Human Cytomegalovirus IE1 Protein Elicits a Type II Interferon-Like Host Cell Response That Depends on Activated STAT1 but Not Interferon-γ

Human cytomegalovirus (hCMV) is a highly prevalent pathogen that, upon primary infection, establishes life-long persistence in all infected individuals. Acute hCMV infections cause a variety of diseases in humans with developmental or acquired immune deficits. In addition, persistent hCMV infection may contribute to various chronic disease conditions even in immunologically normal people. The pathogenesis of hCMV disease has been frequently linked to inflammatory host immune responses triggered by virus-infected cells. Moreover, hCMV infection activates numerous host genes many of which encode pro-inflammatory proteins. However, little is known about the relative contributions of individual viral gene products to these changes in cellular transcription. We systematically analyzed the effects of the hCMV 72-kDa immediate-early 1 (IE1) protein, a major transcriptional activator and antagonist of type I interferon (IFN) signaling, on the human transcriptome. Following expression under conditions closely mimicking the situation during productive infection, IE1 elicits a global type II IFN-like host cell response. This response is dominated by the selective up-regulation of immune stimulatory genes normally controlled by IFN-γ and includes the synthesis and secretion of pro-inflammatory chemokines. IE1-mediated induction of IFN-stimulated genes strictly depends on tyrosine-phosphorylated signal transducer and activator of transcription 1 (STAT1) and correlates with the nuclear accumulation and sequence-specific binding of STAT1 to IFN-γ-responsive promoters. However, neither synthesis nor secretion of IFN-γ or other IFNs seems to be required for the IE1-dependent effects on cellular gene expression. Our results demonstrate that a single hCMV protein can trigger a pro-inflammatory host transcriptional response via an unexpected STAT1-dependent but IFN-independent mechanism and identify IE1 as a candidate determinant of hCMV pathogenicity

A next-generation liquid xenon observatory for dark matter and neutrino physics

The nature of dark matter and properties of neutrinos are among the most pressing issues in contemporary particle physics. The dual-phase xenon time-projection chamber is the leading technology to cover the available parameter space for weakly interacting massive particles, while featuring extensive sensitivity to many alternative dark matter candidates. These detectors can also study neutrinos through neutrinoless double-beta decay and through a variety of astrophysical sources. A next-generation xenon-based detector will therefore be a true multi-purpose observatory to significantly advance particle physics, nuclear physics, astrophysics, solar physics, and cosmology. This review article presents the science cases for such a detector

Coleção subdural na criança: fisiopatologia e tratamento Subdural effusions in children: pathophysiology and treatment

Nove crianças portadoras de coleção subdural (CSD) foram tratadas por meio de derivação subduro-peritoneal. Todas foram submetidas a controle com tomografia computadorizada do encéfalo. O tamanho da coleção subdural foi avaliado por medida de sua área no corte tomográfico por meio de morfologia quantitativa com planímetro. Ocorreu regressão completa ou quase completa da CSD em oito pacientes. Os resultados funcionais foram excelentes em quatro pacientes, bons em três e maus em dois. Foi feita uma revisão da fisiopatologia e do tratamento da CSD na criança.<br>Nine children harboring subdural effusions were treated by subduro peritoneal shunt. These patients were followed-up by CT scans. The area of the subdural effusions was measured by quantitative morphology with a planimeter. With the surgical treatment, the subdural effusion disappeared completely or near completely in 8 patients. The patient's functional state were excellent in 4, good in 3 and bad in 2 in the postoperative follow-up. We aldo reviewed the literature as far as the pathophysiology and the treatment of the subdural effusions are concerned