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https://www.readbyqxmd.com/read/27910743/decoding-the-polyphyletic-flexibility-of-allosteric-modular-networks-progress-and-perspectives
#1
Yanan Yu, Zhong Wang, Yongyan Wang
Advances in identifying architecture of modules and elucidating their modes of action are gradually improving the decoding of complex relationships between phenotypic robustness and genotypic networks. However, approaches to detecting modules have largely focused on identifying modules in static graphs. In this review, we attempt to reveal the mechanism of polyphyletic architectural transformation based on modular boundary evolutions and different oscillating factors. With the rapid progress in probing into the detailed structural model of modular networks, flexible modular organization manifests a key adaptive balancing ability of allosterically regulating or reconstructing intermodular and intramodular states to uncover the novel biological alterations beyond engineering properties...
2016: Critical Reviews in Eukaryotic Gene Expression
https://www.readbyqxmd.com/read/27909846/benzimidazole-inhibitors-of-protein-kinase-ck2-potently-inhibit-the-activity-of-atypical-protein-kinase-rio1
#2
Konrad Kubiński, Maciej Masłyk, Andrzej Orzeszko
Benzimidazole derivatives of 5,6-dichlorobenzimidazole 1-β-D-ribofuranoside (DRB) comprise the important class of protein kinase CK2 inhibitors. Depending on the structure, benzimidazoles inhibit CK2 with different selectivity and potency. Besides CK2, the compounds can inhibit, with similar activity, other classical eukaryotic protein kinases (e.g. PIM, DYRK, and PKD). The present results show that a majority of the most common CK2 inhibitors can affect the atypical kinase Rio1 in a nanomolar range. Kinetic data confirmed the mode of action of benzimidazoles as typical ATP-competitive inhibitors...
December 1, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27909235/a-simple-and-sensitive-high-content-assay-for-the-characterization-of-antiproliferative-therapeutic-antibodies
#3
Andreas Stengl, David Hörl, Heinrich Leonhardt, Jonas Helma
Monoclonal antibodies (mAbs) have become a central class of therapeutic agents in particular as antiproliferative compounds. Their often complex modes of action require sensitive assays during early, functional characterization. Current cell-based proliferation assays often detect metabolites that are indicative of metabolic activity but do not directly account for cell proliferation. Measuring DNA replication by incorporation of base analogues such as 5-bromo-2'-deoxyuridine (BrdU) fills this analytical gap but was previously restricted to bulk effect characterization in enzyme-linked immunosorbent assay formats...
December 1, 2016: Journal of Biomolecular Screening
https://www.readbyqxmd.com/read/27908417/biphasic-action-of-iodine-in-excess-at-different-doses-on-ovary-in-adult-rats
#4
Dakshayani Mahapatra, Amar K Chandra
Iodine consumption in excess of its recommended levels over a prolonged period of time is well known to cause thyroid disorders. The thyroid hormones on the other hand are responsible in maintenance of the physiology of the reproductive system. Excess iodine intake affects male reproductive physiology. However, the effects of excess iodine on the ovarian structure and function is yet to be established. The present study has thus been undertaken to investigate the effect of excess iodine on the ovarian physiology...
January 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/27907224/single-versus-combination-intravenous-anti-pseudomonal-antibiotic-therapy-for-people-with-cystic-fibrosis
#5
REVIEW
Heather E Elphick, Alison Scott
BACKGROUND: Choice of antibiotic, and the use of single or combined therapy are controversial areas in the treatment of respiratory infection due to Pseudomonas aeruginosa in cystic fibrosis (CF). Advantages of combination therapy include wider range of modes of action, possible synergy and reduction of resistant organisms; advantages of monotherapy include lower cost, ease of administration and reduction of drug-related toxicity. Current evidence does not provide a clear answer and the use of intravenous antibiotic therapy in cystic fibrosis requires further evaluation...
December 1, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27907217/natural-products-from-myxobacteria-novel-metabolites-and-bioactivities
#6
REVIEW
J Herrmann, A Abou Fayad, R Müller
Covering: 2011-July 2016Myxobacteria are a rich source for structurally diverse secondary metabolites with intriguing biological activities. Here we report on new natural products that were isolated from myxobacteria in the period of 2011 to July 2016. Some examples of recent advances on modes-of-action are also summarised along with a more detailed overview on five compound classes currently assessed in preclinical studies.
December 1, 2016: Natural Product Reports
https://www.readbyqxmd.com/read/27906251/electrically-pumped-ultraviolet-lasing-in-polygonal-hollow-microresonators-investigation-on-optical-cavity-effect
#7
Zhifeng Shi, Ying Li, Yuantao Zhang, Di Wu, Tingting Xu, Baolin Zhang, Lei Liang, Xinjian Li, Guotong Du
Electrically driven ultraviolet lasing was realized in two-dimensional ZnO nanowall networks from Au/MgO/n-ZnO/n-GaN/In structure, and whispering gallery type resonant modes are responsible for the lasing action. We present a comparative study on lasing action based on nanowall networks with different micro-hole sizes. The representative diode (Device II) with a moderate micro-hole size exhibits an ultralow threshold current density of 1.01  A/cm<sup>2</sup>, and the lasing action can be sustained at a temperature up to ∼413  K, showing a good temperature tolerance...
December 1, 2016: Optics Letters
https://www.readbyqxmd.com/read/27905828/procedural-and-short-term-safety-of-bronchial-thermoplasty-in-clinical-practice-evidence-from-a-national-registry-and-hospital-episode-statistics
#8
Julie Burn, Andrew J Sims, Kim Keltie, Hannah Patrick, Sally A Welham, Liam G Heaney, Robert Niven
OBJECTIVE: Bronchial thermoplasty (BT) is a novel treatment for severe asthma. Its mode of action and ideal target patient group remain poorly defined, though clinical trials provided some evidence on efficacy and safety. This study presents procedural and short-term safety evidence from routine UK clinical practice. METHODS: Patient characteristics and safety outcomes (procedural complications, 30-day readmission and A&E attendance, length of stay) were assessed using two independent data sources, the British Thoracic Society UK Difficult Asthma Registry (DAR) and Hospital Episodes Statistics (HES) database...
December 1, 2016: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/27905535/bordetella-pertussis-outer-membrane-vesicle-vaccine-confers-equal-efficacy-in-mice-with-milder-inflammatory-responses-compared-to-a-whole-cell-vaccine
#9
René H M Raeven, Jolanda Brummelman, Jeroen L A Pennings, Larissa van der Maas, Wichard Tilstra, Kina Helm, Elly van Riet, Wim Jiskoot, Cécile A C M van Els, Wanda G H Han, Gideon F A Kersten, Bernard Metz
The demand for improved pertussis vaccines is urgent due to the resurgence of whooping cough. A deeper understanding of the mode of action of pertussis vaccines is required to achieve this improvement. The vaccine-induced effects of a candidate outer membrane vesicle vaccine (omvPV) and a classical protective but reactogenic whole cell vaccine (wPV) were comprehensively compared in mice. The comparison revealed essential qualitative and quantitative differences with respect to immunogenicity and adverse effects for these vaccines...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905163/fungal-glycolipid-hydrolase-inhibitors-and-their-effect-on-cryptococcus-neoformans
#10
Andres Gonzalez Santana, Christina Tysoe, Guanggan Hu, James Kronstad, Ethan Goddard-Borger, Stephen Withers
Pathogenic fungi kill an estimated 1.3 million people each year. This number is predicted to rise as drug resistance spreads, thus antifungal drugs with novel modes of action are urgently required. Fungal endoglycoceramidase-related proteins 1 and 2 (EGCrP-1 and -2), which hydrolyse glucosylceramide and ergosteryl beta-glucoside, respectively, are important for fungal cell growth and have been identified as potential targets for drug development. A library of iminosugar derivatives was screened against EGCrP-1 and -2, thereby identifying a number of competitive inhibitors with nanomolar affinities...
November 30, 2016: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/27904654/augmentation-of-histone-deacetylase-3-hdac3-epigenetic-signature-at-the-interface-of-proinflammation-and-insulin-resistance-in-patients-with-type-2-diabetes
#11
Chandrakumar Sathishkumar, Paramasivam Prabu, Mahalingam Balakumar, Raji Lenin, Durai Prabhu, Ranjith Mohan Anjana, Viswanathan Mohan, Muthuswamy Balasubramanyam
BACKGROUND: A role of proinflammation has been implicated in the pathogenesis of diabetes, but the up-stream regulatory signals and molecular signatures are poorly understood. While histone modifications such as changes in histone deacetylase (HDAC) are emerging as novel epigenetic biomarkers, there is lack of studies to demonstrate their clinical relevance in diabetes. Therefore, we investigated the extent of HDAC machinery and inflammatory signals in peripheral blood mononuclear cells (PBMCs) from patients with type 2 diabetes mellitus (T2DM) compared to control subjects...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27904397/antibacterial-activity-of-indian-borage-plectranthus-amboinicus-benth-leaf-extracts-in-food-systems-and%C3%A2-against-natural-microflora-in-chicken-meat
#12
Sandeep Kumar Gupta, Pradeep Singh Negi
The ability of acetone and ethyl acetate extracts of the leaves of a traditional Indian medicinal plant, Indian borage (Plectranthus amboinicus Benth) to prevent spoilage of artificially inoculated model food systems (cabbage and papaya) and natural microflora of chicken meat was evaluated. These extracts were able to reduce the bacterial counts in all food systems; however, the effective concentration varied with the complexity of the system (cabbage<papaya<chicken). A probable mode of action of extracts was investigated by analyzing the changes they cause in bacterial cell wall and leakage of nucleic acid from bacterial cells...
March 2016: Food Technology and Biotechnology
https://www.readbyqxmd.com/read/27903606/epha2-is-a-functional-receptor-for-the-growth-factor-progranulin
#13
Thomas Neill, Simone Buraschi, Atul Goyal, Catherine Sharpe, Elizabeth Natkanski, Liliana Schaefer, Andrea Morrione, Renato V Iozzo
Although the growth factor progranulin was discovered more than two decades ago, the functional receptor remains elusive. Here, we discovered that EphA2, a member of the large family of Ephrin receptor tyrosine kinases, is a functional signaling receptor for progranulin. Recombinant progranulin bound with high affinity to EphA2 in both solid phase and solution. Interaction of progranulin with EphA2 caused prolonged activation of the receptor, downstream stimulation of mitogen-activated protein kinase and Akt, and promotion of capillary morphogenesis...
November 30, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27902392/microbiological-sentinel-events-at-neurological-hospital-a-retrospective-cohort-study
#14
Annalia Asti, Elio Marmondi, Carmine Tinelli, Marta Corbella, Annalisa de Silvestri, Gaetano Bernardi, Franco Andreini, Anna Preti, Monica Bricchi
AbstractThe purpose of this study is to describe the epidemiological surveillance of microbiological sentinel events (SE) carried out between 2012-2014 at the Neurological Hospital Carlo Besta, Milano, Italy. The Setting is inpatient care with Multi- Drug-Resistance infections. The aim of the procedure is to formalize the management mode, the reporting and transmission of SE. Categorical variables were described by counts and percentages, those quantitatives as mean and standard deviation or median and interquartile range...
October 20, 2016: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/27901217/factors-associated-with-problematic-drug-use-among-psychiatric-outpatients
#15
Clarissa Mendonça Corradi-Webster, Edilaine Cristina da Silva Gherardi-Donato
Objective: to examine the factors associated with problematic drug use among psychiatric outpatients. Method: a cross-sectional study was carried out in two mental health services. Eligible individuals were patients of these mental health services, who used them within the data collection period. Instruments: standardized questionnaire with sociodemographic, social network, social harm, and clinical information; Alcohol, Smoking and Substance Involvement Screening Test; Barratt Impulsiveness Scale; Holmes and Rahe Stress Scale...
November 28, 2016: Revista Latino-americana de Enfermagem
https://www.readbyqxmd.com/read/27901171/role-of-lewis-acid-additives-in-a-palladium-catalyzed-directed-c-h-functionalization-reaction-of-benzohydroxamic-acid-to-isoxazolone
#16
C Athira, Raghavan B Sunoj
Metallic salts as well as protic additives are widely employed in transition metal catalyzed C-H bond functionalization reactions to improve the efficiency of catalytic protocols. In one such example, ZnCl2 and pivalic acid are used as additives in a palladium catalyzed synthesis of isoxazolone from a readily available benzohydroxamic acid under one pot conditions. In this article, we present some important mechanistic insights into the role of ZnCl2 and pivalic acid, gained by using density functional theory (M06) computations...
November 30, 2016: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/27901159/a-portable-and-reconfigurable-multi-organ-platform-for-drug-development-with-onboard-microfluidic-flow-control
#17
J R Coppeta, M J Mescher, B C Isenberg, A J Spencer, E S Kim, A R Lever, T J Mulhern, R Prantil-Baun, J C Comolli, J T Borenstein
The drug development pipeline is severely limited by a lack of reliable tools for prediction of human clinical safety and efficacy profiles for compounds at the pre-clinical stage. Here we present the design and implementation of a platform technology comprising multiple human cell-based tissue models in a portable and reconfigurable format that supports individual organ function and crosstalk for periods of up to several weeks. Organ perfusion and crosstalk are enabled by a precision flow control technology based on electromagnetic actuators embedded in an arrayed format on a microfluidic platform...
November 30, 2016: Lab on a Chip
https://www.readbyqxmd.com/read/27901075/membrane-core-specific-antimicrobial-action-of-cathelicidin-ll-37-peptide-switches-between-pore-and-nanofibre-formation
#18
Mahdi Shahmiri, Marta Enciso, Christopher G Adda, Brian J Smith, Matthew A Perugini, Adam Mechler
Membrane-disrupting antimicrobial peptides provide broad-spectrum defence against localized bacterial invasion in a range of hosts including humans. The most generally held consensus is that targeting to pathogens is based on interactions with the head groups of membrane lipids. Here we show that the action of LL-37, a human antimicrobial peptide switches the mode of action based on the structure of the alkyl chains, and not the head groups of the membrane forming lipids. We demonstrate that LL-37 exhibits two distinct interaction pathways: pore formation in bilayers of unsaturated phospholipids and membrane modulation with saturated phospholipids...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899918/mechanistic-basis-of-antimicrobial-actions-of-silver-nanoparticles
#19
REVIEW
Tikam Chand Dakal, Anu Kumar, Rita S Majumdar, Vinod Yadav
Multidrug resistance of the pathogenic microorganisms to the antimicrobial drugs has become a major impediment toward successful diagnosis and management of infectious diseases. Recent advancements in nanotechnology-based medicines have opened new horizons for combating multidrug resistance in microorganisms. In particular, the use of silver nanoparticles (AgNPs) as a potent antibacterial agent has received much attention. The most critical physico-chemical parameters that affect the antimicrobial potential of AgNPs include size, shape, surface charge, concentration and colloidal state...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27899534/substituted-pthalimide-ac94377-is-a-selective-agonist-of-the-gibberellin-receptor-gid1
#20
Kai Jiang, Masato Otani, Hiroaki Shimotakahara, Jung-Min Yoon, Seung-Hyun Park, Tomoko Miyaji, Takeshi Nakano, Hidemitsu Nakamura, Masatoshi Nakajima, Tadao Asami
Gibberellin (GA) is a major plant hormone that regulates plant growth and development, and is widely used as a plant growth regulator in agricultural production. There is an increasing demand for function-limited GA mimics due to the limitations on the agronomical application of GA to crops, including GA's high cost of producing and its leading to the crops' lodging. AC94377, a substituted phthalimide, is a chemical that mimics the growth-regulating activity of GAs in various plants, despite its structural difference...
November 29, 2016: Plant Physiology
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