Behavioural stress responses predict environmental perception in European sea bass (Dicentrarchus labrax)

Individual variation in the response to environmental challenges depends partly on innate reaction norms, partly on experience-based cognitive/emotional evaluations that individuals make of the situation. The goal of this study was to investigate whether pre-existing differences in behaviour predict the outcome of such assessment of environmental cues, using a conditioned place preference/avoidance (CPP/CPA) paradigm. A comparative vertebrate model (European sea bass, Dicentrarchus labrax) was used, and ninety juvenile individuals were initially screened for behavioural reactivity using a net restraining test. Thereafter each individual was tested in a choice tank using net chasing as aversive stimulus or exposure to familiar conspecifics as appetitive stimulus in the preferred or non preferred side respectively (called hereafter stimulation side). Locomotor behaviour (i.e. time spent, distance travelled and swimming speed in each tank side) of each individual was recorded and analysed with video software. The results showed that fish which were previously exposed to appetitive stimulus increased significantly the time spent on the stimulation side, while aversive stimulus led to a strong decrease in time spent on the stimulation side. Moreover, this study showed clearly that proactive fish were characterised by a stronger preference for the social stimulus and when placed in a putative aversive environment showed a lower physiological stress responses than reactive fish. In conclusion, this study showed for the first time in sea bass, that the CPP/CPA paradigm can be used to assess the valence (positive vs. negative) that fish attribute to different stimuli and that individual behavioural traits is predictive of how stimuli are perceived and thus of the magnitude of preference or avoidance behaviour.European Commission [265957]; Portuguese Fundacao para a Ciencia e Tecnologia (FCT) [FRH/BPD/72952/2010]; FCT [SFRH/BD/80029/2011

Off the Couch and Onto the Streets: Toward an Ethnographic Psychoanalysis

Psychoanalysis has much to gain by incorporating ethnographic methods into its repertoire. Recent works in ethnographic psychoanalysis demonstrate how psychoanalysis stands to function better as both community intervention and participatory action research. This article describes the historical convergence between psychoanalysis and cultural anthropology and situates ethnographic psychoanalysis within interdisciplinary theory and practice

The Ocular Conjunctiva as a Mucosal Immunization Route: A Profile of the Immune Response to the Model Antigen Tetanus Toxoid

Background: In a quest for a needle-free vaccine administration strategy, we evaluated the ocular conjunctiva as an alternative mucosal immunization route by profiling and comparing the local and systemic immune responses to the subcutaneous or conjunctival administration of tetanus toxoid (TTd), a model antigen. Materials and methods: BALB/c and C57BL/6 mice were immunized either subcutaneously with TTd alone or via the conjunctiva with TTd alone, TTd mixed with 2% glycerol or TTd with merthiolate-inactivated whole-cell B. pertussis (wBP) as adjuvants. Mice were immunized on days 0, 7 and 14 via both routes, and an evaluation of the local and systemic immune responses was performed two weeks after the last immunization. Four weeks after the last immunization, the mice were challenged with a lethal dose (2 x LD50) of tetanus toxin. Results: The conjunctival application of TTd in BALB/c mice induced TTd-specific secretory IgA production and skewed the TTd-specific immune response toward a Th1/Th17 profile, as determined by the stimulation of IFN gamma and IL-17A secretion and/or the concurrent pronounced reduction of IL-4 secretion, irrespective of the adjuvant. In conjunctivaly immunized C57BL/6 mice, only TTd administered with wBP promoted the establishment of a mixed Th1/Th17 TTd-specific immune response, whereas TTd alone or TTd in conjunction with glycerol initiated a dominant Th1 response against TTd. Immunization via the conjunctiva with TTd plus wBP adjuvant resulted in a 33% survival rate of challenged mice compared to a 0% survival rate in non-immunized animals (p lt 0.05). Conclusion: Conjunctival immunization with TTd alone or with various adjuvants induced TTd-specific local and systemic immune responses, predominantly of the Th1 type. The strongest immune responses developed in mice that received TTd together with wBP, which implies that this alternative route might tailor the immune response to fight intracellular bacteria or viruses more effectively

Genetic Determinants of Time Perception Mediated by the Serotonergic System

Background: The present study investigates neurobiological underpinnings of individual differences in time perception. Methodology: Forty-four right-handed Russian Caucasian males (18–35 years old) participated in the experiment. The polymorphism of the genes related to the activity of serotonin (5-HT) and dopamine (DA)-systems (such as 5-HTT, 5HT2a, MAOA, DAT, DRD2, COMT) was determined upon the basis of DNA analysis according to a standard procedure. Time perception in the supra-second range (mean duration 4.8 s) was studied, using the duration discrimination task and parametric fitting of psychometric functions, resulting in individual determination of the point of subjective equality (PSE). Assuming the ‘dual klepsydra model ’ of internal duration representation, the PSE values were transformed into equivalent values of the parameter k (kappa), which is a measure of the ‘loss rate ’ of the duration representation. An association between time representation parameters (PSE and k, respectively) and 5-HT-related genes was found, but not with DArelated genes. Higher ‘loss rate ’ (k) of the cumulative duration representation were found for the carriers of genotypes characterized by higher 5-HT transmission, i.e., 1) lower 5-HT reuptake, known for the 5-HTTLPR SS polymorphism compared with LL, 2) lower 5-HT degradation, described for the ‘low expression ’ variant of MAOA VNTR gene compared with ‘high expression ’ variant, and 3) higher 5-HT2a receptor density, proposed for the TT polymorphism of 5-HT2a T102C gene compared with CC

Comparison study on k-word statistical measures for protein: From sequence to 'sequence space'

<p>Abstract</p> <p>Background</p> <p>Many proposed statistical measures can efficiently compare protein sequence to further infer protein structure, function and evolutionary information. They share the same idea of using <it>k</it>-word frequencies of protein sequences. Given a protein sequence, the information on its related protein sequences hasn't been used for protein sequence comparison until now. This paper proposed a scheme to construct protein 'sequence space' which was associated with protein sequences related to the given protein, and the performances of statistical measures were compared when they explored the information on protein 'sequence space' or not. This paper also presented two statistical measures for protein: <it>gre.k </it>(generalized relative entropy) and <it>gsm.k </it>(gapped similarity measure).</p> <p>Results</p> <p>We tested statistical measures based on protein 'sequence space' or not with three data sets. This not only offers the systematic and quantitative experimental assessment of these statistical measures, but also naturally complements the available comparison of statistical measures based on protein sequence. Moreover, we compared our statistical measures with alignment-based measures and the existing statistical measures. The experiments were grouped into two sets. The first one, performed via ROC (Receiver Operating Curve) analysis, aims at assessing the intrinsic ability of the statistical measures to discriminate and classify protein sequences. The second set of the experiments aims at assessing how well our measure does in phylogenetic analysis. Based on the experiments, several conclusions can be drawn and, from them, novel valuable guidelines for the use of protein 'sequence space' and statistical measures were obtained.</p> <p>Conclusion</p> <p>Alignment-based measures have a clear advantage when the data is high redundant. The more efficient statistical measure is the novel <it>gsm.k </it>introduced by this article, the <it>cos.k </it>followed. When the data becomes less redundant, <it>gre.k </it>proposed by us achieves a better performance, but all the other measures perform poorly on classification tasks. Almost all the statistical measures achieve improvement by exploring the information on 'sequence space' as word's length increases, especially for less redundant data. The reasonable results of phylogenetic analysis confirm that <it>Gdis.k </it>based on 'sequence space' is a reliable measure for phylogenetic analysis. In summary, our quantitative analysis verifies that exploring the information on 'sequence space' is a promising way to improve the abilities of statistical measures for protein comparison.</p

5-HTTLPR Polymorphism Impacts Task-Evoked and Resting-State Activities of the Amygdala in Han Chinese

Background: Prior research has shown that the amygdala of carriers of the short allele (s) of the serotonin transporter (5-HTT) gene (5-HTTLPR) have a larger response to negative emotional stimuli and higher spontaneous activity during the resting state than non-carriers. However, recent studies have suggested that the effects of 5-HTTLPR may be specific to different ethnic groups. Few studies have been conducted to address this issue. Methodology/Principal Findings: Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) was conducted on thirty-eight healthy Han Chinese subjects (l/l group, n = 19; s/s group, n = 19) during the resting state and during an emotional processing task. Compared with the s/s group, the l/l group showed significantly increased regional homogeneity or local synchronization in the right amygdala during the resting state (|t|.2.028, p,0.05, corrected), but no significant difference was found in the bilateral amygdala in response to negative stimuli in the emotional processing task. Conclusions/Significance: 5-HTTLPR can alter the spontaneous activity of the amygdala in Han Chinese. However, the effect of 5-HTTLPR on the amygdala both in task state and resting state in Asian population was no similar with Caucasians. The

Glycogen synthase kinase-3 inhibition disrupts nuclear factor-kappaB activity in pancreatic cancer, but fails to sensitize to gemcitabine chemotherapy

<p>Abstract</p> <p>Background</p> <p>Aberrant activation NF-kappaB has been proposed as a mechanism of drug resistance in pancreatic cancer. Recently, inhibition of glycogen synthase kinase-3 has been shown to exert anti-tumor effects on pancreatic cancer cells by suppressing NF-kappaB. Consequently, we investigated whether inhibition of GSK-3 sensitizes pancreatic cancer cells to the chemotherapeutic agent gemcitabine.</p> <p>Methods</p> <p>GSK-3 inhibition was achieved using the pharmacological agent AR-A014418 or siRNA against GSK-3 alpha and beta isoforms. Cytotoxicity was measured using a Sulphorhodamine B assay and clonogenic survival following exposure of six different pancreatic cancer cell lines to a range of doses of either gemcitabine, AR-A014418 or both for 24, 48 and 72 h. We measured protein expression levels by immunoblotting. Basal and TNF-alpha induced activity of NF-kappaB was assessed using a luciferase reporter assay in the presence or absence of GSK-3 inhibition.</p> <p>Results</p> <p>GSK-3 inhibition reduced both basal and TNF-alpha induced NF-kappaB luciferase activity. Knockdown of GSK-3 beta reduced nuclear factor kappa B luciferase activity to a greater extent than GSK-3 alpha, and the greatest effect was seen with dual knockdown of both GSK-3 isoforms. GSK-3 inhibition also resulted in reduction of the NF-kappaB target proteins XIAP, Bcl-X_L, and cyclin D1, associated with growth inhibition and decreased clonogenic survival. In all cell lines, treatment with either AR-A014418, or gemcitabine led to growth inhibition in a dose- and time-dependent manner. However, with the exception of PANC-1 where drug synergy occurred with some dose schedules, the inhibitory effect of combined drug treatment was additive, sub-additive, or even antagonistic.</p> <p>Conclusion</p> <p>GSK-3 inhibition has anticancer effects against pancreatic cancer cells with a range of genetic backgrounds associated with disruption of NF-kappaB, but does not significantly sensitize these cells to the standard chemotherapy agent gemcitabine. This lack of synergy might be context or cell line dependent, but could also be explained on the basis that although NF-kappaB is an important mediator of pancreatic cancer cell survival, it plays a minor role in gemcitabine resistance. Further work is needed to understand the mechanisms of this effect, including the potential for rational combination of GSK3 inhibitors with other targeted agents for the treatment of pancreatic cancer.</p

Assessment of predictive models for chlorophyll-a concentration of a tropical lake

<p>Abstract</p> <p>Background</p> <p>This study assesses four predictive ecological models; Fuzzy Logic (FL), Recurrent Artificial Neural Network (RANN), Hybrid Evolutionary Algorithm (HEA) and multiple linear regressions (MLR) to forecast chlorophyll- a concentration using limnological data from 2001 through 2004 of unstratified shallow, oligotrophic to mesotrophic tropical Putrajaya Lake (Malaysia). Performances of the models are assessed using Root Mean Square Error (RMSE), correlation coefficient (r), and Area under the Receiving Operating Characteristic (ROC) curve (AUC). Chlorophyll-a have been used to estimate algal biomass in aquatic ecosystem as it is common in most algae. Algal biomass indicates of the trophic status of a water body. Chlorophyll- a therefore, is an effective indicator for monitoring eutrophication which is a common problem of lakes and reservoirs all over the world. Assessments of these predictive models are necessary towards developing a reliable algorithm to estimate chlorophyll- a concentration for eutrophication management of tropical lakes.</p> <p>Results</p> <p>Same data set was used for models development and the data was divided into two sets; training and testing to avoid biasness in results. FL and RANN models were developed using parameters selected through sensitivity analysis. The selected variables were water temperature, pH, dissolved oxygen, ammonia nitrogen, nitrate nitrogen and Secchi depth. Dissolved oxygen, selected through stepwise procedure, was used to develop the MLR model. HEA model used parameters selected using genetic algorithm (GA). The selected parameters were pH, Secchi depth, dissolved oxygen and nitrate nitrogen. RMSE, r, and AUC values for MLR model were (4.60, 0.5, and 0.76), FL model were (4.49, 0.6, and 0.84), RANN model were (4.28, 0.7, and 0.79) and HEA model were (4.27, 0.7, and 0.82) respectively. Performance inconsistencies between four models in terms of performance criteria in this study resulted from the methodology used in measuring the performance. RMSE is based on the level of error of prediction whereas AUC is based on binary classification task.</p> <p>Conclusions</p> <p>Overall, HEA produced the best performance in terms of RMSE, r, and AUC values. This was followed by FL, RANN, and MLR.</p

Statistical Epistasis and Functional Brain Imaging Support a Role of Voltage-Gated Potassium Channels in Human Memory

Despite the current progress in high-throughput, dense genome scans, a major portion of complex traits' heritability still remains unexplained, a phenomenon commonly termed “missing heritability.” The negligence of analytical approaches accounting for gene-gene interaction effects, such as statistical epistasis, is probably central to this phenomenon. Here we performed a comprehensive two-way SNP interaction analysis of human episodic memory, which is a heritable complex trait, and focused on 120 genes known to show differential, memory-related expression patterns in rat hippocampus. Functional magnetic resonance imaging was also used to capture genotype-dependent differences in memory-related brain activity. A significant, episodic memory-related interaction between two markers located in potassium channel genes (KCNB2 and KCNH5) was observed (Pnominal combined = 0.000001). The epistatic interaction was robust, as it was significant in a screening (Pnominal = 0.0000012) and in a replication sample (Pnominal = 0.01). Finally, we found genotype-dependent activity differences in the parahippocampal gyrus (Pnominal = 0.001) supporting the behavioral genetics finding. Our results demonstrate the importance of analytical approaches that go beyond single marker statistics of complex traits

Differential hypoglycaemic, anorectic, autonomic and emetic effects of the glucagon-like peptide receptor agonist, exendin-4, in the conscious telemetered ferret.

Background: Rodents are incapable of emesis and consequently the emetic potential of glucagon-like peptide-1 receptor (GLP-1R) agonists in studies designed to assess a potential blood glucose lowering action of the compound was missed. Therefore, we investigated if the ferret, a carnivore with demonstrated translation capability in emesis research, would identify the emetic potential of the GLP-1R agonist, exendin-4, and any associated effects on gastric motor function, appetite and cardiovascular homeostasis. Methods: The biological activity of the GLP-1R ligands was investigated in vivo using a glucose tolerance test in pentobarbitone-anesthetised ferrets and in vitro using organ bath studies. Radiotelemetry was used to investigate the effect of exendin-4 on gastric myoelectric activity (GMA) and cardiovascular function in conscious ferrets; behaviour was also simultaneously assessed. Western blot was used to characterize GLP-1R distribution in the gastrointestinal and brain tissues. Results: In anesthetised ferrets, exendin-4 (30 nmol/kg, s.c.) reduced experimentally elevated blood glucose levels by 36.3%, whereas the GLP-1R antagonist, exendin (9–39) (300 nmol/kg, s.c.) antagonised the effect and increased AUC0–120 by 31.0% when injected alone (P < 0.05). In animals with radiotelemetry devices, exendin-4 (100 nmol/kg, s.c.) induced emesis in 1/9 ferrets, but inhibited food intake and decreased heart rate variability (HRV) in all animals (P < 0.05). In the animals not exhibiting emesis, there was no effect on GMA, mean arterial blood pressure, heart rate, or core body temperature. In the ferret exhibiting emesis, there was a shift in the GMA towards bradygastria with a decrease in power, and a concomitant decrease in HRV. Western blot revealed GLP-1R throughout the gastrointestinal tract but exendin-4 (up to 300 nM) and exendin (9–39), failed to contract or relax isolated ferret gut tissues. GLP-1R were found in all major brain regions and the levels were comparable those in the vagus nerve. Conclusions: Peripherally administered exendin-4 reduced blood glucose and inhibited feeding with a low emetic potential similar to that in humans (11% vs 12.8%). A disrupted GMA only occurred in the animal exhibiting emesis raising the possibility that disruption of the GMA may influence the probability of emesis occurring in response to treatment with GLP-1R agonists