Mathematical model for adaptive evolution of populations based on a complex domain

A mutation is ultimately essential for adaptive evolution in all populations. It arises all the time, but is mostly fixed by enzymes. Further, most do consider that the evolution mechanism is by a natural assortment of variations in organisms in line for random variations in their DNA, and the suggestions for this are overwhelming. The altering of the construction of a gene, causing a different form that may be communicated to succeeding generations, produced by the modification of single base units in DNA, or the deletion, insertion, or rearrangement of larger units of chromosomes or genes. This altering is called a mutation. In this paper, a mathematical model is introduced to this reality. The model describes the time and space for the evolution. The tool is based on a complex domain for the space. We show that the evolution is distributed with the hypergeometric function. The Boundedness of the evolution is imposed by utilizing the Koebe function.     

Detecting protein atom correlations using correlation of probability of recurrence

The dynamic cross‐correlation Map(DCCM) technique has been used extensively to study protein dynamics. In this work, we introduce the use of the method of correlation of probability of recurrence (CPR) as a complementary method to detect correlations between protein residue atoms. Time series of the distances of the C_α atoms of the β‐lactamase inhibitory protein (BLIP) from a reference position are analyzed using CPR and mutual information (MI). The results are compared to those provided by DCCM. In comparison to MI, CPR is found to detect more of the correlations present in DCCM. It is also able to detect a small number of significant correlations between distant residues that are not detected by DCCM. Proteins 2014; 82:2180–2189. © 2014 Wiley Periodicals, Inc.     

Alteration of dopaminergic innervation and voluntary movements after long period of thirst in a semi-desert rodent, Meriones shawi: Behavioral and immunohistochemical studies

Dehydration is a powerful stimulus causing disequilibrium in homeostasis of water and electrolytes resulting from depletion in total body water. Most studies have focused on domestic and laboratory animals; however, the study of desert animals allows improved understanding about water balance and resistance to dehydration and associated behavioral changes, including those related to voluntary movements. Meriones shawi (Shaw's Jird) is a desert rodent characterized by its resistance to long periods of thirst that can extend for several months. In the present study, M. shawi were subjected to water deprivation for 1 month. We used tyrosine hydroxylase immunohistochemistry (TH: the key enzyme of catecholamine biosynthesis) to evaluate the effects of prolonged dehydration on the dopaminergic system in both substancia nigra pars compacta and ventral tegmental area (SNpc and VTA), which are the main sources of dopamine input to several brain areas; the immunolabelling was performed also in both the medial forebrain bundle and the caudate putamen (striatum). In addition, the open-field test was used to evaluate the effect of dehydration on locomotor activity in M. shawi. The results showed an increase in TH immunolabelling in both SNpc and VTA following 1 month of dehydration compared to control levels. The same results were obtained with fibers in both MFB and striatum. This augmentation of TH immunoreactivity was accompanied by noticeable changes in locomotor activity behavior of Meriones, the recording test shows the hyperactivity of animals which is probably caused by dehydration. Overall, the results indicate that dehydration is able to increase dopaminergic neurotransmission, which might be involved in generating hyperactivity in this desert animal.     

Reactive oxygen species mediate thymoquinone-induced apoptosis and activate ERK and JNK signaling

Thymoquinone (TQ), a component of black seed essential oil, is known to induce apoptotic cell death and oxidative stress, however, the direct involvement of oxidants in TQ-induced cell death has not been established yet. Here, we show that TQ inhibited the proliferation of a panel of human colon cancer cells (Caco-2, HCT-116, LoVo, DLD-1 and HT-29), without exhibiting cytotoxicity to normal human intestinal FHs74Int cells. Further investigation in DLD-1 revealed that apoptotic cell death is the mechanism for TQ-induced growth inhibition as confirmed by flow cytometry, M30 cytodeath and caspase-3/7 activation. Apoptosis was induced via the generation of reactive oxygen species (ROS) as evidenced by the abrogation of TQ apoptotic effect in cells preincubated with the strong antioxidant N-acetyl cysteine (NAC). TQ increased the phosphorylation states of the mitogen-activated protein kinases (MAPK) JNK and ERK, but not of p38. Their activation was completely abolished in the presence of NAC. Using PD98059 and SP600125, specific ERK and JNK inhibitors, the two kinases were found to possess pro-survival activities in TQ-induced cell death. These data present evidence linking the pro-oxidant effects of TQ with its apoptotic effects in colon cancer and prove a protective role of MAPK.     

Phorbol ester-induced differentiation of L6 myogenic cells involves phospholipase D activation

TPA, a potent PKC activator, inhibits myogenic differentiation and activates phospholipase D (PLD). We evaluated the involvement of PLD in the TPA effects on L6 myoblasts differentiation. TPA, at concentrations inhibiting differentiation of L6 cells, induced a strong, though transient, PLD activation. Surprisingly, at nanomolar concentration, TPA induced both myogenic differentiation and sustained activation of PLD. Differential effect of TPA can be ascribed to PKC downregulation induced by highest TPA concentrations. TPA-induced differentiation was inhibited by 1-butanol, confirming the involvement of PLD in this effect. These data suggest that prolonged elevation of PLD activity is required for myogenic differentiation.     

Novel inhibitors of fatty acid oxidation as potential metabolic modulators

We describe the synthesis of novel inhibitors of fatty acid oxidation as potential metabolic modulators for the treatment of stable angina. Replacement of the 2H-benzo[d]1,3-dioxolene ring system in our initial lead 3 with different benzthiazoles, benzoxazoles and introducing small alkyl substituents into the piperazine ring resulted in analogues with enhanced inhibitory activity against 1-(14)[C]-palmitoyl-CoA oxidation in isolated rat heart mitochondria (6, IC(50)=70 nM; 25, IC(50)=23 nM).