St. Jude Children's Research Hospital

About: St. Jude Children's Research Hospital is a healthcare organization based out in Memphis, Tennessee, United States. It is known for research contribution in the topics: Population & Virus. The organization has 9344 authors who have published 19233 publications receiving 1233399 citations. The organization is also known as: St. Jude Children's Hospital & St. Jude Hospital.

Role of the Reelin Signaling Pathway in Central Nervous System Development

Abstract: The neurological mutant mouse reeler has played a critical role in the evolution of our understanding of normal brain development. From the earliest neuroanatomic studies of reeler, it was anticipated that the characterization of the gene responsible would elucidate important molecular and cellular principles governing cell positioning and the formation of synaptic circuits in the developing brain. Indeed, the identification of reelin has challenged many of our previous notions and has led to a new vision of the events involved in the migration of neurons. Several neuronal populations throughout the brain secrete Reelin, which binds to transmembrane receptors located on adjacent cells triggering a tyrosine kinase cascade. This allows neurons to complete migration and adopt their ultimate positions in laminar structures in the central nervous system. Recent studies have also suggested a role for the Reelin pathway in axonal branching, synaptogenesis, and pathology underlying neurodegeneration.

Lethal H5N1 influenza viruses escape host anti-viral cytokine responses.

Abstract: The H5N1 influenza viruses transmitted to humans in 1997 were highly virulent, but the mechanism of their virulence in humans is largely unknown. Here we show that lethal H5N1 influenza viruses, unlike other human, avian and swine influenza viruses, are resistant to the antiviral effects of interferons and tumor necrosis factor alpha. The nonstructural (NS) gene of H5N1 viruses is associated with this resistance. Pigs infected with recombinant human H1N1 influenza virus that carried the H5N1 NS gene experienced significantly greater and more prolonged viremia, fever and weight loss than did pigs infected with wild-type human H1N1 influenza virus. These effects required the presence of glutamic acid at position 92 of the NS1 molecule. These findings may explain the mechanism of the high virulence of H5N1 influenza viruses in humans.

Targeting bacterial membrane function: an underexploited mechanism for treating persistent infections

Abstract: Persistent infections involving slow-growing or non-growing bacteria are hard to treat with antibiotics that target biosynthetic processes in growing cells. Consequently, there is a need for antimicrobials that can treat infections containing dormant bacteria. In this Review, we discuss the emerging concept that disrupting the bacterial membrane bilayer or proteins that are integral to membrane function (including membrane potential and energy metabolism) in dormant bacteria is a strategy for treating persistent infections. The clinical applicability of these approaches is exemplified by the efficacy of lipoglycopeptides that damage bacterial membranes and of the diarylquinoline TMC207, which inhibits membrane-bound ATP synthase. Despite some drawbacks, membrane-active agents form an important new means of eradicating recalcitrant, non-growing bacteria.

Genomics Identifies Medulloblastoma Subgroups That Are Enriched for Specific Genetic Alterations

Abstract: Purpose Traditional genetic approaches to identify gene mutations in cancer are expensive and laborious. Nonetheless, if we are to avoid rejecting effective molecular targeted therapies, we must test these drugs in patients whose tumors harbor mutations in the drug target. We hypothesized that gene expression profiling might be a more rapid and cost-effective method of identifying tumors that contain specific genetic abnormalities. Materials and Methods Gene expression profiles of 46 samples of medulloblastoma were generated using the U133av2 Affymetrix oligonucleotide array and validated using real-time reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. Genetic abnormalities were confirmed using fluorescence in situ hybridization (FISH) and direct sequencing. Results Unsupervised analysis of gene expression profiles partitioned medulloblastomas into five distinct subgroups (subgroups A to E). Gene expression signatures that distinguished these subgroups predicted the prese...