Medicine and Health Sciences Commons^™

A Case Series Of Primary Cutaneous B-Cell Lymphomas With Atypical Presentations: Diagnostic And Therapeutic Challenges, Emily Correia, Jisun Cha, Shalini Krishnasamy, Megan O'Donnell, Wenyin Shi, Pierluigi Porcu, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

The Effect Of Scan And Patient Parameters On The Diagnostic Performance Of Ai For Detecting Coronary Stenosis On Coronary Ct Angiography, Rebecca Jonas, Emil Barkovich, Andrew D Choi, William F Griffin, Joanna Riess, Hugo Marques, Hyuk-Jae Chang, Jung Hyun Choi, Joon-Hyung Doh, Ae-Young Her, Bon-Kwon Koo, Chang-Wook Nam, Hyung-Bok Park, Sang-Hoon Shin, Jason Cole, Alessia Gimelli, Muhammad Akram Khan, Bin Lu, Yang Gao, Faisal Nabi, Ryo Nakazato, U Joseph Schoepf, Roel S Driessen, Michiel J Bom, Randall C Thompson, James J Jang, Michael Ridner, Chris Rowan, Erick Avelar, Philippe Généreux, Paul Knaapen, Guus A De Waard, Gianluca Pontone, Daniele Andreini, Marco Guglielmo, Mouaz H Al-Mallah, Robert S Jennings, Tami R Crabtree, James P Earls

Division of Internal Medicine Faculty Papers & Presentations

Objectives: To determine whether coronary computed tomography angiography (CCTA) scanning, scan preparation, contrast, and patient based parameters influence the diagnostic performance of an artificial intelligence (AI) based analysis software for identifying coronary lesions with ≥50% stenosis.

Background: CCTA is a noninvasive imaging modality that provides diagnostic and prognostic benefit to patients with coronary artery disease (CAD). The use of AI enabled quantitative CCTA (AI-QCT) analysis software enhances our diagnostic and prognostic ability, however, it is currently unclear whether software performance is influenced by CCTA scanning parameters.

Methods: CCTA and quantitative coronary CT (QCT) data from 303 stable patients (64 ± …

A Comprehensive Review On The Risk Of Metabolic Syndrome And Cardiovascular Disease After Liver Transplantation, Kashyap Chauhan, Adnan Khan, Salil Chowdhury, Heather Ross, Natali Salinas, Dina Halegoua-De Marzio

Division of Internal Medicine Faculty Papers & Presentations

Survival rates after liver transplantation have increased dramatically over the past 20 years. Cardiovascular disease is the most common extra-hepatic cause of mortality in the long-term post liver transplant. This is intimately linked with both the higher pre-existing rates of metabolic syndrome in these patients as well as increased propensity to develop de novo metabolic syndrome post-transplant. This unfavorable metabolic profile that contributes to cardiovascular disease is multifactorial and largely preventable. This review explores metabolic syndrome and cardiovascular disease and their contributory factors post liver transplantation to highlight areas for potential intervention and thus reduce the significant morbidity and mortality …

Patterns Of Crystallin Gene Expression In Differentiation State Specific Regions Of The Embryonic Chicken Lens, Zhiwei Ma, Daniel Chauss, Joshua Disatham, Xiaodong Jiao, Lisa Ann Brennan, A Sue Menko, Marc Kantorow, J Fielding Hejtmancik

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Purpose: Transition from lens epithelial cells to lens fiber cell is accompanied by numerous changes in gene expression critical for lens transparency. We identify expression patterns of highly prevalent genes including ubiquitous and enzyme crystallins in the embryonic day 13 chicken lens.

Methods: Embryonic day 13 chicken lenses were dissected into central epithelial cell (EC), equatorial epithelial cell (EQ), cortical fiber cell (FP), and nuclear fiber cell (FC) compartments. Total RNA was prepared, subjected to high-throughput unidirectional mRNA sequencing, analyzed, mapped to the chicken genome, and functionally grouped.

Results: A total of 77,097 gene-specific transcripts covering 17,450 genes were expressed, …

Skin Cancer Biopsy And Detection Rates With Total Body Skin Examination: A Cross-Sectional Retrospective Analysis., Alexander Sherban, Shayan Waseh, Audra Hugo, Michael Bui, Constantine Daskalakis, Elizabeth Jones

Department of Dermatology and Cutaneous Biology Faculty Papers

Research Letter

Implementation Of Clinical Practice Guidelines For Hospitalized Patients With Covid-19 In Academic Medical Centers, Amy Chang Berger, Noa Simchoni, Andrew Auerbach, W Michael Brode, Ethan Kuperman, Katie Raffel, Alan Kubey

Department of Medicine Faculty Papers

No abstract provided.

Does Age-Related Macular Degeneration (Amd) Treatment Influence Patient Falls And Mobility? A Systematic Review., Hannah Garrigan, Jacquelyn N. Hamati, Parth Lalakia, Rosemary Frasso, Brooke Salzman, Leslie Hyman

Student Papers, Posters & Projects

PURPOSE: Age-related macular degeneration (AMD), a leading cause of irreversible blindness, increases fall risk through impaired central vision. Falls place an enormous economic burden on healthcare systems. We hypothesized that AMD treatments may reduce patients' falls risk. This systematic review (ID #: 172623) synthesized the current understanding of wet and dry AMD treatments' impact on patient falls and mobility, connecting these two public health issues.

METHODS: On April 17, 2020, PubMed, Scopus, CINAHL, and the Cochrane Central Register of Controlled Trials were queried. Clinical trials and observational studies were included, while non-English and non-primary studies were excluded. Two authors screened, …

Medical Factors Associated With Caregiver Intention To Vaccinate Their Children Against Covid-19, Thao-Ly Phan, Paul T Enlow, Michael King, Amanda M Lewis, Anne E Kazak, Jonathan M Miller

Department of Medicine Faculty Papers

Objective: To describe medical factors that are associated with caregiver intention to vaccinate their children against COVID-19.

Methods: We conducted a cross-sectional study of families receiving primary care in a mid-Atlantic pediatric healthcare system, linking caregiver-reported data from a survey completed March 19 to April 16, 2021 to comprehensive data from the child's EHR.

Results: 513 families were included (28% Black, 16% Hispanic, 44% public insurance, 21% rural, child age range 0-21 years). 44% of caregivers intended to vaccinate their children against COVID-19, while 41% were not sure and 15% would not. After adjusting for socio-demographics, the only medical factors …

Hepatitis B Virus-Associated Hepatocellular Carcinoma And Chronic Stress, Nicholas Noverati, Rukaiya Bashir, Dina Halegoua-De Marzio, Hie-Won Hann

Department of Medicine Faculty Papers

The Hepatitis B virus is one of the most significant hepatocarcinogens globally. The carcinogenic mechanisms of this virus are complex, and may include interactions with the host's immune system. Certain factors, such as stress on the body, can also potentiate these mechanisms. Stress, although adaptive in an acute form, is deleterious to health when chronic and can both suppress and activate the host's defense system. In hepatocellular carcinoma, this can lead to tumor initiation and progression. Those that are more prone to stress, or exposed to situations that incite stress, may be at higher risk of developing cancer. Racial disparities, …

Longitudinal Analysis Of The Impact Of Oral Contraceptive Use On The Gut Microbiome, Xinwei Hua, Yueming Cao, David M Morgan, Kaia Miller, Samantha M Chin, Danielle Bellavance, Hamed Khalili

Department of Medicine Faculty Papers

Introduction. Evidence has linked exogenous and endogenous sex hormones with the human microbiome.Hypothesis/Gap statement. The longitudinal effects of oral contraceptives (OC) on the human gut microbiome have not previously been studied.Aim. We sought to examine the longitudinal impact of OC use on the taxonomic composition and metabolic functions of the gut microbiota and endogenous sex steroid hormones after initiation of OC use.Methodology. We recruited ten healthy women who provided blood and stool samples prior to OC use, 1 month and 6 months after starting OC. We measured serum levels of sex hormones, including estradiol, progesterone, sex hormone-binding …

Enzymatic Depletion Of Mitochondrial Inorganic Polyphosphate (Polyp) Increases The Generation Of Reactive Oxygen Species (Ros) And The Activity Of The Pentose Phosphate Pathway (Ppp) In Mammalian Cells, Vedangi Hambardikar, Mariona Guitart-Mampel, Ernest Scoma, Pedro Urquiza, Gowda Nagana, Daniel Raftery, John Collins, Maria Solesio

Department of Orthopaedic Surgery Faculty Papers

Inorganic polyphosphate (polyP) is an ancient biopolymer that is well preserved throughout evolution and present in all studied organisms. In mammals, it shows a high co-localization with mitochondria, and it has been demonstrated to be involved in the homeostasis of key processes within the organelle, including mitochondrial bioenergetics. However, the exact extent of the effects of polyP on the regulation of cellular bioenergetics, as well as the mechanisms explaining these effects, still remain poorly understood. Here, using HEK293 mammalian cells under Wild-type (Wt) and MitoPPX (cells enzymatically depleted of mitochondrial polyP) conditions, we show that depletion of polyP within mitochondria …

Arsenic Toxicity On Metabolism And Autophagy In Adipose And Muscle Tissues, Seung-Hyun Ro, Jiyoung Bae, Yura Jang, Jacob Myers, Soonkyu Chung, Jiujiu Yu, Sathish Kumar Natarajan, Rodrigo Franco, Hyun-Seob Song

Department of Microbiology and Immunology Faculty Papers

Arsenic, a naturally occurring metalloid derived from the environment, has been studied worldwide for its causative effects in various cancers. However, the effects of arsenic toxicity on the development and progression of metabolic syndrome, including obesity and diabetes, has received less attention. Many studies suggest that metabolic dysfunction and autophagy dysregulation of adipose and muscle tissues are closely related to the development of metabolic disease. In the USA, arsenic contamination has been reported in some ground water, soil and grain samples in major agricultural regions, but the effects on adipose and muscle tissue metabolism and autophagy have not been investigated …

Otolaryngology Subspecialty Surgical Rescheduling Rates During The Covid-19 Pandemic, Emily S Sagalow, Alexander Duffy, Priyanga Selvakumar, David Cognetti

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Objective: In the beginning of the COVID-19 pandemic in spring 2020, elective and oncologic surgical cases were cancelled. After adequate safety protocols were established, each subspecialty within otolaryngology faced unique challenges in reengaging patients for surgical scheduling.

Study design: Retrospective review from March to May 2020.

Setting: Single academic institution.

Methods: Patients whose otolaryngology surgery was cancelled due to COVID-19 hospital precautions were identified. Rescheduling rates were analyzed by subspecialty. Case completion was determined as the percentage of initially cancelled cases that were completed within 6 months of their original planned dates.

Results: Of 833 otolaryngology cases scheduled between March …

A Standardized Diagnostic Pathway For Suspected Appendicitis In Children Reduces Unnecessary Imaging, Roshan J. D'Cruz, Allison F. Linden, Courtney L. Devon, Jillian Savage, Arezoo Zomorrodi, Kirk W. Reichard, Arabinda Choudhary, Loren Berman

Department of Surgery Faculty Papers

Introduction:

Ultrasound (US) for the diagnosis of acute appendicitis is often nondiagnostic, and additional imaging is required. A standardized approach may reduce unnecessary imaging.

Methods:

We retrospectively analyzed all patients who had imaging for appendicitis in our emergency department in 2017 and evaluated patient characteristics associated with nondiagnostic US. Using these results, we developed a pediatric appendicitis score (PAS)-based imaging pathway and compared imaging trends prepathway and postpathway implementation.

Results:

A total of 971 patients received imaging for suspected appendicitis prepathway in 2017. Female sex, obesity, and low/intermediate PAS were significantly associated with nondiagnostic US, but not magnetic resonance imaging …

Functions Of Adp-Ribose Transferases In The Maintenance Of Telomere Integrity, Daniela Muoio, Natalie Laspata, Elise Fouquerel

Department of Biochemistry and Molecular Biology Faculty Papers

The ADP-ribose transferase (ART) family comprises 17 enzymes that catalyze mono- or poly-ADP-ribosylation, a post-translational modification of proteins. Present in all subcellular compartments, ARTs are implicated in a growing number of biological processes including DNA repair, replication, transcription regulation, intra- and extra-cellular signaling, viral infection and cell death. Five members of the family, PARP1, PARP2, PARP3, tankyrase 1 and tankyrase 2 are mainly described for their crucial functions in the maintenance of genome stability. It is well established that the most describedrole of PARP1, 2 and 3 is the repair of DNA lesions while tankyrases 1 and 2 are crucial …

Idiopathic Midaortic Syndrome, David Saul, Rahul Nikam, Vinay Kandula, Achala Donuru

Department of Radiology Faculty Papers

Midaortic syndrome (MAS) is characterized by narrowing of the descending aorta between the distal aortic arch and the aortic bifurcation. We present the case of a 4-year-old male presenting with a murmur and diagnosed with MAS. He was treated with a thoracoabdominal bypass graft.

Coeliac Plexus Radiosurgery For Pain Management In Patients With Advanced Cancer : Study Protocol For A Phase Ii Clinical Trial, Galia Jacobson, Ronen Fluss, Amira Dany-Benshushan, Talia Golan, Tikva Meron, Camilla Zimmermann, Laura A Dawson, Aisling Barry, Marcin Miszczyk, Michael Buckstein, Dayssy Diaz Pardo, Artur Aguiar, Liat Hammer, Adam Dicker, Maoz Ben-Ailan, Ofir Morag, David Hausner, Zvi Symon, Yaacov R Lawrence

Department of Radiation Oncology Faculty Papers

Introduction: Pancreatic cancer is characterised by severe mid-back and epigastric pain caused by tumour invasion of the coeliac nerve plexus. This pain is often poorly managed with standard treatments. This clinical trial investigates a novel approach in which high-dose radiation (radiosurgery) is targeted to the retroperitoneal coeliac plexus nerve bundle. Preliminary results from a single institution pilot trial are promising: pain relief is substantial and side effects minimal. The goals of this study are to validate these findings in an international multisetting, and investigate the impact on quality of life and functional status among patients with terminal cancer.

Methods and …

Implicit Bias Training In Student Registered Nurse Anesthetists, Iteona Roundtree, Bsn, Rn, Srna, Jodi-Ann Smith, Bsn, Rn, Srna

College of Nursing Posters

Research Question:

In first-year DNP student registered nurse anesthetists (SRNAs), will an implicit bias training activity increase self-awareness and knowledge of implicit bias and its implications in healthcare?

Use Of Functional Mri In Deep Brain Stimulation In Parkinson's Diseases: A Systematic Review., Jingya Miao, Mohamed Tantawi, Victoria Koa, Ashley B Zhang, Veronica Zhang, Ashwini Sharan, Chengyuan Wu, Caio M Matias

Department of Neurosurgery Faculty Papers

Deep brain stimulation (DBS) has been used to modulate aberrant circuits associated with Parkinson's disease (PD) for decades and has shown robust therapeutic benefits. However, the mechanism of action of DBS remains incompletely understood. With technological advances, there is an emerging use of functional magnetic resonance imaging (fMRI) after DBS implantation to explore the effects of stimulation on brain networks in PD. This systematic review was designed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to summarize peer-reviewed articles published within the past 10 years in which fMRI was employed on patients with PD-DBS. Search in …

Return To School After Anterior Cruciate Ligament Reconstruction: A Prospective Study Of Adolescents And Young Adults., Joseph Brutico, Ryan W. Paul, Margaret Wright, Steven Cohen, Michael G. Ciccotti, Christopher C Dodson, Kevin Freedman, Sommer Hammoud

Rothman Institute Papers

Background: The ability to return to school after orthopaedic surgery is an important consideration for young patients, as there is substantial literature indicating that school attendance is correlated strongly with academic performance.

Purpose: To evaluate the time to return to school, the barriers that students encounter when returning to school, and the academic effect of anterior cruciate ligament reconstruction (ACLR) in high school (HS) and college students.

Study design: Cohort study; Level of evidence, 2.

Methods: Full-time HS and college/graduate school (C/GS) students who underwent ACLR during the 2017 to 2018 and 2018 to 2019 academic periods were included in …

Parents' Reports Of Children's Physical And Sedentary Behavior Engagement Among Parents In Weight Management, Catherine Van Fossen, Haley Kiser, Callie Lambert Brown, Joseph Skelton, Keeley Jean Pratt

Department of Psychiatry and Human Behavior Faculty Papers

Background: The purpose of this study was to explore the associations between demographics, family exercise participation, family discouragement of exercise, and the children's physical and sedentary behaviors to identify specific areas of physical activity intervention for children with parents engaged in medical weight management (MWM).

Methods: Parents (n = 294) of children aged 2-18 years old were recruited from two university MWM programs to complete a one-time survey. Bivariate analyses tested associations.

Results: Parents reported that sedentary activity was higher for children who identified as racial minorities (t(141) = -2.05, p < 0.05). Mobile phone and tablet use was higher for adolescents compared to school age and young children (H(2) = 10.96, p < 01) Exercise game use was higher for racial minority children compared to white children (U = 9440.5, z = 2.47, p ≤ 0.03). Male children (t(284) = 1.83, p < 0.07), children perceived to have a healthy weight status (t(120) = 4.68, p < 0.00), and younger children (t(289) = 1.79, p < 0.08) all engaged in more strenuous physical activity. Family exercise participation (t(162) = -2.93, p < 0.01) and family discouragement of exercise (U = 7813.50, z = -2.06, p ≤ 0.04) were significantly higher for children in racial minority families.

Conclusions: Future work should determine methods to engage children …

Ovarian Reserve Parameters And Ivf Outcomes In 510 Women With Poor Ovarian Response (Por) Treated With Intraovarian Injection Of Autologous Platelet Rich Plasma (Prp), Yigit Cakiroglu, Aysen Yuceturk, Ozge Karaosmanoglu, Sule Yildirim Kopuk, Zeynep Ece Utkan Korun, Nola Herlihy, Richard T. Scott, Bulent Tiras, Emre Seli

Department of Obstetrics and Gynecology Faculty Papers

The aim of the current study was to characterize ovarian reserve parameters and IVF outcomes in women with a history of poor ovarian response (POR) treated with intraovarian injection of autologous platelet rich plasma (PRP). Reproductive age women (N=510; age range 30-45yo) diagnosed with POR based on Poseidon criteria were included in the study. PRP treatment resulted in higher AFC, higher serum AMH, lower serum FSH, and a higher number of mature oocytes and cleavage and blastocyst stage embryos. After PRP injection, 22 women (4.3%) conceived spontaneously, 14 (2.7%) were lost to follow up, and 474 (92.9%) attempted IVF. Among …

Mechanisms Of Mitochondrial Promoter Recognition In Humans And Other Mammalian Species, Angelica Zamudio-Ochoa, Yaroslav I Morozov, Azadeh Sarfallah, Michael Anikin, Dmitry Temiakov

Department of Biochemistry and Molecular Biology Faculty Papers

Recognition of mammalian mitochondrial promoters requires the concerted action of mitochondrial RNA polymerase (mtRNAP) and transcription initiation factors TFAM and TFB2M. In this work, we found that transcript slippage results in heterogeneity of the human mitochondrial transcripts in vivo and in vitro. This allowed us to correctly interpret the RNAseq data, identify the bona fide transcription start sites (TSS), and assign mitochondrial promoters for > 50% of mammalian species and some other vertebrates. The divergent structure of the mammalian promoters reveals previously unappreciated aspects of mtDNA evolution. The correct assignment of TSS also enabled us to establish the precise register of …

The Pro-Fibrotic Response Of Mesenchymal Leader Cells To Lens Wounding Involves Hyaluronic Acid, Its Receptor Rhamm, And Vimentin, A. Sue Menko, Alison Romisher, Janice L Walker

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Hyaluronic Acid/Hyaluronan (HA) is a major component of the provisional matrix deposited by cells post-wounding with roles both in regulating cell migration to repair a wound and in promoting a fibrotic outcome to wounding. Both are mediated through its receptors CD44 and RHAMM. We now showed that HA is present in the provisional matrix assembled on the substrate surface in a lens post-cataract surgery explant wound model in which mesenchymal leader cells populate the wound edges to direct migration of the lens epithelium across the adjacent culture substrate onto which this matrix is assembled. Inhibiting HA expression with 4-MU blocked …

A Forward-Thinking Approach To Addressing The New Synthetic Opioid 2-Benzylbenzimidazole Nitazene Analogs By Liquid Chromatography-Tandem Quadrupole Mass Spectrometry (Lc-Qqq-Ms), Sara E Walton, Alex J Krotulski, Barry K Logan

College of Life Sciences Faculty Papers

Novel psychoactive substances (NPS) continue to represent a threat to public health and safety. The number of new drugs in the latest emergent synthetic opioid class-the 2-benzylbenzimidazole analogs-also called the nitazenes-has begun to dominate the current new synthetic opioid (NSO) subclass of NPS. We describe a liquid chromatography-tandem quadrupole mass spectrometry method for the quantification of nine analogs and/or metabolites of drugs in this series: isotonitazene, metonitazene, protonitazene, etonitazene, clonitazene, flunitazene, N-desethyl isotonitazene, 5-amino isotonitazene and 4'-hydroxy nitazene in human whole blood, urine, and tissue. Samples were prepared for analysis using a basic liquid-liquid extraction. Chromatographic separation was achieved using …

Tangential Cranial Gunshot Wound In An Infant In Historical Context: Illustrative Case, Jeffrey Campbell, Joseph Piatt

Department of Pediatrics Faculty Papers

BACKGROUND

Military neurosurgeons have long known that tangential cranial gunshot wounds can be associated with intracranial complications out of proportion to the external appearance of the injury. This phenomenon seems not to have been described in infancy.

OBSERVATIONS

An infant suffered a massive, acute subdural hemorrhage from a contralateral tangential gunshot wound that did not facture the skull.

LESSONS

Similar to adults, infants are subject to catastrophic intracranial injury from gunshots that do not penetrate the skull. The nature of the injury in this case reflected distinctive aspects of the tissue characteristics and proportions of the infant head.

Pharmacologic Ascorbic Acid As Early Therapy For Hospitalized Patients With Covid-19: A Randomized Clinical Trial, Dagan Coppock, Pierre-Christian Violet, Gustavo Vasquez, Katherine Belden, Michael Foster, Bret Mullin, Devon Magee, Isabelle Mikell, Lokesh Shah, Victoria Powers, Brian Curcio, Daniel A. Monti, Mark Levine

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Despite the widespread availability of effective vaccines, new cases of infection with severe acute respiratory syndrome coronavirus-2, the cause of coronavirus disease 2019 (COVID-19), remain a concern in the settings of vaccine hesitancy and vaccine breakthrough. In this randomized, controlled, phase 2 trial, we hypothesized that high-dose ascorbic acid delivered intravenously to achieve pharmacologic concentrations may target the high viral phase of COVID-19 and thus improve early clinical outcomes. Sixty-six patients admitted with COVID-19 and requiring supplemental oxygen were randomized to receive either escalating doses of intravenous ascorbic acid plus standard of care or standard of care alone. The demographic …

68-Year Old Man With Progressive Weakness And Ventilator Dependent Respiratory Failure: A Case Report Of Sporadic Late Onset Nemaline Myopathy, P. Kirupaharan, Daniel Kramer, Alan Gandler, Lawrence C. Kenyon, Ross Summer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Neuromuscular pathologies must be considered when caring for patients with persistent or progressive respiratory failure. Pertinent disease states may involve skeletal muscles of respiration or associated neurologic structures including motor neurons, peripheral neurons and the neuromuscular junction. Diagnosis may require pulmonary function testing, neurophysiologic studies, imaging, and/or muscle biopsy.

Case presentation: A 68-year-old male was transferred to our intensive care unit (ICU) for management of ventilator dependent respiratory failure. Upon further historical review, he described gradually worsening gait instability and muscle weakness, which was previously attributed to vascular Parkinsonism in the setting of known cerebrovascular disease. Upon arrival to …

Fluorescence Imaging Detection Of Nanodomain Redox Signaling Events At Organellar Contacts, David M. Booth, Péter Várnai, Suresh K Joseph, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

This protocol describes how to visualize, detect, and analyze redox signals (oxidative bursts) at the ER-mitochondrial interface. It uses drug-inducible crosslinking to target the genetically encoded glutathione redox sensor Grx1roGFP2 to organellar contact sites to measure local redox changes associated with transient depolarizations of the mitochondrial membrane potential (flickers). The strategy allows imaging of the oxidized to reduced glutathione ratio (GSSG:GSH) in subcellular regions below the diffraction limit with good temporal resolution and minimum phototoxicity. Moreover, the strategy also applies to diverse parameters including pH, H2O2, and Ca2+.

Uncontrolled Mitochondrial Calcium Uptake Underlies The Pathogenesis Of Neurodegeneration In Micu1-Deficient Mice And Patients, Raghavendra Singh, Adam Bartok, Melanie Paillard, Ashley L. Tyburski, Melanie B Elliott, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Dysregulation of mitochondrial Ca2+ homeostasis has been linked to neurodegenerative diseases. Mitochondrial Ca2+ uptake is mediated via the calcium uniporter complex that is primarily regulated by MICU1, a Ca2+-sensing gatekeeper. Recently, human patients with MICU1 loss-of-function mutations were diagnosed with neuromuscular and cognitive impairments. While studies in patient-derived cells revealed altered mitochondrial calcium signaling, the neuronal pathogenesis was difficult to study. To fill this void, we created a neuron-specific MICU1-KO mouse model. These animals show progressive, abnormal motor and cognitive phenotypes likely caused by the degeneration of motor neurons in the spinal cord and the cortex. We found increased susceptibility …