Analysis of Sex-Specific Prostanoid Production Using a Mouse Model of Selective Cyclooxygenase-2 Inhibition

Background: Prostanoids are a family of lipid mediators formed from arachidonic acid by cyclooxygenase enzymes and serve as biomarkers of vascular function. Prostanoid production may be different in males and females indicating that different therapeutic approaches may be required during disease. Objecti ves: We examined sex-dependent differences in COX-related metabolites in genetically modified mice that produce a cyclooxygenase- 2 (COX2) enzyme containing a tyrosine 385 to phenylalanine (Y385F) mutation. This mutation renders the COX2 enzyme unable to form a key intermediate radical required for complete arachidonic acid metabolism and provides a model of selective COX2 inhibition. Design and Methods: Mice heterozygous for the Y385F mutation in COX2 were mated to produce cohorts of wild-type, heterozygous, and COX2 mutant mice. We investigated whether the genotype distribution followed Mendelian genetics and studied whether sex-specific differences could be found in certain prostanoid levels measured in peritoneal macrophages and in urinary samples. Results : The inheritance of the COX2 mutation displayed a significant deviation with respect to Mendel’s laws of genetics, with a lowerthan- expected progeny of weaned COX2 mutant pups. In macrophages, prostaglandin E2 (PGE2) production following lipopolysaccharide (LPS) and interferon gamma (IFNγ) stimulation was COX2-dependent in both males and females, and data indicated that crosstalk between the nitric oxide (NO) and COX2 pathways may be sex specific. We observed significant differences in urinary PGE2 production by male and female COX2 mutant mice, with the loss of COX2 activity in male mice decreasing their ability to produce urinary PGE2. Finally, female mice across all 3 genotypes produced similar levels of urinary thromboxane (measured as 11-dehydro TxB2) at significantly higher levels than males, indicating a sex-related difference that is likely COX1-derived. Conclusions: Our findings clearly demonstrate that sex-related differences in COX-derived metabolites can be observed, and that other pathways (such as the NO pathway) are affected

Intention Understanding in Autism

When we observe a motor act (e.g. grasping a cup) done by another individual, we extract, according to how the motor act is performed and its context, two types of information: the goal (grasping) and the intention underlying it (e.g. grasping for drinking). Here we examined whether children with autistic spectrum disorder (ASD) are able to understand these two aspects of motor acts. Two experiments were carried out. In the first, one group of high-functioning children with ASD and one of typically developing (TD) children were presented with pictures showing hand-object interactions and asked what the individual was doing and why. In half of the “why” trials the observed grip was congruent with the function of the object (“why-use” trials), in the other half it corresponded to the grip typically used to move that object (“why-place” trials). The results showed that children with ASD have no difficulties in reporting the goals of individual motor acts. In contrast they made several errors in the why task with all errors occurring in the “why-place” trials. In the second experiment the same two groups of children saw pictures showing a hand-grip congruent with the object use, but within a context suggesting either the use of the object or its placement into a container. Here children with ASD performed as TD children, correctly indicating the agent's intention. In conclusion, our data show that understanding others' intentions can occur in two ways: by relying on motor information derived from the hand-object interaction, and by using functional information derived from the object's standard use. Children with ASD have no deficit in the second type of understanding, while they have difficulties in understanding others' intentions when they have to rely exclusively on motor cues

The Physics of the B Factories

This work is on the Physics of the B Factories. Part A of this book contains a brief description of the SLAC and KEK B Factories as well as their detectors, BaBar and Belle, and data taking related issues. Part B discusses tools and methods used by the experiments in order to obtain results. The results themselves can be found in Part C

Measurement of the Ratio of b Quark Production Cross Sections in Antiproton-Proton Collisions at 630 GeV and 1800 GeV

We report a measurement of the ratio of the bottom quark production cross section in antiproton-proton collisions at 630 GeV to 1800 GeV using bottom quarks with transverse momenta greater than 10.75 GeV identified through their semileptonic decays and long lifetimes. The measured ratio sigma(630)/sigma(1800) = 0.171 +/- .024 +/- .012 is in good agreement with next-to-leading order (NLO) quantum chromodynamics (QCD)

The behaviour of giant clams (Bivalvia: Cardiidae: Tridacninae)

Giant clams, the largest living bivalves, live in close association with coral reefs throughout the Indo-Pacific. These iconic invertebrates perform numerous important ecological roles as well as serve as flagship species—drawing attention to the ongoing destruction of coral reefs and their associated biodiversity. To date, no review of giant clams has focussed on their behaviour, yet this component of their autecology is critical to their life history and hence conservation. Almost 100 articles published between 1865 and 2014 include behavioural observations, and these have been collated and synthesised into five sections: spawning, locomotion, feeding, anti-predation, and stress responses. Even though the exact cues for spawning in the wild have yet to be elucidated, giant clams appear to display diel and lunar periodicities in reproduction, and for some species, peak breeding seasons have been established. Perhaps surprisingly, giant clams have considerable mobility, ranging from swimming and gliding as larvae to crawling in juveniles and adults. Chemotaxis and geotaxis have been established, but giant clams are not phototactic. At least one species exhibits clumping behaviour, which may enhance physical stabilisation, facilitate reproduction, or provide protection from predators. Giant clams undergo several shifts in their mode of acquiring nutrition; starting with a lecithotrophic and planktotrophic diet as larvae, switching to pedal feeding after metamorphosis followed by the transition to a dual mode of filter feeding and phototrophy once symbiosis with zooxanthellae (Symbiodinium spp.) is established. Because of their shell weight and/or byssal attachment, adult giant clams are unable to escape rapidly from threats using locomotion. Instead, they exhibit a suite of visually mediated anti-predation behaviours that include sudden contraction of the mantle, valve adduction, and squirting of water. Knowledge on the behaviour of giant clams will benefit conservation and restocking efforts and help fine-tune mariculture techniques. Understanding the repertoire of giant clam behaviours will also facilitate the prediction of threshold levels for sustainable exploitation as well as recovery rates of depleted clam populations