Shotgun Lipidomics Discovered Diurnal Regulation of Lipid Metabolism Linked to Insulin Sensitivity in Nondiabetic Men.

CONTEXT: Meal timing affects metabolic homeostasis and body weight, but how composition and timing of meals affect plasma lipidomics in humans is not well studied. OBJECTIVE: We used high throughput shotgun plasma lipidomics to investigate effects of timing of carbohydrate and fat intake on lipid metabolism and its relation to glycemic control. DESIGN: 29 nondiabetic men consumed (1) a high-carb test meal (MTT-HC) at 09.00 and a high-fat meal (MTT-HF) at 15.40; or (2) MTT-HF at 09.00 and MTT-HC at 15.40. Blood was sampled before and 180 minutes after completion of each MTT. Subcutaneous adipose tissue (SAT) was collected after overnight fast and both MTTs. Prior to each investigation day, participants consumed a 4-week isocaloric diet of the same composition: (1) high-carb meals until 13.30 and high-fat meals between 16.30 and 22:00 or (2) the inverse order. RESULTS: 12 hour daily lipid patterns showed a complex regulation by both the time of day (67.8%) and meal composition (55.4%). A third of lipids showed a diurnal variation in postprandial responses to the same meal with mostly higher responses in the morning than in the afternoon. Triacylglycerols containing shorter and more saturated fatty acids were enriched in the morning. SAT transcripts involved in fatty acid synthesis and desaturation showed no diurnal variation. Diurnal changes of 7 lipid classes were negatively associated with insulin sensitivity, but not with glucose and insulin response or insulin secretion. CONCLUSIONS: This study identified postprandial plasma lipid profiles as being strongly affected by meal timing and associated with insulin sensitivity

Assembling proteomics data as a prerequisite for the analysis of large scale experiments

<p>Abstract</p> <p>Background</p> <p>Despite the complete determination of the genome sequence of a huge number of bacteria, their proteomes remain relatively poorly defined. Beside new methods to increase the number of identified proteins new database applications are necessary to store and present results of large- scale proteomics experiments.</p> <p>Results</p> <p>In the present study, a database concept has been developed to address these issues and to offer complete information via a web interface. In our concept, the Oracle based data repository system SQL-LIMS plays the central role in the proteomics workflow and was applied to the proteomes of <it>Mycobacterium tuberculosis</it>, <it>Helicobacter pylori</it>, <it>Salmonella typhimurium </it>and protein complexes such as 20S proteasome. Technical operations of our proteomics labs were used as the standard for SQL-LIMS template creation. By means of a Java based data parser, post-processed data of different approaches, such as LC/ESI-MS, MALDI-MS and 2-D gel electrophoresis (2-DE), were stored in SQL-LIMS. A minimum set of the proteomics data were transferred in our public 2D-PAGE database using a Java based interface (Data Transfer Tool) with the requirements of the PEDRo standardization. Furthermore, the stored proteomics data were extractable out of SQL-LIMS via XML.</p> <p>Conclusion</p> <p>The Oracle based data repository system SQL-LIMS played the central role in the proteomics workflow concept. Technical operations of our proteomics labs were used as standards for SQL-LIMS templates. Using a Java based parser, post-processed data of different approaches such as LC/ESI-MS, MALDI-MS and 1-DE and 2-DE were stored in SQL-LIMS. Thus, unique data formats of different instruments were unified and stored in SQL-LIMS tables. Moreover, a unique submission identifier allowed fast access to all experimental data. This was the main advantage compared to multi software solutions, especially if personnel fluctuations are high. Moreover, large scale and high-throughput experiments must be managed in a comprehensive repository system such as SQL-LIMS, to query results in a systematic manner. On the other hand, these database systems are expensive and require at least one full time administrator and specialized lab manager. Moreover, the high technical dynamics in proteomics may cause problems to adjust new data formats. To summarize, SQL-LIMS met the requirements of proteomics data handling especially in skilled processes such as gel-electrophoresis or mass spectrometry and fulfilled the PSI standardization criteria. The data transfer into a public domain via DTT facilitated validation of proteomics data. Additionally, evaluation of mass spectra by post-processing using MS-Screener improved the reliability of mass analysis and prevented storage of data junk.</p

Allele-Specific, Age-Dependent and BMI-Associated DNA Methylation of Human MCHR1

Background: Melanin-concentrating hormone receptor 1 (MCHR1) plays a significant role in regulation of energy balance, food intake, physical activity and body weight in humans and rodents. Several association studies for human obesity showed contrary results concerning the SNPs rs133072 (G/A) and rs133073 (T/C), which localize to the first exon of MCHR1. The variations constitute two main haplotypes (GT, AC). Both SNPs affect CpG dinucleotides, whereby each haplotype contains a potential methylation site at one of the two SNP positions. In addition, 15 CpGs in close vicinity of these SNPs constitute a weak CpG island. Here, we studied whether DNA methylation in this sequence context may contribute to population- and age-specific effects of MCHR1 alleles in obesity. \ud Principal Findings: We analyzed DNA methylation of a 315 bp region of MCHR1 encompassing rs133072 and rs133073 and the CpG island in blood samples of 49 individuals by bisulfite sequencing. The AC haplotype shows a significantly higher methylation level than the GT haplotype. This allele-specific methylation is age-dependent. In young individuals (20â\u80\u9330 years) the difference in DNA methylation between haplotypes is significant; whereas in individuals older than 60 years it is not detectable. Interestingly, the GT allele shows a decrease in methylation status with increasing BMI, whereas the methylation of the AC allele is not associated with this phenotype. Heterozygous lymphoblastoid cell lines show the same pattern of allele-specific DNA methylation. The cell line, which exhibits the highest difference in methylation levels between both haplotypes, also shows allele-specific transcription of MCHR1, which can be abolished by treatment with the DNA\ud methylase inhibitor 5-aza-2&apos;-deoxycytidine.\ud Conclusions:We show that DNA methylation at MCHR1 is allele-specific, age-dependent, BMI-associated and affects transcription. Conceivably, this epigenetic regulation contributes to the age- and/or population specific effects reported for MCHR1 in several human obesity studies.\ud \ud doi: 10.1371/journal.pone.0017711\u

Evidence for Novel Hepaciviruses in Rodents

Hepatitis C virus (HCV) is among the most relevant causes of liver cirrhosis and hepatocellular carcinoma. Research is complicated by a lack of accessible small animal models. The systematic investigation of viruses of small mammals could guide efforts to establish such models, while providing insight into viral evolutionary biology. We have assembled the so-far largest collection of small-mammal samples from around the world, qualified to be screened for bloodborne viruses, including sera and organs from 4,770 roden

Classification of acute and delayed contrast media-induced reactions: proposal of a three-step system

Physicians and scientists use a broad spectrum of terms to classify contrast media (CM)-induced adverse reactions. In particular, the designation of hypersensitivity reactions is quite varied. Consequently, comparisons of different papers dealing with this subject are difficult or even impossible. Moreover, general descriptions may lead to problems in understanding reactions in patients with a history of adverse CM-reactions, and in efficiently managing these patients. Therefore, the goal of this paper is to suggest an easy system to clearly classify these reactions. The proposed three-step systems (3SS) is built up as follows: step 1 exactly describes the clinical features, including their severity; step 2 categorizes the time point of the onset (immediate or nonimmediate); and step 3 generally classifies the reaction (hypersensitivity or nonhypersensitivity reaction). The 3SS may facilitate better understanding of the clinical manifestations of adverse CM reactions and may support the prevention of these reactions on the basis of personalized medicine approaches

Reduktion der Befund-Turn-around-Time in der Klinik für Strahlendiagnostik - Prozessoptimierung nach der Six Sigma Methode

Die zunehmende Ökonomisierung des Gesundheitswesens erfordert von den wirtschaftlich und medizinisch Verantwortlichen neue Lösungskonzepte, um wirtschaftlich bestehen zu können und dabei weiterhin gleich hohe Qualität in der Patientenversorgung zu gewährleisten. Die Optimierung über Personalabbau, Bildung von „Einkaufsgemeinschaften“ und die Volldigitalisierung der radiologischen Abteilungen ist weitgehend ausgereizt, so dass der nächste Schritt die konsequente Optimierung der Prozesse ist. Im Vergleich radiologischer Kliniken wird die Zeit zwischen Durchführung einer Untersuchung und fachärztlicher Vidierung (report turn around time - RTAT) zunehmend als Leistungsindikator angesehen, da sie gemeinsam mit der zeitnahen Verfügbarkeit radiologischer Diagnostik unmittelbaren Einfluss auf die Patientenverweildauer und damit auf den wirtschaftlichen Erfolg eines Klinikums hat. Zur Optimierung der RTAT setzten wir die aus der produzierenden Industrie bekannte Six-Sigma-Methode ein. Ihr Kernelement ist die Beschreibung, Messung, Analyse, Verbesserung und Überwachung von Prozessen mit statistischen Mitteln. Zudem bietet die klar strukturierte Herangehensweise an Prozesse eine hervorragende Grundlage für den Einstieg in prozessorientiertes Management. Mit der Six Sigma Methode gelang es, die RTAT der betrachteten Modalitäten CR, CT und MRT über die Monate Juli bis Dezember 2008, je nach betrachtetem Zeitintervall (4h ,8h, 24h) und betrachteter Modalität (CR, CT, MR), zwischen 3% und 20% zu verbessern. Der Anteil der Langläufer &gt; 24 h RTAT konnte von 9,2% auf 3,9% aller Befunde gesenkt werden. Es werden nun also unabhängig von Wochentag oder Tageszeit 96,1% aller Befunde innerhalb von 24 Stunden nach Bilderstellung fachärztlich vidiert. Das Ziel, die Langläufer vollständig zu eliminieren, konnte nicht erreicht werden. Sowohl im Regeldienst als auch im Bereitschaftsdienst entstehen weiterhin prozesskonforme Langläufer, 37% auf Grund verlängerter Befunderfassung, 57% auf Grund verzögerter Vidierung. Die Anzahl der nicht prozesskonformen Langläufer konnte von ca. 40% auf 6% gesenkt werden. Zusätzlich führte der Einsatz von Six-Sigma bei allen Mitarbeitern zu einem arbeitsplatzübergreifenden Verständnis der internen Prozesse. Prozesstransparenz gepaart mit konsequenter Fehlervermeidung ermöglicht eine deutlich höhere Leistung bei identischem Einsatz von Personal- und Technik-Ressourcen