Chelation-controlled regioselective alkylation of pyrimidine 2′-deoxynucleosides

Protection-deprotection steps, which are usually needed for regioselective alkylation of pyrimidine deoxynucleosides, can be avoided by choosing the appropriate solvent. The combined effects of low dielectric constant and possible sodium chelation by pyrimidine nucleosides may account for the unexpected regioselectivity observed in THF.     

Early diet of preterm infants and development of allergic or atopic disease: randomised prospective study.

OBJECTIVE--To study the effect of early diet on the development of allergic reactions in infants born preterm. DESIGN--Two randomised prospective trails. In trail A infants were randomly allocated banked donor milk or preterm formula as their sole diet or (separately randomised) as a supplement to their mother''s expressed breast milk. In trial B infants were allocated term or preterm formula. A blind follow up examination was done 18 months after the expected date of birth. SETTING--Neonatal units of hospitals in Cambridge, Ipswich, King''s Lynn, Norwich, and Sheffield. Outpatient follow up. PARTICIPANTS--777 Infants with a birth weight less than 1850 g born during 1982 to 1984. MAIN OUTCOME MEASURES--Development of eczema, allergic reactions to food or drugs, and asthma or wheezing by nine and 18 months after term. Whenever possible the observations were confirmed by rechallenge or clinical examination. RESULTS--At 18 months after term there was no difference in the incidence of allergic reactions between dietary groups in either trial. In the subgroup of infants with a family history of atopy, however, those in trial A who received preterm formula rather than human milk had a significantly greater risk of developing one or more allergic reactions (notably eczema) by 18 months (odds ratio 3.6; 95% confidence interval 1.4 to 9.1). CONCLUSIONS--Feeding neonates on formulas based on cows'' milk, including those with a high protein content, did not increase the overall risk of allergy. Nevertheless, in the subgroup with a family history of atopy early exposure to cows'' milk increased the risk of a wide range of allergic reactions, especially eczema.     

Chronic hyperammonemia alters in opposite ways membrane expression of GluA1 and GluA2 AMPA receptor subunits in cerebellum. Molecular mechanisms involved

Hyperammonemia contributes to altered neurotransmission and cognition in patients with hepatic encephalopathy. Hyperammonemia in rats affects differently high- and low-affinity AMPA receptors (AMPARs) in cerebellum. We hypothesized that hyperammonemia would alter differently membrane expression of AMPARs GluA1 and GluA2 subunits by altering its phosphorylation. This work aims were: 1) assess if hyperammonemia alters GluA1 and GluA2 subunits membrane expression in cerebellum and 2) analyze the underlying mechanisms.Hyperammonemia reduces membrane expression of GluA2 and enhances membrane expression of GluA1 in vivo. We show that changes in GluA2 and GluA1 membrane expression in hyperammonemia would be due to enhanced NMDA receptors activation which reduces cGMP levels and phosphodiesterase 2 (PDE2) activity, resulting in increased cAMP levels. This leads to increased protein kinase A (PKA) activity which activates phospholipase C (PLC) and protein kinase C (PKC) thus increasing phosphorylation of GluA2 in Ser880, which reduces GluA2 membrane expression, and phosphorylation of GluA1 in Ser831, which increases GluA1 membrane expression. Blocking NMDA receptors or inhibiting PKA, PLC or PKC normalizes GluA2 and GluA1 phosphorylation and membrane expression in hyperammonemic rats.Altered GluA2 and GluA1 membrane expression would alter signal transduction which may contribute to cognitive and motor alterations in hyperammonemia and hepatic encephalopathy.     

Phototrophic marine benthic microbiomes: the ecophysiology of these biological entities

Phototrophic biofilms are multispecies, self-sustaining and largely closed microbial ecosystems. They form macroscopic structures such as microbial mats and stromatolites. These sunlight-driven consortia consist of a number of functional groups of microorganisms that recycle the elements internally. Particularly, the sulfur cycle is discussed in more detail as this is fundamental to marine benthic microbial communities and because recently exciting new insights have been obtained. The cycling of elements demands a tight tuning of the various metabolic processes and require cooperation between the different groups of microorganisms. This is likely achieved through cell-to-cell communication and a biological clock. Biofilms may be considered as a macroscopic biological entity with its own physiology. We review the various components of some marine phototrophic biofilms and discuss their roles in the system. The importance of extracellular polymeric substances (EPS) as the matrix for biofilm metabolism and as substrate for biofilm microorganisms is discussed. We particularly assess the importance of extracellular DNA, horizontal gene transfer and viruses for the generation of genetic diversity and innovation, and for rendering resilience to external forcing to these biological entities.