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.

Immunologic Correlates of the Abscopal Effect in a Patient with Melanoma

Abstract: The abscopal effect is a phenomenon in which local radiotherapy is associated with the regression of metastatic cancer at a distance from the irradiated site. The abscopal effect may be mediated by activation of the immune system. Ipilimumab is a mono‑ clonal antibody that inhibits an immunologic checkpoint on T cells, cytotoxic T‑lymphocyte–associated antigen 4 (CTLA ‑ 4). We report a case of the abscopal effect in a patient with melanoma treated with ipilimumab and radiotherapy. Temporal associations were noted: tumor shrinkage with antibody responses to the cancer– testis antigen NY‑ ESO‑ 1, changes in peripheral‑ blood immune cells, and increases in antibody responses to other antigens after radiotherapy. (Funded by the National Institutes of Health and others.)

Thinning of the cerebral cortex in aging

Abstract: The thickness of the cerebral cortex was measured in 106 non-demented participants ranging in age from 18 to 93 years For each participant, multiple acquisitions of structural T1-weighted magnetic resonance imaging (MRI) scans were averaged to yield high-resolution, high-contrast data sets Cortical thickness was estimated as the distance between the gray/white boundary and the outer cortical surface, resulting in a continuous estimate across the cortical mantle Global thinning was apparent by middle age Men and women showed a similar degree of global thinning, and did not differ in mean thickness in the younger or older groups Age-associated differences were widespread but demonstrated a patchwork of regional atrophy and sparing Examination of subsets of the data from independent samples produced highly similar age-associated patterns of atrophy, suggesting that the specific anatomic patterns within the maps were reliable Certain results, including prominent atrophy of prefrontal cortex and relative sparing of temporal and parahippocampal cortex, converged with previous findings Other results were unexpected, such as the finding of prominent atrophy in frontal cortex near primary motor cortex and calcarine cortex near primary visual cortex These findings demonstrate that cortical thinning occurs by middle age and spans widespread cortical regions that include primary as well as association cortex

X-ray structure of a voltage-dependent K+ channel

Abstract: Voltage-dependent K+ channels are members of the family of voltage-dependent cation (K+, Na+ and Ca2+) channels that open and allow ion conduction in response to changes in cell membrane voltage. This form of gating underlies the generation of nerve and muscle action potentials, among other processes. Here we present the structure of KvAP, a voltage-dependent K+ channel from Aeropyrum pernix. We have determined a crystal structure of the full-length channel at a resolution of 3.2 A, and of the isolated voltage-sensor domain at 1.9 A, both in complex with monoclonal Fab fragments. The channel contains a central ion-conduction pore surrounded by voltage sensors, which form what we call 'voltage-sensor paddles'-hydrophobic, cationic, helix-turn-helix structures on the channel's outer perimeter. Flexible hinges suggest that the voltage-sensor paddles move in response to membrane voltage changes, carrying their positive charge across the membrane.

A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p.

Abstract: Trapoxin is a microbially derived cyclotetrapeptide that inhibits histone deacetylation in vivo and causes mammalian cells to arrest in the cell cycle. A trapoxin affinity matrix was used to isolate two nuclear proteins that copurified with histone deacetylase activity. Both proteins were identified by peptide microsequencing, and a complementary DNA encoding the histone deacetylase catalytic subunit (HD1) was cloned from a human Jurkat T cell library. As the predicted protein is very similar to the yeast transcriptional regulator Rpd3p, these results support a role for histone deacetylase as a key regulator of eukaryotic transcription.