bluuebunny/crossref_metadata_2025 huggingface dataset:
Glioblastoma occurring at the site of a previous medulloblastoma following a 5‐year remission period
Authors: Martin Sarah E. , Brat Daniel J. , Vance Gail H. , Stohler Ryan , Choi Haki , Douglas‐Akinwande Annette C. , Hattab Eyas M.
Published: December 2011

We describe a case of a 14‐year‐old boy who developed a cerebellar and brainstem glioblastoma 5 years after treatment for a medulloblastoma. The patient first presented in 2003 with 9 months of vomiting and a 9‐kg weight loss. A head MRI showed a heterogeneously enhancing posterior fossa mass with hydrocephalus. Gross total resection was performed and the tumor was consistent with a classic medulloblastoma. Postoperative chemotherapy and craniospinal radiation was administered. The patient remained tumor‐free until 2008, at which time he presented with right‐sided weakness and numbness, left eye pain, vomiting and weight loss. Imaging showed abnormalities within the posterior pons, medulla, inferior cerebellar peduncles, cerebellar hemispheres and cervicomedullary junction with expansion of the medulla and cervical spinal cord. Due to the location of the lesion, biopsy was felt to be too risky and was avoided. Despite receiving chemotherapy, his symptoms continued to worsen and he died 4 months later. Post mortem examination limited to the brain and spinal cord confirmed the radiographic extent of the tumor. Microscopic examination showed a highly cellular infiltrative glial neoplasm with extensive palisading necrosis. A diagnosis of glioblastoma was rendered. The question of whether the first and second tumors were related is of potential clinical and academic interest. The first tumor was synaptophysin‐positive and GFAP‐negative, consistent with medulloblastoma. The second tumor was synaptophysin‐negative and focally GFAP‐positive, consistent with glioblastoma. The glioblastoma displayed EGF receptor amplification, and interestingly, it also displayed MYCN amplification; both tumors showed low level PTEN deletion. The medulloblastoma displayed a signal pattern consistent with an isochromosome 17q, while the glioblastoma showed some cells with an isochromosome 17q signal pattern amid a background of cells with abundant chromosomal instability. The relationship between these two tumors, particularly with regard to various molecular events, is discussed.
Matrix metalloproteinase‐9 expression in the nuclear compartment of neurons and glial cells in aging and stroke
Authors: Pirici Daniel , Pirici Ionica , Mogoanta Laurentiu , Margaritescu Otilia , Tudorica Valerica , Margaritescu Claudiu , Ion Daniela A. , Simionescu Cristiana , Coconu Marieta
Published: December 2011

Matrix metalloproteinases (MMPs) are well‐recognized denominators for extracellular matrix remodeling in the pathology of both ischemic and hemorrhagic strokes. Recent data on non‐nervous system tissue showed intracellular and even intranuclear localizations for different MMPs, and together with this, a plethora of new functions have been proposed for these intracellular active enzymes, but are mostly related to apoptosis induction and malign transformation. In neurons and glial cells, on human tissue, animal models and cell cultures, different active MMPs have been also proven to be located in the intra‐cytoplasmic or intra‐nuclear compartments, with no clear‐cut function. In the present study we show for the first time on human tissue the nuclear expression of MMP‐9, mainly in neurons and to a lesser extent in astrocytes. We have studied ischemic and hemorrhagic stroke patients, as well as aged control patients. Age and ischemic suffering seemed to be the best predictors for an elevated MMP‐9 nuclear expression, and there was no evidence of a clear‐cut extracellular proteolytic activity for this compartment, as revealed by intact vascular basement membranes and assessment of vascular densities. More, the majority of the cells expressing MMP‐9 in the nuclear compartment also co‐expressed activated‐caspase 3, indicating a possible link between nuclear MMP‐9 localization and apoptosis in neuronal and glial cells following an ischemic or hemorrhagic event. These results, besides showing for the first time the nuclear localization of MMP‐9 on a large series of human stroke and aged brain tissues, raise new questions regarding the unknown spectrum of the functions MMPs in human CNS pathology.
Saudi Arabian nurses' experiences of studying Masters degrees in Australia
Authors: Clerehan R. , McCall L. , McKenna L. , Alshahrani K.
Published: December 2011

CLEREHAN R., MCCALL L., MCKENNA L. & ALSHAHRANI K. (2012) Saudi Arabian nurses' experiences of studying Masters degrees in Australia. International Nursing Review59, 215–221

Aim:  This paper presents findings from a study which explored a group of Saudi Arabian nurses' experiences of studying for a Masters degree in Australia.

Background:  Arab states in the Middle East, Saudi Arabia in particular, have high expatriate nursing populations, and governments in the region have allocated considerable funding to up‐skilling their health workforce, often at Western universities. However, there has been little research into the learning experiences of nursing students from Middle East nations.

Methods:  A descriptive qualitative study design was used. Middle Eastern students undertaking Masters courses in a School of Nursing and Midwifery at one Australian university were invited to participate in a semi‐structured interview. Ten Saudi students participated and data were analysed using content analysis.

Findings:  Students experienced challenges related to the transition to very different forms of study; to managing relationships and family. They were resourceful, employing strategies to manage multiple demands, including differences in culture, and stressed the significance of strong personal relationships with staff. Students acknowledged being changed, even transformed, by their experience, and saw themselves as future change agents.

Conclusion:  Highly skilled local nursing professionals are being sought in many Middle Eastern countries and may undertake post‐graduate studies in Western contexts quite different from their own. Students reported that, in spite of difficulties, their experience prompted transformational change: intellectually, psychologically and developmentally. It is necessary for staff to understand expectations and learning preferences of these students to ensure fruitful learning outcomes and benefits to nursing in their home countries.
Basic fibroblast growth factor and tumour necrosis factor alpha in vitiligo and other hypopigmented disorders: suggestive possible therapeutic targets
Authors: Seif El Nasr H. , Shaker O.G. , Fawzi M.M.T. , El‐Hanafi G.
Published: December 2011

Background  In healthy skin, there is a molecular microenvironment that favours the survival of melanocytes and regulates their function. Keratinocytes synthesize and secrete several cytokines that have stimulatory and inhibitory effects on melanocytes.

Aim of the work  This work was conducted to evaluate the expression of basic fibroblast growth factor (bFGF) and tumour necrosis factor alpha (TNF‐α) mRNA levels in lesional skin of vitiligo, hypopigmented mycosis fungoides and hypopigmented tinea versicolor.

Patients and Methods  Forty eight patients (25 vitiligo, 14 hypopigmented mycosis fungoides, 9 hypopigmented tinea versicolor) and 10 healthy controls were included. A 4 mm punch skin biopsy was taken from lesional skin of patients, and the normal skin of controls for quantitative PCR examination of TNF‐α and bFGF mRNA.

Results  The level of TNF‐α mRNA in lesional skin of the three studied disorders was significantly higher than in the control group, while the level of bFGF mRNA was significantly lower in lesional skin of the three diseases than the control skin. A significant inverse correlation was demonstrated between the mRNA levels of the two studied cytokines in vitiligo and hypopigmented MF lesions.

Conclusion  The study’s findings demonstrate that the studied hypopigmented (vitiligo, hypopigmented MF, hypopigmented TV) disorders show similar changes in their cutaneous microenvironment with increased TNF‐α and decreased bFGF mRNA expression. This cytokine microenvironment change may be implicated in the pigment loss and hence these cytokines may have future therapeutic implications.
Why Athletic Doping Should Be Banned
Authors: CHWANG ERIC
Published: December 2011

abstract

So long as a ban is enforceable, large private athletic institutions—such as Major League Baseball and the National Collegiate Athletic Association—should not allow their athletes to take performance‐enhancing drugs. The argument I present is game‐theoretic: though each athlete prefers unilateral permission to dope over a universal ban, he also prefers a universal ban over universal permission to dope. That is because, while doping improves absolute measures of performance, it does not improve relative performance if many athletes dope. Large private athletic institutions should honour their athletes' preferences and should not enact any policy that gives only some athletes but not others permission to dope. Thus, they should ban doping. My paper examines and defends this game‐theoretic argument. After explaining the argument, I compare it (favourably) to other arguments for the same conclusion. I then discuss whether the game‐theoretic argument counterintuitively fails to justify banning some forms of doping (no), and whether it counterintuitively justifies banning things other than doping (also no). After arguing that a doping ban on game‐theoretic grounds is neither wrongly paternalistic or nor wrongfully coercive, I end by discussing some limitations of the argument.
Gastrointestinal Effects of the Addition of Ascorbic Acid to Aspirin
Authors: Patel Vrunda , Fisher Matt , Voelker Michael , Gessner Uwe
Published: December 2011

Nonsteroidal anti‐inflammatory drugs (NSAIDs), including aspirin, have been associated with the damage to the gastrointestinal tract. One proposed mechanism of injury to the gastrointestinal mucosa by NSAIDs is oxygen radical‐dependent microvascular injury. There is reasonable evidence to support the benefit of the addition of ascorbic acid, an ingredient with antioxidant properties, to moderate the adverse gastrointestinal (GI) effects of aspirin. Pharmacokinetic data have demonstrated that aspirin and ascorbic acid combination therapy can assist in mitigating the decrease in levels of ascorbic acid secondary to aspirin monotherapy. Endoscopic evaluation has demonstrated that the addition of ascorbic acid to aspirin significantly improves Lanza scores and rates of blood loss when compared to aspirin administration alone. When taken with ascorbic acid, the patient‐reported tolerability of aspirin has been shown to be comparable to paracetamol and placebo. The existing body of evidence is relevant to short‐term therapy with analgesic aspirin doses, and extrapolation to long‐term therapy with low‐dose aspirin is not appropriate. The purported benefit of an aspirin and ascorbic acid combination is a local observance and is not suspected to influence the adverse GI effects experienced as a result of systemic prostaglandin inhibition. Nevertheless, ascorbic acid may be a viable addition to the strategies employed to improve the gastrointestinal tolerability of aspirin.
Pontomedullary Lacerations in Falls from a Height—A Retrospective Autopsy Study*
Authors: Živković Vladimir , Nikolić Slobodan , Babić Dragan , Djonić Danijela , Atanasijević Tatjana , Djurić Marija
Published: December 2011

Abstract:  Brainstem pontomedullary laceration (PML) in falls from a height appears as isolated cases and usually in feet‐first impacts with a ring fracture. The aim of this study was to determine the frequency of PML in falls from a height, as well as the frequency of concomitant head and neck injuries. Out of 261 cases, PML was present in 40. An impact to the chin, as well as a feet‐ or buttocks‐first impact, most often led to PML owing to transmission of the impact force. Also, a lateral, frontal, or posterior head impact, with subsequent hinge fracture, as well as the frontoposterior hyperextension of the head associated with an upper spine fracture, could be possible mechanisms of PML in falls from a height. The jawbone and other facial bones act as shock absorbers, and their fracture diminishes energy transfer toward the skull and protects the brain and brainstem from injury.
Detection of Amitriptyline, Citalopram, and Metabolites in Porcine Bones Following Extended Outdoor Decomposition*
Authors: Desrosiers Nathalie A. , Watterson James H. , Dean Dorothy , Wyman John F.
Published: December 2011

Abstract:  Skeletal remains of a domestic pig were assessed for relative distribution of amitriptyline, citalopram, and metabolites. Following acute exposure and outdoor decomposition for 2 years, drugs and metabolites were analyzed in 13 different bones. Bones were pulverized following a simple wash procedure, and drugs were extracted by passive incubation in methanol, followed by solid‐phase extraction. Samples were analyzed by ultra‐high performance liquid chromatography (UHPLC) and confirmed with gas chromatography–mass spectrometry. The Kruskall–Wallis test showed that bone type was a main effect with respect to drug level for all analytes, with levels varying from 33‐ to 166‐fold. Ratios of levels of drug to that of the corresponding metabolite were less variable, varying roughly one‐ to eightfold. This suggests limitations in the interpretive value of drug measurements in bone and that relative levels of drug and metabolites should be further investigated in terms of forensic value.
Development of a Real‐Time Method to Detect DNA Degradation in Forensic Samples*
Authors: Nicklas Janice A. , Noreault‐Conti Trisha , Buel Eric
Published: December 2011

Abstract:  Knowledge of the degradation state of evidentiary DNA samples would allow selection of the appropriate analysis method (standard short tandem repeats [STRs] vs. mini STRs vs. mtDNA). This article describes the development of a Plexor® technology/real‐time PCR DNA degradation detection assay, which uses a common forward primer and two reverse primers (different fluorophores) to generate two Alu amplicons (63 and 246 bp). This very sensitive assay was optimized for reaction volume, cycle number, anneal/extend time, and temperature. Using DNA samples degraded with DNaseI, the ratio of the concentration of the short amplicon to the concentration of the long amplicon (degradation ratio) was increased versus time of degradation. Experiments were performed on a variety of environmentally degraded samples (age, sunlight, heat) and with seven commonly encountered forensic inhibitors. The degradation ratio was found to predict the observed loss of larger STR loci seen in the analysis of comprised samples.
Responses ofLucilia sericataMeigen (Diptera: Calliphoridae) to Cadaveric Volatile Organic Compounds*
Authors: Frederickx Christine , Dekeirsschieter Jessica , Verheggen Francois J. , Haubruge Eric
Published: December 2011

Abstract: Flies of the Calliphoridae Family are the most forensically important insects because of their abundance on the decedent during the first minutes following death. Necrophagous insects are attracted at a distance by a decomposing body, through the use of volatile chemical cues. We tested the possible attractive role of some volatile organic chemicals (VOCs) released by decaying cadavers, on male and female ofLucilia sericataMeigen (Diptera: Calliphoridae). Two complementary approaches were used. Electroantennography (EAG) allowed identifying the semiochemicals that are detected by the olfactory system ofL. sericata. Dose–response tests with EAG showed that dimethyl disulfide (DMDS) and butan‐1‐ol elicited the highest responses. Behavioral assays showed that, among the VOCs tested, DMDS and butan‐1‐ol are attractive forL. sericata, while the other VOCs are repulsive or do not cause any behavior. Our results may have potential implications in a better understanding of attractiveness of blowflies toward a corpse.
The long‐term impacts of predators on prey: inducible defenses, population dynamics, and indirect effects
Authors: Hoverman Jason T. , Relyea Rick A.
Published: December 2011

Despite the amount of research on the inducible defenses of prey against predators, our understanding of the long‐term significance of non‐lethal predators on prey phenotypes, prey population dynamics, and community structure has rarely been explored. Our objectives were to assess the effects of predators on prey defenses, prey population dynamics, and the relative magnitude of density‐ versus trait‐mediated indirect interactions (DMIIs and TMIIs) over multiple prey generations. Using a freshwater snail and three common snail predators, we constructed a series of community treatments with pond mesocosms that manipulated trophic structure, the identity of the top predator, and whether predators were caged or uncaged. We quantified snail phenotypes, snail population size, and resource abundance over multiple snail generations. We found that snails were expressing inducible defenses in our system although the magnitude of the responses varied over time and across predator species. Despite the expression of inducible defenses, caged predators did not reduce snail population size. There also was no evidence of TMIIs throughout the experiment suggesting that TMIIs have a minimal role in the long‐term structure of our communities. The absence of TMIIs was largely driven by the lack of predator‐induced reductions in resource consumption and the lack of consistent reductions in population size with predator cues. In contrast, we detected strong DMIIs associated with lethal predators suggesting that DMIIs are the dominant long‐term mechanism influencing community structure. Our results demonstrate that although predators can have significant effects on prey phenotypes and sometimes cause short‐term TMIIs, there may be few long‐term consequences of these responses on population dynamics and indirect interactions, at least within simple food webs. Research directed towards addressing the long‐term consequences of predator–prey interactions within communities will help to reveal whether the conclusions and predictions generated from short‐term experiments are applicable over ecological and evolutionary timescales.
The Prediction and Cost of Futility in the NICU
Authors: Meadow William , Cohen‐Cutler Sally , Spelke Bridget , Kim Anna , Plesac Melissa , Weis Kirsten , Lagatta Joanne
Published: December 2011

Aim:  To quantify the cost and prediction of futile care in the Neonatal Intensive Care Unit (NICU).

Methods:  We observed 1813 infants on 100 000 NICU bed days between 1999 and 2008 at the University of Chicago. We determined costs and assessed predictions of futility for each day the infant required mechanical ventilation.

Results:  Only 6% of NICU expenses were spent on nonsurvivors, and in this sense, they were futile. If only money spent after predictions of death is considered, futile expenses fell to 4.5%. NICU care was preferentially directed to survivors for even the smallest infants, at the highest risk to die. Over 75% of ventilated NICU infants were correctly predicted to survive on every day of ventilation by every caretaker. However, predictions of ‘die before discharge’ were wrong more than one time in three. Attendings and neonatology fellows tended to be optimistic, while nurses and neonatal nurse practitioners tended to be pessimistic.

Conclusions:  Criticisms of the expense of NICU care find little support in these data. Rather, NICU care is remarkably well targeted to patients who will survive, particularly when contrasted with care in adult ICUs. We continue to search for better prognostic tools for individual infants.
A GENERAL METHOD FOR THE CONSISTENT VOLUME ASSESSMENT OF COMPLEX HYDROCARBON TRAPS
Authors: Beha A. , Christensen J.E. , Young R.
Published: December 2011

Complex hydrocarbon traps are those in which a number of different trapping elements have to work favourably and simultaneously in order to allow access to the full hydrocarbon volume potential of the prospect. The probability of success varies across the prospect and the volume distribution.

A consistent assessment of the probability of success relative to the volume uncertainty of hydrocarbon traps is essential for unbiased prospect characterisation and vital for decision making, portfolio management and for delivering predicted value. It is relatively straightforward to assess the probability of geological success and volume uncertainty of simple anticlines or domal structures. Unfortunately, simple four‐way closures are usually drilled early in the exploration of a basin or play and become increasingly less common with exploration maturity. As a consequence, prospects available for drilling in mature exploration areas are typically complex traps, i.e. they possess a combination of different trapping elements. In such cases, trapping of the full volume potential requires that many geological elements work concurrently.

Complex traps are often perceived to carry a comparatively lower probability of geological success. However, the introduction of additional factors in a multiplicative chance estimation model may not reflect the true probability of finding hydrocarbons at the prospect location. Evaluations which involve multiplying additional chance factors may lead to an under‐estimation of the probability of geological success and an over‐estimation of the hydrocarbon volume.

A solution to this problem is to calculate the probability of occurrence of each possible success scenario or outcome. This paper describes a straightforward method for assessing volume uncertainty in complex traps which is independent of the model or method used to estimate the probability of geological success. A faulted four‐way closure is used as an example for the detailed description of the suggested workflow.
Inflammation and Cancer: A Comparative View
Authors: Morrison Wallace B.
Published: December 2011

Rudolph Virchow first speculated on a relationship between inflammation and cancer more than 150 years ago. Subsequently, chronic inflammation and associated reactive free radical overload and some types of bacterial, viral, and parasite infections that cause inflammation were recognized as important risk factors for cancer development and account for one in four of all human cancers worldwide. Even viruses that do not directly cause inflammation can cause cancer when they act in conjunction with proinflammatory cofactors or when they initiate or promote cancer via the same signaling pathways utilized in inflammation. Whatever its origin, inflammation in the tumor microenvironment has many cancer‐promoting effects and aids in the proliferation and survival of malignant cells and promotes angiogenesis and metastasis. Mediators of inflammation such as cytokines, free radicals, prostaglandins, and growth factors can induceDNAdamage in tumor suppressor genes and post‐translational modifications of proteins involved in essential cellular processes including apoptosis,DNArepair, and cell cycle checkpoints that can lead to initiation and progression of cancer.
Symmetry and parity in Frobenius action on cohomology
Authors: Suh Junecue
Published: December 2011

We prove that the Newton polygons of Frobenius on the crystalline cohomology of proper smooth varieties satisfy a symmetry that results, in the case of projective smooth varieties, from Poincaré duality and the hard Lefschetz theorem. As a corollary, we deduce that the Betti numbers in odd degrees of any proper smooth variety over a field are even (a consequence of Hodge symmetry in characteristic zero), answering an old question of Serre. Then we give a generalization and a refinement for arbitrary varieties over finite fields, in response to later questions of Serre and of Katz.
Effects of Heat Treatment on Mechanical Property and Microstructure of Aluminum/Stainless Steel Bimetal Plate
Authors: Hwang Weng-Sing , Wu Tian-I , Sung Wen-Chung
Published: December 2011

The effects of postrolling heat treatment on the mechanical property and microstructure of 1050 aluminum alloy and 304 stainless steel (SS) clad metals were investigated. Clad metals were made by cold rolling after surface treatments of both sheets followed by heat treatment at 500 °C for various annealing times. The effects of transformation of microstructure at the interface on bonding strength are discussed. The initial clad roll bonding of Al/stainless steel clad metal was bonded by mechanical locking at the interface. The protruding stainless steel in the interface is the diffusion route and forms the better joint with aluminum in the annealing process, which results in the enhancement of the bonding strength. Intermediate layers were formed for over 2 h. It resulted in the weakening of the bonding strength and the fracture surface transforms into a brittle structure. As Al/stainless steel clad metals were under 13% reduction ratio, it had the optimum bond strength with a heat treatment for 1 h at 500 °C.
Entertainment Value: Should the Media Pay for Nature Conservation?
Authors: Jepson Paul , Jennings Steve , Jones Kate E. , Hodgetts Timothy
Published: December 2011

Many films and TV shows profit by extracting value from nature without contributing their fair share to conservation funding.
Is €80 Billion on the Horizon for European Research?
Authors: Reardon Sara
Published: December 2011

A proposal to increase overall E.U. research funding from roughly €57 billion for the current 7-year period (2007–13) to €80 billion ($108 billion) for 2014 to 2020 was announced on 30 November.
Genes Confirm Europeans' Blow to Native Americans
Authors: Balter Michael
Published: December 2011

A study published this week concludes that about 500 years ago, the number of reproductively active Native American women quickly plunged by half, indicating a "widespread and severe" contraction in population size.
Saudi Universities Offer Cash in Exchange for Academic Prestige
Authors: Bhattacharjee Yudhijit
Published: December 2011

Two Saudi institutions are aggressively acquiring the affiliations of overseas scientists with an eye to gaining visibility in research journals.
Hobi-Like Pestivirus in Aborted Bovine Fetuses
Authors: Decaro Nicola , Lucente Maria Stella , Mari Viviana , Sciarretta Rossana , Pinto Pierfrancesco , Buonavoglia Domenico , Martella Vito , Buonavoglia Canio
Published: December 2011

An outbreak of abortion affecting multiparous cows was associated with Hobi-like pestivirus infection. Viral RNA and antigens were detected in the tissues of two aborted fetuses. Molecular assays for other common abortogenic agents tested negative. At the genetic level, the Hobi-like pestivirus displayed the closest relatedness to Italian, Australian, and South American viruses, whereas it diverged from the prototype Thai isolate. These findings may have important implications for the pestivirus control/eradication programs in cattle herds.
Multiplex Real-Time PCR Assay and Melting Curve Analysis for Identifying Mycobacterium tuberculosis Complex and Nontuberculous Mycobacteria
Authors: Kim Jeong-Uk , Cha Choong-Hwan , An Hae-Kyong
Published: December 2011

A multiplex real-time PCR assay and melting curve analysis for identifying 23 mycobacterial species was developed and evaluated using 77 reference strains and 369 clinical isolates. Concordant results were obtained for all 189 (100%) isolates of the
Mycobacterium tuberculosis
complex and 169 (93.9%) isolates of nontuberculous mycobacteria. Our results showed that this multiplex real-time PCR assay is an effective tool for the mycobacterial identification from cultures.
Structural Determinants for Nuclear Envelope Localization and Function of Pseudorabies Virus pUL34
Authors: Schuster Franziska , Klupp Barbara G. , Granzow Harald , Mettenleiter Thomas C.
Published: December 2011

Herpesvirus proteins pUL34 and pUL31 form a complex at the inner nuclear membrane (INM) which is necessary for efficient nuclear egress. Pseudorabies virus (PrV) pUL34 is a type II membrane protein of 262 amino acids (aa). The transmembrane region (TM) is predicted to be located between aa 245 and 261, leaving only one amino acid in the C terminus that probably extends into the perinuclear space. It is targeted to the nuclear envelope in the absence of other viral proteins, pointing to intrinsic localization motifs, and shows structural similarity to cellular INM proteins like lamina-associated polypeptide (Lap) 2ß and Emerin. To investigate which domains of pUL34 are relevant for localization and function, we constructed chimeric proteins by replacing parts of pUL34 with regions of cellular INM proteins. First the 18 C-terminal amino acids encompassing the TM were exchanged with TM regions and C-terminal domains of Lap2ß and Emerin or with the first TM region of the polytopic lamin B receptor (LBR), including the nine following amino acids. All resulting chimeric proteins complemented the replication defect of PrV-ΔUL34, demonstrating that the substitution of the TM and the extension of the C-terminal domain does not interfere with the function of pUL34. Complementation was reduced but not abolished when the C-terminal 50 aa were replaced by corresponding Lap2ß sequences (pUL34-LapCT50). However, replacing the C-terminal 100 aa (pUL34-LapCT100) resulted in a nonfunctional protein despite continuing pUL31 binding, pointing to an important functional role of this region. The replacement of the N-terminal 100 aa (pUL34-LapNT100) had no effect on nuclear envelope localization but abrogated pUL31 binding and function.
A Single-Amino-Acid Polymorphism in Reovirus Protein μ2 Determines Repression of Interferon Signaling and Modulates Myocarditis
Authors: Irvin Susan C. , Zurney Jennifer , Ooms Laura S. , Chappell James D. , Dermody Terence S. , Sherry Barbara
Published: December 2011

Myocarditis is indicated as the second leading cause of sudden death in young adults. Reovirus induces myocarditis in neonatal mice, providing a tractable model system for investigation of this important disease. Alpha/beta-interferon (IFN-α/β) treatment improves cardiac function and inhibits viral replication in patients with chronic myocarditis, and the host IFN-α/β response is a determinant of reovirus strain-specific differences in induction of myocarditis. Virus-induced IFN-β stimulates a signaling cascade that establishes an antiviral state and further induces IFN-α/β through an amplification loop. Reovirus strain-specific differences in induction of and sensitivity to IFN-α/β are associated with the viral M1, L2, and S2 genes. The reovirus M1 gene-encoded μ2 protein is a strain-specific repressor of IFN-β signaling, providing one possible mechanism for the variation in resistance to IFN and induction of myocarditis between different reovirus strains. We report here that μ2 amino acid 208 determines repression of IFN-β signaling and modulates reovirus induction of IFN-β in cardiac myocytes. Moreover, μ2 amino acid 208 determines reovirus replication, both in initially infected cardiac myocytes and after viral spread, by regulating the IFN-β response. Amino acid 208 of μ2 also influences the cytopathic effect in cardiac myocytes after spread. Finally, μ2 amino acid 208 modulates myocarditis in neonatal mice. Thus, repression of IFN-β signaling mediated by reovirus μ2 amino acid 208 is a determinant of the IFN-β response, viral replication and damage in cardiac myocytes, and myocarditis. These results demonstrate that a single amino acid difference between viruses can dictate virus strain-specific differences in suppression of the host IFN-β response and, consequently, damage to the heart.
Prionemia and Leukocyte-Platelet-Associated Infectivity in Sheep Transmissible Spongiform Encephalopathy Models
Authors: Lacroux Caroline , Vilette Didier , Fernández-Borges Natalia , Litaise Claire , Lugan Séverine , Morel Nathalie , Corbière Fabien , Simon Stéphanie , Simmons Hugh , Costes Pierrette , Weisbecker Jean-Louis , Lantier Isabelle , Lantier Frederic , Schelcher François , Grassi Jacques , Castilla Joaquin , Andréoletti Olivier
Published: December 2011

The dynamics of the circulation and distribution of transmissible spongiform encephalopathy (TSE) agents in the blood of infected individuals remain largely unknown. This clearly limits the understanding of the role of blood in TSE pathogenesis and the development of a reliable TSE blood detection assay. Using two distinct sheep scrapie models and blood transfusion, this work demonstrates the occurrence of a very early and persistent prionemia. This ability to transmit disease by blood transfusion was correlated with the presence of infectivity in white blood cells (WBC) and peripheral blood mononucleated cells (PBMC) as detected by bioassay in mice overexpressing the ovine prion protein PrP (tg338 mice) and with the identification of abnormal PrP in WBC after using protein misfolding cyclic amplification (PMCA). Platelets and a large variety of leukocyte subpopulations also were shown to be infectious. The use of endpoint titration in tg338 mice indicated that the infectivity in WBC (per ml of blood) was 10
6.5
-fold lower than that in 1 g of posterior brainstem sample. In both WBC and brainstem, infectivity displayed similar resistance to PK digestion. The data strongly support the concept that WBC are an accurate target for reliable TSE detection by PMCA. The presence of infectivity in short-life-span blood cellular elements raises the question of the origin of prionemia.
Conformational Changes in Sindbis Virus Induced by Decreased pH Are Revealed by Small-Angle Neutron Scattering
Authors: He Lilin , Piper Amanda , Meilleur Flora , Hernandez Raquel , Heller William T. , Brown Dennis T.
Published: December 2011

Alphaviruses, such as Sindbis virus, undergo dramatic changes in three-dimensional structure upon exposure to low pH, and such exposure can establish conditions allowing fusion of the virus membrane with a cell plasma membrane upon return to neutral pH. While exposure to low pH is not required for entry of Sindbis virus into vertebrate or invertebrate cells, the conformational changes occurring at low pH may mimic those occurring upon virus-receptor interaction. Here, we employed small-angle neutron scattering with contrast variation to probe how the structure of a mammalian-grown Sindbis virus responds to moderately acidic pH. Several changes took place throughout the virion structure when the pH decreased from 7.2 to 6.4. Specifically, the RNA in the virion core underwent a conformational change. Additionally, the protein was redistributed. A significant amount of protein moved from the layer containing the lipid bilayer to the exterior of the virion. The results improve our understanding of the pH-driven alteration of Sindbis virus structure.
Contrasting patterns of territoriality and foraging mode in two stream-dwelling salmonids, Arctic char (Salvelinus alpinus) and brown trout (Salmo trutta)
Authors: Gunnarsson Guðmundur Smári , Steingrímsson Stefán Óli
Published: December 2011

Territoriality and foraging behaviour play major roles in determining the abundance and distribution of mobile animals. To date, territorial behaviour of young-of-the-year (YOY) salmonids is typically described for sit-and-wait individuals that defend territories from one foraging station, but rarely for more mobile fish. We examined the territorial behaviour and foraging mode of 31 YOY Arctic char ( Salvelinus alpinus ) and 30 YOY brown trout ( Salmo trutta ) in relation to ecological factors in six rivers in northern Iceland. Arctic char used larger territories than brown trout, corresponding with high and low mobility prior to attacking prey, respectively. Within species, more mobile fish also used larger territories. Territory size increased with body size and declined with increased food abundance as predicted, but surprisingly increased with rising intruder pressure. Finally, Arctic char territories overlapped more and were less exclusively defended than brown trout territories. This study shows that territories of mobile individuals may not always pertain to the same rules as single central-place territories and highlights that territorial behaviour, and its role in population regulation, may vary between salmonid species.
AC conductivity and dielectric analysis of graphite–clay nanocomposite
Authors: Goswami R. , Chakravartty S.C. , Krishna J.B.M. , Bose E. , Das D. , Chaudhury S.K. , Mukherjee S. , Saha P. , Mukherjee U. , Das P.K. , Banerjee R.
Published: December 2011

A number of graphite–clay composites with varying percentages of graphite in the clay host have been prepared and their AC conductivities and dielectric behaviours have been studied in the frequency range from 42 Hz to 5 MHz. Measurements have been done for various concentrations of graphite filler to characterize their behaviour and develop composites with the desired conductivity for possible practical applications. The AC conductivity, σ(ω), increased with ω and followed a power law σ(ω) ∝ ωs with s ≤ 1, signifying conduction by hopping mechanism. The dielectric behaviour and loss tangents of the samples have been characterized by loss peaks for all of the samples, suggesting the presence of relaxation dipoles. The broad asymmetric loss peaks of the dielectric response were analyzed using the Havriliak–Negami function and associated parameters relaxation time, τ; broadening, γ; and asymmetry, β, have been obtained.
Characterization of bacteriophages with a lytic effect on various Salmonella serotypes and Escherichia coli O157:H7
Authors: López-Cuevas Osvaldo , Castro-del Campo Nohelia , León-Félix Josefina , González-Robles Arturo , Chaidez Cristóbal
Published: December 2011

Four phages isolated from cattle and poultry feces were analyzed for their ability to lyse Salmonella serotypes and Escherichia coli O157:H7. The phage one-step growth curves, morphology, and genetic characteristics were determined. All phages showed a lytic effect on various Salmonella serotypes and E. coli O157:H7, which lysed at least 70% of the 234 strains tested. The phages had latent periods ranging from 10 to 15 min and generation times of 30 to 45 min, while burst size fluctuated between 154 and 426 PFU/cell. Phages morphology showed isometric and elongated heads and rigid contractile tails, consistent with morphology of the Myoviridae family. Phages’ DNA dendrograms showed a distinctive RFLP when digested by HindIII and EcoRV, and SDS–PAGE profile showed distinctive proteins expression as well. In vitro phage challenge showed a total reduction of E. coli O157:H7, Salmonella Typhimurium and Saintpaul counts at 2 h, whereas for Salmonella Montevideo a reduction and retardation growth, at a multiplicity of infection (MOI) of 100, was observed; however, under a MOI of 10 000, no viable cells were detected after 4 h. The wide host ranges of these phages suggested they could be used for simultaneous biocontrol of some Salmonella serotypes and E. coli O157:H7.
DIFFUSION IN ONE-DIMENSIONAL DISORDERED LATTICE
Authors: HUNG P. K. , MUNG T. V. , HONG N. V.
Published: December 2011

The diffusion in one-dimensional (1D) lattices with different types of energetic disorders has been investigated using both analytical method and Monte Carlo (MC) simulation. In single-particle case of two-level and uniform distributions the calculation shows a good agreement between analytical and simulation results for certain diffusion quantities. The expression for temperature dependence of diffusion coefficient DS is not Arrhenius one, but it tends to have Arrhenius type in the regime of low temperature. For many-particle case the simulation revealed two specific effects: first effect concerning the correlation factor FM decreases the diffusion coefficient DM as the coverage increases, second one relating to the mean time between two consecutive hops τ jump M conversely increase DM. For all 1D lattices the diffusion coefficient decreases with the coverage due to that first effect is stronger than second one. Furthermore, we have demonstrated that the ratio DM/DS weakly depends on temperature, although FM/FS and τ jump M/τ jump S strongly vary in the considered temperature interval.
Effects of body temperature maintenance on glucose, insulin, and corticosterone responses to acute hypoxia in the neonatal rat
Authors: Guenther Mitchell A. , Bruder Eric D. , Raff Hershel
Published: December 2011

One of the biggest challenges of premature birth is acute hypoxia. Hypothermia during acute hypoxic periods may be beneficial. We hypothesized that prevention of hypothermia during neonatal hypoxia disrupts glucose homeostasis and places additional metabolic challenges on the neonate. Pups at PD2 and PD8 were exposed to 8% O2 for 3 h, during which they were allowed to either spontaneously cool or were kept isothermic. There was also a time control group that was subjected to normoxia and kept isothermic. Plasma glucose, insulin, C-peptide, corticosterone, and catecholamines were measured from samples collected at baseline, 1 h, 2 h, and 3 h. In postnatal day 2 (PD2) rats, hypoxia alone resulted in no change in plasma glucose by 1 h, an increase by 2 h, and a subsequent decrease below baseline values by 3 h. Hypoxia with isothermia in PD2 rats elicited a large increase in plasma insulin at 1 h. In PD8 rats, hypoxia with isothermia resulted in an initial increase in plasma glucose, but by 3 h, glucose had decreased significantly to below baseline levels. Hypoxia with and without isothermia elicited an increase in plasma corticosterone at both ages and an increase in plasma epinephrine in PD8 rats. We conclude that the insulin response to hypoxia in PD8 rats is associated with an increase in glucose similar to an adult; however, insulin responses to hypoxia in PD2 rats were driven by something other than glucose. Prevention of hypothermia during hypoxia further disrupts glucose homeostasis and increases metabolic challenges.
Herpes Simplex Virus Hepatitis in an Immunocompetent Adult: A Fatal Outcome due to Liver Failure
Authors: Poley Rachel A. , Snowdon Jaime F. , Howes Daniel W.
Published: December 2011

Objective. To present a case of a healthy 41-year-old female who developed fulminant hepatic failure leading to death. The cause of hepatic failure identified on postmortem exam was herpes simplex virus hepatitis.Design. Observation of a single patient.Setting. Intensive care unit of a tertiary care university teaching hospital in Canada.Patient. 41-year-old previously healthy female presenting with a nonspecific viral illness and systemic inflammatory response syndrome.Intervention. The patient was treated with intravenous fluids and broad-spectrum antibiotics. On the second day of admission, she was found to have elevated transaminases, and, over 48 hours, she progressed to fulminant liver failure with disseminated intravascular coagulopathy, refractory lactic acidosis, and shock. She progressed to respiratory failure requiring intubation and mechanical ventilation. She was started on N-acetylcysteine, a bicarbonate infusion, hemodialysis, and multiple vasopressors and inotropes.Measurements and Main Results. Despite treatment, the patient died roughly 70 hours after her initial presentation to hospital. Her postmortem liver biopsy revealed herpes simplex virus hepatitis as her cause of death.Conclusions. Herpes simplex virus must be considered in all patients presenting with liver failure of unknown cause. If suspected, prompt treatment with acyclovir should be initiated.
Effect of Apheresis for ABO and HLA Desensitization on Anti-Measles Antibody Titers in Renal Transplantation
Authors: Schönermarck Ulf , Kauke Teresa , Jäger Gundula , Habicht Antje , Wendler Thorsten , Andrassy Joachim , Guba Markus , Stangl Manfred , Fischereder Michael
Published: December 2011

Desensitization strategies for ABO-incompatible renal transplants with plasma exchange (PE) or specific immunoadsorption (IA) decrease immunoglobulin levels. After recent measles outbreak and decreasing vaccination rates, we studied the impact of apheresis on anti-measles antibodies. Anti-measles antibodies were measured before desensitization, before transplantation and during followup in 12 patients with ABO incompatibility (2x PE only, 8x IA only, and 2x IA and PE) and 3 patients with donor-specific HLA antibodies (all PE). Patients received rituximab, IVIG, and standard immunosuppressive therapy. All patients had detectable anti-measles antibodies before desensitization (mean 3238 mU/l, range 560–8100). After 3–6 PE sessions, titers decreased significantly to 1710 mU/l (), in one patient to nondetectable values, while IA only maintained protective titers. After a median followup of 64 days, anti-measles antibodies returned to baseline in all patients. Immunity against measles was temporarily reduced by apheresis but remained detectable in most patients at time of transplantation. Desensitization maintains long-term protective immunity against measles.
Capacity-Preserved, Energy-Enhanced Hybrid Topology Management Scheme in Wireless Sensor Networks for Hazardous Applications
Authors: Jawahar A. , Radha S. , Sharath Kumar R.
Published: December 2011

A wireless sensor network is composed of large number of sensor nodes and they are densely deployed in the field to monitor the environment, collect the data and route it to a sink. The main constraint is that the nodes in such a network have a battery of limited stored energy the network lifetime gets reduced. There are various topology management schemes such as SPAN, STEM, GAF, BEES and so forth, for improving network parameters such as capacity, lifetime, coverage and latency. These schemes do not improve all the mentioned network parameters. Sustainable Physical Activity in Neighbourhood (SPAN) scheme, preserves network capacity, decreases latency but provides less energy savings. Sparse Topology and Energy Management (STEM) scheme does not preserve capacity resulting in great energy savings and high latency. In the proposed scheme, new coordinator rule is implemented in SPAN, and then integrated with STEM. It is observed that the energy conserved increases by about 3.18% to 4.17% without sacrificing network capacity. Due to definite path in the proposed scheme the latency is reduced by almost half the latency of STEM scheme.
Inherited Variation at Chromosome 12p13.33, Including RAD52, Influences the Risk of Squamous Cell Lung Carcinoma
Authors: Shi Jianxin , Chatterjee Nilanjan , Rotunno Melissa , Wang Yufei , Pesatori Angela C. , Consonni Dario , Li Peng , Wheeler William , Broderick Peter , Henrion Marc , Eisen Timothy , Wang Zhaoming , Chen Wei , Dong Qiong , Albanes Demetrius , Thun Michael , Spitz Margaret R. , Bertazzi Pier Alberto , Caporaso Neil E. , Chanock Stephen J. , Amos Christopher I. , Houlston Richard S. , Landi Maria Teresa
Published: December 2011

Although lung cancer is largely caused by tobacco smoking, inherited genetic factors play a role in its etiology. Genome-wide association studies in Europeans have only robustly demonstrated 3 polymorphic variations that influence the risk of lung cancer. Tumor heterogeneity may have hampered the detection of association signal when all lung cancer subtypes were analyzed together. In a genome-wide association study of 5,355 European ever-smoker lung cancer patients and 4,344 smoking control subjects, we conducted a pathway-based analysis in lung cancer histologic subtypes with 19,082 single-nucleotide polymorphisms mapping to 917 genes in the HuGE-defined “inflammation” pathway. We identified a susceptibility locus for squamous cell lung carcinoma at 12p13.33 (RAD52, rs6489769) and replicated the association in 3 independent studies totaling 3,359 squamous cell lung carcinoma cases and 9,100 controls (OR = 1.20, Pcombined = 2.3 × 10−8).

Significance: The combination of pathway-based approaches and information on disease-specific subtypes can improve the identification of cancer susceptibility loci in heterogeneous diseases. Cancer Discovery; 2(2); 131–9. © 2011 AACR.

Read the Commentary on this article by Sellers and Chen, p. 110.

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