Systems biology of stored blood cells: can it help to extend the expiration date?

Efst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinnWith increasingly stringent regulations regarding deferral and elimination of blood donors it will become increasingly important to extend the expiration date of blood components beyond the current allowed storage periods. One reason for the storage time limit for blood components is that platelets and red blood cells develop a condition called storage lesions during their storage in plastic blood containers. Systems biology provides comprehensive bio-chemical descriptions of organisms through quantitative measurements and data integration in mathematical models. The biological knowledge for a target organism can be translated in a mathematical format and used to compute physiological properties. The use of systems biology represents a concrete solution in the study of blood cell storage lesions, and it may open up new avenues towards developing better storage methods and better storage media, thereby extending the storage period of blood components. This article is part of a Special Issue entitled: Integrated omics.info:eu-repo/grantAgreement/EC/FP7/23281

NEUTRAL LOSS ANALYSIS OF AMINO ACIDS BY DESORPTION ELECTROSPRAY IONIZATION USING AN UNMODIFIED TANDEM QUADRUPOLE MASS SPECTROMETER.

A new method to analyze free amino acids using desorption electrospray ionization (DESI) has been implemented. The method is based on the neutral loss mode determination of underivatized amino acids using a tandem quadrupole mass spectrometer equipped with an unmodified atmospheric interface. Qualitative and quantitative optimization of DESI parameters, including ESI voltage, solvent flow rate, angle of collection and incidence, gas flow and temperatures, was performed for amino acids detection. The parameters for DESI analysis were evaluated using a mixture of valine, leucine, methionine, phenylalanine and tyrosine standards. A few microliters of this mixture were deposited on a slide, dried and analyzed at a flow rate of 2mL/min. The optimal ionization response was obtained using laboratory glass slides and an equivalent solution of water/methanol doped with 2% of formic acid. The method specificity was evaluated by comparing product ion spectra and neutral loss analysis of amino acids obtained either by DESI or by electrospray ionization flow injection analysis (ESI-FIA). To evaluate the quantitative response on amino acids analyzed by DESI, calibration curves were performed on amino acid standard solutions spiked with a fixed amount of labelled amino acids. The method was also employed to analyze free amino acids from blood spots, after a rapid solvent extraction without other sample pretreatment, from positive and negative subjects. The method enables one to analyze biological samples and to discriminate healthy subjects from patients affected by inherited metabolic diseases. The intrinsic high-throughput analysis of DESI represents an opportunity, because of its potential application in clinical chemistry.....

Effects of abiotic stressors on lutein production in the green microalga Dunaliella salina.

BackgroundRecent years have witnessed a rising trend in exploring microalgae for valuable carotenoid products as the demand for lutein and many other carotenoids in global markets has increased significantly. In green microalgae lutein is a major carotenoid protecting cellular components from damage incurred by reactive oxygen species under stress conditions. In this study, we investigated the effects of abiotic stressors on lutein accumulation in a strain of the marine microalga D. salina which had been selected for growth under stress conditions of combined blue and red lights by adaptive laboratory evolution.ResultsNitrate concentration, salinity and light quality were selected as three representative influencing factors and their impact on lutein production in batch cultures of D. salina was evaluated using response surface analysis. D. salina was found to be more tolerant to hyper-osmotic stress than to hypo-osmotic stress which caused serious cell damage and death in a high proportion of cells while hyper-osmotic stress increased the average cell size of D. salina only slightly. Two models were developed to explain how lutein productivity depends on the stress factors and for predicting the optimal conditions for lutein productivity. Among the three stress variables for lutein production, stronger interactions were found between nitrate concentration and salinity than between light quality and the other two. The predicted optimal conditions for lutein production were close to the original conditions used for adaptive evolution of D. salina. This suggests that the conditions imposed during adaptive evolution may have selected for the growth optima arrived at.ConclusionsThis study shows that systematic evaluation of the relationship between abiotic environmental stresses and lutein biosynthesis can help to decipher the key parameters in obtaining high levels of lutein productivity in D. salina. This study may benefit future stress-driven adaptive laboratory evolution experiments and a strategy of applying stress in a step-wise manner can be suggested for a rational design of experiments

Stainless Steel Valves with Enhanced Fatigue And Corrosion Performance Through Microstructure Optimization

In order to increase the energy efficiency of refrigerators, compressors, incorporating valves with new geometries have been developed over the past few years. In addition, higher stresses are increasingly placed upon the valve itself during operation. Hence, higher demands are set on the steel strip used to produce such valves. Today, compressor valves for refrigerators are mainly manufactured from hardened and tempered martensitic stainless steels. The main design criterion for the material selection is the endurance limit of the material under bending. However, impact loads and corrosive atmospheres often act additionally on the valve. To fulfil the increased demands for such new valves, the microstructure of the most commonly used stainless steel grade is refined. Through this method a new grade Zapp Super-Fatigue is developed, whereby the yield strength, ultimate tensile strength and bending fatigue are increased. In addition, the corrosion resistance of the material is also significantly increased. All the tests are performed with industrial scale processes and material. The properties are determined with samples taken from various production lots. Tensile properties as well as bending fatigue tests are performed on a strip with thickness typical for valves used for refrigerators. Current density potential measurements are conducted to confirm and explain the corrosion test results. Finally, the microstructure is characterized using a scanning electron microscopy with the electron back scatter diffraction method. For the first time, the microstructures of the most commonly used stainless steel and the improved grade Zapp Super-Fatigue are compared. It is demonstrated how the fatigue limit and the corrosion resistance of a martensitic stainless steel can be enhanced by tailoring the microstructure

Improvement of Tuberculosis Laboratory Capacity on Pemba Island, Zanzibar: A Health Cooperation Project.

Low-income countries with high Tuberculosis burden have few reference laboratories able to perform TB culture. In 2006, the Zanzibar National TB Control Programme planned to decentralize TB diagnostics. The Italian Cooperation Agency with the scientific support of the "L. Spallanzani" National Institute for Infectious Diseases sustained the project through the implementation of a TB reference laboratory in a low-income country with a high prevalence of TB. The implementation steps were: 1) TB laboratory design according to the WHO standards; 2) laboratory equipment and reagent supplies for microscopy, cultures, and identification; 3) on-the-job training of the local staff; 4) web- and telemedicine-based supervision. From April 2007 to December 2010, 921 sputum samples were received from 40 peripheral laboratories: 120 TB cases were diagnosed. Of all the smear-positive cases, 74.2% were culture-positive. During the year 2010, the smear positive to culture positive rate increased up to 100%. In March 20, 2010 the Ministry of Health and Social Welfare of Zanzibar officially recognized the Public Health Laboratory- Ivo de Carneri as the National TB Reference Laboratory for the Zanzibar Archipelago. An advanced TB laboratory can represent a low cost solution to strengthen the TB diagnosis, to provide capacity building and mid-term sustainability

Elucidating dynamic metabolic physiology through network integration of quantitative time-course metabolomics.

Efst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.The increasing availability of metabolomics data necessitates novel methods for deeper data analysis and interpretation. We present a flux balance analysis method that allows for the computation of dynamic intracellular metabolic changes at the cellular scale through integration of time-course absolute quantitative metabolomics. This approach, termed "unsteady-state flux balance analysis" (uFBA), is applied to four cellular systems: three dynamic and one steady-state as a negative control. uFBA and FBA predictions are contrasted, and uFBA is found to be more accurate in predicting dynamic metabolic flux states for red blood cells, platelets, and Saccharomyces cerevisiae. Notably, only uFBA predicts that stored red blood cells metabolize TCA intermediates to regenerate important cofactors, such as ATP, NADH, and NADPH. These pathway usage predictions were subsequently validated through (13)C isotopic labeling and metabolic flux analysis in stored red blood cells. Utilizing time-course metabolomics data, uFBA provides an accurate method to predict metabolic physiology at the cellular scale for dynamic systems.National Heart Lung and Blood Institute European Research Council U.S. Department of Energ

Erratum to: Break in volition: a virtual reality study in patients with obsessive-compulsive disorder

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Unbiased metabolomic investigation of Alzheimer's disease brain points to dysregulation of mitochondrial aspartate metabolism

Alzheimer's disease (AD) is the most common cause of adult dementia. Yet the complete set of molecular changes accompanying this inexorable, neurodegenerative disease remains elusive. Here we adopted an unbiased lipidomics and metabolomics approach to surveying frozen frontal cortex samples from clinically characterized AD patients (n = 21) and age-matched controls (n = 19), revealing marked molecular differences between them. Then, by means of metabolomic pathway analysis, we incorporated the novel molecular information into the known biochemical pathways and compared it with the results of a metabolomics meta-analysis of previously published AD research. We found six metabolic pathways of the central metabolism as well as glycerophospholipid metabolism predominantly altered in AD brains. Using targeted metabolomics approaches and MS imaging, we confirmed a marked dysregulation of mitochondrial aspartate metabolism. The altered metabolic pathways were further integrated with clinical data, showing various degrees of correlation with parameters of dementia and AD pathology. Our study highlights specific, altered biochemical pathways in the brains of individuals with AD compared with those of control subjects, emphasizing dysregulation of mitochondrial aspartate metabolism and supporting future venues of investigation

Sustained response off therapy after fostamatinib: A chronic refractory ITP case report

Fostamatinib is a SYK-inhibitor drug recently approved by the FDA and EMA for treating chronic immune thrombocytopenia. This drug induces a response in about 40% of patients and has a good toxicity profile. It is known that discontinuing thrombopoietin receptor agonists (TRAs) with the maintenance of sustained response off therapy is possible. On fostamatinib, we do not yet have such information. In this case report, we describe the story of a woman with a multirefractory immune thrombocytopenia (steroids, splenectomy, rituximab, both available TRAs). After 16 years from diagnosis, she started fostamatinib therapy within a clinical trial and achieved a complete response. Grade 1-2 headache and diarrhea occurred during the first months of therapy. These adverse events were resolved with dose reduction of fostamatinib. Despite the dose reduction, the platelet count remained steadily above 80 x 109/L. After 4 years, fostamatinib was gradually reduced and finally discontinued with no drop in platelet count. This is the first case in which fostamatinib discontinuation resulted in a sustained response off therapy

Correction to: Longitudinal Assessment of Chlorpyrifos Exposure in Farmers and Residents of an Italian Alpine Region

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