Gut Microbiome: Profound Implications For Diet And Disease

The gut microbiome plays an important role in human health and influences the development of chronic diseases ranging from metabolic disease to gastrointestinal disorders and colorectal cancer. Of increasing prevalence in Western societies, these conditions carry a high burden of care. Dietary patterns and environmental factors have a profound effect on shaping gut microbiota in real time. Diverse populations of intestinal bacteria mediate their beneficial effects through the fermentation of dietary fiber to produce short-chain fatty acids, endogenous signals with important roles in lipid homeostasis and reducing inflammation. Recent progress shows that an individual’s starting microbial profile is a key determinant in predicting their response to intervention with live probiotics. The gut microbiota is complex and challenging to characterize. Enterotypes have been proposed using metrics such as alpha species diversity, the ratio of Firmicutes to Bacteroidetes phyla, and the relative abundance of beneficial genera (e.g., Bifidobacterium, Akkermansia) versus facultative anaerobes (E. coli), pro-inflammatory Ruminococcus, or nonbacterial microbes. Microbiota composition and relative populations of bacterial species are linked to physiologic health along different axes. We review the role of diet quality, carbohydrate intake, fermentable FODMAPs, and prebiotic fiber in maintaining healthy gut flora. The implications are discussed for various conditions including obesity, diabetes, irritable bowel syndrome, inflammatory bowel disease, depression, and cardiovascular disease

Quantitative Interpretation of a Genetic Model of Carcinogenesis Using Computer Simulations

The genetic model of tumorigenesis by Vogelstein et al. (V theory) and the molecular definition of cancer hallmarks by Hanahan and Weinberg (W theory) represent two of the most comprehensive and systemic understandings of cancer. Here, we develop a mathematical model that quantitatively interprets these seminal cancer theories, starting from a set of equations describing the short life cycle of an individual cell in uterine epithelium during tissue regeneration. The process of malignant transformation of an individual cell is followed and the tissue (or tumor) is described as a composite of individual cells in order to quantitatively account for intra-tumor heterogeneity. Our model describes normal tissue regeneration, malignant transformation, cancer incidence including dormant/transient tumors, and tumor evolution. Further, a novel mechanism for the initiation of metastasis resulting from substantial cell death is proposed. Finally, model simulations suggest two different mechanisms of metastatic inefficiency for aggressive and less aggressive cancer cells. Our work suggests that cellular de-differentiation is one major oncogenic pathway, a hypothesis based on a numerical description of a cell's differentiation status that can effectively and mathematically interpret some major concepts in V/W theories such as progressive transformation of normal cells, tumor evolution, and cancer hallmarks. Our model is a mathematical interpretation of cancer phenotypes that complements the well developed V/W theories based upon description of causal biological and molecular events. It is possible that further developments incorporating patient- and tissue-specific variables may build an even more comprehensive model to explain clinical observations and provide some novel insights for understanding cancer

Dysmorphometrics: the modelling of morphological abnormalities

<p>Abstract</p> <p>Background</p> <p>The study of typical morphological variations using quantitative, morphometric descriptors has always interested biologists in general. However, unusual examples of form, such as abnormalities are often encountered in biomedical sciences. Despite the long history of morphometrics, the means to identify and quantify such unusual form differences remains limited.</p> <p>Methods</p> <p>A theoretical concept, called dysmorphometrics, is introduced augmenting current geometric morphometrics with a focus on identifying and modelling form abnormalities. Dysmorphometrics applies the paradigm of detecting form differences as outliers compared to an appropriate norm. To achieve this, the likelihood formulation of landmark superimpositions is extended with outlier processes explicitly introducing a latent variable coding for abnormalities. A tractable solution to this augmented superimposition problem is obtained using Expectation-Maximization. The topography of detected abnormalities is encoded in a dysmorphogram.</p> <p>Results</p> <p>We demonstrate the use of dysmorphometrics to measure abrupt changes in time, asymmetry and discordancy in a set of human faces presenting with facial abnormalities.</p> <p>Conclusion</p> <p>The results clearly illustrate the unique power to reveal unusual form differences given only normative data with clear applications in both biomedical practice & research.</p

Biological Roles of the O-Methyl Phosphoramidate Capsule Modification in Campylobacter jejuni.

Campylobacter jejuni is a major cause of bacterial gastroenteritis worldwide, and the capsular polysaccharide (CPS) of this organism is required for persistence and disease. C. jejuni produces over 47 different capsular structures, including a unique O-methyl phosphoramidate (MeOPN) modification present on most C. jejuni isolates. Although the MeOPN structure is rare in nature it has structural similarity to some synthetic pesticides. In this study, we have demonstrated, by whole genome comparisons and high resolution magic angle spinning NMR, that MeOPN modifications are common to several Campylobacter species. Using MeOPN biosynthesis and transferase mutants generated in C. jejuni strain 81-176, we observed that loss of MeOPN from the cell surface correlated with increased invasion of Caco-2 epithelial cells and reduced resistance to killing by human serum. In C. jejuni, the observed serum mediated killing was determined to result primarily from activation of the classical complement pathway. The C. jejuni MeOPN transferase mutant showed similar levels of colonization relative to the wild-type in chickens, but showed a five-fold drop in colonization when co-infected with the wild-type in piglets. In Galleria mellonella waxmoth larvae, the MeOPN transferase mutant was able to kill the insects at wild-type levels. Furthermore, injection of the larvae with MeOPN-linked monosaccharides or CPS purified from the wild-type strain did not result in larval killing, indicating that MeOPN does not have inherent insecticidal activity

Effects on 3-Mercaptohexan-1-ol Precursor Concentrations from Prolonged Storage of Sauvignon Blanc Grapes Prior to Crushing and Pressing

Formation of wine thiol precursors is a dynamic process, which can be influenced by vineyard and winery processing operations. With the aim of increasing thiol precursor concentrations, a study of the effects of storing machine-harvested Sauvignon blanc grapes prior to crushing and pressing was undertaken on a commercial scale. 3-Mercaptohexan-1-ol (3-MH) precursors, 2-<i>S</i>-glutathionylcaftaric acid (grape reaction product, GRP), glutathione (GSH) and a number of C6 compounds were assessed at several time points during the experiment. The concentration of the cysteine precursor to 3-MH doubled within 8 h and tripled after 30 h while the GSH and cysteinylglycine precursors increased in concentration roughly 1.5 times. (<i>E</i>)-2-Hexenal and GSH levels decreased as thiol precursors, GRP and C6 alcohols increased during storage. Principal component analysis revealed that precursors contributed to most of the variation within the samples over the storage period, with additional influence, primarily from GSH and GRP, as well as (<i>E</i>)-2-hexenal and (<i>Z</i>)-3-hexen-1-ol. Early storage time points were associated with higher concentrations of GSH and some unsaturated C6 compounds while longer storage times were most closely associated with higher thiol precursor and GRP concentrations. This study provides a detailed overview of interactions related to thiol precursor formation on a commercial scale and highlights the ability to manipulate precursor concentrations prior to grape crushing

Chemical Modification of a Bridging Ligand Inside a Metal–Organic Framework while Maintaining the 3D Structure

A new metal–organic framework (MOF) with amino groups situated inside the pores has been synthesized. This MOF has been modified by post-synthesis with two different functionalities. The crystal structures of the two functionalized MOFs clearly demonstrate that it is possible to transform the cavities of a MOF without modifying its original 3D structure. These unprecedented results open up tremendous possibilities in the field of MOF chemistry because many potential applications in the fields of catalysis, material science or nanochemistry can be envisaged when applying the reported synthetic pathway

3-D Lanthanide Metal-Organic Frameworks: Structure, Photoluminescence, and Magnetism

A series of isostructural three-dimensional metal-organic frameworks [Pr2(N-BDC)3(dmf)4]∞ (1), {[Eu2(N-BDC)3- (dmf)4] · 2DMF}∞ (2 · 2DMF), [Gd2(N-BDC)3(dmf)4]∞ (3), {[Tb2(N-BDC)3(dmf)4] · 2DMF}∞ (4 · 2DMF), {[Dy2(NBDC) 3(dmf)4] · 2DMF}∞ (5 · 2DMF) (N-H2BDC ) 2-amino1,4-benzenedicarboxylic acid; DMF ) N,N′-dimethylformamide) with cubic 412 · 63 topology have been synthesized using solvothermal conditions. The networks were generated via formation of a dinuclear Ln2 secondary building block, involving the dicarboxylate ligand as a bridge. The luminescent properties of the TbIII and EuIII complexes were studied and showed characteristic emissions at room temperature. Antiferromagnetic interactions between LnIII ions were observed from magnetic susceptibility data