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https://www.readbyqxmd.com/read/28213514/peripheral-membrane-interactions-boost-the-engagement-by-an-anti-hiv-1-broadly-neutralizing-antibody
#1
Edurne Rujas, José M M Caaveiro, Sara Insausti, Miguel García-Porras, Kouhei Tsumoto, José L Nieva
The 4E10 antibody displays an extreme breadth of HIV-1 neutralization and therefore constitutes a suitable model system for structure- guided vaccine design and immunotherapeutics against AIDS. In this regard, the relevance of auto- reactivity with membrane lipids for the biological function of this antibody is still a subject of controversy. To address this dispute, herein we have compared the membrane-partitioning ability of the 4E10 antibody and several of its variants, which were mutated at the region of the paratope surface in contact with the membrane-interface...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28183182/a-redox-active-fluorescent-ph-indicator-for-detecting-plasmodium-falciparum-strains-with-reduced-responsiveness-to-quinoline-antimalarial-drugs
#2
Mouhamad Jida, Cecilia P Sanchez, Karène Urgin, Katharina Ehrhardt, Saravanan Mounien, Aurelia Geyer, Mourad Elhabiri, Michael Lanzer, Elisabeth Davioud-Charvet
Mutational changes in the Plasmodium falciparum chloroquine resistance transporter (PfCRT) have been associated with differential responses to a wide spectrum of biologically active compounds including current and former quinoline and quinoline-like antimalarial drugs. PfCRT confers altered drug responsiveness by acting as a transport system, expelling drugs from the parasite's digestive vacuole where these drugs exert, at least part of, their antiplasmodial activity. To preserve the efficacy of these invaluable drugs, novel functional tools are required for epidemiological surveys of parasite strains carrying mutant PfCRT variants and for drug development programs aimed at inhibiting or circumventing the action of PfCRT...
February 10, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28115930/transanal-irrigation-for-refractory-chronic-idiopathic-constipation-patients-perceive-a-safe-and-effective-therapy
#3
Kevin J Etherson, Ian Minty, Iain M Bain, Jeremy Cundall, Yan Yiannakou
Background. Transanal irrigation (TAI) can successfully treat neurogenic bowel dysfunction (NBD), but patient perception of its use in chronic idiopathic constipation (CIC) is unknown. Objective. To evaluate patient perceptions of the efficacy and safety of TAI for CIC and whether there are predictive factors of perceived treatment response. Methods. Prospective data collection of baseline physiology and symptom severity; retrospective evaluation of efficacy and safety perceptions using a snapshot survey. All patients fulfilling the Rome III criteria for functional constipation with chronic idiopathic aetiology were included...
2017: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/28107182/the-nitrobenzoxadiazole-derivative-mc3181-blocks-melanoma-invasion-and-metastasis
#4
Anastasia De Luca, Debora Carpanese, Maria Cristina Rapanotti, Tara Mayte Suarez Viguria, Maria Antonietta Forgione, Dante Rotili, Chiara Fulci, Egidio Iorio, Luigi Quintieri, Sergio Chimenti, Luca Bianchi, Antonio Rosato, Anna Maria Caccuri
The novel nitrobenzoxadiazole (NBD) derivative MC3181 is endowed with remarkable therapeutic activity in mice bearing both sensitive and vemurafenib-resistant human melanoma xenografts. Here, we report that subtoxic concentrations of this compound significantly reduced invasiveness of BRAF-V600D mutated WM115 and WM266.4 melanoma cell lines derived from the primary lesion and related skin metastasis of the same patient, respectively. The strong antimetastatic activity of MC3181 was observed in both 2D monolayer cultures and 3D multicellular tumor spheroids, and confirmed in vivo by the significant decrease in the number of B16-F10 melanoma lung metastases in drug-treated mice...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28103530/an-anti-oxidant-%C3%AE-lipoic-acid-conjugated-oleoyl-sn-phosphatidylcholineas-a-helper-lipid-in-cationic-liposomal-formulations
#5
Priya Dharmalingam, Balakrishna Marrapu, Chandrashekhar Voshavar, Rasagna Nadella, Vignesh Kumar Rangasami, R V Shaji, Salar Abbas, R B N Prasad, Shiva Shanker Kaki, Srujan Marepally
Development of safe non-viral carrier systems for efficient intra-cellular delivery of drugs and genes hold promise in the area of translational research. Liposome based delivery systems have emerged as one of the attractive strategies for efficient delivery of drugs and nucleic acids. To this end, number of investigations was carried on liposomal formulations using lipids for achieving higher efficiency in transfection with lower cytotoxicities. In our efforts to develop safer and efficient liposomal delivery systems, we synthesized a novel anti-oxidant lipid, α-lipoyl, oleyl-sn-phosphatidylcholine (LOPC) and used as a helper lipid in combination with a cationic amphiphile, Di-Stearyl Dihydroxy Ethyl Ammonium Chloride (DSDEAC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) at varying concentrations of LOPC...
January 10, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28098307/a-ratiometric-fluorescence-probe-for-imaging-sulfur-dioxide-derivatives-in-the-mitochondria-of-living-cells
#6
Yongfei Wang, Qingtao Meng, Run Zhang, Hongmin Jia, Xuehu Zhang, Zhiqiang Zhang
Although sulfur dioxide (SO2) plays an essential role in several physiological processes, monitoring of intracellular SO2 at subcellular levels remains challenging due to the lack of rapid and sensitive methods for its quantification in a 100% aqueous solution. Herein, a new hemicyanine dyes-based fluorescence probe, NBD-Id, was designed and synthesized for the detection of SO2 derivatives in pure aqueous solution and living cells. By virtue of a specific 1,4-addition reaction of SO3(2-)HSO3(-) and the polymethine chain of hemicyanine, significant changes in the absorption and fluorescence emission spectra were observed in less than 20 seconds...
January 18, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28094889/selective-electrochemical-bleaching-of-the-outer-leaflet-of-fluorescently-labeled-giant-liposomes
#7
Ana Isabel Perez Jimenez, Lylian Challier, Eric Aït-Yahiatène, Jérôme Delacotte, Eric Labbé, Olivier Buriez
Electrochemistry and confocal fluorescence microscopy were successfully combined to selectively bleach and monitor the fluorescence of NBD (7-nitrobenz-2-oxa-1,3-diazole)-labeled phospholipids of giant liposomes. Three types of giant unilamellar vesicles have been investigated, the fluorescent phospholipids being localized either mainly on their outer-, inner-, or both inner/outer leaflets. We established that only the fluorescent lipids incorporated in the outer leaflet of the vesicles underwent electrochemical bleaching upon reduction...
January 17, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28092606/molecular-characterization-and-expression-analysis-of-the-nlr-family-card-containing-five-transcripts-in-the-pig
#8
Q Y Yang, T Chen, Y B Chen, D L Lan
The NOD-like receptor (NLR) family caspase recruitment domain-containing 5 (NLRC5) is one of the newly discovered and largest NLR family members. The NLRC5 has recently received extensive attention because of its important role in regulating innate and adaptive immune responses. The NLRC5 in many vertebrates, such as humans, mice, cattle, and horses, has already been proven and studied. However, the NLRC5 gene characteristics of pigs remain unclear. Thus, we completely cloned the NLRC5 cDNA sequence of the pig using the rapid amplification of cDNA ends(RACE) technology...
December 1, 2016: Polish Journal of Veterinary Sciences
https://www.readbyqxmd.com/read/28051765/exploring-conformational-equilibria-of-a-heterodimeric-abc-transporter
#9
M Hadi Timachi, Cedric Aj Hutter, Michael Hohl, Tufa Assafa, Simon Böhm, Anshumali Mittal, Markus A Seeger, Enrica Bordignon
ABC exporters pump substrates across the membrane by coupling ATP-driven movements of nucleotide binding domains (NBDs) to the transmembrane domains (TMDs), which switch between inward- and outward-facing (IF, OF) orientations. DEER measurements on the heterodimeric ABC exporter TM287/288 from Thermotoga maritima, which contains a non-canonical ATP binding site, revealed that in the presence of nucleotides the transporter exists in an IF/OF equilibrium. While ATP binding was sufficient to partially populate the OF state, nucleotide trapping in the pre- or post-hydrolytic state was required for a pronounced conformational shift...
January 4, 2017: ELife
https://www.readbyqxmd.com/read/28028694/a-new-model-of-flavonoids-affinity-towards-p-glycoprotein-genetic-algorithm-support-vector-machine-with-features-selected-by-a-modified-particle-swarm-optimization-algorithm
#10
Ying Cui, Qinggang Chen, Yaxiao Li, Ling Tang
Flavonoids exhibit a high affinity for the purified cytosolic NBD (C-terminal nucleotide-binding domain) of P-glycoprotein (P-gp). To explore the affinity of flavonoids for P-gp, quantitative structure-activity relationship (QSAR) models were developed using support vector machines (SVMs). A novel method coupling a modified particle swarm optimization algorithm with random mutation strategy and a genetic algorithm coupled with SVM was proposed to simultaneously optimize the kernel parameters of SVM and determine the subset of optimized features for the first time...
December 27, 2016: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28013220/potentiation-of-drug-induced-phospholipidosis-in-vitro-through-peglyated-graphene-oxide-as-the-nanocarrier
#11
Liecheng Yang, Xiaoyan Zhong, Qian Li, Xihui Zhang, Yangyun Wang, Kai Yang, Leshuai W Zhang
Cationic amphiphilic drugs (CADs) are small molecules that can induce phospholipidosis (PLD), causing the intracellular accumulation of phospholipid in the lamellar bodies. Nanotechnology based drug delivery systems have been used widely, while it is unknown if drug-induced PLD (DIP) can be potentiated through drug retention by indigestible nanocarriers. Due to the high drug loading capacity of graphene, we investigated if PEGylated graphene oxide (PEG-GO) loaded with CAD could potentiate DIP. Tamoxifen induced the accumulation of NBD-PE, a fluorescence labeled phospholipid in human hepatoma HepG2 cells, while PEG-GO loaded with tamoxifen (PEG-GO/tamoxifen) further potentiated PLD...
December 24, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28013030/interaction-of-e-coli-hsp90-with-dnak-involves-the-dnaj-binding-region-of-dnak
#12
Andrea N Kravats, Shannon M Doyle, Joel R Hoskins, Olivier Genest, Erin Doody, Sue Wickner
The 90-kDa heat shock protein (Hsp90) is a widely conserved and ubiquitous molecular chaperone that participates in ATP-dependent protein remodeling in both eukaryotes and prokaryotes. It functions in conjunction with Hsp70 and the Hsp70 cochaperones, an Hsp40 (J-protein) and a nucleotide exchange factor. In Escherichia coli, the functional collaboration between Hsp90Ec and Hsp70, DnaK, requires that the two chaperones directly interact. We used molecular docking to model the interaction of Hsp90Ec and DnaK...
December 21, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28011176/alkyl-substituted-phenylamino-derivatives-of-7-nitrobenz-2-oxa-1-3-diazole-as-uncouplers-of-oxidative-phosphorylation-and-antibacterial-agents-involvement-of-membrane-proteins-in-the-uncoupling-action
#13
Yuri N Antonenko, Stepan S Denisov, Ljudmila S Khailova, Pavel A Nazarov, Tatyana Rokitskaya, Vadim N Tashlitsky, Alexander M Firsov, Galina A Korshunova, Elena A Kotova
In search for new effective uncouplers of oxidative phosphorylation, we studied 4-aryl amino derivatives of a fluorescent group 7-nitrobenz-2-oxa-1,3-diazol (NBD). In our recent work (Denisov et al., Bioelectrochemistry, 2014), NBD-conjugated alkyl amines (NBD-Cn) were shown to exhibit uncoupling activity. It was concluded that despite a pKa value being about 10, the expected hindering of the uncoupling activity could be overcome by insertion of an alkyl chain. There is evidence in the literature that the introduction of an aryl substituent in the 4-amino NBD group shifts the pKa to neutral values...
December 21, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27994156/linking-parasite-populations-in-hosts-to-parasite-populations-in-space-through-taylor-s-law-and-the-negative-binomial-distribution
#14
Joel E Cohen, Robert Poulin, Clément Lagrue
The spatial distribution of individuals of any species is a basic concern of ecology. The spatial distribution of parasites matters to control and conservation of parasites that affect human and nonhuman populations. This paper develops a quantitative theory to predict the spatial distribution of parasites based on the distribution of parasites in hosts and the spatial distribution of hosts. Four models are tested against observations of metazoan hosts and their parasites in littoral zones of four lakes in Otago, New Zealand...
January 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27956761/nemo-binding-domain-peptide-attenuates-lipopolysaccharide-induced-acute-lung-injury-by-inhibiting-the-nf-%C3%AE%C2%BAb-signaling-pathway
#15
Jianhua Huang, Li Li, Weifeng Yuan, Linxin Zheng, Zhenhui Guo, Wenjie Huang
The aim of the present study is to investigate the protective effects and relevant mechanisms exerted by NEMO-binding domain peptide (NBD) against lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice. The ALI model was induced by intratracheally administered atomized LPS (5 mg/kg) to BABL/c mice. Half an hour before LPS administration, we treated the mice with increasing concentrations of intratracheally administered NBD or saline aerosol. Two hours after LPS administration, each group of mice was sacrificed...
2016: Mediators of Inflammation
https://www.readbyqxmd.com/read/27933796/structural-dynamics-of-the-heterodimeric-abc-transporter-tm287-288-induced-by-atp-and-substrate-binding
#16
Tadaomi Furuta, Yukiko Sato, Minoru Sakurai
TM287/288 is a heterodimeric ATP-binding cassette (ABC) transporter, which harnesses the energy of ATP binding and hydrolysis at the nucleotide-binding domains (NBDs) to transport a wide variety of molecules through the transmembrane domains (TMDs) by alternating inward- and outward-facing conformations. Here, we conducted multiple 100 ns molecular dynamics simulations of TM287/288 in different ATP- and substrate-bound states to elucidate the effects of ATP and substrate binding. As a result, the binding of two ATP molecules to the NBDs induced the formation of the consensus ATP-binding pocket (ABP2) or the NBD dimerization, whereas these processes did not occur in the presence of a single ATP molecule or when the protein was in its apo state...
December 6, 2016: Biochemistry
https://www.readbyqxmd.com/read/27917812/nasobiliary-drainage-for%C3%A2-benign-recurrent-intrahepatic-cholestasis%C3%A2-in-patients-refractory-to-standard-therapy
#17
Tolga Yakar, Mehmet Demir, Huseyin S Gokturk, Ayse G Unler Kanat, Alper Parlakgumus, Birol Ozer, Ender Serin
PURPOSE: Benign recurrent intrahepatic cholestasis (BRIC) is characterized by episodic cholestasis and pruritus without anatomical obstruction. The aim of this study was to evaluate the safety and efficacy of nasobiliary drainage (NBD) in patients with BRIC refractory to medical therapy and to determine whether the use of NBD prolongs the episode duration. METHODS: This was a multicenter retrospective study consisting of 33 patients suffering from BRIC. All patients were administrated medical treatment and 16 patients who were refractory to standard medical therapies improved on treatment with temporary endoscopic NBD...
1, 2016: Clinical and Investigative Medicine. Médecine Clinique et Experimentale
https://www.readbyqxmd.com/read/27914246/tract-based-analysis-of-white-matter-integrity-in-psychotic-and-nonpsychotic-bipolar-disorder
#18
Andrew Ji, Douglass Godwin, Jerrel Rutlin, Sridhar Kandala, Joshua S Shimony, Daniel Mamah
BACKGROUND: At least 50% of individuals with bipolar disorder (BD) present with psychosis during their lifetime. Psychotic symptoms have sometimes been linked to specific genetic and phenotypic markers. This study aims to explore potential differences between bipolar disorder subtypes by measuring white matter integrity of the brain and relationships with clinical measures. METHODS: Diffusion tensor imaging and clinical measures were acquired from 102 participants, grouped as psychotic bipolar disorder (PBD) (n=48), non-psychotic bipolar disorder (NBD) (n=24), and healthy controls (n=30)...
February 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/27912062/atomic-structure-of-the-cystic-fibrosis-transmembrane-conductance-regulator
#19
Zhe Zhang, Jue Chen
The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel evolved from the ATP-binding cassette (ABC) transporter family. In this study, we determined the structure of zebrafish CFTR in the absence of ATP by electron cryo-microscopy to 3.7 Å resolution. Human and zebrafish CFTR share 55% sequence identity, and 42 of the 46 cystic-fibrosis-causing missense mutational sites are identical. In CFTR, we observe a large anion conduction pathway lined by numerous positively charged residues...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27908240/new-fluorescent-macrolide-derivatives-for-studying-interactions-of-antibiotics-and-their-analogs-with-the-ribosomal-exit-tunnel
#20
A G Tereshchenkov, A V Shishkina, V V Karpenko, V A Chertkov, A L Konevega, P S Kasatsky, A A Bogdanov, N V Sumbatyan
Novel fluorescent derivatives of macrolide antibiotics related to tylosin bearing rhodamine, fluorescein, Alexa Fluor 488, BODIPY FL, and nitrobenzoxadiazole (NBD) residues were synthesized. The formation of complexes of these compounds with 70S E. coli ribosomes was studied by measuring the fluorescence polarization depending on the ribosome amount at constant concentration of the fluorescent substance. With the synthesized fluorescent tylosin derivatives, the dissociation constants for ribosome complexes with several known antibiotics and macrolide analogs previously obtained were determined...
October 2016: Biochemistry. Biokhimii︠a︡
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