk assessment. Environmental science and pollution research international 9 31030397
2018 FS-7 inhibits MGC-803 cells growth in vitro and in vivo via down-regulating glycolysis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 9 30551420
2014 Development and application of a novel method for high-throughput determination of PCDD/Fs and PCBs in sediments. Environmental toxicology and chemistry 9 24648260
2013 Assessment of emissions and removal of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) at start-up periods in a hazardous waste incinerator. Journal of the Air & Waste Management Association (1995) 9 23926848
2012 Neuronal Differentiation of a Human Induced Pluripotent Stem Cell Line (FS-1) Derived from Newborn Foreskin Fibroblasts. International journal of stem cells 9 24298367
2006 Association between tofu intake and serum polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in the elderly Taiwanese. Environment international 9 17113646