Avert the Dirt:On the Design of Scalable Antifouling Polymer Coatings

Whether it be your house, clothes, phone, or precious record collection; everything gets dirty eventually. While we can simply hop in the shower or clean most of our belongings using basic cleaning supplies, the same does not apply to medical, marine, and industrial devices. Here, the uncontrollable and unwanted adhesion of all kinds of material, generally known as fouling, leads to serious complications related to health risks, pollution, and financial losses, which cannot be easily solved by the mere power of detergent. As a response, we strived to develop a novel antifouling coating, specifically designed for large-scale underwater applications. This protective layer consists of polymers: very long and flexible molecules. By attaching these individual polymers or polymer clusters to a surface one by one, a brush is formed, also known as a polymer brush. By repeating this adsorption step, but with a different type of polymer (cluster), the density of the brush is increased. Because of the high brush density and the used polymers’ antifouling character, fouling particles are unable to adhere to the coated surface and the surface remains clean. This simple two-step adsorption strategy has enabled the formation of an effective and reversible antifouling layer, which should allow the straightforward coating and protection of large-scale (underwater) applications. This way, we hope to contribute to a cleaner and more sustainable future

Strong Anionic/Charge-Neutral Block Copolymers from Cu(0)-Mediated Reversible Deactivation Radical Polymerization

[Image: see text] Despite recent developments in controlled polymerization techniques, the straightforward synthesis of block copolymers that feature both strong anionic and charge-neutral segments remains a difficult endeavor. In particular, solubility issues may arise during the direct synthesis of strong amphiphiles and typical postpolymerization deprotection often requires harsh conditions. To overcome these challenges, we employed Cu(0)-mediated reversible deactivation radical polymerization (Cu(0)-RDRP) on a hydrophobic isobutoxy-protected 3-sulfopropyl acrylate. Cu(0)-RDRP enables the rapid synthesis of the polymer, reaching high conversions and low dispersities while using a single solvent system and low amounts of copper species. These macromolecules are straightforward to characterize and can subsequently be deprotected in a mild yet highly efficient fashion to expose their strongly charged nature. Furthermore, a protected sulfonate segment could be grown from a variety of charge-neutral macroinitiators to produce, after the use of the same deprotection chemistry, a library of amphiphilic, double-hydrophilic as well as thermoresponsive block copolymers (BCPs). The ability of these various BCPs to self-assemble in aqueous media was further studied by dynamic light scattering, ζ-potential measurements as well as atomic force and electron microscopy

Full Genome Characterisation of Bluetongue Virus Serotype 6 from the Netherlands 2008 and Comparison to Other Field and Vaccine Strains

In mid September 2008, clinical signs of bluetongue (particularly coronitis) were observed in cows on three different farms in eastern Netherlands (Luttenberg, Heeten, and Barchem), two of which had been vaccinated with an inactivated BTV-8 vaccine (during May-June 2008). Bluetongue virus (BTV) infection was also detected on a fourth farm (Oldenzaal) in the same area while testing for export. BTV RNA was subsequently identified by real time RT-PCR targeting genome-segment (Seg-) 10, in blood samples from each farm. The virus was isolated from the Heeten sample (IAH “dsRNA virus reference collection” [dsRNA-VRC] isolate number NET2008/05) and typed as BTV-6 by RT-PCR targeting Seg-2. Sequencing confirmed the virus type, showing an identical Seg-2 sequence to that of the South African BTV-6 live-vaccine-strain. Although most of the other genome segments also showed very high levels of identity to the BTV-6 vaccine (99.7 to 100%), Seg-10 showed greatest identity (98.4%) to the BTV-2 vaccine (RSAvvv2/02), indicating that NET2008/05 had acquired a different Seg-10 by reassortment. Although Seg-7 from NET2008/05 was also most closely related to the BTV-6 vaccine (99.7/100% nt/aa identity), the Seg-7 sequence derived from the blood sample of the same animal (NET2008/06) was identical to that of the Netherlands BTV-8 (NET2006/04 and NET2007/01). This indicates that the blood contained two different Seg-7 sequences, one of which (from the BTV-6 vaccine) was selected during virus isolation in cell-culture. The predominance of the BTV-8 Seg-7 in the blood sample suggests that the virus was in the process of reassorting with the northern field strain of BTV-8. Two genome segments of the virus showed significant differences from the BTV-6 vaccine, indicating that they had been acquired by reassortment event with BTV-8, and another unknown parental-strain. However, the route by which BTV-6 and BTV-8 entered northern Europe was not established

Genetic predisposition to mosaic Y chromosome loss in blood.

Mosaic loss of chromosome Y (LOY) in circulating white blood cells is the most common form of clonal mosaicism1-5, yet our knowledge of the causes and consequences of this is limited. Here, using a computational approach, we estimate that 20% of the male population represented in the UK Biobank study (n = 205,011) has detectable LOY. We identify 156 autosomal genetic determinants of LOY, which we replicate in 757,114 men of European and Japanese ancestry. These loci highlight genes that are involved in cell-cycle regulation and cancer susceptibility, as well as somatic drivers of tumour growth and targets of cancer therapy. We demonstrate that genetic susceptibility to LOY is associated with non-haematological effects on health in both men and women, which supports the hypothesis that clonal haematopoiesis is a biomarker of genomic instability in other tissues. Single-cell RNA sequencing identifies dysregulated expression of autosomal genes in leukocytes with LOY and provides insights into why clonal expansion of these cells may occur. Collectively, these data highlight the value of studying clonal mosaicism to uncover fundamental mechanisms that underlie cancer and other ageing-related diseases.This research has been conducted using the UK Biobank Resource under application 9905 and 19808. This work was supported by the Medical Research Council [Unit Programme number MC_UU_12015/2]. Full study-specific and individual acknowledgements can be found in the supplementary information

Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.Peer reviewe

ExomeChip-Wide Analysis of 95 626 Individuals Identifies 10 Novel Loci Associated With QT and JT Intervals

BACKGROUND: QT interval, measured through a standard ECG, captures the time it takes for the cardiac ventricles to depolarize and repolarize. JT interval is the component of the QT interval that reflects ventricular repolarization alone. Prolonged QT interval has been linked to higher risk of sudden cardiac arrest.METHODS AND RESULTS: We performed an ExomeChip-wide analysis for both QT and JT intervals, including 209 449 variants, both common and rare, in 17 341 genes from the Illumina Infinium HumanExome BeadChip. We identified 10 loci that modulate QT and JT interval duration that have not been previously reported in the literature using single-variant statistical models in a meta-analysis of 95 626 individuals from 23 cohorts (comprised 83 884 European ancestry individuals, 9610 blacks, 1382 Hispanics, and 750 Asians). This brings the total number of ventricular repolarization associated loci to 45. In addition, our approach of using coding variants has highlighted the role of 17 specific genes for involvement in ventricular repolarization, 7 of which are in novel loci.CONCLUSIONS: Our analyses show a role for myocyte internal structure and interconnections in modulating QT interval duration, adding to previous known roles of potassium, sodium, and calcium ion regulation, as well as autonomic control. We anticipate that these discoveries will open new paths to the goal of making novel remedies for the prevention of lethal ventricular arrhythmias and sudden cardiac arrest

Factors associated with contraceptive use among women living with HIV in Canada: a controlled, cross-sectional study

Background: Multiple contraindications to combined hormonal contraceptives (CHC) use exist. The impact of these factors on contraceptive choice, particularly among women living with HIV (WLWH), is not well understood. We measured and compared the prevalence of contraceptive use and contraindications among WLWH and women not living with HIV (controls). Methods: We examined cross-sectional survey and medical chart data from 83 WLWH and 62 controls, aged 16–49 and sexually active, from 2013–2017. We compared the age-adjusted prevalence and types of contraceptives used in the last month and the proportion of women with CHC contraindications, including drug interactions, medical comorbidities, and smoking at ≥ 35 years old. All WLWH received care at an interdisciplinary, women-centred HIV clinic. Results: Compared to controls, WLWH were older (median [IQR)] 39 [34–43] vs 31 [23–41] years; p = 0.003), had less post-secondary education (37% vs 73%; p < 0.001), and more often had household income < $15,000/year (49% vs 30%; p = 0.006). WLWH trended to higher contraceptive prevalence than controls (80% vs 63%; p = 0.06 adjusted for age). Overall hormonal contraceptive use was similar. However, despite controlling for age, WLWH used CHC less (4% vs 18%; p = 0.006) than controls, and had more frequently undergone tubal ligation (12% vs 2%; p = 0.03). WLWH also experienced more CHC contraindications (54% vs 13%; p = 0.0001), including smoking at ≥ 35 years old (30% vs 6%; p = 0.0003) or a CHC-related drug interaction (all antiretroviral related) (25% vs 0%; p = 0.0001). Conclusions: WLWH attending our interdisciplinary clinic used hormonal contraception at similar rates as controls, though with different types. Differences may reflect different distributions of CHC contraindications. CHC contraindications present barriers to accessing the full range of contraceptive choices for WLWH. Guidelines and education for care providers and WLWH regarding contraceptive choices and drug interactions are needed, especially when care is provided without the benefit of an interdisciplinary women-centered healthcare team.Medicine, Faculty ofNon UBCEndocrinology, Division ofExperimental Medicine, Division ofMedicine, Department ofObstetrics and Gynaecology, Department ofPathology and Laboratory Medicine, Department ofReviewedFacultyResearche

The Apertif Radio Transient System (ARTS): Design, Commissioning, Data Release, and Detection of the first 5 Fast Radio Bursts

Fast Radio Bursts must be powered by uniquely energetic emission mechanisms. This requirement has eliminated a number of possible source types, but several remain. Identifying the physical nature of Fast Radio Burst (FRB) emitters arguably requires good localisation of more detections, and broadband studies enabled by real-time alerting. We here present the Apertif Radio Transient System (ARTS), a supercomputing radio-telescope instrument that performs real-time FRB detection and localisation on the Westerbork Synthesis Radio Telescope (WSRT) interferometer. It reaches coherent-addition sensitivity over the entire field of the view of the primary dish beam. After commissioning results verified the system performed as planned, we initiated the Apertif FRB survey (ALERT). Over the first 5 weeks we observed at design sensitivity in 2019, we detected 5 new FRBs, and interferometrically localised each of these to 0.4--10 sq. arcmin. All detections are broad band and very narrow, of order 1 ms duration, and unscattered. Dispersion measures are generally high. Only through the very high time and frequency resolution of ARTS are these hard-to-find FRBs detected, producing an unbiased view of the intrinsic population properties. Most localisation regions are small enough to rule out the presence of associated persistent radio sources. Three FRBs cut through the halos of M31 and M33. We demonstrate that Apertif can localise one-off FRBs with an accuracy that maps magneto-ionic material along well-defined lines of sight. The rate of 1 every ~7 days next ensures a considerable number of new sources are detected for such study. The combination of detection rate and localisation accuracy exemplified by the 5 first ARTS FRBs thus marks a new phase in which a growing number of bursts can be used to probe our Universe