Isolation of AMP-activated protein kinase (AMPK) alleles required for neuronal maintenance in Drosophila melanogaster.

The maintenance of energetic homeostasis in the face of limited available nutrients is a complex problem faced by all organisms. One important mechanism to maintain energetic homeostasis involves the activation of the energy sensor AMP-activated protein kinase (AMPK). AMPK is a cell-autonomous energy sensor that is highly sensitive to and regulated by the ATP to ADP and ATP to AMP ratios.

Clinical evaluation of safety and efficacy of a new topical treatment for onychomycosis.

Objective: This clinical study assessed the safety and efficacy of an investigational topical product for the treatment of onychomycosis (nail fungus).

Method: A prospective, multi-center, single-arm, self-controlled clinical investigation was done with adult subjects that met the inclusion criteria, primarily culture-confirmed dermatophyte infection of at least one great toe. Subjects self-treated in a weekly regimen of topical application for six months, with clinical assessment at one, three, and six months.

LKB1 and AMPK maintain epithelial cell polarity under energetic stress.

LKB1 is mutated in both familial and spontaneous tumors, and acts as a master kinase that activates the PAR-1 polarity kinase and the adenosine 5'monophosphate-activated kinase (AMPK). This has led to the hypothesis that LKB1 acts as a tumor suppressor because it is required to maintain cell polarity and growth control through PAR-1 and AMPK, respectively. However, the genetic analysis of LKB1-AMPK signaling in vertebrates has been complicated by the existence of multiple redundant AMPK subunits.

A yeast 2-hybrid analysis of human GTP cyclohydrolase I protein interactions.

The yeast 2-hybrid system was used to identify protein domains involved in the oligomerization of human guanosine 5'-triphosphate (GTP) Cyclohydrolase I (GCH1) and the interaction of GCH1 with its regulatory partner, GCH1 feedback regulatory protein (GFRP). When interpreted within the structural framework derived from crystallography, our results indicate that the GCH1 N-terminal alpha-helices are not the only domains involved in the formation of dimers from monomers and also suggest an important role for the C-terminal alpha-helix in the assembly of dimers to form decamers. Moreover, a previously unknown role of the extended N-terminal alpha-helix in the interaction of GCH1 and GFRP was revealed.

A novel forward genetic screen for identifying mutations affecting larval neuronal dendrite development in Drosophila melanogaster.

Vertebrate and invertebrate dendrites are information-processing compartments that can be found on both central and peripheral neurons. Elucidating the molecular underpinnings of information processing in the nervous system ultimately requires an understanding of the genetic pathways that regulate dendrite formation and maintenance. Despite the importance of dendrite development, few forward genetic approaches have been used to analyze the latest stages of dendrite development, including the formation of F-actin-rich dendritic filopodia or dendritic spines.