Horizontal transmission of Escherichia coli O157:H7 during cattle housing, survival kinetics in feces and water of Escherichia coli O157:H7 and characterisation of E. coli O157:H7 isolates from cattle faeces and a feedlot environment

End of project reportTeagasc acknowledges with gratitude the support of European Union Structural Funds (EAGGF) in financing this research projectEscherichia coli O157:H7 can cause severe illness and in some cases leading to death. Cattle are the main reservoir with transmission to humans occurring through contamination of food or the environment. Improved understanding of the survival and transmission and survival of E. coli O157:H7 on the farm is essential for developing future controls of this pathogen. This study showed that transmission of E. coli O157:H7 can occur rapidly in groups of housed cattle, with contamination of the pens and hides occurring in 24 hrs. The inoculation dose for cattle is lower than previously reported. Ingestion of bacteria from the hide through social grooming is important for pathogen transmission in housed cattle along with faecal contamination of the environment. Sampling hide will improve the estimation of prevalence of E. coli O157:H7 in pens

Early Deletion and Late Positive Selection of T-Cells Expressing a Male-Specific Receptor in T-Cell Receptor Transgenic Mice

The ontogeny of T cells in T-cell receptor (TCR) transgenic mice, which express a transgenic αβ heterodimer, specific for the male (H-Y) antigen in association with H-2Db, was determined. The transgenic α chain was expressed on about 10% of the fetal thymocytes on day 14 of gestation. About 50% of day-15 fetal thymocytes expressed both α and β transchains and virtually all fetal thymocytes expressed the transgenicαβ heterodimer by day 17. The early expression of the transgenic TCR on CD4-8- thymocytes prevented the development of γδ cells, and led to accelerated growth of thymocytes and an earlier expression of CD4 and CD8 molecules. Up to day 17, no significant differences in T-cell development could be detected between female and male thymuses. By day 18 of gestation, the male transgenic thymus contained more CD4-8- thymocytes than the female transgenic thymus. The preponderance of CD4-8- thymocytes in the male transgenic thymus increased until birth and was a consequence of the deletion of the CD4+8+ thymocytes and their CD4-8+ precursors. By the time of birth, the male transgenic thymus contained half the number of cells as the female transgenic thymus. The deletion of autospecific precursor cells in the male transgenic mouse began only at day 18 of gestation, despite the fact that the ligand could already be detected by day 16

Fv antibodies to aflatoxin B1 derived from a pre-immunized antibody phage display library system

The production and characterization of recombinant antibodies to aflatoxin B[SUB1] (AFB[SUB1]), a potent mycotoxin and carcinogen is described. The antibody fragments produced were then applied for use in a surface plasmon resonance-based biosensor (BIAcore), which measures biomolecular interactions in 'real-time'. Single chain Fv (scFv) antibodies were generated to aflatoxin B1 from an established phage display system, which incorporated a range of different plasmids for efficient scFv expression. The scFv's were used in the development of a competitive ELISA, and also for the development of surface plasmon resonance (SPR)-based inhibition immunoassays. They were found to be suitable for the detection of AFB[SUB1], in this format, with the assays being sensitive and reproducible

Assessing the practicalities of joint snakebite and dog rabies control programs:Commonalities and potential pitfalls

Both rabies and snakebite primarily affect underserved and impoverished communities globally, with an estimated 200,000 people dying from these diseases annually, and the greatest burden being in Africa and Asia. Both diseases have been neglected and have thus been denied appropriate prioritization, support, and interventions, and face many of the challenges common to all neglected tropical diseases (NTDs). In line with the call for integrated approaches between NTDs in the recent NTD Roadmap, we sought to build upon previous conceptualizations for an integrated approach by identifying the commonalities between snakebite and rabies to explore the feasibility of an integrated approach. While multiple areas for potential integration are identified, we highlight the potential pitfalls to integrating rabies and snakebite programs, considering the nuances that make each disease and its intervention program unique. We conclude that health system strengthening, and capacity building should be the focus of any integrated approach among NTDs, and that by strengthening overall health systems, both rabies and snakebite can advocate for further support from governments and stakeholders

Interaction between Metformin, Folate and Vitamin B 12 and the Potential Impact on Fetal Growth and Long-Term Metabolic Health in Diabetic Pregnancies

From MDPI via Jisc Publications RouterHistory: accepted 2021-05-25, pub-electronic 2021-05-28Publication status: PublishedFunder: Medical Research Council; Grant(s): MR/R023166/1, MR/T001828/1Funder: British Heart Foundation; Grant(s): FS/4yPhD/F/20/34130Metformin is the first-line treatment for many people with type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) to maintain glycaemic control. Recent evidence suggests metformin can cross the placenta during pregnancy, thereby exposing the fetus to high concentrations of metformin and potentially restricting placental and fetal growth. Offspring exposed to metformin during gestation are at increased risk of being born small for gestational age (SGA) and show signs of ‘catch up’ growth and obesity during childhood which increases their risk of future cardiometabolic diseases. The mechanisms by which metformin impacts on the fetal growth and long-term health of the offspring remain to be established. Metformin is associated with maternal vitamin B12 deficiency and antifolate like activity. Vitamin B12 and folate balance is vital for one carbon metabolism, which is essential for DNA methylation and purine/pyrimidine synthesis of nucleic acids. Folate:vitamin B12 imbalance induced by metformin may lead to genomic instability and aberrant gene expression, thus promoting fetal programming. Mitochondrial aerobic respiration may also be affected, thereby inhibiting placental and fetal growth, and suppressing mammalian target of rapamycin (mTOR) activity for cellular nutrient transport. Vitamin supplementation, before or during metformin treatment in pregnancy, could be a promising strategy to improve maternal vitamin B12 and folate levels and reduce the incidence of SGA births and childhood obesity. Heterogeneous diagnostic and screening criteria for GDM and the transient nature of nutrient biomarkers have led to inconsistencies in clinical study designs to investigate the effects of metformin on folate:vitamin B12 balance and child development. As rates of diabetes in pregnancy continue to escalate, more women are likely to be prescribed metformin; thus, it is of paramount importance to improve our understanding of metformin’s transgenerational effects to develop prophylactic strategies for the prevention of adverse fetal outcomes

Computer Science Research Institute 2005 annual report of activities.

This report summarizes the activities of the Computer Science Research Institute (CSRI) at Sandia National Laboratories during the period January 1, 2005 to December 31, 2005. During this period, the CSRI hosted 182 visitors representing 83 universities, companies and laboratories. Of these, 60 were summer students or faculty. The CSRI partially sponsored 2 workshops and also organized and was the primary host for 3 workshops. These 3 CSRI sponsored workshops had 105 participants, 78 from universities, companies and laboratories, and 27 from Sandia. Finally, the CSRI sponsored 12 long-term collaborative research projects and 3 Sabbaticals