Intra- and inter-individual variation of BIS-index® and Entropy® during controlled sedation with midazolam/remifentanil and dexmedetomidine/remifentanil in healthy volunteers: an interventional study

INTRODUCTION: We studied intra-individual and inter-individual variability of two online sedation monitors, BIS and Entropy, in volunteers under sedation. METHODS: Ten healthy volunteers were sedated in a stepwise manner with doses of either midazolam and remifentanil or dexmedetomidine and remifentanil. One week later the procedure was repeated with the remaining drug combination. The doses were adjusted to achieve three different sedation levels (Ramsay Scores 2, 3 and 4) and controlled by a computer-driven drug-delivery system to maintain stable plasma concentrations of the drugs. At each level of sedation, BIS and Entropy (response entropy and state entropy) values were recorded for 20 minutes. Baseline recordings were obtained before the sedative medications were administered. RESULTS: Both inter-individual and intra-individual variability increased as the sedation level deepened. Entropy values showed greater variability than BIS(R) values, and the variability was greater during dexmedetomidine/remifentanil sedation than during midazolam/remifentanil sedation. CONCLUSIONS: The large intra-individual and inter-individual variability of BIS and Entropy values in sedated volunteers makes the determination of sedation levels by processed electroencephalogram (EEG) variables impossible. Reports in the literature which draw conclusions based on processed EEG variables obtained from sedated intensive care unit (ICU) patients may be inaccurate due to this variability. TRIAL REGISTRATION: clinicaltrials.gov Nr. NCT00641563

Identification of two new recessive MC1R alleles in red-coloured Evolèner cattle and other breeds

Sequence variations in the melanocortin-1 receptor (MC1R) gene are associated with melanism in different animal species. Six functionally relevant alleles have been described in cattle to date. In a hypothesis-free approach we performed a genome-wide allelic association study with black, red and wild-coloured cattle of three Alpine cattle breeds (Eringer, Evolèner and Valdostana), revealing a single significant association signal close to the MC1R gene. We searched for candidate causative variants by sequencing the entire coding sequence and identified two novel protein-changing variants. We propose designating the mutant alleles at MC1R:c.424C>T as ev1 and at MC1R:c.263G>A as ev2. Both affect conserved amino acid residues in functionally important transmembrane domains (p.Arg142Cys and p.Ser88Asn). Both alleles segregate predominantly in the Swiss Evolèner breed. They occur in other European cattle breeds such as Abondance and Rotes Höhenvieh as well. We observed almost perfect association between the MC1R genotypes and the coat colour phenotype in a cohort of 513 black, red and wild-coloured cattle. Animals carrying two copies of MC1R loss-of-function alleles or that were compound heterozygous for e, ev1, or ev2 have a red to dark red (chestnut-like red) coat colour. These findings expand the spectrum of causal MC1R variants causing recessive red in cattle

Sustainability assessments of energy scenarios: citizens’ preferences for and assessments of sustainability indicators

Background: Given the multitude of scenarios on the future of our energy systems, multi-criteria assessments are increasingly called for to analyze and assess desired and undesired effects of possible pathways with regard to their environmental, economic and social sustainability. Existing studies apply elaborate lists of sustainability indicators, yet these indicators are defined and selected by experts and the relative importance of each indicator for the overall sustainability assessments is either determined by experts or is computed using mathematical functions. Target group-specific empirical data regarding citizens’ preferences for sustainability indicators as well as their reasoning behind their choices are not included in existing assessments. Approach and results: We argue that citizens’ preferences and values need to be more systematically analyzed. Next to valid and reliable data regarding diverse sets of indicators, reflections and deliberations are needed regarding what different societal actors, including citizens, consider as justified and legitimate interventions in nature and society, and what considerations they include in their own assessments. For this purpose, we present results from a discrete choice experiment. The method originated in marketing and is currently becoming a popular means to systematically analyze individuals’ preference structures for energy technology assessments. As we show in our paper, it can be fruitfully applied to study citizens’ values and weightings with regard to sustainability issues. Additionally, we present findings from six focus groups that unveil the reasons behind citizens’ preferences and choices. Conclusions: Our combined empirical methods provide main insights with strong implications for the future development and assessment of energy pathways: while environmental and climate-related effects significantly influenced citizens’ preferences for or against certain energy pathways, total systems and production costs were of far less importance to citizens than the public discourse suggests. Many scenario studies seek to optimize pathways according to total systems costs. In contrast, our findings show that the role of fairness and distributional justice in transition processes featured as a dominant theme for citizens. This adds central dimensions for future multi-criteria assessments that, so far, have been neglected by current energy systems models

The complete genome sequence and comparative genome analysis of the high pathogenicity Yersinia enterocolitica strain 8081

The human enteropathogen, Yersinia enterocolitica, is a significant link in the range of Yersinia pathologies extending from mild gastroenteritis to bubonic plague. Comparison at the genomic level is a key step in our understanding of the genetic basis for this pathogenicity spectrum. Here we report the genome of Y. enterocolitica strain 8081 (serotype 0:8; biotype 1B) and extensive microarray data relating to the genetic diversity of the Y. enterocolitica species. Our analysis reveals that the genome of Y. enterocolitica strain 8081 is a patchwork of horizontally acquired genetic loci, including a plasticity zone of 199 kb containing an extraordinarily high density of virulence genes. Microarray analysis has provided insights into species-specific Y. enterocolitica gene functions and the intraspecies differences between the high, low, and nonpathogenic Y. enterocolitica biotypes. Through comparative genome sequence analysis we provide new information on the evolution of the Yersinia. We identify numerous loci that represent ancestral clusters of genes potentially important in enteric survival and pathogenesis, which have been lost or are in the process of being lost, in the other sequenced Yersinia lineages. Our analysis also highlights large metabolic operons in Y. enterocolitica that are absent in the related enteropathogen, Yersinia pseudotuberculosis, indicating major differences in niche and nutrients used within the mammalian gut. These include clusters directing, the production of hydrogenases, tetrathionate respiration, cobalamin synthesis, and propanediol utilisation. Along with ancestral gene clusters, the genome of Y. enterocolitica has revealed species-specific and enteropathogen-specific loci. This has provided important insights into the pathology of this bacterium and, more broadly, into the evolution of the genus. Moreover, wider investigations looking at the patterns of gene loss and gain in the Yersinia have highlighted common themes in the genome evolution of other human enteropathogens

Telomeric expression sites are highly conserved in trypanosoma brucei

Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs). The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs) were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology

The \u3cem\u3eChlamydomonas\u3c/em\u3e Genome Reveals the Evolution of Key Animal and Plant Functions

Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the ∼120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella

Integrated Multidimensional Sustainability Assessment of Energy System Transformation Pathways

Sustainable development embraces a broad spectrum of social, economic and ecological aspects. Thus, a sustainable transformation process of energy systems is inevitably multidimensional and needs to go beyond climate impact and cost considerations. An approach for an integrated and interdisciplinary sustainability assessment of energy system transformation pathways is presented here. It first integrates energy system modeling with a multidimensional impact assessment that focuses on life cycle‐based environmental and macroeconomic impacts. Then, stakeholders’ preferences with respect to defined sustainability indicators are inquired, which are finally integrated into a comparative scenario evaluation through a multi‐criteria decision analysis (MCDA), all in one consistent assessment framework. As an illustrative example, this holistic approach is applied to the sustainability assessment of ten different transformation strategies for Germany. Applying multi‐criteria decision analysis reveals that both ambitious (80%) and highly ambitious (95%) carbon reduction scenarios can achieve top sustainability ranks, depending on the underlying energy transformation pathways and respective scores in other sustainability dimensions. Furthermore, this research highlights an increasingly dominant contribution of energy systems’ upstream chains on total environmental impacts, reveals rather small differences in macroeconomic effects between different scenarios and identifies the transition among societal segments and climate impact minimization as the most important stakeholder preferences

The pig X and Y Chromosomes: structure, sequence, and evolution.

We have generated an improved assembly and gene annotation of the pig X Chromosome, and a first draft assembly of the pig Y Chromosome, by sequencing BAC and fosmid clones from Duroc animals and incorporating information from optical mapping and fiber-FISH. The X Chromosome carries 1033 annotated genes, 690 of which are protein coding. Gene order closely matches that found in primates (including humans) and carnivores (including cats and dogs), which is inferred to be ancestral. Nevertheless, several protein-coding genes present on the human X Chromosome were absent from the pig, and 38 pig-specific X-chromosomal genes were annotated, 22 of which were olfactory receptors. The pig Y-specific Chromosome sequence generated here comprises 30 megabases (Mb). A 15-Mb subset of this sequence was assembled, revealing two clusters of male-specific low copy number genes, separated by an ampliconic region including the HSFY gene family, which together make up most of the short arm. Both clusters contain palindromes with high sequence identity, presumably maintained by gene conversion. Many of the ancestral X-related genes previously reported in at least one mammalian Y Chromosome are represented either as active genes or partial sequences. This sequencing project has allowed us to identify genes--both single copy and amplified--on the pig Y Chromosome, to compare the pig X and Y Chromosomes for homologous sequences, and thereby to reveal mechanisms underlying pig X and Y Chromosome evolution.This work was funded by BBSRC grant BB/F021372/1. The Flow Cytometry and Cytogenetics Core Facilities at the Wellcome Trust Sanger Institute and Sanger investigators are funded by the Wellcome Trust (grant number WT098051). K.B., D.C.-S., and J.H. acknowledge support from the Wellcome Trust (WT095908), the BBSRC (BB/I025506/1), and the European Molecular Biology Laboratory. The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 222664 (“Quantomics”).This is the final version of the article. It first appeared from Cold Spring Harbor Laboratory Press via http://dx.doi.org/10.1101/gr.188839.11