NMDA Receptor antagonists prevent acute ammonia toxicity in mice

We proposed that acute ammonia toxicity is mediated by activation of NMDA receptors. To confirm this hypothesis we have tested whether different NMDA receptor antagonists, acting on different sites of NMDA receptors, prevent death of mice induced by injection of 14 mmol/Kg of ammonium acetate, a dose that induces death of 95% of mice. MK-801, phencyclidine and ketamine, which block the ion channel of NMDA receptors, prevent death of at least 75% of mice. CPP, AP-5, CGS 19755, and CGP 40116, competitive antagonists acting on the binding site for NMDA, also prevent death of at least 75% of mice. Butanol, ethanol and methanol which block NMDA receptors, also prevent death of mice. There is an excellent correlation between the EC₅₀ for preventing ammonia-induced death and the IC₅₀ for inhibiting NMDA-induced currents. Acute ammonia toxicity is not prevented by antagonists of kainate/AMPA receptors, of muscarinic or nicotinic acetylcholine receptors or of GABA receptors. Inhibitors of nitric oxide synthase afford partial protection against ammonia toxicity while inhibitors of calcineurin, of glutamine synthetase or antioxidants did not prevent ammonia-induced death of mice. These results strongly support the idea that acute ammonia toxicity is mediated by activation of NMDA receptors.     

Building bridges: an integrated strategy for sustainable food production throughout the value chain

The food production and processing value chain is under pressure from all sides—increasing demand driven by a growing and more affluent population; dwindling resources caused by urbanization, land erosion, pollution and competing agriculture such as biofuels; and increasing constraints on production methods driven by consumers and regulators demanding higher quality, reduced chemical use, and most of all environmentally beneficial practices ‘from farm to fork’. This pressure can only be addressed by developing efficient and sustainable agricultural practices that are harmonized throughout the value chain, so that renewable resources can be exploited without damaging the environment. Bridges must, therefore, be built between the diverse areas within the food production and processing value chain, including bridges between different stages of production, between currently unlinked agronomic practices, and between the different levels and areas of research to achieve joined-up thinking within the industry, so that the wider impact of different technologies, practices and materials on productivity and sustainability is understood at the local, regional, national and global scales. In this article, we consider the challenges at different stages and levels of the value chain and how new technologies and strategies could be used to build bridges and achieve more sustainable food/feed production in the future.     

Serotypes and Clonal Diversity of Streptococcus pneumoniae Causing Invasive Disease in the Era of PCV13 in Catalonia,Spain

The aim of this study was to study the serotypes and clonal diversity of pneumococci causing invasive pneumococcal disease in Catalonia, Spain, in the era of 13-valent pneumococcal conjugate vaccine (PCV13). In our region, this vaccine is only available in the private market and it is estimated a PCV13 vaccine coverage around 55% in children. A total of 1551 pneumococcal invasive isolates received between 2010 and 2013 in the Molecular Microbiology Department at Hospital Sant Joan de Déu, Barcelona, were included. Fifty-two serotypes and 249 clonal types—defined by MLST—were identified. The most common serotypes were serotype 1 (n = 182; 11.7%), 3 (n = 145; 9.3%), 19A (n = 137; 8.8%) and 7F (n = 122; 7.9%). Serotype 14 was the third most frequent serotype in children < 2 years (15 of 159 isolates). PCV7 serotypes maintained their proportion along the period of study, 16.6% in 2010 to 13.4% in 2013, whereas there was a significant proportional decrease in PCV13 serotypes, 65.3% in 2010 to 48.9% in 2013 (p<0.01). This decrease was mainly attributable to serotypes 19A and 7F. Serotype 12F achieved the third position in 2013 (n = 22, 6.4%). The most frequent clonal types found were ST306 (n = 154, 9.9%), ST191 (n = 111, 7.2%), ST989 (n = 85, 5.5%) and ST180 (n = 80, 5.2%). Despite their decrease, PCV13 serotypes continue to be a major cause of disease in Spain. These results emphasize the need for complete PCV13 vaccination.     

Chronic hyperammonemia alters protein phosphorylation and glutamate receptor-associated signal transduction in brain

There is substantial evidence that hyperammonemia is one of the main factors contributing to the neurological alterations found in hepatic encephalopathy. The mechanisms by which chronic moderate hyperammonemia affects brain function involves alterations in neurotransmission at different steps. This article reviews the effects of hyperammonemia on phosphorylation of key brain proteins involved in neurotransmission (the microtubule-associated protein (MAP-2), Na+/K+-ATPase and NMDA receptors). The physiological function of these proteins is modulated by phosphorylation and its altered phosphorylation in hyperammonemia may contribute to impairment of neurotransmission. The effects of chronic hyperammonemia on signal transduction pathways associated to glutamate receptors, such as the glutamate-nitric oxide (NO)-cGMP pathway, are also reviewed. The possible contribution of the impairment of this pathway in brain in vivo to the neurological alterations present in patients with hepatic encephalopathy is discussed.     

Neospora caninum and coxiella burnetii seropositivity are related to endocrine pattern changes during gestation in lactating dairy cows

Q fever is a zoonotic infection caused by Coxiella burnetii that is endemic worldwide. Domestic ruminants are a source of infection for humans. Given the suggestion that the bacterium recrudesces during pregnancy in cattle, this study was designed to determine whether C. burnetii infection affects hormonal patterns, such as progesterone, cortisol, pregnancy associated glycoproteins (PAG), and prolactin during gestation in lactating cows. Possible interactions with Neospora caninum were also explored. The study was performed on 58 gestating non-aborting cows. Blood samples for hormone determinations were collected on Days 40, 90, 120, 150, 180, and 210 of gestation. For antibody determinations, blood was collected at day 40 postinsemination and postpartum. By GLM repeated measures analysis of variance, we established the effects of production and reproductive variables as well as Coxiella and Neospora seropositivity related to changes on cortisol, PAG, progesterone, and prolactin levels. Coxiella antibody levels were significantly related to cortisol, PAG, and plasma progesterone concentrations, whereas Neospora seropositivity was linked to plasma progesterone concentrations. The interaction between Coxiella and Neospora seropositivity was correlated with cortisol and plasma progesterone levels, whereas the interaction seropositivity against C. burnetii-plasma cortisol concentration was related to plasma PAG levels. Finally, an effect of lactation number only was observed on plasma prolactin. Our findings suggest that both the N. caninum and C. burnetii infection or the presence of both modify endocrine patterns throughout gestation. Cows seropositive to both, Neospora and Coxiella, showed higher plasma progesterone levels than the remaining animals examined. Seropositivity to C. burnetii was associated with placental damage and diminishing PAG levels throughout the second half of gestation, along with increased plasma cortisol levels on Day 180 of gestation.     

Kinetic and structural features of betaine aldehyde dehydrogenases: Mechanistic and regulatory implications

The betaine aldehyde dehydrogenases (BADH; EC 1.2.1.8) are so-called because they catalyze the irreversible NAD(P)⁺-dependent oxidation of betaine aldehyde to glycine betaine, which may function as (i) a very efficient osmoprotectant accumulated by both prokaryotic and eukaryotic organisms to cope with osmotic stress, (ii) a metabolic intermediate in the catabolism of choline in some bacteria such as the pathogen Pseudomonas aeruginosa, or (iii) a methyl donor for methionine synthesis. BADH enzymes can also use as substrates aminoaldehydes and other quaternary ammonium and tertiary sulfonium compounds, thereby participating in polyamine catabolism and in the synthesis of γ-aminobutyrate, carnitine, and 3-dimethylsulfoniopropionate. This review deals with what is known about the kinetics and structural properties of these enzymes, stressing those properties that have only been found in them and not in other aldehyde dehydrogenases, and discussing their mechanistic and regulatory implications.     

Factors affecting the fertility of high producing dairy herds in northeastern Spain

Infertility has been often correlated to a rising milk yield in high producing dairy cattle. The aim of the present study was to evaluate, using logistic regression procedures, the effects of several management indicators on the fertility of four dairy herds in northeastern Spain. Data derived from 10,965 artificial insemination (AI). The factors examined were: herd, milking frequency (three versus two milkings per day), lactation number, previous twinning and disorders such as placenta retention and pyometra, milk production at AI, the inseminating bull, season (warm versus cool period) and year effects, AI technician and repeat breeding syndrome (cows undergoing four or more AI). Our findings indicated no effects on fertility of the herd, year of AI, previous twining, placenta retention and pyometra and milk production at AI. Based on the odds ratios, the likelihood of pregnancy decreased: in cows milked three times per day (by a factor of 0.62); for each one unit increase in lactation number (by a factor of 0.92); for inseminations performed during the warm period (by a factor of 0.67); in repeat breeder cows (by a factor of 0.73); and when 3 of the 45 inseminating bulls included in the study were used (by factors of 0.35, 0.43 and 0.44, respectively). Of the 13 AI technicians participating in the study, 3 were related to a fertility rate improved by odds ratios of 1.86, 1.84 and 1.30, respectively, whereas 2 technicians gave rise to fertility rates reduced by odds ratios of 0.64 and 0.49, respectively. Under our study conditions, management practices were able to compensate for the effects of previous twining and reproductive disorders such as placenta retention and pyometra. However, fertility was significantly affected by the factors milking frequency, AI technician, inseminating bull, repeat breeding syndrome, lactation number and AI season.     

Immobilization of chloroperoxidase on silica-based materials for 4,6-dimethyl dibenzothiophene oxidation

Silica-based materials have been used as effective supports for the immobilization of enzymes. Moreover, the understanding on the oxidation of sulfur compounds by immobilized chloroperoxidase represents a step further in the development of a biocatalytic desulfurization process of fossil fuels. Here, chloroperoxidase from Caldariomyces fumago was immobilized on amorphous and structured silica-based materials either physically or covalently using an organosilane derivative for the oxidation of a recalcitrant organosulfur compound currently found in gas oil and diesel, such as 4,6-dimethyldibenzothiophene (4,6-DMDBT). Such materials were characterized by FTIR, N₂-adsorption, XRD, SEM and TEM. We have found that the chemical differences on the silanol/siloxane groups of SG/67 and SBA15 mesoporous materials deeply modify the enzymatic load, activity, thermal stability and reusability. The physical immobilization of CPO was characterized by a high adsorption capacity (q_m) and affinity constants (K_m) when compared to the covalent approach, but it resulted more sensitive to temperature than free, the silanized and covalently immobilized enzyme. The thermal residual activity as well as reusability of CPO were first improved by silanization, then by covalent immobilization in a support with a large pore size and high silanol/siloxane ratio.