The Dogger Bank: A special ecological region in the central North Sea

This paper is a review of the present state of knowledge about the ecology of the Dogger Bank, a shallow area in the central southern North Sea. The biological situation in this region is different from other regions in the North Sea; phytoplankton production occurs throughout the year, connected with low periodicity in macrofaunal abundance and condition of fish. Against prevailing opinions, the Dogger Bank, an offshore region, seems to be affected by eutrophication and pollution.     

SNCA triplication Parkinson's patient's iPSC-derived DA neurons accumulate α-synuclein and are susceptible to oxidative stress

Parkinson's disease (PD) is an incurable age-related neurodegenerative disorder affecting both the central and peripheral nervous systems. Although common, the etiology of PD remains poorly understood. Genetic studies infer that the disease results from a complex interaction between genetics and environment and there is growing evidence that PD may represent a constellation of diseases with overlapping yet distinct underlying mechanisms. Novel clinical approaches will require a better understanding of the mechanisms at work within an individual as well as methods to identify the specific array of mechanisms that have contributed to the disease. Induced pluripotent stem cell (iPSC) strategies provide an opportunity to directly study the affected neuronal subtypes in a given patient. Here we report the generation of iPSC-derived midbrain dopaminergic neurons from a patient with a triplication in the α-synuclein gene (SNCA). We observed that the iPSCs readily differentiated into functional neurons. Importantly, the PD-affected line exhibited disease-related phenotypes in culture: accumulation of α-synuclein, inherent overexpression of markers of oxidative stress, and sensitivity to peroxide induced oxidative stress. These findings show that the dominantly-acting PD mutation is intrinsically capable of perturbing normal cell function in culture and confirm that these features reflect, at least in part, a cell autonomous disease process that is independent of exposure to the entire complexity of the diseased brain.     

Incident Subjective Cognitive Decline Does Not Predict Mortality in the Elderly – Results from the Longitudinal German Study on Ageing,Cognition, and Dementia (AgeCoDe)

Objective

Subjective cognitive decline (SCD) might represent the first symptomatic representation of Alzheimer’s disease (AD), which is associated with increased mortality. Only few studies, however, have analyzed the association of SCD and mortality, and if so, based on prevalent cases. Thus, we investigated incident SCD in memory and mortality.

Methods

Data were derived from the German AgeCoDe study, a prospective longitudinal study on the epidemiology of mild cognitive impairment (MCI) and dementia in primary care patients over 75 years covering an observation period of 7.5 years. We used univariate and multivariate Cox regression analyses to examine the relationship of SCD and mortality. Further, we estimated survival times by the Kaplan Meier method and case-fatality rates with regard to SCD.

Results

Among 971 individuals without objective cognitive impairment, 233 (24.0%) incidentally expressed SCD at follow-up I. Incident SCD was not significantly associated with increased mortality in the univariate (HR = 1.0, 95% confidence interval = 0.8–1.3, p = .90) as well as in the multivariate analysis (HR = 0.9, 95% confidence interval = 0.7–1.2, p = .40). The same applied for SCD in relation to concerns. Mean survival time with SCD was 8.0 years (SD = 0.1) after onset.

Conclusion

Incident SCD in memory in individuals with unimpaired cognitive performance does not predict mortality. The main reason might be that SCD does not ultimately lead into future cognitive decline in any case. However, as prevalence studies suggest, subjectively perceived decline in non-memory cognitive domains might be associated with increased mortality. Future studies may address mortality in such other cognitive domains of SCD in incident cases.     

Transport of Photoassimilates in Young Trees of Fraxinus and Sorbus: Measurement of Translocation in vivo

Abstract: Translocation of photoassimilates was studied on 2-year-old trees of Fraxinus excelsior and Sorbus aucuparia using the short-lived isotope ¹¹C. Leaflets of different leaves on the same plants were radiolabeled showing that both carbon distribution and speeds of transport may vary with leaf position. Within 2 h after pulse feeding with ¹¹CO₂, mainly the lower leaves distributed radiolabel to the roots in Fraxinus, whereas in Sorbus, the upper leaves were also involved. By repeated pulse applications to selected leaves, temporal profiles of ¹¹C transport were followed on individual plants from April to October. Early in the season, within 2 h after pulse labelling, 30–40% of the fixed radiolabel was exported from leaves in Fraxinus and about 20% in Sorbus. Thereafter export started to decline, particularly in Fraxinus, and the distribution of radiolabel between stem and roots could alter depending on the position of the feed leaf. Speeds of translocation obtained along the rachis and stem showed high variability, but they did not necessarily slow down before the end of the season. The speeds monitored at the rachis of Fraxinus leaves (30–75 cm h^?1) were generally lower than those found on Sorbus (50–130 cm h^?1). As reported in the literature, the two tree species translocate different carbohydrates and show remarkable differences in the ultrastructure of their vascular systems. In that context it is interesting that the temporal profiles of ¹¹C radioactivity obtained from F. excelsior and S. aucuparia could clearly be distinguished by their characteristic shapes. The results are discussed in terms of anatomical characteristics of the conducting tissues and possible differences in phloem loading.     

The molecular genetics of early neurogenesis in Drosophila melanogaster

The extent of neurogenesis in Drosophila is under the control of the so-called neurogenic genes, named for their mutant phenotype of causing neural hyperplasia. Their wild-type products appear to be responsible for a signal chain that decides the fate of ectodermal cells in the embryo. Various kinds of data, from cell transplantation experiments as well as from genetic and molecular analyses, suggest that the proteins encoded by the genes Notch and Delta may act at the membrane of the signal-transmitting cells to provide a ligand to a still unknown receptor molecule; in contrast, the locus of Enhancer of split codes for several functions related to the transduction and further processing of the signal.     

How to account for the lipid effect on carbon stable-isotope ratio (δ13C): sample treatment effects and model bias

This study investigated the impact of lipid extraction, CaCO₃ removal and of both treatments combined on fish tissue δ¹³C, δ¹⁵N and C:N ratio. Furthermore, the suitability of empirical δ¹³C lipid normalization and correction models was examined. δ¹⁵N was affected by lipid extraction (increase of up to 1·65‰) and by the combination of both treatments, while acidification alone showed no effect. The observed shift in δ¹⁵N represents a significant bias in trophic level estimates, i.e. lipid-extracted samples are not suitable for δ¹⁵N analysis. C:N and δ¹³C were significantly affected by lipid extraction, proportional to initial tissue lipid content. For both variables, rates of change with lipid content (ΔC:N and Δδ¹³C) were species specific. All tested lipid normalization and correction models produced biased estimates of fish tissue δ¹³C, probably due to a non-representative database and incorrect assumptions and generalizations the models were based on. Improved models need a priori more extensive and detailed studies of the relationships between lipid content, C:N and δ¹³C, as well as of the underlying biochemical processes.     

Evidence that paternal expression of the epsilon-sarcoglycan gene accounts for reduced penetrance in myoclonus-dystonia

Myoclonus-dystonia (M-D) is a movement disorder characterized by rapid muscle contractions and sustained twisting and repetitive movements and has recently been associated with mutations in the epsilon-sarcoglycan gene (SGCE). The mode of inheritance is autosomal dominant with reduced penetrance upon maternal transmission, suggesting a putative maternal imprinting mechanism. We present an apparently sporadic M-D case and two patients from an M-D family with seemingly autosomal recessive inheritance. In both families, we detected an SGCE mutation that was inherited from the patients' clinically unaffected fathers in an autosomal dominant fashion. Whereas, in the first family, RNA expression studies revealed expression of only the mutated allele in affected individuals and expression of the normal allele exclusively in unaffected mutation carriers, the affected individual of the second family expressed both alleles. In addition, we identified differentially methylated regions in the promoter region of the SGCE gene as a characteristic feature of imprinted genes. Using a rare polymorphism in the promoter region in a family unaffected with M-D as a marker, we demonstrated methylation of the maternal allele, in keeping with maternal imprinting of the SGCE gene. Loss of imprinting in the patient with M-D who had biallelic expression of the SGCE gene was associated with partial loss of methylation at several CpG dinucleotides.     

The significance of the 20-carbonyl group of progesterone in steroid receptor binding: a molecular dynamics and structure-based ligand design study

Polar functional groups in the A- and D-ring (positions 3 and 17beta or 20) are common to all natural and synthetic steroid hormones. It was assumed that these pharmacophoric groups are involved in strong hydrogen bonding interactions with the respective steroid receptors. High resolution X-ray structures of the estrogen and androgen receptors have confirmed these assumptions. Also site-directed mutagenesis studies of the human progesterone receptor (hPR) suggest an important role for Cys891 in the recognition of the progesterone 20-carbonyl group. Surprisingly, the crystal structure of the hPR ligand binding domain (LBD) in complex with progesterone suggests that the carbonyl oxygen in position 20 (O20) is not involved in hydrogen bond contacts. To investigate these surprising and contradicting results further, we performed a molecular dynamics simulation of the hPR-progesterone complex in an aqueous environment. The simulation revealed hPR-Cys891 as the sole but weak hydrogen bonding partner of progesterone in the D-ring. In contrast to the site-directed mutagenesis data a major role of hPR-Cys891 in progesterone recognition could not be confirmed. Isolated hydrogen bond acceptors, such as the prosterone O20 group, in a relatively lipophilic environment of the receptor led to a decrease in affinity of the ligand. Based on this consideration and the structure of the PR, we designed compounds lacking such an acceptor function. If the X-ray structure and the calculations were right, these compounds should bind with comparable or higher affinity versus that of progesterone. E-17-Halomethylene steroids were synthesized and pharmacologically characterized in vitro and in vivo. Although the compounds are unable to form hydrogen bonds with the hPR in the D-ring region, they bind with superior affinity and exert stronger in vivo progestational effects than progesterone itself. Our investigations have confirmed the results of the X-ray structure and disproved the old pharmacophore model for progestogenic activity, comprising two essential polar functional groups on both ends of the steroid core. The 20-carbonyl group of progesterone is likely to play a role beyond PR-binding, e.g. in the context of other functions via the androgen and mineralocorticoid receptors and as a site of metabolic inactivation.