Search

3β,23,28-Trihydroxy-12-oleanene 3β-caffeate (compound 1) is a neuritogenic pentacyclic triterpenoid, which was isolated from Desmodium sambuensebased on a PC12 cell bioassay system. Compound 1induced neurite outgrowth dose-dependently in PC12 cells and primary cortical neurons at doses of 0.1, 0.3, and 1 μM. The potential target of compound 1was predicted by ChemProteoBase profiling, and the mechanism of action was investigated using specific inhibitors, Western blot analysis, and PC12 [rasN17] and PC12 [mtGAP] mutants. Compound 1activates endoplasmic reticulum (ER) as an ER stress inducer, and the maker of ER stress GRP78 protein significantly increased after treatment with compound 1. The inhibitors of tyrosine kinase B (TrkB), insulin-like growth factor 1 receptor (IGF-1R), mitogen-activated protein kinase (MEK), and phosphatidylinositol 3 kinase (PI3K) significantly decreased the neurite outgrowth induced by compound 1. Furthermore, the increases of phosphorylation of TrkB, IGF-1R, extracellular signal-regulated kinase (ERK), and protein kinase B (AKT) were observed in the compound 1-treated group, and the phosphorylation of these proteins was diminished by corresponding inhibitors. Thus, the compound-1-induced neuritogenic activity depended on the activation of slight ER stress and associated BDNF–TrkB/Ras/Raf/ERK and IGF-1R/PI3K/AKT signaling pathways in PC12 cells.

Three state‐of‐the‐art operational wave forecast model systemsare implemented on fine‐resolution grids for the Northwest Atlantic. These models are: (1) a composite model system consisting of SWAN implemented within WAVEWATCHIII®(the latter is hereafter, WW3) on a nested system of traditional structured grids, (2) an unstructured grid finite‐volume wave model denoted “SWAVE,” using SWAN physics, and (3) an unstructured grid finite element wind wave model denoted as “WWM” (for “wind wave model”) which uses WW3 physics. Models are implemented on grid systems that include relatively large domains to capture the wave energy generated by the storms, as well as including fine‐resolution nearshore regions of the southern Gulf of Maine with resolution on the scale of 25 m to simulate areas where inundation and coastal damage have occurred, due to the storms. Storm cases include three intense midlatitude cases: a spring Nor'easter storm in May 2005, the Patriot's Day storm in 2007, and the Boxing Day storm in 2010. Although these wave model systems have comparable overall properties in terms of their performance and skill, it is found that there are differences. Models that use more advanced physics, as presented in recent versions of WW3, tuned to regional characteristics, as in the Gulf of Maine and the Northwest Atlantic, can give enhanced results. Three modern wave forecast model systems are compared on fine‐resolution grids for the Northwest Atlantic: WAVEWATCHIII (WW3), SWAN, SWAVEThree intense midlatitude storm cases: a spring Nor'easter in May 2005, the Patriots Day storm in 2007, and the Boxing Day storm in 2010Models that use advanced physics, like ST4, tuned to regional characteristics for the Northwest Atlantic can give enhanced results

One new (1, SZMT01) and one known (2) anti-aging substances were isolated from Shenzhou honey peach fruit. Their structures were elucidated by spectroscopic methods and chemical derivatization, and the result reveals that these two compounds are sesquiterpene glucosides. SZMT01 possesses a new glycosylation with an ester linkage at one terminal in an acyclic sesquiterpenoid which is the end of a double bond at another terminal. Both compounds extend the replicative lifespan of K6001 yeast strain at doses of 7.5 and 25 μM. Then, to understand the action mechanism involved, we performed an anti-oxidative experiment on SZMT01. The result revealed that treatment with SZMT01 increased the survival rate of yeast under oxidative stress. Moreover, the lifespans of sod1and sod2mutant yeast strains with a K6001 background were not affected by SZMT01. These results demonstrate that anti-oxidative stress performs important roles in anti-aging effects of SZMT01.

A high‐resolution (up to 2 km), unstructured‐grid, fully ice‐sea coupled Arctic Ocean Finite‐Volume Community Ocean Model (AO‐FVCOM) was used to simulate the sea ice in the Arctic over the period 1978–2014. The spatial‐varying horizontal model resolution was designed to better resolve both topographic and baroclinic dynamics scales over the Arctic slope and narrow straits. The model‐simulated sea ice was in good agreement with available observed sea ice extent, concentration, drift velocity and thickness, not only in seasonal and interannual variability but also in spatial distribution. Compared with six other Arctic Ocean models (ECCO2, GSFC, INMOM, ORCA, NAME, and UW), the AO‐FVCOM‐simulated ice thickness showed a higher mean correlation coefficient of ∼0.63 and a smaller residual with observations. Model‐produced ice drift speed and direction errors varied with wind speed: the speed and direction errors increased and decreased as the wind speed increased, respectively. Efforts were made to examine the influences of parameterizations of air‐ice external and ice‐water interfacial stresses on the model‐produced bias. The ice drift direction was more sensitive to air‐ice drag coefficients and turning angles than the ice drift speed. Increasing or decreasing either 10% in water‐ice drag coefficient or 10° in water‐ice turning angle did not show a significant influence on the ice drift velocity simulation results although the sea ice drift speed was more sensitive to these two parameters than the sea ice drift direction. Using the COARE 4.0‐derived parameterization of air‐water drag coefficient for wind stress did not significantly influence the ice drift velocity simulation. The 37 year simulated sea ice was in good agreement with available observed sea ice extent, concentration, drift velocity, and thicknessIntermodel comparisons show that the high‐resolution AO‐FVCOM provided better performance in the ice thickness simulationSensitivity experiments were made to examine parameterizations of external and ice‐water interfacial stresses on model‐produced bias.

A high‐resolution (up to 2 km), unstructured‐grid, fully coupled Arctic sea ice‐ocean Finite‐Volume Community Ocean Model (AO‐FVCOM) was employed to simulate the flow and transport through the Canadian Arctic Archipelago (CAA) over the period 1978–2013. The model‐simulated CAA outflow flux was in reasonable agreement with the flux estimated based on measurements across Davis Strait, Nares Strait, Lancaster Sound, and Jones Sounds. The model was capable of reproducing the observed interannual variability in Davis Strait and Lancaster Sound. The simulated CAA outflow transport was highly correlated with the along‐strait and cross‐strait sea surface height (SSH) difference. Compared with the wind forcing, the sea level pressure (SLP) played a dominant role in establishing the SSH difference and the correlation of the CAA outflow with the cross‐strait SSH difference can be explained by a simple geostrophic balance. The change in the simulated CAA outflow transport through Davis Strait showed a negative correlation with the net flux through Fram Strait. This correlation was related to the variation of the spatial distribution and intensity of the slope current over the Beaufort Sea and Greenland shelves. The different basin‐scale surface forcings can increase the model uncertainty in the CAA outflow flux up to 15%. The daily adjustment of the model elevation to the satellite‐derived SSH in the North Atlantic region outside Fram Strait could produce a larger North Atlantic inflow through west Svalbard and weaken the outflow from the Arctic Ocean through east Greenland. A high‐resolution Arctic Ocean FVCOM is capable of simulating the CAA outflowThe basin‐scale sea level pressure is a major driver of the CAA outflowThe volume flux through Davis Strait is negatively correlated with the flux through Fram Strait

Tetradecyl 2,3-dihydroxybenzoate (ABG-001) is a lead compound derived from neuritogenic gentisides. In the present study, we investigated the mechanism by which ABG-001 induces neurite outgrowth in a rat adrenal pheochromocytoma cell line (PC12). Inhibitors of insulin-like growth factor 1 (IGF-1) receptor, phosphatidylinositol 3-kinase (PI3K), and extracellular signal-regulated kinase (ERK) 1/2 significantly decreased ABG-001–induced neurite outgrowth. Western blot analysis revealed that ABG-001 significantly induced phosphorylation of IGF-1 receptor, protein kinase B (Akt), ERK, and cAMP responsive element-binding protein (CREB). These effects were markedly reduced by addition of the corresponding inhibitors. We also found that ABG-001–induced neurite outgrowth was reduced by protein kinase C inhibitor as well as small-interfering RNA against the IGF-1 receptor. Furthermore, like ABG-001, IGF-1 also induced neurite outgrowth of PC12 cells, and low-dose nerve growth factor augmented the observed effects of ABG-001 on neurite outgrowth. These results suggest that ABG-001 targets the IGF-1 receptor and activates PI3K, mitogen-activated protein kinase, and their downstream signaling cascades to induce neurite outgrowth.

The Integrated Ocean Observing System Super‐regional Coastal Modeling Testbed had one objective to evaluate the capabilities of three unstructured‐grid fully current‐wave coupled ocean models (ADCIRC/SWAN, FVCOM/SWAVE, SELFE/WWM) to simulate extratropical storm‐induced inundation in the US northeast coastal region. Scituate Harbor (MA) was chosen as the extratropical storm testbed site, and model simulations were made for the 24–27 May 2005 and 17–20 April 2007 (“Patriot's Day Storm”) nor'easters. For the same unstructured mesh, meteorological forcing, and initial/boundary conditions, intermodel comparisons were made for tidal elevation, surface waves, sea surface elevation, coastal inundation, currents, and volume transport. All three models showed similar accuracy in tidal simulation and consistency in dynamic responses to storm winds in experiments conducted without and with wave‐current interaction. The three models also showed that wave‐current interaction could (1) change the current direction from the along‐shelf direction to the onshore direction over the northern shelf, enlarging the onshore water transport and (2) intensify an anticyclonic eddy in the harbor entrance and a cyclonic eddy in the harbor interior, which could increase the water transport toward the northern peninsula and the southern end and thus enhance flooding in those areas. The testbed intermodel comparisons suggest that major differences in the performance of the three models were caused primarily by (1) the inclusion of wave‐current interaction, due to the different discrete algorithms used to solve the three wave models and compute water‐current interaction, (2) the criterions used for the wet‐dry point treatment of the flooding/drying process simulation, and (3) bottom friction parameterizations. Evaluation of ADCIRC, FVCOM, SELFE for nor'easter coastal inundationWave‐current interaction important in forecasting nor'easter coastal inundation.Model performances depend on methods of current‐wave coupling

This study used a replicative lifespan assay of K6001 yeast to screen anti-aging food factors in commercial flavonoids. Hesperidin derived from the Citrusgenus extended the lifespan of yeast at doses of 5 and 10 μMas compared with the control group (p<0.01, p<0.01). Reactive oxygen species (ROS), real-time PCR (RT-PCR), and lifespan assays of uth1and skn7mutants with the K6001 background were used to study the anti-aging mechanisms in yeast. The results indicate that hesperidin significantly inhibits the ROS of yeast, and UTH1gene expression, and that SKN7gene are involved in hesperidin-mediated lifespan extension. Further, increases in the Sir2 homolog, SIRT1 activity, and SODgene expression were confirmed at doses of 5 (p<0.01) and 10 μM(p<0.05). This suggests that Sir2, UTH1genes, and ROS inhibition after administration of hesperidin have important roles in the anti-aging effects of yeast. However, the aglycon hesperetin did not exhibit anti-aging effects in yeast.

A new steroidal saponin was isolated from Ophiopogon japonicus. This saponin possesses a modification by 2-hydroxy-3-methylvalerylation of the hydroxyl group at C-4′ of the sugar, linked to C-1 of the aglycone. It exhibited significant neuritogenic activity for PC12 cells. The structure-activity relationship revealed the aglycone, rather than the sugar moieties and acylation, to be important for the neuritogenic activity.

The anti-aging effects of phloridzin on the yeast Saccharomyces cerevisiaewere investigated by employing a replicative lifespan assay of the K6001 yeast strain. After administrating phloridzin at doses of 3, 10, and 30 μM, the lifespan of the yeast was significantly prolonged in comparison with the untreated group (p<0.01, p<0.001). To determine the mechanism of action, anti-oxidative experiments and ROS assay were performed. Phloridzin improved the viability of the yeast dose-dependently under oxidative stress by 7.5 mMH2O2, and a low dose of phloridzin inhibited ROS of the yeast. Further, SOD1, SOD2, and Sir2gene expression was examined by reverse transcription-polymerase chain reaction (RT-PCR), and was found to be significantly increased. Finally, superoxide dismutase (SOD) and SIRT1 activity assays showed that phloridzin notably increased the activity of SOD and SIRT1. These results suggest that SODand Sir2have important roles in phloridzin-regulated lifespan extension of yeast, and potentially anti-aging effects for mammalian cells viaSIRT1.

Two new anti-aging compounds, ganodermasides C and D, were isolated and their structures elucidated. They are novel ergosterols possessing a 4,6,8(14),22-tetraene-3-one unit with unique hydroxylation at C-9. Both of them significantly extended the replicative lifespan of the K6001 yeast strain. Ganodermasides C and D regulated the expression of the gene for UTH1to prolong the replicative lifespan of yeast.

Bacillus mojavensisstrain RO-H-1 produces a posttranslationally modified hexapeptide, the ComXRO-H-1pheromone, that stimulates natural genetic competence controlled by quorum sensing. LC/ESI-MS analysis of partially purification of the ComXRO-H-1pheromone suggested a precise modification in its tryptophan residue. The corresponding ComXRO-H-1pheromone prepared by solid-phase synthesis was identical to the natural pheromone, and showed significant biological activity. These results indicated that the posttranslational modification of the ComXRO-H-1pheromone was geranylation on the tryptophan residue, resulting in the formation of a tricyclic structure. The ComXRO-H-1pheromone was immediately dehydrated by acid because of its extreme acid lability.

Two prostaglandins, PGA2and PGB2, were isolated from the Okinawan zoanthid, Palythoa kochii, during a search for paclitaxel-like neurite-degenerating compounds from natural sources using a cell-based assay method. In the presence of PGA2at 30 μM, the neuronal processes induced in PC12 cells by the nerve growth factor (NGF) degenerated over 24 h, whereas PGB2had no effect on the neuronal processes of PC12 cells. This activity of PGA2was similar to that of the microtubule-stabilizing agents, paclitaxel (Taxol®) and epothilone A, unlike the microtubule-depolymerizing agent, colchicine, which brought about quick neurite degeneration within 3 h. PGA2stimulated tubulin polymerization, although less potently than paclitaxel. An examination of structure-activity relationships across several PGs suggests that the cyclopentenone ring structure and the orientation of its dipolar moment played an important role in the paclitaxel-like neurite-degenerating activity. These results suggest that the cyclopentenone-type PGs can interact with microtubules to inhibit their function like paclitaxel.

The biosynthetic gene cluster for the polyene antifungal antibiotic, 2′-O-methylmyxalamide D, was cloned from myxobacterium Cystobacter fuscusAJ-13278. A sequence analysis of the 12.8-kb region in the gene cluster revealed the presence of two type I polyketide synthase genes, mmxBand mmxC. The involvement of these two genes in the biosynthesis of 2′-O-methylmyxalamide D was confirmed by a gene disruption experiments. In addition, an S-adenosylmethionine-dependent methyltransferase gene (mmxM) was found downstream of the gene cluster and demonstrated, by a gene disruption analysis, to be responsible for converting the known unmethylated precursor, myxalamide D, into 2′-O-methylmyxalamide D.

A bacterial artificial chromosome (BAC) library was constructed to isolate the biosynthetic gene cluster for the polyketide/peptide hybrid-type antibiotic cystothiazole A from the myxobacterium Cystobacter fuscusstrain AJ-13278. Sequence analysis of a 63.9 kb contiguous region that encompasses the biosynthetic gene cluster (cta) led to the identification of a polyketide synthase (PKS)/nonribosomal peptide synthetase (NRPS) hybrid gene cluster 32.1 kb in size, which consists of six open reading frames (ORFs), ctaBto ctaG, as well as downstream genes ctaJand ctaK(1.0 and 0.9 kb, respectively) responsible for the final biosynthetic steps. The genes ctaB, ctaE, and ctaFencode PKSs, the genes ctaCand ctaGencode NRPSs, and ctaDencodes an NRPS-PKS hybrid enzyme. Disruption of ctaDimpaired cystothiazole A production. Additionally, two downstream genes, ctaJand ctaK, which encode a nitrilase and an O-methyltransferase, respectively, must be responsible for the final methyl ester formation in the cystothiazole A biosynthesis.

Xestoquinone and related metabolites (the xestoquinone family) occur in marine sponges and are known to show a variety of biological activities. In this study, the first comprehensive evaluation of antifungal activity was performed for xestoquinone and nine natural and unnatural analogues in comparison with their cytotoxicity. The cytotoxicity against two human squamous cell carcinoma cell lines, A431 and Nakata, indicated that the terminal quinone structure of the polycyclic molecules was important (xestoquinone, etc.) and that the presence of a ketone group at C-3 of the opposite terminus dramatically diminished the activity (halenaquinone, etc.). In contrast, a ketone group at C-3 enhanced the antifungal activity against the plant pathogen, Phytophthora capsici, regardless of the presence of a quinone moiety. The cytotoxicity and antifungal activity of the xestoquinone family were negatively correlated with each other.

The novel cerebroside, termitomycesphin I (1), and two known cerebrosides (2and 3) were isolated from the edible mushroom, Termitomyces titanicus. The structures of 1–3 were determined and identified by interpreting the spectroscopic data.

Two new cerebrosides, termitomycesphins G and H, were isolated from the edible Chinese mushroom, Termitomyces albuminosus(Berk.) Herm., and exhibited neuritogenic activity against PC12 cells. Their structures and absolute stereochemistry were elucidated by spectroscopic methods and by a comparison of the specific rotation of the hydrogenated products from termitomycesphins H and C. These cerebrosides possessed a unique modification by a hydroxyl group at the middle of the long-chain base, like earlier congeners termitomycesphins A–F. Termitomycesphin G with a 16-carbon-chain fatty acid showed higher neuritogenic activity than that of termitomycesphin H with an 18-carbon-chain fatty acid. This effect was observed within the termitomycesphins, suggesting that the chain length of the fatty acyl moiety played a key role in the neuritogenic activity.

A search for neuritogenic compounds in Chinese herbs resulted in the isolation of two known substances, ostruthin and (-)-bornyl ferulate, from Notopterygium incisum(and/or N. forbesii). Both compounds induced comparable neurite-like structures in 20% of rat PC12 cells at 2 μg/ml, and showed cytotoxicity at concentrations higher than 3 μg/ml.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

For Abstract see ChemInform Abstract in Full Text.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.