Epidemic Keratoconjunctivitis-Causing Adenoviruses Induce MUC16 Ectodomain Release To Infect Ocular Surface Epithelial Cells

ABSTRACT Human adenoviruses (HAdVs) are double-stranded DNA viruses that cause infections across all mucosal tissues in the body. At the ocular surface, HAdVs cause keratoconjunctivitis (E. Ford, K. E. Nelson, and D. Warren, Epidemiol Rev 9:244–261, 1987, and C. M. Robinson, D. Seto, M. S. Jones, D. W. Dyer, and J. Chodosh, Infect Genet Evol 11:1208–1217, 2011, doi:10.1016/j.meegid.2011.04.031)—a highly contagious infection that accounts for nearly 60% of conjunctivitis cases in the United States (R. P. Sambursky, N. Fram, and E. J. Cohen, Optometry 78:236–239, 2007, doi:10.1016/j.optm.2006.11.012, and A. M. Pihos, J Optom 6:69–74, 2013, doi:10.1016/j.optom.2012.08.003). The infection begins with HAdV entry within ocular surface epithelial cells; however, the mechanisms used by HAdVs to transit the otherwise protective mucosal barrier of ocular surface epithelial cells prior to entry remain unknown. Here, we report that the highly virulent keratoconjunctivitis-causing HAdV-D37 induces release of the extracellular domain (ectodomain) of MUC16, a major component of the mucosal barrier of ocular surface epithelial cells, prior to infecting underlying cells. Currently, there is no specific treatment for controlling this infection. Understanding the early steps involved in the pathogenesis of keratoconjunctivitis and using this information to intercept adenoviral entry within cells may guide the development of novel strategies for controlling the infection. Human adenoviruses (HAdV), species D in particular (HAdV-D), are frequently associated with epidemic keratoconjunctivitis (EKC). Although the infection originates at the ocular surface epithelium, the mechanisms by which HAdV-Ds bypass the membrane-associated mucin (MAM)-rich glycocalyx of the ocular surface epithelium to trigger infection and inflammation remain unknown. Here, we report that an EKC-causing adenovirus (HAdV-D37), but not a non-EKC-causing one (HAdV-D19p), induces ectodomain release of MUC16—a MAM with barrier functions at the ocular surface—from cultured human corneal and conjunctival epithelial cells. HAdV-D37, but not HAdV-D19p, is also found to decrease the glycocalyx barrier function of corneal epithelial cells, as determined by rose bengal dye penetrance assays. Furthermore, results from quantitative PCR (qPCR) amplification of viral genomic DNA using primers specific to a conserved region of the E1B gene show that, in comparison to infection by HAdV-D19p, infection by HAdV-D37 is significantly increased in corneal epithelial cells. Collectively, these results point to a MUC16 ectodomain release-dependent mechanism utilized by the EKC-causing HAdV-D37 to initiate infection at the ocular surface. These findings are important in terms of understanding the pathogenesis of adenoviral keratoconjunctivitis. Similar MAM ectodomain release mechanisms may be prevalent across other mucosal epithelia in the body (e.g., the airway epithelium) that are prone to adenoviral infection. IMPORTANCE Human adenoviruses (HAdVs) are double-stranded DNA viruses that cause infections across all mucosal tissues in the body. At the ocular surface, HAdVs cause keratoconjunctivitis (E. Ford, K. E. Nelson, and D. Warren, Epidemiol Rev 9:244–261, 1987, and C. M. Robinson, D. Seto, M. S. Jones, D. W. Dyer, and J. Chodosh, Infect Genet Evol 11:1208–1217, 2011, doi:10.1016/j.meegid.2011.04.031)—a highly contagious infection that accounts for nearly 60% of conjunctivitis cases in the United States (R. P. Sambursky, N. Fram, and E. J. Cohen, Optometry 78:236–239, 2007, doi:10.1016/j.optm.2006.11.012, and A. M. Pihos, J Optom 6:69–74, 2013, doi:10.1016/j.optom.2012.08.003). The infection begins with HAdV entry within ocular surface epithelial cells; however, the mechanisms used by HAdVs to transit the otherwise protective mucosal barrier of ocular surface epithelial cells prior to entry remain unknown. Here, we report that the highly virulent keratoconjunctivitis-causing HAdV-D37 induces release of the extracellular domain (ectodomain) of MUC16, a major component of the mucosal barrier of ocular surface epithelial cells, prior to infecting underlying cells. Currently, there is no specific treatment for controlling this infection. Understanding the early steps involved in the pathogenesis of keratoconjunctivitis and using this information to intercept adenoviral entry within cells may guide the development of novel strategies for controlling the infection.

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Single cell RNA sequencing and lineage tracing confirm mesenchyme to epithelial transformation (MET) contributes to repair of the endometrium at menstruation

10.1101/2021.12.20.473495 ◽

2021 ◽

Author(s):

Phoebe M Kirkwood ◽

Douglas A Gibson ◽

Isaac Shaw ◽

Ross Dobie ◽

Olympia Kelepouri ◽

...

Keyword(s):

Epithelial Cells ◽

Mesenchymal Cell ◽

Cell Types ◽

Lineage Tracing ◽

Surface Epithelium ◽

Variable Response ◽

Stromal Fibroblasts ◽

Stromal Compartment ◽

Mucosal Tissues ◽

Transgenic Lines

The human endometrium experiences repetitive cycles of tissue wounding characterised by piecemeal shedding of the surface epithelium and rapid restoration of tissue homeostasis. In this study we used a validated mouse model of endometrial repair in combination with three transgenic lines of mice to investigate whether epithelial cells that become incorporated into the newly formed luminal epithelium have their origins in one or more of the mesenchymal cell types present in the stromal compartment of the cycling endometrium. Using scRNAseq we identified a novel population of PDGFRb+ cells that arose in the endometrium in response to endometrial breakdown/repair. These cells expressed genes usually considered specific to epithelial cells and in silico trajectory analysis suggested they arose from stromal fibroblasts and were in transition to becoming epithelial cells. To confirm our hypothesis we used a lineage tracing strategy to compare the fate of stromal fibroblasts (PDGFRa+) and stromal perivascular cells (NG2+). We demonstrate for the first time that stromal fibroblasts can undergo a mesenchyme to epithelial transformation and become incorporated into the re-epithelialised luminal surface of the repaired tissue. This study is the first to discover a novel population of wound-responsive, plastic endometrial stromal fibroblasts that contribute to restoration of tissue integrity during endometrial repair. These findings form a platform for comparisons both to endometrial pathologies which involve a fibrotic response (Ashermans syndrome, endometriosis) as well as other mucosal tissues which have a variable response to wounding.

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Intoxication with Ricin - Biochemical Weapon

Revista de Chimie ◽

10.37358/rc.17.6.5668 ◽

2017 ◽

Vol 68 (6) ◽

pp. 1329-1332 ◽

Cited By ~ 2

Author(s):

Madalina Diac ◽

Mioara Calipsoana Matei ◽

Cristiana Manea ◽

Cristina Schiopu ◽

Diana Bulgaru Iliescu ◽

...

Keyword(s):

Castor Oil ◽

Chemical Structure ◽

Correct Diagnosis ◽

Specific Treatment ◽

The United States ◽

Cellular Adhesion ◽

The Body ◽

Processing Plants ◽

Oil Plant ◽

Post Mortem Findings

Ricin, a toxic glycoprotein found in the seeds of castor oil plant, is capable of irreversible cellular adhesion and inhibition of protein synthesis. The authors performed an up to date review concerning the chemical structure, mechanism of action, poisoning symptoms and treatment, and potential uses of ricin as a biochemical weapon. Castor oil plant is easy to cultivate and harvest worldwide and, except the United States of America, cultures and processing plants are not supervised. Ricin extraction does not require laborious and costly technique and it is undetectable once in the body (except for urine in case of ricin ingestion). Poisoning generates nonspecific symptoms and is potentially fatal with no antidote or specific treatment available. Forensic specialists must be aware of symptoms and post-mortem findings in order to make a correct diagnosis of ricin poisoning.

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Female sex steroid induced gallbladder epithelium changes and gallstone deposits in female hamsters: TEM and SEM aspects

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100147612 ◽

1993 ◽

Vol 51 ◽

pp. 354-355

Author(s):

S. Karkare ◽

J. Gilloteaux ◽

T. R. Kelly

Keyword(s):

Hormone Receptors ◽

Corn Oil ◽

Estrogen Therapy ◽

Gallstone Formation ◽

The United States ◽

Sex Steroid ◽

Estradiol Valerate ◽

Surface Epithelium ◽

Female Sex ◽

Purina Chow

Approximately 1 million people in the United States alone develop gallstones each year. The incidence is higher in women than in men and the ratio being 4 ≥ 1. A correlation has also been suggested between oral contraceptives and cholelithiasis. In addition, postmenopausal or cancer estrogen therapy has been reported to be a factor responsible for gallstone formation. Female sex hormone receptors have been detected not only in the gallbladder musculature, but also in its epithelium. As a follow up to experiments effectuated in the male and the ovariectomized Syrian hamster, this report shows that, a combination of a low cholesterol diet with female sex steroid treatment contributes to the formation of gallstone-like deposits, while modifying the surface epithelium morphology. Syrian hamsters (F1B strain, BioBreeders, Watertown MA) were housed under 12h light: 12 h dark cycle, at 20 °C, fed Purina chow and water ad libitum. Several duration/treatment groups were studied, but this report will focus on data obtained with the group injected weekly with estradiol valerate (E weekly, s.c. 8-10 μg/100 g.b.w., in corn oil) and with i.m. medroxyprogesterone acetate (DepoProvera Upjohn Co., Kalamazoo, MI; 8-10 mg/100 g.b.w.) for a 3-month period. Other parameters (blood and bile) were also studied but not reported here.

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Comparison of Ocular Surface Cytological Appearance in Glaucoma Patient Treated with Timolol Maleat 0,5% Latanoprost 0,005% and Timolol-Latanoprost Fixed Combination Preservative Free Eye Drop

Ophthalmologica Indonesiana ◽

10.35749/journal.v44i2.167 ◽

2019 ◽

Vol 44 (2) ◽

pp. 82

Author(s):

Maretha Amrayni ◽

Elsa Gustianty ◽

Susi Heryati ◽

Andika Prahasta ◽

Maula Rifada ◽

...

Keyword(s):

Epithelial Cells ◽

Cell Density ◽

Goblet Cell ◽

Ocular Surface ◽

Fixed Combination ◽

Cell Contact ◽

Corneal Epithelial ◽

Preservative Free ◽

Goblet Cell Density ◽

Epithelial Metaplasia

Introduction : The longterm use of topical antiglaucoma might cause ocular surface instability due to active substance or preservative used. Impression cytology examination may reveal superficial epithelial cells on conjunctiva and cornea, including goblet cells. Goblet cell density decrease is the most important parameter on evaluation of ocular surface disorder. Objective : This study was to understand ocular surface remodeling due to active substance of topical antiglaucoma with impression cytology examination among the patient prior and 3 months after therapy. Methods : This was a randomized controlled trial study with single blind masking. A total of 45 eyes from 31 patients were used as subject and distributed onto three groups treatment, which were timolol maleat 0.5%, latanoprost 0.005%, and latanoprost-timolol maleat fixed combination. All topical antiglaucoma in this study were preservative free. Result : There were differences between 3 groups in goblet cells density after 3 months therapy (p=0,030). Goblet cell density in timolol group was lower than latanoprost (p=0,041) and fixed combination (p=0,045). There was no significantly difference between 3 groups in conjunctival epithelial metaplasia degree (p=0,706) and cell to cell contact degree in corneal epithelial cells (p=0.66) after 3 months therapy. Conjunctival epithelial metaplasia degree were increased among group of timolol (p=0,008) and fixed combination (p=0,046). Conclusion : Timolol maleat 0,5% caused lower goblet cell density after 3 months therapy compare with latanoprost and fixed combination. There was no significantly difference in conjunctival epithelial metaplasia and cell to cell contact degree in corneal epithelial cells among these glaucoma treatment groups.

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The Body Snatchers: How the Writ of Habeas Corpus was taken from the People of the United States

SSRN Electronic Journal ◽

10.2139/ssrn.2800670 ◽

2016 ◽

Author(s):

Joshua J. Schroeder

Keyword(s):

United States ◽

The United States ◽

The Body ◽

Habeas Corpus ◽

The People

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Capturing the surge of public interest towards Hydroxychloroquine, Azithromycin and BCG vaccine during COVID-19 Pandemic (Preprint)

10.2196/preprints.19482 ◽

2020 ◽

Author(s):

Shabbir Syed-Abdul ◽

Shwetambara Malwade ◽

Sim-Mei Choo

Keyword(s):

Social Media ◽

Preventive Measures ◽

Healthcare Providers ◽

Specific Treatment ◽

Drug Effects ◽

The United States ◽

Bcg Vaccine ◽

Public Interests ◽

Treatment Regimes ◽

Appropriate Treatment

UNSTRUCTURED The outbreak of COVID-19 that started in December 2019, was declared a pandemic in March 2020. Currently, there is no specific treatment recommended and healthcare providers are struggling to find appropriate treatment regimes. Medication misinformation spread through social media has caused panic situations and self-prescription leading to harmful drug effects. The situation worsened following false propaganda via social media, leading to shortage of some medications. Our study shows the frequency of search for the medications Hydroxychloroquine (HCQ), Azithromycin and Bacillus Calmette-Guérin (BCG) vaccine in Google Trends, across 6 countries. Public interests from the United States, Italy and Spain leaned towards HCQ, whereas those from Taiwan, Japan and South Korea were keen towards learning about the BCG vaccine. Our article aimed to inform the general public of the adverse drug reactions to avoid self-prescription or yield to the assumptions of leaders and unanimous social media posts. Proactive participation and preventive measures such as social distancing, use of face masks and hand sanitizers are recommended to help curb COVID-19 and other infections.

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Psychosocial Consequences of Body Weight and Obesity

The Oxford Handbook of Integrative Health Science ◽

10.1093/oxfordhb/9780190676384.013.15 ◽

2018 ◽

pp. 274-286

Author(s):

Deborah Carr ◽

Vera K. Tsenkova

Keyword(s):

Body Weight ◽

Interpersonal Relationships ◽

Large Scale ◽

Well Being ◽

The United States ◽

Overweight And Obesity ◽

The Body ◽

Integrative Health ◽

Psychosocial Consequences ◽

Adults And Children

The body weight of U.S. adults and children has risen markedly over the past three decades. The physical health consequences of obesity are widely documented, and emerging research from the Midlife in the United States study and other large-scale surveys reveals the harmful impact of obesity on adults’ psychosocial and interpersonal well-being. This chapter synthesizes recent research on the psychosocial implications of body weight, with attention to explanatory mechanisms and subgroup differences in these patterns. A brief statistical portrait of body weight is provided, documenting rates and correlates of obesity, with a focus on race, gender, and socioeconomic status disparities. The consequences of body weight for three main outcomes are described: institutional and everyday discrimination, interpersonal relationships, and psychological well-being. The chapter concludes with a discussion of the ways that recent integrative health research on the psychosocial consequences of overweight and obesity inform our understanding of population health.

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Cervical arthroplasty: what does the labeling say?

Neurosurgical FOCUS ◽

10.3171/2016.11.focus16414 ◽

2017 ◽

Vol 42 (2) ◽

pp. E2 ◽

Cited By ~ 12

Author(s):

Mazda K. Turel ◽

Mena G. Kerolus ◽

Owoicho Adogwa ◽

Vincent C. Traynelis

Keyword(s):

Outcome Measures ◽

Revision Surgery ◽

Controlled Trial ◽

Neck Disability Index ◽

Specific Treatment ◽

The United States ◽

Cervical Disc ◽

Cervical Arthroplasty ◽

Single Level ◽

Level Group

OBJECTIVE The aim of this paper was to comprehensively review each of the Food and Drug Administration (FDA)–approved labels of 7 total cervical disc replacements, assess the exact methodology in which the trial was conducted, and provide a broad comparison of these devices to allow each surgeon to determine which disc best suits his or her specific treatment goals based on the specific labels and not the studies published. METHODS The FDA-approved labels for each of the 7 artificial discs were obtained from the official FDA website. These labels were meticulously compared with regard to the statistical analysis performed, the safety and efficacy data, and the randomized controlled trial that each artificial disc was involved in to obtain the FDA approval for the product or device. Both single-level and 2-level approvals were examined, and primary and secondary end points were assessed. RESULTS In the single-level group, 4 of the 7 artificial discs—Prestige LP, Prestige ST, Bryan, and Secure-C—showed superiority in overall success. Prestige ST showed superiority in 3 of 4 outcome measures (neurological success, revision surgery, and overall success), while the other aforementioned discs showed superiority in 2 or fewer measures (Prestige LP, neurological and overall success; Bryan, Neck Disability Index [NDI] and overall success; Secure-C, revision surgery and overall success; Pro-Disc C, revision surgery). The PCM and Mobi-C discs demonstrated noninferiority across all outcome measures. In the 2-level group, Prestige LP and Mobi-C demonstrated superiority in 3 outcome measures (NDI, secondary surgery, and overall success) but not neurological success. CONCLUSIONS This paper provides a comprehensive analysis of 7 currently approved and distributed artificial discs in the United States. It compares specific outcome measures of these devices against those following the standard of care, which is anterior cervical discectomy and fusion. This information will provide surgeons the opportunity to easily answer patients' questions and remain knowledgeable when discussing devices with manufacturers.

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