Autotaxin

Autotaxin is a protein of approximately 900 amino acids discovered in the early 1990s. Over the past 15 years, a strong association between cancer cells and autotaxin production has been observed. Recent publications indicate that autotaxin and the capacity of cancer to metastasise are intimately linked. The discovery of new molecular targets in pharmacology is a mixture of pure luck, hard work and industrial strategy. Despite a crucial and desperate need for new therapeutic tools, many targets are approached in oncology, but only a few are validated and end up at the patient bed. Outside the busy domain of kinases, few targets have been discovered that can be useful in treating cancer, particularly metastatic processes. The fortuitous relationship between autotaxin and lysophosphatidic acid renders the results of observations made in the diabetes/obesity context considerably important. The literature provides observations that may aid in redesigning experiments to validate autotaxin as a potential oncology target.     

Changes to cellular water and element content induced by nucleolar stress: investigation by a cryo-correlative nano-imaging approach

The cell is a crowded volume, with estimated mean mass percentage of macromolecules and of water ranging from 7.5 to 45 and 55 to 92.5 %, respectively. However, the concentrations of macromolecules and water at the nanoscale within the various cell compartments are unknown. We recently developed a new approach, correlative cryo-analytical scanning transmission electron microscopy, for mapping the quantity of water within compartments previously shown to display GFP-tagged protein fluorescence on the same ultrathin cryosection. Using energy-dispersive X-ray spectrometry (EDXS), we then identified various elements (C, N, O, P, S, K, Cl, Mg) in these compartments and quantified them in mmol/l. Here, we used this new approach to quantify water and elements in the cytosol, mitochondria, condensed chromatin, nucleoplasm, and nucleolar components of control and stressed cancerous cells. The water content of the control cells was between 60 and 83 % (in the mitochondria and nucleolar fibrillar centers, respectively). Potassium was present at concentrations of 128–462 mmol/l in nucleolar fibrillar centers and condensed chromatin, respectively. The induction of nucleolar stress by treatment with a low dose of actinomycin-D to inhibit rRNA synthesis resulted in both an increase in water content and a decrease in the elements content in all cell compartments. We generated a nanoscale map of water and elements within the cell compartments, providing insight into their changes induced by nucleolar stress.     

La phosphatase des os et le mécanisme général de l'ossification

Summary A general survey of the actual knowledges on the bone phosphatase is given. The enzyme plays an important rôle in the calcification of bone and teeth, this process being unable to proceed at a physiological speed without the participation of a phosphatase. The biological function of the enzyme is thus to accelerate and not to promote the calcification.The knowledge of the mechanism of phosphatase activity in the skeletal organs and of the chemical composition of the bone salt cannot lead to a full understanding of the physiology of ossification. A prominent function in this field is devoted to the proteins of the ground substance of bone and to their evolution. The study of the protein matrix of bone is now the most important subject of work for the biochemistry of ossification.

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Conférence faite le 28 mai 1946 au Hallerianum de l'Université de Berne.     

Hot Jupiters from secular planet-planet interactions

About 25 per cent of 'hot Jupiters' (extrasolar Jovian-mass planets with close-in orbits) are actually orbiting counter to the spin direction of the star. Perturbations from a distant binary star companion can produce high inclinations, but cannot explain orbits that are retrograde with respect to the total angular momentum of the system. Such orbits in a stellar context can be produced through secular (that is, long term) perturbations in hierarchical triple-star systems. Here we report a similar analysis of planetary bodies, including both octupole-order effects and tidal friction, and find that we can produce hot Jupiters in orbits that are retrograde with respect to the total angular momentum. With distant stellar mass perturbers, such an outcome is not possible. With planetary perturbers, the inner orbit's angular momentum component parallel to the total angular momentum need not be constant. In fact, as we show here, it can even change sign, leading to a retrograde orbit. A brief excursion to very high eccentricity during the chaotic evolution of the inner orbit allows planet-star tidal interactions to rapidly circularize that orbit, decoupling the planets and forming a retrograde hot Jupiter.     

A transient placental source of serotonin for the fetal forebrain

Serotonin (5-hydroxytryptamine or 5-HT) is thought to regulate neurodevelopmental processes through maternal-fetal interactions that have long-term mental health implications. It is thought that beyond fetal 5-HT neurons there are significant maternal contributions to fetal 5-HT during pregnancy but this has not been tested empirically. To examine putative central and peripheral sources of embryonic brain 5-HT, we used Pet1(-/-) (also called Fev) mice in which most dorsal raphe neurons lack 5-HT. We detected previously unknown differences in accumulation of 5-HT between the forebrain and hindbrain during early and late fetal stages, through an exogenous source of 5-HT which is not of maternal origin. Using additional genetic strategies, a new technology for studying placental biology ex vivo and direct manipulation of placental neosynthesis, we investigated the nature of this exogenous source. We uncovered a placental 5-HT synthetic pathway from a maternal tryptophan precursor in both mice and humans. This study reveals a new, direct role for placental metabolic pathways in modulating fetal brain development and indicates that maternal-placental-fetal interactions could underlie the pronounced impact of 5-HT on long-lasting mental health outcomes.