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Full-Text Articles in Medicine and Health Sciences
Fungal Mediator Tail Subunits Contain Classical Transcriptional Activation Domains, Zhongle Liu, Lawrence C. Myers
Fungal Mediator Tail Subunits Contain Classical Transcriptional Activation Domains, Zhongle Liu, Lawrence C. Myers
Dartmouth Scholarship
Classical activation domains within DNA-bound eukaryotic transcription factors make weak interactions with coactivator complexes, such as Mediator, to stimulate transcription. How these interactions stimulate transcription, however, is unknown. The activation of reporter genes by artificial fusion of Mediator subunits to DNA binding domains that bind to their promoters has been cited as evidence that the primary role of activators is simply to recruit Mediator. We have identified potent classical transcriptional activation domains in the C termini of several tail module subunits of Saccharomyces cerevisiae, Candida albicans, and Candida dubliniensis Mediator, while their N-terminal domains are necessary and sufficient for their …
Telomeric Orfs (Tlos) In Candida Spp. Encode Mediator Subunits That Regulate Distinct Virulence Traits, John Haran, Hannah Boyle, Karsten Hokamp, Tim Yeomans, Zhongle Liu, Michael Church, Alastair B. Fleming, Matthew Z. Anderson, Judith Berman, Lawrence C. Meyers, Derek J. Sullivan, Gary P. Morgan
Telomeric Orfs (Tlos) In Candida Spp. Encode Mediator Subunits That Regulate Distinct Virulence Traits, John Haran, Hannah Boyle, Karsten Hokamp, Tim Yeomans, Zhongle Liu, Michael Church, Alastair B. Fleming, Matthew Z. Anderson, Judith Berman, Lawrence C. Meyers, Derek J. Sullivan, Gary P. Morgan
Dartmouth Scholarship
The TLO genes are a family of telomere-associated ORFs in the fungal pathogens Candida albicans and C. dubliniensis that encode a subunit of the Mediator complex with homology to Med2. The more virulent pathogen C. albicans has 15 copies of the gene whereas the less pathogenic species C. dubliniensis has only two (CdTLO1 and CdTLO2). In this study we used C. dubliniensis as a model to investigate the role of TLO genes in regulating virulence and also to determine whether TLO paralogs have evolved to regulate distinct functions. A C. dubliniensis tlo1Δ/tlo2Δ mutant is unable …
Role Of Adaptor Trfa And Clppc In Controlling Levels Of Ssra-Tagged Proteins And Antitoxins In Staphylococcus Aureus, Niles P. Donegan, Jonathan S. Marvin, Ambrose L. Cheung
Role Of Adaptor Trfa And Clppc In Controlling Levels Of Ssra-Tagged Proteins And Antitoxins In Staphylococcus Aureus, Niles P. Donegan, Jonathan S. Marvin, Ambrose L. Cheung
Dartmouth Scholarship
Staphylococcus aureus responds to changing extracellular environments in part by adjusting its proteome through alterations of transcriptional priorities and selective degradation of the preexisting pool of proteins. In Bacillus subtilis, the proteolytic adaptor protein MecA has been shown to play a role in assisting with the proteolytic degradation of proteins involved in competence and the oxidative stress response. However, the targets of TrfA, the MecA homolog in S. aureus, have not been well characterized. In this work, we investigated how TrfA assists chaperones and proteases to regulate the proteolysis of several classes of proteins in S. aureus. …
Importance Of Bacillithiol In The Oxidative Stress Response Of Staphylococcus Aureus, Ana C. Posada, Stacey L. Kolar, Renata G. Dusi, Patrica Francois
Importance Of Bacillithiol In The Oxidative Stress Response Of Staphylococcus Aureus, Ana C. Posada, Stacey L. Kolar, Renata G. Dusi, Patrica Francois
Dartmouth Scholarship
In Staphylococcus aureus, the low-molecular-weight thiol called bacillithiol (BSH), together with cognate S-transferases, is believed to be the counterpart to the glutathione system of other organisms. To explore the physiological role of BSH in S. aureus, we constructed mutants with the deletion of bshA (sa1291), which encodes the glycosyltransferase that catalyzes the first step of BSH biosynthesis, and fosB (sa2124), which encodes a BSH-S-transferase that confers fosfomycin resistance, in several S. aureus strains, including clinical isolates. Mutation of fosB or bshA caused a 16- to 60-fold reduction in fosfomycin resistance in these S. aureus strains. High-pressure liquid chromatography analysis, which …
Neurovascular Unit Dysfunction With Blood-Brain Barrier Hyperpermeability Contributes To Major Depressive Disorder: A Review Of Clinical And Experimental Evidence, Souhel Najjar, Daniel M. Pearlman, Orrin Devinsky, Amanda Najjar, David Zagzag
Neurovascular Unit Dysfunction With Blood-Brain Barrier Hyperpermeability Contributes To Major Depressive Disorder: A Review Of Clinical And Experimental Evidence, Souhel Najjar, Daniel M. Pearlman, Orrin Devinsky, Amanda Najjar, David Zagzag
Dartmouth Scholarship
About one-third of people with major depressive disorder (MDD) fail at least two antidepressant drug trials at 1 year. Together with clinical and experimental evidence indicating that the pathophysiology of MDD is multifactorial, this observation underscores the importance of elucidating mechanisms beyond monoaminergic dysregulation that can contribute to the genesis and persistence of MDD. Oxidative stress and neuroinflammation are mechanistically linked to the presence of neurovascular dysfunction with blood-brain barrier (BBB) hyperpermeability in selected neurological disorders, such as stroke, epilepsy, multiple sclerosis, traumatic brain injury, and Alzheimer’s disease. In contrast to other major psychiatric disorders, MDD is frequently comorbid with …
The Fungal Pathogen Aspergillus Fumigatus Regulates Growth, Metabolism, And Stress Resistance In Response To Light, Kevin K. Fuller, Carol S. Ringelberg, Jennifer J. Loros, Jay C. Dunlap
The Fungal Pathogen Aspergillus Fumigatus Regulates Growth, Metabolism, And Stress Resistance In Response To Light, Kevin K. Fuller, Carol S. Ringelberg, Jennifer J. Loros, Jay C. Dunlap
Dartmouth Scholarship
Light is a pervasive environmental factor that regulates development, stress resistance, and even virulence in numerous fungal species. Though much research has focused on signaling pathways in Aspergillus fumigatus, an understanding of how this pathogen responds to light is lacking. In this report, we demonstrate that the fungus does indeed respond to both blue and red portions of the visible spectrum. Included in the A. fumigatus light response is a reduction in conidial germination rates, increased hyphal pigmentation, enhanced resistance to acute ultraviolet and oxidative stresses, and an increased susceptibility to cell wall perturbation. By performing gene deletion analyses, we …
A Serratia Marcescens Oxyr Homolog Mediates Surface Attachment And Biofilm Formation, Robert M. Q. Shanks, Nicholas A. Stella, Eric J. Kalivoda, Megan R. Doe
A Serratia Marcescens Oxyr Homolog Mediates Surface Attachment And Biofilm Formation, Robert M. Q. Shanks, Nicholas A. Stella, Eric J. Kalivoda, Megan R. Doe
Dartmouth Scholarship
OxyR is a conserved bacterial transcription factor with a regulatory role in oxidative stress response. From a genetic screen for genes that modulate biofilm formation in the opportunistic pathogen Serratia marcescens, mutations in an oxyR homolog and predicted fimbria structural genes were identified. S. marcescens oxyR mutants were severely impaired in biofilm formation, in contrast to the hyperbiofilm phenotype exhibited by oxyR mutants of Escherichia coli and Burkholderia pseudomallei. Further analysis revealed that OxyR plays a role in the primary attachment of cells to a surface. Similar to what is observed in other bacterial species, S. marcescens OxyR …