Developmental Exposure to Fluoxetine Modulates the Serotonin System in Hypothalamus

The selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLU, Prozac®) is commonly prescribed for depression in pregnant women. This results in SSRI exposure of the developing fetus. However, there are knowledge gaps regarding the impact of SSRI exposure during development. Given the role of serotonin in brain development and its cross-talk with sex hormone function, we investigated effects of developmental exposure to pharmacologically relevant concentrations of FLU (3 and 30 nM (measured)) on brain neurotransmitter levels, gonadal differentiation, aromatase activity in brain and gonads, and the thyroid system, using the Xenopus tropicalis model. Tadpoles were chronically exposed (8 weeks) until metamorphosis. At metamorphosis brains were cryosectioned and levels of serotonin, dopamine, norepinephrine, and their metabolites 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid, and homovanillic acid were measured in discrete regions (telencephalon, hypothalamus and the reticular formation) of the cryosections using high-performance liquid chromatography. Exposure to 30 nM FLU increased the concentration of 5-hydroxyindoleacetic acid in hypothalamus compared with controls. FLU exposure did not affect survival, time to metamorphosis, thyroid histology, gonadal sex differentiation, or aromatase activity implying that the effect on the serotonergic neurotransmitter system in the hypothalamus region was specific. The FLU concentration that impacted the serotonin system is lower than the concentration measured in umbilical cord serum, suggesting that the serotonin system of the developing brain is highly sensitive to in utero exposure to FLU. To our knowledge this is the first study showing effects of developmental FLU exposure on brain neurochemistry. Given that SSRIs are present in the aquatic environment the current results warrant further investigation into the neurobehavioral effects of SSRIs in aquatic wildlife.     

Bacterioplankton in the acidified Lake Gårdsjön

Total bacterial numbers in different strata of lake water and in inlet and outlet streams have been recorded during a yearly cycle. A calculated mean cell volume of 0.342 µm² has then been used to estimate bacterial biomass in the lake. Change of biomass during the year was substantial and the range was from about 0.1 g · m^–3 to about 1.0–1.2 g · m^–3. The seasonal development included a spring-early summer increase followed by a decrease to the minimum in July–August. Correlation between epi- and hypolimnion was high and in both strata two dominant autumn peaks in biomass appeared. With the exception of the last autumn peak the development of bacterial biomass was closely related to development of phytoplankton biomass and production.     

Ultrastructure of myocardial widened Z bands and endocardial cells in two teleostean species

Summary Widened myocardial Z bands and endocardial cells are described in two teleostean species Cichlasoma meeki and Corydoras aeneus. Widened Z bands containing mainly amorphous and electron-dense material were seen in a number of myocardial cells. Further, similar material may occur in large amounts beneath the sarcolemma and at intercellular junctions. Occasionally, we observed continuity between the latter material and that in expanded Z bands.In C. meeki the ventricular endocardial layer consists of two structurally different cell types, whereas in C. aeneus only one cell type was seen. The functional aspects of widened Z bands are discussed.     

Regulating biocontrol agents: a historical perspective and a critical examination comparing microbial and macrobial agents

Ever since the inclusion of microbial biocontrol agents (MBCAs) within the regulatory frameworks initially designed for chemical pesticides, there has been awareness that these frameworks are not optimal for assessment and registration of new microbial biocontrol products. It is often claimed that the regulatory situation has contributed to a relatively slow uptake of microbial biocontrol in practice. In contrast to the MBCAs, non-indigenous invertebrate biocontrol agents (IBCAs) are regulated in many countries through quarantine and other biosecurity related legislation for prevention of introduction of alien organisms, whereas use of indigenous IBCAs are generally unregulated. In this study, we investigate what scientific support there is for performing evaluations of these two main groups of biocontrol agents (BCAs) within different frameworks. We compare potential risks of MBCAs and IBCAs, present a retrospective analysis of the development and implementation of the regulatory frameworks, and compare current requirements for MBCAs with those for other applications with microorganisms. One conclusion is that the ecological risks are of similar types between the two groups of BCAs, and that for both groups the environmental safety is most pertinently evaluated according to biological and ecological principles. The main difference between MBCAs and IBCAs with respect to human health is that the former may cause infectious disease. However, we found no evidence that this hazard is more serious for microorganisms for biocontrol than for microbes used in other types of applications, which generally have substantially lower regulatory demands than those for MBCAs. Several international initiatives have produced helpful guidelines and recommendations for simplified assessments and authorisations of BCAs. Still, we conclude that as long as MBCAs are evaluated within systems initially developed for chemicals, the risk for inappropriate emphasis of chemical hazards and therefore unnecessarily complicated assessments will be maintained. Therefore, this study supports the idea that development of new systems for the regulatory oversight of MBCAs, possibly a mutual framework covering all living BCAs, should be considered. Research issues that need to be further explored are to what extent utilisation of MBCAs actually results in increased exposure of non-targets to microorganisms, the biogeography and microbial ecology of representative MBCAs, and finally development of better methodology for determining potential human toxicity and pathogenicity of candidate MBCAs.     

Crystal Structures of the Human G3BP1 NTF2-Like Domain Visualize FxFG Nup Repeat Specificity

Ras GTPase Activating Protein SH3 Domain Binding Protein (G3BP) is a potential anti-cancer drug target implicated in several cellular functions. We have used protein crystallography to solve crystal structures of the human G3BP1 NTF2-like domain both alone and in complex with an FxFG Nup repeat peptide. Despite high structural similarity, the FxFG binding site is located between two alpha helices in the G3BP1 NTF2-like domain and not at the dimer interface as observed for nuclear transport factor 2. ITC studies showed specificity towards the FxFG motif but not FG and GLFG motifs. The unliganded form of the G3BP1 NTF2-like domain was solved in two crystal forms to resolutions of 1.6 and 3.3 Å in space groups P2₁2₁2₁ and P6₃22 based on two different constructs, residues 1–139 and 11–139, respectively. Crystal packing of the N-terminal residues against a symmetry related molecule in the P2₁2₁2₁ crystal form might indicate a novel ligand binding site that, however, remains to be validated. The crystal structures give insight into the nuclear transportation mechanisms of G3BP and provide a basis for future structure based drug design.     

Effects of a transient oxic period on mineralization of organic matter to CH4 and CO2 in anoxic peat incubations

Rates of organic matter mineralization in peatlands, and hence production of the greenhouse gases CH₄ and CO₂, are highly dependent on the distribution of oxygen in the peat. Using laboratory incubations of peat, we investigated the sensitivity of the anoxic production of CH₄ and CO₂ to a transient oxic period of a few weeks’ duration. Production rates during 3 successive anoxic periods were compared with rates in samples incubated in the presence of oxygen during the second period. In surface peat (5–10‐cm depth), with an initially high level of CH₄ production, oxic conditions during period 2 did not result in a lower potential CH₄ production rate during period 3, although production was delayed ～1 week. In permanently anoxic, deep peat (50–55‐cm depth) with a comparatively low initial production of CH₄, oxic conditions during period 2 resulted in zero production of CH₄ during period 3. Thus, the methanogens in surface peal—but not in deep peat—remained viable after several weeks of oxic conditions. In contrast to CH₄ production, the oxic period had a negligible effect on anoxic CO₂ production during period 3, in surface as well as deep peat. In both surface and deep peat, CO₂ production was several times higher under oxic than under anoxic conditions. However, for the first 2 weeks of oxic conditions, CO₂ production in the deep peat was very low. Still, deep peat obviously contained facultative microorganisms that, after a relatively short period, were able to maintain a considerably higher rate of organic matter mineralization under oxic than under anoxic conditions.