High-Resolution Genetics Identifies the Lipid Transfer Protein Sec14p as Target for Antifungal Ergolines.

Invasive infections by fungal pathogens cause more deaths than malaria worldwide. We found the ergoline compound NGx04 in an antifungal screen, with selectivity over mammalian cells. High-resolution chemogenomics identified the lipid transfer protein Sec14p as the target of NGx04 and compound-resistant mutations in Sec14p define compound-target interactions in the substrate binding pocket of the protein. Beyond its essential lipid transfer function in a variety of pathogenic fungi, Sec14p is also involved in secretion of virulence determinants essential for the pathogenicity of fungi such as Cryptococcus neoformans, making Sec14p an attractive antifungal target. Consistent with this dual function, we demonstrate that NGx04 inhibits the growth of two clinical isolates of C. neoformans and that NGx04-related compounds have equal and even higher potency against C. neoformans. Furthermore NGx04 analogues showed fungicidal activity against a fluconazole resistant C. neoformans strain. In summary, we present genetic evidence that NGx04 inhibits fungal Sec14p and initial data supporting NGx04 as a novel antifungal starting point

Anthropogenic Space Weather

Anthropogenic effects on the space environment started in the late 19th century and reached their peak in the 1960s when high-altitude nuclear explosions were carried out by the USA and the Soviet Union. These explosions created artificial radiation belts near Earth that resulted in major damages to several satellites. Another, unexpected impact of the high-altitude nuclear tests was the electromagnetic pulse (EMP) that can have devastating effects over a large geographic area (as large as the continental United States). Other anthropogenic impacts on the space environment include chemical release ex- periments, high-frequency wave heating of the ionosphere and the interaction of VLF waves with the radiation belts. This paper reviews the fundamental physical process behind these phenomena and discusses the observations of their impacts.Comment: 71 pages, 35 figure

Scaling anomaly in cosmic string background

We show that the classical scale symmetry of a particle moving in cosmic string background is broken upon inequivalent quantization of the classical system, leading to anomaly. The consequence of this anomaly is the formation of single bound state in the coupling interval \gamma\in(-1,1). The inequivalent quantization is characterized by a 1-parameter family of self-adjoint extension parameter \omega. It has been conjectured that the formation of loosely bound state in cosmic string background may lead to the so called anomalous scattering cross section for the particles, which is usually seen in molecular physics.Comment: 4 pages,1 figur

Oesophageal rhabdomyoma

Extracardiac rhabdomyomas are rare benign tumours showing striated muscle differentiation. Seventy percent of these lesions occur in the head and neck region. The most common sites for these lesions are the larynx, pharynx, and the floor of the mouth. There has been only one previous report of a rhabdomyoma of the oesophagus; two further cases are described. Key Words: rhabdomyoma • oesophagu