Engineering biofilms for biocatalysis

Biofilm, friend not foe: Single species biofilms can be engineered to form robust biocatalysts with greater catalytic activity and significantly improved catalytic longevity than purified and immobilised enzymes. We report the engineering, structural analysis and biocatalytic capability of a biofilm that can mediate the conversion of serine and haloindoles to halotryptophans

Chronic amphetamine enhances visual input to and suppresses visual output from the superior colliculus in withdrawal

Heightened distractibility is a core symptom of Attention Deficit Hyperactivity Disorder (ADHD). Effective treatment is normally with chronic orally administered psychostimulants including amphetamine.Treatment prevents worsening of symptoms but the site of therapeutic processes, and their nature, is unknown. Mounting evidence suggests that the superior colliculus (SC) is a key substrate in distractibility and a therapeutic target, so we assessed whether therapeutically-relevant changes are induced in this structure by chronic oral amphetamine. We hypothesized that amphetamine would alter visual responses and morphological measures. Six-week old healthy male rats were treated with oral amphetamine (2, 5 or 10 mg/kg) or a vehicle for one month after which local field potential and multiunit recordings were made from the superficial layers of the SC in response to whole-field light flashes in withdrawal. Rapid Golgi staining was also used to assess dendritic spines, and synaptophysin staining was used to assess synaptic integrity. Chronic amphetamine increased local field potential responses at higher doses, and increased synaptophysin expression, suggesting enhanced visual input involving presynaptic remodelling. No comparable increases in multiunit activity were found suggesting a mphetamine suppresses collicular output activity, counterbalancing the increased input. We also report,for the first time, five different dendritic spine types in the superficial layers and show these to be unaffected by amphetamine, indicating that suppression does not involve gross postsynaptic structural alterations. In conclusion, we suggest that amphetamine produces changes at the collicular level that potentially stabilise the structure and may prevent the worsening of symptoms in disorders like ADHD

Ambulatory Blood Pressure Monitoring in Individuals with HIV: A Systematic Review and Meta-Analysis

Introduction Abnormal diurnal blood pressure (BP) rhythms may contribute to the high cardiovascular disease risk in HIV-positive (HIV+) individuals. To synthesize the current literature on ambulatory BP monitoring (ABPM) in HIV+ individuals, a systematic literature review and meta-analysis were performed. Methods Medical databases were searched through November 11, 2015 for studies that reported ABPM results in HIV+ individuals. Data were extracted by 2 reviewers and pooled differences between HIV+ and HIV-negative (HIV-) individuals in clinic BP and ABPM measures were calculated using random-effects inverse variance weighted models. Results Of 597 abstracts reviewed, 8 studies with HIV+ cohorts met the inclusion criteria. The 420 HIV+ and 714 HIV- individuals in 7 studies with HIV- comparison groups were pooled for analyses. The pooled absolute nocturnal systolic and diastolic BP declines were 3.16% (95% confidence interval [CI]: 1.13%, 5.20%) and 2.92% (95% CI: 1.64%, 4.19%) less, respectively, in HIV+ versus HIV- individuals. The pooled odds ratio for non-dipping systolic BP (nocturnal systolic BP decline <10%) in HIV+ versus HIV- individuals was 2.72 (95% CI: 1.92, 3.85). Differences in mean clinic, 24-hour, daytime, or nighttime BP were not statistically significant. I2 and heterogeneity chi-squared statistics indicated the presence of high heterogeneity for all outcomes except percent DBP dipping and non-dipping SBP pattern. Conclusions An abnormal diurnal BP pattern may be more common among HIV+ versus HIV- individuals. However, results were heterogeneous for most BP measures, suggesting more research in this area is needed

Waterfowl recently infected with low pathogenic avian influenza exhibit reduced local movement and delayed migration

Understanding relationships between infection and wildlife movement patterns is important for predicting pathogen spread, especially for multispecies pathogens and those that can spread to humans and domestic animals, such as avian influenza viruses (AIVs). Although infection with low pathogenic AIVs is generally considered asymptomatic in wild birds, prior work has shown that influenza-infected birds occasionally delay migration and/or reduce local movements relative to their uninfected counterparts. However, most observational research to date has focused on a few species in northern Europe; given that influenza viruses are widespread globally and outbreaks of highly pathogenic strains are increasingly common, it is important to explore influenza–movement relationships across more species and regions. Here, we used telemetry data to investigate relationships between influenza infection and movement behavior in 165 individuals from four species of North American waterfowl that overwinter in California, USA. We studied both large-scale migratory and local overwintering movements and found that relationships between influenza infection and movement patterns varied among species. Northern pintails (Anas acuta) with antibodies to avian influenza, indicating prior infection, made migratory stopovers that averaged 12 days longer than those with no influenza antibodies. In contrast, greater white-fronted geese (Anser albifrons) with antibodies to avian influenza made migratory stopovers that averaged 15 days shorter than those with no antibodies. Canvasbacks (Aythya valisineria) that were actively infected with influenza upon capture in the winter delayed spring migration by an average of 28 days relative to birds that were uninfected at the time of capture. At the local scale, northern pintails and canvasbacks that were actively infected with influenza used areas that were 7.6 and 4.9 times smaller than those of uninfected ducks, respectively, during the period of presumed active influenza infection. We found no evidence for an influence of active influenza infection on local movements of mallards (Anas platyrhynchos). These results suggest that avian influenza can influence waterfowl movements and illustrate that the relationships between avian influenza infection and wild bird movements are context- and species-dependent. More generally, understanding and predicting the spread of multihost pathogens requires studying multiple taxa across space and time

Pathways for avian influenza virus spread: GPS reveals wild waterfowl in commercial livestock facilities and connectivity with the natural wetland landscape

Zoonotic diseases are of considerable concern to the human population and viruses such as avian influenza (AIV) threaten food security, wildlife conservation and human health. Wild waterfowl and the natural wetlands they use are known AIV reservoirs, with birds capable of virus transmission to domestic poultry populations. While infection risk models have linked migration routes and AIV outbreaks, there is a limited understanding of wild waterfowl presence on commercial livestock facilities, and movement patterns linked to natural wetlands. We documented 11 wild waterfowl (three Anatidae species) in or near eight commercial livestock facilities in Washington and California with GPS telemetry data. Wild ducks used dairy and beef cattle feed lots and facility retention ponds during both day and night suggesting use for roosting and foraging. Two individuals (single locations) were observed inside poultry facility boundaries while using nearby wetlands. Ducks demonstrated high site fidelity, returning to the same areas of habitats (at livestock facilities and nearby wetlands), across months or years, showed strong connectivity with surrounding wetlands, and arrived from wetlands up to 1251 km away in the week prior. Telemetry data provides substantial advantages over observational data, allowing assessment of individual movement behaviour and wetland connectivity that has significant implications for outbreak management. Telemetry improves our understanding of risk factors for waterfowl–livestock virus transmission and helps identify factors associated with coincident space use at the wild waterfowl–domestic livestock interface. Our research suggests that even relatively small or isolated natural and artificial water or food sources in/near facilities increases the likelihood of attracting waterfowl, which has important consequences for managers attempting to minimize or prevent AIV outbreaks. Use and interpretation of telemetry data, especially in near-real-time, could provide key information for reducing virus transmission risk between waterfowl and livestock, improving protective barriers between wild and domestic species, and abating outbreaks

Challenges for modelling interventions for future pandemics

Funding: This work was supported by the Isaac Newton Institute (EPSRC grant no. EP/R014604/1). MEK was supported by grants from The Netherlands Organisation for Health Research and Development (ZonMw), grant number 10430022010001, and grant number 91216062, and by the H2020 Project 101003480 (CORESMA). RNT was supported by the UKRI, grant number EP/V053507/1. GR was supported by Fundação para a Ciência e a Tecnologia (FCT) project reference 131_596787873. and by the VERDI project 101045989 funded by the European Union. LP and CO are funded by the Wellcome Trust and the Royal Society (grant 202562/Z/16/Z). LP is also supported by the UKRI through the JUNIPER modelling consortium (grant number MR/V038613/1) and by The Alan Turing Institute for Data Science and Artificial Intelligence. HBS is funded by the Wellcome Trust and Royal Society (202562/Z/16/Z), and the Alexander von Humboldt Foundation. DV had support from the National Council for Scientific and Technological Development of Brazil (CNPq - Refs. 441057/2020-9, 424141/2018-3, 309569/2019-2). FS is supported by the UKRI through the JUNIPER modelling consortium (grant number MR/V038613/1). EF is supported by UKRI (Medical Research Council)/Department of Health and Social Care (National Insitute of Health Research) MR/V028618/1. JPG's work was supported by funding from the UK Health Security Agency and the UK Department of Health and Social Care.Mathematical modelling and statistical inference provide a framework to evaluate different non-pharmaceutical and pharmaceutical interventions for the control of epidemics that has been widely used during the COVID-19 pandemic. In this paper, lessons learned from this and previous epidemics are used to highlight the challenges for future pandemic control. We consider the availability and use of data, as well as the need for correct parameterisation and calibration for different model frameworks. We discuss challenges that arise in describing and distinguishing between different interventions, within different modelling structures, and allowing both within and between host dynamics. We also highlight challenges in modelling the health economic and political aspects of interventions. Given the diversity of these challenges, a broad variety of interdisciplinary expertise is needed to address them, combining mathematical knowledge with biological and social insights, and including health economics and communication skills. Addressing these challenges for the future requires strong cross-disciplinary collaboration together with close communication between scientists and policy makers.Publisher PDFPeer reviewe

Factors Associated With Delayed Hepatitis B Viral Suppression on Tenofovir Among Patients Coinfected With HBV-HIV in the CNICS Cohort

Despite widespread use in HIV and hepatitis B virus (HBV) infection, the effectiveness of tenofovir (TDF) has not been studied extensively outside of small HBV-HIV coinfected cohorts. We examined the effect of prior lamivudine treatment (3TC) and other factors on HBV DNA suppression with TDF in a multi-site clinical cohort of coinfected patients

De novo mutations in histone modifying genes in congenital heart disease

Congenital heart disease (CHD) is the most frequent birth defect, affecting 0.8% of live births1. Many cases occur sporadically and impair reproductive fitness, suggesting a role for de novo mutations. By analysis of exome sequencing of parent-offspring trios, we compared the incidence of de novo mutations in 362 severe CHD cases and 264 controls. CHD cases showed a significant excess of protein-altering de novo mutations in genes expressed in the developing heart, with an odds ratio of 7.5 for damaging mutations. Similar odds ratios were seen across major classes of severe CHD. We found a marked excess of de novo mutations in genes involved in production, removal or reading of H3K4 methylation (H3K4me), or ubiquitination of H2BK120, which is required for H3K4 methylation2–4. There were also two de novo mutations in SMAD2; SMAD2 signaling in the embryonic left-right organizer induces demethylation of H3K27me5. H3K4me and H3K27me mark `poised' promoters and enhancers that regulate expression of key developmental genes6. These findings implicate de novo point mutations in several hundred genes that collectively contribute to ~10% of severe CHD

Life, time, and the organism:Temporal registers in the construction of life forms

In this paper, we articulate how time and temporalities are involved in the making of living things. For these purposes, we draw on an instructive episode concerning Norfolk Horn sheep. We attend to historical debates over the nature of the breed, whether it is extinct or not, and whether presently living exemplars are faithful copies of those that came before. We argue that there are features to these debates that are important to understanding contemporary configurations of life, time and the organism, especially as these are articulated within the field of synthetic biology. In particular, we highlight how organisms are configured within different material and semiotic assemblages that are always structured temporally. While we identify three distinct structures, namely the historical, phyletic and molecular registers, we do not regard the list as exhaustive. We also highlight how these structures are related to the care and value invested in the organisms at issue. Finally, because we are interested ultimately in ways of producing time, our subject matter requires us to think about historiographical practice reflexively. This draws us into dialogue with other scholars interested in time, not just historians, but also philosophers and sociologists, and into conversations with them about time as always multiple and never an inert background