Proteomic analysis of Bifidobacterium longum subsp. infantis reveals the metabolic insight on consumption of prebiotics and host glycans.

Bifidobacterium longum subsp. infantis is a common member of the intestinal microbiota in breast-fed infants and capable of metabolizing human milk oligosaccharides (HMO). To investigate the bacterial response to different prebiotics, we analyzed both cell wall associated and whole cell proteins in B. infantis. Proteins were identified by LC-MS/MS followed by comparative proteomics to deduce the protein localization within the cell. Enzymes involved in the metabolism of lactose, glucose, galactooligosaccharides, fructooligosaccharides and HMO were constitutively expressed exhibiting less than two-fold change regardless of the sugar used. In contrast, enzymes in N-Acetylglucosamine and sucrose catabolism were induced by HMO and fructans, respectively. Galactose-metabolizing enzymes phosphoglucomutase, UDP-glucose 4-epimerase and UTP glucose-1-P uridylytransferase were expressed constitutively, while galactokinase and galactose-1-phosphate uridylyltransferase, increased their expression three fold when HMO and lactose were used as substrates for cell growth. Cell wall-associated proteomics also revealed ATP-dependent sugar transport systems associated with consumption of different prebiotics. In addition, the expression of 16 glycosyl hydrolases revealed the complete metabolic route for each substrate. Mucin, which possesses O-glycans that are structurally similar to HMO did not induced the expression of transport proteins, hydrolysis or sugar metabolic pathway indicating B. infantis do not utilize these glycoconjugates

TOX3 mutations in breast cancer

TOX3 maps to 16q12, a region commonly lost in breast cancers and recently implicated in the risk of developing breast cancer. However, not much is known of the role of TOX3 itself in breast cancer biology. This is the first study to determine the importance of TOX3 mutations in breast cancers. We screened TOX3 for mutations in 133 breast tumours and identified four mutations (three missense, one in-frame deletion of 30 base pairs) in six primary tumours, corresponding to an overall mutation frequency of 4.5%. One potentially deleterious missense mutation in exon 3 (Leu129Phe) was identified in one tumour (genomic DNA and cDNA). Whilst copy number changes of 16q12 are common in breast cancer, our data show that mutations of TOX3 are present at low frequency in tumours. Our results support that TOX3 should be further investigated to elucidate its role in breast cancer biology.Breast Cancer Research Foundation grant; University of Cambridge; Cancer Research UK; Hutchison Whampoa Limited; NIHR Cambridge Biomedical Research Centre; Marie Curie Career Integration Grant; Cancer Research UK [16942]; National Institute for Health Research [NF-SI-0611-10154

Emotional Graphic Cigarette Warning Labels Reduce the Electrophysiological Brain Response to Smoking Cues

There is an ongoing public debate about the new graphic warning labels (GWLs) that the Food and Drug Administration (FDA) proposes to place on cigarette packs. Tobacco companies argued that the strongly emotional images FDA proposed to include in the GWLs encroached on their constitutional rights. The court ruled that FDA did not provide sufficient scientific evidence of compelling public interest in such encroachment. This study\u27s objectives were to examine the effects of the GWLs on the electrophysiological and behavioral correlates of smoking addiction and to determine whether labels rated higher on the emotional reaction (ER) scale are associated with greater effects. We studied 25 non-treatment-seeking smokers. Event-related potentials (ERPs) were recorded while participants viewed a random sequence of paired images, in which visual smoking (Cues) or non-smoking (non-Cues) images were preceded by GWLs or neutral images. Participants reported their cigarette craving after viewing each pair. Dependent variables were magnitude of P300 ERPs and self-reported cigarette craving in response to Cues. We found that subjective craving response to Cues was significantly reduced by preceding GWLs, whereas the P300 amplitude response to Cues was reduced only by preceding GWLs rated high on the ER scale. In conclusion, our study provides experimental neuroscience evidence that weighs in on the ongoing public and legal debate about how to balance the constitutional and public health aspects of the FDA-proposed GWLs. The high toll of smoking-related illness and death adds urgency to the debate and prompts consideration of our findings while longitudinal studies of GWLs are underway

Estrogen-Dependent Epigenetic Regulation of Soluble Epoxide Hydrolase via DNA Methylation

To elucidate molecular mechanisms responsible for the sexually dimorphic phenotype of soluble epoxide hydrolase (sEH) expression, we tested the hypothesis that female-specific down-regulation of sEH expression is driven by estrogen-dependent methylation of the Ephx2 gene. Mesenteric arteries isolated from male, female, ovariectomized female (OV), and OV with estrogen replacement (OVE) mice, as well as the human cell line (HEK293T) were used. Methylation-specific PCR and bisulfite genomic sequencing analysis indicate significant increases in DNA/CG methylation in vessels of female and OVE compared with those of male and OV mice. The same increase in CG methylation was also observed in male vessels incubated with a physiological concentration of 17beta-estradiol (17beta-E2) for 48 hours. All vessels that displayed increases in CG methylation were concomitantly associated with decreases in their Ephx2 mRNA and protein, suggesting a methylation-induced gene silencing. Transient transfection assays indicate that the activity of Ephx2 promoter-coding luciferase was significantly attenuated in HEK293T cells treated with 17beta-E2, which was prevented by additional treatment with an estrogen receptor antagonist (ICI). ChIP analysis indicates significantly reduced binding activities of transcription factors (including SP1, AP-1, and NF-kappaB with their binding elements located in the Ephx2 promoter) in vessels of female mice and human cells treated with 17beta-E2, responses that were prevented by ICI and Decitabine (DNA methyltransferase inhibitor), respectively. In conclusion, estrogen/estrogen receptor-dependent methylation of the promoter of Ephx2 gene silences sEH expression, which is involved in specific transcription factor-directed regulatory pathways

Lithium in the Intermediate-Age Open Cluster, NGC 3680

High-dispersion spectra centered on the Li 6708 A line have been obtained for 70 potential members of the open cluster NGC 3680, with an emphasis on stars in the turnoff region. A measurable Li abundance has been derived for 53 stars, 39 of which have radial velocities and proper motions consistent with cluster membership. After being transferred to common temperature and abundance scales, previous Li estimates have been combined to generate a sample of 49 members, 40 of which bracket the cluster Li-dip. Spectroscopic elemental analysis of 8 giants and 5 turnoff stars produces [Fe/H] = -0.17 +/- 0.07 (sd) and -0.07 +/- 0.02 (sd), respectively. We also report measurements of Ca, Si and Ni which are consistent with scaled-solar ratios within the errors. Adopting [Fe/H] = -0.08 (Sect. 3.6), Y^2 isochrone comparisons lead to an age of 1.75 +/- 0.10 Gyr and an apparent modulus of (m-M) = 10.30 +/- 0.15 for the cluster, placing the center of the Li-dip at 1.35 +/- 0.03 solar masses. Among the giants, 5 of 9 cluster members are now known to have measurable Li with A(Li) near 1.0. A combined sample of dwarfs in the Hyades and Praesepe is used to delineate the Li-dip profile at 0.7 Gyr and [Fe/H] = +0.15, establishing its center at 1.42 +/- 0.02 solar masses and noting the possible existence of secondary dip on its red boundary. When evolved to the typical age of the clusters NGC 752, IC 4651 and NGC 3680, the Hyades/Praesepe Li-dip profile reproduces the observed morphology of the combined Li-dip within the CMD's of the intermediate-age clusters while implying a metallicity dependence for the central mass of the Li-dip given by Mass = (1.38 +/-0.04) + (0.4 +/- 0.2)[Fe/H]. The implications of the similarity of the Li-dichotomy among giants in NGC 752 and IC 4651 and the disagreement with the pattern among NGC 3680 giants are discussed.Comment: Latex ms. is 56 pages, including 10 figures and 4 tables. Accepted for the Astronomical Journa

The quest for modernisation of traditional Chinese medicine.

Traditional Chinese medicine (TCM) is an integral part of mainstream medicine in China. Due to its worldwide use, potential impact on healthcare and opportunities for new drug development, TCM is also of great international interest. Recently, a new era for modernisation of TCM was launched with the successful completion of the Good Practice in Traditional Chinese Medicine Research in the Post-genomic Era (GP-TCM) project, the European Union's Seventh Framework Programme (FP7) coordination action on TCM research. This 3.5-year project that involved inputs from over 200 scientists resulted in the production of 20 editorials and in-depth reviews on different aspects of TCM that were published in a special issue of Journal of Ethnopharmacology (2012; volume 140, issue 3). In this narrative review, we aim to summarise the findings of the FP7 GP-TCM project and highlight the relevance of TCM to modern medicine within a historical and international context. Advances in TCM research since the 1950s can be characterised into three phases: Phase I (1950s-1970s) was fundamental for developing TCM higher education, research and hospital networks in China; Phase II (1980s-2000s) was critical for developing legal, economic and scientific foundations and international networks for TCM; and Phase III (2011 onwards) is concentrating on consolidating the scientific basis and clinical practice of TCM through interdisciplinary, interregional and intersectoral collaborations. Taking into account the quality and safety requirements newly imposed by a globalised market, we especially highlight the scientific evidence behind TCM, update the most important milestones and pitfalls, and propose integrity, integration and innovation as key principles for further modernisation of TCM. These principles will serve as foundations for further research and development of TCM, and for its future integration into tomorrow's medicine.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

Nuclearity of Semigroup C*-algebras

We study the semigroup C*-algebra of a positive cone P of a weakly quasi-lattice ordered group. That is, P is a subsemigroup of a discrete group G with P\cap P^{-1}=\{e\} and such that any two elements of P with a common upper bound in P also have a least upper bound. We find sufficient conditions for the semigroup C*-algebra of P to be nuclear. These conditions involve the idea of a generalised length function, called a "controlled map", into an amenable group. Here we give a new definition of a controlled map and discuss examples from different sources. We apply our main result to establish nuclearity for semigroup C*-algebras of a class of one-relator semigroups, motivated by a recent work of Li, Omland and Spielberg. This includes all the Baumslag--Solitar semigroups. We also analyse semidirect products of weakly quasi-lattice ordered groups and use our theorem in examples to prove nuclearity of the semigroup C*-algebra. Moreover, we prove that the graph product of weak quasi-lattices is again a weak quasi-lattice, and show that the corresponding semigroup C*-algebra is nuclear when the underlying groups are amenable.Comment: 36 pages, to appear in Journal of Functional Analysis, minor changes from previous versio