Glabrene and isoliquiritigenin as tyrosinase inhibitors from licorice roots

Tyrosinase is known to be a key enzyme in melanin biosynthesis, involved in determining the color of mammalian skin and hair. Various dermatological disorders, such as melasama, age spots, and sites of actinic damage, arise from the accumulation of an excessive level of epidermal pigmentation. The inadequacy of current therapies to treat these conditions as well as high cytotoxicity and mutagenicity, poor skin penetration, and low stability of formulations led us to seek new whitening agents to meet the medical requirements for depigmenting agents. The inhibitory effect of licorice extract on tyrosinase activity was higher than that expected from the level of glabridin in the extract. This led us to test for other components that may contribute to this strong inhibitory activity. Results indicated that glabrene and isoliquiritigenin (2',4',4-trihydroxychalcone) in the licorice extract can inhibit both mono- and diphenolase tyrosinase activities. The IC(50) values for glabrene and isoliquiritigenin were 3.5 and 8.1 microM, respectively, when tyrosine was used as substrate. The effects of glabrene and isoliquiritigenin on tyrosinase activity were dose-dependent and correlated to their ability to inhibit melanin formation in melanocytes. This is the first study indicating that glabrene and isoliquiritigenin exert varying degrees of inhibition on tyrosinase-dependent melanin biosynthesis, suggesting that isoflavenes and chalcones may serve as candidates for skin-lightening agents.     

Effects of retirement on lifestyle in relation to changes in weight and waist circumference in Dutch men: a prospective study

OBJECTIVE: To study changes in lifestyle in relation to changes in body weight and waist circumference associated with occupational retirement in men. DESIGN: A prospective cohort study with 5 years of follow-up. At baseline and at follow-up, questionnaires were completed and body weight and waist circumference were measured. SETTING: The Doetinchem Cohort Study, consisting of inhabitants of Doetinchem, a town in a rural area of The Netherlands.Subjects: In total 288 healthy men aged 50-65 years at baseline, who either remained employed or retired over follow-up. RESULTS: The effect of retirement on changes in weight and waist circumference was dependent on type of former occupation. Increase in body weight and waist circumference was higher among men who retired from active jobs (0.42 kg year(-1) and 0.77 cm year(-1), respectively) than among men who retired from sedentary jobs (0.08 kg year(-1) and 0.23 cm year(-1), respectively). Weight gain and increase in waist circumference were associated with a decrease in fruit consumption and fibre density of the diet, with an increase in frequency of eating breakfast, and with a decrease in several physical activities, such as household activities, bicycling, walking and doing odd jobs. CONCLUSION: Retirement was associated with an increase in weight and waist circumference among those with former active jobs, but not among those with former sedentary jobs. Retirement may bring opportunities for healthy changes in diet and physical activity, which could be used in health promotion programmes.     

A molecular basis for MHC class II--associated autoimmunity

Class II major histocompatibility (MHC) molecules have an immunoregulatory role. These cell-surface glycoproteins present fragments of protein antigens (or peptides) to thymus-derived lymphocytes (T cells). Nucleotide sequence polymorphism in the genes that encode the class II MHC products determines the specificity of the immune response and is correlated with the development of autoimmune diseases. This study identifies certain class II polymorphic amino acid residues that are strongly associated with susceptibility to insulin-dependent diabetes mellitus, rheumatoid arthritis, and pemphigus vulgaris. These findings implicate particular class II MHC isotypes in susceptibility to each disease and suggest new prophylactic and therapeutic strategies.     

Structure,mechanism, and regulation of the Neurospora plasma membrane H+-ATPase

Proton pumps in the plasma membrane of plants and yeasts maintain the intracellular pH and membrane potential. To gain insight into the molecular mechanisms of proton pumping, we built an atomic homology model of the proton pump based on the 2.6 angstrom x-ray structure of the related Ca2+ pump from rabbit sarcoplasmic reticulum. The model, when fitted to an 8 angstrom map of the Neurospora proton pump determined by electron microscopy, reveals the likely path of the proton through the membrane and shows that the nucleotide-binding domain rotates by approximately 70 degrees to deliver adenosine triphosphate (ATP) to the phosphorylation site. A synthetic peptide corresponding to the carboxyl-terminal regulatory domain stimulates ATPase activity, suggesting a mechanism for proton transport regulation.     

Microearthquakes in the ahuachapan geothermal field, el salvador, central america

Microearthquakes occur on a steeply dipping plane interpreted here as the fault that allows hot water to circulate to the surface in the geothermal region. These small earthquakes are common in many geothermal areas and may occur because of the physical or chemical effects of fluids and fluid pressure.     

Homo erectus calvarium from the Pleistocene of Java

A Homo erectus calvarium [Sambungmacan 4 (Sm 4)] was recovered from Pleistocene sediments at Sambungmacan in central Java. Micro-computed tomography analysis shows a modern human-like cranial base flexion associated with a low platycephalic vault, implying that the evolution of human cranial globularity was independent of cranial base flexion. The overall morphology of Sm 4 is intermediate between that of earlier and later Javanese Homo erectus; apparent morphological specializations are more strongly expressed in the latter. This supports the hypothesis that later Pleistocene Javanese populations were substantially isolated and made minimal contributions to the ancestry of modern humans.     

Domain dynamics during ferroelectric switching

The utility of ferroelectric materials stems from the ability to nucleate and move polarized domains using an electric field. To understand the mechanisms of polarization switching, structural characterization at the nanoscale is required. We used aberration-corrected transmission electron microscopy to follow the kinetics and dynamics of ferroelectric switching at millisecond temporal and subangstrom spatial resolution in an epitaxial bilayer of an antiferromagnetic ferroelectric (BiFeO(3)) on a ferromagnetic electrode (La(0.7)Sr(0.3)MnO(3)). We observed localized nucleation events at the electrode interface, domain wall pinning on point defects, and the formation of ferroelectric domains localized to the ferroelectric and ferromagnetic interface. These results show how defects and interfaces impede full ferroelectric switching of a thin film.     

Independently evolved virulence effectors converge onto hubs in a plant immune system network

Plants generate effective responses to infection by recognizing both conserved and variable pathogen-encoded molecules. Pathogens deploy virulence effector proteins into host cells, where they interact physically with host proteins to modulate defense. We generated an interaction network of plant-pathogen effectors from two pathogens spanning the eukaryote-eubacteria divergence, three classes of Arabidopsis immune system proteins, and ~8000 other Arabidopsis proteins. We noted convergence of effectors onto highly interconnected host proteins and indirect, rather than direct, connections between effectors and plant immune receptors. We demonstrated plant immune system functions for 15 of 17 tested host proteins that interact with effectors from both pathogens. Thus, pathogens from different kingdoms deploy independently evolved virulence proteins that interact with a limited set of highly connected cellular hubs to facilitate their diverse life-cycle strategies.     

Realizing all-spin-based logic operations atom by atom

An ultimate goal of spintronic research is the realization of concepts for atomic-scale all-spin-based devices. We combined bottom-up atomic fabrication with spin-resolved scanning tunneling microscopy to construct and read out atomic-scale model systems performing logic operations. Our concept uses substrate-mediated indirect exchange coupling to achieve logical interconnection between individual atomic spins. Combined with spin frustration, this concept enables various logical operations between inputs, such as NOT and OR.