Scientific publications

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The goal of this session is to provide an overview of the principles of language intervention for children from ages 3–18 years of age and review the evidence base for selection of treatments for language disorders in preschool-aged and school-aged children, with special attention to interventions aimed at addressing pragmatic and social communication disorders.


Avian eggshell formation reveals a new paradigm for vertebrate mineralization via vesicular amorphous calcium carbonate


Lilian Stapane, Nathalie Le Roy, Jacky Ezagal, Alejandro B. Rodriguez-Navarro, Valérie Labas, Lucie Combes-Soia, Maxwell T.Hincke, Joël Gautron

DOI https://doi.org/10.1074/jbc.RA120.014542
Scientific Field Life & Health Sciences
Fellow Prof. Maxwell Hincke
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Amorphous calcium carbonate (ACC) is an unstable mineral phase, which is progressively transformed into aragonite or calcite in biomineralization of marine invertebrate shells or avian eggshells, respectively. We have previously proposed a model of vesicular transport to provide stabilized ACC in chicken uterine fluid where eggshell mineralization takes place. Herein, we report further experimental support for this model. We confirmed the presence of extracellular vesicles (EVs) using transmission EM and showed high levels of mRNA of vesicular markers in the oviduct segments where eggshell mineralization occurs. We also demonstrate that EVs contain ACC in uterine fluid using spectroscopic analysis. Moreover, proteomics and immunofluorescence confirmed the presence of major vesicular, mineralization-specific and eggshell matrix proteins in the uterus and in purified EVs. We propose a comprehensive role for EVs in eggshell mineralization, in which annexins transfer calcium into vesicles and carbonic anhydrase 4 catalyzes the formation of bicarbonate ions (HCO[Formula: see text]), for accumulation of ACC in vesicles. We hypothesize that ACC is stabilized by ovalbumin and/or lysozyme or additional vesicle proteins identified in this study. Finally, EDIL3 and MFGE8 are proposed to serve as guidance molecules to target EVs to the mineralization site. We therefore report for the first-time experimental evidence for the components of vesicular transport to supply ACC in a vertebrate model of biomineralization.


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The separation of arma and amor that can be found in the chivalric tales of the fifteenth century allows the authors of these works to devote as much attention to the relationships between knights as to those between a knight and his lady. In particular, the bonds between knights who are also brothers are examined in various texts of the period, such as the Burgundian prose reworking of Florence de Rome, in which the brothers Milon and Esmeré, two young knights from Hungary, vie with each other for the hand of the eponymous heroine. In the version of this romance illustrated by the artist known as the « Wavrin Master » (Chantilly, Bibliothèque du château, ms. 652) the tensions between brotherhood and knighthood are foregrounded in both the narrative and its accompanying miniatures to the extent of taking on a political and ethical dimension. As I argue here, the way in which the two brothers act towards each other can be seen as an indicator of their suitability not only as the lady’s prospective husband but also as the future ruler of a realm, thus providing a trenchant and incisive lesson on chivalric mores at the end of the Middle Ages.


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Background: This paper would be a starting point addressed to a methodology to minimize the effects on livings of man made Electromagnetic Fields (EMFs) pollution. Methods: Given that previous literature highlighted that the most relevant EMFs effects on biological systems can be due to resonance phenomena between electromagnetic field and organic matter, it was proposed here an algorithm to obtain values of frequencies of an applied electromagnetic field far from resonant frequencies, depending on the natural frequencies and viscous damper of a biological system. These frequencies have been named non-resonant frequencies. Results: The displacement of the α-helices in cellular membrane channels due to EMFs has been proposed as a relevant parameter for quantifying the result of the interaction between an applied EMF and organic matter, in order to find both the natural frequencies of a biological system and the resonant frequencies at which α-helices displacement should be maximum. Conclusion: The non-resonant frequencies can be obtained using the algorithm proposed here.


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At the colonization site of a foreign entity, plant cells alter their trajectory of growth and development. The resulting structure – a plant gall – accommodates various needs of the foreigner, which are phylogenetically diverse: viruses, bacteria, protozoa, oomycetes, true fungi, parasitic plants, and many types of animals, including rotifers, nematodes, insects, and mites. The plant species that make galls also are diverse. We assume gall production costs the plant. All is well if the foreigner provides a gift that makes up for the cost. Nitrogen‐fixing nodule‐inducing bacteria provide nutritional services. Gall wasps pollinate fig trees. Unfortunately for plants, most galls are made for foes, some of which are deeply studied pathogens and pests: Agrobacterium tumefaciens, Rhodococcus fascians, Xanthomonas citri, Pseudomonas savastanoi, Pantoea agglomerans, ‘Candidatus’ phytoplasma, rust fungi, Ustilago smuts, root knot and cyst nematodes, and gall midges. Galls are an understudied phenomenon in plant developmental biology. We propose gall inception for discovering unifying features of the galls that plants make for friends and foes, talk about molecules that plants and gall‐inducers use to get what they want from each other, raise the question of whether plants colonized by arbuscular mycorrhizal fungi respond in a gall‐like manner, and present a research agenda.


Simulation and Theory of Antibody Binding to Crowded Antigen-Covered Surfaces


Cristiano de Michele, Paolo de los Rios, Giuseppe Foffi, Francesco Piazza, Yanay Ofran

DOI https://doi.org/10.1371/journal.pcbi.1004752
Scientific Field Life & Health Sciences
Fellow Dr Cristiano De Michele
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In this paper we introduce a fully flexible coarse-grained model of immunoglobulin G (IgG) antibodies parametrized directly on cryo-EM data and simulate the binding dynamics of many IgGs to antigens adsorbed on a surface at increasing densities. Moreover, we work out a theoretical model that allows to explain all the features observed in the simulations. Our combined computational and theoretical framework is in excellent agreement with surface-plasmon resonance data and allows us to establish a number of important results. (i) Internal flexibility is key to maximize bivalent binding, flexible IgGs being able to explore the surface with their second arm in search for an available hapten. This is made clear by the strongly reduced ability to bind with both arms displayed by artificial IgGs designed to rigidly keep a prescribed shape. (ii) The large size of IgGs is instrumental to keep neighboring molecules at a certain distance (surface repulsion), which essentially makes antigens within reach of the second Fab always unoccupied on average. (iii) One needs to account independently for the thermodynamic and geometric factors that regulate the binding equilibrium. The key geometrical parameters, besides excluded-volume repulsion, describe the screening of free haptens by neighboring bound antibodies. We prove that the thermodynamic parameters govern the low-antigen-concentration regime, while the surface screening and repulsion only affect the binding at high hapten densities. Importantly, we prove that screening effects are concealed in relative measures, such as the fraction of bivalently bound antibodies. Overall, our model provides a valuable, accurate theoretical paradigm beyond existing frameworks to interpret experimental profiles of antibodies binding to multi-valent surfaces of different sorts in many contexts.


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The recently discovered conserved quantity associated with Kepler rescaling is generalized by an extension of Noether’s theorem which involves the classical action integral as an additional term. For a free particle, the familiar Schrödinger dilations are recovered. A general pattern arises for homogeneous potentials. The associated conserved quantity allows us to derive the virial theorem. The relation to the Bargmann framework is explained and illustrated by exact plane gravitational waves.


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The integrals of the motion associated with conformal Killing vectors of a curved space–time with an additional electromagnetic background are studied for massive particles. They involve a new term which might be non-local. The difficulty disappears for pp-waves, for which explicit, local conserved charges are found. Alternatively, the mass can be taken into account by “distorting” the conformal Killing vectors. The relation of these non-point symmetries to the charges is analysed both in the Lagrangian and Hamiltonian approaches, as well as in the framework of Eisenhart–Duval lift.


Yeast-extract improved biosynthesis of lignans and neolignans in cell suspension cultures of Linum usitatissimum L.


Muhammad Nadeem, Bilal Haider Abbasi, Laurine Garros, Samantha Drouet, Adnan Zahir, Waqar Ahmad, Nathalie Giglioli-Guivarc’h, Christophe Hano

DOI https://doi.org/10.1007/s11240-018-1468-8
Scientific Field Life & Health Sciences
Fellow Dr Bilal Haider Abbasi
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Lignans and neolignans are important biologically active ingredients (BAIs) biosynthesized by Linum usitatissimum. These BAIs have multi-dimensional effects against cancer, diabetes and cardio vascular diseases. In this study, yeast extract (YE) was employed as an elicitor to evaluate its effects on dynamics of biomass, BAIs and antioxidant activities in L. usitatissimum cell cultures. During preliminary experiments, flax cultures were grown on different concentrations of YE (0–1000 mg/L), and 200 mg/L YE was found to be optimum to enhance several biochemical parameters in these cell cultures. A two-fold increase in fresh (FW) and dry weight (DW) over the control was observed in cultures grown on MS medium supplemented with 200 mg/L YE. Similarly, total phenolic (TPC; 16 mg/g DW) and flavonoids content (TFC; 5.1 mg/g DW) were also positively affected by YE (200 mg/L). Stimulatory effects of YE on biosynthesis of lignans and neolignans was also noted. Thus, 200 mg/L of YE enhanced biosynthesis of secoisolariciresinol diglucoside (SDG; 3.36-fold or 10.1 mg/g DW), lariciresinol diglucoside (LDG; 1.3-fold or 11.0 mg/g DW) and dehydrodiconiferyl alcohol glucoside (DCG; 4.26-fold or 21.3 mg/g DW) in L. usitatissimum cell cultures with respect to controls. This elicitation strategy could be scaled up for production of commercially feasible levels of these precious metabolites by cell cultures of Linum.


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Breast cancer is one of the most commonly diagnosed cancers around the globe and accounts for a large proportion of fatalities in women. Despite the advancement in therapeutic and diagnostic procedures, breast cancer still represents a major challenge. Current anti-breast cancer approaches include surgical removal, radiotherapy, hormonal therapy and the use of various chemotherapeutic drugs. However, drug resistance, associated serious adverse effects, metastasis and recurrence complications still need to be resolved which demand safe and alternative strategies. In this scenario, phytochemicals have recently gained huge attention due to their safety profile and cost-effectiveness. These phytochemicals modulate various genes, gene products and signalling pathways, thereby inhibiting breast cancer cell proliferation, invasion, angiogenesis and metastasis and inducing apoptosis. Moreover, they also target breast cancer stem cells and overcome drug resistance problems in breast carcinomas. Phytochemicals as adjuvants with chemotherapeutic drugs have greatly enhanced their therapeutic efficacy. This review focuses on the recently recognized molecular mechanisms underlying breast cancer chemoprevention with the use of phytochemicals such as curcumin, resveratrol, silibinin, genistein, epigallocatechin gallate, secoisolariciresinol, thymoquinone, kaempferol, quercetin, parthenolide, sulforaphane, ginsenosides, naringenin, isoliquiritigenin, luteolin, benzyl isothiocyanate, α-mangostin, 3,3′-diindolylmethane, pterostilbene, vinca alkaloids and apigenin.