Protein turnover of the Wallenda/DLK kinase regulates a retrograde response to axonal injury

Regenerative responses to axonal injury involve changes in gene expression; however, little is known about how such changes can be induced from a distant site of injury. In this study, we describe a nerve crush assay in Drosophila melanogaster to study injury signaling and regeneration mechanisms. We find that Wallenda (Wnd), a conserved mitogen-activated protein kinase (MAPK) kinase kinase homologous to dual leucine zipper kinase, functions as an upstream mediator of a cell-autonomous injury signaling cascade that involves the c-Jun NH(2)-terminal kinase MAPK and Fos transcription factor. Wnd is physically transported in axons, and axonal transport is required for the injury signaling mechanism. Wnd is regulated by a conserved E3 ubiquitin ligase, named Highwire (Hiw) in Drosophila. Injury induces a rapid increase in Wnd protein concomitantly with a decrease in Hiw protein. In hiw mutants, injury signaling is constitutively active, and neurons initiate a faster regenerative response. Our data suggest that the regulation of Wnd protein turnover by Hiw can function as a damage surveillance mechanism for responding to axonal injury

Molecular mechanisms that enhance synapse stability despite persistent disruption of the spectrin/ankyrin/microtubule cytoskeleton

Neuromuscular junctions crippled by a disrupted microtubule cytoskeleton are rescued by stress-induced activation of MAPK-JNK-Fos signaling

Case Study of H.R. 695: The Security and Freedom Through Encryption (SAFE) Act

This paper reviews the history of encryption policy, and analyzes the course of actions taken by the President, Congress, business and public interests, and various bureaucratic entities toward an updated, coherent policy on the encryption issue through the medium of H.R. 695. A summary assessment of the present situation and likely results are offered. Statement of Issue Technology at the turn of the millennium emulates the state of atomic energy fifty years ago. At the end of the war, following the destruction of Hiroshima and Nagasaki, attention turned to the peaceful application of atomic energy. The ability to split the atom was viewed as the bane of civilization, but potentially a boon as well. Nuclear power is the most pervasive and lasting example of peacetime use. Ironically, the U.S. is the one country least at peace about the role and residue of atomic energy. In similar fashion, the application of technology is considered a potential silver bullet, a leveler of the playing field through providing seemingly limitless power, space, and access to the person sitting at the keyboard. The present administration, and Vice President Al Gore most particularly, has agressively pursued a technology leadership role for the U.S. in the global marketplace, and has mandated widespread use of computer technology in a vast arena of federally managed programs. The technical progress in electronic communications, both voice and data, has expanded broadly the ability to transact legal and illegal business through electronic means. Legal business uses involving encryption include private messaging, secure transactions, database security, and source authentication. Criminal uses include preventing detection and obscuring evidence. These contradictory uses have resulted in the adm..

Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus

International audienceAspergillus fumigatus is exceptional among microorganisms in being both a primary and opportunistic pathogen as well as a major allergen. Its conidia production is prolific, and so human respiratory tract exposure is almost constant. A. fumigatus is isolated from human habitats and vegetable compost heaps. In immunocompromised individuals, the incidence of invasive infection can be as high as 50% and the mortality rate is often about 50% (ref. 2). The interaction of A. fumigatus and other airborne fungi with the immune system is increasingly linked to severe asthma and sinusitis. Although the burden of invasive disease caused by A. fumigatus is substantial, the basic biology of the organism is mostly obscure. Here we show the complete 29.4-megabase genome sequence of the clinical isolate Af293, which consists of eight chromosomes containing 9,926 predicted genes. Microarray analysis revealed temperature-dependent expression of distinct sets of genes, as well as 700 A. fumigatus genes not present or significantly diverged in the closely related sexual species Neosartorya fischeri, many of which may have roles in the pathogenicity phenotype. The Af293 genome sequence provides an unparalleled resource for the future understanding of this remarkable fungus