Remodeling of the Residual Gastric Mucosa after Roux-En-Y Gastric Bypass or Vertical Sleeve Gastrectomy in Diet-Induced Obese Rats

Whereas the remodeling of intestinal mucosa after bariatric surgeries has been the matter of numerous studies to our knowledge, very few reported on the remodeling of the residual gastric mucosa. In this study, we analyzed remodeling of gastric mucosa after Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) in rats. Diet-induced obese rats were subjected to RYGB, VSG or sham surgical procedures. All animals were assessed for food intake, body-weight, fasting blood, metabolites and hormones profiling, as well as insulin and glucose tolerance tests before and up to 5 weeks post-surgery. Remodeling of gastric tissues was analyzed by routine histology and immunohistochemistry studies, and qRT-PCR analyses of ghrelin and gastrin mRNA levels. In obese rats with impaired glucose tolerance, VSG and RYGB caused substantial weight loss and rats greatly improved their oral glucose tolerance. The remaining gastric mucosa after VSG and gastric pouch (GP) after RYGB revealed a hyperplasia of the mucous neck cells that displayed a strong immunoreactivity for parietal cell H⁺/K⁺-ATPase. Ghrelin mRNA levels were reduced by 2-fold in remaining fundic mucosa after VSG and 10-fold in GP after RYGB. In the antrum, gastrin mRNA levels were reduced after VSG in line with the reduced number of gastrin positive cells. This study reports novel and important observations dealing with the remaining gastric mucosa after RYGB and VSG. The data demonstrate, for the first time, a hyperplasia of the mucous neck cells, a transit cell population of the stomach bearing differentiating capacities into zymogenic and peptic cells.     

MicA sRNA links the PhoP regulon to cell envelope stress

Numerous small RNAs regulators of gene expression exist in bacteria. A large class of them binds to the RNA chaperone Hfq and act by base pairing interactions with their target mRNA, thereby affecting their translation and/or stability. They often have multiple direct targets, some of which may be regulators themselves, and production of a single sRNA can therefore affect the expression of dozens of genes. We show in this study that the synthesis of the Escherichia coli pleiotropic PhoPQ two‐component system is repressed by MicA, a σ^E‐dependent sRNA regulator of porin biogenesis. MicA directly pairs with phoPQ mRNA in the translation initiation region of phoP and presumably inhibits translation by competing with ribosome binding. Consequently, MicA downregulates several members of the PhoPQ regulon. By linking PhoPQ to σ^E, our findings suggest that major cellular processes such as Mg²⁺ transport, virulence, LPS modification or resistance to antimicrobial peptides are modulated in response to envelope stress. In addition, we found that Hfq strongly affects the expression of phoP independently of MicA, raising the possibility that even more sRNAs, which remain to be identified, could regulate PhoPQ synthesis.     

Sugar sensing by enterocytes combines polarity, membrane bound detectors and sugar metabolism

Sugar consumption and subsequent sugar metabolism are known to regulate the expression of genes involved in intestinal sugar absorption and delivery. Here we investigate the hypothesis that sugar-sensing detectors in membranes facing the intestinal lumen or the bloodstream can also modulate intestinal sugar absorption. We used wild-type and GLUT2-null mice, to show that dietary sugars stimulate the expression of sucrase-isomaltase (SI) and L-pyruvate kinase (L-PK) by GLUT2-dependent mechanisms, whereas the expression of GLUT5 and SGLT1, did not rely on the presence of GLUT2. By providing sugar metabolites, sugar transporters, including GLUT2, fuelled a sensing pathway. In Caco2/TC7 enterocytes, we could disconnect the sensing triggered by detector from that produced by metabolism, and found that GLUT2 generated a metabolism-independent pathway to stimulate the expression of SI and L-PK. In cultured enterocytes, both apical and basolateral fructose could increase the expression of GLUT5, conversely, basolateral sugar administration could stimulate the expression of GLUT2. Finally, we located the sweet-taste receptors T1R3 and T1R2 in plasma membranes, and we measured their cognate G alpha Gustducin mRNA levels. Furthermore, we showed that a T1R3 inhibitor altered the fructose-induced expression of SGLT1, GLUT5, and L-PK. Intestinal gene expression is thus controlled by a combination of at least three sugar-signaling pathways triggered by sugar metabolites and membrane sugar receptors that, according to membrane location, determine sugar-sensing polarity. This provides a rationale for how intestine adapts sugar delivery to blood and dietary sugar provision.     

Diversity of Monomers in Nonribosomal Peptides: towards the Prediction of Origin and Biological Activity

Nonribosomal peptides (NRPs) are molecules produced by microorganisms that have a broad spectrum of biological activities and pharmaceutical applications (e.g., antibiotic, immunomodulating, and antitumor activities). One particularity of the NRPs is the biodiversity of their monomers, extending far beyond the 20 proteogenic amino acid residues. Norine, a comprehensive database of NRPs, allowed us to review for the first time the main characteristics of the NRPs and especially their monomer biodiversity. Our analysis highlighted a significant similarity relationship between NRPs synthesized by bacteria and those isolated from metazoa, especially from sponges, supporting the hypothesis that some NRPs isolated from sponges are actually synthesized by symbiotic bacteria rather than by the sponges themselves. A comparison of peptide monomeric compositions as a function of biological activity showed that some monomers are specific to a class of activities. An analysis of the monomer compositions of peptide products predicted from genomic information (metagenomics and high-throughput genome sequencing) or of new peptides detected by mass spectrometry analysis applied to a culture supernatant can provide indications of the origin of a peptide and/or its biological activity.Nonribosomal peptides (NRPs) are molecules produced by microorganisms and synthesized by huge multienzymatic complexes (38, 41), called nonribosomal peptide synthetases (NRPSs). These megaenzymes are organized into modules, one for each amino acid to be built into the peptide product. This is accomplished by division of each catalytic step into specialized semiautonomous domains. The basic set of domains (adenylation, thiolation, and condensation) within a module can be extended by substrate-modifying domains, including domains for substrate epimerization, β hydroxylation, N methylation, and heterocyclic ring formation. The peptide release is catalyzed by a thioesterase domain which can also, in many cases, be involved in an intramolecular reaction leading to a cyclic or partially cyclic peptide or, in fewer cases, in the oligomerization of peptide units (iterative biosynthesis). NRPs show a broad spectrum of biological activities and pharmaceutical applications. They can harbor antimicrobial, immunomodulator, or antitumor activities. Cyclosporine (5), an immunosuppressant drug widely used in organ transplantation, daptomycin (60) (marketed in the United States under the trade name Cubicin), used in the treatment of certain infections caused by Gram-positive bacteria, aminoadipyl-cysteinyl-valine (ACV)-tripeptide, which is the precursor of cephalosporin and penicillin (29), the most famous antibiotic, and also bleomycin (57), used in the treatment of several cancers, are some common examples of NRPs of high therapeutic importance. Two main structural traits distinguish these peptides from ribosomally synthesized peptides: first, their primary structure is more frequently cyclic (partially or totally) branched or polycyclic rather than linear and, second, the biodiversity of monomers incorporated in NRPs goes far beyond the 20 proteogenic amino acids residues. NRP monomers include modified versions of the proteogenic amino acids (e.g., methylated, hydroxylated, and d-forms) but also other monomers, such as, for example, 2-aminoisobutyric acid (Aib), hydroxyphenylglycine (Hpg), and 2,3-dihydroxybenzoic acid (diOH-Bz). However, essential characteristics of this diversity and its relationship with biological functions and producing organisms have been poorly understood until now.The development of the Norine database, the first resource entirely dedicated to NRPs (8, 9), filled this gap. Based on Norine data, we performed the first large-scale analysis of about a thousand peptides which represent a total coverage of more than 10,000 monomer occurrences, revealing the presence of as many as 500 different monomer types. A data-mining analysis of the monomeric compositions of NRPs allowed us to reveal a strong relationship between certain monomeric characteristics of NRPs and their biological function and producing organism. In addition to providing a comprehensive overview of monomeric biodiversity in NRPs, this work demonstrated (i) a dissimilarity of structural properties between bacterial and fungal NRPs; (ii) a significant relationship between NRPs synthesized by bacteria and those isolated from metazoa, especially from sponges, supporting the hypothesis that the peptides isolated from sponges are in reality synthesized by symbiotic bacteria rather than by the sponges themselves; and (iii) a certain monomer specificity to a class of biological activities. Those observations are supported by successful statistical predictions of biological activities of NRPs based on their monomeric compositions.     

Attitudes to and knowledge about oral health care among nursing home personnel--an area in need of improvement

doi: 10.1111/j.1741‐2358.2011.00562.x
Attitudes to and knowledge about oral health care among nursing home personnel – an area in need of improvement Background: In 1999, a dental reform became law in Sweden that regulated both dental care to dependent individuals and training in oral health care for nursing home personnel. Substantial resources have been channelled into these efforts, but the outcome of these efforts has not been evaluated. The aim of this study was to explore attitudes to and knowledge about oral health care among nursing home personnel more than 5 years after the law was adopted, that being 2005. Methods: A total of 454 individuals employed at nursing homes answered a questionnaire of 16 multiple‐choice items concerning attitudes to and knowledge about oral health care. Results: Eighty‐nine per cent considered oral health care to be an important part of good nursing. The answers indicated problems, however, when it came to its implementation and knowledge, and 35% stated that they had had no formal education in oral health care. Conclusions: Despite generally positive oral health care attitudes, it is important that oral health care education is available to and made of interest for all nursing home personnel, especially in light of the increase in number of natural teeth and frequency of crowns and bridges among dependent elderly.     

Modeling of phenoxy acid herbicide mineralization and growth of microbial degraders in 15 soils monitored by quantitative real-time PCR of the functional tfdA gene

Mineralization potentials, rates, and kinetics of the three phenoxy acid (PA) herbicides, 2,4-dichlorophenoxyacetic acid (2,4-D), 4-chloro-2-methylphenoxyacetic acid (MCPA), and 2-(4-chloro-2-methylphenoxy)propanoic acid (MCPP), were investigated and compared in 15 soils collected from five continents. The mineralization patterns were fitted by zero/linear or exponential growth forms of the three-half-order models and by logarithmic (log), first-order, or zero-order kinetic models. Prior and subsequent to the mineralization event, tfdA genes were quantified using real-time PCR to estimate the genetic potential for degrading PA in the soils. In 25 of the 45 mineralization scenarios, ～60% mineralization was observed within 118 days. Elevated concentrations of tfdA in the range 1 × 10(5) to 5 × 10(7) gene copies g(-1) of soil were observed in soils where mineralization could be described by using growth-linked kinetic models. A clear trend was observed that the mineralization rates of the three PAs occurred in the order 2,4-D > MCPA > MCPP, and a correlation was observed between rapid mineralization and soils exposed to PA previously. Finally, for 2,4-D mineralization, all seven mineralization patterns which were best fitted by the exponential model yielded a higher tfdA gene potential after mineralization had occurred than the three mineralization patterns best fitted by the Lin model.