bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbial responses to xenobiotic compounds. Identification of genes that allow Pseudomonas putida KT2440 to cope with 2,4,6‐trinitrotoluene
Authors: Fernández Matilde , Duque Estrella , Pizarro‐Tobías Paloma , Van Dillewijn Pieter , Wittich Rolf‐Michael , Ramos Juan L. 
Published: February 2009

Summary Pseudomonas putida KT2440 grows in M9 minimal medium with glucose in the presence of 2,4,6‐trinitrotoluene (TNT) at a similar rate than in the absence of TNT, although global transcriptional analysis using DNA microarrays revealed that TNT exerts some stress. Response to TNT stress is regulated at the transcriptional level, as significant changes in the level of expression of 65 genes were observed. Of these genes, 39 appeared upregulated, and 26 were downregulated. The identity of upregulated genes suggests that P. putida uses two kinds of strategies to overcome TNT toxicity: (i) induction of genes encoding nitroreductases and detoxification‐related enzymes (pnrA, xenD, acpD) and (ii) induction of multidrug efflux pump genes (mexEF/oprN) to reduce intracellular TNT concentrations. Mutants of 13 up‐ and 7 downregulated genes were analysed with regards to TNT toxicity revealing the role of the MexE/MexF/OprN pump and a putative isoquinoline 1‐oxidoreductase in tolerance to TNT. The ORF PP1232 whose transcriptional level did not change in response to TNT affected growth in the presence of nitroaromatic compounds and it was found in a screening of 4000 randomly generated mutants.
Effect of asthma compliance enhancement training on asthma control in patients on combination therapy with salmeterol/fluticasone propionate: a randomised controlled trial
Authors: Ulrik Charlotte Suppli , Claudius Birgitte Kjor , Tamm Michael , Harving Henrik , Siersted Hans Christian , Backer Vibeke , Hellquist Birthe , Dahl Ronald , Høgholm Asbjørn , Jøhnk Ida Karina 
Published: February 2009

AbstractObjective:  We investigated if a higher proportion of adults with previously uncontrolled asthma can achieve total control when given salmeterol/fluticasone propionate (50/250 µg) bid and compliance enhancement training (CET) compared to those given medication alone.Methods:  Open comparison of stable, but uncontrolled, adult asthmatics. After a 12‐week treatment period on salmeterol/fluticasone propionate (period 1), patients who failed to achieve control were randomised to continuing treatment with or without CET for 12 weeks (period 2). The primary end point was the proportion achieving total control of their asthma in 7 of the last 8 consecutive weeks of period 2.Results:  A total of 361 subjects (50.4% males, mean age 40.0 ± 14.4 years) in 29 centres were included, of whom 75.9% were randomised into treatment period 2 (n = 140 in the intervention group). The proportion of subjects achieving total asthma control was 8.8% and 7.6%, respectively, in the intervention and control group [not significant (NS)]. Mean morning peak flow, forced expiratory volume in one second (FEV1), asthma symptom score and quality of life improved significantly over the study period in both treatment groups. Furthermore, proportion of days with use of rescue medication declined from 59.7% ± 34.6% (55.7% ±  35.3%) during screening to 20.3% ± 29.2% (19.4% ± 30.9%) during treatment period 2 (NS).Conclusion:  CET failed to increase the likelihood of achieving total control in asthmatics on salmeterol/fluticasone propionate compared to subjects receiving medication only. However, both groups had a significant improvement in asthma control.(Clinical Trials.gov number, NCT00351143)Please cite this paper as: Ulrik CS, Claudius BK, Tamm M, Harving H, Siersted HC, Backer V, Hellquist B, Dahl R, Høgholm A and Jøhnk IK. Effect of asthma compliance enhancement training on asthma control in patients on combination therapy with salmeterol/fluticasone propionate: a randomised controlled trial. The Clinical Respiratory Journal 2009; 3: 161–168.
Negative Regulation of VEGF Signaling in Human Coronary Artery Endothelial Cells by G Protein‐Coupled Receptor Kinase 5
Authors: Zhou Rui‐Hai , Pesant Stephanie , Cohn Heather I. , Soltys Stephen , Koch Walter J. , Eckhart Andrea D. 
Published: February 2009

AbstractG protein‐coupled receptor kinase 5 (GRK5) is present in endothelial cells (ECs) and has the potential to regulate EC function through seven transmembrane‐spanning receptor (7TMR) signaling. Recently, it has been appreciated that GRKs can affect receptor tyrosine kinases (RTKs). VEGF, an RTK, is one of the most potent mediators for EC function and angiogenesis; therefore, we determined the role GRK5 plays in VEGF signaling in human coronary artery ECs (HCAECs). GRK5 levels were increased by VEGF treatment in HCAECs. Adenoviral overexpression of GRK5 inhibited migration and proliferation of HCAECs in response to VEGF. GRK5 overexpression in HCAECs significantly suppressed both acute and late activation of Akt and extracellular signal‐related kinase (ERKs) as well as the phosphorylationof GSK‐3β, an endogenous substrate of Akt. Coimmunoprecipitations revealed that GRK5 is physically associated with Akt. This study shows for the first time that GRK5 negatively regulates VEGF signaling in HCAECs and suggests that targeted intervention of GRK5 in ECs might be a novel therapeutic strategy to prevent and treat disorders involving altered EC function.
Optimized Systemic Dosing with CpG DNA Enhances Dendritic Cell‐Mediated Rejection of a Poorly Immunogenic Mammary Tumor in BALB/c Mice
Authors: Cai Quan , Kublo Lyubov , Cumberland Rachel , Gooding William , Baar Joseph 
Published: February 2009

AbstractTo model a clinical trial of dendritic cell (DC) therapy of a poorly immunogenic mammary tumor, we treated BALB/c mice bearing an established TS/A mammary tumor with lysate‐pulsed DCs and CpG DNA. We observed that the dose of CpG DNA required to activate DCs in vitro was insufficient to mediate tumor rejection in vivo. We therefore undertook in vivo studies to identify an optimized dose of CpG DNA for tumor therapy, defined as the lowest and least frequently administered dose of CpG DNA that mediated complete tumor rejection. We show that one priming dose of 15 nanomoles and one booster dose of 10 nanomoles of CpG DNA given 7 days apart, respectively, with lysate‐loaded DCs were sufficient to mediate complete tumor rejection in vivo. This dose of CpG DNA was 42‐fold higher than that required to activate DCs in vitro but was not associated with any toxicity in mice. Also, the cured mice rejected a subsequent challenge with fresh TS/A tumor, and both CD4+ and CD8+ T cells were required for tumor rejection. We conclude that effective DC‐based therapy of a poorly immunogenic TS/A tumor is enhanced by optimized dosing of CpG DNA. Our data have important implications for DC‐based clinical trials of breast cancer immunotherapy.
Prevention of Trauma/Hemorrhagic Shock‐Induced Lung Apoptosis by IL‐6‐Mediated Activation of Stat3
Authors: Moran Ana , Tsimelzon Anna I. , Mastrangelo Mary‐Ann A. , Wu Yong , Yu Bi , Hilsenbeck Susan G. , Poli Valeria , Tweardy David J. 
Published: February 2009

AbstractAcute lung injury (ALI) occurs in up to 37% of patients following trauma/hemorrhagic shock (T/HS) and, in other settings, is due to alveolar epithelial cell (AEC) apoptosis. To determine if AEC apoptosis is a key contributor to ALI following T/HS and whether or not signal transducer and activator of translation (Stat)3 activation can prevent it, rats were pretreated with a Stat3 inhibitor or placebo and subjected to T/HS or sham protocol and resuscitated without or with interleukin (IL)‐6. T/HS induced apoptosis in up to 15% of lung cells, 82% of which were AEC. Apoptosis increased with increasing duration of shock and required resuscitation. IL‐6 treatment stimulated lung Stat3 activation and prevented AEC apoptosis. Pretreatment of rats with a Stat3 inhibitor blocked the antiapoptotic effect of IL‐6. Mice deficient in Stat3β, a naturally occurring dominant negative isoform of Stat3, were resistant to T/HS‐induced lung apoptosis. T/HS altered the expression of 87% of apoptosis‐related genes. IL‐6 treatment normalized expression of 75% of the genes altered by T/HS; Stat3 inhibition prevented normalization of 65% of the gene whose expression was normalized by IL‐6. Thus, T/HS‐induced AEC apoptosis, which depended on the duration of hypotension, required resuscitation and was prevented by IL‐6‐mediated activation of Stat3, which acted to normalize the apoptosis transcriptome.
In vivo Remote Delivery of DNA Encoding for Hypoxia‐inducible Factor 1 Alpha Reduces Myocardial Infarct Size
Authors: Czibik Gabor , Martinov Vladimir , Ruusalepp Arno , Sagave Julia , Skare Øivind , Valen Guro 
Published: February 2009

AbstractWe tested if remote gene delivery of hypoxia‐inducible factor 1 alpha (HIF‐1α) protected hearts against induced ischemia, hypothesizing that gene delivery into skeletal muscle may lead to secretion of proteins with actions elsewhere.Murine quadriceps muscles were transfected with DNA encoding for human HIF‐1α, which resulted in a local, but lasting expression (mRNA and protein, where the latter had nuclear localization). Subjection of isolated hearts to global ischemia and reperfusion 1, 4, and 8 weeks after gene delivery resulted in infarct size reduction (p < 0.05). Supporting that this was due to paracrine effects, HL‐1 cells treated with conditioned media from cells transfected with HIF‐1α or serum from HIF‐1α‐treated mice were protected against H2O2‐induced cell death (p < 0.05, respectively). The latter protection was reduced when a heme oxygenase activity blocker was used. Taqman low‐density array of 47 HIF‐1α‐regulated genes at the treatment site showed nine specific upregulations (p < 0.05). Of the corresponding proteins, PDGF‐B and adrenomedullin were upregulated in the heart. HIF‐1α treatment induced an increased vascularization of the heart and skeletal muscle.In conclusion, remote delivery of DNAfor HIF‐1α was cardioprotective, represented by consistent infarct size reduction, which may be due to release of paracrine factors from the transfected muscle.
The Emergence of Extensively Drug‐Resistant Tuberculosis: A Global Health Crisis Requiring New Interventions: Part II: Scientific Advances that May Provide Solutions
Authors: Ellner Jerrold J. 
Published: February 2009

AbstractThe need for new tuberculosis (TB) diagnostics has never been greater as TB in the HIV‐infected is often sputum smear negative or extrapulmonary and may progress rapidly unless diagnosed and treated appropriately. In addition, the empirical treatment of patients with drug‐resistant TB leads to the acquisition of additional resistance. Fortunately there is a robust and adequately funded developments pipeline including investigational rapid diagnostics that may replace smear, culture, and drug susceptibility testing. The dogma that drug resistance usually develops as a consequence of patient nonadherence has never been entirely plausible. Recent observations indicate that certain mutations in drug resistance genes promote the acquisition of additional resistance. Further, Mycobacterium tuberculosis (MTB) may demonstrate tolerant phenotypes due to induction of a multidrug‐resistant like pump. It will be difficult to “treat our way” out of the problem of extensively drug‐resistant (XDR)‐TB without access to new interventions. Vaccines in development offer a distant hope. Promising new therapeutics in clinical trials may shorten the duration of treatment of TB, which will lessen the development of drug resistance or provide potent new and MTB specific agents that should be effective in treatment of XDR‐TB.
Sunitinib‐Induced Cardiotoxicity Is Mediated by Off‐Target Inhibition of AMP‐Activated Protein Kinase
Authors: Kerkela Risto , Woulfe Kathleen C. , Durand Jean‐Bernard , Vagnozzi Ronald , Kramer David , Chu Tammy F. , Beahm Cara , Chen Ming Hui , Force Thomas 
Published: February 2009

AbstractTyrosine kinase inhibitors (TKIs) are transforming the treatment of patients with malignancies. One such agent, sunitinib (Sutent, Pfizer, New York, NY, USA), has demonstrated activity against a variety of solid tumors. Sunitinib is “multitargeted,” inhibiting growth factor receptors that regulate both tumor angiogenesis and tumor cell survival. However, cardiac dysfunction has been associated with its use. Identification of the target of sunitinib‐associated cardiac dysfunction could guide future drug design to reduce toxicity while preserving anticancer activity. Herein we identify severe mitochondrial structural abnormalities in the heart of a patient with sunitinib‐induced heart failure. In cultured cardiomyocytes, sunitinib induces loss of mitochondrial membrane potential and energy rundown. Despite the latter, 5′ adenosine monophosphate‐activated protein kinase (AMPK) activity, which should be increased in the setting of energy compromise, is reduced in hearts of sunitinib‐treated mice and cardiomyocytes in culture, and this is due to direct inhibition of AMPK by sunitinib. Critically, we find that adenovirus‐mediated gene transfer of an activated mutant of AMPK reduces sunitinib‐induced cell death. Our findings suggest AMPK inhibition plays a central role in sunitinib cardiomyocyte toxicity, highlighting the potential of off‐target effects of TKIs contributing to cardiotoxicity. While multitargeting can enhance tumor cell killing, this must be balanced against the potential increased risk of cardiac dysfunction.
Dangerous Friends: The Second and the Later English Duel
Authors: BANKS STEVE 
Published: February 2009

AbstractThe paper considers honour disputes and duelling in the English society of the late eighteenth and early nineteenth centuries. Its author argues that it was the seconds, or friends, of the disputants, who made both the peaceful resolution of disputes socially possible and, if necessary, the carefully structured violence of the duel containable. The second, an independent man of reputation who assayed the honour of his principal, has oft been neglected in modern duelling studies. Here the author examines the nuances, privileges and obligations of his situation and the indispensable role that he played in sustaining honour culture.
Cultivation of a perennial grass for bioenergy on a boreal organic soil – carbon sink or source?
Authors: SHURPALI NARASINHA J. , HYVÖNEN NIINA P. , HUTTUNEN JARI T. , CLEMENT ROBERT J. , REICHSTEIN MARKUS , NYKÄNEN HANNU , BIASI CHRISTINA , MARTIKAINEN PERTTI J. 
Published: February 2009

AbstractThe area under the cultivation of perennial bioenergy crops on organic soils in the northern countries is fast increasing. To understand the impact of reed canary grass (RCG, Phalaris arundinaceae L.) cultivation on the carbon dioxide (CO2) balance of an organic soil, net ecosystem CO2 exchange (NEE) was measured for four years in a RCG cultivated cutover peatland in eastern Finland using the eddy covariance technique. There were striking differences among the years in the annual precipitation. The annual precipitation was higher during 2004 and 2007 and lower during 2005 and 2006 than the 1971–2000 regional mean. During wet growing seasons, moderate temperatures, high surface soil moisture and low evaporative demand favoured high CO2 uptake. During dry seasons, owing to soil moisture and atmospheric stress, photosynthetic activity was severely restricted. The CO2 uptake [gross primary productivity (GPP)] was positively correlated with soil moisture, air temperature and inversely with vapour pressure deficit. Total ecosystem respiration (TER) increased with increasing soil temperature but decreased with increasing soil moisture. The relative responses of GPP and TER to moisture stress were different. While changes in TER for a given change in soil moisture were moderate, variations in GPP were drastic. Also, the seasonal variations in TER were not as conspicuous as those in GPP implying that GPP is the primary regulator of the interannual variability in NEE in this ecosystem. The ecosystem accumulated a total of 398 g C m−2 from the beginning of 2004 until the end of 2007. It retained some carbon during a wet year such as 2004 even after accounting for the loss of carbon in the form of harvested biomass. Based on this CO2 balance analysis, RCG cultivation is found to be a promising after‐use option on an organic soil.
Stability and the Fourier–Mukai transform II
Authors: Yoshioka Kōta 
Published: February 2009

AbstractWe consider the problem of preservation of stability under the Fourier–Mukai transform ℱℰ:D(X)→D(Y) on an abelian surface and aK3 surface. IfYis the moduli space ofμ-stable sheaves onXwith respect to a polarizationH, we have a canonical polarization$\widehat {H}$onYand we have a correspondence between (X,H) and$(Y,\widehat {H})$. We show that the stability with respect to these polarizations is preserved under ℱℰ, if the degree of stable sheaves onXis sufficiently large.
Geometric Weil representation: local field case
Authors: Lafforgue Vincent , Lysenko Sergey 
Published: February 2009

AbstractLet k be an algebraically closed field of characteristic greater than 2, and let F=k((t)) and G=𝕊p2d. In this paper we propose a geometric analog of the Weil representation of the metaplectic group $\widetilde G(F)$. This is a category of certain perverse sheaves on some stack, on which $\widetilde G(F)$ acts by functors. This construction will be used by Lysenko (in [Geometric theta-lifting for the dual pair S𝕆2m, 𝕊p2n, math.RT/0701170] and subsequent publications) for the proof of the geometric Langlands functoriality for some dual reductive pairs.
Analytic vectors in continuousp-adic representations
Authors: Schmidt Tobias 
Published: February 2009

AbstractGiven a compactp-adic Lie groupGover a finite unramified extensionL/ℚplet GL/ℚpbe the product over all Galois conjugates ofG. We construct an exact and faithful functor from admissibleG-Banach space representations to admissible locallyL-analyticGL/ℚp-representations that coincides with passage to analytic vectors in the caseL=ℚp. On the other hand, we study the functor ‘passage to analytic vectors’ and its derived functors over general basefields. As an application we compute the higher analytic vectors in certain locally analytic induced representations.
Prospective Observational Study of the Impact of VIM-1 Metallo-β-Lactamase on the Outcome of Patients with
Klebsiella pneumoniae
Bloodstream Infections
Authors: Daikos George L. , Petrikkos Panayiotis , Psichogiou Mina , Kosmidis Chris , Vryonis Evangelos , Skoutelis Athanasios , Georgousi Kleoniki , Tzouvelekis Leonidas S. , Tassios Panayotis T. , Bamia Christina , Petrikkos George 
Published: February 2009

ABSTRACT

VIM-1-producing
Klebsiella pneumoniae
(VPKP) is an emerging pathogen. A prospective observational study was conducted to evaluate the importance of VIM production on outcome of patients with
K. pneumoniae
bloodstream infections (BSIs). Consecutive patients with
K. pneumoniae
BSIs were identified and followed up until patient discharge or death. A total of 162 patients were included in the analysis; 67 (41.4%) were infected with VPKP, and 95 were infected with non-VPKP. Fourteen of the patients infected with VPKP were carbapenem resistant (Carb
r
) (MIC > 4 μg/ml), whereas none of the non-VPKP exhibited carbapenem resistance. The patients infected with a Carb
r
organism were more likely (odds ratio, 4.08; 95% confidence interval [CI], 1.29 to 12.85;
P
= 0.02) to receive inappropriate empirical therapy. The all-cause 14-day mortality rates were 15.8% (15 of 95) for patients infected with VIM-negative organisms, 18.9% (10 of 53) for those infected with VIM-positive carbapenem-susceptible organisms, and 42.9% (6 of 14) for those infected with VIM-positive Carb
r
organisms (
P
= 0.044). In Cox regression analysis, age (hazard ratio [HR], 1.03; 95% CI, 1.01 to 1.06;
P
= 0.021), rapidly fatal underlying disease (HR, 2.84; 95% CI, 1.26 to 6.39;
P
= 0.012), and carbapenem resistance (HR, 2.83; 95% CI, 1.08 to 7.41;
P
= 0.035) were independent predictors of death. After adjustment for inappropriate empirical or definitive therapy, the effect of carbapenem resistance on outcome was reduced to a level of nonsignificance. In patients with
K. pneumoniae
BSIs, carbapenem resistance, advanced, age, and severity of underlying disease were independent predictors of outcome, whereas VIM production had no effect on mortality. The higher mortality associated with carbapenem resistance was probably mediated by the failure to provide effective therapy.
Triple Combinations of Lower and Longer Alkyl Gallates and Oxacillin Improve Antibiotic Synergy against Methicillin-Resistant
Staphylococcus aureus
Authors: Shibata Hirofumi , Nakano Tatsuro , Parvez M. Anowar Khasru , Furukawa Yoshihiro , Tomoishi Akio , Niimi Shingo , Arakaki Naokatu , Higuti Tomihiko 
Published: February 2009

ABSTRACT

Using liposome systems, we found that gallates with short alkyl chains were located in the external medium and those with longer alkyl chains were located in the surface region of lipid bilayer. Combinations of these gallates remarkably reduced oxacillin MICs against methicillin-resistant
Staphylococcus aureus
to below the antibiotic breakpoint (≤2 μg/ml).
Chemical Modifications of Antisense Morpholino Oligomers Enhance Their Efficacy against Ebola Virus Infection
Authors: Swenson Dana L. , Warfield Kelly L. , Warren Travis K. , Lovejoy Candace , Hassinger Jed N. , Ruthel Gordon , Blouch Robert E. , Moulton Hong M. , Weller Dwight D. , Iversen Patrick L. , Bavari Sina 
Published: February 2009

ABSTRACT
Phosphorodiamidate morpholino oligomers (PMOs) are uncharged nucleic acid-like molecules designed to inactivate the expression of specific genes via the antisense-based steric hindrance of mRNA translation. PMOs have been successful at knocking out viral gene expression and replication in the case of acute viral infections in animal models and have been well tolerated in human clinical trials. We propose that antisense PMOs represent a promising class of therapeutic agents that may be useful for combating filoviral infections. We have previously shown that mice treated with a PMO whose sequence is complementary to a region spanning the start codon of VP24 mRNA were protected against lethal Ebola virus challenge. In the present study, we report on the abilities of two additional VP24-specific PMOs to reduce the cell-free translation of a VP24 reporter, to inhibit the in vitro replication of Ebola virus, and to protect mice against lethal challenge when the PMOs are delivered prior to infection. Additionally, structure-activity relationship evaluations were conducted to assess the enhancement of antiviral efficacy associated with PMO chemical modifications that included conjugation with peptides of various lengths and compositions, positioning of conjugated peptides to either the 5′ or the 3′ terminus, and the conferring of charge modifications by the addition of piperazine moieties. Conjugation with arginine-rich peptides greatly enhanced the antiviral efficacy of VP24-specific PMOs in infected cells and mice during lethal Ebola virus challenge.
Inhibitory and Bactericidal Activities of Daptomycin, Vancomycin, and Teicoplanin against Methicillin-Resistant
Staphylococcus aureus
Isolates Collected from 1985 to 2007
Authors: Traczewski Maria M. , Katz Bradley D. , Steenbergen Judith N. , Brown Steven D. 
Published: February 2009

ABSTRACT

The inhibitory and bactericidal activities of daptomycin, vancomycin, and teicoplanin against a collection of 479 methicillin-resistant
Staphylococcus aureus
isolates were assessed. The isolates were collected from U.S. and European hospitals from 1985 to 2007 and were primarily from blood and abscess cultures. The MICs and minimum bactericidal concentrations (MBCs) of the three agents were determined, and the MBC/MIC ratios were calculated to determine the presence or absence of tolerance. Tolerance was defined as an MBC/MIC ratio of ≥32 or an MBC/MIC ratio of ≥16 when the MBC was greater than or equal to the breakpoint for resistance. Tolerance to vancomycin and teicoplanin was observed in 6.1% and 18.8% of the strains, respectively. Tolerance to daptomycin was not observed.