bluuebunny/crossref_metadata_2025 huggingface dataset:
The Terminally Redundant, Nonpermuted Genome ofListeriaBacteriophage A511: a Model for the SPO1-Like Myoviruses of Gram-Positive Bacteria
Authors: Klumpp Jochen , Dorscht Julia , Lurz Rudi , Bielmann Regula , Wieland Matthias , Zimmer Markus , Calendar Richard , Loessner Martin J.
Published: June 2008

Only little information on a particular class of myoviruses, the SPO1-like bacteriophages infecting low-G+C-content, gram-positive host bacteria (Firmicutes), is available. We present the genome analysis and molecular characterization of the large, virulent, broad-host-rangeListeriaphage A511. A511 contains a unit (informational) genome of 134,494 bp, encompassing 190 putative open reading frames (ORFs) and 16 tRNA genes, organized in a modular fashion common among theCaudovirales. Electron microscopy, enzymatic fragmentation analyses, and sequencing revealed that the A511 DNA molecule contains linear terminal repeats of a total of 3,125 bp, encompassing nine small putative ORFs. This particular genome structure explains why A511 is unable to perform general transduction. A511 features significant sequence homologies toListeriaphage P100 and other morphologically related phages infectingFirmicutessuch asStaphylococcusphage K andLactobacillusphage LP65. Equivalent but more-extensive terminal repeats also exist in phages P100 (∼6 kb) and K (∼20 kb). High-resolution electron microscopy revealed, for the first time, the presence of long tail fibers organized in a sixfold symmetry in these viruses. Mass spectrometry-based peptide fingerprinting permitted assignment of individual proteins to A511 structural components. On the basis of the data available for A511 and relatives, we propose that SPO1-like myoviruses are characterized by (i) their infection of gram-positive, low-G+C-content bacteria; (ii) a wide host range within the host bacterial genus and a strictly virulent lifestyle; (iii) similar morphology, sequence relatedness, and collinearity of the phage genome organization; and (iv) large double-stranded DNA genomes featuring nonpermuted terminal repeats of various sizes.
Precise Determination, Cross-Recognition, and Functional Analysis of the Double-Strand Origins of the Rolling-Circle Replication Plasmids in Haloarchaea
Authors: Zhou Ligang , Zhou Meixian , Sun Chaomin , Han Jing , Lu Qiuhe , Zhou Jian , Xiang Hua
Published: June 2008

The precise nick site in the double-strand origin (DSO) of pZMX201, a 1,668-bp rolling-circle replication (RCR) plasmid from the haloarchaeon
Natrinema
sp. CX2021, was determined by electron microscopy and DSO mapping. In this plasmid, DSO nicking occurred between residues C404 and G405 within a heptanucleotide sequence (TCTC/GGC) located in the stem region of an imperfect hairpin structure. This nick site sequence was conserved among the haloarchaeal RCR plasmids, including pNB101, suggesting that the DSO nick site might be the same for all members of this plasmid family. Interestingly, the DSOs of pZMX201 and pNB101 were found to be cross-recognized in RCR initiation and termination in a hybrid plasmid system. Mutation analysis of the DSO from pZMX201 (DSO
Z
) in this hybrid plasmid system revealed that: (i) the nucleotides in the middle of the conserved TCTCGGC sequence play more-important roles in the initiation and termination process; (ii) the left half of the hairpin structure is required for initiation but not for termination; and (iii) a 36-bp sequence containing TCTCGGC and the downstream sequence is essential and sufficient for termination. In conclusion, these haloarchaeal plasmids, with novel features that are different from the characteristics of both single-stranded DNA phages and bacterial RCR plasmids, might serve as a good model for studying the evolution of RCR replicons.
UvrD and UvrD252 Counteract RecQ, RecJ, and RecFOR in a
rep
Mutant of
Escherichia coli
Authors: Lestini Roxane , Michel Bénédicte
Published: June 2008

Rep and UvrD are two related
Escherichia coli
helicases, and inactivating both is lethal. Based on the observation that the synthetic lethality of
rep
and
uvrD
inactivation is suppressed in the absence of the recombination presynaptic proteins RecF, RecO, or RecR, it was proposed that UvrD is essential in the
rep
mutant to counteract a deleterious RecFOR-dependent RecA binding. We show here that the synthetic lethality of
rep
and
uvrD
mutations is also suppressed by
recQ
and
recJ
inactivation but not by
rarA
inactivation. Furthermore, it is independent of the action of UvrD in nucleotide excision repair and mismatch repair. These observations support the idea that UvrD counteracts a deleterious RecA binding to forks blocked in the
rep
mutant. An ATPase-deficient mutant of UvrD [
uvrD(R284A)
] is dominant negative in a
rep
mutant, but only in the presence of all RecQJFOR proteins, suggesting that the UvrD(R284A) mutant protein is deleterious when it counteracts one of these proteins. In contrast, the
uvrD252
mutant (G30D), which exhibits a strongly decreased ATPase activity, is viable in a
rep
mutant, where it allows replication fork reversal. We conclude that the residual ATPase activity of UvrD252 prevents a negative effect on the viability of the
rep
mutant and allows UvrD to counteract the action of RecQ, RecJ, and RecFOR at forks blocked in the
rep
mutant. Models for the action of UvrD at blocked forks are proposed.
Direct Visualization of the Outer Membrane of Mycobacteria and Corynebacteria in Their Native State
Authors: Zuber Benoît , Chami Mohamed , Houssin Christine , Dubochet Jacques , Griffiths Gareth , Daffé Mamadou
Published: June 2008

The cell envelope of mycobacteria, which include the causative agents of tuberculosis and leprosy, is crucial for their success as pathogens. Despite a continued strong emphasis on identifying the multiple chemical components of this envelope, it has proven difficult to combine its components into a comprehensive structural model, primarily because the available ultrastructural data rely on conventional electron microscopy embedding and sectioning, which are known to induce artifacts. The existence of an outer membrane bilayer has long been postulated but has never been directly observed by electron microscopy of ultrathin sections. Here we have used cryo-electron microscopy of vitreous sections (CEMOVIS) to perform a detailed ultrastructural analysis of three species belonging to the
Corynebacterineae
suborder, namely,
Mycobacterium bovis
BCG,
Mycobacterium smegmatis
, and
Corynebacterium glutamicum
, in their native state. We provide new information that accurately describes the different layers of the mycobacterial cell envelope and challenges current models of the organization of its components. We show a direct visualization of an outer membrane, analogous to that found in gram-negative bacteria, in the three bacterial species examined. Furthermore, we demonstrate that mycolic acids, the hallmark of mycobacteria and related genera, are essential for the formation of this outer membrane. In addition, a granular layer and a low-density zone typifying the periplasmic space of gram-positive bacteria are apparent in CEMOVIS images of mycobacteria and corynebacteria. Based on our observations, a model of the organization of the lipids in the outer membrane is proposed. The architecture we describe should serve as a reference for future studies to relate the structure of the mycobacterial cell envelope to its function.
Genome-Wide Analysis of Ruminant
Staphylococcus aureus
Reveals Diversification of the Core Genome
Authors: Ben Zakour Nouri L. , Sturdevant Daniel E. , Even Sergine , Guinane Caitriona M. , Barbey Corinne , Alves Priscila D. , Cochet Marie-Françoise , Gautier Michel , Otto Michael , Fitzgerald J. Ross , Le Loir Yves
Published: June 2008

Staphylococcus aureus
causes disease in humans and a wide array of animals. Of note,
S. aureus
mastitis of ruminants, including cows, sheep, and goats, results in major economic losses worldwide. Extensive variation in genome content exists among
S. aureus
pathogenic clones. However, the genomic variation among
S. aureus
strains infecting different animal species has not been well examined. To investigate variation in the genome content of human and ruminant
S. aureus
, we carried out whole-genome PCR scanning (WGPS), comparative genomic hybridizations (CGH), and the directed DNA sequence analysis of strains of human, bovine, ovine, and caprine origin. Extensive variation in genome content was discovered, including host- and ruminant-specific genetic loci. Ovine and caprine strains were genetically allied, whereas bovine strains were heterogeneous in gene content. As expected, mobile genetic elements such as pathogenicity islands and bacteriophages contributed to the variation in genome content between strains. However, differences specific for ruminant strains were restricted to regions of the conserved core genome, which contained allelic variation in genes encoding proteins of known and unknown function. Many of these proteins are predicted to be exported and could play a role in host-pathogen interactions. The genomic regions of difference identified by the whole-genome approaches adopted in the current study represent excellent targets for studies of the molecular basis of
S. aureus
host adaptation.
Mitochondrial matrix metalloproteinase activation decreases myocyte contractility in hyperhomocysteinemia
Authors: Moshal Karni S. , Tipparaju Srinivas M. , Vacek Thomas P. , Kumar Munish , Singh Mahavir , Frank Iluiana E. , Patibandla Phani K. , Tyagi Neetu , Rai Jayesh , Metreveli Naira , Rodriguez Walter E. , Tseng Michael T. , Tyagi Suresh C.
Published: June 2008

Cardiomyocyte N-methyl-d-aspartate receptor-1 (NMDA-R1) activation induces mitochondrial dysfunction. Matrix metalloproteinase protease (MMP) induction is a negative regulator of mitochondrial function. Elevated levels of homocysteine [hyperhomocysteinemia (HHCY)] activate latent MMPs and causes myocardial contractile abnormalities. HHCY is associated with mitochondrial dysfunction. We tested the hypothesis that HHCY activates myocyte mitochondrial MMP (mtMMP), induces mitochondrial permeability transition (MPT), and causes contractile dysfunction by agonizing NMDA-R1. The C57BL/6J mice were administered homocystinemia (1.8 g/l) in drinking water to induce HHCY. NMDA-R1 expression was detected by Western blot and confocal microscopy. Localization of MMP-9 in the mitochondria was determined using confocal microscopy. Ultrastructural analysis of the isolated myocyte was determined by electron microscopy. Mitochondrial permeability was measured by a decrease in light absorbance at 540 nm using the spectrophotometer. The effect of MK-801 (NMDA-R1 inhibitor), GM-6001 (MMP inhibitor), and cyclosporine A (MPT inhibitor) on myocyte contractility and calcium transients was evaluated using the IonOptix video edge track detection system and fura 2-AM. Our results demonstrate that HHCY activated the mtMMP-9 and caused MPT by agonizing NMDA-R1. A significant decrease in percent cell shortening, maximal rate of contraction (−dL/d t), and maximal rate of relaxation (+dL/d t) was observed in HHCY. The decay of calcium transient amplitude was faster in the wild type compared with HHCY. Furthermore, the HHCY-induced decrease in percent cell shortening, −dL/d t, and +dL/d t was attenuated in the mice treated with MK-801, GM-6001, and cyclosporin A. We conclude that HHCY activates mtMMP-9 and induces MPT, leading to myocyte mechanical dysfunction by agonizing NMDA-R1.
Effects of hypoxia on relationships between cytosolic and mitochondrial NAD(P)H redox and superoxide generation in coronary arterial smooth muscle
Authors: Gao Qun , Wolin Michael S.
Published: June 2008

Since controversy exists on how hypoxia influences vascular reactive oxygen species (ROS) generation, and our previous work provided evidence that it relaxes endothelium-denuded bovine coronary arteries (BCA) in a ROS-independent manner by promoting cytosolic NADPH oxidation, we examined how hypoxia alters relationships between cytosolic and mitochondrial NAD(P)H redox and superoxide generation in BCA. Methods were developed to image and interpret the effects of hypoxia on NAD(P)H redox based on its autofluorescence in the cytosolic, mitochondrial, and nuclear regions of smooth muscle cells isolated from BCA. Aspects of anaerobic glycolysis and cytosolic NADH redox in BCA were assessed from measurements of lactate and pyruvate. Imaging changes in mitosox and dehydroethidium fluorescence were used to detect changes in mitochondrial and cytosolic-nuclear superoxide, respectively. Hypoxia appeared to increase mitochondrial and decrease cytosolic-nuclear superoxide under conditions associated with increased cytosolic NADH (lactate/pyruvate), mitochondrial NAD(P)H, and hyperpolarization of mitochondria detected by tetramethylrhodamine methyl-ester perchlorate fluorescence. Rotenone appeared to increase mitochondrial NAD(P)H and superoxide, suggesting hypoxia could increase superoxide generation by complex I. However, hypoxia decreased mitochondrial superoxide in the presence of contraction to 30 mM KCl, associated with decreased mitochondrial NAD(P)H. Thus, while hypoxia augments NAD(P)H redox associated with increased mitochondrial superoxide, contraction with KCl reverses these effects of hypoxia on mitochondrial superoxide, suggesting mitochondrial ROS increases do not mediate hypoxic relaxation in BCA. Since hypoxia lowers pyruvate, and pyruvate inhibits hypoxia-elicited relaxation and NADPH oxidation in BCA, mitochondrial control of pyruvate metabolism associated with cytosolic NADPH redox regulation could contribute to sensing hypoxia.
Phospholipase C-δ1modulates sustained contraction of rat mesenteric small arteries in response to noradrenaline, but not endothelin-1
Authors: Clarke Christopher J. , Forman Simon , Pritchett James , Ohanian Vasken , Ohanian Jacqueline
Published: June 2008

Vasoconstrictors activate phospholipase C (PLC), which hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2), leading to calcium mobilization, protein kinase C activation, and contraction. Our aim was to investigate whether PLC-δ1, a PLC isoform implicated in α1-adrenoreceptor signaling and the pathogenesis of hypertension, is involved in noradrenaline (NA) or endothelin (ET-1)-induced PIP2hydrolysis and contraction. Rat mesenteric small arteries were studied. Contractility was measured by pressure myography, phospholipids or inositol phosphates were measured by radiolabeling with33Pi or myo-[3H]inositol, and caveolae/rafts were prepared by discontinuous sucrose density centrifugation. PLC-δ1was localized by immunoblot analysis and neutralized by delivery of PLC-δ1antibody. The PLC inhibitor U73122, but not the negative control U-73342, markedly inhibited NA and ET-1 contraction but had no effect on potassium or phorbol ester contraction, implicating PLC activity in receptor-mediated smooth muscle contraction. PLC-δ1was present in caveolae/rafts, and NA, but not ET-1, stimulated a rapid twofold increase in PLC-δ1levels in these domains. PLC-δ1is calcium dependent, and removal of extracellular calcium prevented its association with caveolae/rafts in response to NA, concomitantly reducing NA-induced [33P]PIP2hydrolysis and [3H]inositol phosphate formation but with no effect on ET-1-induced [33P]PIP2hydrolysis. Neutralization of PLC-δ1by PLC-δ1antibody prevented its caveolae/raft association and attenuated the sustained contractile response to NA compared with control antibodies. In contrast, ET-1-induced contraction was not affected by PLC-δ1antibody. These results indicate the novel and selective role of caveolae/raft localized PLC-δ1in NA-induced PIP2hydrolysis and sustained contraction in intact vascular tissue.
High-dose but not low-dose mainstream cigarette smoke suppresses allergic airway inflammation by inhibiting T cell function
Authors: Thatcher Thomas H. , Benson Randi P. , Phipps Richard P. , Sime Patricia J.
Published: June 2008

Epidemiological studies have identified childhood exposure to environmental tobacco smoke as a significant risk factor for the onset and exacerbation of asthma, but studies of smoking in adults are less conclusive, and mainstream cigarette smoke (MCS) has been reported to both enhance and attenuate allergic airway inflammation in animal models. We sensitized mice to ovalbumin (OVA) and exposed them to MCS in a well-characterized exposure system. Exposure to MCS (600 mg/m3total suspended particulates, TSP) for 1 h/day suppresses the allergic airway response, with reductions in eosinophilia, tissue inflammation, goblet cell metaplasia, IL-4 and IL-5 in bronchoalveolar lavage (BAL) fluid, and OVA-specific antibodies. Suppression is associated with a loss of antigen-specific proliferation and cytokine production by T cells. However, exposure to a lower dose of MCS (77 mg/m3TSP) had no effect on the number of BAL eosinophils or OVA-specific antibodies. This is the first report to demonstrate, using identical smoking methodologies, that MCS inhibits immune responses in a dose-dependent manner and may explain the observation that, although smoking provokes a systemic inflammatory response, it also inhibits T cell-mediated responses involved in a number of diseases.
Disproportionality Measures of Concentration, Specialization, and Localization
Authors: Bickenbach Frank , Bode Eckhardt
Published: June 2008

This article extends the methodological toolbox of measures of regional concentration of industries and industrial specialization of regions. It first defines disproportionality measures of concentration and specialization and proposes a taxonomy of these measures. This taxonomy is based on three characteristic features of any disproportionality measure. It helps researchers define the measure that fits their research purpose and data best. The article then generalizes this taxonomy to cover disproportionality measures of economic localization that evaluate specialization and concentration simultaneously and spatial disproportionality measures that deal with the checkerboard problem and the modifiable areal unit problem.
Radical Economics and Social Change Movements: Strengthening the Links between Academics and Activists
Authors: Stanford Jim
Published: June 2008

The article considers the barriers to closer cooperation between progressive economists and progressive social change movements. The author provides some examples of successful cooperation, but suggests that these are the exception rather than the norm. The article makes five concrete suggestions for each side that would help to strengthen the relationships between them, and engage progressive economists more fully in social change campaigns.
Elements of a Radical Counter-movement to Neoliberalism: Employment-led Development
Authors: Kaboub Fadhel
Published: June 2008

After highlighting the failure of mainstream economic theory in dealing with the rising global inequality and economic struggles brought about by neoliberal economic policies, the paper presents the outline of an alternative policy proposal to create full employment and price stability, and to restore financial sovereignty to developing countries. Under the Employer of Last Resort (ELR) program, the government guarantees employment to all through a decentralized community-based job creation policy. Projects are selected by local community groups based on community needs and the availability of skills in the unemployment pool. Funding is provided by a central/federal fiscal authority and requires policy coordination with the central bank.
Puzzles, Paradoxes, and Regularities: Cyclical and Structural Productivity in the United States (1950–2005)
Authors: Jeon Yongbok , Vernengo Matías
Published: June 2008

Changes in labor productivity have been a source of puzzlement and paradoxical results for economists. We suggest that puzzles and paradoxes vanish once two simple regularities are properly acknowledged. Okun's and Verdoorn's laws explain 87 percent of all the variations in labor productivity. Also, our estimation method and our results suggest that conventional measures of Okun's Law have overestimated the value of the Okun coefficient, and accepted a greater degree of variability than is actually guaranteed by the empirical evidence. Okun's Law has been relatively stable through time, and there has been no significant decrease in the value of the parameter since the 1960s.
Examining Team Planning Through an Episodic Lens
Authors: DeChurch Leslie A. , Haas Craig D.
Published: June 2008

Three types of team planning processes differing in terms of timing and adaptation capacity are investigated. Deliberate planning and contingency planning occur during team transition phases; deliberate planning specifies a primary course of action whereas contingency planning specifies backup plans. Reactive adjustment is planning that occurs during the action phase when teams adapt plans to account for evolving task conditions. The current study uses data from a scavenger hunt game involving a total of 38 teams randomly assigned to preplanning or control conditions. While instructing teams to plan increased deliberate planning, it does not increase the adaptation-enabling processes of contingency planning and reactive adjustment. Team effectiveness is determined most strongly by reactive adjustment, then by contingency planning, and least so by deliberate planning.
Teaching with game-based learning management systems: Exploring a pedagogical dungeon
Authors: Carron Thibault , Marty Jean-Charles , Heraud Jean-Mathias
Published: June 2008

The work reported here takes place in the educational domain. The authors propose a learning environment based on a graphical representation of a course. The emergence of online multiplayer games led the authors to apply the following metaphor to the digital work environments: The method of acquiring knowledge during a learning session is similar to the exploration of a dungeon, where each student collects knowledge related to a learning activity. In the first part of this article, the authors focuses on a description of how concepts of learning activities can be represented in the dungeon view. The second part deals with the support of the observation task for the teacher during a learning session and more generally with providing users with awareness. The authors thus propose a multiagent system using data collected from traces resulting from the collaborative learning activity. Finally, this environment allowed the authors to set up experiments with students at their university.
Limits to Modeling: Balancing Ambition and Outcome in Astrophysics and Cosmology
Authors: Ruphy Stéphanie
Published: June 2008

Computer simulations of complex physical objects and processes for which data are very sparse or inexistent have become a major tool of scientific investigation in astrophysics and cosmology. However, one must ask how these simulations acquire their epistemic credentials and whether their realistic ambition is legitimate. A close look at two model-building processes—one in galactic astrophysics, the other in cosmology—reveals heretofore underappreciated features of simulations, such as path dependency. This article argues that such features undermine our confidence in the outcomes of the simulation. Case studies presented here reveal a general tension in computer simulation between realistic ambitions and the possibility of empirical confirmation. The analysis will thus lead to a reassessment of the epistemic goals actually achieved by composite models of complex astrophysical and cosmological phenomena.
A Systemic-Constructivist Approach to the Facilitation and Debriefing of Simulations and Games
Authors: Kriz Willy Christian
Published: June 2008

This article introduces some basic concepts of a systemic-constructivist perspective. These show that gaming simulation corresponds closely to a systemic-constructivist approach to learning and instruction. Some quality aspects of facilitating and debriefing simulation games are described from a systemic-constructivist point of view. Finally, a structure for debriefing, and some concrete examples of systemic-constructivist debriefing-methods are presented.
Is There a Place for Sexuality in the Holistic Care of Patients in the Palliative Care Phase of Life?
Authors: Redelman Margaret J.
Published: June 2008

Being diagnosed with a life-limiting condition is a traumatic event. The journey to the moment of death is usually only done once—so it is a time of fears and uncertainty. Sexuality is particularly vulnerable at this time. It may be difficult for both patient and partner to deal with the changes in sexuality without professional assistance. It is “sexuality” rather than “sex” that defines the meaningful relationships people have with themselves and significant others. When sexuality is lost or changed, important benefits may be lost. Studies show that many patients do value sexuality and want assistance in making the best of their sexual potential during the palliative care phase. Health professionals regularly acknowledge the importance of sexuality for their patients but have difficulties acting on their beliefs. Sexuality, within the patient's functional ability and desire for it, must be acknowledged and included in holistic management. It is the health professional's responsibility to raise this issue.
Exploratory and Confirmatory Factor Analyses of the Structured Interview for Disorders of Extreme Stress
Authors: Scoboria Alan , Ford Julian , Lin Hsiu-ju , Frisman Linda
Published: June 2008

Two studies were conducted to provide the first empirical examination of the factor structure of a revised version of the clinically derived Structured Interview for Disorders of Extreme Stress, a structured interview designed to assess associated features of posttraumatic stress disorder (PTSD) thought to be related to early onset, interpersonal, and prolonged traumatic exposure. Five factors representing demoralization, somatic dysregulation, anger dysregulation, risk/self-harm, and altered sexuality were derived from an exploratory factor analysis conducted with adult trauma survivors in substance abuse treatment. They provided a good fit in a confirmatory factor analysis conducted in a second study with a nonclinical sample of ethnoculturally diverse, socioeconomically disadvantaged, incarcerated adults. Evidence of the derived factors' internal consistency and convergent and discriminant validity is reported. Evidence supported the association of these factors with interpersonal trauma (physical and/or sexual), its repetition, and its earlier onset. Implications for clinical assessment of complex posttraumatic stress disorder are discussed.
Cross-Validation of Levenson's Psychopathy Scale in a Sample of Federal Female Inmates
Authors: Brinkley Chad A. , Diamond Pamela M. , Magaletta Philip R. , Heigel Caron P.
Published: June 2008

Levenson, Kiehl, and Fitzpatrick's Self-Report Psychopathy Scale (LSRPS) is evaluated to determine the factor structure and concurrent validity of the instrument among 430 federal female inmates. Confirmatory factor analysis fails to validate the expected 2-factor structure. Subsequent exploratory factor analysis reveals a 3-factor structure (egocentric, antisocial, and callous), where each factor accounts for significant variance in scores on several theoretically relevant measures. Higher scores on the antisocial factor of the LSRPS are associated with a history of varied psychopathological and negative legal outcomes, suggesting evidence of concurrent validity. However, the egocentric and callous factors do not seem to measure precisely the same construct as the primary psychopathy factor from the Levenson et al. study. The 3-factor structure proposed here has been proposed by other researchers and found in other samples of psychopathy in female inmates. Implications for both research and clinical practice using the LSRPS with female inmates are discussed.
Parent-Focused Child Maltreatment Prevention
Authors: Self-Brown Shannon , Whitaker Daniel J.
Published: June 2008

The goal of this article is to examine how technology has been and can be utilized to enhance parent-focused child maltreatment (CM) prevention efforts. The authors begin with a brief discussion of the current state of the CM prevention field. In the sections that follow, they review studies that have examined the use of technology across three facets of prevention: identification of CM, administration/augmentation of CM prevention programs, and broad dissemination and implementation of evidenced-based CM prevention programs. They conclude with a discussion of limitations and problems related to the use of technology as a tool to enhance CM prevention and future directions.
Predictions by early indicators of the time and height of the peaks of yearly influenza outbreaks in Sweden
Authors: Andersson Eva , Kühlmann-Berenzon Sharon , Linde Annika , Schiöler Linus , Rubinova Sandra , Frisén Marianne
Published: June 2008

Aims: Methods for prediction of the peak of the influenza from early observations are suggested. These predictions can be used for planning purposes. Methods: In this study, new robust methods are described and applied to weekly Swedish data on influenza-like illness (ILI) and weekly laboratory diagnoses of influenza (LDI). Both simple and advanced rules for how to predict the time and height of the peak of LDI are suggested. The predictions are made using covariates calculated from data in early LDI reports. The simple rules are based on the observed LDI values, while the advanced ones are based on smoothing by unimodal regression. The suggested predictors were evaluated by cross-validation and by application to the observed seasons. Results: The relationship between ILI and LDI was investigated, and it was found that the ILI variable is not a good proxy for the LDI variable. The advanced prediction rule regarding the time of the peak of LDI had a median error of 0.9 weeks, and the advanced prediction rule for the height of the peak had a median deviation of 28%. Conclusions: The statistical methods for predictions have practical usefulness.
Real or Virtual? Response Behavior in Video-Enhanced Self-Administered Computer Interviews
Authors: Gerich Joachim
Published: June 2008

This article compares response behavior in video-enhanced self-administered questionnaires with three standard methods: paper-and-pencil, face-to-face, and audio-enhanced self-administered questionnaires. Although its scope is limited, and only small mode differences were observed, preliminary results suggest that video-enhanced interviews may produce more valid responses in that they are less contaminated by social desirability. Knowledge of video elements integrated in self-administered questionnaires has so far been limited. This study attempts to build a tentative theoretical framework for the interpretation of the mode differences established in the course of this research.
Reflecting on the Experience Sampling Method in the Qualitative Research Context: Focus on Knowledge Production and Power during the Data-Collection Process
Authors: Koro-Ljungberg Mirka , Bussing Regina , Williamson Pamela , M'Cormack-Hale Fredline
Published: June 2008

In this conceptual article, we discuss how the conventional experience sampling method (ESM) was applied to a qualitative research project to increase participants' agency and empowerment during data collection. Specifically we outline the conceptual and methodological tensions, complexities, and power shifts that emerged during our data-collection process. Research examples illustrate the location of knowers (researchers and study participants), the knowers' relationship to various tangible objects of research (e.g., protocols, digital devices), and how these notions shape power and data that is constructed within a research study. We conclude that it is important to analyze and reflect on how researchers conduct themselves during the data-collection process, and how research can be adapted to reflect the needs and social circumstances of the participants. Our experiences suggest that greater awareness of power shifts during the data-collection process will help researchers better understand the nuances and situated meanings within their data.
A Comparison of Spelling Performance Across Young Adults With and Without Dyslexia
Authors: Coleman Chris , Gregg Noël , McLain Lisa , Bellair Leslie W.
Published: June 2008

In this study, the authors analyzed 2,056 spelling errors produced by 130 young adults (65 with dyslexia, 65 typically achieving), which came from two sources: a standardized spelling test and an impromptu essay-writing task. Students with dyslexia exhibited higher spelling error rates across both tasks. To characterize the inaccurate spelling attempts of both groups, the authors conducted linguistic and item-level analyses. Among unconstrained errors (essay), students with dyslexia had more difficulty than their typically achieving peers with familiar, low-level items (indexed by word frequency and number of syllables). Among constrained errors (spelling dictation), group differences in phonetic plausibility, morphological awareness, and visual accuracy varied by item. These analyses were telling on low-frequency items for which the groups obtained similar (dichotomous) accuracy rates. The authors suggest that diagnosticians and educators employ error analysis to obtain critical information not typically reflected in the standard scores used to make learning disability identification decisions.
Locally produced C5a binds to T cell–expressed C5aR to enhance effector T-cell expansion by limiting antigen-induced apoptosis
Authors: Lalli Peter N. , Strainic Michael G. , Yang Min , Lin Feng , Medof M. Edward , Heeger Peter S.
Published: June 2008

Our recent studies have shown that immune cell–produced complement provides costimulatory and survival signals to naive CD4+ T cells. Whether these signals are similarly required during effector cell expansion and what molecular pathways link locally produced complement to T-cell survival were not clarified. To address this, we stimulated monoclonal and polyclonal T cells in vitro and in vivo with antigen-presenting cells (APCs) deficient in the complement regulatory protein, decay accelerating factor (DAF), and/or the complement component C3. We found that T-cell expansion induced by DAF-deficient APCs was augmented with diminished T-cell apoptosis, whereas T-cell expansion induced by C3−/− APCs was reduced because of enhanced T-cell apoptosis. These effects were traced to locally produced C5a, which through binding to T cell–expressed C5aR, enhanced expression of Bcl-2 and prevented Fas up-regulation. The results show that C5aR signal transduction in T cells is important to allow optimal T-cell expansion, as well as to maintain naive cell viability, and does so by suppressing programmed cell death.
Solitary skull metastasis as initial manifestation of hepatocellular carcinoma
Authors: Shim Yu Shik , Ahn Jung Yong , Cho Jun Hyung , Lee Kyu Sung
Published: June 2008

Background

A solitary skull metastasis from hepatocellular carcinoma (HCC) prior to diagnosis of the primary tumor without liver dysfunction is a very rare event.

Case presentation

A 71-year-old male, without known liver disease, presented to our institution with a palpable occipital scalp mass. On brain magnetic resonance imaging (MRI), a highly enhanced and osteolytic skull tumor was observed. The histological diagnosis obtained from the percutaneous needle biopsy was a cranial metastasis from HCC. The metastatic tumor was removed via occipital craniectomy, and the two primary liver mass lesions were subsequently treated by transarterial chemoembolization.

Conclusion

An isolated skull metastasis may be the sole initial presentation of HCC. Early diagnosis is essential in order to treat the primary disease. A skull metastasis from HCC should be considered in the differential diagnosis in patients with subcutaneous scalp mass and osteolytic defects on X-ray.
Transcriptional patterns, biomarkers and pathways characterizing nasopharyngeal carcinoma of Southern China
Authors: Fang Weiyi , Li Xin , Jiang Qingping , Liu Zhen , Yang Huiling , Wang Shuang , Xie Siming , Liu Qiuzhen , Liu Tengfei , Huang Jing , Xie Weibing , Li Zuguo , Zhao Yingdong , Wang Ena , Marincola Francesco M , Yao Kaitai
Published: June 2008

Background

The pathogenesis of nasopharyngeal carcinoma (NPC) is a complicated process involving genetic predisposition, Epstein-Bar Virus infection, and genetic alterations. Although some oncogenes and tumor suppressor genes have been previously reported in NPC, a complete understanding of the pathogenesis of NPC in the context of global gene expression, transcriptional pathways and biomarker assessment remains to be elucidated.

Methods

Total RNA from 32 pathologically-confirmed cases of poorly-differentiated NPC was divided into pools inclusive of four consecutive specimens and each pool (T1 to T8) was co-hybridized with pooled RNA from 24 normal non-cancerous nasopharyngeal tissues (NP) to a human 8K cDNA array platform. The reliability of microarray data was validated for selected genes by semi-quantitative RT-PCR and immunohistochemistry.

Results

Stringent statistical filtering parameters identified 435 genes to be up-regulated and 257 genes to be down-regulated in NPC compared to NP. Seven up-regulated genes including CYC1, MIF, LAMB3, TUBB2, UBE2C and TRAP1 had been previously proposed as candidate common cancer biomarkers based on a previous extensive comparison among various cancers and normal tissues which did not, however, include NPC or NP. In addition, nine known oncogenes and tumor suppressor genes, MIF, BIRC5, PTTG1, ATM, FOXO1A, TGFBR2, PRKAR1A, KLF5 and PDCD4 were identified through the microarray literature-based annotation search engine MILANO, suggesting these genes may be specifically involved in the promotion of the malignant conversion of nasopharyngeal epithelium. Finally, we found that these differentially expressed genes were involved in apoptosis, MAPK, VEGF and B cell receptor signaling pathways and other functions associated with cell growth, signal transduction and immune system activation.

Conclusion

This study identified potential candidate biomarkers, oncogenes/tumor suppressor genes involved in several pathways relevant to the oncogenesis of NPC. This information may facilitate the determination of diagnostic and therapeutic targets for NPC as well as provide insights about the molecular pathogenesis of NPC.
GMODWeb: a web framework for the generic model organism database
Authors: O'Connor Brian D , Day Allen , Cain Scott , Arnaiz Olivier , Sperling Linda , Stein Lincoln D
Published: June 2008

The Generic Model Organism Database (GMOD) initiative provides species-agnostic data models and software tools for representing curated model organism data. Here we describe GMODWeb, a GMOD project designed to speed the development of model organism database (MOD) websites. Sites created with GMODWeb provide integration with other GMOD tools and allow users to browse and search through a variety of data types. GMODWeb was built using the open source Turnkey web framework and is available from http://turnkey.sourceforge.net.
Monocistronic mRNAs containing defective hepatitis C virus-like picornavirus internal ribosome entry site elements in their 5′ untranslated regions are efficiently translated in cells by a cap-dependent mechanism
Authors: Belsham Graham J. , Nielsen Inge , Normann Preben , Royall Elizabeth , Roberts Lisa O.
Published: June 2008

The initiation of protein synthesis on mRNAs within eukaryotic cells is achieved either by a 5′ cap-dependent mechanism or through internal initiation directed by an internal ribosome entry site (IRES). Picornavirus IRES elements, located in the 5′ untranslated region (5′UTR), contain extensive secondary structure and multiple upstream AUG codons. These features can be expected to inhibit cap-dependent initiation of translation. However, we have now shown that certain mutant hepatitis C virus-like picornavirus IRES elements (from porcine teschovirus-1 and avian encephalomyelitis virus), which are unable to direct internal initiation, are not significant barriers to efficient translation of capped monocistronic mRNAs that contain these defective elements within their 5′UTRs. Moreover, the translation of these mRNAs is highly sensitive to the expression of an enterovirus 2A protease (which induces cleavage of eIF4G) and is also inhibited by hippuristanol, a specific inhibitor of eIF4A function, in contrast to their parental wild-type IRES elements. These results provide a possible basis for the evolution of viral IRES elements within the context of functional mRNAs that are translated by a cap-dependent mechanism.
Peptide release on the ribosome depends critically on the 2′ OH of the peptidyl–tRNA substrate
Authors: Brunelle Julie L. , Shaw Jeffrey J. , Youngman Elaine M. , Green Rachel
Published: June 2008

Peptide release on the ribosome is catalyzed by protein release factors (RFs) on recognition of stop codons positioned in the A site of the small ribosomal subunit. Here we show that the 2′ OH of the peptidyl–tRNA substrate plays an essential role in catalysis of the peptide release reaction. These observations parallel earlier studies of the mechanism of the peptidyl transfer reaction and argue that related mechanisms are at the heart of catalysis for these reactions.
Minor-class splicing occurs in the nucleus of the Xenopus oocyte
: FIGURE 1.
Authors: Friend Kyle , Kolev Nikolay G. , Shu Mei-Di , Steitz Joan A.
Published: June 2008

A small fraction of premessenger RNA introns in certain eukaryotes is excised by the minor spliceosome, which contains low-abundance small nuclear ribonucleoproteins (snRNPs). Recently, it was suggested that minor-class snRNPs are localized to and function in the cytoplasm of vertebrate cells. To test whether U12-type splicing occurs in the cytoplasm of Xenopus oocytes, we performed microinjections of the well-characterized P120 minor-class splicing substrate into the nucleus or into the cytoplasm. Our results demonstrate that accurate splicing of this U12-dependent intron occurs exclusively in the nuclear compartment of the oocyte, where U12 and U6atac snRNPs are primarily localized. We further demonstrate that splicing of both a major-class and a minor-class intron is inhibited after nuclear envelope breakdown during meiosis.
Inhibition of expression of virulence genes of Yersinia pestis in Escherichia coli by external guide sequences and RNase P
Authors: Ko Jae-hyeong , Izadjoo Mina , Altman Sidney
Published: June 2008

External guide sequences (EGSs) targeting virulence genes from Yersinia pestis were designed and tested in vitro and in vivo in Escherichia coli. Linear EGSs and M1 RNA-linked EGSs were designed for the yscN and yscS genes that are involved in type III secretion in Y. pestis. RNase P from E. coli cleaves the messages of yscN and yscS in vitro with the cognate EGSs, and the expression of the EGSs resulted in the reduction of the levels of these messages of the virulence genes when those genes were expressed in E. coli.
Human DNMT2 methylates tRNAAsp molecules using a DNA methyltransferase-like catalytic mechanism
Authors: Jurkowski Tomasz P. , Meusburger Madeleine , Phalke Sameer , Helm Mark , Nellen Wolfgang , Reuter Gunter , Jeltsch Albert
Published: June 2008

Although their amino acid sequences and structure closely resemble DNA methyltransferases, Dnmt2 proteins were recently shown by Goll and colleagues to function as RNA methyltransferases transferring a methyl group to the C5 position of C38 in tRNAAsp. We observe that human DNMT2 methylates tRNA isolated from Dnmt2 knock-out Drosophila melanogaster and Dictyostelium discoideum. RNA extracted from wild type D. melanogaster was methylated to a lower degree, but in the case of Dictyostelium, there was no difference in the methylation of RNA isolated from wild-type and Dnmt2 knock-out strains. Methylation of in vitro transcribed tRNAAsp confirms it to be a target of DNMT2. Using site directed mutagenesis, we show here that the enzyme has a DNA methyltransferase-like mechanism, because similar residues from motifs IV, VI, and VIII are involved in catalysis as identified in DNA methyltransferases. In addition, exchange of C292, which is located in a CFT motif conserved among Dnmt2 proteins, strongly reduced the catalytic activity of DNMT2. Dnmt2 represents the first example of an RNA methyltransferase using a DNA methyltransferase type of mechanism.
Improving Time-Critical Decision Making in Life-Threatening Situations: Observations and Insights
Authors: Cohen Izack
Published: June 2008

In this article we present our concept of time-critical decision making, sometimes even in life-threatening situations, and compare it to the process of non-time-critical decision making. Decision-making methodologies have been extensively researched, and some of the published research deals with decision making within the context of everyday life. However, in many organizations it is customary for decisions to be made under pressure and in conditions of uncertainty. Such organizations may benefit from a generic decision-making approach. Two case studies were used to research the characteristics of time-critical decision making. A qualitative analysis of these case studies and previous research insights were integrated. The insights that were found enable us to offer a practical generic approach toward improving the process of time-critical decision making. The suggested approach combines components that were mentioned in previous research with new ones. It contains two phases: The first identifies various decision-making situations in the organization and their classification according to the extent (severity) of time criticality in making and implementing the decision. This classification determines the necessary decision making and implementation procedures, whether they are cognitive or not. The second deals with the relevant components for improving the quality of the decision making. Application of this approach is very simple, and it suits not only military organizations, but also organizations and individuals that will benefit from making better decisions in stressful situations. The approach can be combined with other existing approaches such as risk management.
From the Editors…
Authors: Keller L. Robin , Kophazi Kelly M.
Published: June 2008

For this Decision Analysis issue, our “From the Editors…” column is co-authored with Managing Editor Kelly M. Kophazi to highlight her contributions to the success of our journal. We report on our success in having Decision Analysis widely known throughout the world, as measured by the country locations of our published and submitting authors, and our associate editors' affiliations. This issue begins with an article by Mort Webster on “Incorporating Path Dependency into Decision-Analytic Methods: An Application to Global Climate-Change Policy.” Next is an article on “Eliciting Subjective Probabilities Through Exchangeable Events: An Advantage and a Limitation,” by Aurélien Baillon. In our third article, Niklas Vareman provides a provocative philosophical analysis on “Norms and Descriptions.” Our final article, by Izack Cohen, is on “Improving Time-Critical Decision Making in Life-Threatening Situations: Observations and Insights.”
Disk Packing in a Square: A New Global Optimization Approach
Authors: Addis B. , Locatelli M. , Schoen F.
Published: June 2008

We present a new computational approach to the problem of placing n identical nonoverlapping disks in the unit square in such a way that their radii are maximized. The problem has been studied in a large number of papers, from both a theoretical and a computational point of view. In this paper, we conjecture that the problem possesses a so-called funneling landscape, a feature that is commonly found in molecular conformation problems. Based on this conjecture, we develop a stochastic search algorithm that displays excellent numerical performance. Thanks to this algorithm, we could improve over previously known putative optima in the range n ≤ 130 in as many as 32 instances, the smallest of which is n = 53.