From 1D coordination polymers to Metal Organic Frameworks by the use of 2-pyridyl oximes.

The synthesis and characterization of coordination polymers and metal-organic frameworks (MOFs) has attracted a significant interest over the last decades due to their fascinating physical properties, as well as their use in a wide range of technological, environmental, and biomedical applications. The initial use of 2-pyridyl oximic ligands such as pyridine-2 amidoxime (H2pyaox) and 2-methyl pyridyl ketoxime (Hmpko) in combination with 1,2,4,5-benzene tetracarboxylic acid (pyromellitic acid), H4pma, provided access to nine new compounds whose structures and properties are discussed in detail. Among them, [Zn2(pma)(H2pyaox)2(H2O)2]n (3) and [Cu4(OH)2(pma)(mpko)2]n (9) are the first MOFs based on a 2-pyridyl oxime with 9 possessing a novel 3,4,5,8-c net topology. [Zn2(pma)(H2pyaox)2]n (2), [Cu2(pma)(H2pyaox)2(DMF)2]n (6), and [Cu2(pma)(Hmpko)2(DMF)2]n (8) join a small family of coordination polymers containing an oximic ligand. 9 exhibits selectivity for FeIII ions adsorption, as was demonstrated by a variety of techniques including UV-vis, EDX, and magnetism. DC magnetic susceptibility studies in 9 revealed the presence of strong antiferromagnetic interactions between the metal centers, which lead to a diamagnetic ground state; it was also found that the magnetic properties of 9 are affected by the amount of the encapsulated Fe3+ ions, which is a very desirable property for the development of magnetism-based sensors

Systemic multicompartmental effects of the gut microbiome on mouse metabolic phenotypes

To characterize the impact of gut microbiota on host metabolism, we investigated the multicompartmental metabolic profiles of a conventional mouse strain (C3H/HeJ) (n=5) and its germ-free (GF) equivalent (n=5). We confirm that the microbiome strongly impacts on the metabolism of bile acids through the enterohepatic cycle and gut metabolism (higher levels of phosphocholine and glycine in GF liver and marked higher levels of bile acids in three gut compartments). Furthermore we demonstrate that (1) well-defined metabolic differences exist in all examined compartments between the metabotypes of GF and conventional mice: bacterial co-metabolic products such as hippurate (urine) and 5-aminovalerate (colon epithelium) were found at reduced concentrations, whereas raffinose was only detected in GF colonic profiles. (2) The microbiome also influences kidney homeostasis with elevated levels of key cell volume regulators (betaine, choline, myo-inositol and so on) observed in GF kidneys. (3) Gut microbiota modulate metabotype expression at both local (gut) and global (biofluids, kidney, liver) system levels and hence influence the responses to a variety of dietary modulation and drug exposures relevant to personalized health-care investigations

Monitoring Healthy Metabolic Trajectories with Nutritional Metabonomics

Metabonomics is a well established analytical approach for the analysis of physiological regulatory processes via the metabolic profiling of biofluids and tissues in living organisms. Its potential is fully exploited in the field of “nutrimetabonomics” that aims at assessing the metabolic effects of active ingredients and foods in individuals. Yet, one of the greatest challenges in nutrition research is to decipher the critical interactions between mammalian organisms and environmental factors, including the gut microbiota. “Nutrimetabonomics” is today foreseen as a powerful approach for future nutritional programs tailored at health maintenance and disease prevention

Cross-linguistic patterns in the acquisition of quantifiers.

Learners of most languages are faced with the task of acquiring words to talk about number and quantity. Much is known about the order of acquisition of number words as well as the cognitive and perceptual systems and cultural practices that shape it. Substantially less is known about the acquisition of quantifiers. Here, we consider the extent to which systems and practices that support number word acquisition can be applied to quantifier acquisition and conclude that the two domains are largely distinct in this respect. Consequently, we hypothesize that the acquisition of quantifiers is constrained by a set of factors related to each quantifier's specific meaning. We investigate competence with the expressions for "all," "none," "some," "some…not," and "most" in 31 languages, representing 11 language types, by testing 768 5-y-old children and 536 adults. We found a cross-linguistically similar order of acquisition of quantifiers, explicable in terms of four factors relating to their meaning and use. In addition, exploratory analyses reveal that language- and learner-specific factors, such as negative concord and gender, are significant predictors of variation.This is the author accepted manuscript. The final version is available from the National Academy of Sciences via http://dx.doi.org/10.1073/pnas.160134111

Role of Biotransformation Studies in Minimizing Metabolism-Related Liabilities in Drug Discovery

Metabolism-related liabilities continue to be a major cause of attrition for drug candidates in clinical development. Such problems may arise from the bioactivation of the parent compound to a reactive metabolite capable of modifying biological materials covalently or engaging in redox-cycling reactions leading to the formation of other toxicants. Alternatively, they may result from the formation of a major metabolite with systemic exposure and adverse pharmacological activity. To avert such problems, biotransformation studies are becoming increasingly important in guiding the refinement of a lead series during drug discovery and in characterizing lead candidates prior to clinical evaluation. This article provides an overview of the methods that are used to uncover metabolism-related liabilities in a pre-clinical setting and offers suggestions for reducing such liabilities via the modification of structural features that are used commonly in drug-like molecules