The influence of recent decisions on future goal selection

Recent decisions about actions and goals can have effects on future choices. Several studies have shown an effect of the previous trial history on neural activity in a subsequent trial. Often, but not always, these effects originate from task requirements that make it necessary to maintain access to previous trial information to make future decisions. Maintaining the information about recent decisions and their outcomes can play an important role in both adapting to new contingencies and learning. Previous goal decisions must be distinguished from goals that are currently being planned to avoid perseveration or more general errors. Output monitoring is probably based on this separation of accomplished past goals from pending future goals that are being pursued. Behaviourally, it has been shown that the history context can influence the location, error rate and latency of successive responses. We will review the neurophysiological studies in the literature, including data from our laboratory, which support a role for the frontal lobe in tracking previous goal selections and outputs when new goals need to be accomplished.     

Mandible strike: the lethal weapon of Odontomachus opaciventris against small prey

In order to study both the hunting efficiency and the flexibility of their predatory behavior, solitary hunters of the trap-jaw ant Odontomachus opaciventris were offered small prey (termites, fruit flies and tenebrionid larvae), presenting different morphological or defensive characteristics. The monomorphic hunters showed a moderately flexible predatory behavior characterized by short capture sequences and a noteworthy efficiency of their mandible strike (76.7-100% of prey retrievals), even when presented with Nasutitermes soldiers. Contrary to most poneromorph ants, antennal palpation of the prey before the attack was always missing, no particular targeted region of the prey's body was preferred, and no 'prudent' posture was ever exhibited. Moreover, stinging was regularly performed on bulky, fast moving fruit flies, very scarcely with sclerotized tenebrionid larvae, but never occurred with Nasutitermes workers or soldiers despite their noxious chemical defense. These results suggest that, whatever the risk linked to potentially dangerous prey, O. opaciventris predatory strategy optimizes venom use giving top priority to the swiftness and strength of the lethal trap-jaw system used by hunters as first strike weapon to subdue rapidly a variety of small prey, ranging from 0.3 to 2 times their own body size and from 0.1 to 2 times their weight. Such risk-prone predatory behavior is likely to be related to the large size of O. opaciventris colonies where the death of a forager might be of lesser vital outcome than in small colony-size species.     

Role of an invariant lysine residue in folate binding on Escherichia coli thymidylate synthase: calorimetric and crystallographic analysis of the K48Q mutant

Thymidylate synthase (TS) catalyzes the reductive methylation of deoxyuridine monophosphate (dUMP) using methylene tetrahydrofolate (CH(2)THF) as cofactor, the glutamate tail of which forms a water-mediated hydrogen bond with an invariant lysine residue of this enzyme. To understand the role of this interaction, we studied the K48Q mutant of Escherichia coli TS using structural and biophysical methods. The k(cat) of the K48Q mutant was 430-fold lower than wild-type TS in activity, while the K(m) for the (R)-stereoisomer of CH(2)THF was 300 microM, about 30-fold larger than K(m) from the wild-type TS. Affinity constants were determined using isothermal titration calorimetry, which showed that binding was reduced by one order of magnitude for folate-like TS inhibitors, such as propargyl-dideazafolate (PDDF) or compounds that distort the TS active site like BW1843U89 (U89). The crystal structure of the K48Q-dUMP complex revealed that dUMP binding is not impaired in the mutant, and that U89 in a ternary complex of K48Q-nucleotide-U89 was bound in the active site with subtle differences relative to comparable wild-type complexes. PDDF failed to form ternary complexes with K48Q and dUMP. Thermodynamic data correlated with the structural determinations, since PDDF binding was dominated by enthalpic effects while U89 had an important entropic component. In conclusion, K48 is critical for catalysis since it leads to a productive CH(2)THF binding, while mutation at this residue does not affect much the binding of inhibitors that do not make contact with this group.     

Inhibition of CD73 improves B cell-mediated anti-tumor immunity in a mouse model of melanoma

CD73 is a cell surface enzyme that suppresses T cell-mediated immune responses by producing extracellular adenosine. Growing evidence suggests that targeting CD73 in cancer may be useful for an effective therapeutic outcome. In this study, we demonstrate that administration of a specific CD73 inhibitor, adenosine 5'-(α,β-methylene)diphosphate (APCP), to melanoma-bearing mice induced a significant tumor regression by promoting the release of Th1- and Th17-associated cytokines in the tumor microenvironment. CD8(+) T cells were increased in melanoma tissue of APCP-treated mice. Accordingly, in nude mice APCP failed to reduce tumor growth. Importantly, we observed that after APCP administration, the presence of B cells in the melanoma tissue was greater than that observed in control mice. This was associated with production of IgG2b within the melanoma. Depletion of CD20(+) B cells partially blocked the anti-tumor effect of APCP and significantly reduced the production of IgG2b induced by APCP, implying a critical role for B cells in the anti-tumor activity of APCP. Our results also suggest that APCP could influence B cell activity to produce IgG through IL-17A, which significantly increased in the tumor tissue of APCP-treated mice. In support of this, we found that in melanoma-bearing mice receiving anti-IL-17A mAb, the anti-tumor effect of APCP was ablated. This correlated with a reduced capacity of APCP-treated mice to mount an effective immune response against melanoma, as neutralization of this cytokine significantly affected both the CD8(+) T cell- and B cell-mediated responses. In conclusion, we demonstrate that both T cells and B cells play a pivotal role in the APCP-induced anti-tumor immune response.     

Exposure to 50 Hz electromagnetic field raises the levels of the anti-apoptotic protein BAG3 in melanoma cells

The expression of the anti‐apoptotic protein BAG3 is induced in several cell types by exposure to high temperature, oxidants, and other stressful agents. We investigated whether exposure to 50 Hz electromagnetic fields raised BAG3 levels in the human melanoma cell line M14, in vitro and in orthotopic xenografts. Exposure of cultured cells or xenografts for 6 h or 4 weeks, respectively, produced a significant (P < 0.01) increase in BAG3 protein amounts. Interestingly, at the same times, we could not detect any significant variation in the levels of HSP70/72 protein or cell apoptosis. These results confirm the stressful effect of exposure to ELF in human cells, by identifying BAG3 protein as a marker of ELF‐induced stress. Furthermore, they suggest that BAG3 induction by ELF may contribute to melanoma cell survival and/or resistance to therapy. J. Cell. Physiol. 226: 2901–2907, 2011. © 2011 Wiley‐Liss, Inc.     

Trichoderma aureoviride URM 5158 and Trichoderma hamatum URM 6656 are Biocontrol Agents that act against Cassava Root rot through different Mechanisms

Trichoderma has been used to manage a large number of pathogens, but there is a gap in the mechanisms used by these biocontrol agents regarding the physiological response of cassava plants (Manihot esculenta) when it is subjected to cassava root rot. The aims of this study were to investigate the antagonist activity of ten Trichoderma isolates against Fusarium solani on potato dextrose Agar (PDA), to quantify the chitinase production, to select and test in vivo the best isolate from each experiment and to assess the physiological response of cassava to the production of oxidative enzyme complex production (ascorbate peroxidase, catalase, peroxidase and polyphenol oxidase). All Trichoderma isolates have shown competitive capability against F. solani, and Trichoderma hamatum URM 6656 showed the highest inhibition of pathogen growth (88.91%). All isolates have shown chitinase activity, but Trichoderma aureoviride URM 5158 produced the highest amount of chitinase. T. hamatum URM 6656 and T. aureoviride URM 5158 were selected to be applied in vivo. The two Trichoderma strains reduced 64 and 60% of the disease severity in the shoot and 82 and 84% in the root. Cassava plants infected with Trichoderma have shown the highest peroxidase and ascorbate peroxidase production. Our results have indicated that T. aureoviride URM 5158 is an effective biocontrol agent against cassava root rot caused by F. solani, because it presented competitive antagonist capability in vitro, the highest chitinase production, and reduced the cassava root rot severity. The application of T. aureoviride has led to the maximum enzyme activity of reactive oxygen species group in cassava plants.     

Cell death induction and nitric oxide biosynthesis in white poplar (Populus alba) suspension cultures exposed to alfalfa saponins

The present work reports on the biological activity of alfalfa (Medicago sativa) saponins on white poplar (Populus alba, cultivar ‘Villafranca’) cell suspension cultures. The extracts from alfalfa roots, aerial parts and seeds were characterized for their saponin content by means of thin layer chromatography (TLC) and electrospray ionisation coupled to mass spectrometry. The quantitative saponin composition from the different plant extracts was determined considering the aglycone moieties and determined by gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS) analyses. Only soyasapogenin I was detected in the seed extract while several other saponins were found in the root and leaf extracts. Actively proliferating white poplar cell cultures were challenged with the different saponin extracts. Only alfalfa root saponins, at 50 µg ml^?1, induced significant cell death rates (75.00 ± 4.90%). Different cell subpopulations with peculiar cell death morphologies were observed and the programmed cell death (PCD)/necrosis ratio was reduced at increasing saponin concentrations. Enhancement of nitric oxide (NO) production was observed in white poplar cells treated with root saponins (RSs) at 50 µg ml^?1 and release of reactive oxygen species (ROS) in the culture medium was also demonstrated. Saponin‐induced NO production was sensitive to sodium azide and N^G‐monomethyl‐l ‐arginine, two specific inhibitors of distinct pathways for NO biosynthesis in plant cells.     

Ontogenetic integration between force production and force reception: a case study in Ctenomys (Rodentia: Caviomorpha)

During ontogeny, complex adaptations undergo changes that sometimes entail different functional capabilities. This fact constrains the behaviour of organisms at each developmental stage. Rodents have ever‐growing incisors for gnawing, and a powerful jaw musculature. The incisors are long enough, relative to their diameter, to be affected by bending stresses. This is particularly true in the subterranean Ctenomys that uses its incisors for digging. We measured bite force (BF) in individuals of different ages using a force transducer. We estimated incisor section modulus Z, a geometrical parameter proportional to bending strength. A relative strength indicator was calculated as S = Z/BF incisor length. We found that ontogenetic BF scales to body mass with positive allometry. However, an anova showed non‐significant differences in S, neither between sexes nor among age classes. This result implies that during growth, incisors might have a rather similar ability to withstand bending stresses from increasing masticatory forces, what may be considered evidence of ontogenetic integration of force production (by muscles) and force reception (by the incisors). This fact well correlates with the observation that pups and juveniles of C. talarum incorporate solid foods shortly after birth, and they are able to dig burrows early in life.     

Paleolirnnological records of carotenoids and carbonaceous particles in sediments of some lakes in Southern Alps

Stratigraphic analyses of organic carbon, organic nitrogen and algal and bacterial carotenoids in short cores of profundal sediments of four alpine lakes (Tovel, Leit, Paione superiore and Tom) were used to reconstruct their trophic history. In addition, depth distribution of carbonaceous particle concentrations provided information on lake contamination from atmospheric deposition. In three lakes (Tovel, Leit and Tom), sedimentary carotenoids unique to sulfur photosynthetic bacteria (okenone and isorenieratene) provide evidence of changes in the oxygen, light and sulfide conditions in the water column. All the lakes are oligotrophic or moderately productive, and the algal community is dominated by Chlorophyta, Pyrrhophyta and Cryptophyta. Cyanobacteria are rather poorly represented. The steep increase of carbonaceous particles in the uppermost sediment layers of all the lakes suggests that lake contamination by atmospheric transport of pollutants began in the 1940s to 1950s. These data, coupled with those from a parallel study on Chrysophycean scale-inferred pH, indicate recent acidification in those which are poorly buffered (Paione superiore and Leit).