Survival, growth and tag retention of juvenile European eel (Anguilla anguilla L.) with implanted 12 mm passive integrated transponder tags and acoustic tags.

To evaluate the efficiency of tagging juvenile European eels with implanted 12 mm passive integrated transponder (PIT) tags or Eel/Lamprey acoustic transmitters (ELATs), the authors studied tag retention, survival and growth of eels (7-25 g). Experimental eels were obtained from an eel farm, tagged and then released in a series of shallow dug-out ponds with a surface area of c. 200 m2 . Tagged and control eels were distributed evenly, with 50 tagged and 50 control eels in each of four ponds, giving a total of 200 tagged and 200 control eels mixed. After 76 days, the ponds were drained, and eels were sampled and measured. A total of 344 eels (86%) were recaptured, indicating high survival. Tag retention was 99% as only one of the recaptured PIT-tagged eels had lost the tag and none of the ELAT tagged. The results demonstrated that tagging juvenile eels >16 cm with these small tags is indeed feasible. The growth of tagged and control fish was differentiated but generally low in length and negative in mass but did not differ between the three groups.

Amyloid beta 42 peptide (Abeta42)-lowering compounds directly bind to Abeta and interfere with amyloid precursor protein (APP) transmembrane dimerization.

Following ectodomain shedding by beta-secretase, successive proteolytic cleavages within the transmembrane sequence (TMS) of the amyloid precursor protein (APP) catalyzed by gamma-secretase result in the release of amyloid-beta (Abeta) peptides of variable length. Abeta peptides with 42 amino acids appear to be the key pathogenic species in Alzheimer's disease, as they are believed to initiate neuronal degeneration. Sulindac sulfide, which is known as a potent gamma-secretase modulator (GSM), selectively reduces Abeta42 production in favor of shorter Abeta species, such as Abeta38. By studying APP-TMS dimerization we previously showed that an attenuated interaction similarly decreased Abeta42 levels and concomitantly increased Abeta38 levels. However, the precise molecular mechanism by which GSMs modulate Abeta production is still unclear. In this study, using a reporter gene-based dimerization assay, we found that APP-TMS dimers are destabilized by sulindac sulfide and related Abeta42-lowering compounds in a concentration-dependent manner. By surface plasmon resonance analysis and NMR spectroscopy, we show that sulindac sulfide and novel sulindac-derived compounds directly bind to the Abeta sequence. Strikingly, the attenuated APP-TMS interaction by GSMs correlated strongly with Abeta42-lowering activity and binding strength to the Abeta sequence. Molecular docking analyses suggest that certain GSMs bind to the GxxxG dimerization motif in the APP-TMS. We conclude that these GSMs decrease Abeta42 levels by modulating APP-TMS interactions. This effect specifically emphasizes the importance of the dimeric APP-TMS as a promising drug target in Alzheimer's disease.

The amyloid precursor protein C-terminal fragment C100 occurs in monomeric and dimeric stable conformations and binds γ-secretase modulators.

The amyloid-ß (Aß) peptide is contained within the C-terminal fragment (ß-CTF) of the amyloid precursor protein (APP) and is intimately linked to Alzheimer's disease. In vivo, Aß is generated by sequential cleavage of ß-CTF within the γ-secretase module. To investigate γ-secretase function, in vitro assays are in widespread use which require a recombinant ß-CTF substrate expressed in bacteria and purified from inclusion bodies, termed C100. So far, little is known about the conformation of C100 under different conditions of purification and refolding. Since C100 dimerization influences the efficiency and specificity of γ-secretase cleavage, it is also of great interest to determine the secondary structure and the oligomeric state of the synthetic substrate as well as the binding properties of small molecules named γ-secretase modulators (GSMs) which we could previously show to modulate APP transmembrane sequence interactions [Richter et al. (2010) Proc. Natl. Acad. Sci. U.S.A. 107, 14597-14602]. Here, we use circular dichroism and continuous-wave electron spin resonance measurements to show that C100 purified in a buffer containing SDS at micelle-forming concentrations adopts a highly stable α-helical conformation, in which it shows little tendency to aggregate or to form higher oligomers than dimers. By surface plasmon resonance analysis and molecular modeling we show that the GSM sulindac sulfide binds to C100 and has a preference for C100 dimers.

Aberrant amyloid precursor protein (APP) processing in hereditary forms of Alzheimer disease caused by APP familial Alzheimer disease mutations can be rescued by mutations in the APP GxxxG motif.

The identification of hereditary familial Alzheimer disease (FAD) mutations in the amyloid precursor protein (APP) and presenilin-1 (PS1) corroborated the causative role of amyloid-beta peptides with 42 amino acid residues (Abeta42) in the pathogenesis of AD. Although most FAD mutations are known to increase Abeta42 levels, mutations within the APP GxxxG motif are known to lower Abeta42 levels by attenuating transmembrane sequence dimerization. Here, we show that aberrant Abeta42 levels of FAD mutations can be rescued by GxxxG mutations. The combination of the APP-GxxxG mutation G33A with APP-FAD mutations yielded a constant 60% decrease of Abeta42 levels and a concomitant 3-fold increase of Abeta38 levels compared with the Gly(33) wild-type as determined by ELISA. In the presence of PS1-FAD mutations, the effects of G33A were attenuated, apparently attributable to a different mechanism of PS1-FAD mutants compared with APP-FAD mutants. Our results contribute to a general understanding of the mechanism how APP is processed by the gamma-secretase module and strongly emphasize the potential of the GxxxG motif in the prevention of sporadic AD as well as FAD.

Comparison of Behavior and Space Use of the European Bullhead Cottus gobio and the Round Goby Neogobius melanostomus in a Simulated Natural Habitat.

The round goby is an invasive fish in Europe and North America that threatens native species by predation and competition. Its habitat preferences are similar to those of the European bullhead, which it displaces from shelters and out-competes for available resources. We assessed the microhabitat preferences, shelter use, and activity of the round goby and European bullhead in single-species experiments in habitat simulator systems to investigate their behavior in a novel environment. Fish were video-recorded for 28 h in the presence of shelter and feed with water velocity ranging from 0.00 to 0.96 m s-1. The two species showed similar behavior under given conditions. A primary difference was in stress-induced behavior in the initial phases of observation. The round goby spent more time in movement when outside the shelter and a longer time in the escape zone in the exploration period during light. Our results confirmed a significant preference of round goby for low velocity areas and a preference for higher velocities in the European bullhead. Both species were able to cope with velocities > 0.7 m s-1. Therefore, the reported invasion success of round goby is probably not driven by space use or activity patterns, but rather by higher adaptability.

Acceptance of Supportive Illustrations for Preparation of Patients for an Orthopedic Telemedical Consultation.

Introduction: Telemedical video consultations are a powerful support for patient-doctor interactions. For optimal digital settings, explanatory illustrations may be helpful for patients. This study analyzed patients' the attitude of patients to illustrations preparing for an orthopedic telemedical consultation (OTC). Methods: A leaflet with eight illustrations was designed and their acceptance and estimated necessity was evaluated among patients who had experienced an OTC (EXP-group) and others who had not (NOV-group) with a 12-item-questionnaire. Results: Sixty patients participated (n = 30 each group). All illustrations were evaluated positively. The EXP-group gave significantly higher ratings than the NOV-group for improved understanding by the given keywords of the illustrations (p = 0.046), preference for being informed by illustrations than by merely by a pure text (p = 0.023), better feeling of preparation for an OTC by the illustrations (p = 0.005), and the impression of a simplified process of the OTC by the illustrations (p = 0.012). Discussion: While the illustrations were well-accepted by the participants, significant differences were revealed between the valuation of single aspects by patients, depending on a previous experience with an OTC. Therefore, a leaflet with explanatory illustrations may be helpful in preparing patients for an OTC to support the digital patient-doctor contact.

Patient-Reported Financial Distress in Cancer: A Systematic Review of Risk Factors in Universal Healthcare Systems.

Financial toxicity is a side effect of cancer that results from the perceived financial distress an individual may experience in the course of the disease. The purpose of this paper is to analyse underlying factors related to subjective financial distress in high-income countries with universal healthcare coverage. A systematic literature review was conducted to identify qualitative and quantitative studies of cancer patient-reported subjective financial distress by performing a search in the databases of PubMed, PsycINFO and CINAHL up to December 2020. A qualitative synthesis was performed linking the time-dependent occurrence of risk factors to derived categories of risk factors. Out of 4321 identified records, 30 quantitative and 16 qualitative studies were eligible. Classification of risk factors resulted in eight categories with a total of 34 subcategories. Subjective financial distress is primarily determined by pre-diagnosis sociodemographic- factors as well as financial and work factors that might change during the course of the disease. The design of healthcare and social security systems shapes the country-specific degree of subjective financial distress. Further research should focus on evolving multidisciplinary intervention schemes and multidimensional instruments for subjective financial distress to account for identified risk factors in universal healthcare systems more precisely.

Intracellular Aß pathology and early cognitive impairments in a transgenic rat overexpressing human amyloid precursor protein: a multidimensional study.

Numerous studies have implicated the abnormal accumulation of intraneuronal amyloid-ß (Aß) as an important contributor to Alzheimer's disease (AD) pathology, capable of triggering neuroinflammation, tau hyperphosphorylation and cognitive deficits. However, the occurrence and pathological relevance of intracellular Aß remain a matter of controversial debate. In this study, we have used a multidimensional approach including high-magnification and super-resolution microscopy, cerebro-spinal fluid (CSF) mass spectrometry analysis and ELISA to investigate the Aß pathology and its associated cognitive impairments, in a novel transgenic rat model overexpressing human APP. Our microscopy studies with quantitative co-localization analysis revealed the presence of intraneuronal Aß in transgenic rats, with an immunological signal that was clearly distinguished from that of the amyloid precursor protein (APP) and its C-terminal fragments (CTFs). The early intraneuronal pathology was accompanied by a significant elevation of soluble Aß42 peptides that paralleled the presence and progression of early cognitive deficits, several months prior to amyloid plaque deposition. Aß38, Aß39, Aß40 and Aß42 peptides were detected in the rat CSF by MALDI-MS analysis even at the plaque-free stages; suggesting that a combination of intracellular and soluble extracellular Aß may be responsible for impairing cognition at early time points. Taken together, our results demonstrate that the intraneuronal development of AD-like amyloid pathology includes a mixture of molecular species (Aß, APP and CTFs) of which a considerable component is Aß; and that the early presence of these species within neurons has deleterious effects in the CNS, even before the development of full-blown AD-like pathology.