bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distribution and genetic diversity of root‐knot nematodes (Meloidogyne spp.) in potatoes from South Africa
Authors: Onkendi E. M. , Moleleki L. N. 
Published: January 2013

A molecular‐based assay was employed to analyse and accurately identify various root‐knot nematodes (Meloidogyne spp.) parasitizing potatoes (Solanum tuberosum) in South Africa. Using the intergenic region (IGS) and the 28S D2–D3 expansion segments within the ribosomal DNA (rDNA), together with the region between the cytochrome oxidase subunit II (COII) and the 16S rRNA gene of the mtDNA, 78 composite potato tubers collected from seven major potato growing provinces were analysed and all Meloidogyne species present were identified. During this study, M. incognita, M. arenaria, M. javanica, M. hapla, M. chitwoodi and M. enterolobii were identified. The three tropical species M. javanica, M. incognita and M. arenaria were identified as the most prevalent species, occurring in almost every region sampled. Meloidogyne hapla and M. enterolobii occurred in Mpumalanga and KwaZulu‐Natal, respectively, while M. chitwoodi was isolated from two growers located within the Free State. Results presented here form part of the first comprehensive surveillance study of root‐knot nematodes to be carried out on potatoes in South Africa using a molecular‐based approach. The three genes were able to distinguish various Meloidogyne populations from one another, providing a reliable and robust method for future use in diagnostics within the potato industry for these phytoparasites.
K‐Ar illite age constraints on the Proterozoic formation and reactivation history of a brittle fault in Fennoscandia
Authors: Viola Giulio , Zwingmann Horst , Mattila Jussi , Käpyaho Asko 
Published: January 2013

AbstractK‐Ar ages of authigenic illite from two drill‐core gouge samples of a fault in the Palaeoproterozoic basement of Finland record two distinct faulting events. The older sample yields apparent ages from 1240 ± 26 to 1006 ± 21 Ma for four grain size fractions between 6 and <0.1 μm. The second sample is structurally younger and yields statistically distinct ages ranging from 978 ± 20 to 886 ± 18 Ma. We interpret the ages of the <0.1 m fractions, which are the youngest, as representing the actual time of faulting. XRD analysis and age modelling exclude significant age contamination of the finest dated fractions with inherited host rock components. These results provide therefore an example of meaningful isotopic dating of illite‐type clay material formed during Precambrian faulting, demonstrate and constrain fault reactivation and give evidence for brittle Sveconorwegian Mesoproterozoic shortening and Neoproterozoic extension in Fennoscandia.
Geophysical constraints on mesozoic disruption of North China Craton by underplating‐triggered lower‐crust flow of the Archaean lithosphere
Authors: Zhang Zhongjie , Wang Yanghua , Deng Yangfan , Chen Lin , Wu Jing , Teng Jiwen , Chen Yun , Fan Weiming , Panza Giuliano 
Published: January 2013

AbstractThe mechanism of the disruption, both lithospheric thinning and oceanization of the commonly accepted long‐term‐stable Archaean craton, is still an open question. The available models, all imply a bottom to top process. With the construction of a 1660‐km‐long transect across the eastern North China Craton (NCC), we demonstrate that both the P‐wave velocity and density in the lowermost crust beneath the central section are significantly higher than in the corresponding parts of the south and north sections on the transect. These features are interpreted as geophysical signature of lower crustal underplating, which supplies sufficiently high gravitational potential energy to trigger lateral flow of the lower crust. This magma underplating‐triggered bilateral lower crust flow may facilitate the lithospheric thinning by means of asthenosphere upwelling and decompression melting, which infill the gap produced by the lower crust flow. The underplating‐triggered lower crustal flow can provide an alternative mechanism to explain the NCC lithosphere disruption, which highlights the crustal feedback to Archaean lithosphere disruption, from top to bottom.
Randomized Phase 2 Trial To Evaluate the Clinical Efficacy of Two High-Dosage Tigecycline Regimens versus Imipenem-Cilastatin for Treatment of Hospital-Acquired Pneumonia
Authors: Ramirez Julio , Dartois Nathalie , Gandjini Hassan , Yan Jean Li , Korth-Bradley Joan , McGovern Paul C. 
Published: January 2013

ABSTRACT

In a previous phase 3 study, the cure rates that occurred in patients with hospital-acquired pneumonia treated with tigecycline at the approved dose were lower than those seen with patients treated with imipenem and cilastatin (imipenem/cilastatin). We hypothesized that a higher dose of tigecycline is necessary in patients with hospital-acquired pneumonia. This phase 2 study compared the safety and efficacy of two higher doses of tigecycline with imipenem/cilastatin in subjects with hospital-acquired pneumonia. Subjects with hospital-acquired pneumonia were randomized to receive one of two doses of tigecycline (150 mg followed by 75 mg every 12 h or 200 mg followed by 100 mg every 12 h) or 1 g of imipenem/cilastatin every 8 h. Empirical adjunctive therapy was administered for initial coverage of methicillin-resistant
Staphylococcus aureus
and
Pseudomonas aeruginosa
infection, depending on the randomization regimen. Clinical response, defined as cure, failure of treatment, or indeterminate outcome, was assessed 10 to 21 days after the last day of therapy. In the clinically evaluable population, clinical cure with tigecycline 100 mg (17/20, 85.0%) was numerically higher than with tigecycline 75 mg (16/23, 69.6%) and imipenem/cilastatin (18/24, 75.0%). No new safety signals with the high-dose tigecycline were identified. A numerically higher clinical response was observed with the 100-mg dose of tigecycline. This supports our hypothesis that a higher area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC ratio) may be necessary to achieve clinical cure in patients with hospital-acquired pneumonia. Further studies are necessary. (The ClinicalTrials.gov identifier for this clinical trial is NCT00707239.)
Immunoadjuvant Chemotherapy of Visceral Leishmaniasis in Hamsters Using Amphotericin B-Encapsulated Nanoemulsion Template-Based Chitosan Nanocapsules
Authors: Asthana Shalini , Jaiswal Anil K. , Gupta Pramod K. , Pawar Vivek K. , Dube Anuradha , Chourasia Manish K. 
Published: January 2013

ABSTRACTThe accessible treatment options for life-threatening neglected visceral leishmaniasis (VL) disease have problems with efficacy, stability, adverse effects, and cost, making treatment a complex issue. Here we formulated nanometric amphotericin B (AmB)-encapsulated chitosan nanocapsules (CNC-AmB) using a polymer deposition technique mediated by nanoemulsion template fabrication. CNC-AmB exhibited good steric stabilityin vitro, where the chitosan content was found to be efficient at preventing destabilization in the presence of protein and Ca2+. A toxicity study on the model cell line J774A and erythrocytes revealed that CNC-AmB was less toxic than commercialized AmB formulations such as Fungizone and AmBisome. The results ofin vitro(macrophage-amastigote system; 50% inhibitory concentration [IC50], 0.19 ± 0.04 μg AmB/ml) andin vivo(Leishmania donovani-infected hamsters; 86.1% ± 2.08% parasite inhibition) experiments in conjunction with effective internalization by macrophages illustrated the efficacy of CNC-AmB at augmenting antileishmanial properties. Quantitative mRNA analysis by real-time PCR (RT-PCR) showed that the improved effect was synergized with the upregulation of tumor necrosis factor alpha (TNF-α), interleukin-12 (IL-12), and inducible nitric oxide synthase and with the downregulation of transforming growth factor β (TGF-β), IL-10, and IL-4. These research findings suggest that a cost-effective CNC-AmB immunoadjuvant chemotherapeutic delivery system could be a viable alternative to the current high-cost commercial lipid-based formulations.
Staphylococcus aureus Biofilms Promote Horizontal Transfer of Antibiotic Resistance
Authors: Savage Victoria J. , Chopra Ian , O'Neill Alex J. 
Published: January 2013

ABSTRACT

Growth as a biofilm facilitates the emergence of antibiotic resistance by mutation in
Staphylococcus aureus
. Here we demonstrate that biofilm growth of this species also dramatically increases horizontal transfer of plasmid-borne antibiotic resistance determinants by conjugation/mobilization and that standard laboratory practices to induce conjugation in staphylococci achieve optimal efficiency owing to the presence of a biofilm.
Evaluation of Recombinant 2009 Pandemic Influenza A (H1N1) Viruses Harboring Zanamivir Resistance Mutations in Mice and Ferrets
Authors: Pizzorno Andrés , Abed Yacine , Rhéaume Chantal , Bouhy Xavier , Boivin Guy 
Published: January 2013

ABSTRACTRecombinant influenza A(H1N1)pdm09 wild-type (WT) and zanamivir-resistant E119G and Q136K neuraminidase mutants were generated to determine their enzymatic and replicative propertiesin vitro, as well as their infectivity and transmissibility in mice and ferrets. Viral titers of recombinant E119G and Q136K mutants were significantly lower than those of the WT in the first 36 h postinoculation (p.i.)in vitro. The E119G and Q136K mutations were both associated with a significant reduction of total neuraminidase (NA) activity at the cell surface of 293T cells, with relative total NA activities of 14% (P< 0.01) and 20% (P< 0.01), respectively, compared to the WT. The E119G mutation significantly reduced the affinity (8-fold increase inKm) but not theVmax. The Q136K mutation increased the affinity (5-fold decrease inKm) with a reduction inVmax(8%Vmaxratio versus the WT). In mice, infection with the E119G and Q136K mutants resulted in lung viral titers that were significantly lower than those of the WT on days 3 p.i. (3.4 × 106± 0.8 × 106and 2.1 × 107± 0.4 × 107PFU/ml, respectively, versus 8.8 × 107± 1.1 × 107;P< 0.05) and 6 p.i. (3.0 × 105± 0.5 × 105and 8.6 × 105± 1.4 ×105PFU/ml, respectively, versus 5.8 × 107± 0.3 × 107;P< 0.01). In experimentally infected ferrets, the E119G mutation rapidly reverted to the WT in donor and contact animals. The Q136K mutation was maintained in ferrets, although nasal wash viral titers from the Q136K contact group were significantly lower than those of the WT on days 3 to 5 p.i. Our results demonstrate that zanamivir-resistant E119G and Q136K mutations compromise viral fitness and transmissibility in A(H1N1)pdm09 viruses.
Role of Enteroaggregative Escherichia coli Virulence Factors in Uropathogenesis
Authors: Boll Erik J. , Struve Carsten , Boisen Nadia , Olesen Bente , Stahlhut Steen G. , Krogfelt Karen A. 
Published: January 2013

ABSTRACT

A multiresistant clonal
Escherichia coli
O78:H10 strain qualifying molecularly as enteroaggregative
Escherichia coli
(EAEC) was recently shown to be the cause of a community-acquired outbreak of urinary tract infection (UTI) in greater Copenhagen, Denmark, in 1991. This marks the first time EAEC has been associated with an extraintestinal disease outbreak. Importantly, the outbreak isolates were recovered from the urine of patients with symptomatic UTI, strongly implying urovirulence. Here, we sought to determine the uropathogenic properties of the Copenhagen outbreak strain and whether these properties are conferred by the EAEC-specific virulence factors. We demonstrated that through expression of aggregative adherence fimbriae, the principal adhesins of EAEC, the outbreak strain exhibited pronouncedly increased adherence to human bladder epithelial cells compared to prototype uropathogenic strains. Moreover, the strain was able to produce distinct biofilms on abiotic surfaces, including urethral catheters. These findings suggest that EAEC-specific virulence factors increase uropathogenicity and may have played a significant role in the ability of the strain to cause a community-acquired outbreak of UTI. Thus, inclusion of EAEC-specific virulence factors is warranted in future detection and characterization of uropathogenic
E. coli
.
A cohort study on psychosocial adjustment and psychopathology in adolescents and young adults with congenital heart disease
Authors: Freitas Isabela Ribeiro , Castro Marta , Sarmento Sofia Lourenço , Moura Cláudia , Viana Victor , Areias José Carlos , Areias Maria Emília Guimarães 
Published: January 2013

ObjectivesOur purpose was to study psychosocial adjustment and psychiatric morbidity of adolescents and young adults with congenital heart disease (CHD).DesignAll assessment measures were obtained on a single occasion. Clinical data was obtained through the patient's clinical records.SettingA teaching and tertiary care facility in Porto, Portugal.ParticipantsWe evaluated 110 CHD patients (62 male) aged from 12 to 26 years (mean=18.00±3.617), 58 cyanotic. All assessment measures were obtained on a single occasion in a tertiary hospital. Demographic information and clinical history were collected.Primary and secondary outcome measuresQuestionnaires regarded topics such as social support, family educational style, self-image and physical limitations, a standardised psychiatric interview Schedule for Affective Disorders and Schizophrenia—Lifetime version (SADS-L), and a self-report questionnaire on psychosocial adjustment, youth self-report or adult self-report. One of the relatives completed an observational version of the same questionnaire (child behaviour checklist (CBCL) or ABCL (adult behaviour checklist)).ResultsWe found a 21.8% lifetime prevalence of psychopathology, 31.3%, in females, 14.5% in males, showing a somewhat increased proneness in CHD patients. Females also showed worse psychosocial adjustment, with more somatic complaints (u=260 000; p=0.011), anxiety/depression (u=984 000; p=0.002), aggressive behaviour (u=920 500; p=0.001), attention problems (u=1123 500; p=0.027), thought problems (u=1069 500; p=0.010), internalisation (u=869 000; p=0.0) and externalisation (u=1163 000; p=0.05). Patients with severe CHD (u=939 000; p=0.03) and surgical repair (u=719 000; p=0.037) showed worse psychosocial adjustment. Those with poor social support showed more withdrawal (u=557 500; p=0.0) and social problems (u=748 500; p=0.023), and patients with unsatisfactory school performance revealed more anxiety/depression (u=916 000; p=0.02) and attention problems (u=861 500; p=0.007).ConclusionsCHD males with good social support and good academic performance have a better psychosocial adjustment.
Effectiveness and cost-effectiveness of a novel, group self-management course for adults with chronic musculoskeletal pain: study protocol for a multicentre, randomised controlled trial (COPERS)
Authors: Carnes Dawn , Taylor Stephanie JC , Homer Kate , Eldridge Sandra , Bremner Stephen , Pincus Tamar , Rahman Anisur , Underwood Martin 
Published: January 2013

IntroductionChronic musculoskeletal pain is a common condition that often responds poorly to treatment. Self-management courses have been advocated as a non-drug pain management technique, although evidence for their effectiveness is equivocal. We designed and piloted a self-management course based on evidence for effectiveness for specific course components and characteristics.Methods/analysisCOPERS (coping with persistent pain, effectiveness research into self-management) is a pragmatic randomised controlled trial testing the effectiveness and cost-effectiveness of an intensive, group, cognitive behavioural-based, theoretically informed and manualised self-management course for chronic pain patients against a control of best usual care: a pain education booklet and a relaxation CD. The course lasts for 15 h, spread over 3 days, with a –2 h follow-up session 2 weeks later. We aim to recruit 685 participants with chronic musculoskeletal pain from primary, intermediate and secondary care services in two UK regions. The study is powered to show a standardised mean difference of 0.3 in the primary outcome, pain-related disability. Secondary outcomes include generic health-related quality of life, healthcare utilisation, pain self-efficacy, coping, depression, anxiety and social engagement. Outcomes are measured at 6 and 12 months postrandomisation. Pain self-efficacy is measured at 3 months to assess whether change mediates clinical effect.Ethics/disseminationEthics approval was given by Cambridgeshire Ethics 11/EE/046. This trial will provide robust data on the effectiveness and cost-effectiveness of an evidence-based, group self-management programme for chronic musculoskeletal pain. The published outcomes will help to inform future policy and practice around such self-management courses, both nationally and internationally.Trial registrationISRCTN24426731.
Targeting the Deregulated Spliceosome Core Machinery in Cancer Cells Triggers mTOR Blockade and Autophagy
Authors: Quidville Virginie , Alsafadi Samar , Goubar Aïcha , Commo Frédéric , Scott Véronique , Pioche-Durieu Catherine , Girault Isabelle , Baconnais Sonia , Le Cam Eric , Lazar Vladimir , Delaloge Suzette , Saghatchian Mahasti , Pautier Patricia , Morice Philippe , Dessen Philippe , Vagner Stéphan , André Fabrice 
Published: January 2013

Abstract
The spliceosome is a large ribonucleoprotein complex that guides pre-mRNA splicing in eukaryotic cells. Here, we determine whether the spliceosome could constitute an attractive therapeutic target in cancer. Analysis of gene expression arrays from lung, breast, and ovarian cancers datasets revealed that several genes encoding components of the core spliceosome composed of a heteroheptameric Sm complex were overexpressed in malignant disease as compared with benign lesions and could also define a subset of highly aggressive breast cancers. siRNA-mediated depletion of SmE (SNRPE) or SmD1 (SNRPD1) led to a marked reduction of cell viability in breast, lung, and melanoma cancer cell lines, whereas it had little effect on the survival of the nonmalignant MCF-10A breast epithelial cells. SNRPE or SNRPD1 depletion did not lead to apoptotic cell death but autophagy, another form of cell death. Indeed, induction of autophagy was revealed by cytoplasmic accumulation of autophagic vacuoles and by an increase in both LC3 (MAP1LC3A) protein conversion and the amount of acidic autophagic vacuoles. Knockdown of SNRPE dramatically decreased mTOR mRNA and protein levels and was accompanied by a deregulation of the mTOR pathway, which, in part, explains the SNRPE-dependent induction of autophagy. These findings provide a rational to develop new therapeutic agents targeting spliceosome core components in oncology. Cancer Res; 73(7); 2247–58. ©2013 AACR.
Biological Characterization of TAK-901, an Investigational, Novel, Multitargeted Aurora B Kinase Inhibitor
Authors: Farrell Pamela , Shi Lihong , Matuszkiewicz Jennifer , Balakrishna Deepika , Hoshino Takashi , Zhang Lilly , Elliott Sarah , Fabrey Robyn , Lee Bumsup , Halkowycz Petro , Sang BiChing , Ishino Seigo , Nomura Toshiyuki , Teratani Mika , Ohta Yoshikazu , Grimshaw Charles , Paraselli Bheema , Satou Takashi , de Jong Ron 
Published: January 2013

Abstract
Protein kinases Aurora A, B, and C play essential roles during mitosis and cell division, are frequently elevated in cancer, and represent attractive targets for therapeutic intervention. TAK-901 is an investigational, multitargeted Aurora B kinase inhibitor derived from a novel azacarboline kinase hinge-binder chemotype. TAK-901 exhibited time-dependent, tight-binding inhibition of Aurora B, but not Aurora A. Consistent with Aurora B inhibition, TAK-901 suppressed cellular histone H3 phosphorylation and induced polyploidy. In various human cancer cell lines, TAK-901 inhibited cell proliferation with effective concentration values from 40 to 500 nmol/L. Examination of a broad panel of kinases in biochemical assays revealed inhibition of multiple kinases. However, TAK-901 potently inhibited only a few kinases other than Aurora B in intact cells, including FLT3 and FGFR2. In rodent xenografts, TAK-901 exhibited potent activity against multiple human solid tumor types, and complete regression was observed in the ovarian cancer A2780 model. TAK-901 also displayed potent activity against several leukemia models. In vivo biomarker studies showed that TAK-901 induced pharmacodynamic responses consistent with Aurora B inhibition and correlating with retention of TAK-901 in tumor tissue. These preclinical data highlight the therapeutic potential of TAK-901, which has entered phase I clinical trials in patients within a diverse range of cancers. Mol Cancer Ther; 12(4); 460–70. ©2013 AACR.
RHOA-FAK Is a Required Signaling Axis for the Maintenance of KRAS-Driven Lung Adenocarcinomas
Authors: Konstantinidou Georgia , Ramadori Giorgio , Torti Francesca , Kangasniemi Kim , Ramirez Rachel E. , Cai Yiran , Behrens Carmen , Dellinger Michael T. , Brekken Rolf A. , Wistuba Ignacio I. , Heguy Adriana , Teruya-Feldstein Julie , Scaglioni Pier Paolo 
Published: January 2013

Abstract
Non–small cell lung cancer (NSCLC) often expresses mutant KRAS together with tumor-associated mutations of the CDKN2A locus, which are associated with aggressive, therapy-resistant tumors. Here, we unravel specific requirements for the maintenance of NSCLC that carries this genotype. We establish that the extracellular signal-regulated kinase (ERK)/RHOA/focal adhesion kinase (FAK) network is deregulated in high-grade lung tumors. Suppression of RHOA or FAK induces cell death selectively in mutant KRAS;INK4A/ARF-deficient lung cancer cells. Furthermore, pharmacologic inhibition of FAK caused tumor regression specifically in the high-grade lung cancer that developed in mutant Kras;Cdkn2a-null mice. These findings provide a rationale for the rapid implementation of genotype-specific targeted therapies using FAK inhibitors in patients with cancer.
Significance: Targeted therapies are effective for only a small fraction of patients with cancer. We report that FAK inhibitors exert potent antitumor effects in NSCLCs that express mutant KRAS in association with INK4A/ARF deficiency. These results reveal a novel genotype-specific vulnerability of cancer cells that can be exploited for therapeutic purposes. Cancer Discov; 3(4); 444–57. ©2013 AACR.
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