Human metabolic phenotypes link directly to specific dietary preferences in healthy individuals

Individual human health is determined by a complex interplay between genes, environment, diet, lifestyle, and symbiotic gut microbial activity. Here, we demonstrate a new "nutrimetabonomic" approach in which spectroscopically generated metabolic phenotypes are correlated with behavioral/psychological dietary preference, namely, "chocolate desiring" or "chocolate indifferent". Urinary and plasma metabolic phenotypes are characterized by differential metabolic biomarkers, measured using 1H NMR spectroscopy, including the postprandial lipoprotein profile and gut microbial co-metabolism. These data suggest that specific dietary preferences can influence basal metabolic state and gut microbiome activity that in turn may have long-term health consequences to the host. Nutrimetabonomics appears as a promising approach for the classification of dietary responses in populations and personalized nutritional management.     

Comparison of the CopB systems of plasmids R1 and Co1V2-K94: A single base alteration in CopB gene is responsible for the increased copy number of the low copy number plasmid CoIV2-K94

Summary We have isolated a deletion mutation and a point mutation in the copB gene of the replication region Repl of the IncFI plasmid Co1V2-K94. Subsequently, this copB gene with and without point mutation was cloned and sequenced, and the point mutation was mapped in the coding region of copB with a change of one amino acid from arginine to serine. Furthermore, this copB mutant had an approximately 10-fold increase in copy number. The CopB-phenotype of Co1V2-K94 could be complemented in trans by the copB gene of coresident IncFII plasmids such as R1 and R538, but not R100, suggesting that ColV2-K94 and R1 or R538 contain the same copB allele.     

Nutritional metabonomics: applications and perspectives

Nowadays, nutrition focuses on improving health of individuals through diet. Current nutritional research aims at health promotion, disease prevention, and performance improvement. Modern analytical platforms allow the simultaneous measurement of multiple metabolites providing new insights in the understanding of the functionalities of cells and whole organisms. Metabonomics, "the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modifications", provides a systems approach to understanding global metabolic regulations of organisms. This concept has arisen from various applications of NMR and MS spectroscopies to study the multicomponent metabolic composition of biological fluids, cells, and tissues. The generated metabolic profiles are processed by multivariate statistics to maximize the recovery of information to be correlated with well-determined stimuli such as dietary intervention or with any phenotypic data or diet habits. Metabonomics is thus uniquely suited to assess metabolic responses to deficiencies or excesses of nutrients and bioactive components. Furthermore, metabonomics is used to characterize the metabolic phenotype of individuals integrating genetic polymorphism, metabolic interactions with commensal and symbiotic partners such as gut microflora, as well as environmental and behavioral factors including dietary preferences. This paper reports several experimental key aspects in nutritional metabonomics, reviews its applications employing targeted and holistic approach analysis for the study of the metabolic responses following dietary interventions. It also reports the assessment of intra- and inter-individual variability in animal and human populations. The potentialities of nutritional metabonomics for the discovery of new biomarkers and the characterization of metabolic phenotypes are discussed in a context of their possible utilizations for personalized nutrition to provide health maintenance at the individual level.     

Tumor metastasis in an orthotopic murine model of head and neck cancer: possible role of TGF-beta 1 secreted by the tumor cells

In an orthotopic murine model of head and neck cancer, combined subcutaneous and intratumoral vaccination with recombinant vaccinia virus expressing interleukin-2 (rvv-IL-2) induced significant tumor regression early on therapy. However, its efficacy was restricted by recurrent tumor growth and loco-regional metastases. In this study, we explored the mechanism of tumor metastasis. We compared the levels of expression of a number of molecules involved in tumor metastasis, which included transforming growth factor-beta1 (TGF-beta1), E-cadherin, matrix metalloproteinases (MMPs): MT1-MMP, MMP-2, MMP-9, their tissue inhibitors (TIMPs): TIMP-1/TIMP-2, and pro-angiogenic factors CD31, VEGF-R2, and iNOS between primary and metastatic tumors by real-time RT-PCR and immunohistochemistry. We detected spontaneous lymph node and tongue metastasis. Metastasis was delayed in rvv-IL-2 treated mice. Cultured tumor cells expressed negligible amount of TGF-beta1. Untreated or metastatic tumors, on the other hand, expressed high levels of TGF-beta1 and secreted TGF-beta1 in the sera of tumor-bearing mice. Levels of TGF-beta1 in the sera suddenly jumped at the time when tumor metastasis started. In the metastatic tumors, levels of MT1-MMP, MMP-2, and MMP-9 were significantly elevated (P < 0.001), while levels of TIMP-1/TIMP-2 and E-cadherin were decreased (P < 0.001) compared to control or primary tumors. Levels of CD31, VEGF-R2, and iNOS were also significantly elevated in the metastatic lesions (P < 0.001). The concurrence of high levels of TGF-beta1 in the sera, expression of proteins involved in metastasis and initiation of metastasis suggested possible role of TGF-beta1 in on setting the metastatic cascade in this model.     

Contributions of traT and iss genes to the serum resistance phenotype of plasmid ColV2-K94

Abstract A genetic determinant for serum resistance, designated iss , has been found previously on the colicinogenic plasmid ColV2-K94. In this work we have identified a second serum resistance gene, traT , on ColV2-K94. The serum resistance mediated by derivatives of ColV2-K94 was due to presence of one or both of the iss and traT genes. Plasmid pWS12 (TraT⁺ Iss⁺) contained the kanamycin (Km) resistance transposon Tn 903 inserted near the origin of replication of ColV2-K94, and plasmids pWS15 (TraT⁺), pWS16 (TraT⁺) and pWS18 (TraT⁺ Iss⁺) were deletion derivatives of pWS12 constructed in vitro and in vivo. pWS12 and pWS18 conferred a 20-fold increase in relative resistance to 20% guinea pig serum when introduced into the serum-susceptible, genetically defined recA strain of Escherichia coli K-12, AB2463. Plasmids pWS15 and pWS16, from which iss had been deleted, still conferred 5-fold increases in relative resistance on AB2463. The level of resistance conferred on this strain by the antibiotic resistance plasmid R100–1 (which expresses the traT serum resistance gene) was comparable to that of plasmids pWS15 and pWS16. The 25-kDa traT gene product was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis of the outer membrane proteins of strain AB2463 carrying ColV2-K94. This protein cross-reacted immunologically with the traT protein expressed by F or R100–1. Our results indicated that both traT and iss are capable of mediating serum resistance in ColV2-K94.     

Gut-associated immune effector responses in immunocompetent and immunocomprimised mice with Giardia lamblia

Abstract Significantly higher Giardia lamblia trophozoites load in the intestine of infected mice accompanied pronounced influx of suppressor/cytotoxic T cells (Lyt 2.2⁺), T cells (Thy 1.2⁺) and significant reduction in IgA-containing cells in the gut during the establishment and peak phases of infection. The induction of helper/inducer T cells (Lyt 1.1⁺) and significant enhancement of IgA-containing cells in gut resulted in the decline of the trophozoite loads. However, the prior treatment of animals with dexamethasone alone resulted in significant reduction in helper/inducer T cells (Lyt 1.1⁺) and the IgA-containing cells in the gut; the percents of suppressor/cytotoxic T cells (Lyt 2.2⁺) and IgM-containing cells remained unaltered. Although the G. lamblia infection in such animals further significantly increased the influx of suppressor/cytotoxic T cells, the late response of helper/inducer T cells and IgA-containing cells was abrogated during the decline phase of infection. The significant reduction in the trophozoite load — despite immuno-suppressive therapy — appeared to be due to unaltered IgM response in such animals which probably took over the function of IgA in defense against G. lamblia . The data of the investigation thus suggested a role of helper/inducer T cells and antibodies producing cells in gut as important effector cells resulting in the termination of primary G. lamblia infection.     

Multi-layered Graphene Silica-Based Tunable Absorber for Infrared Wavelength Based on Circuit Theory Approach

Graphene can be utilized as a tunable material for a wide range of infrared wavelength regions due to its tunable conductivity property. In this paper, we use Y-shaped silver material resonator placed over the top of multiple graphene silica-layered structures to realize the perfect absorption over the infrared wavelength region. We propose four different designs by placing the graphene sheet over silica. The absorption and reflectance performance of the structures have been explored for 1500- to 1600-nm wavelength range. The proposed design also explores the absorption tunability of the structure for the different values of graphene chemical potential. We have reported the negative impedance for the perfect absorption for proposed metamaterial absorber structures. All the metamaterial absorbers have reported 99% of its absorption peaks in the infrared wavelength region. These designs can be used as a tunable absorber for narrowband and wideband applications. The proposed designs will become the basic building block of large photonics design which will be applicable for polariser, sensor, and solar applications.

     

Design of a New Peptide Substrate Probe of the Putative Biomarker Legumain with Potential Application in Prostate Cancer Diagnosis Ex Vivo

International Journal of Peptide Research and Therapeutics - The lysosomal endoprotease legumain (asparaginyl endoprotease) has been proposed as a putative biomarker in prostate tumours, in which...