A Transcriptome-wide Translational Program Defined by LIN28B Expression Level

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Small and Large Ribosomal Subunit Deficiencies Lead to Distinct Gene Expression Signatures that Reflect Cellular Growth Rate

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Antifungal chemical compounds identified using a C. elegans pathogenicity assay

There is an urgent need for the development of new antifungal agents. A facile in vivo model that evaluates libraries of chemical compounds could solve some of the main obstacles in current antifungal discovery. We show that Candida albicans, as well as other Candida species, are ingested by Caenorhabditis elegans and establish a persistent lethal infection in the C. elegans intestinal track. Importantly, key components of Candida pathogenesis in mammals, such as filament formation, are also involved in nematode killing. We devised a Candida-mediated C. elegans assay that allows high-throughput in vivo screening of chemical libraries for antifungal activities, while synchronously screening against toxic compounds. The assay is performed in liquid media using standard 96-well plate technology and allows the study of C. albicans in non-planktonic form. A screen of 1,266 compounds with known pharmaceutical activities identified 15 (approximately 1.2%) that prolonged survival of C. albicans-infected nematodes and inhibited in vivo filamentation of C. albicans. Two compounds identified in the screen, caffeic acid phenethyl ester, a major active component of honeybee propolis, and the fluoroquinolone agent enoxacin exhibited antifungal activity in a murine model of candidiasis. The whole-animal C. elegans assay may help to study the molecular basis of C. albicans pathogenesis and identify antifungal compounds that most likely would not be identified by in vitro screens that target fungal growth. Compounds identified in the screen that affect the virulence of Candida in vivo can potentially be used as "probe compounds" and may have antifungal activity against other fungi.     

The road from The Microbial world to Microbe.

The year 2007 commemorates the 50th anniversary of the publication of The Microbial World, the seminal microbiology textbook that shattered the microbiology world and whose first edition was coauthored by Roger Y. Stanier, Michael Doudoroff and Edward A. Adelberg. The year 2007 marks also twenty-five years of Stanier's passing away. The Spanish Society for Microbiology (SEM) with the support of Fundación Ramón Areces has organized a Symposium, in the frame of the 21st national congress of the SEM (Seville, 17-20 September 2007), to commemorate those anniversaries, and has invited us (Schaechter, Ingraham and Neidhardt) to contribute to this celebration.     

Structures of proteins of biomedical interest from the Center for Eukaryotic Structural Genomics

The Center for Eukaryotic Structural Genomics (CESG) produces and solves the structures of proteins from eukaryotes. We have developed and operate a pipeline to both solve structures and to test new methodologies. Both NMR and X-ray crystallography methods are used for structure solution. CESG chooses targets based on sequence dissimilarity to known structures, medical relevance, and nominations from members of the scientific community. Many times proteins qualify in more than one of these categories. Here we review some of the structures that have connections to human health and disease.