Now showing items 1-20 of 1115

    • Cadmium Exchange with Zinc in the Non-Classical Zinc Finger Protein Tristetraprolin

      Zalesak-Kravek, Stephanie; Brandis, Joel E. P.; Michel, Sarah L. J.; Kane, Maureen A. (2021)
    • Virtual Face to Face with Dr. Bruce Jarrell: Teaching About Medical Cannabis

      Jarrell, Bruce E.; Coop, Andrew; Sera, Leah; Likowski, Alex (2021-09-23)
    • The Association of Antiretroviral Treatment and Early Menopause in Women Aging with the Human Immunodeficiency Virus

      Bozzi, Laura; dosReis, Susan; 0000-0001-5326-6521 (2021)
      Women living with HIV (WLWH) have irregular menses with several periods of prolonged amenorrhea but their risk of early menopause, clinically defined as before age 45 years, is unknown. This is largely because there is no gold standard method to confirm menopause. Antimullerian hormone (AMH) is a biomarker indicative of ovarian reserve; however, no prior study has used this to confirm menopause. This study aimed to 1) confirm menopause using AMH; 2) determine if WLWH are at an increased risk of early menopause compared to at-risk, uninfected women; and 3) evaluate the relationship between time-varying ART use with early menopause in WLWH. Data were derived from the Women’s Interagency HIV Study, which had four enrollment waves from 1994 through 2016 across 11 US clinic sites. Women were followed prospectively from their baseline visit until menopause confirmation, loss to follow up, or end of study (12/31/2018), whichever came first. The study cohort was women ages 18 or older with no history of: menopause; hysterectomy/uterine cancer/double oophorectomy; any type of cancer, except skin cancer. Women were censored if they experienced any aforementioned events in follow-up. The study measures confirm menopause were at least 12 months of amenorrhea without resumption of menses and an undetectable AMH (<0.10ng/mL). Age at menopause was determined upon confirmation of final menstrual period. A Cox Proportional Hazards model determined the risk of early menopause among WLWH relative to at-risk uninfected women. Marginal Structural Cox Proportional Hazards models with stabilized weights estimated the effect of >75% adherence to ART, modeled as a time-varying covariate, on the risk of early menopause. Age at confirmed menopause with undetectable AMH was 48.6±4.3 years as compared to 41.2±5.6 years for women with amenorrhea without menses resumption and detectable AMH. WLWH reached menopause at significantly earlier ages and had a two-fold increased risk of experiencing early menopause than at-risk, uninfected women. There was a non-significant protective effect of ≥75% ART adherence on early menopause. AMH can improve the precision in determining age of menopause, which is an integral part of understanding the risk for early menopausal and future planning for postmenopausal care in WLWH.
    • Transparency of COVID-19 vaccine trials: decisions without data

      Tanveer, Sarah; Rowhani-Farid, Anisa; Hong, Kyungwan; Jefferson, Tom; Doshi, Peter (BMJ Publishing Group, 2021-08-09)
    • Maryland Poison Center Annual Report 2020

      University of Maryland, Baltimore. Maryland Poison Center, 2020
    • Tracking COVID-19 Cases, Hospitalizations, and Deaths in U.S Nursing Homes Throughout the Pandemic

      Wallem, Alexandra; Kepczynska, Paulina; Simoni-Wastila, Linda; Qato, Danya; Fleming, Sean; Le, Tham; Yang, Jeanne (2021-04-30)
    • Bile Acids as Biomarkers and Evolutionary Phenotypes

      Shiffka, Stephanie; Swaan, Peter W.; Kane, Maureen A.; 0000-0002-3571-1836 (2021)
      Bile acids (BAs) are the amphipathic end products of cholesterol metabolism and represent a critical means of cholesterol excretion. BAs have a plethora of functions, including digestive roles, homeostatic feedback loops, energy metabolism, regulation of the microbiome, inflammation, and more. These effects implicate BAs in physiological and pathological processes throughout the body, not just within the enterohepatic circuit. To date, BAs have been linked to the pathogenesis of multiple types of cancer, type 2 diabetes mellitus, metabolic syndrome, and neurological disorders, among others. In health, BA homeostasis is precisely regulated by a process termed enterohepatic circulation (EHC). Several transport proteins are instrumental to this process, and disruptions in any of these transport systems lead to dysregulation of BA homeostasis, further leading to complications such as cholestasis and liver disease. BA metabolism and the EHC are conserved throughout vertebrate evolution, but the BA pool of more modern species has been modified to be more hydrophilic while still retaining properties of digestive surfactants. Though EHC is well-characterized, the understanding of eukaryotic transporters in this process is lacking, especially at the molecular level. Despite the recognition of bile acids as signaling molecules involved in disease progression, there remain numerous BAs that are poorly characterized. This is especially important because BAs are an extremely diverse group of molecules that represent the effects of host and microbiome metabolism. Furthermore, the unique physicochemical properties of these variations confer these molecules with differential levels of cytotoxicity and divergent, sometimes opposing, activation of cell signaling pathways. Thus, the scope of this dissertation is two-fold: first, to further characterize the BA pool in health and injury using cell and animal models; secondly, to use this information in order to probe the transporter responsible for the first step of the enterohepatic circulation, ASBT (SLC10A2). Completion of the first objective yielded improved understanding of BA metabolism in cell culture models and non-human primate laboratory models, as well as in radiation injury in the latter model. Accomplishment of the second objective returned insight into ASBT and BA evolution through the use of multiple vertebrate orthologs.
    • Targeting Zinc Finger Proteins with Exogenous Metals and Molecules: Lessons Learned from Tristetraprolin, a CCCH type Zinc Finger

      Ok, Kiwon; Michel, Sarah L. J.; 0000-0002-7724-8860 (2021)
      Zinc (Zn) plays a key role in inflammatory response, including regulating the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. Among the signaling proteins involved in the NF-κB pathway, many are known zinc finger proteins (ZFs), including Tristetraprolin (TTP). TTP is a non-classical CCCH-type Zinc Finger protein (ZF), that contains two Cys3His zinc binding domains and is a key regulator of the inflammatory response. TTP is a potential target for exogenous gold (Au) and copper (Cu), as well as hydrogen sulfide, an emerging gasotransmitter. To understand how TTP is targeted by other metals, the interactions of TTP were investigated using a combination of bioinorganic chemistry tools including as optical spectroscopy, native electrospray ionization mass spectrometry (ESI-MS), and X-ray absorption study (XAS). The first metal investigated was Cu(I). I discovered that Cu(I) can bind to the tandem ZF construct of TTP (TTP-2D) and disrupt structure and function. This finding indicates a potential relationship between Cu toxicity and metal-regulation of ZFs. The second metal investigated was Au(III). I discovered that the reactivity of TTP-2D with gold complex leads to Au exchange forming a series of Aux-TTP-2D complexes, with reduction of the gold from Au(III) to Au(I). These protein species are then functionally inactive (no RNA binding). When the same experiments were performed with TTP bound to RNA, the Zn-TTP/RNA complex is not disrupted by the Au-complex suggesting a protective role for RNA. To understand how H2S, a signaling molecule, targets Zn-TTP-2D, its reactivity was determined using a combination of cryo-ESI-MS, fluorescence, and electron paramagnetic resonance (EPR) spectroscopies. We found that the H2S oxidizes the cysteine residues of Zn-TTP via a mechanism that involves atmospheric oxygen, a persulfide intermediate and a radical reaction. The results of these biochemical studies of TTP will be presented in the context of TTP’s biological role. In addition, development of a method to follow Zn speciation in inflammatory cells via liquid chromatography connected to inductively coupled plasma (LC-ICP-MS), will be presented. Here, I use THP-1 cells, which are a human monocyte cell line as a model for inflammation, and demonstrate an approach to separate the zinc-proteome.