In vitro evidence for senescent multinucleated melanocytes as a source for tumor-initiating cells

Oncogenic signaling in melanocytes results in oncogene-induced senescence (OIS), a stable cell-cycle arrest frequently characterized by a bi- or multinuclear phenotype that is considered as a barrier to cancer progression. However, the long-sustained conviction that senescence is a truly irreversible process has recently been challenged. Still, it is not known whether cells driven into OIS can progress to cancer and thereby pose a potential threat. Here, we show that prolonged expression of the melanoma oncogene N-RAS61K in pigment cells overcomes OIS by triggering the emergence of tumor-initiating mononucleated stem-like cells from senescent cells. This progeny is dedifferentiated, highly proliferative, anoikis-resistant and induces fast growing, metastatic tumors. Our data describe that differentiated cells, which are driven into senescence by an oncogene, use this senescence state as trigger for tumor transformation, giving rise to highly aggressive tumor-initiating cells. These observations provide the first experimental in vitro evidence for the evasion of OIS on the cellular level and ensuing transformation

Resource theory of quantum uncomplexity

Quantum complexity is emerging as a key property of many-body systems, including black holes, topological materials, and early quantum computers. A state's complexity quantifies the number of computational gates required to prepare the state from a simple tensor product. The greater a state's distance from maximal complexity, or “uncomplexity,” the more useful the state is as input to a quantum computation. Separately, resource theories—simple models for agents subject to constraints—are burgeoning in quantum information theory. We unite the two domains, confirming Brown and Susskind's conjecture that a resource theory of uncomplexity can be defined. The allowed operations, fuzzy operations, are slightly random implementations of two-qubit gates chosen by an agent. We formalize two operational tasks, uncomplexity extraction and expenditure. Their optimal efficiencies depend on an entropy that we engineer to reflect complexity. We also present two monotones, uncomplexity measures that decline monotonically under fuzzy operations, in certain regimes. This work unleashes on many-body complexity the resource-theory toolkit from quantum information theory

Characterization of Testing Locations for Developing Cool-Season Grass Species

The identification of best testing locations facilitates the allocation of resources in a breeding program, allowing emphasis to be placed at the sites best suited for identifying superior plant materials for the target environment. The objective of this study was the identification of best locations for the evaluation and testing of cool-season grass species within the Northern Great Plains and Intermountain regions of the USA. This study also sought to subdivide the locations into meaningful environmental groupings based on similar entry performance. The study characterized initial stand frequency and forage production (over a 3-yr period) of crested wheatgrass [Agropyron cristatum (L.) Gaertn.; A. desertorum (Fisch. ex Link) Schultes; A. fragile (Roth) Candargy], intermediate wheatgrass [Thinopyrum intermedium (Host) Barkworth & D.R. Dewey], and smooth bromegrass (Bromus inermis Leyss.) at six locations within these regions. Results suggested the existence of best testing locations and environmental groupings for each of the species. For example, the Ithaca, NE, location was consistently a good location for testing forage production. Although there were some consistencies, generally, the best testing locations and environmental groupings were species and trait specific. Thus, the targeted use of locations appeared to be most useful on an individual species basis, rather than considered across the cool-season grass species

EDITH - experimental in-torus maintenance system for fusion reactors. Final report

Experimentelles Handhabungssystem für Wartungsarbeiten im Torus eines Fusionsreaktors Wegen der besonderen Umgebungsbedingungen - erhöhte -Strahlung und Temperatur - können Reparaturarbeiten in der Plasmakammer eines Fusionsreaktors wie NET/ITER nur mittels eines fernbedienten Handhabungssystems durchgeführt werden. EDITH (Experimental Device for In-Torus Handling) ist der Prototyp eines solchen Systems. Es basiert auf einem Vielgelenkarm, der für die jeweiligen Aufgaben mit verschiedenen Endeffektoren bzw. Werkzeugen ausgerüstet ist. EDITH ist die zentrale Komponente eines Teststandes, mit dem in Originalgröße in einem nachgebildeten Ausschnitt einer Plasmakammer Fernhantierungsvorgänge experimentell untersucht werden. Exemplarisch für solche Aufgaben wurde der fernbediente Austausch von Schutzziegeln und Divertorplatten durchgeführt. Um den Operateuren eine schnelle und zuverlässige Durchführung der Arbeiten zu ermöglichen, wurde ein neuartiges Leit- und Steuersystem entwickelt. Das Leitsystem bildet in Form einer Fernhandhabungs-Arbeitsstation zusammen mit den Servomanipulatoren die Mensch-Maschine-Schnittstelle zur Steuerung und Überwachung aller Geräte. Die Arbeitsstation unterstützt die Operateure bei allen manuell zu steuernden Arbeiten, bei der Planung, Simulation und Programmierung automatisch durchzuführender Teilaufgaben und dient mit ihrem multimedialen Dokumentationssystem als ständig verfügbare Informationsquelle. Bei der Konzeption der Steuerung standen das dynamische Verhalten, die Betriebssicherheit und die Kopplung an das Leitsystem im Vordergrund. Qualifikationstests und erste Experimentiererfahrungen bestätigten, daß mit der bei FZK entwickelten Fernhantierungstechnik die gestellten Aufgaben sicher, zuverlässig und in vertretbarer Zeit ausgeführt werden können

Multiple origins of hydrogenosomes:functional and phylogenetic evidence from the ADP/ATP carrier of the anaerobic chytrid Neocallimastix sp.

A mitochondrial-type ADP/ATP carrier (AAC) has been identified in the hydrogenosomes of the anaerobic chytridiomycete fungus Neocallimastix sp. L2. Biochemical and immunocytochemical studies revealed that this ADP/ATP carrier is an integral component of hydrogenosomal membranes. Expression of the corresponding cDNA in Escherichia coli confers the ability on the bacterial host to incorporate ADP at significantly higher rates than ATP - similar to isolated mitochondria of yeast and animals. Phylogenetic analysis of this AAC gene (hdgaac ) confirmed with high statistical support that the hydrogenosomal ADP/ATP carrier of Neocallimastix sp. L2 belongs to the family of veritable mitochondrial-type AACs. Hydrogenosome-bearing anaerobic ciliates possess clearly distinct mitochondrial-type AACs, whereas the potential hydrogenosomal carrier Hmp31 of the anaerobic flagellate Trichomonas vaginalis and its homologue from Trichomonas gallinae do not belong to this family of proteins. Also, phylogenetic analysis of genes encoding mitochondrial-type chaperonin 60 proteins (HSP 60) supports the conclusion that the hydrogenosomes of anaerobic chytrids and anaerobic ciliates had independent origins, although both of them arose from mitochondria

Immersive multi-user decision training games with ARLearn

Serious gaming approaches so far focus mainly on skill development, motivational aspects or providing immersive learning situations. Little work has been reported to foster awareness and decision competencies in complex deci-sion situations involving incomplete information and multiple stakeholders. We address this issue exploring the technical requirements and possibilities to de-sign games for such situations in three case studies: a hostage taking situation, a multi-stakeholder logistics case, and a health-care related emergency case. To implement the games, we use a multi-user enabled mobile game development platform (ARLearn). We describe the underlying real world situations and edu-cational challenges and analyse how these are reflected in the ARLearn games realized. Based on these cases we propose a way to increase the immersiveness of mobile learning games.SALOM

Cancer-associated cells release citrate to support tumour metastatic progression

Citrate is important for lipid synthesis and epigenetic regulation in addition to ATP production. We have previously reported that cancer cells import extracellular citrate via the pmCiC transporter to support their metabolism. Here, we show for the first time that citrate is supplied to cancer by cancer-associated stroma (CAS) and also that citrate synthesis and release is one of the latter’s major metabolic tasks. Citrate release from CAS is controlled by cancer cells through cross-cellular communication. The availability of citrate from CAS regulated the cytokine profile, metabolism and features of cellular invasion. Moreover, citrate released by CAS is involved in inducing cancer progression especially enhancing invasiveness and organ colonisation. In line with the in vitro observations, we show that depriving cancer cells of citrate using gluconate, a specific inhibitor of pmCiC, significantly reduced the growth and metastatic spread of human pancreatic cancer cells in vivo and muted stromal activation and angiogenesis. We conclude that citrate is supplied to tumour cells by CAS and citrate uptake plays a significant role in cancer metastatic progression