Medicine and Health Sciences Commons^™

Dmbt1 Inhibition Of Pseudomonas Aeruginosa Twitching Motility Involves Its N-Glycosylation And Cannot Be Conferred By The Scavenger Receptor Cysteine-Rich Bacteria-Binding Peptide Domain., Jianfang Li, Stephanie J Wan, Matteo M E Metruccio, Sophia Ma, Kamran Nazmi, Floris J Bikker, David J. Evans, Suzanne M J Fleiszig

Faculty Publications & Research of the TUC College of Pharmacy

The scavenging capacity of glycoprotein DMBT1 helps defend mucosal epithelia against microbes. DMBT1 binding to multiple bacterial species involves its conserved Scavenger Receptor Cysteine-Rich (SRCR) domains, localized to a 16-mer consensus sequence peptide, SRCRP2. Previously, we showed that DMBT1 bound Pseudomonas aeruginosa pili, and inhibited twitching motility, a pilus-mediated movement important for virulence. Here, we determined molecular characteristics required for twitching motility inhibition. Heat-denatured DMBT1 lost capacity to inhibit twitching motility and showed reduced pili binding (~40%). Size-exclusion chromatography of Lys-C-digested native DMBT1 showed that only high-Mw fractions retained activity, suggesting involvement of the N-terminal containing repeated SRCR domains with …

Applying Contemporary Management Principles To Implementing And Evaluating Value-Added Pharmacist Services., Shane P. Desselle, Leticia R Moczygemba, Antoinette B Coe, Karl Hess, David P Zgarrick

Faculty Publications & Research of the TUC College of Pharmacy

Value-added pharmacy services encompass traditional and emerging services provided by pharmacists to individual and entire populations of persons increasingly under the auspices of a public health mandate. The success of value-added pharmacy services is enhanced when they are carried out and assessed using appropriate theory-based paradigms. Many of the more important management theories for pharmacy services consider the "servicescape" of these services recognizing the uniqueness of each patient and service encounter that vary based upon health needs and myriad other factors. In addition, implementation science principles help ensure the financial viability and sustainability of these services. This commentary reviews some …

Co-Located Retail Clinics And Pharmacies: An Opportunity To Provide More Primary Care., Katherine K. Knapp, Keith Yoshizuka, Debra Sasaki-Hill, Rory Caygill-Walsh

Faculty Publications & Research of the TUC College of Pharmacy

This paper proposes that co-located retail clinics (RCs) and community pharmacies can increase opportunities to provide more accessible, affordable, and patient-friendly primary care services in the United States. RCs are small businesses of about 150-250 square feet with a clientele of about 10-30 patients each day and most frequently staffed by nurse practitioners (NPs). Community pharmacies in the U.S. at ~67,000 far outnumber RCs at ~2800, thereby opening substantial opportunity for growth. Community pharmacies and pharmacists have been working to increase on-site clinical services, but progress has been slowed by the relative isolation from other practitioners. An ideal merged facility …

A Randomized, Controlled Trial On The Effects Of Almonds On Lipoprotein Response To A Higher Carbohydrate, Lower Fat Diet In Men And Women With Abdominal Adiposity., Paul T. Williams, Nathalie Bergeron, Sally Chiu, Ronald M. Krauss

Faculty Publications & Research of the TUC College of Pharmacy

BACKGROUND: Almonds have been shown to lower LDL cholesterol but there is limited information regarding their effects on the dyslipidemia characterized by increased levels of very low density lipoproteins (VLDL) and small, dense low-density lipoprotein (LDL) particles that is associated with abdominal adiposity and high carbohydrate intake. The objective of the present study was to test whether substitution of almonds for other foods attenuates carbohydrate-induced increases in small, dense LDL in individuals with increased abdominal adiposity.

METHODS: This was a randomized cross-over study of three 3wk diets, separated by 2wk washouts: a higher-carbohydrate (CHO) reference diet (CHO

RESULTS: Relative to …

The Impact Of Concomitant Empiric Cefepime On Patient Outcomes Of Methicillin-Resistant Staphylococcus Aureus Bloodstream Infections Treated With Vancomycin, Evan J. Zasowski, Trang D. Trinh, Safana M. Atwan, Marina Merzlyakova, Abdalhamid M. Langf, Sahil Bhatia, Michael J. Rybak

Faculty Publications & Research of the TUC College of Pharmacy

Background: Data suggest that vancomycin + β-lactam combinations improve clearance of methicillin-resistant Staphylococcus aureus(MRSA) bloodstream infections (BSIs). However, it is unclear which specific β-lactams confer benefit. This analysis evaluates the impact of concomitant empiric cefepime on outcomes of MRSA BSIs treated with vancomycin.

Methods: Retrospective cohort study of adults with MRSA BSI from 2006 to 2017. Vancomycin + cefepime therapy was defined as ≥24 hours of cefepime during the first 72 hours of vancomycin. The primary outcome was microbiologic failure, defined as BSI duration ≥7 days and/or 60-day recurrence. Multivariable logistic regression was used to evaluate the association between …

Novel Flexible Heteroarotinoid, Sl-1-39, Inhibits Her2-Positive Breast Cancer Cell Proliferation By Promoting Lysosomal Degradation Of Her2., Hongye Zou, Mary B. Sevigny, Shengquan Liu, David T. Madden, Maggie C. Louie

Faculty Publications & Research of the TUC College of Pharmacy

SL-1-39 [1-(4-chloro-3-methylphenyl)-3-(4-nitrophenyl)thiourea] is a new flexible heteroarotinoid (Flex-Het) analog derived from the parental compound, SHetA2, previously shown to inhibit cell growth across multiple cancer types. The current study aims to determine growth inhibitory effects of SL-1-39 across the different subtypes of breast cancer cells and delineate its molecular mechanism. Our results demonstrate that while SL-1-39 blocks cell proliferation of all breast cancer subtypes tested, it has the highest efficacy against HER2+ breast cancer cells. Molecular analyses suggest that SL-1-39 prevents S phase progression of HER2+ breast cancer cells (SKBR3 and MDA-MB-453), which is consistent with reduced expression of key cell-cycle …

Impact Of Individual Traits, Saturated Fat, And Protein Source On The Gut Microbiome., Jennifer M Lang, Calvin Pan, Rita M Cantor, W H Wilson Tang, Jose Carlos Garcia-Garcia, Ira Kurtz, Stanley L Hazen, Nathalie Bergeron, Ronald M Krauss, Aldons J Lusis

Faculty Publications & Research of the TUC College of Pharmacy

Interindividual variation in the composition of the human gut microbiome was examined in relation to demographic and anthropometric traits, and to changes in dietary saturated fat intake and protein source. One hundred nine healthy men and women aged 21 to 65, with BMIs of 18 to 36, were randomized, after a two-week baseline diet, to high (15% total energy [E])- or low (7%E)-saturated-fat groups and randomly received three diets (four weeks each) in which the protein source (25%E) was mainly red meat (beef, pork) (12%E), white meat (chicken, turkey) (12%E), and nonmeat sources (nuts, beans, soy) (16%E). Taxonomic characterization using …

Microneedle-Assisted Delivery Of Anti-Migraine Drugs Across Porcine Skin: Almotriptan Malate And Naratriptan Hydrochloride, Iqra Ahmad, Kevin B. Ita, Matthew J. Morra, Inna E. Popova

Faculty Publications & Research of the TUC College of Pharmacy

Migraine is a common neurological disorder characterized by nausea, vomiting, photophobia, aching, fever, pain and chills. Triptans are selective serotonin agonists which can used to relieve migraine symptoms. Almotriptan malate and naratriptan hydrochloride are currently used for the management of migraine in the form of oral tablets. Oral tablets may be problematic for patients experiencing nausea and vomiting which are often associated with migraine. The microneedle-assisted transdermal drug delivery of these triptans may improve patient compliance. A vertical six-celled, static Franz diffusion cell system was used to conduct in vitro permeation experiments on porcine ear skin to determine the influence …

An Improved Tobacco Mosaic Virus (Tmv)-Conjugated Multiantigen Subunit Vaccine Against Respiratory Tularemia, Ahd A. Mansour, Sukalyani Banik, Ragavan V. Suresh, Hardeep Kaur, Meenakshi Malik, Alison A. Mccormick, Chandra Bakshi

Faculty Publications & Research of the TUC College of Pharmacy

Francisella tularensis, the causative agent of the fatal human disease known as tularemia is classified as a Category A Select Agent by the Centers for Disease Control. No licensed vaccine is currently available for prevention of tularemia in the United States. Previously, we published that a tri-antigen tobacco mosaic virus (TMV) vaccine confers 50% protection in immunized mice against respiratory tularemia caused by F. tularensis. In this study, we refined the TMV-vaccine formulation to improve the level of protection in immunized C57BL/6 mice against respiratory tularemia. We developed a tetra-antigen vaccine by conjugating OmpA, DnaK, Tul4, and SucB proteins of …

Surveys Of Substance Use Disorders Education In Us Pharmacy Programs, Kelan L. Thomas, Andrew J. Muzyk

Faculty Publications & Research of the TUC College of Pharmacy

Introduction: Substance use disorders (SUDs) are a significant US health problem affecting roughly 20 million Americans, but there continues to be limited access to SUD treatment and inadequate addiction medicine training. Therefore, it is important to understand how SUD education is being delivered to US health professionals, including pharmacists.

Methods: A recent survey of US pharmacy programs' neuropsychiatry curricula was evaluated to identify any progress made toward increasing SUD education since the last national survey in 2004 and determine any remaining gaps between what is currently being taught and American Association of Colleges of Pharmacy (AACP) curricular guidelines for SUD …

Real-World Usage And Clinical Outcomes Of Alectinib Among Post-Crizotinib Progression Anaplastic Lymphoma Kinase Positive Non-Small-Cell Lung Cancer Patients In The Usa, Marco D. Dibonaventura, William Wong, Bijal M. Shah-Manek, Mathias Schulz

Faculty Publications & Research of the TUC College of Pharmacy

Background: Alectinib is an approved treatment for anaplastic lymphoma kinase (ALK)-positive patients with advanced non-small-cell lung cancer. Despite positive supporting clinical data, there is a lack of real-world information on the usage and patient outcomes of those treated with alectinib post-crizotinib progression.

Methods: Participating oncologists (N=95) in the USA were recruited from an online physician panel to participate in a retrospective patient chart review. Physicians randomly selected eligible patients (ie, patients who progressed on crizotinib as their first ALK inhibitor and were treated with alectinib as their second ALK inhibitor), collected demographics and clinical history from their medical charts, and …

Epithelial Cell Lysates Induce Exos Expression And Secretion By Pseudomonas Aeruginosa, Victoria Hritonenko, Matteo Metruccio, David J. Evans, Suzanne Fleiszig

Faculty Publications & Research of the TUC College of Pharmacy

No abstract provided.

Intranasal Administration Of A Two-Dose Adjuvanted Multi-Antigen Tmv-Subunit Conjugate Vaccine Fully Protects Mice Against Francisella Tularensis Lvs Challenge, Alison A. Mccormick, Aisha Shakeel, Chris Yi, Hardeep Kaur, Ahd M. Mansour, Chandra Shekhar Bakshi

Faculty Publications & Research of the TUC College of Pharmacy

Tularemia is a fatal human disease caused by Francisella tularensis, a Gram-negative encapsulated coccobacillus bacterium. Due to its low infectious dose, ease of aerosolized transmission, and lethal effects, the CDC lists F. tularensis as a Category A pathogen, the highest level for a potential biothreat agent. Previous vaccine studies have been conducted with live attenuated, inactivated, and subunit vaccines, which have achieved partial or full protection from F. tularensis live vaccine strain (LVS) challenge, but no vaccine has been approved for human use. We demonstrate the improved efficacy of a multi-antigen subunit vaccine by using Tobacco Mosaic virus (TMV) as …

Divergent Humoral Responses To 23-Valent Pneumococcal Polysaccharide Vaccine In Critically-Ill Burn And Neurosurgical Patients, Scott W. Mueller, Laura J. Baumgartner, Rob Maclaren, Robert Neumann, Arek J. Wiktor, Tyree H. Kiser, Gordon Lindberg, Luis Cava, Douglas N. Fish, Edward N. Janoff

Faculty Publications & Research of the TUC College of Pharmacy

INTRODUCTION: Critically ill hospitalized patients are at increased risk of infection so we assessed the immunogenicity of 23-valent pneumococcal polysaccharide vaccine (PPSV23) administered within six days of injury.

METHODS: This prospective observational study compared the immunogenicity of PPSV23 among critically ill burn and neurosurgical patients at a tertiary, academic medical center. Patients received PPSV23 vaccination within six days of ICU admission per standard of care. Consent was obtained to measure concentrations of vaccine-specific IgG to 14 of 23 serotype capsule-specific IgG in serum prior to and 14-35 days following PPSV23. A successful immunologic response was defined as both a ≥2-fold …

Il-1r And Myd88 Contribute To The Absence Of A Bacterial Microbiome On The Healthy Murine Cornea, Stephanie J. Wan, Aaron B. Sullivan, Peyton Shieh, Matteo M. E. Metruccio, David J. Evans, Carolyn R. Bertozzi, Suzanne M. J. Fleiszig

Faculty Publications & Research of the TUC College of Pharmacy

Microbial communities are important for the health of mucosal tissues. Traditional culture and gene sequencing have demonstrated bacterial populations on the conjunctiva. However, it remains unclear if the cornea, a transparent tissue critical for vision, also hosts a microbiome. Corneas of wild-type, IL-1R (-/-) and MyD88 (-/-) C57BL/6 mice were imaged after labeling with alkyne-functionalized D-alanine (alkDala), a probe that only incorporates into the peptidoglycan of metabolically active bacteria. Fluorescence in situ hybridization (FISH) was also used to detect viable bacteria. AlkDala labeling was rarely observed on healthy corneas. In contrast, adjacent conjunctivae harbored filamentous alkDala-positive forms, that also labeled …

Gender-Based Differences Among Pharmacy Students Involved In Academically Dishonest Behavior, Eric J. Ip, Jai Pal, Shadi Doroudgar, Monica K. Bidwal, Bijal M. Shah-Manek

Faculty Publications & Research of the TUC College of Pharmacy

Objective. To determine whether differences based on gender exist among pharmacy students involved in cases of admitted cheating or other academic dishonesty and to assess perceptions of academic dishonesty.

Methods. Two cohorts of second-year male and female pharmacy students from four Northern California pharmacy programs were invited to complete a 45-item cross-sectional survey. Descriptive statistics and Pearson’s chi-squared test were used for statistical analysis.

Results. There were 330 surveys completed with a 59% response rate. No significant gender-based differences were found regarding admitted cheating in pharmacy school and in regards to participating in various forms of academically dishonest behavior. Female …

Population Pharmacokinetic/Pharmacodynamic Modeling Of Depot Testosterone Cypionate In Healthy Male Subjects, Youwei Bi, Paul J. Perry, Michael Ellerby, Daryl J. Murry

Faculty Publications & Research of the TUC College of Pharmacy

A randomized, double-blind clinical trial was conducted to investigate long-term abuse effects of testosterone cypionate (TC). Thirty-one healthy men were randomized into a dose group of 100, 250, or 500 mg/wk and received 14 weekly injections of TC. A pharmacokinetic/pharmacodynamic (PK/PD) model was developed to characterize testosterone concentrations and link exposure to change in luteinizing hormone and spermatogenesis following long-term TC administration. A linear one-compartment model best described the concentration-time profile of total testosterone. The population mean estimates for testosterone were 2.6 kL/day for clearance and 14.4 kL for volume of distribution. Weight, albumin, and their changes from baseline were …

Laptop Versus Longhand Note Taking In A Professional Doctorate Course: Student Performance, Attitudes, And Behaviors, Shane P. Desselle, Patricia A. Shane

Faculty Publications & Research of the TUC College of Pharmacy

Objective: To determine the relationship between longhand note taking versus laptop note taking on pharmacy students’ examination performance and identify differences in attitudes and behaviors as it relates to the note taking process.

Methods: A small group of students consented voluntarily to take longhand notes, doing away with their laptops during portions of the course administered by study investigators. Analyses were conducted on block examination performance, with each student’s score on the first examination serving as a performance benchmark to assess change. Laptop and longhand note takers completed a survey regarding various aspects of their note taking attitudes …

Pharmacy Technician-Administered Vaccines: On Perceptions And Practice Reality, Alex J. Adams, Shane P. Desselle, Kimberly C. Mckeirnan

Faculty Publications & Research of the TUC College of Pharmacy

Doucette and Schommer recently surveyed U.S. community pharmacy technicians on their willingness to perform tasks including the administration of vaccines. They found that 47.1% of technicians reported they were “unwilling” to administer a vaccine, although this finding must be placed into proper context. The first nationwide survey of U.S. pharmacist perceptions on immunizations in 1998 revealed only 2.2% of pharmacist respondents had administered adult vaccines and only 0.9% had administered childhood vaccines. They also found pharmacists to be “slightly negative on administering immunizations” with many perceived barriers. Nonetheless, pharmacist-provided immunizations have been an unqualified public health success. The theory of …

Cellular Senescence Is Induced By The Environmental Neurotoxin Paraquat And Contributes To Neuropathology Linked To Parkinson’S Disease, Shankar J. Chinta, Georgia Woods, Marco Demaria, Anand Rane, Ying Zou, Amanda Mcquade, David T. Madden

Faculty Publications & Research of the TUC College of Pharmacy

Exposure to the herbicide paraquat (PQ) is associated with an increased risk of idiopathic Parkinson’s disease (PD). Therapies based on PQ’s presumed mechanisms of action have not, however, yielded effective disease therapies. Cellular senescence is an anticancer mechanism that arrests proliferation of replication-competent cells and results in a pro-inflammatory senescence-associated secretory phenotype (SASP) capable of damaging neighboring tissues. Here, we demonstrate that senescent cell markers are preferentially present within astrocytes in PD brain tissues. Additionally, PQ was found to induce astrocytic senescence and an SASP in vitro and in vivo, and senescent cell depletion in the latter protects against …

The Impact Of Exos On Pseudomonas Aeruginosa Internalization By Epithelial Cells Is Independent Of Fleq And Correlates With Bistability Of Type Three Secretion System Gene Expression, Abby R. Kroken, Camille K. Chen, David J. Evans, Timothy L. Yahr, Suzanne M. J. Fleiszig

Faculty Publications & Research of the TUC College of Pharmacy

Pseudomonas aeruginosa is internalized into multiple types of epithelial cell in vitro and in vivo and yet is often regarded as an exclusively extracellular pathogen. Paradoxically, ExoS, a type three secretion system (T3SS) effector, has antiphagocytic activities but is required for intracellular survival of P. aeruginosaand its occupation of bleb niches in epithelial cells. Here, we addressed mechanisms for this dichotomy using invasive (ExoS-expressing) P. aeruginosaand corresponding effector-null isogenic T3SS mutants, effector-null mutants of cytotoxic P. aeruginosa with and without ExoS transformation, antibiotic exclusion assays, and imaging using a T3SS-GFP reporter. Except for effector-null PA103, all strains were internalized while …

Ethics: A Problem In Pharmacy?, Keith I. Yoshizuka

Faculty Publications & Research of the TUC College of Pharmacy

Ethics, or the lack or attenuation thereof, is an important issue facing practicing pharmacists today. There are both statutory and regulatory provisions to support the requirement of ongoing education and training in ethics. Evidence of formal disciplinary actions by the California State Board of Pharmacy faced requiring pharmacists to take a formal course in ethics as a condition of retention of licensure is sufficient to demonstrate that pharmacists are deviating from the expectations consistent with ethical behavior. Periodic review of the principles of beneficence, non-malfeasance, autonomy, and justice would benefit pharmacists in practice, as evidence infers that a pharmacist’s moral …

Anti-Inflammatory And Neuroprotective Role Of Natural Product Securinine In Activated Glial Cells: Implications For Parkinson’S Disease, Dmitri Leonoudakis, Anand Rane, Suzanne Angeli, Gordon J. Lithgow, Julie K. Andersen, Shankar J. Chinta

Faculty Publications & Research of the TUC College of Pharmacy

Glial activation and subsequent release of neurotoxic proinflammatory factors are believed to play an important role in the pathogenesis of several neurological disorders including Parkinson’s disease (PD). Inhibition of glial activation and inflammatory processes may represent a therapeutic target to alleviate neurodegeneration. Securinine, a major natural alkaloid product from the root of the plant Securinega suffruticosa, has been reported to have potent biological activity and is used in the treatment of neurological conditions such as amyotrophic lateral sclerosis, poliomyelitis, and multiple sclerosis. In this study, we explored the underlying mechanisms of neuroprotection elicited by securinine, particularly its anti-inflammatory effects …

Relationship Between Grit With Academic Performance And Attainment Of Postgraduate Training In Pharmacy Students, Adrian Jason L. Palisoc, Rae Reiko Matsumoto, Jackie Ho, Paul J. Perry, Terrill T. Tang, Eric J. Ip

Faculty Publications & Research of the TUC College of Pharmacy

Objective. To determine if Grit-S scores correlate with academic success in a doctor of pharmacy (PharmD) program, as well as the pursuit and attainment of pharmacy postgraduate (residency or fellowship) training.

Methods. A 28-item survey was administered to third- and fourth-year (P3 and P4) pharmacy students. Variables queried included Grit-S score, demographics, pharmacy experience prior to the PharmD program, and factors that may affect academic performance during didactic coursework. Didactic coursework GPA was used as a surrogate for academic success. Information about pursuit and attainment of a postgraduate training position was also documented and used in the analyses. …

Human Tear Fluid Reduces Culturability Of Contact Lens-Associated Pseudomonas Aeruginosa Biofilms But Induces Expression Of The Virulence-Associated Type Iii Secretion System, Yvonne T. Wu, Connie Tam, Lucia S. Zhu, David J. Evans, Suzanne M. J. Fleiszig

Faculty Publications & Research of the TUC College of Pharmacy

Purpose

The type III secretion system (T3SS) is a significant virulence determinant for Pseudomonas aeruginosa. Using a rodent model, we found that contact lens(CL)-related corneal infections were associated with lens surface biofilms. Here, we studied the impact of human tear fluid on CL-associated biofilm growth and T3SS expression.

Methods

P. aeruginosa biofilms were formed on contact lenses for up to 7 days with or without human tear fluid, then exposed to tear fluid for 5 or 24 h. Biofilms were imaged using confocal microscopy. Bacterial culturability was quantified by viable counts, and T3SS gene expression measured …

Single Low-Dose Lipopolysaccharide Preconditioning: Neuroprotective Against Axonal Injury And Modulates Glial Cells, Ryan C. Turner, Zachary J. Naser, Brandon P. Lucke-Wold, Aric F. Logsdon, Reyna L. Vangilder, Rae Reiko Matsumoto, Jason D. Huber

Faculty Publications & Research of the TUC College of Pharmacy

AIM: Over 7 million traumatic brain injuries (TBI) are reported each year in the United States. However, treatments and neuroprotection following TBI are limited because secondary injury cascades are poorly understood. Lipopolysaccharide (LPS) administration before controlled cortical impact can contribute to neuroprotection. However, the underlying mechanisms and whether LPS preconditioning confers neuroprotection against closed-head injuries remains unclear.

METHODS: The authors hypothesized that preconditioning with a low dose of LPS (0.2 mg/kg) would regulate glial reactivity and protect against diffuse axonal injury induced by weight drop. LPS was administered 7 days prior to TBI. LPS administration reduced locomotion, which recovered completely …

Benzylideneoxymorphone: A New Lead For Development Of Bifunctional Mu/Delta Opioid Receptor Ligands, Jason R. Healy, Padmavani Bezawada, Nicholas W. Griggs, Andrea L. Devereaux, Rae Reiko Matsumoto, John R. Traynor, Christopher W. Cunningham

Faculty Publications & Research of the TUC College of Pharmacy

Opioid analgesic tolerance remains a considerable drawback to chronic pain management. The finding that concomitant administration of delta opioid receptor (DOR) antagonists attenuates the development of tolerance to mu opioid receptor (MOR) agonists has led to interest in producing bifunctional MOR agonist/DOR antagonist ligands. Herein, we present 7-benzylideneoxymorphone (6, UMB 246) displaying MOR partial agonist/DOR antagonist activity, representing a new lead for designing bifunctional MOR/DOR ligands.

Mucosal Fluid Glycoprotein Dmbt1 Suppresses Twitching Motility And Virulence Of The Opportunistic Pathogen Pseudomonas Aeruginosa, Jianfang Li, Matteo E. O. Metruccio, David J. Evans, Suzanne M. J. Fleiszig

Faculty Publications & Research of the TUC College of Pharmacy

It is generally thought that mucosal fluids protect underlying epithelial surfaces against opportunistic infection via their antimicrobial activity. However, our published data show that human tear fluid can protect against the major opportunistic pathogen Pseudomonas aeruginosa independently of bacteriostatic activity. Here, we explored the mechanisms for tear protection, focusing on impacts of tear fluid on bacterial virulence factor expression. Results showed that tear fluid suppressed twitching motility, a type of surface-associated movement conferred by pili. Previously, we showed that twitching is critical for P. aeruginosa traversal of corneal epithelia, exit from epithelial cells after internalization, and corneal virulence. Inhibition …

Piwi Is Required To Limit Exhaustion Of Aging Somatic Stem Cells, Pedro Sousa-Victor, Arshad Ayyaz, Rippei Hayashi, Yanyan Qi, David T. Madden, Victoria V. Lunyak, Heinrich Jasper

Faculty Publications & Research of the TUC College of Pharmacy

Please see the graphical abstract in the supplemental files.

Contributions Of Myd88-Dependent Receptors And Cd11c-Positive Cells To Corneal Epithelial Barrier Function Against Pseudomonas Aeruginosa, Matteo M. E. Metruccio, Connie Tam, David J. Evans, Anna L. Xie, Michael E. Stern, Suzanne M. J. Fleiszig

Faculty Publications & Research of the TUC College of Pharmacy

Previously we reported that corneal epithelial barrier function against Pseudomonas aeruginosa was MyD88-dependent. Here, we explored contributions of MyD88-dependent receptors using vital mouse eyes and confocal imaging. Uninjured IL-1R (−/−) or TLR4 (−/−) corneas, but not TLR2 (−/−), TLR5 (−/−), TLR7 (−/−), or TLR9 (−/−), were more susceptible to P. aeruginosa adhesion than wild-type (3.8-fold, 3.6-fold respectively). Bacteria adherent to the corneas of IL-1R (−/−) or TLR5 (−/−) mice penetrated beyond the epithelial surface only if the cornea was superficially-injured. Bone marrow chimeras showed that bone marrow-derived cells contributed to IL-1R-dependent barrier function. In vivo, but not ex vivo …