bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sonication of Explanted Cardiac Implants Improves Microbial Detection in Cardiac Device Infections
Authors: Oliva Alessandra , Nguyen Bich Lien , Mascellino Maria T. , D'Abramo Alessandra , Iannetta Marco , Ciccaglioni Antonio , Vullo Vincenzo , Mastroianni Claudio M. 
Published: November 2012

ABSTRACT

The sonication technique has been shown to be a promising tool for microbiological diagnosis of device-related infections. We evaluated the usefulness of the sonication method for pathogen detection in 80 explanted cardiac components collected from 40 patients, and the results were compared with those of conventional cultures. Forty subjects undergoing cardiac device removal were studied: 20 had cardiac device infection, and 20 subjects underwent elective generator replacement or revision in the absence of infection. Sonication of explanted devices was more sensitive than traditional culture for microbial detection (67% and 50%, respectively;
P
= 0.0005). The bacterial count detected in sonication fluid culture was significantly higher than that detected in traditional culture in both infected (
P
= 0.019) and uninfected (
P
= 0.029) devices. In the infected patients, sonication fluid culture yielded a significantly higher rate of pathogen detection in explanted electrodes than traditional culture (65% versus 45%;
P
= 0.02), while no differences were found in the generators. Ten strains were detected only through sonication fluid culture: 6
Staphylococcus epidermidis
strains, 1
Staphylococcus hominis
strain, 2
Corynebacterium striatum
strains, and 1
Brevundimonas
sp. Neither the type nor the duration of antimicrobial therapy before device removal had an effect on the diagnostic performance of sonication fluid culture (
P
= 0.75 and
P
= 0.56, respectively). In the patients without infection, sonication fluid culture was positive in 8 cases (40%), whereas conventional culture was positive in only 4 (20%). In summary, the sonication technique improves the microbiological diagnosis of explanted cardiac devices.
Receptor Characterization and Susceptibility of Cotton Rats to Avian and 2009 Pandemic Influenza Virus Strains
Authors: Blanco Jorge C. G. , Pletneva Lioubov M. , Wan Hongquan , Araya Yonas , Angel Matthew , Oue Raymonde O. , Sutton Troy C. , Perez Daniel R. 
Published: November 2012

ABSTRACT

Animal influenza viruses (AIVs) are a major threat to human health and the source of pandemic influenza. A reliable small-mammal model to study the pathogenesis of infection and for testing vaccines and therapeutics against multiple strains of influenza virus is highly desirable. We show that cotton rats (
Sigmodon hispidus
) are susceptible to avian and swine influenza viruses. Cotton rats express α2,3-linked sialic acid (SA) and α2,6-linked SA residues in the trachea and α2,6-linked SA residues in the lung parenchyma. Prototypic avian influenza viruses (H3N2, H9N2, and H5N1) and swine-origin 2009 pandemic H1N1 viruses replicated in the nose and in the respiratory tract of cotton rats without prior adaptation and produced strong lung pathology that was characterized by early lung neutrophilia, followed by subsequent pneumonia. Consistent with other natural and animal models of influenza, only the H5N1 virus was lethal for cotton rats. More importantly, we show that the different avian and pandemic H1N1 strains tested are strong activators of the type I interferon (IFN)-inducible MX-1 gene both locally and systemically. Our data indicate that the cotton rat is a suitable small-mammal model to study the infection of animal influenza viruses and for validation of vaccines and therapeutics against these viruses.
Intramuscular Inoculation of Mice with the Live-Attenuated Recombinant Rabies Virus TriGAS Results in a Transient Infection of the Draining Lymph Nodes and a Robust, Long-Lasting Protective Immune Response against Rabies
Authors: Schutsky Keith , Curtis Dana , Bongiorno Emily K. , Barkhouse Darryll A. , Kean Rhonda B. , Dietzschold Bernhard , Hooper D. Craig , Faber Milosz 
Published: November 2012

ABSTRACT
A single intramuscular application of the live but not UV-inactivated recombinant rabies virus (RABV) variant TriGAS in mice induces the robust and sustained production of RABV-neutralizing antibodies that correlate with long-term protection against challenge with an otherwise lethal dose of the wild-type RABV. To obtain insight into the mechanism by which live TriGAS induces long-lasting protective immunity, quantitative PCR (qPCR) analysis of muscle tissue, draining lymph nodes, spleen, spinal cord, and brain at different times after TriGAS inoculation revealed the presence of significant copy numbers of RABV-specific RNA in muscle, lymph node, and to a lesser extent, spleen for several days postinfection. Notably, no significant amounts of RABV RNA were detected in brain or spinal cord at any time after TriGAS inoculation. Differential qPCR analysis revealed that the RABV-specific RNA detected in muscle is predominantly genomic RNA, whereas RABV RNA detected in draining lymph nodes is predominantly mRNA. Comparison of genomic RNA and mRNA obtained from isolated lymph node cells showed the highest mRNA-to-genomic-RNA ratios in B cells and dendritic cells (DCs), suggesting that these cells represent the major cell population that is infected in the lymph node. Since RABV RNA declined to undetectable levels by 14 days postinoculation of TriGAS, we speculate that a transient infection of DCs with TriGAS may be highly immunostimulatory through mechanisms that enhance antigen presentation. Our results support the superior efficacy and safety of TriGAS and advocate for its utility as a vaccine.
Tombusvirus Y-Shaped Translational Enhancer Forms a Complex with eIF4F and Can Be Functionally Replaced by Heterologous Translational Enhancers
Authors: Nicholson Beth L. , Zaslaver Olga , Mayberry Laura K. , Browning Karen S. , White K. Andrew 
Published: November 2012

ABSTRACT

Certain plus-strand RNA plant viruses that are uncapped and nonpolyadenylated rely on RNA elements in their 3′ untranslated region, termed 3′-cap-independent translational enhancers (3′CITEs), for efficient translation of their proteins. Here, we have investigated the properties of the Y-shaped class of 3′CITE present in the tombusvirus
Carnation Italian ringspot virus
(CIRV). While some types of 3′CITE have been found to function through recruitment of translation initiation factors to the viral genome, no
trans
-acting translation-related factors have yet been identified for the Y-shaped 3′CITE. Our results indicate that the CIRV 3′CITE complexes with eIF4F and eIFiso4F, with the former mediating translation more efficiently than the latter. In nature, some classes of 3′CITE are present in several different viral genera, suggesting that these elements hold a high degree of modularity. Here, we test this concept by engineering chimeric viruses containing heterologous 3′CITEs and show that the Y-shaped class of 3′CITE in CIRV can be replaced by two alternative types of 3′CITE, i.e., a
Panicum mosaic virus
-like 3′CITE or an I-shaped 3′CITE, without any major loss in
in vitro
translation or replication efficiency in protoplasts. The heterologous 3′CITEs also mediated whole-plant infections of
Nicotiana benthamiana
, where distinct symptoms were observed for each of the alternative 3′CITEs and 3′CITE evolution occurred during serial passaging. Our results supply new information on Y-shaped 3′CITE function and provide insights into 3′CITE virus-host compatibilities.
Analysis of Viral Membranes Formed in Cells Infected by a Vaccinia Virus L2-Deletion Mutant Suggests Their Origin from the Endoplasmic Reticulum
Authors: Maruri-Avidal Liliana , Weisberg Andrea S. , Bisht Himani , Moss Bernard 
Published: November 2012

ABSTRACT
Assembly of the poxvirus immature virion (IV) membrane is a poorly understood event that occurs within the cytoplasm. At least eight viral proteins participate in formation of the viral membrane. Of these, A14, A17, and D13 are structural components whereas A6, A11, F10, H7, and L2 participate in membrane biogenesis. L2, the object of this study, is conserved in all chordopoxviruses, expressed early in infection, and associated with the endoplasmic reticulum (ER) throughout the cell and at the edges of crescent-shaped IV precursors. Previous studies with an inducible L2 mutant revealed abortive formation of the crescent membrane. However, possible low-level L2 synthesis under nonpermissive conditions led to ambiguity in interpretation. Here, we constructed a cell line that expresses L2, which allowed the creation of an L2-deletion mutant. In noncomplementing cells, replication was aborted prior to formation of mature virions and two types of aberrant structures were recognized. One consisted of short crescents, at the surface of dense masses of viroplasm, which were labeled with antibodies to the A11, A14, A17, and D13 proteins. The other structure consisted of “empty” IV-like membranes, also labeled with antibodies to the viral proteins, which appeared to be derived from adjacent calnexin-containing ER. A subset of 25 proteins examined, exemplified by components of the entry-fusion complex, were greatly diminished in amount. The primary role of L2 may be to recruit ER and modulate its transformation to viral membranes in juxtaposition with the viroplasm, simultaneously preventing the degradation of viral proteins dependent on viral membranes for stability.
Neurotropic Arboviruses Induce Interferon Regulatory Factor 3-Mediated Neuronal Responses That Are Cytoprotective, Interferon Independent, and Inhibited by Western Equine Encephalitis Virus Capsid
Authors: Peltier Daniel C. , Lazear Helen M. , Farmer Jocelyn R. , Diamond Michael S. , Miller David J. 
Published: November 2012

ABSTRACT
Cell-intrinsic innate immune responses mediated by the transcription factor interferon regulatory factor 3 (IRF-3) are often vital for early pathogen control, and effective responses in neurons may be crucial to prevent the irreversible loss of these critical central nervous system cells after infection with neurotropic pathogens. To investigate this hypothesis, we used targeted molecular and genetic approaches with cultured neurons to study cell-intrinsic host defense pathways primarily using the neurotropic alphavirus western equine encephalitis virus (WEEV). We found that WEEV activated IRF-3-mediated neuronal innate immune pathways in a replication-dependent manner, and abrogation of IRF-3 function enhanced virus-mediated injury by WEEV and the unrelated flavivirus St. Louis encephalitis virus. Furthermore, IRF-3-dependent neuronal protection from virus-mediated cytopathology occurred independently of autocrine or paracrine type I interferon activity. Despite being partially controlled by IRF-3-dependent signals, WEEV also disrupted antiviral responses by inhibiting pattern recognition receptor pathways. This antagonist activity was mapped to the WEEV capsid gene, which disrupted signal transduction downstream of IRF-3 activation and was independent of capsid-mediated inhibition of host macromolecular synthesis. Overall, these results indicate that innate immune pathways have important cytoprotective activity in neurons and contribute to limiting injury associated with infection by neurotropic arboviruses.
Stem cells, angiogenesis and muscle healing: a potential role in massage therapies?
Authors: Best Thomas M , Gharaibeh Burhan , Huard Johnny 
Published: November 2012

Skeletal muscle injuries are among the most common and frequently disabling injuries sustained by athletes.Repair of injured skeletal muscle is an area that continues to present a challenge for sports medicine clinicians and researchers due, in part, to complete muscle recovery being compromised by development of fibrosis leading to loss of function and susceptibility to re-injury.Injured skeletal muscle goes through a series of coordinated and interrelated phases of healing including degeneration, inflammation, regeneration and fibrosis. Muscle regeneration initiated shortly after injury can be limited by fibrosis which affects the degree of recovery and predisposes the muscle to reinjury. It has been demonstrated in animal studies that antifibrotic agents that inactivate transforming growth factor (TGF)-β1 have been effective at decreasing scar tissue formation. Several studies have also shown that vascular endothelial growth factor (VEGF) can increase the efficiency of skeletal muscle repair by increasing angiogenesis and, at the same time, reducing the accumulation of fibrosis. We have isolated and thoroughly characterised a population of skeletal muscle-derived stem cells (MDSCs) that enhance repair of damaged skeletal muscle fibres by directly differentiating into myofibres and secreting paracrine factors that promote tissue repair. Indeed, we have found that MDSCs transplanted into skeletal and cardiac muscles have been successful at repair probably because of their ability to secrete VEGF that works in a paracrine fashion. The application of these techniques to the study of sport-related muscle injuries awaits investigation. Other useful strategies to enhance skeletal muscle repair through increased vascularisation may include gene therapy, exercise, neuromuscular electrical stimulation and, potentially, massage therapy. Based on recent studies showing an accelerated recovery of muscle function from intense eccentric exercise through massage-based therapies, we believe that this treatment modality offers a practical and non-invasive form of therapy for skeletal muscle injuries. However, the biological mechanism(s) behind the beneficial effect of massage are still unclear and require further investigation using animal models and potentially randomised, human clinical studies.
Public perceptions and behaviours related to the risk of infection with Aedes mosquito-borne diseases: a cross-sectional study in Southeastern France
Authors: Raude Jocelyn , Chinfatt Kimberly , Huang Peiching , Betansedi Charles Olivier , Katumba Kenneth , Vernazza Nicole , Bley Daniel 
Published: November 2012

ObjectivesTo explore public perceptions and behaviours related to the risk of flavivirus and alphavirus infection in Southeastern regions of France following the recent colonisation of the Asian tiger mosquito,Aedes albopictus, and the identification of four autochthonous cases of dengue and chikungunya fever in these regions.DesignCross-sectional telephone survey using a proportional random digit dialling selection method.SettingInterviews were conducted from 28 November 2011 to 29 January 2012 using a computer-assisted telephone interviewing system.Participants1506 French speaking adults aged 18 years or older residing in French Mediterranean regions.ResultsProtective health behaviours were found to be performed less frequently among men (AOR=0.65, 95% CI 0.52% to 0.80%), residents with lower educational status (AOR=0.61, 95% CI 0.43% to 0.85% for respondents with primary school education; AOR=0.69, 95% CI 0.53% to 0.90% for those with some secondary school education), and those living in regions where the Aedes mosquito is objectively rare (AOR=0.60, 95% CI 0.36% to 0.98% for Aude; AOR=0.63, 95% CI 0.44% to 0.89% for Herault; AOR=0.56, 95% CI 0.34% to 0.93% for Eastern Pyrenees). Empirical results also suggest that behavioural responses to infection risk are greater shaped by the perceived exposure to Aedes, notably the perceived frequency of mosquito bites (AOR=2.07, 95% CI 1.84% to 2.32%) and visual identification of Aedes mosquitoes in one's immediate environment (AOR=1.98, 95% CI 1.45% to 2.71%) rather than by other common predictors of protective behaviours.ConclusionsThese findings may help with the development of innovative instruments designed to make more visible and personal the threat of flavivirus and alphavirus infections induced by the presence ofA albopictusin order to promote significant behavioural changes among populations at risk.
Targeting Folate Receptors to Treat Invasive Urinary Bladder Cancer
Authors: Dhawan Deepika , Ramos-Vara José A. , Naughton James F. , Cheng Liang , Low Philip S. , Rothenbuhler Ryan , Leamon Christopher P. , Parker Nikki , Klein Patrick J. , Vlahov Iontcho R. , Reddy Joseph A. , Koch Michael , Murphy Linda , Fourez Lindsey M. , Stewart Jane C. , Knapp Deborah W. 
Published: November 2012

Abstract
Folate receptors (FR) may be of use for targeted delivery of cytotoxic drugs in invasive urothelial carcinoma (iUC), for which improved therapy is needed. FR expression and function in iUC were explored and the antitumor activity and toxicity of a folate-targeted vinblastine conjugate were evaluated in dogs with naturally occurring iUC, an excellent model for human iUC. FR immunohistochemistry was carried out on iUC and normal human and dog bladder tissues together with nuclear scintigraphy in dogs to monitor iUC folate uptake. Dose escalation of a folate-targeted vinblastine compound, EC0905, was conducted in dogs with biopsy-confirmed, FR-positive iUC. FRs were detected by immunohistochemistry (PU17) in most primary iUC and many nodal and lung metastases from dogs, and scintigraphy confirmed folate uptake in both primary and metastatic lesions. The maximum tolerated dose of EC0905 in dogs was 0.25 mg/kg IV weekly, with neutropenia at higher doses. Tumor responses included partial remission (≥50% reduction in tumor volume) in five dogs and stable disease (&lt;50% change in tumor volume) in four dogs. Immunoreactivity to PU17 was similar in humans (78% of primary iUC, 80% of nodal metastases). Less immunoreactivity to mab343 (22% of cases) occurred. FR-β was noted in 21% of human iUC cases. Our findings suggest folate-targeted therapy holds considerable promise for treating iUC, where FR-β may be important in addition to FR-α. Cancer Res; 73(2); 875–84. ©2012 AACR.
Distinct roles for the α, β and γ1 isoforms of protein phosphatase 1 in the outside-in αIIbβ3 integrin signalling-dependent functions
Authors: Khatlani Tanvir , Kailasam Lavanya , Alrehani Nawaf , Pradhan Subhashree , Vijayan Vinod K. 
Published: November 2012

SummaryAlthough protein kinases and phosphatases participate in integrin αIIbβ3 signalling, whether integrin functions are regulated by the catalytic subunit of protein phosphatase 1 (PP1c) isoforms are unclear. We show that siRNA mediated knockdown of all PP1c isoforms (α, β and γ1) in 293 αIIbβ3 cells decreased adhesion to immobilised fibrinogen and fibrin clot retraction. Selective knockdown of only PP1cγ1 did not alter adhesion or clot retraction, while depletion of PP1cβ decreased both functions. Unexpectedly, knockdown of PP1cα enhanced αIIbβ3 adhesion to fibrinogen and clot retraction. Protein interaction studies revealed that all PP1c isoforms can interact with the integrin αIIb subunit. Phospho-profiling studies revealed an enhanced activation of mitogen- activated protein kinase (MAPK) p38 in the PP1cα depleted cells. Enhanced adhesive phenotype displayed by the PP1cα-depleted 293 αIIbβ3 cells was blocked by pharmacological inhibition of p38. Conversely, the decreased adhesion of PP1cα overexpressing cells was rescued by the expression of constitutively active p38α or p38γ. Thus, PP1c isoforms have distinct contribution to the outside-in αIIbβ3 signalling- dependent functions in 293 αIIbβ3 cells. Moreover, PP1cα negatively regulates integrin function by suppressing the p38 pathway.
Risk of recurrence in patients with pulmonary embolism: Predictive role of D-dimer and of residual perfusion defects on lung scintigraphy
Authors: Cenci Caterina , Antonucci Emilia , Grifoni Elisa , Arcangeli Chiara , Prisco Domenico , Abbate Rosanna , Miniati Massimo , Poli Daniela 
Published: November 2012

SummaryThe stratification of recurrence risk after a first episode of venous thromboembolism (VTE) is an important topic of research, especially in patients with pulmonary embolism (PE). Elevated D-dimer levels and residual vein obstruction (RVO) at compression ultrasonography have been studied as predictors of recurrence after withdrawing oral anticoagulant treatment (OAT). It is still unknown if residual perfusion defects (PD) on lung scintigraphy are related to recurrent PE. In the present study, we evaluated the association of PD with PE recurrence. The relationship between PD, elevated D-dimer levels, and RVO was also investigated. We prospectively followed 236 consecutive patients who survived a first episode of objectively confirmed PE, with or without deep-vein thrombosis. After at least three months of OAT, treatment was withdrawn in 139 patients. D-dimer levels were evaluated at one month of OAT withdrawal, RVO was measured, and perfusion lung scan (P-scan) was performed to evaluate PD. During follow-up, 20 patients experienced a recurrent episode of VTE. Elevated D-dimer levels were significantly associated with VTE recurrence, (p=0.003). RVO was present in 22% of the patients with recurrence and in 7.5% of those without (p=0.07). No significant association was found between PD >10% and VTE recurrence, D-dimer, or RVO. In conclusion, we confirmed the positive predictive value of elevated D-dimer levels for recurrent VTE. Residual PD on lung scintigraphy are neither predictive of recurrence nor related to D-dimer levels or RVO.
Adrenal-Specific Scavenger Receptor BI Deficiency Induces Glucocorticoid Insufficiency and Lowers Plasma Very-Low-Density and Low-Density Lipoprotein Levels in Mice
Authors: Hoekstra Menno , van der Sluis Ronald J. , Van Eck Miranda , Van Berkel Theo J.C. 
Published: November 2012

Objective—
We determined the physiological consequences of adrenocortical-specific deletion of scavenger receptor BI (SR-BI) function in C57BL/6 wild-type mice.

Methods and Results—

One adrenal from 10-day-old SR-BI knockout (KO) mice or wild-type controls was transplanted under the renal capsule of adrenalectomized C57BL/6 recipient mice. The fasting plasma corticosterone level increased over time in transplanted mice. Corticosterone values in SR-BI KO transplanted mice remained ≈50% lower (
P
<0.001) as compared with wild-type transplanted mice, which coincided with adrenocortical lipid depletion. A 6.5-fold higher (
P
<0.01) plasma adrenocorticotropic hormone level was present in SR-BI KO transplanted mice reminiscent of primary glucocorticoid insufficiency. On feeding with cholic acid-containing high cholesterol/high fat diet, SR-BI KO transplanted mice exhibited a 26% (
P
<0.05) reduction in their liver triglyceride level. Hepatic myosin regulatory light chain interacting protein/inducible degrader of the low-density lipoprotein receptor mRNA expression was 48% (
P
<0.01) decreased in adrenal-specific SR-BI KO mice, which was paralleled by a marked decrease (–46%;
P
<0.01) in proatherogenic very-low-density and low-density lipoprotein levels.

Conclusion—
Adrenal-specific disruption of SR-BI function induces glucocorticoid insufficiency and lowers plasma very-low-density and low-density lipoprotein levels in atherogenic diet-fed C57BL/6 mice. These findings further highlight the interaction between adrenal high-density lipoprotein-cholesterol uptake by SR-BI, adrenal steroidogenesis, and the regulation of hepatic lipid metabolism.