The role of tryptophan in protein fibrillogenesis: relevance of Trp7 and Trp14 to the amyloidogenic properties of myoglobin

In order to understand the role of tryptophan in the mechanisms of fibrils formation, the ability of a series of analogs of the residue 7-18 span of myoglobin to form amyloid-like fibrils was investigated. Alternatively one or both tryptophans were substituted with alanine and leucine, to determine the contribution of hydrophobicity and aromaticity. The scale of aggregation propensity of the peptides determined indicates that tryptophan is crucial for the amyloidogenic process. Since the rare tryptophan residue is generally engaged in structural roles in proteins, or when exposed serves as binding sites, we surmise that its exposure in the amyloidogenic fragments allows for intermolecular clustering with residues from other molecules leading to the formation of amyloid aggregates.     

Crosstalk between the AMP-activated kinase and insulin signaling pathways rescues murine blastocyst cells from insulin resistance

Maternal insulin resistance results in poor pregnancy outcomes. In vivo and in vitro exposure of the murine blastocyst to high insulin or IGF1 results in the down-regulation of the IGF1 receptor (IGF1R). This in turn leads to decreased glucose uptake, increased apoptosis, as well as pregnancy resorption and growth restriction. Recent studies have shown that blastocyst activation of AMP-activated protein kinase (AMPK) reverses these detrimental effects; however, the mechanism was not clear. The objective of this study was to determine how AMPK activation rescues the insulin-resistant blastocyst. Using trophoblast stem (TS) cells derived from the blastocyst, insulin resistance was recreated by transfecting with siRNA to Igf1r and down-regulating expression of the protein. These cells were then exposed to AMPK activators 5-aminoimidazole-4-carboxamide riboside and phenformin, and evaluated for apoptosis, insulin-stimulated 2-deoxyglucose uptake, PI3-kinase activity, and levels of phospho-AKT, phospho-mTor, and phospho-70S6K. Surprisingly, disrupted insulin signaling led to decreased AMPK activity in TS cells. Activators reversed these effects by increasing the AMP/ATP ratio. Moreover, this treatment increased insulin-stimulated 2-deoxyglucose transport and cell survival, and led to an increase in PI3-kinase activity, as well as increased P-mTOR and p70S6K levels. This study is the first to demonstrate significant crosstalk between the AMPK and insulin signaling pathways in embryonic cells, specifically the enhanced response of PI3K/AKT/mTOR to AMPK activation. Decreased insulin signaling also resulted in decreased AMPK activation. These findings provide mechanistic targets in the AMPK signaling pathway that may be essential for improved pregnancy success in insulin-resistant states.     

High-Throughput Analysis of Algal Crude Oils Using High Resolution Mass Spectrometry

Lipid analysis often needs to be specifically optimized for each class of compounds due to its wide variety of chemical and physical properties. It becomes a serious bottleneck in the development of algae-based next generation biofuels when high-throughput analysis becomes essential for the optimization of various process conditions. We propose a high-resolution mass spectrometry-based high-throughput assay as a ‘quick-and-dirty’ protocol to monitor various lipid classes in algal crude oils. Atmospheric pressure chemical ionization was determined to be most effective for this purpose to cover a wide range of lipid classes. With an autosampler-LC pump set-up, we could analyze algal crude samples every one and half minutes, monitoring several lipid species such as TAG, DAG, squalene, sterols, and chlorophyll a. High-mass resolution and high-mass accuracy of the orbitrap mass analyzer provides confidence in the identification of these lipid compounds. MS/MS and MS3 analysis could be performed in parallel for further structural information, as demonstrated for TAG and DAG. This high-throughput method was successfully demonstrated for semi-quantitative analysis of algal oils after treatment with various nanoparticles.     

Precision Oncology via NMR-Based Metabolomics: A Review on Breast Cancer

Precision oncology is an emerging approach in cancer care. It aims at selecting the optimal therapy for the right patient by considering each patient’s unique disease and individual health status. In the last years, it has become evident that breast cancer is an extremely heterogeneous disease, and therefore, patients need to be appropriately stratified to maximize survival and quality of life. Gene-expression tools have already positively assisted clinical decision making by estimating the risk of recurrence and the potential benefit from adjuvant chemotherapy. However, these approaches need refinement to further reduce the proportion of patients potentially exposed to unnecessary chemotherapy. Nuclear magnetic resonance (NMR) metabolomics has demonstrated to be an optimal approach for cancer research and has provided significant results in BC, in particular for prognostic and stratification purposes. In this review, we give an update on the status of NMR-based metabolomic studies for the biochemical characterization and stratification of breast cancer patients using different biospecimens (breast tissue, blood serum/plasma, and urine).     

Properties of rice bran oil‐derived functional ingredients

Lipid ingredients that demonstrate high stability and positive health profiles without the use of trans‐fats are needed in the food supply. Rice bran oil can be fractionated at low temperatures to create a series of spreads that show promise as functional ingredients. A rice bran oil‐derived spread can extend the fry life of soybean oil and can also be incorporated into baked goods such as bread and granola as a trans‐fat free alternative to butter or shortening.     

How to get residents/owners in housing cooperatives to agree on sustainable renovation

What factors increase the chance that residents/owners in housing cooperatives agree on sustainable energy efficient renovation? Based on 30 qualitative interviews with professional advisors in cooperative housing associations and chairman/board and residents in three chosen case studies, an analysis of opportunities and barriers for making a common decision on renovation is performed. Success criteria and barriers are found on the societal level as well as on the organizational/individual level. The barriers and success criteria identified on the societal level are: knowledge level on energy-efficient renovation among relevant actors, owner structure of the housing cooperative, and existing regulations and incentives. On the organizational and individual level, the following categories influencing renovation processes were identified: the time frame and organization of the process, understanding the residents` needs, economy, the information given, and the existence of available exemplary projects and role models. Based on the results of the study, ten guidelines that contribute to more successful decision making processes and increase the chances of sustainable energy efficient renovation in housing cooperatives are presented.     

Solutionizing effects on deformation-induced phase transformations in 2014 aluminum composite

A solutionizing heat treatment of 2014 aluminum alloy reinforced with 0.15 volume fraction of alumina particles (VFAP) results in deformation-induced precipitation during rolling and tensile deformation, with 0.10 VFAP, at room temperature. The extent of precipitation increases with increase in time and/or temperature of solutionizing. An attempt has been made to identify the various types of precipitates in the samples deformed to a given strain and in fractured conditions. The work-hardening curves and tensile properties of the composites have been shown to be dependent on the time and temperature combination of the solutionizing process.