The limit fold change model: A practical approach for selecting differentially expressed genes from microarray data

BACKGROUND: The biomedical community is developing new methods of data analysis to more efficiently process the massive data sets produced by microarray experiments. Systematic and global mathematical approaches that can be readily applied to a large number of experimental designs become fundamental to correctly handle the otherwise overwhelming data sets. RESULTS: The gene selection model presented herein is based on the observation that: (1) variance of gene expression is a function of absolute expression; (2) one can model this relationship in order to set an appropriate lower fold change limit of significance; and (3) this relationship defines a function that can be used to select differentially expressed genes. The model first evaluates fold change (FC) across the entire range of absolute expression levels for any number of experimental conditions. Genes are systematically binned, and those genes within the top X% of highest FCs for each bin are evaluated both with and without the use of replicates. A function is fitted through the top X% of each bin, thereby defining a limit fold change. All genes selected by the 5% FC model lie above measurement variability using a within standard deviation (SD(within)) confidence level of 99.9%. Real time-PCR (RT-PCR) analysis demonstrated 85.7% concordance with microarray data selected by the limit function. CONCLUSION: The FC model can confidently select differentially expressed genes as corroborated by variance data and RT-PCR. The simplicity of the overall process permits selecting model limits that best describe experimental data by extracting information on gene expression patterns across the range of expression levels. Genes selected by this process can be consistently compared between experiments and enables the user to globally extract information with a high degree of confidence

The proportion of lycopene isomers in human plasma is modulated by lycopene isomer profile in the meal but not by lycopene preparation

Dietary lycopene consists mostly of the (all-E) isomer. Upon absorption, (all-E) lycopene undergoes isomerisation into various (Z)-isomers. Because these isomers offer potentially better health benefits than the (all-E) isomer, the aim of the present study was to investigate if the profile of lycopene isomers in intestinal lipoproteins is affected by the profile of lycopene isomers in the meal and by the tomato preparation. Six postprandial, crossover tests were performed in healthy men. Three meals provided about 70% of the lycopene as (Z)-isomers, either mainly as 5-(Z) or 13-(Z), or as a mixture of 9-(Z) and 13-(Z) lycopene, while three tomato preparations provided lycopene mainly as the (all-E) isomer. Consumption of the 5-(Z) lycopene-rich meal led to a high (60%) proportion of this isomer in TAG-rich lipoproteins (TRL), indicating a good absorption and/or a low intestinal conversion of this isomer. By contrast, consumption of meals rich in 9-(Z) and 13-(Z) lycopene isomers resulted in a low level of these isomers but high amounts of the 5-(Z) and (all-E) isomers in TRL. This indicates that the 9-(Z) and 13-(Z) isomers were less absorbed or were converted into 5-(Z) and (all-E) isomers. Dietary (Z)-lycopene isomers were, therefore, differently isomerised and released in TRL during their intestinal absorption in men. Consuming the three meals rich in (all-E) lycopene resulted in similar proportions of lycopene isomers in TRL: 60% (all-E), 20% 5-(Z), 9% 13-(Z), 2% 9-(Z) and 9% unidentified (Z)-isomers. These results show that the tomato preparation has no impact on the lycopene isomerisation occurring during absorption in human

Twins in YAl_3(BO_3)_4 and K_2Al_2B_2O_7 Crystals as Revealed by Changes in Optical Activity

Many borate crystals feature nonlinear optical properties that allow for efficient frequency conversion of common lasers down into the ultraviolet spectrum. Twinning may degrade crystal quality and affect nonlinear optical properties, in particular if crystals are composed of twin domains with opposing polarities. Here, we use measurements of optical activity to demonstrate the existence of inversion twins within single crystals of YAl_3(BO_3)_4 (YAB) and K_2 Al_2 B_2 O_7 (KABO). We determine the optical rotatory dispersion of YAB and KABO throughout the visible spectrum using a spectrophotometer with rotatable polarizers. Space-resolved measurements of the optical rotation can be related to the twin structure and give estimates on the extent of twinning. The reported dispersion relations for the rotatory power of YAB and KABO may be used to assess crystal quality and to select twin-free specimens

Twins in YAl_3(BO_3)_4 and K_2Al_2B_2O_7 Crystals as Revealed by Changes in Optical Activity

Many borate crystals feature nonlinear optical properties that allow for efficient frequency conversion of common lasers down into the ultraviolet spectrum. Twinning may degrade crystal quality and affect nonlinear optical properties, in particular if crystals are composed of twin domains with opposing polarities. Here, we use measurements of optical activity to demonstrate the existence of inversion twins within single crystals of YAl_3(BO_3)_4 (YAB) and K_2 Al_2 B_2 O_7 (KABO). We determine the optical rotatory dispersion of YAB and KABO throughout the visible spectrum using a spectrophotometer with rotatable polarizers. Space-resolved measurements of the optical rotation can be related to the twin structure and give estimates on the extent of twinning. The reported dispersion relations for the rotatory power of YAB and KABO may be used to assess crystal quality and to select twin-free specimens

Defining a Continuous Glucose Baseline to assess the impact of nutritional interventions

Accurate and robust estimation of individuals’ basal glucose level is a crucial measure in nutrition research but is typically estimated from one or more morning fasting samples. The use of Continuous Glucose Monitoring (CGM) devices presents an opportunity to define more robust basal glucose levels, which estimates can be generalized to any time of the day. However, to date, no standardized method has been delineated. The current paper seeks to define a reliable algorithm to characterize the individual’s basal glucose level over 24 h from CGM measurements. Data drawn from four nutritional intervention studies performed on adults free from chronic diseases were used to define that basal glucose levels were optimally estimated using the 40th percentile of the previous 24 h CGM data. This simple algorithm provides a Continuous Glucose Baseline over 24 h (24 h-CGB) that is an unbiased and highly correlated estimator (r = 0.86, p-value < 0.01) of standard fasting glucose. We conclude that 24-CGB can provide reliable basal glucose estimates across the day while being more robust to interference than standard fasting glucose, adaptable to evolving daily routines and providing useful reference values for free-living nutritional intervention research in non-diabetic individuals

An ADAMTS3 Missense Variant is Associated with Norwich Terrier Upper Airway Syndrome

In flat-faced dog breeds, air resistance caused by skull conformation is believed to be a major determinant of Brachycephalic Obstructive Airway Syndrome (BOAS). The clinical presentation of BOAS is heterogeneous, suggesting determinants independent of skull conformation contribute to airway disease. Norwich Terriers, a mesocephalic breed, are predisposed to Upper Airway Syndrome (UAS), a disease whose pathological features overlap with BOAS. Our health screening clinic examined and scored the airways of 401 Norwich terriers by laryngoscopy. Genome-wide association analyses of UAS-related pathologies revealed a genetic association on canine chromosome 13 (rs9043975, p = 7.79x10-16). Whole genome resequencing was used to identify causal variant(s) within a 414 kb critical interval. This approach highlighted an error in the CanFam3.1 dog assembly, which when resolved, led to the discovery of a c.2786G>A missense variant in exon 20 of the positional candidate gene, ADAM metallopeptidase with thrombospondin type 1 motif 3 (ADAMTS3). In addition to segregating with UAS amongst Norwich Terriers, the ADAMTS3 c.2786G>A risk allele frequency was enriched among the BOAS-susceptible French and (English) Bulldogs. Previous studies indicate that ADAMTS3 loss of function results in lymphoedema. Our results suggest a new paradigm in the understanding of canine upper airway disease aetiology: airway oedema caused by disruption of ADAMTS3 predisposes dogs to respiratory obstruction. These findings will enhance breeding practices and could refine the prognostics of surgical interventions that are often used to treat airway obstruction

Twins in YAl3(BO3)4 and K2Al2B2O7 crystals as revealed by changes in optical activity

Many borate crystals feature nonlinear optical properties that allow for efficient frequency conversion of common lasers down into the ultraviolet spectrum. Twinning may degrade crystal quality and affect nonlinear optical properties, in particular if crystals are composed of twin domains with opposing polarities. Here, we use measurements of optical activity to demonstrate the existence of inversion twins within single crystals of YAl3(BO3)4 (YAB) and K2Al2B2O7 (KABO). We determine the optical rotatory dispersion of YAB and KABO throughout the visible spectrum using a spectrophotometer with rotatable polarizers. Space-resolved measurements of the optical rotation can be related to the twin structure and give estimates on the extent of twinning. The reported dispersion relations for the rotatory power of YAB and KABO may be used to assess crystal quality and to select twin-free specimens

Assessment of Glycemic Response to Model Breakfasts Varying in Glycemic Index (GI) in 5–7-Year-Old School Children

Reduced Glycemic Index (GI) of breakfast has been linked to improved cognitive performance in both children and adult populations across the morning. However, few studies have profiled the post-prandial glycemic response (PPGR) in younger children. The aim of this study was to assess PPGR to breakfast interventions differing in GI in healthy children aged 5–7 years. Eleven subjects completed an open-label, randomized, cross-over trial, receiving three equicaloric test beverages (260 kcal) consisting of 125 mL semi-skimmed milk and 50 g sugar (either glucose, sucrose, or isomaltulose). On a fourth occasion, the sucrose beverage was delivered as intermittent supply. PPGR was measured over 180 min using Continuous Glucose Monitoring (CGM). The incremental area under the curve (3h-iAUC) was highest for the glucose beverage, followed by intermittent sucrose (−21%, p = 0.288), sucrose (−27%, p = 0.139), and isomaltulose (−48%, p = 0.018). The isomaltulose beverage induced the smallest Cmax (7.8 mmol/L vs. >9.2 mmol/L for others) and the longest duration with moderate glucose level, between baseline value and 7.8 mmol/L (150 vs. <115 min for others). These results confirm that substituting mid-high GI sugars (e.g., sucrose and glucose) with low GI sugars (e.g., isomaltulose) during breakfast are a viable strategy for sustained energy release and glycemic response during the morning even in younger children