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Industrially originated trans-fatty acids (I-tFAs), such as elaidic acid (EA), and ruminant trans-fatty acids (R-tFAs), such as trans-palmitoleic acid (TPA), may have opposite effects on metabolic health. The objective was to compare the effects of consuming 2–3% I-tFA or R-tFA on the gut microbiome and fecal metabolite profile in mice after 7 and 28 days. Forty C57BL/6 mice were assigned to one of the four prepared formulations: lecithin nanovesicles, lecithin nanovesicles with EA or TPA, or water. Fecal samples and animals’ weights were collected on days 0, 7, and 28. Fecal samples were used to determine gut microbiome profiles by 16S rRNA sequencing and metabolite concentrations by GC/MS. At 28 days, TPA intake decreased the abundance of Staphylococcus sp55 but increased Staphylococcus sp119. EA intake also increased the abundance of Staphylococcus sp119 but decreased Ruminococcaceae UCG-014, Lachnospiraceae, and Clostridium sensu stricto 1 at 28 days. Fecal short-chain fatty acids were increased after TPA while decreased after EA after 7 and 28 days. This study shows that TPA and EA modify the abundance of specific microbial taxa and fecal metabolite profiles in distinct ways.

Preterm infants are deficient in long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), a fatty acid (FA) associated with an increase in bronchopulmonary dysplasia (BPD). In two previous randomized control trials, DHA supplementation did not reduce the risk of BPD. We examined the breast milk FA profile, collected 14 days after birth, of mothers who delivered before 29 weeks of gestation and who were supplemented with DHA-rich algae oil or a placebo within 72 h after birth as part of the MOBYDIck trial. Milk FA were analyzed by gas chromatography. The total amount of FA (mg/mL) was similar in both groups but the supplementation increased DHA (expressed as % of total FA, mean ± SD, treatment vs placebo, 0.95 ± 0.44% vs 0.34 ± 0.20%; P

Unlike large dams which favor methylation of Hg in flooded soils over long periods, run-of-river dams are designed to flood a limited area of soils and are therefore not expected to significantly affect mercury (Hg) cycling or carbon processing. We studied the Hg and carbon cycles within food webs from several sectors along the Saint-Maurice River, Quebec, Canada, that differ in how they are influenced by two run-of-river dams and other watershed disturbances. We observed peak Hg concentrations in fish five-year postimpoundment, but these levels were reduced three years after this peak. Methylmercury concentrations in low trophic level fish and invertebrates were related to their carbon source (δ13C) rather than their trophic positions (δ15N). Biomagnification, measured by trophic magnification slopes, was driven mainly by methylmercury concentrations in low-trophic level organisms and environmental factors related to organic matter degradation and Hg-methylation. River sectors, δ13C and δ15N, predicted up to 80% of the variability in food web methylmercury concentrations. The installation of run-of-river dams and the related pondages, in association with other watershed disturbances, altered carbon processing, promoted Hg-methylation and its accumulation at the base of the food web, and led to a temporary increase in Hg levels in fish.

Lack of dystrophin causes muscle degeneration, which is exacerbated by chronic inflammation and reduced regenerative capacity of muscle stem cells in Duchenne Muscular Dystrophy (DMD). To date, glucocorticoids remain the gold standard for the treatment of DMD. These drugs are able to slow down the progression of the disease and increase lifespan by dampening the chronic and excessive inflammatory process; however, they also have numerous harmful side effects that hamper their therapeutic potential. Here, we investigated Resolvin-D2 as a new therapeutic alternative having the potential to target multiple key features contributing to the disease progression. Our in vitro findings showed that Resolvin-D2 promotes the switch of macrophages toward their anti-inflammatory phenotype and increases their secretion of pro-myogenic factors. Moreover, Resolvin-D2 directly targets myogenic cells and promotes their differentiation and the expansion of the pool of myogenic progenitor cells leading to increased myogenesis. These effects are ablated when the receptor Gpr18 is knocked-out, knocked-down, or blocked by the pharmacological antagonist O-1918. Using different mouse models of DMD, we showed that Resolvin-D2 targets both inflammation and myogenesis leading to enhanced muscle function compared to glucocorticoids. Overall, this preclinical study has identified a new therapeutic approach that is more potent than the gold-standard treatment for DMD., Glucocorticoids delay muscle wasting in Duchenne Muscular Dystrophy by reducing inflammation; but also have harmful side effects. Here, the authors show that Resolvin-D2 is more effective than glucocorticoids in mitigating muscular dystrophy in mouse models, due to its ability to dampen inflammation and target myogenic cells to improve muscle regeneration.

Background High-dose vitamin C is increasingly used for sepsis and more recently for coronavirus disease 2019 (COVID-19) infections. Proponents argue that the low cost and near perfect safety profile of vitamin C support its early adoption. Yet, adverse events might be underreported and underappreciated. Case presentation We report a 73-year-old non-diabetic white man with end-stage renal disease on peritoneal dialysis admitted to the intensive care unit with septic shock that was suspected to be due to peritonitis. The patient was enrolled in LOVIT (Lessening Organ Dysfunction with VITamin C; ClinicalTrials.gov identifier: NCT03680274), a randomized placebo-controlled trial of high-dose intravenous vitamin C. He developed factitious hyperglycemia, as measured with a point-of-care glucometer, that persisted for 6 days after discontinuation of the study drug, confirmed to be vitamin C after unblinding. He also had short-lived iatrogenic coma because of hypoglycemia secondary to insulin administration. These events triggered a protocol amendment. Conclusions Although factitious hyperglycemia has been reported before using certain glucometers in patients treated with high-dose vitamin C, the persistence of this phenomenon for 6 days after the discontinuation of the therapy is a distinguishing feature. This case highlights the importance of monitoring glucose with a core laboratory assay for up to a week in specific populations, such as patients on peritoneal dialysis.

F2-IsoProstanes (F2-IsoPs) are major biomarkers of oxidative stress and are associated with type 2 diabetes (T2D). Further, plasma levels of F2-IsoPs may be modified by dairy products. The aim is to investigate the effect of high dairy product (HD) consumption compared to an adequate dairy product (AD) consumption on the level of F2-IsoPs among hyperinsulinemic subjects. In this crossover study, participants were randomized in two groups: HD (≥4 servings/day), or AD (≤2 servings/day) for six weeks. Fasting blood glucose and insulin were measured. The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. Six isomers of F2-IsoPs were quantified by HPLC-MS/MS. Twenty-seven subjects with hyperinsulinemia (mean age, 55 ± 13 years, BMI, 31.4 ± 3.3 kg/m2) were included. Fasting glucose, insulin and HOMA-IR were unchanged after HD or AD intervention. After HD intake, the total level of F2-IsoPs (p = 0.03), 5-F2t-IsoP (p = 0.002), and 8-F2t-IsoP (p = 0.004) decreased compared to AD. The 15-F2t-IsoP tended to be positively correlated with fasting blood glucose (r = 0.39, p = 0.08). Generally, F2-IsoPs levels were higher among men compared to women regardless of the dairy intake. Overall, intake of HD decreased plasma levels of F2-IsoPs compared to AD without modifying glycemic parameters.

Run-of-river power plants (RoRs) are expected to triple in number over the next decades in Canada. These structures are not anticipated to considerably promote the mobilization and transport of mercury (Hg) and its subsequent microbial transformation to methylmercury (MeHg), a neurotoxin able to biomagnify in food webs up to humans. To test whether construction of RoRs had an effect on Hg transport and transformation, we studied Hg and MeHg concentrations, organic matter contents and methylating microbial community abundance and composition in the sediments of a section of the St. Maurice River (Quebec, Canada). This river section has been affected by the construction of two RoR dams and its watershed has been disturbed by a forest fire, logging, and the construction of wetlands. Higher total Hg (THg) and MeHg concentrations were observed in the surface sediments of the flooded sites upstream of the RoRs. These peaks in THg and MeHg were correlated with organic matter proportions in the sediments (r2 = 0.87 and 0.82, respectively). In contrast, the proportion of MeHg, a proxy for methylation potential, was best explained by the carbon to nitrogen ratio suggesting the importance of terrigenous organic matter as labile substrate for Hg methylation in this system. Metagenomic analysis of Hg-methylating communities based on the hgcA functional gene marker indicated an abundance of methanogens, sulfate reducers and fermenters, suggesting that these metabolic guilds may be primary Hg methylators in these surface sediments. We propose that RoR pondages act as traps for sediments, organic matter and Hg, and that this retention can be amplified by other disturbances of the watershed such as forest fire and logging. RoR flooded sites can be conducive to Hg methylation in sediments and may act as gateways for bioaccumulation and biomagnification of MeHg along food webs, particularly in disturbed watersheds.

Nutritional compounds may have an influence on different OMICs levels, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, and metagenomics. The integration of OMICs data is challenging but may provide new knowledge to explain the mechanisms involved in the metabolism of nutrients and diseases. Traditional statistical analyses play an important role in description and data association; however, these statistical procedures are not sufficiently enough powered to interpret the large integrated multiple OMICs (multi-OMICS) datasets. Machine learning (ML) approaches can play a major role in the interpretation of multi-OMICS in nutrition research. Specifically, ML can be used for data mining, sample clustering, and classification to produce predictive models and algorithms for integration of multi-OMICs in response to dietary intake. The objective of this review was to investigate the strategies used for the analysis of multi-OMICs data in nutrition studies. Sixteen recent studies aimed to understand the association between dietary intake and multi-OMICs data are summarized. Multivariate analysis in multi-OMICs nutrition studies is used more commonly for analyses. Overall, as nutrition research incorporated multi-OMICs data, the use of novel approaches of analysis such as ML needs to complement the traditional statistical analyses to fully explain the impact of nutrition on health and disease.

Reservoirs are known to accelerate the mobilization and cycling of mercury and carbon as aresult of flooding of terrestrial organic matter, which can lead to environmental concerns at local andbroader spatial scales. We explored the covariation of mercury (Hg) and carbon (C) functional pools innatural and recently dammed portions of the aquatic network of the Romaine River watershed in NorthernQuebec, Canada, to understand how the fate of these elements varies across systems with contrastinghydrology and environmental conditions. We found that total Hg (THg) concentrations in surface waterswere relatively constant along the network, whereas both the concentrations and proportions of MeHgtended to increase in reservoirs compared to surrounding nonooded systems, and along the cascade ofreservoirs. Whereas THg was related to total and terrestrial pools of dissolved organic carbon (DOC), MeHgwas weakly related to DOC but strongly linked to surface concentrations of CO2, as well as toconcentrations of iron and manganese. The latter are proxies of cumulative organic matter processing withinthe network, presumably in anoxic portions of shallow bays, deep reservoir waters, and river sediments,as well as in prior seasons (e.g., under ice). Our results suggest that these deep boreal reservoirs acted more astransformation sites for Hg that was already present than as mobilizers of new Hg, and that under icemetabolism plays a role in MeHg production in these systems as we found strong dichotomies in MeHgpatterns between spring and summer.

This cross-sectional study examined the moderating role of support from three key figures (mothers, teachers, friends) in the association between peer victimization and parasomnias in childhood. The sample consisted of 1150 children aged 8 years who attended elementary school. Controlling for potential confounders, hierarchical multiple regressions revealed that peer victimization was associated with a higher level of parasomnias, equally for both girls and boys. However, for girls, the predictive association of peer victimization with parasomnias was moderated by the level of support in relationships with either their parents, their teachers, or their friends. The findings suggest that somatic symptoms such as sleep problems may be a first indicator that a child is being bullied. Because parents, teachers as well as friends can play a key role in preventing the development of parasomnias, it may be useful to help bullied children develop strong bonds within at least one of these relationships.

OBJECTIVES: We hypothesized that the intake of industrially originated trans-fatty acids (elaidic acid (EA trans 18: 1n-9)) and ruminant trans fatty acids (trans-palmitoleic acid (TPA t16:1 n-7)) will differentially modify gut microbiota and short-chain fatty acids (SCFA) profiles. The objective is to compare the long- and short-term effects of EA and TPA on the fecal microbiome and SCFAs profiles in mice. METHODS: Forty C57BL/6 mice were divided to 4 groups. Each group was given one of the following 4 formulations in the drinking water: lecithin nanovesicles, nanovesicles containing either lecithin with EA or TPA (86:14 (w/w)) or water alone (control) for 28 days with a normal fat diet. Fecal samples were collected at days 0, 7 and 28. Gut microbiota profiles were determined by 16S rRNA gene sequencing. SCFAs were measured by headspace gas chromatography coupled to a single quadrupole mass spectrometer. Baseline data (relative abundance of bacteria or levels of SCFAs) was pooled and then compared with data from day 7 or day 28 for each formulation. RESULTS: After 7 days of lecithin, 16S rRNA analysis revealed an increase in the relative abundance of Lactobacillus. After 28 days of lecithin, an increase in the relative abundance of Lactobacillus, Erysipelotrichaceae, and Enterobacteriaceae together with a decrease in Bacteroidaceae was observed. Further, a tendency to increase level of butyric acid (P = 0.053) was observed after 28 days of lecithin. After 7 days of EA, an increase in the relative abundance of Lactobacillus, whereas a decrease in the relative abundance of Parabacteroides, Bacteroides, Rumininococcaceae, Lachnospiraceae and Peptococcaceae was observed. After 7 days of TPA, results show a decreased level of isovaleric acid (P = 0.04) and valeric acid (P = 0.03). After 28 days of TPA, data demonstrates an increase in the level of butyric acid (P = 0.01) and propionic acid (P = 0.01). Water intake for 28 days decreased the level of valeric acid (P = 0.02). CONCLUSIONS: Consumption of industrial and ruminant trans-fatty acids modify differentially bacterial taxa present in the gut microbiome and SCFA profiles. FUNDING SOURCES: NSERC, CMDO.

In aluminum electrolysis cells, a ledge of frozen electrolyte is formed on the sides. Controlling the side ledge thickness (a few centimeters) is essential to maintain a reasonable life span of the electrolysis cell, as the ledge acts as a protective layer against chemical attacks from the electrolyte bath used to dissolve alumina. The numerical modeling of the side ledge thickness, by using, for example, finite element analysis, requires some input data on the thermal transport properties of the side ledge. Unfortunately, there is a severe lack of experimental data, in particular, for the main constituent of the side ledge, the cryolite (Na3AlF6). The aim of this study is twofold. First, the thermal transport properties of cryolite, not available in the literature, were measured experimentally. Second, the experimental data were compared with previous theoretical predictions based on first principle calculations. This was carried out to evaluate the capability of first principle methods in predicting the thermal transport properties of complex insulating materials. The thermal diffusivity of a porous synthetic cryolite sample containing 0.9 wt % of alumina was measured over a wide range of temperature (473–810 K), using the monotone heating method. Because of limited computational resources, the first principle method can be used only to determine the thermal properties of single crystals. The dependence of thermal diffusivity of the Na3AlF6 + 0.9 wt % Al2O3 mixture on the microstructural parameters is discussed. A simple analytical function describing both thermal diffusivity and thermal conductivity of cryolite as a function of temperature is proposed.

At the La Grande hydroelectric complex (Quebec, Canada), total mercury concentrations were measured in more than 25 000 fish over a 20-year period. Fish population characteristics, such as fishing yield, growth rate, condition factor, and recruitment, were also monitored. In reservoirs, total mercury concentrations in all species increased rapidly after impoundment, peaking after 4 to 9 years in nonpiscivorous fish and after 9 to 11 years in piscivorous species, at levels three to seven times those measured in surrounding natural lakes, then declined gradually and significantly. Despite this increase, most species showed increases in fishing yields (by factors ranging from 2 to 8), growth rates, and condition factors (for more than a decade). The percentage of small specimens of the main species was generally maintained or increased in the first years after flooding, indicating good recruitment.

Optimization of pyridine-based noncatalytic site integrase inhibitors (NCINIs) based on compound 2 has led to the discovery of molecules capable of inhibiting virus harboring N124 variants of HIV integrase (IN) while maintaining minimal contribution of enterohepatic recirculation to clearance in rat. Structure-activity relationships at the C6 position established chemical space where the extent of enterohepatic recirculation in the rat is minimized. Desymmetrization of the C4 substituent allowed for potency optimization against virus having the N124 variant of integrase. Combination of these lessons led to the discovery of compound 20, having balanced serum-shifted antiviral potency and minimized excretion in to the biliary tract in rat, potentially representing a clinically viable starting point for a new treatment option for individuals infected with HIV.

A high-throughput screen based on a viral replication assay was used to identify inhibitors of the human cytomegalovirus. Using this approach, hit compound 1 was identified as a 4 μM inhibitor of HCMV that was specific and selective over other herpes viruses. Time of addition studies indicated compound 1 exerted its antiviral effect early in the viral life cycle. Mechanism of action studies also revealed that this series inhibited infection of MRC-5 and ARPE19 cells by free virus and via direct cell-to-cell spread from infected to uninfected cells. Preliminary structure-activity relationships demonstrated that the potency of compound 1 could be improved to a low nanomolar level, but metabolic stability was a key optimization parameter for this series. A strategy focused on minimizing metabolic hydrolysis of the N1-amide led to an alternative scaffold in this series with improved metabolic stability and good pharmacokinetic parameters in rat.

This study examined the moderating role of parental behaviors in the longitudinal link between peer victimization and sleep problems during preschool. The sample consisted of 1,181 children (594 girls) attending day care between the ages of 3 and 6 years. Participants were part of the Quebec Longitudinal Study of Child Development, a longitudinal study of child development led by the Institut de la Statistique du Quebec. Controlling for potential confounders, latent growth curve analyses revealed that the association between peer victimization and sleep problems varied depending on parents’ behaviors. Coercive parenting exacerbated the link between peer victimization and parasomnias. In contrast, positive parenting mitigated the link between peer victimization and insomnia. The findings suggest that persistent sleep problems at a young age may be an indicator of chronic peer victimization but that parents’ behaviors can play a key role in victimized children’s sleep problems.

We hypothesized that the mild physiological oxidative stress present during pregnancy could increase both, plasma F 2 -isoprostanes (F 2 -isoPs) by lipid oxidation and trans fatty acids (TFA) through cis-trans isomerization respectively. Plasma samples collected at 12–18 weeks (MIROS cohort; n =65) and 38–41 weeks of pregnancy (CHUL cohort; n =21) were subjected to alkaline hydrolysis followed by liquid–liquid extraction in order to extract total F 2 -isoPs for quantification by HPLC–MS/MS. Several positive correlations were found between F 2 -isoPs and TFA, measured by GC-FID in plasma phospholipids, such as 6 t -18:1, 9 t -18:1 and 9 t ,12 c -18:2 ( r >0.306; p t ,12 c -18:2 trans isomer, known to be associated to cardiovascular diseases, showed the most significant correlations with F 2 -isoPs. No correlation was observed between F 2 -isoPs and 9 t -16:1 or 11 t -18:1. In summary, this study suggests either a concomitant phenomenon or a competition between lipid peroxidation and cis - trans isomerisation of the cis precursor fatty acid in vivo during pregnancy.

A scaffold replacement approach was used to identifying the pyridine series of noncatalytic site integrase inhibitors. These molecules bind with higher affinity to a tetrameric form compared to a dimeric form of integrase. Optimization of the C6 and C4 positions revealed that viruses harboring T124 or A124 amino acid substitutions are highly susceptible to these inhibitors, but viruses having the N124 amino acid substitution are about 100-fold less susceptible. Compound 20 had EC50 values10 nM against viruses having T124 or A124 substitutions in IN and800 nM in viruses having N124 substitions. Compound 20 had an excellent in vitro ADME profile and demonstrated reduced contribution of biliary excretion to in vivo clearance compared to BI 224436, the lead compound from the quinoline series of NCINIs.

An assay recapitulating the 3' processing activity of HIV-1 integrase (IN) was used to screen the Boehringer Ingelheim compound collection. Hit-to-lead and lead optimization beginning with compound 1 established the importance of the C3 and C4 substituent to antiviral potency against viruses with different aa124/aa125 variants of IN. The importance of the C7 position on the serum shifted potency was established. Introduction of a quinoline substituent at the C4 position provided a balance of potency and metabolic stability. Combination of these findings ultimately led to the discovery of compound 26 (BI 224436), the first NCINI to advance into a phase Ia clinical trial.

In vitro cell model studies have shown that oxidative stress may affect beta-cell function. It is unknown whether oxidative stress may affect metabolic health in human fetuses/newborns. In a singleton pregnancy cohort (n = 248), we studied maternal (24–28 weeks gestation) and cord plasma biomarkers of oxidative stress [malondialdehyde (MDA), F2-isoprostanes] in relation to fetal metabolic health biomarkers including cord plasma glucose-to-insulin ratio (an indicator of insulin sensitivity), proinsulin-to-insulin ratio (an indicator of beta-cell function), insulin, IGF-I, IGF-II, leptin, adiponectin and ghrelin concentrations. Strong positive correlations were observed between maternal and cord plasma biomarkers of oxidative stress (r = 0.33 for MDA, r = 0.74 for total F2-isoprostanes, all p

A full overview of the decarboxylative cross-coupling reaction between heteroaromatic carboxylic acids and aryl halides is described. This transformation employs palladium catalysts with short reaction times providing facile synthesis of aryl-substituted heteroaromatics. The effect of each reaction parameter including solvent, base, and additive employed as well as the full substrate scope of this transformation are reported. Mechanistic evidence is also disclosed that sheds light on possible reaction pathways.

Preeclampsia (PE) has long been associated with early oxidative stress, although the symptoms occur later in pregnancy. We have hypothesized that the oxidative stress in PE, as characterized by the presence of F2-isoprostane (F2-isoP) isomers in late pregnancy, should already be present in plasma at the first regular visit of the obstetrical follow-up. There are 64 possible isomers of F2-isoPs derived from the oxidation of arachidonic acid (AA), but only one of these isomers has been investigated so far in PE, the classical 8-iso-PGF2α. Here, we have investigated two regioisomers of class III (8-iso-15(R)-PGF2α and 8-iso-PGF2α) and a mix of two isomers of class VI ((±)5-iPF2α-VI) in plasma samples collected prospectively at 12-18 weeks from normotensive controls (n = 60) and pregnant mothers who developed PE later in pregnancy (n = 33). The plasma samples were subjected to alkaline hydrolysis followed by liquid-liquid extraction to extract total F2-isoPs for later quantification by HPLC-MS/MS. The F2-isoPs were normalized to either plasma volume or polyunsaturated fatty acid (PUFA) levels measured by GC-FID in plasma phospholipids. Early in pregnancy, only the class VI F2-isoP isomers were found at concentrations significantly higher in women developing PE later in pregnancy (+13%; p = 0.0074). Normalization of F2-isoPs to their substrate, AA, or the omega-3 to omega-6 ratio improved the predictability of PE as determined by receiver operating characteristic (from area under the curve of 0.67 to 0.68 and 0.70 respectively). Interestingly, omega-3 fatty acids were 25% higher in the control group than in the PE group (P = 0.0225). Omega-6 PUFAs correlated with F2-Isop isomers only in cases of PE (r > 0.377; P >0.03, Spearman correlation). In sum, this study indicates that specific isomers of class VI are significant predictors of PE. This work also suggests that F2-isoP isomers are not all generated and eliminated to the same extent and are influenced by the PUFA composition of plasma phospholipids.

Nitric oxide (NO) is a free radical produced by the action of NO synthases (NOS) and is known to be involved in the regulation of many reproductive events that occur in the oviducts. The oviducts are highly specialized organs that play crucial roles in reproduction by providing an optimal environment for the final maturation of gametes, fertilization, and early embryo development. In this study, we analyzed the expression, hormonal regulation, and cellular distribution of neuronal, inducible, and endothelial NOS in different bovine oviduct segments to better understand the roles played by these enzymes in oviductal functions in vivo. Quantitative RT-PCR analysis revealed that NOS isoforms are hormonally regulated and differentially expressed along the oviduct throughout the estrous cycle. All NOS were highly expressed around the time of estrus, and immunohistochemistry studies determined that neuronal NOS, inducible NOS (iNOS), and endothelial NOS are differentially distributed in cells along the oviduct. Interestingly, our results showed that estradiol selectively up-regulates iNOS expression in the oviduct during the periovulatory period corresponding to the window of ovulation, oocyte transport, and fertilization. The resulting NO production by this high-output NOS may be of crucial importance for reproductive events that occur in the oviduct. This study provided the first demonstration that NO production is hormonally regulated in the mammalian oviducts in vivo. Our results suggest that neuronal NOS, iNOS, and endothelial NOS contribute to oviductal functions in a timely and site-specific manner.

The oviduct plays a crucial role in mammalian reproduction by providing an optimal environment for the final maturation and transport of gametes, fertilization, and early embryonic development. It is now recognized that these reproductive events in vitro can be either negatively or positively affected by reactive oxygen species such as hydrogen peroxide and lipid hydroperoxides. In the current study, we analyzed the expression of the phospholipid hydroperoxide glutathione peroxidase (PHGPx or GPx-4), a selenoenzyme that directly reduces membrane-bound lipid hydroperoxides in the bovine oviduct. Using in situ hybridization, we demonstrated that GPx-4 expression is almost restricted to the oviductal luminal epithelium in contrast to GPx-1, which is widely distributed, and GPx-2 and -3, which are mainly detected in the epithelial cells and lamina propria. Interestingly, real-time quantitative RT-PCR analysis showed that GPx-4 expression was highest during the follicular and postovulatory phases. In addition, GPx-4 expression was highest in the isthmus proximal to the dominant follicle during the follicular stage and remained high during the postovulatory period. This increased in expression of GPx-4 corresponded to increased GPx-4 enzymatic activity. Based on intrauterine infusion of estradiol, we determined that the increase in expression and activity of GPx-4 is estrogen mediated. This work clearly demonstrates that GPx-4 gene expression is influenced by the proximity of the dominant follicle in the oviduct in vivo. We propose that GPx-4 has an important role in the physiological control of peroxide tone in the bordering cells of the oviductal lumen.

In models which allow for random jumps, statistical tests for jumps are typically non-standard and nuisance parameter-dependent. To handle these problems, we combine bounds and Monte-Carlo (MC) simulation techniques to derive nuisance-parameter-free bounds and obtain level-exact p-values for a wide class of processes with random jumps and time varying heteroskedasticity. When identified nuisance parameters are absent under the null, we show that MC p-values are finite sample, level-exact. To illustrate this easy-to-implement approach, we analyze the spot prices of four commodities (aluminium, copper, gold and lead) and the closing prices of four technology stocks (Intel, Microsoft, Oracle and Sun). We find significant jumps in these time series. Our approach can easily be extended to other nuisance-parameter dependent tests.

Preeclampsia is a leading cause of maternal and neonatal mortality and morbidity. It is a complex syndrome of undetermined etiologic origin, usually diagnosed during the second half of pregnancy, with clinical features of hypertension, proteinuria, and edema. No cure for preeclampsia exists, except premature delivery. There is increasing evidence that oxidative stress is an important contributing factor to the pathogenesis of preeclampsia. Oxidative stress is defined as an imbalance between reactive oxygen species (ROS), such as nitric oxide(NO · ), superoxide anion (O 2 ·↔ ), and hydrogen peroxide (H 2 O 2 ), and antioxidants, favouring an overabundance of ROS. The consequence of an overproduction of ROS can be observed as increased levels of markers of oxidative stress, such as lipid peroxides.Pregnant women affected by preeclampsia may have abnormal ROS production, particularly NO · and O 2 ·↔ , abnormal levels of antioxidant defences, and increased placental lipid peroxidation. Several observations suggest that decreased bioavailability of endothelium-derived NO · , due to oxidative destruction of NO · by ROS, might contribute to the impaired endothelium-dependent vasodilatory responses and multisystemie pathology of preeclampsia, a phenomenon in which antioxidant vitamins may play a beneficial role. This review focuses on the rationale for vitamins C and E supplementation toward prevention of preeclampsia, with an emphasis on the limit of our scientific knowledge concerning the deleterious oxidative events taking place in this pathology.

The balanced presence of reactive oxygen species and antioxidants has a positive impact on sperm functions, oocyte maturation, fertilization, and embryo development in vitro. The mammalian oviduct is likely to provide an optimal environment for final gamete maturation, sperm-egg fusion, and early embryonic development. However, the expression and distribution of antioxidant enzymes in the bovine oviduct are poorly characterized. We analyzed the mRNA expression and enzymatic activities of major antioxidants glutathione peroxidase (GPx), superoxide dismutase (Cu,ZnSOD), and catalase in the bovine oviduct throughout the estrous cycle. The high levels of expression for GPx-3 in the isthmus were in contrast to expression of GPx1 and GPx-2, which occurred mostly in the ampulla and infundibulum of the oviduct. The highest levels of mRNA expression for GPx-1 were observed toward the end of the estrous cycle before ovulation, whereas GPx-2 was mostly expressed at midcycle. Catalase and Cu,ZnSOD mRNA analyses revealed a homogenous expression along the oviduct. The highest levels of glutathione and enzymatic activities for GPx and catalase occurred at the middle (10‐12 days) and end (18‐20 days) of the estrous cycle, whereas total SOD activity remained constant throughout the estrous cycle in the oviductal fluids. These findings underscore the importance of hydrogen peroxide and hydroperoxide removal by GPx in the oviduct. The heterogeneous expression of antioxidants such as GPx along the oviduct is a possible indication of their physiological role in the events leading to successful fertilization and implantation in vivo. fallopian tubes, female reproductive tract, fertilization, oviduct, ovulatory cycle

A modified polysulfone containing benzylamine groups was synthesized as a reactive membrane material. Polysulfone was activated at the ortho-sulfone site by direct lithiation with n-butyllithium, and the resulting lithiated polysulfone was then reacted with benzonitrile; this yielded a polymer with pendant benzimine groups. The structure was confirmed by NMR and IR spectroscopy and by the transformation of imine to ketone by acid hydrolysis. The polymeric benzimine was also reduced to benzylamine with sodium cyanoborohydride in an acidic medium. The structure and degree of substitution of both benzylamine derivatives were determined by NMR and IR spectroscopy. The modified polysulfone containing benzylamine groups initiated the polymerization of N-carboxyanhydride of γ-benzyl-L-glutamate [Glu(OBzl)–NCA]. The side-chain oligopeptide of Glu(OBzl)–NCA attached to polysulfone was converted into molecular recognition sites. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 1316–1329, 2003

Reactive oxygen species formation is strongly suspected to play a role in multistep carcinogenesis, notably in tumor promotion. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) induces peroxide production, oxidative damage to DNA and inflammation in mouse skin. TPA is also known to cause a decrease in the activity of several anti-oxidant enzymes including glutathione peroxidases (GPx). The observation that several anti-oxidants can inhibit TPA-mediated tumor promotion suggests that a decline in GPx activity could contribute to tumor promotion. We report here the effects of TPA on GPx activity in the skin of transgenic GPx mice that contain human GPx-1 transgenes under the regulation of a metallothionein IIA promoter. As expected, no significant difference in basal level of skin GPx activity was detected in the 3 lines of tg-MT-GPx mice investigated compared with non-transgenic controls. A single topical application of TPA induced gradually, over 20 hr, a small but detectable increase in GPx mRNA and protein levels in skin of non-transgenic mice and a contrasting decrease in both selenium-dependent and selenium-independent GPx activity. The extent of GPx induction was more pronounced in transgenic mice, and in contrast with non-transgenic mice, no significant loss of GPx activity was observed in the TPA-treated skin of these mice. Transgenic mice may, therefore, offer a novel model suitable to assess the role of GPx-1 in skin carcinogenesis, without the potential disadvantage of abnormally high levels of GPx activity produced constitutively in other transgenic models. Int. J. Cancer 80:863–867, 1999. © 1999 Wiley-Liss, Inc.

Plasma F2-isoprostanes (F2-isoPs) are reliable biomarkers of oxidative stress. Several possible F2-isoPs are generated by the oxidation of arachidonic acid esterified in phospholipids. The separation of these isomers represents a technical challenge for rapid and selective determination. We have developed a HPLC-MS/MS method for the simultaneous determination of seven plasma F2-isoPs, namely 8-iso-15(R)-prostaglandin F2α (PGF2α), 8-iso-PGF2α, 15(R)-PGF2α, iPF2α-IV, iPF2α-VI, 5-iPF2α-VI, and (±)5-8,12-iso-iPF2α-VI. We have validated this method in plasma of pregnant women, a mild physiological oxidative stress known to increase F2-isoPs. Thus, plasma samples of women collected at the third trimester of pregnancy (n = 20) were subjected to alkaline hydrolysis followed by liquid-liquid extraction in order to extract total F2-isoPs. The F2-isoPs were separated within 16.5 min using a column packed with core-shell particles. The class VI isomers were the most abundant, accounting for 65% of the total level of all quantified F2-isoPs in plasma of pregnant women (P < 0.05). The 15(R)-PGF2α was the most abundant of the class III isomers quantified. This method allowed fast and selective separation of seven isomers from three different classes of F2-isoP regioisomers.

A two-dimensional model is developed for the growth of ultrafine metal powders in a thermal plasma reactor. The model accounts for particle formation by nucleation, and growth by condensation and Brownian coagulation. Transport of particles occurs by convection, thermophoresis, and Brownian diffusion. The conservation equations for the moments of the particle size distribution are solved, coupled to the equation for the conservation of metal vapor. Elliptic conservation equations result from the consideration of both axial and radial diffusion of the particles. This allows for simulations in complex, recirculating flows, which are likely to occur for numerous reactor configurations and parameters. A progressive grid refining technique is used to accelerate convergence. The model is applied to the case of a typical thermal plasma reactor for the production of ultrafine iron powders. The fields of the macroscopic properties of the aerosol population and the contribution of the different mechanisms ...

A mathematical model of biomass gasification in a fluidized bed has been developed. It considers axial variations of concentrations and temperature in the bubble and emulsion phases. The mass balance involves instantaneous oxidation and equilibrium devolatilization of the biomass, kinetics of solid-gas gasification reactions as well as of gaseous phase reactions and interphase mass transfer and gas convection. The energy balance is solved locally for each vertical volume element, and globally on the reactor by iteration on the temperature at the bottom of the bed. Three parameters have been adjusted based on the experimental results: the heat transfer coefficient at the wall, the weighting of the kinetics of the water-gas shift reaction and the fraction of biomass carbon remaining as char after devolatilization. The model is used to simulate a pilot scale (50 kg/h) biomass gasifier, and its predictions compared to experimental measurements. The temperature and gaseous concentrations are estimated with good accuracy for the experiments using a wood feedstock, except for the concentration of hydrogen which is overestimated.

Two related stereoselective syntheses of 3,7-dimethylnonadecane, a sex pheromone of the alfalfa leafminer, are described to show that pulegone can serve as a useful starting material for the preparation of chiral aliphatic isoprenoid compounds. The schemes are designed to place the stereogenic center of pulegone at C.3 in one synthesis and at C.7 in the other so that the optical properties of the products can be compared with one another and with the values calculated using Brewster's rules. Key words: chiral hydrocarbons, stereoselective synthesis, pheromone, Agromyza frontella.

The balanced presence of reactive oxygen species and antioxidants has a positive impact on sperm functions, oocyte maturation, fertilization, and embryo development in vitro. The mammalian oviduct is likely to provide an optimal environment for final gamete maturation, sperm-egg fusion, and early embryonic development. However, the expression and distribution of antioxidant enzymes in the bovine oviduct are poorly characterized. We analyzed the mRNA expression and enzymatic activities of major antioxidants glutathione peroxidase (GPx), superoxide dismutase (Cu,ZnSOD), and catalase in the bovine oviduct throughout the estrous cycle. The high levels of expression for GPx-3 in the isthmus were in contrast to expression of GPx-1 and GPx-2, which occurred mostly in the ampulla and infundibulum of the oviduct. The highest levels of mRNA expression for GPx-1 were observed toward the end of the estrous cycle before ovulation, whereas GPx-2 was mostly expressed at midcycle. Catalase and Cu,ZnSOD mRNA analyses revealed a homogenous expression along the oviduct. The highest levels of glutathione and enzymatic activities for GPx and catalase occurred at the middle (10-12 days) and end (18-20 days) of the estrous cycle, whereas total SOD activity remained constant throughout the estrous cycle in the oviductal fluids. These findings underscore the importance of hydrogen peroxide and hydroperoxide removal by GPx in the oviduct. The heterogeneous expression of antioxidants such as GPx along the oviduct is a possible indication of their physiological role in the events leading to successful fertilization and implantation in vivo.

Polysulfones with rigid backbone structures and silyl-containing substituents were prepared as membrane materials with potentially enhanced gas transport properties. Tetramethylbisphenol-A polysulfone (TMPSf) and tetramethylbiphenol polysulfone (TMPPSf) were made by polycondensation then post-modified to introduce trimethylsilyl (TMS) groups by bromination and lithiation methodology. Substitution of high levels of TMS groups at the ortho-sulfone sites was achieved using direct lithiation followed by addition of a trimethylsilane electrophile. In an approach to increase the overall TMS substitution level as well as introduce these groups on the bisphenol segment, both TMPSf and TMPPSf were cleanly brominated to a degree of substitution (DS) of 2.0 for bromine. While the subsequent lithium舑halogen exchange and reaction with TMS electrophile did not give high regioselectivity because of steric hindrance, the overall DS of TMS in the polymers was increased when excess n-butyllithium was used to activate both brominated and ortho-sulfone sites. The polymer structures were characterized by NMR spectroscopy. Their thermal properties as well as O2, N2, CO2 and CH4 gas transport properties were measured. Polymers with a high DS of TMS had very high CO2 and O2 permeabilities and good permselectivities from N2. The permselectivities of CO2/N2 were at or close to the Robeson upper-bound performance line, available, unlimited, public

The commercial polyimide Matrimid was modified by bromination for the purpose of improving its membrane-transport properties as a gas-separation material and providing functional group reactivity for further modifications. The unmodified and brominated polymers were characterized by elemental analysis and one-dimensional and two-dimensional NMR, which revealed that one bromine atomper repeat unit was incorporated regioselectively onto the indane aromatic ring. The thermal and physical properties of the polymers before and after bromination were also investigated. The gas-transport properties of the unmodified and brominated polymers were compared., available, unlimited, public