scholarly journals Theories and methods of virus isoelectric point estimation (Minireview)

2020 ◽  
Author(s):  
Joe Heffron ◽  
Brooke K. Mayer
Keyword(s):  
Surface Charge ◽  
Isoelectric Point ◽  
Electrostatic Interactions ◽  
3D Structure ◽  
Point Estimation ◽  
Electrostatic Model ◽  
Diverse Range ◽  
Enveloped Virus ◽  
The Impact ◽  
Exclusion Method

Much of virus fate, both in the environment and physical/chemical treatment, is dependent on electrostatic interactions. Developing an accurate means of predicting virion isoelectric point (pI) would help to understand and anticipate virus fate and transport, especially for viruses that are not readily propagated in the lab. One simple approach to predicting pI estimates the pH at which the sum of charges from ionizable amino acids in capsid proteins approaches zero. However, predicted pIs based on capsid charges frequently deviate by several pH units from empirically measured pIs. Recently, the discrepancy between empirical and predicted pI was attributed to the electrostatic neutralization of predictable polynucleotide-binding regions (PBRs) of the capsid interior. In this paper, we review models presupposing the A) influence of the viral polynucleotide on surface charge, or B) contribution of only exterior residues to surface charge. We then compare these models to the approach of excluding only PBRs and hypothesize a conceptual electrostatic model that aligns with this approach. The PBR exclusion method outperformed methods based on 3D structure and accounted for major discrepancies in predicted pIs without adversely affecting pI prediction for a diverse range of viruses. In addition, the PBR exclusion method was determined to be the best available method for predicting virus pI since: A) PBRs are predicted independently of the impact on pI, B) PBR prediction relies on proteome sequences rather than detailed structural models, and C) PBR exclusion was successfully demonstrated on a diverse set of viruses. These models apply to nonenveloped viruses only. A similar model for enveloped viruses is complicated by lack of data on enveloped virus pI, as well as uncertainties regarding the influence of the phospholipid envelope on charge and ion gradients.

scholarly journals Improved virus isoelectric point estimation by exclusion of known and predicted genome-binding regions

2020 ◽  
Author(s):  
Joe Heffron ◽  
Brooke K. Mayer
Keyword(s):  
Isoelectric Point ◽  
Electrostatic Interactions ◽  
Point Estimation ◽  
General Interest ◽  
Simple Explanation ◽  
Sequence Motifs ◽  
Virus Capsid ◽  
Charge Model ◽  
Binding Regions ◽  
Mean Differences

AbstractAccurate prediction of the isoelectric point (pI) of viruses is beneficial for modeling virus behavior in environmental transport and physical/chemical treatment applications. However, the empirically measured pIs of many viruses have thus far defied simple explanation, let alone prediction, based on the ionizable amino acid composition of the virus capsid. Here, we suggest an approach for predicting virus pI by excluding capsid regions that stabilize the virus polynucleotide via electrostatic interactions. This method was applied first to viruses with known polynucleotide-binding regions (PBRs) and/or 3D structures. Then, PBRs were predicted in a group of 32 unique viral capsid proteome sequences via conserved structures and sequence motifs. Removing predicted PBRs resulted in a significantly better fit to empirical pI values. After modification, mean differences between theoretical and empirical pI values were reduced from 2.1 ± 2.4 to 0.1 ± 1.7 pH units.ImportanceThis model is the first to fit predicted pIs to empirical values for a diverse set of viruses. The results suggest that many previously-reported discrepancies between theoretical and empirical virus pIs can be explained by coulombic neutralization of PBRs of the inner capsid. Given the diversity of virus capsid structures, this nonarbitrary, heuristic approach to predicting virus pI offers an effective alternative to a simplistic, one-size-fits-all charge model of the virion. The accurate, structure-based prediction of PBRs of the virus capsid employed here may also be of general interest to structural virologists.

The Oxford Handbook of Adult Cognitive Disorders

2019 ◽  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
Neurodevelopmental Disorders ◽  
Brain Aging ◽  
Cognitive Disorders ◽  
Diverse Range ◽  
Medical Specialties ◽  
Psychiatric Illnesses ◽  
Medical Disorders ◽  
The Impact

The prevalence of cognitive impairment caused by neurodegenerative diseases and other neurologic disorders associated with aging is expected to rise dramatically between now and year 2050, when the population of Americans aged 65 or older will nearly double. Cognitive impairment also commonly occurs in other neurologic conditions, as well as in non-neurologic medical disorders (and their treatments), idiopathic psychiatric illnesses, and adult neurodevelopmental disorders. Cognitive impairment can thus infiltrate all aspects of healthcare, making it necessary for clinicians and clinical researchers to have an integrated knowledge of the spectrum of adult cognitive disorders. The Oxford Handbook of Adult Cognitive Disorders is meant to serve as an up-to-date, scholarly, and comprehensive volume covering most diseases, conditions, and injuries resulting in impairments in cognitive function in adults. Topics covered include normal cognitive and brain aging, the impact of medical disorders (e.g., cardiovascular, liver, pulmonary) and psychiatric illnesses (e.g., depression and bipolar disorder) on cognitive function, adult neurodevelopmental disorders (e.g., Down Syndrome, Attention Deficit/Hyperactivity Disorder), as well as the various neurological conditions (e.g., Alzheimer’s disease, chronic traumatic encephalopathy, concussion). A section of the Handbook is also dedicated to unique perspectives and special considerations for the clinicians and clinical researchers, covering topics such as cognitive reserve, genetics, diversity, and neuroethics. The target audience of this Handbook includes: (1) clinicians, particularly psychologists, neuropsychologists, neurologists (including behavioral and cognitive neurologists), geriatricians, and psychiatrists (including neuropsychiatrists), who provide clinical care and management for adults with a diverse range of cognitive disorders; (2) clinical researchers who investigate cognitive outcomes and functioning in adult populations; and (3) graduate level students and post-doctoral trainees studying psychology, clinical neuroscience, and various medical specialties.

scholarly journals Surface charge modulation of rifampicin-loaded PLA nanoparticles to improve antibiotic delivery in Staphylococcus aureus biofilms

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
David Da Costa ◽  
Chloé Exbrayat-Héritier ◽  
Basile Rambaud ◽  
Simon Megy ◽  
Raphaël Terreux ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Surface Charge ◽  
Treatment Efficacy ◽  
Particle Migration ◽  
Bacterial Biofilm ◽  
Poly Lactic Acid ◽  
Retention Capacity ◽  
The Impact ◽  
Positively Charged ◽  
Antibiotic Delivery

Abstract Background After the golden age of antibiotic discovery, bacterial infections still represent a major challenge for public health worldwide. The biofilm mode of growth is mostly responsible for chronic infections that current therapeutics fail to cure and it is well-established that novel strategies must be investigated. Particulate drug delivery systems are considered as a promising strategy to face issues related to antibiotic treatments in a biofilm context. Particularly, poly-lactic acid (PLA) nanoparticles present a great interest due to their ability to migrate into biofilms thanks to their submicronic size. However, questions still remain unresolved about their mode of action in biofilms depending on their surface properties. In the current study, we have investigated the impact of their surface charge, firstly on their behavior within a bacterial biofilm, and secondly on the antibiotic delivery and the treatment efficacy. Results Rifampicin-loaded PLA nanoparticles were synthetized by nanoprecipitation and characterized. A high and superficial loading of rifampicin, confirmed by an in silico simulation, enabled to deliver effective antibiotic doses with a two-phase release, appropriate for biofilm-associated treatments. These nanoparticles were functionalized with poly-l-lysine, a cationic peptide, by surface coating inducing charge reversal without altering the other physicochemical properties of these particles. Positively charged nanoparticles were able to interact stronger than negative ones with Staphylococcus aureus, under planktonic and biofilm modes of growth, leading to a slowed particle migration in the biofilm thickness and to an improved retention of these cationic particles in biofilms. While rifampicin was totally ineffective in biofilms after washing, the increased retention capacity of poly-l-lysine-coated rifampicin-loaded PLA nanoparticles has been associated with a better antibiotic efficacy than uncoated negatively charged ones. Conclusions Correlating the carrier retention capacity in biofilms with the treatment efficacy, positively charged rifampicin-loaded PLA nanoparticles are therefore proposed as an adapted and promising approach to improve antibiotic delivery in S. aureus biofilms.

scholarly journals Cooperation/Competition between Halogen Bonds and Hydrogen Bonds in Complexes of 2,6-Diaminopyridines and X-CY3 (X = Cl, Br; Y = H, F)

Symmetry ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 766
Author(s):  
Barbara Bankiewicz ◽  
Marcin Palusiak
Keyword(s):  
Complex Formation ◽  
Hydrogen Bonds ◽  
Dft Calculations ◽  
Electrostatic Interactions ◽  
Dipole Moments ◽  
Main Role ◽  
Halogen Bonds ◽  
Topological Parameters ◽  
Leading Role ◽  
The Impact

The DFT calculations have been performed on a series of two-element complexes formed by substituted 2,6-diaminopyridine (R−PDA) and pyridine (R−Pyr) with X−CY3 molecules (where X = Cl, Br and Y = H, F). The primary aim of this study was to examine the intermolecular hydrogen and halogen bonds in the condition of their mutual coexistence. Symmetry/antisymmetry of the interrelation between three individual interactions is addressed. It appears that halogen bonds play the main role in the stabilization of the structures of the selected systems. However, the occurrence of one or two hydrogen bonds was associated with the favourable geometry of the complexes. Moreover, the impact of different substituent groups attached in the para position to the aromatic ring of the 2,6-diaminopyridine and pyridine on the character of the intermolecular hydrogen and halogen bonds was examined. The results indicate that the presence of electron-donating substituents strengthens the bonds. In turn, the presence of electron-withdrawing substituents reduces the strength of halogen bonds. Additionally, when hydrogen and halogen bonds lose their leading role in the complex formation, the nonspecific electrostatic interactions between dipole moments take their place. Analysis was based on geometric, energetic, and topological parameters of the studied systems.

Transport of Ions and Molecules in Nanofluidic Devices

2008 ◽  
Author(s):  
Rohit Karnik ◽  
Chuanhua Duan ◽  
Kenneth Castelino ◽  
Rong Fan ◽  
Peidong Yang ◽  
...  
Keyword(s):  
Surface Charge ◽  
Surface Area ◽  
Field Effect ◽  
Electrostatic Interactions ◽  
Surface Reactions ◽  
Molecular Transport ◽  
Large Surface Area ◽  
Ionic Concentrations ◽  
Nanofluidic Devices ◽  
Transport Of Ions

Interesting transport phenomena arise when fluids are confined to nanoscale dimensions in the range of 1–100 nm. We examine three distinct effects that influence ionic and molecular transport as the size of fluidic channels is decreased to the nanoscale. First, the length scale of electrostatic interactions in aqueous solutions becomes comparable to nanochannel size and the number of surface charges becomes comparable to the number of ions in the channel. Second, the size of the channel becomes comparable to the size of biomolecules such as proteins and DNA. Third, large surface area-to-volume ratios result in rapid rates of surface reactions and can dramatically affect transport of molecules through the channel. These phenomena enable us to control transport of ions and molecules in unique ways that are not possible in larger channels. Electrostatic interactions enable local control of ionic concentrations and transport inside nanochannels through field effect in a nanofluidic transistor, which is analogous to the metal-oxide-semiconductor field effect transistor. Furthermore, by controlling surface charge in nanochannels, it is possible to create a nanofluidic diode that rectifies ionic transport through the channel. Biological binding events result in partial blockage of the channel, and can thus be sensed by a decrease in nanochannel conductance. At low ionic concentrations, the effect of biomolecular charge is dominant and it can lead to an increase in conductance. Surface reactions can also be used to control transport of molecules though the channel due to the large surface area-to-volume ratios. Rapid surface reactions enable a new technique of diffusion-limited patterning (DLP), which is useful for patterning of biomolecules and surface charge in nanochannels. These examples illustrate how electrostatic interactions, biomolecular size, and surface reactions can be used for controlling ionic and molecular transport through nanochannels. These phenomena may be useful for operations such as analyte focusing, pH and ionic concentration control, and biosensing in micro- and nanofluidic devices.

scholarly journals Elucidating Binding Sites and Affinities of ERα Agonist and Antagonist to Human Alpha-Fetoprotein by in silico Modeling and Point Mutagenesis

2019 ◽  
Author(s):  
Nurbubu T. Moldogazieva ◽  
Daria S. Ostroverkhova ◽  
Nikolai N. Kuzmich ◽  
Vladimir V. Kadochnikov ◽  
Alexander A. Terentiev ◽  
...  
Keyword(s):  
Binding Sites ◽  
In Silico ◽  
Disulfide Bonds ◽  
Electrostatic Interactions ◽  
Molecular Mechanisms ◽  
3D Structure ◽  
Scoring Function ◽  
Alpha Fetoprotein ◽  
Ligand Interaction ◽  
Ligand Interactions

Alpha-fetoprotein (AFP) is a major embryo- and tumor-associated protein capable of binding and transporting variety of hydrophobic ligands including estrogens. AFP has been shown to inhibit estrogen receptor (ER)-positive tumor growth and this can be attributed to its estrogen-binding ability. Despite AFP has long been investigated, its three-dimensional (3D) structure has not been experimentally resolved and molecular mechanisms underlying AFP-ligand interaction remain obscure. In our study we constructed homology-based 3D model of human AFP (HAFP) with the purpose to perform docking of ERα ligands, three agonists (17β-estradiol, estrone and diethylstilbestrol) and three antagonists (tamoxifen, afimoxifene and endoxifen) into the obtained structure. Based on ligand docked scoring function, we identified three putative estrogen- and antiestrogen-binding sites with different ligand binding affinities. Two high-affinity sites were located in (i) a tunnel formed within HAFP subdomains IB and IIA and (ii) opposite side of the molecule in a groove originating from cavity formed between domains I and III, while (iii) the third low-affinity site was found at the bottom of the cavity. 100 ns MD simulation allowed studying their geometries and showed that HAFP-estrogen interactions occur due to van der Waals forces, while both hydrophobic and electrostatic interactions were almost equally involved in HAFP-antiestrogen binding. MM/GBSA rescoring method estimated binding free energies (ΔGbind) and showed that antiestrogens have higher affinities to HAFP as compared to estrogens. We performed in silico point substitutions of amino acid residues to confirm their roles in HAFP-ligand interactions and showed that Thr132, Leu138, His170, Phe172, Ser217, Gln221, His266, His316, Lys453, and Asp478 residues along two disulfide bonds, Cys224-Cys270 and Cys269-Cys277 have key roles in both HAFP-estrogen and HAFP-antiestrogen binding. Data obtained in our study contribute to understanding mechanisms underlying protein-ligand interactions and anti-cancer therapy strategies based on ER-binding ligands.

scholarly journals Wetting transition of ionic liquids at metal surfaces: A computational molecular approach to electronic screening using a virtual Thomas-Fermi fluid

2020 ◽  
Author(s):  
Alexander Schlaich ◽  
Dongliang Jin ◽  
Lyderic Bocquet ◽  
Benoit Coasne
Keyword(s):  
Ionic Liquids ◽  
Energy Storage ◽  
Electrostatic Interactions ◽  
Debye Length ◽  
Wetting Transition ◽  
Molecular Fluids ◽  
Thomas Fermi ◽  
Electronic Screening ◽  
Novel Approach ◽  
The Impact

Abstract Of particular relevance to energy storage, electrochemistry and catalysis, ionic and dipolar liquids display a wealth of unexpected fundamental behaviors – in particular in confinement. Beyond now well-documented adsorption, overscreening and crowding effects1,2,3, recent experiments have highlighted novel phenomena such as unconventional screening4 and the impact of the electronic nature – metallic versus insulating – of the confining surface on wetting/phase transitions5,6. Such behaviors, which challenge existing theoretical and numerical modeling frameworks, point to the need for new powerful tools to embrace the properties of confined ionic/dipolar liquids. Here, we introduce a novel atom-scale approach which allows for a versatile description of electronic screening while capturing all molecular aspects inherent to molecular fluids in nanoconfined/interfacial environments. While state of the art molecular simulation strategies only consider perfect metal or insulator surfaces, we build on the Thomas-Fermi formalism for electronic screening to develop an effective approach that allows dealing with any imperfect metal between these asymptotes. The core of our approach is to describe electrostatic interactions within the metal through the behavior of a `virtual' Thomas-Fermi fluid of charged particles, whose Debye length sets the Thomas-Fermi screening length λ in the metal. This easy-to-implement molecular method captures the electrostatic interaction decay upon varying λ from insulator to perfect metal conditions, while describing very accurately the capacitance behavior – and hence the electrochemical properties – of the metallic confining medium. By applying this strategy to a nanoconfined ionic liquid, we demonstrate an unprecedented wetting transition upon switching the confining medium from insulating to metallic. This novel approach provides a powerful framework to predict the unsual behavior of ionic liquids, in particular inside nanoporous metallic structures, with direct applications for energy storage and electrochemistry.

scholarly journals Effectiveness of Three Post-Harvest Rehabilitation Treatments for Runoff and Sediment Reduction on Skid Trails in the Hyrcanian Forests

2020 ◽  
Vol 41 (2) ◽  
pp. 309-324
Author(s):  
Meghdad Jourgholami ◽  
Masoumeh Ahmadi ◽  
Farzam Tavankar ◽  
Rodolfo Picchio
Keyword(s):  
Leaf Litter ◽  
Sediment Yield ◽  
Rainfall Intensity ◽  
Regression Equations ◽  
Negative Effects ◽  
Diverse Range ◽  
Straw Mulch ◽  
The Impact ◽  
Different Levels ◽  
Runoff And Sediment Yield

Ground-based skidding operations can lead to soil compaction and displacement, which could cause negative effects on forest soil. Hence, some efforts such as forestry best management practices (BMPs) must be implemented in the prone area to mitigate these possible impacts. Several materials and treatments have been adopted to suppress these adverse effects by increasing the ground cover. However, the effects of mulch treatments on runoff and sediment yield are inconclusive with a diverse range of effectiveness. For these reasons, in this research mulch treatments were tested as to determine how the application of organic mulch amendments such as straw and leaf litter and contour-felled logs would alleviate the runoff and sediment yield on machine operating trails and ensure successful hillslope stabilization. The aims of the study were to analyse and compare the effectiveness of leaf litter (LM) and straw mulch (SM) rate and different distances of contour-felled logs (CFL) to mitigate the runoff and sediment yield, and examine the impact of rainfall intensity on effectiveness of litter mulch, straw mulch, and contour-felled logs. Totally, 30 bounded runoff plots in the machine operating trails and four treatments including litter mulch (LMR1: 0.62, LMR2: 1.24, and LMR3: 1.86 kg m-2), straw mulch (SMR1: 0.45, SMR2: 0.92, and SMR3: 1.34 kg m-2), contour-felled logs (CFL10: 10, CFL20: 20, and CFL30: 30 m), and untreated area were established in triplicate with 4 m width and 100 m length. During the study period, the runoff and sediment yield in the untreated trails (U) were 2.36 mm and 11.84 g m-2. Straw (from 41.5 to 60.6%) and litter mulch (from 38.1 to 55.1%), and contour-felled logs treatments (from 70.8 to 88.1%) significantly decreased the runoff, compared to U treatment. Results show that mulch treatments with three different levels of Litter Mulch Rate, LMR1, LMR2, and LMR3 decreased mean sediment by 46.6, 64.0 and 71.8%, in the treatments with three different levels of Straw Mulch Rate, SMR1, SMR2, and SMR3 decreased mean sediment by 42.9, 62.1, and 69.9%, and in the treatments with three different distances of Contour-Felled Logs, CFL10, CFL20, and CFL30 decreased mean sediment by 90.6, 94.7 and 88.3% comparing to U, respectively. The relationships of the runoff and sediment responses to increasing mulching rate of litter and straw followed as negative logarithmic curves, but the decreasing-increasing trends were observed in runoff and sediment yield as the distance between contour-felled logs increased from 10 to 30 m. Polynomial regression equations were developed for predicting the runoff and sediment yield as a function of the application rate of litter and straw mulch and the distance between contour-felled logs, and rainfall intensity. We concluded that contour-felled logs treatment was more effective than both litter and straw mulch to mitigate the runoff, runoff coefficient, and sediment yield on machine operating trails. As a management measure, it could be possible to propose that the contour-felled logs with a distance of 20 m be prescribed to protect the machine operating trails from the negative effects of surface waterflow.

scholarly journals Методичні підходи до оцінки впливу ксенобіотиків на білкові молекули

2012 ◽  
Vol 3 (1) ◽  
pp. 18-23
Author(s):  
M. V. Gorelaya
Keyword(s):  
Research Methods ◽  
Isoelectric Point ◽  
Methodological Approach ◽  
Protein Molecules ◽  
Immunochemical Methods ◽  
Xenobiotic Compounds ◽  
Living Organisms ◽  
The Impact

It was tested and integrated the methodological approach to the research of xenobiotic compounds impact on protein molecules. For this purpose three groups of research methods were used: turbidimetry, immunochemistry and study of the impact on isoelectric point of proteins. The immunochemical methods are most specific. The turbidimetric methods are fastest and informative. Actually, the proposed methodological approach is integrated and versatile. These methods are effective for studying the xenobiotic influence on proteins in living organisms on the assumption of its complex applications. It was proved that this methodological approach is adequate, informative and easy to use. 

scholarly journals Wording of Daily Diary Questions Matters: An Investigation of the Effect of Daily Diary Instructional Phrases on Respondents’ Recall Time frames (Preprint)

2019 ◽  
Author(s):  
Arthur A. Stone ◽  
Cheng K. Fred Wen ◽  
Stefan Schneider ◽  
Doerte U. Junghaenel
Keyword(s):  
Medical Science ◽  
Daily Diary ◽  
Time Frame ◽  
Affective States ◽  
Diverse Range ◽  
Daily Experience ◽  
Time Periods ◽  
Waking Up ◽  
Time Frames ◽  
The Impact

BACKGROUND Daily diaries are extensively used for examining participants' daily experience in behavioral and medical science. Whether participants recall their experiences within the time frames prescribed by task has received little attention. OBJECTIVE The objectives of this study are to describe survey respondents' self-reported recall timeframe and to evaluate the impact of different daily diary items on respondents reported affective states. METHODS In this study, 577 participants completed a mood survey with one of four time frame instructions: 1) today, 2) since waking up today, 3) during the last 24 hours, or 4) in the last day. They were also asked to indicate the time periods they considered when answering these items and to recall the instructional phrases associated with the items. RESULTS Almost all participants in the "Today" (97%) and "Since waking up today" (94%)" conditions reported using time periods consistent with our expectations, while a lower proportion was observed in the "during the last 24 hours" (69%) condition. A diverse range of responses was observed in the "In the last day" condition. Furthermore, the instructions influenced the levels of some self-reported affects, although exploratory analyses were not able to identify the mechanism underlying this finding. CONCLUSIONS Overall, these results indicate that "Today" and "Since waking up today" are the most effective instructional phrases for inquiring about daily experience and that investigators should use caution when using the other two instructional phrases.

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