Why highly expressed proteins evolve slowly

Much recent work has explored molecular and population-genetic constraints on the rate of protein sequence evolution. The best predictor of evolutionary rate is expression level, for reasons which have remained unexplained. Here, we hypothesize that selection to reduce the burden of protein misfolding will favor protein sequences with increased robustness to translational missense errors. Pressure for translational robustness increases with expression level and constrains sequence evolution. Using several sequenced yeast genomes, global expression and protein abundance data, and sets of paralogs traceable to an ancient whole-genome duplication in yeast, we rule out several confounding effects and show that expression level explains roughly half the variation in Saccharomyces cerevisiae protein evolutionary rates. We examine causes for expression's dominant role and find that genome-wide tests favor the translational robustness explanation over existing hypotheses that invoke constraints on function or translational efficiency. Our results suggest that proteins evolve at rates largely unrelated to their functions, and can explain why highly expressed proteins evolve slowly across the tree of life.Comment: 40 pages, 3 figures, with supporting informatio

Reduction of volatile acidity of wines by selected yeast strains

Herein we isolate and characterize wine yeasts with ability to reduce volatile acidity of wines using a refermentation process, which consists in mixing the acidic wine with freshly crushed grapes or musts or, alternatively, in the incubation with the residual marc. From a set of 135 yeast isolates, four strains revealed ability to use glucose and acetic acid simultaneously. Three of them were identified as Saccharomyces cerevisiae and one as Lachancea thermotolerans. Among nine commercial S. cerevisiae strains, strains S26, S29 and S30 display similar glucose and acetic acid initial simultaneous consumption pattern and were assessed in refermentation assays. In a medium containing an acidic wine with high glucose/low ethanol concentrations, under low oxygen availability, strain S29 is the most efficient one, whereas L. thermotolerans 44C is able to decrease significantly acetic acid similar to the control strain Zygosaccharomyces bailii ISA 1307, but only under aerobic conditions. Conversely, for low glucose/high ethanol concentrations, under aerobic conditions, S26 is the most efficient acid degrading strain, while under limited-aerobic conditions, all the S. cerevisiae strains studied display acetic acid degradation efficiencies identical to Z. bailii. Moreover, S26 strain also reveals capacity to decrease volatile acidity of wines. Together, the S. cerevisiae strains characterized herein appear promising for the oenological removal of volatile acidity of acidic wines.Fundação para a Ciência e a Tecnologia (FCT) - Programa POCI 2010 (FEDER/FCT, POCI/AGR/56102/2004, PTDC/AGRALI/71460/2006

Isolation, characterisation, and selection of wine yeast strains in Etyek-Buda wine district, Hungary

Initiated by the Association “Wine Route of Etyek Wine District”, the objectives of this study were to isolate and identify autochthonous yeast strains from local wines and to determine their oenologically important properties. The first aim of this work was to characterize the taxonomic and phenotypic diversity of the representative Saccharomyces yeast strains that dominate the spontaneous fermentations in this wine district. The results obtained by molecular ribotyping (ARDRA) revealed a strong dominance of S. cerevisiae, but S. bayanus var. uvarum was also present sporadically. Some of the natural isolates exhibited high volatile acid production or poor fermentation capacity, which imply a quality risk in spontaneous fermentations. Most of the isolates, however, displayed good oenological features during lab scale fermentations. As the second aim of this work, the most promising, selected strains were further tested for oenological properties in microvinification scale and, finally, in large scale fermentations. The analytical and sensory analysis proved that selected strains, including S. bayanus var. uvarum, can be used as local starter cultures, which may contribute to the typicality of the local wines in comparison with commercial starters

Finding needles in haystacks: linking scientific names, reference specimens and molecular data for Fungi

DNA phylogenetic comparisons have shown that morphology-based species recognition often underestimates fungal diversity. Therefore, the need for accurate DNA sequence data, tied to both correct taxonomic names and clearly annotated specimen data, has never been greater. Furthermore, the growing number of molecular ecology and microbiome projects using high-throughput sequencing require fast and effective methods for en masse species assignments. In this article, we focus on selecting and re-annotating a set of marker reference sequences that represent each currently accepted order of Fungi. The particular focus is on sequences from the internal transcribed spacer region in the nuclear ribosomal cistron, derived from type specimens and/or ex-type cultures. Re-annotated and verified sequences were deposited in a curated public database at the National Center for Biotechnology Information (NCBI), namely the RefSeq Targeted Loci (RTL) database, and will be visible during routine sequence similarity searches with NR_prefixed accession numbers. A set of standards and protocols is proposed to improve the data quality of new sequences, and we suggest how type and other reference sequences can be used to improve identification of Fungi

Spatio-Temporal Characteristics of Global Warming in the Tibetan Plateau during the Last 50 Years Based on a Generalised Temperature Zone - Elevation Model

Temperature is one of the primary factors influencing the climate and ecosystem, and examining its change and fluctuation could elucidate the formation of novel climate patterns and trends. In this study, we constructed a generalised temperature zone elevation model (GTEM) to assess the trends of climate change and temporal-spatial differences in the Tibetan Plateau (TP) using the annual and monthly mean temperatures from 1961-2010 at 144 meteorological stations in and near the TP. The results showed the following: (1) The TP has undergone robust warming over the study period, and the warming rate was 0.318°C/decade. The warming has accelerated during recent decades, especially in the last 20 years, and the warming has been most significant in the winter months, followed by the spring, autumn and summer seasons. (2) Spatially, the zones that became significantly smaller were the temperature zones of -6°C and -4°C, and these have decreased 499.44 and 454.26 thousand sq km from 1961 to 2010 at average rates of 25.1% and 11.7%, respectively, over every 5-year interval. These quickly shrinking zones were located in the northwestern and central TP. (3) The elevation dependency of climate warming existed in the TP during 1961-2010, but this tendency has gradually been weakening due to more rapid warming at lower elevations than in the middle and upper elevations of the TP during 1991-2010. The higher regions and some low altitude valleys of the TP were the most significantly warming regions under the same categorizing criteria. Experimental evidence shows that the GTEM is an effective method to analyse climate changes in high altitude mountainous regions

Chronic hepatitis caused by persistent parvovirus B19 infection

<p>Abstract</p> <p>Background</p> <p>Human infection with parvovirus B19 may lead to a diverse spectrum of clinical manifestations, including benign erythema infectiosum in children, transient aplastic crisis in patients with haemolytic anaemia, and congenital hydrops foetalis. These different diseases represent direct consequences of the ability of parvovirus B19 to target the erythroid cell lineage. However, accumulating evidence suggests that this virus can also infect other cell types resulting in diverse clinical manifestations, of which the pathogenesis remains to be fully elucidated. This has prompted important questions regarding the tropism of the virus and its possible involvement in a broad range of infectious and autoimmune medical conditions.</p> <p>Case Presentation</p> <p>Here, we present an unusual case of persistent parvovirus B19 infection as a cause of chronic hepatitis. This patient had persistent parvovirus B19 viraemia over a period of more than four years and displayed signs of chronic hepatitis evidenced by fluctuating elevated levels of ALAT and a liver biopsy demonstrating chronic hepatitis. Other known causes of hepatitis and liver damage were excluded. In addition, the patient was evaluated for immunodeficiency, since she had lymphopenia both prior to and following clearance of parvovirus B19 infection.</p> <p>Conclusions</p> <p>In this case report, we describe the current knowledge on the natural history and pathogenesis of parvovirus B19 infection, and discuss the existing evidence of parvovirus B19 as a cause of acute and chronic hepatitis. We suggest that parvovirus B19 was the direct cause of this patient's chronic hepatitis, and that she had an idiopathic lymphopenia, which may have predisposed her to persistent infection, rather than bone marrow depression secondary to infection. In addition, we propose that her liver involvement may have represented a viral reservoir. Finally, we suggest that clinicians should be aware of parvovirus B19 as an unusual aetiology of chronic hepatitis, when other causes have been ruled out.</p

Tourists' consumption and interpretation of sport event imagery

In an era when popular and mass cultures are positioned further up the symbolic hierarchy, sport events are deemed by cities to be a valuable image or branding tools. Event strategies are often justified by their envisaged image effects and the celebrities, iconic structures and media exposure associated with sport events means that they are viewed as being particularly effective for this purpose. This paper evaluates the image effects of strategies deployed by three English cities; Birmingham, Manchester and Sheffield. Each of these cities has used a combination of regular sport fixtures, ‘mega’ sport events and event bids to further their reputations as tourist destinations. Semi-structured interviews with a representative sample of potential tourists were used to provide evidence of the impacts of these initiatives. Despite some participants making connections with traffic chaos and violence, in general sport events appear to have encouraged positive connotations amongst potential tourists, including modernity, progress and vitality. Events seem to be regarded favourably at a cultural level, generating widespread positive meanings even when individual preferences vary. This has positive implications for cities deploying sport events as re-imaging or branding tools

Evaluation of cell-free DNA approaches for multi-cancer early detection

In the Circulating Cell-free Genome Atlas (NCT02889978) substudy 1, we evaluate several approaches for a circulating cell-free DNA (cfDNA)-based multi-cancer early detection (MCED) test by defining clinical limit of detection (LOD) based on circulating tumor allele fraction (cTAF), enabling performance comparisons. Among 10 machine-learning classifiers trained on the same samples and independently validated, when evaluated at 98% specificity, those using whole-genome (WG) methylation, single nucleotide variants with paired white blood cell background removal, and combined scores from classifiers evaluated in this study show the highest cancer signal detection sensitivities. Compared with clinical stage and tumor type, cTAF is a more significant predictor of classifier performance and may more closely reflect tumor biology. Clinical LODs mirror relative sensitivities for all approaches. The WG methylation feature best predicts cancer signal origin. WG methylation is the most promising technology for MCED and informs development of a targeted methylation MCED test