National population prevalence of antibodies to SARS-CoV-2 in Scotland during the first and second waves of the COVID-19 pandemic.

OBJECTIVES: Studies that measure the prevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ('seroprevalence') are essential to understand population exposure to SARS-CoV-2 among symptomatic and asymptomatic individuals. We aimed to measure seroprevalence in the Scottish population over the course of the COVID-19 pandemic - from before the first recorded case in Scotland through to the second pandemic wave. STUDY DESIGN: The study design of this study is serial cross sectional. METHODS: We tested 41,477 residual samples retrieved from primary and antenatal care settings across Scotland for SARS-CoV-2 antibodies over a 12-month period from December 2019-December 2020 (before rollout of COVID-19 vaccination). Five-weekly rolling seroprevalence estimates were adjusted for the sensitivity and specificity of the assays and weighted to reference populations. Temporal trends in seroprevalence estimates and weekly SARS-CoV-2 notifications were compared. RESULTS: Five-weekly rolling seroprevalence rates were 0% until the end of March, when they increased contemporaneously with the first pandemic wave. Seroprevalence rates remained stable through the summer (range: 3%-5%) during a period of social restrictions, after which they increased concurrently with the second wave, reaching 9.6% (95% confidence interval [CI]: 8.4%-10.8%) in the week beginning 28th December in 2020. Seroprevalence rates were lower in rural vs. urban areas (adjusted odds ratio [AOR]: 0.70, 95% CI: 0.61-0.79) and among individuals aged 20-39 years and 60 years and older (AOR: 0.74, 95% CI: 0.64-0.86; AOR: 0.80, 95% CI: 0.69-0.91, respectively) relative to those aged 0-19 years. CONCLUSIONS: After two waves of the COVID-19 pandemic, less than one in ten individuals in the Scottish population had antibodies to SARS-CoV-2. Seroprevalence may underestimate the true population exposure as a result of waning antibodies among individuals who were infected early in the first wave.

Genome mining and characterisation of a novel transaminase with remote stereoselectivity.

Microbial enzymes from pristine niches can potentially deliver disruptive opportunities in synthetic routes to Active Pharmaceutical Ingredients and intermediates in the Pharmaceutical Industry. Advances in green chemistry technologies and the importance of stereochemical control, further underscores the application of enzyme-based solutions in chemical synthesis. The rich tapestry of microbial diversity in the oceanic ecosystem encodes a capacity for novel biotransformations arising from the chemical complexity of this largely unexplored bioactive reservoir. Here we report a novel ω-transaminase discovered in a marine sponge Pseudovibrio sp. isolate. Remote stereoselection using a transaminase has been demonstrated for the first time using this novel protein. Application to the resolution of an intermediate in the synthesis of sertraline highlights the synthetic potential of this novel biocatalyst discovered through genomic mining. Integrated chemico-genomics revealed a unique substrate profile, while molecular modelling provided structural insights into this 'first in class' selectivity at a remote chiral centre.

Mammalian Adaptation of an Avian Influenza A Virus Involves Stepwise Changes in NS1.

Influenza A viruses (IAVs) are common pathogens of birds that occasionally establish endemic infections in mammals. The processes and mechanisms that result in IAV mammalian adaptation are poorly understood. The viral nonstructural 1 (NS1) protein counteracts the interferon (IFN) response, a central component of the host species barrier. We characterized the NS1 proteins of equine influenza virus (EIV), a mammalian IAV lineage of avian origin. We showed that evolutionarily distinct NS1 proteins counteract the IFN response using different and mutually exclusive mechanisms: while the NS1 proteins of early EIVs block general gene expression by binding to cellular polyadenylation-specific factor 30 (CPSF30), NS1 proteins from more evolved EIVs specifically block the induction of IFN-stimulated genes by interfering with the JAK/STAT pathway. These contrasting anti-IFN strategies are associated with two mutations that appeared sequentially and were rapidly selected for during EIV evolution, highlighting the importance of evolutionary processes in immune evasion mechanisms during IAV adaptation.IMPORTANCE Influenza A viruses (IAVs) infect certain avian reservoir species and occasionally transfer to and cause epidemics of infections in some mammalian hosts. However, the processes by which IAVs gain the ability to efficiently infect and transmit in mammals remain unclear. H3N8 equine influenza virus (EIV) is an avian-origin virus that successfully established a new lineage in horses in the early 1960s and is currently circulating worldwide in the equine population. Here, we analyzed the molecular evolution of the virulence factor nonstructural protein 1 (NS1) and show that NS1 proteins from different time periods after EIV emergence counteract the host innate immune response using contrasting strategies, which are associated with two mutations that appeared sequentially during EIV evolution. The results shown here indicate that the interplay between virus evolution and immune evasion plays a key role in IAV mammalian adaptation.

2'-Deoxyribosyltransferase from Leishmania mexicana, an efficient biocatalyst for one-pot, one-step synthesis of nucleosides from poorly soluble purine bases.

Processes catalyzed by enzymes offer numerous advantages over chemical methods although in many occasions the stability of the biocatalysts becomes a serious concern. Traditionally, synthesis of nucleosides using poorly water-soluble purine bases, such as guanine, xanthine, or hypoxanthine, requires alkaline pH and/or high temperatures in order to solubilize the substrate. In this work, we demonstrate that the 2'-deoxyribosyltransferase from Leishmania mexicana (LmPDT) exhibits an unusually high activity and stability under alkaline conditions (pH 8-10) across a broad range of temperatures (30-70 °C) and ionic strengths (0-500 mM NaCl). Conversely, analysis of the crystal structure of LmPDT together with comparisons with hexameric, bacterial homologues revealed the importance of the relationships between the oligomeric state and the active site architecture within this family of enzymes. Moreover, molecular dynamics and docking approaches provided structural insights into the substrate-binding mode. Biochemical characterization of LmPDT identifies the enzyme as a type I NDT (PDT), exhibiting excellent activity, with specific activity values 100- and 4000-fold higher than the ones reported for other PDTs. Interestingly, LmPDT remained stable during 36 h at different pH values at 40 °C. In order to explore the potential of LmPDT as an industrial biocatalyst, enzymatic production of several natural and non-natural therapeutic nucleosides, such as vidarabine (ara A), didanosine (ddI), ddG, or 2'-fluoro-2'-deoxyguanosine, was carried out using poorly water-soluble purines. Noteworthy, this is the first time that the enzymatic synthesis of 2'-fluoro-2'-deoxyguanosine, ara G, and ara H by a 2'-deoxyribosyltransferase is reported.

A functional BH3 domain in an aquaporin from Leishmania infantum.

Despite the absence of sequences showing significant similarity to any of the members of the Bcl-2 family of proteins in protozoa, experiments carried out in yeast or trypanosomatids have demonstrated that ectopic expression of some of these members alters their response to different death stimuli. Because the BH3 domain is the smallest common signature in all the proteins of this family of apoptosis regulators and also because they are essential for molecular interactions between antagonistic members, we looked for sequences with significant similarity to the BH3 motif in the Leishmania infantum genome. Among the top scoring ones, we found the MYLALQNLGDEV amino-acid stretch at the C terminus of a previously described aquaporin, now renamed as Li-BH3AQP. This motif is highly conserved in homologous proteins from other species of the Leishmania genus. The association of Li-BH3AQP with human Bcl-XL was demonstrated by both co-immunoprecipitation and yeast two-hybrid experiments. Ectopic expression of Li-BH3AQP reduced viability of HeLa cells and this deleterious effect was abrogated by the simultaneous overexpression of Bcl-XL. Although we were not able to demonstrate a reduction in parasite viability when the protein was overexpressed in Leishmania promastigotes, a prodeath effect could be observed when the parasites overexpressing Li-BH3AQP were treated with staurosporine or antimycin A. Surprisingly, these parasites were more resistant, compared with wild-type parasites, to hypotonic stress or nutrient deprivation. The prodeath activity was abolished upon replacement of two highly conserved amino acids in this BH3 domain. Taken together, these results point to Li-BH3AQP as the first non-enzymatic protein ever described in trypanosomatids that is involved in cell death.

Extensive multiplex PCR diagnostics reveal new insights into the epidemiology of viral respiratory infections.

Viral respiratory infections continue to pose a major global healthcare burden. At the community level, the co-circulation of respiratory viruses is common and yet studies generally focus on single aetiologies. We conducted the first comprehensive epidemiological analysis to encompass all major respiratory viruses in a single population. Using extensive multiplex PCR diagnostic data generated by the largest NHS board in Scotland, we analysed 44230 patient episodes of respiratory illness that were simultaneously tested for 11 virus groups between 2005 and 2013, spanning the 2009 influenza A pandemic. We measured viral infection prevalence, described co-infections, and identified factors independently associated with viral infection using multivariable logistic regression. Our study provides baseline measures and reveals new insights that will direct future research into the epidemiological consequences of virus co-circulation. In particular, our study shows that (i) human coronavirus infections are more common during influenza seasons and in co-infections than previously recognized, (ii) factors associated with co-infection differ from those associated with viral infection overall, (iii) virus prevalence has increased over time especially in infants aged <1 year, and (iv) viral infection risk is greater in the post-2009 pandemic era, likely reflecting a widespread change in the viral population that warrants further investigation.

Efectos inmediatos de la manipulación occipito-atlo-axoidea en el apoyo podal: estudio baropodométrico / Immediate effects of occipito-atloaxoid manipulation on foot support: baropodometric study

Introducción: El equilibrio postural es mantenido gracias a un sistema de aferencias y eferencias en continua adaptación. El objetivo de estas adaptaciones es el mantenimiento de la horizontalidad de la mirada y los centros laberínticos. Para esto el raquis cervical superior tiene un rol importante asegurando la orientación de la cabeza en el espacio. Este estudio trata de evaluar el efecto sobre el apoyo de la normalización propioceptiva del raquis suboccipital. Objetivos: Evaluar cambios inmediatos en la distribución de presiones en el apoyo plantar tras la técnica de thrust occipitoatlo-axoidea (TOAA). Material y Métodos: Se realizó un estudio experimental controlado aleatorizado (ECCA) de carácter explicativo, simple ciego con estrategia de evaluador cegado. Se evaluó a cada sujeto antes y después de la intervención o placebo mediante plataforma de presión. Los sujetos fueron evaluados sin calzado y recibiendo órdenes protocolizadas. La muestra fue de 46 sujetos (25 hombres / 22 mujeres) con una edad media de 24,98±3,04 años. Se utilizó para la comparación intergrupal de la varianza el estadístico ANOVA para las variables paramétricas y la prueba U de Mann Whitney para las no paramétricas. Resultados: Se observó aumento de la «presión máxima» (p=0,044) y del «Porcentaje de carga sobre el pie izquierdo» (p=0,048) acercándolo al reparto equitativo bilateral. Conclusiones: La manipulación occipito-atlo-axoidea aumenta la presión máxima de apoyo y aproxima el porcentaje de carga al reparto equitativo bilateral en sujetos sanos. Los resultados inducen a pensar de cambios en el apoyo tras la técnica, lo cual debe ser comprobado en estudios posteriores con muestras más amplias (AU)

Introduction: Postural balance is maintained thanks to a continually changing system of inputs and outputs. The goal of these changes is to maintain the sight and labyrinthine centres horizontal. To do this, the upper cervical spine has an important role, ensuring the head’s direction within the area. This study is about assessing the effect on the support of proprioceptive normalisation of the suboccipital spine. Objectives: To assess immediate changes in pressure distribution on the arch support after occipito-atlo-axoid thrust (OAAT). Material and methods: A single blind randomised controlled trial (RCT) of an experimental explanatory nature was carried out using the strategy of a blind (no connection between the assessor and inspector) assessor. Each subject was assessed before and after the procedure or placebo using a pressure platform. The subjects were assessed without footwear receiving standardised orders. The sample had 46 subjects (25 men and 22 women) with an average age of 24.98±3.04. For comparison between groups of the variance for parametric variables, the ANOVA statistic was used and for the non-parametric variables the Mann Whitney U test was used. Results: An increase was seen in the «maximum pressure» (p=0.044) and in the «load percentage on the left foot» (p=0.048) coming close to equitable bilateral distribution. Conclusions: Occipito-atlo-axoid manipulation increases the maximum support pressure and approaches the percentage for equitable bilateral load distribution in healthy subjects. The results could lead to considering changes in support after the technique, which must be verified in later studies with larger samples (AU)

Co-circulation of diverse paramyxoviruses in an urban African fruit bat population.

Bats constitute a reservoir of zoonotic infections and some bat paramyxoviruses are capable of cross-species transmission, often with fatal consequences. Determining the level of viral diversity in reservoir populations is fundamental to understanding and predicting viral emergence. This is particularly relevant for RNA viruses where the adaptive mutations required for cross-species transmission can be present in the reservoir host. We report the use of non-invasively collected, pooled, neat urine samples as a robust sample type for investigating paramyxoviruses in bat populations. Using consensus PCR assays we have detected a high incidence and genetic diversity of novel paramyxoviruses in an urban fruit bat population over a short period of time. This may suggest a similarly unique relationship between bats and the members of the family Paramyxoviridae as proposed for some other viral families. Additionally, the high rate of bat-human contact at the study site calls for the zoonotic potential of the detected viruses to be investigated further.

Cluster of cases of malignant schwannoma in cattle.

Between 1998 and 2001, several cases of ataxia and paresis followed by recumbency and death were reported in cows from different farms in a restricted area of the Argentinian Patagonia. Five cases of this cluster were studied and a diagnosis of malignant schwannoma was established. Electron microscopy (em) of tumour samples from three of the animals revealed intracytoplasmic or interstitial structures resembling retroviral particles. Attempts to isolate a viral agent from the tumours were unsuccessful but the epidemiological data and the em findings suggest a viral aetiology.

Imaginarios ambeentales: voces emergentes desde la vida cotidiana / Environmental maaginaries: emergent voices from daiyy life

El presente escrito está fundamentado en la investigación titulada "Vida ambiental universitaria. Una construcción desde los imaginarios cotidianos", inscrito en la Vicerrectoría de Investigaciones y Postgrados de la Universidad de Caldas en octubre del año 2006, el cual pretende comprender los imaginarios que sobre el ambiente se entretejen en el bullicio del cotidiano universitario. Un primer acercamiento a los imaginarios ambientales en la Universidad de Caldas fue realizado desde fuentes documentales institucionales como: el Proyecto Educativo Institucional, la Revista Luna Azul y Catálogos de Investigación; este permitió navegar por los sentidos generales que dibujan los imaginarios irradiados en el perímetro instituciona (1). Son relevantes en esta revisión como imaginarios instituidos (2), entre otros: la protección ambiental, la identificación de los responsables de problemas ambientales, la caracterización de la naturaleza (animada e inanimada) y la educación ambiental. Como imaginarios instituyentes (3) sobresalen: formas de educación alterna (es decir diferente a los estilos tradicionales o previstos por la ley), relación interdependiente del ser humano y la naturaleza, la imaginación como potencia de cambio, y transformación y construcción del futuro. Un segundo acercamiento entraña el flujo de imaginarios ambientales desde la cotidianidad universitaria. Los resultados muestran una fuerte configuración de imaginarios instituidos a partir de la concepción del ambiente como naturaleza (flora y fauna generalmente), una segunda configuración de imaginarios instituyentes fue dibujada desde aspectos sociales orientados hacia la cultura; y una tercera configuración desde imaginarios radicales (4), orientada desde la noción de magma, entorno (todo lo que nos rodea) y tecnología.

The present writing is based on the ongoing study entitled "university environmental Life. A construction based on daily life imaginaries", registered in the Vice-rectory or Research and Postgrades of the Universidad de Caldas in October 2006, which attempts to understand imaginaries constructed regarding the environment within the clatter of daily college life. A first approach to environmental imaginaries at the Universidad de Caldas was carried out using institutional documentary sources such as the Institutional Educative Project, Luna Azul Journal and research catalogues, permitting to sail through the general senses drawn by the imaginaries irradiated within the institutional perimeter. In this revision, instituted imaginaries include environmental protection, the identification of the people responsible for environmental problems, the characterization of nature (animated and unanimated) and environmental education. Instituting imaginaries include: alternate education forms, which is to say, different from traditional styles, interdependent relationship between humans and nature, imagination as a change, transformation and construction potent for the future. A second approach involves the flow of environmental imaginaries from university daily life. The results show a strong configuration of instituted imaginaries from the conception of seeing the environment as nature (generally flora and fauna), a second configuration of instituting imaginaries was drawn from social aspects oriented towards culture; and a third configuration based on radical imaginaries, connected to the notion of magma, surroundings (everything what surrounds us) and technology.

Ovine pulmonary adenomatosis in Patagonia, Argentina.

An outbreak of pulmonary adenomatosis (OPA) occurred in sheep in Patagonia, Argentina's southernmost region. On the affected farm, nine animals died over a 6-month period with pulmonary lesions of OPA. In all cases, the histology of the lungs was characterized by proliferation of cuboideal and prismatic cells lining the alveoli. Inflammatory exudates and accumulation of alveolar macrophages were marked in most cases, but in six of the cases there was no excess fluid in the airways. The presence of the Jaagsiekte retrovirus was demonstrated in the lungs by immunocytochemistry and PCR. To the best of our knowledge, this is the first report of OPA in Patagonia.