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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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-flim-supported-investigation-on-temperature-dependent-penetration-of-dopamine-in-dmpg-lipid-bilayer
#7
Shrabanti Das, Pradipta Purkayastha
Distribution of dopamine, an essential neurotransmitter in mammalian central and peripheral nervous system, in lipid bilayer and at the surface of DMPG vesicles has been studied herein. To track the progress of dopamine through different regions of the lipid vesicle, the vesicles were synthesized using 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) labeled phospholipid molecules either tagged to the head group (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...
June 29, 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-micro-chemical-pen
#8
Sifeng Mao, Yong Zhang, Weifei Zhang, Hulie Zeng, Hizuru Nakajima, Jin-Ming Lin, Katsumi Uchiyama
A four-aperture micro chemical pen was used to produce a stable convection-diffusion layer in an "open space" for micro-reaction and microfabrication. The process represents a new method for micro-reactions and microfabrication in a convection-diffusion layer. To prove the concept of convection-diffusion layer in an "open space", bovine serum albumin (BSA) was labeled with 4-Fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) to confirm that the small convection-diffusion layer was effective for local surface treatment...
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
#9
Maël Baudin, Jana A Hassan, Karl 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 NBD-LRR domain-containing (NLR) proteins to recognize specific T3SEs. The AtZAR1 NLR induces strong defense responses against P. syringae and X. campestris. The P. syringae T3SE HopZ1a is an acetyltransferase that acetylates the pseudokinase AtZED1, and triggers recognition by AtZAR1...
June 26, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28650498/two-step-fret-mediated-metal-ion-induced-signalling-responses-in-a-probe-appended-with-three-fluorophores
#10
Biswonath Biswal, Ajoy Pal, Bamaprasad Bag
A tri-fluorophoric molecular probe (1) with three different derivatized fluorophores, i.e. anthracene (An), 7-nitrobenz-2-oxa-1,3-diazole (NBD) and rhodamine-B (Rh) appended on to a Tren [tris-(2-aminoethyl)amine] receptor was demonstrated to exhibit metal ion induced ratiometric fluorescence signalling through the initiation of a two-step fluorescence resonance energy transfer (FRET) process owing to a compatible and substantial spectral overlap of electronic absorption and fluorescence of initial donor-intermediate donor/acceptor-final acceptor pairs...
July 18, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28629562/3t-mr-defecography-a-feasibility-study-in-sensorimotor-complete-spinal-cord-injured-patients-with-neurogenic-bowel-dysfunction
#11
Cornelia Putz, Celine D Alt, Cornelia Hensel, Björn Wagner, Simone Gantz, Hans-Jürgen Gerner, Norbert Weidner, Lars Grenacher
INTRODUCTION: To investigate whether MR-defecography can be employed in sensorimotor complete spinal cord injury (SCI) subjects as a potential diagnostic tool to detect defecational disorders associated with neurogenic bowel dysfunction (NBD) using standard parameters for obstructed defecation. MATERIAL AND METHODS: In a prospective single centre clinical trial, we developed MR-defecography in traumatic sensorimotor complete paraplegic SCI patients with upper motoneuron type injury (neurological level of injury T1 to T10) using a conventional 3T scanner...
June 2017: European Journal of Radiology
https://www.readbyqxmd.com/read/28619991/evidence-that-differentiation-inducing-factor-1-controls-chemotaxis-and-cell-differentiation-at-least-in-part-via-mitochondria-in-d-discoideum
#12
Yuzuru Kubohara, Haruhisa Kikuchi, Van Hai Nguyen, Hidekazu Kuwayama, Yoshiteru Oshima
Differentiation-inducing factor-1 [1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)hexan-1-one (DIF-1)] is an important regulator of cell differentiation and chemotaxis in the development of the cellular slime mold Dictyostelium discoideum However, the entire signaling pathways downstream of DIF-1 remain to be elucidated. To characterize DIF-1 and its potential receptor(s), we synthesized two fluorescent derivatives of DIF-1, boron-dipyrromethene (BODIPY)-conjugated DIF-1 (DIF-1-BODIPY) and nitrobenzoxadiazole (NBD)-conjugated DIF-1 (DIF-1-NBD), and investigated their biological activities and cellular localization...
June 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28603639/folding-correction-of-abc-transporter-abcb1-by-pharmacological-chaperones-a-mechanistic-concept
#13
Matthias Spork, Muhammad Imran Sohail, Diethart Schmid, Gerhard F Ecker, Michael Freissmuth, Peter Chiba, Thomas Stockner
Point mutations of ATP-binding cassette (ABC) proteins are a common cause of human diseases. Available crystal structures indicate a similarity in the architecture of several members of this protein family. Their molecular architecture makes these proteins vulnerable to mutation, when critical structural elements are affected. The latter preferentially involve the two transmembrane domain (TMD)/nucleotide-binding domain (NBD) interfaces (transmission interfaces), formation of which requires engagement of coupling helices of intracellular loops with NBDs...
June 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28601781/cysteine-residues-244-and-458-459-within-the-catalytic-subunit-of-na-k-atpase-control-the-enzyme-s-hydrolytic-and-signaling-function-under-hypoxic-conditions
#14
Irina Yu Petrushanko, Vladimir A Mitkevich, Valentina A Lakunina, Anastasia A Anashkina, Pavel V Spirin, Peter M Rubtsov, Vladimir S Prassolov, Nikolay B Bogdanov, Pascal Hänggi, William Fuller, Alexander A Makarov, Anna Bogdanova
Our previous findings suggested that reversible thiol modifications of cysteine residues within the actuator (AD) and nucleotide binding domain (NBD) of the Na,K-ATPase may represent a powerful regulatory mechanism conveying redox- and oxygen-sensitivity of this multifunctional enzyme. S-glutathionylation of Cys244 in the AD and Cys 454-458-459 in the NBD inhibited the enzyme and protected cysteines' thiol groups from irreversible oxidation under hypoxic conditions. In this study mutagenesis approach was used to assess the role these cysteines play in regulation of the Na,K-ATPase hydrolytic and signaling functions...
May 31, 2017: Redox Biology
https://www.readbyqxmd.com/read/28598056/neuro-behcet-s-disease-presenting-as-a-young-stroke
#15
Nishit Biniwale, Rutuja Kibe, Avanti Biniwale
Neuro-Behcet's disease (NBD) is a rare neurological manifestation of the systemic small vessel vasculitis called Behcet's disease. It can present in various ways with predilection for the brain stem, thalamo- hypothalamic regions, cerebellum and basal ganglia. In this case, we describe a case of young stroke that was later attributed to NBD.
May 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/28592871/incorporation-of-fluorescence-ceramide-based-hplc-assay-for-rapidly-and-efficiently-assessing-glucosylceramide-synthase-in-vivo
#16
Sachin K Khiste, Salman B Hosain, Yixuan Dong, Mohammad B Uddin, Kartik R Roy, Ronald A Hill, Zhijun Liu, Yong-Yu Liu
Glucosylceramide synthase (GCS) is a rate-limiting enzyme catalyzing ceramide glycosylation, thereby regulating cellular ceramide levels and the synthesis of glycosphingolipids (GSLs) in cellular membranes. Alterations of GCS not only affect membrane integrity, but also closely correlate with stem cell pluripotency, cancer drug resistance, GSL storage disorders and other diseases. Enzyme activities measured conventionally with currently available ex-vivo methods do not enable reliable assessment of the roles played by GCS in vivo...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28588242/photoswitchable-phospholipid-fret-acceptor-detergent-free-intermembrane-transfer-assay-of-fluorescent-lipid-analogs
#17
Mariko Sumi, Asami Makino, Takehiko Inaba, Yasushi Sako, Fumihiro Fujimori, Peter Greimel, Toshihide Kobayashi
We have developed and characterized a novel photoswitchable phospholipid analog termed N-nitroBIPS-DPPG. The fluorescence can be switched on and off repeatedly with minimal photobleaching by UV or visible light exposure, respectively. The rather large photochromic head group is inserted deeply into the interfacial membrane region conferring a conical overall lipid shape, preference for a positive curvature and only minimal intermembrane transfer. Utilizing the switchable NBD fluorescence quenching ability of N-nitroBIPS-DPPG, a detergent free intermembrane transfer assay system for NBD modified lipids was demonstrated and validated...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28578011/homology-modeling-and-in-silico-prediction-of-ulcerative-colitis-associated-polymorphisms-of-nod1
#18
Ishani Majumdar, Isha Nagpal, Jaishree Paul
Cytosolic pattern recognition receptors play key roles in innate immune response. Nucleotide binding and oligomerisation domain containing protein 1 (NOD1) belonging to the Nod-like receptor C (NLRC) sub-family of Nod-like receptors (NLRs) is important for detection and clearance of intra-cellular Gram negative bacteria. NOD1 is involved in activation of pro-inflammatory pathways. Limited structural data is available for NOD1. Using different templates for each domain of NOD1, we determined the full-length homology model of NOD1...
May 31, 2017: Molecular and Cellular Probes
https://www.readbyqxmd.com/read/28570808/development-and-characterization-of-a-fluorescent-tracer-for-the-free-fatty-acid-receptor-2-ffa2-gpr43
#19
Anders Højgaard Hansen, Eugenia Sergeev, Sunil K Pandey, Brian D Hudson, Elisabeth Christiansen, Graeme Milligan, Trond Ulven
The free fatty acid receptor 2 (FFA2/GPR43) is considered a potential target for treatment of metabolic and inflammatory diseases. Here we describe the development of the first fluorescent tracer for FFA2 intended as a tool for assessment of thermodynamic and kinetic binding parameters of unlabeled ligands. Starting with a known azetidine FFA2 antagonist, we used a carboxylic acid moiety known not to be critical for receptor interaction as attachment point for a nitrobenzoxadiazole (NBD) fluorophore. This led to the development of 4 (TUG-1609), a fluorescent tracer for FFA2 with favorable spectroscopic properties and high affinity, as determined by bioluminescence resonance energy transfer (BRET)-based saturation and kinetic binding experiments, as well as a high specific to nonspecific BRET binding signal...
June 16, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28566962/impact-of-neuro-beh%C3%A3-et-disease-immunoglobulin-g-on-neuronal-apoptosis
#20
Murat Giriş, Sinem Bireller, Cem İsmail Küçükali, Haşmet Hanağasi, Sevgin Değirmencioğlu, Erdem Tüzün
INTRODUCTION: Parenchymal neuro-Behçet disease (NBD) is encountered in 5%-15% of Behçet disease (BD) patients and is characterized by inflammation of the brainstem and diencephalon structures. Neuronal apoptosis has been shown to participate in neuronal cell loss. Anti-neuronal antibodies have been identified in NBD patients. However, the pathogenic properties of these antibodies have not been studied. METHODS: To delineate the potential pathogenic activity of serum antibodies on neurons, pooled sera from seven NBD patients and seven healthy controls were divided into purified immunoglobulin G (IgG) and IgG-depleted serum fractions, and each fraction was administered to cultured SH-SY5Y neuroblastoma cells...
March 2017: Noro Psikiyatri Arsivi
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