ARTreat Project: Three-Dimensional Numerical Simulation of Plaque Formation and Development in the Arteries

Atherosclerosis is a progressive disease characterized by the accumulation of lipids and fibrous elements in arteries. It is characterized by dysfunction of endothelium and vasculitis, and accumulation of lipid, cholesterol, and cell elements inside blood vessel wall. In this study, a continuum-based approach for plaque formation and development in 3-D is presented. The blood flow is simulated by the 3-D Navier-Stokes equations, together with the continuity equation while low-density lipoprotein (LDL) transport in lumen of the vessel is coupled with Kedem-Katchalsky equations. The inflammatory process was solved using three additional reaction-diffusion partial differential equations. Transport of labeled LDL was fitted with our experiment on the rabbit animal model. Matching with histological data for LDL localization was achieved. Also, 3-D model of the straight artery with initial mild constriction of 30% plaque for formation and development is presented

Recurrent acquisition of cytosine methyltransferases into eukaryotic retrotransposons

Transposable elements are in a constant arms race with the silencing mechanisms of their host genomes. One silencing mechanism commonly used by many eukaryotes is dependent on cytosine methylation, a covalent modification of DNA deposited by C5 cytosine methyltransferases (DNMTs). Here, we report how two distantly related eukaryotic lineages, dinoflagellates and charophytes, have independently incorporated DNMTs into the coding regions of distinct retrotransposon classes. Concomitantly, we show that dinoflagellates of the genus Symbiodinium have evolved cytosine methylation patterns unlike any other eukaryote, with most of the genome methylated at CG dinucleotides. Finally, we demonstrate the ability of retrotransposon DNMTs to methylate CGs de novo, suggesting that retrotransposons could self-methylate retrotranscribed DNA. Together, this is an example of how retrotransposons incorporate host-derived genes involved in DNA methylation. In some cases, this event could have implications for the composition and regulation of the host epigenomic environment

The genome of the crustacean Parhyale hawaiensis, a model for animal development, regeneration, immunity and lignocellulose digestion

The amphipod crustacean Parhyale hawaiensis is a blossoming model system for studies of developmental mechanisms and more recently regeneration. We have sequenced the genome allowing annotation of all key signaling pathways, transcription factors, and non-coding RNAs that will enhance ongoing functional studies. Parhyale is a member of the Malacostraca clade, which includes crustacean food crop species. We analysed the immunity related genes of Parhyale as an important comparative system for these species, where immunity related aquaculture problems have increased as farming has intensified. We also find that Parhyale and other species within Multicrustacea contain the enzyme sets necessary to perform lignocellulose digestion ('wood eating'), suggesting this ability may predate the diversification of this lineage. Our data provide an essential resource for further development of Parhyale as an experimental model. The first malacostracan genome will underpin ongoing comparative work in food crop species and research investigating lignocellulose as an energy source

Inequalities in mortality by socioeconomic factors and Roma ethnicity in the two biggest cities in Slovakia:a multilevel analysis

Background: The socioeconomic and ethnic composition of urban neighbourhoods may affect mortality, but evidence on Central European cities is lacking. The aim of this study was to assess the associations between socioeconomic and ethnic neighbourhood indicators and the mortality of individuals aged 20-64 years old in the two biggest cities of the Slovak Republic. Methods: We obtained data on the characteristics of neighbourhoods and districts (educational level, unemployment, income and share of Roma) and on individual mortality of residents aged 20-64 years old, for the two largest cities in the Slovak Republic (Bratislava and Kosice) in the period 2003-2005. We performed multilevel Poisson regression analyses adjusted for age and gender on the individual (mortality), neighbourhood (education level and share of Roma in population) and district levels (unemployment and income). Results: The proportions of Roma and of low-educated residents were associated with mortality at the neighbourhood level in both cities. Mutually adjusted, only the association with the proportion of Roma remained in the model (risk ratio 1.02; 95 % confidence interval 1.01-1.04). The area indicators - high education, income and unemployment - were not associated with mortality. Conclusion: The proportion of Roma is associated with early mortality in the two biggest cities in the Slovak Republic

The genome of the crustacean Parhyale hawaiensis, a model for animal development, regeneration, immunity and lignocellulose digestion

The amphipod crustacean Parhyale hawaiensis is a blossoming model system for studies of developmental mechanisms and more recently regeneration. We have sequenced the genome allowing annotation of all key signaling pathways, transcription factors, and non-coding RNAs that will enhance ongoing functional studies. Parhyale is a member of the Malacostraca clade, which includes crustacean food crop species. We analysed the immunity related genes of Parhyale as an important comparative system for these species, where immunity related aquaculture problems have increased as farming has intensified. We also find that Parhyale and other species within Multicrustacea contain the enzyme sets necessary to perform lignocellulose digestion ('wood eating'), suggesting this ability may predate the diversification of this lineage. Our data provide an essential resource for further development of Parhyale as an experimental model. The first malacostracan genome will underpin ongoing comparative work in food crop species and research investigating lignocellulose as an energy source

Regional socioeconomic indicators and ethnicity as predictors of regional infant mortality rate in Slovakia

OBJECTIVE: Exploring the associations of regional differences in infant mortality with selected socioeconomic indicators and ethnicity could offer important clues for designing public health policy measures. METHODS: Data included perinatal and infant mortality in the 79 districts of the Slovak population in 2004. Linear regression was used to analyse the contribution of education, unemployment, income and proportion of Roma population on regional differences in perinatal and infant mortality rates. RESULTS: All the explored socioeconomic indicators and ethnicity individually contributed significantly to both perinatal and infant mortality, with the exception of income. In the model exploring the influence of all these variables together on perinatal and infant mortality, only the effect of the proportion of Roma population remained significant. This model explained 34.9% of the variance for perinatal and 36.4% of the variance for infant mortality. CONCLUSIONS: Living in Roma settlements indicates an accumulation of socioeconomic disadvantage. Health literacy, health-related behaviour and many other factors might contribute to the explanation of the differences in infant mortality, and a better understanding of these processes might help us to design tailored interventions

Improving Cry8Ka toxin activity towards the cotton boll weevil (Anthonomus grandis)

<p>Abstract</p> <p>Background</p> <p>The cotton boll weevil (<it>Anthonomus grandis</it>) is a serious insect-pest in the Americas, particularly in Brazil. The use of chemical or biological insect control is not effective against the cotton boll weevil because of its endophytic life style. Therefore, the use of biotechnological tools to produce insect-resistant transgenic plants represents an important strategy to reduce the damage to cotton plants caused by the boll weevil. The present study focuses on the identification of novel molecules that show improved toxicity against the cotton boll weevil. <it>In vitro </it>directed molecular evolution through DNA shuffling and phage display screening was applied to enhance the insecticidal activity of variants of the Cry8Ka1 protein of <it>Bacillus thuringiensis</it>.</p> <p>Results</p> <p>Bioassays carried out with <it>A. grandis </it>larvae revealed that the LC₅₀of the screened mutant Cry8Ka5 toxin was 3.15-fold higher than the wild-type Cry8Ka1 toxin. Homology modelling of Cry8Ka1 and the Cry8Ka5 mutant suggested that both proteins retained the typical three-domain Cry family structure. The mutated residues were located mostly in loops and appeared unlikely to interfere with molecular stability.</p> <p>Conclusions</p> <p>The improved toxicity of the Cry8Ka5 mutant obtained in this study will allow the generation of a transgenic cotton event with improved potential to control <it>A. grandis</it>.</p

Spt6 is a maintenance factor for centromeric CENP-A

Replication and transcription of genomic DNA requires partial disassembly of nucleosomes to allow progression of polymerases. This presents both an opportunity to remodel the underlying chromatin and a danger of losing epigenetic information. Centromeric transcription is required for stable incorporation of the centromere-specific histone dCENP-A in M/G1 phase, which depends on the eviction of previously deposited H3/H3.3-placeholder nucleosomes. Here we demonstrate that the histone chaperone and transcription elongation factor Spt6 spatially and temporarily coincides with centromeric transcription and prevents the loss of old CENP-A nucleosomes in both Drosophila and human cells. Spt6 binds directly to dCENP-A and dCENP-A mutants carrying phosphomimetic residues alleviate this association. Retention of phosphomimetic dCENP-A mutants is reduced relative to wildtype, while non-phosphorylatable dCENP-A retention is increased and accumulates at the centromere. We conclude that Spt6 acts as a conserved CENP-A maintenance factor that ensures long-term stability of epigenetic centromere identity during transcription-mediated chromatin remodeling

Rearrangement bursts generate canonical gene fusions in bone and soft tissue tumors

Sarcomas are cancers of the bone and soft tissue often defined by gene fusions. Ewing sarcoma involves fusions between EWSR1, a gene encoding an RNA binding protein, and E26 transformation-specific (ETS) transcription factors. We explored how and when EWSR1-ETS fusions arise by studying the whole genomes of Ewing sarcomas. In 52 of 124 (42%) of tumors, the fusion gene arises by a sudden burst of complex, loop-like rearrangements, a process called chromoplexy, rather than by simple reciprocal translocations. These loops always contained the disease-defining fusion at the center, but they disrupted multiple additional genes. The loops occurred preferentially in early replicating and transcriptionally active genomic regions. Similar loops forming canonical fusions were found in three other sarcoma types. Chromoplexy-generated fusions appear to be associated with an aggressive form of Ewing sarcoma. These loops arise early, giving rise to both primary and relapse Ewing sarcoma tumors, which can continue to evolve in parallel