Simulated brain tumor growth dynamics using a three-dimensional cellular automaton

We have developed a novel and versatile three-dimensional cellular automaton model of brain tumor growth. We show that macroscopic tumor behavior can be realistically modeled using microscopic parameters. Using only four parameters, this model simulates Gompertzian growth for a tumor growing over nearly three orders of magnitude in radius. It also predicts the composition and dynamics of the tumor at selected time points in agreement with medical literature. We also demonstrate the flexibility of the model by showing the emergence, and eventual dominance, of a second tumor clone with a different genotype. The model incorporates several important and novel features, both in the rules governing the model and in the underlying structure of the model. Among these are a new definition of how to model proliferative and non-proliferative cells, an isotropic lattice, and an adaptive grid lattice.     

Compositions of fungal secretomes indicate a greater impact of phylogenetic history than lifestyle adaptation

Background

Since the first fungal genome sequences became available, investigators have been employing comparative genomics to understand how fungi have evolved to occupy diverse ecological niches. The secretome, i.e. the entirety of all proteins secreted by an organism, is of particular importance, as by these proteins fungi acquire nutrients and communicate with their surroundings.

Results

It is generally assumed that fungi with similar nutritional lifestyles have similar secretome compositions. In this study, we test this hypothesis by annotating and comparing the soluble secretomes, defined as the sets of proteins containing classical signal peptides but lacking transmembrane domains of fungi representing a broad diversity of nutritional lifestyles. Secretome size correlates with phylogeny and to a lesser extent with lifestyle. Plant pathogens and saprophytes have larger secretomes than animal pathogens. Small secreted cysteine-rich proteins (SSCPs), which may comprise many effectors important for the interaction of plant pathogens with their hosts, are defined here to have a mature length of ≤ 300 aa residues, at least four cysteines, and a total cysteine content of ≥5%. SSCPs are found enriched in the secretomes of the Pezizomycotina and Basidiomycota in comparison to Saccharomycotina. Relative SSCP content is noticeably higher in plant pathogens than in animal pathogens, while saprophytes were in between and closer to plant pathogens. Expansions and contractions of gene families and in the number of occurrences of functional domains are largely lineage specific, e.g. contraction of glycoside hydrolases in Saccharomycotina, and are only weakly correlated with lifestyle. However, within a given lifestyle a few general trends exist, such as the expansion of secreted family M14 metallopeptidases and chitin-binding proteins in plant pathogenic Pezizomycotina.

Conclusions

While the secretomes of fungi with similar lifestyles share certain characteristics, the expansion and contraction of gene families is largely lineage specific, and not shared among all fungi of a given lifestyle.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-722) contains supplementary material, which is available to authorized users.     

Future climate‐driven shifts in distribution of Calanus finmarchicus

Calanus finmarchicus is a key‐structural species of the North Atlantic polar biome. The species plays an important trophic role in subpolar and polar ecosystems as a grazer of phytoplankton and as a prey for higher trophic levels such as the larval stages of many fish species. Here, we used a recently developed ecological niche model to assess the ecological niche (sensu Hutchinson) of C. finmarchicus and characterize its spatial distribution. This model explained about 65% of the total variance of the observed spatial distribution inferred from an independent dataset (data of the continuous plankton recorder survey). Comparisons with other types of models (structured population and ecophysiological models) revealed a clear similarity between modeled spatial distributions at the scale of the North Atlantic. Contemporary models coupled with future projections indicated a progressive reduction of the spatial habitat of the species at the southern edge and a more pronounced one in the Georges Bank, the Scotian Shelf and the North Sea and a potential increase in abundance at the northern edge of its spatial distribution, especially in the Barents Sea. These major changes will probably lead to a major alteration of the trophodynamics of North Atlantic ecosystems affecting the trophodynamics and the biological carbon pump.     

The relationship between sea surface temperature and population change of Great Cormorants Phalacrocorax carbo breeding near Disko Bay,Greenland

Arctic seas have warmed and sea ice has retreated. This has resulted in range contraction and population declines in some species, but it could potentially be a boon for others. Great Cormorants Phalacrocorax carbo have a partially wettable plumage and seem poorly suited to foraging in Arctic waters. We show that rates of population change of Cormorant colonies around Disko Bay, Greenland, are positively correlated with sea surface temperature, suggesting that they may benefit from a warming Arctic. However, although Cormorant populations may increase in response to Arctic warming, the extent of expansion of their winter range may ultimately be limited by other factors, such as sensory constraints on foraging behaviour during long Arctic nights.     

Role of the tubulin-microtubule system in lymphocyte activation

The role of the tubulin-microtubule system was examined in human peripheral blood leukocytes after activation with phytohemagglutinin (PHA). Soluble tubulin and microtubules were measured with a [(3)H]colchicine-binding assay. It was found that the tubulin content of PHA-activated lymphocytes was consistently increased relative to total protein content after 36 h of culture. There was no increase in the proportion of total tubulin synthesis which was present as microtubules at 36 h. Nevertheless, as a result of increased tubulin synthesis, there was a two-to three-fold increase in total microtubular mass. Colchicine, which disrupts microtubles, was used to assess the role of microtubule assembly in the sequence of events which follow lymphocyte activation, namely lymphokine release, protein synthesis, RNA synthesis, and DNA synthesis. Colchicine consistently inhibited DNA synthesis but did not inhibit release of the lymphokine, osteoclast activating factor (OAF). Protein and RNA syntheses were inhibited much less than DNA synthesis. The fact that some effects of PHA on lymphocytes appear to require intact microtubules and at least one does not suggest that the microtubule dependent step in PHA-stimulated lymphocyte activation occurs at a stage after propagation of the signal from the membrane to the cell interior.     

Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by Delta

Lateral inhibition, mediated by Notch signaling, leads to the selection of cells that are permitted to become neurons within domains defined by proneural gene expression. Reduced lateral inhibition in zebrafish mib mutant embryos permits too many neural progenitors to differentiate as neurons. Positional cloning of mib revealed that it is a gene in the Notch pathway that encodes a RING ubiquitin ligase. Mib interacts with the intracellular domain of Delta to promote its ubiquitylation and internalization. Cell transplantation studies suggest that mib function is essential in the signaling cell for efficient activation of Notch in neighboring cells. These observations support a model for Notch activation where the Delta-Notch interaction is followed by endocytosis of Delta and transendocytosis of the Notch extracellular domain by the signaling cell. This facilitates intramembranous cleavage of the remaining Notch receptor, release of the Notch intracellular fragment, and activation of target genes in neighboring cells.     

Water flow drives biodiversity by mediating rarity in marine benthic communities

In aquatic ecosystems, water flow mediates the delivery of reproductive propagules, competition and predation, each of which may have contrasting effects on biodiversity. Here, we show that water flow has a net positive effect on the biodiversity of benthic invertebrate communities in three biogeographic regions. In Palau and Alaska, flow velocity predicted 55-91% of the variance in species richness in natural communities. In experimental communities in Alaska and Maine, enhanced water flow treatments resulted in higher levels of species density (+56%) and richness (+74%), which were predicted by the abundance of locally rare species. Additionally, the richness of recruitment was higher in experimentally enhanced flows (+46%). Thus, the data suggest that flow drives diversity by mediating the delivery of rare species in multiple biogeographic regions. Consequently, flow velocity should be included in future developments of diversity theory and conservation strategy.     

A revision of Aceratherium blanfordi Lydekker, 1884 (Mammalia: Rhinocerotidae) from the Early Miocene of Pakistan: postcranials as a key

Rhinocerotids are particularly abundant and diversified in Neogene deposits of the Indian subcontinent, but their systematics is far from being well defined. Based on the revision of old collections and new findings from the Early Miocene of the Bugti Hills and Zinda Pir, Pakistan, ‘Aceratherium blanfordi Lydekker, 1884’ is a chimera, consisting of two dentally convergent but postcranially distinct rhinocerotid taxa: Pleuroceros blanfordi and Mesaceratherium welcommi sp. nov. Postcranial features appear to be much more diagnostic than craniodental morphology in this case. A phylogenetic analysis based on 282 morphological characters scored for 28 taxa (four outgroups and ingroup including both taxa of interest and a ‘branching group’) strengthens this statement and supports Pleuroceros and Mesaceratherium as monophyletic genera within Rhinocerotinae. Both genera are recognized for the first time outside Europe. In the Bugti Hills, P. blanfordi and M. welcommi are part of an exceptionally diversified rhinocerotid fauna, with up to nine species associated in the same locality (Kumbi 4f). This rhinocerotid assemblage confirms the earliest Miocene age (Agenian/Aquitanian) of the upper member of the Chitarwata Formation as a whole. Coeval homotaxic rhinocerotid faunas from Europe (France, Czech Republic) and East Africa (Uganda, Kenya) support broad and sustainable rhinocerotid interchanges amongst South Asia, Europe, and Africa under compatible environmental conditions throughout earliest Miocene times. © 2010 The Linnean Society of London, Zoological Journal of the Linnean Society, 2010, 160 , 139–194.