bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel function for CUGBP2 in controlling the pro‐inflammatory stimulus in H9c2 cells: subcellular trafficking of messenger molecules
Authors: Moraes Karen C. M. , Monteiro Cíntia Júnia , Pacheco‐Soares Cristina
Published: August 2013

Accumulating evidence demonstrates that chronic inflammation plays an important role in heart hypertrophy and cardiac diseases. However, the fine‐tuning of cellular and molecular mechanisms that connect inflammatory process and cardiac diseases is still under investigation. Many reports have demonstrated that the overexpression of the cyclooxygenase‐2 (COX‐2), a key enzyme in the conversion of arachidonic acid to prostaglandins and other prostanoids, is correlated with inflammatory processes. Increased level of prostaglandin E2 was also found in animal model of left ventricle of hypertrophy. Based on previous observations that demonstrated a regulatory loop between COX‐2 and the RNA‐binding protein CUGBP2, we studied cellular and molecular mechanisms of a pro‐inflammatory stimulus in a cardiac cell to verify if the above two molecules could be correlated with the inflammatory process in the heart. A cellular model of investigation was established and H9c2 was used. We also demonstrated a regulatory connection between COX‐2 and CUGBP2 in the cardiac cells. Based on a set of different assays including gene silencing and fluorescence microscopy, we describe a novel function for the RNA‐binding protein CUGBP2 in controlling the pro‐inflammatory stimulus: subcellular trafficking of messenger molecules to specific cytoplasmic stress granules to maintain homeostasis.
Multidimensional control of cell structural robustness
Authors: Grinev Vasily V. , Ramanouskaya Tatsiana V. , Gloushen Sergey V.
Published: August 2013

Ample adaptive and functional opportunities of a living cell are determined by the complexity of its structural organisation. However, such complexity gives rise to a problem of maintenance of the coherence of inner processes in macroscopic interims and in macroscopic volumes which is necessary to support the structural robustness of a cell. The solution to this problem lies in multidimensional control of the adaptive and functional changes of a cell as well as its self‐renewing processes in the context of environmental conditions. Six mechanisms (principles) form the basis of this multidimensional control: regulatory circuits with feedback loops, redundant inner diversity within a cell, multilevel distributed network organisation of a cell, molecular selection within a cell, continuous informational flows and functioning with a reserve of power. In the review we provide detailed analysis of these mechanisms, discuss their specific functions and the role of the superposition of these mechanisms in the maintenance of cell structural robustness in a wide range of environmental conditions.
Methods for rearing Mesostoma ehrenbergii in the laboratory for cell biology experiments, including identification of factors that influence production of different egg types
Authors: Hoang Carina , Ferraro‐Gideon Jessica , Gauthier Kimberley , Forer Arthur
Published: August 2013

Mesostoma ehrenbergii spermatocytes are uniquely useful to study various aspects of cell division. Their chromosomes are large in size and few in number, with only three bivalent and four univalent chromosomes. During prometaphase, bipolar bivalents oscillate regularly to and from the poles for 1–2 hours. The univalents remain at the poles but occasionally move from one pole to the other. In addition, a precocious cleavage furrow forms during prometaphase and remains partially constricted until anaphase. Attempts to rear these animals indefinitely in laboratory conditions, however, have been mostly unsuccessful because of their reproductive strategy. M. ehrenbergii are hermaphroditic flatworms that can produce viviparous offspring (termed S eggs) and/or diapausing eggs (termed D eggs) and they follow either one of two reproductive patterns: (1) they first form S eggs and following the delivery of these eggs produce D eggs, or (2) they only produce D eggs. When only D eggs are formed, which is common under laboratory conditions, the stocks die out until the D eggs hatch, which is irregular and creates unpredictable wait times. Consequently, in order to maintain M. ehrenbergii stocks to study their spermatocytes, we examined various factors that might influence egg‐type production. Feeding them daily and keeping them at 25°C favours S egg production. Currently, our cultures have reached the 53rd generation. We herein describe our rearing and dissection methods, and some experiments which led to our present rearing methods.
Overexpression of CD147 in ovarian cancer is initiated by the hypoxic microenvironment
Authors: Yang Hong , Zou Wei , Chen Biliang
Published: August 2013

Ovarian cancer is a lethal malignant tumour characterised by activated invasion, distant metastasis, anti‐cancer drug resistance, angiogenesis and metabolism. CD147, an extracellular matrix metalloproteinase inducer, is overexpressed in most ovarian tumours and plays an important role in the progression of ovarian cancer and other malignant tumours. However, the factor(s) initiating this overexpression is unknown. Because of rapid reproduction and their hypoxic microenvironment, malignant tumours use glycolysis for energy, and lactic acid produced is harmful to the cells. For survival, excessive lactate needs to be transported by monocarboxylate transporters (MCTs). Functioning of MCT1 and MCT4 require the ancillary of CD147. The gene for CD147 possesses two hypoxia‐inducible factors binding sites in its 3′‐flank. It is logical to postulate that the hypoxic microenvironment is a major initiator of the overexpression of CD147, thus conferring on ovarian cancers their malignant properties. A model that can represent spontaneous ovarian cancer is necessary to verify this hypothesis.
Nuclear structures in Tribolium castaneum oocytes
Authors: Bogolyubov Dmitry S. , Batalova Florina M. , Kiselyov Artyom M. , Stepanova Irina S.
Published: August 2013

The first ultrastructural and immunomorphological characteristics of the karyosphere (karyosome) and extrachromosomal nuclear bodies in the red flour beetle, Tribolium castaneum, are presented. The karyosphere forms early in the diplotene stage of meiotic prophase by the gathering of all oocyte chromosomes in a limited nuclear volume. Using the BrUTP assay, T. castaneum oocyte chromosomes united in the karyosphere maintain their transcriptional activity until the end of oocyte growth. Hyperphosphorylated RNA polymerase II and basal transcription factors (TFIID and TFIIH) were detected in the perichromatin region of the karyosphere. The T. castaneum karyosphere has an extrachromosomal capsule that separates chromosomes from the rest of the nucleoplasm. Certain structural proteins (F‐actin, lamin B) were found in the capsule. Unexpectedly, the karyosphere capsule in T. castaneum oocytes was found to be enriched in TMG‐capped snRNAs, which suggests that the capsule is not only a structural support for the karyosphere, but may be involved in biogenesis of snRNPs. We also identified the counterparts of ‘universal’ extrachromosomal nuclear domains, Cajal bodies (CBs) and interchromatin granule clusters (IGCs). Nuclear bodies containing IGC marker protein SC35 display some features unusual for typical IGCs. SC35 domains in T. castaneum oocytes are predominantly fibrillar complex bodies that do not contain trimethyl guanosine (TMG)‐capped small nuclear (sn) RNAs. Microinjections of 2′‐O‐methyl (U)22 probes into the oocytes allowed revealing poly(A)+ RNAs in these nuclear domains. Several proteins related to mRNA export (heterogeneous ribonucleoprotein core protein A1, export adapters Y14 and Aly and export receptor NXF1) were also detected there. We believe that unusual SC35 nuclear domains of T. castaneum oocytes are possibly involved in mRNP but not snRNP biogenesis.
C3G overexpression promotes the survival of rat‐derived H9C2 cardiomyocytes by p‐ERK1/2
Authors: Zhang Xu , Li Gang , Zhang Lei , Yang Dongyan , Zhang Zhisheng , Yan An , Linghu Hua
Published: August 2013

Integrin β1 subunit and its downstream molecules, such as integrin‐linked kinase and focal adhesion kinase, are imperative for promotion of cell proliferation, survival and anti‐apoptosis in cardiomyocytes by activation of their downstream pro‐survival signalling molecules, such as the phosphorylated extracellular signal‐regulated kinase1/2 (p‐ERK1/2). As a component of the integrin pathway, C3G (Crk‐SH3 domain guanine nucleotide exchange factor) protein may be involved in the promotion of cell proliferation and survival and anti‐apoptosis in the H9C2 cardiomyocytes. Rat‐derived H9C2 cardiomyocytes were transfected with pCXN2‐flag‐hC3G, a human C3G overexpression eukaryotic recombinant plasmid. Apoptosis, cell proliferation and survival were analysed in the H9C2 cardiomyocytes either treated with hypoxia/reoxygenation (H/R). Human C3G mRNA overexpression significantly elevated C3G protein expression in H9C2 cardiomyocytes whether treated with H/R or not. C3G overexpression promoted proliferation and survival and anti‐apoptosis, and attenuated the proliferative and survival inhibition, and apoptosis induced by H/R by activation of its downstream pro‐survival signalling molecule, p‐ERK1/2. The results suggest that C3G acts as a pro‐survival molecule in H9C2 cardiomyocytes by activation of p‐ERK1/2.
Bortezomib induces apoptosis of endometrial cancer cells through microRNA‐17‐5p by targeting p21
Authors: Shen Yuan , Lu Lin , Xu Jianping , Meng Wei , Qing Yanwei , Liu Yuan , Zhang Bei , Hu Haiyan
Published: August 2013

Bortezomib suppresses ubiquitin (Ub)‐dependent protein degradation and preferentially kills various tumour cells in vitro and in animal models. However, its mechanism of action is not fully understood. We report that bortezomib inhibits the proliferation and proteasomal activity of human endometrial cancer cells and induces G2/M arrest and apoptosis by modulating the miRNA level. By miRNA microarray, iR‐17‐5p was the most downregulated of all those in HTB‐111 and Ishikawa cells after bortezomib treatment. This observation was confirmed by quantitative real‐time PCR (qRT‐PCR). Target prediction using TargetScan software identified p21 as a potential target for miR‐17‐5p, which was confirmed by luciferase reporter, qRT‐PCR and Western blot assays. The transfection of miR‐17‐5p mimics or siRNA‐p21 reversed the effect of bortezomib on HTB‐111 and Ishikawa cells, indicating that miR‐17‐5p may mediate the function of bortezomib by targeting p21 in endometrial cancer cells. These findings show novel mechanisms by which bortezomib inhibits proliferation and promotes the apoptosis of human endometrial cancer cells.
Effect of laminated hydroxyapatite/gelatin nanocomposite scaffold structure on osteogenesis using unrestricted somatic stem cells in rat
Authors: Tavakol Shima , Azami Mahmoud , Khoshzaban Ahad , Ragerdi Kashani Iraj , Tavakol Behnaz , Hoveizi Elham , Rezayat Sorkhabadi Seyed Mahdi
Published: August 2013

Bone matrix consists of two major phases at the nanoscale: organic and hydroxyapatite. Nanotechnology as a diverse and interdisciplinary area of research has the capacity to revolutionise many areas of applications such as bone tissue engineering. Nanohydroxyapatite/gelatin composite has higher osteoblast attachment and proliferation than micro‐sized ones, and shorter culturing period and lower cell seeding density compared to pure gelatin. A nanostructured scaffold was fabricated by three methods for bone repair using nanohydroxyapatite and gelatin as the main components. Its biocompatibility, alizarin red test on the 14th and 21st days, gene expression on the 21st day in in vitro using and histomorphometry after 4 and 8 weeks post‐implantation in the rat were investigated. Cultured unrestricted somatic stem cells used for in vitro study showed an excellent level of cell attachment to the scaffold. Cells induced more osteoblast differentiation on the scaffold than in 2D cell culture. Osteoblast differentiation and bone regeneration results of in vitro and in vivo investigation on scaffold were extremely significant, better than control and treatment groups. These effects could be attributed to the shape and size of nanoHA particles and good architecture of the scaffold. The results confirm the feasibility of bone regeneration using synthesised scaffold as a temporary bone substitute.
In vitro effects of IL‐17 on angiogenic properties of endothelial cells in relation to oxygen levels
Authors: Krstić Jelena , Jauković Aleksandra , Mojsilović Slavko , Đorđević Ivana Okić , Trivanović Drenka , Ilić Vesna , Santibañez Juan F. , Bugarski Diana
Published: August 2013

The aim of this study has been to elucidate how different oxygen levels impact the effects of Interleukin‐17 (IL‐17) on angiogenic properties of endothelial cells. Two endothelial cell lines, mouse MS‐1 and human EA.hy 926, were grown in 20% and 3% O2 and their angiogenic abilities analyzed after IL‐17 treatment: proliferation, apoptosis, migration and tubulogenesis. Expression of endothelial nitric oxide synthase (eNOS) and cyclooxygenase‐2 (Cox‐2) was also measured. Considering EA.hy 926 cell line, hypoxia alone reduced proliferation, survival and migration, but not their ability to form tubules. When cultured at 20% O2, IL‐17 stimulated proliferation, migration and tubulogenesis, whereas a hypoxic environment did not affect their migration and proliferation, but increased their survival and tubulogenic properties. Expression of eNOS and Cox‐2 increased by both IL‐17 and hypoxia, as well as with their combination. With the MS‐1 cell line hypoxia did not affect proliferation, survival, migration and tubule formation. At 20% O2, IL‐17 did not alter their proliferation,but inhibited migration and stimulated tubule formation. At 3% O2, only the stimulating effect of IL‐17 on tubulogenesis was evident. The constitutive expression of eNOS was unaffected by oxygen concentrations or IL‐17 supplementation, whereas both IL‐17 and hypoxia upregulated Cox‐2 expression. Thus the effects of IL‐17 on the angiogenic properties of endothelial cells depend on both the cell line used and the oxygen concentration.
Estrogen‐related receptor alpha interacts cooperatively with peroxisome proliferator‐activated receptor‐gamma coactivator‐1alpha to regulate osteocalcin gene expression
Authors: Wang Haibin , Wang Junjian
Published: August 2013

Osteocalcin is one of the most abundant non‐collagenous proteins in bone that is commonly used as a preliminary biomarker in bone formation. Osteocalcin also regulates energy metabolism as a hormone. Estrogen‐related receptor alpha (ERRα) is primarily thought to regulate energy homeostasis through interacting with peroxisome proliferator‐activated receptor gamma coactivator‐1α (PGC‐1α). Intriguingly, ERRα may play a functional role in bone formation. We have found there are 3 ERRα response elements (ERR response element, ERRE) in the osteocalcin promoter, and ERRα interacted cooperatively with PGC‐1α could improve the osteocalcin promoter activity, whereas ERRα specific antagonist, XCT‐790, inhibits this enhancement. XCT‐790 inhibits osteocalcin and ERRα target gene PDKs expression in osteoblast cells. Thus ERRs might have physiological roles in bone formation and energy metabolism through modulating osteocalcin gene expression.
Osteopontin mediating cyclosporine A induced epithelial‐to‐mesenchymal transition on rat renal tubular epithelial cells
Authors: Xu Dongliang , Chen Xia , Deng Zhonglei , Tan Ruoyun , Liu Chao , Lu Pei , Zhang Wei , Gu Min
Published: August 2013

Osteopontin (OPN) is highly correlated with cyclosporine A (CsA) nephrotoxicity. As epithelial‐to‐mesenchymal transition (EMT) of renal tubular epithelial cells plays an important role in CsA nephropathy, we investigated whether OPN mediated EMT of renal tubular epithelial cells upon CsA stimulation. OPN knockdown suppresses CsA induced EMT on NRK52E cells, and it also attenuates downregulation of E‐cadherin and upregulation of α‐smooth muscle actin (α‐SMA) and fibronectin (FN) that are induced by CsA. OPN alone can induce EMT on NRK52E cells, which also results in upregulation of TGF‐β1. Thus, OPN is a causative factor in mediating CsA induced EMT on NRK52E cells.
Enhanced chondrogenesis through specific growth factors in a buffalo embryonic stem cell model
Authors: Sritanaudomchai Hathaitip , Kitiyanant Yindee , Tong‐ngam Pirut , Thonabulsombat Chareonsri , White Kenneth L. , Kusamran Thanit
Published: August 2013

Chondrogenic differentiation of embryonic stem cells (ESCs) via embryoid bodies (EBs) is an established model to investigate chondrogenesis signaling pathways and molecular mechanisms in vitro. Our aim has been to improve upon the number of differentiated cells needed for the in vitro development of functional cartilage. Chondrogenic differentiation of buffalo ESCs was modulated by bone morphogenetic protein 2 (BMP‐2), fibroblast growth factor 10 (FGF‐10), transforming growth factor‐beta1 (TGF‐β1) individually and their combination. ESCs differentiation into chondrocytes was characterized by the appearance of Alcian blue‐stained nodules and the expression of cartilage‐associated genes (RT‐PCR) and protein (immunocytochemistry). BMP‐2 or FGF‐10 treatment enhanced chondrogenic differentiation, whereas TGF‐β1 treatment inhibited buffalo ESC‐derived chondrogenesis. The combination of BMP‐2 and FGF‐10 was the most effective treatment. This treatment resulted in a higher number of Alcian blue‐positive nodules by 15.2‐fold, expression of the mesenchymal cell marker scleraxis gene by 3.25‐fold, and the cartilage matrix protein collagen II gene and protein 1.9‐ and 7‐fold, respectively, compared to the untreated control group. Chondrogenesis was also recapitulated from mesenchymal and chondrogenic progenitor cells, resulting in the establishment of mature chondrocytes. Thus, buffalo ESCs can be successfully triggered in vitro to differentiate into chondrocyte‐like cells by specific growth factors, which may provide a novel in vitro model for further investigation of the regulatory mechanism(s) involved.
Positioning of integrin β1, caveolin‐1 and focal adhesion kinase on the adhered membrane of spreading cells
Authors: Zemljič Jokhadar Špela , Majhenc Janja , Svetina Saša , Batista Urška
Published: August 2013

We have investigated the relationship between the spreading of anchorage‐dependent cells and the surface‐density distribution of plasma membrane adhesion proteins. The surface positioning and density of integrin β1, caveolin‐1 (cav‐1), the phosphorylated caveolin‐1 (p‐cav‐1) and the focal adhesion kinase (FAK) located on the adhering cell membrane (ACM) of HUVEC cells was studied. Imaging with TIRF microscopy was used, which enabled us to observe a few‐nanometers‐thin section of the cell above the plasma membrane in combination with image‐based analyses. Integrin β1 and cav‐1 have spatial interdependence on the ACM. Cells treated with substances that act on cell spreading caused changes in the size of the ACM area, as well as a redistribution of several proteins under investigation. Changes to the ACM area correlated positively with those to the surface density of the cav‐1. The high integrin β1 and the low cav‐1 surface density, and vice versa, following the treatments show that the presence of one of them not only spatially excludes, but also reduces, the occurrence of the other protein on the ACM, which indicates a regulative mechanism between integrin β1 and cav‐1.
Isoliquiritigenin‐induced effects on Nrf2 mediated antioxidant defence in the HL‐60 cell monocytic differentiation
Authors: Chen Hongmei , Zhang Bo , Yuan Xuan , Yao Ying , Zhao Hong , Sun Xiling , Zheng Quisheng
Published: August 2013

To evaluate the role of redox homeostasis in differentiation in human promyelocytic leukemia cells (HL‐60) induced by isoliquiritigenin (ISL) through modulation of the nuclear erythroid‐related factor 2/antioxidant responsive element (Nrf2/ARE) pathway. Morphological changes, cell surface markers CD11b/CD14, and nitroblue tetrazolium (NBT)‐reducing ability were used to determine the differentiation of HL‐60, and 2,7‐dichlorofluorescein was used to detect the level of intracellular reactive oxygen species (ROS). Thiobarbituric acid test was utilised to determine the levels of malondialdehyde production in ISL‐treated HL‐60. The study determines and presents the redox state of the ratio of reduced/oxidised glutathione as a consequence of progression from differentiation in HL‐60. Expression levels of the Nrf2/ARE downstream target genes were determined by quantitative polymerase chain reaction. Nicotinamide adenine dinucleotide phosphate‐oxidase (NADPH oxidase) inhibitors, apocynin (APO), and diphenyleneiodonium (DPI) were used for the preliminary study to determine the potential downstream targets regulated by NADPH oxidase in ISL‐induced HL‐60 differentiation. The data showed a strong dose–response relationship between ISL exposure and the characteristics of HL‐60 differentiation, namely, morphology changes, NBT reductive activities, and expression levels of surface antigens CD11b/CD14. Intercellular redox homeostasis changes toward oxidation during drug exposure are necessary to support ISL‐induced differentiation. The unique expression levels of the Nrf2/ARE downstream target genes in the differentiation of HL‐60 recorded a statistically significant and dose‐dependent increase (P < 0.05), which were suppressed by NADPH oxidase inhibitor, APO, and DPI. ISL as a differentiation‐inducing agent with mechanisms involved in the Nrf2/ARE pathway to modulate intercellular redox homeostasis, and thus, facilitate differentiation.
Combination of BMP‐2 and 5‐AZA is advantageous in rat bone marrow‐derived mesenchymal stem cells differentiation into cardiomyocytes
Authors: Hou Jing , Lü An‐Lin , Liu Bo‐Wu , Xing Yu‐Jie , Da Jing , Hou Zhao‐Lei , Ai Shi‐Yi
Published: August 2013

Bone morphogenetic protein‐2 (BMP‐2) has a crucial role in the development of cardiogenesis, and is used in inducing bone marrow mesenchymal stem cells (BMMSCs) to differentiate into cardiomyocytes. We have examined a combination of BMP‐2 and 5‐azacytidine (5‐AZA) in inducing these differentiation effects. BMMSCs were collected and purified from bone marrow of 4‐week‐old Sprague‐Dawley (SD) rats by density‐gradient centrifugation and differential attachment. The fourth passage subculture of BMMSCs, selected by cytometry for purity and identification, was divided into four groups: a control group, BMP‐2 treated, 5‐AZA treated, and a combination of BMP‐2 and 5‐AZA treatment. Expression of cardiac Troponin I (cTnI) and Connexin 43 (CX‐43) in BMMSCs after induction were detected by immunofluorescence and Western blot. Flow cytometry analysis was used for differentiation rates and apoptosis of induced BMMSCs, through the expression of cardiac Troponin T (cTnT) and Annexin V‐FITC & PI kit, respectively. BMP‐2 can ameliorate apoptosis of BMMSCs caused by 5‐AZA and promote the differentiation of BMMSCs into cardiomyocyte‐like cells. Thus a combination of BMP‐2 and 5‐AZA can significantly improve the cardiac differentiation with fewer cell damage effects, making it a safe and effective method of induction in vitro.
The lectin of Dolichos biflorus agglutinin recognises glycan epitopes on the surface of a subset of cardiac progenitor cells
Authors: Chen Zhanfeng , Wang Man , Xiang Qiang , Sun Zhenliang , Zhang Rong
Published: August 2013

The discovery of adult cardiac progenitor cells (CPCs) provides a promising way for treating heart disease; however, their surface characteristics that play a critical role in regulating their maintenance, self‐renewal, migration, and differentiation have not been fully investigated. One subpopulation of Dolichos biflorus agglutinin (DBA)‐positive cells was identified in the heart of adult mice. Flow cytometry showed that 3.7% of heart cells could be labeled by FITC conjugated DBA. BrdU pulse‐chase showed that 55–75% of DBA+ cells were CPCs. Evidences from 5‐FU‐induced myelosuppression along with BrdU pulse‐chasing suggests that DBA‐positive cells are proliferative. Furthermore, DBA positive cells display a cologenic appearance in vivo. Our findings suggest that DBA‐positive cells in the heart of adult mouse contained a subset of CPCs, and DBA reactivity is one novel surface characteristic on CPCs.
Optimization of a Multiple Impinging Jets Cavitation Reactor Using Zero‐Valent Iron Powder as Catalyst
Authors: Basiri Parsa J. , Ebrahimzadeh Zonouzian S. A.
Published: August 2013

The effect of a combination of impinging jets and hydrodynamic cavitation technology was investigated by a multiple impinging jets cavitation reactor (MIJCR). Zero‐valent iron (ZVI) powder and rhodamine B were chosen as heterogeneous catalyst and model pollutant, respectively. ZVI addition resulted in more than five times higher decolorization efficiency compared to runs without ZVI. In situ generation of Fenton reagents suggested an advanced Fenton process to explain the enhancing effect of the applied catalyst. Impinging jets and aeration led to significant enhancement of the process, and optimum values of inter‐nozzle distance and initial catalyst concentration favored the decolorization of rhodamine B.
Multitasking Water‐Soluble Synthetic G‐Quartets: From Preferential RNA–Quadruplex Interaction to Biocatalytic Activity
Authors: Haudecoeur Romain , Stefan Loic , Monchaud David
Published: August 2013

Natural G‐quartets, a cyclic and coplanar array of four guanine residues held together through a Watson–Crick/Hoogsteen hydrogen‐bond network, have received recently much attention due to their involvement in G‐quadruplex DNA, an alternative higher‐order DNA structure strongly suspected to play important roles in key cellular events. Besides this, synthetic G‐quartets (SQ), which artificially mimic native G‐quartets, have also been widely studied for their involvement in nanotechnological applications (i.e., nanowires, artificial ion channels, etc.). In contrast, intramolecular synthetic G‐quartets (iSQ), also named template‐assembled synthetic G‐quartets (TASQ), have been more sparingly investigated, despite a technological potential just as interesting. Herein, we report on a particular iSQ named PNADOTASQ, which demonstrates very interesting properties in terms of DNA and RNA interaction (notably its selective recognition of quadruplexes according to a bioinspired process) and catalytic activities, through its ability to perform peroxidase‐like hemin‐mediated oxidations either in an autonomous fashion (i.e., as pre‐catalyst for TASQzyme reactions) or in conjunction with quadruplex DNA (i.e., as enhancing agents for DNAzyme processes). These results provide a solid scientific basis for TASQ to be used as multitasking tools for bionanotechnological applications.
Highly Efficient Construction of Bisspirooxindoles Containing Vicinal Spirocenters through an Organocatalytic Modified Feist–Bénary Reaction
Authors: Ahadi Somayeh , Khavasi Hamid Reza , Bazgir Ayoob
Published: August 2013

We have developed an organocatalytic modified Feist–Bénary reaction of cyclic dicarbonyl compounds, isatins and cyclic α‐bromo dicarbonyl compounds. This method affords bisspirooxindole‐fused dihydrofurans containing two vicinal spiro centers. To the best of our knowledge, employing cyclic α‐halo dicarbonyl compounds for the synthesis of bisspirooxindole‐fused dihydrofurans has not been previously reported.
A Combined Experimental and Computational Study of Linear Ruthenium(II) Coordination Oligomers with End‐Capping Organic Redox Sites: Insight into the Light Absorption and Charge Delocalization
Authors: Yao Chang‐Jiang , Zheng Ren‐Hui , Nie Hai‐Jing , Cui Bin‐Bin , Shi Qiang , Yao Jiannian , Zhong Yu‐Wu
Published: August 2013

Two series of linear ruthenium coordination oligomers, [(Ntpy)Run(tppz)n−1(tpy)]2n+ (mono‐Ntpy series, n=1–3) and [(Ntpy)2Run(tppz)n−1]2n+ (bis‐Ntpy series, n=1–3) have been prepared, where Ntpy is the capping ligand 4′‐di‐p‐anisylamino‐2,2′:6′,2′′‐terpyridine, tppz is tetra‐2‐pyridylpyrazine, and tpy is 2,2′:6′,2′′‐terpyridine. The electrochemical measurements evidence oxidation events from both the amine segments and the metal centers and reduction waves from tppz and the capping ligands. Both series complexes display much enhanced light absorption with respect to model complexes without terminal amine units. Density functional theory (DFT) calculations have been performed on both series and time‐dependent DFT (TD‐DFT) calculations have been performed on the bis‐Ntpy‐series compounds (n=1–4) to characterize their electronic structures and excited states and predict the electronic properties of long‐chain polymers. Upon one‐electron oxidation, the mono‐Ntpy‐series monoruthenium and diruthenium complexes display N+‐localized transitions and metal‐to‐nitrogen charge‐transfer (MNCT) transitions in the near‐infrared (NIR) region. DFT and TD‐DFT computations on the one‐electron‐oxidized forms of the mono‐Ntpy‐series compounds (n=1–4) provide insight into the nature of the MNCT transitions and the degree of charge delocalization.
Donor–Acceptor (D–A)‐Substituted Polyyne Chromophores: Modulation of Their Optoelectronic Properties by Varying the Length of the Acetylene Spacer
Authors: Štefko Martin , Tzirakis Manolis D. , Breiten Benjamin , Ebert Marc‐Olivier , Dumele Oliver , Schweizer W. Bernd , Gisselbrecht Jean‐Paul , Boudon Corinne , Beels Marten T. , Biaggio Ivan , Diederich François
Published: August 2013

A series of donor–acceptor‐substituted alkynes, 2 a–f, was synthesized in which the length of the π‐conjugated polyyne spacer between the N,N‐diisopropylanilino donor and the 1,1,4,4‐tetracyanobuta‐1,3‐diene (TCBD) acceptor was systematically changed. The effect of this structural change on the optoelectronic properties of the molecules and, ultimately, their third‐order optical nonlinearity was comprehensively investigated. The branched N,N‐diisopropyl groups on the anilino donor moieties combined with the nonplanar geometry of 2 a–f imparted exceptionally high solubility to these chromophores. This important property allowed for performing INADEQUATE NMR measurements without 13C labeling, which, in turn, resulted in a complete assignment of the carbon skeleton in chromophores 2 a–f and the determination of the 13C–13C coupling constants. This body of data provided unprecedented insight into characteristic 13C chemical shift patterns in push–pull‐substituted polyynes. Electrochemical and UV/Vis spectroscopic studies showed that the HOMO–LUMO energy gap decreases with increasing length of the polyyne spacer, while this effect levels off for spacers with more than four acetylene units. The third‐order optical nonlinearity of this series of molecules was determined by measuring the rotational averages of the third‐order polarizabilities (γrot) by degenerate four‐wave mixing (DFWM). These latter studies revealed high third‐order optical nonlinearities for the new chromophores; most importantly, they provided fundamental insight into the effect of the conjugated spacer length in D–A polyynes, that can be exploited in the future design of suitable charge‐transfer chromophores for applications in optoelectronic devices.
19F NMR Spectroscopy as a Probe of Cytoplasmic Viscosity and Weak Protein Interactions in Living Cells
Authors: Ye Yansheng , Liu Xiaoli , Zhang Zeting , Wu Qiong , Jiang Bin , Jiang Ling , Zhang Xu , Liu Maili , Pielak Gary J. , Li Conggang
Published: August 2013

Protein mobility in living cells is vital for cell function. Both cytosolic viscosity and weak protein–protein interactions affect mobility, but examining viscosity and weak interaction effects is challenging. Herein, we demonstrate the use of 19F NMR spectroscopy to measure cytoplasmic viscosity and to characterize nonspecific protein–protein interactions in living Escherichia coli cells. The origins of resonance broadening in Escherichia coli cells were also investigated. We found that sample inhomogeneity has a negligible effect on resonance broadening, the cytoplasmic viscosity is only about 2–3 times that of water, and ubiquitous transient weak protein–protein interactions in the cytosol play a significant role in governing the detection of proteins by using in‐cell NMR spectroscopy.
Control of Exchange Interactions in π Dimers of 6‐Oxophenalenoxyl Neutral π Radicals: Spin‐Density Distributions and Multicentered–Two‐Electron Bonding Governed by Topological Symmetry and Substitution at the 8‐Position
Authors: Nishida Shinsuke , Kawai Junya , Moriguchi Miki , Ohba Tomohiro , Haneda Naoki , Fukui Kozo , Fuyuhiro Akira , Shiomi Daisuke , Sato Kazunobu , Takui Takeji , Nakasuji Kazuhiro , Morita Yasushi
Published: August 2013

The tri‐tert‐butylphenalenyl (TBPLY) radical exists as a π dimer in the crystal form with perfect overlapping of the singly occupied molecular orbitals (SOMOs) causing strong antiferromagnetic exchange interactions. 2,5‐Di‐tert‐butyl‐6‐oxophenalenoxyl (6OPO) is a phenalenyl‐based air‐stable neutral π radical with extensive spin delocalization and is a counter analogue of phenalenyl in terms of the topological symmetry of the spin density distribution. X‐ray crystal structure analyses showed that 8‐tert‐butyl‐ and 8‐(p‐XC6H4)‐6OPOs (X=I, Br) also form π dimers in the crystalline state. The π‐dimeric structure of 8‐tert‐butyl‐6OPO is seemingly similar to that of TBPLY even though its SOMO–SOMO overlap is small compared with that of TBPLY. The 8‐(p‐XC6H4) derivatives form slipped stacking π dimers in which the SOMO–SOMO overlaps are greater than in 8‐tert‐butyl‐6OPO, but still smaller than in TBPLY. The solid‐state electronic spectra of the 6OPO derivatives show much weaker intradimer charge‐transfer bands, and SQUID measurements for 8‐(p‐BrC6H4)‐6OPO show a weak antiferromagnetic exchange interaction in the π dimer. These results demonstrate that the control of the spin distribution patterns of the phenalenyl skeleton switches the mode of exchange interaction within the phenalenyl‐based π dimer. The formation of the relevant multicenter–two‐electron bonds is discussed.
Cyclisation versus 1,1‐Carboboration: Reactions of B(C6F5)3 with Propargyl Amides
Authors: Melen Rebecca L. , Hansmann Max M. , Lough Alan J. , Hashmi A. Stephen K. , Stephan Douglas W.
Published: August 2013

A series of propargyl amides were prepared and their reactions with the Lewis acidic compound B(C6F5)3 were investigated. These reactions were shown to afford novel heterocycles under mild conditions. The reaction of a variety of N‐substituted propargyl amides with B(C6F5)3 led to an intramolecular oxo‐boration cyclisation reaction, which afforded the 5‐alkylidene‐4,5‐dihydrooxazolium borate species. Secondary propargyl amides gave oxazoles in B(C6F5)3 mediated (catalytic) cyclisation reactions. In the special case of disubstitution adjacent to the nitrogen atom, 1,1‐carboboration is favoured as a result of the increased steric hindrance (1,3‐allylic strain) in the 5‐alkylidene‐4,5‐dihydrooxazolium borate species.
Copper‐Mediated Deoxygenative Trifluoromethylation of Benzylic Xanthates: Generation of a CCF3 Bond from an O‐Based Electrophile
Authors: Zhu Lingui , Liu Shasha , Douglas Justin T. , Altman Ryan A.
Published: August 2013

The conversion of an alcohol‐based functional group, into a trifluoromethyl analogue is a desirable transformation. However, few methods are capable of converting O‐based electrophiles into trifluoromethanes. The copper‐mediated trifluoromethylation of benzylic xanthates using Umemoto’s reagent as the source of CF3 to form CCF3 bonds is described. The method is compatible with an array of benzylic xanthates bearing useful functional groups. A preliminary mechanistic investigation suggests that the CCF3 bond forms by reaction of the substrate with in situ generated CuCF3 and CuOTf. Further evidence suggests that the reaction could proceed via a radical cation intermediate.
Fractional Countercurrent Crystallization for the Production of Highly Purified Pharmaceuticals
Authors: Temmel Erik , Wloch Sebastian , Müller Uwe , Grawe Detlef , Eilers Robert , Lorenz Heike , Seidel‐Morgenstern Andreas
Published: August 2013

Bei Verunreinigungen, die partielle feste Lösungen mit der Zielsubstanz bilden, sind bei der Aufreinigung gebräuchlichen Kristallisationsverfahren Grenzen gesetzt. Für dieses Problem stellt die fraktionierende Kristallisation eine Alternative dar. In diesem Beitrag soll die Anwendung einer Kristallisationskaskade zur Herstellung eines hochreinen Wirkstoffs gezeigt werden. Durch den ausschließlichen Transport flüssiger Phasen kann dieser Prozess automatisch betrieben, ein Gegenstrom zwischen den Phasen hergestellt und dadurch die Effizienz der fraktionierenden Kristallisation deutlich gesteigert werden. Es werden die Massenbilanzen für den mehrstufigen Prozess hergeleitet und die Ergebnisse von Simulationsstudien mit einer experimentellen Fallstudie verglichen.
Exceptional Adsorption and Separation Properties of the Molecular Sieve ZIF‐8
Authors: Böhme Ulrike , Paula Carolin , Reddy Marthala V. R. , Caro Jürgen , Hartmann Martin
Published: August 2013

Die Trennung von Olefin/Paraffin‐Gemischen erfolgt nach derzeitigem Stand der Technik durch Tieftemperaturrektifikation. Eine Alternative zu diesem energie‐ und kostenintensiven Verfahren könnte die Adsorption an mikroporösen Koordinationspolymeren sein. Insbesondere zeolithische Imidazolatnetzwerke, beispielsweise das hier untersuchte ZIF‐8, zeigen in dieser Hinsicht interessante Eigenschaften, da die Alkane gegenüber den Alkenen bevorzugt adsorbiert werden. Die im Rahmen dieser Arbeit aufgenommenen Reinstoffadsorptionsisothermen und Durchbruchsexperimente für C2‐ bis C4‐Kohlenwasserstoffe demonstrieren das Potenzial dieses Adsorbens für die Olefin/Paraffin‐Trennung.
Response to Dissociation Between Severity of Takotsubo Cardiomyopathy and Presentation With Shock or Hypotension
Authors: Yalcinkaya Emre , Celik Murat , Yuksel Uygar , Yildirim Erkan , Bugan Baris
Published: August 2013

Chong CR et al. Clin Cardiol. 2013;36:401–406
Resiliency of the plasma membrane and actin cortex to large‐scale deformation
Authors: Haase Kristina , Pelling Andrew E.
Published: August 2013

The tight coupling between the plasma membrane and actin cortex allows cells to rapidly change shape in response to mechanical cues and during physiological processes. Mechanical properties of the membrane are critical for organizing the actin cortex, which ultimately governs the conversion of mechanical information into signaling. The cortex has been shown to rapidly remodel on timescales of seconds to minutes, facilitating localized deformations and bundling dynamics that arise during the exertion of mechanical forces and cellular deformations. Here, we directly visualized and quantified the time‐dependent deformation and recovery of the membrane and actin cortex of HeLa cells in response to externally applied loads both on‐ and off‐nucleus using simultaneous confocal and atomic force microscopy. The local creep‐like deformation of the membrane and actin cortex depends on both load magnitude and duration and does not appear to depend on cell confluency. The membrane and actin cortex rapidly recover their initial shape after prolonged loading (up to 10 min) with large forces (up to 20 nN) and high aspect ratio deformations. Cytoplasmic regions surrounding the nucleus are shown to be more resistant to long‐term creep than nuclear regions. These dynamics are highly regulated by actomyosin contractility and an intact actin cytoskeleton. Results suggest that in response to local deformations, the nucleus does not appear to provide significant resistance or play a major role in cell shape recovery. The membrane and actin cortex clearly possess remarkable mechanical stability, critical for the transduction of mechanical deformation into long term biochemical signals and cellular remodeling. © 2013 Wiley Periodicals, Inc.
Effect of prophylactic cranial irradiation on survival in elderly patients with limited‐stage small cell lung cancer
Authors: Eaton Bree R. , Kim Sungjin , Marcus David M. , Prabhu Roshan , Chen Zhengjia , Ramalingam Suresh S. , Curran Walter J. , Higgins Kristin A.
Published: August 2013

BACKGROUND

Prophylactic cranial irradiation (PCI) improves survival in patients with limited‐stage small cell lung cancer (SCLC) who have a complete response to chemotherapy and radiotherapy, yet to the best of the authors' knowledge, data specific to the elderly population are lacking.

METHODS

Using the Surveillance, Epidemiology, and End Results (SEER) database, the authors identified 1926 patients aged ≥ 70 years who were diagnosed with limited‐stage SCLC between 1988 and 1997. Overall survival (OS) for patients who received PCI versus those who did not were estimated using the Kaplan‐Meier method and compared with the log‐rank test. A Cox proportional hazards model was further fitted to estimate the effect of PCI on OS after adjusting for age, race, sex, tumor size, lymph node status, stage of disease, and receipt of thoracic radiotherapy and surgery.

RESULTS

The median age of the patients was 75 years (range, 70 years‐94 years) and 138 patients (7.2 %) received PCI. The 2‐year and 5‐year OS rates were 33.3% (95% confidence interval [95% CI], 25.6%‐41.2%) and 11.6% (95% CI, 6.9%‐17.6%), respectively, among patients who received PCI versus 23.1% (95% CI, 21.2%‐25.1%) and 8.6% (95% CI, 7.3%‐9.9%), respectively, among patients who did not receive PCI (P = .028). On multivariable analysis, PCI was found to be an independent predictor of OS (hazards ratio, 0.72; 95% CI, 0.54‐0.97 [P = .032]). On subgroup analysis, PCI remained an independent predictor of OS among patients aged ≥ 75 years, but not among patients aged ≥ 80 years.

CONCLUSIONS

The receipt of PCI is associated with improved OS in patients aged ≥ 70 years with SCLC, suggesting that the benefit of PCI is maintained in the elderly population. Cancer 2013;119:3753–3760. © 2013 American Cancer Society.
Efficacy and safety profile of long‐term exposure to lenalidomide in patients with recurrent multiple myeloma
Authors: Fouquet Guillemette , Tardy Stéphanie , Demarquette Hélène , Bonnet Sarah , Gay Julie , Debarri Houria , Herbaux Charles , Guidez Stéphanie , Michel Jessica , Perrot Aurore , Serrier Caroline , Miljkovic Darko , Avet Loiseau Hervé , Facon Thierry , Hulin Cyrille , Leleu Xavier
Published: August 2013

BACKGROUND

Lenalidomide in combination with dexamethasone (Len/Dex) is indicated for patients with recurrent/refractory multiple myeloma (RRMM) who were treated with 1 prior therapy until evidence of disease progression. The objective of the current study was to determine the efficacy and safety profile of long‐term exposure to Len/Dex.

METHODS

A total of 50 patients with RRMM who were treated with long‐term Len for ≥ 2 years from 2 Intergroupe Francophone du Myélome (IFM) centers (Lille and Nancy) were included in the current study.

RESULTS

The median age of the patients was 58 years, with 30% of the patients aged > 65 years, 49% having an International Staging System stage of 2 and 3, 12% having severe renal insufficiency, and 8% demonstrating an adverse result on fluorescence in situ hybridization. Approximately 56% of the patients received treatment with Len/Dex for ≥ 3 years. The median duration of treatment with Len/Dex was 3 years (range, 2 years‐7 years). The response rates for partial response or better and very good partial response or better for the overall cohort were 96% and 74%, respectively, which is similar to patients exposed to Len for ≥ 3 years. With a median follow‐up of 4 years, 19 (38%) patients had stopped treatment with Len/Dex. The time to disease progression rate at 37 months was 78% and 91%, respectively, in patients exposed to Len for 2 years to < 3 years and for ≥ 3 years (P = 025). The safety profile was manageable, similar to that of Len when administered for a shorter period of time; 16% of patients had grade 3 to 4 neutropenia, 6% had thrombopenia, 6% had anemia, and 20% experienced thromboembolic events, all of venous type. The annual incidence rate of second primary malignancy was 1.96% in the current series.

CONCLUSIONS

The results of the current study confirmed that the Len/Dex combination is feasible for long‐term use in patients with RRMM, with a significant benefit noted in terms of time to disease progression for prolonged treatment with Len/Dex. Cancer 2013;119:3680–3686. © 2013 American Cancer Society.
Cost effectiveness of alternative strategies for incorporating bevacizumab into the primary treatment of ovarian cancer
Authors: Barnett Jason C. , Alvarez Secord Angeles , Cohn David E. , Leath Charles A. , Myers Evan R. , Havrilesky Laura J.
Published: August 2013

BACKGROUND

The objective of this study was to evaluate the comparative effectiveness of strategies that incorporated bevacizumab into the primary platinum‐based treatment of ovarian cancer: 1) no bevacizumab; 2) concurrent and maintenance bevacizumab for all; 3) bevacizumab for suboptimally debulked stage III and stage IV disease (high‐risk cohort); and the evaluation of an alternative exploratory strategy of 4) directed bevacizumab therapy based on a predictive test for bevacizumab responsiveness.

METHODS

A modified Markov state transition model with a 3‐year time horizon that simulated publically available International Collaboration on Ovarian Neoplasms (ICON7) trial outcomes was used to evaluate the cost effectiveness of each strategy. Costs and adverse events were incorporated. An alternative strategy was used to model the impact on overall survival of a genetic‐based predictive test. A Monte Carlo simulation simultaneously accounted for uncertainty in key parameters.

RESULTS

The incorporation of bevacizumab for high‐risk patients had an incremental cost‐effectiveness ratio of $168,000 per quality‐adjusted life‐year (QALY) saved compared with chemotherapy alone and dominated a strategy of giving bevacizumab to all patients with ovarian cancer. Monte Carlo simulation acceptability curves indicated that, at a willingness‐to‐pay threshold of $200,000 per QALY, the treatment of high‐risk women with bevacizumab was the strategy of choice in 84% of simulations. A predictive test had an incremental cost‐effectiveness ratio of $129,000 per QALY compared with chemotherapy alone and dominated other bevacizumab treatment strategies.

CONCLUSIONS

The selective treatment of women with suboptimal and/or stage IV ovarian cancer was a more cost‐effective use of bevacizumab than universal treatment but still did not fall within the limits of common willingness‐to‐pay thresholds. Continued investigation of potentially cost‐effective strategies, such as a predictive test, is necessary to optimize the use of this expensive treatment. Cancer 2013;119:3653–3661. © 2013 American Cancer Society.