Left−Right Asymmetry Defect in the Hippocampal Circuitry Impairs Spatial Learning and Working Memory in iv Mice

Although left-right (L−R) asymmetry is a fundamental feature of higher-order brain function, little is known about how asymmetry defects of the brain affect animal behavior. Previously, we identified structural and functional asymmetries in the circuitry of the mouse hippocampus resulting from the asymmetrical distribution of NMDA receptor GluR ε2 (NR2B) subunits. We further examined the ε2 asymmetry in the inversus viscerum (iv) mouse, which has randomized laterality of internal organs, and found that the iv mouse hippocampus exhibits right isomerism (bilateral right-sidedness) in the synaptic distribution of theε2 subunit, irrespective of the laterality of visceral organs. To investigate the effects of hippocampal laterality defects on higher-order brain functions, we examined the capacity of reference and working memories of iv mice using a dry maze and a delayed nonmatching-to-position (DNMTP) task, respectively. The iv mice improved dry maze performance more slowly than control mice during acquisition, whereas the asymptotic level of performance was similar between the two groups. In the DNMTP task, the iv mice showed poorer accuracy than control mice as the retention interval became longer. These results suggest that the L−R asymmetry of hippocampal circuitry is critical for the acquisition of reference memory and the retention of working memory

Cyclo-oxygenase-2 selective inhibitors and nonsteroidal anti-inflammatory drugs: balancing gastrointestinal and cardiovascular risk

<p>Abstract</p> <p>Background</p> <p>Differences between gastrointestinal and cardiovascular effects of traditional NSAID or cyclooxygenase-2 selective inhibitor (coxib) are affected by drug, dose, duration, outcome definition, and patient gastrointestinal and cardiovascular risk factors. We calculated the absolute risk for each effect.</p> <p>Methods</p> <p>We sought studies with large amounts of information to calculate annualised rates for clearly defined gastrointestinal (complicated upper gastrointestinal perforations, ulcers, or bleeds, but not symptomatic or endoscopic ulcers) and serious cardiovascular outcomes (antiplatelet trial collaborators – APTC – outcome of fatal or nonfatal myocardial infarction or stroke, or vascular death).</p> <p>Results</p> <p>Meta-analyses and large randomised trials specifically analysing serious gastrointestinal bleeding or cardiovascular events occurring with five different coxibs had appropriate data. In total there were 439 complicated upper gastrointestinal events in 49,006 patient years of exposure and 948 serious cardiovascular events in 99,400 patient years of exposure. Complicated gastrointestinal events occurred less frequently with coxibs than NSAIDs; serious cardiovascular events occurred at approximately equal rates. For each coxib, the reduction in complicated upper gastrointestinal events was numerically greater than any increase in APTC events. In the overall comparison, for every 1000 patients treated for a year with coxib rather than NSAID, there would be eight fewer complicated upper gastrointestinal events, but one more fatal or nonfatal heart attack or stroke. Three coxib-NSAID comparisons had sufficient numbers of events for individual comparisons. For every 1000 patients treated for a year with celecoxib rather than an NSAID there would be 12 fewer upper gastrointestinal complications, and two fewer fatal or nonfatal heart attacks or strokes. For rofecoxib there would be six fewer upper gastrointestinal complications, but three more fatal or nonfatal heart attacks or strokes. For lumiracoxib there would be eight fewer upper gastrointestinal complications, but one more fatal or nonfatal heart attack or stroke.</p> <p>Conclusion</p> <p>Calculating annualised event rates for gastrointestinal and cardiovascular harm shows that while complicated gastrointestinal events occur more frequently with NSAIDs than coxibs, serious cardiovascular events occur at approximately equal rates. For each coxib, the reduction in complicated upper gastrointestinal events was numerically greater than any increase in APTC events.</p

Exopolysaccharides produced by Lactococcus lactis: from genetic engineering to improved rheological properties

Over the last years, important advances have been made in the study of the production of exopolysaccharides (EPS) by several lactic acid bacteria, including Lactococcus lactis. From different EPS-producing lactococcal strains the specific eps gene clusters have been characterised. They contain eps genes, which are involved in EPS repeating unit synthesis, export, polymerisation, and chain length determination. The function of the glycosyltransferase genes has been established and the availability of these genes opened the way to EPS engineering. In addition to the eps genes, biosynthesis of EPS requires a number of housekeeping genes that are involved in the metabolic pathways leading to the EPS-building blocks, the nucleotide sugars. The identification and characterisation of several of these housekeeping genes (galE, galU, rfbABCD) allows the design of metabolic engineering strategies that should lead to increased EPS production levels by L. lactis. Finally, model development has been initiated in order to predict the physicochemical consequences of the addition of a EPS to a product