208 results on '"Herzyk, P."'
Search Results
2. Overexpression of Brassica napus COMT1 in Arabidopsis heightens UV-B-mediated resistance to Plutella xylostella herbivory
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McInnes, Kirsty J., van der Hooft, Justin J. J., Sharma, Ashutosh, Herzyk, Pawel, Hundleby, Penny A. C., Schoonbeek, Henk-Jan, Amtmann, Anna, Ridout, Christopher, and Jenkins, Gareth I.
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- 2023
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3. A simple program to improve the appropriateness of red blood cell transfusions in non-bleeding hospital patients: a before-and-after study
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Jan Herzyk, Dawid Wilczek, Renata Kopczyńska, and Piotr F. Czempik
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blood transfusion ,patient blood management ,red blood cell transfusion ,transfusion guidelines ,standard operating procedure ,Medicine - Abstract
Introduction Transfusion of red blood cells (RBCs) is not devoid of risks; nor is anemia. The aim of the study was to assess the usefulness of a program designed to improve the appropriateness of RBC transfusions in hospital patients. Methods We retrospectively analyzed time periods before and after program implementation. Results: Before program implementation 415 out of 23492 (1.8%) patients received at least 1 RBC, whereas after implementation 162 out of 25062 (0.6%) did so. The percentage of appropriate RBC transfusions increased from 23.6 to 37.1%. Results Before program implementation 415 out of 23492 (1.8%) patients received at least 1 RBC, whereas after implementation 162 out of 25062 (0.6%) did so. The percentage of appropriate RBC transfusions increased from 23.6 to 37.1%. Conclusions A simple program may lead to a 3-fold decrease in transfusion rate and a significant increase in the percentage of appropriate RBC transfusions.
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- 2024
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4. Supercritical Extraction Techniques for Obtaining Biologically Active Substances from a Variety of Plant Byproducts
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Filip Herzyk, Dorota Piłakowska-Pietras, and Małgorzata Korzeniowska
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supercritical extraction ,bioactive compounds ,carbon dioxide ,green extraction technique ,byproducts ,Chemical technology ,TP1-1185 - Abstract
Supercritical fluid extraction (SFE) techniques have garnered significant attention as green and sustainable methods for obtaining biologically active substances from a diverse array of plant byproducts. This paper comprehensively reviews the use of supercritical fluid extraction (SFE) in obtaining bioactive compounds from various plant residues, including pomace, seeds, skins, and other agricultural byproducts. The main purpose of supercritical fluid extraction (SFE) is the selective isolation and recovery of compounds, such as polyphenols, essential oils, vitamins, and antioxidants, that have significant health-promoting properties. Using supercritical carbon dioxide as the solvent, supercritical fluid extraction (SFE) not only eliminates the need for hazardous organic solvents, e.g., ethanol, and methanol, but also protects heat-sensitive bioactive compounds. Moreover, this green extraction technique contributes to waste valorisation by converting plant byproducts into value-added extracts with potential applications in the food, pharmaceutical, and cosmetic industries. This review highlights the advantages of SFE, including its efficiency, eco-friendliness, and production of residue-free extracts, while discussing potential challenges and future prospects for the utilisation of SFE in obtaining biologically active substances from plant byproducts.
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- 2024
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5. Central nervous system involvement in childhood acute lymphoblastic leukemia is linked to upregulation of cholesterol biosynthetic pathways
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Cousins, A., Olivares, O., Markert, E., Manoharan, A., Bubnova, X., Bresolin, S., Degn, M., Li, Z., Silvestri, D., McGregor, G., Tumanov, S., Sumpton, D., Kamphorst, J. J., Michie, A. M., Herzyk, P., Valsecchi, M. G., Yeoh, A. E., Schmiegelow, K., te Kronnie, G., Gottlieb, E., and Halsey, C.
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- 2022
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6. Let Us Know Transfusion Triggers for Prophylactic Use of Platelet Concentrate—Analysis of Compliance with Recent Transfusion Guidelines in a Large Academic Medical Center
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Piotr F. Czempik, Jan Herzyk, and Dawid Wilczek
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decision making ,guideline ,platelet concentrate ,thrombocytopenia ,transfusion ,Medicine - Abstract
Platelet concentrate (PC) is a blood component that is used to prevent or manage bleeding associated with thrombocytopenia or impaired platelet function. The aim of our study was to assess the compliance of ordering physicians with the most recent PC transfusion guidelines in our academic medical center. All PC transfusions performed between January 2019 and December 2022 were analyzed. The appropriateness of PC transfusions was assessed based on the most recent PC transfusion guidelines. During 2019–2022, there were 362 (0.2%) PC recipients out of 161,762 hospitalized patients. There were 971 PCs transfused during the analyzed period. Inappropriate transfusions accounted for 53.3% of cases, and most of them were given prophylactically (80.2%). Compliance with platelet transfusion guidelines varied among departments. The overall percentage of inappropriately transfused PC ranged from 50.7% to 60.8% in successive years. Educational activities should target clinicians performing procedures associated with high rates of inappropriate PC transfusions. Implementing clinical decision support systems can help reduce unnecessary PC transfusions and associated costs. The majority of inappropriate PC transfusions in our medical center were given as prophylaxis against bleeding. Prescribers should be educated about evidence-based transfusion triggers for the prophylactic use of PC in various clinical scenarios.
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- 2023
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7. Appropriateness of Allogeneic Red Blood Cell Transfusions in Non-Bleeding Patients in a Large Teaching Hospital: A Retrospective Study
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Piotr F. Czempik, Dawid Wilczek, Jan Herzyk, and Łukasz J. Krzych
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anemia ,hemoglobin ,indication ,patient blood management ,red blood cell ,transfusion ,Medicine - Abstract
In hemodynamically stable patients, both anemia and red blood cell (RBC) transfusion may be detrimental to patients; hence, a decision regarding RBC transfusion should be based on thorough risk–benefit assessment. According to hematology and transfusion medicine organizations, RBC transfusion is indicated when recommended hemoglobin (Hb) triggers are met, and symptoms of anemia are present. The aim of our study was to examine the appropriateness of RBC transfusions in non-bleeding patients at our institution. We performed a retrospective analysis of all RBC transfusions performed between January 2022 and July 2022. The appropriateness of RBC transfusion was based on the most recent Association for the Advancement of Blood and Biotherapies (AABB) guidelines and some additional criteria. The overall incidence of RBC transfusions at our institution was 10.2 per 1000 patient-days. There were 216 (26.1%) RBC units appropriately transfused and 612 (73.9%) RBC units that were transfused with no clear indications. The incidence of appropriate and inappropriate RBC transfusions were 2.6 and 7.5 per 1000 patient-days, respectively. The most frequent clinical situations when RBC transfusion was classified as appropriate were: Hb < 70 g/L plus cognitive problems/headache/dizziness (10.1%), Hb < 60 g/L (5.4%), and Hb < 70 g/L plus dyspnea despite oxygen therapy (4.3%). The most frequent causes of inappropriate RBC transfusions were: no Hb determination pre-RBC transfusion (n = 317) and, among these, RBC transfused as a second unit in a single-transfusion episode (n = 260); absence of anemia sings/symptoms pre-transfusion (n = 179); and Hb concentration ≥80 g/L (n = 80). Although the incidence of RBC transfusions in non-bleeding inpatients in our study was generally low, the majority of RBC transfusions were performed outside recommended indications. Red blood cell transfusions were evaluated as inappropriate mainly due to multiple-unit transfusion episodes, absence of anemia signs and/or symptoms pre- transfusion, and liberal transfusion triggers. There is still the need to educate physicians on appropriate indications for RBC transfusion in non-bleeding patients.
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- 2023
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8. Metabolic adaptation of acute lymphoblastic leukemia to the central nervous system microenvironment depends on stearoyl-CoA desaturase
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Savino, Angela Maria, Fernandes, Sara Isabel, Olivares, Orianne, Zemlyansky, Anna, Cousins, Antony, Markert, Elke K., Barel, Shani, Geron, Ifat, Frishman, Liron, Birger, Yehudit, Eckert, Cornelia, Tumanov, Sergey, MacKay, Gillian, Kamphorst, Jurre J., Herzyk, Pawel, Fernández-García, Jonatan, Abramovich, Ifat, Mor, Inbal, Bardini, Michela, Barin, Ersilia, Janaki-Raman, Sudha, Cross, Justin R., Kharas, Michael G., Gottlieb, Eyal, Izraeli, Shai, and Halsey, Christina
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- 2020
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9. A T-cell-dependent antibody response study using a murine surrogate anti-PD-1 monoclonal antibody as an alternative to a non-human primate model
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Lisa M. Plitnick, Beth Hutchins, Sheri Dubey, Nianyu Li, Rupesh P. Amin, Stephanie Born, Ruban Mangadu, Joseph H. Phillips, Venkataraman Sriram, and Danuta J. Herzyk
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anti-pd-1 ,vaccination ,murine ,alternate model ,Immunologic diseases. Allergy ,RC581-607 ,Toxicology. Poisons ,RA1190-1270 - Abstract
The programmed cell death 1 (PD-1) pathway represents a major immune checkpoint which may be engaged by cells in a tumor microenvironment to overcome active T-cell immune surveillance. Pembrolizumab (Keytruda®) is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/κ isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. The current work was focused on developing a mouse T-Dependent Antibody Response (TDAR) model using a murinized rat anti-mouse PD-1 antibody (muDX400; a rodent surrogate for pembrolizumab) to evaluate the potential impact of treatment with a PD-1 inhibitor on immune responses to an antigen challenge (e.g. HBsAg in Hepatitis B vaccine). Despite the lower binding affinity and T1/2 compared to pembrolizumab, ligand blocking data indicated muDX400 had appropriate pharmacological activity and demonstrated efficacy in mouse tumor models, thus was suitable for pharmacodynamic and vaccination studies in mice. In a vaccination study in which mice were concomitantly administered muDX400 and the Hepatitis B vaccine, muDX400 was well-tolerated and did not result in any immune-mediated adverse effects. The treatment with muDX400 was associated with a shift in the ratio between naive and memory cells in both CD4+ and CD8+ T-lymphocytes in the spleen but did not affect anti-HBsAg antibody response profile. The mouse TDAR model using the Hepatitis B vaccine and the surrogate anti-PD1 monoclonal antibody was a useful tool in the evaluation of the potential immune-mediated effects of pembrolizumab following vaccination and appears to be a suitable alternative for the nonhuman primate TDAR models utilized for other checkpoint inhibitors.
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- 2020
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10. Hospital-Acquired Anemia in Patients Hospitalized in the Intensive Care Unit: A Retrospective Cohort Study
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Piotr F. Czempik, Dawid Wilczek, Jan Herzyk, and Łukasz J. Krzych
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anemia ,blood loss ,coagulation ,hemoglobin ,intensive care unit ,transfusion ,Medicine - Abstract
Hospital-acquired anemia (HAA) is prevalent in patients hospitalized in the intensive care unit (ICU). Iatrogenic blood loss (IBL) may aggravate existing anemia or lead to a need for red blood cell (RBC) transfusion. The aim of our study was to analyze hemoglobin (Hb) concentration changes in up to 14 days, as well as all potential sources of IBL, in consecutive patients admitted to the intensive care unit (ICU) in the years 2020–2021. Patients admitted due to bleeding were excluded. Anemia on admission was present in 218 (58.8%) patients—47 (48.9%) surgical and 171 (62.2%) non-surgical (p = 0.02). Gradual decrease in Hb was seen in all ICU patients. Eighty-one (21.8%) patients required RBC transfusion. The first unit of RBC was transfused on day 7 (IQR 2–13) and the second on day 11 (IQR 4–15) of ICU hospitalization. The median admission Hb in patients who required RBC transfusion was 10.2 (IQR 8.5–11.8) and, in those who did not require transfusion, it was 12.0 (IQR 10.2–13.6) g/dL (p < 0.01). Anemia on admission was associated with a need for RBC transfusion (p < 0.01). Average decrease in Hb during the first week of ICU hospitalization in patients with and without anemia on admission was 1.2 (IQR 0.2–2.3) and 2.8 (IQR 1.1–3.8) g/dL (p < 0.01), respectively. Percentage of patients who bled at the insertion site of invasive devices was as follows: percutaneous tracheostomy—46.7%, therapeutic plasma exchange (TPE) catheter—23.8%, dialysis catheter—13.3%, gastrostomy—9.5%, central venous catheter—7.8%. Moreover, circuit clotting occurred in 17.7 and 9.5% of patients undergoing dialysis and TPE, respectively. Median blood loss for repeated laboratory testing in our study population was 13.7 (IQR 9.9–19.3) mL per patient daily. Anemia is highly prevalent among medical and surgical patients on admission to ICU and is associated with RBC transfusion. Patients who required RBC transfusion had significantly lower daily Hb concentrations. Severity of disease did not seem to have impact on Hb concentration. IBL associated with invasive devices and extracorporeal therapies is frequent in ICU patients and may lead to a gradual decrease in Hb concentration. Further studies are required to analyze causes of HAA in the ICU.
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- 2022
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11. SEC31Amay be associated with pituitary hormone deficiency and gonadal dysgenesis
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Tobias, Edward S., Lucas-Herald, Angela K., Sagar, Danielle, Montezano, Augusto C., Rios, Francisco J., De Lucca Camargo, Livia, Hamilton, Graham, Gazdagh, Gabriella, Diver, Louise A., Williams, Nicola, Herzyk, Pawel, Touyz, Rhian M., Greenfield, Andy, McGowan, Ruth, and Ahmed, S. Faisal
- Abstract
Purpose: Disorders/differences of sex development (DSD) result from variants in many different human genes but, frequently, have no detectable molecular cause. Methods: Detailed clinical and genetic phenotyping was conducted on a family with three children. A Sec31aanimal model and functional studies were used to investigate the significance of the findings. Results: By trio whole-exome DNA sequencing we detected a heterozygous de novo nonsense SEC31Avariant, in three children of healthy non-consanguineous parents. The children had different combinations of disorders that included complete gonadal dysgenesis and multiple pituitary hormone deficiency. SEC31Aencodes a component of the COPII coat protein complex, necessary for intracellular anterograde vesicle-mediated transport between the endoplasmic reticulum (ER) and Golgi. CRISPR-Cas9 targeted knockout of the orthologous Sec31agene region resulted in early embryonic lethality in homozygous mice. mRNA expression of ER-stress genes ATF4and CHOPwas increased in the children, suggesting defective protein transport. The pLI score of the gene, from gnomAD data, is 0.02. Conclusions: SEC31Amight underlie a previously unrecognised clinical syndrome comprising gonadal dysgenesis, multiple pituitary hormone deficiencies, dysmorphic features and developmental delay. However, a variant that remains undetected, in a different gene, may alternatively be causal in this family.
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- 2024
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12. Beyond the consensus: dissecting within-host viral population diversity of foot-and-mouth disease virus using next-generation genome sequencing
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Morelli, Marco J., Wright, Caroline F., Thébaud, Gaël, Knowles, Nick J., Herzyk, Pawel, Paton, David J., Haydon, Daniel T., and King, Donald P.
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Quantitative Biology - Genomics - Abstract
The sequence diversity of viral populations within individual hosts is the starting material for selection and subsequent evolution of RNA viruses such as foot-and-mouth disease virus (FMDV). Using next-generation sequencing (NGS) performed on a Genome Analyzer platform (Illumina), this study compared the viral populations within two bovine epithelial samples (foot lesions) from a single animal with the Inoculum used to initiate experimental infection. Genomic sequences were determined in duplicate sequencing runs, and the consensus sequence determined by NGS, for the Inoculum, was identical to that previously determined using the Sanger method. However, NGS reveals the fine polymorphic sub-structure of the viral population, from nucleotide variants present at just below 50% frequency to those present at fractions of 1%. Some of the higher frequency polymorphisms identified encoded changes within codons associated with heparan sulphate binding and were present in both feet lesions revealing intermediate stages in the evolution of a tissue-culture adapted virus replicating within a mammalian host. We identified 2,622, 1,434 and 1,703 polymorphisms in the Inoculum, and in the two foot lesions respectively: most of the substitutions occurred only in a small fraction of the population and represent the progeny from recent cellular replication prior to onset of any selective pressures. We estimated an upper limit for the genome-wide mutation rate of the virus within a cell to be 7.8 x 10-4 per nt. The greater depth of detection, achieved by NGS, demonstrates that this method is a powerful and valuable tool for the dissection of FMDV populations within-hosts.
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- 2011
13. Host-associated niche metabolism controls enteric infection through fine-tuning the regulation of type 3 secretion
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James P. R. Connolly, Sabrina L. Slater, Nicky O’Boyle, Robert J. Goldstone, Valerie F. Crepin, David Ruano-Gallego, Pawel Herzyk, David G. E. Smith, Gillian R. Douce, Gad Frankel, and Andrew J. Roe
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Science - Abstract
Infection of mice with Citrobacter rodentium is a common model of infection with attaching-and-effacing pathogens. Here, Connolly et al. analyse the transcriptome of C. rodentium during mouse infection, showing host-induced coordinated upregulation of virulence factors and 1,2-propanediol metabolism.
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- 2018
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14. Environmental Regulation of PndbA600, an Auto-Inducible Promoter for Two-Stage Industrial Biotechnology in Cyanobacteria
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Mary Ann Madsen, Graham Hamilton, Pawel Herzyk, and Anna Amtmann
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cyanobacteria ,biotechnology ,two-stage cultivation strategy ,stationary phase ,promoter ,transcriptomics ,Biotechnology ,TP248.13-248.65 - Abstract
Cyanobacteria are photosynthetic prokaryotes being developed as sustainable platforms that use renewable resources (light, water, and air) for diverse applications in energy, food, environment, and medicine. Despite the attractive promise that cyanobacteria offer to industrial biotechnology, slow growth rates pose a major challenge in processes which typically require large amounts of biomass and are often toxic to the cells. Two-stage cultivation strategies are an attractive solution to prevent any undesired growth inhibition by de-coupling biomass accumulation (stage I) and the industrial process (stage II). In cyanobacteria, two-stage strategies involve costly transfer methods between stages I and II, and little work has been focussed on using the distinct growth and stationary phases of batch cultures to autoregulate stage transition. In the present study, we identified and characterised a growth phase-specific promoter, which can serve as an auto-inducible switch to regulate two-stage bioprocesses in cyanobacteria. First, growth phase-specific genes were identified from a new RNAseq dataset comparing two growth phases and six nutrient conditions in Synechocystis sp. PCC 6803, including two new transcriptomes for low Mg and low K. A type II NADH dehydrogenase (ndbA) showed robust induction when the cultures transitioned from exponential to stationary phase growth. Behaviour of a 600-bp promoter sequence (PndbA600) was then characterised in detail following the expression of PndbA600:GFP in Synechococcus sp. PCC 7002. Culture density and growth media analyses showed that PndbA600 activation was not dependent on increases in culture density per se but on N availability and on another activating factor present in the spent media of stationary phase cultures (Factor X). PndbA600 deactivation was dependent on the changes in culture density and in either N availability or Factor X. Electron transport inhibition studies revealed a photosynthesis-specific enhancement of active PndbA600 levels. Our findings are summarised in a model describing the environmental regulation of PndbA600, which can now inform the rational design of two-stage industrial processes in cyanobacteria.
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- 2021
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15. De novo repeat interruptions are associated with reduced somatic instability and mild or absent clinical features in myotonic dystrophy type 1
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Cumming, Sarah A., Hamilton, Mark J., Robb, Yvonne, Gregory, Helen, McWilliam, Catherine, Cooper, Anneli, Adam, Berit, McGhie, Josephine, Hamilton, Graham, Herzyk, Pawel, Tschannen, Michael R., Worthey, Elizabeth, Petty, Richard, Ballantyne, Bob, The Scottish Myotonic Dystrophy Consortium, Warner, Jon, Farrugia, Maria Elena, Longman, Cheryl, and Monckton, Darren G.
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- 2018
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16. De novo transcriptome assembly, annotation and comparison of four ecological and evolutionary model salmonid fish species
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Madeleine Carruthers, Andrey A. Yurchenko, Julian J. Augley, Colin E. Adams, Pawel Herzyk, and Kathryn R. Elmer
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Salmonids ,Transcriptome ,RNA-seq ,Annotation ,BLAST ,Gene Ontology (GO) analysis ,Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Background Salmonid fishes exhibit high levels of phenotypic and ecological variation and are thus ideal model systems for studying evolutionary processes of adaptive divergence and speciation. Furthermore, salmonids are of major interest in fisheries, aquaculture, and conservation research. Improving understanding of the genetic mechanisms underlying traits in these species would significantly progress research in these fields. Here we generate high quality de novo transcriptomes for four salmonid species: Atlantic salmon (Salmo salar), brown trout (Salmo trutta), Arctic charr (Salvelinus alpinus), and European whitefish (Coregonus lavaretus). All species except Atlantic salmon have no reference genome publicly available and few if any genomic studies to date. Results We used paired-end RNA-seq on Illumina to generate high coverage sequencing of multiple individuals, yielding between 180 and 210 M reads per species. After initial assembly, strict filtering was used to remove duplicated, redundant, and low confidence transcripts. The final assemblies consisted of 36,505 protein-coding transcripts for Atlantic salmon, 35,736 for brown trout, 33,126 for Arctic charr, and 33,697 for European whitefish and are made publicly available. Assembly completeness was assessed using three approaches, all of which supported high quality of the assemblies: 1) ~78% of Actinopterygian single-copy orthologs were successfully captured in our assemblies, 2) orthogroup inference identified high overlap in the protein sequences present across all four species (40% shared across all four and 84% shared by at least two), and 3) comparison with the published Atlantic salmon genome suggests that our assemblies represent well covered (~98%) protein-coding transcriptomes. Thorough comparison of the generated assemblies found that 84-90% of transcripts in each assembly were orthologous with at least one of the other three species. We also identified 34-37% of transcripts in each assembly as paralogs. We further compare completeness and annotation statistics of our new assemblies to available related species. Conclusion New, high-confidence protein-coding transcriptomes were generated for four ecologically and economically important species of salmonids. This offers a high quality pipeline for such complex genomes, represents a valuable contribution to the existing genomic resources for these species and provides robust tools for future investigation of gene expression and sequence evolution in these and other salmonid species.
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- 2018
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17. Lymphomas driven by Epstein–Barr virus nuclear antigen-1 (EBNA1) are dependant upon Mdm2
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AlQarni, Sana, Al-Sheikh, Yazeed, Campbell, Donald, Drotar, Mark, Hannigan, Adele, Boyle, Shelagh, Herzyk, Pawel, Kossenkov, Andrew, Armfield, Kate, Jamieson, Lauren, Bailo, Mariarca, Lieberman, Paul M., Tsimbouri, Penelope, and Wilson, Joanna B.
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- 2018
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18. Use of bacterial whole-genome sequencing to investigate local persistence and spread in bovine tuberculosis
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Hannah Trewby, David Wright, Eleanor L. Breadon, Samantha J. Lycett, Tom R. Mallon, Carl McCormick, Paul Johnson, Richard J. Orton, Adrian R. Allen, Julie Galbraith, Pawel Herzyk, Robin A. Skuce, Roman Biek, and Rowland R. Kao
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Bacterial evolution ,Livestock disease ,Molecular epidemiology ,Mycobacterium bovis ,Phylogeography ,Infectious and parasitic diseases ,RC109-216 - Abstract
Mycobacterium bovis is the causal agent of bovine tuberculosis, one of the most important diseases currently facing the UK cattle industry. Here, we use high-density whole genome sequencing (WGS) in a defined sub-population of M. bovis in 145 cattle across 66 herd breakdowns to gain insights into local spread and persistence. We show that despite low divergence among isolates, WGS can in principle expose contributions of under-sampled host populations to M. bovis transmission. However, we demonstrate that in our data such a signal is due to molecular type switching, which had been previously undocumented for M. bovis. Isolates from farms with a known history of direct cattle movement between them did not show a statistical signal of higher genetic similarity. Despite an overall signal of genetic isolation by distance, genetic distances also showed no apparent relationship with spatial distance among affected farms over distances
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- 2016
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19. CT angiography in the setting of suspected acute mesenteric ischemia: prevalence of ischemic and alternative diagnoses
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Henes, Frank Oliver, Pickhardt, Perry J., Herzyk, Andrzej, Lee, Scott J., Motosugi, Utaroh, Derlin, Thorsten, Lubner, Meghan G., Adam, Gerhard, Schön, Gerhard, and Bannas, Peter
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- 2017
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20. Regulation of transcription by the Arabidopsis UVR8 photoreceptor involves a specific histone modification
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Velanis, Christos N., Herzyk, Pawel, and Jenkins, Gareth I.
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- 2016
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21. Correction to: De novo transcriptome assembly, annotation and comparison of four ecological and evolutionary model salmonid fish species
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Carruthers, Madeleine, Yurchenko, Andrey A., Augley, Julian J., Adams, Colin E., Herzyk, Pawel, and Elmer, Kathryn R.
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- 2018
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22. Cancer Immunotherapy: Factors Important for the Evaluation of Safety in Nonclinical Studies
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Herzyk, Danuta J. and Haggerty, Helen G.
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- 2018
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23. De novo transcriptome assembly, annotation and comparison of four ecological and evolutionary model salmonid fish species
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Carruthers, Madeleine, Yurchenko, Andrey A., Augley, Julian J., Adams, Colin E., Herzyk, Pawel, and Elmer, Kathryn R.
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- 2018
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24. Sterol 14α-demethylase mutation leads to amphotericin B resistance in Leishmania mexicana.
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Roy Mwenechanya, Julie Kovářová, Nicholas J Dickens, Manikhandan Mudaliar, Pawel Herzyk, Isabel M Vincent, Stefan K Weidt, Karl E Burgess, Richard J S Burchmore, Andrew W Pountain, Terry K Smith, Darren J Creek, Dong-Hyun Kim, Galina I Lepesheva, and Michael P Barrett
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
Amphotericin B has emerged as the therapy of choice for use against the leishmaniases. Administration of the drug in its liposomal formulation as a single injection is being promoted in a campaign to bring the leishmaniases under control. Understanding the risks and mechanisms of resistance is therefore of great importance. Here we select amphotericin B-resistant Leishmania mexicana parasites with relative ease. Metabolomic analysis demonstrated that ergosterol, the sterol known to bind the drug, is prevalent in wild-type cells, but diminished in the resistant line, where alternative sterols become prevalent. This indicates that the resistance phenotype is related to loss of drug binding. Comparing sequences of the parasites' genomes revealed a plethora of single nucleotide polymorphisms that distinguish wild-type and resistant cells, but only one of these was found to be homozygous and associated with a gene encoding an enzyme in the sterol biosynthetic pathway, sterol 14α-demethylase (CYP51). The mutation, N176I, is found outside of the enzyme's active site, consistent with the fact that the resistant line continues to produce the enzyme's product. Expression of wild-type sterol 14α-demethylase in the resistant cells caused reversion to drug sensitivity and a restoration of ergosterol synthesis, showing that the mutation is indeed responsible for resistance. The amphotericin B resistant parasites become hypersensitive to pentamidine and also agents that induce oxidative stress. This work reveals the power of combining polyomics approaches, to discover the mechanism underlying drug resistance as well as offering novel insights into the selection of resistance to amphotericin B itself.
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- 2017
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25. Author Correction: Host-associated niche metabolism controls enteric infection through fine-tuning the regulation of type 3 secretion
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James P. R. Connolly, Sabrina L. Slater, Nicky O’Boyle, Robert J. Goldstone, Valerie F. Crepin, David Ruano-Gallego, Pawel Herzyk, David G. E. Smith, Gillian R. Douce, Gad Frankel, and Andrew J. Roe
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Science - Abstract
The original version of this Article contained an error in the spelling of the author David Ruano-Gallego, which was incorrectly given as David R. Gallego. This has now been corrected in both the PDF and HTML versions of the Article.
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- 2018
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26. Correction to: De novo transcriptome assembly, annotation and comparison of four ecological and evolutionary model salmonid fish species
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Madeleine Carruthers, Andrey A. Yurchenko, Julian J. Augley, Colin E. Adams, Pawel Herzyk, and Kathryn R. Elmer
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Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Following the publication of this article [1], the authors noticed found that they incorrectly reported the BUSCO completeness for the PhyloFish brown trout and European whitefish transcriptomes. This was due to an error in their TransDecoder pipeline and restricted to those two datasets and their interpretation. They apologise for this misreported result and thank the authors of the PhyloFish database for bringing it to their attention.
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- 2018
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27. Intrinsic potential for immediate biodegradation of toluene in a pristine, energy-limited aquifer
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Herzyk, Agnieszka, Maloszewski, Piotr, Qiu, Shiran, Elsner, Martin, and Griebler, Christian
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- 2014
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28. Pre- and Post-Natal Stress Programming: Developmental Exposure to Glucocorticoids Causes Long-Term Brain-Region Specific Changes to Transcriptome in the Precocial Japanese Quail
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Marasco, V., Herzyk, P., Robinson, J., and Spencer, K. A.
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- 2016
29. Insertional mutagenesis and deep profiling reveals gene hierarchies and a Myc/p53-dependent bottleneck in lymphomagenesis.
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Camille A Huser, Kathryn L Gilroy, Jeroen de Ridder, Anna Kilbey, Gillian Borland, Nancy Mackay, Alma Jenkins, Margaret Bell, Pawel Herzyk, Louise van der Weyden, David J Adams, Alistair G Rust, Ewan Cameron, and James C Neil
- Subjects
Genetics ,QH426-470 - Abstract
Retroviral insertional mutagenesis (RIM) is a powerful tool for cancer genomics that was combined in this study with deep sequencing (RIM/DS) to facilitate a comprehensive analysis of lymphoma progression. Transgenic mice expressing two potent collaborating oncogenes in the germ line (CD2-MYC, -Runx2) develop rapid onset tumours that can be accelerated and rendered polyclonal by neonatal Moloney murine leukaemia virus (MoMLV) infection. RIM/DS analysis of 28 polyclonal lymphomas identified 771 common insertion sites (CISs) defining a 'progression network' that encompassed a remarkably large fraction of known MoMLV target genes, with further strong indications of oncogenic selection above the background of MoMLV integration preference. Progression driven by RIM was characterised as a Darwinian process of clonal competition engaging proliferation control networks downstream of cytokine and T-cell receptor signalling. Enhancer mode activation accounted for the most efficiently selected CIS target genes, including Ccr7 as the most prominent of a set of chemokine receptors driving paracrine growth stimulation and lymphoma dissemination. Another large target gene subset including candidate tumour suppressors was disrupted by intragenic insertions. A second RIM/DS screen comparing lymphomas of wild-type and parental transgenics showed that CD2-MYC tumours are virtually dependent on activation of Runx family genes in strong preference to other potent Myc collaborating genes (Gfi1, Notch1). Ikzf1 was identified as a novel collaborating gene for Runx2 and illustrated the interface between integration preference and oncogenic selection. Lymphoma target genes for MoMLV can be classified into (a) a small set of master regulators that confer self-renewal; overcoming p53 and other failsafe pathways and (b) a large group of progression genes that control autonomous proliferation in transformed cells. These findings provide insights into retroviral biology, human cancer genetics and the safety of vector-mediated gene therapy.
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- 2014
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30. Gene array analysis reveals a common Runx transcriptional programme controlling cell adhesion and survival
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Wotton, S, Terry, A, Kilbey, A, Jenkins, A, Herzyk, P, Cameron, E, and Neil, J C
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- 2008
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31. Cloning and expression analysis of candidate genes involved in wax deposition along the growing barley (Hordeum vulgare) leaf
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Richardson, Andrew, Boscari, Alexandre, Schreiber, Lukas, Kerstiens, Gerhard, Jarvis, Mike, Herzyk, Pawel, and Fricke, Wieland
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- 2007
- Full Text
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32. Functional correlates of positional and gender-specific renal asymmetry in Drosophila.
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Venkateswara R Chintapalli, Selim Terhzaz, Jing Wang, Mohammed Al Bratty, David G Watson, Pawel Herzyk, Shireen A Davies, and Julian A T Dow
- Subjects
Medicine ,Science - Abstract
BACKGROUND:In humans and other animals, the internal organs are positioned asymmetrically in the body cavity, and disruption of this body plan can be fatal in humans. The mechanisms by which internal asymmetry are established are presently the subject of intense study; however, the functional significance of internal asymmetry (outside the brain) is largely unexplored. Is internal asymmetry functionally significant, or merely an expedient way of packing organs into a cavity? METHODOLOGY/PRINCIPAL FINDINGS:Like humans, Drosophila shows internal asymmetry, with the gut thrown into stereotyped folds. There is also renal asymmetry, with the rightmost pair of renal (Malpighian) tubules always ramifying anteriorly, and the leftmost pair always sitting posteriorly in the body cavity. Accordingly, transcriptomes of anterior-directed (right-side) and posterior-directed (left-side) Malpighian (renal) tubules were compared in both adult male and female Drosophila. Although genes encoding the basic functions of the tubules (transport, signalling) were uniformly expressed, some functions (like innate immunity) showed positional or gender differences in emphasis; others, like calcium handling or the generation of potentially toxic ammonia, were reserved for just the right-side or left-side tubules, respectively. These findings correlated with the distinct locations of each tubule pair within the body cavity. Well known developmental genes (like dorsocross, dachshund and doublesex) showed continuing, patterned expression in adult tubules, implying that somatic tissues maintain both left-right and gender identities throughout life. Gender asymmetry was also noted, both in defence and in male-specific expression of receptors for neuropeptide F and sex-peptide: NPF elevated calcium only in male tubules. CONCLUSIONS/SIGNIFICANCE:Accordingly, the physical asymmetry of the tubules in the body cavity is directly adaptive. Now that the detailed machinery underlying internal asymmetry is starting to be delineated, our work invites the investigation, not just of tissues in isolation, but in the context of their unique physical locations and milieux.
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- 2012
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33. Transforming growth factor-beta signaling via ALK1 and ALK5 regulates distinct functional pathways in vein graft intimal hyperplasia
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Low, EL, primary, Schwartze, JT, additional, Kurkiewicz, A, additional, Pek, M, additional, Kelly, DJ, additional, Shaw, AS, additional, Thorikay, M, additional, McClure, J, additional, McBride, M, additional, Arias-Rivas, S, additional, Francis, SE, additional, Morrell, NW, additional, Delles, C, additional, Herzyk, P, additional, Havenga, MJ, additional, Nicklin, SA, additional, Ten Dijke, P, additional, Baker, AH, additional, and Bradshaw, AC, additional
- Published
- 2019
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- View/download PDF
34. Relationships between antibodies against human soluble complement receptor 1 (hsCR1) from various species
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Ruggieri, Elizabeth V., Bugelski, Peter J., Kaplan, Johanne M., Everitt, Daniel, Lipani, John, Jorkasky, Diane K., Boike, Steven C., DeClement, Frederick, Moore, Jr., Francis D., and Herzyk, Danuta J.
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- 1996
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35. Predicting the outer membrane proteome of Pasteurella multocida based on consensus prediction enhanced by results integration and manual confirmation
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E-komon Teerasak, Burchmore Richard, Herzyk Pawel, and Davies Robert
- Subjects
Computer applications to medicine. Medical informatics ,R858-859.7 ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background Outer membrane proteins (OMPs) of Pasteurella multocida have various functions related to virulence and pathogenesis and represent important targets for vaccine development. Various bioinformatic algorithms can predict outer membrane localization and discriminate OMPs by structure or function. The designation of a confident prediction framework by integrating different predictors followed by consensus prediction, results integration and manual confirmation will improve the prediction of the outer membrane proteome. Results In the present study, we used 10 different predictors classified into three groups (subcellular localization, transmembrane β-barrel protein and lipoprotein predictors) to identify putative OMPs from two available P. multocida genomes: those of avian strain Pm70 and porcine non-toxigenic strain 3480. Predicted proteins in each group were filtered by optimized criteria for consensus prediction: at least two positive predictions for the subcellular localization predictors, three for the transmembrane β-barrel protein predictors and one for the lipoprotein predictors. The consensus predicted proteins were integrated from each group into a single list of proteins. We further incorporated a manual confirmation step including a public database search against PubMed and sequence analyses, e.g. sequence and structural homology, conserved motifs/domains, functional prediction, and protein-protein interactions to enhance the confidence of prediction. As a result, we were able to confidently predict 98 putative OMPs from the avian strain genome and 107 OMPs from the porcine strain genome with 83% overlap between the two genomes. Conclusions The bioinformatic framework developed in this study has increased the number of putative OMPs identified in P. multocida and allowed these OMPs to be identified with a higher degree of confidence. Our approach can be applied to investigate the outer membrane proteomes of other Gram-negative bacteria.
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- 2012
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36. RNA-Seq analysis of differentiated keratinocytes reveals a massive response to late events during human papillomavirus 16 infection, including loss of epithelial barrier function
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Klymenko, T., Gu, Q., Herbert, I., Stevenson, A., Iliev, V., Watkins, G., Pollock, C., Bhatia, R., Cuschieri, K., Herzyk, P., Gatherer, D., and Graham, S.V.
- Abstract
The human papillomavirus (HPV) replication cycle is tightly linked to epithelial cell differentiation. To examine HPV-associated changes in the keratinocyte transcriptome, RNAs isolated from undifferentiated and differentiated cell populations of normal, spontaneously immortalised, keratinocytes (NIKS), and NIKS stably transfected with HPV16 episomal genomes (NIKS16), were compared using RNASeq. HPV16 infection altered expression of 2862 cellular genes. Next, to elucidate the role of keratinocyte gene expression in late events during the viral life cycle, RNASeq was carried out on triplicate differentiated populations of NIKS (uninfected) and NIKS16 (infected). Of the top 966 genes altered (>log2 = 1.8, 3.5-fold change) 670 genes were downregulated and 296 genes were up-regulated. HPV down-regulated many genes involved in epithelial barrier function that involves structural resistance to the environment and immunity to infectious agents. For example, HPV infection repressed expression of the differentiated keratinocyte-specific pattern recognition receptor TLR7, the Langerhans cell chemoattractant, CCL20, and proinflammatory cytokines, IL1A and IL1B. However, IRF1, IFNκ and viral restriction factors (IFIT1, 2, 3, 5, OASL, CD74, RTP4) were up-regulated. HPV infection abrogated gene expression associated with the physical epithelial barrier, including keratinocyte cytoskeleton, intercellular junctions and cell adhesion. qPCR and western blotting confirmed changes in expression of seven of the most significantly altered mRNAs. Expression of three genes showed statistically significant changes during cervical disease progression in clinical samples. Taken together, the data indicate that HPV infection manipulates the differentiating keratinocyte transcriptome to create an environment conducive to productive viral replication and egress. IMPORTANCE: Human papillomavirus (HPV) genome amplification and capsid formation takes place in differentiated keratinocytes. The viral life cycle is intimately associated with host cell differentiation. Deep sequencing (RNASeq) of RNA from undifferentiated and differentiated uninfected and HPV16-positive keratinocytes showed that almost 3000 genes were differentially expressed in keratinocyte due to HPV16 infection. Strikingly, the epithelial barrier function of differentiated keratinocytes, comprising keratinocyte immune function and cellular structure, was found to be disrupted. These data provide new insights into virus-host interaction crucial for production of infectious virus and reveal that HPV infection remodels keratinocytes for completion of the virus replication cycle.
- Published
- 2017
37. Androgen-responsive non-coding small RNAs extend the potential of HCG stimulation to act as a bioassay of androgen sufficiency
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Rodie, M.E., Mudaliar, M.A.V., Herzyk, P., McMillan, M., Boroujerdi, M., Chudleigh, S., Tobias, E.S., and Ahmed, S.F.
- Subjects
endocrine system - Abstract
Background: It is unclear whether a short-term change in circulating androgens is associated with changes in the transcriptome of the peripheral blood mononuclear cells (PBMC).\ud Aims & Methods: To explore the effect of hCG-stimulation on the PBMC-transcriptome, 12 boys with a median age (range) of 0.7yrs (0.3, 11.2) who received intramuscular hCG 1500u on 3 consecutive days as part of their investigations underwent transcriptomic array analysis on RNA extracted from peripheral blood mononuclear cells before and after hCG stimulation.\ud Results: Median pre and post hCG testosterone for the overall group was 0.7nmol/l (
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- 2017
38. Updates on ion and water transport by the Malpighian tubule
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Dow, Julian A T, Krause, Sue Ann, and Herzyk, Pawel
- Abstract
[Display omitted]
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- 2021
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39. A gene signature for post-infectious chronic fatigue syndrome
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Cannon Celia, Behan Peter O, Herzyk Pawel, Hagan Suzanne, Gow John W, and Chaudhuri Abhijit
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Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background At present, there are no clinically reliable disease markers for chronic fatigue syndrome. DNA chip microarray technology provides a method for examining the differential expression of mRNA from a large number of genes. Our hypothesis was that a gene expression signature, generated by microarray assays, could help identify genes which are dysregulated in patients with post-infectious CFS and so help identify biomarkers for the condition. Methods Human genome-wide Affymetrix GeneChip arrays (39,000 transcripts derived from 33,000 gene sequences) were used to compare the levels of gene expression in the peripheral blood mononuclear cells of male patients with post-infectious chronic fatigue (n = 8) and male healthy control subjects (n = 7). Results Patients and healthy subjects differed significantly in the level of expression of 366 genes. Analysis of the differentially expressed genes indicated functional implications in immune modulation, oxidative stress and apoptosis. Prototype biomarkers were identified on the basis of differential levels of gene expression and possible biological significance Conclusion Differential expression of key genes identified in this study offer an insight into the possible mechanism of chronic fatigue following infection. The representative biomarkers identified in this research appear promising as potential biomarkers for diagnosis and treatment.
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- 2009
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40. Automatic generation of 3D motifs for classification of protein binding sites
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Herzyk Pawel, Nebel Jean-Christophe, and Gilbert David R
- Subjects
Computer applications to medicine. Medical informatics ,R858-859.7 ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background Since many of the new protein structures delivered by high-throughput processes do not have any known function, there is a need for structure-based prediction of protein function. Protein 3D structures can be clustered according to their fold or secondary structures to produce classes of some functional significance. A recent alternative has been to detect specific 3D motifs which are often associated to active sites. Unfortunately, there are very few known 3D motifs, which are usually the result of a manual process, compared to the number of sequential motifs already known. In this paper, we report a method to automatically generate 3D motifs of protein structure binding sites based on consensus atom positions and evaluate it on a set of adenine based ligands. Results Our new approach was validated by generating automatically 3D patterns for the main adenine based ligands, i.e. AMP, ADP and ATP. Out of the 18 detected patterns, only one, the ADP4 pattern, is not associated with well defined structural patterns. Moreover, most of the patterns could be classified as binding site 3D motifs. Literature research revealed that the ADP4 pattern actually corresponds to structural features which show complex evolutionary links between ligases and transferases. Therefore, all of the generated patterns prove to be meaningful. Each pattern was used to query all PDB proteins which bind either purine based or guanine based ligands, in order to evaluate the classification and annotation properties of the pattern. Overall, our 3D patterns matched 31% of proteins with adenine based ligands and 95.5% of them were classified correctly. Conclusion A new metric has been introduced allowing the classification of proteins according to the similarity of atomic environment of binding sites, and a methodology has been developed to automatically produce 3D patterns from that classification. A study of proteins binding adenine based ligands showed that these 3D patterns are not only biochemically meaningful, but can be used for protein classification and annotation.
- Published
- 2007
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41. Graph-based iterative Group Analysis enhances microarray interpretation
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Amtmann Anna, Breitling Rainer, and Herzyk Pawel
- Subjects
Computer applications to medicine. Medical informatics ,R858-859.7 ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background One of the most time-consuming tasks after performing a gene expression experiment is the biological interpretation of the results by identifying physiologically important associations between the differentially expressed genes. A large part of the relevant functional evidence can be represented in the form of graphs, e.g. metabolic and signaling pathways, protein interaction maps, shared GeneOntology annotations, or literature co-citation relations. Such graphs are easily constructed from available genome annotation data. The problem of biological interpretation can then be described as identifying the subgraphs showing the most significant patterns of gene expression. We applied a graph-based extension of our iterative Group Analysis (iGA) approach to obtain a statistically rigorous identification of the subgraphs of interest in any evidence graph. Results We validated the Graph-based iterative Group Analysis (GiGA) by applying it to the classic yeast diauxic shift experiment of DeRisi et al., using GeneOntology and metabolic network information. GiGA reliably identified and summarized all the biological processes discussed in the original publication. Visualization of the detected subgraphs allowed the convenient exploration of the results. The method also identified several processes that were not presented in the original paper but are of obvious relevance to the yeast starvation response. Conclusions GiGA provides a fast and flexible delimitation of the most interesting areas in a microarray experiment, and leads to a considerable speed-up and improvement of the interpretation process.
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- 2004
- Full Text
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42. Iterative Group Analysis (iGA): A simple tool to enhance sensitivity and facilitate interpretation of microarray experiments
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Amtmann Anna, Breitling Rainer, and Herzyk Pawel
- Subjects
Computer applications to medicine. Medical informatics ,R858-859.7 ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background The biological interpretation of even a simple microarray experiment can be a challenging and highly complex task. Here we present a new method (Iterative Group Analysis) to facilitate, improve, and accelerate this process. Results Our Iterative Group Analysis approach (iGA) uses elementary statistics to identify those functional classes of genes that are significantly changed in an experiment and at the same time determines which of the class members are most likely to be differentially expressed. iGA does not require that all members of a class change and is therefore robust against imperfect class assignments, which can be derived from public sources (e.g. GeneOntologies) or automated processes (e.g. key word extraction from gene names). In contrast to previous non-iterative approaches, iGA does not depend on the availability of fixed lists of differentially expressed genes, and thus can be used to increase the sensitivity of gene detection especially in very noisy or small data sets. In the extreme, iGA can even produce statistically meaningful results without any experimental replication. The automated functional annotation provided by iGA greatly reduces the complexity of microarray results and facilitates the interpretation process. In addition, iGA can be used as a fast and efficient tool for the platform-independent comparison of a microarray experiment to the vast number of published results, automatically highlighting shared genes of potential interest. Conclusions By applying iGA to a wide variety of data from diverse organisms and platforms we show that this approach enhances and accelerates the interpretation of microarray experiments.
- Published
- 2004
43. RESPONSE OF BLOOD PRESSURE TO RENAL DENERVATION IS NOT ASSOCIATED WITH GENETIC VARIANTS
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Delles, Christian, Schmieder, Roland E., Daly, Ronan, Hamilton, Graham, Schmid, Axel, Herzyk, Pawel, and Mahfoud, Felix
- Published
- 2023
- Full Text
- View/download PDF
44. FlyAtlas: database of gene expression in the tissues of drosophila melanogaster
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Robinson, S.W., Herzyk, P., Dow, J.A.T., and Leader, D.P.
- Subjects
fungi - Abstract
The FlyAtlas resource contains data on the expression of the genes of Drosophila melanogaster in different tissues (currently 25—17 adult and 8 larval) obtained by hybridization of messenger RNA to Affymetrix Drosophila Genome 2 microarrays. The microarray probe sets cover 13 250 Drosophila genes, detecting 12 533 in an unambiguous manner. The data underlying the original web application (http://flyatlas.org) have been restructured into a relational database and a Java servlet written to provide a new web interface, FlyAtlas 2 (http://flyatlas.gla.ac.uk/), which allows several additional queries. Users can retrieve data for individual genes or for groups of genes belonging to the same or related ontological categories. Assistance in selecting valid search terms is provided by an Ajax ‘autosuggest’ facility that polls the database as the user types. Searches can also focus on particular tissues, and data can be retrieved for the most highly expressed genes, for genes of a particular category with above-average expression or for genes with the greatest difference in expression between the larval and adult stages. A novel facility allows the database to be queried with a specific gene to find other genes with a similar pattern of expression across the different tissues.
- Published
- 2013
45. Data-mining the FlyAtlas online resource to identify core functional motifs across transporting epithelia
- Author
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Chintapalli, V.R., Wang, J., Herzyk, P., Davies, S.A., and Dow, J.A.T.
- Abstract
Background\ud Comparative analysis of tissue-specific transcriptomes is a powerful technique to uncover tissue functions. Our FlyAtlas.org provides authoritative gene expression levels for multiple tissues of Drosophila melanogaster (1). Although the main use of such resources is single gene lookup, there is the potential for powerful meta-analysis to address questions that could not easily be framed otherwise. Here, we illustrate the power of data-mining of FlyAtlas data by comparing epithelial transcriptomes to identify a core set of highly-expressed genes, across the four major epithelial tissues (salivary glands, Malpighian tubules, midgut and hindgut) of both adults and larvae.\ud \ud Method\ud Parallel hypothesis-led and hypothesis-free approaches were adopted to identify core genes that underpin insect epithelial function. In the former, gene lists were created from transport processes identified in the literature, and their expression profiles mapped from the flyatlas.org online dataset. In the latter, gene enrichment lists were prepared for each epithelium, and genes (both transport related and unrelated) consistently enriched in transporting epithelia identified.\ud \ud Results:\ud A key set of transport genes, comprising V-ATPases, cation exchangers, aquaporins, potassium and chloride channels, and carbonic anhydrase, was found to be highly enriched across the epithelial tissues, compared with the whole fly. Additionally, a further set of genes that had not been predicted to have epithelial roles, were co-expressed with the core transporters, extending our view of what makes a transporting epithelium work. Further insights were obtained by studying the genes uniquely overexpressed in each epithelium; for example, the salivary gland expresses lipases, the midgut organic solute transporters, the tubules specialize for purine metabolism and the hindgut overexpresses still unknown genes.\ud \ud Conclusion\ud Taken together, these data provide a unique insight into epithelial function in this key model insect, and a framework for comparison with other species. They also provide a methodology for function-led datamining of FlyAtlas.org and other multi-tissue expression datasets.
- Published
- 2013
46. Alternative splicing mediates responses of the arabidopsis circadian clock to temperature changes
- Author
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James, A.B., Syed, N.H., Bordage, S., Marshall, J., Nimmo, G.M., Jenkins, G.I., Herzyk, P., Brown, J.W.S., and Nimmo, H.G.
- Abstract
Alternative splicing plays crucial roles by influencing the diversity of the transcriptome and proteome and regulating protein structure/function and gene expression. It is widespread in plants, and alteration of the levels of splicing factors leads to a wide variety of growth and developmental phenotypes. The circadian clock is a complex piece of cellular machinery that can regulate physiology and behavior to anticipate predictable environmental changes on a revolving planet. We have performed a system-wide analysis of alternative splicing in clock components in Arabidopsis thaliana plants acclimated to different steady state temperatures or undergoing temperature transitions. This revealed extensive alternative splicing in clock genes and dynamic changes in alternatively spliced transcripts. Several of these changes, notably those affecting the circadian clock genes LATE ELONGATED HYPOCOTYL (LHY) and PSEUDO RESPONSE REGULATOR7, are temperature-dependent and contribute markedly to functionally important changes in clock gene expression in temperature transitions by producing nonfunctional transcripts and/or inducing nonsense-mediated decay. Temperature effects on alternative splicing contribute to a decline in LHY transcript abundance on cooling, but LHY promoter strength is not affected. We propose that temperature-associated alternative splicing is an additional mechanism involved in the operation and regulation of the plant circadian clock.
- Published
- 2012
47. Scanning peptide array analysis identify overlapping binding sites for the signaling scaffold proteins, beta-arestin and RACK1 in the cAMP-specific phosphodiesterase, PDE4D5
- Author
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Bolger, G.B., Baillie, G.S., Li, X., Lynch, M.J., Herzyk, P., Mohamed, A., Mitchell, L., McCahill, A., Hundsrucker, C., Klussmann, E., Adams, D.R., and Houslay, M.D.
- Subjects
QR355 - Abstract
The cAMP-specific phosphodiesterase PDE4D5 can interact with the signalling scaffold proteins RACK (receptors for activated C-kinase) 1 and β-arrestin. Two-hybrid and co-immunoprecipitation analyses showed that RACK1 and β-arrestin interact with PDE4D5 in a mutually exclusive manner. Overlay studies with PDE4D5 scanning peptide array libraries showed that RACK1 and β-arrestin interact at overlapping sites within the unique N-terminal region of PDE4D5 and at distinct sites within the conserved PDE4 catalytic domain. Screening scanning alanine substitution peptide arrays, coupled with mutagenesis and truncation studies, allowed definition of RACK1 and β-arrestin interaction sites. Modelled on the PDE4D catalytic domain, these form distinct well-defined surface-exposed patches on helices-15–16, for RACK1, and helix-17 for β-arrestin. siRNA (small interfering RNA)-mediated knockdown of RACK1 in HEK-293 (human embryonic kidney) B2 cells increased β-arrestin-scaffolded PDE4D5 approx. 5-fold, increased PDE4D5 recruited to the β2AR (β2-adrenergic receptor) upon isoproterenol challenge approx. 4-fold and severely attenuated (approx. 4–5 fold) both isoproterenol-stimulated PKA (protein kinase A) phosphorylation of the β2AR and activation of ERK (extracellular-signal-regulated kinase). The ability of a catalytically inactive form of PDE4D5 to exert a dominant negative effect in amplifying isoproterenol-stimulated ERK activation was ablated by a mutation that blocked the interaction of PDE4D5 with β-arrestin. In the present study, we show that the signalling scaffold proteins RACK1 and β-arrestin compete to sequester distinct ‘pools’ of PDE4D5. In this fashion, alterations in the level of RACK1 expression may act to modulate signal transduction mediated by the β2AR.
- Published
- 2006
48. Iterative Group Analysis (iGA): a simple tool to enhance sensitivity and facilitate interpretation of microarray experiments
- Author
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Breitling, R., Amtmann, A., and Herzyk, P.
- Subjects
Genome ,Genome, Human ,QH ,Gene Expression Profiling ,Software Validation ,Methodology Article ,Arabidopsis ,Computational Biology ,lcsh:Computer applications to medicine. Medical informatics ,Genes, Plant ,Sensitivity and Specificity ,Rats ,Mice ,lcsh:Biology (General) ,Genes ,Confidence Intervals ,lcsh:R858-859.7 ,Animals ,Humans ,QH426 ,lcsh:QH301-705.5 ,Genome, Plant ,Software ,Oligonucleotide Array Sequence Analysis - Abstract
Background The biological interpretation of even a simple microarray experiment can be a challenging and highly complex task. Here we present a new method (Iterative Group Analysis) to facilitate, improve, and accelerate this process. Results Our Iterative Group Analysis approach (iGA) uses elementary statistics to identify those functional classes of genes that are significantly changed in an experiment and at the same time determines which of the class members are most likely to be differentially expressed. iGA does not require that all members of a class change and is therefore robust against imperfect class assignments, which can be derived from public sources (e.g. GeneOntologies) or automated processes (e.g. key word extraction from gene names). In contrast to previous non-iterative approaches, iGA does not depend on the availability of fixed lists of differentially expressed genes, and thus can be used to increase the sensitivity of gene detection especially in very noisy or small data sets. In the extreme, iGA can even produce statistically meaningful results without any experimental replication. The automated functional annotation provided by iGA greatly reduces the complexity of microarray results and facilitates the interpretation process. In addition, iGA can be used as a fast and efficient tool for the platform-independent comparison of a microarray experiment to the vast number of published results, automatically highlighting shared genes of potential interest. Conclusions By applying iGA to a wide variety of data from diverse organisms and platforms we show that this approach enhances and accelerates the interpretation of microarray experiments.
- Published
- 2003
49. Use of bacterial whole-genome sequencing to investigate local persistence and spread in bovine tuberculosis.
- Author
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Trewby, Hannah, Wright, David, Breadon, Eleanor L., Lycett, Samantha J., Mallon, Tom R., McCormick, Carl, Johnson, Paul, Orton, Richard J., Allen, Adrian R., Galbraith, Julie, Herzyk, Pawel, Skuce, Robin A., Biek, Roman, and Kao, Rowland R.
- Abstract
Mycobacterium bovis is the causal agent of bovine tuberculosis, one of the most important diseases currently facing the UK cattle industry. Here, we use high-density whole genome sequencing (WGS) in a defined sub-population of M. bovis in 145 cattle across 66 herd breakdowns to gain insights into local spread and persistence. We show that despite low divergence among isolates, WGS can in principle expose contributions of under-sampled host populations to M. bovis transmission. However, we demonstrate that in our data such a signal is due to molecular type switching, which had been previously undocumented for M. bovis . Isolates from farms with a known history of direct cattle movement between them did not show a statistical signal of higher genetic similarity. Despite an overall signal of genetic isolation by distance, genetic distances also showed no apparent relationship with spatial distance among affected farms over distances <5 km. Using simulations, we find that even over the brief evolutionary timescale covered by our data, Bayesian phylogeographic approaches are feasible. Applying such approaches showed that M. bovis dispersal in this system is heterogeneous but slow overall, averaging 2 km/year. These results confirm that widespread application of WGS to M. bovis will bring novel and important insights into the dynamics of M. bovis spread and persistence, but that the current questions most pertinent to control will be best addressed using approaches that more directly integrate WGS with additional epidemiological data. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
50. FlyAtlas: database of gene expression in the tissues of Drosophila melanogaster
- Author
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Robinson, S. W., primary, Herzyk, P., additional, Dow, J. A. T., additional, and Leader, D. P., additional
- Published
- 2012
- Full Text
- View/download PDF
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