Evolutionary constraints on yeast protein size

BACKGROUND: Despite a strong evolutionary pressure to reduce genome size, proteins vary in length over a surprisingly wide range also in very compact genomes. Here we investigated the evolutionary forces that act on protein size in the yeast Saccharomyces cerevisiae utilizing a system-wide bioinformatics approach. Data on yeast protein size was compared to global experimental data on protein expression, phenotypic pleiotropy, protein-protein interactions, protein evolutionary rate and biochemical classification. RESULTS: Comparing the experimentally determined abundance of individual proteins, highly expressed proteins were found to be consistently smaller than lowly expressed proteins, in accordance with the biosynthetic cost minimization hypothesis. Yeast proteins able to maintain a high expression level despite a large size tended to belong to a very distinct set of protein families, notably nuclear transport and translation initiation/elongation. Large proteins have significantly more protein-protein interactions than small proteins, suggesting that a requirement for multiple interaction domains may constitute a positive selective pressure for large protein size in yeast. The higher frequency of protein-protein interactions in large proteins was not accompanied by a higher phenotypic pleiotropy. Hence, the increase in interactions may not reflect an increase in function differentiation. Proteins of different sizes also evolved at similar rates. Finally, whereas the biological process involved was found to have little influence on protein size the biochemical activity exerted by the protein represented a dominant factor. More than one third of all biochemical activity classes were enriched in one or more size intervals. CONCLUSION: In yeast, there is an inverse relationship between protein size and protein expression such that highly expressed proteins tend to be of smaller size. Also, protein size is moderately affected by protein connectivity and strongly affected by biochemical activity. Phenotypic pleiotropy does not seem to affect protein size

The search for a sustainable city : thoughts on sustainability and an application of BREEAM Communities on Bo01

Detta examensarbete är resultatet av arbetet under sista delen av min landskapsarkitektutbildning på Alnarp, SLU. Arbetet riktar sig främst till de med ett intresse för frågor som hållbar stadsbyggnad och stadsplanering. Arbetets grund ligger i en utvärdering av stadsdelen Bo01 i Malmö enligt ett certifieringssystem för hela stadsdelar – BREEAM Communities. Som upptakt till detta görs en omvärldsanalys och introduktion av aktuella miljöfrågor, och då i synnerhet sådana med relation till staden. Med hjälp av de bedömningsverktyg BREEAM Communities erbjuder görs en utvärdering av ett antal aspekter på Bo01. Dessa aspekter spänner över områden såsom transport, energi, plats, ekologi, resurser, tillgänglighet och samhälle. Utvärderingen av Bo01 grundar sig i litteraturstudier då stora delar av Bo01 redan blivit utvärderat i andra sammanhang. Totalt används 25 av de 62 aspekter som finns i BREEAM Communities för att utvärdera Bo01. Som avslutning diskuteras miljösatsningarna på Bo01, BREEAM som system, metoder för att arbeta med hållbarhet, samt landskapsarkitektens roll i detta arbete.This master’s thesis is the results of the work during the last part of my masters’ degree in landscape architecture at Alnarp, SLU. The paper is mainly written for those with an interest in topics such as sustainable cities and planning. The work is based upon an assessment of the Bo01-district in Malmö, Sweden according to a certification used on the district level – BREEAM Communities. The work starts with a broad introduction to some current environmental issues, and especially those that relate to the city. Some aspects of the the city district of Bo01 in Malmö is then assessed according to BREEAM Communities criteria. These aspects span across topics such as transport, energy, place, ecology, resources, accessibility and community. The assessment of Bo01 is done with a literature study as basis, as many other assessments have been done of Bo01. A total of 25 of the 62 issues presented by BREEAM Communities are used in this assessment. The thesis ends with a discussion of environmental achievements and efforts at Bo01, the system of BREEAM Communities, methodology for working with sustainability, as well as the role for the landscape architect in this field

Gröna tak som del i ett hållbart stadsbyggande

Green roofs have seen a revival in the society of today. They provide many functions of which both society as a whole and the individual can take part. In particular extensive green roofs, that requires little or even zero maintenance, provides very valuable functions. Green roofs affect our environment and our economy in a positive manner as well as the physical expression of buildings. In this bachelor thesis the impact of green roofs on society has been examined throughout literature studies. The result as a compilation of contemporary research in this field is presented together with a discussion about the use of green roofs in general. The two major arguments for an extended use of green roofs are, the high stormwater retention capacity and the cost-benefits seen over time compared to a conventional roof. Green roofs can hold and delay major amounts of stormwater. Furthermore the costs for a conventional roof, over time, are seen to be as high or even higher than those of a green roof. Additionally, green roofs contribute to a greater biodiversity in cities, better sound isolation of buildings as well as cleaner air. Since results from different reports differentiate somewhat, more research in the field is preferred

PROPHECY—a database for high-resolution phenomics

The rapid recent evolution of the field phenomics—the genome-wide study of gene dispensability by quantitative analysis of phenotypes—has resulted in an increasing demand for new data analysis and visualization tools. Following the introduction of a novel approach for precise, genome-wide quantification of gene dispensability in Saccharomyces cerevisiae we here announce a public resource for mining, filtering and visualizing phenotypic data—the PROPHECY database. PROPHECY is designed to allow easy and flexible access to physiologically relevant quantitative data for the growth behaviour of mutant strains in the yeast deletion collection during conditions of environmental challenges. PROPHECY is publicly accessible at http://prophecy.lundberg.gu.se

Kvinnor och mäns självskattade status efter gastrointestinal kirurgi

Bakgrund: Kvinnor är generellt mer smärtpåverkade, mår oftare illa och kräks efter kirurgi än män. Kvinnor upplever också ett större missnöje med vården och behandlingen som ges på sjukhus. Syfte: Syftet med studien var att undersöka kvinnor och mäns självskattade status och upplevelser av vården efter gastrointestinal kirurgi. Metod: Kvantitativ enkätstudie. Undersökningsdeltagarna var kvinnor och män som opererats för gastrointestinal kirurgi. För analys användes Mann-Whitney test och Chi-två test. Resultat: Ingen signifikant skillnad förekom mellan kvinnor och mäns tillfredställelse av den smärtlindrande behandlingen postoperativt, dock självskattade sig kvinnor högre på NRS-skalan. Fler kvinnor var postoperativt illamående, kräktes och önskade vara mer delaktiga i sin operationsplanering. Studiedeltagarna upplevde ett respektfullt bemötande av personalen. Konklusion: Undersökningsdeltagarna i studien var otillräckligt smärtlindrande postoperativt och en könsskillnad kring vård och behandling kunde urskiljas

Relationship between antipyretic effects and cytokine levels in uncomplicated falciparum malaria during different treatment regimes

We have previously shown that both chloroquine and paracetamol (acetaminophen) have antipyretic activity during treatment of acute uncomplicated Plasmodium falciparum malaria in children 1-4 years old. Here, we studied if this effect was accompanied by changes in plasma cytokine levels. The 104 children were treated with either chloroquine or sulfadoxine/pyrimethamine (SP) alone, SP + chloroquine or SP + paracetamol for 4 days. Cytokine levels were determined days 0, 2 and 3, body temperature every sixth hour until 72 h and parasitemia once daily for 4 days. At admission, body temperature correlated with levels of IL-10, IFN-γ and IL-6, and parasitemia correlated with IL-10 and IL-6. Except for TNF-α and IL-1β, where no significant effect was found, all cytokine levels (IL-10, IFN-γ, IL-6, IL-12, IL-13, IL-18 and IL-4) decreased up to day 2 (p \u3c 0.05). IL-6 levels continued to fall from days 2 to 3 (p \u3c 0.05), whereas increased levels were found for several cytokines (IL-12, IL-13, IL-18 and IL-1β) (p \u3c 0.05). The antipyretic effects of chloroquine and paracetamol could not be related to any specific changes in the evaluated cytokine production or in Th1/Th2 or inflammatory/anti-inflammatory cytokine ratios. Alternative mechanisms for antipyretic effects and associations between fever and cytokine levels during uncomplicated P. falciparum malaria are therefore discussed. © 2006 Elsevier B.V. All rights reserved

Эпидемиология злокачественных новообразований полости рта по Витебской области

РОТОВОЙ ПОЛОСТИ НОВООБРАЗОВАНИЯЭПИДЕМИОЛОГИ

A CRISPR Interference Screen of Essential Genes Reveals that Proteasome Regulation Dictates Acetic Acid Tolerance in Saccharomyces cerevisiae

CRISPR interference (CRISPRi) is a powerful tool to study cellular physiology under different growth conditions, and this technology provides a means for screening changed expression of essential genes. In this study, a Saccharomyces cerevisiae CRISPRi library was screened for growth in medium supplemented with acetic acid. Acetic acid is a growth inhibitor challenging the use of yeast for the industrial conversion of lignocellulosic biomasses. Tolerance to acetic acid that is released during biomass hydrolysis is crucial for cell factories to be used in biorefineries. The CRISPRi library screened consists of .9,000 strains, where .98% of all essential and respiratory growth-essential genes were targeted with multiple guide RNAs (gRNAs). The screen was performed using the high-throughput, high-resolution Scan-o-matic platform, where each strain is analyzed separately. Our study identified that CRISPRi targeting of genes involved in vesicle formation or organelle transport processes led to severe growth inhibition during acetic acid stress, emphasizing the importance of these intracellular membrane structures in maintaining cell vitality. In contrast, strains in which genes encoding subunits of the 19S regulatory particle of the 26S proteasome were downregulated had increased tolerance to acetic acid, which we hypothesize is due to ATP salvage through an increased abundance of the 20S core particle that performs ATP-independent protein degradation. This is the first study where high-resolution CRISPRi library screening paves the way to understanding and bioengineering the robustness of yeast against acetic acid stress

CRISPRi screen highlights chromatin regulation to be involved in formic acid tolerance in Saccharomyces cerevisiae

Formic acid is one of the main weak acids in lignocellulosic hydrolysates that is known to be inhibitory to yeast growth even at low concentrations. In this study, we employed a CRISPR interference (CRISPRi) strain library comprising >9000 strains encompassing >98% of all essential and respiratory growth-essential genes, to study formic acid tolerance in Saccharomyces cerevisiae. To provide quantitative growth estimates on formic acid tolerance, the strains were screened individually on solid medium supplemented with 140 mM formic acid using the Scan-o-Matic platform. Selected resistant and sensitive strains were characterized in liquid medium supplemented with formic acid and in synthetic hydrolysate medium containing a combination of inhibitors. Strains with gRNAs targeting genes associated with chromatin remodeling were significantly enriched for strains showing formic acid tolerance. In line with earlier findings on acetic acid tolerance, we found genes encoding proteins involved in intracellular vesicle transport enriched among formic acid sensitive strains. The growth of the strains in synthetic hydrolysate medium followed the same trend as when screened in medium supplemented with formic acid. Strains sensitive to formic acid had decreased growth in the synthetic hydrolysate and all strains that had improved growth in the presence of formic acid also grew better in the hydrolysate medium. Systematic analysis of CRISPRi strains allowed identification of genes involved in tolerance mechanisms and provided novel engineering targets for bioengineering strains with increased resistance to inhibitors in lignocellulosic hydrolysates