Tobacco carcinogens induce Akt activation and lung carcinogenesis. We previously demonstrated that deguelin, a natural plant product, specifically inhibits the proliferation of premalignant and malignant human bronchial epithelial cells by blocking Akt activation. To evaluate the ability of deguelin to block tobacco carcinogen-induced lung tumorigenesis, we evaluated the in vivo effects of deguelin on Akt activation and lung tumorigenesis in transgenic mice in which Akt expression was induced by tamoxifen and in 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK)/benzo(a)pyrene (BaP)-treated A/J mice. Deguelin suppressed Akt activation in vivo, as measured by immunohistochemistry and immunoblotting, and statistically significantly reduced NNK/BaP-induced lung tumor multiplicity, volume, and load in A/J mice, as monitored by microcomputed tomography image analysis, with no detectable toxicity. These results indicate that deguelin warrants consideration as a chemopreventive agent for early-stage lung carcinogenesis in a clinical lung cancer chemoprevention trial.

Abstract. Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe datasets and a methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics and model estimates and their interpretation by a broad scientific community. We discuss changes compared to previous estimates consistency within and among components, alongside methodology and data limitations. CO2 emissions from fossil-fuel combustion and cement production (EFF) are based on energy statistics, while emissions from Land-Use Change (ELUC), including deforestation, are based on combined evidence from land-cover change data, fire activity in regions undergoing deforestation, and models. The global atmospheric CO2 concentration is measured directly and its rate of growth (GATM) is computed from the annual changes in concentration. The mean ocean CO2 sink (SOCEAN) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. The variability in SOCEAN is evaluated for the first time in this budget with data products based on surveys of ocean CO2 measurements. The global residual terrestrial CO2 sink (SLAND) is estimated by the difference of the other terms of the global carbon budget and compared to results of Dynamic Global Vegetation Models. All uncertainties are reported as ± 1 sigma, reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. For the last decade available (2003–2012), EFF was 8.6 ± 0.4 GtC yr−1, ELUC 0.8 ± 0.5 GtC yr−1, GATM 4.3 ± 0.1 GtC yr−1, SOCEAN 2.6 ± 0.5 GtC yr−1, and SLAND 2.6 ± 0.8 GtC yr−1. For year 2012 alone, EFF grew to 9.7 ± 0.5 GtC yr−1, 2.2% above 2011, reflecting a continued trend in these emissions; GATM was 5.2 ± 0.2 GtC yr−1, SOCEAN was 2.9 ± 0.5 GtC yr−1, and assuming and ELUC of 0.9 ± 0.5 GtC yr−1 (based on 2001–2010 average), SLAND was 2.5 ± 0.9 GtC yr−1. GATM was high in 2012 compared to the 2003–2012 average, almost entirely reflecting the high EFF. The global atmospheric CO2 concentration reached 392.52 ± 0.10 ppm on average over 2012. We estimate that EFF will increase by 2.1% (1.1–3.1%) to 9.9 ± 0.5 GtC in 2013, 61% above emissions in 1990, based on projections of World Gross Domestic Product and recent changes in the carbon intensity of the economy. With this projection, cumulative emissions of CO2 will reach about 550 ± 60 GtC for 1870–2013, 70% from EFF (390 ± 20 GtC) and 30% from ELUC (160 ± 55 GtC). This paper is intended to provide a baseline to keep track of annual carbon budgets in the future. All data presented here can be downloaded from the Carbon Dioxide Information Analysis Center (10.3334/CDIAC/GCP_2013_v1.1).

Numerous numbers of biologically active agents have been identified for their diverse therapeutic functions. Detailed investigations of phytochemicals for antiviral activities have assumed greater importance in the last few decades. A wide variety of active phytochemicals, including the flavonoids, terpenoids, organosulfur compounds, limonoids, lignans, sulphides, polyphenolics, coumarins, saponins, chlorophyllins, furyl compounds, alkaloids, polyines, thiophenes, proteins and peptides have been found to have therapeutic applications against different genetically and functionally diverse viruses. The antiviral mechanism of these agents may be explained on basis of their antioxidant activities, scavenging capacities, inhibiting DNA, RNA synthesis, inhibition of the viral entry, or inhibiting the viral reproduction etc. Large number candidate substances such as phytochemicals and their synthetic derivatives have been identified by a combination of in vitro and in vivo studies in different biological assays. In this article we have made attempts to extensively review and provide comprehensive description of different phyto-antiviral agents. We have examined the recent developments in the field of plant derived antiviral agents. The major advances in the field of viral interactions in various biological assays have been summarized. In addition sources of origin, major viral studies mechanistic action and phase trials of various phytoantiviral agents have been included in the review.

For the discovery of new cancer chemopreventive agents, we have studied the potential of plant extracts to inhibit phorbol ester-induced ornithine decarboxylase (ODC) activity in cell culture. Four active rotenoids were obtained from the African plant Mundulea sericea (Leguminosae). These isolates were highly potent when evaluated for inhibition of chemically induced preneoplastic lesions in mammary organ culture and inhibition of papillomas in the two-stage mouse skin model, and they appear to function by a unique mechanism at the level of ODC messenger RNA expression. Based on our findings, rotenoids can be regarded as promising new chemopreventive or anticancer agents.

The synthetic utility of organohypervalent iodine reagents will be illustrated by their use in the alpha-hydroxydimethylacetal formation reaction from enolizable ketones, alpha-hydroxylation, alpha-tosyloxylation, alpha-alkoxylation and arylation of ketones, carbon-carbon bond formation, and intramolecular cyclopropanation using iodonium ylides. The uses of these reagents in the Hunsdiecker reaction of carboxylic acids and Hofmann rearrangement of carboxamides is presented. Specific transformation in the cubane series are discussed. The syntheses of a wide range of heterocycle structures are also presented. A unifying pathway for virtually all these diverse reactions is offered; the central features being initial attack at the iodonium center, ligand coupling, with reductive elimination of iodobenzene to yield the product.

Cellular α-glucosidases I and II are enzymes that sequentially trim the three terminal glucoses in the N-linked oligosaccharides of viral envelope glycoproteins. This process is essential for the proper folding of viral glycoproteins and subsequent assembly of many enveloped viruses, including dengue virus (DENV). Imino sugars are substrate mimics of α-glucosidases I and II. In this report, we show that two oxygenated alkyl imino sugar derivatives, CM-9-78 and CM-10-18, are potent inhibitors of both α-glucosidases I and II in vitro and in treated animals, and efficiently inhibit DENV infection of cultured human cells. Pharmacokinetic studies reveal that both compounds are well tolerated at doses up to 100mg/kg in rats and have favorable pharmacokinetic properties and bioavailability in mice. Moreover, we showed that oral administration of either CM-9-78 or CM-10-18 reduces the peak viremia of DENV in mice. Interestingly, while treatment of DENV infected mice with ribavirin alone did not reduce the viremia, combination therapy of ribavirin with sub-effective dose of CM-10-18 demonstrated a significantly enhanced antiviral activity, as indicated by a profound reduction of the viremia. Our findings thus suggest that combination therapy of two broad-spectrum antiviral agents may provide a practically useful approach for the treatment of DENV infection.

Abstract. Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe datasets and a methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics and model estimates and their interpretation by a broad scientific community. We discuss changes compared to previous estimates, consistency within and among components, alongside methodology and data limitations. CO2 emissions from fossil fuel combustion and cement production (EFF) are based on energy statistics and cement production data, respectively, while emissions from Land-Use Change (ELUC), mainly deforestation, are based on combined evidence from land-cover change data, fire activity associated with deforestation, and models. The global atmospheric CO2 concentration is measured directly and its rate of growth (GATM) is computed from the annual changes in concentration. The mean ocean CO2 sink (SOCEAN) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. The variability in SOCEAN is evaluated with data products based on surveys of ocean CO2 measurements. The global residual terrestrial CO2 sink (SLAND) is estimated by the difference of the other terms of the global carbon budget and compared to results of independent Dynamic Global Vegetation Models forced by observed climate, CO2 and land cover change (some including nitrogen-carbon interactions). We compare the variability and mean land and ocean fluxes to estimates from three atmospheric inverse methods for three broad latitude bands. All uncertainties are reported as ±1σ, reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. For the last decade available (2004–2013), EFF was 8.9 ± 0.4 GtC yr−1, ELUC 0.9 ± 0.5 GtC yr−1, GATM 4.3 ± 0.1 GtC yr−1, SOCEAN 2.6 ± 0.5 GtC yr−1, and SLAND 2.9 ± 0.8 GtC yr−1. For year 2013 alone, EFF grew to 9.9 ± 0.5 GtC yr−1, 2.3% above 2012, contining the growth trend in these emissions. ELUC was 0.9 ± 0.5 GtC yr−1, GATM was 5.4 ± 0.2 GtC yr−1, SOCEAN was 2.9 ± 0.5 GtC yr−1 and SLAND was 2.5 ± 0.9 GtC yr−1. GATM was high in 2013 reflecting a steady increase in EFF and smaller and opposite changes between SOCEAN and SLAND compared to the past decade (2004–2013). The global atmospheric CO2 concentration reached 395.31 ± 0.10 ppm averaged over 2013. We estimate that EFF will increase by 2.5% (1.3–3.5%) to 10.1 ± 0.6 GtC in 2014 (37.0 ± 2.2 GtCO2 yr−1), 65% above emissions in 1990, based on projections of World Gross Domestic Product and recent changes in the carbon intensity of the economy. From this projection of EFF and assumed constant ELUC for 2014, cumulative emissions of CO2 will reach about 545 ± 55 GtC (2000 ± 200 GtCO2) for 1870–2014, about 75% from EFF and 25% from ELUC. This paper documents changes in the methods and datasets used in this new carbon budget compared with previous publications of this living dataset (Le Quéré et al., 2013, 2014). All observations presented here can be downloaded from the Carbon Dioxide Information Analysis Center (doi:10.3334/CDIAC/GCP_2014). Italic font highlights significant methodological changes and results compared to the Le Quéré et al. (2014) manuscript that accompanies the previous version of this living data.

Brassinin [3-(S-methyldithiocarbamoyl)aminomethyl indole], a phytoalexin first identified as a constituent of cabbage, was synthesized and evaluated for cancer chemopreventive activity. Dose-dependent inhibition of 7,12-dimethylbenz[a]anthracene (DMBA)-induced preneoplastic lesion formation was observed with mouse mammary glands in organ culture, as was dose-dependent inhibition of DMBA-induced mouse skin tumors that were promoted by treatment with 12-O-tetradecanoylphorbol-13-acetate. Cyclobrassinin is a biologically derived product of the oxidative cyclization of brassinin, and was as active as the parent compound in inhibiting the formation of preneoplastic mammary lesions in culture; however, 2-methylbrassinin was not significantly active in this process. Therefore, oxidative cyclization may be an effective metabolic activation step. As judged by these tumor inhibition studies in conjunction with potential to induce phase II enzymes in mice or cell culture, brassinin may be effective as a chemopreventive agent during both the initiation and promotion phases of carcinogenesis. This is the first report documenting the chemopreventive potential of structurally novel indole-based phytoalexins that are naturally occurring in cruciferous vegetables, and the synthetic route described herein has proven amenable for scale-up production. The bifunctional structural nature of brassinin, bearing both an indole nucleus and a dithiocarbamoyl-aminomethyl moiety, is notably similar to the individual structural elements of other known chemopreventive agents such as indole-3-carbinol or benzylisothiocyanate. The favorable biological activity demonstrated by the compound may originate from the presence of these two moieties.