Growth differentiation factor 11 signals through the transforming growth factor-beta receptor ALK5 to regionalize the anterior-posterior axis

Growth differentiation factor 11 (GDF11) contributes to regionalize the mouse embryo along its anterior-posterior axis by regulating the expression of Hox genes. The identity of the receptors that mediate GDF11 signalling during embryogenesis remains unclear. Here, we show that GDF11 can interact with type I receptors ALK4, ALK5 and ALK7, but predominantly uses ALK4 and ALK5 to activate a Smad3-dependent reporter gene. Alk5 mutant embryos showed malformations in anterior-posterior patterning, including the lack of expression of the posterior determinant Hoxc10, that resemble defects found in Gdf11-null mutants. A heterozygous mutation in Alk5, but not in Alk4 or Alk7, potentiated Gdf11(-/-)-like phenotypes in vertebral, kidney and palate development in an Acvr2b(-/-) background, indicating a genetic interaction between the two receptor genes. Thus, the transforming growth factor-beta (TGF-beta) receptor ALK5, which until now has only been associated with the biological functions of TGF-beta1 to TGF-beta3 proteins, mediates GDF11 signalling during embryogenesis.     

DNPTrapper: an assembly editing tool for finishing and analysis of complex repeat regions

Background  

Many genome projects are left unfinished due to complex, repeated regions. Finishing is the most time consuming step in sequencing and current finishing tools are not designed with particular attention to the repeat problem.     

Altered expression of key cellular gene products accompanies development of resistance to nitric oxide

NALM-6 is a pre-B leukemia cell line sensitive to exogenous nitric oxide (NO), which enters into apoptosis during 24 h of exposure to low doses of the NO donors SNAP (100 microM) or DETA-NO (250 microM). By culturing NALM-6 with repeated and increasing concentrations of SNAP, we obtained a variant (NALM-6R) that retains >95% viability and does not enter into apoptosis during 24 h culture in the presence of up to 500 microM SNAP or 750 microM DETA-NO. A power blot screen performed with 277 antibodies on cell lysates from NALM-6 and NALM-6R cultured without NO donors served to determine the altered constitutive expression of 19 proteins in NALM-6R. Proteins affected in the less sensitive cell line NALM6-R are involved in the regulation of apoptosis, the cell cycle, cell interactions, signal transduction, cell morphology, and cell motility. This model shows that repeated exposure of tumor cells to NO may either select NO-resistant cells or contribute to NO-sensitive conversion into NO-resistant cells. The identification of the proteins that are affected during this transition may help us to define the mechanisms that are involved in cell resistance to NO-cytotoxicity which often accompany clinical progression.     

Does immune function influence population fluctuations and level of parasitism in the cyclic geometrid moth?

Populations of the autumnal moth, Epirrita autumnata, exhibit cycles with high amplitudes in northernmost Europe, culminating in devastating outbreak densities at favourable sites. Parasitism by hymenopteran parasitoids has been hypothesised to operate with a delayed density dependence capable of producing the observed dynamics. It has also been hypothesised that insects in crowded conditions invest greatly in their immunity as a counter-measure to increased risk of parasitism and pathogen infections. Furthermore, inducible plant defences consequent to grazing by herbivorous insects may be linked to the performance of parasitoids and pathogens through increased immunocompetence of the herbivore feeding on the foliage, in which the defence induction has taken place. At ten sampling sites, we quantified larval abundance, outbreak status and percentage larval parasitism during an extended peak phase of a population cycle. These population level covariates, together with an individual pupal mass, were used to explain differences in the immune defence, measured as an encapsulation reaction to artificial antigen. We also conducted a field study for an investigation of the susceptibility of autumnal moth pupae to naturally occurring pupal parasitoids. We did not find obvious differences between the encapsulation rate of autumnal moths originating from the sites with different past and current larval densities and risks for parasitism. The best ranked statistical models included pupal mass and outbreak status as explanatory variables, although both showed only slight effects on the encapsulation rate. The host resistance test revealed positive relationships between the encapsulation rate, body size and percentage parasitism of the exposed pupae, indicating that pupal parasitoids chose, and/or survived better, in large host individuals irrespective of their encapsulation ability. Thus, our results do not provide support for the hypothesis that variation in the immune function drives or modulates population cycles of autumnal moths. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Social Transfer of Predation Risk Information Reduces Food Locating Ability in European Minnows (Phoxinus phoxinus)

Little is known about how food location ability of animals is affected by social information of predation risk. This question was therefore addressed in an experimental study where naïve ‘observer’ European minnows (Phoxinus phoxinus) were allowed to search for food in a maze in the presence or absence of a predator (Salmo trutta). Observer minnows were accompanied by conspecific demonstrators which had previously been trained in the same maze either in the presence or absence of the predator. Observer minnows were most likely to locate food when the predator was absent both during their trial and during the pre‐training of demonstrators. When demonstrators had been trained with predators, observer success in locating the food was halved, although they were never exposed to predation risk themselves. When observers were exposed to predation risk their probability of locating food was further reduced regardless of the experience of their demonstrators. Our results show that predation risk can affect the foraging ability of minnows both directly and indirectly through social information from conspecifics. We conclude that social information may influence and constrain individual behavioural decisions, especially in rapidly changing environments where private information is often insufficient.     

Motif Yggdrasil: sampling sequence motifs from a tree mixture model.

In phylogenetic foot-printing, putative regulatory elements are found in upstream regions of orthologous genes by searching for common motifs. Motifs in different upstream sequences are subject to mutations along the edges of the corresponding phylogenetic tree, consequently taking advantage of the tree in the motif search is an appealing idea. We describe the Motif Yggdrasil sampler; the first Gibbs sampler based on a general tree that uses unaligned sequences. Previous tree-based Gibbs samplers have assumed a star-shaped tree or partially aligned upstream regions. We give a probabilistic model (MY model) describing upstream sequences with regulatory elements and build a Gibbs sampler with respect to this model. The model allows toggling, i.e., the restriction of a position to a subset of nucleotides, but does not require aligned sequences nor edge lengths, which may be difficult to come by. We apply the collapsing technique to eliminate the need to sample nuisance parameters, and give a derivation of the predictive update formula. We show that the MY model improves the modeling of difficult motif instances and that the use of the tree achieves a substantial increase in nucleotide level correlation coefficient both for synthetic data and 37 bacterial lexA genes. We investigate the sensitivity to errors in the tree and show that using random trees MY sampler still has a performance similar to the original version.     

Experimental adaptation of Salmonella typhimurium to mice

Experimental evolution is a powerful approach to study the dynamics and mechanisms of bacterial niche specialization. By serial passage in mice, we evolved 18 independent lineages of Salmonella typhimurium LT2 and examined the rate and extent of adaptation to a mainly reticuloendothelial host environment. Bacterial mutation rates and population sizes were varied by using wild-type and DNA repair-defective mutator (mutS) strains with normal and high mutation rates, respectively, and by varying the number of bacteria intraperitoneally injected into mice. After <200 generations of adaptation all lineages showed an increased fitness as measured by a faster growth rate in mice (selection coefficients 0.11-0.58). Using a generally applicable mathematical model we calculated the adaptive mutation rate for the wild-type bacterium to be >10(-6)/cell/generation, suggesting that the majority of adaptive mutations are not simple point mutations. For the mutator lineages, adaptation to mice was associated with a loss of fitness in secondary environments as seen by a reduced metabolic capability. During adaptation there was no indication that a high mutation rate was counterselected. These data show that S. typhimurium can rapidly and extensively increase its fitness in mice but this niche specialization is, at least in mutators, associated with a cost.