RNA-Seq of \u3cem\u3eBorrelia burgdorferi\u3c/em\u3e in Multiple Phases of Growth Reveals Insights into the Dynamics of Gene Expression, Transcriptome Architecture, and Noncoding RNAs

Borrelia burgdorferi, the agent of Lyme disease, differentially expresses numerous genes and proteins as it cycles between mammalian hosts and tick vectors. Insights on regulatory mechanisms have been provided by earlier studies that examined B. burgdorferi gene expression patterns during cultivation. However, prior studies examined bacteria at only a single time point of cultivation, providing only a snapshot of what is likely a dynamic transcriptional program driving B. burgdorferi adaptations to changes during culture growth phases. To address that concern, we performed RNA sequencing (RNA-Seq) analysis of B. burgdorferi cultures at early-exponential, mid-exponential, and early-stationary phases of growth. We found that expression of nearly 18% of annotated B. burgdorferi genes changed significantly during culture maturation. Moreover, genome-wide mapping of the B. burgdorferi transcriptome in different growth phases enabled insight on transcript boundaries, operon structures, and identified numerous putative non-coding RNAs. These RNA-Seq data are discussed and presented as a resource for the community of researchers seeking to better understand B. burgdorferi biology and pathogenesis

Diabetes and tuberculosis: the impact of the diabetes epidemic on tuberculosis incidence.

BACKGROUND: Tuberculosis (TB) remains a major cause of mortality in developing countries, and in these countries diabetes prevalence is increasing rapidly. Diabetes increases the risk of TB. Our aim was to assess the potential impact of diabetes as a risk factor for incident pulmonary tuberculosis, using India as an example. METHODS: We constructed an epidemiological model using data on tuberculosis incidence, diabetes prevalence, population structure, and relative risk of tuberculosis associated with diabetes. We evaluated the contribution made by diabetes to both tuberculosis incidence, and to the difference between tuberculosis incidence in urban and rural areas. RESULTS: In India in 2000 there were an estimated 20.7 million adults with diabetes, and 900,000 incident adult cases of pulmonary tuberculosis. Our calculations suggest that diabetes accounts for 14.8% (uncertainty range 7.1% to 23.8%) of pulmonary tuberculosis and 20.2% (8.3% to 41.9%) of smear-positive (i.e. infectious) tuberculosis. We estimate that the increased diabetes prevalence in urban areas is associated with a 15.2% greater smear-positive tuberculosis incidence in urban than rural areas - over a fifth of the estimated total difference. CONCLUSION: Diabetes makes a substantial contribution to the burden of incident tuberculosis in India, and the association is particularly strong for the infectious form of tuberculosis. The current diabetes epidemic may lead to a resurgence of tuberculosis in endemic regions, especially in urban areas. This potentially carries a risk of global spread with serious implications for tuberculosis control and the achievement of the United Nations Millennium Development Goals.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Calcitonin Gene Peptides: The Diagnostic Value of Measurement in Medullary Thyroid Carcinoma

The calcitonin gene encodes a family of peptides, at least three of which normally circulate in man: calcitonin (CT), a calcium-lowering hormone; katacalcin (KC), a peptide of unknown function; and calcitonin gene-related peptide (CGRP), a neuropeptide and potent vasodilator. In a study of 45 patients with medullary thyroid carcinoma (MTC), plasma CGRP was elevated in approximately 50% of cases. Furthermore, CGRP levels did not correlate with CT levels. However, plasma KC was elevated in all cases, with a good correlation with CT levels, as has been noted previously. Measurement of CT or KC appears to be superior to measurement of CGRP for the detection of MTC

Quantitative analyses of interactions between SpoVG and RNA/DNA

The Borrelia burgdorferi SpoVG protein has previously been found to be a DNA- and RNA-binding protein. To aid in the elucidation of ligand motifs, affinities for numerous RNAs, ssDNAs, and dsDNAs were measured and compared. The loci used in the study were spoVG, glpFKD, erpAB, bb0242, flaB, and ospAB, with particular focus on the untranslated 5′ portion of the mRNAs. Performing binding and competition assays yielded that the 5′ end of spoVG mRNA had the highest affinity while the lowest observed affinity was to the 5’ end of flaB mRNA. Mutagenesis studies of spoVG RNA and ssDNA sequences suggested that the formation of SpoVG-nucleic acid complexes are not entirely dependent on either sequence or structure. Additionally, exchanging uracil for thymine in ssDNAs did not affect protein-nucleic acid complex formation

Saturated and trans-fatty acids in UK takeaway food

The aim of the study was to analyze the saturated fatty acid (SFA) and trans-fatty acid (TFA) contents of popular takeaway foods in the UK (including English, pizza, Chinese, Indian and kebab cuisine). Samples of meals were analyzed by an accredited public analyst laboratory for SFA and TFA. The meals were highly variable for SFA and TFA. English and Pizza meals had the highest median amount of SFA with 35.7 g/meal; Kebab meals were high in TFA with up to 5.2 g/meal. When compared to UK dietary reference values, some meals exceeded SFA and TFA recommendations from just one meal. Takeaway food would be an obvious target to reduce SFA and TFA contents and increase the potential of meeting UK recommendations. Strategies such as reformulation and smaller takeaway portion sizes warrant investigation

\u3cem\u3eBorrelia burgdorferi\u3c/em\u3e SpoVG DNA- and RNA-Binding Protein Modulates the Physiology of the Lyme Disease Spirochete

The SpoVG protein of Borrelia burgdorferi, the Lyme disease spirochete, binds to specific sites of DNA and RNA. The bacterium regulates transcription of spoVG during the natural tick-mammal infectious cycle and in response to some changes in culture conditions. Bacterial levels of spoVG mRNA and SpoVG protein did not necessarily correlate, suggesting that posttranscriptional mechanisms also control protein levels. Consistent with this, SpoVG binds to its own mRNA, adjacent to the ribosome-binding site. SpoVG also binds to two DNA sites in the glpFKD operon and to two RNA sites in glpFKD mRNA; that operon encodes genes necessary for glycerol catabolism and is important for colonization in ticks. In addition, spirochetes engineered to dysregulate spoVG exhibited physiological alterations

The Victorian Newsletter (Fall 1981)

The Victorian Newsletter is sponsored for the Victorian Group of Modern Language Association by the Western Kentucky University and is published twice annually.Tennyson and Carlyle: A Source for "The Eagle" / Paul F. Mattheisen -- The Schooling of John Bull: Form and Moral in Talbot Baines Reed's Boys' Stories and in Kipling's Stalky & Co. / Patrick Scott -- How It Struck A Contemporary: Tennyson's "Lancelot and Elaine" and Pre-Raphaelite Art / Catherine Barnes Stevenson -- Amours de Voyage and Matthew Arnold in Love: An Inquiry / Eugene R. August -- Tennyson's "Ulysses" as Rhetorical Monologue / Mary Saunders -- The Mathematical References to the Adoption of the Gregorian Calendar in Lewis Carroll's Alice's Adventures in Wonderland / Laurence Dreyer -- Self-Helpers and Self-Seekers: Some Changing Attitudes to Wealth, 1840-1910 / J. L. Winte

Effects of the pattern of glucocorticoid replacement on neural processing, emotional reactivity and well-being in healthy male individuals:study protocol for a randomised controlled trial

BACKGROUND: Deviation from the physiological glucocorticoid dynamics (circadian and underlying ultradian rhythmicity) is a common characteristic of various neuropsychiatric and endocrine disorders as well as glucocorticoid-based therapeutics. These states may be accompanied by neuropsychiatric symptomatology, suggesting continuous dynamic glucocorticoid equilibrium is essential for brain homeostasis. METHODS/DESIGN: The study consists of two parts. The preliminary stage of the study aims to validate (technically and pharmacologically) and optimise three different patterns of systemic cortisol administration in man. These patterns are based on the combinatory administration of metyrapone, to suppress endogenous cortisol production, and concurrent hydrocortisone replacement. The second, subsequent, core part of the study is a randomised, double-blinded, placebo-controlled, crossover study, where participants (healthy male individuals aged 18–60 years) will undergo all three hydrocortisone replacement schemes. During these infusion regimes, we plan a number of neurobehavioural tests and imaging of the brain to assess neural processing, emotional reactivity and perception, mood and self-perceived well-being. The psychological tests include: ecological momentary assessment, P1vital Oxford Emotional Test Battery and Emotional Potentiated Startle Test, Leeds Sleep Evaluation Questionnaire and the visual working memory task (n-back). The neuroimaging protocol combines magnetic resonance sequences that capture data related to the functional and perfusion status of the brain. DISCUSSION: Results of this clinical trial are designed to evaluate the impact (with possible mechanistic insights) of different patterns of daily glucocorticoid dynamics on neural processing and reactivity related to emotional perception and mood. This evidence should contribute to the optimisation of the clinical application of glucocorticoid-based therapeutics. TRIAL REGISTRATION: UK Clinical Research Network, IRAS Ref: 106181, UKCRN-ID-15236 (23 October 2013

Transcriptomic analysis of Clostridium thermocellum ATCC 27405 cellulose fermentation

<p>Abstract</p> <p>Background</p> <p>The ability of C<it>lostridium thermocellum </it>ATCC 27405 wild-type strain to hydrolyze cellulose and ferment the degradation products directly to ethanol and other metabolic byproducts makes it an attractive candidate for consolidated bioprocessing of cellulosic biomass to biofuels. In this study, whole-genome microarrays were used to investigate the expression of <it>C. thermocellum </it>mRNA during growth on crystalline cellulose in controlled replicate batch fermentations.</p> <p>Results</p> <p>A time-series analysis of gene expression revealed changes in transcript levels of ~40% of genes (~1300 out of 3198 ORFs encoded in the genome) during transition from early-exponential to late-stationary phase. K-means clustering of genes with statistically significant changes in transcript levels identified six distinct clusters of temporal expression. Broadly, genes involved in energy production, translation, glycolysis and amino acid, nucleotide and coenzyme metabolism displayed a decreasing trend in gene expression as cells entered stationary phase. In comparison, genes involved in cell structure and motility, chemotaxis, signal transduction and transcription showed an increasing trend in gene expression. Hierarchical clustering of cellulosome-related genes highlighted temporal changes in composition of this multi-enzyme complex during batch growth on crystalline cellulose, with increased expression of several genes encoding hydrolytic enzymes involved in degradation of non-cellulosic substrates in stationary phase.</p> <p>Conclusions</p> <p>Overall, the results suggest that under low substrate availability, growth slows due to decreased metabolic potential and <it>C. thermocellum </it>alters its gene expression to (i) modulate the composition of cellulosomes that are released into the environment with an increased proportion of enzymes than can efficiently degrade plant polysaccharides other than cellulose, (ii) enhance signal transduction and chemotaxis mechanisms perhaps to sense the oligosaccharide hydrolysis products, and nutrient gradients generated through the action of cell-free cellulosomes and, (iii) increase cellular motility for potentially orienting the cells' movement towards positive environmental signals leading to nutrient sources. Such a coordinated cellular strategy would increase its chances of survival in natural ecosystems where feast and famine conditions are frequently encountered.</p

Absorption of silicon from artesian aquifer water and its impact on bone health in postmenopausal women: a 12 week pilot study

<p>Abstract</p> <p>Background</p> <p>Decreased bone mineral density and osteoporosis in postmenopausal women represents a growing source of physical limitations and financial concerns in our aging population. While appropriate medical treatments such as bisphosphonate drugs and hormone replacement therapy exist, they are associated with serious side effects such as osteonecrosis of the jaw or increased cardiovascular risk. In addition to calcium and vitamin D supplementation, previous studies have demonstrated a beneficial effect of dietary silicon on bone health. This study evaluated the absorption of silicon from bottled artesian aquifer water and its effect on markers of bone metabolism.</p> <p>Methods</p> <p>Seventeen postmenopausal women with low bone mass, but without osteopenia or osteoporosis as determined by dual x-ray absorptiometry (DEXA) were randomized to drink one liter daily of either purified water of low-silicon content (PW) or silicon-rich artesian aquifer water (SW) (86 mg/L silica) for 12 weeks. Urinary silicon and serum markers of bone metabolism were measured at baseline and after 12 weeks and analyzed with two-sided t-tests with p < 0.05 defined as significant.</p> <p>Results</p> <p>The urinary silicon level increased significantly from 0.016 ± 0.010 mg/mg creatinine at baseline to 0.037 ± 0.014 mg/mg creatinine at week 12 in the SW group (p = 0.003), but there was no change for the PW group (0.010 ± 0.004 mg/mg creatinine at baseline vs. 0.009 ± 0.006 mg/mg creatinine at week 12, p = 0.679). The urinary silicon for the SW group was significantly higher in the silicon-rich water group compared to the purified water group (p < 0.01). NTx, a urinary marker of bone resorption did not change during the study and was not affected by the silicon water supplementation. No significant change was observed in the serum markers of bone formation compared to baseline measurements for either group.</p> <p>Conclusions</p> <p>These findings indicate that bottled water from artesian aquifers is a safe and effective way of providing easily absorbed dietary silicon to the body. Although the silicon did not affect bone turnover markers in the short-term, the mineral's potential as an alternative prevention or treatment to drug therapy for osteoporosis warrants further longer-term investigation in the future.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier: NCT01067508</p