Extended LTA, TNF, LST1 and HLA Gene Haplotypes and Their Association with Rubella Vaccine-Induced Immunity

Recent studies have suggested the importance of HLA genes in determining immune responses following rubella vaccine. The telomeric class III region of the HLA complex harbors several genes, including lymphotoxin alpha (LTA), tumor necrosis factor (TNF) and leukocyte specific transcript -1 (LST1) genes, located between the class I B and class II DRB1 loci. Apart from HLA, little is known about the effect of this extended genetic region on HLA haplotypic backgrounds as applied to immune responses.We examined the association between immune responses and extended class I-class II-class III haplotypes among 714 healthy children after two doses of rubella vaccination. These extended haplotypes were then compared to the HLA-only haplotypes. The most significant association was observed between haplotypes extending across the HLA class I region, ten-SNP haplotypes, and the HLA class II region (i.e. A-C-B-LTA-TNF-LST1-DRB1-DQA1-DQB1-DPA1-DPB1) and rubella-specific antibodies (global p-value of 0.03). Associations were found between both extended A*02-C*03-B*15-AAAACGGGGC-DRB1*04-DQA1*03-DQB1*03-DPA1*01-DPB1*04 (p = 0.002) and HLA-only A*02-C*03-B*15-DRB1*04-DQA1*03-DQB1*03-DPA1*01-DPB1*04 haplotypes (p = 0.009) and higher levels of rubella antibodies. The class II HLA-only haplotype DRB1*13-DQA1*01-DQB1*06-DPA1*01-DPB1*04 (p = 0.04) lacking LTA-TNF-LST1 SNPs was associated with lower rubella antibody responses. Similarly, the class I-class II HLA-only A*01-C*07-B*08-DRB1*03-DQA1*05-DQB1*02-DPA1*01-DPB1*04 haplotype was associated with increased TNF-alpha secretion levels (p = 0.009). In contrast, the extended AAAACGGGGC-DRB1*01-DQA1*01-DQB1*05-DPA1*01-DPB1*04 (p = 0.01) haplotype was found to trend with decreased rubella-specific IL-6 secretion levels.These data suggest the importance of examining both HLA genes and genes in the class III region as part of the extended haplotypes useful in understanding genomic drivers regulating immune responses to rubella vaccine

The impact of microbial composition on postprandial glycaemia and lipidaemia: A systematic review of current evidence

Postprandial hyperglycaemia is associated with increased risk of cardiovascular disease. Recent studies highlight the role of the gut microbiome in influencing postprandial glycaemic (PPG) and lipidaemic (PPL) responses. The authors of this review sought to address the question: “To what extent does individual gut microbiome diversity and composition contribute to PPG and PPL responses?” CINAHL Plus, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from January 2010 to June 2020. Following screening, 22 studies were eligible to be included in the current review. All trials reported analysis of gut microbiome diversity and composition and PPG and/or PPL. Results were reported according to the ‘Preferred Reporting Items for Systematic Reviews and Meta-Analysis’ (PRISMA) statement. Individual microbiota structure was found to play a key role in determining postprandial metabolic responses in adults and is attributed to a complex interplay of diet, microbiota composition, and metagenomic activity, which may be predicted by metagenomic analysis. Alterations of gut microbiota, namely relative abundance of bacterial phylum Actinobacteria and Proteobacteria, along with Enterobacteriaceae, were associated with individual variation in postprandial glycaemic response in adults. The findings of the current review present new evidence to support a personalised approach to nutritional recommendations and guidance for optimal health, management, and treatment of common metabolic disorders. In conclusion, personalised nutrition approaches based on individual microbial composition may improve postprandial regulation of glucose and lipids, providing a potential strategy to ameliorate cardiometabolic health outcomes

Addressing fluorogenic real-time qPCR inhibition using the novel custom Excel file system 'FocusField2-6GallupqPCRSet-upTool-001' to attain consistently high fidelity qPCR reactions

The purpose of this manuscript is to discuss fluorogenic real-time quantitative polymerase chain reaction (qPCR) inhibition and to introduce/define a novel Microsoft Excel-based file system which provides a way to detect and avoid inhibition, and enables investigators to consistently design dynamically-sound, truly LOG-linear qPCR reactions very quickly. The qPCR problems this invention solves are universal to all qPCR reactions, and it performs all necessary qPCR set-up calculations in about 52 seconds (using a pentium 4 processor) for up to seven qPCR targets and seventy-two samples at a time – calculations that commonly take capable investigators days to finish. We have named this custom Excel-based file system "FocusField2-6GallupqPCRSet-upTool-001" (FF2-6-001 qPCR set-up tool), and are in the process of transforming it into professional qPCR set-up software to be made available in 2007. The current prototype is already fully functional

Whose Science and whose Religion? Reflections on the Relations between Scientific and Religious Worldviews

Arguments about the relationship between science and religion often proceed by identifying a set of essential characteristics of scientific and religious worldviews and arguing on the basis of these characteristics for claims about a relationship of conflict or compatibility between them. Such a strategy is doomed to failure because science, to some extent, and religion, to a much larger extent, are cultural phenomena that are too diverse in their expressions to be characterized in terms of a unified worldview. In this paper I follow a different strategy. Having offered a loose characterization of the nature of science, I pose five questions about specific areas where religious and scientific worldviews may conflict - questions about the nature of faith, the belief in a God or Gods, the authority of sacred texts, the relationship between scientific and religious conceptions of the mind/soul, and the relationship between scientific and religious understandings of moral behavior. My review of these questions will show that they cannot be answered unequivocally because there is no agreement amongst religious believers as to the meaning of important religious concepts. Thus, whether scientific and religious worldviews conflict depends essentially upon whose science and whose religion one is considering. In closing, I consider the implications of this conundrum for science education

Marketing Renewable Energy in the United Kingdom

This chapter focuses on the renewable energy market in the UK. First we discuss the impact of privatization, then show what preconditions might be important. The main conclusion drawn from the analysis is that in the UK, as well as in other countries, new policy frameworks need to guide the transition from an energy system designed to achieve short-term efficiencies through market operation to a long-term approach that would embrace new uncertainties. Both market interests and environmental protection need to be secured in order to guarantee the levels of investment needed in the UK’s renewable energy market

Computing the effective action with the functional renormalization group

The \u201cexact\u201d or \u201cfunctional\u201d renormalization group equation describes the renormalization group flow of the effective average action \u393 k. The ordinary effective action \u393 0 can be obtained by integrating the flow equation from an ultraviolet scale k= \u39b down to k= 0. We give several examples of such calculations at one-loop, both in renormalizable and in effective field theories. We reproduce the four-point scattering amplitude in the case of a real scalar field theory with quartic potential and in the case of the pion chiral Lagrangian. In the case of gauge theories, we reproduce the vacuum polarization of QED and of Yang\u2013Mills theory. We also compute the two-point functions for scalars and gravitons in the effective field theory of scalar fields minimally coupled to gravity. \ua9 2016, The Author(s)

Pyrimidine biosynthesis is not an essential function for trypanosoma brucei bloodstream forms

<p>Background: African trypanosomes are capable of both pyrimidine biosynthesis and salvage of preformed pyrimidines from the host, but it is unknown whether either process is essential to the parasite.</p> <p>Methodology/Principal Findings: Pyrimidine requirements for growth were investigated using strictly pyrimidine-free media, with or without single added pyrimidine sources. Growth rates of wild-type bloodstream form Trypanosoma brucei brucei were unchanged in pyrimidine-free medium. The essentiality of the de novo pyrimidine biosynthesis pathway was studied by knocking out the PYR6-5 locus that produces a fusion product of orotate phosphoribosyltransferase (OPRT) and Orotidine Monophosphate Decarboxylase (OMPDCase). The pyrimidine auxotroph was dependent on a suitable extracellular pyrimidine source. Pyrimidine starvation was rapidly lethal and non-reversible, causing incomplete DNA content in new cells. The phenotype could be rescued by addition of uracil; supplementation with uridine, 2′deoxyuridine, and cytidine allowed a diminished growth rate and density. PYR6-5−/− trypanosomes were more sensitive to pyrimidine antimetabolites and displayed increased uracil transport rates and uridine phosphorylase activity. Pyrimidine auxotrophs were able to infect mice although the infection developed much more slowly than infection with the parental, prototrophic trypanosome line.</p> <p>Conclusions/Significance: Pyrimidine salvage was not an essential function for bloodstream T. b. brucei. However, trypanosomes lacking de novo pyrimidine biosynthesis are completely dependent on an extracellular pyrimidine source, strongly preferring uracil, and display reduced infectivity. As T. brucei are able to salvage sufficient pyrimidines from the host environment, the pyrimidine biosynthesis pathway is not a viable drug target, although any interruption of pyrimidine supply was lethal.</p&gt

Automated Counting of Bacterial Colony Forming Units on Agar Plates

Manual counting of bacterial colony forming units (CFUs) on agar plates is laborious and error-prone. We therefore implemented a colony counting system with a novel segmentation algorithm to discriminate bacterial colonies from blood and other agar plates