Medicine and Health Sciences Commons^™

Autophagy, Apoptosis, The Unfolded Protein Response, And Lung Function In Idiopathic Pulmonary Fibrosis, Pawan Sharma, Javad Alizadeh, Maya Juarez, Afshin Samali, Andrew J Halayko, Nicholas J Kenyon, Saeid Ghavami, Amir A Zeki

Center for Translational Medicine Faculty Papers

Autophagy, apoptosis, and the unfolded protein response (UPR) are fundamental biological processes essential for manifold cellular functions in health and disease. Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal pulmonary disorder associated with aging that has limited therapies, reflecting our incomplete understanding. We conducted an observational study linking molecular markers of cell stress response pathways (UPR: BiP, XBP1; apoptosis: cleaved caspase-3; autophagy: LC3β) in lung tissues from IPF patients and correlated the expression of these protein markers to each subject's lung function measures. We hypothesized that changes in lung tissue expression of apoptosis, autophagy, and UPR markers correlate with …

A Rare Fatal Case Of Adenovirus Serotype 4 Associated Acute Disseminated Encephalomyelitis In An Adult: A Case Report, Zahra Qamar, Catherine Tucker, Lawrence C. Kenyon, Tricia. Royer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Acute disseminated encephalomyelitis (ADEM) is an autoimmune demyelinating disease directed against the myelin sheath of the central nervous system that typically presents 1–4 weeks after an infection or vaccination, most commonly in children. We describe a case of a young female who presented with rapidly progressive mental deterioration and died secondary to ADEM following an adenovirus upper respiratory tract infection.

Nox4 Signaling Mediates Cancer Development And Therapeutic Resistance Through Her3 In Ovarian Cancer Cells., Wen-Jing Liu, Ying-Xue Huang, Wei Wang, Ye Zhang, Bing-Jie Liu, Jian-Ge Qiu, Bing-Hua Jiang, Ling-Zhi Liu

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Development of resistance to therapy in ovarian cancer is a major hinderance for therapeutic efficacy; however, new mechanisms of the resistance remain to be elucidated. NADPH oxidase 4 (NOX4) is responsible for higher NADPH activity to increase reactive oxygen species (ROS) production. In this study, we showed that higher levels of NOX4 were detected in a large portion of human ovarian cancer samples. To understand the molecular mechanism of the NOX4 upregulation, we showed that NOX4 expression was induced by HIF-1α and growth factor such as IGF-1. Furthermore, our results indicated that NOX4 played a pivotal role in chemotherapy and …

Emerging Advances Of Nanotechnology In Drug And Vaccine Delivery Against Viral Associated Respiratory Infectious Diseases (Varid), Amir Seyfoori, Mahdieh Shokrollahi Barough, Pooneh Mokarram, Mazaher Ahmadi, Parvaneh Mehrbod, Alireza Sheidary, Tayyebeh Madrakian, Mohammad Kiumarsi, Tavia Walsh, Kielan D Mcalinden, Chandra C Ghosh, Pawan Sharma, Amir A Zeki, Saeid Ghavami, Mohsen Akbari

Center for Translational Medicine Faculty Papers

Viral-associated respiratory infectious diseases are one of the most prominent subsets of respiratory failures, known as viral respiratory infections (VRI). VRIs are proceeded by an infection caused by viruses infecting the respiratory system. For the past 100 years, viral associated respiratory epidemics have been the most common cause of infectious disease worldwide. Due to several drawbacks of the current anti-viral treatments, such as drug resistance generation and non-targeting of viral proteins, the development of novel nanotherapeutic or nano-vaccine strategies can be considered essential. Due to their specific physical and biological properties, nanoparticles hold promising opportunities for both anti-viral treatments and …

Mutagenic Analysis Of The Putative Abcc6 Substrate-Binding Cavity Using A New Homology Model, Flóra Szeri, Valentina Corradi, Fatemeh Niaziorimi, Sylvia Donnelly, Gwenaëlle Conseil, Susan P C Cole, D Peter Tieleman, Koen Van De Wetering

Department of Dermatology and Cutaneous Biology Faculty Papers

Inactivating mutations in ABCC6 underlie the rare hereditary mineralization disorder pseudoxanthoma elasticum. ABCC6 is an ATP-binding cassette (ABC) integral membrane protein that mediates the release of ATP from hepatocytes into the bloodstream. The released ATP is extracellularly converted into pyrophosphate, a key mineralization inhibitor. Although ABCC6 is firmly linked to cellular ATP release, the molecular details of ABCC6-mediated ATP release remain elusive. Most of the currently available data support the hypothesis that ABCC6 is an ATP-dependent ATP efflux pump, an un-precedented function for an ABC transporter. This hypothesis implies the presence of an ATP-binding site in the substrate-binding cavity of …

Learning From Nature: From A Marine Natural Product To Synthetic Cyclooxygenase-1 Inhibitors By Automated De Novo Design., Lukas Friedrich, Gino Cingolani, Ying-Hui Ko, Mariaclara Iaselli, Morena Miciaccia, Maria Grazia Perrone, Konstantin Neukirch, Veronika Bobinger, Daniel Merk, Robert Klaus Hofstetter, Oliver Werz, Andreas Koeberle, Antonio Scilimati, Gisbert Schneider

Department of Biochemistry and Molecular Biology Faculty Papers

The repertoire of natural products offers tremendous opportunities for chemical biology and drug discovery. Natural product-inspired synthetic molecules represent an ecologically and economically sustainable alternative to the direct utilization of natural products. De novo design with machine intelligence bridges the gap between the worlds of bioactive natural products and synthetic molecules. On employing the compound Marinopyrrole A from marine Streptomyces as a design template, the algorithm constructs innovative small molecules that can be synthesized in three steps, following the computationally suggested synthesis route. Computational activity prediction reveals cyclooxygenase (COX) as a putative target of both Marinopyrrole A and the de …

Comprehensive And Compassionate Responses For Opioid Use Disorder Among Pregnant And Parenting Women., Dennis J. Hand, Alice C. Fischer, Meghan L. Gannon, Kimberly A. Mclaughlin, Vanessa L. Short, Diane J. Abatemarco

Department of Obstetrics and Gynecology Faculty Papers

Pregnant and parenting women with opioid use disorder face multiple challenges to recovery. Trauma histories, poverty, stigma and discrimination, and lack of access to treatment intersect to marginalise this population. It is important that pregnant and parenting women with opioid use disorder receive comprehensive care to improve their health, the health of their child(ren), and prevent the intergenerational transmission of opioid and other substance use disorders. For nearly 50 years the Maternal Addiction Treatment, Education, and Research program has provided an evolving and expanding range of comprehensive services for treating opioid and other substance use disorders in this population. In …

The Utility Of Continuous Passive Motion After Anterior Cruciate Ligament Reconstruction: A Systematic Review Of Comparative Studies, Taylor D'Amore, Somnath Rao, John Corvi, Robert Jack Ii, Fotios Tjoumakaris, Michael G. Ciccotti, Kevin Freedman

Department of Orthopaedic Surgery Faculty Papers

Background: The application of continuous passive motion (CPM) after anterior cruciate ligament reconstruction (ACLR) was popularized in the 1990s, but advancements in the understanding of ACLR rehabilitation have made the application of CPM controversial. Many sports medicine fellowship–trained surgeons report using CPM machines postoperatively. Purpose: To determine the efficacy of CPM use for recovery after ACLR with respect to knee range of motion (ROM), knee swelling, postoperative pain, and postoperative complications. Study Design: Systematic review; Level of evidence, 3. Methods: The PubMed (MEDLINE), EMBASE, Cochrane, Cumulative Index of Nursing, and Allied Health Literature databases were searched from inception to January …

The Evaluation Of Medical Student International Mission Trips: A Rapid Review, Andrew Kamel

Master of Public Health Capstone Presentations

Previous reviews of the literature on medical mission trips have noted that there is a dearth of rigorous data collection and evaluation of the efficacy of medical missions to low- and middle-income countries (LMICs). Medical students are increasingly participating in these trips as global health curriculums become more popular and prevalent, and the literature about these international experiences has not been well-described. This rapid review aims to characterize the evaluation of medical mission trips for medical students to LMICs. This article is a rapid review of the literature using PRIMSA guidelines to search PubMed for studies about the evaluation of …

Prevalence Of Pressure Ulcers In Long-Term Care Facilities: A Focus On Older Adults, Joseph M. Callaghan, Iii

Master of Public Health Capstone Presentations

Pressure Ulcers (PUs) are wounds resulting from skin breakdown. They are common among those who have mobility limitations, and older adults, particularly those residing in nursing homes (NHs) and long-term care facilities (LTCFs). PUs cost U.S. and international healthcare systems millions of dollars per year. For all of these reasons, PUs represent a continuing public health threat.

Our review provides an update on the prevalence of PUs in LTCFs and NHs, especially regarding older adults. We used a single-reviewer, modified PRISMA-P process to conduct a rapid review of the literature. Relevant search terminology were input into PubMed and Scopus^{® …}

Circumcision As An Intervening Strategy Against Hiv Acquisition In The Male Genital Tract, Adhikarimayum Lakhikumar Sharma, Joseph Hokello, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Unsafe sex with HIV-infected individuals remains a major route for HIV transmission, and protective strategies, such as the distribution of free condoms and pre-or post-prophylaxis medication, have failed to control the spread of HIV, particularly in resource-limited settings and high HIV prevalence areas. An additional key strategy for HIV prevention is voluntary male circumcision (MC). International health organizations (e.g., the World Health Organization, UNAIDS) have recommended this strategy on a larger scale, however, there is a general lack of public understanding about how MC effectively protects against HIV infection. This review aims to discuss the acquisition of HIV through the …

The Effect Of Ametropia On Glaucomatous Visual Field Loss., Eun Young Choi, Raymond C.S. Wong, Thuzar Thein, Louis R. Pasquale, Lucy Q. Shen, Mengyu Wang, Dian Li, Qingying Jin, Hui Wang, Neda Baniasadi, Michael V. Boland, Siamak Yousefi, Sarah R. Wellik, Carlos G. De Moraes, Jonathan S. Myers, Peter J. Bex, Tobias Elze

Wills Eye Hospital Papers

Myopia has been discussed as a risk factor for glaucoma. In this study, we characterized the relationship between ametropia and patterns of visual field (VF) loss in glaucoma. Reliable automated VFs (SITA Standard 24-2) of 120,019 eyes from 70,495 patients were selected from five academic institutions. The pattern deviation (PD) at each VF location was modeled by linear regression with ametropia (defined as spherical equivalent (SE) starting from extreme high myopia), mean deviation (MD), and their interaction (SE × MD) as regressors. Myopia was associated with decreased PD at the paracentral and temporal VF locations, whereas hyperopia was associated with …

The Development Of Lived Experience-Centered Word Clouds To Support Research Uncertainty Gathering In Degenerative Cervical Myelopathy: Results From An Engagement Process And Protocol For Their Evaluation, Via A Nested Randomized Controlled Trial, Benjamin M Davies, Oliver D Mowforth, Danyal Z Khan, Xiaoyu Yang, Sybil R L Stacpoole, Olesja Hazenbiller, Toto Gronlund, Lindsay Tetreault, Sukhvinder Kalsi-Ryan, Michelle L Starkey, Iwan Sadler, Ellen Sarewitz, Delphine Houlton, Julia Carter, Evangeline Howard, Vafa Rahimi-Movaghar, James D Guest, Bizhan Aarabi, Brian K Kwon, Shekar N Kurpad, James Harrop, Jefferson R Wilson, Robert Grossman, Emma K Smith, Angus G K Mcnair, Michael G Fehlings, Mark R N Kotter

Department of Neurosurgery Faculty Papers

OBJECTIVES: AO Spine REsearch objectives and Common Data Elements for Degenerative Cervical Myelopathy [RECODE-DCM] is a multi-stakeholder consensus process aiming to promote research efficiency in DCM. It aims to establish the top 10 research uncertainties, through a James Lind Alliance Priority Setting Partnership [PSP]. Through a consensus process, research questions are generated and ranked. The inclusion of people with cervical myelopathy [PwCM] is central to the process. We hypothesized that presenting PwCM experience through word cloud generation would stimulate other key stakeholders to generate research questions better aligned with PwCM needs. This protocol outlines our plans to evaluate this as …

Long-Term Efficacy And Tolerability Of Adjunctive Brivaracetam In Adults With Focal To Bilateral Tonic-Clonic (Secondary Generalized) Seizures: Post Hoc Pooled Analysis, Brian D Moseley, Svetlana Dimova, Sami Elmoufti, Cédric Laloyaux, Aliakbar Asadi-Pooya

Department of Neurology Faculty Papers

This post hoc analysis was conducted to evaluate the efficacy, tolerability, and health-related quality of life during long-term adjunctive brivaracetam (BRV) treatment in adult patients with focal to bilateral tonic-clonic seizures (FBTCS). Patients (≥ 16 years) were included in this post hoc analysis if they were randomized to BRV or placebo in double-blind, placebo-controlled (N01252 [NCT00490035], N01253 [NCT00464269], N01358 [NCT01261325]; core) trials, and received adjunctive BRV in the corresponding long-term follow-up (N01125 [NCT00175916], N01199 [NCT00150800], N01379 [NCT01339559]) trials, and reported FBTCS during the 8-week prospective baseline (core trial). Efficacy (concomitant levetiracetam excluded) and tolerability (concomitant levetiracetam included) were assessed from …

Sars-Cov-2 Viral Proteins Nsp1 And Nsp13 Inhibit Interferon Activation Through Distinct Mechanisms, Christine Vazquez, Sydnie E Swanson, Seble G Negatu, Mark Dittmar, Jesse Miller, Holly Ramage, Sara Cherry, Kellie A Jurado

Department of Microbiology and Immunology Faculty Papers

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a devastating global pandemic, infecting over 43 million people and claiming over 1 million lives, with these numbers increasing daily. Therefore, there is urgent need to understand the molecular mechanisms governing SARS-CoV-2 pathogenesis, immune evasion, and disease progression. Here, we show that SARS-CoV-2 can block IRF3 and NF-κB activation early during virus infection. We also identify that the SARS-CoV-2 viral proteins NSP1 and NSP13 can block interferon activation via distinct mechanisms. NSP1 antagonizes interferon signaling by suppressing host mRNA translation, while NSP13 downregulates interferon and NF-κB promoter signaling by limiting TBK1 …

On The Road From Phenotypic Plasticity To Stem Cell Therapy., Lorraine Iacovitti

Farber Institute for Neuroscience Faculty Papers

In 1981, I published a paper in the first issue of The Journal of Neuroscience with my postdoctoral mentor, Richard Bunge. At that time, the long-standing belief that each neuron expressed only one neurotransmitter, known as Dale's Principle (Dale, 1935), was being hotly debated following a report by French embryologist Nicole Le Douarin showing that neural crest cells destined for one transmitter phenotype could express characteristics of another if transplanted to alternate sites in the developing embryo (Le Douarin, 1980). In the Bunge laboratory, we were able to more directly test the question of phenotypic plasticity in the controlled environment …

Amplified Pain Syndrome In Children, Catherine Soprano, Md, Katherine S. Salamon, Phd

Department of Family & Community Medicine Presentations and Grand Rounds

Objectives

• Describe chronic pain conditions
• Define chronic pain from biopsychosocial perspective
• Learn ways to describe treatment philosophy of pediatric chronic pain to families

Therapeutic Potential Of Hla-I Polyreactive Mabs Mimicking The Hla-I Polyreactivity And Immunoregulatory Functions Of Ivig, Mepur H Ravindranath, Fatiha El Hilali, Edward Filippone

Department of Medicine Faculty Papers

HLA class-I (HLA-I) polyreactive monoclonal antibodies (mAbs) reacting to all HLA-I alleles were developed by immunizing mice with HLA-E monomeric, α-heavy chain (αHC) open conformers (OCs). Two mAbs (TFL-006 and TFL-007) were bound to the αHC’s coated on a solid matrix. The binding was inhibited by the peptide117AYDGKDY123, present in all alleles of the six HLA-I isoforms but masked by β2-microglobulin (β2-m) in intact HLA-I trimers (closed conformers, CCs). IVIg preparations administered to lower anti-HLA Abs in pre-and post-transplant patients have also shown HLA-I polyreactivity. We hypothesized that the mAbs that mimic IVIg HLA-I polyreactivity might also possess the immunomodulatory …

Seeking Similarities Rather Than Differences With Adults To Aid In Therapeutic Advancement For Children., Mara L. Becker, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

No abstract provided.

Trends In Leadership At Orthopaedic Surgery Sports Medicine Fellowships, Nicholas C. Schiller, Andrew J. Sama, Amanda F. Spielman, Chester J. Donnally, Benjamin I. Schachner, Dhanur M. Damodar, Christopher C. Dodson, Michael G. Ciccotti

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: Fellowship directors (FDs) in sports medicine influence the future of trainees in the field of orthopaedics. Understanding the characteristics these leaders share must be brought into focus. For all current sports medicine FDs, our group analyzed their demographic background, institutional training, and academic experience.

AIM: To serve as a framework for those aspiring to achieve this position in orthopaedics and also identify opportunities to improve the position.

METHODS: Fellowship programs were identified using both the American Orthopaedic Society for Sports Medicine and the Arthroscopy Association of North America Sports Medicine Fellowship Directories. The demographic and educational background data for …

Examining The Unseen Trauma Endured By 911 Telecommunicators, Angela Gibilante

Master of Public Health Capstone Presentations

First responders of all types are at risk for the development of mental and behavioral health conditions as a result of the repeated exposure to trauma they face. Much research has explored their lived experiences and work has been done to evaluate interventions to mitigate the stress associated with this type of work. However, the majority of this research fails to include 911 Telecommunicators as first responders even though they are also at risk for experiencing trauma (SAMHSA, 2018; Skeffington et al., 2016; Camaro et al., 2020; Stabile, 2015). The purpose of this study was to examine the experiences and …

Outpatient Anticoagulation Management, Anne Du Breuil, Md

Department of Family & Community Medicine Presentations and Grand Rounds

Objectives

• Warfarin Management
• Anticoagulation Module in Epic
• Brief summary of Direct Oral Anticoagulants (DOACs)
• Brief Perioperative Anticoagulation Tips

Outcomes Of Rescue Endovascular Treatment Of Emergent Large Vessel Occlusion In Patients With Underlying Intracranial Atherosclerosis: Insights From Star., Sami Al Kasab, Eyad Almallouhi, Ali Alawieh, Stacey Wolfe, Kyle M. Fargen, Adam S. Arthur, Nitin Goyal, Travis Dumont, Peter Kan, Joon-Tae Kim, Reade De Leacy, Ilko Maier, Joshua Osbun, Ansaar Rai, Pascal Jabbour, Jonathan A. Grossberg, Min S. Park, Robert M. Starke, Roberto Crosa, Alejandro M. Spiotta

Department of Neurosurgery Faculty Papers

Background: Some emergent large vessel occlusions (ELVOs) are refractory to reperfusion because of underlying intracranial atherosclerosis (ICAS), often requiring rescue therapy (RT) with balloon angioplasty, stenting, or both. In this study, we investigate the safety, efficacy, and long-term outcomes of RT in the setting of mechanical thrombectomy for ICAS-related ELVO.

Methods and Results: We queried the databases of 10 thrombectomy‐capable centers in North America and Europe included in STAR (Stroke Thrombectomy and Aneurysm Registry). Patients with ELVO who underwent ICAS‐related RT were included. A matched sample was produced for variables of age, admission National Institute of Health Stroke …

Are Guidelines Important? Results Of A Prospective Quality Improvement Lumbar Fusion Project., James Harrop, Alexandra Emes, Ameet Chitale, Chengyuan Wu, Fadi Al-Saiegh, Geoffrey Stricsek, Glenn A. Gonzalez, Jack Jallo, Joshua Heller, Kevin Hines, Lucas Philipp, Sara Thalheimer, Srinivas K. Prasad, Thiago Montenegro, Umma Fatema, Ashwini Sharan

Department of Neurosurgery Faculty Papers

BACKGROUND: United States (U.S.) healthcare is a volume-based inefficient delivery system. Value requires the consideration of quality, which is lacking in most healthcare disciplines.

OBJECTIVE: To assess whether patients who met specific evidence-based medicine (EBM)-based criteria preoperatively for lumbar fusion would achieve higher rates of achieving the minimal clinical important difference (MCID) than those who did not meet the EBM indications.

METHODS: All elective lumbar fusion cases, March 2018 to August 2019, were prospectively evaluated and categorized based on EBM guidelines for surgical indications. The MCID was defined as a reduction of ≥5 points in Oswestry Disability Index (ODI). Multiple …

Facing Death: Attitudes Toward Physician-Assisted End Of Life Among Physicians Working At A Tertiary-Care-Hospital In Israel, Keren Dopelt, Dganit Cohen, Einat Amar-Krispel, Nadav Davidovitch, Paul Barach

College of Population Health Faculty Papers

The demand for medical assistance in dying remains high and controversial with a large knowledge gap to support optimal patient care. The study aimed to explore physicians’ attitudes regarding euthanasia and examine the factors that related to these attitudes. We surveyed 135 physicians working at a tertiary-care hospital in Israel. The questionnaire was comprised of demographic and background information, DNR procedure information, encounters with terminally ill patients, familiarity with the law regarding end-of-life questions, and Attitudes toward Euthanasia. About 61% agreed that a person has the right to decide whether to expedite their own death, 54% agreed that euthanasia should …

Cinnamomum Tamala Leaf Extract Stabilized Zinc Oxide Nanoparticles: A Promising Photocatalyst For Methylene Blue Degradation, Sajina Narath, Supin Karonnan Koroth, Sarojini Sharath Shankar, Bini George, Vasundhara Mutta, Stanislaw Waclawek, Miroslav Cernik, Vinod Vellora Theekae Padil, Rajender S. Varma

Department of Medicine Faculty Papers

A facile green synthetic method is proposed for the synthesis of zinc oxide nanoparticles (ZnO NPs) using the bio-template Cinnamomum tamala (C. tamala) leaves extract. The morphological, functional, and structural characterization of synthesized ZnO NPs were studied by adopting different techniques such as energy dispersive X-ray analysis (EDX), high-resolution transmission electron microscopy (HR-TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), UV-Visible spectroscopy, fourier transform infrared (FTIR) spectroscopy, raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). The fabricated ZnO NPs exhibit an average size of 35 nm, with a hexagonal nanostructure. Further, the well-characterized ZnO NPs were employed for the photocatalytic degradation …

Leveraging Advancements In Tissue Engineering For Bioprinting Dental Tissues, Devin Grace Morrison, Ryan E. Tomlinson

Department of Orthopaedic Surgery Faculty Papers

3D bioprinting allows biocompatible materials and cells to be deposited in precise locations in three-dimensional space, enabling researchers to surpass the limitations of traditional 2D cell culture and to create innovative therapies. 3D bioprinting is one of the newest tools developed in the field of tissue engineering, which has traditionally utilized a paradigm revolving around scaffolds, cells, and signals. In this review, we discuss how new developments in each of these three research areas relates to bioprinting dental tissues – specifically teeth, periodontal ligament, and alveolar bone. Important considerations include how scaffold materials and geometry affect regeneration of dental tissues, …

Covid-19 Treatment Combinations And Associations With Mortality In A Large Multi-Site Healthcare System., Dagan Coppock, Michael Baram, Anna Marie Chang, Patricia Henwood, Alan Kubey, Ross Summer, John Zurlo, Michael Li, Bryan Hess

Division of Infectious Diseases and Environmental Medicine Faculty Papers

INTRODUCTION: During the early months of the COVID-19 pandemic, mortality associated with the disease declined in the United States. The standard of care for pharmacological interventions evolved during this period as new and repurposed treatments were used alone and in combination. Though these medications have been studied individually, data are limited regarding the relative impact of different medication combinations. The objectives of this study were to evaluate the association of COVID-19-related mortality and observed medication combinations and to determine whether changes in medication-related practice patterns and measured patient characteristics, alone, explain the decline in mortality seen early in the COVID-19 …

Designer Benzodiazepines: A Review Of Toxicology And Public Health Risks, Pietro Brunetti, Raffaele Giorgetti, Adriano Tagliabracci, Marilyn A. Huestis, Francesco Paolo Busardò

Institute of Emerging Health Professions Faculty Papers

The rising use of designer benzodiazepines (DBZD) is a cat-and-mouse game between organized crime and law enforcement. Non-prohibited benzodiazepines are introduced onto the global drug market and scheduled as rapidly as possible by international authorities. In response, DBZD are continuously modified to avoid legal sanctions and drug seizures and generally to increase the abuse potential of the DBZD. This results in an unpredictable fluctuation between the appearance and disappearance of DBZD in the illicit market. Thirty-one DBZD were considered for review after consulting the international early warning database, but only 3-hydroxyphenazepam, adinazolam, clonazolam, etizolam, deschloroetizolam, diclazepam, flualprazolam, flubromazepam, flubromazolam, meclonazepam, …

Polθ Reverse Transcribes Rna And Promotes Rna-Templated Dna Repair, Gurushankar Chandramouly, Jiemin Zhao, Shane Mcdevitt, Timur Rusanov, Trung Hoang, Nikita Borisonnik, Taylor Treddinick, Felicia Wednesday Lopezcolorado, Tatiana Kent, Labiba Siddique, Joseph Mallon, Jacklyn Huhn, Zainab Shoda, Ekaterina Kashkina, Alessandra Brambati, Jeremy M Stark, Xiaojiang S Chen, Richard Pomerantz

Department of Biochemistry and Molecular Biology Faculty Papers

Genome-embedded ribonucleotides arrest replicative DNA polymerases (Pols) and cause DNA breaks. Whether mammalian DNA repair Pols efficiently use template ribonucleotides and promote RNA-templated DNA repair synthesis remains unknown. We find that human Polθ reverse transcribes RNA, similar to retroviral reverse transcriptases (RTs). Polθ exhibits a significantly higher velocity and fidelity of deoxyribonucleotide incorporation on RNA versus DNA. The 3.2-Å crystal structure of Polθ on a DNA/RNA primer-template with bound deoxyribonucleotide reveals that the enzyme undergoes a major structural transformation within the thumb subdomain to accommodate A-form DNA/RNA and forms multiple hydrogen bonds with template ribose 2'-hydroxyl groups like retroviral RTs. …