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https://www.readbyqxmd.com/read/28820574/thiol-containing-metallo-%C3%AE-lactamase-inhibitors-resensitize-resistant-gram-negative-bacteria-to-meropenem
#1
Kamaleddin Haj Mohammad Ebrahim Tehrani, Nathaniel I Martin
The prevalence of infections caused by metallo-β-lactamase (MBL) expressing Gram-negative bacteria has grown at an alarming rate in recent years. Despite the fact that MBLs can deactivate virtually all β-lactams antibiotics, there are as of yet no approved drugs available that inhibit their activity. We here examine the ability of previously reported thiol-based MBL inhibitors to synergize with meropenem against a panel of Gram-negative carbapenem-resistant isolates expressing different β-lactamases. Among the compounds tested, thiomandelic acid 3 and 2-merpto-3-phenylpropionic acid 4 were found to efficiently potentiate the activity of meropenem, especially against an IMP producing strain of K...
August 18, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28820312/architecture-of-the-atg2b-wdr45-complex-and-an-aromatic-y-hf-motif-crucial-for-complex-formation
#2
Jing-Xiang Zheng, Yan Li, Yue-He Ding, Jun-Jie Liu, Mei-Jun Zhang, Meng-Qiu Dong, Hong-Wei Wang, Li Yu
PtdIns3P signaling is critical for dynamic membrane remodeling during autophagosome formation. Proteins in the Atg18/WIPI family are PtdIns3P-binding effectors which can form complexes with proteins in the Atg2 family, and both families are essential for macroautophagy/autophagy. However, little is known about the biophysical properties and biological functions of the Atg2-Atg18/WIPI complex as a whole. Here, we demonstrate that an ortholog of yeast Atg18, mammalian WDR45/WIPI4 has a stronger binding capacity for mammalian ATG2A or ATG2B than the other 3 WIPIs...
August 18, 2017: Autophagy
https://www.readbyqxmd.com/read/28820033/unregulated-saphenous-vein-graft-distension-decreases-tissue-viscoelasticity
#3
Eric S Wise, Kyle M Hocking, Brian C Evans, Craig L Duvall, Joyce Cheung-Flynn, Colleen M Brophy
OBJECTIVES: Unregulated intraoperative distension of human saphenous vein (SV) graft leads to supraphysiologic luminal pressures and causes acute physiologic and cellular injury to the conduit. The effect of distension on tissue viscoelasticity, a biophysical property critical to a successful graft, is not well described. In this investigation, we quantify the loss of viscoelasticity in SV deformed by distension and compare the results to tissue distended in a pressure-controlled fashion...
September 2017: Perfusion
https://www.readbyqxmd.com/read/28819979/the-influence-of-a-novel-dimeric-ceramide-molecule-on-the-nanostructure-and-the-thermotropic-phase-behavior-of-a-stratum-corneum-model-mixture
#4
Sören Stahlberg, Adina Eichner, Stefan Sonnenberger, Andrej Kovacik, Stefan Lange, Thomas Schmitt, Bruno Demé, Thomas Hauss, Bodo Dobner, Reinhard H H Neubert, Daniel Huster
The stratum corneum (SC) is the outermost layer of the skin and composed of a multilayered assembly of mostly ceramids (Cer), free fatty acids, cholesterol (Chol), and cholesterol sulphate (Chol-S). Due to the tight packing of these lipids, the SC features unique barrier properties defending the skin from environmental influences. Under pathological conditions, where the skin barrier function is compromised, topical application of molecules that rigidify the SC may lead to a restored barrier function. To this end, molecules are required that incorporate into the SC and bring back the original rigidity of the skin barrier...
August 18, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28819690/conductance-based-refractory-density-approach-comparison-with-experimental-data-and-generalization-to-lognormal-distribution-of-input-current
#5
Anton V Chizhov
The conductance-based refractory density (CBRD) approach is an efficient tool for modeling interacting neuronal populations. The model describes the firing activity of a statistical ensemble of uncoupled Hodgkin-Huxley-like neurons, each receiving individual Gaussian noise and a common time-varying deterministic input. However, the approach requires experimental validation and extension to cases of distributed input signals (or input weights) among different neurons of such an ensemble. Here the CBRD model is verified by comparing with experimental data and then generalized for a lognormal (LN) distribution of the input weights...
August 17, 2017: Biological Cybernetics
https://www.readbyqxmd.com/read/28819329/efficient-computation-of-electrograms-and-ecgs-in-human-whole-heart-simulations-using-a-reaction-eikonal-model
#6
Aurel Neic, Fernando O Campos, Anton J Prassl, Steven A Niederer, Martin J Bishop, Edward J Vigmond, Gernot Plank
Anatomically accurate and biophysically detailed bidomain models of the human heart have proven a powerful tool for gaining quantitative insight into the links between electrical sources in the myocardium and the concomitant current flow in the surrounding medium as they represent their relationship mechanistically based on first principles. Such models are increasingly considered as a clinical research tool with the perspective of being used, ultimately, as a complementary diagnostic modality. An important prerequisite in many clinical modeling applications is the ability of models to faithfully replicate potential maps and electrograms recorded from a given patient...
October 1, 2017: Journal of Computational Physics
https://www.readbyqxmd.com/read/28819244/light-scattering-by-optically-trapped-vesicles-affords-unprecedented-temporal-resolution-of-lipid-raft-dynamics
#7
Liam Collard, David Perez-Guaita, Bayan H A Faraj, Bayden R Wood, Russell Wallis, Peter W Andrew, Andrew J Hudson
A spectroscopic technique is presented that is able to identify rapid changes in the bending modulus and fluidity of vesicle lipid bilayers on the micrometer scale, and distinguish between the presence and absence of heterogeneities in lipid-packing order. Individual unilamellar vesicles have been isolated using laser tweezers and, by measuring the intensity modulation of elastic back-scattered light, changes in the biophysical properties of lipid bilayers were revealed. Our approach offers unprecedented temporal resolution and, uniquely, physical transformations of lipid bilayers can be monitored on a length scale of micrometers...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819146/liquid-liquid-phase-separation-of-the-microtubule-binding-repeats-of-the-alzheimer-related-protein-tau
#8
Susmitha Ambadipudi, Jacek Biernat, Dietmar Riedel, Eckhard Mandelkow, Markus Zweckstetter
The protein Tau aggregates into tangles in the brain of patients with Alzheimer's disease. In solution, however, Tau is intrinsically disordered, highly soluble, and binds to microtubules. It is still unclear what initiates the conversion from an innocuous phase of high solubility and functionality to solid-like neurotoxic deposits. Here, we show that the microtubule-binding repeats of Tau, which are lysine-rich, undergo liquid-liquid phase separation in solution. Liquid-liquid demixing causes molecular crowding of amyloid-promoting elements of Tau and drives electrostatic coacervation...
August 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28818915/collaborative-environmental-governance-achieving-collective-action-in-social-ecological-systems
#9
REVIEW
Örjan Bodin
Managing ecosystems is challenging because of the high number of stakeholders, the permeability of man-made political and jurisdictional demarcations in relation to the temporal and spatial extent of biophysical processes, and a limited understanding of complex ecosystem and societal dynamics. Given these conditions, collaborative governance is commonly put forward as the preferred means of addressing environmental problems. Under this paradigm, a deeper understanding of if, when, and how collaboration is effective, and when other means of addressing environmental problems are better suited, is needed...
August 18, 2017: Science
https://www.readbyqxmd.com/read/28818694/diffusion-time-dependence-of-microstructural-parameters-in-fixed-spinal-cord
#10
REVIEW
Sune Nørhøj Jespersen, Jonas Lynge Olesen, Brian Hansen, Noam Shemesh
Biophysical modelling of diffusion MRI is necessary to provide specific microstructural tissue properties. However, estimating model parameters from data with limited diffusion gradient strength, such as clinical scanners, has proven unreliable due to a shallow optimization landscape. On the other hand, estimation of diffusion kurtosis (DKI) parameters is more robust, and its parameters may be connected to microstructural parameters, given an appropriate biophysical model. However, it was previously shown that this procedure still does not provide sufficient information to uniquely determine all model parameters...
August 14, 2017: NeuroImage
https://www.readbyqxmd.com/read/28818314/comparison-of-disaggregative-effect-of-a-type-egcg-dimer-and-egcg-monomer-on-the-preformed-bovine-insulin-amyloid-fibrils
#11
Rong-Zu Nie, Wei Zhu, Jin-Ming Peng, Zhen-Zhen Ge, Chun-Mei Li
In the present study, the disruptive effects of epigallocatechin-3-gallate (EGCG) and A-type dimeric epigallocatechin-3-gallate (A-type EGCG dimer) on the preformed bovine insulin amyloid fibrils were studied by several biophysical methods including thioflavin-T (ThT) fluorescence assay, 1-anilinonaphthalene-8-sulfonic (ANS) fluorescence assay, Congo red (CR) binding assay, dynamic light scattering (DLS), transmission electron microscopy (TEM), Gel electrophoresis (SDS-PAGE) and Bradford assay. Our results demonstrated that A-type EGCG dimer showed significantly more potential disaggregative effects on the bovine insulin amyloid fibrils than EGCG...
July 31, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28817666/assessing-the-sustainable-development-and-intensification-potential-of-beef-cattle-production-in-sumbawa-indonesia-using-a-system-dynamics-approach
#12
Dahlanuddin, Benjamin Henderson, Kanar Dizyee, Hermansyah, Andrew Ash
The intensification of beef cattle production in dryland areas of East Indonesia has the potential to substantially raise the incomes of smallholder farmers that dominate the sector. In this study we assess the potential for intensifying beef production on Sumbawa Island, by introducing a household feedlot production system (2-20 animals) based on the Leucaena leucocephala (leucanea) tree legume as an improved source of feed. We used a system dynamics approach to model the entire value chain, accounting for herd dynamics, demand dynamics and seasonality...
2017: PloS One
https://www.readbyqxmd.com/read/28817100/modulatory-effects-of-exogenously-applied-polyamines-on-postharvest-physiology-antioxidant-system-and-shelf-life-of-fruits-a-review
#13
REVIEW
Sunil Sharma, Sunil Pareek, Narashans Alok Sagar, Daniel Valero, Maria Serrano
Polyamines (PAs) are natural compounds involved in many growth and developmental processes in plants, and, specifically in fruits, play a vital role regulating its development, ripening and senescence processes. Putrescine (PUT), spermine (SPE), and spermidine (SPD) are prominent PAs applied exogenously to extend shelf life of fruits. They also originate endogenously during developmental phases of horticultural crops and simultaneously affect the quality attributes and shelf life. Their anti-ethylene nature is being exploited to enhance the shelf life when exogenously applied on fruits...
August 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28816316/hydrogel-scaffolds-for-differentiation-of-adipose-derived-stem-cells
#14
REVIEW
Qiutong Huang, Yijie Zou, Maria C Arno, Shuai Chen, Tao Wang, Jingyi Gao, Andrew P Dove, Jianzhong Du
Natural extracellular matrices (ECMs) have been widely used as a support for the adhesion, migration, differentiation, and proliferation of adipose-derived stem cells (ADSCs). However, poor mechanical behavior and unpredictable biodegradation properties of natural ECMs considerably limit their potential for bioapplications and raise the need for different, synthetic scaffolds. Hydrogels are regarded as the most promising alternative materials as a consequence of their excellent swelling properties and their resemblance to soft tissues...
August 17, 2017: Chemical Society Reviews
https://www.readbyqxmd.com/read/28815923/biophysical-screening-of-a-focused-library-for-the-discovery-of-cyp121-inhibitors-as-novel-antimycobacterials
#15
Christian Brengel, Andreas Thomann, Alexander Schifrin, Giuseppe Allegretta, Ahmed A M Kamal, Joerg Haupenthal, Isabell Schnorr, Sang Hyun Cho, Scott Gary Franzblau, Martin Empting, Jens Eberhard, Rolf W Hartmann
The development of novel antimycobacterial agents against Mycobacterium tuberculosis (Mtb) is urgently required due to the appearance of multi-drug resistance (MDR) combined with a complicated long-term treatment. CYP121 was shown to be a promising novel target for inhibition of mycobacterial growth. In this study, we describe the rational discovery of new CYP121 inhibitors by a systematic screening based on biophysical and microbiological methods. Best hits originating from only one structural class gave first information about molecular motifs required for binding and activity...
August 16, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28815596/use-of-first-trimester-placenta-growth-factor-concentration-to-predict-hypertensive-disorders-of-pregnancy-in-a-low-risk-asian-population
#16
Manisha Kumar, Karuna Sharma, Shalini Singh, Ritu Singh, Abha Singh, Jayashree Bhattacharjee
OBJECTIVE: To determine the value of placenta growth factor (PlGF) for predicting hypertensive disorders of pregnancy (HDP) in a low-risk population when used either alone or in combination with other markers. METHODS: A prospective observational cohort study was conducted among women with singleton pregnancy in the first trimester in New Delhi, India, between October 1, 2013, and September 30, 2016. First-trimester measures included maternal history, body mass index (BMI), mean arterial pressure (MAP), Doppler uterine artery pulsatility index, and serum levels of biomarkers (including PlGF)...
August 17, 2017: International Journal of Gynaecology and Obstetrics
https://www.readbyqxmd.com/read/28814780/adaptive-simulations-towards-interactive-protein-ligand-modeling
#17
Daniel Lecina, Joan F Gilabert, Victor Guallar
Modeling the dynamic nature of protein-ligand binding with atomistic simulations is one of the main challenges in computational biophysics, with important implications in the drug design process. Although in the past few years hardware and software advances have significantly revamped the use of molecular simulations, we still lack a fast and accurate ab initio description of the binding mechanism in complex systems, available only for up-to-date techniques and requiring several hours or days of heavy computation...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28813610/poloxamer-decorated-polymer-nanoparticles-for-lung-surfactant-compatibility
#18
Moritz Beck-Broichsitter, Adam Bohr, Christian Arnold Ruge
Lung-delivered polymer nanoparticles provoked dysfunction of the essential lung surfactant system. A steric shielding of the nanoparticle surface with poloxamers could minimize the unwanted interference of polymer nanoparticles with the biophysical function of lung surfactant. The extent of poly(styrene) and poly(lactide) nanoparticle-induced lung surfactant inhibition could be related to the type and content of the applied poloxamer. Escalations of the adsorbed coating layer thickness (>3 nm) as well as concentration (brush- rather than mushroom-like conformation of poly(ethylene glycol), chain-to-chain distance of <5 nm) on the colloidal surface were capable of circumventing bioadverse effects...
August 16, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28813460/mechanisms-for-pattern-specificity-of-deep-brain-stimulation-in-parkinson-s-disease
#19
Osvaldo Matías Velarde, Germán Mato, Damián Dellavale
Deep brain stimulation (DBS) has become a widely used technique for treating advanced stages of neurological and psychiatric illness. In the case of motor disorders related to basal ganglia (BG) dysfunction, several mechanisms of action for the DBS therapy have been identified which might be involved simultaneously or in sequence. However, the identification of a common key mechanism underlying the clinical relevant DBS configurations has remained elusive due to the inherent complexity related to the interaction between the electrical stimulation and the neural tissue, and the intricate circuital structure of the BG-thalamocortical network...
2017: PloS One
https://www.readbyqxmd.com/read/28813456/a-simple-molecular-mechanism-explains-multiple-patterns-of-cell-size-regulation
#20
Morgan Delarue, Daniel Weissman, Oskar Hallatschek
Increasingly accurate and massive data have recently shed light on the fundamental question of how cells maintain a stable size trajectory as they progress through the cell cycle. Microbes seem to use strategies ranging from a pure sizer, where the end of a given phase is triggered when the cell reaches a critical size, to pure adder, where the cell adds a constant size during a phase. Yet the biological origins of the observed spectrum of behavior remain elusive. We analyze a molecular size-control mechanism, based on experimental data from the yeast S...
2017: PloS One
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