No abstract

Processive proteases can unfold proteins and cleave them into fragments of a characteristic size. The detailed mechanism by which product sizes are controlled is still in question. One possible mechanism for the control of product sizes would be translocation of unfolded polypeptides to the protease active sites in units of defined length. We have investigated the mechanism by which ClpAP, an energy-dependent protease from Escherichia coli, controls the sizes of its peptide products. We show that ClpAP generates peptide products with a distribution of sizes that has a pronounced peak at a peptide length of 6-8 amino acid residues. This product size distribution, which is similar to that observed previously for the proteasome, is robust to perturbations that interfere with translocation or proteolysis. To explain these results, we propose a mechanism in which translocation alternates with proteolysis, allowing peptides of more or less uniform length to be cleaved processively from a translocating substrate. To estimate the rate and energy efficiency of ClpAP-catalyzed measurements of product sizes, we apply information theory to quantify how precisely the product sizes are controlled. This analysis may also prove to be useful in characterizing the mechanisms of other proteases and nucleases, such as the proteasome and Dicer, which control the sizes of their products.

We investigated physiological and subjective responses to morning light exposure of commercially available LED lighting with different correlated colour temperatures to predict how LED-based smart lighting employed in future learning environments will impact students. The classical markers of the circadian system (melatonin and cortisol), as well as the subjective perception of sleepiness, mood, and visual comfort, were compared. Fifteen university students underwent an hour of morning light exposure to both warm (3,500 K) and blue-enriched (6,500 K) white lights at recommended illuminance levels for classrooms and lecture halls (500 lux). The decline of melatonin levels was significantly greater after the exposure to blue-enriched white light. Exposure to blue-enriched white light significantly improved subjective perception of alertness, mood, and visual comfort. With regard to cortisol, we did not find a significant difference in the cortisol decrement between the two light conditions. Our findings suggest that the sensitivity of physiological and subjective responses to white LED light is blue-shifted. These findings, extending the already known effects of short-wavelength light on human physiology, reveal interesting practical implications. Blue-enriched LED light seems to be a simple yet effective potential countermeasure for morning drowsiness and dozing off in class, particularly in schools with insufficient daylight.

This study aims to investigate the effects of lighting color temperatures on elementary students' performance, and thereby propose a dynamic lighting system for a smart learning environment. Three empirical studies were conducted: First, physiological responses were measured as a potential mediator of performance. Second, cognitive and behavioral responses were observed during academic and recess activities. Lastly, the experiment was carried out in a real-life setting with prolonged exposure. With a comprehensive analysis of the three studies, three lighting presets-3500 K, 5000 K, and 6500 K-are suggested for easy, standard, and intensive activity, respectively. The study is expected to act as a good stepping stone for developing dynamic lighting systems to support students' performance in learning environments.

No abstract

The structural perturbation induced by C(alpha)-->N(alpha) exchange in azaamino acid-containing peptides was predicted by ab initio calculation of the 6-31G* and 3-21G* levels. The global energy-minimum conformations for model compounds, For-azaXaa-NH2 (Xaa=Gly, Ala, Leu) appeared to be the beta-turn motif with a dihedral angle of phi= +/- 90 degrees, psi=0 degrees. This suggests that incorporation of the azaXaa residue into the i+2 position of designed peptides could stabilize the beta-turn structure. The model azaLeu-containing peptide, Boc-Phe-azaLeu-Ala-OMe, which is predicted to adopt a beta-turn conformation was designed and synthesized in order to experimentally elucidate the role of the azaamino acid residue. Its structural preference in organic solvents was investigated using 1H NMR, molecular modelling and IR spectroscopy. The temperature coefficients of amide protons, the characteristic NOE patterns, the restrained molecular dynamics simulation and IR spectroscopy defined the dihedral angles [ (phi i+1, psi i+1) (phi i+2, psi i+2)] of the Phe-azaLeu fragment in the model peptide, Boc-Phe-azaLeu-Ala-OMe, as [(-59 degrees, 127 degrees) (107 degrees, -4 degrees)]. This solution conformation supports a betaII-turn structural preference in azaLeu-containing peptides as predicted by the quantum chemical calculation. Therefore, intercalation of the azaamino acid residue into the i+2 position in synthetic peptides is expected to provide a stable beta-turn formation, and this could be utilized in the design of new peptidomimetics adopting a beta-turn scaffold.

The aim of present study was to establish normative data for the distribution of nuchal translucency (NT) thickness in normal Korean fetuses. The data were collected from pregnant women with singleton pregnancies in whom fetal ultrasound was performed and the fetal NT thickness was measured between 11 and 14 weeks of gestation. Among them, a total of 2,577 fetuses with a known normal outcome were included in this study. The distribution of multiple of median (MoM) values of the NT thickness with crown-rump length (CRL) in 10-mm intervals and the 95th percentile of MoM were calculated with the linear regression method. The present study showed that NT measurements increase with increasing CRL and a false positive rate increases with increasing gestational age. Therefore, a fixed cut-off point through the first trimester was not appropriate and each NT measurement should be examined according to the gestational age. The present study offers normative data of the fetal NT thickness in a Korean population, which can be used as reference for screening chromosomal aberrations or other congenital abnormalities in the first trimester.

SUMMARY The lack of small-molecule inhibitors for anion-selective transporters and channels has impeded our understanding of the complex mechanisms that underlie ion passage. The ubiquitous CLC “Chloride Channel” family represents a unique target for biophysical and biochemical studies because its distinctive protein fold supports both passive chloride channels and secondary-active chloride-proton transporters. Here, we describe the synthesis and characterization of the first specific small-molecule inhibitor directed against a CLC antiporter (ClC-ec1). This compound, 4,4′-octanamidostilbene-2,2′-disulfonate (OADS), inhibits ClC-ec1 with low micromolar affinity and has no specific effect on a CLC channel (ClC-1). Inhibition of ClC-ec1 occurs by binding to two distinct intracellular sites. The location of these sites and the lipid-dependence of inhibition suggest potential mechanisms of action. The discovery of this compound will empower research to elucidate differences between antiporter and channel mechanisms and to develop treatments for CLC-mediated disorders.