Hydrogen-poor superluminous stellar explosions.

Supernovae are stellar explosions driven by gravitational or thermonuclear energy that is observed as electromagnetic radiation emitted over weeks or more. In all known supernovae, this radiation comes from internal energy deposited in the outflowing ejecta by one or more of the following processes: radioactive decay of freshly synthesized elements (typically (56)Ni), the explosion shock in the envelope of a supergiant star, and interaction between the debris and slowly moving, hydrogen-rich circumstellar material. Here we report observations of a class of luminous supernovae whose properties cannot be explained by any of these processes. The class includes four new supernovae that we have discovered and two previously unexplained events (SN 2005ap and SCP 06F6) that we can now identify as members of the same class. These supernovae are all about ten times brighter than most type Ia supernova, do not show any trace of hydrogen, emit significant ultraviolet flux for extended periods of time and have late-time decay rates that are inconsistent with radioactivity. Our data require that the observed radiation be emitted by hydrogen-free material distributed over a large radius (∼10(15) centimetres) and expanding at high speeds (>10(4) kilometres per second). These long-lived, ultraviolet-luminous events can be observed out to redshifts z > 4.

Sperm competition and the evolution of gametic compatibility in externally fertilizing taxa.

Proteins expressed on the surface of sperm and egg mediate gametic compatibility and these proteins can be subject to intense positive selection. In this review, we discuss what is known about the patterns of adaptive evolution of gamete recognition proteins (GRPs). We focus on species that broadcast eggs and sperm into the environment for external fertilization, as the ease of observing and manipulating gamete interactions has allowed for greater advances in the understanding of GRP evolution, uncomplicated by confounding behavioral and physiological components that offer alternative evolutionary targets in internal fertilizers. We discuss whether interspecific mechanisms, such as selection to avoid fertilization between species (reinforcement selection), or intraspecific mechanisms, such as selection to increase (or decrease) the affinity between eggs and sperm based on the intensity of sperm competition, may be responsible for the pattern of GRP evolution observed. Variation in these proteins appears to influence gametic compatibility; GRP divergence among species is a better predictor of hybrid fertilization than neutral genetic markers and GRP variation within species predicts reproductive success among individuals within a population. Evidence suggests that sperm competition may play a large role in the evolution of gametic compatibility.

Asymmetric conspecific sperm precedence in relation to spawning times in the Montastraea annularis species complex (Cnidaria: Scleractinia).

In broadcast spawners, prezygotic reproductive isolation depends on differences in the spatial and temporal patterns of gamete release and gametic incompatibility. Typically, gametic incompatibility is measured in no-choice crosses, but conspecific sperm precedence (CSP) can prevent hybridization in gametes that are compatible in the absence of sperm competition. Broadcast spawning corals in the Montastraea annularis species complex spawn annually on the same few evenings. Montastraea franksi spawns an average of 110 min before M. annularis, with a minimum gap of approximately 40 min. Gametes are compatible in no-choice heterospecific assays, but it is unknown whether eggs exhibit choice when in competition. Hybridization depends on either M. franksi eggs remaining unfertilized and in proximity to M. annularis when the latter species spawns or M. franksi sperm remaining in sufficient viable concentrations when M. annularis spawns. We found that the eggs of the early spawning M. franksi demonstrate strong CSP, whereas CSP appears to be lacking for M. annularis eggs. This study provides evidence of diverging gamete affinities between these recently separated species and suggests for the first time that selection may favour CSP in earlier spawning species when conspecific sperm is diluted and aged and is otherwise at a numeric and viability disadvantage with heterospecific sperm.

Influence of temperature on linear stability in buoyancy-driven fingering of reaction-diffusion fronts.

A vertical Hele-Shaw cell was used to study the influence of temperature on Rayleigh-Taylor instabilities on reaction-diffusion fronts. The propagation of the chemical front can thus be observed, and experimental results can be obtained via image treatment. A chemical front produced by the coupling between molecular diffusion and the auto-catalysis of the chlorite-tetrathionate reaction, descends through the cell, consuming the reactants below while the product is formed above. Buoyancy-driven instabilities are formed due to the density difference between reactants and products, and the front takes a fingering pattern, whose growth rate has temperature dependence. In this study, the effect of temperature on the linear regime of the instability (that is, when the effects of such instability start to appear) was analyzed. To measure the instability, Fourier transform analysis is performed, in order to obtain the different wave numbers and their power as a function of time. Thus, the growth rate for each wave number and the most unstable wave number is obtained for each of the temperatures under study. Based on repeated experiments, a decrease in the growth rate for the most unstable wave number can be observed with the increase of temperature.

Rationale for hyperbaric oxygen therapy in traumatic injury and wound care in small animal veterinary practice.

Hyperbaric oxygen therapy is in wide use in human medicine around the world. Although hyperbaric oxygen therapy is available for veterinary use, it is still significantly underutilised. The physical principles, gas laws and physiologic mechanisms by which hyperbaric oxygen therapy is therapeutic, especially in traumatic injuries and complicated wound care, are discussed. Then, considerations are offered for the implementation of hyperbaric oxygen therapy in veterinary practices. Finally, a review of clinical indications for veterinary practices, including a presentation of select literature, is provided. Applying hyperbaric oxygen therapy in an earlier and more consistent manner could improve short- and long-term outcomes in complicated wounds. The authors also hope this information may stimulate interest in the design of future, prospective studies for the various clinical situations described.

An assessment of the carcinogenic potential of ezetimibe using nonclinical data in a weight-of-evidence approach.

Ezetimibe blocks intestinal absorption of sterols via interaction with the Neimann-Pick C1-Like 1 (NPC1L1) transporter and is approved for use in the treatment of primary hyperlipidemia (heterozygous familial and non-familial), homozygous familial hypercholesterolemia, and homozygous sitosterolemia. A recently completed randomized clinical trial [simvastatin and ezetimibe in aortic stenosis (SEAS)] testing the effectiveness of Vytorin (a combination of simvastatin and ezetimibe) in patients with aortic stenosis reported an unexpected safety finding: an increase in overall cancer incidence and cancer-associated mortality (all types) in the treated groups relative to the placebo control. A subsequent meta-analysis utilizing a much larger database from two ongoing clinical trials indicated that the observed findings in the SEAS trial were likely due to chance and not a true drug-induced effect. Nonetheless, it has been suggested by various commentators on the SEAS trial that ezetimibe may be carcinogenic. The extensive nonclinical database for ezetimibe was used to test the hypothesis that ezetimibe may be a direct or indirect carcinogen. Using two different in silico approaches, ezetimibe showed no structural alerts for genetic toxicity or carcinogenicity. Ezetimibe was not genotoxic in two reverse mutation assays, one in vitro clastogenicity assay, and two mouse micronucleus assays. No evidence of proliferative lesions was observed in three species in studies of 1-12 months in duration. Ezetimibe was not carcinogenic in standard 2-year bioassays in mice and rats. Additionally, in these 2-year bioassays, no drug-related non-neoplastic lesions were noted. The absence of drug-induced non-neoplastic or proliferative lesions in these studies indicates that ezetimibe treatment was not associated with findings characteristic of carcinogens (i.e., DNA reactivity or cell proliferation) Administration of pharmacologic doses of ezetimibe to mice did not alter hepatic expression patterns of genes associated with apoptosis, cell proliferation, or epithelial-mesenchymal transition. No evidence of drug-induced tumors was observed in mice in which the molecular target of ezetimibe (NPC 1L1) was knocked out over the life span of the animal. In conclusion, the nonclinical data do not support the proposed hypothesis based on the single observation from the SEAS trial and, rather, support the conclusion that ezetimibe does not represent a carcinogenic hazard to humans using this drug in a therapeutic setting.

Stellar dynamics. The fastest unbound star in our Galaxy ejected by a thermonuclear supernova.

Hypervelocity stars (HVSs) travel with velocities so high that they exceed the escape velocity of the Galaxy. Several acceleration mechanisms have been discussed. Only one HVS (US 708, HVS 2) is a compact helium star. Here we present a spectroscopic and kinematic analysis of US 708. Traveling with a velocity of ~1200 kilometers per second, it is the fastest unbound star in our Galaxy. In reconstructing its trajectory, the Galactic center becomes very unlikely as an origin, which is hardly consistent with the most favored ejection mechanism for the other HVSs. Furthermore, we detected that US 708 is a fast rotator. According to our binary evolution model, it was spun-up by tidal interaction in a close binary and is likely to be the ejected donor remnant of a thermonuclear supernova.

Insensitivity of bonnet monkeys to (D-Ala6, Des-Gly10) LHRH ethylamide, a potent new luteinizing hormone releasing hormone analogue in rats and mice.

The Luteinizing Hormone Releasing Hormone (LHRH) activity of (D-Ala6, Des-Gly10) LHRH ethylamide was compared with that of LHRH in oöphorectomized bonnet monkeys by determining serum LH and FSH concentrations at various time intervals after a sc injection of 100 mug of LHRH and either 100 mug or 1 mg of the analogue. Following administration of synthetic LHRH, a significant rise in both serum LH and FSH was observed. In contrast, no discernible change in serum gonadotropin concentrations was noted following injection of the analogue (D-Ala6, Des-Gly10) LHRH ethylamide, previously reported to have greatly increased potency in rats and mice.

Fertilization selection on egg and jelly-coat size in the sand dollar Dendraster excentricus.

Organisms with external fertilization are often sperm limited, and in echinoids, larger eggs have a higher probability of fertilization than smaller eggs. This difference is thought to be a result of the more frequent sperm-egg collisions experienced by larger targets. Here we report how two components of egg target size, the egg cell and jelly coat, contributed to fertilization success in a selection experiment. We used a cross-sectional analysis of correlated characters to estimate the selection gradients on egg and jelly-coat size in five replicate male pairs of the sand dollar Dendraster excentricus. Results indicated that eggs with larger cells and jelly coats were preferentially fertilized under sperm limitation in the laboratory. The selection gradients were an average of 922% steeper for egg than for jelly-coat size. The standardized selection gradients for egg and jelly-coat size were similar. Our results suggest that fertilization selection can act on both egg-cell and jelly-coat size but that an increase in egg-cell volume is much more likely to increase fertilization success than an equal change in jelly-coat volume. The strengths of the selection gradients were inversely related to the correlation of egg traits across replicate egg clutches. This result suggests the importance of replication in studies of selection of correlated characters.

The role of jelly coats in sperm-egg encounters, fertilization success, and selection on egg size in broadcast spawners.

Sperm limitation may be an important selective force influencing gamete traits such as egg size. The relatively inexpensive extracellular structures surrounding many marine invertebrate eggs might serve to enhance collision rates without the added cost of increasing the egg cell. However, despite decades of research, the effects of extracellular structures on fertilization have not been conclusively documented. Here, using the sea urchin Lytechinus variegatus, we remove jelly coats from eggs, and we quantify sperm collisions to eggs with jelly coats, eggs without jelly coats, and inert plastic beads. We also quantify fertilization success in both egg treatment groups. We find that sperm-egg collision rates increase as a function of sperm concentration and target size and that sperm are not chemotactically attracted to eggs nor to jelly coats in this species. In fertilization assays, the presence of the jelly coat is correlated with a significant but smaller-than-expected improvement in fertilization success. A pair of optimality models predict that, despite the large difference in the energetic value of egg contents and jelly material, the presence of the jelly coat does not diminish selection for larger egg cell size when sperm are limiting.

Sperm velocity and longevity trade off each other and influence fertilization in the sea urchin Lytechinus variegatus.

The theoretical prediction that fast sperm should be more effective at fertilizing eggs has never been documented empirically. Interspecific comparisons suggest an inverse relationship between sperm velocity and sperm longevity but this trade-off has never been demonstrated within a species. Here I investigate how sperm velocity and sperm longevity influence the patterns of fertilization in the sea urchin Lytechinus variegatus. In the laboratory I examined 11 male female pairs of sea urchins for variation in sperm velocity and sperm longevity, and determined the correlations of these traits with the percentage of eggs fertilized with serially diluted sperm. Males with faster sperm had higher rates of fertilization than males with slower sperm. Within individual males, as sperm aged they slowed down and showed a reduced percentage activity and lower rates of fertilization. Across males, the average velocity of freshly spawned sperm was inversely related to sperm longevity. These results establish the possibility that sperm traits are adapted for varying conditions along a continuum from sperm limitation to sperm competition.

Mutation of the conserved N-terminal cysteine (Cys92) of human presenilin 1 causes increased A beta42 secretion in mammalian cells but impaired Notch/lin-12 signalling in C. elegans.

The presenilin proteins are involved in the proteolytic processing of transmembrane proteins such as Notch/lin-12 and the beta-amyloid precursor protein (betaAPP). Mutation of a conserved cysteine (Cys60Ser) in the C. elegans presenilin sel-12 has a loss-of-function effect on Notch/lin-12 processing similar to that of null mutations in sel-12. In contrast, in mammalian cells, most missense mutations increase gamma-secretase cleavage of betaAPP. We report here that mutation of this conserved cysteine (Cys92Ser) in human presenilin 1 confers a loss-of-function effect in C. elegans, but causes increased A beta42 secretion in mammalian cells. These data suggest that the role of presenilins in Notch/lin-12 signalling and betaAPP processing are either separately regulated activities or independent activities of the presenilins.

Peripheral blood mononuclear cell dihydropyrimidine dehydrogenase activity in volunteers with and without diabetes mellitus.

It has been reported that cancer patients with diabetes mellitus receiving a continuous infusion of 5-fluorouracil (5-FU) have more toxicity and higher plasma 5-FU levels that patients without diabetes mellitus. Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-FU. DPD activity in peripheral blood mononuclear cells has been reported to correlate inversely with 5-FU plasma levels in patients. We therefore undertook a study to compare the activity of DPD in peripheral blood mononuclear cells of human subjects with and without diabetes mellitus. The study groups comprised 43 volunteers with and 39 without diabetes mellitus, and peripheral blood mononuclear cell DPD activity was assayed on samples obtained between 8 a.m. and 11 a.m. DPD activity was not decreased in diabetic subjects. There was no relationship between DPD activity and gender body mass index, or race. There was a modest correlation between DPD activity and age (r=0.19, P =0.08). We conclude that increases in 5-FU-related toxicities in diabetics must be related to factors other than peripheral blood mononuclear cell DPD activity.

Effects of dorsal and ventral lateral hypothalamic lesions on voluntary alcohol consumption by rats.

Ventral lateral hypothalamic lesions, made before electrical stimulation, blocked the acquisition of a preference for alcohol by rats; but dorsal lateral hypothalamic lesions did not alter their alcohol consumption. Rats offered alcohol on alternate days, without stimulation, increased their alcohol intake but did not develop a stable preference for alcohol.