Sensitivity of Oncogenic KRAS-Expressing Cells to CDK9 Inhibition.

Oncogenic forms of KRAS proteins are known to be drivers of pancreatic, colorectal, and lung cancers. The goal of this study is to identify chemical leads that inhibit oncogenic KRAS signaling. We first developed an isogenic panel of mouse embryonic fibroblast (MEF) cell lines that carry wild-type RAS, oncogenic KRAS, and oncogenic BRAF.

The effect of prolonged-release melatonin on sleep measures and psychomotor performance in elderly patients with insomnia.

Objectives of this study were to investigate the effects of prolonged-release melatonin 2 mg (PRM) on sleep and subsequent daytime psychomotor performance in patients aged > or =55 years with primary insomnia, as defined by fourth revision of the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association. Patients (N = 40) were treated nightly single-blind with placebo (2 weeks), randomized double-blind to PRM or placebo (3 weeks) followed by withdrawal period (3 weeks). Sleep was assessed by polysomnography, all-night sleep electroencephalography spectral analysis and questionnaires.

Effects of a moderate nocturnal cold stress on daytime sleep in humans.

The effects of a nocturnal exposure to a cool environment on daytime recovery sleep was studied in eight young (20-25 years old) healthy volunteers. A set of standardized clothing (KSU ensemble type) was provided to each individual (estimated total thermal resistance: 0.6 clo).

Interaction of M(3+) Lanthanide Cations with Amide, Pyridine, and Phosphoryl O=PPh(3) Ligands: A Quantum Mechanics Study.

We report an ab initio quantum mechanical study on the interaction of M(n)()(+) cations (M(n)()(+) = La(3+), Eu(3+), Yb(3+), Sr(2+), and Na(+)) with model ligands L for lanthanide or actinide cations: several substituted amides, pyridines, and the phosphoryl-containing OPPh(3) ligand. The interaction energies DeltaE follow trends expected from the cation hardness and ligand basicity or softness in the amide series (primary < secondary-cis < secondary-trans < tertiary) as well as in the pyridine series (para-NO(2) < H < Me < NMe(2)). Among all ligands studied, OPPh(3) is clearly the best, while the (best) tertiary amide binds lanthanides slightly less than the (best) pyridine-NMe(2) ligand.

Central effects of acamprosate: part 2. Acamprosate modifies the brain in-vivo proton magnetic resonance spectrum in healthy young male volunteers.

Although acamprosate is a drug which is successfully used for therapy in maintaining alcohol abstinence following alcohol withdrawal in chronic alcoholism, little is understood about its mechanism of action in the central nervous system. Our objective was to assess the effects of acamprosate on the central nervous system in healthy subjects by dynamic proton magnetic resonance spectroscopy (MRS) measurements localized in brain tissue in vivo. Recordings were performed after intravenous administration of acamprosate or placebo to eight healthy male volunteers participating in a double-blind, randomized, cross-over, placebo-controlled study.

Enhancement of NMDA receptor maturation by BDNF in cultured mouse cerebellar granule cells.

The N-methyl-D-aspartate (NMDA) subtype of glutamate receptor, which is essential during organogenesis for neuronal differentiation and formation of synaptic connections in the developing brain, changes its receptor properties during development by differential expression of multiple subunits. Using a combined electrophysiological and pharmacological approach on primary cultures of mouse cerebellar neurones, we investigated the evolution of the NMDA receptor and the potential effect of the neurotrophin BDNF on its expression. We showed that 1) the current density of NMDA responses increased with time of culture; 2) epsilon 1 subunit expression increased with time in culture relative to epsilon 2 subunit expression; and 3) the time course of the increase in NMDA responses was accelerated by about 2 days in the presence of BDNF.

First-night effect in normal subjects and psychiatric inpatients.

The goal of the present study was to evaluate the first-night effect in psychiatric inpatients using large subject samples (n > 30) in order to obtain a good statistical evaluation. Thirty-two normal subjects and 94 psychiatric inpatients (38 depressives and 56 insomniacs) were studied for three consecutive nights in the hospital sleep laboratory. Our results showed clearly that there was a first-night effect in normal subjects, similar to that reported in previously published data, characterized by a longer rapid eye movement (REM) sleep latency (p < 0.

Renin as a biological marker of the NREM-REM sleep cycle: effect of REM sleep suppression.

We have previously described that, in normal man, the nocturnal oscillations of plasma renin activity (PRA) exactly reflect the rapid eye movement (REM)-non(N)REM sleep cycles, with increasing PRA levels during NREM sleep and decreasing levels during REM sleep. This study was carried out to determine whether REM sleep suppression affects nocturnal renin profiles and to define which sleep stage is essential for renin release. In a first experimental series, REM sleep was suppressed by using clomipramine, a tricyclic antidepressant.

Thermoregulatory adjustments during continuous heat exposure.

Body temperature regulation was studied in 6 male subjects during an acclimation procedure involving uninterrupted heat exposure for 5 successive days and nights in a hot dry environment (ambient temperature = 35 degrees C, dew-point temperature = 7 degrees C; air velocity = 0.2 m.s-1).

Effects of triazolam on heart rate level and on phasic cardiac response to noise during sleep.

The influence of triazolam on cardiac and respiratory activity of healthy male subjects was examined during nights disturbed by airplane noises and during undisturbed nights. Twenty-four subjects, divided into three groups of eight, slept in the laboratory for 7 nights (N0-N6). Following a double blind design, group A (control group) received a placebo every night.