Activity-Dependent Non-Coding RNA MAPK Interactome of the Human Epileptic Brain.

The human brain has evolved to have extraordinary capabilities, enabling complex behaviors. The uniqueness of the human brain is increasingly posited to be due in part to the functions of primate-specific, including human-specific, long non-coding RNA (lncRNA) genes, systemically less conserved than protein-coding genes in evolution. Patients who have surgery for drug-resistant epilepsy are subjected to extensive electrical recordings of the brain tissue that is subsequently removed in order to treat their epilepsy. Precise localization of brain tissues with distinct electrical properties offers a rare opportunity to explore the effects of brain activity on gene expression. Here, we identified 231 co-regulated, activity-dependent lncRNAs within the human MAPK signaling cascade. Six lncRNAs, four of which were antisense to known protein-coding genes, were further examined because of their high expression and potential impact on the disease phenotype. Using a model of repeated depolarizations in human neuronal-like cells (Sh-SY5Y), we show that five out of six lncRNAs were electrical activity-dependent, with three of four antisense lncRNAs having reciprocal expression patterns relative to their protein-coding gene partners. Some were directly regulated by MAPK signaling, while others effectively downregulated the expression of the protein-coding genes encoded on the opposite strands of their genomic loci. These lncRNAs, therefore, likely contribute to highly evolved and primate-specific human brain regulatory functions that could be therapeutically modulated to treat epilepsy.

HPV-57 Verruca Vulgaris Mimicking Epidermodysplasia Verruciformis.

ABSTRACT: Human papilloma virus (HPV) is the causative agent for a variety of cutaneous lesions including verruca vulgaris (VV) and epidermodysplasia verruciformis (EDV). There are more than 200 known genotypes of HPV, and specific HPV types are associated with different clinical manifestations and malignant potentials. Herein, we describe a case of a 43-year-old immunocompetent woman who presented with morphologically distinct lesions that were most consistent with EDV on clinical examination. However, further histopathological and viral analysis confirmed the lesions as HPV-57-positive VV. The risk of malignant transformation, and therefore treatment and surveillance, is dramatically different in VV versus EDV. Therefore, this case highlights the importance of a proper histopathological diagnosis with HPV viral testing when clinical presentations may vary or mimic other diseases.

Diagnosis of cutaneous mycobacterial spindle cell pseudotumor in the absence of typical inflammatory cells: A case report.

Mycobacterial spindle cell pseudotumor (MSP) is a non-neoplastic condition that is characterized by spindle-shaped histiocytes colonized by mycobacteria. MSP is most commonly diagnosed in the immunocompromised and, while MSP can occur throughout the body, the most common sites of MSP involvement are the lymph nodes and the skin. To diagnose MSP, histopathological analysis typically demonstrates the presence of inflammatory cells, in addition to spindle cells and the unequivocal mycobacteria, which guides the diagnosis away from potential neoplasms. If properly diagnosed and treated with appropriate antibiotic therapy, patients tend to experience almost complete resolution of their symptoms. MSP is a rare condition; to our knowledge, there have only been 11 documented cases of cutaneous MSP, including the one introduced in this report. Here, we present a unique case of a 50-year-old female on chronic immunosuppressive therapy diagnosed with cutaneous MSP in the absence of inflammatory cells on pathology.

Reduced juvenile long-term depression in tuberous sclerosis complex is mitigated in adults by compensatory recruitment of mGluR5 and Erk signaling.

Tuberous sclerosis complex (TSC) is a multisystem genetic disease that manifests with mental retardation, tumor formation, autism, and epilepsy. Heightened signaling through the mammalian target of rapamycin (mTOR) pathway is involved in TSC pathology, however it remains unclear how other signaling pathways are perturbed and contribute to disease symptoms. Reduced long-term depression (LTD) was recently reported in TSC mutant mice. We find that although reduced LTD is a feature of the juvenile mutant hippocampus, heightened expression of metabotropic glutamate receptor 5 and constitutively activated Erk signaling in the adult hippocampus drives wild-type levels of LTD. Increased mGluR5 and Erk results in a novel mTOR-independent LTD in CA1 hippocampus of adult mice, and contributes to the development of epileptiform bursting activity in the TSC2(+/-) CA3 region of the hippocampus. Inhibition of mGluR5 or Erk signaling restores appropriate mTOR-dependence to LTD, and significantly reduces epileptiform bursting in TSC2(+/-) hippocampal slices. We also report that adult TSC2(+/-) mice exhibit a subtle perseverative behavioral phenotype that is eliminated by mGluR5 antagonism. These findings highlight the potential of modulating the mGluR5-Erk pathway in a developmental stage-specific manner to treat TSC.