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Debabrata Dhara, Pankaj Kalita, Subhadip Mondal, Ramakirushnan Suriya Narayanan, Kaustubh R Mote, Volker Huch, Michael Zimmer, Cem B Yildiz, David Scheschkewitz, Vadapalli Chandrasekhar, Anukul Jana
Diphosphene TerMes P = PTerMes ( 1 ; TerMes = 2,6-Mes2 C6 H3 ; Mes = 2,4,6-Me3 C6 H2 ) and NHCMe4 2 (NHCMe4 = 1,3,4,5-tetramethylimidazol-2-ylidene) exist in an equilibrium mixture with the NHCMe4 -coordinated diphosphene 3 . While uncoordinated 1 is inert to hydrolysis, the NHC adduct 3 readily undergoes hydrolysis to afford a phosphino-substituted phosphine oxide with the liberation of NHCMe4 . On this basis, conditions suitable for the catalytic use of NHCMe4 were identified. Similarly, while the hydrogenation of free diphosphene 1 with H3 N·BH3 is very slow, 3 reacts instantaneously with H3 N·BH3 at room temperature to afford a dihydrodiphosphane...
May 14, 2018: Chemical Science
Titel Jurca, Theresa Dellermann, Naomi E Stubbs, Diego A Resendiz-Lara, George R Whittell, Ian Manners
Precatalysts active for the dehydropolymerisation of primary amine-boranes are generally based on mid or late transition metal. We have found that the activity of the precatalyst system formed from CpR 2 TiCl2 and 2 n BuLi towards the dehydrogenation of the secondary amine-borane Me2 NH·BH3 , to yield the cyclic diborazane [Me2 N-BH2 ]2 , increases dramatically with increasing electron-donating character of the cyclopentadienyl rings (CpR ). Application of the most active precatalyst system (CpR = η-C5 Me5 ) to the primary amine-borane MeNH2 ·BH3 enabled the first synthesis of high molar mass poly( N -methylaminoborane), [MeNH-BH2 ] n , the BN analogue of polypropylene, by an early transition metal such as catalyst...
April 7, 2018: Chemical Science
Ziemowit Bańkosz, Sławomir Winiarski
The aim of this study was to determine the correlations between angular velocities in individual joints and racket velocity for different topspin forehand and backhand strokes in table tennis. Ten elite female table tennis players participated, presenting different kinds of topspin forehands and backhands - after a no-spin ball (FH1, BH1), after a backspin ball (FH2, BH2) and "heavy" topspin (FH3, BH3). Range of motion was measured with the BTS Smart-E (BTS Bioengineering, Milan, Italy) motion analysis system with a specially developed marker placement protocol for the upper body parts and an acoustic sensor attached to the racket to identify ball-racket contact...
June 2018: Journal of Sports Science & Medicine
Lanfei Feng, Snezana Vujicic, Michael E Dietrich, Natalia Litbarg, Suman Setty, Angelika Antoni, Joyce Rauch, Jerrold S Levine
The consequences of apoptosis extend beyond mere death of the cell. We have shown that receptor-mediated recognition of apoptotic target cells by viable kidney proximal tubular epithelial cells (PTECs) inhibits PTEC proliferation, growth, and survival. Here we tested the hypothesis that continual exposure to apoptotic targets can induce a phenotypic change in responding PTECs, as in other instances of natural selection. In particular, we demonstrate that repeated exposure to apoptotic targets leads to emergence of a PTEC line (denoted BU...
May 16, 2018: Journal of Biological Chemistry
Janet H Zheng, Christy R Grace, Cristina D Guibao, Dan E McNamara, Fabien Llambi, Yue-Ming Wang, Taosheng Chen, Tudor Moldoveanu
The effector B cell lymphoma-2 (BCL-2) protein BCL-2 ovarian killer (BOK) induces mitochondrial outer membrane permeabilization (MOMP) to initiate apoptosis upon inhibition of the proteasome. How BOK mediates MOMP is mechanistically unknown. The NMR structure of the BCL-2 core of human BOK reveals a conserved architecture with an atypical hydrophobic groove that undergoes conformational exchange. Remarkably, the BCL-2 core of BOK spontaneously associates with purified mitochondria to release cytochrome c in MOMP assays...
May 15, 2018: Cell Reports
Santiago Rodríguez-Jiménez, Alexis S Barltrop, Nicholas G White, Humphrey L C Feltham, Sally Brooker
Two isomeric pyrimidine-based Rdpt-type triazole ligands were made: 4-(4-methylphenyl)-3-(2-pyrimidyl)-5-phenyl-4 H-1,2,4-triazole (L2pyrimidine ) and 4-(4-methylphenyl)-3-(4-pyrimidyl)-5-phenyl-4 H-1,2,4-triazole (L4pyrimidine ). When reacted with [FeII (pyridine)4 (NCE)2 ], where E = S, Se, or BH3 , two families of mononuclear iron(II) complexes are obtained, including six solvatomorphs, giving a total of 12 compounds: [FeII (L2pyrimidine )2 (NCS)2 ] (1), [FeII (L2pyrimidine )2 (NCSe)2 ] (2), 2·1.5H2 O, [FeII (L2pyrimidine )2 (NCBH3 )2 ]·2CHCl3 (3·2CHCl3 ), 3 and 3·2H2 O, [FeII (L4pyrimidine )2 (NCS)2 ] (4), 4·H2 O, [FeII (L4pyrimidine )2 (NCSe)2 ] (5), 5·2CH3 OH, 5·1...
May 16, 2018: Inorganic Chemistry
Kyle Crassini, Yandong Shen, William S Stevenson, Richard Christopherson, Chris Ward, Stephen P Mulligan, O Giles Best
The survival and proliferation of chronic lymphocytic leukaemia (CLL) cells is driven by multiple signalling pathways, including those mediated by the B cell, Toll-like and chemokine receptors. Many of these pathways converge on the same signalling molecules, including those involved in the Raf-1/MEK/Erk1/2-MAPK pathway. We investigated the effects of the MEK1/2 (also termed MAP2K1/2) inhibitor, binimetinib, against CLL cells cultured under conditions that mimic aspects of the tumour microenvironment. Binimetinib blocked CLL cell survival induced by stroma-conditioned media and phorbol myristylate (PMA)...
May 16, 2018: British Journal of Haematology
Tian-Hua Yao, Parekejiang Pataer, Krishna Prasad Regmi, Xi-Wen Gu, Quan-Yan Li, Jing-Ting Du, Su-Meng Ge, Jun-Bo Tu
The use of propranolol for the treatment of infantile hemangioma (IH) has been widely investigated in recent years. However, the underlying therapeutic mechanism of propranolol for the treatment of IH remains poorly understood. The aim of the present study was to investigate the expression of proteins regulated by cellular tumor antigen p53 (p53) in associated apoptosis pathways in IH endothelial cells (HemECs) treated with propranolol. Furthermore, the present study aimed to investigate the exact apoptotic pathway underlying the therapeutic effect of propranolol against IH...
May 14, 2018: Molecular Medicine Reports
Clement Chung
PURPOSE: The relevance of apoptosis to cancer development and pharmacologic agents that target this pathway in selected malignancies are described. SUMMARY: Apoptosis is a tightly regulated biological process mediated by both proapoptotic (i.e., prodeath) and antiapoptotic (i.e., prosurvival) proteins. While apoptosis represents a well-established effector mechanism induced by conventional chemotherapy in many malignancies, the development of apoptosis-based targeted therapy is relatively new...
May 14, 2018: American Journal of Health-system Pharmacy: AJHP
Jingchao Wang, Danrui Cui, Shanshan Gu, Xiaoyu Chen, Yanli Bi, Xiufang Xiong, Yongchao Zhao
Apoptosis and autophagy mutually regulate various cellular physiological and pathological processes. The crosstalk between autophagy and apoptosis is multifaceted and complicated. Elucidating the molecular mechanism of their crosstalk will advance the therapeutic applications of autophagy for treating cancer and other diseases. NOXA, a BH3-only member of the BCL-2 family, was reported to induce apoptosis and promote autophagy. Here, we report that autophagy regulates apoptosis by targeting NOXA for degradation...
May 11, 2018: Biochimica et Biophysica Acta
Tianlin Liu, Juanxiu Qi, Binshen Wang, Yunhe Jin, Chao Yan, Yi Wang, Qinghua Zhang
The design and synthesis of new hypergolic ionic liquids (HILs) as replacements for toxic hydrazine derivatives have been the focus of current academic research in the field of liquid bipropellant fuels. In most cases, however, the requirements of excellent ignition performances, good hydrolytic stability, and low synthetic costs are often contradictory which make the development of high-performance HILs an enormous challenge. Here we show how a fuel-rich boranophosphate anion was rationally designed and used to synthesize a series of high-performance HILs with excellent comprehensive properties...
May 14, 2018: Chemistry: a European Journal
Corey J Ketchem, Cory Kucera, Aditya Barve, Levi J Beverly
BACKGROUND: Successful treatment of leukemia requires new medications to combat drug resistance, but the development of novel therapies is an arduous and risky endeavor. Repurposing currently approved drugs or those already in clinical development to treat other indications is a more practical approach. Moreover, combinatorial therapeutics are often more efficacious than single agent therapeutics because the former can simultaneously target multiple pathways that mitigate tumor aggressiveness and induce cancer cell death...
May 2018: American Journal of the Medical Sciences
Francisco Javier García-Rodríguez, Carmen Martínez-Fernández, David Brena, Dmytro Kukhtar, Xènia Serrat, Ernest Nadal, Mike Boxem, Sebastian Honnen, Antonio Miranda-Vizuete, Alberto Villanueva, Julián Cerón
Cisplatin and derivatives are commonly used as chemotherapeutic agents. Although the cytotoxic action of cisplatin on cancer cells is very efficient, clinical oncologists need to deal with two major difficulties: (i) the onset of resistance to the drug, and (ii) the cytotoxic effect in patients. Here we use Caenorhabditis elegans to investigate factors influencing the response to cisplatin in multicellular organisms. In this hermaphroditic model organism, we observed that sperm failure is a major cause in cisplatin-induced infertility...
May 10, 2018: Disease Models & Mechanisms
Cheng-Wei Chu, Ming-Chang Yang, Chia-Hua Chou, Wen-Sheng Huang, Bo-Xiu Hsiao, Yeng-Tseng Wang, Shean-Jaw Chiou, Joon-Khim Loh, Yi-Ren Hong
BH3 domains, classified initially as BCL2 homology domains, participate in both apoptosis and autophagy. Beclin‑1 contains a BH3 domain, which is required for binding to antiapoptotic BCL2 homologs and BCL2‑mediated inhibition of autophagy. BCL2‑like 12 (BCL2L12) also harbors a BH3‑like domain, which is 12 residues long and contains a LXXXAE/D motif. In a yeast two‑hybrid system performed in the present study, BCL2L12 shared similar binding partnerships to antiapoptotic BCL2 homologs, such as Beclin‑1...
May 11, 2018: International Journal of Molecular Medicine
Guilherme Fleury Perini, Glaciano Nogueira Ribeiro, Jorge Vaz Pinto Neto, Laura Tojeiro Campos, Nelson Hamerschlak
Disruption of the physiologic balance between cell proliferation and cell death is an important step of cancer development. Increased resistance to apoptosis is a key oncogenic mechanism in several hematological malignancies and, in many cases, especially in lymphoid neoplasias, has been attributed to the upregulation of BCL-2. The BCL-2 protein is the founding member of the BCL-2 family of apoptosis regulators and was the first apoptosis modulator to be associated with cancer. The recognition of the important role played by BCL-2 for cancer development and resistance to treatment made it a relevant target for therapy for many diseases, including solid tumors and hematological neoplasias...
May 11, 2018: Journal of Hematology & Oncology
Clare E Weeden, Casey Ah-Cann, Aliaksei Z Holik, Julie Pasquet, Jean-Marc Garnier, Delphine Merino, Guillaume Lessene, Marie-Liesse Asselin-Labat
Genetic alterations in the fibroblast growth factor receptors (FGFRs) have been described in multiple solid tumours including bladder cancer, head and neck and lung squamous cell carcinoma (SqCC). However, recent clinical trials showed limited efficacy of FGFR-targeted therapy in lung SqCC, suggesting combination therapy may be necessary to improve patient outcomes. Here we demonstrate that FGFR therapy primes SqCC for cell death by increasing the expression of the pro-apoptotic protein BIM. We therefore hypothesised that combining BH3-mimetics, potent inhibitors of pro-survival proteins, with FGFR-targeted therapy may enhance the killing of SqCC cells...
May 10, 2018: Oncogene
Yiru Zhang, Chiaki Tsuge Ishida, Chang Shu, Giulio Kleiner, Maria J Sanchez-Quintero, Elena Bianchetti, Catarina M Quinzii, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D Siegelin
Recent data suggest that glioblastomas (GBM) activate the c-MET signaling pathway and display increased levels in anti-apoptotic Bcl-2 family members. Therefore, targeting these two deregulated pathways for therapy might yield synergistic treatment responses. We applied extracellular flux analysis to assess tumor metabolism. We found that combined treatment with ABT263 and Crizotinib synergistically reduces the proliferation of glioblastoma cells, which was dependent on dual inhibition of Bcl-2 and Bcl-xL. The combination treatment led to enhanced apoptosis with loss of mitochondrial membrane potential and activation of caspases...
May 9, 2018: Scientific Reports
Damien Zanker, Kenneth Pang, Sara Oveissi, Chunni Lu, Pierre Faou, Cameron Nowell, George Williams Mbogo, Sebastian Carotta, Cathy Quillici, Guna Karupiah, Margaret Hibbs, Stephen L Nutt, Paul Neeson, Hamsa Puthalakath, Weisan Chen
The role of the immunoproteasome is perceived as confined to adaptive immune responses given its ability to produce peptides ideal for MHC Class-I binding. Here, we demonstrate that the immunoproteasome subunit, LMP2, has functions beyond its immunomodulatory role. Using LMP2-deficient mice, we demonstrate that LMP2 is crucial for lymphocyte development and survival in the periphery. Moreover, LMP2-deficient lymphocytes show impaired degradation of key BH3-only proteins, resulting in elevated levels of pro-apoptotic BIM and increased cell death...
May 8, 2018: Immunology and Cell Biology
M Angeles Alvarez, Melodie Casado-Ruano, M Esther García, Daniel García-Vivó, Miguel A Ruiz
The high unsaturation of the title complex enabled it to react with a wide variety of molecules under mild conditions, whereby the agostic methyl ligand underwent unusual or unprecedented processes. Methane elimination occurred in the reactions with PPh2H and SiPh2H2, this being followed in the latter case by Si-H bond oxidative addition to give the hydride silylene derivative [Mo2Cp2H(μ-PtBu2)(μ-SiPh2)(CO)]. Dehydrogenation, however, was the dominant process in the room temperature reaction with [Fe2(CO)9], to give the unsaturated methylidyne cluster [Mo2FeCp2(μ3-CH)(μ-PtBu2)(CO)5] (Mo-Mo = 2...
May 8, 2018: Chemistry: a European Journal
Bahriye Karakas, Yeliz Ozmay, Huveyda Basaga, Ozgur Gul, Ozgur Kutuk
Despite the development of novel targeted therapies, de novo or acquired chemoresistance remains a significant factor for treatment failure in breast cancer therapeutics. Neratinib and dacomitinib are irreversible panHER inhibitors, which block their autophosphorylation and downstream signaling. Moreover, neratinib and dacomitinib have been shown to activate cell death in HER2-overexpressing cell lines. Here we showed that increased MCL1 and decreased BIM and PUMA mediated resistance to neratinib in ZR-75-30 and SKBR3 cells while increased BCL-XL and BCL-2 and decreased BIM and PUMA promoted neratinib resistance in BT474 cells...
May 4, 2018: Biochimica et Biophysica Acta
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