Recent Submissions

  • IGS Insider Newsletter 2024

    University of Maryland, Baltimore. School of Medicine., 2024
  • Elder Abuse in Family Settings: Findings from Western Nepal

    Shrestha, Aman; Kafle, Bharat; Bhattarai, Preeti; Bhattarai, Pratik; Saruna, Ghimire (2024-02-22)
  • The Journal of the Alumni Association of the College of Physicians and Surgeons, Baltimore, Volumes 17 and 18

    College of Physicians and Surgeons (Baltimore, Md.). Alumni Association (1916)
  • The Journal of the Alumni Association of the College of Physicians and Surgeons, Baltimore, Volume 15

    College of Physicians and Surgeons (Baltimore, Md.). Alumni Association (1912)
  • The Journal of the Alumni Association of the College of Physicians and Surgeons, Baltimore Volumes 11 and 12

    College of Physicians and Surgeons (Baltimore, Md.). Alumni Association (1910)
  • The Journal of the Alumni Association of the College of Physicians and Surgeons, Baltimore, Volume 14

    College of Physicians and Surgeons (Baltimore, Md.). Alumni Association (1912)
  • The Journal of the Alumni Association of the College of Physicians and Surgeons, Baltimore, Volume 13

    College of Physicians and Surgeons (Baltimore, Md.). Alumni Association (1911)
  • The Journal of the Alumni Association of the College of Physicians and Surgeons, Baltimore, Volume 9

    College of Physicians and Surgeons (Baltimore, Md.). Alumni Association (1907)
  • The Journal of the Alumni Association of the College of Physicians and Surgeons, Baltimore, Volume 10

    College of Physicians and Surgeons (Baltimore, Md.). Alumni Association (1907)
  • Door in- Door out Times: A Comprehensive Stroke Center Review

    Schrier, Chad; Palmisano, Caitlin; Phipps, Michael, M.D. (2024-02-07)
  • On vs. Off-hours Arrival to Groin Time: Identifying Gaps in a Comprehensive Stroke Center

    Schrier, Chad; Palmisano, Caitlin; Phipps, Michael, M.D. (2024-02-08)
  • Effects of Nanodysferlins on Recovery of Voltage-Induced SR Calcium Release after Osmotic Shock in Muscle Fibers from Dysferlin-null mice

    Lukyanenko, Valeriy; Muriel, Joaquin M.; Bloch, Robert J. (2024-02-10)
    Earlier we showed using shock injury (OSI) that dysferlin modulates the coupling of excitation to Ca2+ release skeletal myofibers (Kerr et al., PNAS, 2013; Lukyanenko et al., Front. Physiol., 2022). Here we studied dysferlin-null A/J mouse FDB myofibers expressing fluorescent variants of nanodysferlins, created by the Sutton and Hirsch laboratories, that are missing different combinations of C2 domains, to assess their abilities to target t-tubules and to support normal Ca2+ signaling. cDNAs encoding nanodysferlins (reduced to 3 or 4 C2 domains plus the Fer/DysF domains) were provided by Drs. Hirsch and Sutton via the Jain Foundation. They were tagged at their N-terminus with Venus and electroporated into A/J FDB muscles. Expression of all four nanodysferlins was poor. When they were detected by confocal microscopy, they located in longitudinal membrane structures overlying the Z-disks typical of a compartment of the ER, not in the punctate structures typical of t-tubules. Nanodysferlins 364, 365, and 431 supported normal Ca2+ transient before OSI but behaved like untreated A/J fibers after OSI. Nanodysferlin 430 reduced the original amplitude of Ca2+ transients by ~20%, but supported their full recovery after OSI. All the nanodysferlins failed to suppress Ca2+ waves typical of CICR in myofibers exposed to OSI. Nanodysferlins with an N-terminal Venus tag express poorly in cultured A/J myofibers, mislocalize to the ER and fail to support normal Ca2+ signaling, especially after OSI. Supported by the Jain Foundation, and NIH (RO1 AR064268)
  • What's the Buzz? 2024

    University of Maryland, Baltimore. School of Medicine, 2024
  • The Journal of the Alumni Association of the College of Physicians and Surgeons, Baltimore, Volume 8

    College of Physicians and Surgeons (Baltimore, Md.). Alumni Association (1906)
  • The Journal of the Alumni Association of the College of Physicians and Surgeons, Baltimore, Volume 7

    College of Physicians and Surgeons (Baltimore, Md.). Alumni Association (1905)
  • The Journal of the Alumni Association of the College of Physicians and Surgeons, Baltimore, Volume 6

    College of Physicians and Surgeons (Baltimore, Md.). Alumni Association (1904)
  • Impact of Host and Parasite Factors on Gametocyte Production in Plasmodium falciparum

    Vareta, Jimmy Amakwa; Laufer, Miriam K.; Takala-Harrison, Shannon (2023)
    Stalled progress in reducing the malaria burden over the past few years suggests the need to develop new interventions to augment existing ones, including interventions aimed at interrupting gametocyte transmission from humans to the mosquito vector. To develop and effectively apply interventions that target gametocytes, there is a need to understand patterns of gametocytemia observed between individuals. Gametocytemia varies by host age, season, symptom status, antimalarial drugs use, and complexity of infection; however, the underlying mechanisms of this variation are not fully understood. Complexity of infection may modulate gametocytemia in P. falciparum; however, mechanisms of how clone composition influences gametocyte production are not clear. Addressing this gap requires a genotyping assay that can detect and estimate relative clone frequency of gametocytes and asexual parasites in infections. The dissertation aims were two-fold: 1) To develop an amplicon sequencing assay to genotype P. falciparum mature gametocytes; and 2) To evaluate the impact of host and parasite factors and gametocyte production in P. falciparum infections. We identified a polymorphic region of the pfs230 gene as a marker to distinguish P. falciparum mature gametocyte clones. When evaluating the impact of host and parasite factors on gametocyte production and gametocytemia, we found that more complex and high parasite density infections were more likely to produce and harbor gametocytes. The proportion of infections that produced gametocytes were similar between age-groups and between symptomatic and asymptomatic individuals, but children and asymptomatic individuals were more likely to harbor gametocytes than adults and symptomatic individuals, respectively. These findings suggest that complexity of infection and parasite density may increase gametocyte production, but additional factors such as host immunity and duration of infection may contribute to the presence or absence of gametocytes after initiation of gametocyte production. Coupled with the development of the gametocyte genotyping assay which will be an important tool for studies aimed at understanding dynamics of gametocyte production in polyclonal infections, understanding the impact of host and parasite factors on gametocyte production and gametocytemia will help explain variation in gametocytemia observed between individuals. This knowledge could inform development and effective deployment of transmission interrupting interventions.
  • An Insight to Further Malaria Vaccine Development: PfSPZ Vaccine Correlates of Protection Appear to be Cross-Reactive Antibodies to Immunodominant Low-Complexity Epitopes

    Berry, Andrea; Takala-Harrison, Shannon (2023)
    Plasmodium falciparum circumsporozoite protein (PfCSP) coats the sporozoite surface and is the target of multiple malaria vaccines in development. Discovery of additional vaccine candidate antigens beyond PfCSP may lead to improved vaccines. To identify new antigens, we used peptide microarrays to map antibody responses to P. falciparum proteins in adults who received a whole organism sporozoite vaccine, PfSPZ Vaccine, and were protected or unprotected after controlled human malaria infection. We discovered antibody responses that correlate with protection, but further examination, including of two monoclonal antibodies derived from protected PfSPZ Vaccine recipients, suggests that some antibodies elicited by PfCSP cross-react with peptides representing non-CSP proteins, a demonstration of inter-protein cross-reactivity. This work provides evidence that PfSPZ Vaccine elicits inter-protein cross-reactivity, provides amino acid-specific detail of putative epitopes, and introduces opportunities for further exploration that may help to elucidate underexplored immunological mechanisms and inform development of next-generation malaria vaccines.
  • Nitric Oxide in Mucormycosis Pathogenesis

    Soare, Alexandra; Bruno, Vincent, Ph.D. (2023)
    Mucormycosis is classified by NIAID as an emerging disease and is caused by Mucorales fungi. The recent surge of mucormycosis cases among COVID-19 patients has thrust the disease and lack of available treatments into the spotlight. Clinical data suggests a lack of inflammatory responses during mucormycosis despite severe fungal angioinvasion and tissue necrosis. In this dissertation, I sought to characterize immune evasion mechanisms by Mucorales, focusing on the interaction between fungi and macrophages. Macrophages infected with Mucorales fungi block the production of nitric oxide, a free radical molecule with strong antimicrobial properties and an important signaling role in immunity. Despite the increased expression of Nos2 mRNA and inducible nitric oxide synthase (iNOS) protein in Mucorales-infected macrophages, these macrophages are unable to produce nitric oxide, even when stimulated with nitric oxide-producing stimuli (LPS and IFN-γ). My results suggest that Mucorales fungi prevent the accumulation of nitric oxide through at least 2 mechanisms: (1) removal of nitric oxide from the surrounding environment, and (2) depletion of nutrients required to make nitric oxide. Additionally, a potent nitric oxide-donor (DETA-NONOate) inhibits in vitro growth of Mucorales fungi indicating that nitric oxide may be have antifungal activity against Mucorales. At lower concentrations of DETA-NONOate that are unable to inhibit growth of Mucorales, I observed downregulation of mRNAs encoding Mucorales virulence proteins including Mucoricin, a ricin-like toxin that is critical for Mucorales pathogenesis. By downregulating these genes, nitric oxide could be attenuating the virulence potential of the fungus, rendering it less pathogenic. My research describes a new immune evasion mechanism by Mucorales fungi and presents nitric oxide as a potential therapeutic for mucormycosis.

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