Crystal structure of triple-BRCT-domain of ECT2 and insights into the binding characteristics to CYK-4

Homo sapiens ECT2 is a cell cycle regulator that plays critical roles in cytokinesis. ECT2 activity is restrained during interphase via intra-molecular interactions that involve its N-terminal triple-BRCT-domain and its C-terminal DH–PH domain. At anaphase, this self-inhibitory mechanism is relieved by Plk1-phosphorylated CYK-4, which directly engages the ECT2 BRCT domain. To provide a structural perspective for this auto-inhibitory property, we solved the crystal structure of the ECT2 triple-BRCT-domain. In addition, we systematically analyzed the interaction between the ECT2 BRCT domains with phospho-peptides derived from its binding partner CYK-4, and have identified Ser164 as the major phospho-residue that links CYK-4 to the second ECT2 BRCT domain.     

The effect of walking speed on local dynamic stability is sensitive to calculation methods

Local dynamic stability has been assessed by the short-term local divergence exponent (λ_S), which quantifies the average rate of logarithmic divergence of infinitesimally close trajectories in state space. Both increased and decreased local dynamic stability at faster walking speeds have been reported. This might pertain to methodological differences in calculating λ_S. Therefore, the aim was to test if different calculation methods would induce different effects of walking speed on local dynamic stability. Ten young healthy participants walked on a treadmill at five speeds (60%, 80%, 100%, 120% and 140% of preferred walking speed) for 3 min each, while upper body accelerations in three directions were sampled. From these time-series, λ_S was calculated by three different methods using: (a) a fixed time interval and expressed as logarithmic divergence per stride-time (λ_S−a), (b) a fixed number of strides and expressed as logarithmic divergence per time (λ_S−b) and (c) a fixed number of strides and expressed as logarithmic divergence per stride-time (λ_S−c). Mean preferred walking speed was 1.16±0.09 m/s. There was only a minor effect of walking speed on λ_S−a. λ_S−b increased with increasing walking speed indicating decreased local dynamic stability at faster walking speeds, whereas λ_S−c decreased with increasing walking speed indicating increased local dynamic stability at faster walking speeds. Thus, the effect of walking speed on calculated local dynamic stability was significantly different between methods used to calculate local dynamic stability. Therefore, inferences and comparisons of studies employing λ_S should be made with careful consideration of the calculation method.     

Co‐regulation proteomics reveals substrates and mechanisms of APC/C‐dependent degradation

Using multiplexed quantitative proteomics, we analyzed cell cycle‐dependent changes of the human proteome. We identified >4,400 proteins, each with a six‐point abundance profile across the cell cycle. Hypothesizing that proteins with similar abundance profiles are co‐regulated, we clustered the proteins with abundance profiles most similar to known Anaphase‐Promoting Complex/Cyclosome (APC/C) substrates to identify additional putative APC/C substrates. This protein profile similarity screening (PPSS) analysis resulted in a shortlist enriched in kinases and kinesins. Biochemical studies on the kinesins confirmed KIFC1, KIF18A, KIF2C, and KIF4A as APC/C substrates. Furthermore, we showed that the APC/C^CDH1‐dependent degradation of KIFC1 regulates the bipolar spindle formation and proper cell division. A targeted quantitative proteomics experiment showed that KIFC1 degradation is modulated by a stabilizing CDK1‐dependent phosphorylation site within the degradation motif of KIFC1. The regulation of KIFC1 (de‐)phosphorylation and degradation provides insights into the fidelity and proper ordering of substrate degradation by the APC/C during mitosis.     

Pain assessment in animal models of osteoarthritis

Assessment of pain in animal models of osteoarthritis is integral to interpretation of a model's utility in representing the clinical condition, and enabling accurate translational medicine. Here we describe behavioral pain assessments available for small and large experimental osteoarthritic pain animal models.     

Feeding and intoxication–detoxification dynamics in two populations of the mussel Mytilus chilensis (Hupé, 1854) with different histories of exposure to paralytic shellfish poisoning (PSP)

Individuals of Mytilus chilensis with different histories of exposure to paralytic shellfish poisoning (PSP) were exposed to a diet containing the dinoflagellate Alexandrium catenella. Feeding and intoxication–detoxification dynamics were evaluated over a period of 12–16?days. Feeding activity was reduced during the first days of exposure, followed by a period of recovery from day 5 to the end of the experiment. Mussels from Corral population (no history of PSP exposure) exceeded the concentration of 80?μg STX eq. 100?g^?1 tissue, although filtration activity was significantly lower compared with individuals from Melinka (frequent PSP exposure). The higher feeding activity and the lower degree of toxin accumulation in the Melinka population appear be associated with frequent exposure to PSP in the natural environment. The use of A. catenella as food resource and the capacity of a rapid intoxication of both populations showed that M. chilensis is an adequate indicator for early detection of PSP.     

Bet hedging in desert winter annual plants: optimal germination strategies in a variable environment

In bet hedging, organisms sacrifice short‐term success to reduce the long‐term variance in success. Delayed germination is the classic example of bet hedging, in which a fraction of seeds remain dormant as a hedge against the risk of complete reproductive failure. Here, we investigate the adaptive nature of delayed germination as a bet hedging strategy using long‐term demographic data on Sonoran Desert winter annual plants. Using stochastic population models, we estimate fitness as a function of delayed germination and identify evolutionarily stable strategies for 12 abundant species in the community. Results indicate that delayed germination meets the criteria as a bet hedging strategy for all species. Density‐dependent models, but not density‐independent ones, predicted optimal germination strategies that correspond remarkably well with observed patterns. By incorporating naturally occurring variation in seed and seedling dynamics, our results present a rigorous test of bet hedging theory within the relevant environmental context.     

The cryptic role of biodiversity in the emergence of host–microbial mutualisms

The persistence of mutualisms in host‐microbial – or holobiont – systems is difficult to explain because microbial mutualists, who bear the costs of providing benefits to their host, are always prone to being competitively displaced by non‐mutualist ‘cheater’ species. This disruptive effect of competition is expected to be particularly strong when the benefits provided by the mutualists entail costs such as reduced competitive ability. Using a metacommunity model, we show that competition between multiple cheaters within the host's microbiome, when combined with the spatial structure of host–microbial interactions, can have a constructive rather than a disruptive effect by allowing the emergence and maintenance of mutualistic microorganisms within the host. These results indicate that many of the microorganisms inhabiting a host's microbiome, including those that would otherwise be considered opportunistic or even potential pathogens, play a cryptic yet critical role in promoting the health and persistence of the holobiont across spatial scales.     

ReformAlign: improved multiple sequence alignments using a profile-based meta-alignment approach

Background

Obtaining an accurate sequence alignment is fundamental for consistently analyzing biological data. Although this problem may be efficiently solved when only two sequences are considered, the exact inference of the optimal alignment easily gets computationally intractable for the multiple sequence alignment case. To cope with the high computational expenses, approximate heuristic methods have been proposed that address the problem indirectly by progressively aligning the sequences in pairs according to their relatedness. These methods however are not flexible to change the alignment of an already aligned group of sequences in the view of new data, resulting thus in compromises on the quality of the deriving alignment. In this paper we present ReformAlign, a novel meta-alignment approach that may significantly improve on the quality of the deriving alignments from popular aligners. We call ReformAlign a meta-aligner as it requires an initial alignment, for which a variety of alignment programs can be used. The main idea behind ReformAlign is quite straightforward: at first, an existing alignment is used to construct a standard profile which summarizes the initial alignment and then all sequences are individually re-aligned against the formed profile. From each sequence-profile comparison, the alignment of each sequence against the profile is recorded and the final alignment is indirectly inferred by merging all the individual sub-alignments into a unified set. The employment of ReformAlign may often result in alignments which are significantly more accurate than the starting alignments.

Results

We evaluated the effect of ReformAlign on the generated alignments from ten leading alignment methods using real data of variable size and sequence identity. The experimental results suggest that the proposed meta-aligner approach may often lead to statistically significant more accurate alignments. Furthermore, we show that ReformAlign results in more substantial improvement in cases where the starting alignment is of relatively inferior quality or when the input sequences are harder to align.

Conclusions

The proposed profile-based meta-alignment approach seems to be a promising and computationally efficient method that can be combined with practically all popular alignment methods and may lead to significant improvements in the generated alignments.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2105-15-265) contains supplementary material, which is available to authorized users.