5 research outputs found
Simulating protein unfolding under pressure with a coarse-grained model
We describe and test a coarse-grained molecular model for the simulation of the effects of pressure on the folding/unfolding transition of proteins. The model is a structure-based one, which takes into account the desolvation barrier for the formation of the native contacts. The pressure is taken into account in a qualitative, mean field approach, acting on the parameters describing the native stabilizing interactions. The model has been tested by simulating the thermodynamic and structural behavior of protein GB1 with a parallel tempering Monte Carlo algorithm. At low effective pressures, the model reproduces the standard two-state thermal transition between the native and denatured states. However, at large pressures a new state appears. Its structural characteristics have been analyzed, showing that it corresponds to a swollen version of the native structure. This swollen state is at equilibrium with the native state at low temperatures, but gradually transforms into the thermally denatured state as temperature is increased. Therefore, our model predicts a downhill transition between the swollen and the denatured states. The analysis of the model permits us to obtain a phase diagram for the pressure-temperature behavior of the simulated system, which is compatible with the known elliptical shape of this diagram for real proteins
Adolescent exposure to the Spice/K2 cannabinoid JWH-018 impairs sensorimotor gating and alters cortical perineuronal nets in a sex-dependent manner.
The consumption of synthetic cannabinoids during adolescence is reported to be a risk factor for the appearance of psychiatric disorders later in life. JWH-018 was identified as one of the primary psychoactive components present in Spice/K2 preparations. This study evaluated the short- and long-term consequences of exposure to JWH-018 during the adolescence in anxiety-like behavior, fear extinction, and sensorimotor gating in male and female mice. Alterations in anxiety varied depending on the time interval between treatment and behavioral analysis along with sex, while no changes were observed in the extinction of fear memory. A decrease in prepulse inhibition of the startle reflex was revealed in male, but not female, mice at short- and long-term. This behavioral disturbance was associated with a reduction in the number of perineuronal nets in the prelimbic and infralimbic regions of the prefrontal cortex in the short-term. Furthermore, adolescent exposure to JWH-018 induced an activation of microglia and astrocytes in the prefrontal cortex of male mice at both time intervals. A transitory decrease in the expression of GAD67 and CB2 cannabinoid receptors in the prefrontal cortex was also found in male mice exposed to JWH-018. These data reveal that the treatment with JWH-018 during the adolescence leads to long-lasting neurobiological changes related to psychotic-like symptoms, which were sex-dependent.post-print2490 K
Time Series Analysis Applied to EEG Shows Increased Global Connectivity during Motor Activation Detected in PD Patients Compared to Controls.
Background: Brain connectivity has shown to be a key characteristic in the study of both
Parkinson’s Disease (PD) and the response of the patients to the dopaminergic medication. Time series
analysis has been used here for the first time to study brain connectivity changes during motor
activation in PD. Methods: A 64-channel EEG signal was registered during unilateral motor activation
and resting-state in 6 non-demented PD patients before and after the administration of levodopa
and in 6 matched healthy controls. Spectral entropy correlation, coherence, and interhemispheric
divergence differences among PD patients and controls were analyzed under the assumption of
stationarity of the time series. Results: During the motor activation test, PD patients showed
an increased correlation coefficient (both hands p < 0.001) and a remarkable increase in coherence in
all frequency range compared to the generalized reduction observed in controls (both hands p < 0.001).
The Kullback–Leibler Divergence (KLD) of the Spectral Entropy between brain hemispheres was
observed to increase in controls (right hand p = 0.01; left hand p = 0.015) and to decrease in PD
patients (right hand p = 0.02; left hand p = 0.002) with motor activation. Conclusions: Our results
suggest that the oscillatory activity of the different cortex areas within healthy brains is relatively
independent of the rest. PD brains exhibit a stronger connectivity which grows during motor
activation. The levodopa mitigates this anomalous performance.post-print2,22 M
Modelos simples para estudiar el efecto de la presiĂłn en el plegamiento de proteĂnas
Tesis inĂ©dita de la Universidad Complutense de Madrid, Facultad de Ciencias QuĂmicas, Departamento de QuĂmica FĂsica I, leĂda el 09-05-2014Depto. de QuĂmica FĂsicaFac. de Ciencias QuĂmicasTRUEunpu