New approaches to the study of sepsis

Models of sepsis have been instructive in understanding the sequence of events in animals and, to an extent, in humans with sepsis. Events developing early in sepsis suggest that a hyperinflammatory state exists, accompanied by a buildup of oxidants in tissues reflective of a redox imbalance. Development of immunosuppression and degraded innate and adaptive immune responses are well‐established complications of sepsis. In addition, there is robust activation of the complement system, which contributes to the harmful effects of sepsis. These events appear to be associated with development of multiorgan failure. The relevance of animal models of sepsis to human sepsis and the failure of human clinical trials are discussed, together with suggestions as to how clinical trial design might be improved. Currently there is no FDA‐approved drug for use in sepsis. This Review discusses the relevance of animal models to human sepsis and the failure of human clinical trials and provides suggestions as to how clinical trial design might be improved.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94452/1/1234_ftp.pd

Evolution of superconductivity in K2-xFe4+ySe5: Spectroscopic studies of X-ray absorption and emission.

This study investigates the evolution of superconductivity in K2-xFe4+ySe5 using temperature-dependent X-ray absorption and resonant inelastic X-ray scattering techniques. Magnetization measurements show that polycrystalline superconducting (SC) K1.9Fe4.2Se5 has a critical temperature (T c) of ∼31 K with a varying superconducting volume fraction, which strongly depends on its synthesis temperature. An increase in Fe-structural/vacancy disorder in SC samples with more Fe atoms occupying vacant 4d sites is found to be closely related to the decrease in the spin magnetic moment of Fe. Moreover, the nearest-neighbor Fe-Se bond length in SC samples exceeds that in the non-SC (NS) sample, K2Fe4Se5, which indicates a weaker hybridization between the Fe 3d and Se 4p states in SC samples. These results clearly demonstrate the correlations among the local electronic and atomic structures and the magnetic properties of K2-xFe4+ySe5 superconductors, providing deeper insight into the electron pairing mechanisms of superconductivity

Supersymmetry enhancement by monopole operators

We describe a method which allows one to study hidden symmetries in a large class of strongly coupled supersymmetric gauge theories in three dimensions. We apply this method to the ABJM theory and to the infrared limit of N=4 SQCD with adjoint and fundamental matter. We show that the U(N) ABJM model with Chern-Simons level k=1 or k=2 has hidden N=8 supersymmetry. Hidden supersymmetry is also shown to occur in N=4 d=3 SQCD with one fundamental and one adjoint hypermultiplet. The latter theory, as well as the U(N) ABJM theory at k=1, are shown to have a decoupled free sector. This provides evidence that both models are dual to the infrared limit of N=8 U(N) super-Yang-Mills theory.Comment: 29 pages, late

Cloning and expression analysis of two distinct HIF-alpha isoforms – gcHIF-1alpha and gcHIF-4alpha – from the hypoxia-tolerant grass carp, Ctenopharyngodon idellus

BACKGROUND: Hypoxia-inducible factors (HIFs) are involved in adaptive and survival responses to hypoxic stress in mammals. In fish, very little is known about the functions of HIFs. RESULTS: We have cloned and characterized two distinct HIF-alpha cDNAs – gcHIF-1alpha and gcHIF-4alpha – from the hypoxia-tolerant grass carp. The deduced gcHIF-1alpha protein is highly similar to the HIF-1alphas (57–68%) from various vertebrate species, while gcHIF-4alpha is a novel isoform, and shows an equivalent degree of amino acid identity (41–47%) to the HIF-1alpha, HIF-2alpha and HIF-3alpha proteins so far described. Parsimony analysis indicated that gcHIF-4alpha is most closely related to the HIF-3alpha proteins. Northern blot analysis showed that mRNA levels of gcHIF-1alpha and gcHIF-4alpha differ substantially under normoxic and hypoxic conditions, while Western blot studies demonstrated that the endogenous protein levels for both gcHIF-1alpha and gcHIF-4alpha are similarly responsive to hypoxia. Our findings suggest that both gcHIF-1alpha and gcHIF-4alpha are differentially regulated at the transcriptional and translational levels. HRE-luciferase reporter assays show that both proteins function as transcription activators and play distinct roles in modulating the hypoxic response in grass carp. CONCLUSION: There are at least two distinct HIF-alpha isoforms – gcHIF-1alpha and gcHIF-4alpha – in the hypoxia-tolerant grass carp, which are differentially expressed and regulated in different fish organs in response to hypoxic stress. Overall, the results suggest that unique molecular mechanisms operate through these two HIF-alpha isoforms, which underpin the hypoxic response in the hypoxia-tolerant grass carp

Predominance of pHK01-like incompatibility group FII plasmids encoding CTX-M-14 among extended-spectrum beta-lactamase-producing Escherichia coli in Hong Kong, 1996-2008

This study assessed the temporal changes in the molecular epidemiology of bacteremic Escherichia coli isolates producing CTX-M-14 in Hong Kong. Blood isolates from 1996 to 1998 (period 1, n = 50) and 2007 to 2008 (period 2, n = 117) were investigated by molecular methods. CTX-M-type ESBL was carried by 98.2% (164/167) of the isolates. In both periods, the CTX-M-9 group and CTX-M-14 allele were the predominant ESBL type. The major clones were found to change from ST68 and ST405 in period 1 to ST131, ST69, and ST12 in period 2. Among 65 CTX-M-14-producing plasmids investigated further, 54 had the FII replicon. Replicon sequence typing and plasmid polymerase chain reaction-restriction fragment length polymorphism showed that 79.6% (43/54) of the FII plasmid subset was similar to the completely sequenced plasmid, pHK01 (human urine, Hong Kong, 2004). These pHK01-like plasmids were found to have spread to the major clones (ST68, ST405, and ST131) and multiple singleton isolates of all 4 phylogenetic groups. © 2012 Elsevier Inc.postprin

De novo sequencing and analysis of the American ginseng root transcriptome using a GS FLX Titanium platform to discover putative genes involved in ginsenoside biosynthesis

<p>Abstract</p> <p>Background</p> <p>American ginseng (<it>Panax quinquefolius </it>L.) is one of the most widely used herbal remedies in the world. Its major bioactive constituents are the triterpene saponins known as ginsenosides. However, little is known about ginsenoside biosynthesis in American ginseng, especially the late steps of the pathway.</p> <p>Results</p> <p>In this study, a one-quarter 454 sequencing run produced 209,747 high-quality reads with an average sequence length of 427 bases. <it>De novo </it>assembly generated 31,088 unique sequences containing 16,592 contigs and 14,496 singletons. About 93.1% of the high-quality reads were assembled into contigs with an average 8-fold coverage. A total of 21,684 (69.8%) unique sequences were annotated by a BLAST similarity search against four public sequence databases, and 4,097 of the unique sequences were assigned to specific metabolic pathways by the Kyoto Encyclopedia of Genes and Genomes. Based on the bioinformatic analysis described above, we found all of the known enzymes involved in ginsenoside backbone synthesis, starting from acetyl-CoA via the isoprenoid pathway. Additionally, a total of 150 cytochrome P450 (CYP450) and 235 glycosyltransferase unique sequences were found in the 454 cDNA library, some of which encode enzymes responsible for the conversion of the ginsenoside backbone into the various ginsenosides. Finally, one CYP450 and four UDP-glycosyltransferases were selected as the candidates most likely to be involved in ginsenoside biosynthesis through a methyl jasmonate (MeJA) inducibility experiment and tissue-specific expression pattern analysis based on a real-time PCR assay.</p> <p>Conclusions</p> <p>We demonstrated, with the assistance of the MeJA inducibility experiment and tissue-specific expression pattern analysis, that transcriptome analysis based on 454 pyrosequencing is a powerful tool for determining the genes encoding enzymes responsible for the biosynthesis of secondary metabolites in non-model plants. Additionally, the expressed sequence tags (ESTs) and unique sequences from this study provide an important resource for the scientific community that is interested in the molecular genetics and functional genomics of American ginseng.</p

Combinatorial RNA Design: Designability and Structure-Approximating Algorithm

In this work, we consider the Combinatorial RNA Design problem, a minimal instance of the RNA design problem which aims at finding a sequence that admits a given target as its unique base pair maximizing structure. We provide complete characterizations for the structures that can be designed using restricted alphabets. Under a classic four-letter alphabet, we provide a complete characterization of designable structures without unpaired bases. When unpaired bases are allowed, we provide partial characterizations for classes of designable/undesignable structures, and show that the class of designable structures is closed under the stutter operation. Membership of a given structure to any of the classes can be tested in linear time and, for positive instances, a solution can be found in linear time. Finally, we consider a structure-approximating version of the problem that allows to extend bands (helices) and, assuming that the input structure avoids two motifs, we provide a linear-time algorithm that produces a designable structure with at most twice more base pairs than the input structure.Comment: CPM - 26th Annual Symposium on Combinatorial Pattern Matching, Jun 2015, Ischia Island, Italy. LNCS, 201

Do rural migrants 'float' in urban China? Neighbouring and neighbourhood sentiment in Beijing

Urban China reached 50% of the nation’s population by 2010, mainly as a result of massive rural–urban migration. There is substantial evidence of their social marginality in terms of occupational and housing opportunities. Here we ask about their incorporation into the neighbourhoods where they live. Rural migrants are called the ‘floating population’ in China, suggesting that their residence in the city is only temporary and that they are unlikely to develop strong local ties. This study contrasts the neighbourhood socialising of migrant tenants with that of urban homeowners who were born in the city. It draws on original survey research in Beijing that included questions on relations with neighbours and neighbourhood sentiment. It is found that migrants are more likely to engage in socialising and exchange of help with neighbours, and consequently their neighbouring helps strengthen their sentiment towards the neighbourhoods where they live. It is argued that contemporary social changes – including rising education and homeownership – may actually reduce neighbouring, while rural migrants’ marginality makes them more dependent on their local social network