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https://www.readbyqxmd.com/read/28820333/protease-dead-separase-inhibits-chromosome-segregation-and-rab-11-vesicle-trafficking
#1
Xiaofei Bai, Joshua N Bembenek
Separase cleaves cohesin to allow chromosome segregation. Separase also regulates cortical granule exocytosis and vesicle trafficking during cytokinesis, both of which involve RAB-11. We investigated whether separase regulates exocytosis through a proteolytic or non-proteolytic mechanism. In C. elegans, protease-dead separase (SEP-1(PD)::GFP) is dominant negative. Consistent with its role in cohesin cleavage, SEP-1(PD)::GFP causes chromosome segregation defects. As expected, partial depletion of cohesin rescues this defect, confirming that SEP-1(PD)::GFP acts through a substrate trapping mechanism...
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28820290/local-histone-acetylation-by-acss2-promotes-gene-transcription-for-lysosomal-biogenesis-and-autophagy
#2
Xinjian Li, Xu Qian, Zhimin Lu
Overcoming metabolic stress is a critical step in tumorigenesis. Acetyl coenzyme A (acetyl-CoA) converted from glucose or acetate is a substrate used for histone acetylation to regulate gene expression. However, how acetyl-CoA is produced under nutritional stress conditions is unclear. Herein we report that nutritional stress induces nuclear translocation of ACSS2 (acyl-CoA synthetase short-chain family member 2). This translocation is mediated by AMP-activated protein kinase (AMPK)-dependent ACSS2 Ser659 phosphorylation and subsequent exposure of the nuclear localization signal of ACSS2 to KPNA1/importin α5 for binding...
August 18, 2017: Autophagy
https://www.readbyqxmd.com/read/28819009/the-aaa-atpase-p97-a-cellular-multitool
#3
REVIEW
Lasse Stach, Paul S Freemont
The AAA+ (ATPases associated with diverse cellular activities) ATPase p97 is essential to a wide range of cellular functions, including endoplasmic reticulum-associated degradation, membrane fusion, NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation and chromatin-associated processes, which are regulated by ubiquitination. p97 acts downstream from ubiquitin signaling events and utilizes the energy from ATP hydrolysis to extract its substrate proteins from cellular structures or multiprotein complexes...
August 17, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28818689/sol-gel-derived-hydroxyapatite-films-over-porous-calcium-polyphosphate-substrates-for-improved-tissue-engineering-of-osteochondral-like-constructs
#4
Whitaik David Lee, Rahul Gawri, Robert M Pilliar, William L Stanford, Rita A Kandel
Integration of in vitro-formed cartilage on a suitable substrate to form tissue-engineered implants for osteochondral defect repair is a considerable challenge. In healthy cartilage, a zone of calcified cartilage (ZCC) act as an intermediary for mechanical force transfer from soft to hard tissue, as well as an effective interlocking structure to better resist interfacial shear forces. We have developed biphasic constructs that consist of scaffold-free cartilage tissue grown in vitro on, and interdigitated with, porous calcium polyphosphate (CPP) substrates...
August 14, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28818459/a-novel-delocalized-lipophilic-cation-chlorambucil-conjugate-inhibits-p-glycoprotein-in-hepg2-adm-cells
#5
Teng Liu, Yongbo Peng, Xiong Li, Lian Liu, Fang Liu, Leye He
Multidrug resistance (MDR) limits the application of a large number of cancer-fighting agents in clinical therapy. One reason is that P-glycoprotein (Pgp) efflux pumps are usually overexpressed and lead to drug efflux in the cancer cells, which limits the viability of many chemotherapeutics. Current available inhibitors which block the Pgp pump efflux are usually not widely used in clinical practice, because they change other drug pharmacokinetic profiles or increase side effects. Here, through covalent linkage of cancer-targeting delocalized lipophilic cation FF and DNA-damaging drug nitrogen mustard chlorambucil (CLB), we rationally designed and synthesized a tumor-targeting anticancer agent FFCLB...
August 4, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28817099/sintering-inhibition-of-silver-nanoparticle-films-via-agcl-nanocrystal-formation
#6
Thomas Öhlund, Magnus Hummelgård, Håkan Olin
Electrically conductive films are key components in most printed and flexible electronics applications. For the solution processing of conductive films, inks containing silver nanoparticles (AgNPs) remain important because of their relatively easy processing and generally low resistivity after a sintering procedure. Because the commonly used, moderate sintering temperatures of 150-300 °C are still too high for most low-cost flexible substrates, expanding the knowledge of surface-ink interactions that affect the sintering temperature is desirable...
August 17, 2017: Nanomaterials
https://www.readbyqxmd.com/read/28816437/selective-targeting-by-a-mechanism-based-inactivator-against-plp-dependent-enzymes-mechanisms-of-inactivation-and-alternative-turnover
#7
Romila Mascarenhas, Hoang V Le, Kenneth D Clevenger, Helaina J Lehrer, Dagmar Ringe, Neil L Kelleher, Richard B Silverman, Dali Liu
Potent mechanism-based inactivators can be rationally designed against PLP-dependent drug targets, such as ornithine aminotransferase (OAT) or γ-aminobutyric acid aminotransferase (GABA-AT). An important challenge, however, is the lack of selectivity towards other PLP-dependent off-target enzymes, because of similarities in mechanisms of all PLP-dependent aminotransferase reactions. On the basis of complex crystal structures, we investigate the inactivation mechanism of OAT, a hepatocellular carcinoma (HCC) target, by (1R,3S,4S)-3-amino-4-fluorocyclopentane-1-carboxylic acid (FCP), a known inactivator of GABA-AT...
August 17, 2017: Biochemistry
https://www.readbyqxmd.com/read/28816044/action-of-gold-nanospikes-based-nanoradiosensitizers-cellular-internalization-radiotherapy-and-autophagy
#8
Ningning Ma, Peidang Liu, Nongyue He, Ning Gu, Fu-Gen Wu, Zhan Chen
A major challenge to achieve effective X-ray radiation therapy is to use a relatively low and safe radiation dose. Various radiosensitizers, which can significantly enhance the radiotherapeutic performance, have been developed. Gold-based nanomaterials, as a new type of nanoparticle-based radiosensitizers, have been extensively used in researches involving cancer radiotherapy. However, the cancer therapeutic effect using the gold nanoparticle-based radiotherapy is usually not significant because of the low cellular uptake efficiency and the autophagy-inducing ability of these gold nanomaterials...
August 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28815420/road-map-for-the-structure-based-design-of-selective-covalent-hcv-ns3-4a-protease-inhibitors
#9
REVIEW
Letitia Shunmugam, Pritika Ramharack, Mahmoud E S Soliman
Over the last 2 decades, covalent inhibitors have gained much popularity and is living up to its reputation as a powerful tool in drug discovery. Covalent inhibitors possess many significant advantages including increased biochemical efficiency, prolonged duration and the ability to target shallow, solvent exposed substrate-binding domains. However, rapidly mounting concerns over the potential toxicity, highly reactive nature and general lack of selectivity have negatively impacted covalent inhibitor development...
August 16, 2017: Protein Journal
https://www.readbyqxmd.com/read/28815028/the-majority-of-hepatitis-c-patients-treated-with-direct-acting-antivirals-are-at-risk-for-relevant-drug-drug-interactions
#10
Elise J Smolders, Floor Ac Berden, Clara Tmm de Kanter, Wietske Kievit, Joost Ph Drenth, David M Burger
BACKGROUND: Direct-acting antivirals have improved treatment of chronic hepatitis C virus infection significantly. Direct-acting antivirals inhibit/induce and can also be substrates of drug-metabolising enzymes and transporters. This increases the risk for drug-drug interactions. OBJECTIVE: The purpose of this study was to predict drug-drug interactions with co-medication used by hepatitis C virus-infected patients. METHODS: We assembled a nationwide cohort of hepatitis C patients and collected cross-sectional data on co-medication use...
August 2017: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/28814953/in-vitro-characterization-of-jellyfish-venom-fibrin-ogen-olytic-enzymes-from-nemopilema-nomurai
#11
Seong Kyeong Bae, Hyunkyoung Lee, Yunwi Heo, Min Jung Pyo, Indu Choudhary, Chang Hoon Han, Won Duk Yoon, Changkeun Kang, Euikyung Kim
BACKGROUND: Because jellyfish are capable of provoking envenomation in humans, they are considered hazardous organisms. Although the effects of their toxins are a matter of concern, information on the venom components, biological activity and pathological mechanisms are still scarce. Therefore, the aim of the present study was to investigate a serine protease component of Nemopilema nomurai jellyfish venom (NnV) and unveil its characteristics. METHODS: To determine the relationship between fibrinolytic activity of NnV and the serine protease, fibrin zymography was performed using metalloprotease and serine protease inhibitors...
2017: Journal of Venomous Animals and Toxins Including Tropical Diseases
https://www.readbyqxmd.com/read/28814790/in-silico-investigation-of-a-kcnq1-mutation-associated-with-short-qt-syndrome
#12
Ismail Adeniran, Dominic G Whittaker, Aziza El Harchi, Jules C Hancox, Henggui Zhang
Short QT syndrome (SQTS) is a rare condition characterized by abnormally 'short' QT intervals on the ECG and increased susceptibility to cardiac arrhythmias and sudden death. This simulation study investigated arrhythmia dynamics in multi-scale human ventricle models associated with the SQT2-related V307L KCNQ1 'gain-of-function' mutation, which increases slow-delayed rectifier potassium current (IKs). A Markov chain (MC) model recapitulating wild type (WT) and V307L mutant IKs kinetics was incorporated into a model of the human ventricular action potential (AP) for investigation of QT interval changes and arrhythmia substrates...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28813525/is-the-detection-of-aquatic-environmental-dna-influenced-by-substrate-type
#13
Andrew S Buxton, Jim J Groombridge, Richard A Griffiths
The use of environmental DNA (eDNA) to assess the presence-absence of rare, cryptic or invasive species is hindered by a poor understanding of the factors that can remove DNA from the system. In aquatic systems, eDNA can be transported out either horizontally in water flows or vertically by incorporation into the sediment. Equally, eDNA may be broken down by various biotic and abiotic processes if the target organism leaves the system. We use occupancy modelling and a replicated mesocosm experiment to examine how detection probability of eDNA changes once the target species is no longer present...
2017: PloS One
https://www.readbyqxmd.com/read/28813014/antibacterial-properties-of-nonwoven-wound-dressings-coated-with-manuka-honey-or-methylglyoxal
#14
Sophie E L Bulman, Giuseppe Tronci, Parikshit Goswami, Chris Carr, Stephen J Russell
Manuka honey (MH) is used as an antibacterial agent in bioactive wound dressings via direct impregnation onto a suitable substrate. MH provides unique antibacterial activity when compared with conventional honeys, owing partly to one of its constituents, methylglyoxal (MGO). Aiming to investigate an antibiotic-free antimicrobial strategy, we studied the antibacterial activity of both MH and MGO (at equivalent MGO concentrations) when applied as a physical coating to a nonwoven fabric wound dressing. When physically coated on to a cellulosic hydroentangled nonwoven fabric, it was found that concentrations of 0...
August 16, 2017: Materials
https://www.readbyqxmd.com/read/28812348/inhibition-of-heterogeneous-ice-nucleation-by-bioinspired-coatings-of-polyampholytes
#15
Zhiyuan He, Liuchun Zheng, Zhenqi Liu, Shenglin Jin, Chuncheng Li, Jianjun Wang
Controlling of heterogeneous ice nucleation (HIN) on foreign surfaces is of great importance for anti-ice nucleation material design. In this work, we studied the HIN behaviors on various ion-modified poly(butylene succinate) (PBS) surfaces via chain-extension reaction. Inspired by antifreeze proteins (AFPs), the PBS-based polyampholytes, containing both negative and positive charge groups on a single chain, show excellent performance of ice nucleation inhibition and freezing delay. Unlike the extremely high price and low availability of AFPs, these PBS-based polyampholytes can be commercially synthesized under mild reaction conditions...
August 16, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28811636/mussel-inspired-polynorepinephrine-functionalized-electrospun-polycaprolactone-microfibers-for-muscle-regeneration
#16
Ying Liu, Guoqiang Zhou, Zhu Liu, Mengyu Guo, Xiumei Jiang, Mehmet Berat Taskin, Zhongyang Zhang, Jing Liu, Jinglong Tang, Ru Bai, Flemming Besenbacher, Menglin Chen, Chunying Chen
Electrospun scaffolds with excellent mechanical properties, high specific surface area and a commendable porous network are widely used in tissue engineering. Improving the hydrophilicity and cell adhesion of hydrophobic substrates is the key point to enhance the effectiveness of electrospun scaffolds. In this study, polycaprolactone (PCL) fibrous membranes with appropriate diameter were selected and coated by mussel-inspired poly norepinephrine (pNE). And norepinephrine is a catecholamine functioning as a hormone and neurotransmitter in the human brain...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811501/characterisation-of-sterol-biosynthesis-and-validation-of-14%C3%AE-demethylase-as-a-drug-target-in-acanthamoeba
#17
Scott Thomson, Christopher A Rice, Tong Zhang, RuAngelie Edrada-Ebel, Fiona L Henriquez, Craig W Roberts
The soil amoebae Acanthamoeba causes Acanthamoeba keratitis, a severe sight-threatening infection of the eye and the almost universally fatal granulomatous amoebic encephalitis. More effective treatments are required. Sterol biosynthesis has been effectively targeted in numerous fungi using azole compounds that inhibit the cytochrome P450 enzyme sterol 14α-demethylase. Herein, using Gas Chromatography Mass Spectrometry (GCMS), we demonstrate that the major sterol of Acanthamoeba castellanii is ergosterol and identify novel putative precursors and intermediate sterols in its production...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811357/autophagy-attenuates-endothelial-to-mesenchymal-transition-by-promoting-snail-degradation-in-human-cardiac-microvascular-endothelial-cells
#18
Jin Zou, Yanhua Liu, Bingong Li, Zeqi Zheng, Xuan Ke, Yanqin Hao, Xuelian Li, Xingxing Li, Fuyou Liu, Zhiyong Zhang
Endothelial-to-mesenchymal transition (EndMT) mainly exists in cardiovascular development and disease progression, and is well known to contribute to cardiac fibrosis. Recent studies indicated that autophagy also participates in the regulation of cardiac fibrosis. However, the precise role of autophagy in cardiac fibrosis and the underlying molecular mechanism remain unclear. This study aimed to explore the role of autophagy in EndMT, reveal the underlying molecular mechanism and seek new therapy for cardiac fibrosis...
August 15, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28810188/novel-tacrine-derivatives-exhibiting-improved-acetylcholinesterase-inhibition-design-synthesis-and-biological-evaluation
#19
Eeda Koti Reddy, Chandran Remya, Kumar Mantosh, Ayyiliath M Sajith, R V Omkumar, C Sadasivan, Shaik Anwar
A novel series of twenty four tacrine derivatives were designed and synthesised. Among these, thirteen were taken for the acetylcholinesterase (AChE) inhibition studies. Three compounds such as 4c, 6c and 6f were found to possess significant AChE inhibitory properties with IC50 values 12.97 ± 0.47 nM, 5.17 ± 0.24 nM and 7.14 ± 0.78 nM respectively. In silico docking studies revealed that these compounds can bind strongly in the active site of the enzyme and prevent enzyme-substrate interactions...
August 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28809437/the-conditional-stimulation-of-rat-organic-cation-transporter-2-but-not-its-human-ortholog-by-mesoridazine-the-possibility-of-the-involvement-of-the-high-affinity-binding-site-of-the-transporter-in-the-stimulation
#20
Sungwoo Hyung, Wonji Pyeon, Ji Eun Park, Yoo-Kyung Song, Suk-Jae Chung
OBJECTIVES: To study the functional consequences of the human and rat forms of OCT2 in the presence of phenothiazines. METHODS: MDCK cells expressing human or rat OCT2 were established, and MPP+ transport was determined by uptake assays. Concentration dependency was studied for the stimulatory/inhibitory effects of phenothiazines on MPP+ transport. KEY FINDINGS: Among the 11 phenothiazines examined, the majority were found to have comparable effects on transporter function between the orthologous forms, while three phenothiazines, particularly mesoridazine, had complex impacts on transporter function...
August 15, 2017: Journal of Pharmacy and Pharmacology
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