Biomedical subjects

D Wolpert

Publications and source records attributed to D Wolpert.

5 recordsLinked to original sources

PubMed2003

Protein flexibility and conformational state: a comparison of collective vibrational modes of wild-type and D96N bacteriorhodopsin.

Far infrared (FIR) spectral measurements of wild-type (WT) and D96N mutant bacteriorhodopsin thin films have been carried out using terahertz time domain spectroscopy as a function of hydration, temperature, and conformational state. The results are compared to calculated spectra generated via normal mode analyses using CHARMM. We find that the FIR absorbance is slowly increasing with frequency and without strong narrow features over the range of 2-60 cm(-1) and up to a resolution of 0.17 cm(-1). The broad absorption shifts in frequency with decreasing temperature as expected with a strongly anharmonic potential and in agreement with neutron inelastic scattering results. Decreasing hydration shifts the absorption to higher frequencies, possibly resulting from decreased coupling mediated by the interior water molecules. Ground-state FIR absorbances have nearly identical frequency dependence, with the mutant having less optical density than the WT. In the M state, the FIR absorbance of the WT increases whereas there is no change for D96N. These results represent the first measurement of FIR absorbance change as a function of conformational state.

Bacteriorhodopsins↗

PubMed2000

Why can't you tickle yourself?

It is well known that you cannot tickle yourself. Here, we discuss the proposal that such attenuation of self-produced tactile stimulation is due to the sensory predictions made by an internal forward model of the motor system. A forward model predicts the sensory consequences of a movement based on the motor command. When a movement is self-produced, its sensory consequences can be accurately predicted, and this prediction can be used to attenuate the sensory effects of the movement. Studies are reviewed that demonstrate that as the discrepancy between predicted and actual sensory feedback increases during self-produced tactile stimulation there is a concomitant decrease in the level of sensory attenuation and an increase in tickliness. Functional neuroimaging studies have demonstrated that this sensory attenuation might be mediated by somatosensory cortex and anterior cingulate cortex: these areas are activated less by a self-produced tactile stimulus than by the same stimulus when it is externally produced. Furthermore, evidence suggests that the cerebellum might be involved in generating the prediction of the sensory consequences of movement. Finally, recent evidence suggests that this predictive mechanism is abnormal in patients with auditory hallucinations and/or passivity experiences.

Biofeedback, Psychology↗

PubMed1998

Internal models for motor control.

The process of moving the hand to a target in space involves a series of sensorimotor transformations that translate visual and other sensory information about the location of the target object and the limbs into a set of motor commands that will bring the hand to the desired position. Recent work at various laboratories has provided strong support for the hypothesis that the CNS learns and maintains internal models of sensorimotor transformations. An internal model is a neural system that mimics the behaviour of the sensorimotor system and objects in the external environment. Internal models enable the CNS to predict the consequences of motor commands and to determine the motor commands required to perform specific tasks. In this chapter, we first summarize recent computational, behavioural and neurophysiological studies that address the theoretical necessity of internal models, the locations of internal models, and the neural mechanism for acquiring internal models through learning. Then, we propose a new computational model of multiple internal models.

Animals↗

PubMed1997

Slower evolution of human immunodeficiency virus type 1 quasispecies during progression to AIDS.

The evolution of human immunodeficiency virus type 1 (HIV-1) quasispecies at the envelope gene was studied from the time of infection in 11 men who experienced different rates of CD4+ cell count decline and 6 men with unknown dates of infection by using DNA heteroduplex mobility assays. Quasispecies were genetically homogeneous near the time of seroconversion. Subsequently, slower proviral genetic diversification and higher plasma viremia correlated with rapid CD4+ cell count decline. Except for the fastest progressors to AIDS, highly diverse quasispecies developed in all subjects within 3 to 4 years. High quasispecies diversity was then maintained for years until again becoming more homogeneous in a subset of late-stage AIDS patients. Individuals who maintained high CD4+ cell counts showed continuous genetic turnover of their complex proviral quasispecies, while more closely related sets of variants were found in longitudinal samples of severely immunocompromised patients. The limited number of variants that grew out in short-term PBMC cocultures were rare in the uncultured proviral quasispecies of healthy, long-term infected individuals but more common in vivo in patients with low CD4+ cell counts. The slower evolution of HIV-1 observed during rapid progression to AIDS and in advanced patients may reflect ineffective host-mediated selection pressures on replicating quasispecies.

Acquired Immunodeficiency Syndrome↗

PubMed1991

Animal rights.

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Animal Welfare↗