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https://www.readbyqxmd.com/read/28819163/fusion-protein-analysis-reveals-the-precise-regulation-between-hsp70-and-hsp100-during-protein-disaggregation
#1
Sayaka Hayashi, Yosuke Nakazaki, Kei Kagii, Hiromi Imamura, Yo-Hei Watanabe
ClpB, a bacterial Hsp100, is a ring-shaped AAA+ chaperone that can reactivate aggregated proteins in cooperation with DnaK, a bacterial Hsp70, and its co-factors. ClpB subunits comprise two AAA+ modules with an interstitial rod-shaped M-domain. The M-domain regulates ClpB ATPase activity and interacts directly with the DnaK nucleotide-binding domain (NBD). Here, to clarify how these functions contribute to the disaggregation process, we constructed ClpB, DnaK, and aggregated YFP fusion proteins in various combinations...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811813/osteonecrosis-in-the-both-femoral-heads-in-a-patient-with-neuro-behcet-s-disease
#2
Asuman Orhan Varoglu, Asude Aksoy
Neuro-Behçet's disease (NBD) is a rare clinical entity that frequently presents neuro-psychiatric symptoms, and mesodiencephalic and pontobulbar lesions. There is only one published report about osteonecrosis in NBD. We report a patient whose first presentation was neurological NBD with presenting bilateral femoral heads osteonecrosis. A 36-year-old male was hospitalized with gait disorder, diplopia and speech disorder. The past medical history of the patient was unremarkable. The MR image showed mesencephalic lesion with oedemaas a hyperintense area...
May 2017: Pakistan Journal of Medical Sciences Quarterly
https://www.readbyqxmd.com/read/28808308/on-the-potential-alternate-binding-change-mechanism-in-a-dimeric-structure-of-pyruvate-phosphate-dikinase
#3
Daniel Ciupka, Holger Gohlke
The pyruvate phosphate dikinase (PPDK) reaction mechanism is characterized by a distinct spatial separation of reaction centers and large conformational changes involving an opening-closing motion of the nucleotide-binding domain (NBD) and a swiveling motion of the central domain (CD). However, why PPDK is active only in a dimeric form and to what extent an alternate binding change mechanism could underlie this fact has remained elusive. We performed unbiased molecular dynamics simulations, configurational free energy computations, and rigidity analysis to address this question...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801111/luminescence-resonance-energy-transfer-spectroscopy-of-atp-binding-cassette-proteins
#4
REVIEW
Maria E Zoghbi, Guillermo A Altenberg
The ATP-binding cassette (ABC) superfamily includes regulatory and transport proteins. Most human ABC exporters pump substrates out of cells using energy from ATP hydrolysis. Although major advances have been made toward understanding the molecular mechanism of ABC exporters, there are still many issues unresolved. During the last few years, luminescence resonance energy transfer has been used to detect conformational changes in real time, with atomic resolution, in isolated ABC nucleotide binding domains (NBDs) and full-length ABC exporters...
August 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28795601/poly-glutamic-dendrimer-based-conjugates-for-cancer-vaccination-a-computational-design-for-targeted-delivery-of-antigens
#5
L I F Moura, N Martinho, L C Silva, T S Barata, S Brocchini, H F Florindo, M Zloh
Computational techniques are useful to predict interaction models and molecular properties for the design of drug delivery systems, such as dendrimers. This work evaluated the impact of surface modifications of mannosamine-conjugated multifunctional poly(glutamic acid) (PG)-dendrimers as nanocarriers of the tumour associated antigens (TAA) MART-1, gp100:44 and gp100:209. Molecular dynamics simulations and docking studies were performed. Nitrobenzoxadiazole (NBD)-PG-G4-dendrimer displayed 64 carboxylic groups, however, the Frontier Molecular Orbital Theory study evidenced that only 32 of those were available to form covalent bonds...
August 10, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28768153/effects-of-mechanical-ventilation-on-gene-expression-profiles-in-renal-allografts-from-brain-dead-rats
#6
Maximilia C Hottenrott, Joerg Krebs, Paolo Pelosi, Thomas Luecke, Patricia R M Rocco, Carsten Sticht, Annette Breedijk, Benito Yard, Charalambos Tsagogiorgas
Pathophysiological changes of brain death (BD) are impairing distal organ function and harming potential renal allografts. Whether ventilation strategies influence the quality of renal allografts from BD donors has not been thoroughly studied. 28 adult male Wistar rats were randomly assigned to four groups: 1) no brain death (NBD) with low tidal volume/low positive endexpiratory pressure (PEEP) titrated to minimal static elastance of the respiratory system (LVT/OLPEEP); 2) NBD with high tidal volume/low PEEP (HVT/LPEEP); 3) brain death (BD) with LVT/OLPEEP; and 4) BD with HVT/LPEEP...
July 30, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28757552/effects-of-p-glycoprotein-on-the-transport-of-dl0410-a-potential-multifunctional-anti-alzheimer-agent
#7
Xiaocong Pang, Lin Wang, De Kang, Ying Zhao, Song Wu, Ai-Lin Liu, Guan-Hua Du
In our study, we attempted to investigate the influences of P-glycoprotein (P-gp) on DL0410, a novel synthetic molecule for Alzheimer's disease (AD) treatment, for intestinal absorption and blood-brain barrier permeability in vitro and related binding mechanisms in silico. Caco-2, MDCK, and MDCK-MDR1 cells were utilized for transport studies, and homology modelling of human P-gp was built for further docking study to uncover the binding mode of DL0410. The results showed that the apparent permeability (Papp) value of DL0410 was approximately 1 × 10(-6) cm/s, indicating the low permeability of DL0410...
July 25, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28755697/proteomic-and-biochemical-assays-of-glutathione-related-proteins-in-susceptible-and-multiple-herbicide-resistant-avena-fatua-l
#8
Erin E Burns, Barbara K Keith, Mohammed Y Refai, Brian Bothner, William E Dyer
Extensive herbicide usage has led to the evolution of resistant weed populations that cause substantial crop yield losses and increase production costs. The multiple herbicide resistant (MHR) Avena fatua L. populations utilized in this study are resistant to members of all selective herbicide families, across five modes of action, available for A. fatua control in U.S. small grain production, and thus pose significant agronomic and economic threats. Resistance to ALS and ACCase inhibitors is not conferred by target site mutations, indicating that non-target site resistance mechanisms are involved...
August 2017: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/28754691/the-hsp70-interdomain-linker-is-a-dynamic-switch-that-enables-allosteric-communication-between-two-structured-domains
#9
Charles A English, Woody Sherman, Wenli Meng, Lila M Gierasch
Hsp70 molecular chaperones play key roles in cellular protein homeostasis by binding to exposed hydrophobic regions of incompletely folded or aggregated proteins. This crucial Hsp70 function relies on allosteric communication between two well-structured domains: an N-terminal nucleotide-binding domain (NBD) and a C-terminal substrate-binding domain (SBD), which are tethered by an interdomain linker. ATP or ADP binding to the NBD alters the substrate-binding affinity of the SBD, triggering functionally essential cycles of substrate binding and release...
July 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28739255/wp1066-a-small-molecule-inhibitor-of-the-jak-stat3-pathway-inhibits-ceramide-glucosyltransferase-activity
#10
Hirotaka Tsurumaki, Hikaru Katano, Kousuke Sato, Ryou Imai, Satomi Niino, Yoshio Hirabayashi, Shinichi Ichikawa
WP1066 is a well-known inhibitor of the JAK/STAT3 signaling pathway. By a screen of known small molecule inhibitors of various enzymes and protein factors, we identified WP1066 as a ceramide glucosyltransferase inhibitor. Ceramide glucosyltransferase catalyzes the first glycosylation step during glycosphingolipid synthesis. We found that WP1066 inhibited the activity of ceramide glucosyltransferase with an IC50 of 7.2 μM, and that its action was independent of JAK/STAT3 pathway blockade. Moreover, the modes of inhibition of ceramide glucosyltransferase were uncompetitive with respect to both C6-NBD-cermide and UDP-glucose...
July 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28735752/conformational-changes-of-cftr-upon-phosphorylation-and-atp-binding
#11
Zhe Zhang, Fangyu Liu, Jue Chen
The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel evolved from an ATP-binding cassette transporter. CFTR channel gating is strictly coupled to phosphorylation and ATP hydrolysis. Previously, we reported essentially identical structures of zebrafish and human CFTR in the dephosphorylated, ATP-free form. Here, we present the structure of zebrafish CFTR in the phosphorylated, ATP-bound conformation, determined by cryoelectron microscopy to 3.4 Å resolution. Comparison of the two conformations shows major structural rearrangements leading to channel opening...
July 27, 2017: Cell
https://www.readbyqxmd.com/read/28728917/global-alteration-of-the-drug-binding-pocket-of-human-p-glycoprotein-abcb1-by-substitution-of-fifteen-conserved-residues-reveals-a-negative-correlation-between-substrate-size-and-transport-efficiency
#12
Shahrooz Vahedi, Eduardo E Chufan, Suresh V Ambudkar
P-glycoprotein (P-gp), an ATP-dependent efflux pump, is linked to the development of multidrug resistance in cancer cells. However, the drug-binding sites and translocation pathways of this transporter are not yet well-characterized. We recently demonstrated the important role of tyrosine residues in regulating P-gp ATP hydrolysis via hydrogen bond formations with high affinity modulators. Since tyrosine is both a hydrogen bond donor and acceptor, and non-covalent interactions are key in drug transport, in this study we investigated the global effect of enrichment of tyrosine residues in the drug-binding pocket on the drug binding and transport of P-gp...
July 17, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28722219/preparation-and-evaluation-of-tert-leucine-derivative-functionalized-polymeric-monoliths-for-micro-liquid-chromatography
#13
Meng Ruan, Qiqin Wang, Huihui Wu, Yuqiang Wang, Hai Han, Zhengjin Jiang
In the present study, a novel functional monomer N-[1-(α-naphthyl)ethylaminocarbonyl]-D-tert-leucine-[2-(methacryloyloxy)ethyl] amide (NA-D-tert-Leu-MA) was synthesized, and then employed to prepare polymeric monoliths (240 mm × 100 μm I.D.) functionalized with tert-leucine derivative through a single step thermo-initiated co-polymerization approach or a multi-step post-modification approach. The multi-step approach involves the post-modification of a thiol-containing monolith with NA-D-tert-Leu-MA via "thiol-ene" click reaction...
July 19, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28706615/novel-effects-of-traditional-wooden-toothbrush-on-bowel-motility-symptoms-in-spinal-cord-injury-patients-findings-from-a-pilot-quasi-experimental-study
#14
Ebrahim Esfandiari, Awat Feizi, Zahra Heidari, Seyed Reza Tabibian, Pooria Shaabani, Bijan Iraj, Payman Adibi, Amrollah Ebrahimi Varzaneh
BACKGROUND: The aim of this study was to investigate the therapeutic effect of traditional wooden toothbrush usage on most severe constipation, which usually occurs in spinal cord injury (SCI) patients. METHODS: In a quasi-experimental study, 61 SCI patients were selected who had injuries in different spinal levels (cervical, thoracic, and lumbar), and severe constipation from one defection in a few days to 3 weeks. They were recommended to use traditional wooden toothbrush for 5 min twice a day, after breakfast and dinner, over a 6 weeks period...
2017: International Journal of Preventive Medicine
https://www.readbyqxmd.com/read/28695900/reliability-validity-and-sensitivity-to-change-of-neurogenic-bowel-dysfunction-score-in-patients-with-spinal-cord-injury
#15
D Erdem, D Hava, P Keskinoğlu, Ç Bircan, Ö Peker, K Krogh, S Gülbahar
STUDY DESIGN: Psychometrics study. OBJECTIVES: The aim of this study is to investigate the validity, reliability and sensitivity to change of neurogenic bowel dysfunction (NBD) score. SETTING: Dokuz Eylül University Faculty of Medicine, Turkey. METHODS: The study included 42 patients with spinal cord injury (SCI). The reliability of NBD score was assessed by test-retest reliability and internal consistency. Cronbach's alpha coefficient was calculated to determine internal consistency...
July 11, 2017: Spinal Cord
https://www.readbyqxmd.com/read/28693733/a-fluorescent-dyad-with-large-emission-shift-for-discrimination-of-cysteine-homocysteine-from-glutathione-and-hydrogen-sulfide-and-the-application-of-bioimaging
#16
Xueling Yang, Longwei He, Kaixin Xu, Weiying Lin
Biothiols, as reactive sulfur species (RSS), play important roles in human physiology, and they have a close connection of generation and metabolism pathways among of them. It is challenging to discriminate biothiols from each other due to the similar chemical structures and properties of them. Herein, we develop a fluorescent hybrid dyad (CS-NBD) for efficiently discriminating cysteine (Cys)/homocysteine (Hcy) from glutathione (GSH) and hydrogen sulfide (H2S) by a dual-channel detection method. CS-NBD performs inherently no fluorescence in ranging from visible to near infrared region...
August 15, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28667859/global-concentration-additivity-and-prediction-of-mixture-toxicities-taking-nitrobenzene-derivatives-as-an-example
#17
Tong Li, Shu-Shen Liu, Rui Qu, Hai-Ling Liu
The toxicity of a mixture depends not only on the mixture concentration level but also on the mixture ratio. For a multiple-component mixture (MCM) system with a definite chemical composition, the mixture toxicity can be predicted only if the global concentration additivity (GCA) is validated. The so-called GCA means that the toxicity of any mixture in the MCM system is the concentration additive, regardless of what its mixture ratio and concentration level. However, many mixture toxicity reports have usually employed one mixture ratio (such as the EC50 ratio), the equivalent effect concentration ratio (EECR) design, to specify several mixtures...
June 28, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28661681/a-fluorescence-lifetime-imaging-microscopy-supported-investigation-on-temperature-dependent-penetration-of-dopamine-in-a-1-2-ditetradecanoyl-sn-glycero-3-phospho-1-rac-glycerol-lipid-bilayer
#18
Shrabanti Das, Pradipta Purkayastha
Distribution of dopamine, an essential neurotransmitter in mammalian central and peripheral nervous systems, in a lipid bilayer and at the surface of 1,2-ditetradecanoyl-sn-glycero-3-phospho-(1'-rac-glycerol) vesicles has been studied herein. To track the progress of dopamine through different regions of the lipid vesicle, these were synthesized using 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD)-labeled phospholipid molecules tagged to either the headgroup (NBDPE) or the acyl chain (NBDPG). Dopamine-induced quenching of NBD fluorescence in the lipid vesicles demonstrates that dopamine has a preference to diffuse into the lipid bilayer...
July 11, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28656651/convection-diffusion-layer-in-an-open-space-for-local-surface-treatment-and-microfabrication-using-a-four-aperture-microchemical-pen
#19
Sifeng Mao, Yong Zhang, Weifei Zhang, Hulie Zeng, Hizuru Nakajima, Jin-Ming Lin, Katsumi Uchiyama
A four-aperture microchemical pen was used to produce a stable convection-diffusion layer in an "open space" for microreactions and microfabrication. The process represents a new method for microreactions and microfabrication in a convection-diffusion layer. To prove the concept of a convection-diffusion layer in an "open space", bovine serum albumin was labeled with 4-fluoro-7-nitro-2,1,3-benzoxadiazole to confirm that the small convection-diffusion layer was effective for local surface treatment. To demonstrate the potential for microfabrication, silver patterns were fabricated on a glass surface with a convection-diffusion layer by using the silver-mirror reaction...
June 27, 2017: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
https://www.readbyqxmd.com/read/28652264/analysis-of-the-zar1-immune-complex-reveals-determinants-for-immunity-and-molecular-interactions
#20
Maël Baudin, Jana A Hassan, Karl J Schreiber, Jennifer D Lewis
Plants depend on innate immunity to prevent disease. Plant pathogenic bacteria, like Pseudomonas syringae and Xanthomonas campestris, use the type III secretion system as a molecular syringe to inject type III secreted effector (T3SE) proteins in plants. The primary function of most T3SEs is to suppress immunity; however, the plant can evolve nucleotide-binding domain-leucine-rich repeat domain-containing proteins to recognize specific T3SEs. The AtZAR1 NLR induces strong defense responses against P. syringae and X...
August 2017: Plant Physiology
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