Polymorphism, subtyping, and type inference in MLsub

We present a type system combining subtyping and ML-style parametric polymorphism. Unlike previous work, our system support type inference and has compact principal types. We demonstrate this system in the minimal language MLsub, which types a strict superset of core ML programs. This is made possible by keeping a strict separation between the types used to describe inputs and those used to describe outputs, and extending the classical unification algorithm to handle subtyping constraints between these input and output types. Principal types are kept compact by type simplification, which exploits deep connections between subtyping and the algebra of regular languages. An implementation is available online

Sulfur sequestration promotes multicellularity during nutrient limitation

The behaviour of Dictyostelium discoideum depends on nutrients. When sufficient food is present these amoebae exist in a unicellular state, but upon starvation they aggregate into a multicellular organism. This biology makes D. discoideum an ideal model for investigating how fundamental metabolism commands cell differentiation and function. Here we show that reactive oxygen species-generated as a consequence of nutrient limitation-lead to the sequestration of cysteine in the antioxidant glutathione. This sequestration limits the use of the sulfur atom of cysteine in processes that contribute to mitochondrial metabolism and cellular proliferation, such as protein translation and the activity of enzymes that contain an iron-sulfur cluster. The regulated sequestration of sulfur maintains D. discoideum in a nonproliferating state that paves the way for multicellular development. This mechanism of signalling through reactive oxygen species highlights oxygen and sulfur as simple signalling molecules that dictate cell fate in an early eukaryote, with implications for responses to nutrient fluctuations in multicellular eukaryotes

The avian cell line AGE1.CR.pIX characterized by metabolic flux analysis

Lohr V, Haedicke O, Genzel Y, et al. The avian cell line AGE1.CR.pIX characterized by metabolic flux analysis. BMC Biotechnology. 2014;14(1): 72.Background: In human vaccine manufacturing some pathogens such as Modified Vaccinia Virus Ankara, measles, mumps virus as well as influenza viruses are still produced on primary material derived from embryonated chicken eggs. Processes depending on primary cell culture, however, are difficult to adapt to modern vaccine production. Therefore, we derived previously a continuous suspension cell line, AGE1.CR.pIX, from muscovy duck and established chemically-defined media for virus propagation. Results: To better understand vaccine production processes, we developed a stoichiometric model of the central metabolism of AGE1.CR.pIX cells and applied flux variability and metabolic flux analysis. Results were compared to literature dealing with mammalian and insect cell culture metabolism focusing on the question whether cultured avian cells differ in metabolism. Qualitatively, the observed flux distribution of this avian cell line was similar to distributions found for mammalian cell lines (e.g. CHO, MDCK cells). In particular, glucose was catabolized inefficiently and glycolysis and TCA cycle seem to be only weakly connected. Conclusions: A distinguishing feature of the avian cell line is that glutaminolysis plays only a minor role in energy generation and production of precursors, resulting in low extracellular ammonia concentrations. This metabolic flux study is the first for a continuous avian cell line. It provides a basis for further metabolic analyses to exploit the biotechnological potential of avian and vertebrate cell lines and to develop specific optimized cell culture processes, e.g. vaccine production processes

Denudation rates during a postglacial sequence in Northern Iceland: example of Laxárdalur valley in the Skagafjörður area

International audienceFor several decades, geomorphologists have focused on the functioning of geomorphic systems after deglaciation. The relative importance of paraglacial vs. periglacial processes has been highly debated. At present, the development of dating techniques allows to contribute to this debate. We reconstruct in this paper the geomorphic evolution of Tindastóll mountain slopes in Laxárdalur valley (Skagafjörður area, central northern Iceland), where a chronological framework can be established through tephrochronology and an assemblage of dated raised beaches. Volumetric calculations of constructed and excavated landforms were created from field data and from DEM and geographical information system techniques. Collectively, our data exhibit a first stage of paraglacial landsliding during the first half of the Holocene, followed by a stage of scree and rockglacier development (during the second half of the Holocene, but before 1100 AD). Our estimations indicate that more than 85% of the total sediment production were due to rock slope failure, and the rate of bedrock denudation due to periglacial processes was about one half of the rate of paraglacial processes. Nevertheless, paraglacial and periglacial processes cannot be seen here as antagonistic processes: they are organized in a sequence during which periglacial processes are conditioned (enhancement of bedrock denudation rates) by fracturing and consequent mass wasting. Screes and concomitant rockglaciers were indeed preconditioned by the landslide, while areas non-affected by landslides have remained mostly intact, characterized by a very low rate of accumulation due to geomorphic (periglacial) activity