Showing 781 - 790 of 2039 Items
Arginine methyltransferase affects interactions and recruitment of mRNA processing and export factors
Date: 2004-08-15
Creator: Michael C. Yu
François Bachand
Anne E. McBride
Suzanne Komili
Jason M., Casolari
Pamela A. Silver
Access: Open access
- Hmt1 is the major type I arginine methyltransferase in the yeast Saccharomyces cerevisiae and facilitates the nucleocytoplasmic transport of mRNA-binding proteins through their methylation. Here we demonstrate that Hmt1 is recruited during the beginning of the transcriptional elongation process. Hmt1 methylates Yra1 and Hrp1, two mRNA-binding proteins important for mRNA processing and export. Moreover, loss of Hmt1 affects interactions between mRNA-binding proteins and Tho2, a component of the TREX (transcription/export) complex that is important for transcriptional elongation and recruitment of mRNA export factors. Furthermore, RNA in situ hybridization analysis demonstrates that loss of Hmt1 results in slowed release of HSP104 mRNA from the sites of transcription. Genome-wide location analysis shows that Hmt1 is bound to specific functional gene classes, many of which are also bound by Tho2 and other mRNA-processing factors. These data suggest a model whereby Hmt1 affects transcriptional elongation and, as a result, influences recruitment of RNA-processing factors.
Genetic interactions of yeast eukaryotic translation initiation factor 5a (eIF5A) reveal connections to poly(A)-binding protein and protein kinase C signaling
Date: 2002-03-14
Creator: Sandro R. Valentini
Jason M. Casolari
Carla C. Oliveira
Pamela A. Silver
Anne E., McBride
Access: Open access
- The highly conserved eukaryotic translation initiation factor eIF5A has been proposed to have various roles in the cell, from translation to mRNA decay to nuclear protein export. To further our understanding of this essential protein, three temperature-sensitive alleles of the yeast TIF51A gene have been characterized. Two mutant eIF5A proteins contain mutations in a proline residue at the junction between the two eIFSA domains and the third, strongest allele encodes a protein with a single mutation in each domain, both of which are required for the growth defect. The stronger tif51A alleles cause defects in degradation of short-lived mRNAs, supporting a role for this protein in mRNA decay. A multicopy suppressor screen revealed six genes, the overexpression of which allows growth of a tif51A-1 strain at high temperature; these genes include PAB1, PKC1, and PKC1 regulators WSC1, WSC2, and WSC3. Further results suggest that eIFSA may also be involved in ribosomal synthesis and the WSC/PKC1 signaling pathway for cell wall integrity or related processes.
How Did Exchange Rates Affect Employment in US Cities?
Date: 2013-05-07
Creator: Yao Tang
Haifang Huang
Access: Open access
- We estimate the effects of real exchange rate movements on employment in US cities between 2003 and 2010. We explore the differences in the composition of local industries to construct city-specific changes in exchange rates and estimate their effects on local employment in manufacturing industries and in nonmanufacturing industries. Controlling for year and city fixed effects, we find that a depreciation of the US dollar increased local employment in the manufacturing industries, our proxy for the tradable sector. The depreciation also increased employment in the nonmanufacturing industries, the nontradable sector. Furthermore, the effects on nonmanufacturing employment were stronger in cities that had a higher fraction of manufacturing employment, indicating the exchange rate movements’ indirect effects through the manufacturing industries. We also consider an alternative definition of the tradable sector that is broadened to include five service industries. The findings are similar.
Interest group issue appeals: Evidence of issue convergence in senate and presidential elections, 2008-2014
Date: 2000-05-01
Creator: Michael M. Franz
Access: Open access
- Interest groups now play a prominent role in the air war. Their collective investment in election campaigns has skyrocketed in the aftermath of Citizens United. Yet questions remain about whether interest group advertising affects the content of the specific issues being discussed. Do groups enter campaigns and engage voters on the same issues as their candidate allies? Or does the presence of more advertisers introduce competitive issue streams? This paper examines ad buys in Senate elections between 2008 and 2014 and the presidential elections of 2008 and 2012. A primary goal of the paper is to uncover the effect of high and low levels of "issue convergence" on election outcomes. Strategists often express concern that too many voices on behalf of a candidate can weaken the impact of ads. One might expect that as convergence between a candidate and his or her allies goes up (meaning the issue content of the ad buys overlaps across advertisers), the impact of ads on votes will increase. Ad effects should be weaker when a candidate's ads discuss different issues from allied groups and party committees. The results, however, suggest that high rates of issue convergence are only weakly related to election outcomes (and not always in consistent ways).
Nonlinear coherent structures in granular crystals
Date: 2017-09-06
Creator: C. Chong
Mason A. Porter
P. G. Kevrekidis
C. Daraio
Access: Open access
- The study of granular crystals, which are nonlinear metamaterials that consist of closely packed arrays of particles that interact elastically, is a vibrant area of research that combines ideas from disciplines such as materials science, nonlinear dynamics, and condensed-matter physics. Granular crystals exploit geometrical nonlinearities in their constitutive microstructure to produce properties (such as tunability and energy localization) that are not conventional to engineering materials and linear devices. In this topical review, we focus on recent experimental, computational, and theoretical results on nonlinear coherent structures in granular crystals. Such structures - which include traveling solitary waves, dispersive shock waves, and discrete breathers - have fascinating dynamics, including a diversity of both transient features and robust, long-lived patterns that emerge from broad classes of initial data. In our review, we primarily discuss phenomena in one-dimensional crystals, as most research to date has focused on such scenarios, but we also present some extensions to two-dimensional settings. Throughout the review, we highlight open problems and discuss a variety of potential engineering applications that arise from the rich dynamic response of granular crystals.
Framing ICT Usage in the Real Estate Industry
Creator: Steven Jones
Access: Open access
- The real estate industry, like many, is one based on a competitive consumer culture in which professionals vie for the business and, ultimately, the loyalty of customers. In this case, those customers are purchasing what, for most, is a significant investment, requiring them to navigate various legal and regulatory processes that might be impossible without the assistance of a knowledgeable, seasoned agent. It is the presence of agency that renders real estate unique from retail and other industries where goods and services trade hands. Furthermore, the rise of various information and communication technologies (ICT) over the course of the past 25 years may have led to new challenges for real estate agents and allied professionals. Some scholars surmise that the increased prevalence of ICTs in various industries can become disruptive to those industries, causing individuals and organizations working within them to either adapt accordingly or become obsolete (Bower and Christensen 1995; Markus, et al. 2006).
Design of a drug discovery course for non-science majors
Date: 2018-07-01
Creator: Danielle H. Dube
Access: Open access
- “Drug Discovery” is a 13-week lecture and laboratory-based course that was developed to introduce non-science majors to foundational chemistry and biochemistry concepts as they relate to the unifying theme of drug discovery. The first part of this course strives to build students' understanding of molecules, their properties, the differences that enable them to be separated from one another, and their abilities to bind to biological receptors and elicit physiological effects. After building students' molecular worldview, the course then focuses on four classes of drugs: antimicrobials, drugs that affect the mind, steroid-based drugs, and anti-cancer drugs. During each of these modules, an emphasis is placed on how understanding the basis of disease and molecular-level interactions empowers us to identify novel medicinal compounds. Periodic in class discussions based on articles pertinent to class topics ranging from the spread of antibiotic resistance, to the molecular basis of addiction, to rational drug design, are held to enable students to relate course material to pressing problems of national and daily concern. In addition to class time, weekly inquiry-based laboratories allow students to critically analyze data related to course concepts, and later in the semester give students an opportunity to design and implement their own experiments to screen for antimicrobial activity. This course provides students with an understanding of the importance of chemistry and biochemistry to human health while emphasizing the process, strategies, and challenges related to drug discovery. © 2018 by The International Union of Biochemistry and Molecular Biology, 46:327–335, 2018.
Partner choice in spontaneous mitotic recombination in wild type and homologous recombination mutants of Candida albicans
Date: 2019-11-01
Creator: Alberto Bellido
Toni Ciudad
Belén Hermosa
Encarnación Andaluz
Anja, Forche
Germán Larriba
Access: Open access
- Candida albicans, the most common fungal pathogen, is a diploid with a genome that is rich in repeats and has high levels of heterozygosity. To study the role of different recombination pathways on direct-repeat recombination, we replaced either allele of the RAD52 gene (Chr6) with the URA-blaster cassette (hisG-URA3-hisG), measured rates of URA3 loss as resistance to 5-fluoroorotic acid (5FOAR) and used CHEF Southern hybridization and SNP-RFLP analysis to identify recombination mechanisms and their frequency in wildtype and recombination mutants. FOAR rates varied little across different strain backgrounds. In contrast, the type and frequency of mechanisms underlying direct repeat recombination varied greatly. For example, wildtype, rad59 and lig4 strains all displayed a bias for URA3 loss via pop-out/deletion vs. inter-homolog recombination and this bias was reduced in rad51 mutants. In addition, in rad51-derived 5FOAR strains direct repeat recombination was associated with ectopic translocation (5%), chromosome loss/truncation (14%) and inter-homolog recombination (6%). In the absence of RAD52, URA3 loss was mostly due to chromosome loss and truncation (80–90%), and the bias of retained allele frequency points to the presence of a recessive lethal allele on Chr6B. However, a few single-strand annealing (SSA)-like events were identified and these were independent of either Rad59 or Lig4. Finally, the specific sizes of Chr6 truncations suggest that the inserted URA-blaster could represent a fragile site.
Development of Rare Bacterial Monosaccharide Analogs for Metabolic Glycan Labeling in Pathogenic Bacteria
Date: 2016-12-16
Creator: Emily L. Clark
Madhu Emmadi
Katharine L. Krupp
Ananda R. Podilapu
Jennifer D., Helble
Suvarn S. Kulkarni
Danielle H. Dube
Access: Open access
- Bacterial glycans contain rare, exclusively bacterial monosaccharides that are frequently linked to pathogenesis and essentially absent from human cells. Therefore, bacterial glycans are intriguing molecular targets. However, systematic discovery of bacterial glycoproteins is hampered by the presence of rare deoxy amino sugars, which are refractory to traditional glycan-binding reagents. Thus, the development of chemical tools that label bacterial glycans is a crucial step toward discovering and targeting these biomolecules. Here, we explore the extent to which metabolic glycan labeling facilitates the studying and targeting of glycoproteins in a range of pathogenic and symbiotic bacterial strains. We began with an azide-containing analog of the naturally abundant monosaccharide N-acetylglucosamine and discovered that it is not broadly incorporated into bacterial glycans, thus revealing a need for additional azidosugar substrates to broaden the utility of metabolic glycan labeling in bacteria. Therefore, we designed and synthesized analogs of the rare deoxy amino d-sugars N-acetylfucosamine, bacillosamine, and 2,4-diacetamido-2,4,6-trideoxygalactose and established that these analogs are differentially incorporated into glycan-containing structures in a range of pathogenic and symbiotic bacterial species. Further application of these analogs will refine our knowledge of the glycan repertoire in diverse bacteria and may find utility in treating a variety of infectious diseases with selectivity.