Electrostatic inactivation of RNA viruses at air-water and liquid-liquid interfaces

Understanding the interactions between viruses and surfaces or interfaces is important, as they provide the principles underpinning the cleaning and disinfection of contaminated surfaces. Yet, the physics of such interactions is currently poorly understood. For instance, there are longstanding experimental observations suggesting that the presence of air-water interfaces can generically inactivate and kill viruses, yet the mechanism underlying this phenomenon remains unknown. Here we use theory and simulations to show that electrostatics provides one such mechanism, and that this is very general. Thus, we predict that the free energy of an RNA virus should increase by several thousands of $k_BT$ as the virion breaches an air-water interface. We also show that the fate of a virus approaching a generic liquid-liquid interface depends strongly on the detailed balance between interfacial and electrostatic forces, which can be tuned, for instance, by choosing different media to contact a virus-laden respiratory droplet. We propose that these results can be used to design effective strategies for surface disinfection. Intriguingly, tunability requires electrostatic and interfacial forces to scale similarly with viral size, which naturally occurs when charges are arranged in a double-shell distribution as in RNA viruses like influenza and all coronaviruses.Comment: 10 pages, 5 figures; minor corrections to the Appendi

Patients' internet use in New Zealand for information about medicines: Implications for policy and practice

BACKGROUND: The ubiquitous use of the internet sees patients increasingly look online for information about their medicines. OBJECTIVE: This study aimed to understand the use of internet to meet medicine information needs of a sample of New Zealand patients. METHOD: Using a descriptive exploratory approach 60 mental health and general medical adult patients at one large urban were interviewed. These semi-structured interviews were audio recorded, transcribed and coded for inductive thematic analysis. FINDINGS: This study found that the internet is frequently used to meet the medicines information needs of patients. Despite the ease of access to information on the internet patients need guidance to locate credible and trustworthy online resources. CONCLUSIONS: Implications from this study relate to both practice and policy, and include the need for health professionals to have enhanced communication skills as they become information brokers who provide supplementary, reliable sources of patient-centric medicines information. Having a New Zealand specific website that includes an extensive section on medicines is a policy recommendation of this study, as is identifying tools to readily identify patients’ needs and preferences for medicines information

What factors are associated with success with insulin pumps?

What factors are associated with success with insulin pumps?Diabetes UK conference gran

Integrating transposable elements in the 3D genome

Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or "topography") of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome

Computation of the Transient in Max-Plus Linear Systems via SMT-Solving

This paper proposes a new approach, grounded in Satisfiability Modulo Theories (SMT), to study the transient of a Max-Plus Linear (MPL) system, that is the number of steps leading to its periodic regime. Differently from state-of-the-art techniques, our approach allows the analysis of periodic behaviors for subsets of initial states, as well as the characterization of sets of initial states exhibiting the same specific periodic behavior and transient. Our experiments show that the proposed technique dramatically outperforms state-of-the-art methods based on max-plus algebra computations for systems of large dimensions.Comment: The paper consists of 22 pages (including references and Appendix). It is accepted in FORMATS 2020 First revisio

Developmental Changes in PON1 Enzyme Activity in Young Children and Effects of PON1 Polymorphisms

BackgroundParaoxonase 1 (PON1) is an enzyme that detoxifies activated organophosphorus pesticides (OPs) and is also involved in oxidative stress pathways.ObjectivesPON1 activity in newborns is lower than in adults, but the ontogeny of PON1 activity is poorly characterized in young children. We examined the effects of age and PON1 genotype on enzyme activity in a birth cohort of Mexican-American children.MethodsWe determined three substrate-specific measures of PON1 activity in 1,143 plasma samples collected longitudinally from 458 children at five time points from birth through 7 years of age, and genotyped PON1 polymorphisms at positions 192 and -108 in these children.ResultsContrary to previous reports that PON1 activities plateau by 2 years of age, we observed an age-dependent increase in all three PON1 measures from birth through 7 years of age (p < 0.0001). The PON1(192) genotype significantly modified the effect of age on paraoxonase (POase) activity (p < 0.0001) such that increases in enzyme activity with age were influenced by the number of R alleles in a dose-dependent manner. Children with the PON1(-108CC192RR) diplotype had significantly higher mean PON1 activities and also experienced steeper increases of POase activity over time compared with children with the PON1(-108TT192QQ) diplotype.ConclusionsLower levels of the PON1 enzyme, which is involved in protection against OPs and oxidative stress, persist in young children past 2 years of age through at least 7 years of age. Future policies addressing pesticide exposure in children should take into account that the window of vulnerability to OPs in young children may last beyond infancy

Block of nicotinic acetylcholine receptors by philanthotoxins is strongly dependent on their subunit composition

Philanthotoxin-433 (PhTX-433) is an active component of the venom from the Egyptian digger wasp, Philanthus triangulum. PhTX-433 inhibits several excitatory ligand-gated ion channels, and to improve selectivity two synthetic analogues, PhTX-343 and PhTX-12, were developed. Previous work showed a 22-fold selectivity of PhTX-12 over PhTX-343 for embryonic muscle-type nicotinic acetylcholine receptors (nAChRs) in TE671 cells. We investigated their inhibition of different neuronal nAChR subunit combinations as well as of embryonic muscle receptors expressed in Xenopus oocytes. Whole-cell currents in response to application of acetylcholine alone or co-applied with PhTX analogue were studied by using two-electrode voltage-clamp. α3β4 nAChRs were most sensitive to PhTX-343 (IC50=12 nM at −80 mV) with α4β4, α4β2, α3β2, α7 and α1β1γδ being 5, 26, 114, 422 and 992 times less sensitive. In contrast α1β1γδ was most sensitive to PhTX-12 along with α3β4 (IC50values of 100 nM) with α4β4, α4β2, α3β2 and α7 being 3, 3, 26 and 49 times less sensitive. PhTX-343 inhibition was strongly voltage-dependent for all subunit combinations except α7, whereas this was not the case for PhTX-12 for which weak voltage dependence was observed. We conclude that PhTX-343 mainly acts as an open-channel blocker of nAChRs with strong subtype selectivity

Anatomical subgroup analysis of the MERIDIAN cohort: failed commissuration

Objective: To assess the contribution of in utero magnetic resonance (iuMR) imaging in fetuses diagnosed with either agenesis of the corpus callosum or hypogenesis of the corpus callosum (grouped as failed commissuration) on antenatal ultrasonography (USS) from the MERIDIAN cohort. Methods: We report a sub-group analysis of fetuses with failed commissuration diagnosed on USS (with or without ventriculomegaly) from the MERIDIAN study who had iuMR imaging within 2 weeks of USS and outcome reference data were available. The diagnostic accuracy of USS and iuMR are reported as well as indicators of diagnostic confidence and effects on prognosis/clinical management. Results: 79 fetuses with failed commissuration are reported (55 with agenesis and 24 with hypogenesis as the USS diagnoses). The diagnostic accuracy for detecting ‘failed commissuration’ as a group label was 34.2% for USS and 94.9% for iuMR (difference = 60.7%, 95% confidence interval 47.6% to 73.9%, p < 0.0001). The diagnostic accuracy for detecting hypogenesis of the corpus callosum as a discrete entity was 8.3% for USS and 87.5% for iuMR whilst the diagnostic accuracy for detecting agenesis of the corpus callosum as a distinct entity was 40.0% for USS and 92.7% for iuMR. There was a statistically significant improvement in ‘appropriate’ diagnostic confidence when using iuMR imaging as assessed by a score-based weighted average’ method (p < 0.0001). Prognostic information given to the women changed in 36/79 (45.6%) cases after iuMR imaging and its overall effect on clinical management was ‘significant’, ‘major’ or ‘decisive’ in 35/79 cases (44.3%). Conclusions: Our data suggests that any woman whose fetus has failed commissuration as the only intracranial finding detected on USS should have iuMR imaging for further evaluation