Information capacity and its approximations under metabolic cost in a simple homogeneous population of neurons

We calculate and analyze the information capacity-achieving conditions and their approximations in a simple neuronal system. The input–output properties of individual neurons are described by an empirical stimulus–response relationship and the metabolic cost of neuronal activity is taken into account. The exact (numerical) results are compared with a popular “low-noise” approximation method which employs the concepts of parameter estimation theory. We show, that the approximate method gives reliable results only in the case of significantly low response variability. By employing specialized numerical procedures we demonstrate, that optimal information transfer can be near-achieved by a number of different input distributions. It implies that the precise structure of the capacity-achieving input is of lesser importance than the value of capacity. Finally, we illustrate on an example that an innocuously looking stimulus–response relationship may lead to a problematic interpretation of the obtained Fisher information values.     

Proteasome activity in experimental diabetes

Numerous studies have indicated that oxidative stress contributes to the development and progression of diabetes and other related complications. Since the ubiquitin-proteasome pathway is involved in degradation of oxidized proteins, it is to be expected that alterations in proteasome-dependent proteolysis accompany diabetes. This paper focuses on the role of the proteasome in alloxan-induced experimental diabetes. The changes in proteasomal activity and oxidative stress indices (protein oxidation and lipid peroxidation) were evaluated. The obtained results revealed increased protein oxidation and lipid peroxidation, as well as alterations in proteasomal activities in diabetic rats. Our data indicates a significant decrease in chymotryptic-like activity; increased tryptic-like activity; and unchanged post-glutamyl peptide hydrolytic-like activity. These findings suggest the presence of oxidative stress in diabetes that appears to result in changes to the ubiquitin-proteasome pathway.     

α-Tocopheryl succinate causes mitochondrial permeabilization by preferential formation of Bak channels

Mitocans are drugs selectively killing cancer cells by destabilizing mitochondria and many induce apoptosis via generation of reactive oxygen species (ROS). However, the molecular events by which ROS production leads to apoptosis has not been clearly defined. In this study with the mitocan α-tocopheryl succinate (α-TOS) the role of the Bcl-2 family proteins in the mechanism of malignant cell apoptosis has been determined. Exposure of several different cancer cell lines to α-TOS increased expression of the Noxa protein, but none of the other proteins of the Bcl-2 family, an event that was independent of the cellular p53 status. α-TOS caused a profound conformational change in the pro-apoptotic protein, Bak, involving oligomerization in all cell types, and this also applied to the Bax protein, but only in non-small cell lung cancer cells. Immunoprecipitation studies indicated that α-TOS activates the two BH1-3 proteins, Bak or Bax, to form high molecular weight complexes in the mitochondria. RNAi knockdown revealed that Noxa and Bak are required for α-TOS-induced apoptosis, and the role of Bak was confirmed using Bak- and/or Bax-deficient cells. We conclude that the major events induced by α-TOS in cancer cells downstream of ROS production leading to mitochondrial apoptosis involve the Noxa-Bak axis. It is proposed that this represents a common mechanism for mitochondrial destabilization activated by a variety of mitocans that induce accumulation of ROS in the early phases of apoptosis.     

Effects of deoxynivalenol and zearalenone on oxidative stress and blood phagocytic activity in broilers

Effects of dietary contamination with various levels of deoxynivalenol (DON) and zearalenone (ZEA) were investigated on Ross 308 hybrid broilers of both sexes. After hatching, all chickens were fed an identical control diet for two weeks. Then chickens of Group 1 received a diet contaminated with DON and ZEA, both being 3.4 mg kg(-1), while Group 2 received DON and ZEA at 8.2 and 8.3 mg kg(-1), respectively. The diet of the control group contained background levels of mycotoxins. Samples of blood and tissues were collected after two weeks. Intake of both contaminated diets resulted in a significantly decreased activity of glutathione peroxidase (GPx) and increased level of malondialdehyde (MDA) in liver tissue, while in kidneys the concentration of MDA was significantly increased only in Group 1. On the other hand, activities of blood GPx and plasma gamma-glutamyltransferase (GGT) were elevated in Group 2 only. Activities of thioredoxin reductase in liver and GPx in duodenal mucosa tissues, superoxide dismutase (SOD) in erythrocytes as well as levels of MDA in duodenal mucosa and alpha-tocopherol in plasma were not affected by dietary mycotoxins. Blood phagocytic activity was significantly depressed in Group 1 and 2. These results demonstrate that diets contaminated with DON and ZEA at medium levels are already able to induce oxidative stress and compromise the blood phagocytic activity in fattening chickens.     

Efficient olfactory coding in the pheromone receptor neuron of a moth

The concept of coding efficiency holds that sensory neurons are adapted, through both evolutionary and developmental processes, to the statistical characteristics of their natural stimulus. Encouraged by the successful invocation of this principle to predict how neurons encode natural auditory and visual stimuli, we attempted its application to olfactory neurons. The pheromone receptor neuron of the male moth Antheraea polyphemus, for which quantitative properties of both the natural stimulus and the reception processes are available, was selected. We predicted several characteristics that the pheromone plume should possess under the hypothesis that the receptors perform optimally, i.e., transfer as much information on the stimulus per unit time as possible. Our results demonstrate that the statistical characteristics of the predicted stimulus, e.g., the probability distribution function of the stimulus concentration, the spectral density function of the stimulation course, and the intermittency, are in good agreement with those measured experimentally in the field. These results should stimulate further quantitative studies on the evolutionary adaptation of olfactory nervous systems to odorant plumes and on the plume characteristics that are most informative for the ‘sniffer’. Both aspects are relevant to the design of olfactory sensors for odour-tracking robots.     

2,5-Diaminopyrimidines and 3,5-disubstituted azapurines as inhibitors of glycogen synthase kinase-3 (GSK-3)

The discovery of two classes of pyrimidine-based inhibitors of GSK-3 is described. Optimization of these series led to inhibitors with IC(50)<10nM and >100-fold selectivity over Aurora A kinase. A proposed binding mode of 21b is presented. One compound (33) of the pyrimidine series showed promising pharmacokinetic parameters.     

Breeding ecology and behaviour of the last wild oriental Northern Bald Ibises (Geronticus eremita) in Syria

A relict colony of Northern Bald Ibis (Geronticus eremita), a critically endangered species, was unexpectedly discovered in Syria in 2002. During six subsequent breeding seasons (2002–2007), the 3, and then 2, breeding pairs of Northern Bald Ibises have shown to be still vital and, when intensively protected, showed a higher average breeding success than that recorded in Morocco, the only other country where these birds still breed in the wild. During the six breeding seasons, a total of 24 chicks fledged and left the breeding area successfully. Between 2004 and 2007, a total of 5 immature ibises have made a return to the colony, separately and later than adults. As a consequence, two recruitment events have taken place (2006 and 2007), partly compensating for the gradual decrease in the number of adults. Breeding adults arrive from migration during the second half of February, separately, and leave together around mid-July. They nest in cavities and ledges of two limestone cliffs of the central Syria desert, located 20 km apart, well protected from the predominant wind. Breeding behaviour and the cycle are described, summarised and compared with data from the wild colonies of Morocco and the colony of Turkey before the extinction. Key threats still in place at the Syrian breeding quarters are human disturbance during settling and incubation, chick depredation by ravens, uncontrolled hunting and habitat degradation. Recommendations on how to enhance the breeding performance and ensure the survival of this colony in the future are given.     

Computed modeling of humeral mid-shaft fracture treated by bundle nailing

Elastic bundle nailing is a method for simple humeral mid-shaft fracture osteosynthesis. The aim of our subsequent numerical simulations was to find out torsional and bending stiffness of an elastic bundle nailed humerus. Parametrical 3D numerical model was developed. The diameter of nails was the varying parameter of 1.8, 2.5, 3 and 4 mm. From our results can be seen that the bending stiffness in bundle nailing technique does not depend on nail diameter. On the contrary the torsional stiffness does highly depend on nail diameter. The dependency of the maximal stress on a nail diameter during bending and torsion of the humerus is non-linear. It can be seen that the higher diameter is used the higher stress occurs. Achieved results allow us for the recommendation of optimal nail diameter for this method, which lies between 2 and 3 mm.