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The Coordinate Actions Of Calcineurin And Hog1 Mediate The Stress Response Through Multiple Nodes Of The Cell Cycle Network, Cassandra M. Leech, Mackenzie J. Flynn, Heather E. Arsenault, Jianhong Ou, Haibo Liu, Lihua Julie Zhu, Jennifer A. Benanti 2020 University of Massachusetts Medical School

The Coordinate Actions Of Calcineurin And Hog1 Mediate The Stress Response Through Multiple Nodes Of The Cell Cycle Network, Cassandra M. Leech, Mackenzie J. Flynn, Heather E. Arsenault, Jianhong Ou, Haibo Liu, Lihua Julie Zhu, Jennifer A. Benanti

Open Access Articles

Upon exposure to environmental stressors, cells transiently arrest the cell cycle while they adapt and restore homeostasis. A challenge for all cells is to distinguish between stress signals and coordinate the appropriate adaptive response with cell cycle arrest. Here we investigate the role of the phosphatase calcineurin (CN) in the stress response and demonstrate that CN activates the Hog1/p38 pathway in both yeast and human cells. In yeast, the MAPK Hog1 is transiently activated in response to several well-studied osmostressors. We show that when a stressor simultaneously activates CN and Hog1, CN disrupts Hog1-stimulated negative feedback to prolong Hog1 ...


Dgts Production As A Phosphate Starvation Response In The Human Fungal Pathogen Candida Albicans, Caleb Wehling 2020 University of Nebraska - Lincoln

Dgts Production As A Phosphate Starvation Response In The Human Fungal Pathogen Candida Albicans, Caleb Wehling

Dissertations and Theses in Biological Sciences

Betaine lipids are a class of membrane lipids with betaine head groups. Three betaine lipids are known - diacylglyceryltrimethylhomoserine (DGTS), diacylglycerylhydroxymethylalanine (DGTA), and diacylglycerylcarboxymethylcholine (DGCC). Betaine lipids are most common in algae, although DGTS, the most common betaine lipid, is also found in many bacteria and fungi. Organisms which produce betaine lipids (especially DGTS) often don’t produce phosphatidylcholine (PtdCho), and DGTS structure resembles PtdCho structure without any phosphorous, leading to the hypothesis that betaine lipids may substitute for phospholipids in some organisms. This has been confirmed by discoveries that some organisms are capable of switching their membrane composition from PtdCho ...


Comprehensive Fitness Maps Of Hsp90 Show Widespread Environmental Dependence, Julia M. Flynn, Ammeret Rossouw, Pamela A. Cote-Hammarlof, Ines Fragata, David Mavor, Carl Hollins III, Claudia Bank, Daniel N. Bolon 2020 University of Massachusetts Medical School

Comprehensive Fitness Maps Of Hsp90 Show Widespread Environmental Dependence, Julia M. Flynn, Ammeret Rossouw, Pamela A. Cote-Hammarlof, Ines Fragata, David Mavor, Carl Hollins Iii, Claudia Bank, Daniel N. Bolon

Open Access Articles

Gene-environment interactions have long been theorized to influence molecular evolution. However, the environmental dependence of most mutations remains unknown. Using deep mutational scanning, we engineered yeast with all 44,604 single codon changes encoding 14,160 amino acid variants in Hsp90 and quantified growth effects under standard conditions and under five stress conditions. To our knowledge, these are the largest determined comprehensive fitness maps of point mutants. The growth of many variants differed between conditions, indicating that environment can have a large impact on Hsp90 evolution. Multiple variants provided growth advantages under individual conditions; however, these variants tended to exhibit ...


Skp, Cullin, F-Box (Scf)-Met30 And Scf-Cdc4-Mediated Proteolysis Of Cenp-A Prevents Mislocalization Of Cenp-A For Chromosomal Stability In Budding Yeast, Wei-Chun Au, Richard E. Baker, Munira A. Basrai 2020 National Institutes of Health

Skp, Cullin, F-Box (Scf)-Met30 And Scf-Cdc4-Mediated Proteolysis Of Cenp-A Prevents Mislocalization Of Cenp-A For Chromosomal Stability In Budding Yeast, Wei-Chun Au, Richard E. Baker, Munira A. Basrai

Open Access Articles

Restricting the localization of the histone H3 variant CENP-A (Cse4 in yeast, CID in flies) to centromeres is essential for faithful chromosome segregation. Mislocalization of CENP-A leads to chromosomal instability (CIN) in yeast, fly and human cells. Overexpression and mislocalization of CENP-A has been observed in many cancers and this correlates with increased invasiveness and poor prognosis. Yet genes that regulate CENP-A levels and localization under physiological conditions have not been defined. In this study we used a genome-wide genetic screen to identify essential genes required for Cse4 homeostasis to prevent its mislocalization for chromosomal stability. We show that two ...


Investigating The Nucleophosmin (Npm1) Protein In The Context Of Protein Aggregation In The Budding Yeast S. Cerevisiae, Tyler Atagozli 2020 University of Iowa

Investigating The Nucleophosmin (Npm1) Protein In The Context Of Protein Aggregation In The Budding Yeast S. Cerevisiae, Tyler Atagozli

Honors Theses at the University of Iowa

The Nucleophosmin (Npm1) protein is a nucleolar protein found in jawed vertebrates. It is primarily involved in ribosome biogenesis. Recent studies have proposed a new role for this protein as a protective agent colocalizing with cellular aggregates like firefly luciferase and the mutant huntingtin protein during stress conditions. In this study, the behavior of Npm1 was investigated in the budding yeast S. cerevisiae by fluorescence microscopy to see if Npm1 colocalizes or otherwise interacts with aggregates. I found that Npm1 redistributes to a subnuclear location after heat shock where it may colocalize with luciferase aggregates. HTTQ103, a mutant huntingtin protein ...


Evaluating Volatile Organic Compounds For Contact-Independent Antagonism Of Pseudogymnoascus Destructans, 2019 Kennesaw State University

Evaluating Volatile Organic Compounds For Contact-Independent Antagonism Of Pseudogymnoascus Destructans

Symposium of Student Scholars

White-nose syndrome (WNS), a disease caused by the fungus Pseudogymnoascus destructans, is responsible for the extensive mortality of bats in the United States. In an effort to develop tools to reduce bat mortality attributed to WNS, an in vitro experiment was conducted to quantify the inhibitory effects of select volatile organic compounds (VOCs) as well as explore potential synergistic activities. The experiment involved exposing mycelial plugs of P. destructans to various concentrations of B23 as well as B23 and decanal together at equimolar ratios. Measurements of the plugs were taken over the course of the 13 day experiment allowing the ...


Oral Fungal Microbiota: To Thrush And Beyond, Dennis J. Baumgardner 2019 Aurora UW Medical Group, Aurora Health Care

Oral Fungal Microbiota: To Thrush And Beyond, Dennis J. Baumgardner

Journal of Patient-Centered Research and Reviews

The oral microbiota is complex, multikingdom, interactive, and involves extensive biofilm formation. While dominated by bacteria, Candida is a frequent member of this microbiota; however, several other potentially pathogenic fungi (among around 100 identified species) appear to reside in some individuals, including Cryptococcus, Aspergillus, and Fusarium. Oral candidiasis may manifest as a variety of disease entities in normal hosts and in the immunocompromised. These include pseudomembranous candidiasis (thrush), hyperplastic or atrophic (denture) candidiasis, linear gingival erythema, median rhomboid glossitis, and angular cheilitis. The purpose of this review is to describe the oral fungal microbiota (ie, oral mycobiota), common mouth diseases ...


Mdt-28/Plin-1 Mediates Lipid Droplet-Microtubule Interaction Via Dlc-1 In Caenorhabditis Elegans, Kang Xie, Peng Zhang, Huimin Na, Yangli Liu, Hong Zhang, Pingsheng Liu 2019 University of Chinese Academy of Sciences

Mdt-28/Plin-1 Mediates Lipid Droplet-Microtubule Interaction Via Dlc-1 In Caenorhabditis Elegans, Kang Xie, Peng Zhang, Huimin Na, Yangli Liu, Hong Zhang, Pingsheng Liu

Open Access Articles

Ectopic lipid accumulation in lipid droplets (LD) has been linked to many metabolic diseases. In this study, DHS-3::GFP was used as a LD marker in C. elegans and a forward genetic screen was carried out to find novel LD regulators. There were 140 mutant alleles identified which were divided into four phenotypic categories: enlarged, aggregated, aggregated and small, and decreased. After genetic mapping, mutations in three known LD regulatory genes (maoc-1, dhs-28, daf-22) and a peroxisome-related gene (acox-3) were found to enlarge LDs, demonstrating the reliability of using DHS-3 as a living marker. In the screen, the cytoskeleton protein ...


Chitosan Biosynthesis And Virulence In The Human Fungal Pathogen Cryptococcus Gattii, Woei C. Lam, Rajendra Upadhya, Charles A. Specht, Abigail E. Ragsdale, Camaron R. Hole, Stuart M. Levitz, Jennifer K. Lodge 2019 Washington University

Chitosan Biosynthesis And Virulence In The Human Fungal Pathogen Cryptococcus Gattii, Woei C. Lam, Rajendra Upadhya, Charles A. Specht, Abigail E. Ragsdale, Camaron R. Hole, Stuart M. Levitz, Jennifer K. Lodge

Open Access Articles

Cryptococcus gattii R265 is a hypervirulent fungal strain responsible for the recent outbreak of cryptococcosis in Vancouver Island of British Columbia in Canada. It differs significantly from Cryptococcus neoformans in its natural environment, its preferred site in the mammalian host, and its pathogenesis. Our previous studies of C. neoformans have shown that the presence of chitosan, the deacetylated form of chitin, in the cell wall attenuates inflammatory responses in the host, while its absence induces robust immune responses, which in turn facilitate clearance of the fungus and induces a protective response. The results of the present investigation reveal that the ...


The Essential Role Of Carbon Metabolism In The Virulence Of Cryptococcus Neoformans, Mara Weigner 2019 Liberty University

The Essential Role Of Carbon Metabolism In The Virulence Of Cryptococcus Neoformans, Mara Weigner

Senior Honors Theses

Cryptococcus neoformans infections are a major cause of meningoencephalitis in immunosuppressed patients worldwide. Inhaled as spores or desiccated yeast cells, C. neoformans can undergo metabolic changes in response to the new host environment that allow it to cross the blood brain barrier and cause deadly central nervous system (CNS) infections. Nutrient acquisition, and specifically carbon metabolism, is critical for survival and proliferation within the host. Notably, efficient carbon metabolism is necessary to produce the polysaccharide capsule, which is arguably C. neoformans’ most important and well-studied virulence factor. As such, a better understanding of carbon acquisition and regulation is essential for ...


Distinct Transcriptional Roles For Histone H3-K56 Acetylation During The Cell Cycle In Yeast, Salih Topal, Pauline Vasseur, Marta Radman-Livaja, Craig L. Peterson 2019 University of Massachusetts Medical School

Distinct Transcriptional Roles For Histone H3-K56 Acetylation During The Cell Cycle In Yeast, Salih Topal, Pauline Vasseur, Marta Radman-Livaja, Craig L. Peterson

Open Access Articles

Dynamic disruption and reassembly of promoter-proximal nucleosomes is a conserved hallmark of transcriptionally active chromatin. Histone H3-K56 acetylation (H3K56Ac) enhances these turnover events and promotes nucleosome assembly during S phase. Here we sequence nascent transcripts to investigate the impact of H3K56Ac on transcription throughout the yeast cell cycle. We find that H3K56Ac is a genome-wide activator of transcription. While H3K56Ac has a major impact on transcription initiation, it also appears to promote elongation and/or termination. In contrast, H3K56Ac represses promiscuous transcription that occurs immediately following replication fork passage, in this case by promoting efficient nucleosome assembly. We also detect ...


Coccidioidomycosis: Medical And Spatio-Temporal Perspectives, Nikias Sarafoglou, Rafael Laniado-Laborin, Menas Kafatos 2019 George Mason University

Coccidioidomycosis: Medical And Spatio-Temporal Perspectives, Nikias Sarafoglou, Rafael Laniado-Laborin, Menas Kafatos

Mathematics, Physics, and Computer Science Faculty Articles and Research

Coccidioidomycosis (CM) is a disease of major public health importance due to the challenges in its diagnosis and treatment. To understand CM requires the attributes of a multidisciplinary network analysis to appreciate the complexity of the medical, the environmental and the social issues involved: public health, public policy, geology, atmospheric science, agronomy, social sciences and finally humanities, all which provide insight into this population transformation.

In section 1 of this paper, we describe the CM-epidemiology, the clinical features, the diagnosis and finally the treatment.

In section 2, we highlight the most important contributions and controversies in the history of the ...


Chitosan Biosynthesis And Virulence In The Human Fungal Pathogen Cryptococcus Gattii, Woei C. Lam, Rajendra Upadhya, Charles A. Specht, Abigail E. Ragsdale, Camaron R. Hole, Stuart M. Levitz, Jennifer K. Lodge 2019 Washington University in St. Louis

Chitosan Biosynthesis And Virulence In The Human Fungal Pathogen Cryptococcus Gattii, Woei C. Lam, Rajendra Upadhya, Charles A. Specht, Abigail E. Ragsdale, Camaron R. Hole, Stuart M. Levitz, Jennifer K. Lodge

University of Massachusetts Medical School Faculty Publications

Cryptococcus gattii R265 is a hyper-virulent fungal strain responsible for the major outbreak of cryptococcosis in Vancouver Island of British Columbia in 1999. It differs significantly from C. neoformans in its natural environment, its preferred site in the mammalian host, and in the nature and mode of pathogenesis. Our previous studies in C. neoformans have shown that the presence of chitosan, the deacetylated form of chitin, in the cell wall attenuates inflammatory responses in the host, while its absence induces robust immune responses, which in turn facilitate clearance of the fungus and induces a protective response. The results of the ...


The Aminoalkylindole, Bml-190, Negatively Regulates Chitosan Synthesis Via The Camp/Pka1 Pathway In Cryptococcus Neoformans, Brian T. Maybruck, Woei C. Lam, Charles A. Specht, Ma Xenia G. Ilagan, Maureen J. Donlin, Jennifer K. Lodge 2019 Washington University in St. Louis

The Aminoalkylindole, Bml-190, Negatively Regulates Chitosan Synthesis Via The Camp/Pka1 Pathway In Cryptococcus Neoformans, Brian T. Maybruck, Woei C. Lam, Charles A. Specht, Ma Xenia G. Ilagan, Maureen J. Donlin, Jennifer K. Lodge

University of Massachusetts Medical School Faculty Publications

Cryptococcus neoformans can cause fatal meningoencephalitis in patients with AIDS or other immune-compromising conditions. Current antifungals are suboptimal to treat this disease, therefore, novel targets and new therapies are needed. Previously, we have shown that chitosan is a critical component of the cryptococcal cell wall, is required for survival in the mammalian host, and that chitosan deficiency results in rapid clearance from the mammalian host. We had also identified several specific proteins that were required for chitosan biosynthesis, and we hypothesize that screening for compounds that inhibit chitosan biosynthesis would identify additional genes/proteins that influence chitosan biosynthesis.


Selectivity Of Infrared Heat Treatment On Inactivation Of Mycotoxigenic Fungi On Stored Grain, Shantae A. Wilson 2019 University of Arkansas, Fayetteville

Selectivity Of Infrared Heat Treatment On Inactivation Of Mycotoxigenic Fungi On Stored Grain, Shantae A. Wilson

Theses and Dissertations

Selective Infrared (IR) heating holds great potential to decontaminate spores of unsafe fungi in corn. The objectives for this study were to investigate the impact of exposing corn to infrared energy at selected peak wavelengths (λ), infrared intensities and treatment durations, followed by tempering for further inactivation of microbes on the grain and explore a method for decontaminating Aspergillus flavus (A. flavus) spores on corn. Freshly harvested corn with initial moisture contents (IMCs) of 16%, 20%, and 24% wet basis (w.b.) were used. The corn samples were treated at different infrared wavelengths (3.2, 4.5, and 5.8 ...


The Effect Of Prescribed Burning On Wood-Decay Fungi In The Forests Of Northwest Arkansas, Nawaf Ibrahim Alshammari 2019 University of Arkansas, Fayetteville

The Effect Of Prescribed Burning On Wood-Decay Fungi In The Forests Of Northwest Arkansas, Nawaf Ibrahim Alshammari

Theses and Dissertations

Prescribed burning is defined as the process of the planned application of fire to a predetermined area under specific environmental conditions in order to achieve a desired outcome such as land management. This project used both morphological and molecular methods to identify and characterize the wood-decay fungi associated with the forests of northwest Arkansas—Pea Ridge National Military Park, Devil’s Den State Park, and the Buffalo National River—through frequent visits made between February 2018 and February 2019. In addition, in order to assess the effects of prescribed burning, incubation chambers were used to compare the growth of fungi ...


Ste5 Membrane Localization Allows Mapk Pathway Signaling In Trans Between Kinases On Separate Scaffold Molecules, Rachel E. Lamson, Matthew J. Winters, Peter M. Pryciak 2019 University of Massachusetts Medical School

Ste5 Membrane Localization Allows Mapk Pathway Signaling In Trans Between Kinases On Separate Scaffold Molecules, Rachel E. Lamson, Matthew J. Winters, Peter M. Pryciak

University of Massachusetts Medical School Faculty Publications

The MAP kinase cascade is a ubiquitous eukaryotic signaling module that can be controlled by a diverse group of scaffold proteins. In budding yeast, activation of the mating MAP kinase cascade involves regulated membrane recruitment of the archetypal scaffold protein Ste5. This event promotes activation of the first kinase, but it also enhances subsequent signal propagation through the remainder of the cascade. By studying this latter effect, we find that membrane recruitment promotes signaling in trans between kinases on separate Ste5 molecules. First, trans signaling requires all Ste5 domains that mediate membrane recruitment, including both protein-binding and membrane-binding domains. Second ...


Amphotercin Washout Of Fungal Peritonitis In Liver Transplant Recipient: A Novel Approach, Ann Thompson DO, Mara Piltin DO, Alyssa Imperatore DO, Ely Sebastian MD, Sandra Paluzzi MD 2019 Rowan University

Amphotercin Washout Of Fungal Peritonitis In Liver Transplant Recipient: A Novel Approach, Ann Thompson Do, Mara Piltin Do, Alyssa Imperatore Do, Ely Sebastian Md, Sandra Paluzzi Md

Stratford Campus Research Day

Invasive fungal infection has a significant prevalence among organ transplant patients and is associated with high rates of morbidity and mortality. Fungal infection is difficult to identify early and subsequently difficult to effectively treat. In this case presentation we have a 45 y/o orthotopic liver transplant recipient who was profoundly sick from fungal peritonitis and due to the appearance of her abdomen and intestines, with the help of infectious disease, decided to proceed with direct amphotercin washout of the abdomen in the operating room. The patient had complete resolution of her fungal peritonitis and is doing well.


Reporting Charcoal Rot In Chia And Developing A Susceptibility Assay, Reis M. Misaka, Hagop S. Atamian Dr., Julien Besnard Dr. 2019 Chapman University

Reporting Charcoal Rot In Chia And Developing A Susceptibility Assay, Reis M. Misaka, Hagop S. Atamian Dr., Julien Besnard Dr.

Student Scholar Symposium Abstracts and Posters

Chia (Salvia Hispanica) cross breeds were planted in the summer of 2018 with the intent of selective breeding for agricultural benefit. Preexisting pathogens in the soil caused 40-50% fatality of adult plants. This was surprising due to the precursory knowledge that chia has antibiotic and antifungal oils (Elshafie et. al. 2018); chia was only recently documented to be susceptible to Fusarium wilt (Fusarium oxysporum). The primary pathogen responsible was identified as Macrophomina phaseolina (aka charcoal rot); a widespread soilborne pathogen which has multiple commercial hosts (Su et. al. 2001).

M. phaesolina on wheat seed vector where used as inoculums (Brandari ...


The Nua4 Acetyltransferase And Histone H4 Acetylation Promote Replication Recovery After Topoisomerase I-Poisoning, Chiaki Noguchi, Tanu Singh, Melissa A. Ziegler, Jasmine D. Peake, Lyne Khair, Ana Aza, Toru M. Nakamura, Eishi Noguchi 2019 Drexel University

The Nua4 Acetyltransferase And Histone H4 Acetylation Promote Replication Recovery After Topoisomerase I-Poisoning, Chiaki Noguchi, Tanu Singh, Melissa A. Ziegler, Jasmine D. Peake, Lyne Khair, Ana Aza, Toru M. Nakamura, Eishi Noguchi

Open Access Articles

BACKGROUND: Histone acetylation plays an important role in DNA replication and repair because replicating chromatin is subject to dynamic changes in its structures. However, its precise mechanism remains elusive. In this report, we describe roles of the NuA4 acetyltransferase and histone H4 acetylation in replication fork protection in the fission yeast Schizosaccharomyces pombe.

RESULTS: Downregulation of NuA4 subunits renders cells highly sensitive to camptothecin, a compound that induces replication fork breakage. Defects in NuA4 function or mutations in histone H4 acetylation sites lead to impaired recovery of collapsed replication forks and elevated levels of Rad52 DNA repair foci, indicating the ...


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