Primary Cilia Structure Is Prolonged in Enteric Neurons of 5xFAD Alzheimer’s Disease Model Mice

Neurodegenerative diseases such as Alzheimer’s disease (AD) have long been acknowledged as mere disorders of the central nervous system (CNS). However, in recent years the gut with its autonomous nervous system and the multitude of microbial commensals has come into focus. Changes in gut properties have been described in patients and animal disease models such as altered enzyme secretion or architecture of the enteric nervous system. The underlying cellular mechanisms have so far only been poorly investigated. An important organelle for integrating potentially toxic signals such as the AD characteristic A-beta peptide is the primary cilium. This microtubule-based signaling organelle regulates numerous cellular processes. Even though the role of primary cilia in a variety of developmental and disease processes has recently been recognized, the contribution of defective ciliary signaling to neurodegenerative diseases such as AD, however, has not been investigated in detail so far. The AD mouse model 5xFAD was used to analyze possible changes in gut functionality by organ bath measurement of peristalsis movement. Subsequently, we cultured primary enteric neurons from mutant mice and wild type littermate controls and assessed for cellular pathomechanisms. Neurite mass was quantified within transwell culturing experiments. Using a combination of different markers for the primary cilium, cilia number and length were determined using fluorescence microscopy. 5xFAD mice showed altered gut anatomy, motility, and neurite mass of enteric neurons. Moreover, primary cilia could be demonstrated on the surface of enteric neurons and exhibited an elongated phenotype in 5xFAD mice. In parallel, we observed reduced β-Catenin expression, a key signaling molecule that regulates Wnt signaling, which is regulated in part via ciliary associated mechanisms. Both results could be recapitulated via in vitro treatments of enteric neurons from wild type mice with A-beta. So far, only a few reports on the probable role of primary cilia in AD can be found. Here, we reveal for the first time an architectural altered phenotype of primary cilia in the enteric nervous system of AD model mice, elicited potentially by neurotoxic A-beta. Potential changes on the sub-organelle level—also in CNS-derived neurons—require further investigations.     

Spatially modulating interfacial properties of transparent conductive oxides: patterning work function with phosphonic Acid self-assembled monolayers

The interface between an organic semiconductor and a transparent conducting oxide is crucial to the performance of organic optoelectronics. We use microcontact printing to pattern pentafluorobenzyl phosphonic acid self-assembled monolayers (SAMs) on indium tin oxide (ITO). We obtain high-fidelity patterns with sharply defined edges and with large work function contrast (comparable to that obtained from phosphonic acid SAMs deposited from solution).     

An actor–partner interdependence model of spousal criticism and depression.

Although perceived criticism is relational, most theory and research concerns only relatives' criticism toward patients and not the converse. With a sample of 33 depressed patients and their spouses, we take a fully relational approach to criticism by testing an actor–partner interdependence model (Kenny, Kashy, & Cook, 2006). Patient intended criticism was especially strongly associated with depressive symptoms for wives, whereas patient perceived criticism was especially negatively related to depressive symptoms for husbands. Nondepressed partner intended criticism was positively related to patient depressive symptoms, but nondepressed wife perceived criticism was negatively related to husband depressive symptoms. The importance of including patient intended and partner perceived criticism as well as examining sex differences in models of criticism and depression are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Bovine milk oligosaccharides decrease gut permeability and improve inflammation and microbial dysbiosis in diet-induced obese mice

Obesity is characterized by altered gut homeostasis, including dysbiosis and increased gut permeability closely linked to the development of metabolic disorders. Milk oligosaccharides are complex sugars that selectively enhance the growth of specific beneficial bacteria in the gastrointestinal tract and could be used as prebiotics. The aim of the study was to demonstrate the effects of bovine milk oligosaccharides (BMO) and Bifidobacterium longum ssp. infantis (B. infantis) on restoring diet-induced obesity intestinal microbiota and barrier function defects in mice. Male C57/BL6 mice were fed a Western diet (WD, 40% fat/kcal) or normal chow (C, 14% fat/kcal) for 7 wk. During the final 2 wk of the study, the diet of a subgroup of WD-fed mice was supplemented with BMO (7% wt/wt). Weekly gavage of B. infantis was performed in all mice starting at wk 3, yet B. infantis could not be detected in any luminal contents when mice were killed. Supplementation of the WD with BMO normalized the cecal and colonic microbiota with increased abundance of Lactobacillus compared with both WD and C mice and restoration of Allobaculum and Ruminococcus levels to that of C mice. The BMO supplementation reduced WD-induced increase in paracellular and transcellular flux in the large intestine as well as mRNA levels of the inflammatory marker tumor necrosis factor α. In conclusion, BMO are promising prebiotics to modulate gut microbiota and intestinal barrier function for enhanced health.     

Nanoparticle Accumulation in Angiogenic Tissues: Towards Predictable Pharmacokinetics

Nanoparticles are increasingly used in medical applications such as drug delivery, imaging, and biodiagnostics, particularly for cancer. The design of nanoparticles for tumor delivery has been largely empirical, owing to a lack of quantitative data on angiogenic tissue sequestration. Using fluorescence correlation spectroscopy, the deposition rate constants of nanoparticles into angiogenic blood vessel tissue are determined. It is shown that deposition is dependent on surface charge. Moreover, the size dependency strongly suggests that nanoparticles are taken up by a passive mechanism that depends largely on geometry. These findings imply that it is possible to tune nanoparticle pharmacokinetics simply by adjusting nanoparticle size.     

Experimental kinetic study of oxidation of uranium monocarbide powders under controlled oxygen partial pressures below 230 °C

Uranium monocarbide (UC) powders are known to be easily oxidised by gas mixtures containing oxygen. In this study, the oxidation of UC micron powders was followed by isothermal thermogravimetry at temperatures ranging from 100 °C to 230 °C in two different gas mixtures: synthetic air and 97%N₂ + 3%O₂. X-ray diffraction tests conducted on powders after their oxidation showed that small crystallites of UO₂ oxide are formed. Furthermore, an analysis of mass gain showed that the carbon initially linked with the uranium is not oxidised but retained in oxide layers. Additionally, this kinetic study revealed that the rate-limiting step mechanism governing the oxidation of UC powders is a diffusive process that follows the Arrhenius law regarding temperature. Finally, it was discovered that cracks occur in grains once a given fractional conversion has been reached, inducing a major increase in the volume of grains.     

Latex coatings containing antifeedants: Formulation,characterization, and application for protection of conifer seedlings against pine weevil feeding

Latex-based coatings for protection of tree seedlings against pest insect feeding are evaluated with respect to surface-, mechanical-, and release properties and antifeedant activity. The latex dispersion Eudragit copolymer (EC) was used to form the coatings, 2,6-di-tert-butyl-4-methylphenol (BHT) and cis-dihydropinidine (Alk) as antifeedants, and a thickener and a alkylglucoside based nonionic surfactant were used as additives to optimize the release- and mechanical properties of coatings. Coating characterization was performed with respect to surface morphology (atomic force microscopy, AFM) and surface wetting (contact angle), as well as to mechanical (tensile stress- and tensile strain at break) properties. Surface smoothness and wettability as well as elasticity increased with addition of the surfactant. The optimized coatings were found to be elastic and water resistant at 3–6 wt.% of BHT and 3 wt.% of surfactant. BHT was released into SDS/water at very low rates. Several formulations of BHT and Alk were efficient in preventing the feeding on conifer bark by a pine insect, Hylobius abietis both in laboratory (no-choice) and in field (3 months) tests.