ASH2L Regulates Ubiquitylation Signaling to MLL: trans-Regulation of H3 K4 Methylation in Higher Eukaryotes

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Highlights? ASH2L WH motif is important for trans-regulation of H3 K4 methylation by H2Bub ? Ub stimulates MLL activity in trans, in contrast to DOT1L regulation by H2Bub ? H2Bub enhances MLL, but not MLL3, methyltransferase activity ? H2Aub directly represses MLL methyltransferase activity     

Hopeahainol A attenuates memory deficits by targeting β‐amyloid in APP/PS1 transgenic mice

Increasing evidence demonstrates that amyloid beta (Aβ) elicits mitochondrial dysfunction and oxidative stress, which contributes to the pathogenesis of Alzheimer's disease (AD). Identification of the molecules targeting Aβ is thus of particular significance in the treatment of AD. Hopeahainol A (HopA), a polyphenol with a novel skeleton obtained from Hopea hainanensis, is potentially acetylcholinesterase‐inhibitory and anti‐oxidative in H₂O₂‐treated PC12 cells. In this study, we reported that HopA might bind to Aβ_1–42 directly and inhibit the Aβ_1–42 aggregation using a combination of molecular dynamics simulation, binding assay, transmission electron microscopic analysis and staining technique. We also demonstrated that HopA decreased the interaction between Aβ_1–42 and Aβ‐binding alcohol dehydrogenase, which in turn reduced mitochondrial dysfunction and oxidative stress in vivo and in vitro. In addition, HopA was able to rescue the long‐term potentiation induction by protecting synaptic function and attenuate memory deficits in APP/PS1 mice. Our data suggest that HopA might be a promising drug for therapeutic intervention in AD.     

CdS nanoparticles‐ enhanced chemiluminescence and determination of baicalin in pharmaceutical preparations

CdS nanoparticles (CdS NPs) of different sizes were synthesized by the citrate reduction method. It was found that CdS NPs could enhance the chemiluminescence (CL) of the luminol‐potassium ferricyanide system and baicalin could inhibit CdS NPs‐enhanced luminol‐potassium ferricyanide CL signals in alkaline solution. Based on this inhibition, a flow‐injection CL method was established for determination of baicalin in pharmaceutical preparations and human urine samples. Under optimized conditions, the linear range for determination of baicalin was 5.0 x 10^?6 to 1.0 x 10^?3 g/L. The detection limit at a signal‐to‐noise ratio of 3 was 1.7 x 10 ^?6 g/L. CL spectra, UV‐visible spectra and transmission electron microscopy (TEM) were used to investigate the CL mechanism. The method described is simple, selective and obviates the need of extensive sample pretreatment. Copyright © 2012 John Wiley & Sons, Ltd.     

Revision of the subfamily Opiinae (Hymenoptera,Braconidae) from Hunan (China), including thirty-six new species and two new genera

The species of the subfamily Opiinae (Hymenoptera: Braconidae) from Hunan (Oriental China) are revised and illustrated. Thirty-six new species are described: Apodesmia bruniclypealis Li & van Achterberg, sp. n., Apodesmia melliclypealis Li & van Achterberg, sp. n., Areotetes albiferus Li & van Achterberg, sp. n., Areotetes carinuliferus Li & van Achterberg, sp. n., Areotetes striatiferus Li & van Achterberg, sp. n., Coleopioides diversinotum Li & van Achterberg, sp. n., Coleopioides postpectalis Li & van Achterberg, sp. n., Fopius dorsopiferus Li, van Achterberg & Tan, sp. n., Indiopius chenae Li & van Achterberg, sp. n., Opiognathus aulaciferus Li & van Achterberg, sp. n., Opiognathus brevibasalis Li & van Achterberg, sp. n., Opius crenuliferus Li & van Achterberg, sp. n., Opius malarator Li, van Achterberg & Tan, sp. n., Opius monilipalpis Li & van Achterberg, sp. n., Opius pachymerus Li & van Achterberg, sp. n., Opius songi Li & van Achterberg, sp. n., Opius youi Li & van Achterberg, sp. n., Opius zengi Li & van Achterberg, sp. n., Phaedrotoma acuticlypeata Li & van Achterberg, sp. n., Phaedrotoma angiclypeata Li & van Achterberg, sp. n., Phaedrotoma antenervalis Li & van Achterberg, sp. n., Phaedrotoma depressiclypealis Li & van Achterberg, sp. n., Phaedrotoma flavisoma Li & van Achterberg, sp. n., Phaedrotoma nigrisoma Li & van Achterberg, sp. n., Phaedrotoma protuberator Li & van Achterberg, sp. n., Phaedrotoma rugulifera Li & van Achterberg, sp. n., Li & van Achterberg,Phaedrotoma striatinota Li & van Achterberg, sp. n., Phaedrotoma vermiculifera Li & van Achterberg, sp. n., Rhogadopsis latipennis Li & van Achterberg, sp. n., Rhogadopsis longicaudifera Li & van Achterberg, sp. n., Rhogadopsis maculosa Li, van Achterberg & Tan, sp. n., Rhogadopsis obliqua Li & van Achterberg, sp. n., Rhogadopsis sculpturator Li & van Achterberg, sp. n., Utetes longicarinatus Li & van Achterberg, sp. n. and Xynobius notauliferus Li & van Achterberg, sp. n. Areotetes van Achterberg & Li, gen. n. (type species: Areotetes carinuliferus sp. n.) and Coleopioides van Achterberg & Li, gen. n. (type species: Coleopioides postpectalis sp. n. are described. All species are illustrated and keyed. In total 30 species of Opiinae are sequenced and the cladograms are presented. Neopius Gahan, 1917, Opiognathus Fischer, 1972, Opiostomus Fischer, 1972, and Rhogadopsis Brèthes, 1913, are treated as a valid genera based on molecular and morphological differences. Opius vittata Chen & Weng, 2005 (not Opius vittatus Ruschka, 1915), Opius ambiguus Weng & Chen, 2005 (not Wesmael, 1835) and Opius mitis Chen & Weng, 2005 (not Fischer, 1963) are primary homonymsandarerenamed into Phaedrotoma depressa Li & van Achterberg, nom. n., Opius cheni Li & van Achterberg, nom. n. andOpius wengi Li & van Achterberg, nom. n., respectively. Phaedrotoma terga (Chen & Weng, 2005) comb. n.,Diachasmimorpha longicaudata (Ashmead, 1905) and Biosteres pavitita Chen & Weng, 2005, are reported new for Hunan, Opiostomus aureliae (Fischer, 1957) comb. n. is new for China and Hunan; Xynobius maculipennis(Enderlein, 1912) comb. n. is new for Hunan and continental China and Rhogadopsis longuria (Chen & Weng, 2005) comb. n. is new for Hunan. The following new combinations are given: Apodesmia puncta (Weng & Chen, 2005) comb. n., Apodesmia tracta (Weng & Chen, 2005) comb. n., Areotetes laevigatus (Weng & Chen, 2005) comb. n., Phaedrotoma dimidia (Chen & Weng, 2005) comb. n., Phaedrotoma improcera (Weng & Chen, 2005) comb. n., Phaedrotoma amputata (Weng & Chen, 2005) comb. n., Phaedrotoma larga (Weng & Chen, 2005) comb. n., Phaedrotoma osculas (Weng & Chen, 2005) comb. n., Phaedrotoma postuma (Chen & Weng, 2005) comb. n., Phaedrotoma rugulosa (Chen & Weng, 2005) comb. n., Phaedrotoma tabularis (Weng & Chen, 2005) comb. n., Rhogadopsis apii (Chen & Weng, 2005) comb. n., Rhogadopsis dimidia (Chen & Weng, 2005) comb. n., Rhogadopsis diutia (Chen & Weng, 2005) comb. n., Rhogadopsis longuria (Chen & Weng, 2005) comb. n., Rhogadopsis pratellae(Weng & Chen, 2005) comb. n., Rhogadopsis pratensis (Weng & Chen, 2005) comb. n., Rhogadopsis sculpta (Chen & Weng, 2005) comb. n., Rhogadopsis sulcifer (Fischer, 1975) comb. n., Rhogadopsis tabidula(Weng & Chen, 2005) comb. n., Xynobius complexus (Weng & Chen, 2005) comb. n., Xynobius indagatrix (Weng & Chen, 2005) comb. n., Xynobius multiarculatus (Chen & Weng, 2005) comb. n.The following (sub)genera are synonymised: Snoflakopius Fischer, 1972, Jucundopius Fischer, 1984, Opiotenes Fischer, 1998, and Oetztalotenes Fischer, 1998, with Opiostomus Fischer, 1971; Xynobiotenes Fischer, 1998, with Xynobius Foerster, 1862; Allotypus Foerster, 1862, Lemnaphilopius Fischer, 1972, Agnopius Fischer, 1982, and Cryptognathopius Fischer, 1984, with Apodesmia Foerster, 1862; Nosopoea Foerster, 1862, Tolbia Cameron, 1907, Brachycentrus Szépligeti, 1907, Baeocentrum Schulz, 1911, Hexaulax Cameron, 1910, Coeloreuteus Roman, 1910, Neodiospilus Szépligeti, 1911, Euopius Fischer, 1967, Gerius Fischer, 1972, Grimnirus Fischer, 1972, Hoenirus Fischer, 1972, Mimirus Fischer, 1972, Gastrosema Fischer, 1972, Merotrachys Fischer, 1972, Phlebosema Fischer, 1972, Neoephedrus Samanta, Tamili, Saha & Raychaudhuri, 1983, Adontopius Fischer, 1984, Kainopaeopius Fischer, 1986, Millenniopius Fischer, 1996, and Neotropopius Fischer, 1999, with Phaedrotoma Foerster, 1862.     

In vitro assembly of minicellulosomes with two scaffoldins on the yeast cell surface for cellulose saccharification and bioethanol production

The present paper reports in vitro strategies for assembly of minicellulosomes with two miniscaffoldins on the Saccharomyces cerevisiae cell surface. It was carried out through incubation of the yeast cells displaying scaffoldins with Escherichia coli lysates containing recombinant cellulases, or using a four-population yeast consortium. The results showed that the display level of miniscaffoldin II was distinctly increased by moving the cellulases production into E. coli or other yeast cells, indicating that the metabolic burden of the yeast host was decreased. The yeast consortium did not show any cellulolytic activity, while the E. coli lysates-treated yeast, whose anchoring miniscaffoldin length was optimized, was able to produce ～1138 mg/L ethanol from microcrystalline cellulose within 4 days. We also confirmed that the yeast-associated minicellulosome moreover showed both higher thermal stability and lower protease accessibility than free minicellulosome. This research promotes the application of S. cerevisiae as a consolidated bioprocessing (CBP) microorganism in cellulosic bioethanol production.     

Novel off-target effect of tamoxifen — Inhibition of acid ceramidase activity in cancer cells

Acid ceramidase (AC), EC 3.5.1.23, a lysosomal enzyme, catalyzes the hydrolysis of ceramide to constituent sphingoid base, sphingosine, and fatty acid. Because AC regulates the levels of pro-apoptotic ceramide and mitogenic sphingosine-1-phosphate, it is considered an apt target in cancer therapy. The present study reveals, for the first time, that the prominent antiestrogen, tamoxifen, is a pan-effective AC inhibitor in the low, single digit micromolar range, as demonstrated in a wide spectrum of cancer cell types, prostate, pancreatic, colorectal, and breast. Prostate cancer cells were chosen for the detailed investigations. Treatment of intact PC-3 cells with tamoxifen produced time- and dose-dependent inhibition of AC activity. Tamoxifen did not impact cell viability nor did it inhibit AC activity in cell-free assays. In pursuit of mechanism of action, we demonstrate that tamoxifen induced time-, as early as 5 min, and dose-dependent, as low as 5 μM, increases in lysosomal membrane permeability (LMP), and time- and dose-dependent downregulation of AC protein expression. Assessing various protease inhibitors revealed that a cathepsin B inhibitor blocked tamoxifen-elicited downregulation of AC protein; however, this action failed to restore AC activity unless assayed in a cell-free system at pH 4.5. In addition, pretreatment with tamoxifen inhibited PC-3 cell migration. Toremifene, an antiestrogen structurally similar to tamoxifen, was also a potent inhibitor of AC activity. This study reveals a new, off-target action of tamoxifen that may be of benefit to enhance anticancer therapies that either incorporate ceramide or target ceramide metabolism.     

Novel Systems for Dynamically Assessing Insulin Action in Live Cells Reveals Heterogeneity in the Insulin Response

Regulated GLUT4 trafficking is a key action of insulin. Quantitative stepwise analysis of this process provides a powerful tool for pinpointing regulatory nodes that contribute to insulin regulation and insulin resistance. We describe a novel GLUT4 construct and workflow for the streamlined dissection of GLUT4 trafficking; from simple high throughput screens to high resolution analyses of individual vesicles. We reveal single cell heterogeneity in insulin action highlighting the utility of this approach – each cell displayed a unique and highly reproducible insulin response, implying that each cell is hard‐wired to produce a specific output in response to a given stimulus. These data highlight that the response of a cell population to insulin is underpinned by extensive heterogeneity at the single cell level. This heterogeneity is pre‐programmed within each cell and is not the result of intracellular stochastic events.     

Deficiency in Clonogenic Endometrial Mesenchymal Stem Cells in Obese Women with Reproductive Failure – a Pilot Study

Objectives

The mechanisms of obesity associated reproductive complications remain poorly understood. Endometrial mesenchymal stem-cells are critical for cyclic renewal and uterine function. Recently, W5C5⁺ cells, with high clonogenicity, capable of producing endometrial stroma in vivo, have been described. We sought to investigate the abundance and cloning efficiency of W5C5⁺ and W5C5⁻ endometrial cells in relation to Body Mass Index, age and reproductive outcome.

Design

W5C5⁺ and W5C5⁻ cells were purified from mid-luteal endometrial biopsies (n = 54) by magnetic bead separation and subjected to in vitro colony-forming assays.

Results

First trimester pregnancy losses were significantly higher in obese subjects (n = 12) compared to overweight (n = 20) and subjects with normal Body Mass Index (n = 22) (P<0.05, P<0.01, respectively). W5C5⁺ cells (%) were significantly lower in obese subjects compared to subjects with normal Body Mass Index (P<0.05). W5C5⁺ cloning efficiency was significantly lower in obese subjects compared to overweight and subjects with normal Body Mass Index (P<0.05, respectively). W5C5⁻ cloning efficiency was significantly lower in obese subjects compared to subjects with normal Body Mass Index (P<0.05). Body Mass Index was significantly negatively correlated with W5C5⁺ cloning efficiency and W5C5⁻ cloning efficiency (P<0.01, respectively), and positively correlated with first trimester loss (P<0.01). We found no significant results with age (P>0.05).

Conclusions

Our observations suggest that the regenerative capacity and plasticity of the endometrium of obese women is suboptimal, which in turn may account for the increased risk of reproductive complications associated with obesity.