bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Novel Sigma Factor-Like Regulator RpoQ Controls Luminescence, Chitinase Activity, and Motility in Vibrio fischeri
Authors: Cao Xiaodan , Studer Sarah V. , Wassarman Karen , Zhang Yuanxing , Ruby Edward G. , Miyashiro Tim 
Published: January 2012

ABSTRACT

Vibrio fischeri
, the bacterial symbiont of the Hawaiian bobtail squid,
Euprymna scolopes
, uses quorum sensing to control genes involved in bioluminescence, host colonization, and other biological processes. Previous work has shown that AinS/R-directed quorum sensing also regulates the expression of
rpoQ
(
VF_A1015
), a gene annotated as an RpoS-like sigma factor. In this study, we demonstrate using phylogenetics that RpoQ is related to, but distinct from, the stationary-phase sigma factor RpoS. Overexpression of
rpoQ
results in elevated chitinase activity but decreased motility and luminescence, three activities associated with symbiosis. The reduction in bacterial luminescence associated with the overexpression of
rpoQ
occurs both in culture and within the light-emitting organ of the squid host. This suppression of bioluminescence is due to the repression of the
luxICDABEG
promoter. Our results highlight RpoQ as a novel regulatory component, embedded in the quorum-signaling network that controls several biological processes in
V. fischeri
.

IMPORTANCE
Quorum signaling is a widely occurring phenomenon that functions in diverse bacterial taxa. It is most often found associated with species that interact with animal or plant hosts, either as mutualists or pathogens, and controls the expression of genes critical to tissue colonization. We present the discovery of
rpoQ
, which encodes a new regulatory component in the quorum-signaling pathway of
Vibrio fischeri
. RpoQ is a novel protein in the RpoS family of stationary-phase sigma factors. Unlike many other regulatory proteins involved in the quorum-signaling pathways of the
Vibrionaceae
, the distribution of RpoQ appears to be restricted to only two closely related species. The role of this regulator is to enhance some quorum-signaling outputs (motility) while suppressing others (luminescence). We propose that RpoQ may be a recently evolved or acquired component in
V. fischeri
that provides this organism with an additional level of regulation to modulate its existing quorum-signaling pathway.
Colonization of geranium foliage by Clonostachys rosea f. catenulata, a biological control agent of botrytis grey mould
Authors: Chatterton S. , Punja Z.K. 
Published: January 2012

The ecological requirements for the colonization of geranium leaves by the biocontrol agent Clonostachys rosea f. catenulata strain J1446 were investigated. Although this biocontrol agent is a soil-inhabiting fungus, treatment of geranium foliage with the agent can reduce grey mould caused by Botrytis cinerea in the greenhouse. To characterize the extent of foliar colonization, a GUS-transformed isolate of C. rosea f. catenulata was applied to foliage of two geranium cultivars, Pelargonium × hortorum and Pelargonium × domesticum . Population levels of C. rosea f. catenulata were found to be highest on senescent leaves and stems, followed by fully expanded leaves, and lowest on newly emerged leaves of both cultivars. Optimum temperature for leaf and petiole colonization was 20–25 °C for both cultivars. The biocontrol agent required at least 12 h of continuous leaf wetness to achieve maximum population densities on the leaves and stems of both cultivars. On whole plants, colonization was significantly higher on wounded leaves, stems, and senescing leaves compared with that on nonwounded leaves, stems, and mature leaves, respectively. GUS staining indicated that the fungus preferentially colonized the wound sites of leaves and the cut portions of stems. Results indicate that this biocontrol agent can successfully colonize the foliage of geraniums, thus demonstrating the endophytic ability of C. rosea f. catenulata in both root and foliar tissues.
Biotic interactions experienced by a new invader: effects of its close relatives at the community scale
Authors: Hill Steven B. , Kotanen Peter M. 
Published: January 2012

The success of nonindigenous species may be influenced by biotic interactions during the initial stages of invasion. Here, we investigated whether a potential invader, Solidago virgaurea L., would experience more damage by natural enemies in communities dominated by close relatives than those without them; interactions with mutualistic mycorrhizae might partially counteract these effects. We monitored damage experienced by S. virgaurea planted into communities with native congeners and without close relatives. Community type was crossed with a vegetation removal treatment to assess the combined effects of herbivory and competition on survival. We also evaluated growth of S. virgaurea in a greenhouse experiment where seedlings were exposed to soil biota sampled from these communities and compared with sterile controls. Overall, community type did not affect levels of herbivory or plant survival. Removal of surrounding vegetation resulted in reduced damage and increased survival; these effects were largest in grass-dominated communities. Soil sterilization reduced root growth and tended to reduce shoot growth, especially when compared with plants inoculated with biota collected near congeners. Overall, our results suggest that the presence of close relatives is unlikely to make old-field communities more resistant to invasion by S. virgaurea; instead, soil biota might facilitate growth in communities dominated by close relatives.
Evidence of sex change inIlex integra
Authors: Takagi Etsuro , Togashi Katsumi 
Published: January 2012

Sex change has been recognised in some plants. The sex change in dioecious woody plants includes a monoecious state, which means that the timing of the change is synchronous in branches or shoots but not synchronous among plants, such as in partial dioecious woody plants. To determine whether such a phenomenon is common in woody plants, we investigated the sex expression in two populations of the bird-dispersed, dioecious woody plant Ilex integra Thunb. (Aquifoliaceae), one of the climax forest species in East Asia, over 3 years. No monoecious trees or hermaphrodite flowers were observed. Sex changes were observed at low frequencies, i.e., both female to male and male to female. This study suggests that I. integra may be a complete dioecious woody plant species and that the sex change occurs at the individual level, indicating that the timing of sex change is synchronous in an individual tree.
The Risk of Information Management Without Knowledge Management: A Case Study
Authors: Dogan Huseyin , Henshaw Michael J. de C. , Ragsdell Gillian 
Published: January 2012

This paper appraises the criticism that "Knowledge Management (KM) is little more than re-packaged Information Management (IM)" through analysis of the relationships and inconsistencies between IM and KM. This is supported by a case study of the loss of an UK Royal Air Force aircraft known as 'Nimrod' as reported in the Haddon-Cave Independent Review. The first part discusses the research methodology adopted and analyses the literature including the theoretical characteristics and practical aspects of IM and KM. This is supported by logical models and relationship tables for comparison. The second part develops an analytical framework by applying evaluation criteria, based on principles for Through Life Management of information, to a case study to address the statement that "information is inadequate without knowledge." The logical models and case study insertions uncovered important conclusions: (1) KM is frequently confused with IM and reliance on IM only can sometimes result in a disaster; (2) it is imperative to understand the distinctions between IM and KM as "management of knowledge" is concerned with socio-technical, hence human, aspects to a greater extent than IM; (3) IM should be considered as a prerequisite to engaging KM; and (4) KM should be perceived as the creation and management of knowledge as a human centred attribute that involves a learning and transformation process. This paper systematically applies the derived logical models and analysis framework to a case study to better understand and illustrate the implications of Through Life Management of information and knowledge.
Characterization and Clinical Evaluation of CD10+ Stroma Cells in the Breast Cancer Microenvironment
Authors: Desmedt Christine , Majjaj Samira , Kheddoumi Naima , Singhal Sandeep K. , Haibe-Kains Benjamin , El Ouriaghli Frank , Chaboteaux Carole , Michiels Stefan , Lallemand Françoise , Journe Fabrice , Duvillier Hughes , Loi Sherene , Quackenbush John , Dekoninck Sophie , Blanpain Cédric , Lagneaux Laurence , Houhou Nawal , Delorenzi Mauro , Larsimont Denis , Piccart Martine , Sotiriou Christos 
Published: January 2012

Abstract
Purpose: There is growing evidence that interaction between stromal and tumor cells is pivotal in breast cancer progression and response to therapy. Based on earlier research suggesting that during breast cancer progression, striking changes occur in CD10+ stromal cells, we aimed to better characterize this cell population and its clinical relevance.
Experimental Design: We developed a CD10+ stroma gene expression signature (using HG U133 Plus 2.0) on the basis of the comparison of CD10 cells isolated from tumoral (n = 28) and normal (n = 3) breast tissue. We further characterized the CD10+ cells by coculture experiments of representative breast cancer cell lines with the different CD10+ stromal cell types (fibroblasts, myoepithelial, and mesenchymal stem cells). We then evaluated its clinical relevance in terms of in situ to invasive progression, invasive breast cancer prognosis, and prediction of efficacy of chemotherapy using publicly available data sets.
Results: This 12-gene CD10+ stroma signature includes, among others, genes involved in matrix remodeling (MMP11, MMP13, and COL10A1) and genes related to osteoblast differentiation (periostin). The coculture experiments showed that all 3 CD10+ cell types contribute to the CD10+ stroma signature, although mesenchymal stem cells have the highest CD10+ stroma signature score. Of interest, this signature showed an important role in differentiating in situ from invasive breast cancer, in prognosis of the HER2+ subpopulation of breast cancer only, and potentially in nonresponse to chemotherapy for those patients.
Conclusions: Our results highlight the importance of CD10+ cells in breast cancer prognosis and efficacy of chemotherapy, particularly within the HER2+ breast cancer disease. Clin Cancer Res; 18(4); 1004–14. ©2012 AACR.
A putative inhibitory mechanism in the tenase complex responsible for loss of coagulation function in acquired haemophilia A patients with anti-C2 autoantibodies
Authors: Matsumoto Tomoko , Ogiwara Kenichi , Shima Midori , Nogami Keiji 
Published: January 2012

SummaryAcquired haemophilia A (AHA) is caused by the development of factor (F)VIII autoantibodies, demonstrating type 1 or type 2 inhibitory behaviour, and results in more serious haemorrhagic symptoms than in congenital severe HA. The reason(s) for this remains unknown, however. The global coagulation assays, thrombin generation tests and clot waveform analysis, demonstrated that coagulation parameters in patients with AHA-type 2 inhibitor were more significantly depressed than those in patients with moderate HA with similar FVIII activities. Thrombin and intrinsic FXa generation tests were significantly depressed in AHA-type 1 and AHA-type 2 compared to severe HA, and more defective in AHA-type 1 than in AHA-type 2. To investigate these inhibitory mechanism(s), anti-FVIII autoantibodies were purified from AHA plasmas. AHA-type 1 autoantibodies, containing an anti-C2 ESH4-epitope, blocked FVIII(a)-phospholipid binding, whilst AHA-type 2, containing an anti-C2 ESH8-epitope, inhibited thrombin-catalysed FVIII activation. The coagulation function in a reconstituted AHA-model containing exogenous ESH4 or ESH8 was more abnormal than in severe HA. The addition of anti-FIX antibody to FVIII-deficient plasma resulted in lower coagulation function than its absence. These results support the concept that global coagulation might be more suppressed in AHA than in severe HA due to the inhibition of FIXa-dependent FX activation by steric hindrance in the presence of FVIII-anti-C2 autoantibodies. Additionally, AHA-type 1 inhibitors prevented FVIIIa-phospholipid binding, essential for the tenase complex, whilst AHA-type 2 antibodies decreased FXa generation by inhibiting thrombin-catalysed FVIII activation. These two distinct mechanisms might, in part, contribute to and exacerbate the serious haemorrhagic symptoms in AHA.Presented in abstract form at the 52nd annual meeting of the American Society of Hematology, Orlando, Florida, USA, December 6, 2010.
Upregulation of CD40 ligand and enhanced monocyte-platelet aggregate formation are associated with worse clinical outcome after ischaemic stroke
Authors: Dworacki Grzegorz , Kufel-Grabowska Joanna , Watala Cezary , Kozubski Wojciech , Lukasik Maria 
Published: January 2012

SummaryThe white blood cell count and mean platelet volume determined shortly after the symptom onset are known as independent predictors for clinical outcome after stroke. In the present study we sought to evaluate the prognostic value of platelet-derived inflammatory biomarkers measured prospectively after an ischaemic event. Using five-colour flow cytometry, the platelet surface expression of CD40L, CD62P and subpopulations of leukocyte-platelet aggregates were assessed in 93 stroke patients on the first (V0), 10th (V1) and 90th (V2) day after stroke, and once in 65 disease controls. The clinical outcome was evaluated using the Scandinavian Stroke Scale (SSS) and modified Rankin Scale (mRS) at the same time points as blood sampling and 24 months after the event. Patients with either CD40L surface expression or the percentage of monocyte-platelet aggregates (M-plt) in the third tertile (T3) at V0 had a significantly lower score on the SSS at V1. Patients with the percentage M-plt at V0 higher than the median value of M-plt in controls were at increased risk of SSS < 40 at V1 (odds ratio: 2.6; 95% confidence interval [CI]: 1.4 – 8.7; p=0.006). Patients with the percentage of M-plt in T3 at V0 showed progressive decline in survival (hazard ratio [HR]: 1.6; 95% CI: 1.1–1.9; p=0.02) and a significantly higher number of recurrent vascular events (HR: 2.64; 95% CI: 1.3–3.2; p=0.02) when compared to the first tertile. In conclusion, increased levels of M-plt could be a predictive marker for both early outcome and long-term prognosis while increased CD40L was correlated with worse clinical outcome.The preliminary results of this study were presented in part during a poster session at the 62nd Annual Meeting of the American Academy of Neurology in Toronto, 7–17 April 2010.
A review of the two major regulatory pathways for non-proprietary low-molecular-weight heparins
Authors: Ofosu Frederick 
Published: January 2012

SummaryWith the expiry or pending expiry of originator low-molecular-weight heparin (LMWH) patents, pharmaceutical companies have invested in developing non-proprietary versions of LMWHs. LMWHs are manufactured by depolymerising highly purified unfractionated heparin. In contrast to traditional synthetic drugs with well-defined chemical structures, LMWHs contain complex oligosaccharide mixtures and the different manufacturing processes for LMWHs add to the heterogeneity in their physicochemical properties such that the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) consider existing originator LMWHs to be distinct medicinal entities that are not clinically interchangeable. The FDA views LMWHs as drugs and has approved two non-proprietary (generic) LMWHs, using the Abbreviated New Drug Application pathway. In contrast, the World Health Organization and the EMA view LMWHs as biological medicines. Therefore, the EMA and also the Scientific and Standardization Subcommittee on Anticoagulation of the International Society on Thrombosis and Haemostasis and the South Asian Society of Atherosclerosis and Thrombosis have all published specific guidelines for assessing non-proprietary (biosimilar) LMWHs. This manuscript reviews why there are two distinct pathways for approving non-proprietary LMWHs. Available literature on non-proprietary LMWHs approved in some jurisdictions is also reviewed in order to assess whether they satisfy the requirements for LMWHs in the three guidance documents. The review also highlights some of the significant difficulties the two pathways pose for manufacturers and an urgent need to develop a consensus governing the manufacture and regulation of non-proprietary LMWHs to make them more widely available.
The thrombin inhibitors hirudin and Refludan® activate the soluble guanylyl cyclase and the cGMP pathway in washed human platelets
Authors: Koessler Juergen , Kehrer Linda , Gambaryan Stepan , Walter Ulrich , Kobsar Anna 
Published: January 2012

SummaryA number of direct thrombin inhibitors are successfully used clinically and experimentally as novel antithrombotics and specific anticoagulants. They are also used as anticoagulants in certain blood collection tubes for the analysis of platelet function. A series of platelet function tests have emerged to measure adequate responses to antiplatelet therapy. For comparative and practical reasons, it would be of advantage to use the same anticoagulant in blood collection tubes for different methods, e.g. thrombin inhibitors. However, there are little data on the effects of thrombin inhibitors on platelet signalling pathways that could influence results. We examined the applicability of thrombin inhibitor containing blood for platelet reactivity index (PRI) measurements of the VASP assay and investigated the effects of two thrombin inhibitors (hirudin and lepirudin) on cAMP- and cGMP-mediated signalling pathways in washed human platelets. We show that induction of VASP phosphorylation by PGE1 is markedly reduced in lepirudin containing blood samples. In consequence, PRI levels were highly variable compared to routinely used citrated blood. Surprisingly, in vitro incubation of platelets with thrombin inhibitors increases platelet cGMP levels and induces NOS independent sGC/PKG-mediated VASP phosphorylation. We conclude that thrombin inhibitors activate sGC/PKG-dependent pathways resulting in an increase of VASP phosphorylation which contributes to deviations in PRI measurements. These effects of thrombin inhibitors on sGC- and cGMP-mediated pathways including increased VASP phosphorylation may indicate the presence of an important additional platelet-based mechanism for the reduction of thrombus formation and thromboembolism by thrombin inhibitors.
Performance of five D-dimer assays for the exclusion of symptomatic distal leg vein thrombosis
Authors: Schwonberg Jan , Hecking Carola , Schindewolf Marc , Zgouras Dimitrios , Lehmeyer Susanne , Lindhoff-Last Edelgard , Luxembourg Beate 
Published: January 2012

SummaryThe diagnostic value of D-dimer (DD) in the exclusion of proximal deep-vein thrombosis (DVT) is well-established but is less well-known in the exclusion of distal (infrapopliteal) DVT. Therefore, we evaluated the diagnostic abilities of five DD assays (Vidas-DD, Liatest-DD, HemosIL-DD, HemosIL-DDHS, Innovance-DD) for excluding symptomatic proximal and distal leg DVT. A total of 243 outpatients whose symptoms were suggestive of DVT received complete compression ultrasonography (cCUS) of the symptomatic leg(s). The clinical probability of DVT (PTP) was assessed by Wells score. Thirty-eight proximal and 31 distal DVTs (17 tibial/fibular DVTs, 14 muscle DVTs) were diagnosed by cCUS. Although all assays showed high sensitivity for proximal DVT (range 97–100%), the sensitivity was poor for distal DVT (range 78–93%). None of the assays were individually able to rule out all DVTs as a stand-alone test (negative predictive value [NPV] 91–96%). However, a negative DD test result combined with a low PTP exhibited a NPV of 100% for all DVTs (including proximal, tibial/fibular, and muscle DVTs) with the HemosIL-DDHS and Innovance-DD. All proximal and tibial/fibular DVTs, but not all muscle DVTs, could be ruled out with this strategy using the Liatest-DD and Vidas-DD. The HemosIL-DD could not exclude distal leg DVT, even in combination with a low PTP. The combination of a negative DD with a low PTP showed a specificity of 32–35% for all DVTs. In conclusion, our study shows that when used in conjunction with a low PTP some DD assays are useful tools for the exclusion of distal leg DVT.
Sphingosine kinase inhibition exerts both pro- and anti-atherogenic effects in low-density lipoprotein receptor-deficient (LDL-R−/−) mice
Authors: Potì Francesco , Bot Martine , Costa Sara , Bergonzini Valeria , Maines Lynn , Varga Georg , Freise Hendrik , Robenek Horst , Simoni Manuela , Nofer Jerzy-Roch 
Published: January 2012

SummarySphingosine 1-phosphate (S1P), a lysosphingolipid associated with high-density lipoprotein (HDL), contributes to the anti-atherogenic potential attributed to this lipoprotein. This study examined whether a reduction of S1P plasma levels affects atherosclerosis in a murine model of disease. LDL-R−/−mice on Western diet were given ABC294640, an inhibitor of sphingosine kinase (SphK) for 16 weeks. ABC294640 decreased plasma S1P by approximately 30%. However, ABC294640 failed to affect atherosclerotic lesion formation. Plasma triglycerides were reduced whereas total and HDL-cholesterol remained unchanged in course of ABC294640 treatment. ABC294640 increased plasma interleukin (IL)-12p70 and RANTES concentration as well as IL-12p70, RANTES and interferon (IFN)-γ production by peritoneal cells and this was paralleled by enhanced activity of peritoneal and spleen dendritic cells as evidenced by up-regulation of CD86 and MHC-II on CD11c+ cells. As a consequence, increased T-cell activation was noted in ABC294640-treated mice as indicated by enhanced CD4+ splenocyte proliferation, IFN-γ and IL-2 production, and CD69 expression. Con-comitantly, however, ABC294640 treatment redistributed CD4+ and CD8+ cells from blood to lymphatic organs and reduced T-cell number within atherosclerotic lesions. In addition, plasma sVCAM-1, sICAM-1, and MCP-1 levels as well as in vivo leukocyte adhesion and CCL19-induced T-cell penetration into peritoneum were lower in ABC294640-treated animals. In vitro experiments demonstrated reduced VCAM-1 and ICAM-1 expression and lymphocyte adhesion to endothelial cells exposed to ABC294640. In conclusion, treatment with SphK inhibitor leads to both pro- and anti-atherogenic effects in LDL-R−/− mice. As a consequence, SphK inhibition fails to affect atherosclerosis despite significant S1P reduction in plasma.