德国柏林墙遗址地区公共空间的保护与规划研究

柏林墙是柏林近代史上重要的一段政治事件遗迹与历史见证。从1990年6月至今,柏林政府对柏林墙遗址地区进行了不同层面的保护和开发。梳理了柏林墙与柏林城市发展的关系,从政府工作、遗址构筑物与户外公共空间3个方面,研究了柏林墙遗址地区的保护与规划内容,认为针对柏林墙遗址地区,德国政府及人民对历史予以足够的尊重,以政府为主导的多维度、持续性的规划工作对遗址地区起到了重要的保护作用。灵活多样、高品质的公共空间营造方式与丰富的纪念性活动,使得衰败的地区得以激活和复兴,为中国遗址地区保护与规划设计提供借鉴。     

Small Molecules Identified from a Quantitative Drug Combinational Screen Resensitize Cisplatin's Response in Drug-Resistant Ovarian Cancer Cells

Drug resistance to chemotherapy occurs in many ovarian cancer patients resulting in failure of treatment. Exploration of drug resistance mechanisms and identification of new therapeutics that overcome the drug resistance can improve patient prognosis. Following a quantitative combination screen of 6060 approved drugs and bioactive compounds in a cisplatin-resistant A2780-cis ovarian cancer cell line, 38 active compounds with IC₅₀s under 1 μM suppressed the growth of cisplatin-resistant ovarian cancer cells. Among these confirmed compounds, CUDC-101, OSU-03012, oligomycin A, VE-821, or Torin2 in a combination with cisplatin restored cisplatin's apoptotic response in the A2780-cis cells, while SR-3306, GSK-923295, SNX-5422, AT-13387, and PF-05212384 directly suppressed the growth of A2780-cis cells. One of the mechanisms for overcoming cisplatin resistance in these cells is mediated by the inhibition of epidermal growth factor receptor (EGFR), though not all the EGFR inhibitors are equally active. The increased levels of total EGFR and phosphorylated-EGFR (p-EGFR) in the A2780-cis cells were reduced after the combined treatment of cisplatin with EGFR inhibitors. In addition, a knockdown of EGFR mRNA reduced cisplatin resistance in the A2780-cis cells. Therefore, the top active compounds identified in this work can be studied further as potential treatments for cisplatin-resistant ovarian cancer. The quantitative combinational screening approach is a useful method for identifying effective compounds and drug combinations against drug-resistant cancer cells.     

Optimization of 5-arylidene barbiturates as potent,selective, reversible LSD1 inhibitors for the treatment of acute promyelocytic leukemia

Histone lysine specific demethylase 1 (LSD1) is overexpressed in diverse hematologic disorders and recognized as a promising target for blood medicines. In this study, molecular docking-based virtual screening united with bioevaluation was utilized to identify novel skeleton of 5-arylidene barbiturate as small-molecule inhibitors of LSD1. Among the synthesized derivatives, 12a exhibited reversible and potent inhibition (IC₅₀?=?0.41?μM) and high selectivity over the MAO-A and MAO-B. Notably, 12a strongly induced differentiation effect on acute promyelocytic leukemia NB4 cell line and distinctly escalated the methylation level on histone 3 lysine 4 (H3K4). Our findings indicate that 5-arylidene barbiturate may represent a new skeleton of LSD1 inhibitors and 12a deserve as a promising agent for the further research.     

Can apneic oxygen insufflation become a novel lung protective ventilation strategy? A randomized,controlled, blinded,single center clinical trial

Objective

The aim of this study was to determine whether a AOI strategy on non-ventilated lung could reduce the regional and systemic proinflammatory cytokine and oxidative stress response associated with esophagectomy, and to evaluate whether AOI can be used as a novel lung protective ventilation strategy. Its impact on oxygenation after OLV, surfactant protein A, B, C (SP-A, B, C), postoperative hospital stay and postoperative pulmonary complications (PPCs) was also evaluated.

Methods

Fifty-four adults (ASA II-III) undergoing esophagectomy with OLV were enrolled in the study. Patients were randomly assigned into 2 groups: control group (group C) and treated group (group T). Group C was treated with traditional OLV mode,while group T was given AOI of 5?L/min oxygen on the non-ventilated lung immediately at the beginning of OLV. Arterial blood gas was analyzed before and after OLV. A bronchoalveolar lavage(BAL) was performed after OLV on the non-ventilated lung. Proinflammatory cytokine, oxidative stress markers(TNF-α, NF-κB,sICAM-1,IL-6,IL-10,SOD,MDA) and SP-A, B, C were analyzed in serum and BALF as the primary endpoint.The clinical outcome determined by PPCs was assessed as the secondary endpoint.

Results

Patients with AOI had better oxygenation in the recovery period, oxygenation index(OI) (394[367–426] and 478[440–497]mmHg, respectively) of group T at T₂ and T₃ were significantly higher than those (332[206–434] and 437[331–512]mmHg, respectively) of group C. OLV resulted in an increase in the measured inflammatory markers in both groups, however, the increase of inflammatory markers upon OLV in the group C was significantly higher than those of group T. OLV resulted in an increase in the measured SP-A, B, C in serum of both groups. However, the levels of SP-A, B, C of group T were lower than those of group C in serum after OLV, and the results in BALF were the opposite. The BALF levels of SOD(23.88[14.70–33.93]U/ml) of group T were higher than those(15.99[10.33–24.16] U/ml) of group C, while the levels of MDA in both serum and BALF of group T(8.60[4.14–9.85] and 1.88[1.33–3.08]nmol/ml, respectively) were all lower than those of group C (11.10[6.57–13.75] and 1.280[1.01–1.83]nmol/ml) after OLV. There was no statistical difference between the two groups in terms of postoperative hospital stay and the incidence of PPCs.

Conclusion

AOI on non-ventilated lung during OLV can improve the oxygenation function after OLV, relieve the inflammatory and oxidative stress response in the systemic and non-ventilated lung after OLV associated with esophagectomy.

Trial registration

ChiCTR-IOR-17011037. Registered on 31 March 2017.

     

NADH-Linked Electron Transfer Induces Cd2+ Movement in Corn Root Plasma Membrane Vesicles

The rate of electron transfer from NADH to ferricyanide associatedwith corn root plasma membrane vesicles was not significantlyaffected by the presence of Ca²⁺, Cd²⁺, Zn²⁺, or Co²⁺. However,unlike Ca²⁺, other tested divalent cations induced an electrontransfer-dependent increase in light scattering by the vesicles.The efficacy in inducing the light scattering increase followedthe order of Cd²⁺>Zn²⁺>Co²⁺. The extent of the light scatteringchange increased as the concentration of added Cd²⁺ increased.Using phase contrast microscopy, the increase in light scatteringwas related to an expansion of the vesicles. Accompanying thevolume increase, a decrease of Cd²⁺ concentration in the externalspace was observed by the use of Arsenazo III, a metallochromophorespecific for divalent cations. Under a specified electron transfercondition, a similar percentage of decrease over a wide rangeof initial Cd²⁺ concentration was detected. The presence ofA23187 [GenBank] decreased the rate and extent of light scattering increaseand its associated Cd²⁺ concentration change. However, A23187 [GenBank] had no effect on scattering changes already established by theelectron transfer and Cd²⁺. These results suggest that the NADHlinked electron transfer reaction may induce a Cd²⁺ uptake bythe vesicles of corn root plasma membrane with inside-out orientation. (Received September 25, 1995; Accepted December 19, 1995)     

Identification and Characterization of two new Fungal Pathogens of Polygonatum odoratum (Angular Solomon's seal) in Italy

Polygonatum odoratum (Mill.) Druce (Angular Solomon's seal) is a well‐known ornamental plant and herbal drug, which is used in traditional medicine. Severe leaf spots were observed in wild Angular Solomon's seal plants in a public park in Trento, Italy. A combination of morphological and molecular characteristics, including sequence data of ITS‐rDNA, large subunit (LSU), beta tubulin (TUB) and glyceraldehyde 3‐phosphate dehydrogenase (GAPDH) led to identification of two species, namely Phoma odoratissimi and Colletotrichum dematium s. str., isolated from these leaf spots. Pathogenicity of the isolates was confirmed on wounded leaves of Po. odoratum; indeed, both species induced leaf spot symptoms on inoculated leaves within 10 days of inoculation. This is the first report of leaf spot disease caused by Ph. odoratissimi and C. dematium s. str. on Po. odoratum, which can be considered a new host for both the species examined in this study. In addition, isolation of Ph. odoratissimi represents a new record for the mycobiota of Italy.     

Experimental Manipulation of Food Accessibility Affects Conflict Management Behaviour in Ravens

Conflict management strategies such as reconciliation and bystander affiliation have been described for a variety of species. A common determinant seems to be a ‘complex’ social life, with individuals relying on affiliate relationships or social bonds. Little is known, however, about the strategic and flexible use of conflict management skills in experimental settings in species other than primates. We here investigated conflict and post‐conflict behaviour of ravens by manipulating the accessibility of food and, thus, the likelihood of aggressive interactions while foraging. Specifically, we presented birds with a certain amount of highly preferred food that varied in the number of pieces (one piece, two pieces or, as a control, small pieces matching the number of participating birds) and observed their agonistic behaviour during feeding and their affiliative behaviour afterwards. The results showed that high levels of conflicts during feeding in the 1‐piece and 2‐piece conditions led to high levels of affiliation after feeding. Depending on the experimental condition, this effect is best explained (a) by the affiliative behaviour of former aggressors (1‐piece condition) and (b) by the affiliation directed to the receivers of aggression after feeding (2‐piece condition). Those dyads that engaged in allo‐preening after feeding also engaged in allo‐preening outside the experimental setting, suggesting that socially bonded individuals provided third‐party affiliation to victims of aggression. Moreover, socially bonded ravens fed close to each other in the experiment when food was clumped, indicating that they actively coordinated their behaviour when there was a high conflict potential. Taken together, these findings support the assumption that ravens use their social bonds to avoid conflicts by choosing with whom to feed, and to buffer effects of conflicts by engaging in third‐party affiliation as post‐conflict behaviour.     

G2 chromosomal radiosensitivity in families with ataxia-telangiectasia

Summary Ataxia-telangiectasia (A-T) is an autosomal recessive disease involving chromosomal instability, susceptibility to cancer and X-ray hypersensitivity. The latter two features are expressed to a limited extent in the heterozygous carriers of A-T mutations. Although fibroblast lines from A-T heterozygotes clearly show increased susceptibility to the lethal effect of X-irradiation, the difference in post-irradiation survival between cell lines and normal controls is not always large enough to allow the use of X-ray sensitivity as a laboratory assay for carrier detection in A-T. Recently, we have shown in a blind study, that the extent of chromatid damage induced in the G₂ phase of the cell cycle by moderate doses of X-rays is markedly higher in A-T heterozygous cells than in normal controls. We have now applied this test to 6 additional obligatory heterozygotes and 24 individuals with different risks of being A-T carriers, from three Israeli A-T families. All 6 cell lines from the obligatory heterozygotes showed the typical hypersensitivity to the clastogenic action of X-rays in G₂; of the 24 cell lines with unknown A-T genotype, 16 showed the same hypersensitivity, and 8 responded in a normal way. The proportion of cell lines showing the A-T-heterozygous phenotype was in accord with the expected value, based on Mendelian chance calculations. Since these observations were made, a daughter of two hypersensitive parents in one of these families has been diagnosed as having A-T. This confirmed the presumed A-T heterozygosity of the parents, as indicated by the laboratory assay.