Endoscopic optical coherence tomography with a flexible fiber bundle

We demonstrate in vivo endoscopic optical coherence tomography (OCT) imaging in the forward direction using a flexible fiber bundle. In comparison to current conventional forward looking probe schemes, our approach simplifies the endoscope design by avoiding the integration of any beam steering components in the distal probe end due to 2D scanning of a focused light beam over the proximal fiber bundle surface. We describe the challenges that arise when OCT imaging with a fiber bundle is performed, such as multimoding or cross-coupling. The performance of different fiber bundles with varying parameters such as numerical aperture, core size and core structure was consequently compared and artifacts that degrade the image quality were described in detail. Based on our findings, we propose an optimal fiber bundle design for endoscopic OCT imaging

Role of cardiac troponin I phosphorylation in cardiac function: From molecule to mouse

Abstract only availableThe regulation of cardiac muscle contraction involves the interplay between a variety of molecules on the thick and thin filaments. One important regulatory molecule is troponin, which consists of three subunits, troponin C (TnC) that binds calcium, troponin T (TnT) that binds tropomyosin, and troponin I (TnI) that binds actin and tends to inhibit contraction. Following muscle excitation, cytoplasmic calcium rises and binds TnC, which causes a conformational change in TnI that reduces its affinity for actin; this, in turn, allows TnT and tropomyosin to shift positions revealing myosin binding sites on actin, leading to muscle contraction. Interestingly, cardiac troponin I (cTnI) has several phosphorylation sites, which are known to modulate this regulatory process. For example, phosphorylation of serines 23 and 24 on cTnI by protein kinase A (PKA) is known to decrease the calcium binding affinity of cardiac TnC and, thus, thought to speed muscle relaxation. On the other hand, phosphorylation of cTnI on serines 43 and 45 and threonine 144 by protein kinase C (PKC) decreases both force production and calcium sensitivity of force and is thought to contribute to depressed ventricular function in failing hearts. In this study we investigated the effects of chronic cTnI phosphorylation on cardiac function from transgenic animals in which either PKA phosphorylation sites (Ser-23/Ser-24) (PP) or both the PKA and PKC phosphorylation sites (Ser-23/Ser-24/Ser-43/Ser-45/T-144) (All-P) were replaced with aspartic acid to mimic phosphorylation. Left ventricular cardiac myocytes from PP transgenic mice exhibited less calcium sensitivity of force while myocytes from All-P transgenic mice exhibited decreased maximal force, decreased calcium sensitivity of force, and decreased power output, implicating a dominate role of PKC phosphorylation sites on myofilament function. Consistent with these single myocyte studies, left ventricular power output also was depressed in All-P mice compared to both WT and PP transgenic ventricles. We next tested the hypothesis that PP transgenic mice would engage in greater voluntary running compared to WT and All-P transgenic animals. In contrast to this idea, WT and All-P mice ran ~3- and ~4-fold more than the PP transgenic mouse, respectively. Overall, these results indicate that PKC phosphorylation of cTnI plays a dominant role in depressing contractility and may contribute to the maladaptive behavior.NIH grant to K.S. McDonal

Genetic association study of UCMA/GRP and OPTN genes (PDB6 locus) with Paget's disease of bone

We performed a genetic association study of rare variants and single nucleotide polymorphisms (SNPs) of UCMA/GRP and OPTN genes, in French-Canadian patients with Paget's disease of bone (PDB) and in healthy controls from the same population. We reproduced the variant found in the UCMA/GRP basal promoter and tested its functionality using in vitro transient transfection assays. Interestingly, this SNP rs17152980 appears to affect the transcription level of UCMA/GRP. In addition, we have identified five rare genetic variants in UCMA/GRP gene, four of them being population-specific, although none were found to be associated with PDB. Six Tag SNPs of UCMA/GRP gene were associated with PDB, particularly the SNP rs17152980 (uncorrected P = 3.8 x 10(-3)), although not significant after Bonferroni's correction. More importantly, we replicated the strong and statistically significant genetic association of two SNPs of the OPTN gene, the rs1561570 (uncorrected P = 5.7 x 10(-7)) and the rs2095388 (uncorrected P = 4.9 x 10(-3)), With PDB. In addition, we identified a very rare variant found to be located close to the basal promoter of the OPTN gene, at -232 bp from its distal transcription start site. Furthermore, depending on the type of allele present (G or A), the binding of several important nuclear factors such as the vitamin D or the retinoic acid receptors is predicted to be altered at this position, suggesting a significant effect in the regulation of transcription of the OPTN gene. In conclusion, we identified a functional SNP located in the basal promoter of the UCMA/GRP gene which provided a weak genetic association with PDB. In addition, we replicated the strong genetic association of two already known SNPs of the OPTN gene, with PDB in a founder effect population. We also identified a very rare variant in the promoter of OPTN, and through bioinformatic analysis, identified putative transcription factor binding sites likely to affect OPTN gene transcription. (C) 2012 Elsevier Inc. All rights reserved.Fonds de la Recherche du Quebec - Sante (FRQS), Canada; Portuguese Science and Technology Foundation, Portugal [SFRH/BPD/48206/2008]; Catalyst Grant (Bone Health) from the Canadian Institutes of Health Research (Canada); CHUQ Foundation (Canada); Groupe de Recherche en Maladies Osseuses (Canada); Canadian Foundation for Innovation (Canada); FRSQ (Canada); Laval University (Canada); CHUQ (CHUL) Research Centre (Canada); Centre of Marine Sciences (CCMAR) (Portugal)info:eu-repo/semantics/publishedVersio

Aboveground forest biomass estimation with Landsat and LiDAR data and uncertainty analysis of the estimates.

Landsat Thematic mapper (TM) image has long been the dominate data source, and recently LiDAR has offered an important new structural data stream for forest biomass estimations. On the other hand, forest biomass uncertainty analysis research has only recently obtained sufficient attention due to the difficulty in collecting reference data. This paper provides a brief overview of current forest biomass estimation methods using both TM and LiDAR data. A case study is then presented that demonstrates the forest biomass estimation methods and uncertainty analysis. Results indicate that Landsat TM data can provide adequate biomass estimates for secondary succession but are not suitable for mature forest biomass estimates due to data saturation problems. LiDAR can overcome TM?s shortcoming providing better biomass estimation performance but has not been extensively applied in practice due to data availability constraints. The uncertainty analysis indicates that various sources affect the performance of forest biomass/carbon estimation. With that said, the clear dominate sources of uncertainty are the variation of input sample plot data and data saturation problem related to optical sensors. A possible solution to increasing the confidence in forest biomass estimates is to integrate the strengths of multisensor data

Serotonin and corticosterone rhythms in mice exposed to cigarette smoke and in patients with COPD:implication for COPD-associated neuropathogenesis

The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events. Daily exposure to cigarette smoke (CS) can lead to alteration in diverse biological and physiological processes. Smoking is associated with mood disorders, including depression and anxiety. Patients with chronic obstructive pulmonary disease (COPD) have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function. Corticosterone (CORT) is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses. Serotonin (5-hydroxytryptamine; 5HT) is a neurohormone, which plays a role in sleep/wake regulation and affective disorders. Secretion of stress hormones (CORT and 5HT) is under the control of the circadian clock in the suprachiasmatic nucleus. Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD. We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d), sub-chronic (10 d) or chronic (6 mo) CS exposure and in plasma from non-smokers, smokers and patients with COPD. Acute and chronic CS exposure affected both the timing (peak phase) and amplitude of the daily rhythm of plasma CORT and 5HT in mice. Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT. As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD. Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD. Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD

Séance spécialisée : géodynamique des bassins océaniques et des marges continentales

Une morphologie de fonds sous-marins bathyaux comportant des indurations liées à des dépôts ferro-manganésifères inclus dans des sédiments hémipélagiques peu ou pas cimentés a été découverte sur une ride volcanique tertiaire au large de la Nouvelle-Calédonie (SW Pacifique). Elle semble être en relation avec des circulations hydrothermales au travers de la couverture sédimentaire pendant l'activité volcanique miocène de la ride des Loyauté. (Résumé d'auteur

If You Would Not Criminalize Poverty, Do Not Medicalize It

American society tends to medicalize or criminalize social problems. Criminal justice reformers have made arguments for a positive role in the relief of poverty that are similar to those aired in healthcare today. The consequences of criminalizing poverty caution against its continued medicalization

LD Hub:a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis

Motivation: LD score regression is a reliable and efficient method of using genome-wide association study (GWAS) summary-level results data to estimate the SNP heritability of complex traits and diseases, partition this heritability into functional categories, and estimate the genetic correlation between different phenotypes. Because the method relies on summary level results data, LD score regression is computationally tractable even for very large sample sizes. However, publicly available GWAS summary-level data are typically stored in different databases and have different formats, making it difficult to apply LD score regression to estimate genetic correlations across many different traits simultaneously. Results: In this manuscript, we describe LD Hub - a centralized database of summary-level GWAS results for 173 diseases/traits from different publicly available resources/consortia and a web interface that automates the LD score regression analysis pipeline. To demonstrate functionality and validate our software, we replicated previously reported LD score regression analyses of 49 traits/diseases using LD Hub; and estimated SNP heritability and the genetic correlation across the different phenotypes. We also present new results obtained by uploading a recent atopic dermatitis GWAS meta-analysis to examine the genetic correlation between the condition and other potentially related traits. In response to the growing availability of publicly accessible GWAS summary-level results data, our database and the accompanying web interface will ensure maximal uptake of the LD score regression methodology, provide a useful database for the public dissemination of GWAS results, and provide a method for easily screening hundreds of traits for overlapping genetic aetiologies. Availability and implementation: The web interface and instructions for using LD Hub are available at http://ldsc.broadinstitute.org/<br/