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Flippase Inhibitors As Antimicrobial Agents, Robert Tancer 2022 Seton Hall University

Flippase Inhibitors As Antimicrobial Agents, Robert Tancer

Seton Hall University Dissertations and Theses (ETDs)

Drug resistant microbes are a considerable challenge for modern medicine to overcome. The research described in this dissertation involved development of lipid flippase inhibitors and investigating their potential as antimicrobial agents against various drug resistant microbes. The microbes primarily investigated were methicillin resistant Staphylococcus aureus (MRSA) & Cryptococcus neoformans. Chapter 1 reviews the historical perspective and summarizes the current state of the field of research. In Chapter 2, the design space of an antimicrobial peptide known as humimycin was explored and the effects of modifications on its structure were observed against MRSA. Several key observations resulted. Most notably, the nanoparticles formed ...


Integration Of Medicinal Fungi Into The Heber W. Youngken Jr. Medicinal Garden, Anthony Makashov 2022 University of Rhode Island

Integration Of Medicinal Fungi Into The Heber W. Youngken Jr. Medicinal Garden, Anthony Makashov

Senior Honors Projects

The Heber W. Youngken Jr. Medicinal Garden is a one-of-a-kind resource that houses close to 300 medicinal plants and is filled to the brim with educational opportunities. For the College of Pharmacy, this garden has been the centerpiece of many classes taught here at the University of Rhode Island and has roots as a physical teaching space. While the garden contains a plethora of plant species, medicinal fungi have yet to have been included in the garden, despite their relevance as both sources of pharmaceutical drug discovery and as natural products with inherent physiological benefits themselves. The purpose of my ...


The C-Terminal Domain Of Sec-10 Is Fundamental For Exocyst Function, Spitzenkörper Organization And Cell Morphogenesis In Neurospora Crassa [Preprint], Alfredo Figueroa-Meléndez, Leonora Martínez-Núñez, Adriana M. Rico-Ramírez, Juan M. Martínez-Andrade, Mary Munson, Meritxell Riquelme 2022 Center for Scientific Research and Higher Education at Ensenada

The C-Terminal Domain Of Sec-10 Is Fundamental For Exocyst Function, Spitzenkörper Organization And Cell Morphogenesis In Neurospora Crassa [Preprint], Alfredo Figueroa-Meléndez, Leonora Martínez-Núñez, Adriana M. Rico-Ramírez, Juan M. Martínez-Andrade, Mary Munson, Meritxell Riquelme

UMass Chan Medical School Faculty Publications

The exocyst is a conserved multimeric complex that participates in the final steps of the secretion of vesicles. In the filamentous fungus Neurospora crassa, the exocyst is crucial for polar growth, morphology, and the organization of the Spitzenkörper (Spk), the apical body where secretory vesicles accumulate before being delivered to the plasma membrane. In the highly polarized cells of N. crassa, the exocyst subunits SEC-3, SEC-5, SEC-6, SEC-8, and SEC-15 were previously found localized at the plasma membrane of the cells’ apices, while EXO-70 and EXO-84 occupied the frontal outer layer of the Spk, occupied by vesicles. The localization of ...


Cryptococcus Neoformans Melanization Incorporates Multiple Catecholamines To Produce Polytypic Melanin, Rosanna P. Baker, Christine Chrissian, Ruth E. Stark, Arturo Casadevall 2021 Johns Hopkins University

Cryptococcus Neoformans Melanization Incorporates Multiple Catecholamines To Produce Polytypic Melanin, Rosanna P. Baker, Christine Chrissian, Ruth E. Stark, Arturo Casadevall

Publications and Research

Melanin is a major virulence factor in pathogenic fungi that enhances the ability of fungal cells to resist immune clearance. Cryptococcus neoformans is an important human pathogenic fungus that synthesizes melanin from exogenous tissue catecholamine precursors during infection, but the type of melanin made in cryptococcal meningoencephalitis is unknown. We analyzed the efficacy of various catecholamines found in brain tissue in supporting melanization using animal brain tissue and synthetic catecholamine mixtures reflecting brain tissue proportions. Solid-state NMR spectra of the melanin pigment produced from such mixtures yielded more melanin than expected if only the preferred constituent dopamine had been incorporated ...


Micronutrient Supplements Can Promote Disruptive Protozoan And Fungal Communities In The Developing Infant Gut, Ana Popovic, Celine Bourdon, Pauline W. Wang, David S. Guttman, Sajid Bashir Soofi, Zulfiqar Ahmed Bhutta, Robert H J. Bandsma, John Parkinson, Lisa G. Pell 2021 Hospital for Sick Children Research Institute, Toronto, Ontario, Canada

Micronutrient Supplements Can Promote Disruptive Protozoan And Fungal Communities In The Developing Infant Gut, Ana Popovic, Celine Bourdon, Pauline W. Wang, David S. Guttman, Sajid Bashir Soofi, Zulfiqar Ahmed Bhutta, Robert H J. Bandsma, John Parkinson, Lisa G. Pell

Centre of Excellence in Women and Child Health

Supplementation with micronutrients, including vitamins, iron and zinc, is a key strategy to alleviate child malnutrition. However, association of gastrointestinal disorders with iron has led to ongoing debate over their administration. To better understand their impact on gut microbiota, we analyse the bacterial, protozoal, fungal and helminth communities of stool samples collected from a subset of 80 children at 12 and 24 months of age, previously enrolled into a large cluster randomized controlled trial of micronutrient supplementation in Pakistan (ClinicalTrials.gov identifier NCT00705445). We show that while bacterial diversity is reduced in supplemented children, vitamins and iron (as well as ...


Deletion Of The Stress Response Gene Ddr48 From Histoplasma Capsulatum Increases Sensitivity To Oxidative Stress, Increases Susceptibility To Antifungals, And Decreases Fitness In Macrophages, Logan T. Blancett, Kauri A. Runge, Gabriella M. Reyes, Lauren A. Kennedy, Sydney C. Jackson, Sarah E. Scheuermann, Mallory B. Harmon, Jamease C. Williams, Glenmore Shearer 2021 University of Southern Mississippi

Deletion Of The Stress Response Gene Ddr48 From Histoplasma Capsulatum Increases Sensitivity To Oxidative Stress, Increases Susceptibility To Antifungals, And Decreases Fitness In Macrophages, Logan T. Blancett, Kauri A. Runge, Gabriella M. Reyes, Lauren A. Kennedy, Sydney C. Jackson, Sarah E. Scheuermann, Mallory B. Harmon, Jamease C. Williams, Glenmore Shearer

Faculty Publications

The stress response gene DDR48 has been characterized in Saccharomyces cerevisiae and Candida albicans to be involved in combating various cellular stressors, from oxidative agents to antifungal compounds. Surprisingly, the biological function of DDR48 has yet to be identified, though it is likely an important part of the stress response. To gain insight into its function, we characterized DDR48 in the dimorphic fungal pathogen Histoplasma capsulatum. Transcriptional analyses showed preferential expression of DDR48 in the mycelial phase. Induction of DDR48 in Histoplasma yeasts developed after treatment with various cellular stress compounds. We generated a ddr48∆ deletion mutant to further characterize ...


Dcp2 C-Terminal Cis-Binding Elements Control Selective Targeting Of The Decapping Enzyme By Forming Distinct Decapping Complexes [Preprint], Feng He, Chan Wu, Allan S. Jacobson 2021 University of Massachusetts Medical School

Dcp2 C-Terminal Cis-Binding Elements Control Selective Targeting Of The Decapping Enzyme By Forming Distinct Decapping Complexes [Preprint], Feng He, Chan Wu, Allan S. Jacobson

UMass Chan Medical School Faculty Publications

A single Dcp1-Dcp2 decapping enzyme targets diverse classes of yeast mRNAs for decapping-dependent 5’ to 3’ decay, but the molecular mechanisms controlling selective mRNA targeting by the enzyme remain elusive. Through extensive genetic analyses we uncover cis-regulatory elements in the Dcp2 C-terminal domain that control selective targeting of the decapping enzyme by forming distinct decapping complexes. Two Upf1-binding motifs target the decapping enzyme to NMD substrates, and a single Edc3-binding motif targets both Edc3 and Dhh1 substrates. Pat1-binding leucine-rich motifs target Edc3 and Dhh1 substrates under selective conditions. Although it functions as a unique targeting component of specific complexes ...


Impact Of Pulse Oximetry On Hospital Referral Acceptance In Children Under 5 With Severe Pneumonia In Rural Pakistan (District Jamshoro): Protocol For A Cluster Randomised Trial, Fatima Mir, Apsara Ali, Suhail Chanar, Amjad Hussain, Arjumand Rizvi, Imran Ahmed, Zahid Memon, Atif Habib, Sajid Bashir Soofi, Zulfiqar Ahmed Bhutta 2021 Aga Khan University

Impact Of Pulse Oximetry On Hospital Referral Acceptance In Children Under 5 With Severe Pneumonia In Rural Pakistan (District Jamshoro): Protocol For A Cluster Randomised Trial, Fatima Mir, Apsara Ali, Suhail Chanar, Amjad Hussain, Arjumand Rizvi, Imran Ahmed, Zahid Memon, Atif Habib, Sajid Bashir Soofi, Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

Background: Pneumonia is a leading cause of death among children under 5 specifically in South Asia and sub-Saharan Africa. Hypoxaemia is a life-threatening complication among children under 5 with pneumonia. Hypoxaemia increases risk of mortality by 4.3 times in children with pneumonia than those without hypoxaemia. Prevalence of hypoxaemia varies with geography, altitude and severity (9%-39% Asia, 3%-10% African countries). In this protocol paper, we describe research methods for assessing impact of Lady Health Workers (LHWs) identifying hypoxaemia in children with signs of pneumonia during household visits on acceptance of hospital referral in district Jamshoro, Sindh.
Methods ...


Molecular Detection Of Aspergillus Flavus In Georgia Peanut, Variety Tifguard., Carolle Zolome 2021 Kennesaw State University

Molecular Detection Of Aspergillus Flavus In Georgia Peanut, Variety Tifguard., Carolle Zolome

Symposium of Student Scholars

Peanuts provide a good source of protein, minerals, and vitamins to consumers. The US peanut industry suffers great losses of nearly $26 million annually due to contamination by Aspergillus species. In spite of strict control measures against Aspergillus species, the industry is still facing economic loss due to contamination by this mold. Poor storage of peanuts in commercial outlets can lead to infection by the mold, releasing aflatoxin which is carcinogenic. A number of DNA based techniques are currently available for identification of the fungal population. This research aims at identifying if peanut, the variety Tifguard which is highly recommended ...


Effects Of Neem Oil On Growth And Development Of Aspergillus Flavus In Peanuts, Onachukwu Nwolisa 2021 Kennesaw State University

Effects Of Neem Oil On Growth And Development Of Aspergillus Flavus In Peanuts, Onachukwu Nwolisa

Symposium of Student Scholars

Effects of Neem Oil On Growth And Development Of Aspergillus flavus in peanuts**

Ona Nwolisa and Premila N Achar1

1Dept. of Molecular and Cellular Biology, Kennesaw State University, Kennesaw, GA.

Aspergillus flavus is known to contaminate peanuts and produce aflatoxin which are carcinogenic metabolites. According to the USDA, more than $1 billion is spent on infection and prevention. Currently there is no single method known to eradicate Aspergillus spp. in peanuts and the industry continue to face the aflatoxin problem. There has been an increased interest in use of plant based antifungal products which are environmentally friendly and ...


A Novel Multifunctional Role For Hsp70 In Binding Post-Translational Modifications On Client Proteins [Preprint], Nitika, Matthew J. Winters, Peter M. Pryciak 2021 University of North Carolina at Charlotte

A Novel Multifunctional Role For Hsp70 In Binding Post-Translational Modifications On Client Proteins [Preprint], Nitika, Matthew J. Winters, Peter M. Pryciak

UMass Chan Medical School Faculty Publications

Hsp70 interactions are critical for cellular viability and the response to stress. Previous attempts to characterize Hsp70 interactions have been limited by their transient nature and inability of current technologies to distinguish direct vs bridged interactions. We report the novel use of cross-linking mass spectrometry (XL-MS) to comprehensively characterize the budding yeast Hsp70 protein interactome. Using this approach, we have gained fundamental new insights into Hsp70 function, including definitive evidence of Hsp70 self-association as well as multi-point interaction with its client proteins. In addition to identifying a novel set of direct Hsp70 interactors which can be used to probe chaperone ...


Fungi: Are They Plants Or Animals?, Himanshu YN, Sufyan Ibrahim, Revathi P. Shenoy Dr 2021 Kasturba Manipal College, Manipal

Fungi: Are They Plants Or Animals?, Himanshu Yn, Sufyan Ibrahim, Revathi P. Shenoy Dr

Manipal Journal of Medical Sciences

The status of fungi in the phylogenetic setup still continues to be an intriguing question in biological sciences. Having long been considered as close relatives of plants, over the years, their resemblance towards animals has been brought into the greater limelight. While the vast diversity of the group demands a separate kingdom, evolution biology coaxes us to trace back their ancestry and establish similarities between different kingdoms and as newer pieces of evidence emerge up, the question as to whether fungi are plants or animals, remains contentious.


Telomeric And Sub-Telomeric Structure And Implications In Fungal Opportunistic Pathogens, Raffaella Diotti, Michelle Esposito, Chang Hui Shen 2021 CUNY Bronx Community College

Telomeric And Sub-Telomeric Structure And Implications In Fungal Opportunistic Pathogens, Raffaella Diotti, Michelle Esposito, Chang Hui Shen

Publications and Research

Telomeres are long non-coding regions found at the ends of eukaryotic linear chromosomes. Although they have traditionally been associated with the protection of linear DNA ends to avoid gene losses during each round of DNA replication, recent studies have demonstrated that the role of these sequences and their adjacent regions go beyond just protecting chromosomal ends. Regions nearby to telomeric sequences have now been identified as having increased variability in the form of duplications and rearrangements that result in new functional abilities and biodiversity. Furthermore, unique fungal telomeric and chromatin structures have now extended clinical capabilities and understanding of pathogenicity ...


Nlrc4 Inhibits Nlrp3 Inflammasome And Abrogates Effective Antifungal Cd8(+) T Cell Responses, Camila O. S. Souza, Natalia Ketelut-Carneiro, Cristiane M. Milanezi, Lucia H. Faccioli, Luiz G. Gardinassi, Joao S. Silva 2021 University of São Paulo

Nlrc4 Inhibits Nlrp3 Inflammasome And Abrogates Effective Antifungal Cd8(+) T Cell Responses, Camila O. S. Souza, Natalia Ketelut-Carneiro, Cristiane M. Milanezi, Lucia H. Faccioli, Luiz G. Gardinassi, Joao S. Silva

Open Access Publications by UMass Chan Authors

The recognition of fungi by intracellular NOD-like receptors (NLRs) induces inflammasome assembly and activation. Although the NLRC4 inflammasome has been extensively studied in bacterial infections, its role during fungal infections is unclear. Paracoccidioidomycosis (PCM) is a pathogenic fungal disease caused by Paracoccidioides brasiliensis. Here, we show that NLRC4 confers susceptibility to experimental PCM by regulating NLRP3-dependent cytokine production and thus protective effector mechanisms. Early after infection, NLRC4 suppresses prostaglandin E2 production, and consequently reduces interleukin (IL)-1beta release by macrophages and dendritic cells in the lungs. IL-1beta is required to control fungal replication via induction of the nitric oxide synthase ...


289— Phenotypic Characterization Of Neurospora Crassa Fsd-1 Overexpression Strains, Hannah Smith 2021 SUNY Geneseo

289— Phenotypic Characterization Of Neurospora Crassa Fsd-1 Overexpression Strains, Hannah Smith

GREAT Day

Neurospora crassa is a model filamentous fungal organism that can reproduce both asexually and sexually. Little is known about the molecular mechanisms that regulate the N. crassa female sexual development cycle. The transcription factor fsd-1 is necessary for sexual development, and fsd-1 deletion strains show delayed development of female reproductive structures and are sterile. Through previous experiments, we have been able to determine that there are three different transcripts of the fsd-1 gene, which differ by the length and intron/exon structure of their 5’ untranslated region. This project focuses on phenotypically characterizing the reproductive ability of strains overexpressing fsd-1 ...


Transcriptome-Wide Investigation Of Stop Codon Readthrough In Saccharomyces Cerevisiae, Kotchaphorn Mangkalaphiban, Feng He, Robin Ganesan, Chan Wu, Richard E. Baker, Allan Jacobson 2021 University of Massachusetts Medical School

Transcriptome-Wide Investigation Of Stop Codon Readthrough In Saccharomyces Cerevisiae, Kotchaphorn Mangkalaphiban, Feng He, Robin Ganesan, Chan Wu, Richard E. Baker, Allan Jacobson

Open Access Publications by UMass Chan Authors

Translation of mRNA into a polypeptide is terminated when the release factor eRF1 recognizes a UAA, UAG, or UGA stop codon in the ribosomal A site and stimulates nascent peptide release. However, stop codon readthrough can occur when a near-cognate tRNA outcompetes eRF1 in decoding the stop codon, resulting in the continuation of the elongation phase of protein synthesis. At the end of a conventional mRNA coding region, readthrough allows translation into the mRNA 3'-UTR. Previous studies with reporter systems have shown that the efficiency of termination or readthrough is modulated by cis-acting elements other than stop codon identity ...


Microbiological Study In A Gneissic Cave From Sri Lanka, With Special Focus On Potential Antimicrobial Activities, Ethige Isuru P. Silva, Pathmakumara Jayasingha, Saman Senanayake, Anura Dandeniya, Dona Helani Munasinghe 2021 University of Sri Jayewardenepura, Sri Lanka

Microbiological Study In A Gneissic Cave From Sri Lanka, With Special Focus On Potential Antimicrobial Activities, Ethige Isuru P. Silva, Pathmakumara Jayasingha, Saman Senanayake, Anura Dandeniya, Dona Helani Munasinghe

International Journal of Speleology

The emergence of antibiotic resistance is a global health crisis, thus the search for novel antimicrobial compounds has become a continuous necessity. Underexplored and extreme environments, such as cave ecosystems, have been identified as a promising potential source for the discovery of novel microorganisms with novel antimicrobial compounds (AMC). This study presents the first cave microbiological investigation in Sri Lanka, with a special preference for bioprospecting of novel AMC. The cave sediment characterization demonstrated the presence of close to strong acidic conditions (pH 3.1 – 3.3) and thus indicates the possibility of isolating acidophilic microorganisms. Eight cave wall/ceiling ...


Swi/Snf Senses Carbon Starvation With A Ph-Sensitive Low Complexity Sequence [Preprint], J. Ignacio Gutiérrez, Gregory P. Brittingham, Yonca Karadeniz, Kathleen D. Tran, Arnob Dutta, Alex S. Holehouse, Craig L. Peterson, Liam J. Holt 2021 University of California - Berkeley

Swi/Snf Senses Carbon Starvation With A Ph-Sensitive Low Complexity Sequence [Preprint], J. Ignacio Gutiérrez, Gregory P. Brittingham, Yonca Karadeniz, Kathleen D. Tran, Arnob Dutta, Alex S. Holehouse, Craig L. Peterson, Liam J. Holt

UMass Chan Medical School Faculty Publications

It is increasingly appreciated that intracellular pH changes are important biological signals. This motivates the elucidation of molecular mechanisms of pH-sensing. We determined that a nucleocytoplasmic pH oscillation was required for the transcriptional response to carbon starvation in S. cerevisiae. The SWI/SNF chromatin remodeling complex is a key mediator of this transcriptional response. We found that a glutamine-rich low complexity sequence (QLC) in the SNF5 subunit of this complex, and histidines within this sequence, were required for efficient transcriptional reprogramming during carbon starvation. Furthermore, the SNF5 QLC mediated pH-dependent recruitment of SWI/SNF to a model promoter in vitro ...


All You Need To Know And More About The Diagnosis And Management Of Rare Mold Infections, Martin Hoenigl, Stuart M. Levitz, Audrey N. Schuetz, Sean X. Zhang, Oliver A. Cornely 2021 Medical University of Graz

All You Need To Know And More About The Diagnosis And Management Of Rare Mold Infections, Martin Hoenigl, Stuart M. Levitz, Audrey N. Schuetz, Sean X. Zhang, Oliver A. Cornely

Open Access Publications by UMass Chan Authors

Invasive mold infections caused by molds other than Aspergillus spp. or Mucorales are emerging. The reported prevalences of infection due to these rare fungal pathogens vary among geographic regions, driven by differences in climatic conditions, susceptible hosts, and diagnostic capabilities. These rare molds-Fusarium, Lomentospora, and Scedosporium species and others-are difficult to detect and often show intrinsic antifungal resistance. Now, international societies of medical mycology and microbiology have joined forces and created the "Global guideline for the diagnosis and management of rare mould infections: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human ...


Sociodemographic, Clinical Characteristics, And Outcomes Of Influenza Pneumonia Patients Admitted In A Tertiary Care Hospital In Karachi, Pakistan: Findings From A Cross-Sectional Study, Fazal Ur Rehman, Muhammad Arslan Ahmed, Kashif Aziz, Mahmooda Jabeen Ashraf, Tazein Amber, Sumera Aziz Ali 2021 Aga Khan University

Sociodemographic, Clinical Characteristics, And Outcomes Of Influenza Pneumonia Patients Admitted In A Tertiary Care Hospital In Karachi, Pakistan: Findings From A Cross-Sectional Study, Fazal Ur Rehman, Muhammad Arslan Ahmed, Kashif Aziz, Mahmooda Jabeen Ashraf, Tazein Amber, Sumera Aziz Ali

Section of Internal Medicine

Objective: To determine the sociodemographic, clinical characteristics, and outcomes of influenza pneumonia patients in tertiary care hospital, Karachi Pakistan.
Study design: A cross-sectional study.
Place and duration of study: The Aga Khan University Hospital Karachi Pakistan from January 2013 to December 2018. Methodology: All adult patients who were older than 18 years and suspected to have viral pneumonia were included in the study. Data were abstracted on 105 patients and were entered on preformed proforma after reviewing the files of patients.
Results: Ninety-four (89.5%) patients were influenza positive and 15.2% (n=16) had been vaccinated. Around 92.4 ...


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