A High-Content Screen Reveals New Small-Molecule Enhancers of Ras/Mapk Signaling as Probes for Zebrafish Heart Development.

Zebrafish is the preferred vertebrate model for high throughput chemical screens to discover modulators of complex biological pathways. We adapted a transgenic zebrafish line, , which reports on fibroblast growth factor (Fgf)/Ras/Mapk activity, into a quantitative, high-content chemical screen to identify novel Fgf hyperactivators as chemical probes for zebrafish heart development and regeneration. We screened 10,000 compounds from the TimTec ActiProbe library, and identified several structurally distinct classes of molecules that enhanced Fgf/Ras/Mapk signaling.

DNAH6 and Its Interactions with PCD Genes in Heterotaxy and Primary Ciliary Dyskinesia.

Heterotaxy, a birth defect involving left-right patterning defects, and primary ciliary dyskinesia (PCD), a sinopulmonary disease with dyskinetic/immotile cilia in the airway are seemingly disparate diseases. However, they have an overlapping genetic etiology involving mutations in cilia genes, a reflection of the common requirement for motile cilia in left-right patterning and airway clearance. While PCD is a monogenic recessive disorder, heterotaxy has a more complex, largely non-monogenic etiology.

A high-content screening assay in transgenic zebrafish identifies two novel activators of fgf signaling.

Zebrafish have become an invaluable vertebrate animal model to interrogate small molecule libraries for modulators of complex biological pathways and phenotypes. We have recently described the implementation of a quantitative, high-content imaging assay in multi-well plates to analyze the effects of small molecules on Fibroblast Growth Factor (FGF) signaling in vivo. Here we have evaluated the capability of the assay to identify compounds that hyperactivate FGF signaling from a test cassette of agents with known biological activities.

Molecular epidemiology of carbapenem-nonsusceptible Acinetobacter baumannii in the United States.

Acinetobacter baumannii is emerging as an important nosocomial pathogen worldwide. We report molecular epidemiology of 65 carbapenem-nonsusceptible A. baumannii isolates identified from hospitals in New York, Pennsylvania, Florida, Missouri, Nevada, and California between 2008 and 2009.

Screening for Acinetobacter baumannii colonization by use of sponges.

There is currently no consensus method for the active screening of Acinetobacter baumannii. The use of swabs to culture nostrils, pharynx, and skin surface of various anatomical sites is known to yield less-than-optimal sensitivity. In the present study, we sought to determine whether the use of sterile sponges to sample large areas of the skin would improve the sensitivity of the detection of A.

Aberrant TGF-beta signaling reduces T regulatory cells in ICAM-1-deficient mice, increasing the inflammatory response to Mycobacterium tuberculosis.

Foxp3+ T regulatory cells are required to prevent autoimmune disease, but also prevent clearance of some chronic infections. While natural T regulatory cells are produced in the thymus, TGF-beta1 signaling combined with T-cell receptor signaling induces the expression of Foxp3 in CD4+ T cells in the periphery. We found that ICAM-1-/- mice have fewer T regulatory cells in the periphery than WT controls, due to a role for ICAM-1 in induction of Foxp3 expression in response to TGF-beta1.