Combining cellular and gene therapy approaches for treatment of intracranial tumors.

New treatments are needed for brain metastasis, which is associated with high morbidity and mortality. Two novel cellular and gene therapy modalities were evaluated in xenograft models for human breast cancer. The individual and especially the combined treatments with alloreactive cytotoxic T lymphocytes and replicating retroviral vectors coding for prodrug activating enzymes followed later with nontoxic prodrug demonstrated efficacy without off-target effects

The long-term temperature record from Markree Observatory, County Sligo, from 1842 to 2011

This study analysed long-term temperature patterns in the north-west of Ireland using a previously unexplored data-set from Markree Observatory, County Sligo. The Markree series extends back to 1842, making it one of the longest instrumental temperature records in Ireland and is renowned for holding the lowest recorded temperature for the island of Ireland, 198C on 16 January 1881. Despite its length, this record has been largely absent from past analyses of Ireland’s long-term temperature trends, rendering spatial coverage for the extended Irish climate chronology incomplete. Daily data stored in a variety of the historical archives were gathered and digitised and monthly records created. Calibrations to account for instrumentation, time of reading and exposure were applied where possible in order to standardise the record. Trends were subsequently investigated for seasonal averages of daily minimum, maximum and mean temperatures, and a comparison with previously published long Irish temperature records was carried out to situate the Markree record among the existing long-term series. Although the Markree series follows similar patterns to the other long-term temperature records, it displays more decadal variability, particularly in its minimum values which show a higher rate of late twentieth century warming compared to the other records. Due to its geographic location and surrounding topography shielding the site from direct ocean influences and prevailing south-westerly winds, Markree displays characteristic features of a more inland station (low minimum temperatures and large diurnal ranges) even though it is located only 7 km from the Atlantic Ocean. Such findings highlight the necessity of including the Markree data-set in future Irish climate change research

Exploitation of SPR to Investigate the Importance of Glycan Chains in the Interaction between Lactoferrin and Bacteria

peer-reviewedBovine lactoferrin (LF) has been shown to prevent adhesion to and invasion of mammalian cell lines by pathogenic bacteria, with evidence for direct bacterial binding by the milk glycoprotein. However, the glycosylation pattern of LF changes over the lactation cycle. In this study, we aim to investigate the effect that this variation has on the milk glycoprotein’s ability to interact with pathogens. Surface plasmon resonance technology was employed to compare the binding of LF from colostrum (early lactation) and mature milk (late lactation) to a panel of pathogenic bacteria (Staphylococcus aureus, Escherichia coli, Cronobacter sakazakii, Streptococcus pneumoniae, Pseudomonas aeruginosa, Listeria monocytogenes and Salmonella typhimurium). Novel interactions with LF were identified for C. sakazakii, S. pneumoniae and P. aeruginosa with the highest binding ability observed for mature milk LF in all cases, with the exception of S. typhimurium. The difference in bacterial binding observed may be as a result of the varying glycosylation profiles. This work demonstrates the potential of LF as a functional food ingredient to prevent bacterial infectio

Genome Sequencing Technologies and Nursing

Background Advances in DNA sequencing technology have resulted in an abundance of personalized data with challenging clinical utility and meaning for clinicians. This wealth of data has potential to dramatically impact the quality of healthcare. Nurses are at the focal point in educating patients regarding relevant healthcare needs; therefore, an understanding of sequencing technology and utilizing these data are critical. Aim The objective of this study was to explicate the role of nurses and nurse scientists as integral members of healthcare teams in improving understanding of DNA sequencing data and translational genomics for patients. Approach A history of the nurse role in newborn screening is used as an exemplar. Discussion This study serves as an exemplar on how genome sequencing has been utilized in nursing science and incorporates linkages of other omics approaches used by nurses that are included in this special issue. This special issue showcased nurse scientists conducting multi-omic research from various methods, including targeted candidate genes, pharmacogenomics, proteomics, epigenomics, and the microbiome. From this vantage point, we provide an overview of the roles of nurse scientists in genome sequencing research and provide recommendations for the best utilization of nurses and nurse scientists related to genome sequencing

Effect of manipulating recombination rates on response to selection in livestock breeding programs

International audienceBackgroundIn this work, we performed simulations to explore the potential of manipulating recombination rates to increase response to selection in livestock breeding programs.MethodsWe carried out ten replicates of several scenarios that followed a common overall structure but differed in the average rate of recombination along the genome (expressed as the length of a chromosome in Morgan), the genetic architecture of the trait under selection, and the selection intensity under truncation selection (expressed as the proportion of males selected). Recombination rates were defined by simulating nine different chromosome lengths: 0.10, 0.25, 0.50, 1, 2, 5, 10, 15 and 20 Morgan, respectively. One Morgan was considered to be the typical chromosome length for current livestock species. The genetic architecture was defined by the number of quantitative trait variants (QTV) that affected the trait under selection. Either a large (10,000) or a small (1000 or 500) number of QTV was simulated. Finally, the proportions of males selected under truncation selection as sires for the next generation were equal to 1.2, 2.4, 5, or 10 %.ResultsIncreasing recombination rate increased the overall response to selection and decreased the loss of genetic variance. The difference in cumulative response between low and high recombination rates increased over generations. At low recombination rates, cumulative response to selection tended to asymptote sooner and the genetic variance was completely eroded. If the trait under selection was affected by few QTV, differences between low and high recombination rates still existed, but the selection limit was reached at all rates of recombination.ConclusionsHigher recombination rates can enhance the efficiency of breeding programs to turn genetic variation into response to selection. However, to increase response to selection significantly, the recombination rate would need to be increased 10- or 20-fold. The biological feasibility and consequences of such large increases in recombination rates are unknown

Bovine glycomacropeptide promotes the growth of Bifidobacterium longum ssp. infantis and modulates its gene expression

peer-reviewedBovine milk glycomacropeptide (GMP) is derived from κ-casein, with exclusively o-linked glycosylation. Glycomacropeptide promoted the growth of Bifidobacterium longum ssp. infantis in a concentration-dependent manner, and this activity was lost following periodate treatment of the GMP (GMP-P), which disables biological recognition of the conjugated oligosaccharides. Transcriptional analysis of B. longum ssp. infantis following exposure to GMP revealed a substantial response to GMP relative to bacteria treated with GMP-P, with a greater number of differentially expressed transcripts and larger fold changes versus the control. Therefore, stimulation of B. longum ssp. infantis growth by GMP is intrinsically linked to the peptide's O-linked glycosylation. The pool of differentially expressed transcripts included 2 glycoside hydrolase (family 25) genes, which were substantially upregulated following exposure to GMP, but not GMP-P. These GH25 genes were present in duplicated genomic islands that also contained genes encoding fibronectin type III binding domain proteins and numerous phage-related proteins, all of which were also upregulated. Homologs of this genomic arrangement were present in other Bifidobacterium species, which suggest it may be a conserved domain for the utilization of glycosylated peptides. This study provides insights into the molecular basis for the prebiotic effect of bovine milk GMP on B. longum ssp. infantis

Mining Milk for Factors which Increase the Adherence of Bifidobacterium longum subsp. infantis to Intestinal Cells

peer-reviewedBifidobacteria play a vital role in human nutrition and health by shaping and maintaining the gut ecosystem. In order to exert a beneficial effect, a sufficient population of bifidobacteria must colonise the host. In this study, we developed a miniaturised high-throughput in vitro assay for assessing the colonising ability of bacterial strains in human cells. We also investigated a variety of components isolated from different milk sources for their ability to increase the adherence of Bifidobacterium longum subsp. infantis ATCC 15697, a common member of the gastrointestinal microbiota of breastfed infants, to HT-29 cells. Both conventional and miniaturised colonisation assays were employed to examine the effect of 13 different milk-derived powders on bacterial adherence, including positive controls which had previously resulted in increased bifidobacterial adherence (human milk oligosaccharides and a combination of 3′- and 6′-sialylactose) to intestinal cells. Immunoglobulin G enriched from bovine whey and goat milk oligosaccharides resulted in increased adhesion (3.3- and 8.3-fold, respectively) of B. infantis to the intestinal cells and the miniaturised and conventional assays were found to yield comparable and reproducible results. This study highlights the potential of certain milk components to favourably modulate adhesion of bifidobacteria to human intestinal cells

Continuation of immunosuppression vs. immunosuppression weaning in potential repeat kidney transplant candidates: a care management perspective

Management of immunosuppression in patients with a failing or failed kidney transplant requires a complete assessment of their clinical condition. One of the major considerations in determining immunosuppression is whether or not such an individual is considered a candidate for re-transplantation. Withdrawal of immunosuppression in a re-transplant candidate can result in allosensitization and markedly reduce the chances of a repeat transplant. In this review, we summarize the effects of immunosuppression reduction on HLA sensitization, discuss the impacts of allosensitization in these patients, and explore reduction protocols and future directions. Risks of chronic immunosuppression, medical management of the failing allograft, and the effect of nephrectomy are covered elsewhere in this issue

Series: Public engagement with research. Part 3: Sharing power and building trust through partnering with communities in primary care research

Background : This article focuses on potential strategies to support primary care researchers in working in partnership with the public and healthcare professionals. Partnership working can potentially to improve the relevance and usefulness of research and ensure better research and health outcomes. Discussion : We describe what we mean by partnership working and the importance of reflecting on power and building trusting relationships. To share power in partnership working, it is essential to critically reflect on the multiple dimensions of power, their manifestations, and your own power. Power can influence relationships and therefore, it is essential to build trust with partners. Next, we outline how the context of primary care research and decisions about who you work with and how to work together, are vital considerations that are imbued with power. Lastly, we suggest different ways of working in partnership to address different dimensions of power. We provide examples from primary care research across Europe regarding how to recognise, tackle, and challenge, invisible, hidden and visible power. Conclusion : We conclude by proposing three calls to actions to encourage researchers working in primary care to consider the multiple dimensions of power and move towards partnership working. First is to use participatory methods to improve the inclusivity of your research. Second is to include patients and the public in decisions about the design, delivery and development of research and its outcomes. Third is to address various systemic and institutional barriers which hinder partnership working