Multivitamin restriction increases adiposity and disrupts glucose homeostasis in mice

A strong association between obesity and low plasma concentrations of vitamins has been widely reported; however, the causality of this relationship is still not established. Our goal was to evaluate the impact of a multivitamin restriction diet (MRD) on body weight, adiposity and glucose homeostasis in mice. The mice were given a standard diet or a diet containing 50 % of the recommended vitamin intake (MRD) for 12 weeks. At the end of the experiment, total body weight was 6 % higher in MRD animals than in the control group, and the adiposity of the MRD animals more than doubled. The HOMA-IR index of the MRD animals was significantly increased. The adipose tissue of MRD animals had lower expression of mRNA encoding adiponectin and Pnpla2 (47 and 32 %, respectively) and 43 % higher leptin mRNA levels. In the liver, the mRNA levels of Pparα and Pgc1α were reduced (29 and 69 %, respectively) in MRD mice. Finally, the level of β-hydroxybutyrate, a ketonic body reflecting fatty acid oxidation, was decreased by 45 % in MRD mice. Our results suggest that MRD promotes adiposity, possibly by decreasing adipose tissue lipolysis and hepatic β-oxidation. These results could highlight a possible role of vitamin deficiency in the etiology of obesity and associated disorders.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-014-0410-x) contains supplementary material, which is available to authorized users.     

Fecal Calprotectin Excretion in Preterm Infants during the Neonatal Period

Background

Fecal calprotectin has been proposed as a non-invasive marker of intestinal inflammation in inflammatory bowel disease in adults and children. Fecal calprotectin levels have been reported to be much higher in both healthy full-term and preterm infants than in children and adults.

Objective

To determine the time course of fecal calprotectin (f-calprotectin) excretion in preterm infants from birth until hospital discharge and to identify factors influencing f-calprotectin levels in the first weeks of life, including bacterial establishment in the gut.

Methodology

F-calprotectin was determined using an ELISA assay in 147 samples obtained prospectively from 47 preterm infants (gestational age, and birth-weight interquartiles 27–29 weeks, and 880–1320 g, respectively) at birth, and at 2-week intervals until hospital discharge.

Principal Findings

Although median f-calprotectin excretion was 138 µg/g, a wide range of inter- and intra-individual variation in f-calprotectin values (from day 3 to day 78) was observed (86% and 67%, respectively). In multivariate regression analysis, f-calprotectin correlated negatively with ante and per natal antibiotic treatment (p = 0.001), and correlated positively with the volume of enteral feeding (mL/kg/d) (p = 0.009), the need to interrupt enteral feeding (p = 0.001), and prominent gastrointestinal colonization by Clostridium sp (p = 0.019) and Staphylococcus sp (p = 0.047).

Conclusion

During the first weeks of life, the high f-calprotectin values observed in preterm infants could be linked to the gut bacterial establishment.     

The chemotherapeutic agent bortezomib induces the formation of stress granules

Background

Cytoplasmic stress granules (SGs) are specialized storage sites of untranslated mRNAs whose formation occurs under different stress conditions and is often associated with cell survival. SGs-inducing stresses include radiations, hypoxia, viral infections, and chemical inhibitors of specific translation initiation factors. The FDA-approved drug bortezomib (Velcade^®) is a peptide boronate inhibitor of the 26S proteasome that is very efficient for the treatment of myelomas and other hematological tumors. Solid tumors are largely refractory to bortezomib. In the present study, we investigated the formation of SGs following bortezomib treatment.

Results

We show that bortezomib efficiently induces the formation of SGs in cancer cells. This process involves the phosphorylation of translation initiation factor eIF2α by heme-regulated inhibitor kinase (HRI). Depletion of HRI prevents bortezomib-induced formation of SGs and promotes apoptosis.

Conclusions

This is the first study describing the formation of SGs by a chemotherapeutic compound. We speculate that the activation of HRI and the formation of SGs might constitute a mechanism by which cancer cells resist bortezomib-mediated apoptosis.

     

Comparative study of vanA gene transfer from Enterococcus faecium to Enterococcus faecalis and to Enterococcus faecium in the intestine of mice

Vancomycin-resistant enterococci represent a large reservoir in animals because of the use of avoparcin as a growth promoter in Europe. These strains of animal origin enter the food chain and can either colonize the human gut or transfer their resistance genes to the human microbiota. In this study, we compared the transfer of vancomycin resistance from resistant animal Enterococcus faecium to sensitive human Enterococcus faecalis and E. faecium. We analysed these transfers in dibiotic mice and human faecal flora-associated mice. VanA transfer from animal E. faecium to human E. faecalis occurred in dibiotic mice. The transconjugants appeared rapidly and persisted at levels between 3.0 and 4.0 log10 colony-forming units g(-1) of faeces. In human faecal flora-associated mice, vanA gene transfer was not detected towards E. faecalis but was possible between E. faecium strains. Our experiments revealed the possibility of vanA transfer from animal E. faecium to human E. faecalis in vitro and in vivo in the intestine of dibiotic mice. However, intraspecies transfer of vanA gene seems more common than interspecies transfer among enterococci.     

Comparison of the Mantel test and alternative approaches for detecting complex multivariate relationships in the spatial analysis of genetic data

The Mantel test is widely used to test the linear or monotonic independence of the elements in two distance matrices. It is one of the few appropriate tests when the hypothesis under study can only be formulated in terms of distances; this is often the case with genetic data. In particular, the Mantel test has been widely used to test for spatial relationship between genetic data and spatial layout of the sampling locations. We describe the domain of application of the Mantel test and derived forms. Formula development demonstrates that the sum-of-squares (SS) partitioned in Mantel tests and regression on distance matrices differs from the SS partitioned in linear correlation, regression and canonical analysis. Numerical simulations show that in tests of significance of the relationship between simple variables and multivariate data tables, the power of linear correlation, regression and canonical analysis is far greater than that of the Mantel test and derived forms, meaning that the former methods are much more likely than the latter to detect a relationship when one is present in the data. Examples of difference in power are given for the detection of spatial gradients. Furthermore, the Mantel test does not correctly estimate the proportion of the original data variation explained by spatial structures. The Mantel test should not be used as a general method for the investigation of linear relationships or spatial structures in univariate or multivariate data. Its use should be restricted to tests of hypotheses that can only be formulated in terms of distances.     

The enigmatic nature of altruism in organ transplantation: a cross-cultural study of transplant physicians' views on altruism

Background

Although altruism is a key principle in our current organ donation and transplantation system, the meanings and implications of the term have been widely debated. Recently, a new type of living organ donation--anonymous and non-directed, also called living altruistic donation (LAD)--has brought the issue into sharper focus. Transplant physicians' views on altruism might influence their attitudes and actions toward living altruistic donors. This study aimed to explore such views among transplant physicians in France and Quebec.

Findings

A total of 27 French and 19 Quebec transplant physicians participated in individual, semi-structured interviews between October 2004 and December 2005. The majority of these participants associated altruism with gratuitousness and saw altruistic acts as multiple and varied, ranging from showing consideration to saving a person's life.

Conclusions

The transplant physicians' discourses on altruism were quite diverse, leading us to question the relevance of the concept in organ transplantation and the appropriateness of the term "living altruistic donation."

     

Hyperfunction of Muscarinic Receptor Maintains Long-Term Memory in 5-HT4 Receptor Knock-Out Mice

Patients suffering from dementia of Alzheimer''s type express less serotonin 4 receptors (5-HTR₄), but whether an absence of these receptors modifies learning and memory is unexplored. In the spatial version of the Morris water maze, we show that 5-HTR₄ knock-out (KO) and wild-type (WT) mice performed similarly for spatial learning, short- and long-term retention. Since 5-HTR₄ control mnesic abilities, we tested whether cholinergic system had circumvented the absence of 5-HTR₄. Inactivating muscarinic receptor with scopolamine, at an ineffective dose (0.8 mg/kg) to alter memory in WT mice, decreased long-term but not short-term memory of 5-HTR₄ KO mice. Other changes included decreases in the activity of choline acetyltransferase (ChAT), the required enzyme for acetylcholine synthesis, in the septum and the dorsal hippocampus in 5-HTR₄ KO under baseline conditions. Training- and scopolamine-induced increase and decrease, respectively in ChAT activity in the septum in WT mice were not detected in the 5-HTR₄ KO animals. Findings suggest that adaptive changes in cholinergic systems may circumvent the absence of 5-HTR₄ to maintain long-term memory under baseline conditions. In contrast, despite adaptive mechanisms, the absence of 5-HTR₄ aggravates scopolamine-induced memory impairments. The mechanisms whereby 5-HTR₄ mediate a tonic influence on ChAT activity and muscarinic receptors remain to be determined.     

Genomic analysis of carbon monoxide utilization and butanol production by Clostridium carboxidivorans strain P7

Increasing demand for the production of renewable fuels has recently generated a particular interest in microbial production of butanol. Anaerobic bacteria, such as Clostridium spp., can naturally convert carbohydrates into a variety of primary products, including alcohols like butanol. The genetics of microorganisms like Clostridium acetobutylicum have been well studied and their solvent-producing metabolic pathways characterized. In contrast, less is known about the genetics of Clostridium spp. capable of converting syngas or its individual components into solvents. In this study, the type of strain of a new solventogenic Clostridium species, C. carboxidivorans, was genetically characterized by genome sequencing. C. carboxidivorans strain P7(T) possessed a complete Wood-Ljungdahl pathway gene cluster, involving CO and CO(2) fixation and conversion to acetyl-CoA. Moreover, with the exception of an acetone production pathway, all the genetic determinants of canonical ABE metabolic pathways for acetate, butyrate, ethanol and butanol production were present in the P7(T) chromosome. The functionality of these pathways was also confirmed by growth of P7(T) on CO and production of CO(2) as well as volatile fatty acids (acetate and butyrate) and solvents (ethanol and butanol). P7(T) was also found to harbour a 19 Kbp plasmid, which did not include essential or butanol production related genes. This study has generated in depth knowledge of the P7(T) genome, which will be helpful in developing metabolic engineering strategies to improve C. carboxidivorans's natural capacity to produce potential biofuels from syngas.