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JOURNAL ARTICLE
S Lori Tausta, Tanya Berbasova, Martin Peverelli, Scott A Strobel
Fluoride is everywhere in the environment, yet it is toxic to living things. How biological organisms detoxify fluoride has been unknown until recently. Fluoride-specific ion transporters in both prokaryotes (Fluoride channel; Fluc) and fungi (Fluoride Exporter; FEX) efficiently export fluoride to the extracellular environment. FEX homologs have been identified throughout the plant kingdom. Understanding the function of FEX in a multicellular organism will reveal valuable knowledge about reducing toxic effects caused by fluoride...
March 21, 2021: Plant Physiology
#22
JOURNAL ARTICLE
S Lori Tausta, Tanya Berbasova, Martin Peverelli, Scott A Strobel
Fluoride is everywhere in the environment, yet it is toxic to living things. How biological organisms detoxify fluoride has been unknown until recently. Fluoride-specific ion transporters in both prokaryotes (Fluoride channel; Fluc) and fungi (Fluoride Exporter; FEX) efficiently export fluoride to the extracellular environment. FEX homologues have been identified throughout the plant kingdom. Understanding the function of FEX in a multicellular organism will reveal valuable knowledge about reducing toxic effects caused by fluoride...
March 21, 2021: Plant Physiology
#23
JOURNAL ARTICLE
Tina Jeoh, Dana E Wong, Scott A Strobel, Kevin Hudnall, Nadia R Pereira, Kyle A Williams, Benjamin M Arbaugh, Julia C Cunniffe, Herbert B Scher
Alginates gel rapidly under ambient conditions and have widely documented potential to form protective matrices for sensitive bioactive cargo. Most commonly, alginate gelation occurs via calcium mediated electrostatic crosslinks between the linear polyuronic acid polymers. A recent breakthrough to form crosslinked alginate microcapsules (CLAMs) by in situ gelation during spray drying ("CLAMs process") has demonstrated applications in protection and controlled delivery of bioactives in food, cosmetics, and agriculture...
2021: PloS One
#24
JOURNAL ARTICLE
Nichole R Johnston, Sunitha Nallur, Patricia B Gordon, Kathryn D Smith, Scott A Strobel
Hydrofluoric acid elicits cell cycle arrest through a mechanism that has long been presumed to be linked with the high affinity of fluoride to metals. However, we have recently found that the acid stress from fluoride exposure is sufficient to elicit many of the hallmark phenotypes of fluoride toxicity. Here we report the systematic screening of genes involved in fluoride resistance and general acid resistance using a genome deletion library in Saccharomyces cerevisiae . We compare these to a variety of acids - 2,4-dinitrophenol, FCCP, hydrochloric acid, and sulfuric acid - none of which has a high metal affinity...
2020: Frontiers in Microbiology
#25
JOURNAL ARTICLE
Joy W Chang, Joel H Rubenstein, Jessica L Mellinger, Ellyn Kodroff, Mary J Strobel, Melissa Scott, Denise Mack, Wendy Book, Kathleen Sable, Scholeigh Kyle, Allisa Paliana, Evan S Dellon
BACKGROUND: Little is known about patient choice in treatment of eosinophilic esophagitis (EoE). AIM: Determine motivators and barriers to using common EoE therapies and describe patient-reported shared decision making (SDM) and satisfaction with treatment. METHODS: We developed and administered a Web-based survey on factors influencing EoE treatment choice, SDM, and satisfaction. Adults with EoE and adult caregivers of pediatric EoE patients were recruited via patient advocacy groups and at two centers...
June 2021: Digestive Diseases and Sciences
#26
MULTICENTER STUDY
Elizabeth T Jensen, Seema S Aceves, Peter A Bonis, Kimberly Bray, Wendy Book, Mirna Chehade, Margaret H Collins, Evan S Dellon, Gary W Falk, Nirmala Gonsalves, Sandeep K Gupta, Ikuo Hirano, David A Katzka, Shay Kyle, Denise Mack, Ellyn Kodroff, John Leung, Vincent A Mukkada, Melissa Scott, Ally Paliana, Kathleen Sable, Jonathan M Spergel, Mary Jo Strobel, Jeffrey Krischer, Marc E Rothenberg, Pablo Abonia
OBJECTIVES: Clinical features of eosinophilic esophagitis (EoE) have been well-described in the literature, however, characterization of features experienced by patients with other eosinophilic gastrointestinal diseases (EGIDs) is lacking. Using data collected from a patient contact registry, we sought to characterize and contrast patient-reported gastrointestinal and extragastrointestinal symptoms and comorbidities in non-EoE EGIDs, including eosinophilic gastritis, gastroenteritis and colitis, relative to EoE...
October 2020: Journal of Pediatric Gastroenterology and Nutrition
#27
JOURNAL ARTICLE
Nneoma Adaku, Hyun Bong Park, Daniel J Spakowicz, Meetu Kaushik Tiwari, Scott A Strobel, Jason M Crawford, Faye A Rogers
Disruption of the tumor suppressor PTEN, either at the protein or genomic level, plays an important role in human cancer development. The high frequency of PTEN deficiency reported across several cancer subtypes positions therapeutic approaches that exploit PTEN loss-of-function with the ability to significantly impact the treatment strategies of a large patient population. Here, we report that an endophytic fungus isolated from a medicinal plant used by Indigenous Amazonians produces an inhibitor of DNA double-strand-break repair...
May 14, 2020: Journal of Natural Products
#28
JOURNAL ARTICLE
David A Hiller, Brian F Dunican, Sunitha Nallur, Nan-Sheng Li, Joseph A Piccirilli, Scott A Strobel
The bacterial toxin RelE cleaves mRNA in the ribosomal A site. Although it shares a global fold with other microbial RNases, the active site contains several positively charged residues instead of histidines and glutamates that are typical of ribonucleases. The pH dependences of wild-type and mutant RelE indicate it uses general acid-base catalysis, but either the general acid (proposed to be R81) or the general base must have a substantially downshifted p K a . However, which group is shifted cannot be determined using available structural and biochemical data...
May 5, 2020: Biochemistry
#29
JOURNAL ARTICLE
Andrew J Knappenberger, Caroline W Reiss, Caroline M Focht, Scott A Strobel
The modularity of protein domains is well-known, but the existence of independent domains that confer function in RNA is less established. Recently, a family of RNA aptamers termed ykkC was discovered; they bind at least four ligands of very different chemical composition, including guanidine, phosphoribosyl pyrophosphate (PRPP), and guanosine tetraphosphate (ppGpp) (graphical abstract). Structures of these aptamers revealed an architecture characterized by two coaxial helical stacks. The first helix appears to be a generic scaffold, while the second helix forms the most contacts to the ligands...
April 7, 2020: Biochemistry
#30
REVIEW
Nichole R Johnston, Scott A Strobel
Fluoride is ubiquitously present throughout the world. It is released from minerals, magmatic gas, and industrial processing, and travels in the atmosphere and water. Exposure to low concentrations of fluoride increases overall oral health. Consequently, many countries add fluoride to their public water supply at 0.7-1.5 ppm. Exposure to high concentrations of fluoride, such as in a laboratory setting often exceeding 100 ppm, results in a wide array of toxicity phenotypes. This includes oxidative stress, organelle damage, and apoptosis in single cells, and skeletal and soft tissue damage in multicellular organisms...
April 2020: Archives of Toxicology
#31
JOURNAL ARTICLE
Chad D Torgerson, David A Hiller, Scott A Strobel
Glycine riboswitches utilize both single- and tandem-aptamer architectures. In the tandem system, the relative contribution of each aptamer toward gene regulation is not well understood. To dissect these contributions, the effects of 684 single mutants of a tandem ON switch from Bacillus subtilis were characterized for the wild-type construct and binding site mutations that selectively restrict ligand binding to either the first or second aptamer. Despite the structural symmetry of tandem aptamers, the response to these mutations was frequently asymmetrical...
May 2020: RNA
#32
RANDOMIZED CONTROLLED TRIAL
Jamie L Todd, Megan L Neely, Robert Overton, Katey Durham, Mridu Gulati, Howard Huang, Jesse Roman, L Kristin Newby, Kevin R Flaherty, Richard Vinisko, Yi Liu, Janine Roy, Ramona Schmid, Benjamin Strobel, Christian Hesslinger, Thomas B Leonard, Imre Noth, John A Belperio, Scott M Palmer
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease for which diagnosis and management remain challenging. Defining the circulating proteome in IPF may identify targets for biomarker development. We sought to quantify the circulating proteome in IPF, determine differential protein expression between subjects with IPF and controls, and examine relationships between protein expression and markers of disease severity. METHODS: This study involved 300 patients with IPF from the IPF-PRO Registry and 100 participants without known lung disease...
October 22, 2019: Respiratory Research
#33
JOURNAL ARTICLE
Nichole R Johnston, Scott A Strobel
Organisms are exposed to fluoride in the air, water, and soil. Yeast and other microbes utilize fluoride channels as a method to prevent intracellular fluoride accumulation and mediate fluoride toxicity. Consequently, deletion of fluoride exporter genes (FEX) in S. cerevisiae resulted in over 1000-fold increased fluoride sensitivity. We used this FEX knockout strain to identify genes, that when overexpressed, are able to partially relieve the toxicity of fluoride exposure. Overexpression of five genes, SSU1, YHB1, IPP1, PHO87, and PHO90, increase fluoride tolerance by 2- to 10-fold...
November 18, 2019: Chemical Research in Toxicology
#34
JOURNAL ARTICLE
Stefan Porubsky, Peter Jessup, Damien Kee, Rajiv Sharma, Ayame Ochi, Huiling Xu, Jens J Froelich, Louise Nott, Clare Scott, Raef Awad, Cristina Moldovan, Ashutosh A Hardikar, Hanibal Bohnenberger, Stefan Küffer, Philipp Ströbel, Alexander Marx
Our aim was to investigate sebaceous differentiation in thymus tumours and to identify new actionable genomic alterations. To this end we screened 35 normal and 23 hyperplastic thymuses, 127 thymomas and 41 thymic carcinomas for the presence of sebaceous differentiation as defined by morphology and expression of adipophilin and androgen receptor (AR). One primary thymic carcinoma showed morphology of sebaceous carcinomas (keratinizing and foam cells, calcifications, giant cells), a strong expression of adipophilin and AR together with squamous markers...
August 10, 2019: Virchows Archiv: An International Journal of Pathology
#35
JOURNAL ARTICLE
Manunya Nuth, Hancheng Guan, Yuhong Xiao, John L Kulp, Michael H Parker, Eric D Strobel, Stuart N Isaacs, Richard W Scott, Allen B Reitz, Robert P Ricciardi
The smallpox virus (variola) remains a bioterrorism threat since a majority of the human population has never been vaccinated. In the event of an outbreak, at least two drugs against different targets of variola are critical to circumvent potential viral mutants that acquire resistance. Vaccinia virus (VACV) is the model virus used in the laboratory for studying smallpox. The VACV processivity factor D4 is an ideal therapeutic target since it is both essential and specific for poxvirus replication. Recently, we identified a tripeptide (Gly-Phe-Ile) motif at the C-terminus of D4 that is conserved among poxviruses and is necessary for maintaining protein function...
December 19, 2018: Antiviral Research
#36
JOURNAL ARTICLE
Chad D Torgerson, David A Hiller, Shira Stav, Scott A Strobel
Riboswitches contain structured aptamer domains that, upon ligand binding, facilitate helical switching in their downstream expression platforms to alter gene expression. To fully dissect how riboswitches function requires a better understanding of the energetic landscape for helical switching. Here, we report a sequencing-based high-throughput assay for monitoring in vitro transcription termination and use it to simultaneously characterize the functional effects of all 522 single point mutants of a glycine riboswitch type-1 singlet...
December 2018: RNA
#37
JOURNAL ARTICLE
Scott A Strobel, Kimberly Allen, Christopher Roberts, Desmond Jimenez, Herbert B Scher, Tina Jeoh
Microencapsulation of plant-beneficial bacteria, such as pink pigmented facultative methylotrophs (PPFM), may greatly extend the shelf life of these Gram-negative microorganisms and facilitate their application to crops for sustainable agriculture. A species of PPFM designated Methylobacterium radiotolerans was microencapsulated in cross-linked alginate microcapsules (CLAMs) prepared by an innovative and industrially scalable process that achieves polymer cross-linking during spray-drying. PPFM survived the spray-drying microencapsulation process with no significant loss in viable population, and the initial population of PPFM in CLAMs exceeded 1010 CFU/g powder...
June 1, 2018: Industrial Biotechnology
#38
REVIEW
Evan S Dellon, Chris A Liacouras, Javier Molina-Infante, Glenn T Furuta, Jonathan M Spergel, Noam Zevit, Stuart J Spechler, Stephen E Attwood, Alex Straumann, Seema S Aceves, Jeffrey A Alexander, Dan Atkins, Nicoleta C Arva, Carine Blanchard, Peter A Bonis, Wendy M Book, Kelley E Capocelli, Mirna Chehade, Edaire Cheng, Margaret H Collins, Carla M Davis, Jorge A Dias, Carlo Di Lorenzo, Ranjan Dohil, Christophe Dupont, Gary W Falk, Cristina T Ferreira, Adam Fox, Nirmala P Gonsalves, Sandeep K Gupta, David A Katzka, Yoshikazu Kinoshita, Calies Menard-Katcher, Ellyn Kodroff, David C Metz, Stephan Miehlke, Amanda B Muir, Vincent A Mukkada, Simon Murch, Samuel Nurko, Yoshikazu Ohtsuka, Rok Orel, Alexandra Papadopoulou, Kathryn A Peterson, Hamish Philpott, Philip E Putnam, Joel E Richter, Rachel Rosen, Marc E Rothenberg, Alain Schoepfer, Melissa M Scott, Neil Shah, Javed Sheikh, Rhonda F Souza, Mary J Strobel, Nicholas J Talley, Michael F Vaezi, Yvan Vandenplas, Mario C Vieira, Marjorie M Walker, Joshua B Wechsler, Barry K Wershil, Ting Wen, Guang-Yu Yang, Ikuo Hirano, Albert J Bredenoord
BACKGROUND & AIMS: Over the last decade, clinical experiences and research studies raised concerns regarding use of proton pump inhibitors (PPIs) as part of the diagnostic strategy for eosinophilic esophagitis (EoE). We aimed to clarify the use of PPIs in the evaluation and treatment of children and adults with suspected EoE to develop updated international consensus criteria for EoE diagnosis. METHODS: A consensus conference was convened to address the issue of PPI use for esophageal eosinophilia using a process consistent with standards described in the Appraisal of Guidelines for Research and Evaluation II...
October 2018: Gastroenterology
#39
JOURNAL ARTICLE
Andrew John Knappenberger, Caroline Wetherington Reiss, Scott A Strobel
Two classes of riboswitches related to the ykkC guanidine-I riboswitch bind phosphoribosyl pyrophosphate (PRPP) and guanosine tetraphosphate (ppGpp). Here we report the co-crystal structure of the PRPP aptamer and its ligand. We also report the structure of the G96A point mutant that prefers ppGpp over PRPP with a dramatic 40,000-fold switch in specificity. The ends of the aptamer form a helix that is not present in the guanidine aptamer and is involved in the expression platform. In the mutant, the base of ppGpp replaces G96 in three-dimensional space...
June 7, 2018: ELife
#40
JOURNAL ARTICLE
Girish Hiremath, Ellyn Kodroff, Mary J Strobel, Melissa Scott, Wendy Book, Cathy Reidy, Shay Kyle, Denise Mack, Kathleen Sable, Pablo Abonia, Jonathan Spergel, Sandeep K Gupta, T Glenn Furuta, Marc E Rothenberg, Evan S Dellon
INTRODUCTION: Eosinophilic gastrointestinal disorders (EGIDs) are a rare but emerging healthcare problem. Patient advocacy groups (PAGs) have an important role in representing the EGID community, and serve as valuable research partners. By leveraging the partnership between medical researchers and PAGs, we examined the unmet needs and barriers to care perceived by individuals affected by EGIDs. Next, we examined if these varied between adult EGID patients and adult caregivers of children with EGID...
October 2018: Clinics and Research in Hepatology and Gastroenterology
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