A PATENT PRIZE SYSTEM TO PROMOTE DEVELOPMENT OF NEW ANTIBIOTICS AND CONSERVATION OF EXISTING ONES

Antibiotics are valuable drugs that fight bacterial infections, but our supply of antibiotics is at risk. Existing antibiotics gradually lose their effectiveness due to bacterial resistance, and few new antibiotics are being developed to replace them. A variety of models have been proposed to promote the conservation of existing antibiotics or incentivize private actors, i.e., drug companies, to develop new ones. Previous models, however, all encourage investment in antibiotic research and development via patent rights, which also create an incentive to oversell antibiotics. Because the inappropriate use of antibiotics accelerates the development of resistance, patent rights put the public health objectives of antibiotic development and conservation in tension with one another. This article proposes an antibiotic-specific patent prize system that uncouples the two policy objectives necessary to achieve a stable antibiotic supply. Although others have proposed patent prize systems to promote drug development generally, the system described here is tailored to address the unique features of antibiotic markets

Book Reviews (Editor: Helen Nickas)

Book Reviews (Editor: Helen Nickas

Vesicle Docking to the Spindle Pole Body Is Necessary to Recruit the Exocyst During Membrane Formation in Saccharomyces cerevisiae

The meiosis II outer plaque (MOP) acts a vesicle tethering complex that is a site for de novo membrane formation. Novel mutants in a MOP protein reveal that interaction of vesicles with the MOP surface is required to recruit a second tethering complex, the exocyst, to the vesicles, suggesting a mechanism by which the MOP promotes vesicle fusion

Yeast Npi3/Bro1 is involved in ubiquitin-dependent control of permease trafficking

AbstractThe membrane traffic and stability of the general amino acid permease Gap1 of Saccharomyces cerevisiae are under nitrogen control. Addition of a preferential nitrogen source such as ammonium to cells growing on a poor nitrogen source induces internalization of the permease and its subsequent degradation in the vacuole. This down-regulation requires ubiquitination of Gap1 through a process involving ubiquitin ligase Npi1/Rsp5, ubiquitin hydrolase Npi2/Doa4, and Bul1/2, two Npi1/Rsp5 interacting proteins. Here we report that yet another protein, Npi3, is involved in the regulation of Gap1 trafficking. We show that Npi3 is required for NH4+-induced down-regulation of Gap1, and particularly for efficient ubiquitination of the permease. Npi3 plays a pleiotropic role in permease down-regulation, since it is also involved in ubiquitination and stress-induced down-regulation of the uracil permease Fur4 and in glucose-induced degradation of hexose transporters Hxt6/7. We further provide evidence that Npi3 is required for direct vacuolar sorting of neosynthesized Gap1 permease as it occurs in npr1 mutant cells. NPI3 is identical to BRO1, a gene encoding a protein of unknown biochemical function and recently proposed to be involved in protein turnover. Npi3/Bro1 homologues include fungal proteins required for proteolytic cleavage of zinc finger proteins and the mouse Aip1 protein involved in apoptosis. We propose that proteins of the Npi3/Bro1 family, including homologues from higher species, may play a conserved role in ubiquitin-dependent control of membrane protein trafficking

A Genomic Approach for the Identification and Classification of Genes Involved in Cell Wall Formation and its Regulation in Saccharomyces Cerevisiae

Using a hierarchical approach, 620 non-essential single-gene yeast deletants generated by EUROFAN I were systematically screened for cell-wall-related phenotypes. By analyzing for altered sensitivity to the presence of Calcofluor white or SDS in the growth medium, altered sensitivity to sonication, or abnormal morphology, 145 (23%) mutants showing at least one cell wall-related phenotype were selected. These were screened further to identify genes potentially involved in either the biosynthesis, remodeling or coupling of cell wall macromolecules or genes involved in the overall regulation of cell wall construction and to eliminate those genes with a more general, pleiotropic effect. Ninety percent of the mutants selected from the primary tests showed additional cell wall-related phenotypes. When extrapolated to the entire yeast genome, these data indicate that over 1200 genes may directly or indirectly affect cell wall formation and its regulation. Twenty-one mutants with altered levels of β1,3-glucan synthase activity and five Calcofluor white-resistant mutants with altered levels of chitin synthase activities were found, indicating that the corresponding genes affect β1,3-glucan or chitin synthesis. By selecting for increased levels of specific cell wall components in the growth medium, we identified 13 genes that are possibly implicated in different steps of cell wall assembly. Furthermore, 14 mutants showed a constitutive activation of the cell wall integrity pathway, suggesting that they participate in the modulation of the pathway either directly acting as signaling components or by triggering the Slt2-dependent compensatory mechanism. In conclusion, our screening approach represents a comprehensive functional analysis on a genomic scale of gene products involved in various aspects of fungal cell wall formation

Steven Parrino : Amphetamine Monster-Mill

Nickas focuses on Parrino's photo-collages under which lies an aesthetic of negativity taken to its limit. The author resituates the artist's interventions in the psychotronic context of punk counterculture in the United States

Painting Abstraction : New elements in abstract painting

Penulis dalam buku ini memperkenalkan isu-isu dalam abstraksi kontemporer dari 80 seniman yang dalam 5 tahun terakhir berpengaruh dalam seni kontemporer.Penyajiannya dengan menampilkan lukisan-lukisan dari para seniman yang diilustrasikan dalam gambar penuh warna dan disertai dengan teks penjelasannya. Abstraksi kontemporer adalah alat referensi penting untuk kurator, kritikus, seniman dan kolektor. Lukisan-lukisan yang dimuat dan diulas dalam buku ini diantaranya adalah karya dari Tomma Abts, Richard Aldrich, John Armleder, Monika Baer, Kristin Baker, dll