Search

Tuberous sclerosis complex (TSC) is a genetic condition with multisystem involvement, characterized by the development of tumors and other abnormalities in organs such as the brain, retina, skin, heart, kidneys, and lungs. Most patients have neuropathological abnormalities such as cortical tubers, white matter radial migration lines, subependymal nodules, and subependymal giant cell astrocytomas (SEGAs). These lesions are associated with different neurological manifestations that are frequently associated with TSC. These manifestations consist of epilepsy, intellectual disability, and neurobehavioral and psychiatric problems, including autism spectrum disorder. Hydrocephalus may also develop in patients with SEGAs due to ventricular obstruction, when this usually slow-growing tumor reaches sufficient size. Surgery has been the classical approach to treat SEGAs, although this treatment is associated with substantial morbidity and does not completely prevent tumor recurrence. Recently, the mammalian target of rapamycin (mTOR) inhibitor, everolimus, has been approved by the Food and Drug Administration and the European Medicines Agency for the treatment of patients with SEGAs associated with TSC. However, the treatment of SEGAs with these agents requires the development of guidelines that establish a differential diagnosis between SENs and SEGAs, in which neuroradiological examinations play an essential role. With the aim of improving the neuroradiological diagnosis and follow-up of the neuropathological abnormalities associated with TSC, a group of experts in this field has reviewed different aspects related to these issues and put together, a series of statements and recommendations intended to provide guidance to specialists involved in the management of TSC.

Members of the tumor necrosis factor receptor (TNFR) family regulate the activation, differentiation, and function of many cell types, including cells of the immune system. TNFR-associated factors (TRAFs) function as adapter molecules controlling signaling pathways triggered by TNFR family members, such as activation of nuclear factor kappaB (NF-kappaB). Despite intensive research, the function of TRAF4 in signaling pathways triggered by TNFR-related proteins remains enigmatic. Intriguingly, our functional studies indicated that TRAF4 augments NF-kappaB activation triggered by glucocorticoid-induced TNFR (GITR), a receptor expressed on T cells, B cells, and macrophages. Further analyses revealed that TRAF4-mediated NF-kappaB activation downstream of GITR depends on a previously mapped TRAF-binding site in the cytoplasmic domain of the receptor and is inhibited by the cytoplasmic protein A20. GITR is thought to inhibit the suppressive function of regulatory T cells (Treg cells) and to promote activation of T cells. Taken together, our studies provide the first indications that TRAF4 elaborates GITR signaling and suggest that TRAF4 can modulate the suppressive functions of Treg cells.

Modern magnetic resonance imaging (MRI) systems consist of several complex, high cost subsystems. The cost and complexity of these systems often makes them impractical for use as routine laboratory instruments, limiting their use to hospitals and dedicated laboratories. However, advances in the consumer electronics industry have led to the widespread availability of inexpensive radio-frequency integrated circuits with exceptional abilities. We have developed a small, low-cost MR system derived from these new components. When combined with inexpensive desktop magnets, this type of MR scanner has the promise of becoming standard laboratory equipment for both research and education. This paper describes the development of a prototype desktop MR scanner utilizing a 0.21 T permanent magnet with an imaging region of approximately 2 cm diameter. The system uses commercially available components where possible and is programmed in LabVIEW software. Results from 3D data sets of resolution phantoms and fixed, newborn mice demonstrate the capability of this system to obtain useful images from a system constructed for approximately $13,500.