Environmental enrichment promotes neural plasticity and cognitive ability in fish

Different kinds of experience during early life can play a significant role in the development of an animal''s behavioural phenotype. In natural contexts, this influences behaviours from anti-predator responses to navigation abilities. By contrast, for animals reared in captive environments, the homogeneous nature of their experience tends to reduce behavioural flexibility. Studies with cage-reared rodents indicate that captivity often compromises neural development and neural plasticity. Such neural and behavioural deficits can be problematic if captive-bred animals are being reared with the intention of releasing them as part of a conservation strategy. Over the last decade, there has been growing interest in the use of environmental enrichment to promote behavioural flexibility in animals that are bred for release. Here, we describe the positive effects of environmental enrichment on neural plasticity and cognition in juvenile Atlantic salmon (Salmo salar). Exposing fish to enriched conditions upregulated the forebrain expression of NeuroD1 mRNA and improved learning ability assessed in a spatial task. The addition of enrichment to the captive environment thus promotes neural and behavioural changes that are likely to promote behavioural flexibility and improve post-release survival.     

Acidic biphenyl derivatives: Synthesis and biological activity of a new series of potent 5-HT4 receptor antagonists

Serotonin (5-hydroxytryptamine, 5-HT) is an important signaling molecule in the central nervous system (CNS) and in non-neuronal tissues and organs. Serotonin mediates a positive chronotropic and inotropic response through 5-HT₄ receptors in the atrium and ventricle of the heart. Recent investigations have revealed increased expression of the 5-HT_4(b) isoform in cardiomyocytes of chronic arrhythmic and failing hearts, and that the use of 5-HT₄ receptor antagonists may be beneficial for treating these conditions. The 5-HT₄ receptor possesses a transmembrane (TM) binding site important for ligand affinity and recognition, as well as a capacity to accommodate bulky ligands. A new series of peripherally-acting 5-HT₄ receptor antagonists were prepared by combining the acidic biphenyl group from the class of angiotensin II receptor blockers (ARBs) with the SB207266 (piboserod) scaffold. The new compounds were pharmacologically evaluated and carboxylic acid 21 was identified as a potent and promising 5-HT₄ receptor antagonist with moderate affinity for the AT₁ receptor. The permeability of carboxylic acid 21 in a Caco-2 assay was low and the corresponding prodrug esters 23a–f were therefore prepared. The pharmacokinetics of methyl ester 20 and n-butyl ester 23c were evaluated in a rat model, revealing incomplete metabolism to carboxylic acid 21. However, methyl ester 20 is a potent 5-HT₄ receptor antagonist with binding affinities in the low picomolar range. Methyl ester 20 has promising oral bioavailability and pharmacokinetics and may target 5-HT₄ receptors in both CNS and peripheral organs.     

Investigation of Hydrogen Sulfide Gas as a Treatment against P. falciparum,Murine Cerebral Malaria,and the Importance of Thiolation State in the Development of Cerebral Malaria

Introduction

Cerebral malaria (CM) is a potentially fatal cerebrovascular disease of complex pathogenesis caused by Plasmodium falciparum. Hydrogen sulfide (HS) is a physiological gas, similar to nitric oxide and carbon monoxide, involved in cellular metabolism, vascular tension, inflammation, and cell death. HS treatment has shown promising results as a therapy for cardio- and neuro- pathology. This study investigates the effects of fast (NaHS) and slow (GYY4137) HS-releasing drugs on the growth and metabolism of P. falciparum and the development of P. berghei ANKA CM. Moreover, we investigate the role of free plasma thiols and cell surface thiols in the pathogenesis of CM.

Methods

P. falciparum was cultured in vitro with varying doses of HS releasing drugs compared with artesunate. Growth and metabolism were quantified. C57Bl/6 mice were infected with P. berghei ANKA and were treated with varying doses and regimes of HS-releasing drugs. Free plasma thiols and cell surface thiols were quantified in CM mice and age-matched healthy controls.

Results

HS-releasing drugs significantly and dose-dependently inhibited P. falciparum growth and metabolism. Treatment of CM did not affect P. berghei growth, or development of CM. Interestingly, CM was associated with lower free plasma thiols, reduced leukocyte+erythrocyte cell surface thiols (infection day 3), and markedly (5-fold) increased platelet cell surface thiols (infection day 7).

Conclusions

HS inhibits P. falciparum growth and metabolism in vitro. Reduction in free plasma thiols, cell surface thiols and a marked increase in platelet cell surface thiols are associated with development of CM. HS drugs were not effective in vivo against murine CM.     

Mechanisms Preserving Insulin Action during High Dietary Fat Intake

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Urinary nucleic acid oxidation product levels show differential associations with pharmacological treatment in patients with type 2 diabetes

The relationship between RNA and DNA oxidation and pharmacological treatment has not been systematically investigated in patients with type 2 diabetes (T2D). We aimed to investigate the association between pharmacological treatments and levels of urinary markers of nucleic acid oxidation in T2D patients. Vejle Diabetes Biobank cohort data was nested into nationwide registry data. Multiple logistic regression was used to associate drug usage with risk of high (above median) RNA and DNA oxidation. Data from 2664 T2D patients (64% male, age range: 25–75) were included. Questionnaire-validated lipid lowering drug use was associated with low RNA oxidation (Odds ratio, OR 0.71, 95% CI: [0.59–0.87]). Insulin and non-specific antidiabetic drugs were associated with low DNA oxidation (insulin: OR 0.60, 95% CI [0.49–0.73]). Oral antidiabetics were associated with high DNA oxidation and RNA oxidation (OR 1.30, 95% CI [1.10–1.53] and OR 1.26, 95% CI [1.07–1.29]). Our findings indicate that diabetes-related drugs are associated with RNA and DNA oxidation and further studies are required to determine causality in T2D patients.     

Development of ten new EST-derived microsatellites in Atlantic cod (Gadus morhua L.)

Ten polymorphic microsatellite markers were developed from approximately 1,300 expressed sequence tags (ESTs) of Atlantic cod (Gadus morhua L.). Thirty two primer pairs were designed for EST sequences containing perfect di- tri- tetra- and pentanucleotide motifs and characterised in 96 unrelated fish. Ten markers were successfully amplified with number of alleles from 2 to 13 per locus and observed and expected heterozygosity ranging from 0.03 to 0.69 and 0.03 to 0.74, respectively. Loci Gmo-C131, C132 and C136 deviated from Hardy-Weinberg equilibrium. Genetic linkage disequilibrium analysis between all pairs of the loci showed significant departure from the null hypothesis between loci Gmo-C131 and Gmo-C132 and C128 and Gmo-C133. The gene identity was determined at five of the loci, confirming the associated microsatellites as Type I markers. The new microsatellites reported in this work can be used for conservation and enhancement of wild stocks for commercial harvesting. Jon-Ivar Westgaard and Tekle Tafese have contributed equally to the work.     

Variable numbers of rRNA gene operons in Bacillus cereus strains

Abstract Ribosornal RNA operon organisation was analysed in two Bacillus cereus strains of different chromosome size, ATCC 10987 (5.4 Mb) and F0837/76 (2.4 Mb). We estimated that there were twelve and nine copies of the rRNA operons in these two strains, respectively. In B. cereus ATCC 10987 six rRNA operons were less than 10 kb apart, while in B. cereus F0837/76 four rRNA operons were similarly clustered. The origin of replication was located in the vicinity of a rRNA operon in both strains.