bluuebunny/crossref_metadata_2025 huggingface dataset:
A Senator's Personal Reflections on Public Service
Authors: Landrieu Mary L.
Published: August 2013

The Honorable Mary Landrieu, U.S. senator from Louisiana since 1997, addressed the 2013 annual meeting of the American Society for Public Administration (ASPA) at a luncheon honoring four Louisianans for their public service. They included General Russel L. Honoré, U.S. Army; Chancellor James L. Llorens, Southern University at Baton Rouge; Mayor Mitch Landrieu, City of New Orleans; and Professor Astrid Merget, Public Administration Institute at Louisiana State University Baton Rouge and honorary co‐chair of the 2013 ASPA Conference. In her remarks, Senator Landrieu reflected on her lineage in public service.
Combining mechanical rhizome removal and cover crops for Elytrigia repens control in organic barley systems
Authors: Melander B , Nørremark M , Kristensen E F
Published: August 2013

Mechanical weed control of perennial weeds in organic crop production over long post‐harvest periods is incompatible with the establishment of cover crops for improving soil quality and preventing nutrient leaching. We suggest a new concept that comprises uprooting and immediate removal of vegetative propagules located within the plough layer to allow for quick re‐establishment of a plant cover. A field experiment comparing the effects of conventional practices (stubble cultivation) with different combinations of rotary cultivation (One, Two or four passes) and cover crops (none vs. rye‐vetch‐mustard mixture) on Elytrigia repens rhizome removal, shoot growth and suppression of a subsequent barley crop was examined in two growing seasons. Four passes with a modified rotary cultivator, where each pass was followed by rhizome removal, reduced E. repens shoot growth in barley by 84% and 97%. In general, the cover crop developed poorly and did not affect barley or E. repens. Barley yield was only affected by treatments in the first season, where yield was negatively correlated with E. repens shoot biomass. The concept has potential for the control of severe E. repens infestations, but future research aimed at identifying more effective smother crops and less intensive methods of rhizome removal is needed.
Gen-3 Thermal Management Technology: Role of Microchannels and Nanostructures in an Embedded Cooling Paradigm
Authors: Bar-Cohen Avram
Published: August 2013

The thermal management challenges facing electronic system developers and the need, as well as challenges, associated with the development of a Gen-3 embedded cooling paradigm are examined. We argue that the inherent limitations of the prevailing “remote cooling” technology have resulted in commercial and military electronic systems that are thermally-limited, performing well below the inherent electrical capability of the device technology they exploit. To overcome these limitations and remove a significant barrier to continued Moore's law progression in electronic components and systems, DARPA is pursuing the aggressive development of thermal management “embedded” in the chip, substrate, and/or package to directly cool the heat generation sites. The options and challenges associated with the development of this “Gen-3” thermal management technology are described.
Computer Vision-Based, Noncontacting Deformation Measurements in Mechanics: A Generational Transformation
Authors: Sutton Michael A.
Published: August 2013

The remarkable increases in computational speed and memory size that have occurred over the past three decades have impacted virtually every area of scientific inquiry. With regard to the measurement community, the digital age has revolutionized the way in which data are acquired, stored, and analyzed to extract the maximum amount of information. For the purposes of this discussion, the focus will be on computer vision–based, noncontacting measurement methods, specifically those commonly known as 2D image correlation, 3D image correlation, and digital volume correlation (also known as volumetric image correlation), and their increasingly significant role in the broad field of solid mechanics. The review closes with a visionary perspective regarding the integration of measurements and models and the impact it may have on the design process.
Modified high power impulse magnetron sputtering process for increased deposition rate of titanium
Authors: Barker Clara M. , Lewin Erik , Patscheider Jörg
Published: August 2013

A modified version of high power impulse magnetron sputtering (HiPIMS) has been used to deposit titanium films at higher deposition rates than for conventional HiPIMS while maintaining similar pulse voltages and peak currents. In the present study, additional control parameters are explored through the chopping of the HiPIMS pulse into a pulse sequence. Experiments show that the use of sequences allows for an increase of the deposition rate of more than 45% compared to conventional HiPIMS. The increase in deposition rate is ascribed to a combination of reduced gas rarefaction effects, prevention of sustained self-sputtering, and a relaxation of ion trapping.
Tailored ion energy distributions on plasma electrodes
Authors: Economou Demetre J.
Published: August 2013

As microelectronic device features continue to shrink approaching atomic dimensions, control of the ion energy distribution on the substrate during plasma etching and deposition becomes increasingly critical. The ion energy should be high enough to drive ion-assisted etching, but not too high to cause substrate damage or loss of selectivity. In many cases, a nearly monoenergetic ion energy distribution (IED) is desired to achieve highly selective etching. In this work, the author briefly reviews: (1) the fundamentals of development of the ion energy distribution in the sheath and (2) methods to control the IED on plasmaelectrodes. Such methods include the application of “tailored” voltage waveforms on an electrode in continuous wave plasmas, or the application of synchronous bias on a “boundary electrode” during a specified time window in the afterglow of pulsed plasmas.
Poverty Impedes Cognitive Function
Authors: Mani Anandi , Mullainathan Sendhil , Shafir Eldar , Zhao Jiaying
Published: August 2013

Burden of Poverty

Lacking money or time can lead one to make poorer decisions, possibly because poverty imposes a cognitive load that saps attention and reduces effort.

Mani
et al.

(p.
976
; see the Perspective by Vohs) gathered evidence from shoppers in a New Jersey mall and from farmers in Tamil Nadu, India. They found that considering a projected financial decision, such as how to pay for a car repair, affects people's performance on unrelated spatial and reasoning tasks. Lower-income individuals performed poorly if the repairs were expensive but did fine if the cost was low, whereas higher-income individuals performed well in both conditions, as if the projected financial burden imposed no cognitive pressure. Similarly, the sugarcane farmers from Tamil Nadu performed these tasks better after harvest than before.
A Uranian Trojan and the Frequency of Temporary Giant-Planet Co-Orbitals
Authors: Alexandersen Mike , Gladman Brett , Greenstreet Sarah , Kavelaars J. J. , Petit Jean-Marc , Gwyn Stephen
Published: August 2013

A Uranian Trojan

Bodies that share their orbit with that of a planet and that trail or lead the planet by 60° are called Trojans. Based on data from the Canada-France-Hawaii Telescope,

Alexandersen
et al.

(p.
994
) have found an object shadowing Uranus that is predicted to remain a Trojan for at least 700,000 years and to stay in co-orbital motion for around one million years before escaping.
Rebirthing Pains
Time Reborn
From the Crisis in Physics to the Future of the Universe

by Lee Smolin

Houghton Mifflin Harcourt, Boston, 2013. 351 pp. $28. ISBN 9780547511726.
Authors: Price Huw
Published: August 2013

Rejecting the position that time is an illusion, Smolin argues that it should be taken as real and that the laws of physics may not be timeless.
The Promise of Poop
Authors: de Vrieze Jop
Published: August 2013

Fecal transplants offer hope for treating many diseases. But they need to be studied more scientifically, says one of the treatment's pioneers.
Investigating the Use of Protein Saver Cards for Storage and Subsequent Detection of Bovine Anti-Brucella abortus Smooth Lipopolysaccharide Antibodies and Gamma Interferon
Authors: Duncombe Lucy , Commander Nicola J. , Erdenlig Sevil , McGiven John A. , Stack Judy
Published: August 2013

Brucella abortus, a smooth strain of the genusBrucella, is the causative agent of bovine brucellosis. To support the ongoing development of diagnostic tests for bovine brucellosis, the use of Protein Saver cards (Whatman) for bovine blood serum and plasma sample collection has been evaluated. These cards offer significant logistical and safety alternatives to transporting and storing liquid samples and may aid in diagnostic programs and validation studies. To evaluate the utility of these cards, 204 bovine blood serum samples fromBrucella-infected and noninfected animals were stored on and eluted from the Protein Saver cards. Anti-Brucellasmooth lipopolysaccharide (sLPS) antibody titers for the serum eluates were compared to those of the unprocessed original serum samples by indirect enzyme-linked immunosorbent assay (ELISA). The results showed a highly significant correlation between titers from the serum eluates and the unprocessed sera. Therefore, under these circumstances, serum eluates and unprocessed serum samples may be used interchangeably. Blood plasma from 113 mitogen-stimulated whole-blood samples was added to and eluted from the Protein Saver cards. The gamma interferon (IFN-γ) titers in the plasma eluates were compared to those of the unprocessed plasma samples obtained by IFN-γ ELISA. The results showed a significant correlation between the plasma eluates and the unprocessed plasma samples. To derive a signal in the plasma eluate, it was necessary to develop a novel and highly sensitive ELISA for the detection of IFN-γ. The serum samples stored on cards at room temperature over a 10-day period showed little variation in antibody titers. However, the plasma eluates showed a progressive loss of IFN-γ recovery over 10 days when stored at room temperature.
Development of an Unbiased Antigen-Mining Approach To Identify Novel Vaccine Antigens and Diagnostic Reagents for Bovine Tuberculosis
Authors: Jones Gareth J. , Khatri Bhagwati L. , Garcia-Pelayo M. Carmen , Kaveh Daryan A. , Bachy Véronique S. , Hogarth Philip J. , Wooff Esen , Golby Paul , Vordermeier H. Martin
Published: August 2013

Previous experiments for the identification of novel diagnostic or vaccine candidates for bovine tuberculosis have followed a targeted approach, wherein specific groups of proteins suspected to contain likely candidates are prioritized for immunological assessment (for example, with
in silico
approaches). However, a disadvantage of this approach is that the sets of proteins analyzed are restricted by the initial selection criteria. In this paper, we describe a series of experiments to evaluate a nonbiased approach to antigen mining by utilizing a Gateway clone set for
Mycobacterium tuberculosis
, which constitutes a library of clones expressing 3,294
M. tuberculosis
proteins. Although whole-blood culture experiments using
Mycobacterium bovis
-infected animals and
M. bovis
BCG-vaccinated controls did not reveal proteins capable of differential diagnosis, several novel immunogenic proteins were identified and prioritized for efficacy studies in a murine vaccination/challenge model. These results demonstrate that Rv3329-immunized mice had lower bacterial cell counts in their spleens following challenge with
M. bovis
. In conclusion, we demonstrate that this nonbiased approach to antigen mining is a useful tool for identifying and prioritizing novel proteins for further assessment as vaccine antigens.
Molecular Typing of “Candidatus Bartonella ancashi,” a New Human Pathogen Causing Verruga Peruana
Authors: Mullins Kristin E. , Hang Jun , Jiang Ju , Leguia Mariana , Kasper Matthew R. , Maguiña Ciro , Jarman Richard G. , Blazes David L. , Richards Allen L.
Published: August 2013

A recently described clinical isolate, “
Candidatus
Bartonella ancashi,” was obtained from a blood sample of a patient presenting with verruga peruana in the Ancash region of Peru. This sample and a second isolate obtained 60 days later from the same patient were molecularly typed using multilocus sequence typing (MLST) and multispacer sequence typing (MST). The isolates were 100% indistinguishable from each other but phylogenetically distant from
Bartonella bacilliformis
and considerably divergent from other known
Bartonella
species, confirming their novelty.
Evaluation of Bactec Mycosis IC/F and Plus Aerobic/F Blood Culture Bottles for Detection of Candida in the Presence of Antifungal Agents
Authors: Köck Robin , Eißing Lea C. , Boschin Matthias G. , Ellger Björn , Horn Dagmar , Idelevich Evgeny A. , Becker Karsten
Published: August 2013

Clinical practice guidelines recommend performing follow-up cultures for patients with candidemia in order to determine the time when
Candida
is cleared from the bloodstream. Since this requires culturing blood samples from patients undergoing antifungal treatment, we evaluated two blood culture bottles (the Bactec Mycosis IC/F [MICF], specifically adapted to the growth of fungi, and the Bactec Plus Aerobic/F [PAF], containing resins to inactivate anti-infective agents) for their effectiveness in detecting
Candida albicans
and
Candida glabrata
when seeded in concentrations of 1 CFU/ml and 10 CFU/ml, respectively, together with human whole blood and various antifungal agents in therapeutic peak serum concentrations (
C
max
). Significant differences between the MICF and PAF vials for the detection of
Candida
spp. were found when inoculated with caspofungin (0/12 versus 8/12) (
P
< 0.001) or amphotericin B (3/12 versus 12/12) (
P
< 0.001). Inoculation of fluconazole or voriconazole did not influence the effectiveness of detection in the MICF and PAF bottles (
P
= 1.0). Neither the MICF nor the PAF bottles detected
Candida
spp. reliably when seeded together with anidulafungin (1/12 versus 1/12) (
P
= 1.0) or micafungin (0/12 versus 1/12) (
P
= 1.0). The times to positivity of both bottles were significantly prolonged when antifungal agents were added compared to those of controls without antimycotic drugs (
P
< 0.001). Overall, the results of this
in vitro
study indicate that the PAF bottles detected
Candida
spp. more reliably than the MICF bottles when supplemented with certain antifungal agents. Consequently, clinical studies should evaluate whether this holds true when blood cultures from patients undergoing antifungal treatment are performed.
Preservation of Dendritic Cell Function during Vesicular Stomatitis Virus Infection Reflects both Intrinsic and Acquired Mechanisms of Resistance to Suppression of Host Gene Expression by Viral M Protein
Authors: Westcott Marlena M. , Ahmed Maryam , Smedberg Jason R. , Rajani Karishma R. , Hiltbold Elizabeth M. , Lyles Douglas S.
Published: August 2013

Inhibition of host-directed gene expression by the matrix (M) protein of vesicular stomatitis virus (VSV) effectively blocks host antiviral responses, promotes virus replication, and disables the host cell. However, dendritic cells (DC) have the capacity to resist these effects and remain functional during VSV infection. Here, the mechanisms of DC resistance to M protein and their subsequent maturation were addressed. Flt3L-derived murine bone marrow dendritic cells (FDC), which phenotypically resemble resident splenic DC, continued to synthesize cellular proteins and matured during single-cycle (high-multiplicity) and multicycle (low-multiplicity) infection with VSV. Granulocyte-macrophage colony-stimulating factor (GM-CSF)-derived myeloid DC (GDC), which are susceptible to M protein effects, were nevertheless capable of maturing, but the response was delayed and occurred only during multicycle infection. FDC resistance was manifested early and was type I interferon (IFN) receptor (IFNAR) and MyD88 independent, but sustained resistance required IFNAR. MyD88-dependent signaling contributed to FDC maturation during single-cycle infection but was dispensable during multicycle infection. Similar to FDC, splenic DC were capable of maturing
in vivo
during the first 24 h of infection with VSV, and neither Toll-like receptor 7 (TLR7) nor MyD88 was required. We conclude that FDC resistance to M protein is controlled by an intrinsic, MyD88-independent mechanism that operates early in infection and is augmented later in infection by type I IFN. In contrast, while GDC are not intrinsically resistant, they can acquire resistance during multicycle infection.
In vivo
, splenic DC resist the inhibitory effects of VSV, and as in multicycle FDC infection, MyD88-independent signaling events control their maturation.
Foot-and-Mouth Disease Virus 3C Protease Induces Fragmentation of the Golgi Compartment and Blocks Intra-Golgi Transport
Authors: Zhou Zhigang , Mogensen Mette M. , Powell Penny P. , Curry Stephen , Wileman Thomas
Published: August 2013

Picornavirus infection can cause Golgi fragmentation and impose a block in the secretory pathway which reduces expression of major histocompatibility antigens at the plasma membrane and slows secretion of proinflammatory cytokines. In this study, we show that Golgi fragmentation and a block in secretion are induced by expression of foot-and-mouth disease virus (FMDV) 3C
pro
and that this requires the protease activity of 3C
pro
. 3C
pro
caused fragmentation of early, medial, and late Golgi compartments, but the most marked effect was on early Golgi compartments, indicated by redistribution of ERGIC53 and membrin. Golgi fragments were dispersed in the cytoplasm and were able to receive a model membrane protein exported from the endoplasmic reticulum (ER). Golgi fragments were, however, unable to transfer the protein to the plasma membrane, indicating a block in intra-Golgi transport. Golgi fragmentation was coincident with a loss of microtubule organization resulting from an inhibition of microtubule regrowth from the centrosome. Inhibition of microtubule regrowth also required 3C
pro
protease activity. The loss of microtubule organization induced by 3C
pro
caused Golgi fragmentation, but loss of microtubule organization does not block intra-Golgi transport. It is likely that the block of intra-Golgi transport is imposed by separate actions of 3C
pro
, possibly through degradation of proteins required for intra-Golgi transport.
A Cholesterol Recognition Amino Acid Consensus Domain in GP64 Fusion Protein Facilitates Anchoring of Baculovirus to Mammalian Cells
Authors: Luz-Madrigal Agustin , Asanov Alexander , Camacho-Zarco Aldo R. , Sampieri Alicia , Vaca Luis
Published: August 2013

Baculoviridaeis a large family of double-stranded DNA viruses that selectively infect insects.Autographa californicamultiple nucleopolyhedrovirus (AcMNPV) is the best-studied baculovirus from the family. Many studies over the last several years have shown that AcMNPV can enter a wide variety of mammalian cells and deliver genetic material for foreign gene expression. While most animal viruses studied so far have developed sophisticated mechanisms to selectively infect specific cells and tissues in an organism, AcMNPV can penetrate and deliver foreign genes into most cells studied to this date. The details about the mechanisms of internalization have been partially described. In the present study, we have identified a cholesterol recognition amino acid consensus (CRAC) domain present in the AcMNPV envelope fusion protein GP64. We demonstrated the association of a CRAC domain with cholesterol, which is important to facilitate the anchoring of the virus at the mammalian cell membrane. Furthermore, this initial anchoring favors AcMNPV endocytosis via a dynamin- and clathrin-dependent mechanism. Under these conditions, efficient baculovirus-driven gene expression is obtained. In contrast, when cholesterol is reduced from the plasma membrane, AcMNPV enters the cell via a dynamin- and clathrin-independent mechanism. The result of using this alternative internalization pathway is a reduced level of baculovirus-driven gene expression. This study is the first to document the importance of a novel CRAC domain in GP64 and its role in modulating gene delivery in AcMNPV.
Genome-Wide Analysis of T Cell Responses during Acute and Latent Simian Varicella Virus Infections in Rhesus Macaques
Authors: Haberthur Kristen , Kraft Aubrey , Arnold Nicole , Park Byung , Meyer Christine , Asquith Mark , Dewane Jesse , Messaoudi Ilhem
Published: August 2013

Varicella zoster virus (VZV) is the etiological agent of varicella (chickenpox) and herpes zoster (HZ [shingles]). Clinical observations suggest that VZV-specific T cell immunity plays a more critical role than humoral immunity in the prevention of VZV reactivation and development of herpes zoster. Although numerous studies have characterized T cell responses directed against select VZV open reading frames (ORFs), a comprehensive analysis of the T cell response to the entire VZV genome has not yet been conducted. We have recently shown that intrabronchial inoculation of young rhesus macaques with simian varicella virus (SVV), a homolog of VZV, recapitulates the hallmarks of acute and latent VZV infection in humans. In this study, we characterized the specificity of T cell responses during acute and latent SVV infection. Animals generated a robust and broad T cell response directed against both structural and nonstructural viral proteins during acute infection in bronchoalveolar lavage (BAL) fluid and peripheral blood. During latency, T cell responses were detected only in the BAL fluid and were lower and more restricted than those observed during acute infection. Interestingly, we identified a small set of ORFs that were immunogenic during both acute and latent infection in the BAL fluid. Given the close genome relatedness of SVV and VZV, our studies highlight immunogenic ORFs that may be further investigated as potential components of novel VZV vaccines that specifically boost T cell immunity.
Systemic Toll-Like Receptor Ligation and Selective Killing of Dendritic Cell Subsets Fail To Dissect Priming Pathways for Anti-Vaccinia Virus CD8+T Cells
Authors: Wong Yik Chun , Smith Stewart A. , Tscharke David C.
Published: August 2013

CD8+T cell responses can be generated by direct or cross-priming mechanisms, and several mouse models have been used to reveal which of these is the most important pathway for various viruses. Among these models is systemic treatment of mice with a CpG-containing oligodeoxynucleotide (CpG) to mature all dendritic cells (DCs), rendering them incapable of cross-presentation. A second is the use of cytochromec(cytc) as a selective poison of the subsets of DCs able to cross-present antigen. In this study, using two vaccinia virus (VACV) strains, namely, WR and MVA, we found that the CpG and cytc methods gave conflicting data. Moreover, we show for both strains of VACV that treatment of mice with CpG and cytc inhibited CD8+T cell responses to antigens designed to prime exclusively by direct presentation. Further investigation of the CpG method found that the extent to which priming is inhibited depends on the antigen examined, immunization route, replication ability of the virus, and, crucially, immunization dose. We suggest that greater caution is required when interpreting data using these methods and that priming pathways for antiviral CD8+T cells are not simply separated according to DC subsets or their maturation state.
Comparative Analysis of the Complete Genome Sequence of the California MSW Strain of Myxoma Virus Reveals Potential Host Adaptations
Authors: Kerr Peter J. , Rogers Matthew B. , Fitch Adam , DePasse Jay V. , Cattadori Isabella M. , Hudson Peter J. , Tscharke David C. , Holmes Edward C. , Ghedin Elodie
Published: August 2013

Myxomatosis is a rapidly lethal disease of European rabbits that is caused by myxoma virus (MYXV). The introduction of a South American strain of MYXV into the European rabbit population of Australia is the classic case of host-pathogen coevolution following cross-species transmission. The most virulent strains of MYXV for European rabbits are the Californian viruses, found in the Pacific states of the United States and the Baja Peninsula, Mexico. The natural host of Californian MYXV is the brush rabbit,
Sylvilagus bachmani
. We determined the complete sequence of the MSW strain of Californian MYXV and performed a comparative analysis with other MYXV genomes. The MSW genome is larger than that of the South American Lausanne (type) strain of MYXV due to an expansion of the terminal inverted repeats (TIRs) of the genome, with duplication of the
M156R
,
M154L
,
M153R
,
M152R
, and
M151R
genes and part of the
M150R
gene from the right-hand (RH) end of the genome at the left-hand (LH) TIR. Despite the extreme virulence of MSW, no novel genes were identified; five genes were disrupted by multiple indels or mutations to the ATG start codon, including two genes,
M008.1L/R
and
M152R
, with major virulence functions in European rabbits, and a sixth gene,
M000.5L/R
, was absent. The loss of these gene functions suggests that
S. bachmani
is a relatively recent host for MYXV and that duplication of virulence genes in the TIRs, gene loss, or sequence variation in other genes can compensate for the loss of
M008.1L/R
and
M152R
in infections of European rabbits.
The Kissing-Loop T-Shaped Structure Translational Enhancer of Pea Enation Mosaic Virus Can Bind Simultaneously to Ribosomes and a 5′ Proximal Hairpin
Authors: Gao Feng , Gulay Suna P. , Kasprzak Wojciech , Dinman Jonathan D. , Shapiro Bruce A. , Simon Anne E.
Published: August 2013

The
Pea Enation Mosaic Virus
(PEMV) 3′ translational enhancer, known as the kissing-loop T-shaped structure (kl-TSS), binds to 40S subunits, 60S subunits, and 80S ribosomes, whereas the
Turnip crinkle virus
(TCV) TSS binds only to 60S subunits and 80S ribosomes. Using electrophoretic mobility gel shift assay (EMSA)-based competition assays, the kl-TSS was found to occupy a different site in the ribosome than the P-site-binding TCV TSS, suggesting that these two TSS employ different mechanisms for enhancing translation. The kl-TSS also engages in a stable, long-distance RNA-RNA kissing-loop interaction with a 12-bp 5′-coding-region hairpin that does not alter the structure of the kl-TSS as revealed by molecular dynamics simulations. Addition of the kl-TSS in
trans
to a luciferase reporter construct containing either wild-type or mutant 5′ and 3′ PEMV sequences suppressed translation, suggesting that the kl-TSS is required in
cis
to function, and both ribosome-binding and RNA interaction activities of the kl-TSS contributed to translational inhibition. Addition of the kl-TSS was more detrimental for translation than an adjacent eIF4E-binding 3′ translational enhancer known as the PTE, suggesting that the PTE may support the ribosome-binding function of the kl-TSS. Results of in-line RNA structure probing, ribosome filter binding, and high-throughput selective 2′-hydroxyl acylation analyzed by primer extension (hSHAPE) of rRNAs within bound ribosomes suggest that kl-TSS binding to ribosomes and binding to the 5′ hairpin are compatible activities. These results suggest a model whereby posttermination ribosomes/ribosomal subunits bind to the kl-TSS and are delivered to the 5′ end of the genome via the associated RNA-RNA interaction, which enhances the rate of translation reinitiation.
The Viral Polymerase Inhibitor 2′-
C
-Methylcytidine Inhibits Norwalk Virus Replication and Protects against Norovirus-Induced Diarrhea and Mortality in a Mouse Model
Authors: Rocha-Pereira Joana , Jochmans Dirk , Debing Yannick , Verbeken Erik , Nascimento Maria S. J. , Neyts Johan
Published: August 2013

Human noroviruses are a major cause of food-borne illness, accountable for 50% of all-etiologies outbreaks of acute gastroenteritis (in both developing and developed countries). There is no vaccine or antiviral drug for the prophylaxis or treatment of norovirus-induced gastroenteritis. We recently reported the inhibitory effect of 2′-
C
-methylcytidine (2CMC), a hepatitis C virus polymerase inhibitor, on the
in vitro
replication of murine norovirus (MNV). Here we evaluated the inhibitory effect of 2CMC on
in vitro
human norovirus replication through a Norwalk virus replicon model and in a mouse model by using AG129 mice orally infected with MNV. Survival, weight, and fecal consistency were monitored, and viral loads in stool samples and organs were quantified. Intestines were examined histologically. 2CMC reduced Norwalk virus replicon replication in a dose-dependent manner and was able to clear cells of the replicon. Treatment of MNV-infected AG129 mice with 2CMC (i) prevented norovirus-induced diarrhea; (ii) markedly delayed the appearance of viral RNA and reduced viral RNA titers in the intestine, mesenteric lymph nodes, spleen, lungs, and stool; (iii) completely prevented virus-induced mortality; and (iv) resulted in protective immunity against a rechallenge. We demonstrate for the first time that a small-molecule inhibitor of norovirus replication protects from virus-induced disease and mortality in a relevant animal model. These findings pave the way for the development of potent and safe antivirals as prophylaxis and therapy of norovirus infection.
Role of DNA Methylation in Expression and Transmission of Porcine Endogenous Retroviruses
Authors: Matoušková Magda , Veselý Pavel , Daniel Petr , Mattiuzzo Giada , Hector Ralph D. , Scobie Linda , Takeuchi Yasuhiro , Hejnar Jiří
Published: August 2013

Porcine endogenous retroviruses (PERV) represent a major safety concern in pig-to-human xenotransplantation. To date, no PERV infection of a xenograft recipient has been recorded; however, PERVs are transmissible to human cells
in vitro
. Some recombinants of the A and C PERV subgroups are particularly efficient in infection and replication in human cells. Transcription of PERVs has been described in most pig cells, but their sequence and insertion polymorphism in the pig genome impede identification of transcriptionally active or silenced proviral copies. Furthermore, little is known about the epigenetic regulation of PERV transcription. Here, we report on the transcriptional suppression of PERV by DNA methylation
in vitro
and describe heavy methylation in the majority of PERV 5′ long terminal repeats (LTR) in porcine tissues. In contrast, we have detected sparsely methylated or nonmethylated proviruses in the porcine PK15 cells, which express human cell-tropic PERVs. We also demonstrate the resistance of PERV DNA methylation to inhibitors of methylation and deacetylation. Finally, we show that the high permissiveness of various human cell lines to PERV infection coincides with the inability to efficiently silence the PERV proviruses by 5′LTR methylation. In conclusion, we suggest that DNA methylation is involved in PERV regulation, and that only a minor fraction of proviruses are responsible for the PERV RNA expression and porcine cell infectivity.
Bilateral ovarian malignant mixed Mullerian tumour: a rare entity
Authors: Kumar Madhu , Goel Madhu Mati , Das Vinita
Published: August 2013

A 52-year-old postmenopausal woman presented with abdominal distension for 2 months. She had no vaginal bleeding and no relevant medical history. A physical examination showed a large palpable pelvic mass. A CT scan showed an ill-defined, heterogeneously enhancing, soft tissue attenuation lesion in the lower abdomen and pelvis involving the right adnexal region with massive ascites, and the left ovary did not reveal any evidence of disease. The omentum was thickened and heterogeneous. The patient underwent a total hysterectomy with infracolic omentectomy. The diagnosis was bilateral ovarian malignant mixed Mullerian tumour (MMMT) with omental deposits. Aggressive treatment includes surgery and chemotherapy. Women with this tumour have a significant increased risk of death compared to women with epithelial ovarian cancer and very poor prognosis. We report a case of MMMT of the ovary with clinicopathological correlation and diagnostic difficulties as malignant epithelial tumour resemble ovarian stromal sarcoma in postmenopausal female.
Giant pilomatricoma in a patient with tuberous sclerosis, both diagnosed in the adult life
Authors: Resende Cristina Isabel Pinho , Gomes Joana , Duarte Maria da Luz , Brito Celeste
Published: August 2013

Pilomatricoma is a relatively common benign skin neoplasm originating from the hair follicle matrix cells. β-Catenin is a subunit of the cadherin protein complex. It acts as an intracellular signal transducer that influences cell differentiation and proliferation. This protein was recently involved in the formation of hair follicle-related tumours, including pilomatricomas. Tuberous sclerosis (TS) is an inherited neurocutaneous disease, which is characterised by pleomorphic features involving many organs, hamartomas in multiple organ systems and by the fact that it is usually diagnosed early in life. We reported a case of a Caucasian patient with TS and a giant pilomatricoma, both diagnosed in the adult life.
Cardiorespiratory arrest secondary to tracheostomy cuff herniation
Authors: Barker Ian R , Stotz Martin
Published: August 2013

This report details the case of a 67-year-old man who required intubation following a fall and multiple rib fractures and underwent surgical tracheostomy. Postoperatively, he deteriorated on the intensive care unit with airway obstruction. Bronchoscopy demonstrated tracheostomy cuff herniation obstructing airflow necessitating conventional orotracheal reintubation. On inspection of the tracheostomy an unusual cuff deformation was noted.
Foul play is associated with injury incidence: an epidemiological study of three FIFA World Cups (2002–2010)
Authors: Ryynänen Jaakko , Junge Astrid , Dvorak Jiri , Peterson Lars , Kautiainen Hannu , Karlsson Jón , Börjesson Mats
Published: August 2013

Background

Foul play has been considered as one of the most important known extrinsic risk factors for injuries in football.

Aims

To compare the incidence and characteristics of foul play injuries and non-foul injuries.

Methods

Team physicians’ postmatch injury reports and official match statistics were obtained from all matches of the 2002, 2006 and 2010 Fédération Internationale de Football Association World Cups.

Results

The number of injuries was associated with the number of fouls in a match. The incidence of foul play injuries (20.6/1000 match-hours, 95% CI 17.3 to 24.4) was significantly lower than that of non-foul injuries (42.6, 37.7 to 47.9), which also applied to all playing positions. The causation of injury (foul/non-foul), match period and teams’ drawing/losing/winning status were associated with the injury incidence. The interactions between the causation of injury (foul/non-foul) and match time, as well as the teams’ drawing/losing/winning status or playing position were not statistically significant. The median (IQR) days of absence resulting from foul play injuries were significantly shorter than that of non-foul injuries. The lower leg and ankle were more common locations for foul play injuries than for non-foul injuries, whereas the opposite was observed for thigh injuries. Contusions were a more common type of foul play injuries than non-foul injuries, while the opposite was found for muscle strains/ruptures/tears.

Conclusions

The numbers of injuries and fouls in a match were significantly associated. No significant differences in the variation of foul play and non-foul injury incidences regarding match period, teams’ current winning/drawing/losing status and playing position were observed, suggesting that foul play injuries and non-foul injuries may share similar underlying risk factors.
Sexual orientation identity in relation to smoking history and alcohol use at age 18/19: cross-sectional associations from the Longitudinal Study of Young People in England (LSYPE)
Authors: Hagger-Johnson Gareth , Taibjee Rafik , Semlyen Joanna , Fitchie Isla , Fish Julie , Meads Catherine , Varney Justin
Published: August 2013

Objectives

Information about the health behaviours of minority groups is essential for addressing health inequalities. We evaluated the association among lesbian, gay or bisexual (LGB) sexual orientation identity and smoking and alcohol use in young people in England.

Design

Data drawn from wave 6 of the Longitudinal Study of Young People in England (LSYPE).

Setting

Self-completion questionnaires during home visits, face-to-face interviews and web-based questionnaires.

Participants

Data from 7698 participants (3762 men) with information on sexual orientation identity and health behaviours at age 18/19.

Outcome measures

Cigarette smoking history, alcohol drinking frequency and risky single occasion drinking (RSOD).

Results

LGB identity was reported by 3.1% of participants (55 gay, 33 lesbian, 35 bisexual male, 111 bisexual female), 3.5% when adjusting for the survey design. Adjusting for a range of covariates, identification as lesbian/gay was found to be associated with smoking (OR=2.23, 95% CI 1.42 to 3.51), alcohol drinking >2 days/week (OR=1.99, 95% CI 1.25 to 3.17) and RSOD (OR=1.80, 95% CI 1.13 to 2.86) more than weekly. Bisexual identity was associated with smoking history (OR=1.84, 95% CI 1.30 to 2.61) but not alcohol drinking >2 days/week (OR=1.20, 95% CI 0.79 to 1.81) or RSOD (OR=1.04, 95% CI 0.71 to 2.86).

Conclusions

In a sample of more than 7600 young people aged 18/19 years in England, lesbian/gay identity is associated with cigarette smoking, drinking alcohol frequency and RSOD. Bisexual identity is associated with smoking but not RSOD or frequent alcohol drinking.
Strong association of fascin expression with triple negative breast cancer and basal-like phenotype in African-American women
Authors: Esnakula Ashwini K , Ricks-Santi Luisel , Kwagyan John , Kanaan Yasmine M , DeWitty Robert L , Wilson Lori L , Gold Bert , Frederick Wayne A I , Naab Tammey J
Published: August 2013

Background

Fascin, an actin bundling protein, plays a critical role in cell motility due to formation of actin rich protrusions called filopodia, important in cell migration, invasion and metastatic spread. Fascin overexpression has been associated with epithelial to mesenchymal transition and correlates with progression and unfavourable prognosis in breast carcinoma.

Objective

To evaluate fascin expression by immunohistochemistry and correlate the expression pattern with clinicopathological parameters in breast cancer in African-American (AA) women, in whom triple negative breast cancer (TNBC), an aggressive subtype, is more prevalent.

Methods

Tissue microarrays were constructed from formalin-fixed, paraffin-embedded blocks of tumour tissue from primary breast carcinomas in 202 AA women. Immunohistochemical detection of fascin was correlated with four major subtypes of breast carcinoma (luminal A, luminal B, human epidermal growth factor receptor 2 and triple negative (TN)) and other clinicopathological factors, including age, grade, tumour size, stage, regional lymph node status and survival.

Results

We observed a significant association between fascin expression and TN subtype, oestrogen receptor (ER) negativity, progesterone receptor (PR) negativity, Elston–Nottingham (EN) grade 3 and decreased overall survival. There was also a significant association between expression of CK 5/6, a marker of basal-like phenotype, and fascin expression.

Conclusion

These results suggest that fascin is a marker for TN subtype having a basal-like phenotype and decreased overall survival. Fascin may represent a target for therapy in TNBC in AA women.
Medical microbiology training needs and trainee experience
Authors: Seale Josephine , Elamin Wael , Millar Michael
Published: August 2013

Background

Training in microbiology is continuing to evolve. Standardisation of this process has, in part, been achieved through the development of a training curriculum by the Royal College of Pathologists (RCPath). A substantial proportion of microbiology training occurs through telephone consultations.

Aims

To ascertain the content of these interactions and the extent to which the necessary skills outlined by the curriculum are attainable via these consultations.

Methods

Records of telephone consultations made by microbiology registrars (SpR) on the Laboratory Information Management System (LIMS) over a 6 month period were analysed with regard to who initiated contact and the type of advice provided.

Results

An average of 426 SpR entries per month were made on the LIMS following telephone consultations. These consultations were predominantly initiated by fellow clinicians as opposed to the SpR. The majority (79%) of advice entailed guidance as to the use of antimicrobials which resulted in an alteration of the current regimen in 54% of cases.

Conclusions

This study represents the first attempt to quantify the telephone consultations of microbiology trainees. It is concluded that although such interactions provide a means of attaining some of the competencies outlined by the RCPath curriculum, the bias towards antimicrobial advice reflects a discrepancy between the needs of the service users and the broad skill set advocated by the current microbiology training programme. Future modifications will need to take this into account to ensure both the training of SpRs and the microbiology service is fit for purpose.
Molecular genetic tests forJAK2V617F, Exon12_JAK2andMPLW515K/L are highly informative in the evaluation of patients suspected to have BCR-ABL1-negative myeloproliferative neoplasms
Authors: dos Santos Marcos Tadeu , Mitne-Neto Miguel , Miyashiro Kozue , Chauffaille Maria de Lourdes L Ferrari , Rizzatti Edgar Gil
Published: August 2013

Polycythaemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (MF), are the most common myeloproliferative neoplasms (MPN) in patients without the BCR-ABL1 gene rearrangement. They are caused by clonal expansion of haematopoietic stem cells and share, as a diagnostic criterion, the identification ofJAK2V617F mutation. Classically, when other clinical criteria are present, aJAK2V617F negative case requires the analysis of Exon12_JAK2for the diagnosis of PV, and ofMPL515K/L mutations for the diagnosis of ET and MF. Here, we evaluated 78 samples from Brazilian patients suspected to have MPN, without stratification for PV, ET or MF. We found that 28 (35.9%) areJAK2V617F carriers; from the 50 remaining samples, one (2%) showed an Exon12_JAK2mutation, and another (2%) was positive forMPLW515L mutation. In summary, the investigation ofJAK2V617F, Exon12_JAK2andMPLW515K/L was relevant for the diagnosis of 38.4% of patients suspected to have BCR-ABL1-negative MPN, suggesting that molecular genetic tests are useful for a quick and unequivocal diagnosis of MPN.
Achieving high and equitable coverage of adolescent HPV vaccine in Scotland
Authors: Sinka Katy , Kavanagh Kimberley , Gordon Ruth , Love John , Potts Alison , Donaghy Martin , Robertson Chris
Published: August 2013

Background and methods

The national immunisation records of over 220 000 girls offered vaccine in the routine or catch-up programme of the Human papillomavirus (HPV) programme in Scotland were analysed. Descriptive statistics and multilevel modelling were used to determine individual and organisational factors associated with uptake. Age, school year, school denomination, deprivation and, for school-leavers, mode of delivery were explored. Additional aggregate data were used to examine the effect of late uptake of missed doses in the routine vaccination programme.

Results

School-based delivery initially achieved over 80% uptake of complete courses in routine and catch-up age groups. Within this context of generally high coverage, there was an association between individual level deprivation and lower uptake, and a decline in in-year course completion over time. However, later uptake of missed doses in the following year substantially decreased these effects. There was no influence on uptake of the type of school (non-denominational/denominational). Vaccination of school-leavers in the catch-up campaign had lower coverage, with 50% starting and 30% completing the course in-year. There was no clear advantage of vaccination through general practice or through Board-run clinics in reaching this group.

Conclusions

School-based vaccination can achieve high and equitable uptake of a multidose vaccine in a routine immunisation programme. Sustained high coverage with HPV vaccine across Scotland provides a stable platform for planning future strategies for cervical screening and understanding the impact of the vaccination at a population level.
Endovascular treatment of pediatric intracranial aneurysms: a retrospective study of 35 aneurysms
Authors: Takemoto Koichiro , Tateshima Satoshi , Golshan Ali , Gonzalez Nestor , Jahan Reza , Duckwiler Gary , Vinuela Fernando
Published: August 2013

Background

Pediatric intracranial aneurysms are rare and not well characterized in comparison with those in adults.

Objective

To analyze our institution’s longitudinal experience of endovascular treatment for pediatric aneurysms to better understand this rare condition.

Methods

A retrospective record review was performed of patients aged <20 years treated with endovascular methods for intracranial aneurysms between 1995 and 2012. There were 31 patients (average 14.4±4.2 years; 20 male, 11 female) with 35 intracranial aneurysms.

Results

The rate of subarachnoid hemorrhage as the initial presentation was 48% and the rates of multiple and giant aneurysms were 13% and 31%, respectively; 28.5% of the cases were posterior circulation aneurysms. Fifteen saccular aneurysms occurred in 14 patients and 17 fusiform aneurysms were noted in 14 patients. Two infectious aneurysms were diagnosed in two patients and one traumatic aneurysm occurred in another patient. Thirty-four aneurysms were treated endovascularly and one had thrombosed spontaneously on a follow-up angiogram. Of the 15 saccular aneurysms, 11 were treated with conventional coiling, one was treated with stent-assisted coiling, one was treated with a flow-diverting stent and two were treated with parent vessel occlusion (PVO). Of the 17 fusiform aneurysms, 15 were treated with PVO with or without prior bypass surgery and one was treated with a flow-diverting stent. The rate of permanent complications and a favorable outcome were 2.9% and 87%, respectively.

Conclusions

Endovascular treatment of pediatric aneurysms is technically feasible with an acceptable complication rate despite the high incidence of fusiform aneurysms.