Mesoscopic simulations of membrane-mediated protein-protein interactions

In this work we use coarse-grained simulations to study the dynamical behavior of transmembrane and membrane-associated proteins. First, we address acylation, a chemical modification ubiquitous in eukaryotic cells. This modification (attaching an acyl chain to a protein), serves as a membrane anchor for soluble proteins. The role of acylation for transmembrane proteins is less clear. We follow up on recent experimental indications that acylations influences trafficking of transmembrane proteins. We find that acylation significantly engances the tilting of transmembrane proteins with respect to the bilayer normal. Also hydrophobic mismatch-driven clustering and partitioning behavior is altered. Our results highlight a possible mechanism of how acylation regulates trafficking of transmembrane proteins. Second, we study monotopic membrane proteins embedded in only one membrane leaflet. We inspect how they perturb the surrounding lipid bilayer in dependence on their radius and hydrophobic length. When two or more proteins are present in the bilayer, they may colocalize. The strength of the membrane-mediated attraction between proteins depends on their geometry and thus the entropic cost of the membrane perturbation they induce. We observed the formation of a multitude of higher-order structures, e.g. corss-leaflet dimerization. We propose that the cross-leaflet dimerization may play a role in intracellular signal transduction, offering an alternative to transmembrane factors

Dynamic Structure Formation of Peripheral Membrane Proteins

Using coarse-grained membrane simulations we show here that peripheral membrane proteins can form a multitude of higher-order structures due to membrane-mediated interactions. Peripheral membrane proteins characteristically perturb the lipid bilayer in their vicinity which supports the formation of protein assemblies not only within the same but surprisingly also across opposing leaflets of a bilayer. In addition, we also observed the formation of lipid-protein domains on heteregeneous membranes. The clustering ability of proteins, as quantified via the potential of mean force, is enhanced when radius and hydrophobic penetration depth of the proteins increases. Based on our data, we propose that membrane-mediated cluster formation of peripheral proteins supports protein assembly in vivo and hence may play a pivotal role in the formation of templates for signaling cascades and in the emergence of transport intermediates in the secretory pathway

Communication Models of Local Self-Government as a Subject of Modern Russian Policy (Based on Local Self-Government Bodies of the Republic of Tatarstan)

Introduction. The article presents the results of a study of communication in the system of local self-government of the Republic of Tatarstan as a subject of the Russian Federation conducted by the authors in November – December 2019. The study included a survey of representatives of regional media and press services of local authorities of the Republic of Tatarstan in order to determine the model of communication in the local government system and the role of PR-activities in the regulation of social interaction in the region. Methods and materials. The main method of studying was the method of expert survey. The authors developed a questionnaire, which was used during an interview with experts. When choosing an expert – a media representative for the interview – the authors took into account three factors: the rating of the represented media, the experience of the respondent in the regional media (at least five years) and the authority to make a key decision on the publication of the material. In order to identify the experts who are representatives of local self-government bodies, the authors of the article determined the following criteria: implementation of information and analytical activities in the structure of local self-government bodies, at least 5 years of experience as a head of a structural unit (public relations / media relations department) of local self-government bodies. Analysis. The analysis showed that the development of social media accelerates the process of establishing a two-way model of communication between the government and the public. Social media have become a full-fledged source of information both for the journalistic community and for the press services of local governments. Moreover, with the help of the content posted in posts on official accounts on social networks, local governments can attract residents of the municipal territory to participate in solving local issues. Constant monitoring, responding to comments, tracking negative content on social media are becoming everyday practices in the work of press services. Results. The results of the study indicate that over the past decade in the Russian Federation the necessary prerequisites have been formed for the formation of a bilateral symmetrical model of communication between local authorities and the population. This model is aimed at providing effective feedback that allows the local government to quickly respond to the aspirations and needs of the population, monitor their dynamics, constantly monitor the attitude and assessments of citizens of decisions made on the development of the city or region

Cholesterol-containing lipid nanodiscs promote an α-synuclein binding mode that accelerates oligomerization

Dysregulation of the biosynthesis of cholesterol and other lipids has been implicated in many neurological diseases, including Parkinson's disease. Misfolding of α-synuclein (α-Syn), the main actor in Parkinson's disease, is associated with changes in a lipid environment. However, the exact molecular mechanisms underlying cholesterol effect on α-Syn binding to lipids as well as α-Syn oligomerization and fibrillation remain elusive, as does the relative importance of cholesterol compared to other factors. We probed the interactions and fibrillation behaviour of α-Syn using styrene–maleic acid nanodiscs, containing zwitterionic and anionic lipid model systems with and without cholesterol. Surface plasmon resonance and thioflavin T fluorescence assays were employed to monitor α-Syn binding, as well as fibrillation in the absence and presence of membrane models. 1H-15N-correlated NMR was used to monitor the fold of α-Syn in response to nanodisc binding, determining individual residue apparent affinities for the nanodisc-contained bilayers. The addition of cholesterol inhibited α-Syn interaction with lipid bilayers and, however, significantly promoted α-Syn fibrillation, with a more than a 20-fold reduction of lag times before fibrillation onset. When α-Syn bilayer interactions were analysed at an individual residue level by solution-state NMR, we observed two different effects of cholesterol. In nanodiscs made of DOPC, the addition of cholesterol modulated the NAC part of α-Syn, leading to stronger interaction of this region with the lipid bilayer. In contrast, in the nanodiscs comprising DOPC, DOPE and DOPG, the NAC part was mostly unaffected by the presence of cholesterol, while the binding of the N and the C termini was both inhibited.publishedVersio

Worldwide Disparities in Recovery of Cardiac Testing 1 Year Into COVID-19

FUNDING SUPPORT AND AUTHOR DISCLOSURES Dr Williams is supported by the British Heart Foundation (FS/ICRF/ 20/26002). Dr Einstein has received speaker fees from Ionetix; has received consulting fees from W. L. Gore & Associates; has received authorship fees from Wolters Kluwer Healthcare – UpToDate; and has received grants or grants pending to his institution from Attralus, Canon Medical Systems, Eidos Therapeutics, GE Healthcare, Pfizer, Roche Medical Systems, W. L. Gore & Associates, and XyloCor Ther- apeutics. Dr Williams has received speaker fees from Canon Medical Systems. Dr Dorbala has received honoraria from Pfizer and GE Healthcare; and has received grants to her institution from Pfizer and GE Healthcare. Dr Sinitsyn has received congress speaker honoraria from Bayer, GE Healthcare, Siemens, and Philips. Dr Kudo has received research grants from Nihon Medi-physics and FUJIFILM Toyama Chemical. Dr Bucciarelli-Ducci is CEO (part-time) of the So- ciety for Cardiovascular Magnetic Resonance; and has received speaker fees from Circle Cardiovascular Imaging, Bayer, and Siemens Healthineers. All other authors have reported that they have no re- lationships relevant to the contents of this paper to disclose.Peer reviewedPublisher PD

The COVID-19 pandemic and its global effects on dental practice : An International survey

Objectives: A multicentre survey was designed to evaluate the impact of COVID-19 outbreak on dental practice worldwide, estimate the COVID-19 related symptoms/signs, work attitudes and behaviour and the routine use of protective measures and Personal Protective Equipment (PPE). Methods: A global survey using a standardized questionnaire with research groups from 36 countries was designed. The questionnaire was developed and pretested during April 2020 and contained three domains: 1) Personal data; 2) COVID-19 positive rate and symptoms/signs presumably related to the coronavirus; 3) Working conditions and PPE adopted after the outbreak. Countries' data were grouped by the Country Positive Rate (CPR) during the survey period and by Gross-National-Income per capita. An ordinal multinomial logistic regression model was carried out with COVID-19 self-reported rate referred by dental professionals as dependent variable to assess the association with questionnaire items. Results: A total of 52,491 questionnaires were returned with a male/female ratio of 0.63. Out of the total respondents, 7,859 dental professionals (15%) reported symptoms/signs compatible with COVID-19. More than half of the sample (n = 27,818; 53%) stated to use FFP2/N95 masks, while 21,558 (41.07%) used eye protection. In the bivariate analysis, CPR and N95/FFP2 were significantly associated (OR = 1.80 95% =5.20 95% 95% CI = 1.60/2.82 and OR CI = 1.44/18.80, respectively), while Gross-National-Income was not statistically associated with CPR (OR = 1.09 CI = 0.97/1.60). The same significant associations were observed in the multivariate analysis. Conclusions: Oral health service provision has not been significantly affected by COVID-19, although access to routine dental care was reduced due to country-specific temporary lockdown periods. While the dental profession has been identified at high-risk, the reported rates of COVID-19 for dental professionals were not significantly different to those reported for the general population in each country. These findings may help to better plan oral health care for future pandemic events

Does Culture Shape Our Understanding of Others’ Thoughts and Emotions? An Investigation Across 12 Countries

Q2Q2Measures of social cognition have now become central in neuropsychology, being essential for early and differential diagnoses, follow-up, and rehabilitation in a wide range of conditions. With the scientific world becoming increasingly interconnected, international neuropsychological and medical collaborations are burgeoning to tackle the global challenges that are mental health conditions. These initiatives commonly merge data across a diversity of populations and countries, while ignoring their specificity. Objective: In this context, we aimed to estimate the influence of participants’ nationality on social cognition evaluation. This issue is of particular importance as most cognitive tasks are developed in highly specific contexts, not representative of that encountered by the world’s population. Method: Through a large international study across 18 sites, neuropsychologists assessed core aspects of social cognition in 587 participants from 12 countries using traditional and widely used tasks. Results: Age, gender, and education were found to impact measures of mentalizing and emotion recognition. After controlling for these factors, differences between countries accounted for more than 20% of the variance on both measures. Importantly, it was possible to isolate participants’ nationality from potential translation issues, which classically constitute a major limitation. Conclusions: Overall, these findings highlight the need for important methodological shifts to better represent social cognition in both fundamental research and clinical practice, especially within emerging international networks and consortia.https://orcid.org/0000-0001-9422-3579https://orcid.org/0000-0001-6529-7077Revista Internacional - IndexadaA2N

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection