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https://www.readbyqxmd.com/read/28551461/revisiting-the-value-of-competition-assays-in-folate-receptor-mediated-drug-delivery
#1
Steven K Jones, Anwesha Sarkar, Daniel P Feldmann, Peter Hoffmann, Olivia M Merkel
Polymeric nanoparticles have been studied for gene and drug delivery. These nanoparticles can be modified to utilize a targeted delivery approach to selectively deliver their payload to specific cells, while avoiding unwanted delivery to healthy cells. One commonly over-expressed receptor which can be targeted by ligand-conjugated nanoparticles is the folate receptor alpha (FRα). The ability to target FRα remains a promising concept, and therefore, understanding the binding dynamics of the receptor with the ligand of the nanoparticle therapeutic can provide valuable insight...
May 22, 2017: Biomaterials
https://www.readbyqxmd.com/read/28550295/effects-of-protein-corona-on-iapp-amyloid-aggregation-fibril-remodelling-and-cytotoxicity
#2
Emily H Pilkington, Yanting Xing, Bo Wang, Aleksandr Kakinen, Miaoyi Wang, Thomas P Davis, Feng Ding, Pu Chun Ke
Aggregation of islet amyloid polypeptide (IAPP), a peptide hormone co-synthesized and co-stored with insulin in pancreatic cells and also co-secreted to the circulation, is associated with beta-cell death in type-2 diabetes (T2D). In T2D patients IAPP is found aggregating in the extracellular space of the islets of Langerhans. Although the physiological environments of these intra- and extra-cellular compartments and vascular systems significantly differ, the presence of proteins is ubiquitous but the effects of protein binding on IAPP aggregation are largely unknown...
May 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28548882/finding-conducting-and-nurturing-science-a-virologist-s-memoir
#3
Anna Marie Ann Skalka Skalka
My laboratory investigations have been driven by an abiding interest in understanding the consequences of genetic rearrangement in evolution and disease, and in using viruses to elucidate fundamental mechanisms in biology. Starting with bacteriophages and moving to the retroviruses, my use of the tools of genetics, molecular biology, biochemistry, and biophysics has spanned more than half a century-from the time when DNA structure was just discovered to the present day of big data and epigenetics. Both riding and contributing to the successive waves of technology, my laboratory has elucidated fundamental mechanisms in DNA replication, repair, and recombination...
May 26, 2017: Annual Review of Virology
https://www.readbyqxmd.com/read/28546316/satellites-reveal-contrasting-responses-of-regional-climate-to-the-widespread-greening-of-earth
#4
Giovanni Forzieri, Ramdane Alkama, Diego G Miralles, Alessandro Cescatti
Changes in vegetation cover associated to the observed greening may affect several biophysical processes, whose net effects on climate are unclear. Here, we analyze remotely sensed dynamics in leaf area index (LAI) and energy fluxes to explore the associated variation in local climate. We show that the increasing trend in LAI contributed to the warming of boreal zones through a reduction of surface albedo, and to an evaporation-driven cooling in arid regions. The interplay between LAI and surface biophysics is amplified up to five times under extreme warm-dry and cold-wet years...
May 25, 2017: Science
https://www.readbyqxmd.com/read/28546283/high-resolution-mapping-of-gastric-slow-wave-recovery-profiles-biophysical-model-methodology-and-demonstration-of-applications
#5
Niranchan Paskaranandavadivel, Leo K Cheng, Peng Du, Jack M Rogers, Gregory O'Grady
Slow waves play a central role in coordinating gastric motor activity. High-resolution mapping of extracellular potentials from the stomach provides spatiotemporal detail on normal and dysrhythmic slow-wave patterns. All mapping studies to date have focused exclusively on tissue activation; however, the recovery phase contains vital information on repolarization heterogeneity, the excitable gap, and refractory tail interactions, but has not been investigated. Here, we report a method to identify the recovery phase in slow-wave mapping data...
May 25, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28545134/structures-of-the-inactive-and-active-states-of-rip2-kinase-inform-on-the-mechanism-of-activation
#6
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/28544964/biophysical-and-biological-studies-of-some-polymer-grafted-metallo-intercalators
#7
Yesaiyan Manojkumar, Subramanian Ambika, Rajendran Senthilkumar, Sankaralingam Arunachalam
Two water-soluble polymer-copper(II) complexes, [Cu(ip)2(BPEI)](ClO4)2·H2O (Complex 1) and [Cu(dppz)2BPEI](ClO4)2·H2O (Complex 2) with different degree of coordination have been synthesized and characterized. The interaction between the prepared complexes and CTDNA has been assessed by various physico-chemical methods The spectroscopic and the cyclic voltammetry studies have revealed that both the complexes interact with CTDNA through intercalation binding mode. Among the two complexes, Complex 2 has higher binding affinity with CTDNA...
May 15, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28544958/impact-of-triblock-copolymers-on-the-biophysical-function-of-naturally-derived-lung-surfactant
#8
Moritz Beck-Broichsitter, Christian A Ruge, Adam Bohr
The current study aimed at investigating the general applicability of triblock copolymers consisting of poly(ethylene glycol) and poly(propylene glycol) (Pluronic(®)) as excipients for lung delivery. After thorough physicochemical characterization of the diverse polymers, their cytotoxicity was evaluated using alveolar epithelial cells. Next, a naturally-derived lung surfactant was challenged with the distinct triblock copolymers with respect to changes in microstructure, adsorption to the air/liquid interface and dynamic surface tension behavior under bubble pulsation...
May 17, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28544846/genomic-dna-interactions-mechanize-peptidotoxin-mediated-anti-cancer-nanotherapy
#9
Santosh K Misra, Aaron S Schwartz-Duval, Dipanjan Pan
Host defense peptides (HDPs) are a class of evolutionarily conserved substances of the innate immune response that has been identified as major players in the defense system in many living organisms. Some of the HDPs are also referred as peptidotoxins which offer immense potential for anti-cancer therapy. However, their therapeutic potential is yet to be fully translated mainly due to their off-target toxicity. Here we show that their nano-enabled delivery may become beneficial in controlling their delivery in intra-cellular space...
May 25, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28544415/inertial-microfluidic-cell-stretcher-imcs-fully-automated-high-throughput-and-near-real-time-cell-mechanotyping
#10
Yanxiang Deng, Steven P Davis, Fan Yang, Kevin S Paulsen, Maneesh Kumar, Rebecca Sinnott DeVaux, Xianhui Wang, Douglas S Conklin, Assad Oberai, Jason I Herschkowitz, Aram J Chung
Mechanical biomarkers associated with cytoskeletal structures have been reported as powerful label-free cell state identifiers. In order to measure cell mechanical properties, traditional biophysical (e.g., atomic force microscopy, micropipette aspiration, optical stretchers) and microfluidic approaches were mainly employed; however, they critically suffer from low-throughput, low-sensitivity, and/or time-consuming and labor-intensive processes, not allowing techniques to be practically used for cell biology research applications...
May 23, 2017: Small
https://www.readbyqxmd.com/read/28544119/common-fibril-structures-imply-systemically-conserved-protein-misfolding-pathways-in%C3%A2-vivo
#11
Karthikeyan Annamalai, Falk Liberta, Marie-Theres Vielberg, William Close, Hauke Lilie, Karl-Heinz Gührs, Angelika Schierhorn, Rolf Koehler, Andreas Schmidt, Christian Haupt, Ute Hegenbart, Stefan Schönland, Matthias Schmidt, Michael Groll, Marcus Fändrich
Systemic amyloidosis is caused by the misfolding of a circulating amyloid precursor protein and the deposition of amyloid fibrils in multiple organs. Chemical and biophysical analysis of amyloid fibrils from human AL and murine AA amyloidosis reveal the same fibril morphologies in different tissues or organs of one patient or diseased animal. The observed structural similarities concerned the fibril morphology, the fibril protein primary and secondary structures, the presence of post-translational modifications and, in case of the AL fibrils, the partially folded characteristics of the polypeptide chain within the fibril...
May 23, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28543811/the-structural-flexibility-of-the-human-copper-chaperone-atox1-insights-from-combined-pulsed-epr-studies-and-computations
#12
Ariel R Levy, Meital Turgeman, Lada Gevorkyan-Aiapetov, Sharon Ruthstein
Metallochaperones are responsible for shuttling metal ions to target proteins. Thus, a metallochaperone's structure must be sufficiently flexible both to hold onto its ion while traversing the cytoplasm and to transfer the ion to or from a partner protein. Here, we sought to shed light on the structure of Atox1, a metallochaperone involved in the human copper regulation system. Atox1 shuttles copper ions from the main copper transporter, Ctr1, to the ATP7b transporter in the Golgi apparatus. Conventional biophysical tools such as X-ray or NMR cannot always target the various conformational states of metallochaperones, owing to a requirement for crystallography or low sensitivity and resolution...
May 20, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28543540/computational-modeling-of-915-mhz-microwave-ablation-comparative-assessment-of-temperature-dependent-tissue-dielectric-models
#13
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/28542952/compensatory-and-decompensatory-alterations-in-cardiomyocyte-ca-2-dynamics-in-hearts-with-diastolic-dysfunction-following-aortic-banding
#14
Sara Gattoni, Åsmund Treu Røe, Jan Magnus Aronsen, Ivar Sjaastad, William E Louch, Nicolas P Smith, Steven A Niederer
KEY POINTS: At the cellular level cardiac hypertrophy causes remodelling, leading to changes in ionic channel, pump and exchanger densities and kinetics. Previous studies have focused on quantifying changes in channels, pumps and exchangers without quantitatively linking these changes with emergent cellular scale functionality. Two biophysical cardiac cell models were created, parameterized and validated and are able to simulate electrophysiology and calcium dynamics in myocytes from control sham operated rats and aortic-banded rats exhibiting diastolic dysfunction...
May 21, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28542469/biophysical-markers-of-the-peripheral-vasoconstriction-response-to-pain-in-sickle-cell-disease
#15
Patjanaporn Chalacheva, Maha Khaleel, John Sunwoo, Payal Shah, Jon A Detterich, Roberta M Kato, Wanwara Thuptimdang, Herbert J Meiselman, Richard Sposto, Jennie Tsao, John C Wood, Lonnie Zeltzer, Thomas D Coates, Michael C K Khoo
Painful vaso-occlusive crisis (VOC), a complication of sickle cell disease (SCD), occurs when sickled red blood cells obstruct flow in the microvasculature. We postulated that exaggerated sympathetically mediated vasoconstriction, endothelial dysfunction and the synergistic interaction between these two factors act together to reduce microvascular flow, promoting regional vaso-occlusions, setting the stage for VOC. We previously found that SCD subjects had stronger vasoconstriction response to pulses of heat-induced pain compared to controls but the relative degrees to which autonomic dysregulation, peripheral vascular dysfunction and their interaction are present in SCD remain unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28542261/considering-reefscape-configuration-and-composition-in-biophysical-models-advance-seascape-genetics
#16
Simon Van Wynsberge, Serge Andréfouët, Nabila Gaertner-Mazouni, Josina Tiavouane, Daphné Grulois, Jérôme Lefèvre, Malin L Pinsky, Cécile Fauvelot
Previous seascape genetics studies have emphasized the role of ocean currents and geographic distances to explain the genetic structure of marine species, but the role of benthic habitat has been more rarely considered. Here, we compared the population genetic structure observed in West Pacific giant clam populations against model simulations that accounted habitat composition and configuration, geographical distance, and oceanic currents. Dispersal determined by geographical distance provided a modelled genetic structure in better agreement with the observations than dispersal by oceanic currents, possibly due to insufficient spatial resolution of available oceanographic and coastal circulation models...
2017: PloS One
https://www.readbyqxmd.com/read/28542206/carbonyl-based-blue-autofluorescence-of-proteins-and-amino-acids
#17
Chamani Niyangoda, Tatiana Miti, Leonid Breydo, Vladimir Uversky, Martin Muschol
Intrinsic protein fluorescence is inextricably linked to the near-UV autofluorescence of aromatic amino acids. Here we show that a novel deep-blue autofluorescence (dbAF), previously thought to emerge as a result of protein aggregation, is present at the level of monomeric proteins and even poly- and single amino acids. Just as its aggregation-related counterpart, this autofluorescence does not depend on aromatic residues, can be excited at the long wavelength edge of the UV and emits in the deep blue. Differences in dbAF excitation and emission peaks and intensities from proteins and single amino acids upon changes in solution conditions suggest dbAF's sensitivity to both the chemical identity and solution environment of amino acids...
2017: PloS One
https://www.readbyqxmd.com/read/28540828/tumor-tissue-transport-after-intraperitoneal-anticancer-drug-delivery
#18
Charlotte Carlier, Ada Mathys, Emiel De Jaeghere, Margo Steuperaert, Olivier De Wever, Wim Ceelen
Intraperitoneal (IP) drug delivery, either as an intraoperative chemoperfusion or as adjuvant, repeated instillation, is an established treatment modality in patients with peritoneal carcinomatosis. The efficacy of IP drugs depends on its ability to penetrate the tumor stroma in order to reach their (sub)cellular target. It is known, that drug penetration after IP delivery is limited to a few millimeters. Here, we review the basic tissue transport mechanisms after IP delivery, and discuss the biophysical barriers and obstacles that limit penetration distance...
March 28, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28540352/dataset-on-galanin-receptor-3-mutants-that-improve-recombinant-receptor-expression-and-stability-in-an-agonist-and-antagonist-bound-form
#19
Thao T Ho, Jasmine T Nguyen, Juping Liu, Pawel Stanczak, Aaron A Thompson, Yingzhuo G Yan, Jasmine Chen, Charles K Allerston, Charles L Dillard, Hao Xu, Nicholas J Shoger, Jill S Cameron, Mark E Massari, Kathleen Aertgeerts
Galanin Receptor 3 (GALR3) is a G-protein-coupled receptor with a widespread distribution in the brain and plays a role in a variety of physiologic processes including cognition/memory, sensory/pain processing, hormone secretion, and feeding behavior. Therefore, GALR3 is considered an attractive CNS drug target (Freimann et al., 2015) [1]. This dataset contains GALR3 point mutants that improve recombinant protein expression and thermal stability of the receptor contained in virus-like particles (VLPs) or obtained by detergent-purification of baculovirus-infected insect cells...
June 2017: Data in Brief
https://www.readbyqxmd.com/read/28539630/functional-characterization-of-the-meiosis-specific-dna-double-strand-break-inducing-factor-spo-11-from-c-elegans
#20
Hsin-Yi Yeh, Sheng-Wei Lin, Yi-Chun Wu, Nei-Li Chan, Peter Chi
The programmed induction of meiotic DNA double-strand breaks (DSBs) by the evolutionarily conserved SPO-11 protein, which is structurally related to archaeal Topo VIA topoisomerases, triggers meiotic recombination. Identification of several meiosis-specific factors that are required for SPO-11-mediated DSB formation raises the question whether SPO-11 alone can cleave DNA. Here, we have developed procedures to express and purify C. elegans SPO-11 in a soluble, untagged, and monodispersed form. Our biochemical and biophysical analyses demonstrate that SPO-11 is monomeric and binds DNA, double-stranded DNA in particular...
May 24, 2017: Scientific Reports
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