Update on biologic pathways in inflammatory bowel disease and their therapeutic relevance.

PubWeight™: 0.98‹?› | Rank: Top 15%

🔗 View Article (PMC 4592148)

Published in J Gastroenterol on January 05, 2012

Authors

Matthew J Hamilton1, Scott B Snapper, Richard S Blumberg

Author Affiliations

1: Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. mjhamilton@partners.org

Articles citing this

Predictors of depression in youth with Crohn disease. J Pediatr Gastroenterol Nutr (2014) 1.42

Multicenter analysis of fecal microbiota profiles in Japanese patients with Crohn's disease. J Gastroenterol (2012) 1.31

Efficacy and safety of adalimumab in Japanese patients with moderately to severely active ulcerative colitis. J Gastroenterol (2013) 1.12

Oral caffeine administration ameliorates acute colitis by suppressing chitinase 3-like 1 expression in intestinal epithelial cells. J Gastroenterol (2013) 0.83

Immunology of inflammatory bowel disease and molecular targets for biologics. Gastroenterol Clin North Am (2014) 0.82

Immune-epithelial crosstalk at the intestinal surface. J Gastroenterol (2014) 0.81

IL-1 in Colon Inflammation, Colon Carcinogenesis and Invasiveness of Colon Cancer. Cancer Microenviron (2015) 0.80

Vitamin K deficiency leads to exacerbation of murine dextran sulfate sodium-induced colitis. J Gastroenterol (2015) 0.78

Pro-inflammatory cytokine interleukin-1β promotes the development of intestinal stem cells. Inflamm Res (2012) 0.77

Characterization of gut microbiota profiles by disease activity in patients with Crohn's disease using data mining analysis of terminal restriction fragment length polymorphisms. Biomed Rep (2014) 0.76

Possible diagnostic role of antibodies to Crohn's disease peptide (ACP): results of a multicenter study in a Japanese cohort. J Gastroenterol (2013) 0.76

Regulation of anergy-related ubiquitin E3 ligase, GRAIL, in murine models of colitis and patients with Crohn's disease. J Gastroenterol (2013) 0.76

Prognostic factors affecting early colectomy in patients with moderate to severe ulcerative colitis treated with calcineurin inhibitors. Exp Ther Med (2016) 0.75

Inflammatory bowel disease-related arthritis - clinical evaluation and possible role of cytokines. Reumatologia (2015) 0.75

FOLH1/GCPII is elevated in IBD patients, and its inhibition ameliorates murine IBD abnormalities. JCI Insight (2016) 0.75

Hematologic malignancies in the Japanese patients with inflammatory bowel disease. J Gastroenterol (2013) 0.75

Articles cited by this

A human gut microbial gene catalogue established by metagenomic sequencing. Nature (2010) 43.63

Autophagy in the pathogenesis of disease. Cell (2008) 34.68

Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol (2007) 33.06

Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nat Genet (2008) 30.20

Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A (2007) 20.60

Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell (2009) 20.29

A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet (2006) 15.14

Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol (2009) 14.33

The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol (2009) 13.87

Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Nature (2008) 11.39

Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science (2005) 11.31

Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe (2008) 11.08

Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol (2008) 11.02

NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell (2011) 9.75

Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol (2006) 8.89

Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature (2009) 8.71

XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell (2008) 8.43

Mucosal flora in inflammatory bowel disease. Gastroenterology (2002) 8.42

Genetics and pathogenesis of inflammatory bowel disease. Nature (2011) 7.79

Impaired on/off regulation of TNF biosynthesis in mice lacking TNF AU-rich elements: implications for joint and gut-associated immunopathologies. Immunity (1999) 7.34

Inflammatory bowel disease. Annu Rev Immunol (2010) 7.10

Antibodies to interleukin 12 abrogate established experimental colitis in mice. J Exp Med (1995) 6.89

Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn's disease. N Engl J Med (2005) 6.33

High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn's disease. Gastroenterology (2004) 5.94

Defective hepatic autophagy in obesity promotes ER stress and causes insulin resistance. Cell Metab (2010) 5.82

The inflammasome NLRs in immunity, inflammation, and associated diseases. Annu Rev Immunol (2011) 5.73

NOD2 is a negative regulator of Toll-like receptor 2-mediated T helper type 1 responses. Nat Immunol (2004) 5.59

Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology. Immunity (2006) 5.40

Natalizumab induction and maintenance therapy for Crohn's disease. N Engl J Med (2005) 5.36

Single nucleotide polymorphisms in TNFSF15 confer susceptibility to Crohn's disease. Hum Mol Genet (2005) 5.35

Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet (2008) 5.32

Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis. J Clin Invest (2004) 5.14

Reduced Paneth cell alpha-defensins in ileal Crohn's disease. Proc Natl Acad Sci U S A (2005) 5.05

Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn's disease. Gastroenterology (1998) 5.02

IL-12 and IL-23: master regulators of innate and adaptive immunity. Immunol Rev (2004) 4.78

Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterology (2005) 4.68

Linking of autophagy to ubiquitin-proteasome system is important for the regulation of endoplasmic reticulum stress and cell viability. Am J Pathol (2007) 4.45

Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet (2008) 4.06

The Crohn's disease protein, NOD2, requires RIP2 in order to induce ubiquitinylation of a novel site on NEMO. Curr Biol (2004) 3.54

Proinflammatory cytokines in the pathogenesis of inflammatory bowel diseases. Gastroenterology (2011) 3.52

CCR6 regulates the migration of inflammatory and regulatory T cells. J Immunol (2008) 3.51

Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL-13-producing NK-T cells. Immunity (2002) 3.46

Impaired autophagy of an intracellular pathogen induced by a Crohn's disease associated ATG16L1 variant. PLoS One (2008) 3.36

A randomized trial of Ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with moderate-to-severe Crohn's disease. Gastroenterology (2008) 3.36

Interleukin 1 (IL-1) gene expression, synthesis, and effect of specific IL-1 receptor blockade in rabbit immune complex colitis. J Clin Invest (1990) 2.86

Mucosal imbalance of IL-1 and IL-1 receptor antagonist in inflammatory bowel disease. A novel mechanism of chronic intestinal inflammation. J Immunol (1995) 2.71

Increased sensitivity to dextran sodium sulfate colitis in IRE1beta-deficient mice. J Clin Invest (2001) 2.67

Common variants in the NLRP3 region contribute to Crohn's disease susceptibility. Nat Genet (2008) 2.67

IL-18, a novel immunoregulatory cytokine, is up-regulated in Crohn's disease: expression and localization in intestinal mucosal cells. J Immunol (1999) 2.58

Bioactive IL-18 expression is up-regulated in Crohn's disease. J Immunol (1999) 2.38

Crohn's disease-associated adherent-invasive E. coli are selectively favoured by impaired autophagy to replicate intracellularly. Cell Microbiol (2009) 2.23

Chronic stimulation of Nod2 mediates tolerance to bacterial products. Proc Natl Acad Sci U S A (2007) 2.20

TL1A (TNFSF15) regulates the development of chronic colitis by modulating both T-helper 1 and T-helper 17 activation. Gastroenterology (2008) 2.06

Mesenchymal cell targeting by TNF as a common pathogenic principle in chronic inflammatory joint and intestinal diseases. J Exp Med (2008) 1.98

Role of TL1A and its receptor DR3 in two models of chronic murine ileitis. Proc Natl Acad Sci U S A (2006) 1.87

Downregulation of epithelial apoptosis and barrier repair in active Crohn's disease by tumour necrosis factor alpha antibody treatment. Gut (2004) 1.82

Interleukin 18 is a primary mediator of the inflammation associated with dextran sulphate sodium induced colitis: blocking interleukin 18 attenuates intestinal damage. Gut (2002) 1.65

Mucosal healing in inflammatory bowel disease: impossible ideal or therapeutic target? Gut (2007) 1.62

Increased expression of CCL20 in human inflammatory bowel disease. J Clin Immunol (2004) 1.50

Fecal short-chain fatty acids in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr (1994) 1.33

Treatment of ulcerative colitis by feeding with germinated barley foodstuff: first report of a multicenter open control trial. J Gastroenterol (2002) 1.30

NOD2 regulation of Toll-like receptor responses and the pathogenesis of Crohn's disease. Gut (2005) 1.17

Suppression of inflammation in ulcerative colitis by interferon-β-1a is accompanied by inhibition of IL-13 production. Gut (2010) 1.17

CCR6 has a non-redundant role in the development of inflammatory bowel disease. Eur J Immunol (2003) 1.12

Short-chain fatty acids act as antiinflammatory mediators by regulating prostaglandin E(2) and cytokines. World J Gastroenterol (2009) 1.10

Association of TNFSF15 with Crohn's disease in Koreans. Am J Gastroenterol (2008) 1.10

MIP-3alpha neutralizing monoclonal antibody protects against TNBS-induced colonic injury and inflammation in mice. Am J Physiol Gastrointest Liver Physiol (2007) 1.00

Articles by these authors

The immunology of mucosal models of inflammation. Annu Rev Immunol (2001) 9.08

XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell (2008) 8.43

The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature (2007) 7.82

Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. N Engl J Med (2009) 7.53

Inflammatory bowel disease. Annu Rev Immunol (2010) 7.10

IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis. J Clin Invest (2008) 6.17

Microbial exposure during early life has persistent effects on natural killer T cell function. Science (2012) 5.90

Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol (2012) 5.66

Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis. J Clin Invest (2004) 5.14

Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation. Immunity (2002) 4.60

Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nat Med (2009) 3.97

Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL-13-producing NK-T cells. Immunity (2002) 3.46

Resolvin E1, an endogenous lipid mediator derived from omega-3 eicosapentaenoic acid, protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis. Proc Natl Acad Sci U S A (2005) 3.32

CEACAM1: contact-dependent control of immunity. Nat Rev Immunol (2006) 2.81

Human neonatal Fc receptor mediates transport of IgG into luminal secretions for delivery of antigens to mucosal dendritic cells. Immunity (2004) 2.79

Receptor-mediated immunoglobulin G transport across mucosal barriers in adult life: functional expression of FcRn in the mammalian lung. J Exp Med (2002) 2.32

CD1d-dependent macrophage-mediated clearance of Pseudomonas aeruginosa from lung. Nat Med (2002) 2.22

Neonatal Fc receptor for IgG regulates mucosal immune responses to luminal bacteria. J Clin Invest (2006) 2.16

Paneth cells as a site of origin for intestinal inflammation. Nature (2013) 2.09

WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility. EMBO J (2003) 1.98

A novel PPAR gamma gene therapy to control inflammation associated with inflammatory bowel disease in a murine model. Gastroenterology (2003) 1.91

Dependence of antibody-mediated presentation of antigen on FcRn. Proc Natl Acad Sci U S A (2008) 1.82

The Wiskott-Aldrich syndrome protein is required for the function of CD4(+)CD25(+)Foxp3(+) regulatory T cells. J Exp Med (2007) 1.81

Protection from lethal septic peritonitis by neutralizing the biological function of interleukin 27. J Exp Med (2006) 1.78

A new method for rapidly generating gene-targeting vectors by engineering BACs through homologous recombination in bacteria. Genome Res (2003) 1.77

Disruption of T helper 2-immune responses in Epstein-Barr virus-induced gene 3-deficient mice. Proc Natl Acad Sci U S A (2002) 1.73

An FcRn-dependent role for anti-flagellin immunoglobulin G in pathogenesis of colitis in mice. Gastroenterology (2009) 1.71

ER stress transcription factor Xbp1 suppresses intestinal tumorigenesis and directs intestinal stem cells. J Exp Med (2013) 1.70

Pulmonary delivery of an erythropoietin Fc fusion protein in non-human primates through an immunoglobulin transport pathway. Proc Natl Acad Sci U S A (2004) 1.69

The recycling and transcytotic pathways for IgG transport by FcRn are distinct and display an inherent polarity. J Cell Biol (2009) 1.68

A crucial role for macrophages in the pathology of K/B x N serum-induced arthritis. Eur J Immunol (2005) 1.65

WASP confers selective advantage for specific hematopoietic cell populations and serves a unique role in marginal zone B-cell homeostasis and function. Blood (2008) 1.65

The Nore1B/Mst1 complex restrains antigen receptor-induced proliferation of naïve T cells. Proc Natl Acad Sci U S A (2008) 1.61

Cortactin regulates cell migration through activation of N-WASP. J Cell Sci (2004) 1.61

IL-10R polymorphisms are associated with very-early-onset ulcerative colitis. Inflamm Bowel Dis (2013) 1.59

Functional reconstitution of human FcRn in Madin-Darby canine kidney cells requires co-expressed human beta 2-microglobulin. J Biol Chem (2002) 1.58

Innate immune response to encephalomyocarditis virus infection mediated by CD1d. Immunology (2003) 1.57

Microsomal triglyceride transfer protein lipidation and control of CD1d on antigen-presenting cells. J Exp Med (2005) 1.57

Bidirectional transepithelial IgG transport by a strongly polarized basolateral membrane Fcgamma-receptor. Mol Biol Cell (2004) 1.54

Neonatal Fc receptor: from immunity to therapeutics. J Clin Immunol (2010) 1.50

Inducible clustering of membrane-targeted SH3 domains of the adaptor protein Nck triggers localized actin polymerization. Curr Biol (2004) 1.50

Hepatitis B virus-induced lipid alterations contribute to natural killer T cell-dependent protective immunity. Nat Med (2012) 1.50

CD1d function is regulated by microsomal triglyceride transfer protein. Nat Med (2004) 1.49

Cd1d-dependent regulation of bacterial colonization in the intestine of mice. J Clin Invest (2009) 1.49

Delineation of a CD1d-restricted antigen presentation pathway associated with human and mouse intestinal epithelial cells. Gastroenterology (2003) 1.45

Regulatory T cells in inflammatory bowel disease. Curr Opin Gastroenterol (2008) 1.44

Neonatal Fc receptor for IgG (FcRn) regulates cross-presentation of IgG immune complexes by CD8-CD11b+ dendritic cells. Proc Natl Acad Sci U S A (2011) 1.44

Peroxisome proliferator-activated receptor gamma-mediated regulation of neural stem cell proliferation and differentiation. J Biol Chem (2006) 1.39

Transepithelial transport of Fc-targeted nanoparticles by the neonatal fc receptor for oral delivery. Sci Transl Med (2013) 1.38

Peroxisome proliferator-activated receptor gamma agonist ligands stimulate a Th2 cytokine response and prevent acute colitis. Inflamm Bowel Dis (2002) 1.35

Gene therapy for Wiskott-Aldrich syndrome: rescue of T-cell signaling and amelioration of colitis upon transplantation of retrovirally transduced hematopoietic stem cells in mice. Blood (2002) 1.35

EBV-induced gene 3 transcription is induced by TLR signaling in primary dendritic cells via NF-kappa B activation. J Immunol (2005) 1.35

Gut-tropic T cells that express integrin α4β7 and CCR9 are required for induction of oral immune tolerance in mice. Gastroenterology (2011) 1.34

CD66a interactions between human melanoma and NK cells: a novel class I MHC-independent inhibitory mechanism of cytotoxicity. J Immunol (2002) 1.34

The simultaneous blockade of chemokine receptors CCR2, CCR5 and CXCR3 by a non-peptide chemokine receptor antagonist protects mice from dextran sodium sulfate-mediated colitis. Int Immunol (2005) 1.34

Endoplasmic reticulum stress in the intestinal epithelium and inflammatory bowel disease. Semin Immunol (2009) 1.33

SHP1 phosphatase-dependent T cell inhibition by CEACAM1 adhesion molecule isoforms. Immunity (2006) 1.33

Wiskott Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development. Proc Natl Acad Sci U S A (2007) 1.31

Fc-fusion proteins and FcRn: structural insights for longer-lasting and more effective therapeutics. Crit Rev Biotechnol (2013) 1.31

CD1d degradation in Chlamydia trachomatis-infected epithelial cells is the result of both cellular and chlamydial proteasomal activity. J Biol Chem (2007) 1.30

Immune and non-immune functions of the (not so) neonatal Fc receptor, FcRn. Semin Immunopathol (2009) 1.29

Rac1 drives melanoblast organization during mouse development by orchestrating pseudopod- driven motility and cell-cycle progression. Dev Cell (2011) 1.29

Eosinophils alter colonic epithelial barrier function: role for major basic protein. Am J Physiol Gastrointest Liver Physiol (2005) 1.28

Crohn's disease: NOD2, autophagy and ER stress converge. Gut (2011) 1.27

Interleukin-35 mediates mucosal immune responses that protect against T-cell-dependent colitis. Gastroenterology (2011) 1.25

Role of the WASP family proteins for Mycobacterium marinum actin tail formation. Proc Natl Acad Sci U S A (2005) 1.25

Autophagy, microbial sensing, endoplasmic reticulum stress, and epithelial function in inflammatory bowel disease. Gastroenterology (2011) 1.24

Induced reactivity of intestinal CD4(+) T cells with an epithelial cell lectin, galectin-4, contributes to exacerbation of intestinal inflammation. Immunity (2004) 1.22

Lymphocyte-dependent and Th2 cytokine-associated colitis in mice deficient in Wiskott-Aldrich syndrome protein. Gastroenterology (2007) 1.21

The actin regulator N-WASp is required for muscle-cell fusion in mice. Proc Natl Acad Sci U S A (2012) 1.20

Intestinal alkaline phosphatase has beneficial effects in mouse models of chronic colitis. Inflamm Bowel Dis (2011) 1.18

Toll-like receptor 4-mediated regulation of spontaneous Helicobacter-dependent colitis in IL-10-deficient mice. Gastroenterology (2009) 1.18

Phosphorylation of WASp is a key regulator of activity and stability in vivo. Proc Natl Acad Sci U S A (2009) 1.18

Essential role for mast cell tryptase in acute experimental colitis. Proc Natl Acad Sci U S A (2010) 1.17

A passionate kiss, then run: exocytosis and recycling of IgG by FcRn. Trends Cell Biol (2005) 1.17

Activation-induced expression of carcinoembryonic antigen-cell adhesion molecule 1 regulates mouse T lymphocyte function. J Immunol (2002) 1.17

Distribution of the IgG Fc receptor, FcRn, in the human fetal intestine. Pediatr Res (2003) 1.16

Specific regulation of T helper cell 1-mediated murine colitis by CEACAM1. J Exp Med (2004) 1.14

MTP regulated by an alternate promoter is essential for NKT cell development. J Exp Med (2007) 1.14

Wiskott-Aldrich syndrome protein (WASP) and N-WASP are critical for peripheral B-cell development and function. Blood (2012) 1.13

Resolvin E1, an endogenous lipid mediator derived from eicosapentaenoic acid, prevents dextran sulfate sodium-induced colitis. Inflamm Bowel Dis (2010) 1.13

Dependence of intestinal granuloma formation on unique myeloid DC-like cells. J Clin Invest (2007) 1.12

N-WASP is required for membrane wrapping and myelination by Schwann cells. J Cell Biol (2011) 1.12

Carcinoembryonic antigen-related cellular adhesion molecule 1 isoforms alternatively inhibit and costimulate human T cell function. J Immunol (2004) 1.11

A novel role for interleukin-27 (IL-27) as mediator of intestinal epithelial barrier protection mediated via differential signal transducer and activator of transcription (STAT) protein signaling and induction of antibacterial and anti-inflammatory proteins. J Biol Chem (2011) 1.11

Neural Wiskott-Aldrich syndrome protein modulates Wnt signaling and is required for hair follicle cycling in mice. J Clin Invest (2010) 1.08

Carcinoembryonic antigen-related cell adhesion molecule 1 inhibits proximal TCR signaling by targeting ZAP-70. J Immunol (2008) 1.08

Primary deficiency of microsomal triglyceride transfer protein in human abetalipoproteinemia is associated with loss of CD1 function. J Clin Invest (2010) 1.06

The immunologic functions of the neonatal Fc receptor for IgG. J Clin Immunol (2012) 1.06

CD1d-restricted T cells regulate dendritic cell function and antitumor immunity in a granulocyte-macrophage colony-stimulating factor-dependent fashion. Proc Natl Acad Sci U S A (2003) 1.06

A defect in hematopoietic stem cell migration explains the nonrandom X-chromosome inactivation in carriers of Wiskott-Aldrich syndrome. Blood (2003) 1.04

MyD88-dependent TLR1/2 signals educate dendritic cells with gut-specific imprinting properties. J Immunol (2011) 1.04

Endoplasmic reticulum stress: implications for inflammatory bowel disease pathogenesis. Curr Opin Gastroenterol (2010) 1.03

Cyclooxygenase-2 deficiency leads to intestinal barrier dysfunction and increased mortality during polymicrobial sepsis. J Immunol (2011) 1.03

Genes and environment: how will our concepts on the pathophysiology of IBD develop in the future? Dig Dis (2010) 1.03

Gamma interferon produced by antigen-specific CD4+ T cells regulates the mucosal immune responses to Citrobacter rodentium infection. Infect Immun (2010) 1.03

IgG transport across mucosal barriers by neonatal Fc receptor for IgG and mucosal immunity. Springer Semin Immunopathol (2006) 1.02

Expansion and function of CD8+ T cells expressing Ly49 inhibitory receptors specific for MHC class I molecules. J Immunol (2004) 1.02

Targeted deletion of integrin-linked kinase reveals a role in T-cell chemotaxis and survival. Mol Cell Biol (2005) 1.01