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Angelo Iannetelli, Graham Tizzard, Simon J Coles, Gareth R Owen
The sodium salt of a monosubstituted borohydride anion containing a 2-mercaptopyridyl unit (mp) is reported herein. This compound was coordinated to a rhodium(I) center providing the complex [Rh{κ3-H,H,S-H3B(mp)}(NBD)] (1) (where NBD = 2,5-norbornadiene) in which the boron-based ligand is coordinated to the rhodium center via the thione donor and two of the B-H bonds of the BH3 unit. Reaction of complex 1 with carbon monoxide results in the activation of the complex leading to the product of a formal intramolecular hydroboration reaction, where the NBD unit has, in effect, inserted into one of the B-H bonds...
December 8, 2017: Inorganic Chemistry
Stefan Petry, Lea Wenskowsky, Herman Schreuder, Volker Derdau, Hans Matter, Julia Volkmar, Till Opatz
A single high-affinity fatty acid binding site in the important human transport protein serum albumin (HSA) is identified and characterized using a NBD (7-nitrobenz-2-oxa-1,3-diazol-4-yl)-C12 fatty acid. This ligand exhibits a 1:1 binding stoichiometry in its HSA complex with high site-specificity. The complex dissociation constant is determined by titration experiments as well as radioactive equilibrium dialysis. Competition experiments with known HSA-binding drugs warfarin and ibuprofen confirm the new binding site to be different from Sudlow-sites I and II...
November 28, 2017: Angewandte Chemie
Verena C Schulze Greiving, Hans L de Boer, Johan G Bomer, Albert van den Berg, Séverine Le Gac
Combining high-resolution imaging and electrophysiological recordings is key for various types of experimentation on lipid bilayers and ion channels. Here, we propose an integrated biosensing platform consisting of a microfluidic cartridge and a dedicated chip-holder to conduct such dual measurements on suspended lipid bilayers, in a user-friendly manner. To illustrate the potential of the integrated platform, we characterize lipid bilayers in terms of thickness and fluidity while simultaneously monitoring single ion channel currents...
November 29, 2017: Electrophoresis
Nick Alderman, Claire Williams, Rodger Ll Wood
PRIMARY OBJECTIVE: Context is critical to the interpretation of measurement instruments that capture acquired brain injury (ABI) outcomes. Ratings reflect behaviours and abilities observed in a particular setting; it cannot be assumed that results are generalizable beyond these. This study explored the utility of a method to convey the impact of context-dependent support given on ratings of neurobehavioural disability (NBD) using the St Andrews-Swansea Neurobehavioural Outcome Scale (SASNOS)...
November 30, 2017: Brain Injury: [BI]
Longwei He, Xueling Yang, Kaixin Xu, Yunzhen Yang, Weiying Lin
A novel multifunctional logic gate based on a triple-chromophore (coumarin-NBD-flavylium, CNF) fluorescent biothiol probe with diverse fluorescence signal patterns was rationally designed and synthetized. On the new triad CNF, diverse logic operations such as OR, TRANSFER, INH, NOT, and YES logic gates were achieved by using biothiols and fluorescence signal patterns as the multiple inputs and outputs, respectively.
November 27, 2017: Chemical Communications: Chem Comm
Sen Zheng, Jun-Ichi Nagao, Mami Nishie, Takeshi Zendo, Kenji Sonomoto
Lantibiotic nukacin ISK-1 is produced by Staphylococcus warneri ISK-1. The dual functional transporter NukT, an ABC transporter maturation and secretion protein, contributes to cleavage of the leader peptide from the prepeptide (modified NukA) and the final transport of nukacin ISK-1. NukT consists of an N-terminal peptidase domain (PEP), a C-terminal nucleotide-binding domain (NBD), and a transmembrane domain (TMD). In this study, NukT and its peptidase-inactive mutant were expressed, purified, and reconstituted into liposomes for analysis of their peptidase and ATPase activities...
November 22, 2017: Applied Microbiology and Biotechnology
Mingjia Yu, Jianming Chen, Yongbo Bao, Jun Li
NF-κB signaling pathway is an evolutionarily conserved pathway that plays highly important roles in several developmental, cellular and immune response processes. With the recent release of the draft Pacific oyster (Crassostra gigas) genome sequence, we have sought to identify the various components of the NF-κB signaling pathway in these mollusks and investigate their gene structure. We further constructed phylogenetic trees to establish the evolutionary relationship of the oyster proteins with their homologues in vertebrates and invertebrates using BLASTX and neighbor-joining method...
November 18, 2017: Fish & Shellfish Immunology
Joe Bender, Jianwen Fang, Richard Simon
BACKGROUND: Drug resistance mediated by P-glycoprotein (P-gp) renders many cancer therapies ineffective. One P-gp substrate is the widely used chemotherapy drug paclitaxel. Co-administration of paclitaxel and another drug that inhibits P-gp may enhance the therapeutic effectiveness of paclitaxel by preventing its efflux from tumor cells. RESULTS: Here we present a computational approach that combines docking studies with mass action kinetic modeling to investigate how kinase inhibitors may inhibit P-gp mediated paclitaxel efflux...
November 21, 2017: BMC Systems Biology
Mercedes Nieves-Morión, Enrique Flores
Cyanobacteria are generally capable of photoautotrophic growth and are widely distributed on Earth. The model filamentous, heterocyst-forming strain Anabaena sp. PCC 7120 has been long considered a strict photoautotroph but is now known to be able to assimilate fructose. We have previously described two components of ABC glucoside uptake transporters from Anabaena that are involved in uptake of the sucrose analog esculin: GlsC (a nucleotide-binding domain subunit [NBD]) and GlsP (a transmembrane component [TMD])...
November 21, 2017: Environmental Microbiology Reports
Jiamin Wang, Linqiang Niu, Jing Huang, Zhijie Yan, Jianhong Wang
Biothiols, such as cysteine (Cys), homocysteine (Hcy) and glutathione (GSH), are involved in a number of biological processes and play crucial roles in biological systems. Thus, the detection of biothiols is highly important for early diagnosis of diseases and evaluation of disease progression. Herein, we developed a new turn-on fluorescent probe 1 based on 7-nitro-2,1,3-benzoxadiazole (NBD) with high selectivity and sensitivity for Cys/Hcy on account of nucleophilic substitution and Smiles rearrangement reaction...
October 28, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
John S Wiener, Kristina D Suson, Jonathan Castillo, Jonathan C Routh, Stacy Tanaka, Tiebin Liu, Elisabeth Ward, Judy Thibadeau, David Joseph, National Spina Bifida Patient Registry
INTRODUCTION: Advances in care have allowed most children with spina bifida (SB) to live to adulthood. The majority have neuropathic bowel dysfunction (NBD), resulting in constipation, incontinence, and diminished quality of life. We sought to 1) describe contemporary NBD management and continence outcomes of adults with SB; 2) describe differences from younger patients; and 3) assess for association with socio-economic factors. METHODS: We analyzed data on NBD management and continence from the National Spina Bifida Patient Registry (NSBPR)...
October 20, 2017: Journal of Pediatric Rehabilitation Medicine
Linan Xu, Weibin Gong, Sarah A Cusack, Huiwen Wu, Harriët M Loovers, Hong Zhang, Sarah Perrett, Gary W Jones
Hsp70 is a highly conserved chaperone that in addition to providing essential cellular functions and aiding in cell survival following exposure to a variety of stresses is also a key modulator of prion propagation. Hsp70 is composed of a nucleotide-binding domain (NBD) and substrate-binding domain (SBD). The key functions of Hsp70 are tightly regulated through an allosteric communication network that coordinates ATPase activity with substrate-binding activity. How Hsp70 conformational changes relate to functional change that results in heat shock and prion-related phenotypes is poorly understood...
November 9, 2017: Cellular and Molecular Life Sciences: CMLS
Ali Taylan, Merih Birlik
Parenchymal neuro-Behçet disease (NBD) is a serious clinic condition with a sub-acute or chronic disease course that results in incapability through pyramidal tract involvement. Though well-known consequences can deter a patient's life, both urinary symptoms and sexual dysfunction are underestimated complications of NBD and closely related in timing. Here, we report the case of a young male patient with parenchymal NBD who developed urinary incontinence and erectile dysfunction in addition to widespread pyramidal tract signs and symptoms...
November 7, 2017: Rheumatology International
Yuma Ishida, Yuka Okamoto, Yuta Matsuoka, Arisa Tada, Jindaporn Janprasit, Mayumi Yamato, Noppawan Phumala Morales, Ken-Ichi Yamada
Oxidized low density lipoprotein (Ox-LDL) is implicated in a variety of oxidative diseases. To clarify the mechanisms involved and facilitate the investigation of therapeutics, we previously developed a detection method for lipid-derived radicals using the fluorescent probe 2,2,6-trimethyl-6-pentyl-4-(4-nitrobenzo[1,2,5]oxadiazol-7-ylamino)piperidine-1-oxyl (NBD-Pen). In this study, NBD-Pen was used to detect lipid-derived radicals in Ox-LDL from in vitro and in vivo samples using an iron overloaded mouse model...
October 28, 2017: Free Radical Biology & Medicine
Yin Jiang, Guansheng Zheng, Ning Cai, Huatang Zhang, Yi Tan, Mengjiao Huang, Yonghe He, Jun He, Hongyan Sun
A facile fluorescent probe (NBD-DOP) has been developed to detect hypochlorous acid (HOCl) in this study. The probe consists of a NBD fluorophore and a dopamine moiety that reacts with HOCl specifically. The dopamine group quenches the fluorescence of NBD efficiently through a photoinduced electron transfer (PET) effect. Experimental data showed that NBD-DOP could detect HOCl with ultrafast response, high sensitivity and high selectivity in a wide pH range. The probe could also be used to detect the myeloperoxidase enzyme that produces HOCl...
November 3, 2017: Chemical Communications: Chem Comm
Daichi Murata, Hiroyuki Okano, Clement Angkawidjaja, Masato Akutsu, Shun-Ichi Tanaka, Kenyu Kitahara, Takuya Yoshizawa, Hiroyoshi Matsumura, Yuji Kado, Eiichi Mizohata, Tsuyoshi Inoue, Satoshi Sano, Yuichi Koga, Shigenori Kanaya, Kazufumi Takano
Serratia marcescens secretes a lipase, LipA, through a type I secretion system (T1SS). The T1SS for LipA, the Lip system, is composed of an inner membrane ABC transporter with its nucleotide-binding domains (NBD), LipB, a membrane fusion protein, LipC, and an outer membrane channel protein, LipD. Passenger protein secreted by this system has been functionally and structurally characterized well, but relatively little information about the transporter complex is available. Here, we report the crystallographic studies of LipC without the membrane anchor region, LipC-, and the NBD of LipB (LipB-NBD)...
November 10, 2017: Biochemistry
Vedagopuram Sreekanth, Nihal Medatwal, Sandeep Kumar, Sanjay Pal, Malyla Vamshikrishna, Animesh Kar, Priyanshu Bhargava, Aaliya Naaz, Nitin Kumar, Sagar Sengupta, Avinash Bajaj
Weakly basic drugs display poor solubility and tend to precipitate in the stomach's acidic environment causing reduced oral bioavailability. Tracing of these orally delivered therapeutic agents using molecular probes is challenged due to their poor absorption in the gastrointestinal tract (GIT). Therefore, we designed a gastric pH stable bile acid derived amphiphile where Tamoxifen (as a model anticancer drug) is conjugated to lithocholic acid derived phospholipid (LCA-Tam-PC). In vitro studies suggested the selective nature of LCA-Tam-PC for cancer cells over normal cells as compared to the parent drug...
November 9, 2017: Bioconjugate Chemistry
Han-I Yeh, Yoshiro Sohma, Katja Conrath, Tzyh-Chang Hwang
Cystic fibrosis (CF) is a channelopathy caused by loss-of-function mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a phosphorylation-activated and adenosine triphosphate (ATP)-gated chloride channel. In the past few years, high-throughput drug screening has successfully realized the first US Food and Drug Administration-approved therapy for CF, called ivacaftor (or VX-770). A more recent CFTR potentiator, GLPG1837 (N-(3-carbamoyl-5,5,7,7-tetramethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-2-yl)-1H-pyrazole-3-carboxamide), has been shown to exhibit a higher efficacy than ivacaftor for the G551D mutation, yet the underlying mechanism of GLPG1837 remains unclear...
October 27, 2017: Journal of General Physiology
Kang-Yang Jih, Wen-Ying Lin, Yoshiro Sohma, Tzyh-Chang Hwang
One major breakthrough in cystic fibrosis research in the past decade is the development of drugs that target the root cause of the disease-dysfunctional CFTR protein. One of the compounds, Ivacaftor or Kalydeco, which has been approved for clinical use since 2012, acts by promoting the gating function of CFTR. Our recent studies have led to a gating model that features energetic coupling between nucleotide-binding domain (NBD) dimerization and gate opening/closing in CFTR's transmembrane domains (TMDs). Based on this model, we showed that ATP analogs can enhance CFTR gating by facilitating NBD dimerization, whereas Ivacaftor works by stabilizing the open channel conformation of the TMDs...
November 5, 2017: Current Opinion in Pharmacology
Lukasz Wieteska, Saeid Shahidi, Anastasia Zhuravleva
BiP is the only Hsp70 chaperone in the endoplasmic reticulum (ER) and similar to other Hsp70s, its activity relies on nucleotide- and substrate-controllable docking and undocking of its nucleotide-binding domain (NBD) and substrate-binding domain (SBD). However, little is known of specific features of the BiP conformational landscape that tune BiP to its unique tasks and the ER environment. We present methyl NMR analysis of the BiP chaperone cycle that reveals surprising conformational heterogeneity of ATP-bound BiP that distinguishes BiP from its bacterial homologue DnaK...
October 24, 2017: ELife
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