Pattern and scale: evaluating generalities in crab distributions and marsh dynamics from small plots to a national scale.

The generality of ecological patterns depends inextricably on the scale at which they are examined. We investigated patterns of crab distribution and the relationship between crabs and vegetation in salt marshes at multiple scales. By using consistent monitoring protocols across 15 U.S. National Estuarine Research Reserves, we were able to synthesize patterns from the scale of quadrats to the entire marsh landscape to regional and national scales. Some generalities emerged across marshes from our overall models, and these are useful for informing broad coastal management policy. We found that crab burrow distribution within a marsh could be predicted by marsh elevation, distance to creek and soil compressibility. While these physical factors also affected marsh vegetation cover, we did not find a strong or consistent overall effect of crabs at a broad scale in our multivariate model, though regressions conducted separately for each site revealed that crab burrows were negatively correlated with vegetation cover at 4 out of 15 sites. This contrasts with recent smaller-scale studies and meta-analyses synthesizing such studies that detected strong negative effects of crabs on marshes, likely because we sampled across the entire marsh landscape, while targeted studies are typically limited to low-lying areas near creeks, where crab burrow densities are highest. Our results suggest that sea-level rise generally poses a bigger threat to marshes than crabs, but there will likely be interactions between these physical and biological factors. Beyond these generalities across marshes, we detected some regional differences in crab community composition, richness, and abundance. However, we found striking differences among sites within regions, and within sites, in terms of crab abundance and relationships to marsh integrity. Although generalities are broadly useful, our findings indicate that local managers cannot rely on data from other nearby systems, but rather need local information for developing salt marsh management strategies.

In Vitro and in Vivo Characterization of MOD-4023, a Long-Acting Carboxy-Terminal Peptide (CTP)-Modified Human Growth Hormone.

MOD-4023 is a novel long-acting version of human growth hormone (hGH), containing the carboxy-terminal peptide (CTP) of human chorionic gonadotropin (hCG). MOD-4023 is being developed as a treatment for adults and children with growth hormone deficiency (GHD), which would require fewer injections than currently available GH formulations and thus reduce patient discomfort and increase compliance. This study characterizes MOD-4023's binding affinities for the growth hormone receptor, as well as the pharmacokinetic and pharmacodynamics, toxicology, and safety profiles of repeated dosing of MOD-4023 in Sprague-Dawley rats and Rhesus monkeys. Although MOD-4023 exhibited reduced in vitro potency and lower affinity to the GH receptor than recombinant hGH (rhGH), administration of MOD-4023 every 5 days in rats and monkeys resulted in exposure comparable to daily rhGH, and the serum half-life of MOD-4023 was significantly longer. Repeated administration of MOD-4023 led to elevated levels of insulin-like growth factor 1 (IGF-1), and twice-weekly injections of MOD-4023 resulted in larger increase in weight gain with fewer injections and a lower accumulative hGH dose. Thus, the increased half-life of MOD-4023 in comparison to hGH may increase the frequency of protein-receptor interactions and compensate for its decreased in vitro potency. MOD-4023 was found to be well-tolerated in rats and monkeys, with minimal adverse events, suggesting an acceptable safety profile. These results provide a basis for the continued clinical development of MOD-4023 as a novel treatment of GHD in children and adults.

Coastal Vertebrate Exposure to Predicted Habitat Changes Due to Sea Level Rise.

Sea level rise (SLR) may degrade habitat for coastal vertebrates in the Southeastern United States, but it is unclear which groups or species will be most exposed to habitat changes. We assessed 28 coastal Georgia vertebrate species for their exposure to potential habitat changes due to SLR using output from the Sea Level Affecting Marshes Model and information on the species' fundamental niches. We assessed forecasted habitat change up to the year 2100 using three structural habitat metrics: total area, patch size, and habitat permanence. Almost all of the species (n = 24) experienced negative habitat changes due to SLR as measured by at least one of the metrics. Salt marsh and ocean beach habitats experienced the most change (out of 16 categorical land cover types) across the three metrics and species that used salt marsh extensively (rails and marsh sparrows) were ranked highest for exposure to habitat changes. Species that nested on ocean beaches (Diamondback Terrapins, shorebirds, and terns) were also ranked highly, but their use of other foraging habitats reduced their overall exposure. Future studies on potential effects of SLR on vertebrates in southeastern coastal ecosystems should focus on the relative importance of different habitat types to these species' foraging and nesting requirements. Our straightforward prioritization approach is applicable to other coastal systems and can provide insight to managers on which species to focus resources, what components of their habitats need to be protected, and which locations in the study area will provide habitat refuges in the face of SLR.

Use of Anecdotal Occurrence Data in Species Distribution Models: An Example Based on the White-Nosed Coati (Nasua narica) in the American Southwest.

Species distributions are usually inferred from occurrence records. However, these records are prone to errors in spatial precision and reliability. Although influence of spatial errors has been fairly well studied, there is little information on impacts of poor reliability. Reliability of an occurrence record can be influenced by characteristics of the species, conditions during the observation, and observer's knowledge. Some studies have advocated use of anecdotal data, while others have advocated more stringent evidentiary standards such as only accepting records verified by physical evidence, at least for rare or elusive species. Our goal was to evaluate the influence of occurrence records with different reliability on species distribution models (SDMs) of a unique mammal, the white-nosed coati (Nasua narica) in the American Southwest. We compared SDMs developed using maximum entropy analysis of combined bioclimatic and biophysical variables and based on seven subsets of occurrence records that varied in reliability and spatial precision. We found that the predicted distribution of the coati based on datasets that included anecdotal occurrence records were similar to those based on datasets that only included physical evidence. Coati distribution in the American Southwest was predicted to occur in southwestern New Mexico and southeastern Arizona and was defined primarily by evenness of climate and Madrean woodland and chaparral land-cover types. Coati distribution patterns in this region suggest a good model for understanding the biogeographic structure of range margins. We concluded that occurrence datasets that include anecdotal records can be used to infer species distributions, providing such data are used only for easily-identifiable species and based on robust modeling methods such as maximum entropy. Use of a reliability rating system is critical for using anecdotal data.

Designing a long-acting human growth hormone (hGH) by fusing the carboxyl-terminal peptide of human chorionic gonadotropin beta-subunit to the coding sequence of hGH.

Chimeric genes were constructed by fusing of human GH (hGH) cDNA to one, two, or three cassettes of the carboxyl-terminal peptide (CTP) of human chorionic gonadotropin (hCG)-beta-subunit. hGH variant genes were inserted into the pCI-DHFR plasmid, transfected into DG44 cells, and stable clones were selected. Bioactivity and pharmacokinetic studies were performed in hypophysectomized Sprague Dawley derived male rats. The results indicated that sc injections of GH-wild-type (WT), Biotropin (commercial), GH-CTP, or CTP-GH (0.6 mg/kg) once every 5 d for 11 d (total dose of 1.2 mg/kg) resulted in an increased weight gain by 4, 4.9, 5.1, and 7 g, respectively. Treatment with CTP-GH-CTP-CTP (GH-LA) or CTP-GH-CTP (0.6 mg/kg) once every 5 d for 11 d or with Biotropin (0.12 mg/kg) daily for 11 d (total dose 1.2 mg/kg) resulted in a dramatic increase in weight gain of 16.5, 16.8, and 17 g, respectively. Repeated injections with different doses of GH-LA, 0.6, 1.8 mg/kg every 4 d or daily injection of 0.12 mg/kg of Biotropin increased the weight gain by 16, 28, and 18 gr, respectively. In addition, the cumulative serum levels of IGF-I after injection of GH-LA was significantly higher than that detected after injection of Biotropin. Pharmacokinetic studies indicated that the half-life, mean residence time, area under the curve, time of maximal plasma concentration, and maximal plasma concentration of GH-LA are dramatically increased compared with Biotropin. This may suggest that the mechanism of GH metabolic clearance is affected by the presence of CTP. These data establish a rationale for using this chimera as a long-acting GH analog.