Digital Commons Network^™

A Spef1-Interacting Microtubule Quartet Protein In Trypanosoma Brucei Promotes Flagellar Inheritance By Regulating Basal Body Segregation, Kieu T M Pham, Qing Zhou, Kyu Joon Lee, Ziyin Li

Faculty, Staff and Student Publications

The human parasite Trypanosoma brucei contains a motile flagellum that determines the plane of cell division, controls cell morphology, and mediates cell-cell communication. During the cell cycle, inheritance of the newly formed flagellum requires its correct positioning toward the posterior of the cell, which depends on the faithful segregation of multiple flagellum-associated cytoskeletal structures including the basal body, the flagellar pocket collar, the flagellum attachment zone, and the hook complex. A specialized group of four microtubules termed the microtubule quartet (MtQ) originates from the basal body and runs through the flagellar pocket collar and the hook complex to extend, along …

Prognostic Serum Biomarkers In Cancer Patients With Covid-19: A Systematic Review, Te-An Lee, Shih-Han Wang, Chun-Tse Kuo, Chia-Wei Li, Louise D Mccullough, Dhimiter Bello, Yun-Ju Lai

Faculty, Staff and Student Publications

Purpose: Cancer patients with COVID-19 likely express biomarker changes in circulation. However, the biomarkers used in SARS-CoV-2 infected cancer patients for COVID-19 severity and prognosis are largely unclear. Therefore, this systematic review aims to determine what biomarkers were measured in cancer patients with COVID-19 and their prognostic utility.

Methods: A systematic literature review in PubMed, Embase, and Scopus was performed on June 16th, 2021. The search keywords coronavirus, neoplasm, biomarkers, and disease progression were used to filter out 17 eligible studies, which were then carefully evaluated.

Results: A total of 4,168 patients, 16 types of cancer, and 60 biomarkers were …

Hypertension In Pregnancy And Adverse Outcomes Among Low-Risk Nulliparous People Expectantly Managed At Or After 39 Weeks: A Secondary Analysis Of A Randomized Controlled Trial, Michal Fishel Bartal, Ashish Premkumar, Madeline Murguia Rice, Uma M Reddy, Alan T N Tita, Robert M Silver, Yasser Y El-Sayed, Ronald J Wapner, Dwight J Rouse, George R Saade, John M Thorp, Maged M Costantine, Edward K Chien, Brian M Casey, Sindhu K Srinivas, Geeta K Swamy, Hyagriv N Simhan, Eunice Kennedy Shriver National Institute Of Child Health And Human Development (Nichd) Maternal-Fetal Medicine Units (Mfmu) Network

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate whether hypertensive disorders of pregnancy (HDP) among low-risk nulliparous women expectantly managed at or after 39 weeks of gestation are associated with adverse outcomes.

DESIGN: Secondary analysis of a randomised trial.

SETTING: Multicentre, USA.

POPULATION: Individuals in the expectantly managed group who delivered on or after 39 weeks.

METHODS: Multivariable analysis to estimate adjusted relative risks (aRR) for binomial outcomes, adjusted odds ratios (aOR) for multinomial outcomes and 95% CI.

MAIN OUTCOME MEASURES: Composite adverse maternal outcome including placental abruption, pulmonary oedema, postpartum haemorrhage, postpartum infection, venous thromboembolism or intensive care unit admission. Secondary outcomes included a …

Minimal Clinically Important Differences Of Promis Pf In Ankle Fracture Patients, Luke Myhre, Patrick Kellam, Graham Dekeyser, Haojia Li, Yue Zhang, Amy M Cizik, Justin Haller

Faculty, Staff and Student Publications

BACKGROUND: Evaluating the minimal clinically important differences (MCIDs) in patient-reported outcome scores is essential for use of clinical outcomes data. The purpose of the current study was to calculate MCID of Patient Reported Outcome Information System Physical Function (PROMIS PF) scores for ankle fracture patients.

METHODS: All patients who underwent operative fixation for ankle fractures at a single level 1 trauma center were identified by

RESULTS: A total of 331 patients were included in the distribution-based analysis, and 195 patients were included in the anchor-based analysis. Mean age was 45.3 years (SD 17.5), and 59.4% of participants were female. MCID …

Michigan Plan For Appropriate Tailored Healthcare In Pregnancy Prenatal Care Recommendations: A Practical Guide For Maternity Care Clinicians, Alex Friedman Peahl, Mark Turrentine, Wanda Barfield, Sean C Blackwell, Christopher M Zahn

Faculty, Staff and Student Publications

Prenatal care is an important preventive service designed to improve the health of pregnant patients and their infants. Prenatal care delivery recommendations have remained unchanged since 1930, when the 12-14 in-person visit schedule was first established to detect preeclampsia. In 2020, the American College of Obstetricians and Gynecologists, in collaboration with the University of Michigan, convened a panel of maternity care experts to determine new prenatal care delivery recommendations. The panel recognized the need to include emerging evidence and experience, including significant changes in prenatal care delivery during the COVID-19 pandemic, pre-existing knowledge of the importance of individualized care plans, …

Impact Of Gap Distance Between Fenestration And Aortic Wall On Target Artery Instability Following Fenestrated-Branched Endovascular Aortic Repair, Jesse Chait, Emanuel R Tenorio, Bernardo C Mendes, Guilherme B Barbosa Lima, Giulianna B Marcondes, Joshua Wong, Thanila A Macedo, Randall R De Martino, Gustavo S Oderich

Faculty, Staff and Student Publications

Objective: Target artery (TA) instability has been the most frequent indication for secondary intervention after fenestrated and branched endovascular aortic repair (FB-EVAR) of pararenal and thoracoabdominal aortic aneurysms (TAAAs). The aim of the present study was to evaluate the effect of the gap distance between the endograft reinforced fenestration and TA origin at the aortic wall (fenestration gap [FG]) on target-related outcomes after FB-EVAR.

Methods: The clinical data and imaging studies of 430 patients enrolled in a prospective, nonrandomized study to evaluate FB-EVAR using manufactured stent grafts were reviewed. Of the 430 patients, 340 (79%) had had more than one …

Respiratory Effects Of Thyrotropin-Releasing Hormone And Its Analogue Taltirelin On Opioid-Induced Respiratory Depression, Marijke H Algera, Joseph F Cotten, Monique Van Velzen, Marieke Niesters, Martijn Boon, Daniel S Shoham, Kaye E Dandrea, Rutger Van Der Schrier, Albert Dahan

Faculty, Staff and Student Publications

No abstract provided.

Efficacy Of Niraparib By Time Of Surgery And Postoperative Residual Disease Status: A Post Hoc Analysis Of Patients In The Prima/Engot-Ov26/Gog-3012 Study, Roisin E O'Cearbhaill, Jose-Alejandro Pérez-Fidalgo, Bradley J Monk, Ignacio Tusquets, Colleen Mccormick, Jose Fuentes, Richard G Moore, Christof Vulsteke, Mark S Shahin, Frédéric Forget, William H Bradley, Sakari Hietanen, David M O'Malley, Anne Dørum, Brian M Slomovitz, Klaus Baumann, Frédéric Selle, Paula M Calvert, Grazia Artioli, Tally Levy, Aalok Kumar, Izabela A Malinowska, Yong Li, Divya Gupta, Antonio González-Martín

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate the association between surgical timing and postoperative residual disease status on the efficacy of niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer at high risk of recurrence.

METHODS: Post hoc analysis of the phase 3 PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) study of niraparib in patients with newly diagnosed primary advanced ovarian, primary peritoneal, or fallopian tube cancer with a complete/partial response to first-line platinum-based chemotherapy. Progression-free survival (PFS) was assessed by surgical status (primary debulking surgery [PDS] vs neoadjuvant chemotherapy/interval debulking surgery [NACT/IDS]) and postoperative residual disease status (no visible residual disease [NVRD] vs visible residual …

Skin Cancer Education Interventions For Primary Care Providers: A Scoping Review, Ashley E Brown, Maleka Najmi, Taylor Duke, Daniel A Grabell, Misha V Koshelev, Kelly C Nelson

Faculty, Staff and Student Publications

Primary care physicians (PCPs) are often the first line of defense against skin cancers. Despite this, many PCPs do not receive a comprehensive training in skin conditions. Educational interventions aimed at skin cancer screening instruction for PCPs offer an opportunity to detect skin cancer at earlier stages and subsequent improved morbidity and mortality. A scoping review was conducted to collect data about previously reported skin cancer screening interventions for PCPs. A structured literature search found 51 studies describing 37 unique educational interventions. Curriculum elements utilized by the interventions were divided into categories that would facilitate comparison including curriculum components, delivery …

Estimated Size Of The Clinical Medical Imaging Physics Workforce In The United States, Sean D Rose, David W Jordan, Nicholas B Bevins, Jaydev K Dave, David E Hintenlang, Brad K Lofton, Pankaj Patel

Faculty, Staff and Student Publications

There is no current authoritative accounting of the number of clinical imaging physicists practicing in the United States. Information about the workforce is needed to inform future efforts to secure training pathways and opportunities. In this study, the AAPM Diagnostic Demand and Supply Projection Working Group collected lists of medical physicists from several state registration and licensure programs and the Conference of Radiation Control Program Directors (CRCPD) registry. By cross-referencing individuals among these lists, we were able to estimate the current imaging physics workforce in the United States by extrapolating based on population. The imaging physics workforce in the United …

Bone Mineral Density, Serum Calcium, And Vitamin D Levels In Adult Thalassemia Major Patients: Experience From A Single Center In Eastern India, Soumya Santra, Kunal Sharma, Ipsita Dash, Shaikat Mondal, Himel Mondal

Faculty, Staff and Student Publications

Background and objective Patients suffering from thalassemia major are at higher risk of osteoporosis. Due to their decreased life expectancy, the number of adult patients is low. However, their bone health is rarely checked in developing countries like India. There is no data available in the literature on the bone mineral density (BMD) of adult (aged ≥18 years) thalassemia major patients in eastern India. In this study, we aimed to measure the BMD and serum calcium and vitamin D levels in adult thalassemia major patients and to compare them with healthy controls. Materials and methods We conducted this cross-sectional observational …

Novel Scoring Systems To Predict The Need For Oxygenation And Icu Care, And Mortality In Hospitalized Covid-19 Patients: A Risk Stratification Tool, Vishakh C Keri, Pankaj Jorwal, Rohit Verma, Piyush Ranjan, Ashish D Upadhyay, Anivita Aggarwal, Radhika Sarda, Kunal Sharma, Shubham Sahni, Chaithra Rajanna

Faculty, Staff and Student Publications

INTRODUCTION: A rapid surge in cases during the COVID-19 pandemic can overwhelm any healthcare system. It is imperative to triage patients who would require oxygen and ICU care, and predict mortality. Specific parameters at admission may help in identifying them.

METHODOLOGY: A prospective observational study was undertaken in a COVID-19 ward of a tertiary care center. All baseline clinical and laboratory data were captured. Patients were followed till death or discharge. Univariable and multivariable logistic regression was used to find predictors of the need for oxygen, need for ICU care, and mortality. Objective scoring systems were developed for the same …

Impact Of Risk-Based Sexually Transmitted Infection Screening In The Emergency Department, Fahd A Ahmad, Kayleigh Fischer, Hongjie Gu, Thomas C Bailey, Donna B Jeffe, Christopher R Carpenter, Philip R O Payne

Faculty, Staff and Student Publications

OBJECTIVES: Sexually transmitted infections (STIs), including chlamydia, gonorrhea, and human immunodeficiency virus (HIV) pose a significant health burden in adolescents. Many adolescents receiving care in the emergency department (ED) are in need of testing, regardless of their chief complaint. Our objective was to determine whether an electronic, risk-based STI screening program in our ED was associated with an increase in STI testing among at-risk adolescents.

METHODS: We conducted a retrospective cohort analysis of patient outcomes in our pediatric ED after integrating an Audio-enhanced Computer-Assisted Self-Interview (ACASI) as standard of care. It obtained a focused sexual history and generated STI testing …

Obscurin Regulates Ankyrin Macromolecular Complex Formation, Janani Subramaniam, Gokay Yamankurt, Shane R Cunha

Faculty, Staff and Student Publications

Obscurin is a large scaffolding protein in striated muscle that maintains sarcolemmal integrity and aligns the sarcoplasmic reticulum with the underlying contractile machinery. Ankyrins are a family of adaptor proteins with some isoforms that interact with obscurin. Previous studies have examined obscurin interacting with individual ankyrins. In this study, we demonstrate that two different ankyrins interact with obscurin's carboxyl terminus via independent ankyrin-binding domains (ABDs). Using in-vitro binding assays, co-precipitation assays, and FLIM-FRET analysis, we show that obscurin interacts with small ankyrin 1.5 (sAnk1.5) and the muscle-specific ankyrin-G isoform (AnkG107). While there is no direct interaction between sAnk1.5 and AnkG107, …

Prolonged Cardiac Nr4a2 Aactivation Causes Dilated Cardiomyopathy In Mice, Sadia Ashraf, Heinrich Taegtmeyer, Romain Harmancey

Faculty, Staff and Student Publications

Transcription factors play a fundamental role in cardiovascular adaptation to stress. Nuclear receptor subfamily 4 group A member 2 (NR4A2; NURR1) is an immediate-early gene and transcription factor with a versatile role throughout many organs. In the adult mammalian heart, and particularly in cardiac myocytes, NR4A2 is strongly up-regulated in response to beta-adrenergic stimulation. The physiologic implications of this increase remain unknown. In this study, we aimed to interrogate the consequences of cardiac NR4A2 up-regulation under normal conditions and in response to pressure overload. In mice, tamoxifen-dependent, cardiomyocyte-restricted overexpression of NR4A2 led to cardiomyocyte hypertrophy, left ventricular dilation, heart failure, …

Guidelines On Models Of Diabetic Heart Disease, Lisa C Heather, Anne D Hafstad, Ganesh V Halade, Romain Harmancey, Kimberley M Mellor, Paras K Mishra, Erin E Mulvihill, Miranda Nabben, Michinari Nakamura, Oliver J Rider, Matthieu Ruiz, Adam R Wende, John R Ussher

Faculty, Staff and Student Publications

Diabetes is a major risk factor for cardiovascular diseases, including diabetic cardiomyopathy, atherosclerosis, myocardial infarction, and heart failure. As cardiovascular disease represents the number one cause of death in people with diabetes, there has been a major emphasis on understanding the mechanisms by which diabetes promotes cardiovascular disease, and how antidiabetic therapies impact diabetic heart disease. With a wide array of models to study diabetes (both type 1 and type 2), the field has made major progress in answering these questions. However, each model has its own inherent limitations. Therefore, the purpose of this guidelines document is to provide the …

Opposing Roles Of Hdac6 In Liver Regeneration And Hepatocarcinogenesis, Sophors Phorl, Azra Memon, Yuri Seo, Thi Oanh Hoang, Trung Nghia Tran, Le Minh Tri Nguyen, Chang Hoon Lee, Woon Kyu Lee, Joo-Yong Lee

Faculty, Staff and Student Publications

Histone deacetylase 6 (HDAC6), a deacetylase of p53, has emerged as a privileged inhibitory target for cancer therapy because of its deacetylating activity for p53 at K120 and K373/382. However, intricate roles of HDAC6 in hepatocellular carcinogenesis have been suggested by recent evidence, namely that HDAC6 ablation suppresses innate immunity, which plays critical roles in tumor immunosurveillance and antitumor immune responses. Therefore, it is valuable to determine whether HDAC6 ablation inhibits hepatocellular carcinogenesis using in vivo animal models. Here, we firstly showed that HDAC6 ablation increased K320 acetylation of p53, known as pro-survival acetylation, in all tested animal models but …

Elimination Of Pseudo-Hfos In Ieeg Using Sparse Representation And Random Forest Classifier, Behrang Fazli Besheli, Zhiyi Sha, Thomas Henry, Jay R Gavvala, Candan Gurses, Sacit Karamursel, Nuri F Ince

Faculty, Staff and Student Publications

High-Frequency Oscillation (HFO) is a promising biomarker of the epileptogenic zone. However, sharp artifacts might easily pass the conventional HFO detectors as real HFOs and reduce the seizure onset zone (SOZ) localization. We hypothesize that, unlike pseudo-HFOs, which originates from artifacts with sharp changes or arbitrary waveform characteristic, real HFOs could be represented by a limited number of oscillatory waveforms. Accordingly, to distinguish true ones from pseudo-HFOs, we established a new classification method based on sparse representation of candidate events that passed an initial detector with high sensitivity but low specificity. Specifically, using the Orthogonal Matching Pursuit (OMP) and a …

Biological Treatment Usage In Patients With Hiv And Rheumatic Disease, 2003-2021: Long-Term Safety And Follow-Up, Benjamin Sornrung Naovarat, Gloria Salazar, Mariko Ishimori, Francis M Williams, John D Reveille

Faculty, Staff and Student Publications

OBJECTIVE: This study examined the safety and efficacy of biological agents, especially tumour necrosis factor (TNF) inhibitors, for HIV-positive rheumatology patients refractory to standard therapy.

METHODS: This study is a retrospective case series including patients derived from a community HIV clinic as well as from two academic centres. Initial visit data collected included: sociodemographic characteristics, CD4 counts, HIV viral load and medication use. Patients with persistent disease activity despite standard conservative therapy were begun on biological agents.The main outcomes were patient and physician global assessment of treatment response and medication side effects in patients with rheumatological disorders treated with biological …

Kalium Channelrhodopsins Are Natural Light-Gated Potassium Channels That Mediate Optogenetic Inhibition, Elena G Govorunova, Yueyang Gou, Oleg A Sineshchekov, Hai Li, Xiaoyu Lu, Yumei Wang, Leonid S Brown, François St-Pierre, Mingshan Xue, John L Spudich

Faculty, Staff and Student Publications

Channelrhodopsins are used widely for optical control of neurons, in which they generate photoinduced proton, sodium or chloride influx. Potassium (K+) is central to neuron electrophysiology, yet no natural K+-selective light-gated channel has been identified. Here, we report kalium channelrhodopsins (KCRs) from Hyphochytrium catenoides. Previously known gated potassium channels are mainly ligand- or voltage-gated and share a conserved K+-selectivity filter. KCRs differ in that they are light-gated and have independently evolved an alternative K+ selectivity mechanism. The KCRs are potent, highly selective of K+ over Na+, and open in less than 1 ms following photoactivation. The permeability ratio PK/PNa of …

Gene-Mapping Study Of Extremes Of Cerebral Small Vessel Disease Reveals Trim47 As A Strong Candidate, Aniket Mishra, Cécile Duplaà, Dina Vojinovic, Hideaki Suzuki, Muralidharan Sargurupremraj, Nuno R Zilhão, Shuo Li, Traci M Bartz, Xueqiu Jian, Wei Zhao, Edith Hofer, Katharina Wittfeld, Sarah E Harris, Sandra Van Der Auwera-Palitschka, Michelle Luciano, Joshua C Bis, Hieab H H Adams, Claudia L Satizabal, Rebecca F Gottesman, Piyush G Gampawar, Robin Bülow, Stefan Weiss, Miao Yu, Mark E Bastin, Oscar L Lopez, Meike W Vernooij, Alexa S Beiser, Uwe Völker, Tim Kacprowski, Aicha Soumare, Jennifer A Smith, David S Knopman, Zoe Morris, Yicheng Zhu, Jerome I Rotter, Carole Dufouil, Maria Valdés Hernández, Susana Muñoz Maniega, Mark Lathrop, Erik Boerwinkle, Reinhold Schmidt, Masafumi Ihara, Bernard Mazoyer, Qiong Yang, Anne Joutel, Elizabeth Tournier-Lasserve, Lenore J Launer, Ian J Deary, Thomas H Mosley, Philippe Amouyel, Charles S Decarli, Bruce M Psaty, Christophe Tzourio, Sharon L R Kardia, Hans J Grabe, Alexander Teumer, Cornelia M Van Duijn, Helena Schmidt, Joanna M Wardlaw, M Arfan Ikram, Myriam Fornage, Vilmundur Gudnason, Sudha Seshadri, Paul M Matthews, William T Longstreth, Thierry Couffinhal, Stephanie Debette

Faculty, Staff and Student Publications

Cerebral small vessel disease is a leading cause of stroke and a major contributor to cognitive decline and dementia, but our understanding of specific genes underlying the cause of sporadic cerebral small vessel disease is limited. We report a genome-wide association study and a whole-exome association study on a composite extreme phenotype of cerebral small vessel disease derived from its most common MRI features: white matter hyperintensities and lacunes. Seventeen population-based cohorts of older persons with MRI measurements and genome-wide genotyping (n = 41 326), whole-exome sequencing (n = 15 965), or exome chip (n = 5249) data contributed 13 …

Worsening Glycemia Increases The Odds Of Intermittent But Not Persistent Staphylococcus Aureus Nasal Carriage In Two Cohorts Of Mexican American Adults, Heather T Essigmann, Craig L Hanis, Stacia M Desantis, William B Perkison, David A Aguilar, Goo Jun, D Ashley Robinson, Eric L Brown

Faculty, Staff and Student Publications

Numerous host and environmental factors contribute to persistent and intermittent nasal Staphylococcus aureus carriage in humans. The effects of worsening glycemia on the odds of S. aureus intermittent and persistent nasal carriage was established in two cohorts from an adult Mexican American population living in Starr County, Texas. The anterior nares were sampled at two time points and the presence of S. aureus determined by laboratory culture and

Validation Of A High Flow Rate Puff Topography System Designed For Measurement Of Sub-Ohm, Third Generation Electronic Nicotine Delivery Systems, Evan Floyd, Toluwanimi Oni, Changjie Cai, Bilal Rehman, Jooyeon Hwang, Tyler Watson

Faculty, Staff and Student Publications

There are few known puff topography devices designed solely for gathering electronic cigarette puff topography information, and none made for high-powered sub-ohm devices. Ten replicate Bernoulli flow cells were designed and 3D printed. The relationship between square root of pressure difference and flow rate was determined across 0−70 L/min. One representative flow cell was used to estimate puff volume and flow rate under six simulated puffing regimes (0.710 L, 2.000 L and 3.000 L, at low and high flow rates) to determine the system’s accuracy and utility of using dual pressure sensors for flow measurement. The relationship between flow rate …

Regulation Of Age-Associated Insulin Resistance By Mt1-Mmp-Mediated Cleavage Of Insulin Receptor, Xuanming Guo, Pallavi Asthana, Susma Gurung, Shuo Zhang, Sheung Kin Ken Wong, Samane Fallah, Chi Fung Willis Chow, Sijia Che, Lixiang Zhai, Zening Wang, Xin Ge, Zhixin Jiang, Jiayan Wu, Yijing Zhang, Xiaoyu Wu, Keyang Xu, Cheng Yuan Lin, Hiu Yee Kwan, Aiping Lyu, Zhongjun Zhou, Zhao-Xiang Bian, Hoi Leong Xavier Wong

Faculty, Staff and Student Publications

Insulin sensitivity progressively declines with age. Currently, the mechanism underlying age-associated insulin resistance remains unknown. Here, we identify membrane-bound matrix metalloproteinase 14 (MT1-MMP/MMP14) as a central regulator of insulin sensitivity during ageing. Ageing promotes MMP14 activation in insulin-sensitive tissues, which cleaves Insulin Receptor to suppress insulin signaling. MT1-MMP inhibition restores Insulin Receptor expression, improving insulin sensitivity in aged mice. The cleavage of Insulin Receptor by MT1-MMP also contributes to obesity-induced insulin resistance and inhibition of MT1-MMP activities normalizes metabolic dysfunctions in diabetic mouse models. Conversely, overexpression of MT1-MMP in the liver reduces the level of Insulin Receptor, impairing hepatic insulin …

An Epidemic Model With Time-Distributed Recovery And Death Rates, Samiran Ghosh, Vitaly Volpert, Malay Banerjee

Faculty, Staff and Student Publications

A compartmental epidemiological model with distributed recovery and death rates is proposed. In some particular cases, the model can be reduced to the conventional SIR model. However, in general, the dynamics of epidemic progression in this model is different. Distributed recovery and death rates are evaluated from COVID-19 data. The model is validated by the epidemiological data for different countries, and it shows better agreement with the data than the SIR model. The time-dependent disease transmission rate is estimated.

Divergent Outer Retinal Circuits Drive Image And Non-Image Visual Behaviors, Corinne Beier, Ulisse Bocchero, Lior Levy, Zhijing Zhang, Nange Jin, Stephen C Massey, Christophe P Ribelayga, Kirill Martemyanov, Samer Hattar, Johan Pahlberg

Faculty, Staff and Student Publications

Image- and non-image-forming vision are essential for animal behavior. Here we use genetically modified mouse lines to examine retinal circuits driving image- and non-image-functions. We describe the outer retinal circuits underlying the pupillary light response (PLR) and circadian photoentrainment, two non-image-forming behaviors. Rods and cones signal light increments and decrements through the ON and OFF pathways, respectively. We find that the OFF pathway drives image-forming vision but cannot drive circadian photoentrainment or the PLR. Cone light responses drive image formation but fail to drive the PLR. At photopic levels, rods use the primary and secondary rod pathways to drive the …

Transmission, Strain Diversity, And Zoonotic Potential Of Chronic Wasting Disease, Sandra Pritzkow

Faculty, Staff and Student Publications

Chronic wasting disease (CWD) is a prion disease affecting several species of captive and free-ranging cervids. In the past few decades, CWD has been spreading uncontrollably, mostly in North America, resulting in a high increase of CWD incidence but also a substantially higher number of geographical regions affected. The massive increase in CWD poses risks at several levels, including contamination of the environment, transmission to animals cohabiting with cervids, and more importantly, a putative transmission to humans. In this review, I will describe the mechanisms and routes responsible for the efficient transmission of CWD, the strain diversity of natural CWD, …

Phosphatidylserine And Phosphatidylethanolamine Asymmetry Have A Negligible Effect On The Global Structure, Dynamics, And Interactions Of The Kras Lipid Anchor, Mussie K Araya, Alemayehu A Gorfe

Faculty, Staff and Student Publications

The intrinsically disordered C-terminus of the prominent oncogenic protein KRAS-4B (KRAS) selectively interacts and clusters with phosphatidylserine (PS) lipids in the plasma membrane (PM). This 11-residue segment, called tK, contains a polybasic domain (PBD) of six contiguous lysine residues and a farnesylated cysteine. Previous molecular dynamics (MD) simulation studies of tK in phosphatidylcholine (PC)/PS bilayers have suggested that backbone conformational dynamics modulate tK-PS interactions. These simulations have been conducted in symmetric membranes whereas the PM is compositionally asymmetric, with the inner leaflet, where KRAS is localized, being enriched with PS and phosphatidylethanolamine (PE) lipids. To examine if bilayer asymmetry affects …

Biochemical, Biophysical, And Immunological Characterization Of Respiratory Secretions In Severe Sars-Cov-2 Infections, Michael J Kratochvil, Gernot Kaber, Sally Demirdjian, Pamela C Cai, Elizabeth B Burgener, Nadine Nagy, Graham L Barlow, Medeea Popescu, Mark R Nicolls, Michael G Ozawa, Donald P Regula, Ana E Pacheco-Navarro, Samuel Yang, Vinicio A De Jesus Perez, Harry Karmouty-Quintana, Andrew M Peters, Bihong Zhao, Maximilian L Buja, Pamela Y Johnson, Robert B Vernon, Thomas N Wight, Carlos E Milla, Angela J Rogers, Andrew J Spakowitz, Sarah C Heilshorn, Paul L Bollyky

Faculty, Staff and Student Publications

Thick, viscous respiratory secretions are a major pathogenic feature of COVID-19, but the composition and physical properties of these secretions are poorly understood. We characterized the composition and rheological properties (i.e., resistance to flow) of respiratory secretions collected from intubated COVID-19 patients. We found the percentages of solids and protein content were greatly elevated in COVID-19 compared with heathy control samples and closely resembled levels seen in cystic fibrosis, a genetic disease known for thick, tenacious respiratory secretions. DNA and hyaluronan (HA) were major components of respiratory secretions in COVID-19 and were likewise abundant in cadaveric lung tissues from these …

A Multi-Ethnic Polygenic Risk Score Is Associated With Hypertension Prevalence And Progression Throughout Adulthood, Nuzulul Kurniansyah, Matthew O Goodman, Tanika N Kelly, Tali Elfassy, Kerri L Wiggins, Joshua C Bis, Xiuqing Guo, Walter Palmas, Kent D Taylor, Henry J Lin, Jeffrey Haessler, Yan Gao, Daichi Shimbo, Jennifer A Smith, Bing Yu, Elena V Feofanova, Roelof A J Smit, Zhe Wang, Shih-Jen Hwang, Simin Liu, Sylvia Wassertheil-Smoller, Joann E Manson, Donald M Lloyd-Jones, Stephen S Rich, Ruth J F Loos, Susan Redline, Adolfo Correa, Charles Kooperberg, Myriam Fornage, Robert C Kaplan, Bruce M Psaty, Jerome I Rotter, Donna K Arnett, Alanna C Morrison, Nora Franceschini, Daniel Levy, Tamar Sofer, Nhlbi Trans-Omics In Precision Medicine (Topmed) Consortium

Faculty, Staff and Student Publications

In a multi-stage analysis of 52,436 individuals aged 17-90 across diverse cohorts and biobanks, we train, test, and evaluate a polygenic risk score (PRS) for hypertension risk and progression. The PRS is trained using genome-wide association studies (GWAS) for systolic, diastolic blood pressure, and hypertension, respectively. For each trait, PRS is selected by optimizing the coefficient of variation (CV) across estimated effect sizes from multiple potential PRS using the same GWAS, after which the 3 trait-specific PRSs are combined via an unweighted sum called "PRSsum", forming the HTN-PRS. The HTN-PRS is associated with both prevalent and incident hypertension at 4-6 …