Photodynamic therapy with redaporfin targets the endoplasmic reticulum and Golgi apparatus

Preclinical evidence depicts the capacity of redaporfin (Redp) to act as potent photosensitizer, causing direct antineoplastic effects as well as indirect immune‐dependent destruction of malignant lesions. Here, we investigated the mechanisms through which photodynamic therapy (PDT) with redaporfin kills cancer cells. Subcellular localization and fractionation studies based on the physicochemical properties of redaporfin revealed its selective tropism for the endoplasmic reticulum (ER) and the Golgi apparatus (GA). When activated, redaporfin caused rapid reactive oxygen species‐dependent perturbation of ER/GA compartments, coupled to ER stress and an inhibition of the GA‐dependent secretory pathway. This led to a general inhibition of protein secretion by PDT‐treated cancer cells. The ER/GA play a role upstream of mitochondria in the lethal signaling pathway triggered by redaporfin‐based PDT. Pharmacological perturbation of GA function or homeostasis reduces mitochondrial permeabilization. In contrast, removal of the pro‐apoptotic multidomain proteins BAX and BAK or pretreatment with protease inhibitors reduced cell killing, yet left the GA perturbation unaffected. Altogether, these results point to the capacity of redaporfin to kill tumor cells via destroying ER/GA function.     

Chronic childhood spinal muscular atrophy in Germany (West-Thüringen) — an epidemiological study

This study presents the most extensive epidemiological data on chronic forms of spinal muscular atrophy in childhood (CSMA) in West-Thüringen in Germany. The incidence of CSMA was calculated to be 1 in 9,420 live births. The prevalence was 1.624 in 100,000 of the general population (as of 31 December 1980).     

FGF treatment of host embryos injected with ES cells increases rates of chimaerism

In spite of the emergence of genome editing tools, ES cell mediated transgenesis remains the most controllable way of creating genetically modified animals. Although tetraploid (4N) complementation of 4N host embryos and ES cells, is the only method guaranteeing that offspring are entirely ES cell derived, this technique is challenging, not always successful and difficult to implement in some laboratory settings. The current study shows that pretreatment of host blastocysts with FGF4 prior to ES cell injection can provide an alternative method for the generation of animals displaying high rates of chimaerism. Chimaerism assessment in E11 fetuses and born pups shows that a large percentage of resulting conceptuses show a high ES cell contribution from implantation onwards and that developing pups do not necessitate c-section for delivery.     

Living in a World of Smart Everyday Objects—Social,Economic, and Ethical Implications

Visions of Pervasive Computing and ambient intelligence involve integrating tiny microelectronic processors and sensors into everyday objects in order to make them “smart.” Smart things can explore their environment, communicate with other smart things, and interact with humans, therefore helping users to cope with their tasks in new, intuitive ways. Although many concepts have already been tested out as prototypes in field trials, the repercussions of such extensive integration of computer technology into our everyday lives are difficult to predict. This article is a first attempt to classify the social, economic, and ethical implications of this development.     

Abiotic synthesis of organic molecules from minerals containing traces of dissolved H2O,CO2 and N2 part I: Basic principles

Oxides and silicates which crystallize in the presence of H₂O, CO₂ and N₂, especially at high pressures, are expected to dissolve traces of these fluid components. In doing so atomic and electronic rearrangements occur between the host lattice and the dissolved molecules which lead to different solute species. These may be simply hydroxyl OH^–, carbonate CO₃ ^2– of similar ions, but other species can also form which are chemically reduced such as molecular H₂, CO₂ ^2– and CO^– or oxidized such as peroxy ions, O₂ ^2–. When the minerals containing such solute species are decompressed and cooled, they eventually become supersaturated with respect to their dissolved impurities. If the relative mobilities of the different solute species are different, diffusion and subsurface segregation lead to spatial separation: the surface and subsurface zone become enriched in the reduced species while the oxidized species remain in the bulk. Upon heating or during chemical dissolution (weathering) the reduced species contained in the surface react leading to the formation of a wide variety of H–C–O–N molecules: not only H₂O, CO₂ and possibly N₂ but also organic molecules. No external reduced atmosphere is needed, according to this hypothesis.     

Morphology of arolia in Auchenorrhyncha (Insecta,Hemiptera)

The pretarsal arolium serves as an attachment device in many groups of insects, enabling them to walk efficiently on smooth surfaces, where claws alone do not provide sufficient foothold. The arolia of representatives of all major lineages of Auchenorrhyncha are described and illustrated, mainly using scanning electron microscopy and histology. Glands inside the lumen of the arolia are described for the first time in this group. It is shown that the morphology of arolia within Auchenorrhyncha differs considerably. Some of them are even distinctly bilobed. The cuticle of the contact zone is thickened and formed of branching chitinous rods. In some cases, two layers of rods oriented in different directions were found. An extended definition of “arolium” is proposed. J. Morphol. 275:1217–1225, 2014. © 2014 Wiley Periodicals, Inc.