Molecular design of a highly selective and strong protein inhibitor against matrix metalloproteinase-2 (MMP-2).

Synthetic inhibitors of matrix metalloproteinases (MMPs), designed previously, as well as tissue inhibitors of metalloproteinases (TIMPs) lack enzyme selectivity, which has been a major obstacle for developing inhibitors into safe and effective MMP-targeted drugs. Here we designed a fusion protein named APP-IP-TIMP-2, in which the ten amino acid residue sequence of APP-derived MMP-2 selective inhibitory peptide (APP-IP) is added to the N terminus of TIMP-2. The APP-IP and TIMP-2 regions of the fusion protein are designed to interact with the active site and the hemopexin-like domain of MMP-2, respectively.

Structural basis for matrix metalloproteinase-2 (MMP-2)-selective inhibitory action of β-amyloid precursor protein-derived inhibitor.

Unlike other synthetic or physiological inhibitors for matrix metalloproteinases (MMPs), the β-amyloid precursor protein-derived inhibitory peptide (APP-IP) having an ISYGNDALMP sequence has a high selectivity toward MMP-2. Our previous study identified amino acid residues of MMP-2 essential for its selective inhibition by APP-IP and demonstrated that the N to C direction of the decapeptide inhibitor relative to the substrate-binding cleft of MMP-2 is opposite that of substrate. However, detailed interactions between the two molecules remained to be clarified.

Partial REM-sleep deprivation increases the dream-like quality of mentation from REM sleep and sleep onset.

Study Objectives: Sleep onset (SO) is cognitively and physiologically similar to rapid eye movement (REM) sleep, supporting the notion that REM sleep-related processes are 'covertly' active at this time. The objective was to determine if SO mentation is sensitive to REM sleep deprivation.

Design: Two-group cross-sectional design; sleep recordings for 3 nights.

Detection of rapid-eye movements in sleep studies.

One of the key features of rapid-eye movement (REM) sleep is the presence of bursts of REMs. Sleep studies routinely use REMs to classify sleep stages. Moreover, REM count or density has been used in studies involving learning and various psychiatric disorders.

Elicitation of sleep-onset REM periods in normal individuals using the sleep interruption technique (SIT).

Use of the sleep interruption technique (SIT) to elicit sleep onset REM periods (SOREMPs) in normal individuals is introduced along with its theoretical bases, empirical findings, and potential applications. Capitalizing upon the circadian and ultradian nature of REM sleep, the SIT has been developed to examine various psychophysiological characteristics related to REM sleep. The SIT allows us to: (1) obtain SOREMPs at the discretion of the researcher; (2) avoid the contaminating effects of preceding non-REM (NREM)-REM stage ordering on subsequent target sleep episodes; and (3) obtain many REM episodes in a short time by repeating the sleep interruptions.

EEG activities during elicited sleep onset REM and NREM periods reflect different mechanisms of dream generation. Electroencephalograms. Rapid eye movement.

Objective: To be the first to compare EEG power spectra during sleep onset REM periods (SOREMP) and sleep onset NREM periods (NREMP) in normal individuals and relate this to dream appearance processes underlying these different types of sleep periods.

Methods: Eight healthy undergraduates spent 7 consecutive nights in the sleep lab including 4 nights for SOREMP elicitation using the Sleep Interruption Technique. This enabled us to control preceding sleep processes between SOREMP and NREMP.

Factors related to the occurrence of isolated sleep paralysis elicited during a multi-phasic sleep-wake schedule.

Study Objectives: To further investigate mechanisms of isolated sleep paralysis (ISP) in normal individuals, we experimentally elicited ISPs by facilitating sleep onset REM periods (SOREMP), a prerequisite of ISPs, and examined behavioral and psychological measurements relating to ISP appearances.

Design: The multi-phasic sleep/wake schedule (MPS) began at approximately midnight and ended when net sleep reached 7.5 hours.