Modern charge density studies: the entanglement of experiment and theory

This tutorial review article is intended to provide a general guidance to a reader interested to learn about the methodologies to obtain accurate electron density mapping in molecules and crystalline solids, from theory or from experiment, and to carry out a sensible interpretation of the results, for chemical, biochemical or materials science applications. The review mainly focuses on X-ray diffraction techniques and refinement of experimental models, in particular multipolar models. Neutron diffraction, which was widely used in the past to fix accurate positions of atoms, is now used for more specific purposes. The review illustrates three principal analyses of the experimental or theoretical electron density, based on quantum chemical, semi-empirical or empirical interpretation schemes, such as the quantum theory of atoms in molecules, the semi-classical evaluation of interaction energies and the Hirshfeld analysis. In particular, it is shown that a simple topological analysis based on a partition of the electron density cannot alone reveal the whole nature of chemical bonding. More information based on the pair density is necessary. A connection between quantum mechanics and observable quantities is given in order to provide the physical grounds to explain the observations and to justify the interpretations.

BMP-2 induces the expression of chondrocyte-specific genes in bovine synovium-derived progenitor cells cultured in three-dimensional alginate hydrogel

OBJECTIVE: According to recent reports, the synovial membrane may contain mesenchymal stem cells with the potential to differentiate into chondrocytes under appropriate conditions. In order to assess the usefulness of synovium-derived progenitor cells for the purposes of cartilage tissue engineering, we explored their requirements for the expression of chondrocyte-specific genes after expansion in vitro. DESIGN: Mesenchymal progenitor cells were isolated from the synovial membranes of bovine shoulder joints and expanded in two-dimensions on plastic surfaces. They were then seeded either as micromass cultures or as single cells within alginate gels, which were cultured in serum-free medium. Under these three-dimensional conditions, chondrogenesis is known to be supported and maintained. Cell cultures were exposed either to bone morphogenetic protein-2 (BMP-2) or to isoforms of transforming growth factor-beta (TGF-beta). The levels of mRNA for Sox9, collagen types I and II and aggrecan were determined by RT-PCR. RESULTS: When transferred to alginate gel cultures, the fibroblast-like synovial cells assumed a rounded form. BMP-2, but not isoforms of TGF-beta, stimulated, in a dose-dependent manner, the production of messenger RNAs (mRNAs) for Sox9, type II collagen and aggrecan. Under optimal conditions, the expression levels of cartilage-specific genes were comparable to those within cultured articular cartilage chondrocytes. However, in contrast to cultured articular cartilage chondrocytes, synovial cells exposed to BMP-2 continued to express the mRNA for alpha1(I) collagen. CONCLUSIONS: This study demonstrates that bovine synovium-derived mesenchymal progenitor cells can be induced to express chondrocyte-specific genes. However, the differentiation process is not complete under the chosen conditions. The stimulation conditions required for full transformation must now be delineated.

Designed ankyrin repeat proteins: a new approach to mimic complex antigens for diagnostic purposes?

Inhibitory antibodies directed against coagulation factor VIII (FVIII) can be found in patients with acquired and congenital hemophilia A. Such FVIII-inhibiting antibodies are routinely detected by the functional Bethesda Assay. However, this assay has a low sensitivity and shows a high inter-laboratory variability. Another method to detect antibodies recognizing FVIII is ELISA, but this test does not allow the distinction between inhibitory and non-inhibitory antibodies. Therefore, we aimed at replacing the intricate antigen FVIII by Designed Ankyrin Repeat Proteins (DARPins) mimicking the epitopes of FVIII inhibitors. As a model we used the well-described inhibitory human monoclonal anti-FVIII antibody, Bo2C11, for the selection on DARPin libraries. Two DARPins were selected binding to the antigen-binding site of Bo2C11, which mimic thus a functional epitope on FVIII. These DARPins inhibited the binding of the antibody to its antigen and restored FVIII activity as determined in the Bethesda assay. Furthermore, the specific DARPins were able to recognize the target antibody in human plasma and could therefore be used to test for the presence of Bo2C11-like antibodies in a large set of hemophilia A patients. These data suggest, that our approach might be used to isolate epitopes from different sets of anti-FVIII antibodies in order to develop an ELISA-based screening assay allowing the distinction of inhibitory and non-inhibitory anti-FVIII antibodies according to their antibody signatures.

English and French causal connectives in contrast

Discourse connectives are often said to be language specific, and therefore not easily paired with a translation equivalent in a target language. However, few studies have assessed the magnitude and the causes of these divergences. In this paper, we provide an overview of the similarities and discrepancies between causal connectives in two typologically related languages: English and French. We first discuss two criteria used in the literature to account for these differences: the notion of domains of use and the information status of the cause segment. We then test the validity of these criteria through an empirical contrastive study of causal connectives in English and French, performed on a bidirectional corpus. Our results indicate that French and English connectives have only partially overlapping profiles and that translation equivalents are adequately predicted by these two criteria.

Taboo Language and Illness Online: The Use of Specific Emoticons and Graphic Signs to Talk about HIV/AIDS in South Africa

South Africa is one of the countries most affected by HIV/AIDS: According to 2014 UNAIDS data 6.8 million South Africans live with HIV/AIDS, which means a 18.9% prevalence rate among adults (15-49 years old). Despite this strong presence of HIV/AIDS in South African society it remains relatively stigmatized and is not openly talked about. The silence about HIV/AIDS maintained in everyday conversations and the superstitions associated with this illness have led to the creation of a taboo language. This study aims at shedding light on how South African users resort to specific emoticons and graphic signs to talk about HIV/AIDS online. For this purpose 368 Facebook status updates and comments concerning HIV/AIDS and its side effects were analysed. All participants, aged 14-48, lived at the moment of data collection in Cape Town, in the Cape Flats area. The online conversations investigated are mainly in English mixed with Afrikaans and/or Xhosa. The emoticons and graphic signs in most cases display a graphic depiction of the physical (and mental) effects of the illness. These linguistic and semiotic practices employed on Facebook provide insight into how Capetonian users, on the one hand, express solidarity and sympathy with people suffering from HIV/AIDS. On the other hand, the emoticons and graphic signs are used to label and position people affected by HIV/AIDS. Thus, in the South African context social network sites have become an important space and means for communicating HIV/AIDS issues.