Serologic survey for viral and bacterial infections in western populations of Canada lynx (Lynx canadensis)

A serologic survey for exposure to pathogens in Canada lynx (Lynx canadensis) in western North America was conducted. Samples from 215 lynx from six study areas were tested for antibodies to feline parvovirus (FPV), feline coronavirus, canine distemper virus, feline calicivirus, feline herpesvirus, Yersinia pestis, and Francisella tularensis. A subset of samples was tested for feline immunodeficiency virus; all were negative. For all other pathogens, evidence for exposure was found in at least one location. Serologic evidence for FPV was found in all six areas but was more common in southern populations. Also, more males than females showed evidence of exposure to FPV. Overall, prevalences were low and did not exceed 8% for any of the pathogens tested. This suggests that free-ranging lynx rarely encounter common feline pathogens.     

Core exploration in optimization of chemokine receptor CCR4 antagonists

The design, synthesis, and SAR studies of 'core' variations led to identification of novel, selective, and potent small molecule antagonist (22) of the CC chemokine receptor-4 (CCR4) with improved in vitro activity and liability profile. Compound 22 was efficacious in a murine allergic inflammation model (ED50 approximately 10 mg/kg).     

Attitudes toward companion animals among Hispanic residents of a Texas border community

The researchers surveyed 206 residents of a Hispanic community on the Texas-Mexico border about their behaviors and attitudes toward companion animals. Selected members of the community administered a telephone survey to a systematic random sample of 206 individuals. The majority of participants believed that free-roaming dogs were a problem in their community, and nearly 81% responded that these dogs sometimes prevented them from walking outdoors. About 24% of dog guardians sometimes let their nonhuman animals roam free in the streets. Most study participants believed it was a good idea to sterilize both male and female dogs and cats, but only 11% of respondents' dogs and 27% of cats were sterilized. About 62% of households chained dogs outdoors; persons with an elementary-level education were 7 times more likely to chain their dogs than those who had completed some high school. The Hispanic population of the United States is growing rapidly; to guide officials charged with protecting animal welfare and the public health, it will become increasingly important to understand Hispanics' attitudes and behaviors toward companion animals.     

Syntheses and initial evaluation of a series of indolo-fused heterocyclic inhibitors of the polymerase enzyme (NS5B) of the hepatitis C virus

Herein, we present initial SAR studies on a series of bridged 2-arylindole-based NS5B inhibitors. The introduction of bridging elements between the indole N1 and the ortho-position of the 2-aryl moiety resulted in conformationally constrained heterocycles that possess multiple additional vectors for further exploration. The binding mode and pharmacokinetic (PK) properties of select examples, including: 13-cyclohexyl-6-oxo-6,7-dihydro-5H-indolo[2,1-d][1,4]benzodiazepine-10-carboxylic acid (7) (IC₅₀ = 0.07 μM, %F = 18), are reported.     

A dynamic epicardial injury response supports progenitor cell activity during zebrafish heart regeneration

Zebrafish possess a unique yet poorly understood capacity for cardiac regeneration. Here, we show that regeneration proceeds through two coordinated stages following resection of the ventricular apex. First a blastema is formed, comprised of progenitor cells that express precardiac markers, undergo differentiation, and proliferate. Second, epicardial tissue surrounding both cardiac chambers induces developmental markers and rapidly expands, creating a new epithelial cover for the exposed myocardium. A subpopulation of these epicardial cells undergoes epithelial-to-mesenchymal transition (EMT), invades the wound, and provides new vasculature to regenerating muscle. During regeneration, the ligand fgf17b is induced in myocardium, while receptors fgfr2 and fgfr4 are induced in adjacent epicardial-derived cells. When fibroblast growth factors (Fgf) signaling is experimentally blocked by expression of a dominant-negative Fgf receptor, epicardial EMT and coronary neovascularization fail, prematurely arresting regeneration. Our findings reveal injury responses by myocardial and epicardial tissues that collaborate in an Fgf-dependent manner to achieve cardiac regeneration.     

Regeneration of amputated zebrafish fin rays from de novo osteoblasts

Determining the cellular source of new skeletal elements is critical for understanding appendage regeneration in amphibians and fish. Recent lineage-tracing studies indicated that zebrafish fin ray bone regenerates through the dedifferentiation and proliferation of spared osteoblasts, with limited if any contribution from other cell types. Here, we examined the requirement for this mechanism by using genetic ablation techniques to destroy virtually all skeletal osteoblasts in adult zebrafish fins. Animals survived this injury and restored the osteoblast population within 2 weeks. Moreover, amputated fins depleted of osteoblasts regenerated new fin ray structures at rates indistinguishable from fins possessing a resident osteoblast population. Inducible genetic fate mapping confirmed that new bone cells do not arise from dedifferentiated osteoblasts under these conditions. Our findings demonstrate diversity in the cellular origins of appendage bone and reveal that de novo osteoblasts can fully support the regeneration of amputated zebrafish fins.     

Initial SAR studies on apamin-displacing 2-aminothiazole blockers of calcium-activated small conductance potassium channels

An initial SAR study on a series of apamin-displacing 2-aminothiazole K(Ca)2 channel blockers is described. Potent inhibitors such as N-(4-methylpyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (13) are disclosed, and for select members of the series, the relationship between the observed activity in a thallium flux, a binding and a whole-cell electrophysiology assay is presented.     

Effect of high boron application on boron content and growth of melons

Synthetic chelates, such as ethylene diamine tetraacetic acid (EDTA), have been shown to enhance phytoextraction of Pb from contaminated soil but also cause leaching of heavy metal-chelate complexes, posing a groundwater contamination threat. In a soil column study, we examined the effect of EDTA and a biodegradable chelate [S,S] isomere of ethylene diamine disuccinate ([S,S]-EDDS), newly introduced in phytoextraction research, on the uptake of Pb by the Chinese cabbage (Brassica rapa) and Pb leaching through the soil profile. Soil water sorption characteristics were modified by acrylamide hydrogel. The addition of 0.1 and 0.2% (w/w) of hydrogel amendments increased soil field water capacity from initial 24.6% to 28.5% and 31.3%, respectively. The additions of 2.5, 5 and 10 mmol EDTA kg^–1 soil were more effective in enhancing Pb plant uptake than comparable [S,S]-EDDS treatments, but caused (as also 10 mmol kg^–1 [S,S]-EDDS additions) unacceptably high Pb leaching in treatments with any soil water sorption conditions tested. The most efficient level of EDTA (10 mmol kg^–1) enhanced plant Pb uptake by 97 times compared to the control. Shoots Pb concentrations reached 500 mg kg^–1 of dry biomass. However, in this treatment 36.2% of total initial Pb was leached from the soil during the first four weeks after chelate addition. Hydrogel soil amendments were more effective in treatments with [S,S]-EDDS than with EDTA. In treatments with 10 mmol kg^–1[S,S]-EDDS hydrogel amended soils, plant Pb uptake was significantly reduced and Pb leach was as high as 44.2% of total initial soil Pb. At lower [S,S]-EDDS concentrations, the effect of hydrogel soil amendment on Pb leaching was the opposite. The addition of 5 mmol kg^–1 [S,S]-EDDS soil to the soil amended with 0.2% hydrogel increased Pb uptake by 18 times while only 0.2% of total initial Pb was leached. In all treatments, the concentrations of Pb in dry plant biomass were far from concentrations required for efficient soil remediation within a reasonable time span.     

In Toto Imaging of Dynamic Osteoblast Behaviors in Regenerating Skeletal Bone

1. Download high-res image (175KB)
2. Download full-size image