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.     

The effect of rainfall on spatio‐temporal variability in cropping systems and duration of crop cover in the Northern Ethiopian Highlands

In the Northern Ethiopian Highlands, ca. 33% of the land is cropland, which is mainly cultivated by smallholders who based on indigenous knowledge plan their cropping system on the basis of spatio‐temporal variability in rainfall. To understand the relationships between rainfall variability and cropping systems, a field campaign was undertaken in the rainy season of 2009 when 118 farmers were interviewed at different locations with different environmental characteristics. Five cropping systems were identified, each having a distinct cropping season length and crop association. Cropping systems with shorter cropping seasons were generally on the valleysides, whereas longer cycles occurred in the valley bottoms. The length of cropping season also increased from north–northeast to south–southwest. Crop associations within cropping systems also varied with altitude. Cropping systems changed in response to variation in annual rainfall. This resulted in shifts of cropping systems at catchment and regional scales, with cropping systems having longer cropping seasons where there was greater annual precipitation. The results were scaled up to the whole region by modelling the spatial distribution of cropping systems at a 8 × 8 km² resolution over the period 1996–2009. The results indicate that indigenous knowledge is important when assessing the impact of climatic variability on agricultural production and that large inter‐annual variability in the duration of crop cover in Northern Ethiopia might be an important, although generally overlooked, explanatory factor for explaining previous land degradation cycles.     

Development of One vs Multiple Ovulatory Follicles and Associated Systemic Hormone Concentrations in Mares

Ablation of follicles ≥  6 mm in diameter and treatment with PGF2α 10 days after ovulation were used to induce the development of ovulatory waves. Comparisons were made between induced waves with one (33 waves, 72%) and multiple (13 waves, 28%) ovulatory follicles. Diameter deviation was defined as the separation of follicles into dominant and subordinate categories. Multiple ovulatory follicles were preceded by more (p < 0.001) follicles ≥ 20 mm at the beginning of deviation, higher LH preceding deviation (approached significance, p < 0.08), lower (p < 0.05) concentrations of FSH on the day of deviation and thereafter, and higher (p < 0.0003) oestradiol by 2 days after deviation. During the peri-ovulatory period, systemic hormone concentrations for waves with multiple ovulations involved higher oestradiol before ovulation (approached significance, p < 0.07), lower FSH (p < 0.04) before and after ovulation, and both higher progesterone (p < 0.05) and lower LH (p < 0.05) beginning the day after ovulation. Results indicated that by the beginning of deviation there were more follicles ≥  20 mm and subsequently greater oestradiol production in waves that led to the development of multiple ovulatory follicles, and during the peri-ovulatory period differences between one and multiple ovulations were consistent with the negative effects of the ovarian hormones on the gonadotropins.     

Fluidity of bound hydration layers

We have measured the shear forces between solid surfaces sliding past each other across aqueous salt solutions, at pressures and concentrations typical of naturally occurring systems. In such systems the surface-attached hydration layers keep the compressed surfaces apart as a result of strongly repulsive hydration forces. We find, however, that the bound water molecules retain a shear fluidity characteristic of the bulk liquid, even when compressed down to films 1.0 +/- 0.3 nanometer thick. We attribute this to the ready exchange (as opposed to loss) of water molecules within the hydration layers as they rub past each other under strong compression.     

The Kondo effect in the presence of ferromagnetism

We measured Kondo-assisted tunneling via C60 molecules in contact with ferromagnetic nickel electrodes. Kondo correlations persisted despite the presence of ferromagnetism, but the Kondo peak in the differential conductance was split by an amount that decreased (even to zero) as the moments in the two electrodes were turned from parallel to antiparallel alignment. The splitting is too large to be explained by a local magnetic field. However, the voltage, temperature, and magnetic field dependence of the signals agree with predictions for an exchange splitting of the Kondo resonance. The Kondo effect leads to negative values of magnetoresistance, with magnitudes much larger than the Julliere estimate.     

Clinical evaluation of dietary modification for treatment of spontaneous chronic renal failure in dogs

OBJECTIVE: To determine whether a diet used for dogs with renal failure (renal food [RF]) was superior to an adult maintenance food (MF) in minimizing uremic crises and mortality rate in dogs with spontaneous chronic renal failure. DESIGN: Double-masked, randomized, controlled clinical trial. ANIMALS: 38 dogs with spontaneous chronic renal failure. PROCEDURE: Dogs were randomly assigned to a group fed adult MF or a group fed RF and evaluated for up to 24 months. The 2 groups were of similar clinical, biochemical, and hematologic status. The effects of diets on uremic crises and mortality rate were compared. Changes in renal function were evaluated by use of serial evaluation of serum creatinine concentrations and reciprocal of serum creatinine concentrations. RESULTS: Compared with the MF, the RF had a beneficial effect regarding uremic crises and mortality rate in dogs with mild and moderate renal failure. Dogs fed the RF had a slower decline in renal function, compared with dogs fed the MF. CONCLUSIONS AND CLINICAL RELEVANCE: Dietary modifications are beneficial in minimizing extrarenal manifestations of uremia and mortality rate in dogs with mild and moderate spontaneous chronic renal failure. Results are consistent with the hypothesis that delay in development of uremic crises and associated mortality rate in dogs fed RF was associated, at least in part, with reduction in rate of progression of renal failure.     

Hexanal and 1-MCP treatments for enhancing the shelf life and quality of sweet cherry (Prunus avium L.)

Sweet cherry has a short post-harvest shelf life and this greatly affects the consumer preference and export of fresh fruits. In this study, the effects of pre-harvest application of a hexanal formulation (enhanced freshness formulation, EFF) and post-harvest application of hexanal vapour and 1-MCP on quality parameters and shelf life of sweet cherry were investigated. Cherries subjected to pre-harvest spray with EFF had better color, brightness and firmness than unsprayed cherries even after 30 days of storage at 4 °C. These EFF-treated cherries also showed higher chroma values indicative of enhanced red color. Post-harvest application of either, hexanal vapour, 1-MCP, or a combination of both, enhanced the firmness of cherries. These treatments also resulted in higher levels of superoxide dismutase and ascorbate peroxidase activities. The levels of anthocyanins and phenolic components were either enhanced or maintained during the 30-day storage period. Our results suggest that a pre-harvest application of EFF combined with post-harvest treatment of hexanal and 1-MCP may enhance the quality and shelf life of sweet cherry.     

Activation of central melanocortin pathways by fenfluramine

D-fenfluramine (d-FEN) was once widely prescribed and was among the most effective weight loss drugs, but was withdrawn from clinical use because of reports of cardiac complications in a subset of patients. Discerning the neurobiology underlying the anorexic action of d-FEN may facilitate the development of new drugs to prevent and treat obesity. Through a combination of functional neuroanatomy, feeding, and electrophysiology studies in rodents, we show that d-FEN-induced anorexia requires activation of central nervous system melanocortin pathways. These results provide a mechanistic explanation of d-FEN's anorexic actions and indicate that drugs targeting these downstream melanocortin pathways may prove to be effective and more selective anti-obesity treatments.     

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.     

Streptomyces sp. RP1A-12 mediated control of peanut stem rot caused by Sclerotium rolfsii

Sclerotium rolfsii Sacc. is a destructive soilborne fungal pathogen with a wide host range that includes peanuts. Biological control offers an interesting alternative to fungicides for sustainable management of soilborne diseases. The current investigation is aimed at evaluating one potential biocontrol agent Streptomyces sp. RP1 A-12 for growth promotion and the management of peanut stem rot disease caused by S. rolfsii under field conditions. Preliminary studies conducted under in vitro and the greenhouse conditions showed promising results against the stem rot pathogen. Further in vitro and pot experiments conducted to assess Streptomyces sp. RP1 A-12 for its growth promoting abilities using whole organisms have shown an increase in seed germination, root and shoot length. Other parameters like nodule number and plant biomass were also significantly increased over control treatments indicating that the test bioagent possesses growth promoting abilities along with disease suppression capabilities. Subsequently field studies were carried out for two consecutive rainy seasons. The bioagent was applied as whole organism and partially purified crude metabolites. Results indicate the bioagent reduced stem rot disease incidence by 64–67% and 22–49% respectively in two field trials conducted with notable increase in yield. Partially purified Streptomyces sp. RP1 A-12 metabolites exhibited an even greater effect in reducing the incidence and severity of stem rot compared to the pathogen inoculated control.