Selective inhibition of monoamine oxidase A by purpurin,an anthraquinone

Monoamine oxidase (MAO) catalyzes the oxidation of monoamines that act as neurotransmitters. During a target-based screening of natural products using two isoforms of recombinant human MAO-A and MAO-B, purpurin (an anthraquinone derivative) was found to potently and selectively inhibit MAO-A, with an IC₅₀ value of 2.50 μM, and not to inhibit MAO-B. Alizarin (also an anthraquinone) inhibited MAO-A less potently with an IC₅₀ value of 30.1 μM. Furthermore, purpurin was a reversible and competitive inhibitor of MAO-A with a K_i value of 0.422 μM. A comparison of their chemical structures suggested the 4-hydroxy group of purpurin might play an important role in its inhibition of MAO-A. Molecular docking simulation showed that the binding affinity of purpurin for MAO-A (?40.0 kcal/mol) was higher than its affinity for MAO-B (?33.9 kcal/mol), and that Ile 207 and Gly 443 of MAO-A were key residues for hydrogen bonding with purpurin. The findings of this study suggest purpurin is a potent, selective, reversible inhibitor of MAO-A, and that it be considered a new potential lead compound for development of novel reversible inhibitors of MAO-A (RIMAs).     

Isoquinoline alkaloids from Coptis japonica stimulate the myoblast differentiation via p38 MAP-kinase and Akt signaling pathway

To overcome the muscle atrophy, such as cachexia and sarcopenia, we tried to find myogenic agents from medicinal plants. From myogenic extract of Coptis japonica, we purified six isoquinoline alkaloids and evaluated their effects on transactivation of myoD and MHC expression in C2C12 cells during differentiation process. Among obtained compounds, magnoflorine most efficiently enhanced the myoblast differentiation by activating the p38 MAP kinase and Akt pathway, and also increased the number of multinucleated and cylinder-shaped myotubes. These results propose that magnoflorine from Coptis japonica might be a promising lead compound for the development of anti-muscle atrophy drug.     

Consumer preference for edible insect‐containing cookies determined by conjoint analysis: An exploratory study of Korean consumers

Consumers are the principal agents of consumption when edible insect cookies are launched into the market; therefore, there is a need for research into consumer perception of this product and the factors that could affect their choice. Therefore, through this study, we aimed to provide such information for the development and launch of edible insect cookies. We investigated the importance of product features of edible insect cookies and the part‐worth of the feature levels while predicting the market share of edible insect cookies that are currently in development. We constructed 16 main and four hold‐out profiles from six product features and 16 levels of features. Following analysis of data collected from 203 of 250 respondents, product features were found to be important in the descending order of “type”, “price”, “size”, “availability of nutrition facts”, “thickness” and “use of edible insects”. When the market share of an edible insect cookie with the optimal combination of product features was analyzed through choice simulation, it had the second‐highest share in the cookie market, thus suggesting a direction for the development of edible insect cookies.     

Does high relatedness promote cheater‐free multicellularity in synthetic lifecycles?

The evolution of multicellularity is one of the key transitions in evolution and requires extreme levels of cooperation between cells. However, even when cells are genetically identical, noncooperative cheating mutants can arise that cause a breakdown in cooperation. How then, do multicellular organisms maintain cooperation between cells? A number of mechanisms that increase relatedness amongst cooperative cells have been implicated in the maintenance of cooperative multicellularity including single‐cell bottlenecks and kin recognition. In this study, we explore how relatively simple biological processes such as growth and dispersal can act to increase relatedness and promote multicellular cooperation. Using experimental populations of pseudo‐organisms, we found that manipulating growth and dispersal of clones of a social amoeba to create high levels of relatedness was sufficient to prevent the spread of cheating mutants. By contrast, cheaters were able to spread under low‐relatedness conditions. Most surprisingly, we saw the largest increase in cheating mutants under an experimental treatment that should create intermediate levels of relatedness. This is because one of the factors raising relatedness, structured growth, also causes high vulnerability to growth rate cheaters.     

Direct association of Bloom’s syndrome gene product with the human mismatch repair protein MLH1

Bloom’s syndrome (BS) is a rare genetic disorder characterised by genomic instability and cancer susceptibility. BLM, the gene mutated in BS, encodes a member of the RecQ family of DNA helicases. Here, we identify hMLH1, which is involved in mismatch repair (MMR) and recombination, as a protein that directly interacts with BLM both in vivo and in vitro, and that the two proteins co-localise to discrete nuclear foci. The interaction between BLM and hMLH1 appears to have been evolutionarily conserved, as Sgs1p, the Saccharomyces cerevisiae homologue of BLM, interacts with yeast Mlh1p. However, cell extracts derived from BS patients show no obvious defects in MMR compared to wild-type- and BLM-complemented BS cell extracts. We conclude that the hMLH1–BLM interaction is not essential for post-replicative MMR, but, more likely, is required for some aspect of genetic recombination.     

Cryptocotyle lata (Trematoda: Heterophyidae) Adult from a Korean Raccoon Dog,Nyctereutes procyonoides koreensis

Total 513 heterophyid flukes were collected from a carcass of wild Korean raccoon dog, Nyctereutes procyonoides koreensis, in Korea. With morphological and molecular characteristics, the flukes were identified to Cryptocotyle lata. The adult C. lata were minute, transparent, pentagonal, 522 μm long by 425 μm wide. Ceca extended into post-testicular region. Ventrogenital sac elliptical, 79 μm by 87 μm with genital pore and ventral sucker. Two testes semielliptical and slightly lobed, located in the posterior region, right testis 173 μm by 155 μm, left testis 130 μm by 134 μm. In a phylogenetic tree, the fluke specimen of this study was grouped with C. lata divergent from Cryptocotyle lingua. We report here N. procyonoides koreensis first as a natural definitive host of C. lata.     

AK2 is an AMP-sensing negative regulator of BRAF in tumorigenesis

The RAS–BRAF signaling is a major pathway of cell proliferation and their mutations are frequently found in human cancers. Adenylate kinase 2 (AK2), which modulates balance of adenine nucleotide pool, has been implicated in cell death and cell proliferation independently of its enzyme activity. Recently, the role of AK2 in tumorigenesis was in part elucidated in some cancer types including lung adenocarcinoma and breast cancer, but the underlying mechanism is not clear. Here, we show that AK2 is a BRAF-suppressor. In in vitro assays and cell model, AK2 interacted with BRAF and inhibited BRAF activity and downstream ERK phosphorylation. Energy-deprived conditions in cell model and the addition of AMP to cell lysates strengthened the AK2-BRAF interaction, suggesting that AK2 is involved in the regulation of BRAF activity in response to cell metabolic state. AMP facilitated the AK2–BRAF complex formation through binding to AK2. In a panel of HCC cell lines, AK2 expression was inversely correlated with ERK/MAPK activation, and AK2-knockdown or -knockout increased BRAF activity and promoted cell proliferation. Tumors from HCC patients showed low-AK2 protein expression and increased ERK activation compared to non-tumor tissues and the downregulation of AK2 was also verified by two microarray datasets (TCGA-LIHC and {"type":"entrez-geo","attrs":{"text":"GSE14520","term_id":"14520"}}GSE14520). Moreover, AK2/BRAF interaction was abrogated by RAS activation in in vitro assay and cell model and in a mouse model of HRAS^G12V-driven HCC, and AK2 ablation promoted tumor growth and BRAF activity. AK2 also bound to BRAF inhibitor-insensitive BRAF mutants and attenuated their activities. These findings indicate that AK2 monitoring cellular AMP levels is indeed a negative regulator of BRAF, linking the metabolic status to tumor growth.Subject terms: Tumour-suppressor proteins, Diagnostic markers, Extracellular signalling molecules