Desynchronization of pulse-coupled oscillators with delayed excitatory coupling

Collective behavior of pulse-coupled oscillators has been investigated widely. As an example of pulse-coupled networks, fireflies display many kinds of flashing patterns. Mirollo and Strogatz (1990) proposed a pulse-coupled oscillator model to explain the synchronization of South East Asian fireflies ({\itshape Pteroptyx malaccae}). However, transmission delays were not considered in their model. In fact, the presence of transmission delays can lead to desychronization. In this paper, pulse-coupled oscillator networks with delayed excitatory coupling are studied. Our main result is that under reasonable assumptions, pulse-coupled oscillator networks with delayed excitatory coupling can not achieve complete synchronization, which can explain why another species of fireflies ({\itshape Photinus pyralis}) rarely synchronizes flashing. Finally, two numerical simulations are given. In the first simulation, we illustrate that even if all the initial phases are very close to each other, there could still be big variations in the times to process the pulses in the pipeline. It implies that asymptotical synchronization typically also cannot be achieved. In the second simulation, we exhibit a phenomenon of clustering synchronization

The leaching of natural colloids from forest surface soils and their role for the P transfer

Soil nanoparticles (d<100nm) and colloids (d<1µm) exert a decisive control on the mobilisation of strongly sorbing compounds such as phosphorus (P). We investigated the nanoparticles and colloids present in forest soil leachates examining their role for the P fixation and for the vertical P transfer in forest soils. Mesocosm experiments with three German forest soils (upper 20 cm) were conducted. The mesocosms were irrigated with artificial rain for 22 months and the nanoparticles and colloids were characterised in the soil leachates with special attention to P. The field flow fractionation (FFF) technique coupled online to UV- and DLS- detectors and inductively coupled plasma mass spectrometry (ICP-MS) or to an organic carbon detector (OCD) enabled a size resolved characterization and quantification of the nanoparticulate and colloidal fractions and their elemental composition (P, Corg, Fe, A, Si, Ca. Mn). To visualise and better characterise the particles present in the leachates, transmission electron microscopy with energy-dispersive x-ray spectroscopy (TEM-EDX) measurements were performed. The translocated particles exhibited sizes up to 350 nm. Using FFF we separated the colloids in three size fractions i) 3-20 nm ii) 20-70 nm and iii) 70-350 nm. The particle fractions showed different chemical compositions. However their composition and characteristics were similar between the three forest sites and comparable to the natural nanoparticles and colloids from soils (“water dispersible colloids”) and streams described in literature. Up to 90% (on average ~45 %) of the leached P was associated with the nanoparticles and colloids. Our qualitative and quantitative analysis of the soil leachates showed that nanoparticles and colloids are crucial vectors controlling the P fluxes in forest ecosystems and could be a significant, but as yet still poorly quantified P loss factor

Spruce Health in Utah Landscapes

Spruces are common trees in cultivated landscapes in Utah. They have varied shapes, attractive foliage color, and can be fairly long-lived. They have pests, but not overly so, and are not very messy

Managing the Spread of Alfalfa Stem Nematodes (Ditylenchus dipsaci): The Relationship Between Crop Rotation Periods and Pest Re-emergence

Alfalfa is a critical cash/rotation crop in the western region of the United States, where it is common to find crops affected by the alfalfa stem nematode (Ditylenchus dipsaci). Understanding the spread dynamics associated with this pest would allow growers to design better management programs and farming practices. This understanding is of particular importance given that there are no nematicides available against alfalfa stem nematodes and control strategies largely rely on crop rotation to non-host crops or by planting resistant varieties of alfalfa. In this paper we present a basic host-parasite model that describes the spread of the alfalfa stem nematode on alfalfa crops. With this discrete time model we are able to portray a relationship between the length of crop rotation periods and the time at which the density of nematode-infested plants becomes larger than that of nematode-free ones in the post-rotation alfalfa. The numerical results obtained are consistent with farming practice observations, suggesting that the model could play a role in the evaluation of management strategies

Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis

DeepWAS: multivariate genotype-phenotype associations by directly integrating regulatory information using deep learning

Genome-wide association studies (GWAS) identify genetic variants associated with traits or diseases. GWAS never directly link variants to regulatory mechanisms. Instead, the functional annotation of variants is typically inferred by post hoc analyses. A specific class of deep learning-based methods allows for the prediction of regulatory effects per variant on several cell type-specific chromatin features. We here describe "DeepWAS", a new approach that integrates these regulatory effect predictions of single variants into a multivariate GWAS setting. Thereby, single variants associated with a trait or disease are directly coupled to their impact on a chromatin feature in a cell type. Up to 61 regulatory SNPs, called dSNPs, were associated with multiple sclerosis (MS, 4,888 cases and 10,395 controls), major depressive disorder (MDD, 1,475 cases and 2,144 controls), and height (5,974 individuals). These variants were mainly non-coding and reached at least nominal significance in classical GWAS. The prediction accuracy was higher for DeepWAS than for classical GWAS models for 91% of the genome-wide significant, MS-specific dSNPs. DSNPs were enriched in public or cohort-matched expression and methylation quantitative trait loci and we demonstrated the potential of DeepWAS to generate testable functional hypotheses based on genotype data alone. DeepWAS is available at https://github.com/cellmapslab/DeepWAS

Elemental Composition of Natural Nanoparticles and Fine Colloids in European Forest Stream Waters and Their Role as Phosphorus Carriers

"This is the peer reviewed version of the following article: Gottselig, N., W. Amelung, J. W. Kirchner, R. Bol, W. Eugster, S. J. Granger, C. Hernández-Crespo, et al. 2017. Elemental Composition of Natural Nanoparticles and Fine Colloids in European Forest Stream Waters and Their Role as Phosphorus Carriers. Global Biogeochemical Cycles 31 (10). American Geophysical Union (AGU): 1592 1607. doi:10.1002/2017gb005657, which has been published in final form at https://doi.org/10.1002/2017GB005657. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."[EN] Biogeochemical cycling of elements largely occurs in dissolved state, but many elements may also be bound to natural nanoparticles (NNP, 1-100 nm) and fine colloids (100-450 nm). We examined the hypothesis that the size and composition of stream water NNP and colloids vary systematically across Europe. To test this hypothesis, 96 stream water samples were simultaneously collected in 26 forested headwater catchments along two transects across Europe. Three size fractions (similar to 1-20 nm, >20-60 nm, and >60 nm) of NNP and fine colloids were identified with Field Flow Fractionation coupled to inductively coupled plasma mass spectrometry and an organic carbon detector. The results showed that NNP and fine colloids constituted between 2 +/- 5% (Si) and 53 +/- 21% (Fe; mean +/- SD) of total element concentrations, indicating a substantial contribution of particles to element transport in these European streams, especially for P and Fe. The particulate contents of Fe, Al, and organic C were correlated to their total element concentrations, but those of particulate Si, Mn, P, and Ca were not. The fine colloidal fractions >60 nm were dominated by clay minerals across all sites. The resulting element patterns of NNP <60 nm changed from North to South Europe from Fe-to Ca-dominated particles, along with associated changes in acidity, forest type, and dominant lithology.The authors gratefully acknowledge the assistance of the following people in locating suitable sampling sites, contacting site operators, performing the sampling, and providing data: A. Avila Castells (Autonomous University of Barcelona), R. Batalla (University of Lleida), P. Blomkvist (Swedish University of Agricultural Sciences), H. Bogena (Julich Research Center), A.K. Boulet (University of Aveiro), D. Estany (University of Lleida), F. Garnier (French National Institute of Agricultural Research), H.J. Hendricks-Franssen (Research Center Julich), L. JacksonBlake (James Hutton Institute, NIVA), T. Laurila (Finnish Meteorological Institute), A. Lindroth (Lund University), M.M. Monerris (Universitat Politecnica de Valencia), M. Ottosson Lofvenius (Swedish University of Agricultural Sciences), I. Taberman (Swedish University of Agricultural Sciences), F. Wendland (Research Center Julich), T. Zetterberg (Swedish University of Agricultural Sciences and The Swedish Environmental Research Institute, IVL) and further unnamed contributors. The Swedish Infrastructure for Ecosystem Science (SITES) and the Swedish Integrated Monitoring, the latter financed by the Swedish Environmental Protection Agency, and ICOS Sweden have supported sampling and provided data for the Swedish sites. J.J.K. gratefully acknowledges the support from CESAM (UID/AMB/50017/2013), funded by the FCT/MCTES (PIDDAC) with cofunding by FEDER through COMPETE. N.G. gratefully acknowledges all those who contributed to organizing and implementing the continental sampling. The raw data can be found at http://hdl.handle.net/2128/14937. This project was partly funded by the German Research Foundation (DFG KL2495/1-1).Gottselig, N.; Amelung, W.; Kirchner, J.; Bol, R.; Eugster, W.; Granger, S.; Hernández Crespo, C.... (2017). Elemental Composition of Natural Nanoparticles and Fine Colloids in European Forest Stream Waters and Their Role as Phosphorus Carriers. Global Biogeochemical Cycles. 31(10):1592-1607. https://doi.org/10.1002/2017GB005657S159216073110Baken, S., Moens, C., van der Grift, B., & Smolders, E. (2016). Phosphate binding by natural iron-rich colloids in streams. Water Research, 98, 326-333. doi:10.1016/j.watres.2016.04.032Baken, S., Regelink, I. C., Comans, R. N. J., Smolders, E., & Koopmans, G. F. (2016). Iron-rich colloids as carriers of phosphorus in streams: A field-flow fractionation study. Water Research, 99, 83-90. doi:10.1016/j.watres.2016.04.060Benedetti, M. F., Van Riemsdijk, W. H., Koopal, L. K., Kinniburgh, D. G., Gooddy, D. C., & Milne, C. J. (1996). Metal ion binding by natural organic matter: From the model to the field. Geochimica et Cosmochimica Acta, 60(14), 2503-2513. doi:10.1016/0016-7037(96)00113-5Binkley, D., Ice, G. G., Kaye, J., & Williams, C. A. (2004). NITROGEN AND PHOSPHORUS CONCENTRATIONS IN FOREST STREAMS OF THE UNITED STATES. Journal of the American Water Resources Association, 40(5), 1277-1291. doi:10.1111/j.1752-1688.2004.tb01586.xBishop, K., Buffam, I., Erlandsson, M., Fölster, J., Laudon, H., Seibert, J., & Temnerud, J. (2008). Aqua Incognita: the unknown headwaters. Hydrological Processes, 22(8), 1239-1242. doi:10.1002/hyp.7049Bol, R., Julich, D., Brödlin, D., Siemens, J., Kaiser, K., Dippold, M. A., … Hagedorn, F. (2016). Dissolved and colloidal phosphorus fluxes in forest ecosystems-an almost blind spot in ecosystem research. Journal of Plant Nutrition and Soil Science, 179(4), 425-438. doi:10.1002/jpln.201600079Buffle, J., & Leppard, G. G. (1995). Characterization of Aquatic Colloids and Macromolecules. 2. Key Role of Physical Structures on Analytical Results. Environmental Science & Technology, 29(9), 2176-2184. doi:10.1021/es00009a005Celi, L., & Barberis, E. (s. f.). Abiotic stabilization of organic phosphorus in the environment. Organic phosphorus in the environment, 113-132. doi:10.1079/9780851998220.0113Dahlqvist, R., Benedetti, M. F., Andersson, K., Turner, D., Larsson, T., Stolpe, B., & Ingri, J. (2004). Association of calcium with colloidal particles and speciation of calcium in the Kalix and Amazon rivers. Geochimica et Cosmochimica Acta, 68(20), 4059-4075. doi:10.1016/j.gca.2004.04.007Darch, T., Blackwell, M. S. A., Hawkins, J. M. B., Haygarth, P. M., & Chadwick, D. (2014). A Meta-Analysis of Organic and Inorganic Phosphorus in Organic Fertilizers, Soils, and Water: Implications for Water Quality. Critical Reviews in Environmental Science and Technology, 44(19), 2172-2202. doi:10.1080/10643389.2013.790752Dynesius, M., & Nilsson, C. (1994). Fragmentation and Flow Regulation of River Systems in the Northern Third of the World. Science, 266(5186), 753-762. doi:10.1126/science.266.5186.753Erickson, H. P. (2009). Size and Shape of Protein Molecules at the Nanometer Level Determined by Sedimentation, Gel Filtration, and Electron Microscopy. Biological Procedures Online, 11(1), 32-51. doi:10.1007/s12575-009-9008-xEspinosa, M., Turner, B. L., & Haygarth, P. M. (1999). Preconcentration and Separation of Trace Phosphorus Compounds in Soil Leachate. Journal of Environmental Quality, 28(5), 1497-1504. doi:10.2134/jeq1999.00472425002800050015xFernández-Martínez, M., Vicca, S., Janssens, I. A., Sardans, J., Luyssaert, S., Campioli, M., … Peñuelas, J. (2014). Nutrient availability as the key regulator of global forest carbon balance. Nature Climate Change, 4(6), 471-476. doi:10.1038/nclimate2177Giddings, J., Yang, F., & Myers, M. (1976). Flow-field-flow fractionation: a versatile new separation method. Science, 193(4259), 1244-1245. doi:10.1126/science.959835Gimbert, L. J., Andrew, K. N., Haygarth, P. M., & Worsfold, P. J. (2003). Environmental applications of flow field-flow fractionation (FIFFF). TrAC Trends in Analytical Chemistry, 22(9), 615-633. doi:10.1016/s0165-9936(03)01103-8Gottselig, N., Bol, R., Nischwitz, V., Vereecken, H., Amelung, W., & Klumpp, E. (2014). Distribution of Phosphorus-Containing Fine Colloids and Nanoparticles in Stream Water of a Forest Catchment. Vadose Zone Journal, 13(7), vzj2014.01.0005. doi:10.2136/vzj2014.01.0005Gottselig, N., Nischwitz, V., Meyn, T., Amelung, W., Bol, R., Halle, C., … Klumpp, E. (2017). Phosphorus Binding to Nanoparticles and Colloids in Forest Stream Waters. Vadose Zone Journal, 16(3), vzj2016.07.0064. doi:10.2136/vzj2016.07.0064Hagedorn , A. G. 2006 EG-Sicherheitsdatenblatt (Gemäß 2001/58/EG)Hart, B. T., Douglas, G. B., Beckett, R., Van Put, A., & Van Grieken, R. E. (1993). Characterization of colloidal and particulate matter transported by the magela creek system, Northern Australia. Hydrological Processes, 7(1), 105-118. doi:10.1002/hyp.3360070111Hassellöv, M., Lyvén, B., Haraldsson, C., & Sirinawin, W. (1999). Determination of Continuous Size and Trace Element Distribution of Colloidal Material in Natural Water by On-Line Coupling of Flow Field-Flow Fractionation with ICPMS. Analytical Chemistry, 71(16), 3497-3502. doi:10.1021/ac981455yHassellov, M., & von der Kammer, F. (2008). Iron Oxides as Geochemical Nanovectors for Metal Transport in Soil-River Systems. Elements, 4(6), 401-406. doi:10.2113/gselements.4.6.401Hens, M., & Merckx, R. (2001). Functional Characterization of Colloidal Phosphorus Species in the Soil Solution of Sandy Soils. Environmental Science & Technology, 35(3), 493-500. doi:10.1021/es0013576Hill, D. M., & Aplin, A. C. (2001). Role of colloids and fine particles in the transport of metals in rivers draining carbonate and silicate terrains. Limnology and Oceanography, 46(2), 331-344. doi:10.4319/lo.2001.46.2.0331Jarvie, H. P., Neal, C., Rowland, A. P., Neal, M., Morris, P. N., Lead, J. R., … Hockenhull, K. (2012). Role of riverine colloids in macronutrient and metal partitioning and transport, along an upland–lowland land-use continuum, under low-flow conditions. Science of The Total Environment, 434, 171-185. doi:10.1016/j.scitotenv.2011.11.061Jiang, X., Bol, R., Nischwitz, V., Siebers, N., Willbold, S., Vereecken, H., … Klumpp, E. (2015). Phosphorus Containing Water Dispersible Nanoparticles in Arable Soil. Journal of Environmental Quality, 44(6), 1772-1781. doi:10.2134/jeq2015.02.0085Kögel-Knabner, I., & Amelung, W. (2014). Dynamics, Chemistry, and Preservation of Organic Matter in Soils. Treatise on Geochemistry, 157-215. doi:10.1016/b978-0-08-095975-7.01012-3Krám, P., Hruška, J., & Shanley, J. B. (2012). Streamwater chemistry in three contrasting monolithologic Czech catchments. Applied Geochemistry, 27(9), 1854-1863. doi:10.1016/j.apgeochem.2012.02.020Lyvén, B., Hassellöv, M., Turner, D. R., Haraldsson, C., & Andersson, K. (2003). Competition between iron- and carbon-based colloidal carriers for trace metals in a freshwater assessed using flow field-flow fractionation coupled to ICPMS. Geochimica et Cosmochimica Acta, 67(20), 3791-3802. doi:10.1016/s0016-7037(03)00087-5Marschner, B., & Kalbitz, K. (2003). Controls of bioavailability and biodegradability of dissolved organic matter in soils. Geoderma, 113(3-4), 211-235. doi:10.1016/s0016-7061(02)00362-2Martin, J.-M., Dai, M.-H., & Cauwet, G. (1995). Significance of colloids in the biogeochemical cycling of organic carbon and trace metals in the Venice Lagoon (Italy). Limnology and Oceanography, 40(1), 119-131. doi:10.4319/lo.1995.40.1.0119Mattsson, T., Kortelainen, P., Laubel, A., Evans, D., Pujo-Pay, M., Räike, A., & Conan, P. (2009). Export of dissolved organic matter in relation to land use along a European climatic gradient. Science of The Total Environment, 407(6), 1967-1976. doi:10.1016/j.scitotenv.2008.11.014Missong, A., Bol, R., Willbold, S., Siemens, J., & Klumpp, E. (2016). Phosphorus forms in forest soil colloids as revealed by liquid-state31P-NMR. Journal of Plant Nutrition and Soil Science, 179(2), 159-167. doi:10.1002/jpln.201500119Montalvo, D., Degryse, F., & McLaughlin, M. J. (2015). Natural Colloidal P and Its Contribution to Plant P Uptake. Environmental Science & Technology, 49(6), 3427-3434. doi:10.1021/es504643fNeubauer, E., Köhler, S. J., von der Kammer, F., Laudon, H., & Hofmann, T. (2013). Effect of pH and Stream Order on Iron and Arsenic Speciation in Boreal Catchments. Environmental Science & Technology, 47(13), 7120-7128. doi:10.1021/es401193jNeubauer, E., v.d. Kammer, F., & Hofmann, T. (2011). Influence of carrier solution ionic strength and injected sample load on retention and recovery of natural nanoparticles using Flow Field-Flow Fractionation. Journal of Chromatography A, 1218(38), 6763-6773. doi:10.1016/j.chroma.2011.07.010Nischwitz, V., & Goenaga-Infante, H. (2012). Improved sample preparation and quality control for the characterisation of titanium dioxide nanoparticles in sunscreens using flow field flow fractionation on-line with inductively coupled plasma mass spectrometry. Journal of Analytical Atomic Spectrometry, 27(7), 1084. doi:10.1039/c2ja10387gRan, Y., Fu, J. ., Sheng, G. ., Beckett, R., & Hart, B. . (2000). Fractionation and composition of colloidal and suspended particulate materials in rivers. Chemosphere, 41(1-2), 33-43. doi:10.1016/s0045-6535(99)00387-2Regelink, I. C., Koopmans, G. F., van der Salm, C., Weng, L., & van Riemsdijk, W. H. (2013). Characterization of Colloidal Phosphorus Species in Drainage Waters from a Clay Soil Using Asymmetric Flow Field-Flow Fractionation. Journal of Environmental Quality, 42(2), 464-473. doi:10.2134/jeq2012.0322Regelink, I. C., Voegelin, A., Weng, L., Koopmans, G. F., & Comans, R. N. J. (2014). Characterization of Colloidal Fe from Soils Using Field-Flow Fractionation and Fe K-Edge X-ray Absorption Spectroscopy. Environmental Science & Technology, 48(8), 4307-4316. doi:10.1021/es405330xRegelink, I. C., Weng, L., & van Riemsdijk, W. H. (2011). The contribution of organic and mineral colloidal nanoparticles to element transport in a podzol soil. Applied Geochemistry, 26, S241-S244. doi:10.1016/j.apgeochem.2011.03.114RICHARDSON, C. J. (1985). Mechanisms Controlling Phosphorus Retention Capacity in Freshwater Wetlands. Science, 228(4706), 1424-1427. doi:10.1126/science.228.4706.1424Roth , C. 2011 Sicherheitsdatenblatt Gemäß Verordnung (EG) Nr. 1907/2006 RepSchmitt, D., Taylor, H. E., Aiken, G. R., Roth, D. A., & Frimmel, F. H. (2002). Influence of Natural Organic Matter on the Adsorption of Metal Ions onto Clay Minerals. Environmental Science & Technology, 36(13), 2932-2938. doi:10.1021/es010271pSix, J., Elliott, E. T., & Paustian, K. (1999). Aggregate and Soil Organic Matter Dynamics under Conventional and No-Tillage Systems. Soil Science Society of America Journal, 63(5), 1350-1358. doi:10.2136/sssaj1999.6351350xStolpe, B., Guo, L., Shiller, A. M., & Hassellöv, M. (2010). Size and composition of colloidal organic matter and trace elements in the Mississippi River, Pearl River and the northern Gulf of Mexico, as characterized by flow field-flow fractionation. Marine Chemistry, 118(3-4), 119-128. doi:10.1016/j.marchem.2009.11.007Tipping, E., & Hurley, M. . (1992). A unifying model of cation binding by humic substances. Geochimica et Cosmochimica Acta, 56(10), 3627-3641. doi:10.1016/0016-7037(92)90158-fTombácz, E., Libor, Z., Illés, E., Majzik, A., & Klumpp, E. (2004). The role of reactive surface sites and complexation by humic acids in the interaction of clay mineral and iron oxide particles. Organic Geochemistry, 35(3), 257-267. doi:10.1016/j.orggeochem.2003.11.002Trostle, K. D., Ray Runyon, J., Pohlmann, M. A., Redfield, S. E., Pelletier, J., McIntosh, J., & Chorover, J. (2016). Colloids and organic matter complexation control trace metal concentration-discharge relationships in Marshall Gulch stream waters. Water Resources Research, 52(10), 7931-7944. doi:10.1002/2016wr019072U.S. Department of Agriculture 1993 Soil survey manual, chapter 3. Selected chemical propertiesVitousek, P. (1982). Nutrient Cycling and Nutrient Use Efficiency. The American Naturalist, 119(4), 553-572. doi:10.1086/283931Wells, M. L., & Goldberg, E. D. (1991). Occurrence of small colloids in sea water. Nature, 353(6342), 342-344. doi:10.1038/353342a0Wen, L.-S., Santschi, P., Gill, G., & Paternostro, C. (1999). Estuarine trace metal distributions in Galveston Bay: importance of colloidal forms in the speciation of the dissolved phase. Marine Chemistry, 63(3-4), 185-212. doi:10.1016/s0304-4203(98)00062-0Zirkler, D., Lang, F., & Kaupenjohann, M. (2012). «Lost in filtration»—The separation of soil colloids from larger particles. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 399, 35-40. doi:10.1016/j.colsurfa.2012.02.02

Long-range DNA looping and gene expression analyses identify DEXI as an autoimmune disease candidate gene

The chromosome 16p13 region has been associated with several autoimmune diseases, including type 1 diabetes (T1D) and multiple sclerosis (MS). CLEC16A has been reported as the most likely candidate gene in the region, since it contains the most disease-associated single-nucleotide polymorphisms (SNPs), as well as an imunoreceptor tyrosine-based activation motif. However, here we report that intron 19 of CLEC16A, containing the most autoimmune disease-associated SNPs, appears to behave as a regulatory sequence, affecting the expression of a neighbouring gene, DEXI. The CLEC16A alleles that are protective from T1D and MS are associated with increased expression of DEXI, and no other genes in the region, in two independent monocyte gene expression data sets. Critically, using chromosome conformation capture (3C), we identified physical proximity between the DEXI promoter region and intron 19 of CLEC16A, separated by a loop of >150 kb. In reciprocal experiments, a 20 kb fragment of intron 19 of CLEC16A, containing SNPs associated with T1D and MS, as well as with DEXI expression, interacted with the promotor region of DEXI but not with candidate DNA fragments containing other potential causal genes in the region, including CLEC16A. Intron 19 of CLEC16A is highly enriched for transcription-factor-binding events and markers associated with enhancer activity. Taken together, these data indicate that although the causal variants in the 16p13 region lie within CLEC16A, DEXI is an unappreciated autoimmune disease candidate gene, and illustrate the power of the 3C approach in progressing from genome-wide association studies results to candidate causal genes