Digital Commons Network^™

Next-Gen Tools In Cancer Neuroscience, Vera Thiel, Debpali Sur, Caroline C Picoli, Tamara Mcerlain, Katalina Couto, David J Simon, Yuan Pan, Karen Olivia Dixon, Rajan P Kulkarni, Sebastien Talbot, Alexander Birbrair

Faculty, Staff and Student Publications

The emerging field of cancer neuroscience is rapidly evolving, driven by novel technologies and tools. These include advances in single-cell and spatial transcriptomics; genetic mouse models paired with automated high-throughput; and innovative optical electrophysiological approaches, optogenetics, chemogenetics, engineered viruses, and new methods for visualizing neuronal activity. Collectively, these technologies are revolutionizing how we investigate, manipulate, and characterize distinct components that contribute to the nervous system-cancer interface. In the present review, we discuss the key technologies that are closing the gap between oncology and neuroscience, highlighting the innovations that are propelling the cancer neuroscience field forward.

Identifying Independent Predictors Of Malignancy In Indeterminate Thyroid Nodules: A Systematic Review, Tirath Patel, Jabez David John, Arnesh Shukla, Ayesha Salma, Dev Patel, Anaya Noor, Gayatri Misra, Pragnesh Kalyandrug, Harshitha Nookala, Nikhilesh Anand

School of Medicine Publications

Introduction: Considering the importance of differentiating between benign and malignant thyroid nodules, this study explores the individual predictors of malignancy. Recent research has focused on individual predictors of isolation, but a comprehensive assessment of these predictors is essential to improve diagnostic accuracy and patient outcomes.

Methods: This comprehensive systematic review included seven articles after a rigorous screening of PubMed, PubMed Central, and MEDLINE databases and thus analyzed 1419 patients with indeterminate thyroid nodules using different determinants, such as genetic, biochemical, clinical, radiological, and cytological.

Results: Numerous independent indicators, such as a history of Hashimoto's thyroiditis, multinodular goiter, and past malignant …

Rna/Dna-Binding Protein Tdp43 Regulates Dna Mismatch Repair Genes With Implications For Genome Stability, Vincent E Provasek, Albino Bacolla, Suganya Rangaswamy, Manohar Kodavati, Joy Mitra, Issa O Yusuf, Vikas H Malojirao, Velmarini Vasquez, Gavin W Britz, Guo-Min Li, Zuoshang Xu, Sankar Mitra, Ralph M Garruto, John A Tainer, Muralidhar L Hegde

Faculty, Staff and Student Publications

TDP43 is an RNA/DNA-binding protein increasingly recognized for its role in neurodegenerative conditions, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). As characterized by its aberrant nuclear export and cytoplasmic aggregation, TDP43 proteinopathy is a hallmark feature in over 95% of ALS/FTD cases, leading to detrimental cytosolic aggregates and a reduction in nuclear functionality in neurons. Building on our prior work linking TDP43 proteinopathy to the accumulation of DNA double-strand breaks (DSBs) in neurons, the present investigation uncovers a novel regulatory relationship between TDP43 and DNA mismatch repair (MMR) gene expression. Here, we show that TDP43 depletion or overexpression …

Sars-Cov-2 Nsp13 Interacts With Tead To Suppress Hippo-Yap Signaling, Fansen Meng, Jong Hwan Kim, Chang-Ru Tsai, Jeffrey D Steimle, Jun Wang, Yufeng Shi, Rich G Li, Bing Xie, Vaibhav Deshmukh, Shijie Liu, Xiao Li, James F Martin

Faculty, Staff and Students Publications

The Hippo pathway controls organ development, homeostasis, and regeneration primarily by modulating YAP/TEAD-mediated gene expression. Although emerging studies report Hippo-YAP dysfunction after viral infection, it is largely unknown in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we analyzed RNA sequencing data from human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and SARS-CoV-2-infected human lung samples, and observed a decrease in YAP target gene expression. In screening SARS-CoV-2 nonstructural proteins, we found that nonstructural protein 13 (NSP13), a conserved coronavirus helicase, inhibits YAP transcriptional activity independent of the upstream Hippo kinases LATS1/2. Consistently, introducing NSP13 into mouse cardiomyocytes suppresses …

Atrial Fibroblast-Derived Macrophage Migration Inhibitory Factor Promotes Atrial Macrophage Accumulation In Postoperative Atrial Fibrillation, Joshua A Keefe, Jose Alberto Navarro-Garcia, Shuai Zhao, Mihail G Chelu, Xander Ht Wehrens

Faculty, Staff and Students Publications

New study: Blocking MIF protein prevents irregular heartbeats after surgery by reducing harmful immune cell buildup in the atria.

Dietary Methionine Restriction Primes T Cell Metabolism For Activation And Tumor Inhibition And Enhances The Efficacy Of Immune Checkpoint Blockade, Xiaoqing Qing, Binita Chakraborty, Panpan Liu, Sandeep Artham, Patrick K Juras, Dongyin Guan, Kristen E Pauken, Ching-Yi Chang, Xia Gao

Faculty, Staff and Students Publications

The proliferation of many cancer cells is methionine dependent and dietary methionine restriction (MR) has shown anti-tumor effects in a wide variety of immunodeficiency preclinical models. Yet, whether MR exerts an anti-tumor effect in the presence of an immune-competent background remains inconclusive. Accumulating evidence has shown an essential role of methionine in immune cell differentiation and function. Thus, competition for methionine between tumor cells and immune cells in the tumor microenvironment may drive tumor growth and tumor response to therapy. Here, we aim to define the impact of MR on tumor growth and associated immunity. We first assessed the effect …

Adsl Deficiency Is A Secondary Mitochondrial Disease Affecting Organelle Homeostasis And Erk2/Akt Signaling In A Linear Genotype-Phenotype Relation, Matteo Bordi, Beatrice Testa, Claudia Compagnucci, Fiorella Colasuonno, Francesca Cipressa, Elisabetta Betterini, Andrea Mancini, Claudia Carsetti, Illari Salvatori, Caterina Ferraina, Ming Yang, Rossella De Cegli, Eugenio Del Prete, Chiara Veroni, Salvatore Rizza, Sofia Mauri, Elena Ziviani, Marina Macchiaiolo, Davide Vecchio, Filippo Maria Panfili, Teresa Rizza, Gerrit Weber, Rosalba Carrozzo, Alberto Ferri, Silvia Campello, Andrea Ballabio, Christian Frezza, Gianluca Cestra, Marco Tartaglia, Andrea Bartuli, Francesco Cecconi

Duncan NRI Faculty and Staff Publications

Adenylosuccinate lyase deficiency (ADSLd) is a rare autosomal recessive purine metabolism disorder with several clinical manifestations. While toxic substrate accumulation is a known hallmark, no additional molecular mechanisms have been established. Here, we show that ADSLd is associated with mitochondrial dysfunction, including increased fragmentation, impaired respiration, and reduced ATP production. The severity of mitochondrial impairment correlates with ADSLd pathology, especially in mitochondria-dependent tissues. We also identify defects in mitochondrial dynamics and transport linked to ERK2 and AKT suppression. Notably, overexpressing constitutively active ERK2 or supplementing purine intermediates partially rescues the mitochondrial phenotype. These findings suggest an alternative disease mechanism and …

Humanization Of Cd47 Enables Development Of Functional Human Neutrophils Via Postirradiation Remodeling Of The Bone Marrow, Esen Sefik, Liang Shan, Et Al.

2020-Current year OA Pubs

Murine and human immune systems differ significantly, particularly within the myeloid lineage. Humanized mice, generated by transplanting human hematopoietic stem, progenitor cells into genetically modified mice, are invaluable to study human immune development and function in vivo. However, a major limitation of current models is suboptimal myelopoiesis, particularly lack of functional human neutrophils, hampering the modeling of human immune responses and chronic diseases. Here, we describe a humanized mouse model, named MaGIC for genes replaced, in the

Use Of Amplified Lewy Body Dementia Fibrils And Autoradiography To Characterize Binding Of Radioligand Tg-1-90b To Alpha-Synuclein Fibrils In Postmortem Brain Tissue, Jennifer Y O'Shea, Dhruva D Dhavale, Helen Hwang, Zachary Smith, Thomas J A Graham, Robert H Mach, Paul T Kotzbauer

2020-Current year OA Pubs

Parkinson's disease (PD) and Lewy Body Dementia (LBD) are defined by accumulation of alpha-synuclein (Asyn) fibrils within Lewy bodies (LBs) and Lewy neurites (LNs). The development of a Positron Emission Tomography (PET) tracer for quantifying Asyn fibrils would improve diagnostic accuracy and provide a biomarker for disease progression. We previously described radioligand [

Immunotherapy For Precision Medicine In Colorectal Cancer, Miao Cao, Michael Xu, Zinah Bairmani, Babar Bashir, Scott A. Waldman, Adam E. Snook

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

INTRODUCTION: Colorectal cancer (CRC) is the fourth most common cancer and second leading cause of cancer-related death in the United States. The implementation of CRC screening has decreased CRC incidence in adults older than 65 years. However, among young adults who experience more aggressive disease progression, CRC incidence has been increasing for decades. Immunotherapy represents a collection of innovative and promising approaches with greater efficacy and safety. In this review, we discuss modalities and selected targets of immunotherapies for CRCs that are guided by precision medicine.

AREAS COVERED: The following review focuses on immunological approaches for CRCs, including therapeutic monoclonal …

Global Variations In Surgical Techniques For Primary Anterior Cruciate Ligament Reconstruction At Minimum 2-Year Follow-Up: A Systematic Review Of Randomized Clinical Trials, Sina Tartibi, Derrick M Knapik, S Ryan Pierson, Christopher K Bozorgmehr, Daniel C Touhey, Matthew J Matava, Matthew V Smith, Robert H Brophy

2020-Current year OA Pubs

BACKGROUND: Regional differences in primary anterior cruciate ligament (ACL) reconstruction (ACLR) remain largely unknown.

PURPOSE: To systematically review the literature examining Level 1 and Level 2 studies to identify global differences in surgical techniques associated with primary ACLR.

STUDY DESIGN: Scoping review; Level of evidence, 1.

METHODS: A literature search was conducted following the 2020 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using keywords and Boolean phrases in Embase, Cochrane, and PubMed on October 25, 2024. A total of 741 articles were identified. The inclusion criteria were as follows: Level 1 and Level 2 human studies reporting …

Retracted: Idea Density And Grammatical Complexity As Neurocognitive Markers, Diego Iacono, Gloria Feltis

Department of Neurology Faculty Papers

Language, a uniquely human cognitive faculty, is fundamentally characterized by its capacity for complex thoughts and structured expressions. This review examines two critical measures of linguistic performance: idea density (ID) and grammatical complexity (GC). ID quantifies the richness of information conveyed per unit of language, reflecting semantic efficiency and conceptual processing. GC, conversely, measures the structural sophistication of syntax, indicative of hierarchical organization and rule-based operations. We explore the neurobiological underpinnings of these measures, identifying key brain regions and white matter pathways involved in their generation and comprehension. This includes linking ID to a distributed network of semantic hubs, like …

Neurofilament Light (Nfl) Chain Levels Predict Clinical Decline In Alzheimer’S Disease: A Systematic Review And Meta-Analysis, Kim Thomas, Paul Spin, Nikita Sir, Kevin Hou, Nicholas J. Ashton, Henrik Zetterberg, Sonya Miller, Carol Pringle, Richard G. Stefanacci, Claude M. Wischik, Serge Gauthier

College of Population Health Faculty Papers

BACKGROUND: Regulatory approval of new investigational Alzheimer's disease (AD) therapies could be accelerated if reasonably likely surrogate endpoints could be used. Neurofilament light chain (NfL) has potential utility as a prognostic biomarker of neurodegeneration in AD.

OBJECTIVE: To synthesize available evidence on the relationship between baseline NfL levels and longitudinal clinical decline.

METHODS: A systematic literature review identified 19 eligible studies, contributing 37 longitudinal statistical models evaluating the association between baseline NfL (plasma or cerebrospinal fluid [CSF]) with subsequent clinical decline based on validated clinical scales including Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale, and Clinical Dementia Rating. …

Interleukin-6 (Il-6) Mediated Pathways In Nonalcoholic Fatty Liver Disease (Nafld) And Its Implications On Magnesium And Zinc Mineral Deficiencies: A Scoping Review, Marianne Koleng, Leann Nguyen

Department of Nutrition Student Projects

The prevalence and incidence of Non-Alcoholic Fatty Liver Disease (NAFLD) is rising. In the United States alone, the prevalence of NAFLD is currently 38% and there has been a 50% increase over the last three decades. The present study investigated the role of ultratrace mineral deficiencies, specifically magnesium (Mg) and zinc (Zn), and if so, what nutritional interventions could be made to ameliorate or protect against the development of NAFLD. The role of trace and ultratrace minerals in pro-inflammatory cytokine pathways contributing to NAFLD, specifically Interleukin-6 (IL-6), were investigated. IL-6 is produced by hepatocytes and plays a crucial role in …

Segmenting The Flour Beetle: Rnai Probes Into Embryonic Gene Function In Tribolium Castaneum, Sydney Do, J. Garcia, Ezzat El-Sherif

Research Colloquium

Background: RNA interference (RNAi) silences specific gene expression through the introduction of double-stranded RNA (dsRNA). In Tribolium castaneum, RNAi enables precise manipulation of gene activity, allowing researchers to study developmental processes and genetic interactions across all life stages. dsRNA is processed by ribonucleases into small interfering RNAs (siRNAs) or microRNAs (miRNAs), which are recruited by the RNA-induced silencing complex (RISC), which targets and degrades specific mRNA molecules, allowing the observation of loss-of-function phenotypes.

T. castaneum offers advantages as a model for RNAi studies, including a fully annotated genome, a strong RNAi response, ease of application, and gene expression dynamics …

High Phosphorus Diets And Bone Health: A Hidden Risk​, Sean Corcoran, Daniela Ramos, Mohammed Razzaque

Research Colloquium

Background: As fast food, high in phosphorus content, becomes a staple in the American diet, the population increases its dietary phosphorus intake above the recommended amount. According to the NIH guidelines, adults over 19 years and older are 700mg per day (NIH, 2021, Wickham). For context, a meal consisting of a big cheeseburger, medium fries, and a can of soda contains around 600mg of phosphorus (Arquette, 2014). Although phosphorus is essential for bone health as it is part of the structural component of bones, consuming excess amounts of phosphorus has been linked to vascular calcification, cardiovascular disease, kidney disease, and …

Murine Typhus Masquerading As A Urinary Tract Infection: A Case From Endemic South Texas, Nida Asif, Yareli Durazo, Corey Haines, Cesar Gutierrez

Research Colloquium

Background: Murine Typhus is a rare flea borne illness caused by Rickettsia typhi, with approximately 100-200 cases reported annually in the United States, primarily in Southern Texas, California and Hawaii, transmitted by fleas from rodents or other animals. It often presents with nonspecific symptoms, making diagnosis challenging. Given its vague clinical presentation and regional endemicity, murine typhus is frequently underrecognized delaying appropriate treatment.

Case presentation:A 77-year-old lady with a known history of HFrEF of 25-30% was presented to the ED due to mild left lower quadrant abdominal pain associated with two episodes of loose bowel movements and decreased appetite …

Determining The Effects Of An Hiv Infective Model On The Development Of Neuropathic Pain In Alzheimer’S Disease Model Mice., Ayesha Usman, Megan W. Szobody, Jose Rios, Mohammed Alnoud, Khalid Benamar

Research Colloquium

The purpose of this study is to determine the effect of the Human Immunodeficiency virus (HIV) in producing neuropathic pain in an Alzheimer’s Disease (AD) mouse model. HIV-1 envelope glycoprotein gp120 is correlated with increased release of thermal hyperalgesia and mechanical allodynia mediators from astrocytes and glial cells in rodents, producing the identifiable symptoms of neuropathic pain. Similarly, studies show that 45.8% of AD patients experience chronic pain. The production of an HIV/AD comorbid mouse model will be useful in determining important pathological pathways for neuropathic pain and is vital to future studies in therapeutic approaches to these conditions. Two …

Role Of Vitamin D In Periodontal Integrity And Cognitive Function Among Older Adults: A Nhanes 2011 Study, John Nicholas Cauba, Noah Al-Hassan, Taha Al-Hassan, Krishi Korrapati, Maria Quiniones, Seratna Guadarrama, Juan Lopez-Alvarenga

Research Colloquium

Background: Periodontal disease, characterized by inflammation and damage to connective tissue due to biofilm accumulation and an inflammatory response, affects 20–50% of the global population. While some studies suggest a link between periodontal disease and cognitive decline, the role of vitamin D in this relationship remains underexplored. Given vitamin D’s involvement in immune modulation, bone remodeling, and possibly cognition, we hypothesize that higher serum 25(OH)D3 levels are associated with reduced periodontal damage and better cognitive performance in older adults.

Methods: We analyzed data from 905 participants (50% female), aged ≥60 years, in the NHANES 2011– 2012 cycle with complete periodontal …

Semax For Parkinson’S Neuroprotection: A Qualitative Review Of Preclinical Evidence, Jefferson Tait, Mohammad Yaman Karkoutly, David Rakay, Edurado Aquino

Research Colloquium

Background: The use of peptides as an alternative treatment for neurological disease is an emerging practice that has had tremendous success. Semax, a synthetic heptapeptide derived from adrenocorticotropic hormone (ACTH 4–10), is well known and used clinically in Russia and Eastern Europe for ischemic stroke therapy. Moreover, Semax has also been reported to modulate monoaminergic systems. Because Parkinson’s disease (PD) involves the loss of dopaminergic neurons, Semax’s neuromodulatory properties make it a potential candidate for the treatment of Parkinson's. Here, we hope to evaluate whether Semax could be an alternative therapy for PD by reviewing evidence on its effects on …

Antiplatelet Effects Of Angelica Dahurica Root Extract Without Gastric Lesion Formation In Rats, Pitiphat Srisom, Kasem Rattanapinyopituk, Uthai Sotanaphun, Rataya Luechapudiporn

The Thai Journal of Pharmaceutical Sciences

Background: Platelet aggregation plays a crucial role in hemostasis; however, excessive platelet activation can lead to thrombus formation, contributing to cardiovascular diseases. While aspirin (acetylsalicylic acid [ASA]) is commonly used as an antiplatelet agent, its longterm use is associated with gastrointestinal side effects. Angelica dahurica (AD), a traditional herbal remedy, has shown in vitro antiplatelet activity and cyclooxygenase enzyme inhibition. However, its in vivo effects on platelet aggregation and gastric safety remain unclear.

Objectives: This study aimed to investigate whether Angelica dahurica root extract (ADE) could inhibit platelet aggregation and prevent aspirin-induced gastric lesions.

Materials and Methods: AD was extracted …

Bone-Sparing Effects Of Pueraria Mirifica Extract On Bone Loss In Androgen-Deficient Cynomolgus Macaques (Macaca Fascicularis), Thaweechai Saetae, Taratorn Kemthong, Sukanya Jaroenporn, Suchinda Malaivijitnond

The Thai Journal of Pharmaceutical Sciences

Background: Synthetic estrogens provide remarkable benefits for bone health in men; however, they also present several drawbacks after long-term use. Pueraria mirifica, a phytoestrogen-rich herb, has garnered attention due to its positive effects and minimal adverse side effects on bone in females. Most research on bone health has been conducted on rodents; however, bone architecture and remodeling in rodents differ from those in humans, making it challenging to apply the results to clinical trials.
Objectives: Thus, this study assessed the bonesparing effects of P. mirifica extract (PME) in androgen-deficient male cynomolgus macaques.

Materials and Methods: Adult male macaques were divided …

Screening And Evaluation Of Thai Herbal Plants As Multifunctional Agents For Targeting Amyloid Β Pathogenesis In Alzheimer's Disease, Ruedeemars Yubolphan, Suchinda Malaivijitnond, Sukanya Jaroenporn

The Thai Journal of Pharmaceutical Sciences

Background: Alzheimer's disease (AD) is a neurodegenerative disorder driven by complex pathophysiological processes. Current therapeutic strategies emphasize the development of multifunctional agents, particularly those derived from natural sources, to target multiple stages of the amyloid β (Aβ) cascade, a central contributor to AD pathology.

Objectives: This study aimed to investigate the anti-Aβ activity of nine Thai herbs and evaluate their potential as multifunctional agents for AD treatment.

Methods: Nine Thai herbs—Caesalpinia sappan (CS), Thunbergia laurifolia (TL), Rhinacanthus nasutus (RN), Tabernaemontana divaricata (TD), Cyperus rotundus (CR), Terminalia chebula (TC), Azadirachta indica (AI), Piper retrofractum (PR), and Asparagus racemosus (AR)—were screened …

Identifying Factors Linked To A Higher Prevalence Of Posttraumatic Stress Disorder Among Younger Us Military Veterans, Jordan Hathorn

Yale School of Medicine Physician Associate Program Theses

Objectives: Posttraumatic stress disorder is a significant public health concern in the U.S., with military veterans disproportionately affected. Although younger veterans exhibit a higher prevalence of PTSD compared to their older counterparts, the mechanisms driving this age-related difference remain unclear. This study examined sociodemographic, trauma-specific, and psychosocial factors that may contribute to the elevated prevalence of PTSD in younger (age < 50) vs. older (age 50 and older) veterans.

Methods: Data were analyzed from the National Health and Resilience in Veterans Study (NHRVS), which surveyed a nationally representative sample of US military veterans (n=4,069).

Results: Younger veterans were three times more likely to screen positive for PTSD compared to …

Medical Guidelines For Fibrodysplasia Ossificans Progressiva, Frederick S. Kaplan, Mona Al Mukaddam, Genevieve Baujat, Alberto Hidalgo Bravo, Matthew Brown, Amanda Cali, Tae-Joon Cho, Corrie Crowe, Carmen L. De Cunto, Patricia L. R. Delai, Robert J. Diecidue, Elisabeth Marelise W Eekhoff, Lisa Friedlander, Clive S. Friedman, Zvi Grunwald, Nobuhiko Haga, Edward C. Hsiao, Richard Keen, Joseph A. Kitterman, Charles Levy, Vrisha Madhuri, Rolf Morhart, J. Coen Netelenbos, Christiaan Scott, Eileen M. Shore, Michael Zasloff, Keqin Zhang, Robert J. Pignolo

Department of Oral and Maxillofacial Surgery Faculty Papers

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic condition characterized by congenital malformations of the great toes and progressive heterotopic ossification (HO) in specific anatomic patterns. Present management summarized here is focused on early diagnosis, assiduous avoidance of injury and iatrogenic harm, symptomatic amelioration of painful flare-ups, and optimization of residual function. Twenty-one members of the International Clinical Council on FOP (ICC) and seven consultants from 15 countries, chosen for their clinical expertise in FOP, developed this summary statement. Further advances in therapeutics will be based on rigorous clinical trials to assess novel and emerging treatment and prevention strategies. A …

Prenatal Metabolomics Analysis And Fetal Congenital Anomalies And Genetic Conditions: A Review Of Current Literature, Sarah Araji, Onur Turkoglu, Mohamad Ali Maktabi, Tracy Ashby, Ignatia B Van Den Veyver

Library Staff Publications

Fetal congenital anomalies and genetic disorders complicate 3%-5% of pregnancies and can have a significant impact on pregnancy outcomes. Precise and individualized prenatal diagnosis is crucial for effective counseling and management. The identification of new biomarkers holds promise for enhancing prenatal screening, diagnosis, and prognostic counseling in affected pregnancies. Recently, metabolomics has emerged as a potential adjunct in the interpretation of genetic variants identified through genome-wide sequencing for rare genetic conditions. To assess the potential of metabolomic profiling as a functional assay capable of providing deeper insights into the pathological processes and genetic findings associated with prenatal congenital anomalies, we …

Protocol For Non-Invasive Pulsed-Doppler Evaluation Of Blood Flow In The Mouse Ophthalmic Artery, Radwa Awad, Emil Martin, Anilkumar K Reddy, Iraida Sharina

Faculty, Staff and Student Publications

The number of reliable and non-invasive techniques to characterize ocular blood flow is limited. Here, we present a protocol for identifying a soft tissue window in the orbital aperture using pulsed-Doppler ultrasonography to offer real-time, non-invasive blood flow velocity monitoring in the mouse ophthalmic artery. We describe steps for preparing a mouse, positioning the ultrasound probe, and acquiring and recording signals. We then detail procedures for analyzing results using a workstation equipped with Doppler flow velocity software. For complete details on the use and execution of this protocol, please refer to Sharina et al.

Grit, A Component Of Resident Well-Being, Nathan W. Olson, Kelly Williamson, Nicholas Hartman, Navneet Cheema, Adriana S. Olson

Journal of Wellness

Introduction: Trainees experiencing burnout, depression, or career dissatisfaction challenge educators and may have patient care consequences. Grit, defined as the “perseverance and passion for long-term goals,” buffers against hopelessness and quantifies an aspect of personality shown to predict fewer career changes. Higher grit has been associated with positive outcomes in physicians, including lower burnout rates. Our objective was to determine the correlation between emergency medicine (EM) resident Short Grit Scale (Grit-S) scores and components of well-being: burnout, a positive depression screen, and career satisfaction.

Methods: This was a prospective, multicenter trial involving ten urban/suburban EM residencies. The subjects …

Blue-Shifted Ancyromonad Channelrhodopsins For Multiplex Optogenetics, Elena G Govorunova, Oleg A Sineshchekov, Hai Li, Yueyang Gou, Hongmei Chen, Shuyuan Yang, Yumei Wang, Stephen Mitchell, Alyssa Palmateer, Leonid S Brown, François St-Pierre, Mingshan Xue, John L Spudich

Duncan NRI Faculty and Staff Publications

Light-gated ion channels from protists (channelrhodopsins or ChRs) are optogenetic tools widely used for controlling neurons and cardiomyocytes. Multiplex optogenetic applications require spectrally separated molecules, which are difficult to engineer without disrupting channel function. Scanning numerous sequence databases, we identified three naturally blue-shifted ChRs from ancyromonads. They form a separate branch on the phylogenetic tree and contain residue motifs characteristic of anion ChRs (ACRs). However, only two conduct chloride, whereas the closely related Nutomonas longa homolog generates inward cation currents in mammalian cells under physiological conditions, significantly exceeding those by previously known tools with similar spectral maxima (peak absorption at …

From Venom To Medicine: Harnessing Animal Toxins For Drug Discovery, Christine Vega, Ying Jia

Research Colloquium

Background: Drug development research has long focused on synthesizing novel therapeutics while overlooking isolation from naturally available sources such as animal venoms. Recently, the discovery of the therapeutic effects of highly bioavailable animal venom caused the field of venom research to soar in popularity. Animal venom serves as a natural, sophisticated tool optimized over millions of years by evolution with the ability to bind to ion channels such as nAChRs, non-specific ligand-gated ion channels distributed throughout the human nervous system. However, purifying individual venom toxins from crude venom is challenging due to its availability. Therefore, synthesizing large quantities of venom …