NMR-based characterization of metabolic alterations in hypertension using an adaptive, intelligent binning algorithm

As with every -omics technology, metabolomics requires new methodologies for data processing. Due to the large spectral size, a standard approach in NMR-based metabolomics implies the division of spectra into equally sized bins, thereby simplifying subsequent data analysis. Yet, disadvantages are the loss of information and the occurrence of artifacts caused by peak shifts. Here, a new binning algorithm, Adaptive Intelligent Binning (AI-Binning), which largely circumvents these problems, is presented. AI-Binning recursively identifies bin edges in existing bins, requires only minimal user input, and avoids the use of arbitrary parameters or reference spectra. The performance of AI-Binning is demonstrated using serum spectra from 40 hypertensive and 40 matched normotensive subjects from the Asklepios study. Hypertension is a major cardiovascular risk factor characterized by a complex biochemistry and, in most cases, an unknown origin. The binning algorithm resulted in an improved classification of hypertensive status compared with that of standard binning and facilitated the identification of relevant metabolites. Moreover, since the occurrence of noise variables is largely avoided, AI-Binned spectra can be unit-variance scaled. This enables the detection of relevant, low-intensity metabolites. These results demonstrate the power of AI-Binning and suggest the involvement of alpha-1 acid glycoproteins and choline biochemistry in hypertension.     

Peniophora lycii phytase is stabile and degrades phytate and solubilises minerals in vitro during simulation of gastrointestinal digestion in the pig

BACKGROUND: Microbial phytases (EC 3.1.3) are widely used in diets for monogastric animals to hydrolyse phytate present in the feed and thereby increase phosphorus and mineral availability. Previous work has shown that phytate solubility is strongly affected by calcium in the feed and by pH in the gastrointestinal (GI) tract, which may have an effect on phytase efficacy. An in vitro model simulating the GI tract of pigs was used to study the survival of Peniophora lycii phytase and the effect of the phytase on phytate degradation, inositol phosphate formation and mineral solubilisation during in vitro digestion of a 30:70 soybean meal/maize meal blend with different calcium levels. RESULTS: The phytase retained 76 and 80% of its initial activity throughout the gastric in vitro digestion. Total phytate hydrolysis by P. lycii phytase was in the same range at total calcium levels of 1.2 and 6.2 mg g^?1 dry matter (DM), despite very large differences in phytate solubility at these calcium levels. However, at 11.2 and 21.2 mg Ca g^?1 DM, phytate hydrolysis was significantly lower. The amount of soluble mineral was generally increased by P. lycii phytase. CONCLUSION: Stability of P. lycii phytase during gastric digestion was not found to be critical for phytate hydrolysis. Furthermore, original phytate solubility was not an absolute requirement for phytate degradation; phytate solubility seemed to be in a steady state, allowing insoluble phytate to solubilise as soluble phytate was degraded. This is new and interesting knowledge that adds to the current understanding of phytate–phytase interaction. Copyright © 2007 Society of Chemical Industry     

Cloning, characterization and functionality of the orotidine-5'-phosphate decarboxylase gene (URA3) of the glycolipid-producing yeast Candida bombicola

Candida bombicola is a yeast species known to synthesize glycolipids. Although these glycolipids find several industrial, cosmetic and pharmaceutical applications, very little is known about the genetics of C. bombicola. A basic tool for genetic study and modification is the availability of an efficient transformation and selection system. In order to develop such a system, the URA3 gene of Candida bombicola was isolated using degenerate PCR and genomic walking. The gene encodes for an enzyme of 262 amino acids and shows high homology with the known orotidine-5'-phosphate decarboxylases of several other yeast species. The functionality of the gene was proved by complementation of a URA3-negative Saccharomyces cerevisiae strain.     

Pathogen-specific incidence rate of clinical mastitis in Flemish dairy herds,severity, and association with herd hygiene

A one-year survey on clinical mastitis was conducted on 50 randomly selected commercial Flemish dairy herds to estimate the pathogen-specific incidence rate of clinical mastitis (IRCM). The severity of the cases and the potential associations with herd hygiene were studied. Participating producers sampled 845 cases and 692 dairy cows. The mean and median IRCM was estimated at 7.4 and 5.3 quarter cases per 10,000 cow-days at risk, respectively. A large between-herd variation was observed (range of 0–21.3). In general, the IRCM was lower in heifers compared with multiparous cows (2.9 vs. 11.0 quarter cases per 10,000 cow-days at risk). However, the overall IRCM in the first week after calving was higher in heifers compared with cows (43.4 vs. 31.6 quarter cases per 10,000 cow-days at risk). Streptococcus uberis (18.2% of the cases) and Escherichia coli (15.5%) were the most frequently isolated pathogens and no growth was observed in 19.9% of the cases. The majority of the cases (63.1%) were mild (only clots in milk). Moderate (hard quarter without general signs) and severe symptoms (systemic illness) were observed in 29.9 and 7.0% of the cases, respectively. Isolation of E. coli (vs. any other culture result) was more likely in moderate and severe cases compared with mild cases. Overall IRCM and E. coli IRCM were higher in dirty compared with clean herds based on udder hygiene scores (9.0 and 1.7 vs. 6.0 and 0.6 quarter cases per 10,000 cow-days at risk, respectively). This study broadens the knowledge on clinical mastitis in Flemish dairy herds and underlines the high risk of CM in early-lactation heifers, the role of the so-called environmental pathogens, and herd hygiene.     

Barriers impairing mineral bioaccessibility and bioavailability in plant-based foods and the perspectives for food processing

Abstract

Plant-based foods gain more importance since they play a key role in sustainable, low-meat and healthy diets. In developing countries, these food products, especially legumes and cereals, are important staple foods. Nevertheless, the question arises on how efficient they are to deliver minerals and if it is useful to encourage their consumption to reduce the prevalence of mineral deficiencies? This review paper focuses on the discrepancy between the mineral content and the amount of minerals that can be released and absorbed from plant-based foods during human digestion which can be attributed to several inherent factors such as the presence of mineral antinutrients (phytic acid, polyphenols and dietary fiber) and physical barriers (surrounding macronutrients and cell wall). Further, this review paper summarizes the effects of different processing techniques (milling, soaking, dehulling, fermentation, germination and thermal processing) on mineral bioaccessibility and bioavailability of plant-based foods. The positive impact of these techniques mostly relies on the fact that antinutrients levels are reduced due to removal of fractions rich in antinutrients and/or due to their leaching into the processing liquid. Although processing can have a positive effect, it also can induce leaching out of minerals and a reduced mineral bioaccessibility and bioavailability.     

Dendritic Cell-Based Immunotherapy in Multiple Myeloma: Challenges,Opportunities, and Future Directions

Immunotherapeutic approaches, including adoptive cell therapy, revolutionized treatment in multiple myeloma (MM). As dendritic cells (DCs) are professional antigen-presenting cells and key initiators of tumor-specific immune responses, DC-based immunotherapy represents an attractive therapeutic approach in cancer. The past years, various DC-based approaches, using particularly ex-vivo-generated monocyte-derived DCs, have been tested in preclinical and clinical MM studies. However, long-term and durable responses in MM patients were limited, potentially attributed to the source of monocyte-derived DCs and the immunosuppressive bone marrow microenvironment. In this review, we briefly summarize the DC development in the bone marrow niche and the phenotypical and functional characteristics of the major DC subsets. We address the known DC deficiencies in MM and give an overview of the DC-based vaccination protocols that were tested in MM patients. Lastly, we also provide strategies to improve the efficacy of DC vaccines using new, improved DC-based approaches and combination therapies for MM patients.     

Tailoring solid-state synthesis routes for high confidence production of phase pure,low impedance Al-LLZO

Lithium lanthanum zirconium oxide (LLZO) garnet is a solid-state lithium ion conducting electrolyte promising all-solid-state batteries (ASSB) with high charge rates and good energy density due to its chemical stability against lithium metal anodes. LLZO has a high room temperature Li ion conductivity of ∼0.1–1 mS/cm in its cubic phase, but the stability of the cubic phase and ionic conductivity are highly sensitive to lithium stoichiometry. Stabilizing agents such as aluminum oxide and excess lithium are needed to preserve the cubic phase and compensate for lithium volatility. With the range of the end LLZO products spanning powders, porous membranes to dense membranes combined with sintering/calcination that often exceeds 1000°C, it is challenging to maintain an ideal lithium content given its high volatility from a single base powder. This study was designed to elucidate the sensitivities of aluminum doped LLZO powder synthesis and processing along its path to being utilized in a ceramic-manufacturing optimized ASSB. By utilizing thermogravimetric analysis in conjunction with in situ X-ray diffraction analysis of solid-state LLZO synthesis, it was discovered that the sensitivity of the LLZO cubic phase to lithium volatility can be reduced via early incorporation of excess lithium carbonate during initial phase formation in direct combination with controlled surface-to-volume ratios of the powders. Isostatically pressed powders of our LLZO sintered at 1100°C for 2 h showed RT ionic conductivity of 0.3–0.4 mS/cm measured via electrochemical impedance spectroscopy, and an improvement in microstructural uniformity with lowered porosity. The improved suppression of lithium volatilization has important implications for the scalable production of LLZO powders and assembly of ASSBs.