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unfolding cases

Carlos A Plata, Zackary N Scholl, Piotr E Marszalek, Antonio Prados
A theoretical framework capable of predicting the first unit that unfolds in pulled modular proteins has been recently introduced, for "fast enough" pulling velocities. Within this picture, we investigate the unfolding pathway in a chain of identical units and predict that the module closest to the pulled end opens first. Steered molecular dynamics of a simple construct, specifically a chain composed of two coiled-coil motives, shows that this is indeed the case. Notwithstanding, the unfolding behavior strongly depends on the terminus (C or N) from which this homopolyprotein is pulled...
May 17, 2018: Journal of Chemical Theory and Computation
Peter D Keightley, Benjamin C Jackson
It is known that the allele ancestral to the variation at a polymorphic site cannot be assigned with certainty, and that the most frequently used method to assign the ancestral state - maximum parsimony - is prone to misinference. Estimates of counts of sites that have a certain number of copies of the derived allele in a sample (the unfolded site frequency spectrum, uSFS) made by parsimony are therefore also biased. We previously developed a maximum likelihood method to estimate the uSFS for a focal species using information from two outgroups while assuming simple models of nucleotide substitution...
May 16, 2018: Genetics
Upendra Kumar Singh, Rajan Patel
In vitro refolding of denatured proteins and influence of alkyl chain of these organic salts on their performance as refolding enhancers was tested using long chain imidazolium chloride salts, 1-methyl-3-octylimidazolium chloride [C8mim][Cl], 1-decyl-3-methylimidazolium chloride [C10mim][Cl]. The horse heart cytochrome c (h-cyt c) was denatured by urea and guanidinium hydrochloride (GdnHCl), as well as base induced denaturation at pH 13 to provide a broad overview of the overall refolding behavior. The variation in alkyl chain of ionic liquids (ILs) showed a profound effect on the refolding of denatured h-cyt c...
May 16, 2018: Molecular Pharmaceutics
Mehmet Cüneyt Özmen, Nilay Dilekmen, Erdem Yüksel, Bahri Aydın, Fikret Akata
Large radial tears of donor Descemet membrane (DM) during the preparation of Descemet membrane endothelial keratoplasty (DMEK) grafts can make the trephination stage impossible because of small graft diameter. This results in irregular-edged grafts. In this study, we report two pseudophakic bullous keratopathy patients who underwent DMEK surgery with irregular-edged Descemet membrane (DM) grafts. Main outcome measures were preoperative and postoperative 1-, 3-, and 6-month best corrected visual acuity (BCVA), endothelial cell density (ECD) and central corneal thickness (CCT)...
April 2018: Turkish Journal of Ophthalmology
Erica Ciotta, Paolo Prosposito, Pietro Tagliatesta, Chiara Lorecchio, Lorenzo Stella, Saulius Kaciulis, Peiman Soltani, Ernesto Placidi, Roberto Pizzoferrato
A novel type of graphene-like nanoparticle, synthesized by oxidation and unfolding of C60 buckminsterfullerene fullerene, showed multiple and reproducible sensitivity to Cu2+ , Pb2+ , Cd2+ , and As(III) through different degrees of fluorescence quenching or, in the case of Cd2+ , through a remarkable fluorescence enhancement. Most importantly, only for Cu2+ and Pb2+ , the fluorescence intensity variations came with distinct modifications of the optical absorption spectrum. Time-resolved fluorescence study confirmed that the common origin of these diverse behaviors lies in complexation of the metal ions by fullerene-derived carbon layers, even though further studies are required for a complete explanation of the involved processes...
May 10, 2018: Sensors
Arnald Puy
Unfolding regularities between population and irrigated agriculture might increase our capacity to predict their co-evolution and better ensure food security and environmental welfare. Here I use three different datasets with detailed information at the national level for c. 70% of the countries of Africa, Asia, the Americas and Europe between 1950-2017 to show that irrigated areas might grow disproportionally for a given increase in population, e.g. with b > 1. The results are robust across continents, time series, population cut-offs and variations in the area accounted for irrigation by official institutions and independent scholars...
May 9, 2018: Ecological Applications: a Publication of the Ecological Society of America
Anne Caclin, Barbara Tillmann
Auditory short-term memory (STM) is a fundamental ability to make sense of auditory information as it unfolds over time. Whether separate STM systems exist for different types of auditory information (music and speech, in particular) is a matter of debate. The present paper reviews studies that have investigated both musical and verbal STM in healthy individuals and in participants with neurodevelopmental and neurological disorders. Overall, the results are in favor of only partly shared networks for musical and verbal STM...
May 9, 2018: Annals of the New York Academy of Sciences
L Montibeller, J de Belleroche
The endoplasmic reticulum (ER) plays an important role in maintenance of proteostasis through the unfolded protein response (UPR), which is strongly activated in most neurodegenerative disorders. UPR signalling pathways mediated by IRE1α and ATF6 play a crucial role in the maintenance of ER homeostasis through the transactivation of an array of transcription factors. When activated, these transcription factors induce the expression of genes involved in protein folding and degradation with pro-survival effects...
May 4, 2018: Cell Stress & Chaperones
Valgardur Sigurdsson, Kenichi Miharada
Hematopoietic stem cells (HSCs) play a central role in hematopoietic regeneration, which has been demonstrated by thorough studies. In contrast, the cell cycle status and metabolic condition of HSCs define these cells as dormant. Recent studies have also revealed that protein metabolism is quite unique, as dormant HSCs have a lower protein synthesis rate and folding capacity. Under proliferative conditions, upon hematopoietic stress, HSCs need to deal with higher requirements of protein production to achieve fast and effective blood replenishment...
May 3, 2018: International Journal of Hematology
Valentina Grande, Francesca Ornaghi, Liliana Comerio, Elena Restelli, Antonio Masone, Alessandro Corbelli, Daniele Tolomeo, Vanessa Capone, Jeffrey M Axten, Nicholas J Laping, Fabio Fiordaliso, Michele Sallese, Roberto Chiesa
Marinesco-Sjögren syndrome (MSS) is a rare, early-onset, autosomal recessive multisystem disorder characterized by cerebellar ataxia, cataracts and myopathy. Most MSS cases are caused by loss-of-function mutations in the gene encoding SIL1, a nucleotide exchange factor for the molecular chaperone BiP which is essential for correct protein folding in the endoplasmic reticulum. Woozy mice carrying a spontaneous Sil1 mutation recapitulate key pathological features of MSS, including cerebellar atrophy with degeneration of Purkinje cells, and progressive myopathy...
April 28, 2018: Human Molecular Genetics
R Aaron Rogers, Aaron M Fleming, Cynthia J Burrows
We have interrogated the isothermal folding behavior of the DNA i-motif of the human telomere, dC19 , and a high-stability i-motif-forming sequence in the promoter of the human DNA repair gene RAD17 using human physiological solution and temperature conditions. We developed a circular-dichroism-spectroscopy-based pH titration method that is followed by analysis of titration curves in the derivative domain and found that the observed pH-dependent folding behavior can be significantly different and, in some cases, multiphasic, with a dependence on how rapidly i-motif folding is induced...
April 24, 2018: Biophysical Journal
Letizia Caronia, Marzia Saglietti
This paper focuses on the epistemic and interactional resources displayed by nurses participating in medical case construction and the ways through which they make a difference in the unfolding of this activity. This paper draws on an ethnographic research in an Italian Intensive Care Unit (ICU) selected according to a purposeful sampling approach out of a national sample of 40 ICUs participating in a larger research project. Our dataset, collected over a period of six months of ethnographic observations, consisted of the observers' field notes and log-books, audio and video-recordings of morning briefings, in-depth interviews, informal conversations and shadowing of bedside practices...
April 19, 2018: Journal of Interprofessional Care
M Romero-Expósito, S Viñals, O Ortega-Gelabert, B Fernández, P Jiménez-Bonilla, J Praena, C Domingo
The proton beam produced in the Nuclear Physics line of the tandem accelerator of the Centro Nacional de Aceleradores was used to generate a neutron field. In particular, 1.912 MeV protons were used to produce well-known epithermal neutrons through the p+7Li → n+7Be reaction. The aim of the work was to characterize this field while testing the performance of a Bonner sphere spectrometer in the epithermal range. Measurements were performed in four locations at different angle (0°, 30°, 60° and 90°) from beam incidence direction in order to study the angular dependence of the field...
April 13, 2018: Radiation Protection Dosimetry
Andrea Arsiccio, Roberto Pisano
PURPOSE: Surfactants are common stabilizers, often added to biopharmaceuticals formulations, but the mechanisms at the basis of their activity are unclear. The aim of this work is to provide insight into the molecular factors underlying surfactant effectiveness as protectants. METHODS: Molecular Dynamics simulations of human growth hormone (hGH) in the presence of Tween 20 were performed. The effect of Tween 20 was compared with the activity of commonly used protectants, such as the disaccharides...
April 10, 2018: European Journal of Pharmaceutics and Biopharmaceutics
Richard A Campbell, Andrea Tummino, Imre Varga, Olga Yu Milyaeva, Michael M Krycki, Shi-Yow Lin, Valerie Laux, Michael Haertlein, Victor Trevor Forsyth, Boris A Noskov
The application of protein deuteration and high flux neutron reflectometry has allowed a comparison of the adsorption properties of lysozyme at the air-water interface from dilute solutions with and without strong denaturants, urea and guanidine hydrochloride (GuHCl). The surface excess and adsorption layer thickness were resolved and complemented by images of the mesoscopic lateral morphology from Brewster angle microscopy. It was revealed that the thickness of the adsorption layer in the absence of added denaturants is less than the short axial length of the lysozyme molecule, which indicates deformation of the globules at the interface...
April 9, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Miguel Luis Podestá, Miguel Podestá
Introduction: Surgical treatment of congenital megaprepuce is challenging and controversial. We report our 10-year experience treating patients with this deformity using a standardized procedure that has similarities to a technique reported by Smeulders et al. (1). Our postoperative complications and mid-term follow-up cosmetic appearance of the genitalia after reconstruction are reviewed. Material and methods: Fifteen patients operated on between 2005 and 2015 were evaluated...
2018: Frontiers in Pediatrics
Wenwei Zheng, Gül H Zerze, Alessandro Borgia, Jeetain Mittal, Benjamin Schuler, Robert B Best
Förster resonance energy transfer (FRET) is a powerful tool for elucidating both structural and dynamic properties of unfolded or disordered biomolecules, especially in single-molecule experiments. However, the key observables, namely, the mean transfer efficiency and fluorescence lifetimes of the donor and acceptor chromophores, are averaged over a broad distribution of donor-acceptor distances. The inferred average properties of the ensemble therefore depend on the form of the model distribution chosen to describe the distance, as has been widely recognized...
March 28, 2018: Journal of Chemical Physics
Nidhi Katyal, Manish Agarwal, Raktim Sen, Vinay Kumar, Shashank Deep
Aggregation of α-synuclein is closely connected to the pathology of Parkinson's disease. The phenomenon involves multiple steps, commenced by partial misfolding and eventually leading to mature amyloid fibril formation. Trehalose, a widely accepted osmolyte, has been shown previously to inhibit aggregation of various globular proteins owing to its ability to prevent the initial unfolding of protein. In this study, we have examined if it behaves in a similar fashion with intrinsically disordered protein α-synuclein and possesses the potential to act as therapeutic agent against Parkinson's disease...
March 30, 2018: ACS Chemical Neuroscience
Bingbing Nie, Deepak Sathyanarayan, Xin Ye, Jeff R Crandall, Matthew B Panzer
OBJECTIVE: Recent field data analysis has demonstrated that knee airbags (KABs) can reduce occupant femur and pelvis injuries but may be insufficient to decrease leg injuries in motor vehicle crashes. An enhanced understanding of the associated injury mechanisms requires accurate assessment of physiological-based occupant parameters, some of which are difficult or impossible to obtain from experiments. This study sought to explore how active muscle response can influence the injury risk of lower extremities during KAB deployment using computational biomechanical analysis...
February 28, 2018: Traffic Injury Prevention
Wenwei Zheng, Robert B Best
Guinier analysis allows model-free determination of the radius of gyration (Rg ) of a biomolecule from X-ray or neutron scattering data, in the limit of very small scattering angles. Its range of validity is well understood for globular proteins, but is known to be more restricted for unfolded or intrinsically disordered proteins (IDPs). We have used ensembles of disordered structures from molecular dynamics simulations to investigate which structural properties cause deviations from the Guinier approximation at small scattering angles...
March 20, 2018: Journal of Molecular Biology
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