Inhibitory effect of the flavonoid silymarin on the erythrocyte hemolysis induced by phenylhydrazine

The flavonoid silymarin, which is used as a therapeutical agent in the treatment of liver diseases, can inhibit the hemolysis and lipid peroxidation induced by phenylhydrazine on erythrocytes obtained from rats treated with the flavonoid. This effect is ascribed to the antioxidant properties as a free radical scavenger exhibited by the flavonoid. Silymarin failed to inhibit the glutathione depletion induced by phenylhydrazine on erythrocytes. It is proposed that the flavonoid acts at the membrane level of the cell avoiding the lipid peroxidative and fluidizing effect of phenylhydrazine.     

Geographical variation in the potential of mice to constrain an ant-seed dispersal mutualism

Pre‐ and post‐dispersal Helleborus foetidus (Ranunculaceae) seed predation by mice Apodemus sylvaticus as well as post‐dispersal seed removal by ants was studied, during two years, in six plant populations within three geographical regions (Caurel, Cazorla and Mágina) of the Iberian Peninsula. An observational approach revealed strong interregional differences in seed predation by mice during the pre‐dispersal phase, with high and similar rates of predation in Cazorla and Mágina and much lower rates in Caurel. There were also significant inter‐annual variations on pre‐dispersal seed predation by mice, while the existing habitat‐related differences (of lower magnitude) were not consistent across regions. Field experiments based on seed‐offering exclosures, showed that, despite some interregional variation, post‐dispersal seed removal by ants was consistently high through all spatial and temporal scales considered, with most seeds being removed within 48 h. Conversely, post‐dispersal seed predation by mice was highly variable among regions, being very high in Cazorla and minimal or absent in Caurel and Mágina. Interestingly, in Cazorla, in presence of mice, the number of seeds removed was rather independent of the presence/absence of ants, while under mice exclusion, it was determined by the presence/absence of ants. Conversely, in Caurel, the number of seeds removed by each remover agent (ants or mice) was independent of the presence/absence of the other agent. Thus, though uniquely in Cazorla, mice limited the number of seeds available to ants and, therefore, in this region could potentially have interfered on the development of seed traits that enable ants to efficiently harvest them. Our results support the notion that geographical variation over the Iberian Peninsula of mice seed predation may have promoted a mosaic of well‐matching and mismatching situations between H. foetidus diaspore traits and the characteristics of ant communities, which is consistent with some recent theories on the geographical structure of interactions.     

Pseudomonas aeruginosa cholinesterase and phosphorylcholine phosphatase: two enzymes contributing to corneal infection

Choline, acetylcholine and betaine used as the sole carbon, nitrogen or carbon and nitrogen source increase cholinesterase activity in addition to phosphorylcholine phosphatase and phospholipase C activities in Pseudomonas aeruginosa. The cholinesterase activity catalyses the hydrolysis of acetylthiocholine (Km approx. 0.13 mM) and propionylthiocholine (Km approx. 0.26 mM), but not butyrylthiocholine, which is a pure competitive inhibitor (Ki 0.05 mM). Increasing choline concentrations in the assay mixture decreased the affinity of cholinesterase for acetylthiocholine, but in all cases prevented inhibition raised by high substrate concentrations. Considering the properties of these enzymes, and the fact that in the corneal epithelium there exists a high acetylcholine concentration and that Pseudomonas aeruginosa produces corneal infection, it is proposed that these enzymes acting coordinately might contribute to the breakdown of the corneal epithelial membrane.     

Regulation of the proapoptotic functions of prostate apoptosis response-4 (Par-4) by casein kinase 2 in prostate cancer cells

The proapoptotic protein, prostate apoptosis response-4 (Par-4), acts as a tumor suppressor in prostate cancer cells. The serine/threonine kinase casein kinase 2 (CK2) has a well-reported role in prostate cancer resistance to apoptotic agents or anticancer drugs. However, the mechanistic understanding on how CK2 supports survival is far from complete. In this work, we demonstrate both in rat and humans that (i) Par-4 is a new substrate of the survival kinase CK2 and (ii) phosphorylation by CK2 impairs Par-4 proapoptotic functions. We also unravel different levels of CK2-dependent regulation of Par-4 between species. In rats, the phosphorylation by CK2 at the major site, S124, prevents caspase-mediated Par-4 cleavage (D123) and consequently impairs the proapoptotic function of Par-4. In humans, CK2 strongly impairs the apoptotic properties of Par-4, independently of the caspase-mediated cleavage of Par-4 (D131), by triggering the phosphorylation at residue S231. Furthermore, we show that human Par-4 residue S231 is highly phosphorylated in prostate cancer cells as compared with their normal counterparts. Finally, the sensitivity of prostate cancer cells to apoptosis by CK2 knockdown is significantly reversed by parallel knockdown of Par-4. Thus, Par-4 seems a critical target of CK2 that could be exploited for the development of new anticancer drugs.     

A Neurocomputational Model of the Mismatch Negativity

The mismatch negativity (MMN) is an event related potential evoked by violations of regularity. Here, we present a model of the underlying neuronal dynamics based upon the idea that auditory cortex continuously updates a generative model to predict its sensory inputs. The MMN is then modelled as the superposition of the electric fields evoked by neuronal activity reporting prediction errors. The process by which auditory cortex generates predictions and resolves prediction errors was simulated using generalised (Bayesian) filtering – a biologically plausible scheme for probabilistic inference on the hidden states of hierarchical dynamical models. The resulting scheme generates realistic MMN waveforms, explains the qualitative effects of deviant probability and magnitude on the MMN – in terms of latency and amplitude – and makes quantitative predictions about the interactions between deviant probability and magnitude. This work advances a formal understanding of the MMN and – more generally – illustrates the potential for developing computationally informed dynamic causal models of empirical electromagnetic responses.