bluuebunny/crossref_metadata_2025 huggingface dataset:
Cognitive closure and risk sensitivity in the fear of crime
Authors: Jackson Jonathan
Published: October 2013

Purpose

This study was designed to answer two questions. First, does the risk sensitivity model of worry about crime replicate in three European countries? Second, can the model be extended to include need for cognitive closure?

Method

A national probability survey in Italy, Bulgaria, and Lithuania measured worry about criminal victimization, risk perception, and need for cognitive closure. Additive and interactive relationships between latent constructs were tested using latent moderated structural equation modelling.

Results

First, perceived likelihood, control, and consequence were statistically significant additive predictors of worry about crime. Second, the association between subjective probability judgements and worry about crime was stronger among people who associated the uncertain event with serious personal consequences and among people who had a high need for cognitive closure. Third, need for cognitive closure was associated with greater perceived consequences of victimization, but not with different perceptions of the likelihood and controllability of personal victimization.

Conclusions

This study provides empirical support for an extended risk sensitivity model in three European countries. Findings suggest that risk perception involves multiple – and interacting – dimensions that constitute sensitivity to risk, as well as individual differences in knowledge construction, information judgement, and processing. Future work should address (1) whether probability judgements shift psychological distance to uncertain future outcomes, and (2) whether the effect of psychological distance on worry about crime is greater among people who construe the outcome to be severe in consequence and who desire definite knowledge and dislike uncertainty in their lives.
A polymorphism linked to RRAS,SCAF1,IRF3 and BCL2L12 genes is associated with cirrhosis in hepatitis C virus carriers
Authors: Real Luis M. , Caruz Antonio , Rivero‐Juarez Antonio , Soriano Vicente , Neukam Karin , Rivero Antonio , Cifuentes Celia , Mira José A. , Macías Juan , Pineda Juan A.
Published: October 2013

Background & Aims

Host genetic factors could play a primary role in determining risk for cirrhosis development in HCV‐infected patients. The aims of this study were to discover new genetic variants associated with this trait and to replicate some associations formerly reported.

Methods

Three hundred and thirty‐seven HCV carriers with available data about liver fibrosis status, who initiated treatment with pegylated interferon plus ribavirin, were included. Of them, 77 (22.85%) were cirrhotic. One hundred and forty‐four SNPs from 40 genes related to cholesterol metabolism/transport, sustained viral response to HCV therapy, liver fibrosis, or immune response, were genotyped in all samples. Plink software was used to perform univariate association analyses. The results obtained were adjusted by other parameters related to cirrhosis using multivariate logistic regression models.

Results

Only the SNP rs12104272, linked to RRAS, SCAF1, IRF3 and BCL2L12 genes, was associated with cirrhosis. It was observed a higher proportion of rs12104272 A allele carriers in the non‐cirrhotic group (60.63%) than in the cirrhotic group (38.15%) (adjusted OR = 0.36, 95% CI = 0.180‐0.746, P = 0.006). This effect was stronger in the background of rs12979860 CC genotype of IL28B (adjusted OR = 0.069, 95% CI = 0.014–0.349, P = 0.001).

Conclusion

The rs12104272 SNP could have clinical value to select those individuals at lower risk for cirrhosis development.
Matrix metalloproteinase‐10 expression is induced during hepatic injury and plays a fundamental role in liver tissue repair
Authors: Garcia‐Irigoyen Oihane , Carotti Simone , Latasa Maria U. , Uriarte Iker , Fernández‐Barrena Maite G. , Elizalde Maria , Urtasun Raquel , Vespasiani‐Gentilucci Umberto , Morini Sergio , Banales Jesús M. , Parks William C. , Rodriguez Jose A. , Orbe Josune , Prieto Jesús , Páramo Jose A. , Berasain Carmen , Ávila Matías A.
Published: October 2013

Background & Aims

Upon tissue injury, the liver mounts a potent reparative and regenerative response. A role for proteases, including serine and matrix metalloproteinases (MMPs), in this process is increasingly recognized. We have evaluated the expression and function of MMP10 (stromelysin‐2) in liver wound healing and regeneration.

Methods

The hepatic expression of MMP10 was examined in two murine models: liver regeneration after two‐thirds partial hepatectomy (PH) and bile duct ligation (BDL). MMP10 was detected in liver tissues by qPCR, western blotting and immunohistochemistry. The effect of growth factors and toll‐like receptor 4 (TLR4) agonists on MMP10 expression was studied in cultured parenchymal and biliary epithelial cells and macrophages respectively. The role of MMP10 was evaluated by comparing the response of Mmp10+/+ and Mmp10−/− mice to PH and BDL. The intrahepatic turnover of the extracellular matrix proteins fibrin (ogen) and fibronectin was examined.

Results

MMP10 mRNA was readily induced after PH and BDL. MMP10 protein was detected in hepatocytes, cholangiocytes and macrophages. In cultured liver epithelial cells, MMP10 expression was additively induced by transforming growth factor‐β and epidermal growth factor receptor ligands. TLR4 ligands also stimulated MMP10 expression in macrophages. Lack of MMP10 resulted in increased liver injury upon PH and BDL. Resolution of necrotic areas was impaired, and Mmp10−/− mice showed increased fibrogenesis and defective turnover of fibrin (ogen) and fibronectin.

Conclusions

MMP10 expression is induced during mouse liver injury and participates in the hepatic wound healing response. The profibrinolytic activity of MMP10 may be essential in this novel hepatoprotective role.
HBV clinical isolates expressing adefovir resistance mutations show similar tenofovir susceptibilities across genotypes B, C and D
Authors: Liu Yang , Miller Michael D. , Kitrinos Kathryn M.
Published: October 2013

Background & Aims

Hepatitis B virus (HBV) genotypes can influence clinical outcomes as well as response to antiviral therapy. This study evaluated the tenofovir (TFV) susceptibility of HBV genotype B, C and D clinical isolates with adefovir resistance‐associated mutations (ADV‐R).

Methods

Full‐length HBV isolates from patients infected with genotype B, C and D virus had rtA181T, rtA181V, rtN236T, rtA181T + rtN236T and rtA181V + rtN236T mutations introduced by site‐directed mutagenesis. Phenotypic analyses were performed in HepG2 cells and susceptibility to TFV and ADV were assessed.

Results

Clinical HBV isolates containing rtA181T, rtA181V or rtN236T as single mutants remained sensitive to TFV across genotypes B, C and D. Clinical isolates containing the rtA181T + rtN236T double mutant remained sensitive to TFV in genotype D but exhibited reduced susceptibility to TFV in genotypes B and C. Viruses containing the double mutant rtA181V + rtN236T in genotypes B and D exhibited reduced susceptibility to TFV with EC50 fold changes (FC) of 3.8 and 2.5, respectively, while genotype C viruses containing rtA181V + rtN236T either remained sensitive (FC = 1.3) or exhibited reduced susceptibility to TFV (FC = 2.9) depending on the isolate. All rtA181V + rtN236T isolates conferred reduced susceptibility to ADV (FC values 2.3–4.2).

Conclusions

Genotype B, C and D isolates with single ADV resistance mutations remained fully sensitive to TFV, while the double mutants rtA181T + rtN236T and rtA181V + rtN236T exhibited either no change or low‐level reduced susceptibility to TFV across genotypes. These results are consistent with the clinical efficacy observed with tenofovir disoproxil fumarate (TDF) treatment across all genotypes in vivo and the limited impact of ADV‐R mutations on TDF therapy.
HBsAg quantification for identification of liver disease in chronic hepatitis B virus carriers
Authors: Larsson Simon B. , Eilard Anders , Malmström Sebastian , Hannoun Charles , Dhillon Amar P. , Norkrans Gunnar , Lindh Magnus
Published: October 2013

Background & Aims

Quantification of hepatitis B surface antigen (HBsAg) has been proposed as a useful diagnostic marker for clinical staging (identification of inactive carrier state) and prognosis of chronic hepatitis B virus (HBV) infection. The aim of this study was to investigate the correlation between HBsAg levels in serum and histological liver damage in patients with chronic infection.

Methods

HBsAg levels in serum (by Abbott Architect) were related to HBV DNA, ALT and histological score (n = 160) and covalently closed circular DNA (cccDNA) (n = 84).

Results

HBsAg levels correlated with cccDNA, serum HBV DNA, ALT and high inflammation scores (P < 0.001). Among HBeAg‐negative patients, an HBsAg level below 3.0 log10 IU/ml identified minimal liver damage (normal ALT and mild inflammation) with a predictive value of 92% (alone) or 96% (in combination with HBV DNA <4.0 log10 copies/ml), whereas an HBsAg level above 3.5 log10 IU/ml identified severe inflammation with a predictive value of 16% (alone) or 33% (in combination with HBV DNA >5.0 log10 copies/ml).

Conclusions

HBsAg levels reflect clinical stage and liver disease, and a combined quantification of HBsAg and HBV DNA may improve clinical staging.
Interannual variability in the biochemical composition of newly hatched larvae of the spider crab Maja brachydactyla (Decapoda, Majidae)
Authors: Rotllant Guiomar , Simeó Carles G. , Guerao Guillermo , Sastre Marta , Cleary Daniel F. R. , Calado Ricardo , Estévez Alicia
Published: October 2013

The spider crab Maja brachydactyla is an important commercial species in Europe and supports intensive fisheries in the NE Atlantic. A field survey was performed to assess long‐term and consecutive interannual (2005–2010) variation of the biochemical composition of newly hatched larvae of M. brachydactyla. Larval biochemical profiles differed significantly among years, with pronounced differences being recorded in 2010. Differences among batches of newly hatched larvae were mainly explained by the contribution of triacylglycerols and, to a lesser degree, by protein and lipid content. The use of different nutrition indices is discussed. The biochemical composition of newly hatched larvae from M. brachydactyla was highly variable, even though surveyed broodstock was obtained from the same local population and was always sampled during the same season. The unpredictable biochemical profiles of newly hatched larvae may condition their survival and recruitment. This largely overlooked aspect of larval variability should be considered in future fisheries management strategies and captive production of marine organisms that still rely on wild seeds.
LONG HORIZONS, HIGH RISK AVERSION, AND ENDOGENOUS SPREADS
Authors: Guasoni Paolo , Muhle‐Karbe Johannes
Published: October 2013

For an investor with constant absolute risk aversion and a long horizon, who trades in a market with constant investment opportunities and small proportional transaction costs, we obtain explicitly the optimal investment policy, its implied welfare, liquidity premium, and trading volume. We identify these quantities as the limits of their isoelastic counterparts for high levels of risk aversion. The results are robust with respect to finite horizons, and extend to multiple uncorrelated risky assets. In this setting, we study a Stackelberg equilibrium, led by a risk‐neutral, monopolistic market maker who sets the spread as to maximize profits. The resulting endogenous spread depends on investment opportunities only, and is of the order of a few percentage points for realistic parameter values.
MEASURING DISTRIBUTION MODEL RISK
Authors: Breuer Thomas , Csiszár Imre
Published: October 2013

We propose to interpret distribution model risk as sensitivity of expected loss to changes in the risk factor distribution, and to measure the distribution model risk of a portfolio by the maximum expected loss over a set of plausible distributions defined in terms of some divergence from an estimated distribution. The divergence may be relative entropy or anotherf‐divergence or Bregman distance. We use the theory of minimizing convex integral functionals under moment constraints to give formulae for the calculation of distribution model risk and to explicitly determine the worst case distribution from the set of plausible distributions. We also evaluate related risk measures describing divergence preferences.
GENERAL INTENSITY SHAPES IN OPTIMAL LIQUIDATION
Authors: Guéant Olivier , Lehalle Charles‐Albert
Published: October 2013

The classical literature on optimal liquidation, rooted in Almgren–Chriss models, tackles the optimal liquidation problem using a trade‐off between market impact and price risk. It answers the general question of optimal scheduling but the very question of the actual way to proceed with liquidation is rarely dealt with. Our model, which incorporates both price risk and nonexecution risk, is an attempt to tackle this question using limit orders. The very general framework we propose to model liquidation with limit orders generalizes existing ones in two ways. We consider a risk‐averse agent, whereas the model of Bayraktar and Ludkovski only tackles the case of a risk‐neutral one. We consider very general functional forms for the execution process intensity, whereas Guéant, Lehalle and Fernandez‐Tapia are restricted to exponential intensity. Eventually, we link the execution cost function of Almgren–Chriss models to the intensity function in our model, providing then a way to see Almgren–Chriss models as a limit of ours.
A NEW LOOK AT SHORT‐TERM IMPLIED VOLATILITY IN ASSET PRICE MODELS WITH JUMPS
Authors: Mijatović Aleksandar , Tankov Peter
Published: October 2013

We analyze the behavior of the implied volatility smile for options close to expiry in the exponential Lévy class of asset price models with jumps. We introduce a new renormalization of the strike variable with the property that the implied volatility converges to a nonconstant limiting shape, which is a function of both the diffusion component of the process and the jump activity (Blumenthal–Getoor) index of the jump component. Our limiting implied volatility formula relates the jump activity of the underlying asset price process to the short‐end of the implied volatility surface and sheds new light on the difference between finite and infinite variation jumps from the viewpoint of option prices: in the latter, the wings of the limiting smile are determined by the jump activity indices of the positive and negative jumps, whereas in the former, the wings have a constant model‐independent slope. This result gives a theoretical justification for the preference of the infinite variation Lévy models over the finite variation ones in the calibration based on short‐maturity option prices.
Simple impact crater shape determination from shadows
Authors: Chappelow J. E.
Published: October 2013

Crater depths, often obtained from shadow measurements, have long been used for several purposes in planetary science. However, the usual method for obtaining depth from shadow length suffers from several drawbacks and limitations. Chappelow and Sharpton (2002) introduced a much improved shadow method, which has the advantages of giving some shape information (as well as depth), and is not limited to shadows that cross the crater bottom. However, it is not general, in that it only gives very approximate crater shape information, in terms of three special cases (parabolic, conical, or flat‐floored). Here, I present a completely generalized method, valid for any conic section shaped crater, and give a proof of concept and demonstration of its use, using Linne crater as a test case. In the process, I find that Linne is neither parabolic nor conical, and that it contains approximately 20 m of bottom fill, which forms a flat floor. I also conclude that the long‐used parabolic paradigm for the shapes of simple craters may need to be revised.
Subjectivity, Hygiene, and STI Prevention: A Normalization Paradox in the Cleanliness Practices of Female Sex Workers in Post‐Socialist China
Authors: Yu Yeon Jung
Published: October 2013

This article illuminates the principal mechanisms that increase the risk of STIs for female sex workers in China. It draws primarily on my 26 months of ethnographic fieldwork (2006–2009) in red‐light district neighborhoods in Haikou that have become centers of internal migration in post‐reform southern China. Chinese sex workers here challenge dominant representations of them as illegal, immoral, and unclean subordinates and understand themselves also as sacrificing, capable, and modern women. I show how the women's conflicted subjectivity, continuously shaped through social networks, affects their personal health decisions and, significantly, leads them to adopt clinically risky practices. I conclude by arguing that public health interventions in southern China in and around certain red‐light districts should take these conflicted subjectivities into account in working to improve sex workers’ health.
Asexual genome evolution in the apomictic Ranunculus auricomus complex: examining the effects of hybridization and mutation accumulation
Authors: Pellino Marco , Hojsgaard Diego , Schmutzer Thomas , Scholz Uwe , Hörandl Elvira , Vogel Heiko , Sharbel Timothy F.
Published: October 2013

Asexual lineages are thought to be prone to extinction because of deleterious mutation accumulation (Muller's ratchet). Here, we analyse genomic effects of hybridity, polyploidy and allelic divergence in apomictic plants, and identify loci under divergent selection among sexual/apomictic lineages. RNAseq was used to sequence the flower‐specific transcriptomes of five genotypes of the Ranunculus auricomus complex, representing three sexual and two apomictic reproductive biotypes. The five sequence libraries were pooled and de novo assembly performed, and the resultant assembly was used as a backbone for a subsequent alignment of each separate library. High‐quality single‐nucleotide (SNP) and insertion–deletion (indel) polymorphisms were mined from each library. Annotated genes for which open reading frames (ORF) could be determined were analysed for signatures of divergent versus stabilizing selection. A comparison between all genotypes supports the hypothesis of Pleistocene hybrid origin of both apomictic genotypes from R. carpaticola and R. cassubicifolius, with subsequent allelic divergence of apomictic lineages (Meselson effect). Pairwise comparisons of nonsynonymous (dN) to synonymous (dS) substitution rate ratios between apomictic and sexual genotypes for 1231 genes demonstrated similar distributions for all comparisons, although 324 genes demonstrated outlier (i.e. elevated) dN/dS ratios. Gene ontology analyses of these outliers revealed significant enrichment of genes associated with reproduction including meiosis and gametogenesis, following predictions of divergent selection between sexual and apomictic reproduction, although no significant signal of genome‐wide mutation accumulation could be identified. The results suggest that gene function should be considered in order to understand effects of mutation accumulation in asexual lineages.
Genetic assignment of recruits reveals short‐ and long‐distance larval dispersal in Pocillopora damicornis on the Great Barrier Reef
Authors: Torda G. , Lundgren P. , Willis B. L. , van Oppen M. J. H.
Published: October 2013

Understanding connectivity of coral populations among and within reefs over ecologically significant timescales is essential for developing evidence‐based management strategies, including the design of marineprotected areas. Here, we present the first assessment of contemporary connectivity among populations of two Molecular Operational Taxonomic Units (MOTUs) of the brooding coral Pocillopora damicornis. We used individual‐based genetic assignment methods to identify the proportions of philopatric and migrant larval recruits, settling over 12 months at sites around Lizard Island (northern Great Barrier Reef [GBR]) and over 24 months at sites around the Palms Islands (central GBR). Overall, we found spatially and temporally variable rates of self‐recruitment and dispersal, demonstrating the importance of variation in local physical characteristics in driving dispersal processes. Recruitment patterns and inferred dispersal distances differed between the two P. damicornis MOTUs, with type α recruits exhibiting predominantly philopatric recruitment, while the majority of type β recruits were either migrants from identified putative source populations or assumed migrants based on genetic exclusion from all known populations. While P. damicornis invests much energy into brooding clonal larvae, we found that only 15% and 7% of type α and type β recruits, respectively, were clones of sampled adult colonies or other recruits, challenging the hypothesis that reproduction is predominantly asexual in this species on the GBR. We explain high rates of self‐recruitment and low rates of clonality in these MOTUs by suggesting that locally retained larvae originate predominantly from spawned gametes, while brooded larvae are mainly vagabonds.
Nitrogen deposition alters plant–fungal relationships: linking belowground dynamics to aboveground vegetation change
Authors: Dean Sarah L. , Farrer Emily C. , Taylor D. Lee , Porras‐Alfaro Andrea , Suding Katharine N. , Sinsabaugh Robert L.
Published: October 2013

Nitrogen (N) deposition rates are increasing globally due to anthropogenic activities. Plant community responses to N are often attributed to altered competitive interactions between plants, but may also be a result of microbial responses to N, particularly root‐associated fungi (RAF), which are known to affect plant fitness. In response to N, Deschampsia cespitosa, a codominant plant in the alpine tundra at Niwot Ridge (CO), increases in abundance, while Geum rossii, its principal competitor, declines. Importantly, G. rossii declines with N even in the absence of its competitor. We examined whether contrasting host responses to N are associated with altered plant–fungal symbioses, and whether the effects of N are distinct from effects of altered plant competition on RAF, using 454 pyrosequencing. Host RAF communities were distinct (only 9.4% of OTUs overlapped). N increased RAF diversity in G. rossii, but decreased it in D. cespitosa. D. cespitosa RAF communities were more responsive to N than G. rossii RAF communities, perhaps indicating a flexible microbial community aids host adaptation to nutrient enrichment. Effects of removing D. cespitosa were distinct from effects of N on G. rossii RAF, and D. cespitosa presence reversed RAF diversity response to N. The most dominant G. rossii RAF order, Helotiales, was the most affected by N, declining from 83% to 60% of sequences, perhaps indicating a loss of mutualists under N enrichment. These results highlight the potential importance of belowground microbial dynamics in plant responses to N deposition.
Genetic signatures of natural selection in response to air pollution in red spruce (Picea rubens, Pinaceae)
Authors: Bashalkhanov Stanislav , Eckert Andrew J. , Rajora Om P.
Published: October 2013

One of the most important drivers of local adaptation for forest trees is climate. Coupled to these patterns, however, are human‐induced disturbances through habitat modification and pollution. The confounded effects of climate and disturbance have rarely been investigated with regard to selective pressure on forest trees. Here, we have developed and used a population genetic approach to search for signals of selection within a set of 36 candidate genes chosen for their putative effects on adaptation to climate and human‐induced air pollution within five populations of red spruce (Picea rubens Sarg.), distributed across its natural range and air pollution gradient in eastern North America. Specifically, we used FST outlier and environmental correlation analyses to highlight a set of seven single nucleotide polymorphisms (SNPs) that were overly correlated with climate and levels of sulphate pollution after correcting for the confounding effects of population history. Use of three age cohorts within each population allowed the effects of climate and pollution to be separated temporally, as climate‐related SNPs (n = 7) showed the strongest signals in the oldest cohort, while pollution‐related SNPs (n = 3) showed the strongest signals in the youngest cohorts. These results highlight the usefulness of population genetic scans for the identification of putatively nonneutral evolution within genomes of nonmodel forest tree species, but also highlight the need for the development and application of robust methodologies to deal with the inherent multivariate nature of the genetic and ecological data used in these types of analyses.
Tracing horizontal Wolbachia movements among bees (Anthophila): a combined approach using multilocus sequence typing data and host phylogeny
Authors: Gerth Michael , Röthe Juliane , Bleidorn Christoph
Published: October 2013

The endosymbiotic bacterium Wolbachia enhances its spread via vertical transmission by generating reproductive effects in its hosts, most notably cytoplasmic incompatibility (CI). Additionally, frequent interspecific horizontal transfer is evident from a lack of phylogenetic congruence between Wolbachia and its hosts. The mechanisms of this lateral transfer are largely unclear. To identify potential pathways of Wolbachia movements, we performed multilocus sequence typing of Wolbachia strains from bees (Anthophila). Using a host phylogeny and ecological data, we tested various models of horizontal endosymbiont transmission. In general, Wolbachia strains seem to be randomly distributed among bee hosts. Kleptoparasite‐host associations among bees as well as other ecological links could not be supported as sole basis for the spread of Wolbachia. However, cophylogenetic analyses and divergence time estimations suggest that Wolbachia may persist within a host lineage over considerable timescales and that strictly vertical transmission and subsequent random loss of infections across lineages may have had a greater impact on Wolbachia strain distribution than previously estimated. Although general conclusions about Wolbachia movements among arthropod hosts cannot be made, we present a framework by which precise assumptions about shared evolutionary histories of Wolbachia and a host taxon can be modelled and tested.
Comparison of population genetic patterns in two widespread freshwater mussels with contrasting life histories in western North America
Authors: Mock K. E. , Brim Box J. C. , Chong J. P. , Furnish J. , Howard J. K.
Published: October 2013

We investigate population genetic structuring in Margaritifera falcata, a freshwater mussel native to western North America, across the majority of its geographical range. We find shallow rangewide genetic structure, strong population‐level structuring and very low population diversity in this species, using both mitochondrial sequence and nuclear microsatellite data. We contrast these patterns with previous findings in another freshwater mussel species group (Anodonta californiensis/A. nuttalliana) occupying the same continental region and many of the same watersheds. We conclude that differences are likely caused by contrasting life history attributes between genera, particularly host fish requirements and hermaphroditism. Further, we demonstrate the occurrence of a ‘hotspot’ for genetic diversity in both groups of mussels, occurring in the vicinity of the lower Columbia River drainage. We suggest that stream hierarchy may be responsible for this pattern and may produce similar patterns in other widespread freshwater species.
Myosin Phosphatase Isoforms as Determinants of Smooth Muscle Contractile Function and Calcium Sensitivity of Force Production
Authors: Dippold Rachael P. , Fisher Steven A.
Published: October 2013

The dephosphorylation of myosin by the MP causes smooth muscle relaxation. MP is also a key target of signals that regulate vascular tone and thus blood flow and pressure. Here, we review studies from the past two decades that support the hypothesis that the regulated expression of MP subunits is a critical determinant of smooth muscle responses to constrictor and dilator signals. In particular, the highly regulated splicing of the regulatory subunit Mypt1 Exon 24 is proposed to tune sensitivity to NO/cGMP‐mediated relaxation. The regulated transcription of the MP inhibitory subunit CPI‐17 is proposed to determine sensitivity to agonist‐mediated constriction. The expression of these subunits is specific in the microcirculation and varies in developmental and disease contexts. To date, the relationship between MP subunit expression and vascular function in these different contexts is correlative; confirmation of the hypothesis will require the generation of genetically engineered mice to test the role of MP subunits and their isoforms in the specificity of vascular smooth muscle responses to constrictor and dilator signals.
Structure–function studies of Escherichia coli RnlA reveal a novel toxin structure involved in bacteriophage resistance
Authors: Wei Yong , Gao Zeng‐Qiang , Otsuka Yuichi , Naka Kenta , Yonesaki Tetsuro , Zhang Heng , Dong Yu‐Hui
Published: October 2013

Escherichia coli RnlA–RnlB is a newly identified toxin–antitoxin (TA) system that plays a role in bacteriophage resistance. RnlA functions as a toxin with mRNA endoribonuclease activity and the cognate antitoxin RnlB inhibits RnlA toxicity in E. coli cells. Interestingly, T4 phage encodes the antitoxin Dmd, which acts against RnlA to promote its own propagation, suggesting that RnlA‐Dmd represents a novel TA system. Here, we have determined the crystal structure of RnlA refined to 2.10 Å. RnlA is composed of three independent domains: NTD (N‐terminal domain), NRD (N repeated domain) and DBD (Dmd‐binding domain), which is an organization not previously observed among known toxin structures. Small‐angle X‐ray scattering (SAXS) analysis revealed that RnlA forms a dimer in solution via interactions between the DBDs from both monomers. The in vitro and in vivo functional studies showed that among the three domains, only the DBD is responsible for recognition and inhibition by Dmd and subcellular location of RnlA. In particular, the helix located at the C‐terminus of DBD plays a vital role in binding Dmd. Our comprehensive studies reveal the key region responsible for RnlA toxicity and provide novel insights into its structure–function relationship.
The ADP‐glucose pyrophosphorylase from Streptococcus mutans provides evidence for the regulation of polysaccharide biosynthesis in Firmicutes
Authors: Asención Diez Matías D. , Demonte Ana M. , Guerrero Sergio A. , Ballicora Miguel A. , Iglesias Alberto A.
Published: October 2013

Streptococcus mutans is the leading cause of dental caries worldwide. The bacterium accumulates a glycogen‐like internal polysaccharide, which mainly contributes to its carionegic capacity. S. mutans has two genes (glgC and glgD) respectively encoding putative ADP‐glucose pyrophosphorylases (ADP‐Glc PPase), a key enzyme for glycogen synthesis in most bacteria. Herein, we report the molecular cloning and recombinant expression of both genes (separately or together) followed by the characterization of the respective enzymes. When expressed individually GlgC had ADP‐Glc PPase activity, whereas GlgD was inactive. Interestingly, the coexpressed GlgC/GlgD protein was one order of magnitude more active than GlgC alone. Kinetic characterization of GlgC and GlgC/GlgD pointed out remarkable differences between them. Fructose‐1,6‐bis‐phosphate activated GlgC by twofold, but had no effect on GlgC/GlgD. Conversely, phospho‐enol‐pyruvate and inorganic salts inhibited GlgC/GlgD without affecting GlgC. However, in the presence of fructose‐1,6‐bis‐phosphate GlgC acquired a GlgC/GlgD‐like behaviour, becoming sensitive to the stated inhibitors. Results indicate that S. mutans ADP‐Glc PPase is an allosteric regulatory enzyme exhibiting sensitivity to modulation by key intermediates of carbohydrates metabolism in the cell. The particular regulatory properties of the S. mutans enzyme agree with phylogenetic analysis, where GlgC and GlgD proteins found in other Firmicutes arrange in distinctive clusters.
Knowledge Spillovers, Search, and Creation in China's Emerging Market
Authors: Li Haiyang , Zhang Yan (Anthea) , Lyles Marjorie
Published: October 2013

Prior research and the articles included in this special issue demonstrate that in emerging markets in general and in China in particular, knowledge spillovers exist between foreign firms and domestic firms. As domestic markets become more sophisticated, and competition between domestic firms and foreign firms becomes stronger, knowledge is flowing to and being sourced in many different directions: from overseas head offices to foreign firms then on to domestic firms; from domestic firms to domestic firms; and from domestic firms to foreign firms, and back to the multinational corporations' head offices in the form of reverse spillovers and reverse innovation. We propose that knowledge spillovers, search, and creation in an emerging market are a dynamic and reciprocal process with knowledge flowing between and among foreign and domestic firms. This represents a fertile field for future research and we have identified a number of areas ripe for study.
External Knowledge Search Strategies in China's Technology Ventures: The Role of Managerial Interpretations and Ties
Authors: Liu Jingjiang , Chen Lu , Kittilaksanawong Wiboon
Published: October 2013

Drawing on the threat-rigidity hypothesis, we examine how managerial opportunity and threat interpretations of external environments affect a technology venture's choice of external knowledge search strategies in an emerging market. Results from a sample of 141 technology ventures in China reveal that opportunity interpretation directly and positively influences both the breadth and depth of external search, whereas threat interpretation directly and negatively influences only external search depth. Furthermore, managerial ties strengthen the positive relationship between opportunity interpretation and external search breadth but weaken the positive relationship on external search depth. Managerial ties weaken the negative relationship between threat interpretation and external search breadth but strengthen the negative relationship on external search depth. Implications for both research and practice are offered.
Loss of FUBP1 expression in gliomas predicts FUBP1 mutation and is associated with oligodendroglial differentiation, IDH1 mutation and 1p/19q loss of heterozygosity
Authors: Baumgarten P. , Harter P. N. , Tönjes M. , Capper D. , Blank A.‐E. , Sahm F. , von Deimling A. , Kolluru V. , Schwamb B. , Rabenhorst U. , Starzetz T. , Kögel D. , Rieker R. J. , Plate K. H. , Ohgaki H. , Radlwimmer B. , Zörnig M. , Mittelbronn M.
Published: October 2013

Aims

The Far Upstream Element [FUSE] Binding Protein 1 (FUBP1) regulates target genes, such as the cell cycle regulators MYC and p21. FUBP1 is up‐regulated in many tumours and acts as an oncoprotein by stimulating proliferation and inhibiting apoptosis. Recently, FUBP1 mutations were identified in approximately 15% of oligodendrogliomas. To date, all reported FUBP1 mutations have been predicted to inactivate FUBP1, which suggests that in contrast to most other tumours FUBP1 may act as a tumour suppressor in oligodendrogliomas.

Methods

As no data are currently available concerning FUBP1 protein levels in gliomas, we examined the FUBP1 expression profiles of human glial tumours by immunohistochemistry and immunofluorescence. We analysed FUBP1 expression related to morphological differentiation, IDH1 and FUBP1 mutation status, 1p/19q loss of heterozygosity (LOH) as well as proliferation rate.

Results

Our findings demonstrate that FUBP1 expression levels are increased in all glioma subtypes as compared with normal central nervous system (CNS) control tissue and are associated with increased proliferation. In contrast, FUBP1 immunonegativity predicted FUBP1 mutation with a sensitivity of 100% and a specificity of 90% in our cohort and was associated with oligodendroglial differentiation, IDH1 mutation and 1p/19q loss of heterozygosity (LOH). Using this approach, we detected a to‐date undescribed FUBP1 mutation in an oligodendroglioma.

Conclusion

In summary, our data indicate an association between of FUBP1 expression and proliferation in gliomas. Furthermore, our findings present FUBP1 immunohistochemical analysis as a helpful additional tool for neuropathological glioma diagnostics predicting FUBP1 mutation.
Possible involvement of cathepsin B/D and caspase‐3 in deferoxamine‐related neuroprotection of early brain injury after subarachnoid haemorrhage in rats
Authors: Yu Z‐Q. , Jia Y. , Chen G.
Published: October 2013

Aims

Deferoxamine (DFX) has recently been shown to have a neuroprotective effect in animal models of subarachnoid haemorrhage (SAH). However, the precise mechanisms underlying these effects remain unclear. Our previous studies found that iron overload in lysosomes leads to lysosomal membrane damage and rupture, and then induces cell apoptosis in the oxidative stress conditions in vitro. We therefore analysed the time‐course of the two of major lysosomal cathepsins (cathepsin B/D) and caspase‐3 expression in brain and evaluated how DFX might affect these proteins and the parameters concerning early brain injury (EBI) after SAH.

Methods

We investigated the time‐course of cathepsin B/D and caspase‐3 expression in the cortex after SAH in rats. Furthermore, we assessed the effect of DFX on regulation of cathepsin B/D and caspase‐3 and EBI following SAH. All SAH animals were subjected to a single injection of autologous blood into the prechiasmatic cistern. Protein concentrations were measured using Western blot analysis and immunohistochemistry. The extent of brain oedema was measured using the wet/dry method. Blood–brain barrier (BBB) permeability was assessed using IgG extravasation. Cortical apoptosis was examined using terminal deoxynucleotidyl transferase‐mediated dUTP nick end labelling (TUNEL).

Results

Cathepsin B/D and caspase‐3 were up‐regulated in the cortices of affected rats after SAH. Levels of both peaked at 48‐h post‐SAH. After intraperitoneal DFX administration, the elevated expression of cathepsin B/D and caspase‐3 was down‐regulated in the cortex 48 h after blood injection. In the DFX‐treated group, early brain damage events, such as brain oedema, BBB impairment, cortical apoptosis, and alterations in clinical behaviour were significantly ameliorated relative to vehicle‐treated SAH rats.

Conclusions

These results suggest that the lysosomal membrane may be damaged after SAH, which leads to the release of proteases (cathepsin B/D) and activates the apoptotic pathway. Iron overload may be one key mechanism underlying SAH‐induced oxidative stress and DFX may protect the lysosomal membrane, inhibit the release of cathepsin B/D, and ameliorate EBI by suppressing iron overload in the acute phase of SAH.
Patterns of microglial cell activation in frontotemporal lobar degeneration
Authors: Lant Suzannah B. , Robinson Andrew C. , Thompson Jennifer C. , Rollinson Sara , Pickering‐Brown Stuart , Snowden Julie S. , Davidson Yvonne S. , Gerhard Alexander , Mann David M. A.
Published: October 2013

Aims

Pathological heterogeneity within patients with frontotemporal lobar degeneration (FTLD) in general precludes the accurate assignment of diagnostic subtype in life. The aim of this study was to assess the extent of microglial cell activation in FTLD in order to determine whether it might be possible to employ this as a diagnostic marker in vivo using PET ligand [11C](R)‐PK11195 in order to differentiate cases of FTLD according to histological subtype.

Methods

The distribution and extent of microglial cell activation was assessed semi‐quantitatively in cortical grey and subcortical white matter of CD68 immunostained sections of frontal and temporal cortex from 78 pathologically confirmed cases of FTLD, 13 of Alzheimer's disease (AD) and 13 controls.

Results

Significantly higher levels of microglial cell activation than controls occurred in all four regions in FTLD, and in three of the four regions in AD. Microglial activation was greater in frontal subcortical white matter in FTLD than AD, whereas it was higher in temporal cortical grey matter in AD than FTLD. Microglial cell activation was significantly higher in temporal subcortical white matter in FTLD‐MAPT than in other genetic (GRN, C9ORF72) or non‐genetic forms of FTLD.

Conclusions

The present study suggests that high levels of microglial cell involvement in temporal lobe (subcortical white matter) might serve as a marker of inherited FTLD associated with intronic mutations in MAPT, with a relatively intense signal in this region in PET studies using [11C](R)‐PK11195 as microglial cell marker could indicate the presence of MAPT mutation in vivo.
Nutritional status of haemodialysis patients: Comparison of Australian cohorts of Aboriginal and European descent
Authors: Todd Alwyn , Carroll Robert , Gallagher Meghan , Meade Anthony
Published: October 2013

Aim

It is not known whether nutritional status differs between Australian Aboriginal and non Aboriginal haemodialysis subjects. The aim of this study was to investigate the nutritional status of Australian Aboriginal and non‐Aboriginal haemodialysis subjects at satellite dialysis centres.

Method

Seventy‐six (25 Aboriginal, 51 non‐Aboriginal) prevalent haemodialysis patients were enrolled in a 3‐month cross‐sectional study. Each month anthropometric and biochemical measurements were collected. Nutritional status (diet history, patient‐generated subjective global assessment (PG‐SGA), handgrip strength) was assessed by a dietitian.

Results

PG‐SGA detected mild to moderate malnutrition in 35% of Aboriginal patients and 25% of non‐Aboriginal patients. The overall physical rating on the PG‐SGA was significantly higher in Aboriginal patients, indicating the presence of a greater deficit in muscle mass in this population. Inter‐dialytic weight gain was significantly greater in Aboriginal subjects (median [range] 3.0 [2.1–5.7] vs 2.5 [−0.3–5.0] kg, P < 0.001). Glucose and HbA1c were significantly higher in Aboriginal subjects with diabetes than in non‐Aboriginal patients with diabetes (median [range] 9.4 [4.9–23.4] vs 5.7 [3.1–12.9], P = 0.002; 7.0 [5.2–11.0] vs 5.8 [4.6–9.0], P < 0.000; respectively). These findings occurred in the setting of each cohort having adequate dialysis parameters (median Kt/V of >1.6 and median normalized protein catabolic rate 1.5). Difficulties were encountered in obtaining dietary information from Aboriginal subjects using the diet history method.

Conclusion

Subjects had acceptable parameters of dialysis adequacy; however, 35% had evidence of malnutrition. Further research should focus on establishing a knowledge base for the nutritional management for Aboriginal dialysis subjects, and the development of a validated individual dietary assessment method for use in this population group.
Families' needs of critical care Muslim patients in Saudi Arabia: a quantitative study
Authors: Al‐Mutair Abbas Saleh , Plummer Virginia , Clerehan Rosemary , O'Brien Anthony (Tony)
Published: October 2013

Aim

To identify the needs of families of adult intensive care unit (ICU) patients in Saudi Arabia as perceived by family members and health care providers.

Background

Family members of critically ill patients are likely to have specific needs that should be addressed by the critical care team and which, if unmet, may produce stress for patients' families and health care providers. The literature has yet to identify the needs of Muslim families in relation to religious beliefs and cultural values in critical care settings in Saudi Arabia.

Design

A cross‐sectional survey design.

Method

A total of 176 family members and 497 intensive health care providers were recruited from eight adult mixed medical‐surgical ICUs between November 2011 and February 2012 utilizing a four‐point Likert type scale self‐administered questionnaire.

Results

The findings revealed that family members and health care providers ranked assurance, information and cultural and spiritual needs as the most important, and support and proximity as least important. There were significant differences in the mean values found between family members and health care providers. A significant finding not identified in other studies was ‘The need to have the health care providers handle the body of the dead Muslim with extreme caution and respect’ which, under the dimension of cultural and spiritual needs, was perceived by family members to be the most important and by the health care providers as the fifth most important need.

Conclusion

The recognition of family needs in the critical care unit informed the development of interventions to meet family needs and improve the care quality.
How much time do nurses need to write an ICU diary?
Authors: Nydahl Peter , Bäckman Carl G , Bereuther Johannes , Thelen Michael
Published: October 2013

Background

Diaries in the Intensive Care Unit (ICU) support patients and relatives during and after a stay on the ICU. Barriers to implementation of the ICU diary are workload, unwanted closeness to patients and lack of time.

Aims and objectives

The purpose of the study was to evaluate the time nurses consume writing an ICU diary. Further questions were to examine whether the first diary entry, which includes a more detailed description about the admission, consumes more time than other entries and whether the time taken depends on experience or workload of the nurses.

Design

Quantitative, prospective, international observational multicentre study in four ICUs within the international diary network in Germany (two ICUs), Sweden and Switzerland (one ICU each).

Method

During a 6‐month period in 2012/2013 nurses measured the time they consumed writing a diary in minutes and seconds, the number of diaries they contributed to and total number of diary entries, the nurse‐patient ratio, their level of experience in writing diaries, interruptions while writing in a diary and additional information like photographs or follow‐up visits.

Results

In summary 29 diaries were collected which included 195 written entries. The first entry needed significantly more time than following entries (first entry: mean 13:33 min versus following entries: mean 5:31, p < 0·001). The mean time for following entries differed significantly between the countries: Switzerland: 6:14, Sweden 5:31 and Germany 3:36 (p < 0·001). Nurses with more experience used more time to write a diary (not significant). With increasing nurse‐patient‐ratio the time decreased for following entries (ratio 1:1: mean 5:42, ratio 1:2: mean 5:27, ratio 1:3: mean 3:12, p = 0·007).

Conclusion

Writing a diary for patients and relatives means an additional amount of time and workload, but according to the increased quality of nursing the time seems to be feasible for implementation. The measured time was self‐reported, thus including possible bias for the results.