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https://www.readbyqxmd.com/read/28935856/sequence-controlled-supramolecular-terpolymerization-directed-by-specific-molecular-recognitions
#1
Takehiro Hirao, Hiroaki Kudo, Tomoko Amimoto, Takeharu Haino
Nature precisely manipulates primary monomer sequences in biopolymers. In synthetic polymer sequences, this precision has been limited because of the lack of polymerization techniques for conventional polymer synthesis. Engineering the primary monomer sequence of a polymer main chain represents a considerable challenge in polymer science. Here, we report the development of sequence-controlled supramolecular terpolymerization via a self-sorting behavior among three sets of monomers possessing mismatched host-guest pairs...
September 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28933554/rational-targeting-of-cellular-cholesterol-in-diffuse-large-b-cell-lymphoma-dlbcl-enabled-by-functional-lipoprotein-nanoparticles-a-therapeutic-strategy-dependent-on-cell-of-origin
#2
Jonathan S Rink, Shuo Yang, Osman Cen, Tim Taxter, Kaylin M McMahon, Sol Misener, Amir Behdad, Richard Longnecker, Leo I Gordon, C Shad Thaxton
Cancer cells have altered metabolism and, in some cases, an increased demand for cholesterol. It is important to identify novel, rational treatments based on biology, and cellular cholesterol metabolism as a potential target for cancer is an innovative approach. Toward this end, we focused on diffuse large B-cell lymphoma (DLBCL) as a model because there is differential cholesterol biosynthesis driven by B-cell receptor (BCR) signaling in germinal center (GC) versus activated B-cell (ABC) DLBCL. To specifically target cellular cholesterol homeostasis, we employed high-density lipoprotein-like nanoparticles (HDL NP) that can generally reduce cellular cholesterol by targeting and blocking cholesterol uptake through the high-affinity HDL receptor, scavenger receptor type B-1 (SCARB1)...
September 21, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28933287/modulation-of-abc-transporters-by-nuclear-receptors-physiological-pathological-and-pharmacological-aspects
#3
Juan Pablo Rigalli, Guillermo Nicolás Tocchetti, Johanna Weiss
ABC transporters are membrane proteins mediating the efflux of endo- and xenobiotics. Transporter expression is not static but instead is subject to a dynamic modulation aiming at responding to changes in the internal environment and thus at maintaining homeostatic conditions. Nuclear receptors are ligand modulated transcription factors that get activated upon changes in the intracellular concentrations of the respective agonists and bind to response elements within the promoter of ABC transporters, thus modulating their expression and, consequently, their activity...
September 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28931644/ufm1-founder-mutation-in-the-roma-population-causes-recessive-variant-of-h-abc
#4
Eline M C Hamilton, Enrico Bertini, Luba Kalaydjieva, Bharti Morar, Dana Dojčáková, Judy Liu, Adeline Vanderver, Julian Curiel, Claudia M Persoon, Daria Diodato, Lorenzo Pinelli, Nathalie L van der Meij, Barbara Plecko, Susan Blaser, Nicole I Wolf, Quinten Waisfisz, Truus E M Abbink, Marjo S van der Knaap
OBJECTIVE: To identify the gene defect in patients with hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) who are negative for TUBB4A mutations. METHODS: We performed homozygosity mapping and whole exome sequencing (WES) to detect the disease-causing variant. We used a Taqman assay for population screening. We developed a luciferase reporter construct to investigate the effect of the promoter mutation on expression. RESULTS: Sixteen patients from 14 families from different countries fulfilling the MRI criteria for H-ABC exhibited a similar, severe clinical phenotype, including lack of development and a severe epileptic encephalopathy...
September 20, 2017: Neurology
https://www.readbyqxmd.com/read/28931636/comparing-two-sequential-monte-carlo-samplers-for-exact-and-approximate-bayesian-inference-on-biological-models
#5
Aidan C Daly, Jonathan Cooper, David J Gavaghan, Chris Holmes
Bayesian methods are advantageous for biological modelling studies due to their ability to quantify and characterize posterior variability in model parameters. When Bayesian methods cannot be applied, due either to non-determinism in the model or limitations on system observability, approximate Bayesian computation (ABC) methods can be used to similar effect, despite producing inflated estimates of the true posterior variance. Owing to generally differing application domains, there are few studies comparing Bayesian and ABC methods, and thus there is little understanding of the properties and magnitude of this uncertainty inflation...
September 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28930692/palbociclib-in-hormone-receptor-positive-advanced-breast-cancer-a-cost-utility-analysis
#6
J Raphael, J Helou, K I Pritchard, D M Naimark
INTRODUCTION: The addition of palbociclib to letrozole improves progression-free survival in the first-line treatment of hormone receptor positive advanced breast cancer (ABC). This study assesses the cost-utility of palbociclib from the Canadian healthcare payer perspective. METHODS: A probabilistic discrete event simulation (DES) model was developed and parameterised with data from the PALOMA 1 and 2 trials and other sources. The incremental cost per quality-adjusted life-month (QALM) gained for palbociclib was calculated...
September 17, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28929558/total-synthesis-of-gracilamine-based-on-oxidative-phenolic-coupling-reaction-and-determination-of-its-absolute-configuration
#7
Kazuo Nagasawa, Minami Odagi, Yoshiharu Yamamoto
The Amaryllidaceae alkaloid (+)-gracilamine (1), isolated from Galanthus gracilis, contains a characteristic pentacyclic ring system with seven consecutive stereogenic centers, including an all-carbon quaternary stereocenter. Herein, we report the first enantioselective total synthesis of (+)-gracilamine (1), featuring a diastereoselective phenolic coupling reaction followed by a regioselective intramolecular aza-Michael reaction to construct the ABCE ring system. The stereochemistry at C3a in 1 is controlled by the stereocenter at C9a, which was selectively generated (91% ee) by utilizing an organocatalytic enantioselective aza-Friedel-Crafts reaction developed by our group...
September 19, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28928941/computational-design-of-molecular-motors-as-nanocircuits-in-leishmaniasis
#8
Dipali Kosey, Shailza Singh
Cutaneous leishmaniasis is the most common form of lesihmaniasis, caused by Leishmania major and is spread by the bite of a sandfly .This species infects the macrophages and dendritic cells Due to multi-drug resistance, there is a need for a new therapeutic technique. Recently, a novel molecular motor of Leishmania, Myosin XXI, was classified and characterized. In addition, the drug resistance in this organism has been linked with the overexpression of ABC transporters. Systems biology aims to study the simulation and modeling of natural biological systems whereas synthetic biology deals with building novel and artificial biological parts and devices  Together they have contributed enormously to drug discovery, vaccine design and development, infectious disease detection and diagnostics...
2017: F1000Research
https://www.readbyqxmd.com/read/28928869/hes1-promotes-colorectal-cancer-cell-resistance-to-5-fu-by-inducing-of-emt-and-abc-transporter-proteins
#9
Lei Sun, Jia Ke, Zhen He, Zexian Chen, Qinghua Huang, Wenjia Ai, Guoqiang Wang, Yisheng Wei, Xiangcai Zou, Shi Zhang, Ping Lan, Chuyuan Hong
Background and Aim: Hairy enhancer of split-1 (HES1) is a downstream transcriptional factor of Notch signaling pathway, which was found to be related to chemoresistance. This study was aimed to investigate the role of HES1 in chemoresistance of colorectal cancer (CRC). Methods: Tissue microarray was used to analyze the clinical significance of HES1 in radical resected (R0) stage II/III CRC patients that received adjuvant chemotherapy. 5-fluorouracil (5-Fu) chemoresistance was examined in CRC cell lines (RKO and HCT8, LOVO) with stable over-expression and inhibition of HES1 gene by cytotoxicity test...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28928319/effect-of-a-brief-smoking-cessation-intervention-on-adult-tobacco-smokers-with-pulmonary-tuberculosis-a-cluster-randomized-controlled-trial-from-north-india
#10
Sonu Goel, Jeyashree Kathiresan, Preeti Singh, Rana J Singh
BACKGROUND: An association between smoking and poor tuberculosis (TB) treatment outcomes has been globally established. Various smoking cessation interventions (SCIs) have been proven worldwide to curb smoking behavior. There is a need for evidence to assess if SCI increases the chance of successful treatment outcome among TB patients. OBJECTIVES: To assess the effectiveness of a brief SCI; The Ask, Brief, Cessation support (ABC) package, on treatment outcomes and smoking cessation in smear-positive adult pulmonary TB patients...
September 2017: Indian Journal of Public Health
https://www.readbyqxmd.com/read/28927344/structural-elucidation-of-transmembrane-domain-zero-tmd0-of-ecdl-a-multidrug-resistance-associated-protein-mrp-family-of-atp-binding-cassette-transporter-protein-revealed-by-atomistic-simulation
#11
Krishnendu Bera, Priyanka Rani, Gaurav Kishor, Shikha Agarwal, Antresh Kumar, Durg Vijay Singh
ATP-Binding cassette (ABC) transporters play an extensive role in the translocation of diverse sets of biologically important molecules across membrane. EchnocandinB (antifungal) and EcdL protein of Aspergillus rugulosus are encoded by the same cluster of genes. Co-expression of EcdL and echinocandinB reflects tightly linked biological functions. EcdL belongs to Multidrug Resistance associated Protein (MRP) subfamily of ABC transporters with an extra transmembrane domain zero (TMD0). Complete structure of MRP subfamily comprising of TMD0 domain, at atomic resolution is not known...
September 20, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28927230/multi-azole-resistant-strains-of-cryptococcus-neoformans-var-grubii-isolated-from-a-flz-resistant-strain-by-culturing-in-medium-containing-voriconazole
#12
Rui Kano, Miki Okubo, Atsuhiko Hasegawa, Hiroshi Kamata
A Cryptococcus neoformans var. grubii strain, NUBS14020, was the first fluconazole (FLZ)-resistant strain isolated from a feline cryptococcosis. Subsequent work demonstrated that multi-azole-resistant strains are readily isolated from FLZ-resistant strains by culturing in medium containing voriconazole (VRZ). The resulting clones were assessed for mutation and expression of known target genes, including the loci encoding lanosterol 14-α demethylase (ERG11), an ATP-binding cassette (ABC) transporter (AFR1), or a multidrug efflux pump (MEP); mutation and/or overexpression of these genes is known to be associated with azole resistance...
September 11, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/28927112/non-small-cell-lung-cancer-pc-9-cells-exhibit-increased-sensitivity-to-gemcitabine-and-vinorelbine-upon-acquiring-resistance-to-egfr-tyrosine-kinase-inhibitors
#13
Junko Hamamoto, Hiroyuki Yasuda, Kaito Aizawa, Makoto Nishino, Shigenari Nukaga, Toshiyuki Hirano, Ichiro Kawada, Katsuhiko Naoki, Tomoko Betsuyaku, Kenzo Soejima
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKIs) are widely used for the treatment of non-small cell lung cancers (NSCLCs) harboring EGFR-activating mutations. However, lung cancer cells inevitably acquire resistance to these EGFR-TKIs. The majority of patients whose lung cancer acquires resistance to EGFR-TKIs are subjected to treatment using cytotoxic agents. The present study aimed to determine if lung cancer cells acquiring resistance to EGFR-TKIs also develop altered sensitivity to cytotoxic agents...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927064/bortezomib-carfilzomib-and-ixazomib-do-not-mediate-relevant-transporter-based-drug-drug-interactions
#14
Jannick Clemens, Lukas Welti, Julia Schäfer, Anja Seckinger, Jürgen Burhenne, Dirk Theile, Johanna Weiss
In order to optimize the clinical application of an increasing number of proteasome inhibitors, investigations into the differences between their respective pharmacodynamic and pharmacokinetic profiles, including their ability to act as a perpetrator in drug-drug interactions, are warranted. Therefore, in the present in vitro study, it was investigated whether bortezomib, carfilzomib and ixazomib are able to alter the expression, and/or the activity, of specific drug transporters generally relevant for pharmacokinetic drug-drug interactions...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28923237/signals-that-drive-t-bet-expression-in-b-cells
#15
Arpita Myles, Patricia J Gearhart, Michael P Cancro
Transcription factors regulate various developmental and functional aspects of B cells. T-bet is a recently appreciated transcription factor associated with "Age-associated B cells" or ABCs, the development of autoimmunity, and viral infections. T-bet expression is favored by nucleic acid-containing antigens and immune complexes and is regulated by interplay between various cytokines, notably, the TFH cytokines IL-21, IL-4 and IFNγ. Adaptive signals by themselves cannot upregulate T-bet; however, they have a synergistic effect on induction of T-bet by innate receptors...
September 11, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28922502/the-three-component-system-esrisr-regulates-a-cell-envelope-stress-response-in-corynebacterium-glutamicum
#16
Britta Kleine, Ava Chattopadhyay, Tino Polen, Daniela Pinto, Thorsten Mascher, Michael Bott, Melanie Brocker, Roland Freudl
When the cell envelope integrity is compromised, bacteria trigger signaling cascades resulting in the production of proteins that counteract these extracytoplasmic stresses. Here, we show that the two-component system EsrSR regulates a cell envelope stress response in the Actinobacterium Corynebacterium glutamicum. The sensor kinase EsrS possesses an amino-terminal phage shock protein C (PspC) domain, a property that sets EsrSR apart from all other two-component systems characterized so far. An integral membrane protein, EsrI, whose gene is divergently transcribed to the esrSR gene locus and which interestingly also possesses a PspC domain, acts as an inhibitor of EsrSR under non-stress conditions...
September 18, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28922409/purification-and-characterisation-of-the-yeast-plasma-membrane-atp-binding-cassette-transporter-pdr11p
#17
Katrine Rude Laub, Magdalena Marek, Lyubomir Dimitrov Stanchev, Sara Abad Herrera, Tamara Kanashova, Adèle Bourmaud, Gunnar Dittmar, Thomas Günther Pomorski
The ATP binding cassette (ABC) transporters Pdr11p and its paralog Aus1p are expressed under anaerobic growth conditions at the plasma membrane of the yeast Saccharomyces cerevisiae and are required for sterol uptake. However, the precise mechanism by which these ABC transporters facilitate sterol movement is unknown. In this study, an overexpression and purification procedure was developed with the aim to characterise the Pdr11p transporter. Engineering of Pdr11p variants fused at the C terminus with green fluorescent protein (Pdr11p-GFP) and containing a FLAG tag at the N terminus facilitated expression analysis and one-step purification, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28922315/validation-of-fear-of-falling-and-balance-confidence-assessment-scales-in-persons-with-dystonia
#18
M J Boyce, L Lam, F Chang, N Mahant, V S C Fung, L Bradnam
BACKGROUND AND PURPOSE: Falls are problematic for people living with neurological disorders and a fear of falling can impact on actual falls. Fear of falling is commonly assessed using the Falls Self-Efficacy Scale International (FES-I) or the Activities-specific Balance Confidence (ABC) Scale. These scales can predict risk of falling. We aimed to validate the FES-I and the ABC in persons with dystonia. METHODS: We conducted an online survey of people with dystonia, collecting information on demographics, 6-month falls history, dystonia disability, and the FES-I and ABC scales...
October 2017: Journal of Neurologic Physical Therapy: JNPT
https://www.readbyqxmd.com/read/28922312/maximum-step-length-test-performance-in-people-with-parkinson-disease-a-cross-sectional-study
#19
Ryan P Duncan, Marie E McNeely, Gammon M Earhart
BACKGROUND AND PURPOSE: The Maximum Step Length Test (MSLT), a measure of one's capacity to produce a large step, has been studied in older adults, but not in people with Parkinson disease (PD). We characterized performance and construct validity of the MSLT in PD. METHODS: Forty participants (mean age: 65.12 ± 8.20 years; 45% female) with idiopathic PD completed the MSLT while "OFF" and "ON" anti-PD medication. Construct validity was investigated by examining relationships between MSLT and measures of motor performance...
October 2017: Journal of Neurologic Physical Therapy: JNPT
https://www.readbyqxmd.com/read/28921988/interaction-of-food-additives-with-intestinal-efflux-transporters
#20
Noora Sjöstedt, Feng Deng, Oskari Rauvala, Tuomas Tepponen, Heidi Kidron
Breast cancer resistance protein (BCRP), multidrug resistance associated protein 2 (MRP2) and P-glycoprotein (P-gp) are ABC transporters that are expressed in the intestine, where they are involved in the efflux of many drugs from enterocytes back into the intestinal lumen. The inhibition of BCRP, MRP2 and P-gp can result in the enhanced absorption and exposure of substrate drugs. Food additives are widely used by the food industry to improve the stability, flavor and consistency of food products. Although they are considered safe for consumption, their interactions with intestinal transporters are poorly characterized...
September 18, 2017: Molecular Pharmaceutics
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