The retinal origin of congenital nystagmus

This thesis describes a revolutionary retinal mechanism leading to nystagmus in mouse models for CSNB. In patients with CSNB and nystagmus, mutations were found that are specifically present in the photoreceptor to ON-bipolar cell synapse, both pre- and postsynaptically. Here, we studied one presynaptic (Cav1.4) and two postsynaptic mutations (mGluR6nob3, Nyxnob) that cause CSNB. We found that all three mouse models show nystagmus and oscillating RGCs, but that they varied phenotypically between the three genotypes. All three mutations lead to an altered membrane potential of the ON-BCs and consequently of the AII ACs as well. The latter are then outside their normal working range and start to intrinsically oscillate. These oscillations are passed on to the RGCs, which also start to oscillate. This includes the ON-DSRGCs, that send an oscillatory retinal slip signal to the AOS, which consequently leads to compensatory, oscillatory eye movements, the nystagmus. The different phenotypes can thereby be explained by the difference in depolarization levels of the ON-BCs due to the different mutations

Population-based patient care study for breast cancer

Background: Different approaches for an effective quality management are funded by the Ministry of Health to verify, to assess and, if necessary to optimize the quality of health care using the tracer diagnoses of breast, rectal, and lung cancer in eight regions in Germany. The conception of these observational studies and initial findings are shown here, using breast cancer in the region of Munich (population 2.4 million) as an example. Patients and Methods: The study started on April 1, 1996. The recruitment phase for all primary boast cancer patients in this region is planned for 2 years with a 3-5-year follow-up. Established documentation sheets are used to document basic medical information of each patient, along with the original reports (pathology: radiotherapy, doctors' reports, etc.), follow-up reports and quality of life questionnaires (QLQ, including the EORTC QLQ C30). Results: In 1996, the Munich region has a crude incidence of 125/100,000 women (world standard 71.5). After almost complete documentation the incidence is 10-15% higher. In the period from April 1 1996 to June 30, 1997 1,360 patients have been recruited into the study. 79% of the patients were 50 years of age or older. pT stages are distributed as follows: pTIS 5%, pT1 54%, pT2 32%, pT3 4%, pT4 6%. 4.5% had primary metastases. Breast-conserving therapy (BCT) was performed in 57% of patients. Five of the 46 departments involved recruited more than 50 patients each within these 14 months. These larger departments treat 59% of all patients. The proportion of older patients and pT4 stages is significantly higher in the smaller departments. BCT is performed significantly more often in the larger departments. First results of quality of life show dependencies on age, but no differences between mastectomy and BCT 3 months after operation. Not only the addressed patients (response rate to QLQ over 80%) but also almost all hospitals and many physicians are milling to support and to partake in quality assurance. 35 hospitals, 46 surgical departments. 80 heads of department and surgically: active general practioners, 330 general practioners. 7 radiotherapy departments, and 13 pathology departments have so far documented for this study. Conclusions: An effective quality management in oncology needs a modern cancer registry which uses documentation sheets as well as original reports and organizes the complicated infrastructure for an interdisciplinary cooperation. To be able to evaluate the health care reality it is necessary to carry out a data analysis and assess each individual case. A feedback of the results have to be available for each physician and each department. The cost of this information management is approximately 0.3% of the health care cost for this group of patients

Organic vs. Conventional Grassland Management: Do 15N and 13C Isotopic Signatures of Hay and Soil Samples Differ?

Distinguishing organic and conventional products is a major issue of food security and authenticity. Previous studies successfully used stable isotopes to separate organic and conventional products, but up to now, this approach was not tested for organic grassland hay and soil. Moreover, isotopic abundances could be a powerful tool to elucidate differences in ecosystem functioning and driving mechanisms of element cycling in organic and conventional management systems. Here, we studied the δ15N and δ13C isotopic composition of soil and hay samples of 21 organic and 34 conventional grasslands in two German regions. We also used Δδ15N (δ15N plant - δ15N soil) to characterize nitrogen dynamics. In order to detect temporal trends, isotopic abundances in organic grasslands were related to the time since certification. Furthermore, discriminant analysis was used to test whether the respective management type can be deduced from observed isotopic abundances. Isotopic analyses revealed no significant differences in δ13C in hay and δ15N in both soil and hay between management types, but showed that δ13C abundances were significantly lower in soil of organic compared to conventional grasslands. Δδ15N values implied that management types did not substantially differ in nitrogen cycling. Only δ13C in soil and hay showed significant negative relationships with the time since certification. Thus, our result suggest that organic grasslands suffered less from drought stress compared to conventional grasslands most likely due to a benefit of higher plant species richness, as previously shown by manipulative biodiversity experiments. Finally, it was possible to correctly classify about two third of the samples according to their management using isotopic abundances in soil and hay. However, as more than half of the organic samples were incorrectly classified, we infer that more research is needed to improve this approach before it can be efficiently used in practice

Mindfulness-based interventions for young offenders: a scoping review

Youth offending is a problem worldwide. Young people in the criminal justice system have frequently experienced adverse childhood circumstances, mental health problems, difficulties regulating emotions and poor quality of life. Mindfulness-based interventions can help people manage problems resulting from these experiences, but their usefulness for youth offending populations is not clear. This review evaluated existing evidence for mindfulness-based interventions among such populations. To be included, each study used an intervention with at least one of the three core components of mindfulness-based stress reduction (breath awareness, body awareness, mindful movement) that was delivered to young people in prison or community rehabilitation programs. No restrictions were placed on methods used. Thirteen studies were included: three randomized controlled trials, one controlled trial, three pre-post study designs, three mixed-methods approaches and three qualitative studies. Pooled numbers (n = 842) comprised 99% males aged between 14 and 23. Interventions varied so it was not possible to identify an optimal approach in terms of content, dose or intensity. Studies found some improvement in various measures of mental health, self-regulation, problematic behaviour, substance use, quality of life and criminal propensity. In those studies measuring mindfulness, changes did not reach statistical significance. Qualitative studies reported participants feeling less stressed, better able to concentrate, manage emotions and behaviour, improved social skills and that the interventions were acceptable. Generally low study quality limits the generalizability of these findings. Greater clarity on intervention components and robust mixed-methods evaluation would improve clarity of reporting and better guide future youth offending prevention programs

Emergence of qualia from brain activity or from an interaction of proto-consciousness with the brain: which one is the weirder? Available evidence and a research agenda

This contribution to the science of consciousness aims at comparing how two different theories can explain the emergence of different qualia experiences, meta-awareness, meta-cognition, the placebo effect, out-of-body experiences, cognitive therapy and meditation-induced brain changes, etc. The first theory postulates that qualia experiences derive from specific neural patterns, the second one, that qualia experiences derive from the interaction of a proto-consciousness with the brain\u2019s neural activity. From this comparison it will be possible to judge which one seems to better explain the different qualia experiences and to offer a more promising research agenda

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

Potential role of ticks as vectors of bluetongue virus

When the first outbreak of bluetongue virus serotype 8 (BTV8) was recorded in North-West Europe in August 2006 and renewed outbreaks occurred in the summer of 2007 and again in 2008, the question was raised how the virus survived the winter. Since most adult Culicoides vector midges are assumed not to survive the northern European winter, and transovarial transmission in Culicoides is not recorded, we examined the potential vector role of ixodid and argasid ticks for bluetongue virus. Four species of ixodid ticks (Ixodes ricinus, Ixodes hexagonus, Dermacentor reticulatus and Rhipicephalus bursa) and one soft tick species, Ornithodoros savignyi, ingested BTV8-containing blood either through capillary feeding or by feeding on artificial membranes. The virus was taken up by the ticks and was found to pass through the gut barrier and spread via the haemolymph into the salivary glands, ovaries and testes, as demonstrated by real-time reverse transcriptase PCR (PCR-test). BTV8 was detected in various tissues of ixodid ticks for up to 21 days post feeding and in Ornithodoros ticks for up to 26 days. It was found after moulting in adult Ixodes hexagonus and was also able to pass through the ovaries into the eggs of an Ornithodoros savignyi tick. This study demonstrates that ticks can become infected with bluetongue virus serotype 8. The transstadial passage in hard ticks and transovarial passage in soft ticks suggest that ticks have potential vectorial capacity for bluetongue virus. Further studies are required to investigate transmission from infected ticks to domestic livestock. This route of transmission could provide an additional clue in the unresolved mystery of the epidemiology of Bluetongue in Europe by considering ticks as a potential overwintering mechanism for bluetongue virus

The Human Nucleolar Protein FTSJ3 Associates with NIP7 and Functions in Pre-rRNA Processing

NIP7 is one of the many trans-acting factors required for eukaryotic ribosome biogenesis, which interacts with nascent pre-ribosomal particles and dissociates as they complete maturation and are exported to the cytoplasm. By using conditional knockdown, we have shown previously that yeast Nip7p is required primarily for 60S subunit synthesis while human NIP7 is involved in the biogenesis of 40S subunit. This raised the possibility that human NIP7 interacts with a different set of proteins as compared to the yeast protein. By using the yeast two-hybrid system we identified FTSJ3, a putative ortholog of yeast Spb1p, as a human NIP7-interacting protein. A functional association between NIP7 and FTSJ3 is further supported by colocalization and coimmunoprecipitation analyses. Conditional knockdown revealed that depletion of FTSJ3 affects cell proliferation and causes pre-rRNA processing defects. The major pre-rRNA processing defect involves accumulation of the 34S pre-rRNA encompassing from site A′ to site 2b. Accumulation of this pre-rRNA indicates that processing of sites A0, 1 and 2 are slower in cells depleted of FTSJ3 and implicates FTSJ3 in the pathway leading to 18S rRNA maturation as observed previously for NIP7. The results presented in this work indicate a close functional interaction between NIP7 and FTSJ3 during pre-rRNA processing and show that FTSJ3 participates in ribosome synthesis in human cells