A Synthetic Earth Gravity Model Designed Specifically for Testing Regional Gravimetric Geoid Determination Algorithms

A synthetic [simulated] Earth gravity model (SEGM) of the geoid, gravity and topography has been constructed over Australia specifically for validating regional gravimetric geoid determination theories, techniques and computer software. This regional high-resolution (1-arc-min by 1-arc-min) Australian SEGM (AusSEGM) is a combined source and effect model. The long-wavelength effect part (up to and including spherical harmonic degree and order 360) is taken from an assumed errorless EGM96 global geopotential model. Using forward modelling via numerical Newtonian integration, the short-wavelength source part is computed from a high-resolution (3-arc-sec by 3-arc-sec) synthetic digital elevation model (SDEM), which is a fractal surface based on the GLOBE v1 DEM. All topographic masses are modelled with a constant mass-density of 2,670 kg/m3. Based on these input data, gravity values on the synthetic topography (on a grid and at arbitrarily distributed discrete points) and consistent geoidal heights at regular 1-arc-min geographical grid nodes have been computed. The precision of the synthetic gravity and geoid data (after a first iteration) is estimated to be better than 30 μ Gal and 3 mm, respectively, which reduces to 1 μ Gal and 1 mm after a second iteration.The second iteration accounts for the changes in the geoid due to the superposed synthetic topographic mass distribution. The first iteration of AusSEGM is compared with Australian gravity and GPS-levelling data to verify that it gives a realistic representation of the Earth’s gravity field. As a by-product of this comparison, AusSEGM gives further evidence of the north–south-trending error in the Australian Height Datum. The freely available AusSEGM-derived gravity and SDEM data, included as Electronic Supplementary Material (ESM) with this paper, can be used to compute a geoid model that, if correct, will agree to in 3 mm with the AusSEGM geoidal heights, thus offering independent verification of theories and numerical techniques used for regional geoid modelling

Deliquescence of NaCl–NaNO(3), KNO(3)–NaNO(3), and NaCl–KNO(3 )salt mixtures from 90 to 120°C

We conducted reversed deliquescence experiments in saturated NaCl–NaNO(3)–H(2)O, KNO(3)–NaNO(3)–H(2)O, and NaCl–KNO(3)–H(2)O systems from 90 to 120°C as a function of relative humidity and solution composition. NaCl, NaNO(3), and KNO(3 )represent members of dust salt assemblages that are likely to deliquesce and form concentrated brines on high-level radioactive waste package surfaces in a repository environment at Yucca Mountain, NV. Discrepancy between model prediction and experiment can be as high as 8% for relative humidity and 50% for dissolved ion concentration. The discrepancy is attributed primarily to the use of 25°C models for Cl–NO(3 )and K–NO(3 )ion interactions in the current Yucca Mountain Project high-temperature Pitzer model to describe the nonideal behavior of these highly concentrated solutions

Soil organic matter and litter chemistry response to experimental N deposition in northern temperate deciduous forest ecosystems

The effects of atmospheric nitrogen (N) deposition on organic matter decomposition vary with the biochemical characteristics of plant litter. At the ecosystem-scale, net effects are difficult to predict because various soil organic matter (SOM) fractions may respond differentially. We investigated the relationship between SOM chemistry and microbial activity in three northern deciduous forest ecosystems that have been subjected to experimental N addition for 2 years. Extractable dissolved organic carbon (DOC), DOC aromaticity, C : N ratio, and functional group distribution, measured by Fourier transform infrared spectra (FTIR), were analyzed for litter and SOM. The largest biochemical changes were found in the sugar maple–basswood (SMBW) and black oak–white oak (BOWO) ecosystems. SMBW litter from the N addition treatment had less aromaticity, higher C : N ratios, and lower saturated carbon, lower carbonyl carbon, and higher carboxylates than controls; BOWO litter showed opposite trends, except for carbonyl and carboxylate contents. Litter from the sugar maple–red oak (SMRO) ecosystem had a lower C : N ratio, but no change in DOC aromaticity. For SOM, the C : N ratio increased with N addition in SMBW and SMRO ecosystems, but decreased in BOWO; N addition did not affect the aromaticity of DOC extracted from mineral soil. All ecosystems showed increases in extractable DOC from both litter and soil in response to N treatment. The biochemical changes are consistent with the divergent microbial responses observed in these systems. Extracellular oxidative enzyme activity has declined in the BOWO and SMRO ecosystems while activity in the SMBW ecosystem, particularly in the litter horizon, has increased. In all systems, enzyme activities associated with the hydrolysis and oxidation of polysaccharides have increased. At the ecosystem scale, the biochemical characteristics of the dominant litter appear to modulate the effects of N deposition on organic matter dynamics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72320/1/j.1365-2486.2005.01001.x.pd

Evaporative evolution of a Na–Cl–NO(3)–K–Ca–SO(4)–Mg–Si brine at 95°C: Experiments and modeling relevant to Yucca Mountain, Nevada

A synthetic Topopah Spring Tuff water representative of one type of pore water at Yucca Mountain, NV was evaporated at 95°C in a series of experiments to determine the geochemical controls for brines that may form on, and possibly impact upon the long-term integrity of waste containers and drip shields at the designated high-level, nuclear-waste repository. Solution chemistry, condensed vapor chemistry, and precipitate mineralogy were used to identify important chemical divides and to validate geochemical calculations of evaporating water chemistry using a high temperature Pitzer thermodynamic database. The water evolved toward a complex "sulfate type" brine that contained about 45 mol % Na, 40 mol % Cl, 9 mol % NO(3), 5 mol % K, and less than 1 mol % each of SO(4), Ca, Mg, ∑CO(2)(aq), F, and Si. All measured ions in the condensed vapor phase were below detection limits. The mineral precipitates identified were halite, anhydrite, bassanite, niter, and nitratine. Trends in the solution composition and identification of CaSO(4 )solids suggest that fluorite, carbonate, sulfate, and magnesium-silicate precipitation control the aqueous solution composition of sulfate type waters by removing fluoride, calcium, and magnesium during the early stages of evaporation. In most cases, the high temperature Pitzer database, used by EQ3/6 geochemical code, sufficiently predicts water composition and mineral precipitation during evaporation. Predicted solution compositions are generally within a factor of 2 of the experimental values. The model predicts that sepiolite, bassanite, amorphous silica, calcite, halite, and brucite are the solubility controlling mineral phases

Rationale and design of the Exercise Intensity Trial (EXCITE): A randomized trial comparing the effects of moderate versus moderate to high-intensity aerobic training in women with operable breast cancer

<p>Abstract</p> <p>Background</p> <p>The Exercise Intensity Trial (EXcITe) is a randomized trial to compare the efficacy of supervised moderate-intensity aerobic training to moderate to high-intensity aerobic training, relative to attention control, on aerobic capacity, physiologic mechanisms, patient-reported outcomes, and biomarkers in women with operable breast cancer following the completion of definitive adjuvant therapy.</p> <p>Methods/Design</p> <p>Using a single-center, randomized design, 174 postmenopausal women (58 patients/study arm) with histologically confirmed, operable breast cancer presenting to Duke University Medical Center (DUMC) will be enrolled in this trial following completion of primary therapy (including surgery, radiation therapy, and chemotherapy). After baseline assessments, eligible participants will be randomized to one of two supervised aerobic training interventions (moderate-intensity or moderate/high-intensity aerobic training) or an attention-control group (progressive stretching). The aerobic training interventions will include 150 mins.wk^-1of supervised treadmill walking per week at an intensity of 60%-70% (moderate-intensity) or 60% to 100% (moderate to high-intensity) of the individually determined peak oxygen consumption (VO_2peak) between 20-45 minutes/session for 16 weeks. The progressive stretching program will be consistent with the exercise interventions in terms of program length (16 weeks), social interaction (participants will receive one-on-one instruction), and duration (20-45 mins/session). The primary study endpoint is VO_2peak, as measured by an incremental cardiopulmonary exercise test. Secondary endpoints include physiologic determinants that govern VO_2peak, patient-reported outcomes, and biomarkers associated with breast cancer recurrence/mortality. All endpoints will be assessed at baseline and after the intervention (16 weeks).</p> <p>Discussion</p> <p>EXCITE is designed to investigate the intensity of aerobic training required to induce optimal improvements in VO_2peakand other pertinent outcomes in women who have completed definitive adjuvant therapy for operable breast cancer. Overall, this trial will inform and refine exercise guidelines to optimize recovery in breast and other cancer survivors following the completion of primary cytotoxic therapy.</p> <p>Trial Registration</p> <p>NCT01186367</p

Embodiment and body awareness in meditators

[EN] Mindfulness practice consists of focusing attention in an intentional way on the experience of the present moment, including bodily sensations, thoughts or feelings, and the environment, with an attitude of acceptance and without judging. The body and, especially, body awareness are key elements in mindfulness. Embodiment or the feeling of being located within one's physical body is a related concept, and it is composed of the sense of ownership, location, and agency of the body. The rubber hand illusion (RHI) is an experimental paradigm that has been used to understand the mechanisms of embodiment, and evidence shows that body awareness modulates this illusion. To our knowledge, no studies have analyzed embodiment processes in meditators. The aim of this study is to use the RHI to analyze the mechanisms of embodiment and its relationship with body awareness and mindfulness in meditators and non-meditators. The sample was composed of long-term meditators (n = 15) and non-meditators (n = 15). Objective and self-report measures for embodiment with the RHI and self-report questionnaires of body awareness and mindfulness were administered. One-way ANOVA revealed significant differences between groups in sense of agency in the rubber hand. Meditators experienced less sense of agency in the rubber hand than non-meditators. Pearson's correlations showed that this lower sense of agency in the rubber hand was associated with higher body awareness and mindfulness. Results highlight the role of body awareness and mindfulness in embodiment mechanisms. This study has clinical implications, especially in psychopathological disorders that can be influenced by disturbances in these processes.The authors would like to acknowledge the "BODYTA" project (Spanish Ministry of Economy and Competitiveness, PSI2014-51928-R), "PROMOSAM" (Spanish Ministry of Economy and Competitiveness, PSI2014-56303-REDT), and "Excellence Research Program PROMETEO II" (Generalitat Valenciana, Conselleria de Educacion, Cultura y Deporte, PROMETEOII/2013/003). CIBERobn is an initiate of the ISCIII. PROMOSAM Excellence in Research Program (PSI2014-56303-REDT), MINECO, Spain.Cebolla, A.; Miragall, M.; Palomo, P.; Llorens Rodríguez, R.; Soler, J.; Demarzo, M.; García Campayo, J.... (2016). Embodiment and body awareness in meditators. Mindfulness. 7(6):1297-1305. https://doi.org/10.1007/s12671-016-0569-xS1297130576Aguado, J., Luciano, J. V., Cebolla, A., Serrano-Blanco, A., Soler, J., & García-Campayo, J. (2015). Bifactor analysis and construct validity of the five facet mindfulness questionnaire (FFMQ) in non-clinical Spanish samples. Frontiers in Psychology, 6, 404.Arzy, S., Thut, G., Mohr, C., Michel, C. M., & Blanke, O. (2006). Neural basis of embodiment: distinct contributions of temporoparietal junction and extrastriate body area. The Journal of Neuroscience, 26(31), 8074–8081.Baer, R. A., Smith, G. T., Hopkins, J., Krietemeyer, J., & Toney, L. (2006). Using self-report assessment methods to explore facets of mindfulness. Assessment, 13(1), 27–45.Bishop, S. R., Lau, M., Shapiro, S., Carlson, L., Anderson, N. D., Carmody, J., et al. (2004). Mindfulness: a proposed operational definition. Clinical Psychology: Science and Practice, 11(3), 230–241.Bornemann, B., Herbert, B. M., Mehling, W. E., & Singer, T. (2015). Differential changes in self-reported aspects of interoceptive awareness through 3 months of contemplative training. Frontiers in Psychology, 5, 1504.Botvinick, M., & Cohen, J. (1998). Rubber hands “feel” touch that eyes see. Nature, 391(6669), 756–756.Calsius, J., Courtois, I., Stiers, J., & De Bie, J. (2015). How do fibromyalgia patients with alexithymia experience their body? A qualitative approach. SAGE Open, 5, 1–10.Cascio, C. J., Foss-Feig, J. H., Burnette, C. P., Heacock, J. L., & Cosby, A. A. (2012). The rubber hand illusion in children with autism spectrum disorders: delayed influence of combined tactile and visual input on proprioception. Autism, 16(4), 406–419.Cebolla, A., Garcia-Palacios, A., Soler, J., Guillen, V., Baños, R., & Botella, C. (2012). Psychometric properties of the Spanish validation of the Five Facets of Mindfulness Questionnaire (FFMQ). The European Journal of Psychiatry, 26(2), 118–126.Cebolla, A., Vara, M. D., Miragall, M., Palomo, P., & Baños, R. M. (2015). Embodied mindfulness: review of the body’s participation in the changes associated with the practice of mindfulness. Actas españolas de Psiquiatría, 43, 36–41.Cioffi, D. (1991). Sensory awareness versus sensory impression: affect and attention interact to produce somatic meaning. Cognition & Emotion, 5(4), 275–294.Cohen, J. (1988). Statistical power analysis for the behavioral sciences (2nd ed.). Hillsdale: Lawrence Erlbaum Associates Inc.Craig, A. D. (2009). How do you feel—now? The anterior insula and human awareness. Nature Reviews Neuroscience, 10(1), 59–70.Dreeben, S. J., Mamberg, M. H., & Salmon, P. (2013). The MBSR body scan in clinical practice. Mindfulness, 4(4), 394–401.Dummer, T., Picot-Annand, A., Neal, T., & Moore, C. (2009). Movement and the rubber hand illusion. Perception, 38(2), 271.Dunn, B. D., Galton, H. C., Morgan, R., Evans, D., Oliver, C., Meyer, M., et al. (2010). Listening to your heart. How interoception shapes emotion experience and intuitive decision making. Psychological Science, 21(12), 1835–1844.Ehrsson, H. H., Spence, C., & Passingham, R. E. (2004). That’s my hand! Activity in premotor cortex reflects feeling of ownership of a limb. Science, 305(5685), 875–877.Eshkevari, E., Rieger, E., Longo, M. R., Haggard, P., & Treasure, J. (2012). Increased plasticity of the bodily self in eating disorders. Psychological Medicine, 42(04), 819–828.Farb, N., Daubenmier, J. J., Price, C. J., Gard, T., Kerr, C., Dunn, B., et al. (2015). Interoception, contemplative practice, and health. Frontiers in Psychology, 6, 763.Fox, K. C., Zakarauskas, P., Dixon, M., Ellamil, M., Thompson, E., Christoff, K., et al. (2012). Meditation experience predicts introspective accuracy. PLoS ONE, 7(9), e45370.Grossman, P., Tiefenthaler-Gilmer, U., Raysz, A., & Kesper, U. (2007). Mindfulness training as an intervention for fibromyalgia: evidence of postintervention and 3-year follow-up benefits in well-being. Psychotherapy and Psychosomatics, 76(4), 226–233.Holmes, N. P., Snijders, H. J., & Spence, C. (2006). Reaching with alien limbs: visual exposure to prosthetic hands in a mirror biases proprioception without accompanying illusions of ownership. Perception & Psychophysics, 68(4), 685–701.Hölzel, B. K., Ott, U., Gard, T., Hempel, H., Weygandt, M., Morgen, K., et al. (2008). Investigation of mindfulness meditation practitioners with voxel-based morphometry. Social Cognitive and Affective Neuroscience, 3(1), 55–61.Hölzel, B. K., Lazar, S. W., Gard, T., Schuman-Olivier, Z., Vago, D. R., & Ott, U. (2011). How does mindfulness meditation work? Proposing mechanisms of action from a conceptual and neural perspective. Perspectives on Psychological Science, 6(6), 537–559.Kalckert, A., & Ehrsson, H. H. (2012). Moving a rubber hand that feels like your own: a dissociation of ownership and agency. Frontiers in Human Neuroscience, 6, 40.Karnath, H. O., & Baier, B. (2010). Right insula for our sense of limb ownership and self-awareness of actions. Brain Structure and Function, 214(5-6), 411–417.Keizer, A., Smeets, M. A., Postma, A., van Elburg, A., & Dijkerman, H. C. (2014). Does the experience of ownership over a rubber hand change body size perception in anorexia nervosa patients? Neuropsychologia, 62, 26–37.Kerr, C. E., Sacchet, M. D., Lazar, S. W., Moore, C. I., & Jones, S. R. (2013). Mindfulness starts with the body: somatosensory attention and top-down modulation of cortical alpha rhythms in mindfulness meditation. Frontiers in Human Neuroscience, 7, 12.Lakhan, S. E., & Schofield, K. L. (2013). Mindfulness-based therapies in the treatment of somatization disorders: a systematic review and meta-analysis. PLoS ONE, 8(8), e71834.Lazar, S. W., Kerr, C. E., Wasserman, R. H., Gray, J. R., Greve, D. N., Treadway, M. T., et al. (2005). Meditation experience is associated with increased cortical thickness. Neuroreport, 16(17), 1893–1897.Longo, M. R., Schüür, F., Kammers, M. P., Tsakiris, M., & Haggard, P. (2008). What is embodiment? A psychometric approach. Cognition, 107(3), 978–998.McManus, F., Surawy, C., Muse, K., Vazquez-Montes, M., & Williams, J. M. G. (2012). A randomized clinical trial of mindfulness-based cognitive therapy versus unrestricted services for health anxiety (hypochondriasis). Journal of Consulting and Clinical Psychology, 80(5), 817–828.Mehling, W. E., Gopisetty, V., Daubenmier, J., Price, C. J., Hecht, F. M., & Stewart, A. (2009). Body awareness: construct and self-report measures. PLoS ONE, 4(5), e5614.Mehling, W. E., Price, C., Daubenmier, J. J., Acree, M., Bartmess, E., & Stewart, A. (2012). The multidimensional assessment of interoceptive awareness (MAIA). PLoS ONE, 7(11), e48230.Mirams, L., Poliakoff, E., Brown, R. J., & Lloyd, D. M. (2013). Brief body-scan meditation practice improves somatosensory perceptual decision making. Consciousness and Cognition, 22(1), 348–359.Moseley, G. L., Olthof, N., Venema, A., Don, S., Wijers, M., Gallace, A., et al. (2008). Psychologically induced cooling of a specific body part caused by the illusory ownership of an artificial counterpart. Proceedings of the National Academy of Sciences, 105(35), 13169–13173.Mussap, A. J., & Salton, N. (2006). A ‘rubber-hand’ illusion reveals a relationship between perceptual body image and unhealthy body change. Journal of Health Psychology, 11(4), 627–639.Naranjo, J. R., & Schmidt, S. (2012). Is it me or not me? Modulation of perceptual-motor awareness and visuomotor performance by mindfulness meditation. BMC Neuroscience, 13(1), 88.Parkin, L., Morgan, R., Rosselli, A., Howard, M., Sheppard, A., Evans, D., et al. (2014). Exploring the relationship between mindfulness and cardiac perception. Mindfulness, 5(3), 298–313.Pollatos, O., Kurz, A. L., Albrecht, J., Schreder, T., Kleemann, A. M., Schöpf, V., et al. (2008). Reduced perception of bodily signals in anorexia nervosa. Eating Behaviors, 9(4), 381–388.Quezada-Berumen, L., González-Ramírez, M. T., Cebolla, A., Soler, J., & García-Campayo, J. (2014). Conciencia corporal y mindfulness: Validación de la versión española de la escala de conexión corporal (SBC). Actas Españolas de Psiquiatría, 42(2), 57–67.Rohde, M., Di Luca, M., & Ernst, M. O. (2011). The rubber hand illusion: feeling of ownership and proprioceptive drift do not go hand in hand. PLoS One, 6(6), e21659.Schauder, K. B., Mash, L. E., Bryant, L. K., & Cascio, C. J. (2015). Interoceptive ability and body awareness in autism spectrum disorder. Journal of Experimental Child Psychology, 131, 193–200.Sze, J. A., Gyurak, A., Yuan, J. W., & Levenson, R. W. (2010). Coherence between emotional experience and physiology: does body awareness training have an impact? Emotion, 10(6), 803–814.Teper, R., & Inzlicht, M. (2013). Meditation, mindfulness and executive control: the importance of emotional acceptance and brain-based performance monitoring. Social Cognitive and Affective Neuroscience, 8(1), 85–92.Thakkar, K. N., Nichols, H. S., McIntosh, L. G., & Park, S. (2011). Disturbances in body ownership in schizophrenia: evidence from the rubber hand illusion and case study of a spontaneous out-of-body experience. PLoS One, 6(10), e27089.Tran, U. S., Glück, T. M., & Nader, I. W. (2013). Investigating the Five Facet Mindfulness Questionnaire (FFMQ): construction of a short form and evidence of a two‐factor higher order structure of mindfulness. Journal of Clinical Psychology, 69(9), 951–965.Tsakiris, M., & Haggard, P. (2005). The rubber hand illusion revisited: visuotactile integration and self-attribution. Journal of Experimental Psychology: Human Perception and Performance, 31(1), 80.Tsakiris, M., Tajadura-Jiménez, A., & Costantini, M. (2011). Just a heartbeat away from one’s body: interoceptive sensitivity predicts malleability of body-representations. Proceedings of the Royal Society of London B: Biological Sciences, 278(1717), 2470–2476.Van Ravesteijn, H., Lucassen, P. L. B. J., Bor, H., Van Weel, C., & Speckens, A. (2013). Mindfulness-based cognitive therapy for patients with medically unexplained symptoms: a randomized controlled trial. Psychotherapy and Psychosomatics, 82(5), 299–310

A canine model of Cohen syndrome: Trapped Neutrophil Syndrome

<p>Abstract</p> <p>Background</p> <p>Trapped Neutrophil Syndrome (TNS) is a common autosomal recessive neutropenia in Border collie dogs.</p> <p>Results</p> <p>We used a candidate gene approach and linkage analysis to show that the causative gene for TNS is <it>VPS13B</it>. We chose <it>VPS13B </it>as a candidate because of similarities in clinical signs between TNS and Cohen syndrome, in human, such as neutropenia and a typical facial dysmorphism. Linkage analysis using microsatellites close to <it>VPS13B </it>showed positive linkage of the region to TNS. We sequenced each of the 63 exons of <it>VPS13B </it>in affected and control dogs and found that the causative mutation in Border collies is a 4 bp deletion in exon 19 of the largest transcript that results in premature truncation of the protein. Cohen syndrome patients present with mental retardation in 99% of cases, but learning disabilities featured in less than half of TNS affected dogs. It has been implied that loss of the alternate transcript of <it>VPS13B </it>in the human brain utilising an alternate exon, 28, may cause mental retardation. Mice cannot be used to test this hypothesis as they do not express the alternate exon. We show that dogs do express alternate transcripts in the brain utilising an alternate exon homologous to human exon 28.</p> <p>Conclusion</p> <p>Dogs can be used as a model organism to explore the function of the alternately spliced transcript of VPS13B in the brain. TNS in Border collies is the first animal model for Cohen syndrome and can be used to study the disease aetiology.</p

The effects of interleukin-8 on airway smooth muscle contraction in cystic fibrosis

<p>Abstract</p> <p>Background</p> <p>Many cystic fibrosis (CF) patients display airway hyperresponsiveness and have symptoms of asthma such as cough, wheezing and reversible airway obstruction. Chronic airway bacterial colonization, associated with neutrophilic inflammation and high levels of interleukin-8 (IL-8) is also a common occurrence in these patients. The aim of this work was to determine the responsiveness of airway smooth muscle to IL-8 in CF patients compared to non-CF individuals.</p> <p>Methods</p> <p>Experiments were conducted on cultured ASM cells harvested from subjects with and without CF (control subjects). Cells from the 2^ndto 5^thpassage were studied. Expression of the IL-8 receptors CXCR1 and CXCR2 was assessed by flow cytometry. The cell response to IL-8 was determined by measuring intracellular calcium concentration ([Ca²⁺]_i), cell contraction, migration and proliferation.</p> <p>Results</p> <p>The IL-8 receptors CXCR1 and CXCR2 were expressed in both non-CF and CF ASM cells to a comparable extent. IL-8 (100 nM) induced a peak Ca²⁺release that was higher in control than in CF cells: 228 ± 7 versus 198 ± 10 nM (p < 0.05). IL-8 induced contraction was greater in CF cells compared to control. Furthermore, IL-8 exposure resulted in greater phosphorylation of myosin light chain (MLC₂₀) in CF than in control cells. In addition, MLC₂₀expression was also increased in CF cells. Exposure to IL-8 induced migration and proliferation of both groups of ASM cells but was not different between CF and non-CF cells.</p> <p>Conclusion</p> <p>ASM cells of CF patients are more contractile to IL-8 than non-CF ASM cells. This enhanced contractility may be due to an increase in the amount of contractile protein MLC₂₀. Higher expression of MLC₂₀by CF cells could contribute to airway hyperresponsiveness to IL-8 in CF patients.</p

Hippocampal Gene Expression Analysis Highlights Ly6a/Sca-1 as Candidate Gene for Previously Mapped Novelty Induced Behaviors in Mice

In this study, we show that the covariance between behavior and gene expression in the brain can help further unravel the determinants of neurobehavioral traits. Previously, a QTL for novelty induced motor activity levels was identified on murine chromosome 15 using consomic strains. With the goal of narrowing down the linked region and possibly identifying the gene underlying the quantitative trait, gene expression data from this F2-population was collected and used for expression QTL analysis. While genetic variation in these mice was limited to chromosome 15, eQTL analysis of gene expression showed strong cis-effects as well as trans-effects elsewhere in the genome. Using weighted gene co-expression network analysis, we were able to identify modules of co-expressed genes related to novelty induced motor activity levels. In eQTL analyses, the expression of Ly6a (a.k.a. Sca-1) was found to be cis-regulated by chromosome 15. Ly6a also surfaced in a group of genes resulting from the network analysis that was correlated with behavior. Behavioral analysis of Ly6a knock-out mice revealed reduced novelty induced motor activity levels when compared to wild type controls, confirming functional importance of Ly6a in this behavior, possibly through regulating other genes in a pathway. This study shows that gene expression profiling can be used to narrow down a previously identified behavioral QTL in mice, providing support for Ly6a as a candidate gene for functional involvement in novelty responsiveness