Jean Méry (1645–1722) and his ideas on the foetal blood flow

We present an analysis, and first full English translation, of a paper by Kant entitled ‘Über die Vulcane im Monde’ (1785). Kant became interested in the question of whether the mountains of the Moon were extinct volcanoes. Stimulated by the work of Herschel, Aepinus, and others, he considered the appearance of the Moon's surface and the possibility of lunar vulcanism. From this, he was led to consider the structures of mountain ranges on the Earth, which he decided were non-volcanic in origin, being produced by eruptions of vapours from the interior of the Earth soon after it formed from an original ‘chaos’. Kant developed his ideas in such a way as to yield a characteristic eighteenth-century ‘theory of the Earth’. We argue that the empirical base of his theory was provided by knowledge of the mountain ranges of Bohemia and Moravia. Analogies based on observations of the Moon further assisted in the construction of the theory. But the reasoning ran in two directions: what was seen on the Moon was construed in terms of what Kant knew of the Earth's topography; and the Earth's topography was presumed to be analogous to that of the Moon, for both the Earth and the Moon (and indeed all heavenly bodies) supposedly had essentially similar origins. Kant's ideas of 1785 are related to his earlier writings of 1754, 1755, and 1756, and also to the lectures on physical geography that he presented at Königsberg.     

A bibliographical study of the introduction of Lavoisier's Traité élémentaire de chimie into Great Britain and America

As the most famous woman scientist of the twentieth century, there has been no shortage of books and articles on the life and career of Marie Curie (1867–1934). Her role as a director of a laboratory-based research school in the new scientific field of radioactivity, a field which embraced both chemistry and physics, however, has never been examined. In recent years, there has been a growing interest in the question of research schools, and Morrell, Ravetz, Geison, and Klosterman, amongst others, have written on this subject. Using, in part, the methodology of Morrell, this paper investigates the role of Marie Curie as a school director in the Paris Faculty in the years 1907–14, examining the work and characteristics of her school and assessing her effectiveness as a director.     

The unconventional secretion of stress-inducible protein 1 by a heterogeneous population of extracellular vesicles

The co-chaperone stress-inducible protein 1 (STI1) is released by astrocytes, and has important neurotrophic properties upon binding to prion protein (PrP^C). However, STI1 lacks a signal peptide and pharmacological approaches pointed that it does not follow a classical secretion mechanism. Ultracentrifugation, size exclusion chromatography, electron microscopy, vesicle labeling, and particle tracking analysis were used to identify three major types of extracellular vesicles (EVs) released from astrocytes with sizes ranging from 20–50, 100–200, and 300–400 nm. These EVs carry STI1 and present many exosomal markers, even though only a subpopulation had the typical exosomal morphology. The only protein, from those evaluated here, present exclusively in vesicles that have exosomal morphology was PrP^C. STI1 partially co-localized with Rab5 and Rab7 in endosomal compartments, and a dominant-negative for vacuolar protein sorting 4A (VPS4A), required for formation of multivesicular bodies (MVBs), impaired EV and STI1 release. Flow cytometry and PK digestion demonstrated that STI1 localized to the outer leaflet of EVs, and its association with EVs greatly increased STI1 activity upon PrP^C-dependent neuronal signaling. These results indicate that astrocytes secrete a diverse population of EVs derived from MVBs that contain STI1 and suggest that the interaction between EVs and neuronal surface components enhances STI1–PrP^C signaling.     

Cell-penetrating peptide secures an efficient endosomal escape of an intact cargo upon a brief photo-induction

Since their discovery, cell-penetrating peptides (CPPs) have provided a novel, efficient, and non-invasive mode of transport for various (bioactive) cargos into cells. Despite the ever-growing number of successful implications of the CPP-mediated delivery, issues concerning their intracellular trafficking, significant targeting to degradative organelles, and limited endosomal escape are still hindering their widespread use. To overcome these obstacles, we have utilized a potent photo-induction technique with a fluorescently labeled protein cargo attached to an efficient CPP, TP10. In this study we have determined some key requirements behind this induced escape (e.g., dependence on peptide-to-cargo ratio, time and cargo), and have semi-quantitatively assessed the characteristics of the endosomes that become leaky upon this treatment. Furthermore, we provide evidence that the photo-released cargo remains intact and functional. Altogether, we can conclude that the photo-induced endosomes are specific large complexes-condensed non-acidic vesicles, where the released cargo remains in its native intact form. The latter was confirmed with tubulin as the cargo, which upon photo-induction was incorporated into microtubules. Because of this, we propose that combining the CPP-mediated delivery with photo-activation technique could provide a simple method for overcoming major limitations faced today and serve as a basis for enhanced delivery efficiency and a subsequent elevated cellular response of different bioactive cargo molecules.     

Dynamic Latent Class Model Averaging for Online Prediction

We consider the problem of online prediction when it is uncertain what the best prediction model to use is. We develop a method called dynamic latent class model averaging, which combines a state‐space model for the parameters of each of the candidate models of the system with a Markov chain model for the best model. We propose a polychotomous regression model for the transition weights to assume that the probability of a change in time depends on the past through the values of the most recent time periods and spatial correlation among the regions. The evolution of the parameters in each submodel is defined by exponential forgetting. This structure allows the ‘correct’ model to vary over both time and regions. In contrast to existing methods, the proposed model naturally incorporates clustering and prediction analysis in a single unified framework. We develop an efficient Gibbs algorithm for computation, and we demonstrate the value of our framework on simulated experiments and on a real‐world problem: forecasting IBM's corporate revenue. Copyright © 2014 John Wiley & Sons, Ltd.     

Mechanisms of cellular invasion by intracellular parasites

Numerous disease-causing parasites must invade host cells in order to prosper. Collectively, such pathogens are responsible for a staggering amount of human sickness and death throughout the world. Leishmaniasis, Chagas disease, toxoplasmosis, and malaria are neglected diseases and therefore are linked to socio-economical and geographical factors, affecting well-over half the world’s population. Such obligate intracellular parasites have co-evolved with humans to establish a complexity of specific molecular parasite–host cell interactions, forming the basis of the parasite’s cellular tropism. They make use of such interactions to invade host cells as a means to migrate through various tissues, to evade the host immune system, and to undergo intracellular replication. These cellular migration and invasion events are absolutely essential for the completion of the lifecycles of these parasites and lead to their for disease pathogenesis. This review is an overview of the molecular mechanisms of protozoan parasite invasion of host cells and discussion of therapeutic strategies, which could be developed by targeting these invasion pathways. Specifically, we focus on four species of protozoan parasites Leishmania, Trypanosoma cruzi, Plasmodium, and Toxoplasma, which are responsible for significant morbidity and mortality.     

Light-dependent phosphorylation of the carboxy tail of mouse melanopsin

Melanopsin-based phototransduction is involved in non-image forming light responses including circadian entrainment, pupil constriction, suppression of pineal melatonin synthesis, and direct photic regulation of sleep in vertebrates. Given that the functions of melanopsin involve the measurement and summation of total environmental luminance, there would appear to be no need for the rapid deactivation typical of other G-protein coupled receptors. In this study, however, we demonstrate that heterologously expressed mouse melanopsin is phosphorylated in a light-dependent manner, and that this phosphorylation is involved in regulating the rate of G-protein activation and the lifetime of melanopsin’s active state. Furthermore, we provide evidence for light-dependent phosphorylation of melanopsin in the mouse retina using an in situ proximity ligation assay. Finally, we demonstrate that melanopsin preferentially interacts with the GRK2/3 family of G-protein coupled receptor kinases through co-immunoprecipitation assays. Based on the complement of G-protein receptor kinases present in the melanopsin-expressing retinal ganglion cells, GRK2 emerges as the best candidate for melanopsin’s cognate GRK.     

Spectrin-based skeleton as an actor in cell signaling

This review focuses on the recent advances in functions of spectrins in non-erythroid cells. We discuss new data concerning the commonly known role of the spectrin-based skeleton in control of membrane organization, stability and shape, and tethering protein mosaics to the cellular motors and to all major filament systems. Particular effort has been undertaken to highlight recent advances linking spectrin to cell signaling phenomena and its participation in signal transduction pathways in many cell types.