LE STUDIUM Multidisciplinary Journal
A novel strategy has been devised that allows a ligation of of thioacids and imidazolyl urea activated amines under aqueous conditions. This approach enables the traceless removal of imidazole and CO2 to directly generate the desired amide bond without affecting the side chain reactive side chain functional groups on the peptide chain. Meanwhile, the novel synthesis of peptide thioacid is also reported.
Periostin (POSTN) is a matricellular protein that plays a key role in development and repair within the biological matrix of the lung. POSTN is highly expressed in several cell types in lung such as epithelial or endothelial cells, fibroblasts, smooth muscle and mast cells, contributing to mucus secretion, alveolar epithelial repair, and lung fibrosis. However, the underlying mechanism how POSTN contributes to the development of lung inflammation remains unclear. In the current study, we attempted to determine whether treatment with a monoclonal anti-POSTN antibody induces a significant inhibition of asthmatic reactions in a mouse asthma model. Mice sensitized and challenged with papain evidenced an increased periostin expression in lung and typical asthmatic reactions, as follows: an increase in the number of eosinophils in bronchoalveolar lavage fluid; a marked influx of inflammatory cells into the lung around blood vessels and airways, and Th2 cytokines including IL-4 and IL-5 and chemokines in the bronchoalveolar lavage (BAL) fluid; emphysema; the detection of thymic stromal lymphopoietin (TSLP) produced by epithelial cells. However, the administration of anti-POSTN prior to the final airway papain challenge resulted in a significant inhibition of all asthmatic reactions. We also demonstrated that anti-POSTN antibody treatment resulted in significant reductions on collagen expression and a reduction in the increased eosinophil. The treatment of animals with anti-POSTN resulted in a significant reduction in the concentrations of the chemokines (CCL-11 and CCL-17) in the airways, without any concomitant increase in the concentration of Th1 cytokines. This study identifies a novel therapeutic strategy for airway hyperresponsiveness, which uses antibodies reactive against POSTN via the inhibition of the Th2 response. It also provides theoretical evidence for the control of allergic asthma and fibrosis by targeting POSTN.
Religious lieux de savoir in premodern Tours and Orléans: A Social and Spatial Approach to Religious Reading in French (c. 1450-c. 1550)
The research has shown to that up to ca. 1550 many of the inhabitants of “average” French towns as Tours and Orléans were literate and that they did have access to religious texts in French, contrarily to ideas regularly expressed in historical scholarship. Archival documents, as well as surviving handwritten texts and printed books have provided information about the wide range of social backgrounds of the readers, from stocking makers in Tours and Orléans, the grandson of Gaultiere who ran the public baths in Tours, to well-off merchants and lawyers. Next to books and their owners, the research has resulted in evidence about the presence and location of libraries, open access texts and books, booksellers and printers. Furthermore, an inventory of a book collection (probably a bookshop) with more than 276 books in French in Tours has given much data about textual cultures and reading interests. The historical data often allow plotting these “lieux de savoir” on historical maps of premodern Tours and Orléans. Further analysis of places of religious knowledge by making use of computerised Geographical Information Systems allow for more refined conclusions about concentrations (near religious institutions and schools) and accessibility (in the heart of urban life). The project has already resulted in one accepted peer-reviewed publication; two other articles and a collection of articles in open access, authored by specialists in the field, are in preparation.
Responsive Nanozeolites: Smart Porosity and Surface Tailoring for Multimodal Imaging and Therapy of Cancer
Effective cancer treatment requires its early diagnosis in combination with safe drug delivery mechanisms. Up to date many therapeutics have failed due to their limited ability to reach the diseased site selectively without damaging healthy cells. Furthermore, none of the existing imaging techniques is absolutely reliable due to the differences in resolution and sensitivity. Therefore, synergistic combination of imaging modalities in one, typically nanodimensional, probe is the key-strategy to benefit from, for example the sensitive and quantifiable PET signal and the high resolution of MRI. Nanozeolites are among the most promising candidates for realization of this concept due to their unique crystalline structure capable of stable hosting of metal-ions with diagnostic and therapeutic properties. Even though, these materials have found many applications in various technologies, their medicinal potential still requires thorough investigations. This project aimed at the design, preparation and testing of novel nanozeolitic probes that can be applied as personalized drugs for diagnostic and therapeutic purposes
Peatlands are key ecosystems in the global carbon balance due in part to the slow microbial degradation of the organic matter (OM) in peat soils. Role of peatlands as powerful carbon storage systems may be threatened by climate change, leading to a potential huge release of greenhouse gases to the atmosphere. Our knowledge on the mechanisms behind the microbial OM degradation is still incomplete, and it is also essential to develop better management strategies and mitigate global change impacts. In the frame of the present fellowship, the microbial extracellular enzymatic mechanisms of the OM degradation in peat soil and pore water were studied in a French altered peatland, assessing changes in soil depth and warming effect during an annual cycle. Additionally, to the research programme, during the present fellowship a new technique for the host laboratory was implemented (protocol to measure extracellular enzyme activities in pore water and peat soil), the fellow participated in several conferences and seminars, three publication were or are in the process of being published, and a new project with the host laboratory is in developing.
A protic ionic liquid is inctroduced for the first time as a solvent for a high energy density vanadium redox flow battery. The proof-of-concept redox flow cell with a concentration of 3 mol L−1 vandyl sulfate electrolyte was tested for a total of 30 cycles at 40°C, showing an open circuit potential of 1.38 V, a nominal capacity of 1900 mAh at a current density of 40 mA cm−1 and energy and coulombic efficiencies of 64 and 90%, respectively. The continuous 16 hours of cycling suggest that the concentrated anolyte and catholyte are thermally stable and cycleable. This study underlines a new route to improve the energy-to-volume ratio of this promising energy storage system.
This Le Studium Fellowship was used to analyze the crystal growth in levitated melts. Furthermore, methodical questions concerning the method EBSD as well as XRD were addressed. Finally, the literature concerning oriented surface nucleation in glasses was completed.
Coordination compounds as antioxidants: activity evaluation by combining first-principle calculations and solid-state NMR
Inspired by the active site of the copper-zinc superoxide dismutase enzyme, we studied the reactivity of imidazolic ligands to improve the design and synthesis of coordination compounds, active against the superoxide radical (responsible of DNA, cellular and tissues damage, leading to illness like cancer, atherosclerosis, heart failures, etc.). By the joint use of first-principle calculations and solid state NMR spectroscopy, we identified the relationship between the structural characteristics and the reactivity of the synthesized compounds, that lead and modulates their antioxidant activity.
Infections with parasitic helminths expose serious health threats to humans and animals alike. Prevention of disease is dependent on the effective treatment using anthelmintics. Unfortunately, anthelmintic resistance (AR) has evolved in many helminth species during the past decades and meanwhile poses a major constraint to established worm control approaches. This project aimed to improve our understanding of the molecular mechanisms by which helminths, particularly the potentially deadly horse parasite Parascaris sp., become capable of withstanding drug treatment. To this end, Parascaris P-glycoproteins (Pgp), belonging to an important group of mediators of anthelmintic resistance, were introduced into the model organism Caenorhabditis elegans using the CRISPR/Cas9 technology. The resulting transgenic lines will subsequently be analyzed to functionally elucidate the role of putatively AR-associated Parascaris Pgp sequence polymorphisms.
Evidence exists that the gonadotropins LH and FSH can substitute to each other under certain circumstances, in addition to the fact that they can act together in granulosa cells. The aim of this study is to investigate how the two human gonadotropins influence each other in granulosa cells expressing both receptors, or by co-culturing cells expressing either the LHCGR or the FSHR (as a model granulosa/theca interaction). Plasmids encoding the c-myc-tagged-LHCGR and the FLAG-tagged FSHR under the control of an inducible coumermycin-responsive or doxycycline-responsive promoter, respectively were produced. These plasmids were used to permanently transfect human granulosa cell-derived KGN cells and HEK293 cells. The following cell lines were obtained and partially characterized: #1 c-myc-tagged-LHCGR-KGN; #2 FLAG-tagged FSHR_HEK293; #3 FLAG-tagged FSHR-KGN; #4 Double, c-myc-tagged-LHCGR and FLAG-tagged FSHR-KGN. After induction of receptor expression, the cell lines #1 and #2 and #3 responded to hCG and FSH stimulation, respectively by producing cAMP. Receptor expression was demonstrated by RT-PCR and flow cytometry. The characterization of the cell line #4 is ongoing. These cell lines are now available for the study of cell signaling and steroid synthesis, as well as in silico modeling, to gain insight into the dynamics of the intertwined cell response to FSH and LH in granulosa cells. These experiments will continue in parallel in both laboratories involved. Our cell lines represent new, very valuable instruments for the study of molecular pharmacology of FSH and LH, in order to improve infertility treatment, (multi)follicular growth for assisted reproduction, ovulation and spermatogenesis.