bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between Glycopeptide Production and Resistance in the Actinomycete Nonomuraea sp. ATCC 39727
Authors: Marcone Giorgia Letizia , Binda Elisa , Carrano Lucia , Bibb Mervyn , Marinelli Flavia 
Published: June 2014

ABSTRACTGlycopeptides and β-lactams inhibit bacterial peptidoglycan synthesis in Gram-positive bacteria; resistance to these antibiotics is studied intensively in enterococci and staphylococci because of their relevance to infectious disease. Much less is known about antibiotic resistance in glycopeptide-producing actinomycetes that are likely to represent the evolutionary source of resistance determinants found in bacterial pathogens.Nonomuraeasp. ATCC 39727, the producer of A40926 (the precursor for the semisynthetic dalbavancin), does not harbor the canonicalvanHAXgenes. Consequently, we investigated the role of the β-lactam-sensitived,d-peptidase/d,d-carboxypeptidase encoded byvanYn, the onlyvan-like gene found in the A40926 biosynthetic gene cluster, in conferring immunity to the antibiotic inNonomuraeasp. ATCC 39727. Taking advantage of the tools developed recently to genetically manipulate this uncommon actinomycete, we variedvanYngene dosage and expressedvanHatAatXatfrom the teicoplanin producerActinoplanes teichomyceticusinNonomuraeasp. ATCC 39727. Knocking outvanYn, complementing avanYnmutant, or duplicatingvanYnhad no effect on growth but influenced antibiotic resistance and, in the cases of complementation and duplication, antibiotic production.Nonomuraeasp. ATCC 39727 was found to be resistant to penicillins, but its glycopeptide resistance was diminished in the presence of penicillin G, which inhibits VanYnactivity. The heterologous expression ofvanHatAatXatincreased A40926 resistance inNonomuraeasp. ATCC 39727 but did not increase antibiotic production, indicating that the level of antibiotic production is not directly determined by the level of resistance. ThevanYn-based self-resistance inNonomuraeasp. ATCC 39727 resembles the glycopeptide resistance mechanism described recently in mutants ofEnterococcus faeciumselectedin vitrofor high-level resistance to glycopeptides and penicillins.
Changes in Antigen-Specific Cytokine and Chemokine Responses to Plasmodium falciparum Antigens in a Highland Area of Kenya after a Prolonged Absence of Malaria Exposure
Authors: Ochola Lyticia A. , Ayieko Cyrus , Kisia Lily , Magak Ng'wena G. , Shabani Estela , Ouma Collins , John Chandy C. 
Published: June 2014

ABSTRACTIndividuals naturally exposed toPlasmodium falciparumlose clinical immunity after a prolonged lack of exposure.P. falciparumantigen-specific cytokine responses have been associated with protection from clinical malaria, but the longevity ofP. falciparumantigen-specific cytokine responses in the absence of exposure is not well characterized. A highland area of Kenya with low and unstable malaria transmission provided an opportunity to study this question. The levels of antigen-specific cytokines and chemokines associated in previous studies with protection from clinical malaria (gamma interferon [IFN-γ], interleukin-10 [IL-10], and tumor necrosis factor alpha [TNF-α]), with increased risk of clinical malaria (IL-6), or with pathogenesis of severe disease in malaria (IL-5 and RANTES) were assessed by cytometric bead assay in April 2008, October 2008, and April 2009 in 100 children and adults. During the 1-year study period, none had an episode of clinicalP. falciparummalaria. Two patterns of cytokine responses emerged, with some variation by antigen: a decrease at 6 months (IFN-γ and IL-5) or at both 6 and 12 months (IL-10 and TNF-α) or no change over time (IL-6 and RANTES). These findings document thatP. falciparumantigen-specific cytokine responses associated in prior studies with protection from malaria (IFN-γ, TNF-α, and IL-10) decrease significantly in the absence ofP. falciparumexposure, whereas those associated with increased risk of malaria (IL-6) do not. The study findings provide a strong rationale for future studies of antigen-specific IFN-γ, TNF-α, and IL-10 responses as biomarkers of increased population-level susceptibility to malaria after prolonged lack ofP. falciparumexposure.
Antibodies to PhnD Inhibit Staphylococcal Biofilms
Authors: Lam Hubert , Kesselly Augustus , Stegalkina Svetlana , Kleanthous Harry , Yethon Jeremy A. 
Published: June 2014

ABSTRACT

Biofilm formation on central lines or peripheral catheters is a serious threat to patient well-being. Contaminated vascular devices can act as a nidus for bloodstream infection and systemic pathogen dissemination. Staphylococcal biofilms are the most common cause of central-line-associated bloodstream infections, and antibiotic resistance makes them difficult to treat. As an alternative to antibiotic intervention, we sought to identify anti-staphylococcal biofilm targets for the development of a vaccine or antibody prophylactic. A screening strategy was devised using a microfluidic system to test antibody-mediated biofilm inhibition under biologically relevant conditions of shear flow. Affinity-purified polyclonal antibodies to target antigen PhnD inhibited both
Staphylococcus epidermidis
and
S. aureus
biofilms. PhnD-specific antibodies blocked biofilm development at the initial attachment and aggregation stages, and deletion of
phnD
inhibited normal biofilm formation. We further adapted our microfluidic biofilm system to monitor the interaction of human neutrophils with staphylococcal biofilms and demonstrated that PhnD-specific antibodies also serve as opsonins to enhance neutrophil binding, motility, and biofilm engulfment. These data support the identification of PhnD as a lead target for biofilm intervention strategies performed either by vaccination or through passive administration of antibodies.
Amino Acid Residues of RegA Important for Interactions with the CbbR-DNA Complex of Rhodobacter sphaeroides
Authors: Dangel Andrew W. , Luther Amanda , Tabita F. Robert 
Published: June 2014

ABSTRACT

CbbR and RegA (PrrA) are transcriptional regulators of the Calvin-Benson-Bassham (CBB) CO
2
fixation pathway (

cbb
I

and

cbb
II

) operons of
Rhodobacter sphaeroides
. The CbbR and RegA proteins interact, but CbbR must be bound to the promoter DNA in order for RegA-CbbR protein-protein interactions to occur. RegA greatly enhances the ability of CbbR to bind the

cbb
I

promoter or greatly enhances the stability of the CbbR/promoter complex. The N-terminal receiver domain and the DNA binding domain of RegA were shown to interact with CbbR. Residues in α-helix 7 and α-helix 8 of the DNA binding domain (helix-turn-helix) of RegA directly interacted with CbbR, with α-helix 7 positioned immediately above the DNA and α-helix 8 located in the major groove of the DNA. A CbbR protein containing only the DNA binding motif and the linker helix was capable of binding to RegA. In contrast, a truncated CbbR containing only the linker helix and recognition domains I and II (required for effector binding) was not able to interact with RegA. The accumulated results strongly suggest that the DNA binding domains of both proteins interact to facilitate optimal transcriptional control over the
cbb
operons.
In vivo
analysis, using constitutively active mutant CbbR proteins, further indicated that CbbR must interact with phosphorylated RegA in order to accomplish transcriptional activation.
Pentaplex PCR Assay for Detection of Hemorrhagic Bacteria from Stool Samples
Authors: Al-Talib Hassanain , Latif Baha , Mohd-Zain Zaini 
Published: June 2014

ABSTRACT

Diarrheal diseases cause illness and death among children younger than 10 years in developing countries. Conventional testing for the detection of hemorrhagic bacteria takes 2 to 5 days to yield complete information on the organism and its antibiotic sensitivity pattern. Hence, in the present study, we developed a molecular-based diagnostic assay that identifies common hemorrhagic bacteria in stool samples. A set of specific primers were designed for the detection of
Salmonella
spp.,
Shigella
spp., enterohemorrhagic
Escherichia coli
(EHEC), and
Campylobacter
spp., suitable for use in a one-tube PCR assay. The assay in the present study simultaneously detected five genes, namely,
ompC
for the
Salmonella
genus,
virA
for the
Shigella
genus,
eaeA
for EHEC, 16S rRNA for the
Campylobacter
genus, and
hemA
for an internal control. Specific primer pairs were successfully designed and simultaneously amplified the targeted genes. Validation with 20 Gram-negative and 17 Gram-positive strains yielded 100% specificity. The limit of detection of the multiplex PCR assay was 1 × 10
3
CFU at the bacterial cell level and 100 pg at the genomic DNA level. Further evaluation of the multiplex PCR with 223 bacterium-spiked stool specimens revealed 100% sensitivity and specificity. We conclude that the developed multiplex PCR assay was rapid, giving results within 4 h, which is essential for the identification of hemorrhagic bacteria, and it might be useful as an additional diagnostic tool whenever time is important in the diagnosis of hemorrhagic bacteria that cause diarrhea. In addition, the presence of an internal control in the multiplex PCR assay is important for excluding false-negative cases.
Diagnosis of Ureaplasma urealyticum Septic Polyarthritis by PCR Assay and Electrospray Ionization Mass Spectrometry in a Patient with Acute Lymphoblastic Leukemia
Authors: Balsat Marie , Galicier Lionel , Wargnier Alain , Pereyre Sabine , Itzykson Raphaël , Zouakh Myriem , Bébéar Cécile , Boissel Nicolas 
Published: June 2014

ABSTRACT

We report a case of polyarthritis with axial involvement in a young female patient treated for acute lymphoblastic leukemia. Detection in the hip fluid of
Ureaplasma urealyticum
by broad-range PCR followed by electrospray ionization mass spectrometry allowed the diagnosis of septic arthritis and
ad integrum
recovery upon adapted antibiotic therapy.
Detection of Chronic Wasting Disease in the Lymph Nodes of Free-Ranging Cervids by Real-Time Quaking-Induced Conversion
Authors: Haley Nicholas J. , Carver Scott , Hoon-Hanks Laura L. , Henderson Davin M. , Davenport Kristen A. , Bunting Elizabeth , Gray Shawn , Trindle Bruce , Galeota Judith , LeVan Ivy , Dubovos Tracy , Shelton Paul , Hoover Edward A. 
Published: June 2014

ABSTRACT
Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of deer, elk, and moose, is the only prion disease affecting free-ranging animals. Since the disease was first identified in northern Colorado and southern Wyoming in 1967, new epidemic foci of the disease have been identified in 20 additional states, as well as two Canadian provinces and the Republic of South Korea. Identification of CWD-affected animals currently requires postmortem analysis of brain or lymphoid tissues using immunohistochemistry (IHC) or an enzyme-linked immunosorbent assay (ELISA), with no practical way to evaluate potential strain types or to investigate the epidemiology of existing or novel foci of disease. Using a standardized real-time (RT)-quaking-induced conversion (QuIC) assay, a seeded amplification assay employing recombinant prion protein as a conversion substrate and thioflavin T (ThT) as an amyloid-binding fluorophore, we analyzed, in a blinded manner, 1,243 retropharyngeal lymph node samples from white-tailed deer, mule deer, and moose, collected in the field from areas with current or historic CWD endemicity. RT-QuIC results were then compared with those obtained by conventional IHC and ELISA, and amplification metrics using ThT and thioflavin S were examined in relation to the clinical history of the sampled deer. The results indicate that RT-QuIC is useful for both identifying CWD-infected animals and facilitating epidemiological studies in areas in which CWD is endemic or not endemic.
Encephalitis Caused by Chikungunya Virus in a Traveler from the Kingdom of Tonga
Authors: Nelson Joanna , Waggoner Jesse J. , Sahoo Malaya K. , Grant Philip M. , Pinsky Benjamin A. 
Published: June 2014

ABSTRACT
Febrile travelers from countries with unique endemic pathogens pose a significant diagnostic challenge. In this report, we describe the case of a Tongan man presenting with fever, rash, and altered mental status. The diagnosis of Chikungunya encephalitis was made using a laboratory-developed real-time RT-PCR and serologic testing.
Addressing the evidence to practice gap for complex interventions in primary care: a systematic review of reviews protocol
Authors: Lau Rosa , Stevenson Fiona , Ong Bie Nio , Dziedzic Krysia , Eldridge Sandra , Everitt Hazel , Kennedy Anne , Kontopantelis Evangelos , Little Paul , Qureshi Nadeem , Rogers Anne , Treweek Shaun , Peacock Richard , Murray Elizabeth 
Published: June 2014

IntroductionGetting the results of research implemented into routine healthcare is often a challenge. The disconnect between the development and implementation of evidence into practice is called the ‘second translational gap’ and is particularly apparent in primary care. To address this gap, we plan to identify, summarise and synthesise currently available evidence by undertaking a systematic review of reviews to: (1) explore barriers and facilitators of implementation of research evidence or complex interventions, and (2) assess the effectiveness of strategies in facilitating implementation of complex interventions in primary care.Methods and analysisThis is a protocol for a systematic review of reviews. We will search MEDLINE, EMBASE, the Cochrane Library, CINAHL and PsycINFO up until December 2013. We will check reference lists of included studies for further studies. Two authors will independently screen the titles and abstracts identified from the search; any discrepancies will be resolved by discussion and consensus. Full-text papers will be obtained and relevant reviews will be selected against inclusion criteria. Eligible reviews have to be based on predominantly primary care in developed countries and examine either factors to implementation or, the effectiveness of strategies to optimise implementation. Data from eligible reviews will be extracted using standardised data abstraction forms. For barriers and facilitators, data will be synthesised using an interpretative meta-synthesis approach. For implementation strategies, findings will be summarised and described narratively and synthesised using a framework approach. All findings will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Ethics and disseminationEthical approval is not required. The review findings will inform the work of the design and implementation of future studies and will be of interest to a wide audience including health professionals, researchers, health service or commissioning managers and policymakers.Trial registration numberProtocol registration number (PROSPERO CRD42014009410).
Effectiveness of the 2005 compulsory personal flotation device (PFD) wearing regulations in reducing drowning deaths among recreational boaters in Victoria, Australia
Authors: Bugeja Lyndal , Cassell Erin , Brodie Lisa R , Walter Simon J 
Published: June 2014

ObjectiveTo investigate whether the Victorian mandatory personal flotation device wearing regulations that came into effect on 1 December 2005 reduced drowning deaths among recreational boaters in Victoria, Australia.DesignA retrospective population-based ‘before and after’ study using Victorian coronial data on drowning deaths of occupants of recreational vessels operating in Victorian waters.MethodsThe annual numbers of deaths in the 5 years after the transition year of the regulations (2005) was compared with the annual numbers of deaths in the 6 years prior to the transition year, using the Mann-Whitney U test.ResultsThere were 59 recreational boating drowning deaths in the 6-year preintervention period (1 December 1998 to 30 November 2004) compared with 16 in the 5-year postintervention period (1 December 2005 to 30 November 2010). The analysis showed a significant decrease in drowning deaths among all recreational boaters (U=30.0, p=0.01) and among these strata: vessel occupants aged 0–29 years (U=28.0, p=0.02) and 30–59 years (U=27.5, p=0.02), vessel occupants engaged in pleasure cruising (U=29.0, p=0.01) and in ‘other’ boating activities (U=25.0, p=0.04), boaters on small powerboats ≤4.8 m in length (U=29.5; p=0.01), boaters on motorised (U=29.5; p=0.01) and sail-powered vessels (U=26.0; p=0.04), and occupants of vessels operating in inland waterways (U=30.0; p=0.01).ConclusionsThese findings provide further support for the adoption of a regulatory approach to personal flotation device wearing to reduce drowning among recreational boaters.
Polarization-Sensitive Multimodal Imaging for Detecting Breast Cancer
Authors: Patel Rakesh , Khan Ashraf , Quinlan Robert , Yaroslavsky Anna N. 
Published: June 2014

Abstract
Intraoperative delineation of breast cancer is a significant problem in surgical oncology. A reliable method for demarcation of malignant breast tissue during surgery would reduce the re-excision rate due to positive margins. We present a novel method of identifying breast cancer margins using combined dye-enhanced wide-field fluorescence polarization imaging for en face cancer margins and polarization-sensitive (PS) optical coherence tomography (OCT) for cross-sectional evaluation. Tumor specimens were collected following breast surgery, stained with methylene blue, and imaged. Wide-field fluorescence polarization images were excited at 640 nm and registered between 660 and 750 nm. Standard and PS OCT images were acquired using a commercial 1,310-nm swept-source system. The imaging results were validated against histopathology. Statistically significant higher fluorescence polarization of cancer as compared with both normal and fibrocystic tumor tissue was measured in all the samples. Fluorescence polarization delineated lateral breast cancer margins with contrast superior to that provided by OCT. However, OCT complemented fluorescence polarization imaging by facilitating cross-sectional inspection of tissue. PS OCT yielded higher contrast between cancer and connective tissue, as compared with standard OCT. Combined PS OCT and fluorescence polarization imaging shows promise for intraoperative delineation of breast cancer. Cancer Res; 74(17); 4685–93. ©2014 AACR.
IL-1β-Mediated Repression of microRNA-101 Is Crucial for Inflammation-Promoted Lung Tumorigenesis
Authors: Wang Lin , Zhang Ling-Fei , Wu Jing , Xu Shu-Jun , Xu Yang-Yang , Li Dangsheng , Lou Jia-Tao , Liu Mo-Fang 
Published: June 2014

Abstract
Inflammatory stimuli clearly contribute to lung cancer development and progression, but the underlying pathogenic mechanisms are not fully understood. We found that the proinflammatory cytokine IL-1β is dramatically elevated in the serum of patients with non–small cell lung cancer (NSCLC). In vitro studies showed that IL-1β promoted the proliferation and migration of NSCLC cells. Mechanistically, IL-1β acted through the COX2–HIF1α pathway to repress the expression of microRNA-101 (miR-101), a microRNA with an established role in tumor suppression. Lin28B was identified as critical effector target of miR-101 with its repression of Lin28B, a critical aspect of tumor suppression. Overall, IL-1β upregulated Lin28B by downregulating miR-101. Interestingly, cyclooxygenase-2 inhibition by aspirin or celecoxib abrogated IL-1β-mediated repression of miR-101 and IL-1β-mediated activation of Lin28B along with their stimulatory effects on NSCLC cell proliferation and migration. Together, our findings defined an IL-1β–miR-101–Lin28B pathway as a novel regulatory axis of pathogenic inflammatory signaling in NSCLC. Cancer Res; 74(17); 4720–30. ©2014 AACR.
Decreased Expression of miR216a Contributes to Non–Small-Cell Lung Cancer Progression
Authors: Wang Ren-Tao , Xu Meng , Xu Cheng-Xiong , Song Zhi-Gang , Jin Hua 
Published: June 2014

Abstract
Purpose: The aim of the present study is to investigate the role and mechanism of miR216a in non–small-cell lung cancer (NSCLC).
Experimental Design: The expression of miR216a in NSCLC cell lines and from NSCLC patient specimens was measured by real-time qRT-PCR. The correlation between gene expression and patient survival was analyzed using Kaplan–Meier methods. The effects of miR216a on NSCLC cell growth and metastasis were examined both in vitro and in vivo by overexpressing or inhibiting miR216a. Finally, the effect of miR216a on chemoresistance was investigated by MTT assay and flow cytometry.
Results: miR216a expression was downregulated in specimens from patients with NSCLC compared with corresponding nontumor lung tissues. Clinical data indicate that decreased miR216a expression is inversely correlated with cancer stage, metastasis, and poor survival in patients with NSCLC. Our data also show that overexpression of miR216a suppresses NSCLC cell growth and metastasis, and enhances cisplatin-induced cell growth inhibition and apoptosis. In contrast, inhibition of miR216a stimulates NSCLC cell growth and metastasis, and suppresses cisplatin-induced cell growth inhibition and apoptosis. Furthermore, we demonstrate that miR216a exerts its role by directly targeting eIF4B and ZEB1.
Conclusion: Our findings suggest that miR216a is a cancer suppressor miRNA and that overexpression of miR216a is a novel NSCLC treatment strategy. In addition, our clinical data indicate that miR216a may be a useful biomarker for predicting NSCLC progression. Clin Cancer Res; 20(17); 4705–16. ©2014 AACR.
Adverse prognosis of incidentally detected ambulatory atrial fibrillation
Authors: Martinez Carlos , Katholing Anja , Freedman Saul Benedict 
Published: June 2014

SummaryIt was the aim of this study to determine prognosis of incidentally detected ambulatory atrial fibrillation (IA-AF) and its response to antithrombotic therapy. We performed a cohort study of 5,555 patients with IA-AF (mean age 70.9 ± 10.1, 38.4% female) and 24,705 age- and gender-matched controls without AF followed three years using UK Clinical Practice Research Datalink. We measured incidence rates of stroke, all-cause mortality, myocardial infarction, major bleeding, and effect of antithrombotic therapy. Patients with IA-AF had mean CHA2DS2VASc score 2.5 ± 1.5, 73% with score ≥2. The stroke incidence rate (IR) was 19.4 (95% confidence interval 17.1 – 21.9)/1,000 person-years vs 8.4 (7.7 – 9.1) in controls (p<0.001), mortality 40.1 (36.8 – 43.6)/1,000 person-years vs 20.9 (19.8 – 22.0) in controls (p<0.001), and myocardial infarction 9.0 (7.5 – 10.8)/1,000 person-years vs 6.5 (5.9 – 7.2) in controls (p<0.001). IRs of all endpoints increased with age. Oral anticoagulant ± antiplatelet therapy received by 51.0% in year following IA-AF was associated with adjusted hazard ratio (HR) of 0.35 (0.17 – 0.71) for stroke, and 0.56 (0.36 – 0.85) for death compared to no therapy, while antiplatelet treatment was associated with a non-significant reduction of HR: 0.81 (0.51 – 1.29) for stroke, and 0.80 (0.55 – 1.15) for death, though both carried a similar small non-significant adjusted excess IR of major bleeding. In conclusion, asymptomatic AF detected incidentally is associated with a significant adverse effect on stroke and death, with reduction in both associated with oral anticoagulant but not antiplatelet treatment. This provides justification to assess cost-effectiveness of community screening to detect unknown AF.