Publications by authors named "Juan Antonio Raygoza Garay"

17 Publications

  • Page 1 of 1

Anti-Microbial Antibody Response is Associated With Future Onset of Crohn's Disease Independent of Biomarkers of Altered Gut Barrier Function, Subclinical Inflammation, and Genetic Risk.

Gastroenterology 2021 Jul 20. Epub 2021 Jul 20.

Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Background And Aims: Altered host immune reactivity to microbial antigens is hypothesized to trigger the onset of Crohn's disease (CD). We aimed to assess whether increased serum anti-microbial antibody response in asymptomatic first-degree relatives (FDRs) of CD patients is an independent risk factor for future CD development.

Methods: We measured host serum antibody response to 6 microbial antigens at enrollment (Prometheus enzyme-linked immunosorbent assay test: anti-Saccharomyces cerevisiae antibodies immunoglobulin A/immunoglobulin G, anti-OmpC, anti-A4-Fla2, anti-FlaX, anti-CBir1) and derived the sum of positive antibodies (AS). We used samples at enrollment of prospectively followed healthy FDRs from a nested case-control cohort of the Crohn's and Colitis Canada Genetics Environment Microbial Project. Those who later developed CD (n = 77) were matched 1:4 by age, sex, follow-up duration, and geographic location with control FDRs remaining healthy (n = 307). To address our research aims, we fitted a multivariable conditional logistic regression model and performed causal mediation analysis.

Results: High baseline AS (≥2) (43% of cases, 11% of controls) was associated with higher risk of developing CD (adjusted odds ratio, 6.5; 95% confidence interval, 3.4-12.7; P < .001). Importantly, this association remained significant when adjusted for markers of gut barrier function, fecal calprotectin, C-reactive protein, and CD-polygenic risk score, and in subjects recruited more than 3 years before diagnosis. Causal mediation analysis showed that the effect of high AS on future CD development is partially mediated (42%) via preclinical gut inflammation.

Conclusions: Our results suggest that increased anti-microbial antibody responses are associated with risk of future development of CD, independent of biomarkers of abnormal gut barrier function, subclinical inflammation, and CD-related genetic risks. This suggests that anti-microbial antibody responses are an early predisease event in the development of CD.
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http://dx.doi.org/10.1053/j.gastro.2021.07.009DOI Listing
July 2021

Integrative analysis of colonic biopsies from inflammatory bowel disease patients identifies an interaction between microbial bile-acid inducible gene abundance and human Angiopoietin-like 4 gene expression.

J Crohns Colitis 2021 Jun 2. Epub 2021 Jun 2.

Division of Gastroenterology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.

Background And Aims: Microbial derived-bile acids can modulate host gene expression, and their fecal abundance is decreased in active inflammatory bowel disease (IBD). We analyzed the impact of endoscopic inflammation on microbial genes involved in bile acid biotransformation, and their interaction with host transcriptome in the intestinal mucosa of IBD patients.

Methods: Endoscopic mucosal biopsies were collected from non-inflamed and inflamed terminal ileum, ascending and sigmoid colon of IBD patients. Prediction of imputed metagenome functional content from 16S rRNA profile and real-time qPCR were utilized to assess microbial bile acid biotransformation gene abundance, and RNA-seq was used for host transcriptome analysis. Linear regression and partial Spearman correlation accounting for age, sex and IBD type were used to assess the association between microbial genes, inflammation and host transcriptomics in each biopsy location. A Bayesian network (BN) analysis was fitted to infer the direction of interactions between IBD traits, microbial and host genes.

Results: Inferred microbial gene pathway involved in secondary bile acid biosynthesis (ko00121 pathway) was depleted in inflamed terminal ileum of IBD patients compared to non-inflamed tissue. In non-inflamed sigmoid colon, the relative abundance of bile acid-inducible (baiCD) microbial genes was positively correlated with the host Angiopoietin-like 4 (Angptl4) gene expression. The BN analysis suggests that the microbial baiCD gene abundance could affect Angptl4 expression, and this interaction appears to be lost in the presence of inflammation.

Conclusions: Endoscopic inflammation affects the abundance of crucial microbial bile acid-metabolizing genes and their interaction with Angptl4 in intestinal mucosa of IBD patients.
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http://dx.doi.org/10.1093/ecco-jcc/jjab096DOI Listing
June 2021

Large-scale association analyses identify host factors influencing human gut microbiome composition.

Nat Genet 2021 02 18;53(2):156-165. Epub 2021 Jan 18.

Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.

To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 × 10) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 × 10), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 10 < P < 5 × 10) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
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http://dx.doi.org/10.1038/s41588-020-00763-1DOI Listing
February 2021

Novel Fecal Biomarkers That Precede Clinical Diagnosis of Ulcerative Colitis.

Gastroenterology 2021 04 10;160(5):1532-1545. Epub 2020 Dec 10.

Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Canada. Electronic address:

Background & Aims: Altered gut microbiota composition and function have been associated with inflammatory bowel diseases, including ulcerative colitis (UC), but the causality and mechanisms remain unknown.

Methods: We applied 16S ribosomal RNA gene sequencing, shotgun metagenomic sequencing, in vitro functional assays, and gnotobiotic colonizations to define the microbial composition and function in fecal samples obtained from a cohort of healthy individuals at risk for inflammatory bowel diseases (pre-UC) who later developed UC (post-UC) and matched healthy control individuals (HCs).

Results: Microbiota composition of post-UC samples was different from HC and pre-UC samples; however, functional analysis showed increased fecal proteolytic and elastase activity before UC onset. Metagenomics identified more than 22,000 gene families that were significantly different between HC, pre-UC, and post-UC samples. Of these, 237 related to proteases and peptidases, suggesting a bacterial component to the pre-UC proteolytic signature. Elastase activity inversely correlated with the relative abundance of Adlercreutzia and other potentially beneficial taxa and directly correlated with known proteolytic taxa, such as Bacteroides vulgatus. High elastase activity was confirmed in Bacteroides isolates from fecal samples. The bacterial contribution and functional significance of the proteolytic signature were investigated in germ-free adult mice and in dams colonized with HC, pre-UC, or post-UC microbiota. Mice colonized with or born from pre-UC-colonized dams developed higher fecal proteolytic activity and an inflammatory immune tone compared with HC-colonized mice.

Conclusions: We have identified increased fecal proteolytic activity that precedes the clinical diagnosis of UC and associates with gut microbiota changes. This proteolytic signature may constitute a noninvasive biomarker of inflammation to monitor at-risk populations that can be targeted therapeutically with antiproteases.
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http://dx.doi.org/10.1053/j.gastro.2020.12.004DOI Listing
April 2021

Associations of NOD2 polymorphisms with Erysipelotrichaceae in stool of in healthy first degree relatives of Crohn's disease subjects.

BMC Med Genet 2020 10 15;21(1):204. Epub 2020 Oct 15.

Department of Medicine, University of Toronto, Toronto, ON, Canada.

Background: Genetic analyses have identified many variants associated with the risk of inflammatory bowel disease (IBD) development. Among these variants, the ones located within the NOD2 gene have the highest odds ratio of all IBD genetic risk variants. Also, patients with Crohn's disease (CD) have been shown to have an altered gut microbiome, which might be a reflection of inflammation itself or an effect of other parameters that contribute to the risk of the disease. Since NOD2 is an intracellular pattern recognition receptor that senses bacterial peptidoglycan in the cytosol and stimulates the host immune response (Al Nabhani et al., PLoS Pathog 13:e1006177, 2017), it is hypothesized that NOD2 variants represent perfect candidates for influencing host-microbiome interactions. We hypothesized that NOD2 risk variants affect the microbiome composition of healthy first degree relative (FDR) of CD patients and thus potentially contribute to an altered microbiome state before disease onset.

Methods: Based on this, we studied a large cohort of 1546 healthy FDR of CD patients and performed a focused analysis of the association of three major CD SNPs in the coding region of the NOD2 gene, which are known to confer a 15-40-fold increased risk of developing CD in homozygous or compound heterozygous individuals.

Results: Our results show that carriers of the C allele at rs2066845 was significantly associated with an increase in relative abundance in the fecal bacterial family Erysipelotrichaceae.

Conclusions: This result suggests that NOD2 polymorphisms contribute to fecal microbiome composition in asymptomatic individuals. Whether this modulation of the microbiome influences the future development of CD remains to be assessed.
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http://dx.doi.org/10.1186/s12881-020-01115-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566148PMC
October 2020

Increased Intestinal Permeability Is Associated With Later Development of Crohn's Disease.

Gastroenterology 2020 12 10;159(6):2092-2100.e5. Epub 2020 Aug 10.

Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Background & Aims: Increased intestinal permeability has been associated with Crohn's disease (CD), but it is not clear whether it is a cause or result of the disease. We performed a prospective study to determine whether increased intestinal permeability is associated with future development of CD.

Methods: We assessed the intestinal permeability, measured by the urinary fractional excretion of lactulose-to-mannitol ratio (LMR) at recruitment in 1420 asymptomatic first-degree relatives (6-35 years old) of patients with CD (collected from 2008 through 2015). Participants were then followed up for a diagnosis of CD from 2008 to 2017, with a median follow-up time of 7.8 years. We analyzed data from 50 participants who developed CD after a median of 2.7 years during the study period, along with 1370 individuals who remained asymptomatic until October 2017. We used the Cox proportional hazards model to evaluate time-related risk of CD based on the baseline LMR.

Results: An abnormal LMR (>0.03) was associated with a diagnosis of CD during the follow-up period (hazard ratio, 3.03; 95% CI, 1.64-5.63; P = 3.97 × 10). This association remained significant even when the test was performed more than 3 years before the diagnosis of CD (hazard ratio, 1.62; 95% CI, 1.051-2.50; P = .029).

Conclusions: Increased intestinal permeability is associated with later development of CD; these findings support a model in which altered intestinal barrier function contributes to pathogenesis. Abnormal gut barrier function might serve as a biomarker for risk of CD onset.
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http://dx.doi.org/10.1053/j.gastro.2020.08.005DOI Listing
December 2020

Analysis of Genetic Association of Intestinal Permeability in Healthy First-degree Relatives of Patients with Crohn's Disease.

Inflamm Bowel Dis 2019 10;25(11):1796-1804

Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada.

Excessive intestinal permeability or intestinal barrier dysfunction as measured by various assays has been observed in various diseases. However, little is known about the factors contributing to altered gut permeability in these diseases. Our objective was to determine the genetic determinants of altered gut permeability as measured by the lactulose mannitol fractional excretion ratio (LacMan ratio) in 1075 healthy first-degree relatives of patients with Crohn's disease (CD). In a targeted analysis of single nucleotide polymorphisms (SNPs) located in genes associated with intestinal barrier function related or not to inflammatory bowel disease, we did not find a significant association with intestinal permeability. In an untargeted genome-wide association analysis, the top 100 associations were located in 22 genomic loci, although they were not statistically significant after correction for multiple testing (raw P values [1.8 × 10-7 - 1.4 × 10-5]. The lowest P value was obtained for rs9616637 (22q13.33, C22orf34), for which the minor allele A was associated with a decreased LacMan ratio. These results suggest that host genetic background has limited contribution toward intestinal permeability. Despite this, our study is currently the largest of its kind assessing gut permeability in vivo. It remains possible that smaller genetic effect sizes on LacMan ratio are not detectable in this sized cohort. Larger studies are warranted to identify the potential genetic contribution to intestinal permeability.
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http://dx.doi.org/10.1093/ibd/izz116DOI Listing
October 2019

Identification of Novel Seroreactive Antigens in Johne's Disease Cattle by Using the Mycobacterium tuberculosis Protein Array.

Clin Vaccine Immunol 2017 Jul 5;24(7). Epub 2017 Jul 5.

Pennsylvania State University, University Park, Pennsylvania, USA

Johne's disease, a chronic gastrointestinal inflammatory disease caused by subspecies , is endemic in dairy cattle and other ruminants worldwide and remains a challenge to diagnose using traditional serological methods. Given the close phylogenetic relationship between subsp. and the human pathogen , here, we applied a whole-proteome protein array to identify seroreactive and diagnostic subsp. antigens. A genome-scale pairwise analysis of amino acid identity levels between orthologous proteins in subsp. and showed an average of 62% identity, with more than half the orthologous proteins sharing >75% identity. Analysis of the protein array probed with sera from subsp. -infected cattle showed antibody binding to 729 proteins, with 58% of them having ≥70% identity to subsp. orthologs. The results showed that only 4 of the top 40 seroreactive antigens were orthologs of previously reported subsp. antigens, revealing the existence of a large number of previously unrecognized candidate diagnostic antigens. Enzyme-linked immunosorbent assay (ELISA) testing of 20 subsp. recombinant proteins, representing reactive and nonreactive orthologs, further confirmed that the array has utility as a screening tool for identifying candidate antigens for Johne's disease diagnostics. Additional ELISA testing of field serum samples collected from dairy herds around the United States revealed that MAP2942c had the strongest seroreactivity with Johne's disease-positive samples. Collectively, our studies have considerably expanded the number of candidate subsp. proteins with potential utility in the next generation of rationally designed Johne's disease diagnostic assays.
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http://dx.doi.org/10.1128/CVI.00081-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498720PMC
July 2017

Genome Sequence of Stenotrophomonas maltophilia Strain SmAs1, Isolated From the Asian Malaria Mosquito Anopheles stephensi.

Genome Announc 2016 Mar 10;4(2). Epub 2016 Mar 10.

Department of Biochemistry and Molecular Biology, Center for Infectious Disease Dynamics, Pennsylvania State University, University Park, Pennsylvania, USA Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, Pennsylvania, USA.

An isolate of Stenotrophomonas maltophilia was cultured from the Asian malaria vector Anopheles stephensi. Here, we present the annotated draft genome sequence of this S. maltophilia strain. This genomic resource will facilitate further characterization of bacteria associated with mosquitoes.
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http://dx.doi.org/10.1128/genomeA.00086-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786654PMC
March 2016

Genome Sequences of Staphylococcus hominis Strains ShAs1, ShAs2, and ShAs3, Isolated from the Asian Malaria Mosquito Anopheles stephensi.

Genome Announc 2016 Mar 10;4(2). Epub 2016 Mar 10.

Department of Biochemistry and Molecular Biology, Center for Infectious Disease Dynamics, Pennsylvania State University, University Park, Pennsylvania, USA Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, Pennsylvania, USA.

Staphylococcus hominis is a culturable component of the bacterial microbiome of Anopheles stephensi. Here, we present the annotated draft genome sequences of three S. hominis isolates from A. stephensi. These genomic resources will facilitate experiments to further our understanding of the role of bacteria in mosquito biology.
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http://dx.doi.org/10.1128/genomeA.00085-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786653PMC
March 2016

Genome Sequence of Elizabethkingia anophelis Strain EaAs1, Isolated from the Asian Malaria Mosquito Anopheles stephensi.

Genome Announc 2016 Mar 10;4(2). Epub 2016 Mar 10.

Department of Biochemistry and Molecular Biology, Center for Infectious Disease Dynamics, Pennsylvania State University, University Park, Pennsylvania, USA Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, Pennsylvania, USA.

We sequenced the genome of a strain of the Gram-negative bacterial species Elizabethkingia anophelis, which is an important component of the Anopheles mosquito microbiome. This genome sequence will add to the list of resources used to examine host-microbe interactions in mosquitoes.
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http://dx.doi.org/10.1128/genomeA.00084-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786652PMC
March 2016

Decoupling of divergent gene regulation by sequence-specific DNA binding factors.

Nucleic Acids Res 2015 Sep 16;43(15):7292-305. Epub 2015 Jun 16.

Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA Center for Eukaryotic Gene Regulation, The Pennsylvania State University, University Park, PA 16802, USA Department of Physics, The Pennsylvania State University, University Park, PA 16802, USA

Divergent gene pairs (DGPs) are abundant in eukaryotic genomes. Since two genes in a DGP potentially share the same regulatory sequence, one might expect that they should be co-regulated. However, an inspection of yeast DGPs containing cell-cycle or stress response genes revealed that most DGPs are differentially-regulated. The mechanism underlying DGP differential regulation is not understood. Here, we showed that co- versus differential regulation cannot be explained by genetic features including promoter length, binding site orientation, TATA elements, nucleosome distribution, or presence of non-coding RNAs. Using time-lapse fluorescence microscopy, we carried out an in-depth study of a differentially regulated DGP, PFK26-MOB1. We found that their differential regulation is mainly achieved through two DNA-binding factors, Tbf1 and Mcm1. Similar to 'enhancer-blocking insulators' in higher eukaryotes, these factors shield the proximal promoter from the action of more distant transcription regulators. We confirmed the blockage function of Tbf1 using synthetic promoters. We further presented evidence that the blockage mechanism is widely used among genome-wide DGPs. Besides elucidating the DGP regulatory mechanism, our work revealed a novel class of insulators in yeast.
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http://dx.doi.org/10.1093/nar/gkv618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4551913PMC
September 2015

Molecular Types of Methicillin-Resistant Staphylococcus aureus and Methicillin-Sensitive S. aureus Strains Causing Skin and Soft Tissue Infections and Nasal Colonization, Identified in Community Health Centers in New York City.

J Clin Microbiol 2015 Aug 10;53(8):2648-58. Epub 2015 Jun 10.

Laboratory of Microbiology and Infectious Diseases, The Rockefeller University, New York, New York, USA

In November 2011, The Rockefeller University Center for Clinical and Translational Science (CCTS), the Laboratory of Microbiology and Infectious Diseases, and Clinical Directors Network (CDN) launched a research and learning collaborative project with six community health centers in the New York City metropolitan area to determine the nature (clonal type) of community-acquired Staphylococcus aureus strains causing skin and soft tissue infections (SSTIs). Between November 2011 and March 2013, wound and nasal samples from 129 patients with active SSTIs suspicious for S. aureus were collected and characterized by molecular typing techniques. In 63 of 129 patients, the skin wounds were infected by S. aureus: methicillin-resistant S. aureus (MRSA) was recovered from 39 wounds and methicillin-sensitive S. aureus (MSSA) was recovered from 24. Most-46 of the 63-wound isolates belonged to the CC8/Panton-Valentine leukocidin-positive (PVL(+)) group of S. aureus clone USA300: 34 of these strains were MRSA and 12 were MSSA. Of the 63 patients with S. aureus infections, 30 were also colonized by S. aureus in the nares: 16 of the colonizing isolates were MRSA, and 14 were MSSA, and the majority of the colonizing isolates belonged to the USA300 clonal group. In most cases (70%), the colonizing isolate belonged to the same clonal type as the strain involved with the infection. In three of the patients, the identity of invasive and colonizing MRSA isolates was further documented by whole-genome sequencing.
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http://dx.doi.org/10.1128/JCM.00591-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508410PMC
August 2015

Complete Genome Sequence of SS52, a Strain of Escherichia coli O157:H7 Recovered from Supershedder Cattle.

Genome Announc 2015 Mar 19;3(2). Epub 2015 Mar 19.

Shiga toxin-producing Escherichia coli O157:H7 causes foodborne infections, and cattle are the primary reservoir. Some animals, known as supershedders, excrete orders of magnitude more E. coli O157:H7 in the feces than normal. Here, we report the complete genome sequence of the SS52 supershedder strain of E. coli O157:H7.
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http://dx.doi.org/10.1128/genomeA.01569-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4395050PMC
March 2015

Comparative analysis of super-shedder strains of Escherichia coli O157:H7 reveals distinctive genomic features and a strongly aggregative adherent phenotype on bovine rectoanal junction squamous epithelial cells.

PLoS One 2015 9;10(2):e0116743. Epub 2015 Feb 9.

Department of Veterinary and Biomedical Science, The Pennsylvania State University, University Park, Pennsylvania, United States of America; The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, Pennsylvania, United States of America.

Shiga toxin-producing Escherichia coli O157:H7 (O157) are significant foodborne pathogens and pose a serious threat to public health worldwide. The major reservoirs of O157 are asymptomatic cattle which harbor the organism in the terminal recto-anal junction (RAJ). Some colonized animals, referred to as "super-shedders" (SS), are known to shed O157 in exceptionally large numbers (>104 CFU/g of feces). Recent studies suggest that SS cattle play a major role in the prevalence and transmission of O157, but little is known about the molecular mechanisms associated with super-shedding. Whole genome sequence analysis of an SS O157 strain (SS17) revealed a genome of 5,523,849 bp chromosome with 5,430 open reading frames and two plasmids, pO157 and pSS17, of 94,645 bp and 37,446 bp, respectively. Comparative analyses showed that SS17 is clustered with spinach-associated O157 outbreak strains, and belongs to the lineage I/II, clade 8, D group, and genotype 1, a subgroup of O157 with predicted hyper-virulence. A large number of non-synonymous SNPs and other polymorphisms were identified in SS17 as compared with other O157 strains (EC4115, EDL933, Sakai, TW14359), including in key adherence- and virulence-related loci. Phenotypic analyses revealed a distinctive and strongly adherent aggregative phenotype of SS17 on bovine RAJ stratified squamous epithelial (RSE) cells that was conserved amongst other SS isolates. Molecular genetic and functional analyses of defined mutants of SS17 suggested that the strongly adherent aggregative phenotype amongst SS isolates is LEE-independent, and likely results from a novel mechanism. Taken together, our study provides a rational framework for investigating the molecular mechanisms associated with SS, and strong evidence that SS O157 isolates have distinctive features and use a LEE-independent mechanism for hyper-adherence to bovine rectal epithelial cells.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0116743PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4321836PMC
October 2015

Stochastic expression and epigenetic memory at the yeast HO promoter.

Proc Natl Acad Sci U S A 2013 Aug 8;110(34):14012-7. Epub 2013 Jul 8.

Center for Eukaryotic Gene Regulation, and Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.

Eukaryotic gene regulation usually involves sequence-specific transcription factors and sequence-nonspecific cofactors. A large effort has been made to understand how these factors affect the average gene expression level among a population. However, little is known about how they regulate gene expression in individual cells. In this work, we address this question by mutating multiple factors in the regulatory pathway of the yeast HO promoter (HOpr) and probing the corresponding promoter activity in single cells using time-lapse fluorescence microscopy. We show that the HOpr fires in an "on/off" fashion in WT cells as well as in different genetic backgrounds. Many chromatin-related cofactors that affect the average level of HO expression do not actually affect the firing amplitude of the HOpr; instead, they affect the firing frequency among individual cell cycles. With certain mutations, the bimodal expression exhibits short-term epigenetic memory across the mitotic boundary. This memory is propagated in "cis" and reflects enhanced activator binding after a previous "on" cycle. We present evidence that the memory results from slow turnover of the histone acetylation marks.
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http://dx.doi.org/10.1073/pnas.1306113110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3752279PMC
August 2013

The taxonomic name resolution service: an online tool for automated standardization of plant names.

BMC Bioinformatics 2013 Jan 16;14:16. Epub 2013 Jan 16.

Department of Ecology and Evolutionary Biology, University of Arizona Tucson, P,O, Box 210088, Tucson, AZ 85721, USA.

Background: The digitization of biodiversity data is leading to the widespread application of taxon names that are superfluous, ambiguous or incorrect, resulting in mismatched records and inflated species numbers. The ultimate consequences of misspelled names and bad taxonomy are erroneous scientific conclusions and faulty policy decisions. The lack of tools for correcting this 'names problem' has become a fundamental obstacle to integrating disparate data sources and advancing the progress of biodiversity science.

Results: The TNRS, or Taxonomic Name Resolution Service, is an online application for automated and user-supervised standardization of plant scientific names. The TNRS builds upon and extends existing open-source applications for name parsing and fuzzy matching. Names are standardized against multiple reference taxonomies, including the Missouri Botanical Garden's Tropicos database. Capable of processing thousands of names in a single operation, the TNRS parses and corrects misspelled names and authorities, standardizes variant spellings, and converts nomenclatural synonyms to accepted names. Family names can be included to increase match accuracy and resolve many types of homonyms. Partial matching of higher taxa combined with extraction of annotations, accession numbers and morphospecies allows the TNRS to standardize taxonomy across a broad range of active and legacy datasets.

Conclusions: We show how the TNRS can resolve many forms of taxonomic semantic heterogeneity, correct spelling errors and eliminate spurious names. As a result, the TNRS can aid the integration of disparate biological datasets. Although the TNRS was developed to aid in standardizing plant names, its underlying algorithms and design can be extended to all organisms and nomenclatural codes. The TNRS is accessible via a web interface at http://tnrs.iplantcollaborative.org/ and as a RESTful web service and application programming interface. Source code is available at https://github.com/iPlantCollaborativeOpenSource/TNRS/.
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http://dx.doi.org/10.1186/1471-2105-14-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554605PMC
January 2013
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