Mathematical Analysis of Copy Number Variation in a DNA Sample Using Digital PCR on a Nanofluidic Device

Copy Number Variations (CNVs) of regions of the human genome have been associated with multiple diseases. We present an algorithm which is mathematically sound and computationally efficient to accurately analyze CNV in a DNA sample utilizing a nanofluidic device, known as the digital array. This numerical algorithm is utilized to compute copy number variation and the associated statistical confidence interval and is based on results from probability theory and statistics. We also provide formulas which can be used as close approximations

Revisiting the five-facet structure of mindfulness

The current study aimed to replicate the development of the Five-Facet Mindfulness Questionnaire (FFMQ) in a sample of 399 undergraduate students. We factor analyzed the Mindful Attention and Awareness Questionnaire (MAAS), the Freiburg Mindfulness Scale, the Southampton Mindfulness Questionnaire (SMQ), the Cognitive Affective Mindfulness Scale Revised (CAMS-R), and the Kentucky Inventory of Mindfulness Skills (KIMS), but also extended the analysis by including a conceptually related measure, the Philadelphia Mindfulness Scale (PHLMS), and a conceptually unrelated measure, the Langer Mindfulness Scale (LMS). Overall, we found a partial replication of the five-factor structure, with the exception of non-reacting and non-judging which formed a single factor. The PHLMS items loaded as expected with theoretically related factors, whereas the LMS items emerged as separate factor. Finally, we found a new factor that was mostly defined by negatively worded items indicating possible item wording artifacts within the FFMQ. Our conceptual validation study indicates that some facets of the FFMQ can be recovered, but item wording factors may threaten the stability of these facets. Additionally, measures such as the LMS appear to measure not only theoretically, but also empirically different constructs

Oligodendrocytes Do Not Export NAA-Derived Aspartate In Vitro.

Oligodendroglial cells are known to de-acetylate the N-acetylaspartate (NAA) synthesized and released by neurons and use it for lipid synthesis. However, the role of NAA regarding their intermediary metabolism remains poorly understood. Two hypotheses were proposed regarding the fate of aspartate after being released by de-acetylation: (1) aspartate is metabolized in the mitochondria of oligodendrocyte lineage cells; (2) aspartate is released to the medium. We report here that aspartoacylase mRNA expression increases when primary rat oligodendrocyte progenitor cells (OPCs) differentiate into mature cells in culture. Moreover, characterising metabolic functions of acetyl coenzyme A and aspartate from NAA catabolism in mature oligodendrocyte cultures after 5 days using isotope-labelled glucose after 5-days of differentiation we found evidence of extensive NAA metabolism. Incubation with [1,6-13C]glucose followed by gas chromatography-mass spectrometry and high performance liquid chromatography analyses of cell extracts and media in the presence and absence of NAA established that the acetate moiety produced by hydrolysis of NAA does not enter mitochondrial metabolism in the form of acetyl coenzyme A. We also resolved the controversy concerning the possible release of aspartate to the medium: aspartate is not released to the medium by oligodendrocytes in amounts detectable by our methods. Therefore we propose that: aspartate released from NAA joins the cytosolic aspartate pool rapidly and takes part in the malate-aspartate shuttle, which transports reducing equivalents from glycolysis into the mitochondria for ATP production and enters the tricarboxylic acid cycle at a slow rate.This work was supported by grants from the UK Multiple Sclerosis Society and from Qatar Foundation. The work was further supported by core funding from the Wellcome Trust and MRC to the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute. The authors acknowledge the excellent technical support in GC-MS and HPLC analysis from Lars Evje (NTNU, Norway).This is the final version of the article. It first appeared from Springer at http://dx.doi.org/10.1007/s11064-016-1985-y

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). 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Population dynamics of a pathogen: the conundrum of vivax malaria

Building a mathematical model of population dynamics of pathogens within their host involves considerations of factors similar to those in ecology, as pathogens can prey on cells in the host. But within the multicellular host, attacked cell types are integrated with other cellular systems, which in turn intervene in the infection. For example, immune responses attempt to sense and then eliminate or contain pathogens, and homeostatic mechanisms try to compensate for cell loss. This review focuses on modeling applied to malarias, diseases caused by single-cell eukaryote parasites that infect red blood cells, with special concern given to vivax malaria, a disease often thought to be benign (if sometimes incapacitating) because the parasite only attacks a small proportion of red blood cells, the very youngest ones. However, I will use mathematical modeling to argue that depletion of this pool of red blood cells can be disastrous to the host if growth of the parasite is not vigorously check by host immune responses. Also, modeling can elucidate aspects of new field observations that indicate that vivax malaria is more dangerous than previously thought

Multiple Mating and Family Structure of the Western Tent Caterpillar, Malacosoma californicum pluviale: Impact on Disease Resistance

Background Levels of genetic diversity can strongly influence the dynamics and evolutionary changes of natural populations. Survival and disease resistance have been linked to levels of genetic diversity in eusocial insects, yet these relationships remain untested in gregarious insects where disease transmission can be high and selection for resistance is likely to be strong. Methodology/Principal Findings Here we use 8 microsatellite loci to examine genetic variation in 12 families of western tent caterpillars, Malacosoma californicum pluviale from four different island populations to determine the relationship of genetic variability to survival and disease resistance. In addition these genetic markers were used to elucidate the population structure of western tent caterpillars. Multiple paternity was revealed by microsatellite markers, with the number of sires estimated to range from one to three per family (mean ± SE = 1.92±0.23). Observed heterozygosity (HO) of families was not associated to the resistance of families to a nucleopolyhedrovirus (NPV) (r = 0.161, F1,12 = 0.271, P = 0.614), a major cause of mortality in high-density populations, but was positively associated with larval survival (r = 0.635, F1,10 = 5.412, P = 0.048). Genetic differentiation among the families was high (FST = 0.269, P<0.0001), and families from the same island were as differentiated as were families from other islands. Conclusion/Significance We have been able to describe and characterize 8 microsatellite loci, which demonstrate patterns of variation within and between families of western tent caterpillars. We have discovered an association between larval survival and family-level heterozygosity that may be relevant to the population dynamics of this cyclic forest lepidopteran, and this will be the topic of future work

Immune response of macrophages from young and aged mice to the oral pathogenic bacterium Porphyromonas gingivalis

Periodontal disease is a chronic inflammatory gum disease that in severe cases leads to tooth loss. Porphyromonas gingivalis (Pg) is a bacterium closely associated with generalized forms of periodontal disease. Clinical onset of generalized periodontal disease commonly presents in individuals over the age of 40. Little is known regarding the effect of aging on inflammation associated with periodontal disease. In the present study we examined the immune response of bone marrow derived macrophages (BMM) from young (2-months) and aged (1-year and 2-years) mice to Pg strain 381. Pg induced robust expression of cytokines; tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10, chemokines; neutrophil chemoattractant protein (KC), macrophage colony stimulating factor (MCP)-1, macrophage inflammatory protein (MIP)-1α and regulated upon activation normal T cell expressed and secreted (RANTES), as well as nitric oxide (NO, measured as nitrite), and prostaglandin E2 (PGE2) from BMM of young mice. BMM from the 2-year age group produced significantly less TNF-α, IL-6 and NO in response to Pg as compared with BMM from 2-months and 1-year of age. We did not observe any difference in the levels of IL-1β, IL-10 and PGE2 produced by BMM in response to Pg. BMM from 2-months and 1-year of age produced similar levels of all chemokines measured with the exception of MCP-1, which was reduced in BMM from 1-year of age. BMM from the 2-year group produced significantly less MCP-1 and MIP-1α compared with 2-months and 1-year age groups. No difference in RANTES production was observed between age groups. Employing a Pg attenuated mutant, deficient in major fimbriae (Pg DPG3), we observed reduced ability of the mutant to stimulate inflammatory mediator expression from BMMs as compared to Pg 381, irrespective of age. Taken together these results support senescence as an important facet of the reduced immunological response observed by BMM of aged host to the periodontal pathogen Pg

Ice-confined construction of a large basaltic volcano—Austurfjöll massif, Askja, Iceland

Austurfjöll is the largest basaltic glaciovolcanic massif at Askja volcano (Central Iceland), and through detailed studies of its volcanological and geochemical characteristics, we provide a detailed account of the sequence and structure of the ice-confined construction of a large Icelandic basaltic volcano. In particular, Austurfjöll represents a geometry of vents, and resulting glaciovolcanic morphology, not previously documented in ice-confined basaltic volcanoes. Austurfjöll was constructed during two major phases of basaltic volcanism, via seven eruptive episodes through disperse fissure-dominated eruptions. The earliest episode involved a rare and poorly exposed example of subaerial activity, and this was succeeded by six episodes involving the eruption of ice-confined pillow lavas and numerous overlapping fissure eruptions of phreatomagmatic tephra. Evidence of local subaerial lavas and tephras indicates the local growth of eruptive centers above englacial lake levels, and subsequent flooding, but no prolonged subaerial activity. Localized ice-contact facies, paleowater levels, and diamictons indicate the position and thickness of the ice was variable during the construction of Austurfjöll, and eruptive activity likely occurred in multiple and variable level meltwater lakes during the last glacial period. Lithofacies evidence including gradational transitions from effusive to explosive deposits, superposition of fragmental facies above coherent facies, and drainage channels suggest that changes in eruptive style were driven largely by external factors such as drainage and the increasing elevation of the massif. This study emphasizes the unique character of Austurfjöll, being composed of large pillow lava sheets, numerous (> 40) overlapping glaciovolcanic tindars, and only localized emergent deposits, as a product of its prolonged ice-confined eruptive history, contrasts with previous descriptions of tuyas and tindars