Digital Commons Network^™

Specialized Astrocytes Mediate Glutamatergic Gliotransmission In The Cns, Roberta De Ceglia, Ada Ledonne, David Gregory Litvin, Barbara Lykke Lind, Giovanni Carriero, Emanuele Claudio Latagliata, Erika Bindocci, Maria Amalia Di Castro, Iaroslav Savtchouk, Ilaria Vitali, Anurag Ranjak, Mauro Congiu, Tara Canonica, William Wisden, Kenneth Harris, Manuel Mameli, Nicola Mercuri, Ludovic Telley, Andrea Volterra

Biomedical Sciences Faculty Research and Publications

Multimodal astrocyte–neuron communications govern brain circuitry assembly and function. For example, through rapid glutamate release, astrocytes can control excitability, plasticity and synchronous activity of synaptic networks, while also contributing to their dysregulation in neuropsychiatric conditions. For astrocytes to communicate through fast focal glutamate release, they should possess an apparatus for Ca2+-dependent exocytosis similar to neurons. However, the existence of this mechanism has been questioned owing to inconsistent data and a lack of direct supporting evidence. Here we revisited the astrocyte glutamate exocytosis hypothesis by considering the emerging molecular heterogeneity of astrocytes and using molecular, bioinformatic and imaging approaches, together with …

[Dataset] Comparison Of Intermittent Fasting And Voluntary Wheel Running On Physical And Cognitive Abilities In High-Fat Diet-Induced Obese Rats, Chaya Gopalan, Paige Niepoetter, Carolyn Butts-Wilmsmeyer, Sai Medavaka, Avery Ogle, Sheyenne Daughrity, Elizabeth Hackmann, Saruveish Mogan, Oskar Lenz

Applied Health Faculty Research, Scholarship, and Creative Activity

Regular physical activity is a proven routine for weight management in addressing obesity. Another method that has gained attention for its health benefits is intermittent fasting (IF). Physical and cognitive abilities while on these routines are poorly understood in the obese population. Sixty-five male Sprague Dawley rats at 7 weeks of age were subjected to diet-induced obesity by feeding a high-fat diet (HFD) or a standard diet (SD) for 8 weeks, after which behavioral testing was performed to detect any changes in physical and cognitive abilities. Rats from the HFD-fed (now considered obese) and SD-fed groups were then subjected to …

Web-Grading-A Tool To Test Personal Grading Of Renal And Prostate Cancer, Glen Kristiansen, Matthias Schmid, Lars Egevad, Hemamali Samaratunga, Murali Varma, Kaan Inam, Hans-Jürgen Thiesen, Brett Delahunt, Yulin Dai

Faculty, Staff and Student Publications

Only a few pathologists have the opportunity to verify their personal grading through objective assessment. This study introduces a web-based grading platform to facilitate and validate the grading of renal cell carcinoma and prostate cancer. Two representative images of two clinically annotated cohorts of 100 cases each of prostate and renal cell carcinoma were used. Each participant was asked to grade a tumor series utilizing a three tiered grading system. Finally, a Kaplan-Meier curve was drawn, and the log-rank test was used for statistical testing of the p-value. The grading of 22 participants (68%) achieved prognostic significance. Further analysis highlighted …

Novel Strategies In Antithrombotic Therapy: Targeting Thrombosis While Preserving Hemostasis, Martha M. S. Sim, Semekidus Shiferawe, Jeremy P. Wood

Saha Cardiovascular Research Center Faculty Publications

Antithrombotic therapy is a delicate balance between the benefits of preventing a thrombotic event and the risks of inducing a major bleed. Traditional approaches have included antiplatelet and anticoagulant medications, require careful dosing and monitoring, and all carry some risk of bleeding. In recent years, several new targets have been identified, both in the platelet and coagulation systems, which may mitigate this bleeding risk. In this review, we briefly describe the current state of antithrombotic therapy, and then present a detailed discussion of the new generation of drugs that are being developed to target more safely existing or newly identified …

Dean's Update, October 2023, Neil W. Schluger

SOM Dean's Research Newsletter

No abstract provided.

Dean's Report- Fall 2023, Marina K. Holz

GSBMS Dean’s Report

No abstract provided.

Molecular And Biochemical Analysis Of Cytochrome P450 2c19 And 2d6, Reema Saleous

Theses

Pharmacogenomics (PGx) is a relatively new field of study. It links genetics to pharmacology since it deals with the influence of the genetic makeup of the individual on their ability to respond to specific medications. Some of the most important genes in this field, dubbed very important pharmacogenes (VIPs), belong to the cytochrome P450 (CYP) superfamily of drug metabolizing enzymes. The two members of this family that are the main focus of this thesis are CYP2C19 and CYP2D6. They play major roles in the metabolism of numerous medications, and it is therefore imperative that variations within those genes in various …

Elongation Of Very Long Chain Fatty Acids-3 (Elovl3) Is Activated By Zhx2 And Is A Regulator Of Cell Cycle Progression, Kate Townsend Creasy, Hui Ren, Jieyun Jiang, Martha L. Peterson, Brett T. Spear

Markey Cancer Center Faculty Publications

Zinc fingers and homeoboxes 2 (Zhx2) are transcriptional regulators of liver gene expression with key functions in embryonic development as well as tissue regeneration in response to damage and disease, presumably through its control of target genes. Previous microarray data suggested that elongation of very long chain fatty acids-3 (Elovl3), a member of the ELOVL family of enzymes that synthesize very long chain fatty acids (VLCFAs), is a putative Zhx2 target gene. VLCFAs are core component of ceramides and other bioactive sphingolipids that are often dysregulated in diseases and regulate key cellular processes including proliferation. Since several previously identified Zhx2 …

Expert Panel Curation Of 113 Primary Mitochondrial Disease Genes For The Leigh Syndrome Spectrum, Elizabeth M Mccormick, Kierstin Keller, Julie P Taylor, Alison J Coffey, Lishuang Shen, Danuta Krotoski, Brian Harding, Xiaowu Gai, Marni J Falk, Zarazuela Zolkipli-Cunningham, Shamima Rahman

Children’s Nutrition Research Center Staff Publications

Objective: Primary mitochondrial diseases (PMDs) are heterogeneous disorders caused by inherited mitochondrial dysfunction. Classically defined neuropathologically as subacute necrotizing encephalomyelopathy, Leigh syndrome spectrum (LSS) is the most frequent manifestation of PMD in children, but may also present in adults. A major challenge for accurate diagnosis of LSS in the genomic medicine era is establishing gene-disease relationships (GDRs) for this syndrome with >100 monogenic causes across both nuclear and mitochondrial genomes.

Methods: The Clinical Genome Resource (ClinGen) Mitochondrial Disease Gene Curation Expert Panel (GCEP), comprising 40 international PMD experts, met monthly for 4 years to review GDRs for LSS. The GCEP …

Pirh2-Dependent Dna Damage In Neurons Induced By The G-Quadruplex Ligand Pyridostatin, Rocio Diaz Escarcega, Abhijeet A Patil, Jose F Moruno-Manchon, Akihiko Urayama, Sean P Marrelli, Nayun Kim, David Monchaud, Louise D Mccullough, Andrey S Tsvetkov

Faculty, Staff and Student Publications

Noncanonical base pairing between four guanines (G) within single-stranded G-rich sequences leads to formation of а G-quartet. Self-stacking of G-quartets results in a columnar four-stranded DNA structure known as the G-quadruplex (G4 or G4-DNA). In cancer cells, G4-DNA regulates multiple DNA-dependent processes, including transcription, replication, and telomere function. How G4s function in neurons is poorly understood. Here, we performed a genome-wide gene expression analysis (RNA-Seq) to identify genes modulated by a G4-DNA ligand, pyridostatin (PDS), in primary cultured neurons. PDS promotes stabilization of G4 structures, thus allowing us to define genes directly or indirectly responsive to G4 regulation. We found …

Multi-Ancestry Genome-Wide Study Identifies Effector Genes And Druggable Pathways For Coronary Artery Calcification, Maryam Kavousi, Maxime M Bos, Hanna J Barnes, Christian L Lino Cardenas, Doris Wong, Haojie Lu, Chani J Hodonsky, Lennart P L Landsmeer, Adam W Turner, Minjung Kho, Natalie R Hasbani, Paul S De Vries, Donald W Bowden, Sandesh Chopade, Joris Deelen, Ernest Diez Benavente, Xiuqing Guo, Edith Hofer, Shih-Jen Hwang, Sharon M Lutz, Leo-Pekka Lyytikäinen, Lotte Slenders, Albert V Smith, Maggie A Stanislawski, Jessica Van Setten, Quenna Wong, Lisa R Yanek, Diane M Becker, Marian Beekman, Matthew J Budoff, Mary F Feitosa, Chris Finan, Austin T Hilliard, Sharon L R Kardia, Jason C Kovacic, Brian G Kral, Carl D Langefeld, Lenore J Launer, Shaista Malik, Firdaus A A Mohamed Hoesein, Michal Mokry, Reinhold Schmidt, Jennifer A Smith, Kent D Taylor, James G Terry, Jeroen Van Der Grond, Joyce Van Meurs, Rozemarijn Vliegenthart, Jianzhao Xu, Kendra A Young, Nuno R Zilhão, Robert Zweiker, Themistocles L Assimes, Lewis C Becker, Daniel Bos, J Jeffrey Carr, L Adrienne Cupples, Dominique P V De Kleijn, Menno De Winther, Hester M Den Ruijter, Myriam Fornage, Barry I Freedman, Vilmundur Gudnason, Aroon D Hingorani, John E Hokanson, M Arfan Ikram, Ivana Išgum, David R Jacobs, Mika Kähönen, Leslie A Lange, Terho Lehtimäki, Gerard Pasterkamp, Olli T Raitakari, Helena Schmidt, P Eline Slagboom, André G Uitterlinden, Meike W Vernooij, Joshua C Bis, Nora Franceschini, Bruce M Psaty, Wendy S Post, Jerome I Rotter, Johan L M Björkegren, Christopher J O'Donnell, Lawrence F Bielak, Patricia A Peyser, Rajeev Malhotra, Sander W Van Der Laan, Clint L Miller

Faculty, Staff and Student Publications

Coronary artery calcification (CAC), a measure of subclinical atherosclerosis, predicts future symptomatic coronary artery disease (CAD). Identifying genetic risk factors for CAC may point to new therapeutic avenues for prevention. Currently, there are only four known risk loci for CAC identified from genome-wide association studies (GWAS) in the general population. Here we conducted the largest multi-ancestry GWAS meta-analysis of CAC to date, which comprised 26,909 individuals of European ancestry and 8,867 individuals of African ancestry. We identified 11 independent risk loci, of which eight were new for CAC and five had not been reported for CAD. These new CAC loci …

The Interaction Between Autophagy, Helicobacter Pylori, And Gut Microbiota In Gastric Carcinogenesis, Ali Nabavi-Rad, Abbas Yadegar, Amir Sadeghi, Hamid Asadzadeh Aghdaei, Mohammad Reza Zali, Daniel J Klionsky, Yoshio Yamaoka

Faculty, Staff and Students Publications

Chronic infection with Helicobacter pylori is the primary risk factor for the development of gastric cancer. Hindering our ability to comprehend the precise role of autophagy during H. pylori infection is the complexity of context-dependent autophagy signaling pathways. Recent and ongoing progress in understanding H. pylori virulence allows new frontiers of research for the crosstalk between autophagy and H. pylori. Novel approaches toward discovering autophagy signaling networks have further revealed their critical influence on the structure of gut microbiota and the metabolome. Here we intend to present a holistic view of the perplexing role of autophagy in H. pylori pathogenesis …

Supplemental Issue Of The Journal Of The Acquired Immune Deficiency Syndromes (Jaids): The Centers For Aids Research (Cfar) Diversity, Equity, And Inclusion Pathway Initiative (Cdeipi), Alan E Greenberg, Anthony K Wutoh, Lisa Bowleg, Manya Magnus, Brandi Robinson, Lorena Segarra, Eric Refsland

Faculty, Staff and Students Publications

No abstract provided.

Cellular Responses After (Neratinib Plus Pemetrexed) Exposure In Nsclc Cells, Laurence Booth, Andrew Poklepovic, John F Hancock, Paul Dent

Faculty, Staff and Student Publications

We previously demonstrated that neratinib interacted with pemetrexed to kill non-small cell lung cancer (NSCLC) cells. From developing other drug combinations, we observed that several days following exposure, cells activated survival mechanisms to counteract drug toxicity. The present studies attempted to define mechanisms that evolve to reduce the efficacy of neratinib and pemetrexed. Neratinib and pemetrexed synergized to kill NSCLC cells expressing wild-type RAS proteins, mutant KRAS (G12S; Q61H; G12A and G12C) or mutant NRAS (Q61K) or mutant ERBB1 (L858R; L858R T790M and exon 19 deletion). Neratinib and pemetrexed interacted in a greater than additive fashion to kill after 24 …

Electrophysiological Responses To Emotional And Cocaine Cues Reveal Individual Neuroaffective Profiles In Cocaine Users, Heather E Webber, Constanza De Dios, Margaret C Wardle, Robert Suchting, Charles E Green, Joy M Schmitz, Scott D Lane, Francesco Versace

Faculty, Staff and Student Publications

Smokers with stronger neuroaffective responses to drug-related cues compared to non-drug-related pleasant images (C>P) are more vulnerable to compulsive smoking than individuals with the opposite brain reactivity profile (P>C). However, it is unknown if these neurobehavioral profiles exist in individuals abusing other drugs. We tested whether individuals with cocaine use disorder (CUD) show similar neuroaffective profiles to smokers. We also monitored eye movements to assess attentional bias toward cues and we further performed exploratory analyses on demographics, personality, and drug use between profiles. Participants with CUD (n=43) viewed pleasant, unpleasant, cocaine, and neutral images while we recorded electroencephalogram. …

The Microtubule Quartet Protein Snap1 In Trypanosoma Brucei Facilitates Flagellum And Cell Division Plane Positioning By Promoting Basal Body Segregation, Martin Carbo-Tano, Mathilde Lapoix, Xinyu Jia, Olivier Thouvenin, Marco Pascucci, François Auclair, Feng B Quan, Shahad Albadri, Vernie Aguda, Younes Farouj, Elizabeth M C Hillman, Ruben Portugues, Filippo Del Bene, Tod R Thiele, Réjean Dubuc, Claire Wyart

Faculty, Staff and Student Publications

The mesencephalic locomotor region (MLR) is a brain stem area whose stimulation triggers graded forward locomotion. How MLR neurons recruit downstream vsx2+ (V2a) reticulospinal neurons (RSNs) is poorly understood. Here, to overcome this challenge, we uncovered the locus of MLR in transparent larval zebrafish and show that the MLR locus is distinct from the nucleus of the medial longitudinal fasciculus. MLR stimulations reliably elicit forward locomotion of controlled duration and frequency. MLR neurons recruit V2a RSNs via projections onto somata in pontine and retropontine areas, and onto dendrites in the medulla. High-speed volumetric imaging of neuronal activity reveals that …

Delivery Outcomes In A Cohort Of Pregnant Patients With Covid-19 With And Without Viral Pneumonia, Brianna Dubose, Yazmeen Tembunde, Katherine E Goodman, Lisa Pineles, Gita Nadimpalli, Jonathan D Baghdadi, Jacqueline G Parchem, Anthony D Harris, Beth L Pineles

Faculty, Staff and Student Publications

Background: Among pregnant people, COVID-19 can lead to adverse outcomes, but the specific pregnancy outcomes that are affected by the disease are unclear. In addition, the effect of the severity of COVID-19 on pregnancy outcomes has not been clearly identified.

Objective: This study aimed to evaluate the associations between COVID-19 with and without viral pneumonia and cesarean delivery, preterm delivery, preeclampsia, and stillbirth.

Study design: We conducted a retrospective cohort study (April 2020-May 2021) of deliveries between 20 and 42 weeks of gestation from US hospitals in the Premier Healthcare Database. The primary outcomes were cesarean delivery, preterm delivery, preeclampsia, …

The Emerging Importance Of Mitochondria In White Adipocytes: Neither Last Nor Least, Juan Cai, Fenfen Wang, Mengle Shao

Faculty, Staff and Student Publications

The growing recognition of mitochondria's crucial role in the regulation of white adipose tissue remodeling and energy balance underscores its significance. The marked metabolic diversity of mitochondria provides the molecular and cellular foundation for enabling adipose tissue plasticity in response to various metabolic cues. Effective control of mitochondrial function at the cellular level, not only in thermogenic brown and beige adipocytes but also in energy-storing white adipocytes, exerts a profound influence on adipose homeostasis. Furthermore, mitochondria play a pivotal role in intercellular communication within adipose tissue via production of metabolites with signaling properties. A more comprehensive understanding of mitochondrial regulation …

Correction To “Inhibition Of Hyaluronan Synthesis Attenuates Pulmonary Hypertension Associated With Lung Fibrosis”, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

No abstract provided.

Comparisons Of Medical Cost Trajectories Between Non-Hispanic Black And Non-Hispanic White Patients With Newly Diagnosed Localized Prostate Cancer, Yu Liu, Shikun Wang, Liang Li, Ying Xu, Yu Shen, Ya-Chen Tina Shih

Faculty, Staff and Student Publications

Objectives: This study applied a recently developed statistical method to compare the mean cost trajectories between non-Hispanic White (NHW) and non-Hispanic Black (NHB) patients with localized prostate cancer conditioning on patients' survival.

Methods: In this observational study, we modeled cost trajectories of NHW and NHB patients with localized prostate cancer for 3 survival durations: 24, 48, and 72 months. We also compared the cost trajectories between NHW and NHB, stratified by comorbidities scores.

Results: We find that the mean cost trajectories of NHB were significantly higher than the trajectories of NHW in the last 12 months before death, regardless of …

Hmg-Coa Reductase Inhibitors For Traumatic Brain Injury, Kalman Katlowitz, Shankar Gopinath, Jovany Cruz Navarro, Claudia Robertson

Faculty, Staff and Students Publications

Traumatic brain injuries (TBIs) are associated with high morbidity and mortality due to both the original insult as well as the destructive biological response that follows. Medical management aims to slow or even halt secondary neurological injury while simultaneously laying the groundwork for recovery. Statins are one class of medications that is showing increased promise in the management of TBI. Used extensively in cardiovascular disease, these drugs were originally developed as competitive inhibitors within the cholesterol production pipeline. They are now used in diverse disease states due to their pleiotropic effects on other biological processes such as inflammation and angiogenesis. …

Fatigue In Patients Receiving Maintenance Hemodialysis: A Review, Maurizio Bossola, S Susan Hedayati, Astrid D H Brys, L Parker Gregg

Faculty, Staff and Students Publications

Fatigue surrounding hemodialysis treatments is a common and often debilitating symptom that impacts patients' quality of life. Intradialytic fatigue develops or worsens immediately before hemodialysis and persists through the dialysis treatment. Little is known about associated risk factors or pathophysiology, although it may relate to a classic conditioning response. Postdialysis fatigue (PDF) develops or worsens after hemodialysis and may persist for hours. There is no consensus on how to measure PDF. Estimates for the prevalence of PDF range from 20%-86%, likely due to variation in methods of ascertainment and participant characteristics. Several hypotheses seek to explain the pathophysiology of PDF, …

A Recombinant Protein Xbb15 Rbd/Alum/Cpg Vaccine Elicits High Neutralizing Antibody Titers Against Omicron Subvariants Of Sars-Cov-2, Syamala Rani Thimmiraju, Rakesh Adhikari, Maria Jose Villar, Jungsoon Lee, Zhuyun Liu, Rakhi Kundu, Yi-Lin Chen, Suman Sharma, Karm Ghei, Brian Keegan, Leroy Versteeg, Portia M Gillespie, Allan Ciciriello, Nelufa Y Islam, Cristina Poveda, Nestor Uzcategui, Wen-Hsiang Chen, Jason T Kimata, Bin Zhan, Ulrich Strych, Maria Elena Bottazzi, Peter J Hotez, Jeroen Pollet

Faculty, Staff and Students Publications

(1) Background: We previously reported the development of a recombinant protein SARS-CoV-2 vaccine, consisting of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, adjuvanted with aluminum hydroxide (alum) and CpG oligonucleotides. In mice and non-human primates, our wild-type (WT) RBD vaccine induced high neutralizing antibody titers against the WT isolate of the virus, and, with partners in India and Indonesia, it was later developed into two closely resembling human vaccines, Corbevax and Indovac. Here, we describe the development and characterization of a next-generation vaccine adapted to the recently emerging XBB variants of SARS-CoV-2. (2) Methods: We conducted preclinical studies …

Bronchopulmonary Dysplasia – Associated Pulmonary Hypertension: An Updated Review, Ahmed El-Saie, Nidhy P Varghese, Melissa K Webb, Natalie Villafranco, Bheru Gandhi, Milenka Cuevas Guaman, Binoy Shivanna

Faculty, Staff and Students Publications

Bronchopulmonary dysplasia (BPD) is the leading cause of chronic lung disease in infants and the commonest complication of prematurity. Advances in respiratory and overall neonatal care have increased the survival of extremely low gestational age newborns, leading to the continued high incidence of BPD. Pulmonary hypertension (PH) represents the severe form of the pulmonary vascular disease associated with BPD, and affects almost one-third of infants with moderate to severe BPD. PH responds suboptimally to pulmonary vasodilators and increases morbidity and mortality in BPD infants. An up-to-date knowledge of the pathogenesis, pathophysiology, diagnosis, treatment, and outcomes of BPD-PH can be helpful …

Recent Insights Into The Pathogenesis And Therapeutic Targets Of Chronic Liver Diseases, Yankai Wen, Lichun Ma, Cynthia Ju

Faculty, Staff and Student Publications

Viral hepatitis, alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are the three major causes of chronic liver diseases, which account for approximately 2 million deaths per year worldwide. The current direct-acting antiviral drugs and vaccinations have effectively reduced and ameliorated viral hepatitis infection, but there are still no effective drug treatments for ALD, NAFLD and liver cancer due to the poor understanding of their pathogenesis. To better understand the pathogenesis, the fifth Chinese American Liver Society/Society of Chinese Bioscientists in America Hepatology Division Annual Symposium, which was held virtually on 21-22 October 2022, focused on the topics …

Meeting The Demand For Fertility Services: The Present And Future Of Reproductive Endocrinology And Infertility In The United States, Eduardo Hariton, Ruben Alvero, Micah J Hill, Jennifer E Mersereau, Shana Perman, David Sable, Fiona Wang, Geoffrey David Adamson, Christos Coutifaris, Latasha B Craig, Pardis Hosseinzadeh, Anthony N Imudia, Erica B Johnstone, Ruth B Lathi, Paul C Lin, Erica E Marsh, Michele Munch, Gloria Richard-Davis, Lauren W Roth, Amy K Schutt, Kim Thornton, Lauren Verrilli, Rachel S Weinerman, Steven L Young, Kate Devine

Faculty, Staff and Students Publications

The field of reproductive endocrinology and infertility (REI) is at a crossroads; there is a mismatch between demand for reproductive endocrinology, infertility and assisted reproductive technology (ART) services, and availability of care. This document's focus is to provide data justifying the critical need for increased provision of fertility services in the United States now and into the future, offer approaches to rectify the developing physician shortage problem, and suggest a framework for the discussion on how to meet that increase in demand. The Society of REI recommend the following: 1. Our field should aggressively explore and implement courses of action …

Texas Developmental Center For Aids Research Cfar Diversity, Equity, And Inclusion Pathway Initiative Program, Fred A Pereira, Alana D Newell, Andrew P Rice

Faculty, Staff and Students Publications

BACKGROUND: The Texas Developmental Center for AIDS Research (D-CFAR) diversity program, termed the CFAR Diversity, Equity, and Inclusion Pathway Initiative (CDEIPI), was created in 2021 to engage high school students and graduate students from Underrepresented Minorities/Black, Indigenous, and People of Color populations.

SETTING: The Texas D-CFAR CDEIPI has partnered with 2 Texas high schools with predominantly economically disadvantaged and minority student populations-Michael E. DeBakey High School for Health Professions in Houston, TX, and the South Texas Independent School District Medical Professions High School in Olmito, TX in the Rio Grande Valley.

METHODS: A total of 370 high school student learners …

The Pre-Adaptation Of A Stroke-Specific Self-Management Program Among Older Adults, Timothy Reistetter, Kimberly Hreha, Julianna M Dean, Monique R Pappadis, Rachel R Deer, Chih-Ying Li, Ickpyo Hong, Annalisa Na, Sara Nowakowski, Hashem M Shaltoni, Suresh K Bhavnani

Faculty, Staff and Students Publications

Objectives:

Managing multimorbidity as aging stroke patients is complex; standard self-management programs necessitate adaptations. We used visual analytics to examine complex relationships among aging stroke survivors’ comorbidities. These findings informed pre-adaptation of a component of the Chronic Disease Self-Management Program.

Methods:

Secondary analysis of 2013–2014 Medicare claims with stroke as an index condition, hospital readmission within 90 days (n=42,938), and 72 comorbidities. Visual analytics identified patient subgroups and co-occurring comorbidities. Guided by the framework for reporting adaptations and modifications to evidence-based interventions (FRAME), an interdisciplinary team developed vignettes that highlighted multimorbidity to customize the self-management program.

Results:

There were five …

A Novel Pathogenic Mutation Of Mecp2 Impairs Chromatin Association Independent Of Protein Levels, Jian Zhou, Claudia Cattoglio, Yingyao Shao, Harini P Tirumala, Carlo Vetralla, Sameer S Bajikar, Yan Li, Hu Chen, Qi Wang, Zhenyu Wu, Bing Tang, Mahla Zahabiyon, Aleksandar Bajic, Xiangling Meng, Jack J Ferrie, Anel Lagrone, Ping Zhang, Jean J Kim, Jianrong Tang, Zhandong Liu, Xavier Darzacq, Nathaniel Heintz, Robert Tjian, Huda Y Zoghbi

Faculty, Staff and Students Publications

Loss-of-function mutations in MECP2 cause Rett syndrome (RTT), a severe neurological disorder that mainly affects girls. Mutations in MECP2 do occur in males occasionally and typically cause severe encephalopathy and premature lethality. Recently, we identified a missense mutation (c.353G>A, p.Gly118Glu [G118E]), which has never been seen before in MECP2, in a young boy who suffered from progressive motor dysfunction and developmental delay. To determine whether this variant caused the clinical symptoms and study its functional consequences, we established two disease models, including human neurons from patient-derived iPSCs and a knock-in mouse line. G118E mutation partially reduces MeCP2 abundance …

A Pancreatic Player In Dementia: Pathological Role For Islet Amyloid Polypeptide Accumulation In The Brain, Angelina S Bortoletto, Ronald J Parchem

Faculty, Staff and Students Publications

Type 2 diabetes mellitus patients have a markedly higher risk of developing dementia. While multiple factors contribute to this predisposition, one of these involves the increased secretion of amylin, or islet amyloid polypeptide, that accompanies the pathophysiology of type 2 diabetes mellitus. Islet amyloid polypeptide accumulation has undoubtedly been implicated in various forms of dementia, including Alzheimer’s disease and vascular dementia, but the exact mechanisms underlying islet amyloid polypeptide’s causative role in dementia are unclear. In this review, we have summarized the literature supporting the various mechanisms by which islet amyloid polypeptide accumulation may cause neuronal damage, ultimately leading to …