Two Variants of the C-Reactive Protein Gene Are Associated with Risk of Pre-Eclampsia in an American Indian Population

Background: The etiology of pre-eclampsia (PE) is unknown; but it is accepted that normal pregnancy represents a distinctive challenge to the maternal immune system. C-reactive protein is a prominent component of the innate immune system; and we previously reported an association between PE and the CRP polymorphism, rs1205. Our aim was to explore the effects of additional CRP variants. The IBC (Cardiochip) genotyping microarray focuses on candidate genes and pathways related to the pathophysiology of cardiovascular disease. Methods: This study recruited 140 cases of PE and 270 matched controls, of which 95 cases met criteria as severe PE, from an American Indian community. IBC array genotypes from 10 suitable CRP SNPs were analyzed. A replication sample of 178 cases and 427 controls of European ancestry was also genotyped. Results: A nominally significant difference (p value <0.05) was seen in the distribution of discordant matched pairs for rs3093068; and Bonferroni corrected differences (P<0.005) were seen for rs876538, rs2794521, and rs3091244. Univariate conditional logistic regression odds ratios (OR) were nominally significant for rs3093068 and rs876538 models only. Multivariate logistic models with adjustment for mother's age, nulliparity and BMI attenuated the effect (OR 1.58, P = 0.066, 95% CI 0.97–2.58) for rs876538 and (OR 2.59, P = 0.050, 95% CI 1.00–6.68) for rs3093068. An additive risk score of the above two risk genotypes shows a multivariate adjusted OR of 2.04 (P = 0.013, 95% CI 1.16–3.56). The replication sample also demonstrated significant association between PE and the rs876538 allele (OR = 1.55, P = 0.01, 95% CI 2.16–1.10). We also show putative functionality for the rs876538 and rs3093068 CRP variants. Conclusion: The CRP variants, rs876538 and rs3093068, previously associated with other cardiovascular disease phenotypes, show suggestive association with PE in this American Indian population, further supporting a possible role for CRP in PE

Caractérisation fonctionnelle chez le poisson zèbre de l'isoforme protéique WNK1/HSN2 mutée dans la neuropathie héréditaire sensitive et autonome de type 2

La neuropathie humaine sensitive et autonome de type 2 (NHSA 2) est une pathologie héréditaire rare caractérisée par une apparition précoce des symptômes et une absence d’affectation motrice. Cette pathologie entraîne la perte de perception de la douleur, de la chaleur et du froid ainsi que de la pression (toucher) dans les membres supérieurs et inférieurs et est due à des mutations autosomales récessives confinées à l’exon HSN2 de la protéine kinase à sérine/thréonine WNK1 (with-no-lysine protein kinase 1). Cet exon spécifique permettrait de conférer une spécificité au système nerveux à l’isoforme protéique WNK1/HSN2. La kinase WNK1 est étudiée en détails, en particulier au niveau du rein, mais son rôle au sein du système nerveux demeure inconnu. Considérant le début précoce de la neuropathie et le manque d’innervation sensorielle révélé par des biopsies chez les patients NHSA2, notre hypothèse de recherche est que les mutations tronquantes menant à la NHSA de type 2 causent une perte de fonction de l’isoforme WNK1/HSN2 spécifique au système nerveux entraînant un défaut dans le développement du système nerveux sensoriel périphérique. Chez l’embryon du poisson zèbre, WNK1/HSN2 est exprimé au niveau des neuromastes de la ligne latérale postérieure, un système mécanosensoriel périphérique. Nous avons obtenu des embryons knockdown pour WNK1/HSN2 par usage d’oligonucléotides morpholino antisens (AMO). Nos trois approches AMO ont révélé des embryons présentant des défauts d’établissement au niveau de la ligne latérale postérieure. Afin de déterminer la voie pathogène impliquant l’isoforme WNK1/HSN2, nous nous sommes intéressés à l’interaction rapportée entre la kinase WNK1 et le co-transporteur neuronal KCC2. Ce dernier est une cible de phosphorylation de WNK1 et son rôle dans la promotion de la neurogenèse est bien connu. Nous avons détecté l’expression de KCC2 au niveau de neuromastes de la ligne latérale postérieure et observé une expression accrue de KCC2 chez les embryons knockdown pour WNK1/HSN2 à l’aide de RT-PCR semi-quantitative. De plus, une sur-expression d’ARN humain de KCC2 chez des embryons a produit des défauts dans la ligne latérale postérieure, phénocopiant le knockdown de WNK1/HSN2. Ces résultats furent validés par un double knockdown, produisant des embryons n’exprimant ni KCC2, ni WNK1/HSN2, dont le phénotype fut atténué. Ces résultats nous mènent à suggérer une voie de signalisation où WNK1/HSN2 est en amont de KCC2, régulant son activation, et possiblement son expression. Nous proposons donc que la perte de fonction de l’isoforme spécifique cause un débalancement dans les niveaux de KCC2 activée, menant à une prolifération et une différenciation réduites des progéniteurs neuronaux du système nerveux périphérique. Les défauts associés à la NHSA de type 2 seraient donc de nature développementale et non neurodégénérative.Human sensory and autonomic neuropathy type 2 (HSNA2) is a rare human hereditary pathology characterized by an early onset severe sensory loss (for all modalities) in the distal limbs. It is due to autosomal recessive mutations confined to exon HSN2 of the WNK1 (with-no-lysine protein kinase 1) serine-threonine kinase; the specific exon confers nervous system specificity to target isoform WNK1/HSN2. While this kinase is widely studied in the kidneys, little is known about its role in the nervous system. Due to its role in HSAN type 2, we hypothesized that the truncating mutations present in the HSN2 exon lead to a loss-of-function of the WNK1 kinase, impairing development of the peripheral sensory system. In order to investigate the mechanisms by which the lack of the WNK1/HSN2 isoform acts to cause HSAN type 2, we examined its expression pattern in our zebrafish model and observed strong expression in neuromasts of the peripheral sensory lateral line system. We then knocked down the HSN2 exon in zebrafish embryos using antisense morpholino oligonucleotides. Our three approaches to knockdown the WNK1/HSN2 isoform led to embryos with a defective lateral line. In order to establish a pathogenic pathway involving the WNK1/HSN2 isoform, we investigated the reported interaction between the WNK1 kinase and neuronal potassium chloride co-transporter KCC2. This transporter is a target of WNK1 phosphorylation and also has a known role in promoting neurogenesis. We have also showed its expression in mature neuromasts of the posterior lateral line, and observed an increased expression of KCC2 in WNK1/HSN2 knockdown embryos by semi-quantitative RT-PCR, lending credence to our interaction hypothesis. Furthermore, overexpression of human KCC2 RNA in embryos led to an impaired mechanosensory lateral line system, phenocopying the WNK1/HSN2 knockdown. We then validated these results by obtaining double knockdown embryos, both for WNK1/HSN2 and KCC2, which alleviated the lateral line defect phenotype. These results led us to suggest a pathway in which WNK1/HSN2 is upstream of the KCC2 co-transporter. WNK1 is believed to regulate the level of activation, and possibly level of expression, of KCC2 and we therefore hypothesize that the loss-of-function of the specific isoform causes an imbalance in the levels of activated KCC2. This would then lead to decreased progenitor proliferation and hindered differentiation of neurons, causing the defects associated with HSAN type 2

Effect of Weight Loss Training Protocol Using Two Different Treadmills for Obese Individuals

The AlterG Anti-Gravity Treadmill allows individuals to walk at reduced body weight by using lower body positive pressure (LBPP). PURPOSE: The purpose of this study was to discern if the AlterG Anti-Gravity Treadmill was an effective tool to use in a weight loss walking program with obese individuals when compared to walking on a traditional treadmill. METHODS: Fifteen male (n = 3) and female (n = 12) obese participants, aged 18-55 years old with an average body mass index [BMI] ≥ 30 kg/m2), were randomly assigned to the AlterG treadmill (AlterG; n = 6) and traditional treadmill (TT; n = 9). Participants followed an 18-week (three 6-week phases) weight loss walking protocol and exercised 3 days a week. Each 6-week phase increased in intensity and duration, and by Phase 3 participants were walking at an intensity of 60-85% HRmax for 60 minutes. The participant’s weight, BMI, and body fat percentage (BFP) were recorded during the program. RESULTS: There was no significant overall weight loss difference determined between the two groups. The AlterG and the TT group lost an average of 2.33 kg and 2.14 kg, respectively. Similarly, no significant overall differences in BMI and BFP were found between the two groups. Significant differences were found among the three phases of the weight loss intervention for weight loss (p = 0.024), BMI reduction (p = 0.021), and BFP reduction (p \u3c 0.0005). Each group exhibited significant decreases in weight, BMI, and BFP by the conclusion of the study. CONCLUSION: This study demonstrated that the walking protocol used with the AlterG Anti-Gravity Treadmill was effective to produce significant weight loss, decreased BMI, and reduced percent body fat in obese individuals

Zebrafish as a Model for the Study of Live in vivo Processive Transport in Neurons

Motor proteins are responsible for transport of vesicles and organelles within the cell cytoplasm. They interact with the actin cytoskeleton and with microtubules to ensure communication and supply throughout the cell. Much work has been done in vitro and in silico to unravel the key players, including the dynein motor complex, the kinesin and myosin superfamilies, and their interacting regulatory complexes, but there is a clear need for in vivo data as recent evidence suggests previous models might not recapitulate physiological conditions. The zebrafish embryo provides an excellent system to study these processes in intact animals due to the ease of genetic manipulation and the optical transparency allowing live imaging. We present here the advantages of the zebrafish embryo as a system to study live in vivo processive transport in neurons and provide technical recommendations for successful analysis

Interventions That Help the Helpers: A Systematic Review and Meta-Analysis of Interventions Targeting Compassion Fatigue, Secondary Traumatic Stress and Vicarious Traumatization in Mental Health Workers

Compassion fatigue, secondary traumatic stress and vicarious traumatization have received widespread attention in the literature due to an increased awareness of negative effects mental health workers experience when working with people who have been traumatized. Mental health workers become more vulnerable to significant stress when they work with trauma victims, which can lead to many negative consequences that can affect their own health as well as their treatment of their clients. While there is much that we are learning about the causes and outcomes of mental health workers\u27 exposure to their clients\u27 trauma, there has been less focus on effectiveness of interventions. It is imperative for both the mental health worker and the clients with whom they work with that it is known what treatment is effective for mental health workers who experience negative effects from exposure to survivors\u27 traumatic material. To date, no systematic review or meta-analysis has been conducted to examine the evidence of effects of interventions on compassion fatigue, secondary traumatic stress and vicarious traumatization. The present study utilized systematic review methods and meta-analysis to quantitatively synthesize research and systematically examine interventions targeting compassion fatigue, secondary traumatic stress and vicarious trauma to examine the effects of interventions on symptoms of compassion fatigue, secondary traumatic stress and vicarious traumatization. A comprehensive search strategy resulted in the identification of two single group pre-posttest studies that met criteria for inclusion in the current study. Effect sizes as well as study, participant and intervention characteristics were coded and analyzed. The meta-analytic findings showed overall medium to very large effects of indicated interventions on the reduction of compassion fatigue and burnout symptoms, and an increase in compassion satisfaction. Though, it was alarming that only two studies met the inclusion criteria. With the constructs of compassion fatigue, secondary traumatic stress and vicarious trauma being heavily present in the literature for the past two decades, it seems warranted to locate more research regarding intervention effectiveness on this topic as the constructs relate to mental health workers

L’évaluation des apprentissages scolaires : une question de justesse

De nombreux chercheurs déplorent l’absence d’un modèle de qualité des résultats d’éva- luation des apprentissages en salle de classe. Après avoir précisé pourquoi le modèle psychométrique, avec ses critères de validité et de fidélité, ne convient pas au domaine scolaire, les auteures proposent le concept de justesse comme critère de qualité des résultats d’évaluation en salle de classe. Ce dernier tient compte de la pertinence de la tâche d’évaluation par rapport aux habiletés visées, de sa cohérence avec l’activité péda- gogique, de sa transparence pour l’élève et de l’absence de désavantage circonstanciel. Many researchers deplore the lack of a good model for learning assessment in the class- room. After clarifying why the psychometric model, with its criteria of validity and reliability, is not appropriate for the school situation, we suggest the concept of soundness as a criterion for the quality of assessment results in the classroom. Soundness takes into account the pertinence of the assessment task relative to the targeted skills, its appro- priateness for the educational activity, its transparency for the student, and the absence of disadvantageous circumstances.

Status of Uncooled Infrared Detector Technology at ULIS, France

The high level of accumulated expertise by ULIS and CEA/LETI on uncooled microbolometers made from amorphous silicon enables ULIS to develop uncooled IRFPA with 17 µm pixel-pitch to enable the development of small power, small weight and power (SWaP) and high performance IR systems. Key characteristics of amorphous silicon based uncooled IR detector is described to highlight the advantage of this technology for system operation. A full range of products from 160 x 120 to 1024 x 768 has been developed and we will focus the paper on the ¼ VGA with 17 µm pixel pitch. Readout integrated circuit (ROIC) architecture is described highlighting innovations that are widely on-chip implemented to enable an easier operation by the user. The detector configuration (integration time, windowing, gain, scanning direction), is driven by a standard I²C link. Like most of the visible arrays, the detector adopts the HSYNC/VSYNC free-run mode of operation driven with only one master clock (MC) supplied to the ROIC which feeds back pixel, line and frame synchronisation. On-chip PROM memory for customer operational condition storage is available for detector characteristics. Low power consumption has been taken into account and less than 60 mW is possible in analogue mode at 60 Hz. A wide electrical dynamic range (2.4V) is maintained despite the use of advanced CMOS node. The specific appeal of this unit lies in the high uniformity and easy operation it provides. The reduction of the pixel-pitch turns this TEC-less ¼ VGA array into a product well adapted for high resolution and compact systems. Noise equivalent temperature difference (NETD) of 35 mK and thermal time constant of 10 ms have been measured leading to 350 mK.ms figure of merit. We insist on NETD trade-off with wide thermal dynamic range, as well as the high characteristics uniformity and pixel operability, achieved thanks to the mastering of the amorphous silicon technology coupled with the ROIC design. This technology node associated with advanced packaging technique, paves the way to compact low power system.Defence Science Journal, 2013, 63(6), pp.545-549, DOI:http://dx.doi.org/10.14429/dsj.63.5753

Dynactin1 depletion leads to neuromuscular synapse instability and functional abnormalities.

Dynactin subunit 1 is the largest subunit of the dynactin complex, an activator of the molecular motor protein complex dynein. Reduced levels of DCTN1 mRNA and protein have been found in sporadic amyotrophic lateral sclerosis (ALS) patients, and mutations have been associated with disease, but the role of this protein in disease pathogenesis is still unknown. We characterized a Dynactin1a depletion model in the zebrafish embryo and combined in vivo molecular analysis of primary motor neuron development with live in vivo axonal transport assays in single cells to investigate ALS-related defects. To probe neuromuscular junction (NMJ) function and organization we performed paired motor neuron-muscle electrophysiological recordings and GCaMP calcium imaging in live, intact larvae, and the synapse structure was investigated by electron microscopy. Here we show that Dynactin1a depletion is sufficient to induce defects in the development of spinal cord motor neurons and in the function of the NMJ. We observe synapse instability, impaired growth of primary motor neurons, and higher failure rates of action potentials at the NMJ. In addition, the embryos display locomotion defects consistent with NMJ dysfunction. Rescue of the observed phenotype by overexpression of wild-type human DCTN1-GFP indicates a cell-autonomous mechanism. Synaptic accumulation of DCTN1-GFP, as well as ultrastructural analysis of NMJ synapses exhibiting wider synaptic clefts, support a local role for Dynactin1a in synaptic function. Furthermore, live in vivo analysis of axonal transport and cytoskeleton dynamics in primary motor neurons show that the phenotype reported here is independent of modulation of these processes. Our study reveals a novel role for Dynactin1 in ALS pathogenesis, where it acts cell-autonomously to promote motor neuron synapse stability independently of dynein-mediated axonal transport

Les pratiques d’évaluation des apprentissages en salle de classe: perceptions des enseignantes et des enseignants

Afin de cerner les pratiques courantes d’évaluation des apprentissages en salle de classe, les chercheuses ont interrogé des enseignantes et des enseignants de diverses régions de l’Ontario afin de mieux connaître les modalités de leurs interventions et leurs besoins de formation en la matière. Même si en général ils estiment s’acquitter convenablement de cette tâche, leurs réponses témoignent d’un décalage important entre leurs pratiques actuelles et celles que nécessitent Le programme d’études commun (MEFO, 1995). Les préoccupations majeures des enseignantes et des enseignants se concentrent autour des questions suivantes: le manque d’uniformité des pratiques et l’absence de directives claires émanant des autorités scolaires à ce sujet, la nécessité d’évaluer les performances, les compétences, les habiletés supérieures de la pensée et les attitudes, puis la pression visant à impliquer les élèves dans le processus d’évaluation. To identify standard practices for evaluating classroom learning, we questioned teachers in various regions of Ontario about the kinds of evaluation methods they use and their evaluation training needs. Although in general teachers consider themselves to be dealing adequately with evaluation, their responses indicate that there is still a wide gap between their current evaluation practices and those required by The Common Curriculum (Ontario Ministry of Education and Training, 1995). Teachers are mainly concerned about (a) the lack of uniformity in evaluation practices combined with the absence of clear instructions on this subject from school authorities, and (b) the necessity to evaluate performance, competencies, attitudes, and higher-order thinking skills, as well as the pressure to include students in the evaluation process.