Definition of a family of tissue-protective cytokines using functional cluster analysis: a proof-of-concept study

The discovery of the tissue-protective activities of erythropoietin (EPO) has underlined the importance of some cytokines in tissue-protection, repair, and remodeling. As such activities have been reported for other cytokines, we asked whether we could define a class of tissue-protective cytokines. We therefore explored a novel approach based on functional clustering. In this pilot study, we started by analyzing a small number of cytokines (30). We functionally classified the 30 cytokines according to their interactions by using the bioinformatics tool STRING (Search Tool for the Retrieval of Interacting Genes), followed by hierarchical cluster analysis. The results of this functional clustering were different from those obtained by clustering cytokines simply according to their sequence. We previously reported that the protective activity of EPO in a model of cerebral ischemia was paralleled by an upregulation of synaptic plasticity genes, particularly early growth response 2 (EGR2). To assess the predictivity of functional clustering, we tested some of the cytokines clustering close to EPO (interleukin-11, IL-11; kit ligand, KITLG; leukemia inhibitory factor, LIF; thrombopoietin, THPO) in an in vitro model of human neuronal cells for their ability to induce EGR2. Two of these, LIF and IL-11, induced EGR2 expression. Although these data would need to be extended to a larger number of cytokines and the biological validation should be done using more robust in vivo models, rather then just one cell line, this study shows the feasibility of this approach. This type of functional cluster analysis could be extended to other fields of cytokine research and help design biological experiments

Method for creating polynucleotide and polypeptide sequences

The invention provides methods for evolving a polynucleotide toward acquisition of a desired property. Such methods entail incubating a population of parental polynucleotide variants under conditions to generate annealed polynucleotides comprising heteroduplexes. The heteroduplexes are then exposed to a cellular DNA repair system to convert the heteroduplexes to parental polynucleotide variants or recombined polynucleotide variants. The resulting polynucleotides are then screened or selected for the desired property

Filamentous Connections between Ediacaran Fronds.

Fossils of the Ediacaran macrobiota (∼571-539 mya) record phylogenetically diverse marine palaeocommunities, including early animals, which pre-date the "Cambrian Explosion" [1-4]. Benthic forms with a frondose gross morphology, assigned to the morphogroups Rangeomorpha [5] and Frondomorpha (see also Arboreomorpha) [6-8], are among the most temporally wide-ranging and environmentally tolerant members of the Ediacaran macrobiota [6] and dominated deep-marine ecosystems ∼571-560 mya [9-11]. Investigations into the morphology [12-14], palaeoecology [10, 15, 16], reproductive strategies [17, 18], feeding methods [9, 19], and morphogenesis of frondose taxa together constrain their phylogenetic position to the metazoan (for Rangeomorpha) or eumetazoan (e.g., Arborea) total groups [14, 20], but tighter constraint is currently lacking. Here, we describe fossils of abundant filamentous organic structures preserved among frond-dominated fossil assemblages in Newfoundland (Canada). The filaments constitute a prominent component of the ecosystems, and exhibit clear physical associations with at least seven frondose taxa. Individual specimens of one uniterminal rangeomorph taxon appear to be directly connected by filaments across distances of centimeters to meters. Such physical linkages are interpreted to reflect evidence for stolonic connections: a conclusion with potential implications for the phylogenetic placement and palaeoecology of frondose organisms. Consideration of extant stoloniferous organisms suggests that Ediacaran frondose taxa were likely clonal and resurrects the possibility that they may have been colonial (e.g., [21, 22]). VIDEO ABSTRACT.NERC National Geographic Geological Society of London Cambridge Philosophical Societ

Biosynthesis of novel carotenoid families based on unnatural carbon backbones: A model for diversification of natural product pathways

We show that the C_(40) carotenoid desaturase CrtI from Pantoea ananatis (Erwinia uredovora) is capable of desaturating unnaturally long C_(45) and C_(50) carotenoid backbones in recombinant E. coli. Desaturation step number in these pathways is not very specific, and at least ten new C_(45) and C_(50) carotenoids were synthesized. We also present evidence for a novel asymmetric C_(40) backbone formed by the condensation of farnesyl diphosphate (C_(15)PP) with farnesylgeranyl diphosphate (C_(25)PP), and the subsequent desaturation of this backbone by CrtI in an atypical manner. Under some conditions, the C_(40), C_(45), and C_(50) carotenoid backbones synthesized in E. coli were monohydroxylated; their desaturation by CrtI in vitro led to yet more novel carotenoids. Challenging CrtI with larger-than-natural substrates in vivo has allowed us to show that this enzyme regulates desaturation step number by sensing the end groups of its substrate. Analysis of the mechanisms by which chemical diversity is generated and propagated through the nascent pathways provides insight into how natural product diversification occurs in nature

AROC outcome benchmarks report inpatient - pathway 3 Anywhere Hospital January 2015 - December 2015

The Outcome Benchmarks Report is a biannual report that provides facilities with the opportunity to evaluate their performance against all other Australian and New Zealand rehabilitation facilities. This report provides impairment level 25th percentile targets which were set by the AROC Scientific and Clinical Advisory Committee as a stretch goal for continuous improvement. The performance measures presented in this report include Casemix Adjusted FIM Efficiency and Casemix Adjusted Length of Stay. The selection of these outcome measures is based on the advice provided by the AROC Scientific and Clinical Advisory Committee. Each facility is provided with a graphical representation of their casemix adjusted performance against all other facilities at the impairment level. A five year trend graph of the outcome measure (not casemix adjusted) is included in this report to demonstrate quality improvement over time