The new culture of electronic publishing

Local conditions in the past often limited opportunities for scholarly exchange. But now these limits are gone and the global workplace has replaced them. It is important to react to these changes. Every academic department must now adopt new methods and rethink processes. Another is the intense national and international debate about open access to scholarly knowledge. The Open Access Initiative shows that a change is taking place in the communication process. This change is also important for service departments within research institutions. Libraries, computer centers and related units have to ask themselves how to react appropriately to the new conditions. What services must be changed or redeveloped, and in what quality and quantity should they be offered? This article focuses on changes in the scholarly publication process. It describes both technological changes and the changes needed in people's attitudes.

The Brazilian electronic theses and dissertations digital library: providing open access for scholarly information

This paper describes a project led by the Instituto Brasileiro de Informações em Ciência e Tecnologia (Ibict), a government institution, to build a national digital library for electronic theses and dissertations - Bibliteca Digital de Teses e Dissertações (BDTD). The project has been a collaborative effort among Ibict, universities and other research centers in Brazil. The developers adopted a system architecture based on the Open Archives Initiative (OAI) in which universities and research centers act as data providers and Ibict as a service provider. A Brazilian metadata standard for electronic theses and dissertations was developed for the digital library. A toolkit including open source package was also developed by Ibict to be distributed to potential data providers. BDTD has been integrated with the international initiative: the Networked Digital Library of Thesis and Dissertation (NDLTD). Discussions in the paper address various issues related to project design, development and management as well as the role played by Ibict. Conclusions highlight some important lessons learned to date and challenges for the future in expanding the BDTD project.

Asexual evolution: do intragenomic parasites maintain sex?

Resolving the paradox of sex, with its twofold cost to genic transmission, remains one of the major unresolved questions in evolutionary biology. Counting this genetic cost has now gone genomic. In this issue of Molecular Ecology, Kraaijeveld et al. (2012) describe the first genome-scale comparative study of related sexual and asexual animal lineages, to test the hypothesis that asexuals bear heavier loads of deleterious transposable elements. A much higher density of such parasites might be expected, due to the inability of asexual lineages to purge transposons via mechanisms exclusive to sexual reproduction. They find that the answer is yes--and no--depending upon the family of transposons considered. Like many such advances in testing theory, more questions are raised by this study than answered, but a door has been opened to molecular evolutionary analyses of how responses to selection from intragenomic parasites might mediate the costs of sex.

Acetylcholinesterase inhibitor treatment for myasthenia gravis.

BACKGROUND: In myasthenia gravis, antibody-mediated blockade of acetylcholine receptors at the neuromuscular junction abolishes the naturally occurring 'safety factor' of synaptic transmission. Acetylcholinesterase inhibitors provide temporary symptomatic treatment of muscle weakness, but there is controversy about their long-term efficacy, dosage and side effects. OBJECTIVES: To evaluate the efficacy of acetylcholinesterase inhibitors in all forms of myasthenia gravis. SEARCH STRATEGY: We searched The Cochrane Neuromuscular Disease Group Specialized Register (5 October 2009), The Cochrane Central Register of Controlled Trials CENTRAL) (The Cochrane Library Issue 3, 2009), MEDLINE (January 1966 to September 2009), EMBASE (January 1980 to September 2009) for randomised controlled trials and quasi-randomised controlled trials regarding usage of acetylcholinesterase inhibitors in myasthenia gravis. Two authors scanned the articles for any study eligible for inclusion. We also contacted the authors and known experts in the field to identify additional published or unpublished data. SELECTION CRITERIA: Types of studies: all randomised or quasi-randomised trials.Types of participants: all myasthenia gravis patients diagnosed by an internationally accepted definition.Types of interventions: treatment with any form of acetylcholinesterase inhibitor.Types of outcome measuresPrimary outcome measureImprovement in the presenting symptoms within 1 to 14 days of the start of treatment.Secondary outcome measures(1) Improvement in the presenting symptoms more than 14 days after the start of treatment.(2) Change in impairment measured by a recognised and preferably validated scale, such as the quantitative myasthenia gravis score within 1 to 14 days and more than 14 days after the start of treatment.(3) Myasthenia Gravis Association of America post-intervention status more than 14 days after start of treatment.(4) Adverse events: muscarinic side effects. DATA COLLECTION AND ANALYSIS: One author (MMM) extracted the data, which were checked by a second author. We contacted study authors for extra information and collected data on adverse effects from the trials. MAIN RESULTS: We did not find any large randomised or quasi-randomised trials of acetylcholinesterase inhibitors in generalised myasthenia gravis. One cross-over randomised trial using intranasal neostigmine in a total of 10 subjects was only available as an abstract. AUTHORS' CONCLUSIONS: Except for one small and inconclusive trial of intranasal neostigmine, no randomised controlled trial has been conducted on the use of acetylcholinesterase inhibitors in myasthenia gravis. Response to acetylcholinesterase inhibitors in observational studies is so clear that a randomised controlled trial depriving participants in the placebo arm of treatment would be difficult to justify.

Social network architecture and the maintenance of deleterious cultural traits.

How have changes in communications technology affected the way that misinformation spreads through a population and persists? To what extent do differences in the architecture of social networks affect the spread of misinformation, relative to the rates and rules by which individuals transmit or eliminate different pieces of information (cultural traits)? Here, we use analytical models and individual-based simulations to study how a 'cultural load' of misinformation can be maintained in a population under a balance between social transmission and selective elimination of cultural traits with low intrinsic value. While considerable research has explored how network architecture affects percolation processes, we find that the relative rates at which individuals transmit or eliminate traits can have much more profound impacts on the cultural load than differences in network architecture. In particular, the cultural load is insensitive to correlations between an individual's network degree and rate of elimination when these quantities vary among individuals. Taken together, these results suggest that changes in communications technology may have influenced cultural evolution more strongly through changes in the amount of information flow, rather than the details of who is connected to whom.

Management of hepatitis C virus (HCV) infection in drug substitution programs.

BACKGROUND: In Switzerland, intravenous drug use (IDU) accounts for 80% of newly acquired hepatitis C virus (HCV) infections. Early HCV treatment has the potential to interrupt the transmission chain and reduce morbidity/mortality due to decompensated liver cirrhosis and hepatocellular carcinoma. Nevertheless, patients in drug substitution programs are often insufficiently screened and treated. OBJECTIVE/METHODS: With the aim to improve HCV management in IDUs, we conducted a cross sectional chart review in three opioid substitution programs in St. Gallen (125 methadone and 71 heroin recipients). Results were compared with another heroin substitution program in Bern (202 patients) and SCCS/SHCS data. RESULTS: Among the methadone/heroin recipients in St. Gallen, diagnostic workup of HCV was better than expected: HCV/HIV-status was unknown in only 1% (2/196), HCV RNA was not performed in 9% (13/146) of anti-HCV-positives and the genotype missing in 15% (12/78) of HCV RNA-positives. In those without spontaneous clearance (two thirds), HCV treatment uptake was 23% (21/91) (HIV-: 29% (20/68), HIV+: 4% (1/23)), which was lower than in methadone/heroin recipients and particularly non-IDUs within the SCCS/SHCS, but higher than in the, mainly psychiatrically focussed, heroin substitution program in Bern (8%). Sustained virological response (SVR) rates were comparable in all settings (overall: 50%, genotype 1: 35-40%, genotype 3: two thirds). In St. Gallen, the median delay from the estimated date of infection (IDU start) to first diagnosis was 10 years and to treatment was another 7.5 years. CONCLUSIONS: Future efforts need to focus on earlier HCV diagnosis and improvement of treatment uptake among patients in drug substitution programs, particularly if patients are HIV-co-infected. New potent drugs might facilitate the decision to initiate treatment.

The evolution of lncRNA repertoires and expression patterns in tetrapods.

Only a very small fraction of long noncoding RNAs (lncRNAs) are well characterized. The evolutionary history of lncRNAs can provide insights into their functionality, but the absence of lncRNA annotations in non-model organisms has precluded comparative analyses. Here we present a large-scale evolutionary study of lncRNA repertoires and expression patterns, in 11 tetrapod species. We identify approximately 11,000 primate-specific lncRNAs and 2,500 highly conserved lncRNAs, including approximately 400 genes that are likely to have originated more than 300 million years ago. We find that lncRNAs, in particular ancient ones, are in general actively regulated and may function predominantly in embryonic development. Most lncRNAs evolve rapidly in terms of sequence and expression levels, but tissue specificities are often conserved. We compared expression patterns of homologous lncRNA and protein-coding families across tetrapods to reconstruct an evolutionarily conserved co-expression network. This network suggests potential functions for lncRNAs in fundamental processes such as spermatogenesis and synaptic transmission, but also in more specific mechanisms such as placenta development through microRNA production.

Electronic Bulletin Board System, HR-345, 1998

The primary objectives of the Electronic Bulletin Board System (BBS) project were to: (1) Provide an electronic communication tool which would link city and county engineering offices to each other and to other governmental agencies for messaging and data sharing; (2) Provide a dial-up site for reference information or files accessible on-demand; and (3) Provide a "stepping stone" to the world of electronic data transfer, recognizing that most local government employees face a huge complex of technology with limited knowledge of computers and communications tools. The system was designed to be as simple as possible, and to require minimal equipment and software cost to the users. The original system was an Apex 386/25 computer with MS-DOS 5.0 software and the final configuration was an HP Vectra XM Pentium 90 with MS-NT 3.51 and Mustang - Wildcat 5.0 software. The users of the BBS were county engineers and their staff, offices in the central office of the Iowa Department of Transportation (DOT) and Resident Construction Engineers at the Iowa DOT. Much of the activity was between the county engineers, and their staffs, and the Iowa DOT offices with which they have ongoing business activities. The BBS contained files for mapping, Internet e-mail service, Accident Location Analysis System (ALAS) data, Iowa DOT bid lettings, and Autocad and Intergraph maps and standards. The 800 line calls were recorded and gave the best indication of the usage and the trends that were being followed. The usage tended to be higher in the winter months when design activities are occurring and lower in the summer months when the construction is in progress. The project was judged a success. The BBS did provide a "stepping stone" to the world of electronic data transfer.

Lipid-bloated subretinal microglial cells are at the origin of drusen appearance in CX3CR1-deficient mice.

Drusen, the white yellowish deposits that can be seen in funduscopy, are a hallmark of age-related macular degeneration. Histologically, drusen are believed to be dome-shaped or more confluent lipid accumulations between the retinal pigment epithelium and the choriocapillaries. Recent advances in mouse funduscopy have revealed the presence of drusen-like structures in chemokine knockout animals in the absence of sizeable dome-shaped material below the retinal pigment epithelium. We show that aged CX3CR1-/- mice present with drusen-like appearance in funduscopy that is associated with a progressive age-related microglial cell accumulation in the subretinal space. We demonstrate that the anatomical equivalent of the drusen-like appearance in these mice are lipid-bloated subretinal microglial cells rather than subretinal pigment epithelium deposits [Combadière C, et al: J Clin Invest 2007;117:2920-2928].

Antibacterial burst-release from minimal Ag-containing plasma polymer coatings.

Biomaterials releasing silver (Ag) are of interest because of their ability to inhibit pathogenic bacteria including antibiotic-resistant strains. In order to investigate the potential of nanometre-thick Ag polymer (Ag/amino-hydrocarbon) nanocomposite plasma coatings, we studied a comprehensive range of factors such as the plasma deposition process and Ag cation release as well as the antibacterial and cytocompatible properties. The nanocomposite coatings released most bound Ag within the first day of immersion in water yielding an antibacterial burst. The release kinetics correlated with the inhibitory effects on the pathogens Pseudomonas aeruginosa or Staphylococcus aureus and on animal cells that were in contact with these coatings. We identified a unique range of Ag content that provided an effective antibacterial peak release, followed by cytocompatible conditions soon thereafter. The control of the in situ growth conditions for Ag nanoparticles in the polymer matrix offers the possibility to produce customized coatings that initially release sufficient quantities of Ag ions to produce a strong adjacent antibacterial effect, and at the same time exhibit a rapidly decaying Ag content to provide surface cytocompatibility within hours/days. This approach seems to be favourable with respect to implant surfaces and possible Ag-resistance/tolerance built-up.

The making of frozen-hydrated, vitreous lamellas from cells for cryo-electron microscopy.

There has been a long standing desire to produce thick (up to 500 nm) cryo-sections of fully hydrated cells and tissue for high-resolution analysis in their natural state by cryo-transmission electron microscopy. Here, we present a method that can successfully produce sections (lamellas in FIB-SEM terminology) of fully hydrated, unstained cells from high-pressure frozen samples by focused ion beam (FIB) milling. The samples are therefore placed in thin copper tubes and vitrified by high-pressure freezing. For transfer, handling and subsequent milling, the tubes are placed in a novel connective device (ferrule) that protects the sample from devitrification and contamination and passes through all operation steps. A piezo driven sample positioning stage (cryo-nano-bench, CNB) with three degrees of freedom was additionally developed to enable accurate milling of frozen-hydrated lamellas. With the CNB, high-pressure frozen samples can be milled to produce either thin lamellas (<100 nm), for direct imaging by high-resolution cryo-TEM or thicker lamellas (300-500 nm) for cryo-electron tomography. The sample remains vitreous throughout the process by using the presented tools and methods. The results are an important step towards investigating larger cells and even tissue in there natural state which in the end will enable us to gain better insights into cellular processes.

CTF/NF1 transcription factors act as potent genetic insulators for integrating gene transfer vectors.

Gene transfer-based therapeutic approaches have greatly benefited from the ability of some viral vectors to efficiently integrate within the cell genome and ensure persistent transmission of newly acquired transgenes to the target cell progeny. However, integration of provirus has been associated with epigenetic repercussions that may influence the expression of both the transgene and cellular genes close to vector integration loci. The exploitation of genetic insulator elements may overcome both issues through their ability to act as barriers that limit transgene silencing and/or as enhancer-blockers preventing the activation of endogenous genes by the vector enhancer. We established quantitative plasmid-based assay systems to screen enhancer-blocker and barrier genetic elements. Short synthetic insulators that bind to nuclear factor-I protein family transcription factors were identified to exert both enhancer-blocker and barrier functions, and were compared to binding sites for the insulator protein CTCF (CCCTC-binding factor). Gamma-retroviral vectors enclosing these insulator elements were produced at titers similar to their non-insulated counterparts and proved to be less genotoxic in an in vitro immortalization assay, yielding lower activation of Evi1 oncogene expression and reduced clonal expansion of bone marrow cells.