Self-citations at the meso and individual levels: effects of different calculation methods

This paper focuses on the study of self-citations at the meso and micro (individual) levels, on the basis of an analysis of the production (1994–2004) of individual researchers working at the Spanish CSIC in the areas of Biology and Biomedicine and Material Sciences. Two different types of self-citations are described: author self-citations (citations received from the author him/herself) and co-author self-citations (citations received from the researchers’ co-authors but without his/her participation). Self-citations do not play a decisive role in the high citation scores of documents either at the individual or at the meso level, which are mainly due to external citations. At micro-level, the percentage of self-citations does not change by professional rank or age, but differences in the relative weight of author and co-author self-citations have been found. The percentage of co-author self-citations tends to decrease with age and professional rank while the percentage of author self-citations shows the opposite trend. Suppressing author self-citations from citation counts to prevent overblown self-citation practices may result in a higher reduction of citation numbers of old scientists and, particularly, of those in the highest categories. Author and co-author self-citations provide valuable information on the scientific communication process, but external citations are the most relevant for evaluative purposes. As a final recommendation, studies considering self-citations at the individual level should make clear whether author or total self-citations are used as these can affect researchers differently

Buffered memory: a hypothesis for the maintenance of functional, virus-specific CD8(+) T cells during cytomegalovirus infection.

Chronic infections have been a major topic of investigation in recent years, but the mechanisms that dictate whether or not a pathogen is successfully controlled are incompletely understood. Cytomegalovirus (CMV) is a herpesvirus that establishes a persistent infection in the majority of people in the world. Like other herpesviruses, CMV is well controlled by an effective immune response and induces little, if any, pathology in healthy individuals. However, controlling CMV requires continuous immune surveillance, and thus, CMV is a significant cause of morbidity and death in immune-compromised individuals. T cells in particular play an important role in controlling CMV and both CD4(+) and CD8(+) CMV-specific T cells are essential. These virus-specific T cells persist in exceptionally large numbers during the infection, traffic into peripheral tissues and remain functional, making CMV an attractive vaccine vector for driving CMV-like T cell responses against recombinant antigens of choice. However, the mechanisms by which these T cells persist and differentiate while remaining functional are still poorly understood, and we have no means to promote their development in immune-compromised patients at risk for CMV disease. In this review, I will briefly summarize our current knowledge of CMV-specific CD8(+) T cells and propose a mechanism that may explain their maintenance and preservation of function during chronic infection

Variability in the Dynamics of Mortality and Immobility Responses of Freshwater Arthropods Exposed to Chlorpyrifos

The species sensitivity distribution (SSD) concept is an important probabilistic tool for environmental risk assessment (ERA) and accounts for differences in species sensitivity to different chemicals. The SSD model assumes that the sensitivity of the species included is randomly distributed. If this assumption is violated, indicator values, such as the 50% hazardous concentration, can potentially change dramatically. Fundamental research, however, has discovered and described specific mechanisms and factors influencing toxicity and sensitivity for several model species and chemical combinations. Further knowledge on how these mechanisms and factors relate to toxicologic standard end points would be beneficial for ERA. For instance, little is known about how the processes of toxicity relate to the dynamics of standard toxicity end points and how these may vary across species. In this article, we discuss the relevance of immobilization and mortality as end points for effects of the organophosphate insecticide chlorpyrifos on 14 freshwater arthropods in the context of ERA. For this, we compared the differences in response dynamics during 96 h of exposure with the two end points across species using dose response models and SSDs. The investigated freshwater arthropods vary less in their immobility than in their mortality response. However, differences in observed immobility and mortality were surprisingly large for some species even after 96 h of exposure. As expected immobility was consistently the more sensitive end point and less variable across the tested species and may therefore be considered as the relevant end point for population of SSDs and ERA, although an immobile animal may still potentially recover. This is even more relevant because an immobile animal is unlikely to survive for long periods under field conditions. This and other such considerations relevant to the decision-making process for a particular end point are discussed

Good agreement of conventional and gel-based direct agglutination test in immune-mediated haemolytic anaemia

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to compare a gel-based test with the traditional direct agglutination test (DAT) for the diagnosis of immune-mediated haemolytic anaemia (IMHA).</p> <p>Methods</p> <p>Canine (n = 247) and feline (n = 74) blood samples were submitted for DAT testing to two laboratories. A subset of canine samples was categorized as having idiopathic IMHA, secondary IMHA, or no IMHA.</p> <p>Results</p> <p>The kappa values for agreement between the tests were in one laboratory 0.86 for canine and 0.58 for feline samples, and in the other 0.48 for canine samples. The lower agreement in the second laboratory was caused by a high number of positive canine DATs for which the gel test was negative. This group included significantly more dogs with secondary IMHA.</p> <p>Conclusions</p> <p>The gel test might be used as a screening test for idiopathic IMHA and is less often positive in secondary IMHA than the DAT.</p

Saffold Virus, a Human Theiler's-Like Cardiovirus, Is Ubiquitous and Causes Infection Early in Life

The family Picornaviridae contains well-known human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and parechovirus). In addition, this family contains a number of viruses that infect animals, including members of the genus Cardiovirus such as Encephalomyocarditis virus (EMCV) and Theiler's murine encephalomyelits virus (TMEV). The latter are important murine pathogens that cause myocarditis, type 1 diabetes and chronic inflammation in the brains, mimicking multiple sclerosis. Recently, a new picornavirus was isolated from humans, named Saffold virus (SAFV). The virus is genetically related to Theiler's virus and classified as a new species in the genus Cardiovirus, which until the discovery of SAFV did not contain human viruses. By analogy with the rodent cardioviruses, SAFV may be a relevant new human pathogen. Thus far, SAFVs have sporadically been detected by molecular techniques in respiratory and fecal specimens, but the epidemiology and clinical significance remained unclear. Here we describe the first cultivated SAFV type 3 (SAFV-3) isolate, its growth characteristics, full-length sequence, and epidemiology. Unlike the previously isolated SAFV-1 and -2 viruses, SAFV-3 showed efficient growth in several cell lines with a clear cytopathic effect. The latter allowed us to conduct a large-scale serological survey by a virus-neutralization assay. This survey showed that infection by SAFV-3 occurs early in life (>75% positive at 24 months) and that the seroprevalence reaches >90% in older children and adults. Neutralizing antibodies were found in serum samples collected in several countries in Europe, Africa, and Asia. In conclusion, this study describes the first cultivated SAFV-3 isolate, its full-length sequence, and epidemiology. SAFV-3 is a highly common and widespread human virus causing infection in early childhood. This finding has important implications for understanding the impact of these ubiquitous viruses and their possible role in acute and/or chronic disease

The role of multiple marks in epigenetic silencing and the emergence of a stable bivalent chromatin state

We introduce and analyze a minimal model of epigenetic silencing in budding yeast, built upon known biomolecular interactions in the system. Doing so, we identify the epigenetic marks essential for the bistability of epigenetic states. The model explicitly incorporates two key chromatin marks, namely H4K16 acetylation and H3K79 methylation, and explores whether the presence of multiple marks lead to a qualitatively different systems behavior. We find that having both modifications is important for the robustness of epigenetic silencing. Besides the silenced and transcriptionally active fate of chromatin, our model leads to a novel state with bivalent (i.e., both active and silencing) marks under certain perturbations (knock-out mutations, inhibition or enhancement of enzymatic activity). The bivalent state appears under several perturbations and is shown to result in patchy silencing. We also show that the titration effect, owing to a limited supply of silencing proteins, can result in counter-intuitive responses. The design principles of the silencing system is systematically investigated and disparate experimental observations are assessed within a single theoretical framework. Specifically, we discuss the behavior of Sir protein recruitment, spreading and stability of silenced regions in commonly-studied mutants (e.g., sas2, dot1) illuminating the controversial role of Dot1 in the systems biology of yeast silencing.Comment: Supplementary Material, 14 page

Chaste: an open source C++ library for computational physiology and biology

Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to "re-invent the wheel" with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials