Neuroprotective effects of a specific multi-nutrient intervention against Aβ42-induced toxicity in rats

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia in the elderly. Substantial evidence suggests a role for nutrition in the management of AD and especially suggests that interventions with combinations of nutrients are more effective than single-nutrient interventions. The specific multi-nutrient combination Fortasyn™Connect (FC), shown to improve memory in AD, provides phosphatide precursors and cofactors and is designed to stimulate the formation of phospholipids, neuronal membranes, and synapses. The composition comprises nucleotides, omega-3 polyunsaturated fatty acids (n3 PUFA), choline, B-vitamins, phospholipids, and antioxidants. The current study explored the protective properties of FC in a membrane toxicity model of AD, the amyloid-β 1-42 (Aβ42) infused rat, which shows reduced exploratory behavior in an Open Field and impaired cholinergic functioning. To this end, rats were fed an FC enriched diet or a control diet and five weeks later infused with vehicle or Aβ42 into the lateral ventricle. Ten weeks post-infusion Aβ42-rats fed the FC diet showed increased membrane n3 PUFA and phosphatidylcholine content while they did not show the reductions in exploratory behavior or in choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) immunoreactivity that were seen in Aβ42-rats fed the control diet. We conclude that FC protects the cholinergic system against Aβ42-induced toxicity and speculate that the effects of FC on membrane formation and composition might be supportive for this protective effect. Based on these data a long-term intervention study was started in the prodromal stages of AD (NTR1705, LipiDiDiet, EU FP7)

A geological cross-section along the Basque Pyrenees and the Parentis Basin (Western Pyrenees)

A new geological cross- section along the North Iberian Margin shows a complete image of the Western Pyrenees and the Parentis Basin as well as the geometric differences and age constraints between both Pyrenean fronts. The South Pyrenean front, developed during Uppermost Cretaceous- Middle Miocene, is represented by a major thrust which accumulates around 20 km of southward displacement. The Basque- Cantabrian basin is a mesozoic extensional basin which was inverted during Paleogene times as a consequence of the Pyrenean orogeny. A basement- involved thrust wedge with an upper south- directed back- thrust characterizes the North Pyrenean Frontal Thrust. The main thrust, emplaced during Late Eocene- Miocene times, shows a displacement around 2 km whereas the back- thrust detached in Paleocene materials shows a displacement about 1.5 km. Northwards, the Landes High, is interpreted as an uplifted plateau where a thick wedge of Upper Cretaceous- Cenozoic synorogenic deposits overlay unconformably the Hercinian basement. This package corresponds with the North Pyrenean foreland basin. More to the north, the Landes fault is the southern margin of the Mesozoic Parentis Basin, a semigraben infilled with a thick package of Triassic to Albian synrift sequence overlied by Cretaceous and Cenozoic deposits. There, inversion structures were poorly developed

Effects of a resistance-training programme on endoplasmic reticulum unfolded protein response and mitochondrial functions in PBMCs from elderly subjects

10 p.Aging has been related with a decline in the ability to handle protein folding, which leads to endoplasmic reticulum stress and alterations in unfolded protein response (UPR). Importantly, physical activity could activate the UPR and attenuate or prevent age-induced endoplasmic reticulum (ER) dysfunction. The current study evaluated the effects of a resistance exercise on UPR and mitochondrial functions in peripheral blood mononuclear cells (PBMCs) from elderly subjects. Thirty healthy women and men (age, 72.8, sx− = 2.2 years) were randomized to a training group, which performed an 8-week resistance training programme, or a control group, which followed their daily routines. The phosphorylation of PERK and IRE1, as well as ATF4, and XBP1 protein expression, significantly increased following the training, while expression of BiP, AFT6 and CHOP remain without changes. Additionally, the intervention also induced an increase in PGC-1α and Mfn1 protein levels, while no changes were found in Drp1 expression. Finally, the resistance protocol was not able to activate PINK1/Parkin and Bnip3/Nix pathways. The results obtained seem to indicate that 8-week resistance exercise activates the UPR, stimulates mitochondrial biogenesis, maintains mitochondrial dynamics and prevents mitophagy activation by unfolded proteins in PBMCs from elderly subjects.S

Barred-beach morphological control on infragravity motion

A conceptual analysis of the coupling between bars and infragravity waves is performed combining laboratory experiments and numerical modeling. Experiments are carried out in a wave flume with a barred profile. The Boussinesq fully-nonlinear model SERR1D is validated with the laboratory data and a sensitivity analysis is performed next to study the influence on the infragravity wave dynamics of bar amplitude and location, and swash zone slope. A novel technique of incident and reflected motions separation that conserves temporal characteristics is applied. We observe that changing bar characteristics induces substantial variations in trapped energy. Interestingly, a modification of swash zone slope has a large influence on the reflected component, controlling amplitude and phase time-lag, and consequently on the resonant pattern. Variations of trapped infragravity energy induced by changes of swash zone slope reach 25 %. These changes in infragravity pattern consequently affect short-wave dynamics by modifying the breakpoint location and the breaking intensity. Our conceptual investigation suggests the existence of a morphological feedback through the action of evolving morphology on infragravity structures which modulates the action of short-waves on the morphology itself

Highly conductive grain boundaries in cold-sintered barium zirconate-based proton conductors

Proton-conducting barium zirconate ceramics have shown large potential for efficient electrochemical conversion and separation processes at intermediate operation temperatures. The high energy efficiency, robustness, and intermediate-temperature operation (500-650 °C) make proton-conducting cells promising candidates for future energy conversion systems. However, the major disadvantages of these materials are the inevitable high-sintering temperatures (>1500 °C), leading to Ba-evaporation and formation of high-resistance grain boundaries, which dominate the electrochemical performance. Here, we introduce a novel processing route for proton-conducting barium zirconates, which, on the one hand, significantly lowers the maximum processing temperature and, on the other hand, overcomes the dominating influence of grain boundaries on total conductivity. The key step of this novel processing route is the cold sintering of the powder using pure water as a sintering aid to consolidate BaZrCeYO (BZCY) at 350 °C. We show that clean grain boundaries with a high acceptor-dopant concentration are preserved thanks to the recovery of the perovskite phase during thermal treatment at 1300 °C. This compensates the interfacial core charge, resulting in highly conductive grain boundaries, which do not limit the total conductivity. Consequently, dense BZCY electrolytes produced by our novel approach outperform the conductivity of conventionally sintered BZCY irrespective of the significantly lower maximum processing temperature and its nanocrystalline microstructure. Our presented approach opens up new possibilities for grain boundary engineering and might facilitate novel co-sintering pathways for barium zirconate-based components.The authors acknowledge Dr Doris Sebold for help with SEM investigations and Dr Yoo Jung Sohn for assistance with HT-XRD measurements. M. K. acknowledges financial support from the DFG under project number MA 1280/69-1. Additionally, D. J. and W. R. thank the DFG for funding within the Emmy Noether program (RH 146/1-1). A. V. expresses gratitude to Dr Ivan Povstugar for his insightful discussions on the quality of APT data and its reconstruction. The authors thank Hitachi High-Technologies for providing access to the HF5000 STEM located at ER-C

Modelling Cross-Shore Shoreline Change on Multiple Timescales and Their Interactions

In this paper, a new approach to model wave-driven, cross-shore shoreline change incorporating multiple timescales is introduced. As a base, we use the equilibrium shoreline prediction model ShoreFor that accounts for a single timescale only. High-resolution shoreline data collected at three distinctly different study sites is used to train the new data-driven model. In addition to the direct forcing approach used in most models, here two additional terms are introduced: a time-upscaling and a time-downscaling term. The upscaling term accounts for the persistent effect of short-term events, such as storms, on the shoreline position. The downscaling term accounts for the effect of long-term shoreline modulations, caused by, for example, climate variability, on shorter event impacts. The multi-timescale model shows improvement compared to the original ShoreFor model (a normalized mean square error improvement during validation of 18 to 59%) at the three contrasted sandy beaches. Moreover, it gains insight in the various timescales (storms to inter-annual) and reveals their interactions that cause shoreline change. We find that extreme forcing events have a persistent shoreline impact and cause 57–73% of the shoreline variability at the three sites. Moreover, long-term shoreline trends affect short-term forcing event impacts and determine 20–27% of the shoreline variability.</jats:p

Treatment challenges in and outside a specialist network setting: Pancreatic neuroendocrine tumours

Pancreatic Neuroendocrine Neoplasms comprise a group of rare tumours with special biology, an often indolent behaviour and particular diagnostic and therapeutic requirements. The specialized biochemical tests and radiological investigations, the complexity of surgical options and the variety of medical treatments that require individual tailoring, mandate a multidisciplinary approach that can be optimally achieved through an organized network. The present study describes currents concepts in the management of these tumours as well as an insight into the challenges of delivering the pathway in and outside a Network