Browsing by Author "IU School of Medicine"

Now showing 1 - 9 of 9
  • Thumbnail Image
    Item
    Aminoacyl tRNA synthetase complex interacting multifunctional protein 1 simultaneously binds Glutamyl-Prolyl-tRNA synthetase and scaffold protein aminoacyl tRNA synthetase complex interacting multifunctional protein 3 of the multi-tRNA synthetase complex
    (Elsevier, 2018-06) Schwarz, Margaret A.; Lee, Daniel D.; Bartlett, Seamus; IU School of Medicine
    Higher eukaryotes have developed extensive compartmentalization of amino acid (aa) - tRNA coupling through the formation of a multi-synthetase complex (MSC) that is composed of eight aa-tRNA synthetases (ARS) and three scaffold proteins: aminoacyl tRNA synthetase complex interacting multifunctional proteins (AIMP1, 2 and 3). Lower eukaryotes have a much smaller complex while yeast MSC consists of only two ARS (MetRS and GluRS) and one ARS cofactor 1 protein, Arc1p (Simos et al., 1996), the homolog of the mammalian AIMP1. Arc1p is reported to form a tripartite complex with GluRS and MetRS through association of the N-terminus GST-like domains (GST-L) of the three proteins (Koehler et al., 2013). Mammalian AIMP1 has no GST-L domain corresponding to Arc1p N-terminus. Instead, AIMP3, another scaffold protein of 18 kDa composed entirely of a GST-L domain, interacts with Methionyl-tRNA synthetase (MARS) (Quevillon et al., 1999) and Glutamyl-Prolyl-tRNA Synthetase (EPRS) (Cho et al., 2015). Here we report two new interactions between MSC members: AIMP1 binds to EPRS and AIMP1 binds to AIMP3. Interestingly, the interaction between AIMP1 and AIMP3 complex makes it the functional equivalent of a single Arc1p polypeptide in yeast. This interaction is not mapped to AIMP1 N-terminal coiled-coil domain, but rather requires an intact tertiary structure of the entire protein. Since AIMP1 also interacts with AIMP2, all three proteins appear to compose a core docking structure for the eight ARS in the MSC complex.
  • Thumbnail Image
    Item
    Commentary: “Personality and intentional binding: an exploratory study using the narcissistic personality inventory”
    (2015) Dimaggio, Giancarlo; Lysaker, Paul H.; IU School of Medicine
    A commentary on Personality and intentional binding: an exploratory study using the narcissistic personality inventory by Hascalovitz AC and Obhi SS. Front. Hum. Neurosci. (2015) 9:13. doi: 10.3389/fnhum.2015.00013
  • Thumbnail Image
    Item
    Coping With Racism: Moderators of the Discrimination-Adjustment Link Among Mexican-Origin Adolescents
    (Wiley, 2018-05) Park, Irene J.K.; Wang, Lijuan; Williams, David R.; Alegria, Margarita; IU School of Medicine
    What strategies help ethnic minority adolescents to cope with racism? The present study addressed this question by testing the role of ethnic identity, social support, and anger expression and suppression as moderators of the discrimination-adjustment link among 269 Mexican-origin adolescents (Mage = 14.1 years), 12-17 years old from the Midwestern U.S. Results from multilevel moderation analyses indicated that ethnic identity, social support, and anger suppression, respectively, significantly attenuated the relations between discrimination and adjustment problems, whereas outward anger expression exacerbated these relations. Moderation effects differed according to the level of analysis. By identifying effective coping strategies in the discrimination-adjustment link at specific levels of analysis, the present findings can guide future intervention efforts for Latino youth.
  • Thumbnail Image
    Item
    COVID-19s Impact on the Hispanic Community: How Understanding Culture Can Improve Outcomes
    (Indiana Medical Student Program for Research and Scholarship (IMPRS), 2020-12-15) Guerra Rodriguez, Yamilet; Hudson, Brenda L.; IU School of Medicine
    Background: A disproportionate burden of SARS-Cov-2 infection, or coronavirus disease 2019 (Covid-19), and death are highest among racial and ethnic minority groups. Based on data available on June 12, 2020, Hispanic people are more likely to acquire COVID-19 and have higher incidence of hospitalization and death compared to their white, non-Hispanic counterparts. While this issue is complex, many have hypothesized that the difference is due to societal factors and communication methods. The aim of this project was to evaluate information related to how the Hispanic population is affected by COVID-19 and how communications about the disease should be designed based on past research, physician input, and cultural sensitivities. Methods: We conducted a thorough literature search on COVID-19 articles, both peer reviewed and grey literature, evaluating race and ethnic differences in disease prevalence and severity. Additionally, we conducted interviews with a small number of Indiana doctors who treat Hispanic patients to obtain a doctor’s perspective on the Hispanic community’s needs during the pandemic and ways to help reduce prevalence. Results: Physicians in Indiana believe the main approach to help the Hispanic community is by utilizing trusted community resources to communicate information and build relationships with patients over time. It is recommended to develop new methods to deliver essential information about COVID-19 through multiple mediums, in a clear way, and in Spanish with focus on the collective good of the family. In addition, it is important not to just translate resources from English to Spanish but to design materials addressing barriers specific to the Hispanic community. Conclusion: More culturally tailored information should be released to educate the Hispanic community about COVID-19. This information will assist in the design of materials and initiatives for the Hispanic community that we hope will improve methods of communication and care delivery related to COVID-19.
  • Thumbnail Image
    Item
    Death Resulting from Pneumocephalus Complicating Endoscopic Food Bolus Retrieval in a Patient with Eosinophilic Esophagitis
    (Sage, 2016-12) Fuhs, Amy K.; Prahlow, Joseph A.; IU School of Medicine
    Pneumocephalus is a rare complication of esophagogastroduodenoscopy (EGD), but existing literature does not discuss pneumocephalus surrounding endoscopic food bolus retrieval. We present a death involving pneumocephalus complicating endoscopic food removal from the esophagus. A 40-year-old man presented with dysphagia and suprasternal discomfort 12 hours following chicken ingestion. On flexible endoscopy, chicken was visualized in the distal esophagus. After successful retrieval, a mucosal laceration was noted where the chicken had been lodged. He was unarousable following the procedure and was emergently transported to a hospital, where computed tomography scanning showed pneumocephalus. He was later declared brain dead. The case was referred for medicolegal autopsy. The brain was examined first, revealing rare air bubbles within meningeal vessels and numerous, diffuse petechiae-like hemorrhages within the brain parenchyma. The esophageal mucosa had focal discoloration and a partial thickness laceration; microscopic examination revealed eosinophilic esophagitis. Eosinophilic esophagitis is a known risk factor for food bolus impaction and should be suspected in such patients. Pneumocephalus is a rare possible complication of EGD for food bolus retrieval. In patients unresponsive after endoscopy, radiographic detection of potential pneumocephalus should be encouraged to enable timely therapy and improved outcomes, or to supplement autopsy in the event of patient death. Forensic pathologists should understand that pneumocephalus is a potential mechanism of injury/death in patients experiencing esophageal trauma, including injury incurred during EGD.
  • Thumbnail Image
    Item
    The Impact of Covid-19 on Inmate Trust in Health Care and Willingness to Seek Treatment - A Qualitative Investigation
    (Indiana Medical Student Program for Research and Scholarship (IMPRS), 2020-12-15) Kumalo, Valarie; Nelson, Alexander; Messmore, Niki; IU School of Medicine
    Background and Objective: The coronavirus has disproportionately impacted vulnerable members of society. With the U.S. as the global leader in incarceration and the difficulties prison systems face implementing many of the mitigation strategies employed by the general population, the incarcerated population is in a uniquely vulnerable position particularly within an already strained prison healthcare system. Given the nature of prisons as total institutions, negative experiences with the virus coupled with a lack of autonomy could lead to a loss of trust in the healthcare system which has the potential to impact health-seeking behaviors. In this study, we aim to examine the effect of Covid-19 on Indiana inmates’ trust in healthcare.  Project Methods: Data from 380 surveys distributed across Indiana’s prison system will be collected and analyzed. These results will be used to develop an interview protocol to conduct at least 25 in-depth interviews which will then be coded using NVivo to identify any emerging themes regarding their experiences with Covid-19. Prior to this, in-depth literature reviews were done on health care in prison populations and trust in healthcare. Results: The surveys and interview protocol will be developed in the ensuing months and thus no data has yet been collected. The literature review revealed that the quality and accessibility of care in prisons is lacking, an issue exacerbated by the pandemic. Because of the disproportionate number of preexisting issues, inmates worried about the ability of prison administrators to properly protect inmates from contracting the virus. Additionally, it was found that trust likely does have an effect on health, and that many commonalities of inmates are poor predictors for trust. Potential Impact: This study aims to identify potential loss of trust in healthcare systems to inform community reentry programs in developing strategies that prioritize inmate health needs and perceptions.  
  • Thumbnail Image
    Item
    Possible Neuroinflammatory Mechanisms Which May Lead to Long-Term Neurological Disorders in COVID-19 Patients
    (Indiana Medical Student Program for Research and Scholarship (IMPRS), 2020-12-15) Lange, Michael; Shi, Riyi; IU School of Medicine
    This review aims to provide insight into the possible long-term neurological complications that COVID-19 patients may experience after the resolution of intense acute inflammation characterized as “cytokine storm.” Neurological symptoms such as fatigue, headache, dizziness, nausea, confusion, dyspnea, anorexia, malaise, myalgia, ataxia, seizure, hypogeusia, and hyposmia are commonly seen in these patients. COVID-19 related encephalitis is also seen sporadically. However, some researchers believe neuroinflammation is more common than what is reported. Neurological abnormalities that are linked to neuroinflammation are of particular concern because neuroinflammation is hypothesized to cause neurological diseases such as Alzheimer’s Disease, Parkinson’s Disease, and Schizophrenia. Many potential routes can lead to inflammation in the nervous system and elicit neuron cell death in COVID-19 patients. These include the potential neurotropic pathway of the novel coronavirus, CNS parenchymal infectability, thrombotic ischemic stroke, cytokine storm, and blood-brain barrier breakdown. Past pandemics of similar neurotropic viruses could also offer insights regarding the long-term neurological effects of COVID-19. In support of our hypothesis, the Spanish Flu pandemic of 1918-1919 saw an increased incidence of neurodegenerative disease, Parkinson’s disease, and schizophrenia. We do not know exactly what the future will hold for COVID-19 however, it is of paramount importance to attempt to anticipate and prepare for the possible chronic neurological sequelae and mitigate or prevent their effects.
  • Thumbnail Image
    Item
    Suicide by Bomb, with Decapitation
    (Sage, 2016-03) McLemore, Amanda M.; Prahlow, Samuel P.; Prahlow, Joseph A.; IU School of Medicine
    Suicide by explosion is rare outside of the context of terrorist activities. We present a case of a man with a history of explosives expertise who committed suicide by bomb/decapitation. The case serves to remind forensic pathologists of several important issues when presented with a case involving explosives, such as ensuring the safety of all those involved in the investigation and the importance of interagency cooperation. Potentially invaluable ancillary tests at autopsy include performing radiology, collecting trace evidence, retaining clothing, ensuring the positive identity of the decedent, and recognizing the importance of documenting injury types and patterns.
  • Thumbnail Image
    Item
    Targeting MLL1 H3K4 methyltransferase activity in mixed-lineage leukemia
    (Elsevier, 2014-01-23) Cao, Fang; Townsend, Elizabeth C.; Karatas, Hacer; Xu, Jing; Li, Li; Lee, Shirley; Liu, Liu; Chen, Yong; Ouillette, Peter; Zhu, Jidong; Hess, Jay L.; Atadja, Peter; Lei, Ming; Qin, Zhaohui; Malek, Sami; Wang, Shaomeng; Dou, Yali; IU School of Medicine
    Here we report a comprehensive characterization of our recently developed inhibitor MM-401 that targets the MLL1 H3K4 methyltransferase activity. MM-401 is able to specifically inhibit MLL1 activity by blocking MLL1-WDR5 interaction and thus the complex assembly. This targeting strategy does not affect other mixed-lineage leukemia (MLL) family histone methyltransferases (HMTs), revealing a unique regulatory feature for the MLL1 complex. Using MM-401 and its enantiomer control MM-NC-401, we show that inhibiting MLL1 methyltransferase activity specifically blocks proliferation of MLL cells by inducing cell-cycle arrest, apoptosis, and myeloid differentiation without general toxicity to normal bone marrow cells or non-MLL cells. More importantly, transcriptome analyses show that MM-401 induces changes in gene expression similar to those of MLL1 deletion, supporting a predominant role of MLL1 activity in regulating MLL1-dependent leukemia transcription program. We envision broad applications for MM-401 in basic and translational research.