bluuebunny/crossref_metadata_2025 huggingface dataset:
Power spectrum of HI intensity fluctuations in DDO 210
Authors: Begum Ayesha , Chengalur Jayaram N. , Bhardwaj Somnath
Published: August 2006

We measure the power spectrum of H i intensity fluctuations in the extremely faint (MB∼−10.9) dwarf galaxy DDO 210 using a visibility-based estimator that is well suited to very low signal-to-noise ratio regimes. DDO 210's H i power spectrum is well fitted by a power law PH i(U) = A Uα, with α= −2.75 ± 0.45 over the length-scales 80 pc to 500 pc. We also find that the power spectrum does not change with an increase in the velocity channel width, indicating that the measured fluctuations correspond mainly to density fluctuations. However, Kolmogorov turbulence (with a velocity structure function spectral slope of 2/3) cannot be ruled out from the present observations. The value of the slope α is similar to that obtained in the Milky Way. Compared with the Milky Way, DDO 210 has three orders of magnitude less H i, no spiral arms, and also no measurable ongoing star formation. The fact that the power spectrum slope is nonetheless similar in these two galaxies (and also similar to the values measured for the LMC and SMC) suggests that there is some universal, star-formation-independent phenomenon responsible for producing fine scale structure in the gas.
Knowing from Testimony
Authors: Lackey Jennifer
Published: August 2006

Testimony is a vital and ubiquitous source of knowledge. Were we to refrain from accepting the testimony of others, our lives would be impoverished in startling and debilitating ways. Despite the vital role that testimony occupies in our epistemic lives, traditional epistemological theories have focused primarily on other sources, such as sense perception, memory, and reason, with relatively little attention devoted specifically to testimony. In recent years, however, the epistemic significance of testimony has been more fully appreciated. I shall here focus on two questions that have received the most attention in recent work in the epistemology of testimony. First, is testimonial knowledge acquired only by being transmitted from speaker to hearer? Second, must a hearer have positive reasons to justifiedly accept a speaker's testimony?
Managing employee expectations during acquisitions
Authors: Hubbard Nancy , Purcell John
Published: August 2006

There is a wide body of evidence that suggests that the management of 'human factors' in post‐acquisition implementation is important and, where it is badly managed, helps to explain why up to half of acquisitions are not deemed to be successful. A central feature in this process is the management of employee expectations. Using research insights drawn from the management and formation of expectations in recruitment and from breaches of the psychological contract, this article reports on research in organisations subject to a takeover within two years of the field work. Detailed findings on two of these cases are used to explore the dimensions of dual expectations in such circumstances. It is suggested that employees in acquired companies have concerns that become expectations concerning both themselves ('me') and their work group ('us'), ranging from immediate job and employment worries on transfer to longer‐term status and behavioural and cultural concerns in the 'new' organisation. These expectations will vary over time and have different facets according to the seniority of the employee, the degree of integration sought by the acquirer and the extent to which expectations formed are proven to be realistic and realisable. The two cases analysed reveal different aspects of unmet expectations in acquisitions. Seven factors were identified as influential in shaping employees' expectations in acquisitions: quality of communication, believability of information, trust in management action, credibility of leadership, fairness of action, consistency of action and communication and logic of management action or behaviour.
Designing and aligning an HR system
Authors: Monks Kathy , McMackin John
Published: August 2006

This article reports the results of a study conducted in the wholesale banking arm of a major international financial institution in Ireland. This took a multi‐level perspective in exploring the construction of the HR system at group, divisional and strategic business unit (SBU) levels within the firm. The findings suggest that it is critical to consider the level of analysis in both the construction of theHR system and in its operation at different levels within the multi‐divisional firm. The research found that it is at SBU level that a coherent HR system is most likely to emerge, as at this level appropriate processes can be adopted to implement HR policies, practices and philosophies. However, the negotiations and interpretations of HR practice that dominate traditional divisional/business unit arrangements may be detrimental to theemergence of a coherent HRsystem.
Perceptions of the value of the HR function
Authors: Buyens Dirk , De Vos Ans
Published: August 2006

This article explores the added value of the HR function as it is perceived by three groups of managers: top managers, HR managers and line managers. Despite the fact that literature about strategic HRM focuses almost exclusively on the value of the HR function as a strategic partner, it was assumed that its perceived value for the business would not be restricted to the area of strategy formulation and implementation. Several 'result domains' can be distinguished in which the HR function can deliver value to the business. Based on our review of the literature, the degree of strategic involvement of the function was used as a second perspective to investigate its perceived added value. To examine our propositions, a qualitative study was carried out in which 97 HR managers, 38 top managers and 178 line managers participated. The results confirm our thesis that the perceived value of the HR function contains more than just the fulfilment of its role as a strategic partner. Based on our results, an integrated model for the perceived value of the function has been developed.
The strategic use of contingent workers in Hong Kong's economic upheaval
Authors: Wong May M. L.
Published: August 2006

This research examines strategy in the use and purposes of contingent employment in four retail firms under different economic conditions in Hong Kong. Data from in‐depth qualitative case studies found that the four firms – three Japanese and one British – had different organisational responses to the economic conditions caused by the increase of sales before the Asian financial crisis of 1997 and the shrinkage of sales afterwards. One such response concerned the companies' employment policies, especially in their use of contingent workers. Some tended to have an ad hoc opportunistic approach to the use of contingent workers, while others were more strategic and incorporate long‐term planning in their labour utilisation strategy. Implications are drawn relating to companies' use of contingent employment to changes in the contextual environment regarding their long‐term development.
Regulating labour management in small firms
Authors: Marlow Susan
Published: August 2006

There is a relative paucity of evidence on the management of labour in smaller firms. Research that has been undertaken, while recognising the heterogeneity of the sector, does note the prevalence of informality regarding employee relations. Such informality could be challenged by the increasing regulation of the employment relationship following the election of successive Labour governments since 1997. To illuminate this discussion further, evidence drawn from a study of employment regulation is offered. A number of smaller firm owners and their employees were interviewed to ascertain their views on the impact of regulation on the employment relationship. Owners were largely resistant to it but felt they could accommodate changes with relatively little disruption to their existing approach to labour management. Meanwhile, most employees felt the effect of regulation would be muted due to their position as smaller firm labour.
Employee perceptions and their influence on training effectiveness
Authors: Santos Amalia , Stuart Mark
Published: August 2006

Studies of the benefits of human resource development (HRD) for organisations have assumed a direct connection between training strategy and a hierarchy of performance outcomes: learning, behavioural change and performance improvement. The influence of workplace practices and employees' experiences on training effectiveness has received little attention. This study investigates evaluation strategies designed to elicit greater training effectiveness, and explores the influence of trainees' perceptions and work environment factors on this. Drawing on detailed case study findings, the authors highlight the importance of management practices, trainees' perceptions of the work environment and systems of reward in explaining behaviour change after training.
What aspects of the job have most effect on nurses?
Authors: Sagie Abraham , Krausz Moshe
Published: August 2006

The study reported here compared the influences of psychological constructs (job demands and scheduling control) and objective work characteristics (shiftwork, night‐work and hospital department type) on job satisfaction, organisational commitment, burnout and withdrawal intentions. Our hypothesis was that psychological constructs have a higher influence on work‐related attitudes than objective characteristics of work schedules. In addition to the main effects, we proposed an interactive hypothesis: poor attitudes would result from high demands and low control rather than from other combinations of both psychological variables. Using a sample of 153 hospital nurses in Israel, the hypotheses were generally supported. As night‐work, shiftwork and working in intensive care units are unavoidable characteristics of the modern medical environment, these findings are meaningful for improving the personal adjustment of hospital nurses.
Putting skills to work: learning and employment at the start of the century
Authors: Grugulis Irena
Published: August 2006

Skills are central to employment, yet they are often poorly understood in theory and underdeveloped in practice. The articles in this issue of HRMJ were originally presented at an ESRC‐funded seminar in Manchester in 2001 and show how working practices, control systems and regulation can have an impact on skills. This article introduces the special issue by considering the interrelationship between the individual expertise, job design and discretion that constitute skill. Drawing on data from the 2001 Skills Survery, it notes that developments in these areas are not necessarily compatible with one another, and reviews the implications for policymakers and practitioners.
Workplace learning and the employment relationship in the public sector
Authors: Rainbird Helen , Munro Anne
Published: August 2006

Training that is relevant to employers is not necessarily enriching for employees, especially those on the lower salary scales. The authors argue that the analysis of training and development needs to be understood in the context of the employment relationship. Drawing on reasearch evidence from six case studies in the public sector, the article examines the impact of changes in work organisation on workplace learning, managers' and employees' own strategies towards it and the limitations of tools such as appraisal. Since employees' existing qualifications are poorly utilised and their development needs often frustrated, issues concerning job design, occupational progression routes and employee entitlements need to be addressed.
National influences on European Works Councils in UK‐ and US‐based companies
Authors: Hall Mark , Hoffmann Aline , Marginson Paul , Müller Torsten
Published: August 2006

The view that the role of European Works Councils (EWCs) is shaped predominantly by national industrial relations (IR) traditions in the company's country of origin derives largely from the experience of EWCs in companies based in continental Europe. This article argues that a more differentiated approach to the influence of national IR factors on EWCs needs to be developed to take account of the circumstances of companies headquartered in the UK and the US, whose national IR arrangements do not provide a strong institutional model for the EWC and, in the case of US‐based companies, where headquarters management has little or no direct involvement in the EWC. Findings from comparative case studies of EWCs in eight UK‐ and US‐based multinationals suggest that their character is shaped by the interplay between ‘country‐of‐origin’ factors,‘country‐of‐location’ factors and structural, company‐specific considerations.
Partnership and the development of trust in British workplaces
Authors: Dietz Graham
Published: August 2006

This article examines the alleged links between ‘partnership’ forms of managing workplace relationships in Britain and the development of intra‐organisational ‘trust’. The potential for mutually complementary linkages between the two are clear, in theory at least. Partnership should produce, nurture and enhance levels of interpersonal trust inside organisations, while trust legitimates and helps reinforce an organisation's ‘partnership’. Qualitative evidence drawn from the self‐reports of key participants in three unionised partnership organisations provides some support for the claimed linkages. But it also highlights weaknesses, discrepancies and pitfalls inherent in the process of pursuing trust through partnership. These offer insights into the process for managers, trade union officials, employee representatives and policy‐makers, as well as suggesting avenues for future research using trust as a theoretical framework.
High performance work systems, organisational culture and firm effectiveness
Authors: Den Hartog Deanne N. , Verburg Robert M.
Published: August 2006

The HRM literature emphasises the importance of people in enhancing firm performance or even creating competitive advantage. This study provides further evidence on the link between so‐called high performance work systems and firm performance and relates these to organisational culture. In total 175 organisations from different sectors in the Netherlands participated. Senior HR managers were questioned on HRM practices and chief executives on organisational culture. Three different groups of personnel are distinguished in the measures: core employees, managers and specialist professional staff. One high performance work system could be distinguished, consisting of a combination of practices with an emphasis on employee development, strict selection and providing an overarching goal or direction. Results of regression analyses controlling for sector, firm size and age show a significant impact of this system on several performance outcomes (perceived economic outcomes, beyond contract and absenteeism), as well as positive relationships with three organisational culture orientations. Practices that are not part of this combination also show some positive (but limited) links with culture and outcomes.
Employee participation and union voice in the National Health Service
Authors: Bach Stephen
Published: August 2006

This article examines the role of trade unions in the health service at workplace level under the Labour government's modernisation agenda, and focuses on the shifting balance between forms of direct and indirect participation drawing on case studies of three acute hospital trusts. There has been a strong growth in forms of direct communication within the case study trusts and some increase in direct participation among professional groups. Despite this ‘dualism’ in employment relations, however, the target culture of the NHS has precluded the development of effective voice mechanisms. The policy implications for trade unions and the implications for the implementation of NHS pay modernisation are considered.
Beyond the enterprise: trade union representation of freelances in the UK
Authors: Heery Edmund , Conley Hazel , Delbridge Rick , Stewart Paul
Published: August 2006

Interest has grown in the methods that trade unions can use to organise and represent the substantial proportion of the workforce engaged in ‘contingent work’. This article examines trade union representation of self‐employed freelances in the UK. Empirical material is presented from case studies of the media and entertainment unions, with their long history of representing freelances, and more recently established unions representing freelance tour guides, interpreters and translators. The analysis indicates that there is a distinctive form of freelance unionism in the UK which is distinguished by its emphasis on organising and representing workers in the external labour market where they seek work and develop a mobile career. This orientation ‘beyond the enterprise’ distinguishes freelance unionism from the dominant form of unionism in Britain.
Work‐life balance and the software worker
Authors: Scholarios Dora , Marks Abigail
Published: August 2006

This article examines the impact of employer flexibility to work‐life issues and negative spillover from work to non‐work life on the attitudes of software developers. Software workers present an interesting case for work‐life balance issues – Ackroyd et al (2000) designate them the key occupation to examine in future studies of ‘knowledge workers’, and Barrett (2001) states that they are the ‘vanguard’ of new working practices, with the separation of work and life being substantially more ‘blurred’ than for more traditional occupations. Despite this general perception of the work‐life boundary, our results show that intrusion of work into private life for this group of workers still has a substantial impact on work‐related attitudes. Work‐life boundary variables affect trust in the organisation which plays a mediational role in these variables' relationship to job satisfaction and organisational commitment. Our results suggest that even within this industry, where employees are relatively individualistic in orientation, highly marketable and unlikely to show attachment to a single organisation, mutual gains for employee and employer can be attained by an accommodating approach to non‐work commitments which may lead to greater organisational attachment.
Organisational communication and supportive employees
Authors: de Ridder Jan A.
Published: August 2006

The importance of the social dimension of organisations is currently a strong focus of emphasis in the literature. From a managerial perspective, however, it is important that the community spirit within an organisation falls in line with its strategic direction. The study discussed in this article shows that high quality internal communication may be important in encouraging such a supportive attitude. What is considered ‘good’ internal communication does not directly engender more support for the organisation's strategic direction. However, evidence from research in five organisations (with 791 respondents distributed across 19 work units) suggests that there are two ways to foster support. One is to create a sense of commitment within the organisation; the other is to establish trust in the management. Both approaches appear to have a positive relationship with good internal communication. The quality of task‐related communication is important in creating commitment. What is vital in creating trust, however, is the quality of non‐task‐related communication. The study at the focus of this article addresses the following question: does organisational communication help foster a positive attitude towards the strategic direction of an organisation?
How organisational image affects employee attitudes
Authors: Herrbach Olivier , Mignonac Karim
Published: August 2006

Organisational image has mostly been studied using an external perspective focused on strategy and marketing issues. Given its salience in employees' symbolic environment, however, image may also have internal as well as external consequences. Yet, the potential impact of image on internal HR aspects has received only pminimal interest from researchers. This article presents the results of a study that explored the impact of perceived external prestige (PEP) on three individual outcomes: job satisfaction, affective organisational commitment and affective well‐being at work. It is based on a survey of 527 French managers. The findings show that all individual outcomes are related to PEP. Moreover, it was found that the impact of corporate image on some of the outcomes was stronger for individuals working in sales/marketing than for other employees.
What makes a good project manager?
Authors: Cheng Mei‐I , Dainty Andrew R.J. , Moore David R.
Published: August 2006

There is a growing awareness within project‐based sectors of the relationship between performance and managers' competencies. This article reports on research that investigated the competency profile of ‘superior’ project managers working within the construction industry, one of the most complex and dynamic project‐based industrial sectors. The study combined an assessment of both their behavioural competencies and job‐task competencies. The results reveal that while their job‐task competencies are highly specific to the industry in which they work, the behavioural competencies of superior project managers are mostly generic in nature and apply to a range of other management positions. This research shows how it is practically possible to identify the competency profile of superior managers and utilise this framework for managing the performance of this key management group.
Graduates' career aspirations and individual characteristics
Authors: Mayrhofer Wolfgang , Steyrer Johannes , Meyer Michael , Strunk Guido , Schiffinger Michael , Iellatchitch Alexander
Published: August 2006

Using the basic distinction between organisational and post‐organisational career orientation, this article examines preferences of business school graduates for different types of career fields and systematic differences between people with different career orientations in terms of behavioural characteristics as well as personality traits. The results show that business school graduates clearly distinguish between organisational and post‐organisational career fields. Graduates with post‐organisational career aspirations display attributes of high flexibility, leadership motivation, selfpromotion/self‐assertion, self‐monitoring, networking and less self‐consciousness. For individuals preferring an organisational career pattern, inverse relationships apply. Some implications of the findings for HR practice are discussed.
Rocket Propulsion with Sparklers
Authors: Gluck Paul
Published: August 2006

A fairly well-known demonstration using a sparkler is the following: Bend the wire where you hold it at 90° to the active part, and insert it into the chuck of a drill. Darken the room, ignite the sparkler, and let the drill rotate slowly. A shower of sparks flies off tangent to the circular motion, much like sparks from a rotating whetstone.
Probeware Modification of a Spectrometer
Authors: Easton Don
Published: August 2006

I'm always amazed by the beauty of the atomic spectra and can imagine the excitement of the early spectroscopists when they realized that the line spectra uniquely identify the elements. I would like physics students to share that excitement, but find that the tedious nature of reading a Vernier scale in a darkened room, reading fractional angles in minutes of degrees, and converting angles in degrees and minutes to decimal notation soon make the exercise so tedious that students lose sight of the intended task of identifying and characterizing the spectral lines. At Acadia University, we have adapted a PASCO rotary motion sensor1 and voltage probe, both interfaced to a computer using a Vernier LabPro,2 to semi-automate our spectrometer3 measurements.
Seeking Sustainability: Israel's Evolving Water Management Strategy
Authors: Tal Alon
Published: August 2006

The water management policies adopted to address Israel's chronic scarcity have not been without environmental consequences. Yet, through a trial-and-error process, a combined strategy of water transport, rainwater harvesting, and wastewater reuse and desalination, along with a variety of water conservation measures, have put the country on a more sustainable path for the future.
Storage of Spatial Information by the Maintenance Mechanism of LTP
Authors: Pastalkova Eva , Serrano Peter , Pinkhasova Deana , Wallace Emma , Fenton André Antonio , Sacktor Todd Charlton
Published: August 2006

Analogous to learning and memory storage, long-term potentiation (LTP) is divided into induction and maintenance phases. Testing the hypothesis that the mechanism of LTP maintenance stores information requires reversing this mechanism in vivo and finding out whether long-term stored information is lost. This was not previously possible. Recently however, persistent phosphorylation by the atypical protein kinase C isoform, protein kinase Mzeta (PKMz), has been found to maintain late LTP in hippocampal slices. Here we show that a cell-permeable PKMz inhibitor, injected in the rat hippocampus, both reverses LTP maintenance in vivo and produces persistent loss of 1-day-old spatial information. Thus, the mechanism maintaining LTP sustains spatial memory.
Argonaute Slicing Is Required for Heterochromatic Silencing and Spreading
Authors: Irvine Danielle V. , Zaratiegui Mikel , Tolia Niraj H. , Goto Derek B. , Chitwood Daniel H. , Vaughn Matthew W. , Joshua-Tor Leemor , Martienssen Robert A.
Published: August 2006

Small interfering RNA (siRNA) guides dimethylation of histone H3 lysine-9 (H3K9me2) via the Argonaute and RNA-dependent RNA polymerase complexes, as well as base-pairing with either RNA or DNA. We show that Argonaute requires the conserved aspartate-aspartate-histidine motif for heterochromatic silencing and for ribonuclease H–like cleavage (slicing) of target messages complementary to siRNA. In the fission yeast
Schizosaccharomyces pombe
, heterochromatic repeats are transcribed by polymerase II. We show that H3K9me2 spreads into silent reporter genes when they are embedded within these transcripts and that spreading requires read-through transcription, as well as slicing by Argonaute. Thus, siRNA guides histone modification by basepairing interactions with RNA.
Lipopolysaccharide, Tumor Necrosis Factor Alpha, or Interleukin-1β Triggers Reactivation of Latent Cytomegalovirus in Immunocompetent Mice
Authors: Cook Charles H. , Trgovcich Joanne , Zimmerman Peter D. , Zhang Yingxue , Sedmak Daniel D.
Published: August 2006

We have previously shown that cytomegalovirus (CMV) can reactivate in lungs of nonimmunosuppressed patients during critical illness. Our recent work has shown that polymicrobial bacterial sepsis can trigger reactivation of latent murine CMV (MCMV). We hypothesize that MCMV reactivation following bacterial sepsis may be caused by inflammatory mediators. To test this hypothesis, BALB/c mice latently infected with Smith strain MCMV received sublethal intraperitoneal doses of lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), or saline. Lung tissue homogenates were evaluated for viral reactivation 3 weeks after mediator injection. Because LPS is known to signal via Toll-like receptor 4 (TLR-4) in mice, further studies blocking this signaling mechanism were performed using monoclonal MTS510. Finally, mice were tested with intravenous TNF-α to determine whether this would cause reactivation. All mice receiving sublethal intraperitoneal doses of LPS, TNF-α, or IL-1β had pulmonary reactivation of latent MCMV 3 weeks following injection, and LPS caused MCMV reactivation with kinetics similar to those for sepsis. When TLR-4 signaling was blocked, exogenous LPS did not reactivate latent MCMV. Intravenous TNF-α administration at near-lethal doses did not reactivate MCMV. Exogenous intraperitoneal LPS, TNF-α, and IL-1β are all capable of reactivating CMV from latency in lungs of previously healthy mice. LPS reactivation of MCMV appears dependent on TLR-4 signaling. Interestingly, intravenous TNF-α did not trigger reactivation, suggesting possible mechanistic differences that are discussed. We conclude that inflammatory disease states besides sepsis may be capable of reactivating CMV from latency.
A Pseudoknot in a Preactive Form of a Viral RNA Is Part of a Structural Switch Activating Minus-Strand Synthesis
Authors: Zhang Jiuchun , Zhang Guohua , Guo Rong , Shapiro Bruce A. , Simon Anne E.
Published: August 2006

RNA can adopt different conformations in response to changes in the metabolic status of cells, which can regulate processes such as transcription, translation, and RNA cleavage. We previously proposed that an RNA conformational switch in an untranslated satellite RNA (satC) of
Turnip crinkle virus
(TCV) regulates initiation of minus-strand synthesis (G. Zhang, J. Zhang, A. T. George, T. Baumstark, and A. E. Simon, RNA 12:147-162, 2006). This model was based on the lack of phylogenetically inferred hairpins or a known pseudoknot in the “preactive” structure assumed by satC transcripts in vitro. We now provide evidence that a second pseudoknot (Ψ
2
), whose disruption reduces satC accumulation in vivo and enhances transcription by the TCV RNA-dependent RNA polymerase in vitro, stabilizes the preactive satC structure. Alteration of either Ψ
2
partner caused nearly identical structural changes, including single-stranded-specific cleavages in the pseudoknot sequences and strong cleavages in a distal element previously proposed to mediate the conformational switch. These results indicate that the preactive structure identified in vitro has biological relevance in vivo and support a requirement for this alternative structure and a conformational switch in high-level accumulation of satC in vivo.
Role for 3-
O
-Sulfated Heparan Sulfate as the Receptor for Herpes Simplex Virus Type 1 Entry into Primary Human Corneal Fibroblasts
Authors: Tiwari Vaibhav , Clement Christian , Xu Ding , Valyi-Nagy Tibor , Yue Beatrice Y. J. T. , Liu Jian , Shukla Deepak
Published: August 2006

Herpes simplex virus type 1 (HSV-1) infection of the corneal stroma remains a major cause of blindness. Primary cultures of corneal fibroblasts (CF) were tested and found susceptible to HSV-1 entry, which was confirmed by deconvolution imaging of infected cells. Plaque assay and real-time PCR demonstrated viral replication and hence a productive infection of CF by HSV-1. A role for glycoprotein D (gD) receptors in cultured CF was determined by gD interference assay. Reverse transcription-PCR analysis indicated expression of herpesvirus entry mediator and 3-
O
-sulfated (3-
O
S) heparan sulfate (HS)-generating enzyme 3-
O
sulfotransferase 3 (3-
O
ST-3) but not nectin-1 or nectin-2. Subsequently, HS isolated from these cells was found to contain two distinct disaccharides (IdoUA2S-AnMan3S and IdoUA2S-AnMan3S6S) that are representative of 3-
O
ST-3 activity. The following lines of evidence supported the important role of 3-
O
S HS as the mediator of HSV-1 entry into CF. (i) Blockage of entry was observed in CF treated with heparinases. The same enzymes had significantly less effect on HeLa cells that use nectin-1 as the entry receptor. (ii) Enzymatic removal of cell surface HS also removed the major gD-binding receptor, as evident from the reduced binding of gD to cells. (iii) Spinoculation assay demonstrated that entry blockage by heparinase treatment included the membrane fusion step. (iv) HSV-1 glycoprotein-induced cell-to-cell fusion was inhibited by either prior treatment of cells with heparinases or by HS preparations enriched in 3-
O
S HS. Taken together, the data in this report provide novel information on the role of 3-
O
S HS in mediating infection of CF, a natural target cell type.
Proteomic Analysis of the Kaposi's Sarcoma-Associated Herpesvirus Terminal Repeat Element Binding Proteins
Authors: Si Huaxin , Verma Subhash C. , Robertson Erle S.
Published: August 2006

Terminal repeat (TR) elements of Kaposi's sarcoma-associated herpesvirus (KSHV), the potential origin sites of KSHV replication, have been demonstrated to play important roles in viral replication and transcription and are most likely also critical for the segregation of the KSHV genome to daughter cells. To search for the cellular proteins potentially involved in KSHV genome maintenance, we performed affinity chromatography analysis, using KSHV TR DNA as the affinity ligand. Proteomic analysis was then carried out to identify the TR-interacting proteins. We identified a total of 123 proteins from both KSHV-positive and -negative cells, among which most were identified exclusively from KSHV-positive cells. These proteins were categorized as proliferation/cell cycle regulatory proteins, proteins involved in spliceosome components, such as heterogeneous nuclear ribonuclear proteins, the DEAD/H family, the switch/sucrose nonfermenting protein family, splicing factors, RNA binding proteins, transcription regulation proteins, replication factors, modifying enzymes, and a number of proteins that could not be broadly categorized. To support the proteomic results, the presence of four candidate proteins, ATR, BRG1, NPM1 and PARP-1, in the elutions was further characterized in this study. The binding and colocalization of these proteins with the TR were verified using chromatin immunoprecipitation and immunofluorescence in situ hybridization analysis. These newly identified TR binding proteins provide a number of clues and potential links to understanding the mechanisms regulating the replication, transcription, and genome maintenance of KSHV. This study will facilitate the generation and testing of new hypotheses to further our understanding of the mechanisms involved in KSHV persistence and its associated pathogenesis.
AIDS Vaccination Studies with an Ex Vivo Feline Immunodeficiency Virus Model: Analysis of the Accessory ORF-A Protein and DNA as Protective Immunogens
Authors: Pistello Mauro , Bonci Francesca , Flynn J. Norman , Mazzetti Paola , Isola Patrizia , Zabogli Elisa , Camerini Valentina , Matteucci Donatella , Freer Giulia , Pelosi Paolo , Bendinelli Mauro
Published: August 2006

Determining which antigen must be included in AIDS vaccines to confer maximum protection is of utmost importance. In primate models, vaccines consisting of or including accessory viral proteins have yielded conflicting results. We investigated the protective potential of the accessory protein ORF-A of feline immunodeficiency virus (FIV) in cats. All three immunization strategies used (protein alone in alum adjuvant, DNA alone, or DNA prime-protein boost) clearly generated detectable immune responses. Upon challenge with ex vivo homologous FIV, ORF-A-immunized cats showed distinct enhancement of acute-phase infection relative to mock-immunized animals given alum or empty vector DNA. This effect was tentatively attributed to increased expression of the FIV receptor CD134 that was observed in the immunized cats. However, at subsequent sampling points that were continued for up to 10 months postchallenge, the average plasma viral loads of the ORF-A-immunized animals were slightly but consistently reduced relative to those of the control animals. In addition, CD4
+
T lymphocytes in the circulation system declined more slowly in immunized animals than in control animals. These findings support the contention that immunization with lentiviral accessory proteins can improve the host's ability to control virus replication and slow down disease progression but also draw attention to the fact that even simple immunogens that eventually contribute to protective activity can transiently exacerbate subsequent lentiviral infections.
Hepatitis C Virus Core Protein Blocks Interferon Signaling by Interaction with the STAT1 SH2 Domain
Authors: Lin Wenyu , Kim Sun Suk , Yeung Elaine , Kamegaya Yoshitaka , Blackard Jason T. , Kim Kyung Ah , Holtzman Michael J. , Chung Raymond T.
Published: August 2006

Emerging data have indicated that hepatitis C virus (HCV) subverts the host antiviral response to ensure its persistence. We previously demonstrated that HCV protein expression suppresses type I interferon (IFN) signaling by leading to the reduction of phosphorylated STAT1 (P-STAT1). We also demonstrated that HCV core protein directly bound to STAT1. However, the detailed mechanisms by which HCV core protein impacts IFN signaling components have not been fully clarified. In this report, we show that the STAT1 interaction domain resides in the N-terminal portion of HCV core (amino acids [aa] 1 to 23). This domain is also required to produce P-STAT1 reduction and inhibit IFN signaling transduction. Conversely, the C-terminal region of STAT1, specifically the SH2 domain (aa 577 to 684), is required for the interaction of HCV core with STAT1. The STAT1 SH2 domain is critical for STAT1 hetero- or homodimerization. We propose a model by which the binding of HCV core to STAT1 results in decreased P-STAT, blocked STAT1 heterodimerization to STAT2, and, therefore, reduced IFN-stimulated gene factor-3 binding to DNA and disrupted IFN-stimulated gene transcription.
Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Interacts with Bromodomain Protein Brd4 on Host Mitotic Chromosomes
Authors: You Jianxin , Srinivasan Viswanathan , Denis Gerald V. , Harrington William J. , Ballestas Mary E. , Kaye Kenneth M. , Howley Peter M.
Published: August 2006

The latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) is required for viral episome maintenance in host cells during latent infection. Two regions of the protein have been implicated in tethering LANA/viral episomes to the host mitotic chromosomes, and LANA chromosome-binding sites are subjects of high interest. Because previous studies had identified bromodomain protein Brd4 as the mitotic chromosome anchor for the bovine papillomavirus E2 protein, which tethers the viral episomes to host mitotic chromosomes (J. You, J. L. Croyle, A. Nishimura, K. Ozato, and P. M. Howley, Cell
117:
349-360, 2004, and J. You, M. R. Schweiger, and P. M. Howley, J. Virol.
79:
14956-14961, 2005), we examined whether KSHV LANA interacts with Brd4. We found that LANA binds Brd4 in vivo and in vitro and that the binding is mediated by a direct protein-protein interaction between the ET (extraterminal) domain of Brd4 and a carboxyl-terminal region of LANA previously implicated in chromosome binding. Brd4 associates with mitotic chromosomes throughout mitosis and demonstrates a strong colocalization with LANA and the KSHV episomes on host mitotic chromosomes. Although another bromodomain protein, RING3/Brd2, binds to LANA in a similar fashion in vitro, it is largely excluded from the mitotic chromosomes in KSHV-uninfected cells and is partially recruited to the chromosomes in KSHV-infected cells. These data identify Brd4 as an interacting protein for the carboxyl terminus of LANA on mitotic chromosomes and suggest distinct functional roles for the two bromodomain proteins RING3/Brd2 and Brd4 in LANA binding. Additionally, because Brd4 has recently been shown to have a role in transcription, we examined whether Brd4 can regulate the CDK2 promoter, which can be transactivated by LANA.
Genome Characterization of Lipid-Containing Marine Bacteriophage PM2 by Transposon Insertion Mutagenesis
Authors: Krupovič Mart , Vilen Heikki , Bamford Jaana K. H. , Kivelä Hanna M. , Aalto Juha-Matti , Savilahti Harri , Bamford Dennis H.
Published: August 2006

Bacteriophage PM2 presently is the only member of the
Corticoviridae
family. The virion consists of a protein-rich lipid vesicle, which is surrounded by an icosahedral protein capsid. The lipid vesicle encloses a supercoiled circular double-stranded DNA genome of 10,079 bp. PM2 belongs to the marine phage community and is known to infect two gram-negative
Pseudoalteromonas
species. In this study, we present a characterization of the PM2 genome made using the in vitro transposon insertion mutagenesis approach. Analysis of 101 insertion mutants yielded information on the essential and dispensable regions of the PM2 genome and led to the identification of several new genes. A number of lysis-deficient mutants as well as mutants displaying delayed- and/or incomplete-lysis phenotypes were identified. This enabled us to identify novel lysis-associated genes with no resemblance to those previously described from other bacteriophage systems. Nonessential genome regions are discussed in the context of PM2 genome evolution.
An Element of the Tertiary Structure of Peach Latent Mosaic Viroid RNA Revealed by UV Irradiation
Authors: Hernández Carmen , Di Serio Francesco , Ambrós Silvia , Daròs José-Antonio , Flores Ricardo
Published: August 2006

Following UV irradiation, denaturing polyacrylamide gel electrophoresis and Northern blot hybridization revealed a cross-link in
Peach latent mosaic viroid
(PLMVd) plus-strand RNA. Primer extension and partial alkaline hydrolysis of the UV-irradiated PLMVd plus-strand RNA resulting from the hammerhead-mediated self-cleavage mapped the cross-link at U81 and at the 3′-terminal C289 (or at a very proximal nucleotide). Supporting this notion, in vitro-synthesized PLMVd plus-strand RNAs with short insertions/deletions at their 3′ termini failed to cross-link. Because U81 and C289 are conserved in PLMVd variants and because the initiation site of PLMVd minus-strand RNA maps at a short double-stranded motif containing C289, the UV-photo-cross-linkable element of tertiary structure may be functionally significant. A second cross-linked species similar in size and sequence to the monomeric circular PLMVd form, observed in some PLMVd variants, probably derives from UV-induced ligation of the two termini resulting from self-cleavage.
Human Cytomegalovirus Inhibits Neuronal Differentiation and Induces Apoptosis in Human Neural Precursor Cells
Authors: Odeberg Jenny , Wolmer Nina , Falci Scott , Westgren Magnus , Seiger Åke , Söderberg-Nauclér Cecilia
Published: August 2006

Human cytomegalovirus (HCMV) is the most common cause of congenital infections in developed countries, with an incidence varying between 0.5 and 2.2% and consequences varying from asymptomatic infection to lethal conditions for the fetus. Infants that are asymptomatic at birth may still develop neurological sequelae, such as hearing loss and mental retardation, at a later age. Infection of neural stem and precursor cells by HCMV and consequent disruption of the proliferation, differentiation, and/or migration of these cells may be the primary mechanism underlying the development of brain abnormalities. In the present investigation, we demonstrate that human neural precursor cells (NPCs) are permissive for HCMV infection, by both the laboratory strain Towne and the clinical isolate TB40, resulting in 55% and 72% inhibition of induced differentiation of human NPCs into neurons, respectively, when infection occurred at the onset of differentiation. This repression of neuronal differentiation required active viral replication and involved the expression of late HCMV gene products. This capacity of HCMV to prevent neuronal differentiation declined within 24 h after initiation of differentiation. Furthermore, the rate of cell proliferation in infected cultures was attenuated. Surprisingly, HCMV-infected cells exhibited an elevated frequency of apoptosis at 7 days following the onset of differentiation, at which time approximately 50% of the cells were apoptotic at a multiplicity of infection of 10. These findings indicate that HCMV has the capacity to reduce the ability of human NPCs to differentiate into neurons, which may offer one explanation for the abnormalities in brain development associated with congenital HCMV infection.
Identification of Amino Acid Residues within Simian Virus 40 Capsid Proteins Vp1, Vp2, and Vp3 That Are Required for Their Interaction and for Viral Infection
Authors: Nakanishi Akira , Nakamura Akiko , Liddington Robert , Kasamatsu Harumi
Published: August 2006

Interaction of simian virus 40 (SV40) major capsid protein Vp1 with the minor capsid proteins Vp2 and Vp3 is an integral aspect of the SV40 architecture. Two Vp3 sequence elements mediate Vp1 pentamer binding in vitro, Vp3 residues 155 to 190, or D1, and Vp3 residues 222 to 234, or D2. Of the two, D1 but not D2 was necessary and sufficient to direct the interaction with Vp1 in vivo. Rational mutagenesis of Vp3 residues (Phe157, Ile158, Pro164, Gly165, Gly166, Leu177, and Leu181) or Vp1 residues (Val243 and Leu245), based on a structural model of the SV40 Vp1 pentamer complexed with Vp3 D1, was carried out to disrupt the interaction between Vp1 and Vp3 and to study the consequences of these mutations for viral viability. Altering these residues to bulky, charged residues blocked the interaction in vitro. When these alterations were introduced into the viral genome, they reduced viral viability. Mutants with alterations in Vp1 Val243, Leu245, or both to glutamate were nearly nonviable, whereas those with Vp3 alterations reduced, but did not eliminate, viability. Our results defined the residues of Vp1 and the minor capsid proteins that are essential for both the interaction of the capsid proteins and viral viability in permissive cells.
Altered Central Nervous System Gene Expression Caused by Congenitally Acquired Persistent Infection with Lymphocytic Choriomeningitis Virus
Authors: Kunz Stefan , Rojek Jillian M. , Roberts Amanda J. , McGavern Dorian B. , Oldstone Michael B. A. , de la Torre Juan Carlos
Published: August 2006

Neonatal infection of most mouse strains with lymphocytic choriomeningitis virus (LCMV) leads to a life-long persistent infection characterized by high virus loads in the central nervous system (CNS) in the absence of inflammation and tissue destruction. These mice, however, exhibit impaired learning and memory. The occurrence of cognitive defects in the absence of overt CNS pathology led us to the hypothesis that chronic virus infection may contribute to neuronal dysfunction by altering the host's gene expression profile. To test this hypothesis, we examined the impact of LCMV persistence on host gene expression in the CNS. To model the natural route of human congenital CNS infection observed with a variety of viruses, we established a persistently infected mouse colony where the virus was maintained via vertical transmission from infected mothers to offspring (LCMV-cgPi). LCMV-cgPi mice exhibited a lifelong persistent infection involving the CNS; the infection was associated with impaired spatial-temporal learning. Despite high viral loads in neurons of the brains of adult LCMV-cgPi mice, we detected changes in the host's CNS gene expression for only 75 genes, 56 and 19 being significantly induced and reduced, respectively. The majority of the genes induced in the brain of LCMV-cgPi mice were interferon (IFN)-stimulated genes (ISGs) and included the transcription factors STAT1 and IRF9, the ISG15 protease UBP43, and the glucocorticoid attenuated-response genes GARG16 and GARG49. Based on their crucial role in antiviral defense, these ISGs may play an important role in limiting viral spread and replication. However, since IFNs have also been implicated in adverse effects on neuronal function, the chronic induction of some ISGs may also contribute to the observed cognitive impairment.