The human GCOM1 complex gene interacts with the NMDA receptor and internexin-alpha

The known functions of the human GCOM1 complex hub gene include transcription elongation and the intercalated disk of cardiac myocytes. However, in all likelihood, the gene's most interesting, and thus far least understood, roles will be found in the central nervous system. To investigate the functions of the GCOM1 gene in the CNS, we have cloned human and rat brain cDNAs encoding novel, 105 kDa GCOM1 combined (Gcom) proteins, designated Gcom15, and identified a new group of GCOM1 interacting genes, termed Gints, from yeast two-hybrid (Y2H) screens. We showed that Gcom15 interacts with the NR1 subunit of the NMDA receptor by co-expression in heterologous cells, in which we observed bi-directional co-immunoprecipitation of human Gcom15 and murine NR1. Our Y2H screens revealed 27 novel GCOM1 interacting genes, many of which are synaptic proteins and/or play roles in neurologic diseases. Finally, we showed, using rat brain protein preparations, that the Gint internexin-alpha (INA), a known interactor of the NMDAR, co-IPs with GCOM1 proteins, suggesting a GCOM1-GRIN1-INA interaction and a novel pathway that may be relevant to neuroprotection

A rare anaerobic cause of vertebral osteomyelitis and psoas abscess: A case study

Parvimonas micra is an obligate anaerobe that forms part of the normal gastrointestinal flora. The advent of matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF) and 16s ribosomal RNA gene sequencing has led to increased detection of many rare anaerobic isolates, including Parvimonas micra. Typical risk factors for Parvimonas micra bacteremia include dental procedures or spinal instrumentation. Here, we report a case of Parvimonas micra spondylodiscitis and psoas abscess in a patient with no obvious antecedent risk factors and explore the challenges in isolation of the organism from tissue samples

A Case of Drug-Induced Liver Injury Secondary to Natalizumab

A 33-year-old Caucasian female with relapsing-remitting multiple sclerosis presented with abdominal pain, nausea, and vomiting and was found to have acute liver injury. After thorough investigation, she was diagnosed with drug-induced liver injury (DILI) thought secondary to redosing of Natalizumab therapy

An Unusual Case of Staphylococcus pasteuri Osteomyelitis

Staphylococcus pasteuri is a gram-positive organism found in food products as well as naturally occurring in air and on surfaces. We present the first known case of Staphylococcus pasteuri osteomyelitis caused by machine injection injury. The patient was treated with emergent surgical debridement as well as doxycycline for a soft tissue infection. Despite targeted therapy, the infection progressed to osteomyelitis and was treated successfully with additional surgical debridement and trimethoprim-sulfamethoxazole. There is sparse information on both infections and treatment of Staphylococcus pasteuri. We present our case report as well as a review of the literature on the epidemiology, susceptibility and treatment recommendations for Staphylococcus pasteuri infections

Selective targeting of brain tumors with gold nanoparticle-induced radiosensitization.

Successful treatment of brain tumors such as glioblastoma multiforme (GBM) is limited in large part by the cumulative dose of Radiation Therapy (RT) that can be safely given and the blood-brain barrier (BBB), which limits the delivery of systemic anticancer agents into tumor tissue. Consequently, the overall prognosis remains grim. Herein, we report our pilot studies in cell culture experiments and in an animal model of GBM in which RT is complemented by PEGylated-gold nanoparticles (GNPs). GNPs significantly increased cellular DNA damage inflicted by ionizing radiation in human GBM-derived cell lines and resulted in reduced clonogenic survival (with dose-enhancement ratio of ~1.3). Intriguingly, combined GNP and RT also resulted in markedly increased DNA damage to brain blood vessels. Follow-up in vitro experiments confirmed that the combination of GNP and RT resulted in considerably increased DNA damage in brain-derived endothelial cells. Finally, the combination of GNP and RT increased survival of mice with orthotopic GBM tumors. Prior treatment of mice with brain tumors resulted in increased extravasation and in-tumor deposition of GNP, suggesting that RT-induced BBB disruption can be leveraged to improve the tumor-tissue targeting of GNP and thus further optimize the radiosensitization of brain tumors by GNP. These exciting results together suggest that GNP may be usefully integrated into the RT treatment of brain tumors, with potential benefits resulting from increased tumor cell radiosensitization to preferential targeting of tumor-associated vasculature

Assessing GNP enhancement with <i>in vitro</i> assays of radiosensitivity.

<p><b>A.</b> Deconvolution imaging of γh2ax foci in U251 cells that were mock-irradiated (upper) or irradiated with 4 Gy (lower). Cells irradiated with 1 mM GNPs display a 1.7-fold higher density of persistent γh2ax foci 24 hours after RT. <b>B.</b> Quantitative analysis of γh2ax foci for N >100 viable nuclei. Error bars, 95% confidence interval. Statistical significance was determined using a two-tailed <i>t</i>-test (α = 0.05), with <i>p</i><0.05 being considered significant. <b>C.</b> Clonogenic assay of U251 cells treated with (red circles) and without (hollow squares) 1 mM GNPs and given radiation doses of 0, 2, 4 and 6 Gy. Error bars represent the mean survival ± s.d. of at least four replicates.</p

Gold nanoparticle characterization.

<p><b>A.</b> Transmission electron micrograph of GNPs having approximately 12 nm cores. <b>B.</b> Representative dynamic light scattering measurement of GNPs. Data was fit to a Gaussian function to determine the peak ± s.d. of nanoparticle hydrodynamic diameter (d_H). <b>C.</b> UV-vis absorption spectrum of GNPs showing characteristic surface plasmon resonance at λ ≈ 522 nm. <b>D.</b> MTT viability assay of U251 cells treated with increasing concentrations of GNPs for 24 hours. Error bars, mean viability ± s.d. of three replicates.</p

GNP administration in combination with RT improves survival in mice with advanced GBM tumors.

<p><b>A.</b> BLI of a representative mouse with advanced orthotopic GBM xenografts (radiance ∼10⁸ p/sec/cm²/sr) used for the survival study. <b>B.</b> Photograph of a brain and resected tumor 48 hours after intravenous injection of GNPs. Tumor shows darkened appearance due to extravasation due to EPR into the tumor. <b>C.</b> Survival data in mice with advanced orthotopic GBM treated with or without GNPs followed by mock-irradiation or given stereotactic RT (20 Gy). The right cerebral hemispheres of nude mice were initially implanted with 350,000 U251 cells, and tumors were allowed to grow until the measured radiance reached ∼10⁸p/sec/cm²/sr (approximately 3–5 weeks post-implantation), at which point the mice were given their respective treatments (<i>n</i> = 5 for GNP+RT and <i>n</i> = 4 for control, GNP, and RT groups). Median and mean survival analysis were obtained with Kaplan-Meier analysis, and comparison between RT versus GNP+RT survival curves showed <i>p</i> = 0.011. Mean survival times are shown with 95% confidence intervals. N.S. in the figure indicates lack of statistical significance, while the asterisk (*) denotes that significance was reached (α = 0.05).</p