Use of the Journal Impact Factor in academic review, promotion, and tenure evaluations.

We analyzed how often and in what ways the Journal Impact Factor (JIF) is currently used in review, promotion, and tenure (RPT) documents of a representative sample of universities from the United States and Canada. 40% of research-intensive institutions and 18% of master's institutions mentioned the JIF, or closely related terms. Of the institutions that mentioned the JIF, 87% supported its use in at least one of their RPT documents, 13% expressed caution about its use, and none heavily criticized it or prohibited its use. Furthermore, 63% of institutions that mentioned the JIF associated the metric with quality, 40% with impact, importance, or significance, and 20% with prestige, reputation, or status. We conclude that use of the JIF is encouraged in RPT evaluations, especially at research-intensive universities, and that there is work to be done to avoid the potential misuse of metrics like the JIF.

The state of OA: a large-scale analysis of the prevalence and impact of Open Access articles.

Despite growing interest in Open Access (OA) to scholarly literature, there is an unmet need for large-scale, up-to-date, and reproducible studies assessing the prevalence and characteristics of OA. We address this need using oaDOI, an open online service that determines OA status for 67 million articles. We use three samples, each of 100,000 articles, to investigate OA in three populations: (1) all journal articles assigned a Crossref DOI, (2) recent journal articles indexed in Web of Science, and (3) articles viewed by users of Unpaywall, an open-source browser extension that lets users find OA articles using oaDOI. We estimate that at least 28% of the scholarly literature is OA (19M in total) and that this proportion is growing, driven particularly by growth in Gold and Hybrid. The most recent year analyzed (2015) also has the highest percentage of OA (45%). Because of this growth, and the fact that readers disproportionately access newer articles, we find that Unpaywall users encounter OA quite frequently: 47% of articles they view are OA. Notably, the most common mechanism for OA is not Gold, Green, or Hybrid OA, but rather an under-discussed category we dub Bronze: articles made free-to-read on the publisher website, without an explicit Open license. We also examine the citation impact of OA articles, corroborating the so-called open-access citation advantage: accounting for age and discipline, OA articles receive 18% more citations than average, an effect driven primarily by Green and Hybrid OA. We encourage further research using the free oaDOI service, as a way to inform OA policy and practice.

A multi-disciplinary perspective on emergent and future innovations in peer review.

Peer review of research articles is a core part of our scholarly communication system. In spite of its importance, the status and purpose of peer review is often contested. What is its role in our modern digital research and communications infrastructure? Does it perform to the high standards with which it is generally regarded? Studies of peer review have shown that it is prone to bias and abuse in numerous dimensions, frequently unreliable, and can fail to detect even fraudulent research. With the advent of web technologies, we are now witnessing a phase of innovation and experimentation in our approaches to peer review. These developments prompted us to examine emerging models of peer review from a range of disciplines and venues, and to ask how they might address some of the issues with our current systems of peer review. We examine the functionality of a range of social Web platforms, and compare these with the traits underlying a viable peer review system: quality control, quantified performance metrics as engagement incentives, and certification and reputation. Ideally, any new systems will demonstrate that they out-perform and reduce the biases of existing models as much as possible. We conclude that there is considerable scope for new peer review initiatives to be developed, each with their own potential issues and advantages. We also propose a novel hybrid platform model that could, at least partially, resolve many of the socio-technical issues associated with peer review, and potentially disrupt the entire scholarly communication system. Success for any such development relies on reaching a critical threshold of research community engagement with both the process and the platform, and therefore cannot be achieved without a significant change of incentives in research environments.

Reduced monomeric CD4 is the preferred receptor for HIV.

CD4 is a co-receptor for binding of T cells to antigen-presenting cells and the primary receptor for the human immunodeficiency virus type 1 (HIV). CD4 exists in three different forms on the cell surface defined by the state of the domain 2 cysteine residues: an oxidized monomer, a reduced monomer, and a covalent dimer linked through the domain 2 cysteines. The disulfide-linked dimer is the preferred immune co-receptor. The form of CD4 that is preferred by HIV was examined in this study. HIV entry and envelope-mediated cell-cell fusion were tested using cells expressing comparable levels of wild-type or disulfide bond mutant CD4 in which the domain 2 cysteines were mutated to alanine. Eliminating the domain 2 disulfide bond increased entry of HIV reporter viruses and enhanced HIV envelope-mediated cell-cell fusion 2-4-fold. These observations suggest that HIV enters susceptible cells preferably through monomeric reduced CD4, whereas dimeric CD4 is the preferred receptor for binding to antigen-presenting cells. Cleavage of the domain 2 disulfide bond is possibly involved in the conformational change in CD4 associated with fusion of the HIV and cell membranes.

Disulfide bond that constrains the HIV-1 gp120 V3 domain is cleaved by thioredoxin.

A functional disulfide bond in both the HIV envelope glycoprotein, gp120, and its immune cell receptor, CD4, is involved in viral entry, and compounds that block cleavage of the disulfide bond in these proteins inhibit HIV entry and infection. The disulfide bonds in both proteins are cleaved at the cell surface by the small redox protein, thioredoxin. The target gp120 disulfide and its mechanism of cleavage were determined using a thioredoxin kinetic trapping mutant and mass spectrometry. A single disulfide bond was cleaved in isolated and cell surface gp120, but not the gp160 precursor, and the extent of the reaction was enhanced when gp120 was bound to CD4. The Cys(32) sulfur ion of thioredoxin attacks the Cys(296) sulfur ion of the gp120 V3 domain Cys(296)-Cys(331) disulfide bond, cleaving the bond. Considering that V3 sequences largely determine the chemokine receptor preference of HIV, we propose that cleavage of the V3 domain disulfide, which is facilitated by CD4 binding, regulates chemokine receptor binding. There are 20 possible disulfide bond configurations, and, notably, the V3 domain disulfide has the same unusual -RHStaple configuration as the functional disulfide bond cleaved in CD4.

Redox control on the cell surface: implications for HIV-1 entry.

Proteins that work outside cells nearly always contain disulfide bonds. The prevailing view is that these bonds have been added during evolution to enhance protein stability. Recent evidence suggests that disulfide bonds can also control protein function. Certain secreted proteins contain one or more disulfide bonds that can control function by breaking and reforming in a controlled way. This review focuses on disulfide exchange events on the cell surface, with a particular reference to two proteins involved in HIV-1 infection. The primary HIV-1 receptor on immune cells, CD4, and the viral envelope glycoprotein, gp120, play a central role in HIV-1 entry. Redox change in a disulfide bond or bonds in one or both of these proteins appears to be important for HIV-1 entry.

Disulfide exchange in domain 2 of CD4 is required for entry of HIV-1.

CD4, a member of the immunoglobulin superfamily of receptors that mediates cell-cell interactions in the immune system, is the primary receptor for HIV-1. The extracellular portion of CD4 is a concatenation of four immunoglobulin-like domains, D1 to D4. The D1, D2 and D4 domains each contain a disulfide bond. We show here that the D2 disulfide bond is redox-active. The redox state of the thiols (disulfide versus dithiol) appeared to be regulated by thioredoxin, which is secreted by CD4(+) T cells. Locking the CD4 and the thioredoxin active-site dithiols in the reduced state with a hydrophilic trivalent arsenical blocked entry of HIV-1 into susceptible cells. These findings indicate that redox changes in CD4 D2 are important for HIV-1 entry and represent a new target for HIV-1 entry inhibitors.