Polymorphic variants in tenascin-C (TNC) are associated with atherosclerosis and coronary artery disease

Tenascin-C (TNC) is an extracellular matrix protein implicated in biological processes important for atherosclerotic plaque development and progression, including smooth muscle cell migration and proliferation. Previously, we observed differential expression of TNC in atherosclerotic aortas compared with healthy aortas. The goal of this study was to investigate whether common genetic variation within TNC is associated with risk of atherosclerosis and coronary artery disease (CAD) in three independent datasets. We genotyped 35 single nucleotide polymorphisms (SNPs), including 21 haplotype tagging SNPs, in two of these datasets: human aorta tissue samples (n?=?205) and the CATHGEN cardiovascular study (n?=?1,325). Eleven of these 35 SNPs were then genotyped in a third dataset, the GENECARD family study of early-onset CAD (n?=?879 families). Three SNPs representing a block of linkage disequilibrium, rs3789875, rs12347433, and rs4552883, were significantly associated with atherosclerosis in multiple datasets and demonstrated consistent, but suggestive, genetic effects in all analyses. In combined analysis rs3789875 and rs12347433 were statistically significant after Bonferroni correction for 35 comparisons, p?=?2?×?10^?6 and 5?×?10^?6, respectively. The SNP rs12347433 is a synonymous coding SNP and may be biologically relevant to the mechanism by which tenascin-C influences the pathophysiology of CAD and atherosclerosis. This is the first report of genetic association between polymorphisms in TNC and atherosclerosis or CAD.     

Inbreeding reveals mode of past selection on male reproductive characters in Drosophila melanogaster

Directional dominance is a prerequisite of inbreeding depression. Directionality arises when selection drives alleles that increase fitness to fixation and eliminates dominant deleterious alleles, while deleterious recessives are hidden from it and maintained at low frequencies. Traits under directional selection (i.e., fitness traits) are expected to show directional dominance and therefore an increased susceptibility to inbreeding depression. In contrast, traits under stabilizing selection or weakly linked to fitness are predicted to exhibit little‐to‐no inbreeding depression. Here, we quantify the extent of inbreeding depression in a range of male reproductive characters and then infer the mode of past selection on them. The use of transgenic populations of Drosophila melanogaster with red or green fluorescent‐tagged sperm heads permitted in vivo discrimination of sperm from competing males and quantification of characteristics of ejaculate composition, performance, and fate. We found that male attractiveness (mating latency) and competitive fertilization success (P₂) both show some inbreeding depression, suggesting they may have been under directional selection, whereas sperm length showed no inbreeding depression suggesting a history of stabilizing selection. However, despite having measured several sperm quality and quantity traits, our data did not allow us to discern the mechanism underlying the lowered competitive fertilization success of inbred (f = 0.50) males.     

The blue streak: a dynamic trait in the mud fiddler crab, Uca pugnax

Mud fiddler crabs, Uca pugnax, have a streak of blue coloration located on the front of the carapace above the mouth and centered between the eyes. We documented that this blue streak is absent in juveniles and develops as crabs become sexually mature. By photographing male crabs under controlled conditions in the laboratory, we demonstrated that the brightness of the blue streak (in comparison with the rest of the carapace) is dynamic, and can dim from bright blue to nearly black in fewer than two minutes. We examined blue streak variability in male crabs in response to physical factors (light and temperature) and social context to begin to understand what causes its dynamic response. The blue streak darkens in response to decreased ambient light, but does not respond to changes in temperature. In the field, it is brighter when crabs are roaming on the mudflat or fighting, but darker when crabs are basking or performing waving displays. The highly visual nature of fiddler crabs and the dynamic character of the blue streak suggest that it may communicate information about the state of a crab or its environment.     

Rats have trouble associating all three parts of the time-place-event memory code

The ability of animals to associate an event with predictable time and place information confers a major biological advantage. The current research uses a variety of procedures and paradigms (e.g. place preference, radial arm maze, Morris water maze, T-maze, go no-go) to show that rats, unlike pigeons [e.g. Anim Learn Behav 22 (1994) 143] do not readily make an event-time-place association. They do make associations between event-time and event-place information, however. These findings are in disagreement with Gallistel's (The Organization of Learning, MIT Press, Cambridge, MA ) theory that claims that animals automatically store a memory code that has these three pieces of information. The present research is in line with the work of others who also find that rats do not readily make daily time-place associations [Behav Processes 23 (1997) 232; Behav Processes 52 (2000) 11; Behav Processes 49 (2000) 21; Anim Learn Behav 28 (2000) 298]. An interesting finding that did emerge from the present research was that at least some rats can use a circadian timer to solve a time-of-day discrimination if the task is a go no-go discrimination.     

Verbesina barrancae (Compositae, Heliantheae), a new species from Jalisco, Mexico

Verbesina barrancae, a new species of Compositae (Heliantheae) from Jalisco, México, is described and illustrated. It is morphologically similar toVerbesina crocata but differs in characteristics of inflorescence, anthers, and achenes as well as in form of pollen, size and number of spinules, size of colpus transversalis, and index of polar area.     

A close keeper-nonhuman animal distance does not reduce undesirable behavior in contact yard goats and sheep

This study investigated the relation between zookeeper-nonhuman animal distance and the undesirable behavior goats and sheep exhibited toward visitors of Zoo Atlanta's contact yard. It hypothesized that a close distance between keeper and animal would be associated with a lower rate of undesirable behavior than would a distant keeper-animal distance. The study recorded rate of undesirable behavior exhibited, number of visitors in the yard, and number of times visitors touched an animal under near and distant keeper-animal distances. Seven African pygmy goats (Capra hircus) and 4 Romanov sheep (Ovis aries) were the subjects. The study used linear regression methods to analyze approximately 48 hr of behavioral data collected using a focal sampling technique. Findings indicated a familiar animal keeper nearby was not associated with lower rates of undesirable behavior toward visitors. Higher rates of undesirable behavior occurred when keepers were nearby than when they were distant. The study also found that undesirable behavior increased as visitors' touching of the animals increased. Applying the study's findings may improve human-animal interactions and increase animal well-being in a contact yard through animal management techniques.     

A novel alloantigen-specific CD8+PD1+ regulatory T cell induced by ICOS-B7h blockade in vivo

Delayed ICOS-B7h signal blockade promotes significant prolongation of cardiac allograft survival in wild-type but not in CD8-deficient C57BL/6 recipients of fully MHC-mismatched BALB/c heart allografts, suggesting the possible generation of CD8(+) regulatory T cells in vivo. We now show that the administration of a blocking anti-ICOS mAb results in the generation of regulatory CD8(+) T cells. These cells can transfer protection and prolong the survival of donor-specific BALB/c, but not third party C3H, heart grafts in CD8-deficient C57BL/6 recipients. This is unique to ICOS-B7h blockade, because B7 blockade by CTLA4-Ig prolongs graft survival in CD8-deficient mice and does not result in the generation of regulatory CD8(+) T cells. Those cells localize to the graft, produce both IFN-gamma and IL-4 after allostimulation in vitro, prohibit the expansion of alloreactive CD4(+) T cells, and appear to mediate a Th2 switch of recipient CD4(+) T cells after adoptive transfer in vivo. Finally, these cells are not confined to the CD28-negative population but express programmed death 1, a molecule required for their regulatory function in vivo. CD8(+)PD1(+) T cells suppress alloreactive CD4(+) T cells but do not inhibit the functions by alloreactive CD8(+) T cells in vitro. These results describe a novel allospecific regulatory CD8(+)PD1(+) T cell induced by ICOS-B7h blockade in vivo.     

Hepatic response to restoration of GLUT4 in skeletal muscle of GLUT4 null mice

Expression of GLUT4 in fast-twitch skeletal muscle fibers of GLUT4 null mice (G4-MO) normalized glucose uptake in muscle and restored peripheral insulin sensitivity. GLUT4 null mice exhibit altered carbohydrate and lipid metabolism in liver and skeletal muscle. To test the hypothesis that increased glucose utilization by G4-MO muscle would normalize the changes seen in the GLUT4 null liver, serum metabolites and hepatic metabolism were compared in control, GLUT4 null, and G4-MO mice. The fed serum glucose and triglyceride levels of G4-MO mice were similar to those of control mice. In addition, the alternations in liver metabolism seen in GLUT4 nulls including increased GLUT2 expression and fatty acid synthesis accompanied by an increase in the oxidative arm of the pentose phosphate pathway were absent in G4-MO mice. The transgene used for GLUT4 restoration in muscle was specific for fast-twitch muscle fibers. The mitochondria hypertrophy/hyperplasia in all GLUT4 null skeletal muscles was absent in transgene-positive extensor digitorum longus muscle but present in transgene-negative soleus muscle of G4-MO mice. Results of this study suggest that the level of muscle GLUT4 expression influences mitochondrial biogenesis. These studies also demonstrate that the type and amount of substrate that muscle takes up and metabolizes, determined in part by GLUT4 expression levels, play a major role in directing hepatic carbohydrate and lipid metabolism.