Indigenous plants promote insect biodiversity in urban greenspaces

The contribution of urban greenspaces to support biodiversity and provide benefits for people is increasingly recognized. However, ongoing management practices favor vegetation oversimplification, often limiting greenspaces to lawns and tree canopy rather than multi-layered vegetation that includes under- and midstorey, and the use of nonnative species. These practices hinder the potential of greenspaces to sustain indigenous biodiversity, particularly for taxa like insects that rely on plants for food and habitat. Yet, little is known about which plant species may maximize positive outcomes for taxonomically and functionally diverse insect communities in greenspaces. Additionally, while cities are expected to experience high rates of introductions, quantitative assessments of the relative occupancy of indigenous vs. introduced insect species in greenspace are rare, hindering understanding of how management may promote indigenous biodiversity while limiting the establishment of introduced insects. Using a hierarchically replicated study design across 15 public parks, we recorded occurrence data from 552 insect species on 133 plant species, differing in planting design element (lawn, midstorey, and tree canopy), midstorey growth form (forbs, lilioids, graminoids, and shrubs) and origin (nonnative, native, and indigenous), to assess (1) the relative contributions of indigenous and introduced insect species and (2) which plant species sustained the highest number of indigenous insects. We found that the insect community was overwhelmingly composed of indigenous rather than introduced species. Our findings further highlight the core role of multi-layered vegetation in sustaining high insect biodiversity in urban areas, with indigenous midstorey and canopy representing key elements to maintain rich and functionally diverse indigenous insect communities. Intriguingly, graminoids supported the highest indigenous insect richness across all studied growth forms by plant origin groups. Our work highlights the opportunity presented by indigenous understory and midstorey plants, particularly indigenous graminoids, in our study area to promote indigenous insect biodiversity in urban greenspaces. Our study provides a blueprint and stimulus for architects, engineers, developers, designers, and planners to incorporate into their practice plant species palettes that foster a larger presence of indigenous over regionally native or nonnative plant species, while incorporating a broader mixture of midstorey growth forms

The primary kinetic hydrogen isotope effect in the deprotonation of a nitroalkane by an intramolecular carboxylate group

The rates of racemization of optically active nitropentanoic acid, and 4-deuteronitropentanoic have been compared. The rate ratio (kie) is k H/kD = 5.68(±0.17) at 31°C, in good agreement with that determined by Lewis et al. for base-catalysed deprotonations using iodine-trapping methods. In a more detailed study, optically active 4-nitro-4-phenylbutanoic acid (NPBA) has also been prepared and rates of racemization measured in dimethox-yethane:water. With less than a full equivalent of triethylamine, rates are proportional to [Et3N:]/[NPBA] . For 1 <[Et3N:]/[NPBA] <2, rates are independent of the ratio, consistent with racemization being dominated by deprotonation of the nitroalkane by the intramolecular carboxylate group. The solvent isotope effect is kH2O/kD2O = 0.73(±0.04) and rates of exchange with D2O are equal to rates of racemization. Comparison with rates of racemization by acetate of the methyl ester yielded an effective molarity (EM = 13.7) for the intramolecular carboxylate. The kie for racemizations of NPBA and 4-deutero-NPBA is kH/kD = 5.78 at 25°C, and for 20 <T <50°C, EaD - EaH = 5.5(±0.1) and AH/AD = 0.63(±1.03). For the acetate catalysed racemizations of the methyl ester, 25°C, k H/kD = 7.43 with EaD - E aH = 5.2 kJ mol-1 and AH/A D = 1.08. In neither case is there any indication of a major tunnelling contribution on the isotopic rate ratio. A hitherto unrecognised mode of decomposition of nitronic acids, involving direct reaction with dissolved oxygen, has been identified. Copyright © 2008 John Wiley & Sons, Ltd

Abstract 2206: Development and characterization of an injectable copper clioquinol formulation: repurposing of a topical antifungal for treatment of cancer

Abstract Clioquinol is an FDA approved antifungal and antiprotozoal drug that has recently garnered attention for its anti-cancer activities. In vitro studies with CQ activity suggest that its mechanism of activity may be dependent its ability to bind and transport copper. CQ binds copper to form a stable dimeric complex (2 mol CQ:1 mol Cu ((CuCQ2)). Although therapeutically interesting, CuCQ2 is virtually insoluble in aqueous solutions and therefore it has been difficult to develop formulations suitable for administration. To address this, a liposomal CuCQ2 formulation was developed and characterized for maximum tolerated dose, pharmacokinetics and efficacy in xenograft models. Liposomes (∼100nm) composed of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and cholesterol (CHOL) (55:45 molar ratio) were prepared to contain 300 mM CuSO4. CQ is added to the outside of these pre-formed liposomes; at the appropriate incubation temperature CQ crosses the liposomal membrane where it can interact with the encapsulated Cu to form the insoluble CuCQ2 complex which becomes trapped. The maximum tolerated dose of the resultant formulation was determined in CD-1 mice. The pharmacokinetics of the formulation (liposomal lipid, CQ and Cu) were measured following intravenous administration at a well tolerated dose. Efficacy was measured in two cancer models (sc U251 glioblastoma and i.p A2780 ovarian). The maximum tolerated dose of liposomal CuCQ2 was 30 mg/kg when administered i.v (q2d for two weeks) and 15 mg/kg when administered i.p (QD for two weeks). Pharmacokinetics studies with liposomalCuCQ2 administered iv at 30 mg/kg indicated an terminal elimination half-life (t1/2) of 5.4 hr and an AUC of 994 ug•hr/mL. Results demonstrate that the CuCQ2 complex remains intact upon injection. When used to treat animals bearing established sc U251 glioblastoma tumors showed 30% smaller tumours than those treated with vehicle alone. The activity of liposomal CuCQ2 in the A2780 intraperitoneal cancer model will be presented. This work describes, for the first time, a novel injectable formulation of CuCQ2; this formulation is active against established xenograft models. The activity of this formulation will now be assessed in the context of copper-dependent inhibition of NFκB signalling. Citation Format: Moe Wehbe, Malathi Anantha, Ian Backstrom, Armaan Malhotra, Katarina Edwards, Marcel Bally. Development and characterization of an injectable copper clioquinol formulation: repurposing of a topical antifungal for treatment of cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2206.</jats:p

Were glacial iceberg surges in the North Atlantic triggered by climatic warming?

High-resolution physical, mineralogical, sedimentological and micropalaeontological studies were carried out on North Atlantic cores from the Reykjanes Ridge at 59degreesN and from the region southwest of the Faeroe Islands. All core sites are situated along the pathway of Iceland-Scotland Overflow Water (ISOW) and the various parameters measured display similar features. Previously identified carbonate oscillations [Keigwin and Jones (1994) J. Geophys. Res., 99, 12397-12410] in the time span back to the Marine Isotope Stage 5-4 transition and Late Glacial lithic events [Bond and Lotti (1995) Science, 267, 1005-1010], such as the Heinrich ice-rafting events, are all represented in the core records. Long-term trends and higher-frequency changes in ISOW intensity were reconstructed on the basis of various independent proxy records. The long-term trends in circulation match theoretical orbitally forced insolation changes. Our observed links between ice-rafted detritus (IRD) input, variations in sea surface temperature (SST) and circulation at greater depth point to the need to re-examine the origin of IRD events. We suggest that these events may have been triggered by enhanced, partly sub-surface, heat transport to the-north. Enhanced northward heat transport may have caused bottom melting of floating outlet glaciers and ice shelves, leading to increased iceberg discharge and ice sheet destabilization. This discharge. resulted in lower SST's and a lower temperature over Greenland. Thus, as shown by our records, this scenario implies a temporary de-coupling of surface processes and circulation at greater depth. A key feature is the occurrence of a-saw-tooth pattern in the marine data, which is similar to the Greenland ice core records. Moreover, the 'warming' theory of IRD events would explain the observed 'out-of-phase' relationship between the Greenland and Antarctic ice-core records and also the rapid establishment of higher temperatures over Greenland immediately after the cold phases (stadials) of the Dansgaard-Oeschger cycles

Nanoscale Reaction Vessels Designed for Synthesis of Copper-Drug Complexes Suitable for Preclinical Development

The development of copper-drug complexes (CDCs) is hindered due to their very poor aqueous solubility. Diethyldithiocarbamate (DDC) is the primary metabolite of disulfiram, an approved drug for alcoholism that is being repurposed for cancer. The anticancer activity of DDC is dependent on complexation with copper to form copper bis-diethyldithiocarbamate (Cu(DDC)(2)), a highly insoluble complex that has not been possible to develop for indications requiring parenteral administration. We have resolved this issue by synthesizing Cu(DDC)(2) inside liposomes. DDC crosses the liposomal lipid bilayer, reacting with the entrapped copper; a reaction that can be observed through a colour change as the solution goes from a light blue to dark brown. This method is successfully applied to other CDCs including the anti-parasitic drug clioquinol, the natural product quercetin and the novel targeted agent CX-5461. Our method provides a simple, transformative solution enabling, for the first time, the development of CDCs as viable candidate anticancer drugs; drugs that would represent a brand new class of therapeutics for cancer patients

Proportional abundance (%) of commercial and commercial-related MLGs in late-stage fermentations from the winery and OG vineyard.

Proportional abundance (%) of commercial and commercial-related MLGs in late-stage fermentations from the winery and OG vineyard.</p

Abstract 3792: PAPSS1 (3’-phosphoadenosine 5’-phosphosulfate synthase 1) inhibition sensitizes non-small cell lung cancer to cisplatin treatment <i>in vivo</i>

Abstract We previously reported that 3’-phosphoadenosine-5’-phosphosulfate (PAPS) synthase 1 (PAPSS1), an enzyme that synthesizes the biologically active form of sulfate (PAPS) for all sulfation reactions, is a novel therapeutic target that when suppressed enhances the activity of multiple DNA damaging agents in NSCLC cells. PAPSS1 was the lead hit in a synthetic lethal screen completed using chemotherapy-naive NSCLC cells exposed to the IC10 of cisplatin (CDDP). PAPSS1 silencing was more effective in potentiating CDDP activity than our positive control (BRACA2). Here, we evaluated PAPSS1 as a CDDP-sensitizing target in three different model systems: 3D spheroids, zebrafish xenografts, and a mouse xenograft model. siRNA-transfected A549 cells were seeded in round bottom ultra-low attachment plates for spheroid formation. Spheroids were formed over a period of three days and then treated with CDDP. The spheroids were imaged using the IncuCyte ZOOM® Live Cell Imaging system every 3 hours for 8 days to monitor changes in spheroid size. To evaluate PAPSS1 in zebrafish, transfected A549 cells were microinjected into the yolk sack of zebrafish embryos and then maintained in CDDP-containing media for 48 hours. The human cells were harvested from 20 fish per treatment group and counted to determine the change in cell number as a measure of tumor growth in vivo. For mouse studies, RAG2M mice were inoculated subcutaneously with 5×106 parental, non-targeting shRNA, or shPAPSS1-expressing A549 cells. The mice were treated 7 days later with 3 mg/kg CDDP (IV, Q4Dx3). Tumor size was measured using an electronic caliper and tumor volumes were calculated using the equation (lxw2)/2. PAPSS1-silenced cells formed spheroids of comparable size as the scramble control. CDDP (12.5μM) was effective against both control and PAPSS1-silenced spheroids with a reduction of 31% and 46% in spheroid size, respectively. PAPSS1-knockdown spheroids were significantly more sensitive to CDDP even when added at an 8-fold lower dose (1.56 μM). At this concentration, the control spheroids grew about 37% in size while the size of the PAPSS1-silenced spheroids was reduced by 21% (p&amp;lt;0.0001). In zebrafish, the number of A549 cells was reduced by approximately 50% with the combination of PAPSS1 knockdown and CDDP treatment relative to non-silencing, CDDP-treated controls. In mice, tumor development was significantly delayed in the shPAPSS1 group relative to both parental (p = 0.008) and non-targeting shRNA (p = 0.026) controls following CDDP treatment. Our study demonstrates for the first time that PAPSS1 knockdown enhances CDDP treatment in vivo. To pursue PAPSS1 as a therapeutic target, a small molecule inhibitor screen is warranted. The availability of a small molecule inhibitor will be essential to understand how PAPSS1 inhibition sensitizes cancer cells (but not normal cells) to DNA damaging agents. Citation Format: Ada W.Y. Leung, Chansey J. Veinotte, Nicole Melong, Ian Backstrom, Corinna Warburton, Edie Dullaghan, Jason N. Berman, Marcel B. Bally. PAPSS1 (3’-phosphoadenosine 5’-phosphosulfate synthase 1) inhibition sensitizes non-small cell lung cancer to cisplatin treatment in vivo. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3792.</jats:p