Medicine and Health Sciences Commons^™

Antiproliferative Activity Of Philippine Marine Sediment-Derived Actinomycetes, Jon Ray M. Maglonzo, Edna M. Sabido, Cristina C. Salibay, Doralyn S. Dalisay, Jonel P. Saludes

Pharmaceutical Sciences and Research

The Philippine archipelago is rich in marine biodiversity and resources that are widely unexplored. Its marine sediments harbor marine microbes that possess secondary metabolites with potent bioactivities. This study aims to determine the antiproliferative activity of the crude extracts of selected Actinomycete isolates (DSD011, DSD017, and DSD042) from Islas de Gigantes, Carles, Iloilo. The antiproliferative screening was done using Saccharomyces cerevisiae as a model organism. Crude extracts of isolates that are active in inhibiting the growth of S. cerevisiae were determined using the broth microdilution method. Afterward, the active extract was tested using antiproliferative and budding yeast assays. With the …

Dpc29 Promotes Mitochondrial Translation Post-Initation In Saccharomyces Cerevisiae, Kyle Andrew Hubble

Graduate School of Biomedical Sciences Theses and Dissertations

Although the cytosolic and bacterial translation systems are well studied, much less is known about translation in mitochondria. In the yeast Saccharomyces cerevisiae, mitochondrial gene expression is predominately regulated by translational activators. These regulators are thought to promote translation by binding the elongated 5’-UTRs on their target mRNAs. Since mammalian mitochondrial mRNAs generally lack 5’-UTRs, they must regulate translation by other mechanisms. As expected, most yeast translational activators lack orthologues in mammals. Recently, a mitochondrial gene-specific translational activator, TACO1, was reported in mice and humans. To better define its role in mitochondrial translation I examined the yeast TACO1 orthologue, DPC29. …

Structure Of The Pre-Mrna Leakage 39-Kda Protein Reveals A Single Domain Of Integrated Zf-C3hc And Rsm1 Modules, Hideharu Hashimoto, Daniel H. Ramirez, Ophélie Lautier, Natalie Pawlak, Günter Blobel, Benoît Palancade, Erik W. Debler

Department of Biochemistry and Molecular Biology Faculty Papers

In Saccharomyces cerevisiae, the pre-mRNA leakage 39-kDa protein (ScPml39) was reported to retain unspliced pre-mRNA prior to export through nuclear pore complexes (NPCs). Pml39 homologs outside the Saccharomycetaceae family are currently unknown, and mechanistic insight into Pml39 function is lacking. Here we determined the crystal structure of ScPml39 at 2.5 Å resolution to facilitate the discovery of orthologs beyond Saccharomycetaceae, e.g. in Schizosaccharomyces pombe or human. The crystal structure revealed integrated zf-C3HC and Rsm1 modules, which are tightly associated through a hydrophobic interface to form a single domain. Both zf-C3HC and Rsm1 modules belong to the Zn-containing BIR (Baculovirus IAP …

Disease-Associated Mutations Within The Yeast Dnajb6 Homolog Sis1 Slow Conformer-Specific Substrate Processing And Can Be Corrected By The Modulation Of Nucleotide Exchange Factors, Ankan K Bhadra, Michael J Rau, Jil A Daw, James A J Fitzpatrick, Conrad C Weihl, Heather L True

2020-Current year OA Pubs

Molecular chaperones, or heat shock proteins (HSPs), protect against the toxic misfolding and aggregation of proteins. As such, mutations or deficiencies within the chaperone network can lead to disease. Dominant mutations within DNAJB6 (Hsp40)-an Hsp70 co-chaperone-lead to a protein aggregation-linked myopathy termed Limb-Girdle Muscular Dystrophy Type D1 (LGMDD1). Here, we used the yeast prion model client in conjunction with in vitro chaperone activity assays to gain mechanistic insights into the molecular basis of LGMDD1. Here, we show how mutations analogous to those found in LGMDD1 affect Sis1 (a functional homolog of human DNAJB6) function by altering the structure of client …

Cdk8 Kinase Module Modifies Expression Of Specific Translation-Related Proteins Before And After Stress, Brittany Friedson, Katrina Cooper

Rowan-Virtua Research Day

Translation is tightly coupled to growth status. Efficient protein synthesis is necessary for cell growth in nutrient rich environments, while global translation inhibition combined with selective translation of stress-responsive mRNAs helps limit growth in times of stress. Environmental stress cues which inhibit the nutrient-sensing complex TORC1 are known to reduce general translation, but how does the cell alter protein synthesis machinery to adapt to these conditions? A few mechanisms to promote cell survival in nitrogen starvation include post-translational modification and selective degradation of specific mRNA-binding translation factors, as well as inhibition of activators of genes whose products are required for …

Selective Inhibition Of Plasmodium Falciparum Atpase 6 By Artemisinins And Identification Of New Classes Of Inhibitors After Expression In Yeast, Catherine M. Moore, Jigang Wang, Qingsong Lin, Pedro Ferreira

Faculty and Student Publications

Treatment failures with artemisinin combination therapies (ACTs) threaten global efforts to eradicate malaria. They highlight the importance of identifying drug targets and new inhibitors and of studying how existing antimalarial classes work. Here, we report the successful development of a heterologous expression-based compoundscreening tool. The validated drug target Plasmodium falciparum ATPase 6 (PfATP6) and a mammalian orthologue (sarco/endoplasmic reticulum calcium ATPase 1a [SERCA1a]) were functionally expressed in Saccharomyces cerevisiae, providing a robust, sensitive, and specific screening tool. Whole-cell and in vitro assays consistently demonstrated inhibition and labeling of PfATP6 by artemisinins. Mutations in PfATP6 resulted in fitness costs that were …

Vulvovaginal Candidiasis: A Review Of The Evidence For The 2021 Centers For Disease Control And Prevention Of Sexually Transmitted Infections Treatment Guidelines., Paul Nyirjesy, Carolyn Brookhart, Gweneth Lazenby, Jane Schwebke, Jack D Sobel

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Vulvovaginal candidiasis (VVC) is a common cause of vulvovaginal itching and discharge. This article discusses the latest CDC STI Treatment Guidelines for VVC.

METHODS: A literature search of relevant topics was performed, and a team of experts was convened to discuss (1) diagnosis/testing modalities; treatment of (2) uncomplicated VVC , (3) complicated VVC, and (4) VVC caused by non-albicans yeast; (5) alternative treatment regimens; (6) susceptibility testing of yeast; Special Populations: (7) pregnancy and (8) HIV and VVC.

RESULTS: Yeast culture remains the gold standard for diagnoses. Newer molecular assays have been developed for the diagnosis of VVC and …