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Fallen Kingdoms And Ancient Monoliths: The Influence Of Atlantis And Egypt In Tolkien’S Númenor, Charlotte J. Brockway Sep 2024

Fallen Kingdoms And Ancient Monoliths: The Influence Of Atlantis And Egypt In Tolkien’S Númenor, Charlotte J. Brockway

Journal of Tolkien Research

In light of the recent publication of The Fall of Númenor, my essay aims to focus on Tolkien’s, somewhat underappreciated, influences on Gondor; particularly Ancient Egypt. This essay looks at Plato's Timaeus and Critias, Ignatius Donnelly's theories, and examines the Atlantean and Egyptian motifs in Tolkien’s version of Westernesse, in particular, the remnants of Atlantean civilization survived by Egyptian colonists which mirror the Realms of Exile (Gondor and Arnor).


Negative Effect Of Treatment With Mglur5 Negative Allosteric Modulator Afq056 On Blood Biomarkers In Young Individuals With Fragile X Syndrome, Dragana Protic, Stephanie Morris, Et Al. Sep 2024

Negative Effect Of Treatment With Mglur5 Negative Allosteric Modulator Afq056 On Blood Biomarkers In Young Individuals With Fragile X Syndrome, Dragana Protic, Stephanie Morris, Et Al.

2020-Current year OA Pubs

BACKGROUND: Fragile X syndrome, with an approximate incidence rate of 1 in 4000 males to 1 in 8000 females, is the most prevalent genetic cause of heritable intellectual disability and the most common monogenic cause of autism spectrum disorder. The full mutation of the Fragile X Messenger Ribonucleoprotein-1 gene, characterized by an expansion of CGG trinucleotide repeats (>200 CGG repeats), leads to fragile X syndrome. Currently, there are no targeted treatments available for fragile X syndrome. In a recent large multi-site trial, FXLEARN, the effects of the mGluR5 negative allosteric modulator, AFQ056 (mavoglurant), were investigated, but did not show …


Interview: Kimi Eisele, Steven M. Schnell Sep 2024

Interview: Kimi Eisele, Steven M. Schnell

The Geographical Bulletin

Kimi Eisele1 is a writer, dancer/choreographer, performer, director, visual artist, and educator based in Tucson, Arizona. Drawing on her MA in geography and a long-standing interest in place and space, she creates works that engage local landscapes, including ecosystems, political systems, and human communities. In 1997, while a graduate student in geography at the University of Arizona, she founded you are here: the journal of creative geography, an interdisciplinary outlet for place-based writing and art, a publication that is still going strong.


Trophic Niche Of A Nonnative Invader And Environmental Drivers Of Its Increasing Populations In The Coastal Everglades, Grace Kahmann, Jennifer S. Rehage, Jordan A. Massie, James A. Nelson, Rolando O. Santos, Natasha M. Viadero, W. Ryan James, Ross E. Boucek, Derek P. Crane, Ryan J. Rezek Sep 2024

Trophic Niche Of A Nonnative Invader And Environmental Drivers Of Its Increasing Populations In The Coastal Everglades, Grace Kahmann, Jennifer S. Rehage, Jordan A. Massie, James A. Nelson, Rolando O. Santos, Natasha M. Viadero, W. Ryan James, Ross E. Boucek, Derek P. Crane, Ryan J. Rezek

Marine Science

The Florida Everglades is a critically important, but highly threatened ecosystem that is becoming increasingly susceptible to the invasion of non-native species. This study investigated the ecological role of the invasive peacock eel (Macrognathus siamensis) within this ecosystem using 15 years of electrofishing data and stable isotope analysis. We investigated the population trends of peacock eels at the marsh-mangrove ecotone of the Shark River Estuary, the environmental factors contributing to their abundance, and the potential interactions they may have with native fish assemblages and coastal food webs. We used stable isotope analysis to provide insights into the basal resource contribution …


S6k1 Controls Dna Damage Signaling Modulated By The Mrn Complex To Induce Radioresistance In Lung Cancer, Ali Calderon-Aparicio, Jun He, Nicole L. Simone Sep 2024

S6k1 Controls Dna Damage Signaling Modulated By The Mrn Complex To Induce Radioresistance In Lung Cancer, Ali Calderon-Aparicio, Jun He, Nicole L. Simone

Department of Radiation Oncology Faculty Papers

Radiation is a mainstay of lung cancer treatment; however, resistance frequently develops. Identifying novel therapeutic targets to increase radiation sensitivity is crucial. S6K1 is a serine/threonine kinase known to regulate protein translation which is associated with radioresistance, but the mechanisms involved are unknown. We proposed to determine whether S6K1 promotes radioresistance by regulating DNA repair in lung cancer. Colony formation, protein expression and proliferation were assessed. S6K1 was modulated pharmacologically by either PF-4708671 or genetically by Crispr-Cas9. Higher radioresistance levels in lung cancer cells were associated with lower phosphoactivation of MRN complex members, a key activator of radiation-induced DNA repair …


The Importance Of Humanities In A Career-Focused Educational Environment, Geoff Zylstra, Jill Belli, Candido Cabo, Sean Macdonald, Robin Michals, Ann Marie Sowder, Christopher B. Swift Sep 2024

The Importance Of Humanities In A Career-Focused Educational Environment, Geoff Zylstra, Jill Belli, Candido Cabo, Sean Macdonald, Robin Michals, Ann Marie Sowder, Christopher B. Swift

Publications and Research

The humanities have the potential to enhance STEM curriculum in career-oriented professional degree programs. As part of a larger college-wide initiative to develop interdisciplinary curricula, the National Endowment for the Humanities (NEH) awarded a grant to New York City College of Technology to explore the relationship between the humanities and career-focused degree programs in STEM departments. This article describes the design and implementation of coursework that bridges the curricular divides between humanities disciplines and technical or career-focused disciplines by bringing the humanities to bear on science and technology-oriented courses. Specifically, the humanities served to improve technical skills for students in …


Inorganic Polyphosphate Promotes Colorectal Cancer Growth Via Trpm8 Receptor Signaling Pathway, Valentina Arrè, Chen Shen, Et Al. Sep 2024

Inorganic Polyphosphate Promotes Colorectal Cancer Growth Via Trpm8 Receptor Signaling Pathway, Valentina Arrè, Chen Shen, Et Al.

2020-Current year OA Pubs

BACKGROUND: Colorectal cancer (CRC) is characterized by a pro-inflammatory microenvironment and features high-energy-supply molecules that assure tumor growth. A still less studied macromolecule is inorganic polyphosphate (iPolyP), a high-energy linear polymer that is ubiquitous in all forms of life. Made up of hundreds of repeated orthophosphate units, iPolyP is essential for a wide variety of functions in mammalian cells, including the regulation of proliferative signaling pathways. Some evidence has suggested its involvement in carcinogenesis, although more studies need to be pursued. Moreover, iPolyP regulates several homeostatic processes in animals, spanning from energy metabolism to blood coagulation and tissue regeneration.

RESULTS: …


Safety Of Dostarlimab In Combination With Chemotherapy In Patients With Primary Advanced Or Recurrent Endometrial Cancer In A Phase Iii, Randomized, Placebo-Controlled Trial (Engot-En6-Nsgo/Gog-3031/Ruby), Annika Auranen, Matthew A Powell, Et Al. Sep 2024

Safety Of Dostarlimab In Combination With Chemotherapy In Patients With Primary Advanced Or Recurrent Endometrial Cancer In A Phase Iii, Randomized, Placebo-Controlled Trial (Engot-En6-Nsgo/Gog-3031/Ruby), Annika Auranen, Matthew A Powell, Et Al.

2020-Current year OA Pubs

BACKGROUND: In Part 1 of the phase III RUBY trial (NCT03981796) in patients with primary advanced or recurrent endometrial cancer (EC), dostarlimab plus carboplatin-paclitaxel (CP) significantly improved progression-free survival and overall survival compared with CP alone. Limited safety data have been reported for the combination of immunotherapies plus chemotherapy in this setting.

OBJECTIVES: The objective of this analysis was to identify the occurrence of treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs) and to describe irAE management in Part 1 of the RUBY trial.

DESIGN: RUBY is a phase III, randomized, double-blind, multicenter study of dostarlimab plus CP compared …


Broad Applicability Of The Goldspire™ Platform For The Treatment Of Solid Tumors, Jenny Zilberberg, Christopher Uhl, Charles B Scott, David W. Andrews, Mark A Exley Sep 2024

Broad Applicability Of The Goldspire™ Platform For The Treatment Of Solid Tumors, Jenny Zilberberg, Christopher Uhl, Charles B Scott, David W. Andrews, Mark A Exley

Department of Neurosurgery Faculty Papers

Goldspire™ is a personalized immunotherapy platform that combines whole tumor-derived cells with antisense oligonucleotide (IMV-001) against Insulin-Like Growth Factor-1 Receptor (IGF-1R) in biodiffusion chambers (BDCs; 0.1 μm pore). BDCs are exposed to 5-6 Gy and implanted at abdominal sites for ∼48 h to deliver an antigenic payload and immunostimulatory factors to train the immune system. Lead product IGV-001 was evaluated in newly diagnosed glioblastoma (ndGBM) patients in Phase 1a and 1b trials (NCT02507583). A Phase 2b study (NCT04485949) recently completed enrollment. Preventative treatment with tumor-specific products manufactured with Goldspire limited tumor progression and extended overall survival in mice challenged with …


Immunomodulation Of Macrophages In Diabetic Wound Individuals By Structurally Diverse Bioactive Phytochemicals, Krishnendu Adhikary, Riya Sarkar, Sriparna Maity, Ishani Sadhukhan, Riya Sarkar, Krishnendu Ganguly, Saurav Barman, Rajkumar Maiti, Sanjoy Chakraborty, Tandra R. Chakraborty, Debasis Bagchi, Pradipta Banerjee Sep 2024

Immunomodulation Of Macrophages In Diabetic Wound Individuals By Structurally Diverse Bioactive Phytochemicals, Krishnendu Adhikary, Riya Sarkar, Sriparna Maity, Ishani Sadhukhan, Riya Sarkar, Krishnendu Ganguly, Saurav Barman, Rajkumar Maiti, Sanjoy Chakraborty, Tandra R. Chakraborty, Debasis Bagchi, Pradipta Banerjee

Publications and Research

Diabetes-related ulcers and slow-healing wounds pose a significant health risk to individuals due to their uncertain causes. Mortality rates for diabetes foot ulcers (DFUs) range from 10% after 16 months to 24% after five years. The use of bioactive phytochemicals can play a key role in healing wounds in a predictable time. Recent literature has demonstrated that various natural substances, including flavonoids, saponins, phenolic compounds, and polysaccharides, play key roles at different stages of the wound-healing process through diverse mechanisms. These studies have categorized the compounds according to their characteristics, bioactivities, and modes of action. In this study, we evaluated …


Volume 55-1 Complete Issue, Steven M. Schnell Sep 2024

Volume 55-1 Complete Issue, Steven M. Schnell

The Geographical Bulletin

Volume 55-1 Complete Issue


Local Regulatory Protection For Ecosystem Services: A Case Study From The Karst Region Of Southeast Minnesota, Usa, Mary A. Williams, Susy Svatek Ziegler Sep 2024

Local Regulatory Protection For Ecosystem Services: A Case Study From The Karst Region Of Southeast Minnesota, Usa, Mary A. Williams, Susy Svatek Ziegler

The Geographical Bulletin

Human communities depend upon a myriad of ecosystem goods and services, which are produced by and depend on natural environmental processes occurring at multiple temporal and spatial scales. Land-use policy seldom recognizes the importance of these services or the environmental processes generating these services. This study examined the degree to which ecosystem services and supporting environmental processes are regulated at two United States municipal levels: city and county. Several ecosystem services but few environmental processes are regulated to some extent. We identified policy needs for environmentally sensitive karst features, aquifer recharge, groundwater quality, plant and animal populations, and flood mitigation. …


Women, Militarism, And Political Representation: The Case Of Armenia, Valentine M. Moghadam, Marisa Goolgasian Sep 2024

Women, Militarism, And Political Representation: The Case Of Armenia, Valentine M. Moghadam, Marisa Goolgasian

Journal of International Women's Studies

How does militarism affect women’s presence in the political process? Through a focus on the Republic of Armenia during the period 1990-2020, we examine the puzzle of women’s political representation. The country’s legacy of communist-era ideology of women’s equality, its democratic transition, women’s high levels of educational attainment and labor force participation, and the 2007 gender quota adoption should have served to place Armenia in the top 50 countries in women’s political representation. Yet for two decades, the country appeared low on international rankings of women’s political empowerment. To unpack this puzzle, we revisit two strands of the women-and-war literature—one …


2024 16th Annual Student Center For Science Engagement Research Symposium, Student Center For Science Engagement Sep 2024

2024 16th Annual Student Center For Science Engagement Research Symposium, Student Center For Science Engagement

Student Center for Science Engagement Research Symposium

Student presentations in Biology, Chemistry, Physics, Earth Science, Environmental Science, Computer Science, Mathematics, & Psychology


The Student Movement Volume 109 Issue 2: Nosotros Somos Andrews!: Hispanic Heritage Month At Andrews, Savannah Tyler, Ayanda Dewa, Ember Clark, Joel Pelletier, Lia Glass, Amelia Stefanescu, Aiko J. Ayala Rios, Anna Rybachek, Reagan Westerman, Charisse Lapuebla, Lexie Dunham, Melissa Moore Sep 2024

The Student Movement Volume 109 Issue 2: Nosotros Somos Andrews!: Hispanic Heritage Month At Andrews, Savannah Tyler, Ayanda Dewa, Ember Clark, Joel Pelletier, Lia Glass, Amelia Stefanescu, Aiko J. Ayala Rios, Anna Rybachek, Reagan Westerman, Charisse Lapuebla, Lexie Dunham, Melissa Moore

The Student Movement V. 109 (2024-2025)

HUMANS

Celebrating Hispanic Heritage, Interviewed by Savannah Tyler

Andrews Senior Alina Weber for Those with Invisible Disablilities, Ayanda Dewa

ARTS & ENTERTAINMENT

"Forward in Faith": An Interview with Professor Meredith Jones Gray, Ember Clark

¡Y, Acción!: Hispanic and Latino Representation in Film, Joel Pelletier

Department of Visual Art, Communication and Design Introduction, Lia Glass

NEWS

Andrews University Partners with Interstride, What It Means for You, Amelia Stefanescu

Students Host Inaugural Event To Honor Mexico's Independence Day, Aiko J. Ayala Rios

Ty Gibson Speaks at Andrews for Week of Prayer, Amelia Stefanescu

IDEAS

Microtrends: A Short Narrative, Anna Rybachek

Opinion: JD …


Multi-Functional Gelatin-Dithiolane Hydrogels For Tissue Engineering, Saad Asim, Cody Tuftee, Asma Talib Qureshi, Rachel Callaghan, Moira L. Geary, Mithun Santra, Vaibhav Pal, Ilayda Namli, Gary Hin Fai Yam, Ibrahim T. Ozbolat, Muhammad Rizwan Sep 2024

Multi-Functional Gelatin-Dithiolane Hydrogels For Tissue Engineering, Saad Asim, Cody Tuftee, Asma Talib Qureshi, Rachel Callaghan, Moira L. Geary, Mithun Santra, Vaibhav Pal, Ilayda Namli, Gary Hin Fai Yam, Ibrahim T. Ozbolat, Muhammad Rizwan

Michigan Tech Publications

Biomaterials that integrate multiple functionalities, mimic the extracellular matrix (ECM) microenvironment to support cellular growth, and adhere robustly to damaged tissues are highly needed to advance tissue engineering. Protein-based biomaterials are promising due to their inherent biocompatibility, biomimicry, biodegradation, and cell-supportive properties. Herein, by leveraging the unique ability of dithiolanes to generate on-demand in situ thiols, a new class of dithiolane-modified, protein-based biomaterial that combines unique, seemingly opposing functions for tissue engineering is developed. Dithiolane-modified gelatin, a model protein used herein, enabled photoinitiator-free photo-crosslinking to form multi-functional gelatin-dithiolane (GelDT) hydrogels, which displayed exceptional long-term stability in cell culture media ( …


The Bison, September, 27, 2024 Sep 2024

The Bison, September, 27, 2024

The Bison Newspapers

No abstract provided.


Volume Cxliv, Number 1, September 27, 2024, Lawrence University Sep 2024

Volume Cxliv, Number 1, September 27, 2024, Lawrence University

The Lawrentian

No abstract provided.


A New Invasive Lepidosaphes Armored Scale (Hemiptera: Coccomorpha: Diaspididae) For Florida: First Records, Natural Enemies, And An Identification Key, Erin C. Powell, Mark Zenoble, Douglass R. Miller, Benjamin B. Normark, Gregory A. Evans Sep 2024

A New Invasive Lepidosaphes Armored Scale (Hemiptera: Coccomorpha: Diaspididae) For Florida: First Records, Natural Enemies, And An Identification Key, Erin C. Powell, Mark Zenoble, Douglass R. Miller, Benjamin B. Normark, Gregory A. Evans

Insecta Mundi

The invasive armored scale, Lepidosaphes laterochitinosa Green 1925 (Hemiptera: Coccomorpha: Diaspididae), was found in the Florida landscape for the first time in November 2022 and is now known from two south Florida counties: Broward and Miami-Dade. In Florida thus far, this polyphagous species has been found on Epipremnum pinnatum (L.) Engl. (Araceae), Dracaena Vand. ex. L. (Asparagaceae), and Breynia disticha J. R. Forst. and G. Forst. (Phyllanthaceae), all common landscape ornamentals. New parasitoid host records are provided for Encarsia lounsburyi (Berlese and Paoli), Encarsia citrina (Craw), and Aphytis lingnanensis Compere (Hymenoptera: Aphelinidae) that emerged from L. laterochitinosa in Broward …


An Edge Platform Streamlining Connectivity Between Modern Edge Devices And Cloud, Anderson Carvalho Sep 2024

An Edge Platform Streamlining Connectivity Between Modern Edge Devices And Cloud, Anderson Carvalho

Theses

The numerous uses of cloud, fog, and edge computing in a variety of industries are thoroughly examined in this thesis, with a special emphasis on smart factories, smart cities, and smart agriculture. It starts with an introduction to cloud computing, going over its history, importance in contemporary digital infrastructures, and related security concerns. It emphasizes the value of cloud computing for processing and storing data while addressing issues like guaranteeing low latency applications and possible improvements from container technologies. The conversation then shifts to fog computing, going over its history, designs, and uses. It focuses on how fog computing might …


Emotional Display Rules Of Deaf Culture, Nicholas M. Gala, Lawrence Pick Sep 2024

Emotional Display Rules Of Deaf Culture, Nicholas M. Gala, Lawrence Pick

JADARA

Emotional display rules refer to the expression of culturally prescribed and socially acceptable emotions across different people and situations (Wu & Schulz, 2020). The display rules among hearing adults across several cultures are well defined and depend on the type of emotion, the individuals involved in the exchange, and the situation. Regarding Deaf culture in the United States, this minoritized group may follow unique display rules (Hosie et al., 2000), but there has been almost no research conducted with this population and the existing studies have focused on youth. The present study explores perceived emotional expressions among a sample of …


2024-09-27 Minutes Of The Academic Senate, University Of Dayton. Academic Senate Sep 2024

2024-09-27 Minutes Of The Academic Senate, University Of Dayton. Academic Senate

Academic Senate Minutes

Approved minutes of a meeting of the Academic Senate of the University of Dayton.


Expanded Gene And Taxon Sampling Of Diplomonads Shows Multiple Switches To Parasitic And Free-Living Lifestyle, Monika Wiśniewska, Erik Salomaki, Jeffrey D. Silberman, Kristina Terpis, Eva Mazancová, Petr Táborský, Vasana Jinathama, Eleni Gentekaki, Ivan Čepička, Martin Kolisko Sep 2024

Expanded Gene And Taxon Sampling Of Diplomonads Shows Multiple Switches To Parasitic And Free-Living Lifestyle, Monika Wiśniewska, Erik Salomaki, Jeffrey D. Silberman, Kristina Terpis, Eva Mazancová, Petr Táborský, Vasana Jinathama, Eleni Gentekaki, Ivan Čepička, Martin Kolisko

Biological Sciences Faculty Publications and Presentations

Background

Diplomonads are anaerobic flagellates classified within Metamonada. They contain both host-associated commensals and parasites that reside in the intestinal tracts of animals, including humans (e.g., Giardia intestinalis), as well as free-living representatives that inhabit freshwater and marine anoxic sediments (e.g., Hexamita inflata). The evolutionary trajectories within this group are particularly unusual as the free-living taxa appear to be nested within a clade of host-associated species, suggesting a reversal from host-dependence to a secondarily free-living lifestyle. This is thought to be an exceedingly rare event as parasites often lose genes for metabolic pathways that are essential to a …


The Association Of The Oral Microbiota With Cognitive Functioning In Adolescence, Oxana Y Naumova, Pavel V Dobrynin, Galina V Khafizova, Elena L Grigorenko Sep 2024

The Association Of The Oral Microbiota With Cognitive Functioning In Adolescence, Oxana Y Naumova, Pavel V Dobrynin, Galina V Khafizova, Elena L Grigorenko

Faculty, Staff and Students Publications

Background: A growing body of research supports the role of the microbial communities residing in the digestive system in the host's cognitive functioning. Most of these studies have been focused on the gut microbiome and its association with clinical phenotypes in middle-aged and older adults. There is an insufficiency of population-based research exploring the association of normative cognitive functioning with the microbiome particularly with the oral microbiota.

Methods: In this study, using metagenomics and metabolomics, we characterized the salivary microbiome diversity in a sample of 51 males of Hispanic and African American origin aged 12-18 years and explored …


Understanding Necrotizing Enterocolitis Endotypes And Acquired Intestinal Injury Phenotypes From A Historical And Artificial Intelligence Perspective., Alain Cuna, Navin Kumar, Venkatesh Sampath Sep 2024

Understanding Necrotizing Enterocolitis Endotypes And Acquired Intestinal Injury Phenotypes From A Historical And Artificial Intelligence Perspective., Alain Cuna, Navin Kumar, Venkatesh Sampath

Manuscripts, Articles, Book Chapters and Other Papers

Necrotizing enterocolitis (NEC) remains a devastating disease in preterm and term neonates. Despite significant progress made in understanding NEC pathogenesis over the last 50 years, the inability of current definitions to discriminate the various pathophysiological processes underlying NEC has led to an umbrella term that limits clinical and research progress. In this mini review, we provide a historical perspective on how NEC definitions and pathogenesis have evolved to our current understanding of NEC endotypes. We also discuss how artificial intelligence-based approaches are influencing our knowledge of risk-factors, classification and prognosis of NEC and other neonatal intestinal injury phenotypes.


Integrating Data-Driven And Mechanism-Driven Modeling In Drug Discovery And Hepatotoxicity Evaluation, Xuelian Jia Sep 2024

Integrating Data-Driven And Mechanism-Driven Modeling In Drug Discovery And Hepatotoxicity Evaluation, Xuelian Jia

Theses and Dissertations

The pharmacological activities and hepatotoxicity significantly influence the success or failure of new drugs during drug discovery and development. Traditional experimental methods, such as animal models, are costly and time-consuming for chemical testing. There is a great need to develop in vitro and computational modeling to help identify the pharmacological activities and hepatotoxicity potential in the early stage of drug discovery and safety evaluation. In this dissertation, new computational models and associated modeling frameworks were described for predicting the biological profile and hepatotoxicity of chemicals. Firstly, a novel data mining and Quantitative Structure-Activity Relationship (QSAR) workflow was developed to construct …


A Basally Active Cgas-Sting Pathway Limits Sars-Cov-2 Replication In A Subset Of Ace2 Positive Airway Cell Models, Maritza Puray-Chavez, Jenna E Eschbach, Ming Xia, Kyle M Lapak, Qianzi Zhou, Ria Jasuja, Jiehong Pan, Jian Xu, Zixiang Zhou, Shawn Mohammed, Qibo Wang, Dana Q Lawson, Sanja Djokic, Gaopeng Hou, Siyuan Ding, Steven L Brody, Michael B Major, Dennis Goldfarb, Sebla B Kutluay Sep 2024

A Basally Active Cgas-Sting Pathway Limits Sars-Cov-2 Replication In A Subset Of Ace2 Positive Airway Cell Models, Maritza Puray-Chavez, Jenna E Eschbach, Ming Xia, Kyle M Lapak, Qianzi Zhou, Ria Jasuja, Jiehong Pan, Jian Xu, Zixiang Zhou, Shawn Mohammed, Qibo Wang, Dana Q Lawson, Sanja Djokic, Gaopeng Hou, Siyuan Ding, Steven L Brody, Michael B Major, Dennis Goldfarb, Sebla B Kutluay

2020-Current year OA Pubs

Host factors that define the cellular tropism of SARS-CoV-2 beyond the cognate ACE2 receptor are poorly defined. Here we report that SARS-CoV-2 replication is restricted at a post-entry step in a number of ACE2-positive airway-derived cell lines due to tonic activation of the cGAS-STING pathway mediated by mitochondrial DNA leakage and naturally occurring cGAS and STING variants. Genetic and pharmacological inhibition of the cGAS-STING and type I/III IFN pathways as well as ACE2 overexpression overcome these blocks. SARS-CoV-2 replication in STING knockout cell lines and primary airway cultures induces ISG expression but only in uninfected bystander cells, demonstrating efficient antagonism …


Nur77 Protects The Bladder Urothelium From Intracellular Bacterial Infection, Christina A Collins, Chevaughn Waller, Ekaterina Batourina, Lokesh Kumar, Cathy L Mendelsohn, Nicole M Gilbert Sep 2024

Nur77 Protects The Bladder Urothelium From Intracellular Bacterial Infection, Christina A Collins, Chevaughn Waller, Ekaterina Batourina, Lokesh Kumar, Cathy L Mendelsohn, Nicole M Gilbert

2020-Current year OA Pubs

Intracellular infections by Gram-negative bacteria are a significant global health threat. The nuclear receptor Nur77 (also called TR3, NGFI-B, or NR4A1) was recently shown to sense cytosolic bacterial lipopolysaccharide (LPS). However, the potential role for Nur77 in controlling intracellular bacterial infection has not been examined. Here we show that Nur77 protects against intracellular infection in the bladder by uropathogenic Escherichia coli (UPEC), the leading cause of urinary tract infections (UTI). Nur77 deficiency in mice promotes the formation of UPEC intracellular bacterial communities (IBCs) in the cells lining the bladder lumen, leading to persistent infection in bladder tissue. Conversely, treatment with …


Massively Parallel Characterization Of Insulator Activity Across The Genome, Clarice K Y Hong, Yawei Wu, Alyssa A Erickson, Jie Li, Arnold J Federico, Barak A Cohen Sep 2024

Massively Parallel Characterization Of Insulator Activity Across The Genome, Clarice K Y Hong, Yawei Wu, Alyssa A Erickson, Jie Li, Arnold J Federico, Barak A Cohen

2020-Current year OA Pubs

A key question in regulatory genomics is whether cis-regulatory elements (CREs) are modular elements that can function anywhere in the genome, or whether they are adapted to certain genomic locations. To distinguish between these possibilities we develop MPIRE (Massively Parallel Integrated Regulatory Elements), a technology for recurrently assaying CREs at thousands of defined locations across the genome in parallel. MPIRE allows us to separate the intrinsic activity of CREs from the effects of their genomic environments. We apply MPIRE to assay three insulator sequences at thousands of genomic locations and find that each insulator functions in locations with distinguishable properties. …


Coral Reef Protection Is Fundamental To Human Rights, Emma F. Camp, Irus Braverman, Genevieve Wilkinson, Christian R. Voolstra Sep 2024

Coral Reef Protection Is Fundamental To Human Rights, Emma F. Camp, Irus Braverman, Genevieve Wilkinson, Christian R. Voolstra

Journal Articles

The intensifying loss of coral reefs from global climate change and local stressors has seen international commitments targeted at conservation and repair, for example the Kunming–Montreal Global Biodiversity Framework. Fulfilling these targets requires decisions to be made on where, when, and how to act, ultimately dictating where limited resources will be deployed. Every choice on action or inaction toward our ocean has direct and indivisible consequences not only for the health of marine ecosystems but also for the health of humans, particularly those who directly depend on marine habitats, both culturally and economically. The well-being of the environment, humans, and …