Immunology of inflammatory bowel diseases.

The pathogenesis of inflammatory diseases involves complex interactions among genetic, environmental and immunologic factors, where the immune system plays a crucial role. The initiating factor may be a commonly present environmental antigen, but the defective mucosal immune response can't downregulate the inflammatory process, the resulting in chronic inflammation and tissue damage. The abnormal amplification of the immune system seems more likely to be a secondary and not a primary factor in the disease. IBD patients exhibit abnormalities in epithelial antigen presentation, and in the cellular and humoral immune system. The role of autoimmunity is unclear in IBD. The inflammatory mediator production and balance is also altered in IBD. Crohn's disease is characterised by a Th1 cytokine profile, while ulcerative colitis is characterised rather by a Th2 cytokine profile. Recent advances in the understanding of the pathogenesis of IBD led to major changes in the treatment of the disease. The newer agents target the key mediators involved in the inflammatory process.     

Screening of two terrestrial cyanobacteria for biotechnological production processes in shaking flasks,bubble columns,and stirred tank reactors

Terrestrial cyanobacteria are rarely used for biotechnological processes, although they show great potential in terms of value-added substances. Cyanobacteria from arid habitats are of particular interest because they tolerate higher temperatures and feature a different product spectrum compared with their aquatic counterparts. In addition, terrestrial cyanobacteria may represent an interesting source of pharmaceutical products. To investigate the future use of these organisms in biotechnological processes, the growth rates of Trichocoleus sociatus (formerly Microcoleus sociatus) and Nostoc muscorum were examined using three different cultivation systems: shaking flasks, bubble columns, and stirred tank reactors. Parameters including pH, temperature, CO₂ level, and power dissipation were investigated quantitatively in the three systems for their impact on growth rate. The highest growth rate of the terrestrial cyanobacteria could be achieved in a stirred tank reactor under enriched CO₂ concentration. In this system, the growth rate was 1.15 day^-1?±?0.08 (2 % vol.) for T. sociatus and 0.72 day^-1?±?0.22 (5 % vol.) for N. muscorum, based on dry weight. Furthermore, a basic mathematical model was created as an add-on to predict growth rates of terrestrial cyanobacteria based on their dependency on temperature, pH, and substrate concentration, in general. This model was used to estimate growth of N. muscorum in stirred tank reactor experiments with an accuracy of 98.8 % and with 75 % accuracy for T. sociatus.     

Oxytocin Receptor Gene Polymorphisms Are Associated with Human Directed Social Behavior in Dogs (Canis familiaris)

The oxytocin system has a crucial role in human sociality; several results prove that polymorphisms of the oxytocin receptor gene are related to complex social behaviors in humans. Dogs'' parallel evolution with humans and their adaptation to the human environment has made them a useful species to model human social interactions. Previous research indicates that dogs are eligible models for behavioral genetic research, as well. Based on these previous findings, our research investigated associations between human directed social behaviors and two newly described (−212AG, 19131AG) and one known (rs8679684) single nucleotide polymorphisms (SNPs) in the regulatory regions (5′ and 3′ UTR) of the oxytocin receptor gene in German Shepherd (N = 104) and Border Collie (N = 103) dogs. Dogs'' behavior traits have been estimated in a newly developed test series consisting of five episodes: Greeting by a stranger, Separation from the owner, Problem solving, Threatening approach, Hiding of the owner. Buccal samples were collected and DNA was isolated using standard protocols. SNPs in the 3′ and 5′ UTR regions were analyzed by polymerase chain reaction based techniques followed by subsequent electrophoresis analysis. The gene–behavior association analysis suggests that oxytocin receptor gene polymorphisms have an impact in both breeds on (i) proximity seeking towards an unfamiliar person, as well as their owner, and on (ii) how friendly dogs behave towards strangers, although the mediating molecular regulatory mechanisms are yet unknown. Based on these results, we conclude that similarly to humans, the social behavior of dogs towards humans is influenced by the oxytocin system.     

Emotion Attribution to a Non-Humanoid Robot in Different Social Situations

In the last few years there was an increasing interest in building companion robots that interact in a socially acceptable way with humans. In order to interact in a meaningful way a robot has to convey intentionality and emotions of some sort in order to increase believability. We suggest that human-robot interaction should be considered as a specific form of inter-specific interaction and that human–animal interaction can provide a useful biological model for designing social robots. Dogs can provide a promising biological model since during the domestication process dogs were able to adapt to the human environment and to participate in complex social interactions. In this observational study we propose to design emotionally expressive behaviour of robots using the behaviour of dogs as inspiration and to test these dog-inspired robots with humans in inter-specific context. In two experiments (wizard-of-oz scenarios) we examined humans'' ability to recognize two basic and a secondary emotion expressed by a robot. In Experiment 1 we provided our companion robot with two kinds of emotional behaviour (“happiness” and “fear”), and studied whether people attribute the appropriate emotion to the robot, and interact with it accordingly. In Experiment 2 we investigated whether participants tend to attribute guilty behaviour to a robot in a relevant context by examining whether relying on the robot''s greeting behaviour human participants can detect if the robot transgressed a predetermined rule. Results of Experiment 1 showed that people readily attribute emotions to a social robot and interact with it in accordance with the expressed emotional behaviour. Results of Experiment 2 showed that people are able to recognize if the robot transgressed on the basis of its greeting behaviour. In summary, our findings showed that dog-inspired behaviour is a suitable medium for making people attribute emotional states to a non-humanoid robot.     

Roles Played by the Na+/Ca2+ Exchanger and Hypothermia in the Prevention of Ischemia-Induced Carrier-Mediated Efflux of Catecholamines into the Extracellular Space: Implications for Stroke Therapy

The release of [³H]dopamine ([³H]DA) and [³H]noradrenaline ([³H]NA) in acutely perfused rat striatal and cortical slice preparations was measured at 37 °C and 17 °C under ischemic conditions. The ischemia was simulated by the removal of oxygen and glucose from the Krebs solution. At 37 °C, resting release rates in response to ischemia were increased; in contrast, at 17 °C, resting release rates were significantly reduced, or resting release was completely prevented. The removal of extracellular Ca²⁺ further increased the release rates of [³H]DA and [³H]NA induced by ischemic conditions. This finding indicated that the Na⁺/Ca²⁺ exchanger (NCX), working in reverse in the absence of extracellular Ca²⁺, fails to trigger the influx of Ca²⁺ in exchange for Na⁺ and fails to counteract ischemia by further increasing the intracellular Na⁺ concentration ([Na⁺]_i). KB-R7943, an inhibitor of NCX, significantly reduced the cytoplasmic resting release rate of catecholamines under ischemic conditions and under conditions where Ca²⁺ was removed. Hypothermia inhibited the excessive release of [³H]DA in response to ischemia, even in the absence of Ca²⁺. These findings further indicate that the NCX plays an important role in maintaining a high [Na⁺]_i, a condition that may lead to the reversal of monoamine transporter functions; this effect consequently leads to the excessive cytoplasmic tonic release of monoamines and the reversal of the NCX. Using HPLC combined with scintillation spectrometry, hypothermia, which enhances the stimulation-evoked release of DA, was found to inhibit the efflux of toxic DA metabolites, such as 3,4-dihydroxyphenylacetaldehyde (DOPAL). In slices prepared from human cortical brain tissue removed during elective neurosurgery, the uptake and release values for [³H]NA did not differ from those measured at 37 °C in slices that were previously maintained under hypoxic conditions at 8 °C for 20 h. This result indicates that hypothermia preserves the functions of the transport and release mechanisms, even under hypoxic conditions. Oxidative stress (H₂O₂), a mediator of ischemic brain injury enhanced the striatal resting release of [³H]DA and its toxic metabolites (DOPAL, quinone). The study supports our earlier findings that during ischemia transmitters are released from the cytoplasm. In addition, the major findings of this study that hypothermia of brain slice preparations prevents the extracellular calcium concentration ([Ca²⁺]_o)-independent non-vesicular transmitter release induced by ischemic insults, inhibiting Na⁺/Cl^?-dependent membrane transport of monoamines and their toxic metabolites into the extracellular space, where they can exert toxic effects.

     

Ca2+-dependent induction of conidiation in submerged cultures of Trichoderma viride

The presence of Ca2+ (up to 0.1 mol/L) in the cultivation media was found to induce the formation of conidia in submerged mycelia of Trichoderma viride in a concentration-dependent manner. Ca2+ dramatically stimulated conidiation after 70 h of cultivation. The effect was present in the dark, and illumination stimulated it only marginally. Low (less than 100 micromol/L) Ca2+ concentrations induced the formation of chlamydospores. Sr2+ could substitute Ca2+ in conidiogenesis with lower efficiency (almost 2 orders of magnitude), while the efficiency of Mg2+, Mn2+, or Ba2+ was lower by almost 3 orders of magnitude. Our results demonstrate that mycelial Ca2+ homeostasis has powerful effects on the conidiation and mycelial morphogenesis in T. viride, and they suggest that there is an additional mechanism of conidiation in addition to those induced by light and starvation.     

Protein kinase C protects from DNA damage-induced necrotic cell death by inhibiting poly(ADP-ribose) polymerase-1

The goal of the current study, conducted in freshly isolated thymocytes was (1) to investigate the possibility that the activation of poly(ADP-ribose) polymerase-1 (PARP-1) in an intact cell can be regulated by protein kinase C (PKC) mediated phosphorylation and (2) to examine the consequence of this regulatory mechanism in the context of cell death induced by the genotoxic agent. In cells stimulated by the PKC activating phorbol esters, DNA breakage was unaffected, PARP-1 was phosphorylated, 1-methyl-3-nitro-1-nitrosoguanidine-induced PARP activation and cell necrosis were suppressed, with all these effects attenuated by the PKC inhibitors GF109203X or G?6976. Inhibition of cellular PARP activity by PKC-mediated phosphorylation may provide a plausible mechanism for the previously observed cytoprotective effects of PKC activators.