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https://www.readbyqxmd.com/read/28545134/structures-of-the-inactive-and-active-states-of-rip2-kinase-inform-on-the-mechanism-of-activation
#1
Erika Pellegrini, Luca Signor, Saurabh Singh, Elisabetta Boeri Erba, Stephen Cusack
Innate immune receptors NOD1 and NOD2 are activated by bacterial peptidoglycans leading to recruitment of adaptor kinase RIP2, which, upon phosphorylation and ubiquitination, becomes a scaffold for downstream effectors. The kinase domain (RIP2K) is a pharmaceutical target for inflammatory diseases caused by aberrant NOD2-RIP2 signalling. Although structures of active RIP2K in complex with inhibitors have been reported, the mechanism of RIP2K activation remains to be elucidated. Here we analyse RIP2K activation by combining crystal structures of the active and inactive states with mass spectrometric characterization of their phosphorylation profiles...
2017: PloS One
https://www.readbyqxmd.com/read/28543540/computational-modeling-of-915-mhz-microwave-ablation-comparative-assessment-of-temperature-dependent-tissue-dielectric-models
#2
Garron Deshazer, Mark Hagmann, Derek Merck, Jan Sebek, Kent B Moore, Punit Prakash
PURPOSE: The objective of this study is to develop a computational model for simulating 915 MHz microwave ablation (MWA), and verify the simulation predictions of transient temperature profiles against experimental measurements. Due to the limited experimental data characterizing temperature-dependent changes of tissue dielectric properties at 915 MHz, we comparatively assess two temperature dependent approaches of modeling of dielectric properties: model A- piecewise linear temperature dependencies based on existing, but limited, experimental data, and model B- similar to model A, but augmented with linear decrease in electrical conductivity above 95 °C, as guided by our experimental measurements...
May 23, 2017: Medical Physics
https://www.readbyqxmd.com/read/28528360/a-spiking-neural-network-model-of-the-midbrain-superior-colliculus-that-generates-saccadic-motor-commands
#3
Bahadir Kasap, A John van Opstal
Single-unit recordings suggest that the midbrain superior colliculus (SC) acts as an optimal controller for saccadic gaze shifts. The SC is proposed to be the site within the visuomotor system where the nonlinear spatial-to-temporal transformation is carried out: the population encodes the intended saccade vector by its location in the motor map (spatial), and its trajectory and velocity by the distribution of firing rates (temporal). The neurons' burst profiles vary systematically with their anatomical positions and intended saccade vectors, to account for the nonlinear main-sequence kinematics of saccades...
May 20, 2017: Biological Cybernetics
https://www.readbyqxmd.com/read/28501599/ph-induced-single-step-shift-of-hydrophobic-patches-followed-by-formation-of-an-mg-state-and-an-amyloidogenic-intermediate-in-lima-bean-trypsin-inhibitor-lbti
#4
Javed Masood Khan, Mohammad A Alsenaidy, Mohd Shahnawaz Khan, Priyankar Sen, Rizwan Hasan Khan, Sadaf Fatima
Lima Bean Trypsin Inhibitor (LBTI) is 83 residues monomeric protein of 9.0 KDa, consisting of six antiparallel β-strands and can undergo concentration dependant dimerization. We have tried to characterize folding intermediates of LBTI under equilibrium denaturation conditions. We have used various spectroscopic and microscopic techniques to understand the folding and misfolding pathways. LBTI forms molten globule structure at pH 2 and amyloidiogenic intermediate state (I(a)) at pH 4. pH induced Shifting of surface exposed hydrophobic patches and that followed by withdrawal of the lone tyrosine residue (Y69) towards nonpolar environment have been reported...
May 10, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28495970/high-throughput-biochemical-profiling-reveals-sequence-determinants-of-dcas9-off-target-binding-and-unbinding
#5
Evan A Boyle, Johan O L Andreasson, Lauren M Chircus, Samuel H Sternberg, Michelle J Wu, Chantal K Guegler, Jennifer A Doudna, William J Greenleaf
The bacterial adaptive immune system CRISPR-Cas9 has been appropriated as a versatile tool for editing genomes, controlling gene expression, and visualizing genetic loci. To analyze Cas9's ability to bind DNA rapidly and specifically, we generated multiple libraries of potential binding partners for measuring the kinetics of nuclease-dead Cas9 (dCas9) interactions. Using a massively parallel method to quantify protein-DNA interactions on a high-throughput sequencing flow cell, we comprehensively assess the effects of combinatorial mismatches between guide RNA (gRNA) and target nucleotides, both in the seed and in more distal nucleotides, plus disruption of the protospacer adjacent motif (PAM)...
May 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28484508/cohort-profile-the-complications-of-long-term-antiretroviral-therapy-study-in-uganda-coltart-a-prospective-clinical-cohort
#6
Billy Nsubuga Mayanja, Ivan Kasamba, Jonathan Levin, Ivan Namakoola, Patrick Kazooba, Jackson Were, Pontiano Kaleebu, Paula Munderi
BACKGROUND: Antiretroviral therapy (ART) improves the survival and quality of life of HIV-positive individuals, but the effects of long-term ART use do eventually manifest. The Complications of Long-Term Antiretroviral Therapy cohort study in Uganda (CoLTART) was established to investigate the metabolic and renal complications of long-term ART use among Ugandan adults. We describe the CoLTART study set-up, aims, objectives, study methods, and also report some preliminary cross-sectional study enrolment metabolic and renal complications data analysis results...
2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28484292/correlation-of-oxidative-stress-markers-with-ultrasound-and-cardiotocography-parameters-with-hypertension-induced-pregnancy
#7
Dragica Draganovic, Nenad Lucic, Dragica Jojic, Snjezana Milicevic
INTRODUCTION: Pregnancy induced hypertension (PIH), especially preeclampsia, is a state of extremely increased oxidative stress (OS), due to decrease of antioxidant capacity in comparison to normotensive pregnant women. The consequences of increased state of oxidative stress with hypertension disorder in pregnancy are disorder of placental blood flow, intrauterine hypoxia of the fetus and disturbance in transfer of O2 manifested as pathological ultrasound (US) parameters (amount of amniotic fluid and biophysical profile of fetus) and cardiotocography parameters (CTG)...
March 2017: Acta Informatica Medica: AIM
https://www.readbyqxmd.com/read/28483196/bacterially-expressed-human-papillomavirus-type-6-and-11-bivalent-vaccine-characterization-antigenicity-and-immunogenicity
#8
Huirong Pan, Zhihai Li, Jin Wang, Shuo Song, Daning Wang, Minxi Wei, Ying Gu, Jun Zhang, Shaowei Li, Ningshao Xia
Human papillomavirus (HPV)-6 and HPV11 are the major etiological causes of condylomata acuminate. HPV neutralization by vaccine-elicited neutralizing antibodies can block viral infection and prevent subsequent disease. Currently, two commercially available HPV vaccines cover these two genotypes, expressed by Saccharomyces cerevisiae. Here we describe another HPV6/11 bivalent vaccine candidate derived from Escherichia coli. The soluble expression of N-terminally truncated L1 proteins was optimized to generate HPV6- and HPV11 L1-only virus-like particles (VLPs) as a scalable process...
May 31, 2017: Vaccine
https://www.readbyqxmd.com/read/28482223/biological-effects-of-%C3%AE-adrenergic-phentolamine-on-erythrocyte-hemeprotein-molecular-insights-from-biorecognition-behavior-protein-dynamics-and-flexibility
#9
Wei Peng, Fei Ding, Yu-Kui Peng, Yong Xie
Phentolamine is one of the most representative nonselective α-adrenoreceptor blocking agents, which have been proved to be owned various pharmacological actions. Unfortunately, whether erythrocytes in the veins intervene in biological behaviors of such drug are largely obscured. With the aid of multiple biophysical techniques, this scenario was to detailed explore the potential biorecognition between phentolamine and the hemeprotein in the cytosol of erythrocytes, and the influences of dynamic characters of protein during the bioreaction...
April 28, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28473001/cohort-profile-the-complications-of-long-term-antiretroviral-therapy-study-in-uganda-coltart-a-prospective-clinical-cohort
#10
Billy Nsubuga Mayanja, Ivan Kasamba, Jonathan Levin, Ivan Namakoola, Patrick Kazooba, Jackson Were, Pontiano Kaleebu, Paula Munderi
BACKGROUND: Antiretroviral therapy (ART) improves the survival and quality of life of HIV-positive individuals, but the effects of long-term ART use do eventually manifest. The Complications of Long-Term Antiretroviral Therapy cohort study in Uganda (CoLTART) was established to investigate the metabolic and renal complications of long-term ART use among Ugandan adults. We describe the CoLTART study set-up, aims, objectives, study methods, and also report some preliminary cross-sectional study enrolment metabolic and renal complications data analysis results...
May 4, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28472147/surface-reflectance-drives-nest-box-temperature-profiles-and-thermal-suitability-for-target-wildlife
#11
Stephen R Griffiths, Jessica A Rowland, Natalie J Briscoe, Pia E Lentini, Kathrine A Handasyde, Linda F Lumsden, Kylie A Robert
Thermal properties of tree hollows play a major role in survival and reproduction of hollow-dependent fauna. Artificial hollows (nest boxes) are increasingly being used to supplement the loss of natural hollows; however, the factors that drive nest box thermal profiles have received surprisingly little attention. We investigated how differences in surface reflectance influenced temperature profiles of nest boxes painted three different colors (dark-green, light-green, and white: total solar reflectance 5.9%, 64...
2017: PloS One
https://www.readbyqxmd.com/read/28464235/multi-criteria-manufacturability-indices-for-ranking-high-concentration-monoclonal-antibody-formulations
#12
Yang Yang, Ajoy Velayudhan, Nina F Thornhill, Suzanne S Farid
The need for high-concentration formulations for subcutaneous delivery of therapeutic monoclonal antibodies (mAbs) can present manufacturability challenges for the final ultrafiltration/diafiltration (UF/DF) step. Viscosity levels and the propensity to aggregate are key considerations for high-concentration formulations. This work presents novel frameworks for deriving a set of manufacturability indices related to viscosity and thermostability to rank high-concentration mAb formulation conditions in terms of their ease of manufacture...
May 2, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28448954/copper-complexes-containing-thiosemicarbazones-derived-from-6-nitropiperonal-antimicrobial-and-biophysical-properties
#13
Floyd A Beckford, Kelsey R Webb
A series of four thiosemicarbazones from 6-nitropiperonal along with the corresponding copper complexes were synthesized. The biophysical characteristics of the complexes were investigated by the binding to DNA and human serum albumin. The binding to DNA is moderate; the binding constants run from (0.49-7.50)×10(4)M(-1). In relation to HSA, the complexes interact strongly with binding constants on the order of 10(5)M(-1). The complexes also display antioxidant behavior as determined by the ability to scavenge diphenylpicrylhydrazyl (dpph) and nitric oxide radicals...
April 20, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28432958/membrane-fusion-between-baculovirus-budded-virus-enveloped-particles-and-giant-liposomes-generated-using-a-droplet-transfer-method-for-the-incorporation-of-recombinant-membrane-proteins
#14
Misako Nishigami, Takaaki Mori, Masahiro Tomita, Kingo Takiguchi, Kanta Tsumoto
Giant proteoliposomes are generally useful as artificial cell membranes in biochemical and biophysical studies, and various procedures for their preparation have been reported. We present here a novel preparation technique that involves the combination of i) cell-sized lipid vesicles (giant unilamellar vesicles, GUVs) that are generated using the droplet-transfer method, where lipid monolayer-coated water-in-oil microemulsion droplets interact with oil/water interfaces to form enclosed bilayer vesicles, and ii) budded viruses (BVs) of baculovirus (Autographa californica nucleopolyhedrovirus) that express recombinant transmembrane proteins on their envelopes...
April 13, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28432143/focal-local-field-potential-lfp-signature-of-the-single-axon-monosynaptic-thalamocortical-connection
#15
Espen Hagen, Janne C Fossum, Klas H Pettersen, Jose-Manuel Alonso, Harvey A Swadlow, Gaute T Einevolla
Recent years have seen a resurgence in use of the extracellularly recorded local field potential (LFP) to investigate neural network activity. To probe monosynaptic thalamic activation of cortical postsynaptic target cells, so called spike-trigger-averaged LFP (stLFP) signatures have been measured. In these experiments the cortical LFP is measured by means of multielectrodes covering several cortical lamina and averaged on spontaneous spikes of thalamocortical (TC) cells. Using a well-established forward-modeling scheme, we investigate the biophysical origin of this stLFP signature with simultaneous synaptic activation of cortical layer 4 neurons, mimicking the effect of a single afferent spike from a single TC neuron...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28414448/substrate-profiling-and-high-resolution-co-complex-crystal-structure-of-a-secreted-c11-protease-conserved-across-commensal-bacteria
#16
Emily J Roncase, Clara Moon, Sandip Chatterjee, Gonzalo E González-Páez, Charles S Craik, Anthony J O'Donoghue, Dennis W Wolan
Cysteine proteases are among the most abundant hydrolytic enzymes produced by bacteria, and this diverse family of proteins have significant biological roles in bacterial viability and environmental interactions. Members of the clostripain-like (C11) family of cysteine proteases from commensal gut bacterial strains have recently been shown to mediate immune responses by inducing neutrophil phagocytosis and activating bacterial pathogenic toxins. Development of substrates, inhibitors, and probes that target C11 proteases from enteric bacteria will help to establish the role of these proteins at the interface of the host and microbiome in health and disease...
April 27, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28410930/ligand-diffusion-in-proteins-via-enhanced-sampling-in-molecular-dynamics
#17
REVIEW
J Rydzewski, W Nowak
Computational simulations in biophysics describe the dynamics and functions of biological macromolecules at the atomic level. Among motions particularly important for life are the transport processes in heterogeneous media. The process of ligand diffusion inside proteins is an example of a complex rare event that can be modeled using molecular dynamics simulations. The study of physical interactions between a ligand and its biological target is of paramount importance for the design of novel drugs and enzymes...
April 1, 2017: Physics of Life Reviews
https://www.readbyqxmd.com/read/28401807/biophysical-stimulation-for-engineering-functional-skeletal-muscle
#18
Sarah Somers, Alexander Spector, Douglas DiGirolamo, Warren L Grayson
Tissue engineering is a promising therapeutic strategy to regenerate skeletal muscle. However, ex vivo cultivation methods typically result in a low differentiation efficiency of stem cells as well as grafts that resemble the native tissues morphologically, but lack contractile function. The application of biomimetic tensile strain provides a potent stimulus for enhancing myogenic differentiation and engineering functional skeletal muscle grafts. We reviewed integrin-dependent mechanisms that potentially link mechanotransduction pathways to the upregulation of myogenic genes...
April 12, 2017: Tissue Engineering. Part B, Reviews
https://www.readbyqxmd.com/read/28400496/pea-border-cell-maturation-and-release-involve-complex-cell-wall-structural-dynamics
#19
Jozef Mravec, Xiaoyuan Guo, Aleksander R Hansen, Julia Schückel, Stjepan Kresimir Kracun, Maria Dalgaard Mikkelsen, Grégory Mouille, Ida Elisabeth Johansen, Peter Ulvskov, David Domozych, William George Tycho Willats
The adhesion of plant cells is vital for support and protection of the plant body and is maintained by a variety of molecular associations between cell wall components. In some specialized cases though, plant cells are programmed to detach and root cap-derived border cells are examples of this. Border cells (in some species known as border-like cells) provide an expendable barrier between roots and the environment. Their maturation and release is an important but poorly characterized cell separation event. To gain a deeper insight into the complex cellular dynamics underlying this process, we undertook a systematic, detailed analysis of pea (Pisum sativum) root tip cell walls...
April 11, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28388481/membrane-lipid-profiles-of-coral-responded-to-zinc-oxide-nanoparticle-induced-perturbations-on-the-cellular-membrane
#20
Chuan-Ho Tang, Ching-Yu Lin, Shu-Hui Lee, Wei-Hsien Wang
Zinc oxide nanoparticles (nZnOs) released from popular sunscreens used during marine recreation apparently endanger corals; however, the known biological effects are very limited. Membrane lipids constitute the basic structural element to create cell a dynamic structure according to the circumstance. Nano-specific effects have been shown to mechanically perturb the physical state of the lipid membrane, and the cells accommodating the actions of nZnOs can be involved in the alteration of the membrane lipid composition...
June 2017: Aquatic Toxicology
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