Aire's partnerships: An answer for many questions and new questions in search of answers

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79190/1/j.1399-5448.2010.00652.x.pd

A critical review of the proposed definitions of fundamental chemical quantities and their impact on chemical communities (IUPAC Technical Report)

In the proposed new SI, the kilogram will be redefined in terms of the Planck constant and the mole will be redefined in terms of the Avogadro constant. These redefinitions will have some consequences for measurements in chemistry. The goal of the Mole Project (IUPAC Project Number 2013-048-1-100) was to compile published work related to the definition of the quantity \u2018amount of substance\u2019, its unit the \u2018mole\u2019, and the consequence of these definitions on the unit of the quantity mass, the kilogram. The published work has been reviewed critically with the aim of assembling all possible aspects in order to enable IUPAC to judge the adequateness of the existing definitions or new proposals. Compilation and critical review relies on the broadest spectrum of interested IUPAC members.Peer reviewed: YesNRC publication: Ye

Definition of the mole (IUPAC Recommendation 2017)

In 2011 the General Conference on Weights and Measures (CGPM) noted the intention of the International Committee for Weights and Measures (CIPM) to revise the entire International System of Units (SI) by linking all seven base units to seven fundamental physical constants. Of particular interest to chemists, new definitions for the kilogram and the mole have been proposed. A recent IUPAC Technical Report discussed these new definitions in relation to immediate consequences for the chemical community. This IUPAC Recommendation on the preferred definition of the mole follows from this Technical Report. It supports a definition of the mole based on a specified number of elementary entities, in contrast to the present 1971 definition.Peer reviewed: YesNRC publication: Ye

Isolated adipocytes from growth hormone-treated obese (ob/ob) mice exhibit insulin resistance

The genetically obese (ob/ob) mouse is a useful model for the study of the diabetogenic action of growth hormone (GH), because treatment of these animals with GH results in decreased responsiveness of their adipose tissue to insulin in vitro. Studies of the mechanisms involved in GH-induced insulin resistance using isolated adipocytes of ob/ob mice have not been possible, however, because of their extreme fragility and the lack of an adequate system for the maintenance of these cells. This study describes a new method for the isolation of ob/ob mouse adipocytes. The isolated cells are stable, viable and metabolically responsive to insulin. In addition, these adipocytes have been maintained in primary culture, in serum-free medium, for up to 3 days. During culture, the cells exhibit large increases in 125I-hGH binding (10-20-fold) and porcine 125I-insulin binding (5-10-fold). The induction of insulin resistance by GH has also been demonstrated in these freshly isolated ob/ob mouse adipocytes. The studies to date indicate that the ob/ob mouse adipocyte system should provide a useful model for detailed studies of the cellular and molecular mechanisms of GH induced insulin resistance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28578/1/0000381.pd

Regulation of the Human Taurine Transporter by Oxidative Stress in Retinal Pigment Epithelial Cells Stably Transformed to Overexpress Aldose Reductase

In diabetes, overexpression of aldose reductase (AR) and consequent glucose-induced impairment of antioxidant defense systems may predispose to oxidative stress and the development of diabetic complications, but the mechanisms are poorly understood. Taurine (2-aminoethanesulfonic acid) functions as an antioxidant, osmolyte, and calcium modulator such that its intracellular depletion could promote cytotoxicity in diabetes. The relationships of oxidative stress and basal AR gene expression to Na+-taurine cotransporter (TT) gene expression, protein abundance, and TT activity were therefore explored in low AR-expressing human retinal pigment epithelial (RPE) 47 cells and RPE 47 cells stably transformed to overexpress AR (RPE 75). Changes in TT gene expression were determined using a 4.6-kb TT promoter-luciferase fusion gene. Compared with RPE 47 cells, in high AR-expressing RPE 75 cells, TT promoter activity was decreased by 46%, which was prevented by an AR inhibitor. TT promoter activity increased up to 900% by prooxidant exposure, which was associated with increased TT peptide abundance and taurine transport. However, induction of TT promoter activity by oxidative stress was attenuated in high AR-expressing cells and partially corrected by AR inhibitor. Finally, exposure of RPE 75 cells to high glucose increased oxidative stress, but down-regulated TT expression. These studies demonstrate for the first time that the TT is regulated by oxidative stress and that overexpression of AR and high glucose impair this response. Abnormal expression of AR may therefore impair antioxidant defense, which may determine tissue susceptibility to chronic diabetic complications. Antioxid. Redox Signal. 7, 1530–1542.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63284/1/ars.2005.7.1530.pd

Definition of the mole (IUPAC Recommendation 2017)

In 2011 the General Conference on Weights and Measures (CGPM) noted the intention of the International Committee for Weights and Measures (CIPM) to revise the entire International System of Units (SI) by linking all seven base units to seven fundamental physical constants. Of particular interest to chemists, new definitions for the kilogram and the mole have been proposed. A recent IUPAC Technical Report discussed these new definitions in relation to immediate consequences for the chemical community. This IUPAC Recommendation on the preferred definition of the mole follows from this Technical Report. It supports a definition of the mole based on a specified number of elementary entities, in contrast to the present 1971 definition

A critical review of the proposed definitions of fundamental chemical quantities and their impact on chemical communities (IUPAC Technical Report)

In the proposed new SI, the kilogram will be redefined in terms of the Planck constant and the mole will be redefined in terms of the Avogadro constant. These redefinitions will have some consequences for measurements in chemistry. The goal of the Mole Project (IUPAC Project Number 2013-048-1-100) was to compile published work related to the definition of the quantity ‘amount of substance', its unit the ‘mole', and the consequence of these definitions on the unit of the quantity mass, the kilogram. The published work has been reviewed critically with the aim of assembling all possible aspects in order to enable IUPAC to judge the adequateness of the existing definitions or new proposals. Compilation and critical review relies on the broadest spectrum of interested IUPAC members

Neurogenic chronic intestinal pseudo-obstruction: antineuronal antibody-mediated activation of autophagy via Fas

Background & Aims: Activation of autoimmune pathways has been implicated as a contributing mechanism to the pathophysiology in some patients with chronic intestinal pseudoobstruction (CIP). In this study we tested the hypothesis that sera from a subpopulation of patients with CIP contain autoantibodies that activate autophagy via a Fas-dependent pathway in cultured human neuroblastoma SH-Sy5Y cells. Methods: Twenty-five patients with established neurogenic CIP (20 women, 5 men; age range, 21-57 y) were investigated and circulating antineuronal antibodies to enteric neurons were found in 6 (24%) patients. The ability of antineuronal antibodies to induce autophagy was assessed using immunohistochemical, Western immunoblot, and molecular techniques. The presence of autophagosomes was monitored using a specific immunohistochemical marker, anti-microtubule-associated light chain immunoreactivity, and colocalization with mitochondrial- and Fas-activated death domain immunofluorescence using appropriate antibodies in cells exposed to sera from matched healthy controls and patients with neurogenic CIP. Results: Exposure of SH-Sy5Y cells to sera from patients with CIP containing antineuronal antibodies revealed increased binding of autoimmune immunoglobulin (IgG class) to the surface of SH-Sy5Y cells and increased formation of autophagosomes showing colocalization with mitochondria and Fas-activated death domain compared with control sera. Pretreatment of sera with either protein L agarose beads or a soluble Fas receptor (extracellular domain) chimera prevented the stimulation of autophagy. Conclusions: We provide novel evidence that antineuronal antibodies may contribute to neuronal dysfunction observed in a subset of patients with neurogenic CIP via autoantibody-mediated activation of autophagy involving the Fas receptor complex

Molecular Analysis of Antimicrobial Resistance Mechanisms in Neisseria gonorrhoeae Isolates from Ontario, Canada▿

Surveillance of gonococcal antimicrobial resistance and the molecular characterization of the mechanisms underlying these resistance phenotypes are essential in order to establish correct empirical therapies, as well as to describe the emergence of new mechanisms in local bacterial populations. To address these goals, 149 isolates were collected over a 1-month period (October-November 2008) at the Ontario Public Health Laboratory, Toronto, Canada, and susceptibility profiles (8 antibiotics) were examined. Mutations in previously identified targets or the presence of some enzymes related to resistance (r), nonsusceptibility (ns) (resistant plus intermediate categories), or reduced susceptibility (rs) to the antibiotics tested were also studied. A significant proportion of nonsusceptibility to penicillin (PEN) (89.2%), tetracycline (TET) (72.3%), ciprofloxacin (CIP) (29%), and macrolides (erythromycin [ERY] and azithromycin; 22.3%) was found in these strains. Multidrug resistance was observed in 18.8% of the collection. Although all the strains were susceptible to spectinomycin and extended-spectrum cephalosporins (ESC) (ceftriaxone and cefixime), 9.4% of them displayed reduced susceptibility to extended-spectrum cephalosporins. PBP 2 mosaic structures were found in all of these ESCrs isolates. Alterations in the mtrR promoter, MtrR repressor (TETr, PENns, ESCrs, and ERYns), porin PIB (TETr and PENns), and ribosomal protein S10 (TETr) and double mutations in gyrA and parC quinolone resistance-determining regions (QRDRs) (CIPr) were associated with and presumably responsible for the resistance phenotypes observed. This is the first description of ESCrs in Canada. The detection of this phenotype indicates a change in the epidemiology of this resistance and highlights the importance of continued surveillance to preserve the last antimicrobial options available