Comparison of water immersion and saline infusion as a means of inducing volume expansion in man.

Although previous studies have demonstrated that water immersion to the neck (NI) results in both central hypervolemia and a significant natriuresis, it is unclear whether the magnitude of the "volume stimulus" of NI is comparable to that induced by the extracellular fluid volume expansion (ECVE) induced by acute saline administration. The present study was undertaken therefore to compare the natriuresis induced by these two different stimuli. All subjects were studied on four occasions while in balance on a diet containing 150 meq of sodium and 80 meq of potassium daily: seated control; seated immersion; and saline administration in both the seated and recumbent posture. The increment in UNaV during NI was indistinguishable from that of seated saline. Similarly, the kaliuretic response during NI was similar to that induced by seated saline infusion. In contrast, supine saline infusion resulted in a greater increment in UNaV than either NI or seated saline. The present data indicate that the "volume stimulus" of immersion is identical with that of standard saline-induced ECVE in normal seated subjects. Furthermore, the ability of NI to induce a natriuresis without a concomitant increase in total blood volume and with a decrease in body weight, rather than the increase which attends saline infusion, suggests that NI may be a preferred investigative tool for assessing the effects of ECVE in man.     

Shared Segment Analysis and Next-Generation Sequencing Implicates the Retinoic Acid Signaling Pathway in Total Anomalous Pulmonary Venous Return (TAPVR)

Most isolated congenital heart defects are thought to be sporadic and are often ascribed to multifactorial mechanisms with poorly understood genetics. Total Anomalous Pulmonary Venous Return (TAPVR) occurs in 1 in 15,000 live-born infants and occurs either in isolation or as part of a syndrome involving aberrant left-right development. Previously, we reported causative links between TAVPR and the PDGFRA gene. TAPVR has also been linked to the ANKRD1/CARP genes. However, these genes only explain a small fraction of the heritability of the condition. By examination of phased single nucleotide polymorphism genotype data from 5 distantly related TAPVR patients we identified a single 25 cM shared, Identical by Descent genomic segment on the short arm of chromosome 12 shared by 3 of the patients and their obligate-carrier parents. Whole genome sequence (WGS) analysis identified a non-synonymous variant within the shared segment in the retinol binding protein 5 (RBP5) gene. The RBP5 variant is predicted to be deleterious and is overrepresented in the TAPVR population. Gene expression and functional analysis of the zebrafish orthologue, rbp7, supports the notion that RBP5 is a TAPVR susceptibility gene. Additional sequence analysis also uncovered deleterious variants in genes associated with retinoic acid signaling, including NODAL and retinol dehydrogenase 10. These data indicate that genetic variation in the retinoic acid signaling pathway confers, in part, susceptibility to TAPVR.     

Conservation and divergence in the AGAMOUS subfamily of MADS-box genes: evidence of independent sub- and neofunctionalization events

The MADS-box gene AGAMOUS (AG) plays a key role in determining floral meristem and organ identities. We identified three AG homologs, EScaAG1, EScaAG2, and EScaAGL11 from the basal eudicot Eschscholzia californica (California poppy). Phylogenetic analyses indicate that EScaAG1 and EScaAG2 are recent paralogs within the AG clade, independent of the duplication in ancestral core eudicots that gave rise to the euAG and PLENA (PLE) orthologs. EScaAGL11 is basal to core eudicot AGL11 orthologs in a clade representing an older duplication event after the divergence of the angiosperm and gymnosperm lineages. Detailed in situ hybridization experiments show that expression of EScaAG1 and EScaAG2 is similar to AG; however, both genes appear to be expressed earlier in floral development than described in the core eudicots. A thorough examination of available expression and functional data in a phylogenetic context for members of the AG and AGL11 clades reveals that gene expression has been quite variable throughout the evolutionary history of the AG subfamily and that ovule-specific expression might have evolved more than twice. Although sub- and neofunctionalization are inferred to have occurred following gene duplication, functional divergence among orthologs is evident, as is convergence, among paralogs sampled from different species. We propose that retention of multiple AG homologs in several paralogous lineages can be explained by the conservation of ancestral protein activity combined with evolutionarily labile regulation of expression in the AG and AGL11 clades such that the collective functions of the AG subfamily in stamen and carpel development are maintained following gene duplication.     

Pyridyl aminothiazoles as potent inhibitors of Chk1 with slow dissociation rates

Pyridyl aminothiazoles comprise a novel class of ATP-competitive Chk1 inhibitors with excellent inhibitory potential. Modification of the core with ethylenediamine amides provides compounds with low picomolar potency and very high residence times. Investigation of binding parameters of such compounds using X-ray crystallography and molecular dynamics simulations revealed multiple hydrogen bonds to the enzyme backbone as well as stabilization of the conserved water molecules network in the hydrophobic binding region.     

Efficacy of selected insecticides against eggs of Euschistus servus and Acrosternum hilare (Hemiptera: Pentatomidae) and the egg parasitoid Telenomus podisi (Hymenoptera: Scelionidae)

Brown stink bug, Euschistus servus (Say), and green stink bug, Acrosternum hilare (Say) (Hemiptera: Pentatomidae), are major agricultural pests. Although various insecticides are used to control nymphs and adults, little is known about how they affect eggs. Laboratory bioassays and field trials were conducted to determine the efficacy of common field rates of acephate, lamda-cyhalothrin, spinosad, and thiamethoxam on developing E. servus and A. hilare eggs, as well as Telenomus podisi Ashmead (Hymenoptera: Scelionidae) parasitoids developing in E. servus eggs. In laboratory bioassays, egg masses were dipped into insecticide and water solutions and assessed for mortality after 2 wk. In the field trials, egg masses on a cloth section were pinned to leaves in each plot ofa randomized complete block and returned to the laboratory 24 h after exposure to insecticide sprays. Mortality was assessed after 2 wk. In dip bioassays, there was a significant effect of insecticide treatment on A. hilare eggs with all insecticides resulting in greater mortality than the water control. However, no effect of treatment occurred in the field with A. hilare or for E. serous eggs in both the laboratory bioassays and the field trials. In contrast, developing T. podisi parasitoids showed significant mortality when exposed to all insecticide treatments, when dipped or field-treated. Spinosad and lamda-cyhalothrin treatments resulted in 100% mortality of T. podisi, and acephate resulted in greater mortality than thiamethoxam. Our results suggest that there is relatively little efficacy from insecticide sprays on stink bugs developing in eggs but that mortality of egg parasitoids may be significant.     

Piscivore Responses to Enhancement of the Channelized Kissimmee River,Florida, U.S.A.

Evaluation of the success of ecosystem restoration projects requires identification of appropriate ecological metrics. Comparison of reconstructed food webs (or subsets thereof) from restored and non‐restored habitats may be a valuable tool to evaluate restoration success because food webs help identify critical predator–prey relationships, keystone species, relative importance of direct and indirect trophic interactions, and other aspects of ecological function. We compared the diets of apex predatory fishes collected from enhanced and non‐enhanced portions of the channelized Kissimmee River, Florida, USA to determine whether food web structure responded to experimental hydrologic manipulations. Diets were reconstructed for black crappie (Pomoxis nigromaculatus), bowfin (Amia calva), chain pickerel (Esox niger), Florida gar (Lepisosteus platyrhincus), largemouth bass (Micropterus salmoides), and warmouth (Lepomis gulosus) collected from enhanced and non‐enhanced portions of the Kissimmee River. Prey eaten by apex predatory fishes in the enhanced portion of the Kissimmee River were quantitatively and qualitatively different from prey eaten in non‐enhanced portions of the river. Predators in the enhanced portion of the river had fewer empty stomachs, more prey items per individual, more prey types per individual, more fish prey per individual, greater overall richness of prey, and a multivariate suite of prey distinct from predators in non‐enhanced portions of the river. Results from hydrologic manipulations suggest that large‐scale restoration of hydrologic linkages between the main channel and floodplain habitats will positively affect food web structure and ecosystem function in the Kissimmee River.     

Conceptual Evaluation of Factors Potentially Affecting Restoration of Habitat Structure within the Channelized Kissimmee River Ecosystem

A critical element of the ongoing effort to restore the ecological integrity of Florida's Kissimmee River ecosystem is the reestablishment of pre-channelization habitat structure and function. Restoration of habitat will form the basis for responses by most biological components of the ecosystem and will provide a key indicator of the success of the restoration effort. This paper evaluates the relative importance of a range of abiotic and biotic habitat parameters in the existing and historic Kissimmee River ecosystem and provides a conceptual framework for predicting expected spatial and temporal responses of river and floodplain habitats to the restoration project. Among the ecological factors and process that influenced the development, dynamics, and maintenance of river and floodplain habitat structure, hydrology is expected to be of central importance in eliciting restoration responses in the Kissimmee River Ecosystem. Based on the assumption that the restoration plan will reestablish historic hydrologic characteristics, predictions are made of expected responses by geomorphic and vegetative components of the Kissimmee River's habitat structure. Recommendations are made regarding key habitat parameters requiring long term tracking and analysis and utilization of a geographic information system(GIS). A hierarchical habitat classification scheme is provided as a foundation for all components of the restoration evaluation program.