Howard Hughes Medical Institute

About: Howard Hughes Medical Institute is a nonprofit organization based out in Chevy Chase, Maryland, United States. It is known for research contribution in the topics: Gene & RNA. The organization has 20371 authors who have published 34677 publications receiving 5247143 citations. The organization is also known as: HHMI & hhmi.org.

Structure of the cross-beta spine of amyloid-like fibrils.

Abstract: Numerous soluble proteins convert to insoluble amyloid-like fibrils that have common properties. Amyloid fibrils are associated with fatal diseases such as Alzheimer's, and amyloid-like fibrils can be formed in vitro. For the yeast protein Sup35, conversion to amyloid-like fibrils is associated with a transmissible infection akin to that caused by mammalian prions. A seven-residue peptide segment from Sup35 forms amyloid-like fibrils and closely related microcrystals, from which we have determined the atomic structure of the cross-β spine. It is a double β-sheet, with each sheet formed from parallel segments stacked in register. Side chains protruding from the two sheets form a dry, tightly self-complementing steric zipper, bonding the sheets. Within each sheet, every segment is bound to its two neighbouring segments through stacks of both backbone and side-chain hydrogen bonds. The structure illuminates the stability of amyloid fibrils, their self-seeding characteristic and their tendency to form polymorphic structures.

Independent Component Analysis of Electroencephalographic Data

Abstract: Because of the distance between the skull and brain and their different resistivities, electroencephalographic (EEG) data collected from any point on the human scalp includes activity generated within a large brain area. This spatial smearing of EEG data by volume conduction does not involve significant time delays, however, suggesting that the Independent Component Analysis (ICA) algorithm of Bell and Sejnowski [1] is suitable for performing blind source separation on EEG data. The ICA algorithm separates the problem of source identification from that of source localization. First results of applying the ICA algorithm to EEG and event-related potential (ERP) data collected during a sustained auditory detection task show: (1) ICA training is insensitive to different random seeds. (2) ICA may be used to segregate obvious artifactual EEG components (line and muscle noise, eye movements) from other sources. (3) ICA is capable of isolating overlapping EEG phenomena, including alpha and theta bursts and spatially-separable ERP components, to separate ICA channels. (4) Nonstationarities in EEG and behavioral state can be tracked using ICA via changes in the amount of residual correlation between ICA-filtered output channels.

An inducible transcription factor activates expression of human immunodeficiency virus in T cells

Abstract: Human immunodeficiency virus (HIV) production from latently infected T lymphocytes can be induced with compounds that activate the cells to secrete lymphokines. The elements in the HIV genome which control activation are not known but expression might be regulated through a variety of DNA elements. The cis-acting control elements of the viral genome are enhancer and promoter regions. The virus also encodes trans-acting factors specified by the tat-III and art genes. We have examined whether products specific to activated T cells might stimulate viral transcription by binding to regions on viral DNA. Activation of T cells, which increases HIV expression up to 50-fold, correlated with induction of a DNA binding protein indistinguishable from a recognized transcription factor, called NF-kappa B, with binding sites in the viral enhancer. Mutation of these binding sites abolished inducibility. That NF-kappa B acts in synergy with the viral tat-III gene product to enhance HIV expression in T cells may have implications for the pathogenesis of AIDS (acquired immune deficiency syndrome).

Dicer is essential for mouse development.

Abstract: To address the biological function of RNA interference (RNAi)-related pathways in mammals, we disrupted the gene Dicer1 in mice. Loss of Dicer1 lead to lethality early in development, with Dicer1-null embryos depleted of stem cells. Coupled with our inability to generate viable Dicer1-null embryonic stem (ES) cells, this suggests a role for Dicer, and, by implication, the RNAi machinery, in maintaining the stem cell population during early mouse development.

A mammalian protein targeted by G1-arresting rapamycin–receptor complex

Abstract: THE structurally related natural products rapamycin and FK506 bind to the same intracellular receptor, FKBP12, yet the resulting complexes interfere with distinct signalling pathways1,2. FKBP12–rapamycin inhibits progression through the Gl phase of the cell cycle in osteosarcoma3, liver4, 5 and T cells6, 7 as well as in yeast8 and interferes with mitogenic signalling pathways that are involved in Gl progression9, 10 namely with activation of the protein p70S6k (refs 5,11–13) and cyclin-dependent kinases3, 14–16. Here we isolate a mammalian FKBP–rapamycin-associated protein (FRAP) whose binding to structural variants of rapamycin complexed to FKBP12 correlates with the ability of these ligands to inhibit cell-cycle progression. Peptide sequences from purified bovine FRAP were used to isolate a human cDNA clone that is highly related to the DRR1/TOR1 and DRR2/TOR2 gene products from Saccharomyces cerevisiae8, 17, 18. Although it has not been previously demonstrated that either of the DRR/TOR gene products can bind the FKBP–rapamycin complex directly17, 19 these yeast genes have been genetically linked to a rapamycin-sensitive pathway and are thought to encode lipid kinases17–20.