Aptamers Selected for Recognizing Amyloid beta-Protein-A Case for Cautious Optimism

Aptamers are versatile oligonucleotide ligands used for molecular recognition of diverse targets. However, application of aptamers to the field of amyloid beta-protein (A beta) has been limited so far. A beta is an intrinsically disordered protein that exists in a dynamic conformational equilibrium, presenting time-dependent ensembles of short-lived, metastable structures and assemblies that have been generally difficult to isolate and characterize. Moreover, despite understanding of potential physiological roles of A beta, this peptide has been linked to the pathogenesis of Alzheimer disease, and its pathogenic roles remain controversial. Accumulated scientific evidence thus far highlights undesirable or nonspecific interactions between selected aptamers and different A beta assemblies likely due to the metastable nature of A beta or inherent affinity of RNA oligonucleotides to beta-sheet-rich fibrillar structures of amyloidogenic proteins. Accordingly, lessons drawn from A beta-aptamer studies emphasize that purity and uniformity of the protein target and rigorous characterization of aptamers' specificity are important for realizing and garnering the full potential of aptamers selected for recognizing A beta or other intrinsically disordered proteins. This review summarizes studies of aptamers selected for recognizing different A beta assemblies and highlights controversies, difficulties, and limitations of such studies

Photo-Induced Cross-Linking of Unmodified Proteins (PICUP) Applied to Amyloidogenic Peptides

The assembly of amyloidogenic proteins into toxic oligomers is a seminal event in the pathogenesis of protein misfolding diseases, including Alzheimer's, Parkinson's, and Huntington's diseases, hereditary amyotrophic lateral sclerosis, and type 2 diabetes. Owing to the metastable nature of these protein assemblies, it is difficult to assess their oligomer size distribution quantitatively using classical methods, such as electrophoresis, chromatography, fluorescence, or dynamic light scattering. Oligomers of amyloidogenic proteins exist as metastable mixtures, in which the oligomers dissociate into monomers and associate into larger assemblies simultaneously. PICUP stabilizes oligomer populations by covalent cross-linking and when combined with fractionation methods, such as sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) or size-exclusion chromatography (SEC), PICUP provides snapshots of the oligomer size distributions that existed before cross-linking. Hence, PICUP enables visualization and quantitative analysis of metastable protein populations and can be used to monitor assembly and decipher relationships between sequence modifications and oligomerization1. Mechanistically, PICUP involves photo-oxidation of Ru2+ in a tris(bipyridyl)Ru(II) complex (RuBpy) to Ru3+ by irradiation with visible light in the presence of an electron acceptor. Ru3+ is a strong one-electron oxidizer capable of abstracting an electron from a neighboring protein molecule, generating a protein radical1,2. Radicals are unstable, highly-reactive species and therefore disappear rapidly through a variety of intra- and intermolecular reactions. A radical may utilize the high energy of an unpaired electron to react with another protein monomer forming a dimeric radical, which subsequently loses a hydrogen atom and forms a stable, covalently-linked dimer. The dimer may then react further through a similar mechanism with monomers or other dimers to form higher-order oligomers. Advantages of PICUP relative to other photo- or chemical cross-linking methods3,4 include short (≤1 s) exposure to non-destructive visible light, no need for pre facto modification of the native sequence, and zero-length covalent cross-linking. In addition, PICUP enables cross-linking of proteins within wide pH and temperature ranges, including physiologic parameters. Here, we demonstrate application of PICUP to cross-linking of three amyloidogenic proteins the 40- and 42-residue amyloid β-protein variants (Aβ40 and Aβ42), and calcitonin, and a control protein, growth-hormone releasing factor (GRF)

Implementation of Epidemic Restrictions to Disrupt the COVID-19 Pandemic in Iran: A Mini-Review

The number of cases infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes COVID-19, has been steadily rising globally. Iran, one of the countries with a relatively high number of positive cases, has an inevitable role to play in controlling the pandemic by implementing effective policies and countermeasures to interrupt the viral transmission chain. Epidemic restrictions implemented following an Iranian presidential mandate were especially effective following the Nowruz holidays—the solar New Year celebration in the Persian-speaking culture. These restrictions started flattening the incidence curve of the epidemic in Iran two weeks after implementation, from 10 April 2020. Supplying sufficient face masks, disinfectants, sanitizers, and medical equipment to all government-run and non-for-profit hospitals were included in the presidential mandate. We believe that continuing this policy strictly will be required for further controlling the pandemic throughout the country. *Corresponding Author: Amin Talebi Bezmin Abadi; Email: [email protected] Please cite this article as: Talebi Bezmin Abadi A, Rahimi F. Implementation of Epidemic Restrictions to Disrupt the COVID-19 Pandemic in Iran: A Mini-Review. Arch Med Lab Sci. 2020;6:e11. https://doi.org/10.22037/amls.v6.3296

RNA aptamers generated against oligomeric Abeta40 recognize common amyloid aptatopes with low specificity but high sensitivity.

Aptamers are useful molecular recognition tools in research, diagnostics, and therapy. Despite promising results in other fields, aptamer use has remained scarce in amyloid research, including Alzheimer's disease (AD). AD is a progressive neurodegenerative disease believed to be caused by neurotoxic amyloid beta-protein (Abeta) oligomers. Abeta oligomers therefore are an attractive target for development of diagnostic and therapeutic reagents. We used covalently-stabilized oligomers of the 40-residue form of Abeta (Abeta40) for aptamer selection. Despite gradually increasing the stringency of selection conditions, the selected aptamers did not recognize Abeta40 oligomers but reacted with fibrils of Abeta40, Abeta42, and several other amyloidogenic proteins. Aptamer reactivity with amyloid fibrils showed some degree of protein-sequence dependency. Significant fibril binding also was found for the naïve library and could not be eliminated by counter-selection using Abeta40 fibrils, suggesting that aptamer binding to amyloid fibrils was RNA-sequence-independent. Aptamer binding depended on fibrillogenesis and showed a lag phase. Interestingly, aptamers detected fibril formation with > or =15-fold higher sensitivity than thioflavin T (ThT), revealing substantial beta-sheet and fibril formation undetected by ThT. The data suggest that under physiologic conditions, aptamers for oligomeric forms of amyloidogenic proteins cannot be selected due to high, non-specific affinity of oligonucleotides for amyloid fibrils. Nevertheless, the high sensitivity, whereby aptamers detect beta-sheet formation, suggests that they can serve as superior amyloid recognition tools

The study of relationship between Maternal Reactions to Children’s Negative Emotions and Children’s Social Skills The role of mediational Emotion Regulation

Introduction: Differences in emotional control and social skills appear to partially reflect differences in longstanding intrapersonal qualities, such as temperament, but parenting characteristics also have emerged as indicators of how children develop emotional and social competence.Methods: The study design was correlational. Sample was 60 children in age preschool (30 boys and 30 girls) and their mothers (60 females) selected using convenience sampling among children were registered for preschool in a private school. Instruments were used in this study include: Coping with Children’s Negative Emotions Scale (CCNES), Behaviour Rating Inventory of Executive Functioning (BRIEF), Social Skills Rating System (SSRS). Data analyzed using simple regression and structural equation modeling (SEM). Results: Data analysis showed that children’s emotion regulation skills predicted their social skill levels (F=69.98, p=0.0001) and Total maternal emotion socialization predicted children’s emotion regulation (F=98.15, p=0.0001) and children’s social skills (F=39.45, p=0.0001). Other result was children’s emotion regulation skills completely mediated relation between reactions to children’s negative emotions and children’s social skills.Conclusions: This research highlighted the important impact of emotion-related parenting behaviours and beliefs on children’s development of social and emotional competence

Usage Monitoring of Helicopter Gearboxes with ADS-B Flight Data

Health and usage monitoring systems (HUMS) are the basis for condition-based maintenance of helicopters. One of the most critical systems in terms of safety and maintenance expense that can be monitored by HUMS are the main gearboxes of helicopters with turbine engines. While the health monitoring part of HUMS aims to model the health state from the collected sensor data with advanced algorithms, such as machine learning, the usage monitoring part tracks the time of use and operating parameters of the system, such as load, to determine lifetime consumption. In the presented work, a combination of automatic dependent surveillance-broadcast (ADS-B) flight data with a generic helicopter performance model is used to acquire torque profiles of the gearboxes. With damage accumulation methods, the load spectra are transformed to aggregated indicators that reflect the individual gearbox usage. The methodology is applied to samples of two helicopters from a five-year ADS-B data set of German helicopter emergency medical services (HEMS) acquired for the study. The results demonstrate the feasibility of the generic approach, which can support maintenance scheduling and new usage-based maintenance services independent of direct access to installed HUMS

THE INFLUENCE OF EFFECTIVE TAX RATE ON THE DISCLOSURE OF FINANCIAL STATEMENTS OF ACCEPTED COMPANIES IN TEHRAN STOCK EXCHANGE

Tax is one of the most major political tools of governments and the most important source of their incomes and costs supplement. The dependency to the oil incomes can be reduced to zero by prevention of tax evasion. For decreasing the dependency to the oil incomes, we are needful to increase the levies in country. The optimized levies and actual taxes not only increase the government's tax incomes but lead to a tax justice. The disclosure of accounting information was notified as one of the most important subjects for researchers from long time ago and the final product is considered as an accounting system. Actually, the final purpose of accounting system is providing information for benefited persons in the form of in and out-organization reports and the complete information disclosure can be an underlie of fiscal justice. This study surveys the relationship between the influences of effective tax rate and the level of financial statements disclosure of accepted companies in Tehran Stock Exchange. In this research, the multi variable regression analysis according to the panel data in order to survey the relationship of effective tax rate with the level of financial statements disclosure during the years of 2011 to 2015. The study sample is included of 94 listed companies in Tehran Stock Exchange for a temporal duration of 5 years. The results show that there is a reverse meaningful relationship between the effective tax rate and the level of mandatory financial statements disclosure; means, as effective tax rate gets higher, the level of mandatory disclosure gets lower and also there isn't any meaningful relationship between effective tax rate and the level of voluntary financial statements disclosure. JEL: G15, E44, O16, H25  Article visualizations

MEASURING INTELLECTUAL CAPITAL USING JUSTIFIED PULIC MODEL AND ITS EFFECT ON THE FINANCIAL PERFORMANCE OF LISTED COMPANIES IN TEHRAN STOCK EXCHANGE

We all know that what gets measured gets done. However, the organizations which pursuing the knowledge management don't have any process for measuring the organizational knowledge or intellectual capitals of assets. The traditional financial reporting cannot measure the actual value of the company (or company) and will suffice the measurement of short-term balance sheet and tangible assets. In fact, the intellectual capital provides a new complete model for observing the actual value of the organizations and through its using; the future value of company can be also measured. Due to the willingness to assess and consider the real value of intangible assets, the intellectual capital has increased more than ever to company, shareholders (investors) and other stakeholder groups. In this study, according to the justified Pulic model (e-VAIC™), the intellectual capital value of listed companies in Tehran Stock Exchange during 10 years period from 2005 to 2015 got measured and then, the relationship between components of intellectual capital and companies' performance was evaluated. In the current study, the statistics method was used and data analysis was conducted with multifold regression and correlation coefficient. The sampling was continuously for a period of 10 years which the company size and financial leverage were considered as control variable. The results indicate that there is a meaningful positive relationship between intellectual capital and financial performance of listed companies in Tehran Stock Exchange. According to the results, using this model for achieving higher profit can be intensely recommended for utilizing companies, shareholders, investors and other beneficiaries. JEL: E44, G15, H25, O16  Article visualizations