The Involvement of Nek2 and Notch in the Proliferation of Rat Adrenal Cortex Triggered by POMC-Derived Peptides

The adrenal gland is a dynamic organ that undergoes constant cell turnover. This allows for rapid organ remodeling in response to the physiological demands of the HPA axis, which is controlled by proopiomelanocortin (POMC)-derived peptides, such as adrenocorticotropic hormone (ACTH) and N-Terminal peptides (N-POMC). In the rat adrenal cortex, POMC-derived peptides trigger a mitogenic effect, and this process increases cyclins D and E, while inhibiting p27Kip1. The goal of the present study was to further explore the mitogenic effect of ACTH and synthetic N-POMC_1–28 peptides by investigating the differences in the expression of key genes involved in the cell cycle of the rat adrenal cortex, following inhibition of the HPA axis. Moreover, we evaluated the differences between the inner and outer fractions of the adrenal cortex (ZF-fraction and ZG-fraction) in terms of their response patterns to different stimuli. In the current study, the inhibition of the HPA axis repressed the expression of Ccnb2, Camk2a, and Nek2 genes throughout the adrenal cortex, while treatments with POMC-derived peptides stimulated Nek2, gene and protein expression, and Notch2 gene expression. Furthermore, Notch1 protein expression was restricted to the subcapsular region of the cortex, an area of the adrenal cortex that is well-known for proliferation. We also showed that different regions of the adrenal cortex respond to HPA-axis inhibition and to induction with POMC-derived peptides at different times. These results suggest that cells in the ZG and ZF fractions could be at different phases of the cell cycle. Our results contribute to the understanding of the mechanisms involved in cell cycle regulation in adrenocortical cells triggered by N-POMC peptides and ACTH, and highlight the involvement of genes such as Nek2 and Notch.     

Nonlinear damping of zonal flows

The modulatonal instability theory for the generation of large-scale (zonal) modes by drift modes has been extended to the second order including the effects of finite amplitude zonal flows, ? _q . The nonlinear (second-order) sidebands are included in the perturbative expansion to derive the nonlinear equation for the evolution of ? _q . It is shown that effects of finite ? _q reduce the growth rate of zonal flow with a possibility of oscillatory regimes at a later stage.     

Design and synthesis of selective keto-1,2,4-oxadiazole-based tryptase inhibitors

Using a scaleable, directed library approach based on orthogonally protected advanced intermediates, we have prepared a series of potent keto-1,2,4-oxadiazoles designed to explore the P(2) binding pocket of human mast cell tryptase, while building in a high degree of selectivity over human trypsin and other serine proteases.     

Contrast agents for nuclear magnetic resonance imaging

Nuclear magnetic resonance imaging relies upon differences in relaxation times for much of its ability to resolve anatomical structures and to detect changes in tissue. The natural differences can be changed by the administration of paramagnetic substances, such as metal complexes and stable organic free radicals, and ferromagnetic materials, such as small particles of magnetite. Detailed studies of the chemistry and biophysics of such substances in the body are required if they are to become safe and effective contrast agents for use in medical NMR imaging.     

Biochemical heterogenity of the left ventricular myocardium: transmural and base-apex gradients on H.E.P. contents of the well oxygenated perfused dog heart.

An investigation into the contents (mumol/g w.w.) of the creatine phosphate (CP) and adenosine triphosphate (ATP) of various myocardial regions was performed on the empty beating isolated blood perfused dog heart. Across the myocardial wall, CP concentration was higher in the outer portion (9.03 +/- 0.18) than in the inner portion (8.59 +/- 0.20) (P less than 0.05). In addition to this transmural gradient, a longitudinal gradient was found: tissue contents of both CP and ATP decrease significantly from the base (CP: 9.70 +/- 0.28, ATP: 5.84 +/- 0.20) to the apex (CP: 8.69 +/- 0.27, ATP: 5.57 +/- 0.17) (P less than 0.01 and P less than 0.05 respectively). The gradients of metabolites in the well oxygenated empty beating heart suggest that a permanent metabolic adaptation to less adequate regional O2 reserves is physiologically operating in the subendocardial layer and the apex region of the left ventricle.     

Assimilation of different cyanobacteria as food and the consequences for internal energy stores of juvenile roach

Juvenile roach Rutilus rutilus fed on the cyanobacterium Aphanizomenon were able to maintain liver glycogen and muscle protein concentrations. In contrast, internal energy stores of fish fed on the cyanobacterium Microcystis were degraded. Liver glycogen, however, was higher than in starved fish, suggesting that roach was able to obtain some nutrients (probably carbohydrates) from the mucus cover of Microcystis . Weak assimilation of radiolabeled Microcystis by roach was detectable, and assimilation rates increased with increasing proportion of Aphanizomenon in a mixture of both cyanobacteria. It is concluded that the incomplete digestion of Microcystis was the main reason for the negative growth rates of roach when fed on this cyanobacterium species.     

Sublethal nickel toxicity shuts off manganese oxidation and pellicle biofilm formation in Pseudomonas putida GB-1

In sediments, the bioavailability and toxicity of Ni are strongly influenced by its sorption to manganese (Mn) oxides, which largely originate from the redox metabolism of microbes. However, microbes are concurrently susceptible to the toxic effects of Ni, which establishes complex interactions between toxicity and redox processes. This study measured the effect of Ni on growth, pellicle biofilm formation and oxidation of the Mn-oxidizing bacteria Pseudomonas putida GB-1. In liquid media, Ni exposure decreased the intrinsic growth rate but allowed growth to the stationary phase in all intermediate treatments. Manganese oxidation was 67% less than control for bacteria exposed to 5 μM Ni and completely ceased in all treatments above 50 μM. Pellicle biofilm development decreased exponentially with Ni concentration (maximum 92% reduction) and was replaced by planktonic growth in higher Ni treatments. In solid media assays, growth was unaffected by Ni exposure, but Mn oxidation completely ceased in treatments above 10 μM of Ni. Our results show that sublethal Ni concentrations substantially alter Mn oxidation rates and pellicle biofilm development in P. putida GB-1, which has implications for toxic metal bioavailability to the entire benthic community and the environmental consequences of metal contamination.     

Differential repair of potentially lethal damage in exponentially growing and quiescent 9L cells

The alteration of potentially lethal damage repair by postirradiation treatment with hypertonic saline (0.5 M PBS) was investigated in exponentially growing and quiescent 9L cells in vitro. A single dose of X rays (8.5 Gy) immediately followed by a 30-min treatment with hypertonic PBS at 37 degrees C reduced the survival of exponentially growing 9L cells by a factor of 13-18 compared to survival of irradiated immediately and delayed-plated cells, while the survival of quiescent cells was reduced by only a factor of 5-8. Survival curves confirmed the relative resistance of the quiescent 9L cells versus exponentially growing 9L cells to X rays plus hypertonic treatment. Both the slope and the shoulder of the survival curve were reduced to a greater extent in exponentially growing cells than in the quiescent cells by hypertonic treatment. The response of quiescent cells cannot be explained by either the duration of hypertonic treatment or the redistribution of the cells into G1 phase. We show that quiescent 9L cells can recover from hypertonically induced potentially lethal damage when incubated under conditions which have been found to delay progression through the cell cycle, and postulate that an altered chromatin structure or an enhanced repair capacity of quiescent 9L cells may be responsible for their resistance.