Algebraic structures generating reaction-diffusion models: The activator-substrate system

We shall construct a class of nonlinear reaction-diffusion equations starting from an infinitesimal algebraic skeleton. Our aim is to explore the possibility of an algebraic foundation of integrability properties and of stability of equilibrium states associated with nonlinear models describing patterns formation.     

Simple assumptions predicts prey selection by piscivorous fishes

Studies on trophic interactions permits the use of community-wide network analyses to evaluate the consequences of human interventions in natural communities. In this paper, we aimed to get insights into the underlying mechanism of prey selection for four piscivorous species, and evaluate behavioral responses to prey selection after an impoundment. We assemble six food web models to search for the hypothesis that best predict observed prey selection pattern of piscivorous fishes combining the following assumptions: (i) predation window, defined as the size range of prey species consumed by a piscivorous fish; (ii) prey strategies to avoid predation (iii) and prey abundance. We tested the probability of each hypothesis to reproduce two empirical data, one before and one after an impoundment with minimum assumptions. Before impoundment, we found that predators presented switching behavior, preying preferably on abundant prey; while after impoundment, predators consumed prey within its predation window. Those results explained better than the null hypotesis and all other assumptions; and corroborate with both theoretical and empirical studies. We conclude that different assumptions drives piscivorous fish behavior in different environments; and modelling procedures can be used to assess gaps in trophic interactions of fish communities.     

Cognitive flexibility deficits in a mouse model for the absence of full‐length dystrophin

Duchenne muscular dystrophy (DMD) is a progressive muscle‐wasting disorder, caused by mutations in the DMD gene and the resulting lack of dystrophin. The DMD gene has seven promoters, giving rise to multiple full‐length and shorter isoforms. Besides the expression of dystrophin in muscles, the majority of dystrophin isoforms is expressed in brain and dystrophinopathy can lead to cognitive deficits, including intellectual impairments and deficits in executive function. In contrast to the muscle pathology, the impact of the lack of dystrophin on the brain is not very well studied. Here, we study the behavioral consequences of a lack of full‐length dystrophin isoforms in mdx mice, particularly with regard to domains of executive functions and anxiety. We observed a deficit in cognitive flexibility in mdx mice in the absence of motor dysfunction or general learning impairments using two independent behavioral tests. In addition, increased anxiety was observed, but its expression depended on the context. Overall, these results suggest that the absence of full‐length dystrophin in mice has specific behavioral effects that compare well to deficits observed in DMD patients.     

Home range size of adult Indo‐Pacific bottlenose dolphins (Tursiops aduncus) in a coastal and estuarine system is habitat and sex‐specific

This study examined sex‐specific differences in home range size of adult Indo‐Pacific bottlenose dolphins off Bunbury, Western Australia. We applied a new kernel density estimation approach that accounted for physical barriers to movements. A Bayesian mixture model was developed to estimate a sex effect in home range size with latent group partitioning constrained by association data. A post hoc analysis investigated group partitioning relating to the proportion of time spent in open vs. sheltered waters. From 2007 to 2013, photographic‐identification data were collected along boat‐based systematic transect lines (n = 586). Analyses focused on adult dolphins of known sex (sighted ≥ 30 times; n = 22 males and 34 females). The 95% utilization distributions of males varied between 27 and 187 km² (; 94.8 ± 48.15) and for females between 20 and 133 km² (65.6 ± 30.9). The mixture model indicated a 99% probability that males had larger home ranges than females. Dolphins mostly sighted in open waters had larger home ranges than those in sheltered waters. Home ranges of dolphins sighted in sheltered waters overlapped with areas of highest human activity. We suggest that sex differences in home ranges are driven by male mating strategies, and home range size differences between habitats may be influenced by prey availability and predation risk.     

Three pairs of weak interactions precisely regulate the G‐loop gate of Kir2.1 channel

Kir2.1 (also known as IRK1) plays key roles in regulation of resting membrane potential and cell excitability. To achieve its physiological roles, Kir2.1 performs a series of conformational transition, named as gating. However, the structural basis of gating is still obscure. Here, we combined site‐directed mutation, two‐electrode voltage clamp with molecular dynamics simulations and determined that H221 regulates the gating process of Kir2.1 by involving a weak interaction network. Our data show that the H221R mutant accelerates the rundown kinetics and decelerates the reactivation kinetics of Kir2.1. Compared with the WT channel, the H221R mutation strengthens the interaction between the CD‐ and G‐loops (E303‐R221) which stabilizes the close state of the G‐loop gate and weakens the interactions between C‐linker and CD‐loop (R221‐R189) and the adjacent G‐loops (E303‐R312) which destabilizes the open state of G‐loop gate. Our data indicate that the three pairs of interactions (E303‐H221, H221‐R189 and E303‐R312) precisely regulate the G‐loop gate by controlling the conformation of G‐loop. Proteins 2016; 84:1929–1937. © 2016 Wiley Periodicals, Inc.     

Structural mutation analysis of PTEN and its genotype‐phenotype correlations in endometriosis and cancer

The phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene encodes a tumor suppressor phosphatase that has recently been found to be frequently mutated in patients with endometriosis, endometrial cancer and ovarian cancer. Here, we present the first computational analysis of 13 somatic missense PTEN mutations associated with these phenotypes. We found that a majority of the mutations are associated in conserved positions within the active site and are clustered within the signature motif, which contain residues that play a crucial role in loop conformation and are essential for catalysis. In silico analyses were utilized to identify the putative effects of these mutations. In addition, coarse‐grained models of both wild‐type (WT) PTEN and mutants were constructed using elastic network models to explore the interplay of the structural and global dynamic effects that the mutations have on the relationship between genotype and phenotype. The effects of the mutations reveal that the local structure and interactions affect polarity, protein structure stability, electrostatic surface potential, and global dynamics of the protein. Our results offer new insight into the role in which PTEN missense mutations contribute to the molecular mechanism and genotypic‐phenotypic correlation of endometriosis, endometrial cancer, and ovarian cancer. Proteins 2016; 84:1625–1643. © 2016 Wiley Periodicals, Inc.     

Simple combined explicit/implicit water model

A simple combined water model (SCW model) for the calculation of the hydration free energy is presented. In the frame of the model a solute is placed in the centre of the spherical cavity with explicit water molecules, which are considered at the atomistic level. Rigid wall potential at the boundary of the cavity restricts the moving of the explicit water molecules. Water outside the sphere is considered as the conducting continuum (implicit part of the model). Simulation is performed in the frame of the NVT ensemble (constant number of particles, volume and temperature), density of water is fixed and equal to experimental value 1 g/cm³. The energy of electrostatic interaction of atomic point charges of the explicit water molecules with conducting continuum is calculated analytically by means of the image charges method. It provides high computational efficiency of the SCW model. For the averaging of the calculated thermodynamic and structural values over microstates of the system the thermodynamic integration method is used. The possible using of SCW for the docking problem is discussed.     

Speeding up Monte Carlo molecular simulation by a non-conservative early rejection scheme

Monte Carlo (MC) molecular simulation describes fluid systems with rich information, and it is capable of predicting many fluid properties of engineering interest. In general, it is more accurate and representative than equations of state. On the other hand, it requires much more computational effort and simulation time. For that purpose, several techniques have been developed in order to speed up MC molecular simulations while preserving their precision. In particular, early rejection schemes are capable of reducing computational cost by reaching the rejection decision for the undesired MC trials at an earlier stage in comparison to the conventional scheme. In a recent work, we have introduced a ‘conservative’ early rejection scheme as a method to accelerate MC simulations while producing exactly the same results as the conventional algorithm. In this paper, we introduce a ‘non-conservative’ early rejection scheme, which is much faster than the conservative scheme, yet it preserves the precision of the method. The proposed scheme is tested for systems of structureless Lennard-Jones particles in both canonical and NVT-Gibbs ensembles. Numerical experiments were conducted at several thermodynamic conditions for different number of particles. Results show that at certain thermodynamic conditions, the non-conservative method is capable of doubling the speed of the MC molecular simulations in both canonical and NVT-Gibbs ensembles.     

Spectral EEG indicator of pressure to enter into deep sleep: its responsiveness to closing the eyes for just a few minutes exhibits a pure exponential buildup during sleep deprivation

According to the two-process model of sleep–wake regulation, a homeostatic sleep pressure, i.e. a pressure to enter into deep non-rapid eyes movement (NREM) sleep, must exhibit a purely exponential buildup during prolonged wakefulness. However, this pressure is usually measured indirectly, i.e. during the following episode of actual deep NREM sleep. The purpose of this paper was to show that, despite a prominent circadian modulation of time course of any waking EEG index, the model-postulated purely exponential buildup of the homeostatic sleep pressure can be directly confirmed. During two days of sleep deprivation experiments, the EEG of healthy adults (N = 30) was recorded every other hour throughout 5-min eyes closed relaxation. Sixteen ln-transformed single-Hz power densities (from 1 to 16 Hz) were computed for each of 5 one-min intervals. Differences between these densities obtained for the first and the following intervals were calculated and averaged. The obtained 16 values were used as the frequency weighting curve for weighting densities of each set of 16 single-Hz power densities. Summing-up of these weighted densities provided a single measure that was found to co-vary with self-rated sleepiness throughout two-day interval of sleep deprivation, thus reflecting the joint influence of the circadian and homeostatic processes. However, two-day time course of responsiveness of this measure to closing the eyes for just a few minutes exhibited a purely exponential buildup. It was concluded that this result provided a direct experimental confirmation of the model-predicted exponential buildup of the homeostatic sleep pressure across prolonged episode of wakefulness.