Digital Commons Network^™

Crispr-Cas9 Base Editing Of Pathogenic Camkiiδ Improves Cardiac Function In A Humanized Mouse Model, Simon Lebek, Xurde M Caravia, Leon G Straub, Damir Alzhanov, Wei Tan, Hui Li, John R Mcanally, Kenian Chen, Lin Xu, Philipp E Scherer, Ning Liu, Rhonda Bassel-Duby, Eric N Olson

Faculty, Staff and Student Publications

Cardiovascular diseases are the most common cause of worldwide morbidity and mortality, highlighting the necessity for advanced therapeutic strategies. Ca2+/calmodulin-dependent protein kinase IIδ (CaMKIIδ) is a prominent inducer of various cardiac disorders, which is mediated by 2 oxidation-sensitive methionine residues within the regulatory domain. We have previously shown that ablation of CaMKIIδ oxidation by CRISPR-Cas9 base editing enables the heart to recover function from otherwise severe damage following ischemia/reperfusion (IR) injury. Here, we extended this therapeutic concept toward potential clinical translation. We generated a humanized CAMK2D knockin mouse model in which the genomic sequence encoding the entire regulatory domain was …

Serine Synthesis Via Reversed Shmt2 Activity Drives Glycine Depletion And Acetaminophen Hepatotoxicity In Masld, Alia Ghrayeb, Alexandra C Finney, Bella Agranovich, Daniel Peled, Sumit Kumar Anand, M Peyton Mckinney, Mahasen Sarji, Dongshan Yang, Natan Weissman, Shani Drucker, Sara Isabel Fernandes, Jonatan Fernández-García, Kyle Mahan, Zaid Abassi, Lin Tan, Philip L Lorenzi, James Traylor, Jifeng Zhang, Ifat Abramovich, Y Eugene Chen, Oren Rom, Inbal Mor, Eyal Gottlieb

Faculty, Staff and Student Publications

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects one-third of the global population. Understanding the metabolic pathways involved can provide insights into disease progression and treatment. Untargeted metabolomics of livers from mice with early-stage steatosis uncovered decreased methylated metabolites, suggesting altered one-carbon metabolism. The levels of glycine, a central component of one-carbon metabolism, were lower in mice with hepatic steatosis, consistent with clinical evidence. Stable-isotope tracing demonstrated that increased serine synthesis from glycine via reverse serine hydroxymethyltransferase (SHMT) is the underlying cause for decreased glycine in steatotic livers. Consequently, limited glycine availability in steatotic livers impaired glutathione synthesis under acetaminophen-induced oxidative …

Cell Cycle Arrest Induces Lipid Droplet Formation And Confers Ferroptosis Resistance, Hyemin Lee, Amber Horbath, Lavanya Kondiparthi, Jitendra Kumar Meena, Guang Lei, Shayani Dasgupta, Xiaoguang Liu, Li Zhuang, Pranavi Koppula, Mi Li, Iqbal Mahmud, Bo Wei, Philip L Lorenzi, Khandan Keyomarsi, Masha V Poyurovsky, Kellen Olszewski, Boyi Gan

Faculty, Staff and Student Publications

How cells coordinate cell cycling with cell survival and death remains incompletely understood. Here, we show that cell cycle arrest has a potent suppressive effect on ferroptosis, a form of regulated cell death induced by overwhelming lipid peroxidation at cellular membranes. Mechanistically, cell cycle arrest induces diacylglycerol acyltransferase (DGAT)-dependent lipid droplet formation to sequester excessive polyunsaturated fatty acids (PUFAs) that accumulate in arrested cells in triacylglycerols (TAGs), resulting in ferroptosis suppression. Consequently, DGAT inhibition orchestrates a reshuffling of PUFAs from TAGs to phospholipids and re-sensitizes arrested cells to ferroptosis. We show that some slow-cycling antimitotic drug-resistant cancer cells, such as …

2024-01-02 Message From The President, Morehead State University. Office Of The President.

Staff Congress Records

A message from the President to the campus community on upcoming events sent on January 2, 2024

2024-01-02 Message From The President, Morehead State University. Office Of The President.

Staff Congress Records

A message from the President to the campus community on spring convocation, upcoming events and the Martin Luther King Jr. commemoration event from January 2, 2024.

Injectable Hydrogel Electrodes As Conduction Highways To Restore Native Pacing, Gabriel J Rodriguez-Rivera, Allison Post, Mathews John, Skylar Buchan, Drew Bernard, Mehdi Razavi, Elizabeth Cosgriff-Hernandez

Faculty, Staff and Students Publications

There is an urgent clinical need for a treatment regimen that addresses the underlying pathophysiology of ventricular arrhythmias, the leading cause of sudden cardiac death. The current report describes the design of an injectable hydrogel electrode and successful deployment in a pig model with access far more refined than any current pacing modalities allow. In addition to successful cardiac capture and pacing, analysis of surface ECG tracings and three-dimensional electroanatomic mapping revealed a QRS morphology comparable to native sinus rhythm, strongly suggesting the hydrogel electrode captures the deep septal bundle branches and Purkinje fibers. In an ablation model, electroanatomic mapping …

Innovative Cyanine-Based Fluorescent Dye For Targeted Mitochondrial Imaging And Its Utility In Whole-Brain Visualization, Xin Yan, Xinqian Chen, Zhiying Shan, Lanrong Bi

Michigan Tech Publications

Conducting in vivo brain imaging can be a challenging task due to the complexity of brain tissue and the strict requirements for safe and effective imaging agents. However, a new fluorescent dye called Cy5-PEG2 has been developed that selectively accumulates in mitochondria, enabling the visualization of these essential organelles in various cell lines. This dye is versatile and can be used for the real-time monitoring of mitochondrial dynamics in living cells. Moreover, it can cross the blood-brain barrier, making it a promising tool for noninvasive in vivo brain imaging. Based on the assessment of glial cell responses in the hippocampus …

Hat: De Novo Variant Calling For Highly Accurate Short-Read And Long-Read Sequencing Data, Jeffrey K Ng, Tychele N Turner

2020-Current year OA Pubs

MOTIVATION: de novo variants (DNVs) are variants that are present in offspring but not in their parents. DNVs are both important for examining mutation rates as well as in the identification of disease-related variation. While efforts have been made to call DNVs, calling of DNVs is still challenging from parent-child sequenced trio data. We developed Hare And Tortoise (HAT) as an automated DNV detection workflow for highly accurate short-read and long-read sequencing data. Reliable detection of DNVs is important for human genomics and HAT addresses this need.

RESULTS: HAT is a computational workflow that begins with aligned read data (i.e. …

Fatty Acid Synthesis Suppresses Dietary Polyunsaturated Fatty Acid Use, Anna Worthmann, Sangeeta Adak, Clay F Semenkovich, Et Al.

2020-Current year OA Pubs

Dietary polyunsaturated fatty acids (PUFA) are increasingly recognized for their health benefits, whereas a high production of endogenous fatty acids - a process called de novo lipogenesis (DNL) - is closely linked to metabolic diseases. Determinants of PUFA incorporation into complex lipids are insufficiently understood and may influence the onset and progression of metabolic diseases. Here we show that fatty acid synthase (FASN), the key enzyme of DNL, critically determines the use of dietary PUFA in mice and humans. Moreover, the combination of FASN inhibition and PUFA-supplementation decreases liver triacylglycerols (TAG) in mice fed with high-fat diet. Mechanistically, FASN inhibition …

Hecatomb: An Integrated Software Platform For Viral Metagenomics, Michael J Roach, Sarah J Beecroft, Kathie A Mihindukulasuriya, Leran Wang, Anne Paredes, Luis Alberto Chica Cárdenas, Kara Henry-Cocks, Lais Farias Oliveira Lima, Elizabeth A Dinsdale, Robert A Edwards, Scott A Handley

2020-Current year OA Pubs

BACKGROUND: Modern sequencing technologies offer extraordinary opportunities for virus discovery and virome analysis. Annotation of viral sequences from metagenomic data requires a complex series of steps to ensure accurate annotation of individual reads and assembled contigs. In addition, varying study designs will require project-specific statistical analyses.

FINDINGS: Here we introduce Hecatomb, a bioinformatic platform coordinating commonly used tasks required for virome analysis. Hecatomb means "a great sacrifice." In this setting, Hecatomb is "sacrificing" false-positive viral annotations using extensive quality control and tiered-database searches. Hecatomb processes metagenomic data obtained from both short- and long-read sequencing technologies, providing annotations to individual sequences …

Genome-Wide And Targeted Crispr Screens Identify Rnf213 As A Mediator Of Interferon Gamma-Dependent Pathogen Restriction In Human Cells, Sumit K Matta, Hinissan P Kohio, Pallavi Chandra, Adam Brown, John G Doench, Jennifer A Philips, Siyuan Ding, L David Sibley

2020-Current year OA Pubs

To define cellular immunity to the intracellular pathogen

Cross-Border Conflict Peacebuilding Practices Of Dassanech, Nyangatom And Hammer Community Of Ethiopia And Turkana Of Kenya, Asmare Shetahun

Journal of African Conflicts and Peace Studies

This study investigated the practices of peacebuilding among Dassanech, Nyangatom, Hammer community of Ethiopia and the Turkana of Kenya cross-border resource based conflicts. Peace is the most important need and value of the pastoral community and conflict is destructive and unimportant by them. To build peace various actors are participated and different approaches are used. The study founded that the role of state, inter-state diplomacy, non-state actors, the civil society organizations, international organizations, intergovernmental organizations and indigenous community based institutions takes the loin share of conflict management, prevention, resolution and peacebuilding. However, the objective of building sustainable peace is still …

The Road To Genocide: Identity Politics Within Former State Institutions, The Case Of Caisse Sociale Du Rwanda, Elly Musafiri, George Gona, Kenneth Ombongi, Aggee Mugabe Shyaka

Journal of African Conflicts and Peace Studies

Scholarly works on the 1994 Genocide against the Tutsi have been too generic with minimal focus on institutional violence. Therefore, this paper addresses this knowledge gap by focusing on the former Caisse Sociale du Rwanda (CSR) as a case study. The research adopted a qualitative approach, with primary data being collected through structured and semi-structured interviews, which were administered to sixty-two (62) participants, and data collection methods were structured and semi-structured interviews, observation method, and secondary sources. Primary data was complemented and reinforced with data from secondary sources.

This research study, which is built on ideological and identitarianism discourses, addresses …

Coverage Of Food Security And Environmental Sustainability Issues In Saudi Arabias Electronic Press, Abdal Halim M. Y. Abdalrazig, Alanoud A. Al-Melhem, Afraa M. Al-Dossary

Journal of Statistics Applications & Probability

This study aimed to investigate the importance of food security and environmental sustainability in achieving the goals of Vision 2023 in Saudi Arabia. Data was collected using a survey approach with a questionnaire administered to 200 male and female students at different educational stages in the Faculty of Education at King Faisal University. Results showed that 82.5% of the total sample read Saudi electronic newspapers for at least one hour a day, with 14% reading for 1-3 hours, and 3.5% reading for three or more hours per day.

On The Way To The Altar: An Illustration Of Transpersonal Psychoanalytic Psychotherapy, Willow Pearson Trimbach

International Journal of Transpersonal Studies Advance Publication Archive

This paper illustrates transpersonal psychoanalytic psychotherapy through a detailed clinical example. A creative synthesis of Voice Dialogue work and Dreamtending, applied through storytelling and active imagination, is presented with a patient who is about to be married. Areas such as the therapeutic relationship including skills, techniques, clinical decisions, goals, interventions and the therapeutic space and presence are explored and discussed throughout the paper as they relate to transpersonal psychoanalytic psychotherapy.

Dreams, Synchrony, And Synchronicity, Terry Marks-Tarlow

International Journal of Transpersonal Studies Advance Publication Archive

No abstract provided.

Faculty Handbook, 2023-2024, University Of Arkansas, Fayetteville

Faculty Handbook

No abstract provided.

Umsl Bulletin 2023-2024, University Of Missouri-St. Louis

Bulletins

The 2023-2024 Bulletin and Course Catalog for the University of Missouri St. Louis.

Graduate Catalog Of Studies, 2023-2024, University Of Arkansas, Fayetteville

Graduate School Catalog of Studies

No abstract provided.

Wildfire And Asylum: A Terrapsychological Approach To Backyard Pilgrimage, Jacob Kaminker

International Journal of Transpersonal Studies Advance Publication Archive

This paper offers a conceptual framework and embodied practice of finding ones’ psychological roots through mythological re-emplacement. The author utilizes the lenses of depth psychology, terrapsychology, ritual and pilgrimage. The method also focuses on experiences of awe in nature as a catalyst for transpersonal experience. This deeply personal account offers a model for the reader’s own symbolic engagement with the physical, natural and historically rich world around them.

Rare And Undiagnosed Liver Diseases: New Insights From Genomic And Single Cell Transcriptomic Analyses, Chigoziri Konkwo

Yale Medicine Thesis Digital Library

Chronic liver disease (CLD) is a major global health problem, leading to an estimatedtwo million annual deaths worldwide. Advances in next generation sequencing (NGS) technologies have revolutionized our ability to diagnose and investigate disease pathogenesis. Our research group has previously shown that genomic analysis is useful in the diagnosis of patients with unexplained CLD, providing a diagnostic yield of up to 30%. Moreover, this approach has revealed a newly described cause of non-cirrhotic portal hypertension and nodular regenerative hyperplasia due to GIMAP5 deficiency, which is recapitulated in a mouse model. Additionally, the growing use of single cell RNA sequencing (scRNA-seq) …

Coming Home Nw: A Compelling Invitation To Connect With Nature For Improving And Sustaining Health, Strengthening Identity, And Deepening Relationship With God, Jennifer Lynn Steinbrenner Hale

Doctor of Leadership

The Covid-19 Pandemic has created an opportunity in local churches of the Pacific Northwest to develop new ways of connecting to God and improving health through movement in nature. The Pandemic damaged physical, mental, and social wellness for individuals and communities, as well as highlighted areas of dysfunction existent before the Pandemic. Research shows that when human beings engage with nature, they experience improved physical, psychological, cognitive, and spiritual health. Through activities such as running, walking, or simply sitting still in a natural environment, participants have the opportunity to deepen their relationship with God and strengthen their identity and understanding …

Trauma-Informed Leadership And Innovation In Adversity: Resilience On The Wings Of Joy: A Guide To Posttraumatic Growth, Jean De Dieu Ndahiriwe

Doctor of Leadership

My current ministry in chaplaincy involves helping those I serve find hope and better coping mechanisms as they deal with life behind bars and to help them remain productive citizens, once released back into the community. Unfortunately, several of these inmates struggle due to countless causes, including unresolved childhood trauma. They often fail to settle back into the community even after release, returning to prison to serve more sentences, a vicious cycle that seems to keep repeating. Similar challenges of failure to thrive are evident among immigrants and refugees, especially child refugees. I was born during a time of civil …

Evaluation Of E-Governance Implementation: A Multi-Attribute Analysis Of E-Government Services Associated With The Annual Hajj Pilgrimage In Saudi Arabia, Moayad Mohammed M. Hakeem

Selected Full Text Dissertations, 2011-

The Hajj pilgrimage is an annual global event in Saudi Arabia. It draws millions of pilgrims worldwide because of its religious significance as the fifth pillar of Islam. Its organization is a massive endeavor for the Saudi government. This research analyzes the Hajj-related E-Government service systems (websites and mobile apps). This research utilizes a multi-attribute evaluative framework to address two areas of Hajj E-Government services: usability (RQ1) and interaction with the services (RQ2). A combination of heuristic evaluation and survey methods was used. The heuristic evaluation by three expert evaluators revealed accessibility, interactivity, and functional issues. Users with disabilities or …

Development Of Bibliotherapy For Emetophobia In Children, Katerina Levy M.S.

Selected Full Text Dissertations, 2011-

Emetophobia has been cited in the literature as one of the least understood and largely understudied anxiety disorders and is estimated to impact 2-7% of the population (Boschen, 2007; Graziano et al., 2010; Hunter & Anthony, 2009; Marks, 1987; Veale & Lambrou, 2006). Even less is known about emetophobia in children, and research has primarily focused on case studies to highlight the phenomenology of emetophobia as well as the trajectory of treatment (Graziano et al., 2010). Given the limited knowledge on emetophobia, few resources exist to aid and facilitate treatment (i.e., children’s storybooks or treatment manuals). Including children’s books in …

Sash: Student Academic Showcase And Honors 2024, Roger Williams University

Student Academic Showcase and Honors

A celebration of scholarship and creative activities for undergraduate and graduate students.

Annual Report Of The Town Officers Northwood, Nh For The Fiscal Year Ending December 31, 2023 And Of The School District For The Fiscal Year Ending June 30, 2023., Northwood Town Representatives

Northwood, NH Annual Reports

This is an annual report containing vital statistics for a town/city in the state of New Hampshire.

Town Of Francestown, New Hampshire 2023 Annual Reports Of The Officials, Departments, And Committee Of The Town Of Francestown For The Calendar Year Ending December 31, 2023., Francestown Town Representatives

Francestown, NH Annual Reports

This is an annual report containing vital statistics for a town/city in the state of New Hampshire.

Homily For Mass Of The Holy Spirit, Dale Launderville Osb

Obsculta

This year, the monks of Saint John’s Abbey, the sponsoring religious order of the Saint John’s School of Theology and Seminary, convened to elect a new abbot, after the retirement of the previous, who had served for twenty years. This homily was given by Father Dale Launderville, OSB at the Mass of the Holy Spirit, which both opened the official election process and was the culmination of a year-long process of discernment and prayer that enable the monks to enter the voting confident of the aid of the Holy Spirit.

Augustine's Analogy: How To Say God, Eric Kalimbiriro Osc

Obsculta

Augustine's analogy of the Trinity regards the question of how to speak about God. Augustine maintained that human language and material images are limited in their ability to wholly capture the essence of God, who is beyond human comprehension. He understood that the language we use to describe God is necessarily metaphorical and analogical, as we cannot fully grasp the transcendent nature of the divine. By using analogy, Augustine aimed to help his audiences come to some rudimentary understanding of the Trinity. This paper argues that Augustine's use of analogy provides a persuasive approach for understanding the Trinity. It focuses …