Hypochlorous acid-induced stress on human spermatozoa. A model for inflammation in the male genital tract

The fertilising ability of human spermatozoa may be impaired by inflammations of the genital tract, although details of these processes are still unknown. Hypochlorous acid (HOCl), an important product of myeloperoxidase released from stimulated neutrophils, induces a concentration-dependent increase in externalisation of phosphatidylserine in ejaculated human spermatozoa as revealed by fluorescence-activated cell sorting (FACS) analysis. The increase of annexin-V binding cells starts already at about 10(-5) mol/l HOCl, while a formation of lysophosphatidylcholines as detected by matrix-assisted laser desorption and ionisation time-of-flight mass spectrometry (MALDI-TOF MS) is only found at HOCl concentrations higher than 10(-4) mol/l. Thus, changes in lipid composition of spermatozoa are unlikely responsible for the phosphatidylcholine (PS)-externalisation. These data gave concomitant evidence that HOCl itself leads to a dramatic damage of the cell membrane. Thus, the neutrophil-derived HOCl contributes to the deterioration of spermatozoa leading to diminished fertilisation ability.     

Anchoring a cationic ligand: the structure of the Fab fragment of the anti-morphine antibody 9B1 and its complex with morphine

The crystal structures of an anti-morphine antibody 9B1 (to 1.6A resolution) and its complex with morphine (to 2.0 A resolution) are reported. The morphine-binding site is described as a shallow depression on the protein surface, an unusual topology for a high-affinity ( Ka approximately 10(9) M(-1)) antibody against a small antigen. The polar part of the ligand is exposed to solvent, and the cationic nitrogen atom of the morphine molecule is anchored at the bottom of the binding site by a salt-bridge to a glutamate side-chain. Additional affinity is provided by a double cation-pi interaction with two tryptophan residues. Comparison of the morphine complex with the structure of the free Fab shows that a domain closure occurs upon binding of the ligand.     

Crossing scales,crossing disciplines: collective motion and collective action in the Global Commons

Two conflicting tendencies can be seen throughout the biological world: individuality and collective behaviour. Natural selection operates on differences among individuals, rewarding those who perform better. Nonetheless, even within this milieu, cooperation arises, and the repeated emergence of multicellularity is the most striking example. The same tendencies are played out at higher levels, as individuals cooperate in groups, which compete with other such groups. Many of our environmental and other global problems can be traced to such conflicts, and to the unwillingness of individual agents to take account of the greater good. One of the great challenges in achieving sustainability will be in understanding the basis of cooperation, and in taking multicellularity to yet a higher level, finding the pathways to the level of cooperation that is the only hope for the preservation of the planet.     

Proteins as micro viscosimeters: Brownian motion revisited

Translational and rotational diffusion coefficients of proteins in solution strongly deviate from the Stokes–Einstein laws when the ambient viscosity is induced by macromolecular co-solutes rather than by a solvent of negligible size as was assumed by A. Einstein one century ago for deriving the laws of Brownian motion and diffusion. Rotational and translational motions experience different micro viscosities and both become a function of the size ratio of protein and macromolecular co-solute. Possible consequences upon fluorescence spectroscopy observations of diffusing proteins within living cells are discussed.     

Comment: analyses of models of ion actions under the combined action of AC and DC magnetic fields

I show that the interaction of weak DC and ELF magnetic fields with contained ions cannot generate significant biological effects through changing the character of the ion orbits.     

Molecular dynamics study of major urinary protein-pheromone interactions: a structural model for ligand-induced flexibility increase

Recently, two independent (15)N NMR relaxation studies indicated that in contrast to the decreased flexibility expected for induced-fit interactions, the backbone flexibility of major urinary protein isoform I (MUP-I) slightly increased upon complex formation with its natural pheromone 2-sec-butyl-4,5-dihydrothiazol. We have investigated the subtle details of molecular interactions by molecular dynamics simulations in explicit solvent. The calculated order parameters S(2) for a free- and ligand-bound protein supply evidence that mobility in various regions of MUP-I can be directly related to small conformational changes of the free- and complexed protein resulting from modifications of the hydrogen bonding network.     

Exploring patterns of interspecific variation in quantitative traits using sequential phylogenetic eigenvector regressions

A number of metrics have been developed for estimating phylogenetic signal in data and to evaluate correlated evolution, inferring broad-scale evolutionary and ecological processes. Here, we proposed an approach called phylogenetic signal-representation (PSR) curve, built upon phylogenetic eigenvector regression (PVR). In PVR, selected eigenvectors extracted from a phylogenetic distance matrix are used to model interspecific variation. In the PSR curve, sequential PVR models are fitted after successively increasing the number of eigenvectors and plotting their R(2) against the accumulated eigenvalues. We used simulations to show that a linear PSR curve is expected under Brownian motion and that its shape changes under alternative evolutionary models. The PSR area, expressing deviations from Brownian motion, is strongly correlated (r= 0.873; P < 0.01) with Blomberg's K-statistics, so nonlinear PSR curves reveal if traits are evolving at a slower or higher rate than expected by Brownian motion. The PSR area is also correlated with phylogenetic half-life under an Ornstein-Uhlenbeck process, suggesting how both methods describe the shape of the relationship between interspecific variation and time since divergence among species. The PSR curve provides an elegant exploratory method to understand deviations from Brownian motion, in terms of acceleration or deceleration of evolutionary rates occurring at large or small phylogenetic distances.     

Fitting models of continuous trait evolution to incompletely sampled comparative data using approximate Bayesian computation

In recent years, a suite of methods has been developed to fit multiple rate models to phylogenetic comparative data. However, most methods have limited utility at broad phylogenetic scales because they typically require complete sampling of both the tree and the associated phenotypic data. Here, we develop and implement a new, tree-based method called MECCA (Modeling Evolution of Continuous Characters using ABC) that uses a hybrid likelihood/approximate Bayesian computation (ABC)-Markov-Chain Monte Carlo approach to simultaneously infer rates of diversification and trait evolution from incompletely sampled phylogenies and trait data. We demonstrate via simulation that MECCA has considerable power to choose among single versus multiple evolutionary rate models, and thus can be used to test hypotheses about changes in the rate of trait evolution across an incomplete tree of life. We finally apply MECCA to an empirical example of body size evolution in carnivores, and show that there is no evidence for an elevated rate of body size evolution in the pinnipeds relative to terrestrial carnivores. ABC approaches can provide a useful alternative set of tools for future macroevolutionary studies where likelihood-dependent approaches are lacking.     

Visual extrapolation under risk: human observers estimate and compensate for exogenous uncertainty

Humans commonly face choices between multiple options with uncertain outcomes. Such situations occur in many contexts, from purely financial decisions (which shares should I buy?) to perceptuo-motor decisions between different actions (where should I aim my shot at goal?). Regardless of context, successful decision-making requires that the uncertainty at the heart of the decision-making problem is taken into account. Here, we ask whether humans can recover an estimate of exogenous uncertainty and then use it to make good decisions. Observers viewed a small dot that moved erratically until it disappeared behind an occluder. We varied the size of the occluder and the unpredictability of the dot''s path. The observer attempted to capture the dot as it emerged from behind the occluded region by setting the location and extent of a ‘catcher’ along the edge of the occluder. The reward for successfully catching the dot was reduced as the size of the catcher increased. We compared human performance with that of an agent maximizing expected gain and found that observers consistently selected catcher size close to this theoretical solution. These results suggest that humans are finely tuned to exogenous uncertainty information and can exploit it to guide action.     

A brain-derived metric for preferred kinetic stimuli

We here address the question of whether there is any correlation between subjective preference for simple configurations within a specific visual domain such as motion and strength of activity in visual areas in which that domain is emphasized. We prepared several distinctive patterns of dots in motion with various characteristics and asked humans to rate them according to their preference, before and while scanning the activity in their brains with functional magnetic resonance imaging. For simplicity, we restricted ourselves to motion in the fronto-parallel plane. Moving patterns produced activity in areas V1, V2, the V3 complex (V3, V3A, V3B) and V5, but only in areas V5, V3A/B and parietal cortex did the preferred kinetic patterns produce stronger activity when compared with the non-preferred ones. In addition, preferred patterns produced activity within field A1 of medial orbito-frontal cortex (mOFC), which is not otherwise activated by kinetic stimuli. Hence, for these areas, stronger neural activity correlated with subjective preference. We conclude that configurations of kinetic stimuli that are subjectively preferred correlate with stronger activity within early visual areas and within mOFC. This opens up the possibility of more detailed studies to relate subjective preferences to strength of activity in early visual areas and to relate activity in them to areas whose activity correlates with the subjective experience of beauty.