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.

Linearity and Normalization in Simple Cells of the Macaque Primary Visual Cortex

Abstract: Simple cells in the primary visual cortex often appear to compute a weighted sum of the light intensity distribution of the visual stimuli that fall on their receptive fields. A linear model of these cells has the advantage of simplicity and captures a number of basic aspects of cell function. It, however, fails to account for important response nonlinearities, such as the decrease in response gain and latency observed at high contrasts and the effects of masking by stimuli that fail to elicit responses when presented alone. To account for these nonlinearities we have proposed a normalization model, which extends the linear model to include mutual shunting inhibition among a large number of cortical cells. Shunting inhibition is divisive, and its effect in the model is to normalize the linear responses by a measure of stimulus energy. To test this model we performed extracellular recordings of simple cells in the primary visual cortex of anesthetized macaques. We presented large stimulus sets consisting of (1) drifting gratings of various orientations and spatiotemporal frequencies; (2) plaids composed of two drifting gratings; and (3) gratings masked by full-screen spatiotemporal white noise. We derived expressions for the model predictions and fitted them to the physiological data. Our results support the normalization model, which accounts for both the linear and the nonlinear properties of the cells. An alternative model, in which the linear responses are subject to a compressive nonlinearity, did not perform nearly as well.

The role of DNA shape in protein–DNA recognition

Abstract: The recognition of specific DNA sequences by proteins is thought to depend on two types of mechanism: one that involves the formation of hydrogen bonds with specific bases, primarily in the major groove, and one involving sequence-dependent deformations of the DNA helix. By comprehensively analysing the three-dimensional structures of protein-DNA complexes, here we show that the binding of arginine residues to narrow minor grooves is a widely used mode for protein-DNA recognition. This readout mechanism exploits the phenomenon that narrow minor grooves strongly enhance the negative electrostatic potential of the DNA. The nucleosome core particle offers a prominent example of this effect. Minor-groove narrowing is often associated with the presence of A-tracts, AT-rich sequences that exclude the flexible TpA step. These findings indicate that the ability to detect local variations in DNA shape and electrostatic potential is a general mechanism that enables proteins to use information in the minor groove, which otherwise offers few opportunities for the formation of base-specific hydrogen bonds, to achieve DNA-binding specificity.