Jennifer L Jones - Academia.edu (original) (raw)
Papers by Jennifer L Jones
PLoS ONE, 2008
Tune deafness (TD) is a central auditory processing disorder characterized by the inability to di... more Tune deafness (TD) is a central auditory processing disorder characterized by the inability to discriminate pitch, reproduce melodies or to recognize deviations in melodic structure, in spite of normal hearing. The cause of the disorder is unknown. To identify a pathophysiological marker, we ascertained a group of severely affected TD patients using the Distorted Tunes Test, an ecologically valid task with a longstanding history, and used electrophysiological methods to characterize the brain's responses to correct and incorrect melodic sequences. As expected, we identified a neural correlate of patients' unawareness of melodic distortions: deviant notes modulated long-latency auditory evoked potentials and elicited a mismatch negativity in controls but not in affected subjects. However a robust P300 was elicited by deviant notes, suggesting that, as in blindsight, TD subjects process stimuli that they cannot consciously perceive. Given the high heritability of TD, these patients may make it possible to use genetic methods to study cellular and molecular mechanisms underlying conscious awareness.
Reading Research Quarterly, 2009
The Reading Teacher, 2013
ABSTRACT When schools and teachers adopt core reading programs they can use them with fidelity or... more ABSTRACT When schools and teachers adopt core reading programs they can use them with fidelity or make intelligent decisions about the texts, lessons and components they select to use. The evidence suggests that these programs are not research-based documents, but rather compromises between what the research suggests about effective reading instruction and what the market wants. Given these compromises and complexity of core reading programs teachers should make decisions about what texts their students will read, what skills and strategies they will teach, and what program components they will use. Teachers should have the prerogative to move students beyond the core program into the wider world of children's literature and informational books. The article outlines eight key decisions that teachers should make.
Alzheimer's Disease
... LARS BERTRAM, DEBORAH BLACKER, ADAM S. CRYSTAL, JENNIFER JONES, DEVON KEENEY, LAURA MacKENZIE... more ... LARS BERTRAM, DEBORAH BLACKER, ADAM S. CRYSTAL, JENNIFER JONES, DEVON KEENEY, LAURA MacKENZIE-INGANO, KRISTINA MULLIN, SANJAY BASU, STEPHEN YHU, MELVIN McINNIS, RODNEY CP GO, ALEISTER J ... Dodel RC, Du Y, Bales KR et al. ...
Proceedings of the Royal Society B: Biological Sciences, 2014
The appearance of farming, from its inception in the Near East around 12 000 years ago, finally r... more The appearance of farming, from its inception in the Near East around 12 000 years ago, finally reached the northwestern extremes of Europe by the fourth millennium BC or shortly thereafter. Various models have been invoked to explain the Neolithization of northern Europe; however, resolving these different scenarios has proved problematic due to poor faunal preservation and the lack of specificity achievable for commonly applied proxies. Here, we present new multi-proxy evidence, which qualitatively and quantitatively maps subsistence change in the northeast Atlantic archipelagos from the Late Mesolithic into the Neolithic and beyond. A model involving significant retention of hunter–gatherer–fisher influences was tested against one of the dominant adoptions of farming using a novel suite of lipid biomarkers, including dihydroxy fatty acids, ω-( o -alkylphenyl)alkanoic acids and stable carbon isotope signatures of individual fatty acids preserved in cooking vessels. These new findi...
Nutrition Research, 2011
The purpose of this study was to correlate biomarkers of metabolic syndrome (MetS), with markers ... more The purpose of this study was to correlate biomarkers of metabolic syndrome (MetS), with markers of inflammation and macronutrient intake in 89 women (25-72 years) with MetS. We hypothesized that waist circumference (WC) would have the stronger correlations with inflammatory parameters and would correlate with carbohydrate intake. Values for WC (108.7 ± 11.1 cm) and plasma triglycerides (202.7 ± 52.1 mg/dL) were elevated, whereas plasma glucose levels varied from 66 to 179 mg/dL, with 42% of women having insulin resistance. Plasma levels of interleukin 6 (0.2-15.9 mg/L), tumor necrosis factor α (1.47-12.3 mg/L), and high-sensitivity C-reactive protein (0.06-3.08 mg/dL) varied widely, with most women being above values considered normal. Subjects had high intake of total sugar (92.3 ± 56.4 g/d), high glycemic index (59.8 ± 6.5), and glycemic load (127.2 ± 56.1), whereas dietary fiber (17.1 ± 9.1 g/d) was below recommended intake. Waist circumference was positively correlated with insulin (r = 0.275, P b .01) and with the inflammatory markers interleukin 6 (r = 0.307, P b .01) and tumor necrosis factor α (r = 0.228, P b .05) and negatively correlated with plasma adiponectin (r = −0.309, P b .0001). In addition, WC was positively correlated with total carbohydrate, added sugar, and glycemic load (P b .05) but not with fat or protein. These results are consistent with central obesity being a key marker of the inflammatory state, and they also suggest that carbohydrates, particularly those that are digested rapidly, contribute to increased risk of central obesity and development of MetS.
Nature Medicine, 2003
A topical microbicide reduces the probability of virus transmission when applied to the vagina or... more A topical microbicide reduces the probability of virus transmission when applied to the vagina or rectum of a person at risk of sexually acquiring HIV-1 infection 1-3. An effective microbicide could significantly reduce the global spread of HIV-1, particularly if women were able to use it covertly to protect themselves. A microbicide could target the incoming virus and either permanently inactivate it or reduce its infectivity, or it could block receptors on susceptible cells near the sites of transmission 1-3. We describe here how vaginal administration of the broadly neutralizing human monoclonal antibody b12 can protect macaques from simian-human immunodeficiency virus (SHIV) infection through the vagina. Only 3 of 12 animals receiving 5 mg b12 vaginally in either saline or a gel and then challenged vaginally (up to 2 h later) with SHIV-162P4 became infected. In contrast, infection occurred in 12 of 13 animals given various control agents under similar conditions. Lower amounts of b12 were less effective, suggesting that protection was dose dependent. These observations support the concept that viral entry inhibitors can help prevent the sexual transmission of HIV-1 to humans.
Journal of Virology, 2012
Following integration, HIV-1 in most cases produces active infection events; however, in some rar... more Following integration, HIV-1 in most cases produces active infection events; however, in some rare instances, latent infection events are established. The latter have major clinical implications, as latent infection allows the virus to persist despite antiretroviral therapy. Both the cellular factors and the viral elements that potentially determine whether HIV-1 establishes active or latent infection events remain largely elusive. We detail here the contribution of different long terminal repeat (LTR) sequences for the establishment of latent HIV-1 infection. Using a panel of full-length replication-competent virus constructs that reflect naturally occurring differences of HIV-1 subtype-specific LTRs and targeted LTR mutants, we found the primary ability of HIV-1 to establish latent infection in this system to be controlled by a four-nucleotide (nt) AP-1 element just upstream of the NF-κB element in the viral promoter. Deletion of this AP-1 site mostly deprived HIV-1 of the ability...
The Journal of infectious diseases, 2009
Methicillin-resistant Staphylococcus aureus is problematic both in hospitals and in the community... more Methicillin-resistant Staphylococcus aureus is problematic both in hospitals and in the community. Currently, we have limited understanding of mechanisms of innate immune evasion used by S. aureus. To that end, we created an isogenic deletion mutant in strain MW2 (USA400) of the saeR/S 2-component gene regulatory system and studied its role in mouse models of pathogenesis and during human neutrophil interaction. In this study, we demonstrate that saeR/S plays a distinct role in S. aureus pathogenesis and is vital for virulence of MW2 in a mouse model of sepsis. Moreover, deletion of saeR/S significantly impaired survival of MW2 in human blood and after neutrophil phagocytosis. Microarray analysis revealed that SaeR/S of MW2 influences expression of a wide variety of genes with diverse biological functions. These data provide new insight into how virulence is regulated in S. aureus and associates a specific staphylococcal gene-regulatory system with invasive staphylococcal disease.
Experimental Brain Research, 2005
The goal of this study was accurate quantification of the amplitude of high-frequency components ... more The goal of this study was accurate quantification of the amplitude of high-frequency components of physiological tremor (PT) in units of displacement, velocity, and acceleration. In addition, changes of amplitude with finger loading were compared within specific frequency bands. Index finger tremor was measured for 20 healthy subjects using a high-resolution laser, simultaneously with an accelerometer, under two conditions, unloaded and loaded (70 g). By use of an accurate filtering technique, oscillations within six predetermined frequency bands were isolated. Results showed that overall mean tremor amplitude under the unloaded condition was 0.0973 mm in displacement units, 4.525 mm s À1 in velocity units, and 301.526 mm s À2 in acceleration units. Although the mean amplitude of oscillations located within the 16.5-30 Hz band was 0.009 mm and represented only 10% of total tremor amplitude, amplitude of acceleration within the 16.5-30 Hz band was 191 mm s À2 and represented 60% of total acceleration amplitude. Mean amplitude increased significantly with loading (displacement, t=À2.67, P=0.015; velocity, t=À4.33, P=0.000; acceleration, t=À3.48, P=0.002) but the magnitude of that change was different in each frequency band and its relative importance depended on the level of signal differentiation. Velocity was the only measure that retained sensitivity to changes in amplitude with loading in the low and high-frequency components of PT. In conclusion, this study provides, for the first time, accurate quantification of the amplitude of oscillation of highfrequency components of PT. In addition, it provides clear evidence that the velocity of tremor oscillation is more suitable for detection of the impact of finger loading because it enables detection of amplitude changes in both the low and high-frequency components of PT.
Early Human Development, 1997
A prospective observational study of 104 women was performed to study whether the insulin-like gr... more A prospective observational study of 104 women was performed to study whether the insulin-like growth factor (IGF) system in pregnancy before labour is associated with reduced fetal growth. Fetal blood was obtained by cordocentesis for prenatal diagnosis or at elective caesarean delivery and a maternal sample was also obtained. IGF-1 and IGF-2 and their binding proteins-1 and-3 were measured by RIA. The 35 cases were smaller than-2S.D.s by ultrasound abdominal circumference and birthweight and were subdivided into fetal growth retardation (FGR, n = 20) and small for gestational age (SGA, n = 15) by Doppler velocimetry and neonatal outcome. Controls (n = 69) were normally grown. Control maternal IGF-1 (r = 0.65, P < 0.0001) and IGFBP-3 (r = 0.46, P = 0.001) increased with advancing gestational age. In FGR cases, maternal IGF-1 was low (P = 0.0001) and IGFBP-1 was high (P = 0.03) and maternal IGF-2 was low in SGA (P = 0.005). In the SGA fetus, IGF-2 was low (P = 0.0009) and IGFBP-3 (P = 0.02) was high. In FGR. IGFBP-1 (P < 0.0001) and IGFBP-3 (P = 0.002) were both elevated. These data do not support the hypothesis that fetal IGF-1 deficiency is a common cause 01 FGR. Elevated binding proteins may lead to a relative deficiency of free IGF but changes in binding proteins may be secondary to metabolic changes. In FGR, maternal IGF-1 was low with high binding proteins, so this system may be important in controlling placental transfer.
Communication Reports, 1997
... loss of personal control (Langer &amp;amp; Rodin, 1976; Lowenthal &amp;amp; R... more ... loss of personal control (Langer &amp;amp; Rodin, 1976; Lowenthal &amp;amp; Robinson, 1976), and widowhood (Creecy, Berg, &amp;amp; Wright, 1985; Kivett, 1979; Lee &amp;amp; ... Kim Crutcher, Karen Gustavson, Jennifer Jones, Lori Laughlin, and Sherry McKown assisted on this project while students in the ...
Clinical Immunology, 2009
Clinical Gastroenterology and Hepatology, 2008
The quantitative relationships between instruments and assays that measure clinical, endoscopic, ... more The quantitative relationships between instruments and assays that measure clinical, endoscopic, and biologic disease activity in patients with Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease are poorly characterized. This study evaluated the correlations between the Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Disease Activity Index (CDAI), the Simple Endoscopic Score for Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Disease (SES-CD), serum high-sensitivity C-reactive protein (hsCRP) (both phenotype and genotype) and interleukin-6 (IL-6), and fecal calprotectin and lactoferrin. A total of 164 patients with Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease undergoing colonoscopy were enrolled. The CDAI and SES-CD scores, serum hsCRP and IL-6, CRP and IL-6 genotypes, and fecal calprotectin and lactoferrin were measured. There were no significant associations between the CDAI and SES-CD scores (Spearman rank correlation coefficient, 0.15) or between the CDAI scores and the serum concentrations of hsCRP and IL-6, or the fecal concentrations of calprotectin and lactoferrin. In contrast, the serum hsCRP and IL-6 concentrations and the fecal calprotectin and lactoferrin concentrations were significantly higher in patients with more severe endoscopic disease activity (SES-CD score…
Clinical Endocrinology, 2000
Complications of childhood cirrhosis include abnormal growth and malnutrition, associated with ab... more Complications of childhood cirrhosis include abnormal growth and malnutrition, associated with abnormalities in circulating IGFs and IGFBPs. Controlled studies suggest that intensive enteral feeding enhances nutritional status. The aim was to ascertain whether nasogastric feeding improves nutritional status in clinical practice and to assess the effect of feeding on serum IGF-I and IGFBPs. Thirty-three children (median age 0.6 years) with biliary atresia and failure to thrive who were treated with nasogastric feeding. Height, weight and triceps skin fold thickness were measured prior to feeding and regularly for 1 year or until feeding was stopped. Serum IGF-I and IGFBPs were measured by immunoassay at the same intervals. The median duration of feeding was 3.7 months. Twenty-two stopped feeding after liver transplantation, while 10 stopped electively and 1 boy died. Before feeding, the children were losing weight and height centile. Triceps skin fold thickness, weight and height SD scores improved with feeding. Baseline serum IGF-I and IGFBP-3 were low, while IGFBP-1 and IGFBP-2 were raised. IGF-I and IGFBP-1 did not change with feeding. IGFBP-2 fell and reached a nadir by 3 months, while IGFBP-3 rose temporarily for 4-6 weeks. Nasogastric feeding improves body composition in paediatric liver disease but circulating IGF-I and IGFBPs remain abnormal and do not play a major role in mediating these changes. This does not exclude a paracrine or autocrine effect of IGF-I.
Clinical Chemistry and Laboratory Medicine, 2009
Polymorphisms of the gene for C-reactive protein (CRP) alter baseline serum CRP concentrations. T... more Polymorphisms of the gene for C-reactive protein (CRP) alter baseline serum CRP concentrations. The impact of polymorphisms of the CRP gene (genotype) on the normal range for CRP concentrations (phenotype) has not been determined. This study evaluated the median serum CRP concentrations in normal subjects stratified for CRP genotype, after adjustment for relevant covariates as well as polymorphisms in tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) genotypes. A total of 423 healthy adults without infectious or inflammatory conditions undergoing phlebotomy for laboratory testing were enrolled in the study. Assays for serum high sensitivity CRP (hs-CRP), IL-6, and TNF-alpha genotypes were measured. The median hs-CRP concentration was 0.96 mg/L (range &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.1-40.15 mg/L). The CRP 1444 C/T heterozygote and homozygote genotype was associated with a significantly higher hs-CRP concentration (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05), even after multivariate analysis controlling for age, gender, body mass index, hypertension, dyslipidemia and obstructive sleep apnea. The CRP 286 C/T/A heterozygote genotype was significant (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) in the multi-variable analysis, univariately was borderline significant (p=0.052). Selected genetic polymorphisms of the CRP gene are independently associated with higher basal hs-CRP concentrations in healthy adults. Larger studies are needed to perform haplotype analyses and to adequately evaluate the relationship between hs-CRP and genetic polymorphisms with lower allelic frequencies.
Biophysical Journal, 2013
Purpose: Microparticles (MP) are non-biological inorganic bacterial-sized particles (0.1-0.7mm) f... more Purpose: Microparticles (MP) are non-biological inorganic bacterial-sized particles (0.1-0.7mm) from endogenous formation (calcium phosphate) or dietary intake (AlSi and Ti02), which may contribute to the pathogenesis of inflammatory bowel disease (IBD). This study was to establish the method for MP detection in human intestine. Methods: Biopsy tissue samples were collected from 5 IBD and 5 cancer screening patients undergoing colonoscopy.Tissue sections were cut at variable thickness (5, 10 and 20 um) prior to analysis on the Very Sensitive Elemental and Structural Probe Employing Radiation from a Synchrotron (VESPERS) microprobe beamline at the Canadian Light Source. They were mapped with micro-X-ray fluorescence spectroscopy to determine the spatial location of the MPs at an X-ray excitation energy of 13 keV. The beam had a spot size of 4 mm with an 8 mm step-size and 15 second dwell time. Tested sample conditions include formalin fixation, section thickness, mounting substrate (regular glass slide and Lexan film), and embedding medium (OCT). Results: Randomly selected areas in the mucosa or submucosa were observed. There was significant contamination in formalin-fixed tissue samples causing non-specific background. VESPERS exhibited greatest sensitivity with tissue sections of 20 um in thickness and demonstrated the best signal versus noise ratio. Specific signals of MPs from samples on Lexan film were much better with relatively lower background than those on glass slide. The OCT was free of contamination. Conclusion: Synchrotron-based X-ray microprobe techniques can be used for detecting and mapping MPs in normal and IBD affected human intestine. This will allow us further elucidation of the immunopathological role of MPs in IBD patients. Frozen fresh tissue sections of 20 um thickness mounted on Lexan film is the superior method of sample processing.
PLoS ONE, 2008
Tune deafness (TD) is a central auditory processing disorder characterized by the inability to di... more Tune deafness (TD) is a central auditory processing disorder characterized by the inability to discriminate pitch, reproduce melodies or to recognize deviations in melodic structure, in spite of normal hearing. The cause of the disorder is unknown. To identify a pathophysiological marker, we ascertained a group of severely affected TD patients using the Distorted Tunes Test, an ecologically valid task with a longstanding history, and used electrophysiological methods to characterize the brain's responses to correct and incorrect melodic sequences. As expected, we identified a neural correlate of patients' unawareness of melodic distortions: deviant notes modulated long-latency auditory evoked potentials and elicited a mismatch negativity in controls but not in affected subjects. However a robust P300 was elicited by deviant notes, suggesting that, as in blindsight, TD subjects process stimuli that they cannot consciously perceive. Given the high heritability of TD, these patients may make it possible to use genetic methods to study cellular and molecular mechanisms underlying conscious awareness.
Reading Research Quarterly, 2009
The Reading Teacher, 2013
ABSTRACT When schools and teachers adopt core reading programs they can use them with fidelity or... more ABSTRACT When schools and teachers adopt core reading programs they can use them with fidelity or make intelligent decisions about the texts, lessons and components they select to use. The evidence suggests that these programs are not research-based documents, but rather compromises between what the research suggests about effective reading instruction and what the market wants. Given these compromises and complexity of core reading programs teachers should make decisions about what texts their students will read, what skills and strategies they will teach, and what program components they will use. Teachers should have the prerogative to move students beyond the core program into the wider world of children's literature and informational books. The article outlines eight key decisions that teachers should make.
Alzheimer's Disease
... LARS BERTRAM, DEBORAH BLACKER, ADAM S. CRYSTAL, JENNIFER JONES, DEVON KEENEY, LAURA MacKENZIE... more ... LARS BERTRAM, DEBORAH BLACKER, ADAM S. CRYSTAL, JENNIFER JONES, DEVON KEENEY, LAURA MacKENZIE-INGANO, KRISTINA MULLIN, SANJAY BASU, STEPHEN YHU, MELVIN McINNIS, RODNEY CP GO, ALEISTER J ... Dodel RC, Du Y, Bales KR et al. ...
Proceedings of the Royal Society B: Biological Sciences, 2014
The appearance of farming, from its inception in the Near East around 12 000 years ago, finally r... more The appearance of farming, from its inception in the Near East around 12 000 years ago, finally reached the northwestern extremes of Europe by the fourth millennium BC or shortly thereafter. Various models have been invoked to explain the Neolithization of northern Europe; however, resolving these different scenarios has proved problematic due to poor faunal preservation and the lack of specificity achievable for commonly applied proxies. Here, we present new multi-proxy evidence, which qualitatively and quantitatively maps subsistence change in the northeast Atlantic archipelagos from the Late Mesolithic into the Neolithic and beyond. A model involving significant retention of hunter–gatherer–fisher influences was tested against one of the dominant adoptions of farming using a novel suite of lipid biomarkers, including dihydroxy fatty acids, ω-( o -alkylphenyl)alkanoic acids and stable carbon isotope signatures of individual fatty acids preserved in cooking vessels. These new findi...
Nutrition Research, 2011
The purpose of this study was to correlate biomarkers of metabolic syndrome (MetS), with markers ... more The purpose of this study was to correlate biomarkers of metabolic syndrome (MetS), with markers of inflammation and macronutrient intake in 89 women (25-72 years) with MetS. We hypothesized that waist circumference (WC) would have the stronger correlations with inflammatory parameters and would correlate with carbohydrate intake. Values for WC (108.7 ± 11.1 cm) and plasma triglycerides (202.7 ± 52.1 mg/dL) were elevated, whereas plasma glucose levels varied from 66 to 179 mg/dL, with 42% of women having insulin resistance. Plasma levels of interleukin 6 (0.2-15.9 mg/L), tumor necrosis factor α (1.47-12.3 mg/L), and high-sensitivity C-reactive protein (0.06-3.08 mg/dL) varied widely, with most women being above values considered normal. Subjects had high intake of total sugar (92.3 ± 56.4 g/d), high glycemic index (59.8 ± 6.5), and glycemic load (127.2 ± 56.1), whereas dietary fiber (17.1 ± 9.1 g/d) was below recommended intake. Waist circumference was positively correlated with insulin (r = 0.275, P b .01) and with the inflammatory markers interleukin 6 (r = 0.307, P b .01) and tumor necrosis factor α (r = 0.228, P b .05) and negatively correlated with plasma adiponectin (r = −0.309, P b .0001). In addition, WC was positively correlated with total carbohydrate, added sugar, and glycemic load (P b .05) but not with fat or protein. These results are consistent with central obesity being a key marker of the inflammatory state, and they also suggest that carbohydrates, particularly those that are digested rapidly, contribute to increased risk of central obesity and development of MetS.
Nature Medicine, 2003
A topical microbicide reduces the probability of virus transmission when applied to the vagina or... more A topical microbicide reduces the probability of virus transmission when applied to the vagina or rectum of a person at risk of sexually acquiring HIV-1 infection 1-3. An effective microbicide could significantly reduce the global spread of HIV-1, particularly if women were able to use it covertly to protect themselves. A microbicide could target the incoming virus and either permanently inactivate it or reduce its infectivity, or it could block receptors on susceptible cells near the sites of transmission 1-3. We describe here how vaginal administration of the broadly neutralizing human monoclonal antibody b12 can protect macaques from simian-human immunodeficiency virus (SHIV) infection through the vagina. Only 3 of 12 animals receiving 5 mg b12 vaginally in either saline or a gel and then challenged vaginally (up to 2 h later) with SHIV-162P4 became infected. In contrast, infection occurred in 12 of 13 animals given various control agents under similar conditions. Lower amounts of b12 were less effective, suggesting that protection was dose dependent. These observations support the concept that viral entry inhibitors can help prevent the sexual transmission of HIV-1 to humans.
Journal of Virology, 2012
Following integration, HIV-1 in most cases produces active infection events; however, in some rar... more Following integration, HIV-1 in most cases produces active infection events; however, in some rare instances, latent infection events are established. The latter have major clinical implications, as latent infection allows the virus to persist despite antiretroviral therapy. Both the cellular factors and the viral elements that potentially determine whether HIV-1 establishes active or latent infection events remain largely elusive. We detail here the contribution of different long terminal repeat (LTR) sequences for the establishment of latent HIV-1 infection. Using a panel of full-length replication-competent virus constructs that reflect naturally occurring differences of HIV-1 subtype-specific LTRs and targeted LTR mutants, we found the primary ability of HIV-1 to establish latent infection in this system to be controlled by a four-nucleotide (nt) AP-1 element just upstream of the NF-κB element in the viral promoter. Deletion of this AP-1 site mostly deprived HIV-1 of the ability...
The Journal of infectious diseases, 2009
Methicillin-resistant Staphylococcus aureus is problematic both in hospitals and in the community... more Methicillin-resistant Staphylococcus aureus is problematic both in hospitals and in the community. Currently, we have limited understanding of mechanisms of innate immune evasion used by S. aureus. To that end, we created an isogenic deletion mutant in strain MW2 (USA400) of the saeR/S 2-component gene regulatory system and studied its role in mouse models of pathogenesis and during human neutrophil interaction. In this study, we demonstrate that saeR/S plays a distinct role in S. aureus pathogenesis and is vital for virulence of MW2 in a mouse model of sepsis. Moreover, deletion of saeR/S significantly impaired survival of MW2 in human blood and after neutrophil phagocytosis. Microarray analysis revealed that SaeR/S of MW2 influences expression of a wide variety of genes with diverse biological functions. These data provide new insight into how virulence is regulated in S. aureus and associates a specific staphylococcal gene-regulatory system with invasive staphylococcal disease.
Experimental Brain Research, 2005
The goal of this study was accurate quantification of the amplitude of high-frequency components ... more The goal of this study was accurate quantification of the amplitude of high-frequency components of physiological tremor (PT) in units of displacement, velocity, and acceleration. In addition, changes of amplitude with finger loading were compared within specific frequency bands. Index finger tremor was measured for 20 healthy subjects using a high-resolution laser, simultaneously with an accelerometer, under two conditions, unloaded and loaded (70 g). By use of an accurate filtering technique, oscillations within six predetermined frequency bands were isolated. Results showed that overall mean tremor amplitude under the unloaded condition was 0.0973 mm in displacement units, 4.525 mm s À1 in velocity units, and 301.526 mm s À2 in acceleration units. Although the mean amplitude of oscillations located within the 16.5-30 Hz band was 0.009 mm and represented only 10% of total tremor amplitude, amplitude of acceleration within the 16.5-30 Hz band was 191 mm s À2 and represented 60% of total acceleration amplitude. Mean amplitude increased significantly with loading (displacement, t=À2.67, P=0.015; velocity, t=À4.33, P=0.000; acceleration, t=À3.48, P=0.002) but the magnitude of that change was different in each frequency band and its relative importance depended on the level of signal differentiation. Velocity was the only measure that retained sensitivity to changes in amplitude with loading in the low and high-frequency components of PT. In conclusion, this study provides, for the first time, accurate quantification of the amplitude of oscillation of highfrequency components of PT. In addition, it provides clear evidence that the velocity of tremor oscillation is more suitable for detection of the impact of finger loading because it enables detection of amplitude changes in both the low and high-frequency components of PT.
Early Human Development, 1997
A prospective observational study of 104 women was performed to study whether the insulin-like gr... more A prospective observational study of 104 women was performed to study whether the insulin-like growth factor (IGF) system in pregnancy before labour is associated with reduced fetal growth. Fetal blood was obtained by cordocentesis for prenatal diagnosis or at elective caesarean delivery and a maternal sample was also obtained. IGF-1 and IGF-2 and their binding proteins-1 and-3 were measured by RIA. The 35 cases were smaller than-2S.D.s by ultrasound abdominal circumference and birthweight and were subdivided into fetal growth retardation (FGR, n = 20) and small for gestational age (SGA, n = 15) by Doppler velocimetry and neonatal outcome. Controls (n = 69) were normally grown. Control maternal IGF-1 (r = 0.65, P < 0.0001) and IGFBP-3 (r = 0.46, P = 0.001) increased with advancing gestational age. In FGR cases, maternal IGF-1 was low (P = 0.0001) and IGFBP-1 was high (P = 0.03) and maternal IGF-2 was low in SGA (P = 0.005). In the SGA fetus, IGF-2 was low (P = 0.0009) and IGFBP-3 (P = 0.02) was high. In FGR. IGFBP-1 (P < 0.0001) and IGFBP-3 (P = 0.002) were both elevated. These data do not support the hypothesis that fetal IGF-1 deficiency is a common cause 01 FGR. Elevated binding proteins may lead to a relative deficiency of free IGF but changes in binding proteins may be secondary to metabolic changes. In FGR, maternal IGF-1 was low with high binding proteins, so this system may be important in controlling placental transfer.
Communication Reports, 1997
... loss of personal control (Langer &amp;amp; Rodin, 1976; Lowenthal &amp;amp; R... more ... loss of personal control (Langer &amp;amp; Rodin, 1976; Lowenthal &amp;amp; Robinson, 1976), and widowhood (Creecy, Berg, &amp;amp; Wright, 1985; Kivett, 1979; Lee &amp;amp; ... Kim Crutcher, Karen Gustavson, Jennifer Jones, Lori Laughlin, and Sherry McKown assisted on this project while students in the ...
Clinical Immunology, 2009
Clinical Gastroenterology and Hepatology, 2008
The quantitative relationships between instruments and assays that measure clinical, endoscopic, ... more The quantitative relationships between instruments and assays that measure clinical, endoscopic, and biologic disease activity in patients with Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease are poorly characterized. This study evaluated the correlations between the Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Disease Activity Index (CDAI), the Simple Endoscopic Score for Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Disease (SES-CD), serum high-sensitivity C-reactive protein (hsCRP) (both phenotype and genotype) and interleukin-6 (IL-6), and fecal calprotectin and lactoferrin. A total of 164 patients with Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease undergoing colonoscopy were enrolled. The CDAI and SES-CD scores, serum hsCRP and IL-6, CRP and IL-6 genotypes, and fecal calprotectin and lactoferrin were measured. There were no significant associations between the CDAI and SES-CD scores (Spearman rank correlation coefficient, 0.15) or between the CDAI scores and the serum concentrations of hsCRP and IL-6, or the fecal concentrations of calprotectin and lactoferrin. In contrast, the serum hsCRP and IL-6 concentrations and the fecal calprotectin and lactoferrin concentrations were significantly higher in patients with more severe endoscopic disease activity (SES-CD score…
Clinical Endocrinology, 2000
Complications of childhood cirrhosis include abnormal growth and malnutrition, associated with ab... more Complications of childhood cirrhosis include abnormal growth and malnutrition, associated with abnormalities in circulating IGFs and IGFBPs. Controlled studies suggest that intensive enteral feeding enhances nutritional status. The aim was to ascertain whether nasogastric feeding improves nutritional status in clinical practice and to assess the effect of feeding on serum IGF-I and IGFBPs. Thirty-three children (median age 0.6 years) with biliary atresia and failure to thrive who were treated with nasogastric feeding. Height, weight and triceps skin fold thickness were measured prior to feeding and regularly for 1 year or until feeding was stopped. Serum IGF-I and IGFBPs were measured by immunoassay at the same intervals. The median duration of feeding was 3.7 months. Twenty-two stopped feeding after liver transplantation, while 10 stopped electively and 1 boy died. Before feeding, the children were losing weight and height centile. Triceps skin fold thickness, weight and height SD scores improved with feeding. Baseline serum IGF-I and IGFBP-3 were low, while IGFBP-1 and IGFBP-2 were raised. IGF-I and IGFBP-1 did not change with feeding. IGFBP-2 fell and reached a nadir by 3 months, while IGFBP-3 rose temporarily for 4-6 weeks. Nasogastric feeding improves body composition in paediatric liver disease but circulating IGF-I and IGFBPs remain abnormal and do not play a major role in mediating these changes. This does not exclude a paracrine or autocrine effect of IGF-I.
Clinical Chemistry and Laboratory Medicine, 2009
Polymorphisms of the gene for C-reactive protein (CRP) alter baseline serum CRP concentrations. T... more Polymorphisms of the gene for C-reactive protein (CRP) alter baseline serum CRP concentrations. The impact of polymorphisms of the CRP gene (genotype) on the normal range for CRP concentrations (phenotype) has not been determined. This study evaluated the median serum CRP concentrations in normal subjects stratified for CRP genotype, after adjustment for relevant covariates as well as polymorphisms in tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) genotypes. A total of 423 healthy adults without infectious or inflammatory conditions undergoing phlebotomy for laboratory testing were enrolled in the study. Assays for serum high sensitivity CRP (hs-CRP), IL-6, and TNF-alpha genotypes were measured. The median hs-CRP concentration was 0.96 mg/L (range &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.1-40.15 mg/L). The CRP 1444 C/T heterozygote and homozygote genotype was associated with a significantly higher hs-CRP concentration (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05), even after multivariate analysis controlling for age, gender, body mass index, hypertension, dyslipidemia and obstructive sleep apnea. The CRP 286 C/T/A heterozygote genotype was significant (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) in the multi-variable analysis, univariately was borderline significant (p=0.052). Selected genetic polymorphisms of the CRP gene are independently associated with higher basal hs-CRP concentrations in healthy adults. Larger studies are needed to perform haplotype analyses and to adequately evaluate the relationship between hs-CRP and genetic polymorphisms with lower allelic frequencies.
Biophysical Journal, 2013
Purpose: Microparticles (MP) are non-biological inorganic bacterial-sized particles (0.1-0.7mm) f... more Purpose: Microparticles (MP) are non-biological inorganic bacterial-sized particles (0.1-0.7mm) from endogenous formation (calcium phosphate) or dietary intake (AlSi and Ti02), which may contribute to the pathogenesis of inflammatory bowel disease (IBD). This study was to establish the method for MP detection in human intestine. Methods: Biopsy tissue samples were collected from 5 IBD and 5 cancer screening patients undergoing colonoscopy.Tissue sections were cut at variable thickness (5, 10 and 20 um) prior to analysis on the Very Sensitive Elemental and Structural Probe Employing Radiation from a Synchrotron (VESPERS) microprobe beamline at the Canadian Light Source. They were mapped with micro-X-ray fluorescence spectroscopy to determine the spatial location of the MPs at an X-ray excitation energy of 13 keV. The beam had a spot size of 4 mm with an 8 mm step-size and 15 second dwell time. Tested sample conditions include formalin fixation, section thickness, mounting substrate (regular glass slide and Lexan film), and embedding medium (OCT). Results: Randomly selected areas in the mucosa or submucosa were observed. There was significant contamination in formalin-fixed tissue samples causing non-specific background. VESPERS exhibited greatest sensitivity with tissue sections of 20 um in thickness and demonstrated the best signal versus noise ratio. Specific signals of MPs from samples on Lexan film were much better with relatively lower background than those on glass slide. The OCT was free of contamination. Conclusion: Synchrotron-based X-ray microprobe techniques can be used for detecting and mapping MPs in normal and IBD affected human intestine. This will allow us further elucidation of the immunopathological role of MPs in IBD patients. Frozen fresh tissue sections of 20 um thickness mounted on Lexan film is the superior method of sample processing.