Theoretical Biology Forum最新文献

Cyclodextrin glycosyltransferase (EC2.4.1.19, CGTase) catalyzes the formation of cyclodextrins from starch. Thermal stability is of great importance for this enzyme. In order to gain better understanding of the thermostability mechanisms of the protein, we herein report structural features of the CGTase B domain at different temperatures. The present study mainly focuses on the contribution of non-covalent intramolecular interaction to protein stability and how they affect the thermal stability of the enzyme. Profile of root mean square fluctuation identifies thermostable and thermosensitive regions of the B domain. Analyses of trajectories in terms of secondary structure content, intramolecular hydrogen bond and salt bridge interactions indicate distinct differences in different temperature simulations. A detailed investigation of this domain suggests that the geometry of this domain is well protected by the critical intramolecular interaction up to 500 K temperature. The results also show clearly that main chain-main chain hydrogen bond and salt bridge are of major importance in protein stability at elevated temperature. Principal component analysis suggests that the motion of the B domain as well as the critical residue is similar at different temperatures. According to above-mentioned observations, the destabilization of region may be compensated by the formation of salt bridge and hydrogen bond that have been used as an evolutionary mechanism by the mesophilic enyme. The present work is an effort to extract more deterministic features of thermal stability from its dynamic nature much during the initial stages of denaturation.

Snake venom is a myriad of biologically active proteins and peptides. Three finger toxins are highly conserved in their molecular structure, but interestingly possess diverse biological functions. During the course of evolution the introduction of subtle mutations in loop regions and slight variations in the three dimensional structure, has resulted in their functional versatility. Cytotoxin-1 (UniProt ID: P01467), isolated from Naja mossambica mossambica, showed the potential to inhibit chymotrypsin and the chymotryptic activity of the 20S proteasome. In the present work we describe a molecular model of cytotoxin-1 in complex with chymotrypsin, prepared by the online server ClusPro. Analysis of the molecular model shows that Cytotoxin-1 (P01467) binds to chymotrypsin through its loop I located near the N-terminus. The concave side of loop I of the toxin fits well in the substrate binding pocket of the protease. We propose Phe10 as the dedicated P1 site of the ligand. Being a potent inhibitor of the 20S proteasome, cytotoxin-1 (P01467) can serve as a potential antitumor agent. Already snake venom cytotoxins have been investigated for their ability as an anticancer agent. The molecular model of cytotoxin-1 in complex with chymotrypsin provides important information towards understanding the complex formation.

It is now widely accepted that the microcirculation plays a role in the complications of atherosclerosis, but the microcirculation response to atherosclerosis risk factors like diabetes, hypercholesterolemia and hypertension, is still unclear. Alterations in the endothelial production of IL6, NO and ET-1 are known to be correlate with these diseases. Simulating the presence of hyperglycemia, hypercholesterolemia and hypertension, this in vitro study investigated the effect of glucose, angiotensin II, and nLDL treatments on IL-6, ET-1 and NO in HMEC-1. The medium concentrations of IL6 and ET-1 were measured by ELISA assay, whereas NO by a colorimetric assay. The mRNA and protein expressions of IL-6, Pre-po-ET-1 and eNOS by extracted cells were also investigated by RT-PCR. NO concentration in the medium of HMEC-1 increased in a dose-dependent manner by glucose after 24 hours and by nLDL both at 6 and 24 h, with higher values at 6 hours. The eNOS mRNA expression at 6h induced by nLDL, showed a parallel trend to the medium NO. No increment dose dependent NO concentration was observed by angiotensin II.nLDL induced a dose-dependent increase of ET-1 medium levels, more accentuated in 6h respect to 24h. The expression of prepro-ET-1 showed a parallel dose-dependent increased after 6 hours. Both glucose and nLDL increased IL-6 levels in a dose-dependent manner at 6 and 24 h. In conclusion, glucose treatment on HMEC-1 cells exerted a mild stimulus on NO and IL-6 production. nLDL treatment showed a similar glucose stimulus on NOx, but it induced an intense pro-inflammatory activity and showed the ability to stimulate ET-1 synthesis.

Connectivity is currently emphasized as a key factor in conservation for its role in enhancing biodiversity of an area and giving benefit to the adjacent areas. For most marine species, connectivity is synonomous of larval dispersal. We applied a spatially explicit meta-population model to test the hypothesis that larval dispersal can affect local demographical features, consequently misleading conservation practice in the marine environment. Simulations were carried out in the Gulf of Lions where coastal circulation displays highly variable temporal and spatial submeso-scale structures. Two different benthic invertebrate species were considered: a soft bottom short lived species and a hard bottom long lived one. In the first case, simulations showed that highest densities at equilibrium do not inform on self-persistent populations location. In the second case, simulations showed that connectivity effects may result in out-of-equilibria demographical structure. We emphasized the caveats in the parameterization of demographical models when local demography is controlled by connectivity.

Every nucleated cell can produce and respond to cytokines, extracellular proteic/glycoproteic mediators that constitute a complex, interconnected, and flexible signaling network, addressed to modulate cell behavior and homeostasis through the interaction with high-affinity surface receptors. These messenger molecules, whose main characteristics are potency, pleiotropism, and redundancy, primarily act in autocrine, paracrine, and juxtacrine way, but can also display systemic activity in endocrine-like modality. They are generally classified according to their cellular sources, three-dimensional structure, or biological functions. Among cytokines, interleukins (ILs) represent a fascinating and multifunctional group of immunomodulators that primarily mediate the leukocyte cross-talk (hence the name), and mainly regulate the immune cell proliferation, differentiation, growth, survival, activation, and functions. Up to 38 ILs have been so far identified, numbered according to the order of discovery, and grouped in different subsets, based on distinguishing structural/functional features. Due to their crucial role in regulating inflammation and immune response, ILs are known to be involved in the pathogenesis of human inflammatory/autoimmune diseases. Therefore, they have increasingly attracted great interest as effective or promising therapeutic targets. The biology and functions of the hitherto identified human ILs are reviewed and discussed: in this first section of the article, ILs from IL-1 to IL-19 are presented.

This paper is a carrying on of the theme examined in (Bazzani, Freguglia 2013) where we discuss a proposal of studying of essential structural aspects of Darwinian Evolution Theory. Also in this case we apply a mathematical ago-antagonist theory inspired by Y. Cherruault's ideas (Cherruault 1998). In the present paper we consider the network structure of genes activity and its dynamics.

We propose two modeling approaches to describe the dynamics of ant battles, starting from laboratory experiments on the behavior of two ant species, the invasive Lasius neglectus and the authocthonus Lasius paralienus. This work is mainly motivated by the need to have realistic models to predict the interaction dynamics of invasive species. The two considered species exhibit different fighting strategies. In order to describe the observed battle dynamics, we start by building a chemical model considering the ants and the fighting groups (for instance two ants of a species and one of the other one) as a chemical species. From the chemical equations we deduce a system of differential equations, whose parameters are estimated by minimizing the difference between the experimental data and the model output. We model the fluctuations observed in the experiments by means of a standard Gillespie algorithm. In order to better reproduce the observed behavior, we adopt a spatial agent-based model, in which ants not engaged in fighting groups move randomly (diffusion) among compartments, and the Gillespie algorithm is used to model the reactions inside a compartment.

The fractal dimension of a non-stellate neuron changes continuously with rotation of the neuronal picture. For a stellate neuron such changes cannot be noticed. During preprocessing for the box counting, non-stellate neurons should be arranged so that the major diameters of their dendrite fields are parallel. It was shown that a non-stellate neuronal picture had the smallest box dimension when the angle between the horizontal or vertical axis and its major diameter was about 45 degrees. The box counting method which uses ImageJ software does not consider the position of a picture on the computer's screen. A dispersion of the box dimension values of a sample is generally rather large so that their mean value is with larger standard deviation. Modified box counting method partly diminishes these findings. To improve a dependence on neuronal rotation for the box counting dimension of nonstellate neurons, prior to applying the box counting, the non-stellate neurons should be arranged so that the major diameters of their dendrite fields are parallel.