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Fibrosis is a common pathological feature observed in muscle from patients with Duchenne muscular dystrophy (DMD). In the dystrophic (mdx) mouse model of DMD, the diaphragm is more severely affected than other skeletal muscles. The level of transforming growth factor-beta1 (TGF-beta1), an inflammatory cytokine, is significantly elevated in mdx diaphragm. However, little is known about the onset of TGF-beta1 messenger ribonucleic acid (mRNA) expression, or which cells express the mRNA. In this study, we characterized the location and time course of expression of TGF-beta1 mRNA in diaphragm from mdx mice. TGF-beta1 mRNA was significantly elevated in mdx diaphragm at 6 and 9 but not 12 weeks of age, and these changes corresponded with changes in type I collagen mRNA and hydroxyproline concentration. Mononucleated cells localized to areas of fiber necrosis highly expressed the TGF-beta1 transcript in mdx diaphragm. Neutralization of TGF-beta1 by decorin administration resulted in a 40% reduction in the level of diaphragm muscle type I collagen mRNA. These findings support a role for TGF-beta1 during the early stages of fibrogenesis in dystrophic diaphragm muscle. Therapeutic interventions aimed at neutralizing this cytokine may be beneficial in slowing the development of fibrosis in DMD.

The reproductive biology of the gonochoric Br/areum asbestinum (Pallas), a common Caribbean gorgonian, was studied in the San Blas Islands (Panama), La Paguera (Puerto Rico) and the Bahamas. Of 721 colonies examined at the height of the reproductive season, during the summers of 1985 to 1988, all were either male or female. No hermaphroditic colonies or polyps were observed. The sexratio of Panama populations was significantly biased in favor of males (2.1:1, n =454) over all four years of the study. A significant male bias was also found in populations sampled in Puerto Rico (2.3:1, n= 143) and in the Bahamas (2.5:1, n=124). The consistency of this geographically widespread skewed sex-ratio is unique among octocorals and scleractinians. Ooyctes appear annually in September and reach maximum diameter (600 to 900 #m) in June and July of the following year. The 3 to 5 mo developmental cycle of spermaries is shorter than that of females and begins in March. Spawning in males is synchronous and occurs following the full moons of June and July. Fertilization is internal. Embryos are released from polyps very early in development, often whilst still in the process of cleaving. Embryos remain attached to the outside of the colony for 3 to 5 d, many becoming entrapped in mucous sheets secreted by the colonies. Larvae are negatively buoyant and settle rapidly once displaced from the colony. Males become reproductive at smaller branch sizes than females. Reproductive effort (gonads polyp -1 and total gonad volume polyp-1) for both males and females increased with increasing branch size and in polyps away from the tip and base of the branch.

BackgroundCoral reefs worldwide are in decline. Much of the mortality can be attributed to coral bleaching (loss of the coral's intracellular photosynthetic algal symbiont) associated with global warming. How corals will respond to increasing oceanic temperatures has been an area of extensive study and debate. Recovery after a bleaching event is dependent on regaining symbionts, but the source of repopulating symbionts is poorly understood. Possibilities include recovery from the proliferation of endogenous symbionts or recovery by uptake of exogenous stress-tolerant symbionts.Methodology/Principal FindingsTo test one of these possibilities, the ability of corals to acquire exogenous symbionts, bleached colonies of Porites divaricata were exposed to symbiont types not normally found within this coral and symbiont acquisition was monitored. After three weeks exposure to exogenous symbionts, these novel symbionts were detected in some of the recovering corals, providing the first experimental evidence that scleractinian corals are capable of temporarily acquiring symbionts from the water column after bleaching. However, the acquisition was transient, indicating that the new symbioses were unstable. Only those symbiont types present before bleaching were stable upon recovery, demonstrating that recovery was from the resident in situ symbiont populations.Conclusions/SignificanceThese findings suggest that some corals do not have the ability to adjust to climate warming by acquiring and maintaining exogenous, more stress-tolerant symbionts. This has serious ramifications for the success of coral reefs and surrounding ecosystems and suggests that unless actions are taken to reverse it, climate change will lead to decreases in biodiversity and a loss of coral reefs.

Mesophotic coral reefs (30–150 m) have recently received increased attention as a potential source of larvae (e.g., the refugia hypothesis) to repopulate a select subset of the shallow water (<30 m) coral fauna. To test the refugia hypothesis we used highly polymorphic Amplified Fragment Length Polymorphism (AFLP) markers as a means to assess small-scale genetic heterogeneity between geographic locations and across depth clines in the Caribbean coral, Montastraea cavernosa. Zooxanthellae-free DNA extracts of coral samples (N = 105) were analyzed from four depths, shallow (3–10 m), medium (15–25 m), deep (30–50 m) and very deep (60–90 m) from Little Cayman Island (LCI), Lee Stocking Island (LSI), Bahamas and San Salvador (SS), Bahamas which range in distance from 170 to 1,600 km apart. Using AMOVA analysis there were significant differences in ΦST values in pair wise comparisons between LCI and LSI. Among depths at LCI, there was significant genetic differentiation between shallow and medium versus deep and very deep depths in contrast there were no significant differences in ΦST values among depths at LSI. The assignment program AFLPOP, however, correctly assigned 95.7% of the LCI and LSI samples to the depths from which they were collected, differentiating among populations as little as 10 to 20 m in depth from one another. Discriminant function analysis of the data showed significant differentiation among samples when categorized by collection site as well as collection depth. FST outlier analyses identified 2 loci under positive selection and 3 under balancing selection at LCI. At LSI 2 loci were identified, both showing balancing selection. This data shows that adult populations of M. cavernosa separated by depths of tens of meters exhibits significant genetic structure, indicative of low population connectivity among and within sites and are not supplying successful recruits to adjacent coral reefs less than 30 m in depth.

We developed a computationally efficient algorithm AMBIENCE, for identifying the informative variables involved in gene-gene (GGI) and gene-environment interactions (GEI) that are associated with disease phenotypes. The AMBIENCE algorithm uses a novel information theoretic metric called phenotypeassociated information (PAI) to search for combinations of genetic variants and environmental variables associated with the disease phenotype. The PAI-based AMBIENCE algorithm effectively and efficiently detected GEI in simulated data sets of varying size and complexity, including the 10K simulated rheumatoid arthritis data set from Genetic Analysis Workshop 15. The method was also successfully used to detect GGI in a Crohn's disease data set. The performance of the AMBIENCE algorithm was compared to the multifactor dimensionality reduction (MDR), generalized MDR (GMDR), and pedigree disequilibrium test (PDT) methods. Furthermore, we assessed the computational speed of AMBIENCE for detecting GGI and GEI for data sets varying in size from 100 to 10 5 variables. Our results demonstrate that the AMBIENCE information theoretic algorithm is useful for analyzing a diverse range of epidemiologic data sets containing evidence for GGI and GEI.

The purpose of our work was to develop heuristics for visualizing and interpreting gene-environment interactions (GEIs) and to assess the dependence of candidate visualization metrics on biological and study-design factors. Two information-theoretic metrics, the k-way interaction information (KWII) and the total correlation information (TCI), were investigated. The effectiveness of the KWII and TCI to detect GEIs in a diverse range of simulated data sets and a Crohn disease data set was assessed. The sensitivity of the KWII and TCI spectra to biological and study-design variables was determined. Head-to-head comparisons with the relevance-chain, multifactor dimensionality reduction, and the pedigree disequilibrium test (PDT) methods were obtained. The KWII and TCI spectra, which are graphical summaries of the KWII and TCI for each subset of environmental and genotype variables, were found to detect each known GEI in the simulated data sets. The patterns in the KWII and TCI spectra were informative for factors such as case-control misassignment, locus heterogeneity, allele frequencies, and linkage disequilibrium. The KWII and TCI spectra were found to have excellent sensitivity for identifying the key disease-associated genetic variations in the Crohn disease data set. In head-to-head comparisons with the relevance-chain, multifactor dimensionality reduction, and PDT methods, the results from visual interpretation of the KWII and TCI spectra performed satisfactorily. The KWII and TCI are promising metrics for visualizing GEIs. They are capable of detecting interactions among numerous single-nucleotide polymorphisms and environmental variables for a diverse range of GEI models.

Abstract. Fertilization rates among marine benthic taxa have implicitly been assumed to be uniformly high in most analyses of life history evolution, but in situ fertilization rates during natural spawning events are rarely measured. Fertilization rates of the Caribbean gorgonians Plexaura kuna and Pseudoplexaura porosa were measured at a site in the San Bias Islands, Panama, by collecting eggs downstream of colonies during synchronous spawning events during the summer months in the years 1988-1994. Eggs collected by divers were incubated, and the proportion of eggs that developed was determined. Proportions of eggs developing suggest fertilization rates that vary from 0% to 100%. Monthly means ranged from 0% to 60.4%. Failure of gametes to develop can be attributed to sperm limitation, as eggs collected during spawning had higher fertilization rates if incubated with an excess of sperm. Plexaura kuna fertilization rates were highest during the July spawning events. Fertilization of Plexaura kuna eggs was usually lower during the first two nights of the 4-6 night spawning event. The proportion of eggs being fertilized when collected from a given place and time was highly variable, with one peak in the frequency distribution at or below 20% fertilization, and a second group of samples with greater fertilization rates. High variance in fertilization rates is evident at all levels of analysis: between replicate samples, times within nights, and among nights and months. This variance can be attributed to a combination of the effects of heterogeneity in the water