Multivariate statistical analysis of three-spatial-dimension TOF-SIMS raw data sets

Three-spatial-dimension (3D) time-of-flight-secondary ion mass spectrometry (TOF-SIMS) analysis can be performed if an X-Y image is saved at each depth of a depth profile. In this paper, we will show how images reconstructed from specified depths, depth profiles generated from specific X-Y coordinates, as well as three-spatial-dimensional rendering provide for a better understanding of the sample than traditional depth profiling where only a single spectrum is collected at each depth. We will also demonstrate, for the first time, that multivariate statistical analysis (MVSA) tools can be used to perform a rapid, unbiased analysis of the entire 3D data set. In the example shown here, retrospective analysis and MVSA revealed a more complete picture of the 3D chemical distribution of the sample than did the as-measured depth profiling alone. Color overlays of the MVSA components as well as animated movies allowing for visualization (in 3D) from various angles will be provided.     

Structural rearrangements near the chromophore influence the maturation speed and brightness of DsRed variants

The red fluorescent protein DsRed has been extensively engineered for use as an in vivo research tool. In fast maturing DsRed variants, the chromophore maturation half-time is approximately 40 min, compared to approximately 12 h for wild-type DsRed. Further, DsRed has been converted from a tetramer into a monomer, a task that entailed mutating approximately 20% of the amino acids. These engineered variants of DsRed have proven extremely valuable for biomedical research, but the structural basis for the improved characteristics has not been thoroughly investigated. Here we present a 1.7 A crystal structure of the fast maturing tetrameric variant DsRed.T4. We also present a biochemical characterization and 1.6 A crystal structure of the monomeric variant DsRed.M1, also known as DsRed-Monomer. Analysis of the crystal structures suggests that rearrangements of Ser69 and Glu215 contribute to fast maturation, and that positioning of the Lys70 side chain modulates fluorescence quantum yield. Despite the 45 mutations in DsRed.M1 relative to wild-type DsRed, there is a root-mean-square deviation of only 0.3 A between the two structures. We propose that novel intramolecular interactions in DsRed.M1 partially compensate for the loss of intermolecular interactions found in the tetramer.     

Dietary-resistant starch improves maternal glycemic control in Goto-Kakizaki rat

Scope: Dietary prebiotics show potential in anti‐diabetes. Dietary resistant starch (RS) has a favorable impact on gut hormone profiles, including glucagon‐like peptide‐1 (GLP‐1) consistently released, a potent anti‐diabetic incretin. Also RS reduced body fat and improved glucose tolerance in rats and mice. In the current project, we hypothesize that dietary‐resistant starch can improve insulin sensitivity and pancreatic β cell mass in a type 2 diabetic rat model. Altered gut fermentation and microbiota are the initial mechanisms, and enhancement in serum GLP‐1 is the secondary mechanism. Methods and results: In this study, GK rats were fed an RS diet with 30% RS and an energy control diet. After 10 wk, these rats were mated and went through pregnancy and lactation. At the end of the study, pancreatic β cell mass, insulin sensitivity, pancreatic insulin content, total GLP‐1 levels, cecal short‐chain fatty acid concentrations and butyrate producing bacteria in cecal contents were greatly improved by RS feeding. The offspring of RS‐fed dams showed improved fasting glucose levels and normal growth curves. Conclusion: Dietary RS is potentially of great therapeutic importance in the treatment of diabetes and improvement in outcomes of pregnancy complicated by diabetes.     

The importance of GLP‐1 and PYY in resistant starch's effect on body fat in mice

Resistant starch (RS) is a dietary fermentable fiber that decreases body fat accumulation, and stimulates the secretion of glucagon‐like peptide‐1 (GLP‐1) and peptide YY (PYY) in rodents. GLP‐1 and PYY are gut‐secreted hormones with antiobesity effect. Thus, blocking the signals of increased GLP‐1 and PYY may also block the effect of dietary RS on body fat. In a 10‐week study, C57BL/6J and GLP‐1 receptor null (GLP‐1R KO) mice were fed control or 30% RS diet, and received daily intraperitoneal injection of either saline or PYY receptor antagonist (BIIE0246, 20 μg/kg body weight). Dietary RS significantly decreased body fat accumulation only in wild‐type mice that has saline injection, but not in GLP‐1R KO mice. PYY receptor antagonist diminished RS action on body fat in wild‐type mice, but did not interfere with GLP‐1R KO mice response to RS. Regardless of genotype and injection received, all RS‐fed mice had increased cumulative food intake, cecal fermentation, and mRNA expression of proglucagon and PYY. Thus, our results suggest that increased GLP‐1 and PYY is important in RS effects on body fat accumulation.     

Relaxation measurements of an MRI system phantom at low magnetic field strengths

Objective

Temperature controlled T₁ and T₂ relaxation times are measured on NiCl₂ and MnCl₂ solutions from the ISMRM/NIST system phantom at low magnetic field strengths of 6.5 mT, 64 mT and 550 mT.

Materials and methods

The T₁ and T₂ were measured of five samples with increasing concentrations of NiCl₂ and five samples with increasing concentrations of MnCl₂. All samples were scanned at 6.5 mT, 64 mT and 550 mT, at sample temperatures ranging from 10 °C to 37 °C.

Results

The NiCl₂ solutions showed little change in T₁ and T₂ with magnetic field strength, and both relaxation times decreased with increasing temperature. The MnCl₂ solutions showed an increase in T₁ and a decrease in T₂ with increasing magnetic field strength, and both T₁ and T₂ increased with increasing temperature.

Discussion

The low field relaxation rates of the NiCl₂ and MnCl₂ arrays in the ISMRM/NIST system phantom are investigated and compared to results from clinical field strengths of 1.5 T and 3.0 T. The measurements can be used as a benchmark for MRI system functionality and stability, especially when MRI systems are taken out of the radiology suite or laboratory and into less traditional environments.

     

In vivo quantitative MRI: T1 and T2 measurements of the human brain at 0.064 T

Objective

To measure healthy brain \({T}_{1}\) and \({T}_{2}\) relaxation times at 0.064 T.

Materials and methods

\({T}_{1}\) and \({T}_{2}\) relaxation times were measured in vivo for 10 healthy volunteers using a 0.064 T magnetic resonance imaging (MRI) system and for 10 test samples on both the MRI and a separate 0.064 T nuclear magnetic resonance (NMR) system. In vivo \({T}_{1}\) and \({T}_{2}\) values are reported for white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) for automatic segmentation regions and manual regions of interest (ROIs).

Results

\({T}_{1}\) sample measurements on the MRI system were within 10% of the NMR measurement for 9 samples, and one sample was within 11%. Eight \({T}_{2}\) sample MRI measurements were within 25% of the NMR measurement, and the two longest \({T}_{2}\) samples had more than 25% variation. Automatic segmentations generally resulted in larger \({T}_{1}\) and \({T}_{2}\) estimates than manual ROIs.

Discussion

\({T}_{1}\) and \({T}_{2}\) times for brain tissue were measured at 0.064 T. Test samples demonstrated accuracy in WM and GM ranges of values but underestimated long \({T}_{2}\) in the CSF range. This work contributes to measuring quantitative MRI properties of the human body at a range of field strengths.