Conformational transitions of glycine induced by vibrational excitation of the O-H stretch

Vibrational energy flow and conformational transitions following excitation of the OH stretching mode of the most stable conformer of glycine are studied by classical trajectories. "On the fly" simulations with the PM3 semiempirical electronic structure method for the potential surface are used. Initial conditions are selected to correspond to the v = 1 excitation of the OH stretch. The main findings are: (1) An an equilibrium-like ratio is established between the populations of the 3 lowest-lying conformers after about 10 picoseconds. (2) There is a high probability throughout the 150 ps of the simulations for finding the molecule in geometries far from the equilibrium structures of the lowest-energy conformers. (3) Energy from the initial excited OH (v = 1) stretch flows preferentially to 5 other vibrational modes, including the bending motion of the H atom. (4) RRK theory yields conformational transition rates that deviate substantially from the classical trajectory results. Possible implication of these results for vibrational energy flow and conformational transitions in small biological molecules are discussed.

Forbidden ordinal patterns of periictal intracranial EEG indicate deterministic dynamics in human epileptic seizures

Epileptic seizures typically reveal a high degree of stereotypy, that is, for an individual patient they are characterized by an ordered and predictable sequence of symptoms and signs with typically little variability. Stereotypy implies that ictal neuronal dynamics might have deterministic characteristics, presumably most pronounced in the ictogenic parts of the brain, which may provide diagnostically and therapeutically important information. Therefore the goal of our study was to search for indications of determinism in periictal intracranial electroencephalography (EEG) studies recorded from patients with pharmacoresistent epilepsy.

Sleep in spousal Alzheimer caregivers: a longitudinal study with a focus on the effects of major patient transitions on sleep

Findings on sleep disturbances in family dementia caregivers are conflicting. We studied the longitudinal effects of dementia caregiving and major transitions in the caregiving situation on caregivers' sleep and the effect of moderating variables.

Effect of chronic dementia caregiving and major transitions in the caregiving situation on kidney function: a longitudinal study

To estimate the glomerular filtration rate (GFR) in relation to the chronic stress of dementia caregiving and major transitions in the caregiving situation.

The IKK inhibitor BMS-345541 affects multiple mitotic cell cycle transitions

The IkappaB kinase (IKK) complex controls processes such as inflammation, immune responses, cell survival and the proliferation of both normal and tumor cells. By activating NFkappaB, the IKK complex contributes to G1/S transition and first evidence has been presented that IKKalpha also regulates entry into mitosis. At what stage IKK is required and whether IKK also contributes to progression through mitosis and cytokinesis, however, has not yet been determined. In this study, we use BMS-345541, a potent allosteric small molecule inhibitor of IKK, to inhibit IKK specifically during G2 and during mitosis. We show that BMS-345541 affects several mitotic cell cycle transitions, including mitotic entry, prometaphase to anaphase progression and cytokinesis. Adding BMS-345541 to the cells released from arrest in S-phase blocked the activation of Aurora A, B and C, Cdk1 activation and histone H3 phosphorylation. Additionally, treatment of the mitotic cells with BMS-345541 resulted in precocious cyclin B1 and securin degradation, defective chromosome separation and improper cytokinesis. BMS-345541 was also found to override the spindle checkpoint in nocodazole-arrested cells. In vitro kinase assays using BMS-345541 indicate that these effects are not primarily due to a direct inhibitory effect of BMS-345541 on mitotic kinases such as Cdk1, Aurora A or B, Plk1 or NEK2. This study points towards a new potential role of IKK in cell cycle progression. Since deregulation of the cell cycle is one of the hallmarks of tumor formation and progression, the newly discovered level of BMS-345541 function could be useful for cell cycle control studies and may provide valuable clues for the design of future therapeutics.

The neurophysiological time pattern of illusionary visual perceptual transitions: a simultaneous EEG and fMRI study

Several divergent cortical mechanisms generating multistability in visual perception have been suggested. Here, we investigated the neurophysiologic time pattern of multistable perceptual changes by means of a simultaneous recording with electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Volunteers responded to the subjective perception of a sudden change between stable patterns of illusionary motion (multistable transition) during a stroboscopic paradigm. We found a global deceleration of the EEG frequency prior to a transition and an occipital-accentuated acceleration after a transition, as obtained by low-resolution electromagnetic tomography analysis (LORETA) analysis. A decrease in BOLD response was found in the prefrontal cortex before, and an increase after the transitions was observed in the right anterior insula, the MT/V5 regions and the SMA. The thalamus and left superior temporal gyrus showed a pattern of decrease before and increase after transitions. No such temporal course was found in the control condition. The multimodal approach of data acquisition allows us to argue that the top-down control of illusionary visual perception depends on selective attention, and that a diminution of vigilance reduces selective attention. These are necessary conditions to allow for the occurrence of a perception discontinuity in absence of a physical change of the stimulus.