Effects of Feeding Bt Maize to Sows during Gestation and Lactation on Maternal and Offspring Immunity and Fate of Transgenic Material

peer-reviewedBackground: We aimed to determine the effect of feeding transgenic maize to sows during gestation and lactation on maternal and offspring immunity and to assess the fate of transgenic material. Methodology/Principal Findings: On the day of insemination, sows were assigned to one of two treatments (n = 12/treatment); 1) non-Bt control maize diet or 2) Bt-MON810 maize diet, which were fed for ~143 days throughout gestation and lactation. Immune function was assessed by leukocyte phenotyping, haematology and Cry1Ab-specific antibody presence in blood on days 0, 28 and 110 of gestation and at the end of lactation. Peripheral-blood mononuclear cell cytokine production was investigated on days 28 and 110 of gestation. Haematological analysis was performed on offspring at birth (n = 12/treatment). Presence of the cry1Ab transgene was assessed in sows' blood and faeces on day 110 of gestation and in blood and tissues of offspring at birth. Cry1Ab protein presence was assessed in sows' blood during gestation and lactation and in tissues of offspring at birth. Blood monocyte count and percentage were higher (P<0.05), while granulocyte percentage was lower (P<0.05) in Bt maize-fed sows on day 110 of gestation. Leukocyte count and granulocyte count and percentage were lower (P<0.05), while lymphocyte percentage was higher (P<0.05) in offspring of Bt maize-fed sows. Bt maize-fed sows had a lower percentage of monocytes on day 28 of lactation and of CD4+CD8+ lymphocytes on day 110 of gestation, day 28 of lactation and overall (P<0.05). Cytokine production was similar between treatments. Transgenic material or Cry1Ab-specific antibodies were not detected in sows or offspring. Conclusions/Significance: Treatment differences observed following feeding of Bt maize to sows did not indicate inflammation or allergy and are unlikely to be of major importance. These results provide additional data for Bt maize safety assessment.The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007–2013) under grant agreement number 211820 and the Teagasc Walsh Fellowship Programme

Evaluation of the Efficacy and Safety of a Marine-Derived Bacillus Strain for Use as an In-Feed Probiotic for Newly Weaned Pigs

peer-reviewedForty eight individual pigs (8.7±0.26 kg) weaned at 28±1 d of age were used in a 22-d study to evaluate the effect of oral administration of a Bacillus pumilus spore suspension on growth performance and health indicators. Treatments (n = 16) were: (1) non-medicated diet; (2) medicated diet with apramycin (200 mg/kg) and pharmacological levels of zinc oxide (2,500 mg zinc/kg) and (3) B. pumilus diet (non-medicated diet + 1010 spores/day B. pumilus). Final body weight and average daily gain tended to be lower (P = 0.07) and feed conversion ratio was worsened (P<0.05) for the medicated treatment compared to the B. pumilus treatment. Ileal E. coli counts were lower for the B. pumilus and medicated treatments compared to the non-medicated treatment (P<0.05), perhaps as a result of increased ileal propionic acid concentrations (P<0.001). However, the medicated treatment reduced fecal (P<0.001) and cecal (P<0.05) Lactobacillus counts and tended to reduce the total cecal short chain fatty acid (SCFA) concentration (P = 0.10). Liver weights were lighter and concentrations of liver enzymes higher (P<0.05) in pigs on the medicated treatment compared to those on the non-medicated or B. pumilus treatments. Pigs on the B. pumilus treatment had lower overall lymphocyte and higher granulocyte percentages (P<0.001) and higher numbers of jejunal goblet cells (P<0.01) than pigs on either of the other two treatments or the non-medicated treatment, respectively. However, histopathological examination of the small intestine, kidneys and liver revealed no abnormalities. Overall, the B. pumilus treatment decreased ileal E. coli counts in a manner similar to the medicated treatment but without the adverse effects on growth performance, Lactobacillus counts, cecal SCFA concentration and possible liver toxicity experienced with the medicated treatment.The study was funded by the Higher Education Authority/Institutes of Technology Ireland Technological Sector Research Strand III Programme

Pilot randomized crossover study comparing the efficacy of transnasal disposable endosheath with standard endoscopy to detect Barrett's esophagus.

BACKGROUND AND STUDY AIMS: The transnasal endosheath endoscope is a new disposable technology with potential applicability to the primary care setting. The aim of this study was to evaluate the efficacy of transnasal endosheath endoscopy (TEE) for the detection of Barrett's esophagus, by comparing the diagnostic accuracy of TEE with that of standard endoscopy. PATIENTS AND METHODS: This was a prospective, randomized, crossover study performed in a single tertiary referral center. Consecutive patients undergoing surveillance for Barrett's esophagus or referred for diagnostic assessment were recruited. All patients were randomized to undergo TEE followed by standard endoscopy or the reverse. Endoscopy experiences and patient preferences were evaluated using a questionnaire. Endoscopic and histologic diagnosis of Barrett's esophagus, and optical image quality of both endoscopic procedures, were compared. RESULTS: A total of 21 of 25 patients completed the study. TEE had sensitivity and specificity of 100 % for an endoscopic diagnosis of Barrett's esophagus, and of 66.7 % and 100 %, respectively, for the histologic diagnosis of Barrett's esophagus. The mean optical quality of standard endoscopy was significantly better than that of TEE (7.11 ± 0.42 vs. 4.06 ± 0.27; P < 0.0001). However, following endoscopy, patients reported a significantly better experience with TEE compared with standard endoscopy (7.05 ± 0.49 vs. 4.35 ± 0.53; P = 0.0006), with 60 % preferring TEE and 25 % preferring sedated standard endoscopy. CONCLUSIONS: In this study, TEE had equal accuracy for an endoscopic diagnosis of Barrett's esophagus compared with standard endoscopy, at the expense of reduced image quality and a lower yield of intestinal metaplasia on biopsy. TEE was better tolerated and preferred by patients. Hence, TEE needs further evaluation in primary care as an initial diagnostic tool.This study was supported by funding from Cambridge Experimental Cancer Medicine Centre, NIHR Cambridge Biomedical Research Centre, and a core grant for RCF from the Medical Research Council. M.K.S. was supported by the BUPA Foundation.This is the author accepted manuscript. The final version is available from Thieme Publishing Group via http://dx.doi.org/10.1055/s-0034-139331

Effects of feeding Bt MON810 maize to sows during first gestation and lactation on maternal and offspring health indicators

A total of twenty-four sows and their offspring were used in a 20-week study to investigate the effects of feeding GM maize on maternal and offspring health. Sows were fed diets containing GM or non-GM maize from service to the end of lactation. GM maize-fed sows were heavier on day 56 of gestation (P< 0·05). Offspring from sows fed GM maize tended to be lighter at weaning (P= 0·08). Sows fed GM maize tended to have decreased serum total protein (P= 0·08), and increased serum creatinine (P< 0·05) and γ-glutamyltransferase activity (P= 0·07) on day 28 of lactation. Serum urea tended to be decreased on day 110 of gestation in GM maize-fed sows (P= 0·10) and in offspring at birth (P= 0·08). Both platelet count (P= 0·07) and mean cell Hb concentration (MCHC; P= 0·05) were decreased on day 110 of gestation in GM maize-fed sows; however, MCHC tended to be increased in offspring at birth (P= 0·08). There was a minimal effect of feeding GM maize to sows during gestation and lactation on maternal and offspring serum biochemistry and haematology at birth and body weight at weaning

Molecular effects of Lapatinib in the treatment of HER2 overexpressing oesophago-gastric adenocarcinoma.

BACKGROUND: Lapatinib, a dual EGFR and HER2 inhibitor has shown disappointing results in clinical trials of metastatic oesophago-gastric adenocarcinomas (OGAs), and in vitro studies suggest that MET, IGFR, and HER3 confer resistance. This trial applied Lapatinib in the curative neoadjuvant setting and investigated the feasibility and utility of additional endoscopy and biopsy for assessment of resistance mechanisms ex vivo and in vivo. METHODS: Patients with HER2 overexpressing OGA were treated for 10 days with Lapatinib monotherapy, and then in combination with three cycles of Oxaliplatin and Capecitabine before surgery. Endoscopic samples were taken for molecular analysis at: baseline including for ex vivo culture +/- Lapatinib to predict in vivo response, post-Lapatinib monotherapy and at surgery. Immunohistochemistry (IHC) and proteomic analysis was performed to assess cell kinetics and signalling activity. RESULTS: The trial closed early (n=10) due to an anastomotic leak in two patients for which a causative effect of Lapatinib could not be excluded. The reduction in Phosphorylated-HER2 (P-HER2) and P-EGFR in the ex vivo-treated biopsy demonstrated good correlation with the in vivo response at day 10. Proteomic analysis pre and post-Lapatinib demonstrated target inhibition (P-ERBB2, P-EGFR, P-PI3K, P-AKT, and P-ERK) that persisted until surgery. There was also significant correlation between the activation of MET with the level of P-Erk (P=0.0005) and P-PI3K : T-PI3K (total PI3K) ratio (P=0.0037). There was no significant correlation between the activation status of IGFR and HER3 with downstream signalling molecules. CONCLUSIONS: Additional endoscopy and biopsy sampling for multiple biomarker endpoints was feasible and confirmed in vitro data that MET is likely to be a significant mechanism of Lapatinib resistance in vivo.This research was funded by the Medical Research Council [Grant SK002].This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/bjc.2015.34

The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003

The SWISS-PROT protein knowledgebase (http://www.expasy.org/sprot/ and http://www.ebi.ac.uk/swissprot/) connects amino acid sequences with the current knowledge in the Life Sciences. Each protein entry provides an interdisciplinary overview of relevant information by bringing together experimental results, computed features and sometimes even contradictory conclusions. Detailed expertise that goes beyond the scope of SWISS-PROT is made available via direct links to specialised databases. SWISS-PROT provides annotated entries for all species, but concentrates on the annotation of entries from human (the HPI project) and other model organisms to ensure the presence of high quality annotation for representative members of all protein families. Part of the annotation can be transferred to other family members, as is already done for microbes by the High-quality Automated and Manual Annotation of microbial Proteomes (HAMAP) project. Protein families and groups of proteins are regularly reviewed to keep up with current scientific findings. Complementarily, TrEMBL strives to comprise all protein sequences that are not yet represented in SWISS-PROT, by incorporating a perpetually increasing level of mostly automated annotation. Researchers are welcome to contribute their knowledge to the scientific community by submitting relevant findings to SWISS-PROT at [email protected]

The Universal Protein Resource (UniProt)

The Universal Protein Resource (UniProt) provides the scientific community with a single, centralized, authoritative resource for protein sequences and functional information. Formed by uniting the Swiss-Prot, TrEMBL and PIR protein database activities, the UniProt consortium produces three layers of protein sequence databases: the UniProt Archive (UniParc), the UniProt Knowledgebase (UniProt) and the UniProt Reference (UniRef) databases. The UniProt Knowledgebase is a comprehensive, fully classified, richly and accurately annotated protein sequence knowledgebase with extensive cross-references. This centrepiece consists of two sections: UniProt/Swiss-Prot, with fully, manually curated entries; and UniProt/TrEMBL, enriched with automated classification and annotation. During 2004, tens of thousands of Knowledgebase records got manually annotated or updated; we introduced a new comment line topic: TOXIC DOSE to store information on the acute toxicity of a toxin; the UniProt keyword list got augmented by additional keywords; we improved the documentation of the keywords and are continuously overhauling and standardizing the annotation of post-translational modifications. Furthermore, we introduced a new documentation file of the strains and their synonyms. Many new database cross-references were introduced and we started to make use of Digital Object Identifiers. We also achieved in collaboration with the Macromolecular Structure Database group at EBI an improved integration with structural databases by residue level mapping of sequences from the Protein Data Bank entries onto corresponding UniProt entries. For convenient sequence searches we provide the UniRef non-redundant sequence databases. The comprehensive UniParc database stores the complete body of publicly available protein sequence data. The UniProt databases can be accessed online (http://www.uniprot.org) or downloaded in several formats (ftp://ftp.uniprot.org/pub). New releases are published every two week

The Universal Protein Resource (UniProt): an expanding universe of protein information

The Universal Protein Resource (UniProt) provides a central resource on protein sequences and functional annotation with three database components, each addressing a key need in protein bioinformatics. The UniProt Knowledgebase (UniProtKB), comprising the manually annotated UniProtKB/Swiss-Prot section and the automatically annotated UniProtKB/TrEMBL section, is the preeminent storehouse of protein annotation. The extensive cross-references, functional and feature annotations and literature-based evidence attribution enable scientists to analyse proteins and query across databases. The UniProt Reference Clusters (UniRef) speed similarity searches via sequence space compression by merging sequences that are 100% (UniRef100), 90% (UniRef90) or 50% (UniRef50) identical. Finally, the UniProt Archive (UniParc) stores all publicly available protein sequences, containing the history of sequence data with links to the source databases. UniProt databases continue to grow in size and in availability of information. Recent and upcoming changes to database contents, formats, controlled vocabularies and services are described. New download availability includes all major releases of UniProtKB, sequence collections by taxonomic division and complete proteomes. A bibliography mapping service has been added, and an ID mapping service will be available soon. UniProt databases can be accessed online at http://www.uniprot.org or downloaded at ftp://ftp.uniprot.org/pub/database

UniProt: the Universal Protein knowledgebase

To provide the scientific community with a single, centralized, authoritative resource for protein sequences and functional information, the Swiss‐Prot, TrEMBL and PIR protein database activities have united to form the Universal Protein Knowledgebase (UniProt) consortium. Our mission is to provide a comprehensive, fully classified, richly and accurately annotated protein sequence knowledgebase, with extensive cross‐references and query interfaces. The central database will have two sections, corresponding to the familiar Swiss‐Prot (fully manually curated entries) and TrEMBL (enriched with automated classification, annotation and extensive cross‐references). For convenient sequence searches, UniProt also provides several non‐redundant sequence databases. The UniProt NREF (UniRef) databases provide representative subsets of the knowledgebase suitable for efficient searching. The comprehensive UniProt Archive (UniParc) is updated daily from many public source databases. The UniProt databases can be accessed online (http://www.uniprot.org) or downloaded in several formats (ftp://ftp.uniprot.org/pub). The scientific community is encouraged to submit data for inclusion in UniPro

Mind the Gap: Factors Which Inhibit Supporting Student Teachers to Engage in Action Research While on School Placement

[EN] In the Irish context, there is an expectation for research to be embedded across the continuum of the teaching profession, including initial teacher education. The Teaching Council has set out the requirement for student teachers to engage in research on their own practice, while on school placement, which links learning in their higher education institutions and the host school. This paper aims to examine some of the factors which inhibit support for student teachers to engage in action research while on school placement. This case study uses a constructivist and interpretivist philosophy. The design and analysis are underpinned by the triangulation of qualitative data collection through questionnaires, focus groups, group interviews and semi-structured interviews. Themes are developed using thematic analysis. Key findings include challenges encountered in supporting student teachers to engage in action research, not least conducting research ethically, and the power dynamics at play in school placement. This study was funded by a Research & Innovation Strategic Endowment (RISE) Scholarship from ATU.Moore, M.; O'donovan, D.; Logue, P. (2023). Mind the Gap: Factors Which Inhibit Supporting Student Teachers to Engage in Action Research While on School Placement. En 9th International Conference on Higher Education Advances (HEAd'23). Editorial Universitat Politècnica de València. 59-66. https://doi.org/10.4995/HEAd23.2023.16145596