High-mobility group box-1 protein, lipopolysaccharide-binding protein, interleukin-6 and C-reactive protein in children with community acquired infections and bacteraemia: a prospective study

<p>Abstract</p> <p>Introduction</p> <p>Even though sepsis is one of the common causes of children morbidity and mortality, specific inflammatory markers for identifying sepsis are less studied in children. The main aim of this study was to compare the levels of high-mobility group box-1 protein (HMGB1), Lipopolysaccharide-binding protein (LBP), Interleukin-6 (IL-6) and C-reactive protein (CRP) between infected children without systemic inflammatory response syndrome (SIRS) and children with severe and less severe sepsis. The second aim was to examine HMGB1, LBP, IL6 and CRP as markers for of bacteraemia.</p> <p>Methods</p> <p>Totally, 140 children with suspected or proven infections admitted to the Children's Clinical University Hospital of Latvia during 2008 and 2009 were included. Clinical and demographical information as well as infection focus were assessed in all patients. HMGB1, LBP, IL-6 and CRP blood samples were determined. Children with suspected or diagnosed infections were categorized into three groups of severity of infection: (i) infected without SIRS (n = 36), (ii) sepsis (n = 91) and, (iii) severe sepsis (n = 13). They were furthermore classified according bacteraemia into (i) bacteremia (n = 30) and (ii) no bacteraemia (n = 74).</p> <p>Results</p> <p>There was no statistically significant difference in HMGB1 levels between children with different levels of sepsis or with and without bacteraemia. The levels of LBP, IL-6 and CRP were statistically significantly higher among patients with sepsis compared to those infected but without SIRS (<it>p </it>< 0.001). Furthermore, LBP, IL-6 and CRP were significantly higher in children with severe sepsis compared to those ones with less severe sepsis (<it>p </it>< 0.001). Median values of LBP, IL6 and CRP were significantly higher in children with bacteraemia compared to those without bacteraemia. The area under the receiver operating curve (ROC) for detecting bacteraemia was 0.87 for both IL6 and CRP and 0.82 for LBP, respectively.</p> <p>Conclusion</p> <p>Elevated levels of LBP, IL-6 and CRP were associated with a more severe level of infection in children. Whereas LBP, IL-6 and CRP seem to be good markers to detect patients with bacteraemia, HMGB1 seem to be of minor importance. LBP, IL-6 and CRP levels may serve as good biomarkers for identifying children with severe sepsis and bacteraemia and, thus, may be routinely used in clinical practice.</p

A Holistic Landscape Description Reveals That Landscape Configuration Changes More over Time than Composition: Implications for Landscape Ecology Studies

International audienceBackground: Space-for-time substitution—that is, the assumption that spatial variations of a system can explain and predict the effect of temporal variations—is widely used in ecology. However, it is questionable whether it can validly be used to explain changes in biodiversity over time in response to land-cover changes.Hypothesis: ere, we hypothesize that different temporal vs spatial trajectories of landscape composition and configuration may limit space-for-time substitution in landscape ecology. Land-cover conversion changes not just the surface areas given over to particular types of land cover, but also affects isolation, patch size and heterogeneity. This means that a small change in land cover over time may have only minor repercussions on landscape composition but potentially major consequences for landscape configuration.Methods: sing land-cover maps of the Paris region for 1982 and 2003, we made a holistic description of the landscape disentangling landscape composition from configuration. After controlling for spatial variations, we analyzed and compared the amplitudes of changes in landscape composition and configuration over time.Results: For comparable spatial variations, landscape configuration varied more than twice as much as composition over time. Temporal changes in composition and configuration were not always spatially matched.Significance: The fact that landscape composition and configuration do not vary equally in space and time calls into question the use of space-for-time substitution in landscape ecology studies. The instability of landscapes over time appears to be attributable to configurational changes in the main. This may go some way to explaining why the landscape variables that account for changes over time in biodiversity are not the same ones that account for the spatial distribution of biodiversity

Carnivore Translocations and Conservation: Insights from Population Models and Field Data for Fishers (Martes pennanti)

Translocations are frequently used to restore extirpated carnivore populations. Understanding the factors that influence translocation success is important because carnivore translocations can be time consuming, expensive, and controversial. Using population viability software, we modeled reintroductions of the fisher, a candidate for endangered or threatened status in the Pacific states of the US. Our model predicts that the most important factor influencing successful re-establishment of a fisher population is the number of adult females reintroduced (provided some males are also released). Data from 38 translocations of fishers in North America, including 30 reintroductions, 5 augmentations and 3 introductions, show that the number of females released was, indeed, a good predictor of success but that the number of males released, geographic region and proximity of the source population to the release site were also important predictors. The contradiction between model and data regarding males may relate to the assumption in the model that all males are equally good breeders. We hypothesize that many males may need to be released to insure a sufficient number of good breeders are included, probably large males. Seventy-seven percent of reintroductions with known outcomes (success or failure) succeeded; all 5 augmentations succeeded; but none of the 3 introductions succeeded. Reintroductions were instrumental in reestablishing fisher populations within their historical range and expanding the range from its most-contracted state (43% of the historical range) to its current state (68% of the historical range). To increase the likelihood of translocation success, we recommend that managers: 1) release as many fishers as possible, 2) release more females than males (55–60% females) when possible, 3) release as many adults as possible, especially large males, 4) release fishers from a nearby source population, 5) conduct a formal feasibility assessment, and 6) develop a comprehensive implementation plan that includes an active monitoring program

Lysogeny with Shiga Toxin 2-Encoding Bacteriophages Represses Type III Secretion in Enterohemorrhagic Escherichia coli

Lytic or lysogenic infections by bacteriophages drive the evolution of enteric bacteria. Enterohemorrhagic Escherichia coli (EHEC) have recently emerged as a significant zoonotic infection of humans with the main serotypes carried by ruminants. Typical EHEC strains are defined by the expression of a type III secretion (T3S) system, the production of Shiga toxins (Stx) and association with specific clinical symptoms. The genes for Stx are present on lambdoid bacteriophages integrated into the E. coli genome. Phage type (PT) 21/28 is the most prevalent strain type linked with human EHEC infections in the United Kingdom and is more likely to be associated with cattle shedding high levels of the organism than PT32 strains. In this study we have demonstrated that the majority (90%) of PT 21/28 strains contain both Stx2 and Stx2c phages, irrespective of source. This is in contrast to PT 32 strains for which only a minority of strains contain both Stx2 and 2c phages (28%). PT21/28 strains had a lower median level of T3S compared to PT32 strains and so the relationship between Stx phage lysogeny and T3S was investigated. Deletion of Stx2 phages from EHEC strains increased the level of T3S whereas lysogeny decreased T3S. This regulation was confirmed in an E. coli K12 background transduced with a marked Stx2 phage followed by measurement of a T3S reporter controlled by induced levels of the LEE-encoded regulator (Ler). The presence of an integrated Stx2 phage was shown to repress Ler induction of LEE1 and this regulation involved the CII phage regulator. This repression could be relieved by ectopic expression of a cognate CI regulator. A model is proposed in which Stx2-encoding bacteriophages regulate T3S to co-ordinate epithelial cell colonisation that is promoted by Stx and secreted effector proteins

Modes of Gene Duplication Contribute Differently to Genetic Novelty and Redundancy, but Show Parallels across Divergent Angiosperms

BACKGROUND: Both single gene and whole genome duplications (WGD) have recurred in angiosperm evolution. However, the evolutionary effects of different modes of gene duplication, especially regarding their contributions to genetic novelty or redundancy, have been inadequately explored. RESULTS: In Arabidopsis thaliana and Oryza sativa (rice), species that deeply sample botanical diversity and for which expression data are available from a wide range of tissues and physiological conditions, we have compared expression divergence between genes duplicated by six different mechanisms (WGD, tandem, proximal, DNA based transposed, retrotransposed and dispersed), and between positional orthologs. Both neo-functionalization and genetic redundancy appear to contribute to retention of duplicate genes. Genes resulting from WGD and tandem duplications diverge slowest in both coding sequences and gene expression, and contribute most to genetic redundancy, while other duplication modes contribute more to evolutionary novelty. WGD duplicates may more frequently be retained due to dosage amplification, while inferred transposon mediated gene duplications tend to reduce gene expression levels. The extent of expression divergence between duplicates is discernibly related to duplication modes, different WGD events, amino acid divergence, and putatively neutral divergence (time), but the contribution of each factor is heterogeneous among duplication modes. Gene loss may retard inter-species expression divergence. Members of different gene families may have non-random patterns of origin that are similar in Arabidopsis and rice, suggesting the action of pan-taxon principles of molecular evolution. CONCLUSION: Gene duplication modes differ in contribution to genetic novelty and redundancy, but show some parallels in taxa separated by hundreds of millions of years of evolution

Evolution of a New Function by Degenerative Mutation in Cephalochordate Steroid Receptors

Gene duplication is the predominant mechanism for the evolution of new genes. Major existing models of this process assume that duplicate genes are redundant; degenerative mutations in one copy can therefore accumulate close to neutrally, usually leading to loss from the genome. When gene products dimerize or interact with other molecules for their functions, however, degenerative mutations in one copy may produce repressor alleles that inhibit the function of the other and are therefore exposed to selection. Here, we describe the evolution of a duplicate repressor by simple degenerative mutations in the steroid hormone receptors (SRs), a biologically crucial vertebrate gene family. We isolated and characterized the SRs of the cephalochordate Branchiostoma floridae, which diverged from other chordates just after duplication of the ancestral SR. The B. floridae genome contains two SRs: BfER, an ortholog of the vertebrate estrogen receptors, and BfSR, an ortholog of the vertebrate receptors for androgens, progestins, and corticosteroids. BfSR is specifically activated by estrogens and recognizes estrogen response elements (EREs) in DNA; BfER does not activate transcription in response to steroid hormones but binds EREs, where it competitively represses BfSR. The two genes are partially coexpressed, particularly in ovary and testis, suggesting an ancient role in germ cell development. These results corroborate previous findings that the ancestral steroid receptor was estrogen-sensitive and indicate that, after duplication, BfSR retained the ancestral function, while BfER evolved the capacity to negatively regulate BfSR. Either of two historical mutations that occurred during BfER evolution is sufficient to generate a competitive repressor. Our findings suggest that after duplication of genes whose functions depend on specific molecular interactions, high-probability degenerative mutations can yield novel functions, which are then exposed to positive or negative selection; in either case, the probability of neofunctionalization relative to gene loss is increased compared to existing models

The Advancement of Biomaterials in Regulating Stem Cell Fate.

Stem cells are well-known to have prominent roles in tissue engineering applications. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can differentiate into every cell type in the body while adult stem cells such as mesenchymal stem cells (MSCs) can be isolated from various sources. Nevertheless, an utmost limitation in harnessing stem cells for tissue engineering is the supply of cells. The advances in biomaterial technology allows the establishment of ex vivo expansion systems to overcome this bottleneck. The progress of various scaffold fabrication could direct stem cell fate decisions including cell proliferation and differentiation into specific lineages in vitro. Stem cell biology and biomaterial technology promote synergistic effect on stem cell-based regenerative therapies. Therefore, understanding the interaction of stem cell and biomaterials would allow the designation of new biomaterials for future clinical therapeutic applications for tissue regeneration. This review focuses mainly on the advances of natural and synthetic biomaterials in regulating stem cell fate decisions. We have also briefly discussed how biological and biophysical properties of biomaterials including wettability, chemical functionality, biodegradability and stiffness play their roles