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108 results on '"Fletcher, Joshua"'

4. Medicinal Chemistry of Plant Naturals as Agonists/Antagonists for Taste Receptors

Author

Fletcher, Joshua N., Pan, Li, Kinghorn, A. Douglas, Bernstein, Peter R., Series editor, Buschauer, Armin, Series editor, Georg, Gunda I., Series editor, Lowe, John A., Series editor, Meanwell, Nicholas A., Series editor, Saxena, Anil Kumar, Series editor, Stilz, Ulrich, Series editor, Supuran, Claudiu T., Series editor, Zhang, Ao, Series editor, and Krautwurst, Dietmar, editor

Published
2017
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5. OPINION: Elon Musk, Twitter, X, and the rise of hate speech - The Maroon

Author

Fletcher, Joshua

Subjects
News, opinion and commentary, Sports and fitness, Twitter (Online social network)
Abstract

Byline: Joshua Fletcher Twitter's rebranding to X is not just a poor visual update to the platform. It represents the app's new identity as a safe haven for hateful content. [...]

Published
2023

7. Outer membrane vesicles displaying engineered glycotopes elicit protective antibodies

Author

Chen, Linxiao, Valentine, Jenny L., Huang, Chung-Jr, Endicott, Christine E., Moeller, Tyler D., Rasmussen, Jed A., Fletcher, Joshua R., Boll, Joseph M., Rosenthal, Joseph A., Dobruchowska, Justyna, Wang, Zhirui, Heiss, Christian, Azadi, Parastoo, Putnam, David, Trent, M. Stephen, Jones, Bradley D., and DeLisa, Matthew P.

Published
2016

8. Human fecal metabolomic profiling could inform Clostridioides difficile infection diagnosis and treatment

Author

Theriot, Casey M. and Fletcher, Joshua R.

Subjects
Fidaxomicin, Metabolites, Amino acids, Infection, Diarrhea, Antibacterial agents, Death, Therapeutics, Colitis, Public health, Vancomycin, Health care industry
Abstract

Clostridioides difficile is a significant public health threat, and diagnosis of this infection is challenging due to a lack of sensitivity in current diagnostic testing. In this issue of the JCI, Robinson et al. use a logistic regression model based on the fecal metabolome that is able to distinguish between patients with non-C. difficile diarrhea and C. difficile infection, and to some degree, patients who are asymptomatically colonized with C. difficile. The authors construct a metabolic definition of human C. difficile infection, which could improve diagnostic accuracy and aid in the development of targeted therapeutics against this pathogen., Antibiotics and the rise of CDI Clostridioides difficile is a spore-forming anaerobic bacterial pathogen. There are approximately 500,000 cases of C. difficile infection (CDI) and 29,000 deaths per year in [...]

Published
2019
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9. Anxiety and How Stress Plays a Part

Author

Fletcher, Joshua

Subjects
Inclusive education, Secondary education, Educational counselling
Abstract

This session will address the topic of anxiety and the role of stress in the creation of excessive anxiety. Why do we sometimes feel excessively anxious? This session invites you to conceptualise worries and stress, as well as providing a way to frame stress for others, helping you as a teacher with anxiety, and/or in understanding the experiences of students and colleagues. Video : https://video.manchester.ac.uk/faculties/8856f85434e41fb156ec49cee2ff2134/d1639402-a272-4f1d-8802-ae3848720f46/ This session was presented at the ‘PGCE Conference 2023: Inclusion and Inspiration - Education for Social Justice’.

Published
2023
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10. What Motivates Veterans to Become Small Business Owners: A Grounded Theory Study

Author

Fletcher, Joshua and Fletcher, Joshua

Abstract

The purpose of this grounded theory qualitative study will be to explore the motivations of veterans that became small business owners. There is currently a gap in research literature on veteran small business owners, even though they make up the largest minority of the entire U.S. small business population at 14 percent. And only about a third of small businesses survive more than ten years. A better understanding of what motivates so many veterans to become small business owners could benefit other current and future small business owners and possibly increase their chances of success, as well as contributing to the existing body of research on small business.

Published
2022

21. In Vivo Targeting of Clostridioides difficile Using Phage-Delivered CRISPR-Cas3 Antimicrobials

Author

Selle, Kurt, primary, Fletcher, Joshua R., additional, Tuson, Hannah, additional, Schmitt, Daniel S., additional, McMillan, Lana, additional, Vridhambal, Gowrinarayani S., additional, Rivera, Alissa J., additional, Montgomery, Stephanie A., additional, Fortier, Louis-Charles, additional, Barrangou, Rodolphe, additional, Theriot, Casey M., additional, and Ousterout, David G., additional

Published
2020
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28. Bacterial lipoproteins and other factors released byFrancisella tularensismodulate human neutrophil lifespan: Effects of aTLR1SNP on apoptosis inhibition

Author

Kinkead, Lauren C., primary, Whitmore, Laura C., additional, McCracken, Jenna M., additional, Fletcher, Joshua R., additional, Ketelsen, Brandi B., additional, Kaufman, Justin W., additional, Jones, Bradley D., additional, Weiss, David S., additional, Barker, Jason H., additional, and Allen, Lee-Ann H., additional

Published
2017
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29. Abstract NS6: Born to Run: Advanced Practice Provider-Led Mobile Stroke Unit Care Measures Up to Vascular Neurologists’ Diagnosis and Management

Author

Alexandrov, Anne W, primary, Dusenbury, Wendy, additional, Swatzell, Victoria, additional, Rike, Joseph, additional, Bouche, Andrew, additional, Crisp, Ira, additional, Jestice, Michael, additional, Fletcher, Joshua, additional, Crockett, Mathew, additional, Ware, Tyrone, additional, Stacks, William, additional, Barber, Ian, additional, McDevitt, Patrick, additional, McDaniel, Stephen, additional, Mathenia, Thomas, additional, Orr, James, additional, McKendry, Chris, additional, Novak, Ted, additional, Bey, Stanley, additional, Bullock, Charles, additional, Harrold, James, additional, Crockett, Christopher, additional, McCormick, Sarah L, additional, Rogers, Keri M, additional, Carlow, Jordan S, additional, Malkoff, Marc, additional, Arthur, Adam, additional, and Alexandrov, Andrei V, additional

Published
2017
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33. Antileishmanial and Cytotoxic Activity of Some Highly Oxidized Abietane Diterpenoids from the Bald Cypress, Taxodium distichum

Author

Naman, C. Benjamin, primary, Gromovsky, Anthony D., additional, Vela, Cory M., additional, Fletcher, Joshua N., additional, Gupta, Gaurav, additional, Varikuti, Sanjay, additional, Zhu, Xiaohua, additional, Zywot, Emilia M., additional, Chai, Heebyung, additional, Werbovetz, Karl A., additional, Satoskar, Abhay R., additional, and Kinghorn, A. Douglas, additional

Published
2016
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41. Outer membrane vesicles displaying engineered glycotopes elicit protective antibodies.

Author

Linxiao Chen, Valentine, Jenny L., Chung-Jr Huang, Endicott, Christine E., Moeller, Tyler D., Rasmussen, Jed A., Fletcher, Joshua R., Boll, Joseph M., Rosenthal, Joseph A., Dobruchowska, Justyna, Zhirui Wang, Heiss, Christian, Azadi, Parastoo, Putnam, David, Trent, M. Stephen, Jones, Bradley D., and DeLisa, Matthew P.

Subjects
VESICLES (Cytology), IMMUNOGLOBULINS, O antigens, GLYCANS, HUMORAL immunity
Abstract

The O-antigen polysaccharide (O-PS) component of lipopolysaccharides on the surface of gram-negative bacteria is both a virulence factor and a B-cell antigen. Antibodies elicited by O-PS often confer protection against infection; therefore, O-PS glycoconjugate vaccines have proven useful against a number of different pathogenic bacteria. However, conventional methods for natural extraction or chemical synthesis of O-PS are technically demanding, inefficient, and expensive. Here, we describe an alternative methodology for producing glycoconjugate vaccines whereby recombinant O-PS biosynthesis is coordinated with vesiculation in laboratory strains of Escherichia coli to yield glycosylated outer membrane vesicles (glycOMVs) decorated with pathogen-mimetic glycotopes. Using this approach, glycOMVs corresponding to eight different pathogenic bacteria were generated. For example, expression of a 17-kb O-PS gene cluster from the highly virulent Francisella tularensis subsp. tularensis (type A) strain Schu S4 in hypervesiculating E. coli cells yielded glycOMVs that displayed F. tularensis O-PS. Immunization of BALB/c mice with glycOMVs elicited significant titers of O-PS–specific serum IgG antibodies as well as vaginal and bronchoalveolar IgA antibodies. Importantly, glycOMVs significantly prolonged survival upon subsequent challenge with F. tularensis Schu S4 and provided complete protection against challenge with two different F. tularensis subsp. holarctica (type B) live vaccine strains, thereby demonstrating the vaccine potential of glycOMVs. Given the ease with which recombinant glycotopes can be expressed on OMVs, the strategy described here could be readily adapted for developing vaccines against many other bacterial pathogens. [ABSTRACT FROM AUTHOR]

Published
2016
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47. The Francisella tularensismigR, trmE, and cphAGenes Contribute to F. tularensisPathogenicity Island Gene Regulation and Intracellular Growth by Modulation of the Stress Alarmone ppGpp

Author

Faron, Matthew, Fletcher, Joshua R., Rasmussen, Jed A., Long, Matthew E., Allen, Lee-Ann H., and Jones, Bradley D.

Abstract

ABSTRACTThe Francisella tularensispathogenicity island (FPI) encodes many proteins that are required for virulence. Expression of these genes depends upon the FevR (PigR) regulator and its interactions with the MglA/SspA and RNA polymerase transcriptional complex. Experiments to identify how transcription of the FPI genes is activated have led to identification of mutations within the migR, trmE, and cphAgenes that decrease FPI expression. Recent data demonstrated that the small alarmone ppGpp, produced by RelA and SpoT, is important for stabilizing MglA/SspA and FevR (PigR) interactions in Francisella. Production of ppGpp is commonly known to be activated by cellular and nutritional stress in bacteria, which indicates that cellular and nutritional stresses act as important signals for FPI activation. In this work, we demonstrate that mutations in migR, trmE, or cphAsignificantly reduce ppGpp accumulation. The reduction in ppGpp levels was similar for each of the mutants and correlated with a corresponding reduction in iglAreporter expression. In addition, we observed that there were differences in the ability of each of these mutants to replicate within various mammalian cells, indicating that the migR, trmE, and cphAgenes are likely parts of different cellular stress response pathways in Francisella. These results also indicate that different nutritional and cellular stresses exist in different mammalian cells. This work provides new information to help understand how Francisellaregulates its virulence genes in response to host cell environments, and it contributes to our growing knowledge of this highly successful bacterial pathogen.

Published
2013
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49. In VivoTargeting of Clostridioides difficileUsing Phage-Delivered CRISPR-Cas3 Antimicrobials

Author

Selle, Kurt, Fletcher, Joshua R., Tuson, Hannah, Schmitt, Daniel S., McMillan, Lana, Vridhambal, Gowrinarayani S., Rivera, Alissa J., Montgomery, Stephanie A., Fortier, Louis-Charles, Barrangou, Rodolphe, Theriot, Casey M., and Ousterout, David G.

Abstract

Clostridioides difficileis a bacterial pathogen responsible for significant morbidity and mortality across the globe. Current therapies based on broad-spectrum antibiotics have some clinical success, but approximately 30% of patients have relapses, presumably due to the continued perturbation to the gut microbiota. Here, we show that phages can be engineered with type I CRISPR-Cas systems and modified to reduce lysogeny and to enable the specific and efficient targeting and killing of C. difficilein vitroand in vivo.Additional genetic engineering to disrupt phage modulation of toxin expression by lysogeny or other mechanisms would be required to advance a CRISPR-enhanced phage antimicrobial for C. difficiletoward clinical application. These findings provide evidence into how phage can be combined with CRISPR-based targeting to develop novel therapies and modulate microbiomes associated with health and disease.

Published
2020
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50. Bacterial lipoproteins and other factors released by <italic>Francisella tularensis</italic> modulate human neutrophil lifespan: Effects of a <italic>TLR1</italic> SNP on apoptosis inhibition.

Author

Kinkead, Lauren C., McCracken, Jenna M., Barker, Jason H., Allen, Lee‐Ann H., Whitmore, Laura C., Kaufman, Justin W., Ketelsen, Brandi B., Jones, Bradley D., Fletcher, Joshua R., and Weiss, David S.

Subjects
NEUTROPHILS, LIPOPROTEIN genetics, FRANCISELLA tularensis, APOPTOSIS inhibition, TOLL-like receptors, BIOCHEMISTRY, PHYSIOLOGY
Abstract

Abstract: Francisella tularensis infects several cell types including neutrophils, and aberrant neutrophil accumulation contributes to tissue destruction during tularaemia. We demonstrated previously that F. tularensis strains Schu S4 and live vaccine strain markedly delay human neutrophil apoptosis and thereby prolong cell lifespan, but the bacterial factors that mediate this aspect of virulence are undefined. Herein, we demonstrate that bacterial conditioned medium (CM) can delay apoptosis in the absence of direct infection. Biochemical analyses show that CM contained F. tularensis surface factors as well as outer membrane components. Our previous studies excluded roles for lipopolysaccharide and capsule in apoptosis inhibition, and current studies of [14C] acetate‐labelled bacteria argue against a role for other bacterial lipids in this process. At the same time, studies of isogenic mutants indicate that TolC and virulence factors whose expression requires FevR or MglA were also dispensable, demonstrating that apoptosis inhibition does not require Type I or Type VI secretion. Instead, we identified bacterial lipoproteins (BLPs) as active factors in CM. Additional studies of isolated BLPs demonstrated dose‐dependent neutrophil apoptosis inhibition via a TLR2‐dependent mechanism that is significantly influenced by a common polymorphism, rs5743618, in human TLR1. These data provide fundamental new insight into pathogen manipulation of neutrophil lifespan and BLP function. [ABSTRACT FROM AUTHOR]

Published
2018
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