Recombination rate and selection strength in HIV intra-patient evolution

The evolutionary dynamics of HIV during the chronic phase of infection is driven by the host immune response and by selective pressures exerted through drug treatment. To understand and model the evolution of HIV quantitatively, the parameters governing genetic diversification and the strength of selection need to be known. While mutation rates can be measured in single replication cycles, the relevant effective recombination rate depends on the probability of coinfection of a cell with more than one virus and can only be inferred from population data. However, most population genetic estimators for recombination rates assume absence of selection and are hence of limited applicability to HIV, since positive and purifying selection are important in HIV evolution. Here, we estimate the rate of recombination and the distribution of selection coefficients from time-resolved sequence data tracking the evolution of HIV within single patients. By examining temporal changes in the genetic composition of the population, we estimate the effective recombination to be r=1.4e-5 recombinations per site and generation. Furthermore, we provide evidence that selection coefficients of at least 15% of the observed non-synonymous polymorphisms exceed 0.8% per generation. These results provide a basis for a more detailed understanding of the evolution of HIV. A particularly interesting case is evolution in response to drug treatment, where recombination can facilitate the rapid acquisition of multiple resistance mutations. With the methods developed here, more precise and more detailed studies will be possible, as soon as data with higher time resolution and greater sample sizes is available.Comment: to appear in PLoS Computational Biolog

Plausible self-reported dietary intakes in a residential facility are not necessarily reliable

Background/Objectives: Comparing reported energy intakes with estimated energy requirements as multiples of basal metabolic rate (Ein:BMR) is an established method of identifying implausible food intake records. The present study aimed to examine the validity of self-reported food intakes believed to be plausible. Subjects/Methods: One hundred and eighty men and women were provided with all food and beverages for two consecutive days in a residential laboratory setting. Subjects self-reported their food and beverage intakes using the weighed food diary method (WDR). Investigators covertly measured subjects’ actual consumption over the same period. Subjects also reported intakes over four consecutive days at home. BMR was measured by indirect calorimetry. Results: Average reported energy intakes were significantly lower than actual intakes (11.2 and 11.8 MJ/d, respectively, P<0.001). Two-thirds (121) of the WDR were under-reported to varying degrees. Only five of these were considered as implausible using an Ein:BMR cut-off value of 1.03*BMR. Under-reporting of food and beverage intakes, as measured by the difference between reported and actual intake, was evident at all levels of Ein;BMR. Reported energy intakes were lower still (10.2 MJ/d) while subjects were at home. Conclusions: Under-recording of self-reported food intake records was extensive but very few under-reported food intake records were identified as implausible using energy intake to BMR ratios. Under-recording was evident at all levels of energy intake

High-level production of violacein by the newly isolated Duganella violaceinigra str. NI28 and its impact on Staphylococcus aureus

A violacein-producing bacterial strain was isolated and identified as a relative of Duganella violaceinigra YIM 31327 based upon phylogenetic analyses using the 16S rRNA, gyrB and vioA gene sequences and a fatty acid methyl ester (FAME) analysis. This new strain was designated D. violaceinigra str. NI28. Although these two strains appear related based upon these analyses, the new isolate was phenotypically different from the type strain as it grew 25% faster on nutrient media and produced 45-fold more violacein. When compared with several other violacein producing strains, including Janthinobacterium lividum, D. violaceinigra str. NI28 was the best violacein producer. For instance, the crude violacein yield with D. violaceinigra str. NI28 was 6.0 mg/OD at 24 hours, a value that was more than two-fold higher than all the other strains. Finally, the antibacterial activity of D. violaceinigra str. NI28 crude violacein was assayed using several multidrug resistant Staphylococcus aureus. Addition of 30 mu M crude violacein led to a 96% loss in the initial S. aureus population while the minimum inhibitory concentration was 1.8 mu M. Consequently, this novel isolate represents a phenotypic variant of D. violaceinigra capable of producing much greater quantities of crude violacein, an antibiotic effective against multidrug resistant S. aureusopen

Characteristics of gauged abrupt wave fronts (walls of water) in flash floods in Scotland

\ua9 2025 David R. Archer et al.Extremely rapid rates of rise in river level and discharge are a subset of flash floods ("abrupt wave front floods", AWFs) and are separate hazards from peak river level. They pose a danger to life to river users and occur mainly in the summer. Using level and discharge records from 260 Scottish gauged catchments, we present the spatial distribution of annual maximum 15 min rises in river level and discharge, along with derived metrics to assess the severity of AWF events. These include normalised and proportional measures of flow change, as well as ratios that characterise the intensity of AWF events. We estimate wave celerity by analysing the time difference in wave onset recorded by successive gauging stations along a river channel. This approach is applied to several AWF events on the river Findhorn in northeast Scotland, allowing for detailed examination of their dynamics. Our findings suggest that flood forecasting models with outputs of peak discharge and river level may not adequately represent the risk posed by rapidly rising flows, especially at national scales where hydroclimatic and geomorphological variability trigger different AWF metrics. We show that AWFs may intensify downstream, with wave fronts steepening as they travel through lowland river reaches, as observed in multiple events on the river Findhorn, showing a necessity of more accurate and frequent river measurements. We conclude that AWFs need better monitoring forecasting and warning, particularly as extreme downpours are becoming more frequent with global warming

Selenium isotope evidence for progressive oxidation of the Neoproterozoic biosphere

Neoproterozoic (1,000–542 Myr ago) Earth experienced profound environmental change, including ‘snowball’ glaciations, oxygenation and the appearance of animals. However, an integrated understanding of these events remains elusive, partly because proxies that track subtle oceanic or atmospheric redox trends are lacking. Here we utilize selenium (Se) isotopes as a tracer of Earth redox conditions. We find temporal trends towards lower δ82/76Se values in shales before and after all Neoproterozoic glaciations, which we interpret as incomplete reduction of Se oxyanions. Trends suggest that deep-ocean Se oxyanion concentrations increased because of progressive atmospheric and deep-ocean oxidation. Immediately after the Marinoan glaciation, higher δ82/76Se values superpose the general decline. This may indicate less oxic conditions with lower availability of oxyanions or increased bioproductivity along continental margins that captured heavy seawater δ82/76Se into buried organics. Overall, increased ocean oxidation and atmospheric O2 extended over at least 100 million years, setting the stage for early animal evolution

Pathogenic copy number variants and SCN1A mutations in patients with intellectual disability and childhood-onset epilepsy

Background Copy number variants (CNVs) have been linked to neurodevelopmental disorders such as intellectual disability (ID), autism, epilepsy and psychiatric disease. There are few studies of CNVs in patients with both ID and epilepsy. Methods We evaluated the range of rare CNVs found in 80 Welsh patients with ID or developmental delay (DD), and childhood-onset epilepsy. We performed molecular cytogenetic testing by single nucleotide polymorphism array or microarray-based comparative genome hybridisation. Results 8.8 % (7/80) of the patients had at least one rare CNVs that was considered to be pathogenic or likely pathogenic. The CNVs involved known disease genes (EHMT1, MBD5 and SCN1A) and imbalances in genomic regions associated with neurodevelopmental disorders (16p11.2, 16p13.11 and 2q13). Prompted by the observation of two deletions disrupting SCN1A we undertook further testing of this gene in selected patients. This led to the identification of four pathogenic SCN1A mutations in our cohort. Conclusions We identified five rare de novo deletions and confirmed the clinical utility of array analysis in patients with ID/DD and childhood-onset epilepsy. This report adds to our clinical understanding of these rare genomic disorders and highlights SCN1A mutations as a cause of ID and epilepsy, which can easily be overlooked in adults

Perspectives and Integration in SOLAS Science

Why a chapter on Perspectives and Integration in SOLAS Science in this book? SOLAS science by its nature deals with interactions that occur: across a wide spectrum of time and space scales, involve gases and particles, between the ocean and the atmosphere, across many disciplines including chemistry, biology, optics, physics, mathematics, computing, socio-economics and consequently interactions between many different scientists and across scientific generations. This chapter provides a guide through the remarkable diversity of cross-cutting approaches and tools in the gigantic puzzle of the SOLAS realm. Here we overview the existing prime components of atmospheric and oceanic observing systems, with the acquisition of ocean–atmosphere observables either from in situ or from satellites, the rich hierarchy of models to test our knowledge of Earth System functioning, and the tremendous efforts accomplished over the last decade within the COST Action 735 and SOLAS Integration project frameworks to understand, as best we can, the current physical and biogeochemical state of the atmosphere and ocean commons. A few SOLAS integrative studies illustrate the full meaning of interactions, paving the way for even tighter connections between thematic fields. Ultimately, SOLAS research will also develop with an enhanced consideration of societal demand while preserving fundamental research coherency. The exchange of energy, gases and particles across the air-sea interface is controlled by a variety of biological, chemical and physical processes that operate across broad spatial and temporal scales. These processes influence the composition, biogeochemical and chemical properties of both the oceanic and atmospheric boundary layers and ultimately shape the Earth system response to climate and environmental change, as detailed in the previous four chapters. In this cross-cutting chapter we present some of the SOLAS achievements over the last decade in terms of integration, upscaling observational information from process-oriented studies and expeditionary research with key tools such as remote sensing and modelling. Here we do not pretend to encompass the entire legacy of SOLAS efforts but rather offer a selective view of some of the major integrative SOLAS studies that combined available pieces of the immense jigsaw puzzle. These include, for instance, COST efforts to build up global climatologies of SOLAS relevant parameters such as dimethyl sulphide, interconnection between volcanic ash and ecosystem response in the eastern subarctic North Pacific, optimal strategy to derive basin-scale CO2 uptake with good precision, or significant reduction of the uncertainties in sea-salt aerosol source functions. Predicting the future trajectory of Earth’s climate and habitability is the main task ahead. Some possible routes for the SOLAS scientific community to reach this overarching goal conclude the chapter

Exploring the tensions of being and becoming a medical educator

BackgroundPrevious studies have identified tensions medical faculty encounter in their roles but not specifically those with a qualification in medical education. It is likely that those with postgraduate qualifications may face additional tensions (i.e., internal or external conflicts or concerns) from differentiation by others, greater responsibilities and translational work against the status quo. This study explores the complex and multi-faceted tensions of educators with qualifications in medical education at various stages in their career.MethodsThe data described were collected in 2013&ndash;14 as part of a larger, three-phase mixed-methods research study employing a constructivist grounded theory analytic approach to understand identity formation among medical educators. The over-arching theoretical framework for the study was Communities of Practice. Thirty-six educators who had undertaken or were undertaking a postgraduate qualification in medical education took part in semi-structured interviews.ResultsParticipants expressed multiple tensions associated with both becoming and being a healthcare educator. Educational roles had to be juggled with clinical work, challenging their work-life balance. Medical education was regarded as having lower prestige, and therefore pay, than other healthcare career tracks. Medical education is a vast speciality, making it difficult as a generalist to keep up-to-date in all its areas. Interestingly, the graduates with extensive experience in education reported no fears, rather asserting that the qualification gave them job variety.ConclusionThis is the first detailed study exploring the tensions of educators with postgraduate qualifications in medical education. It complements and extends the findings of the previous studies by identifying tensions common as well as specific to active students and graduates. These tensions may lead to detachment, cynicism and a weak sense of identity among healthcare educators. Postgraduate programmes in medical education can help their students identify these tensions in becoming and develop coping strategies. Separate career routes, specific job descriptions and academic workload models for medical educators are recommended to further the professionalisation of medical education

Defining motility in the Staphylococci

The ability of bacteria to move is critical for their survival in diverse environments and multiple ways have evolved to achieve this. Two forms of motility have recently been described for Staphylococcus aureus, an organism previously considered to be non-motile. One form is called spreading, which is a type of sliding motility and the second form involves comet formation, which has many observable characteristics associated with gliding motility. Darting motility has also been observed in Staphylococcus epidermidis. This review describes how motility is defined and how we distinguish between passive and active motility. We discuss the characteristics of the various forms of Staphylococci motility, the molecular mechanisms involved and the potential future research directions

Anthropogenic perturbation of the carbon fluxes from land to ocean

A substantial amount of the atmospheric carbon taken up on land through photosynthesis and chemical weathering is transported laterally along the aquatic continuum from upland terrestrial ecosystems to the ocean. So far, global carbon budget estimates have implicitly assumed that the transformation and lateral transport of carbon along this aquatic continuum has remained unchanged since pre-industrial times. A synthesis of published work reveals the magnitude of present-day lateral carbon fluxes from land to ocean, and the extent to which human activities have altered these fluxes. We show that anthropogenic perturbation may have increased the flux of carbon to inland waters by as much as 1.0 Pg C yr-1 since pre-industrial times, mainly owing to enhanced carbon export from soils. Most of this additional carbon input to upstream rivers is either emitted back to the atmosphere as carbon dioxide (~0.4 Pg C yr-1) or sequestered in sediments (~0.5 Pg C yr-1) along the continuum of freshwater bodies, estuaries and coastal waters, leaving only a perturbation carbon input of ~0.1 Pg C yr-1 to the open ocean. According to our analysis, terrestrial ecosystems store ~0.9 Pg C yr-1 at present, which is in agreement with results from forest inventories but significantly differs from the figure of 1.5 Pg C yr-1 previously estimated when ignoring changes in lateral carbon fluxes. We suggest that carbon fluxes along the land–ocean aquatic continuum need to be included in global carbon dioxide budgets.Peer reviewe