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11.
Jing Guo Tomer Fishman Yao Wang Alessio Miatto Wendy Wuyts Licheng Zheng Heming Wang Hiroki Tanikawa 《Journal of Industrial Ecology》2021,25(1):162-175
Construction materials are considerable forces of global environmental impacts, but their dynamics vis‐à‐vis urban development are poorly documented, in part because their long lifespans require elusive and sometimes nonexistent decade‐long high‐resolution data. This study analyzes the construction material flow and stock trends that shaped and were shaped by the development, decline, and renewal of the Tiexi district of Shenyang, a microcosm of China's urban transformations since the early 20th century. Chronicling building‐by‐building the material flows and stock accumulations involved in the buildup of this area, we shed light on the physical resource context of its socioeconomic history. We find that 42 million tonnes of construction materials were needed to develop the Tiexi district from 1910 to 2018, and 18 million tonnes of material outflows were generated by end‐of‐life building demolition. However, over 55% of inflows and 93% of outflows occurred since 2002 during a complete redevelopment of the district. Only small portions of end‐of‐life materials could have been reused or recycled because of temporal and typological mismatches of supply and demand and technical limitations. Our analysis reveals a dramatic decrease in median building lifetimes to as low as 6 years in the early 21st century. These findings contribute to the discussion of long‐term environmental efficiency and sustainability of societal development through construction and reflect on the challenges of urban renewal processes not only in China but also in other developing and developed countries that lost (or may lose) their traditional economic base and restructure their urban forms. This article met the requirements for a Silver/Silver JIE data openness badge described at http://jie.click/badges . 相似文献
12.
Aleksandrs Pustenko Alessio Nocentini Anastasija Balašova Ahmed Alafeefy Mikhail Krasavin Raivis Žalubovskis 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):245-254
Abstract A new series of homosulfocoumarins (3H-1,2-benzoxathiepine 2,2-dioxides) possessing various substitution patterns and moieties in the 7, 8 or 9 position of the heterocylic ring were prepared by original procedures and investigated for the inhibition of four physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the human (h) hCA I, II, IX and XII. The 8-substituted homosulfocoumarins were the most effective hCA IX/XII inhibitors followed by the 7-substituted derivatives, whereas the substitution pattern in position 9 led to less effective binders for the transmembrane, tumour-associated isoforms IX/XII. The cytosolic isoforms hCA I and II were not inhibited by these compounds, similar to the sulfocoumarins/coumarins investigated earlier. As hCA IX and XII are validated anti-tumour targets, with one sulphonamide (SLC-0111) in Phase Ib/II clinical trials, finding derivatives with better selectivity for inhibiting the tumour-associated isoforms over the cytosolic ones, as the homosulfocoumarins reported here, is of crucial importance. 相似文献
13.
Adeline C Ledoux Hélène Sellier Katie Gillies Alessio Iannetti John James Neil D Perkins 《Cell cycle (Georgetown, Tex.)》2013,12(18):3052-3062
Activation of the NFκB signaling pathway allows the cell to respond to infection and stress and can affect many cellular processes. As a consequence, NFκB activity must be integrated with a wide variety of parallel signaling pathways. One mechanism through which NFκB can exert widespread effects is through controlling the expression of key regulatory kinases. Here we report that NFκB regulates the expression of genes required for centrosome duplication, and that Polo-like kinase 4 (PLK4) is a direct NFκB target gene. RNA interference, chromatin immunoprecipitation, and analysis of the PLK4 promoter in a luciferase reporter assay revealed that all NFκB subunits participate in its regulation. Moreover, we demonstrate that NFκB regulation of PLK4 expression is seen in multiple cell types. Significantly long-term deletion of the NFκB2 (p100/p52) subunit leads to defects in centrosome structure. This data reveals a new component of cell cycle regulation by NFκB and suggests a mechanism through which deregulated NFκB activity in cancer can lead to increased genomic instability and uncontrolled proliferation. 相似文献
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Peptidomimetics effective in modulating protein-protein interactions and resistant to proteolysis have potential in therapeutic applications. An appealing yet underperforming peptidomimetic strategy is to employ D-amino acids and reversed sequences to mimic a lead peptide conformation, either separately or as the combined retro-inverso peptide. In this work, we examine the conformations of inverse, reverse and retro-inverso peptides of p53(15–29) using implicit solvent molecular dynamics simulation and circular dichroism spectroscopy. In order to obtain converged ensembles for the peptides, we find enhanced sampling is required via the replica exchange molecular dynamics method. From these replica exchange simulations, the D-peptide analogues of p53(15–29) result in a predominantly left-handed helical conformation. When the parent sequence is reversed sequence as either the L-peptide and D-peptide, these peptides display a greater helical propensity, feature reflected by NMR and CD studies in TFE/water solvent. The simulations also indicate that, while approximately similar orientations of the side-chains are possible by the peptide analogues, their ability to mimic the parent peptide is severely compromised by backbone orientation (for D-amino acids) and side-chain orientation (for reversed sequences). A retro-inverso peptide is disadvantaged as a mimic in both aspects, and further chemical modification is required to enable this concept to be used fruitfully in peptidomimetic design. The replica exchange molecular simulation approach adopted here, with its ability to provide detailed conformational insights into modified peptides, has potential as a tool to guide structure-based design of new improved peptidomimetics. 相似文献
15.
Natalia Y. Boynak Federico Rojas Cecilia D’Alessio Salomé C. Vilchez Larrea Vanina Rodriguez Pablo D. Ghiringhelli María T. Téllez-I?ón 《PloS one》2013,8(11)
Regulation of eukaryotic cell cycle progression requires sequential activation and inactivation of cyclin-dependent kinases (CDKs). Activation of the cyclin B-cdc2 kinase complex is a pivotal step in mitotic initiation and the tyrosine kinase Wee1 is a key regulator of cell cycle sequence during G2/M transition and inhibits mitotic entry by phosphorylating the inhibitory tyrosine 15 on the cdc2 M-phase-inducing kinase. Wee1 degradation is essential for the exit from the G2 phase. In trypanosomatids, little is known about the genes that regulate cyclin B-cdc2 complexes at the G2/M transition of their cell cycle. Although canonical tyrosine kinases are absent in the genome of trypanosomatids, phosphorylation on protein tyrosine residues has been reported in Trypanosoma brucei. Here, we characterized a Wee1-like protein kinase gene from T. brucei. Expression of TbWee1 in a Schizosaccharomyces pombe strain null for Wee1 inhibited cell division and caused cell elongation. This demonstrates the lengthening of G2, which provided cells with extra time to grow before dividing. The Wee1-like protein kinase was expressed in the procyclic and bloodstream proliferative slender forms of T. brucei and the role of Wee1 in cell cycle progression was analyzed by generating RNA interference cell lines. In the procyclic form of T. brucei, the knock-down of TbWee1 expression by RNAi led to inhibition of parasite growth. Abnormal phenotypes showing an increase in the percentage of cells with 1N0K, 0N1K and 2N1K were observed in these RNAi cell lines. Using parasites with a synchronized cell cycle, we demonstrated that TbWee1 is linked to the G2/M phase. We also showed that TbWee1 is an essential gene necessary for proper cell cycle progression and parasite growth in T. brucei. Our results provide evidence for the existence of a functional Wee1 in T. brucei with a potential role in cell division at G2/M. 相似文献
16.
Alessio Cimmino Anna Andolfi Fabiana Avolio Abbas Ali Nurhayat Tabanca Ikhlas A. Khan Antonio Evidente 《化学与生物多样性》2013,10(7):1239-1251
Aedes aegypti L. is the major vector of the arboviruses responsible for dengue fever, one of the most devastating human diseases. From a preliminary screening of fungal phytotoxins, cyclopaldic acid ( 1 ), seiridin ( 2 ), sphaeropsidin A ( 4 ), and papyracillic acid ( 5 ) were evaluated for their biting deterrent and larvicidal activities against Ae. aegypti L. Because compounds 1, 2, 4 , and 5 exhibited mosquito biting deterrent activities and 1 and 4 demonstrated larvicidal activities, further structure? activity relationship studies were initiated on these toxins. In biting‐deterrence bioassays, 1, 2, 4 , and 5 , 3,8‐didansylhydrazone of cyclopaldic acid, 1F , 5‐azidopentanoate of cyclopaldic acid A, 1G , the reduced derivative of cyclopaldic acid, 1 H , isoseiridin ( 3 ), 2′‐O‐acetylseiridin ( 2A ), 2′‐oxoseiridin ( 2C ), 6‐O‐acetylsphaeropsidin A ( 4A ), 8,14‐methylensphaeropsidin A methyl ester ( 4B ), and sphaeropsidin B ( 4C ) showed activities higher than the solvent control. Sphaeropsidin B ( 4C ) was the most active compound followed by 2A , while the other compounds were less active. Biting‐deterrence activity of compound 4C was statistically similar to DEET. In the larvicidal screening bioassays, only compounds 1 and 4 demonstrated larvicidal activities. Based on LD50 values, compound 4 (LD50 36.8 ppm) was significantly more active than compound 1 (LD50 58.2 ppm). However, the activity of these compounds was significantly lower than permethrin. 相似文献
17.
Alessio Cimmino Anna Andolfi Fabiana Avolio Abbas Ali Nurhayat Tabanca Ikhlas A. Khan Antonio Evidente 《化学与生物多样性》2013,10(12):2302-2302
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Luca Madaro Fabrizio Antonangeli Annarita Favia Bianca Esposito Filippo Biamonte Marina Bouché Elio Ziparo Gigliola Sica Antonio Filippini Alessio D'Alessio 《Journal of cellular biochemistry》2013,114(8):1843-1851
Caveolin‐1 (CAV1) is the principal structural component of caveolae which functions as scaffolding protein for the integration of a variety of signaling pathways. In this study, we investigated the involvement of CAV1 in endothelial cell (EC) functions and show that siRNA‐induced CAV1 silencing in the human EC line EA.hy926 induces distinctive morphological changes, such as a marked increase in cell size and formation of stress fibers. Design‐based stereology was employed in this work to make unbiased quantification of morphometric properties such as volume, length, and surface of CAV1 silenced versus control cells. In addition, we showed that downregulation of CAV1 affects cell cycle progression at G1/S phase transition most likely by perturbation of AKT signaling. With the aim to assess the contribution of CAV1 to typical biological processes of EC, we report here that CAV1 targeting affects cell migration and matrix metalloproteinases (MMPs) activity, and reduces angiogenesis in response to VEGF, in vitro. Taken together our data suggest that the proper expression of CAV1 is important not only for maintaining the appropriate morphology and size of ECs but it might represent a prospective molecular target for studying key biological mechanisms such as senescence and tumorigenesis. J. Cell. Biochem. 114: 1843–1851, 2013. © 2013 Wiley Periodicals, Inc. 相似文献