Analysis of an optimal hidden Markov model for secondary structure prediction

Background  

Secondary structure prediction is a useful first step toward 3D structure prediction. A number of successful secondary structure prediction methods use neural networks, but unfortunately, neural networks are not intuitively interpretable. On the contrary, hidden Markov models are graphical interpretable models. Moreover, they have been successfully used in many bioinformatic applications. Because they offer a strong statistical background and allow model interpretation, we propose a method based on hidden Markov models.     

Exploring the evolutionary history of centrosomes

The centrosome is the main organizer of the microtubule cytoskeleton in animals, higher fungi and several other eukaryotic lineages. Centrosomes are usually located at the centre of cell in tight association with the nuclear envelope and duplicate at each cell cycle. Despite a great structural diversity between the different types of centrosomes, they are functionally equivalent and share at least some of their molecular components. In this paper, we explore the evolutionary origin of the different centrosomes, in an attempt to understand whether they are derived from an ancestral centrosome or evolved independently from the motile apparatus of distinct flagellated ancestors. We then discuss the evolution of centrosome structure and function within the animal lineage.     

Fructosamine 3-kinase and other enzymes involved in protein deglycation

FN3K is a recently identified enzyme that phosphorylates both low-molecular-weight and protein-bound fructosamines. Fructosamine 3-phosphates are unstable, breaking down spontaneously to 3-deoxyglucosone, inorganic phosphate and the amino compound that originally reacted with glucose. FN3K is therefore a ‘deglycating’ enzyme. Evidence has been provided for the fact that this enzyme indeed removes a significant proportion of the fructosamine residues that form on hemoglobin in erythrocytes. Recent results obtained with FN3K-deficient mice confirm that FN3K acts as a protein deglycating enzyme in tissues.Unlike FN3K, FN3K-RP does not act on fructosamines, but it does phosphorylate ketoamines with a D configuration in C3 (ribulosamines, erythrulosamines and, with a lower affinity, psicosamines). The ketoamine 3-phosphates that are formed by FN3K-RP are also unstable and their spontaneous decomposition leads to the regeneration of a free amino group, indicating that FN3K-RP is also a protein repair enzyme. This role has been confirmed in human erythrocytes, which are rich in FN3K-RP. Remarkably, the single FN3K–FN3K-RP homologue that is present in fishes, plants and bacteria appears to be also a ribulosamine/erythrulosamine 3-kinase, indicating that the repair of ribulosamines or erythrulosamines may be more important than the removal of fructosamines.Ribulosamines and erythrulosamines most likely arise through a reaction of proteins with ribose 5-phosphate and erythrose 4-phosphate, two extremely potent glycating agents. The ribulosamine 5-phosphates and erythrulosamine 4-phosphates that are formed in this way must be dephosphorylated by a phosphatase that still needs to be identified. Glucose 6-phosphate is also a potent glycating agent, and a phosphatase acting best on protein-bound fructosamine 6-phosphates has recently been identified.In conclusion, protein deglycation appears to involve a whole set of enzymes. A key question for future investigations is why it is important to rid proteins of their sugar adducts rather than replace them with newly synthesized macromolecules.     

An Integrated Approach to Assess the Role of Chemical Exposure in Obesity

The evidence that developmental exposure of humans to chemicals plays a role in onset of obesity is convincing, yet controversial as it challenges traditional views on the etiology of obesity. OBELIX, one of the largest pan‐European studies researching the obesogen hypothesis, is accruing experimental and epidemiologic data on major classes of endocrine disrupting chemicals (EDCs) in both laboratory animal and prospective human cohort studies. Though still underway, this integrated and multidisciplinary project is adding new insights to the weight of evidence for effects of EDCs on obesity. Animal studies indicate divergent sex‐specific effects of perinatal exposure on the development of overweight. In vitro mechanistic studies have shown that EDCs enhance murine adipocyte differentiation, an effect that is accompanied by global DNA demethylation. Epidemiological studies have revealed an inverse relationship between prenatal polychlorinated biphenyl exposure and birth weight, and suggest differences in pre‐ and postnatal exposure on growth trajectories in children.     

Neutral hybridization can overcome a strong Allee effect by improving pollination quality

Small populations of plant species can be susceptible to demographic Allee effects mainly due to pollen limitation. Although sympatry with a common, co-flowering species may somewhat alleviate the problem of pollinator visitation (pollination quantity), the interspecific pollen transfer, IPT, (pollination quality) may remain a barrier to reproduction in small populations such as new introductions. However, if the two species are crosscompatible, our hypothesis is that neutral hybridization can help the small founding population overcome the Allee effect by improving the quality of pollination. We tested this hypothesis by using a novel modelling approach based on the theory of kinetic reactions wherein pollinators act as enzymes to catalyse the reaction between the two substrates: pollen and unselfed ovule. Using a single locus, two-allele genetic model, we developed a generic model that allows for hybridization between the invading and the native genotypes. Analysing the stability properties of the trivial equilibria in hybridization model as compared with the single genotype invasion model, we found that hybridization can either remove or reduce the Allee effect by making an otherwise stable trivial equilibrium unstable. Our study suggests that hybridization can be neutral but still be the key driver of a successful invasion by mediating pollen limitation. Conservation programmes should therefore account for this cryptic role that hybridization could play in plant invasions.