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https://www.readbyqxmd.com/read/28646658/investigation-and-structural-elucidation-of-a-new-impurity-in-bulk-drug-of-cilostazol-by-lc-ms-ms-ft-ir-and-nmr
#1
Zhaoxia Hu, Sanguo Gao, Jue Gao
A new impurity was detected in bulk cilostazol (CIL) crude during routine analysis. The impurity (∼4%, the specification for unknown impurity in crude is not more than 0.20%) has a relative retention time of 1.46. Based on MS, NMR and IR spectral data, the impurity was identified as 6,6'-bis(4-(1-cyclohexyl-1H-tetrazol-5-yl) butoxy)-3,3',4,4'-tetrahydro-[7,7'-biquinoline]-2,2'(1H,1'H)-dione(CIL-dimer). The precursor of CIL-dimer is an oxidative product of starting material 6-Hydroxy-3,4-dyhydro-1H-quinolin-2-one(6-HQ), CIL-dimer was formed in the following reaction with 5-(3-Chloro-propyl)-1-cyclohexyl-1H-tetrazol(CHCBT)...
June 15, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28646414/dynamic-meso-scale-anchorage-of-gpi-anchored-receptors-in-the-plasma-membrane-prion-protein-vs-thy1
#2
Yuri L Nemoto, Roger J Morris, Hiroko Hijikata, Taka A Tsunoyama, Akihiro C E Shibata, Rinshi S Kasai, Akihiro Kusumi, Takahiro K Fujiwara
The central mechanism for the transmission of the prion protein misfolding is the structural conversion of the normal cellular prion protein to the pathogenic misfolded prion protein, by the interaction with misfolded prion protein. This process might be enhanced due to the homo-dimerization/oligomerization of normal prion protein. However, the behaviors of normal prion protein in the plasma membrane have remained largely unknown. Here, using single fluorescent-molecule imaging, we found that both prion protein and Thy1, a control glycosylphosphatidylinositol-anchored protein, exhibited very similar intermittent transient immobilizations lasting for a few seconds within an area of 24...
June 24, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28645916/structures-and-dynamics-of-hibernating-ribosomes-from-staphylococcus-aureus-mediated-by-intermolecular-interactions-of-hpf
#3
Iskander Khusainov, Quentin Vicens, Rustam Ayupov, Konstantin Usachev, Alexander Myasnikov, Angelita Simonetti, Shamil Validov, Bruno Kieffer, Gulnara Yusupova, Marat Yusupov, Yaser Hashem
In bacteria, ribosomal hibernation shuts down translation as a response to stress, through reversible binding of stress-induced proteins to ribosomes. This process typically involves the formation of 100S ribosome dimers. Here, we present the structures of hibernating ribosomes from human pathogen Staphylococcus aureus containing a long variant of the hibernation-promoting factor (SaHPF) that we solved using cryo-electron microscopy. Our reconstructions reveal that the N-terminal domain (NTD) of SaHPF binds to the 30S subunit as observed for shorter variants of HPF in other species...
June 23, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28645898/dna-pk-facilitates-piggybac-transposition-by-promoting-paired-end-complex-formation
#4
Yan Jin, Yaohui Chen, Shimin Zhao, Kun-Liang Guan, Yuan Zhuang, Wenhao Zhou, Xiaohui Wu, Tian Xu
The involvement of host factors is critical to our understanding of underlying mechanisms of transposition and the applications of transposon-based technologies. Modified piggyBac (PB) is one of the most potent transposon systems in mammals. However, varying transposition efficiencies of PB among different cell lines have restricted its application. We discovered that the DNA-PK complex facilitates PB transposition by binding to PB transposase (PBase) and promoting paired-end complex formation. Mass spectrometry analysis and coimmunoprecipitation revealed physical interaction between PBase and the DNA-PK components Ku70, Ku80, and DNA-PKcs Overexpression or knockdown of DNA-PK components enhances or suppresses PB transposition in tissue culture cells, respectively...
June 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28645115/a-comprehensive-review-of-heregulins-her3-and-her4-as-potential-therapeutic-targets-in-cancer
#5
REVIEW
Jose Mauricio Mota, Katharine Ann Collier, Ricardo Lima Barros Costa, Timothy Taxter, Aparna Kalyan, Caio A Leite, Young Kwang Chae, Francis J Giles, Benedito A Carneiro
Heregulins (HRGs) bind to the receptors HER3 or HER4, induce receptor dimerization, and trigger downstream signaling that leads to tumor progression and resistance to targeted therapies. Increased expression of HRGs has been associated with worse clinical prognosis; therefore, attempts to block HRG-dependent tumor growth have been pursued. This manuscript summarizes the function and signaling of HRGs and review the preclinical evidence of its involvement in carcinogenesis, prognosis, and treatment resistance in several malignancies such as colorectal cancer, non-small cell lung cancer, ovarian cancer, and breast cancer...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28644884/ligand-induced-rapid-skeletal-muscle-atrophy-in-hsa-fv2e-perk-transgenic-mice
#6
Masato Miyake, Masashi Kuroda, Hiroshi Kiyonari, Kenji Takehana, Satoshi Hisanaga, Masatoshi Morimoto, Jun Zhang, Miho Oyadomari, Hiroshi Sakaue, Seiichi Oyadomari
BACKGROUND: Formation of 43S and 48S preinitiation complexes plays an important role in muscle protein synthesis. There is no muscle-wasting mouse model caused by a repressed 43S preinitiation complex assembly. OBJECTIVE: The aim of the present study was to develop a convenient mouse model of skeletal muscle wasting with repressed 43S preinitiation complex assembly. MATERIAL AND METHODS: A ligand-activatable PERK derivative Fv2E-PERK causes the phosphorylation of eukaryotic initiation factor 2α (eIF2α), which inhibits 43S preinitiation complex assembly...
2017: PloS One
https://www.readbyqxmd.com/read/28644670/effective-forces-between-quantum-bound-states
#7
Alexander Rokash, Evgeny Epelbaum, Hermann Krebs, Dean Lee
Recent ab initio lattice studies have found that the interactions between alpha particles (^{4}He nuclei) are sensitive to seemingly minor details of the nucleon-nucleon force, such as interaction locality. In order to uncover the essential physics of this puzzling phenomenon without unnecessary complications, we study a simple model involving two-component fermions in one spatial dimension. We probe the interaction between two bound dimers for several different particle-particle interactions and measure an effective potential between the dimers using external point potentials which act as numerical tweezers...
June 9, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/28644649/role-of-a-neighbor-ion-in-the-fragmentation-dynamics-of-covalent-molecules
#8
A Méry, A N Agnihotri, J Douady, X Fléchard, B Gervais, S Guillous, W Iskandar, E Jacquet, J Matsumoto, J Rangama, F Ropars, C P Safvan, H Shiromaru, D Zanuttini, A Cassimi
Fragmentation of molecular nitrogen dimers (N_{2})_{2} induced by collision with low energy 90 keV Ar^{9+} ions is studied to evidence the influence of a molecular environment on the fragmentation dynamics of N_{2} cations. Following the capture of three or four electrons from the dimer, the three-body N_{2}^{+}+N^{m+}+N^{n+} [with (m,n)=(1,1) or (1, 2)] fragmentation channels provide clean experimental cases where molecular fragmentation may occur in the presence of a neighbor molecular cation. The effect of the environment on the fragmentation dynamics within the dimer is investigated through the comparison of the kinetic energy release (KER) spectra for these three-body channels and for isolated N_{2}^{(m+n)+} monomer cations...
June 9, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/28644618/exploring-new-assembly-modes-of-uranyl-terephthalate-templated-syntheses-and-structural-regulation-of-a-series-of-rare-2d-%C3%A2-3d-polycatenated-frameworks
#9
Lei Mei, Cong-Zhi Wang, Liu-Zheng Zhu, Zeng-Qiang Gao, Zhi-Fang Chai, John K Gibson, Wei-Qun Shi
The reaction of uranyl nitrate with terephthalic acid (H2TP) under hydrothermal conditions in the presence of an organic base, 1,3-(4,4'-bispyridyl)propane (BPP) or 4,4'-bipyridine (BPY), provided four uranyl terephthalate compounds with different entangled structures by a pH-tuning method. [UO2(TP)1.5](H2BPP)0.5·2H2O (1) obtained in a relatively acidic solution (final aqueous pH, 4.28) crystallizes in the form of a noninterpenetrated honeycomb-like two-dimensional network structure. An elevation of the solution pH (final pH, 5...
June 23, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28643533/evaluation-of-variation-in-coagulation-among-children-with-mycoplasma-pneumoniae-pneumonia-a-case-control-study
#10
Tianhua Li, Haiying Yu, Weina Hou, Zhiyong Li, Chunfang Han, Lihong Wang
Objective Acute organ embolism in children with Mycoplasma pneumoniae pneumonia (MPP) has been reported, but changes in coagulation are unclear. This study aimed to investigate changes in coagulation in children with MPP. Methods A total of 185 children with MMP (cases) and 117 healthy children (controls) were recruited. We measured prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and plasma fibrinogen (FIB) and D-dimer levels. Results Plasma FIB (3.39 ± 0.96 g/L vs 2...
January 1, 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28643414/associating-and-dissociating-nanodimer-analysis-for-quantifying-ultra-small-amounts-of-dna
#11
Keunsuk Kim, Jeong-Wook Oh, Young Kwang Lee, Jiwoong Son, Jwa-Min Nam
Amplification- and enzyme-free quantification of DNA at ultra-low concentrations, on the orders of 10-1,000 targets, is highly beneficial, but is extremely challenging. To address this challenge, true detection signals should be reliably discriminated from false or noise signals. Here, we developed the dynamically associating and dissociating nanodimer analysis (ADNA) method that allows for collecting maximum detection signals from true target-binding events while keeping nonspecific signals at minimum level...
June 23, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28643192/on-the-kinetics-of-body-versus-end-evaporation-and-addition-of-supramolecular-polymers
#12
Nitin S Tiwari, Paul van der Schoot
The kinetics of the self-assembly of supramolecular polymers is dictated by how monomers, dimers, trimers etc., attach to and detach from each other. It is for this reasons that researchers have proposed a plethora of pathways to explain the kinetics of various self-assembling supramolecules, including sulfur, linear micelles, living polymers and protein fibrils. Recent observations hint at the importance of a hitherto ignored molecular aggregation pathway that we refer to as "body evaporation and addition"...
June 2017: European Physical Journal. E, Soft Matter
https://www.readbyqxmd.com/read/28642369/replisome-mediated-translesion-synthesis-by-a-cellular-replicase
#13
Philip Nevin, Carolina C Gabbai, Kenneth J Marians
Genome integrity relies on the ability of the replisome to navigate ubiquitous DNA damage during DNA replication. The Escherichia coli replisome transiently stalls at leading-strand template lesions and can either reinitiate replication downstream of the lesion or recruit specialized DNA polymerases that can bypass the lesion via translesion synthesis. Previous results had suggested that the E. coli replicase might play a role in lesion bypass, but this possibility has not been tested in reconstituted DNA replication systems...
June 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28642239/a-novel-single-domain-antibody-against-von-willebrand-factor-a1-domain-resolves-leukocyte-recruitment-and-vascular-leakage-during-inflammation
#14
Gabriel Aymé, Frédéric Adam, Paulette Legendre, Amine Bazaa, Valérie Proulle, Cécile V Denis, Olivier D Christophe, Peter J Lenting
OBJECTIVE: von Willebrand factor (VWF) is crucial to hemostasis, but also plays a role in inflammatory processes. Unfortunately, no proper monoclonal antibodies to study VWF function in mice are currently available. We therefore aimed to generate single-domain antibodies (sdAbs) recognizing murine VWF and blocking its function in vivo. APPROACH AND RESULTS: Llama-derived sdAbs recognizing both human and murine VWF were isolated via phage display technology. One of them (designated KB-VWF-006) recognized the VWF A1 domain with picomolar affinity...
June 22, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28642126/molecular-and-hydrodynamic-properties-of-human-epidermal-growth-factor-receptor-her2-extracellular-domain-and-its-homodimer-experiments-and-multi-scale-simulations
#15
J F Vega, J Ramos, V Cruz, E Vicente-Alique, E Sánchez-Sánchez, A Sánchez-Fernández, Y Wang, P Hu, J Cortés, J Martínez-Salazar
BACKGROUND: In a broad range of human carcinomas gene amplification leads to HER2 overexpression, which has been proposed to cause spontaneous dimerization and activation in the absence of ligand. This makes HER2 attractive as a therapeutic target. However, the HER2 homodimerization mechanism remains unexplored. It has been suggested that the "back-to-back" homodimer does not form in solution. Notwithstanding, very recently the crystal structure of the HER2 extracellular domain homodimer formed with a "back-to-head" interaction has been resolved...
June 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28641682/health-effects-of-airline-cabin-environments-in-simulated-8-hour-flights
#16
(no author information available yet)
INTRODUCTION: Commercial air travel is usually without health incidents. However, there is a view that cabin environments may be detrimental to health, especially flights of 8 h or more. Concerns have been raised about deep vein thrombosis, upper respiratory tract infections, altitude sickness, and toxins from the engines. METHODS: Passenger cabin simulators were used to achieve a comparative observational study with 8-h flights at pressures equivalent to terrestrial altitudes of ground, 4000, 6000, and 8000 ft...
July 1, 2017: Aerospace Medicine and Human Performance
https://www.readbyqxmd.com/read/28641648/-change-of-thrombelastography-in-children-s-dic-and-analysis-of-its-sensitivity-and-specificity-for-diagnosis-of-dic
#17
Wen-Hao Yuan, Han-Chu Liu, Ling-Kong Zeng, Xiao-Yan Liu, Ling-Xia Zhao, Lu-Xia Mo
OBJECTIVE: To investigate the influence of thrombelastography index changes on its sensitivity and specificity for diagnosis of disseminated intravascular coagulation (DIC) in children. METHODS: A total of 149 children with DIC in our hospital from June 2013 to June 2016 were selected in DIC group, while 106 cases of non-DIC, including healthy children and children with diseases easily confused with DIC, were selected as non-DIC(control) group. The thrombelastography, D-dimer, coagulation functions including prothrombintime (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB) and fibin degradation product (FDP), congental coagulation disorders and platelet count were detected in DIC and non-DIC groups; the statistics of data was performed and the sensitivity and specificity of thromelastraphy indexes such as R time, α angle MA value and A value were evaluated; the relationship of DIC with indexes was analyzed...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28641567/biomarkers-in-acute-aortic-syndromes
#18
Mustafa Yildiz, Dogac Oksen, Michael Behnes, Ibrahim Akin
BACKGROUND: Acute aortic syndromes, being mostly underdiagnosed due to unspecific symptoms, are associated with high morbidity and mortality. Diagnosis carried out by transesophageal echocardiography, computed tomography and magnetic resonance imaging. However, there are lots of biochemical assays being investigated, but none of them used reliably to identify acute aortic syndromes. Biomarkers could accelerate the diagnostic time with cost effective way and could get place in definitive diagnostic algorithm of acute aortic syndrome...
June 14, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28641562/structural-characterization-of-amyloid-%C3%AE-17-42-dimer-by-potential-of-mean-force-analysis-insights-from-molecular-dynamics-simulations
#19
Mary Dutta, Rajkalyan Chutia, Venkata Satish Kumar Mattaparthi
Recent experiments with Amyloid β1-42 peptide have indicated that the initial dimerization of Aβ1-42 monomers to form amyloid dimers stand out as a key event in the generation of toxic oligomers. However, the structural characterization of Aβ1-42 dimer at the atomistic level and the dimerization mechanism by which Aβ1-42 peptides co-aggregate still remains not clear. In the present study, the process of Aβ17-42 peptide dimerization which is known to play an important role in the plaque formation was evaluated in terms of potential of mean force, which provided free energies along the reaction coordinates...
June 20, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28641463/a-new-dimeric-diarylpropane-from-horsfieldia-tetratepala
#20
Shou-Zhen Du, Fang Kuang, Ying Liu, Ye-Gao Chen, Rui Zhan
Five compounds, including a new dimeric diarylpropane, were isolated from the petroleum ether extract of the twigs and leaves of Horsfieldia tetratepala. The structures of these compounds were elucidated by spectroscopic analysis. Moreover, the antiproliferative activities of these compounds were tested on cancer cell lines, but none is active.
June 23, 2017: Natural Product Research
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