Ulcerative colitis and Crohn's disease are the two main forms of inflammatory bowel disease (IBD). Here we report the first trans-ancestry association study of IBD, with genome-wide or Immunochip genotype data from an extended cohort of 86,640 European individuals and Immunochip data from 9,846 individuals of East Asian, Indian or Iranian descent. We implicate 38 loci in IBD risk for the first time. For the majority of the IBD risk loci, the direction and magnitude of effect are consistent in European and non-European cohorts. Nevertheless, we observe genetic heterogeneity between divergent populations at several established risk loci driven by differences in allele frequency (NOD2) or effect size (TNFSF15 and ATG16L1) or a combination of these factors (IL23R and IRGM). Our results provide biological insights into the pathogenesis of IBD and demonstrate the usefulness of trans-ancestry association studies for mapping loci associated with complex diseases and understanding genetic architecture across diverse populations.

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Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations

Drought alone causes more annual loss in crop yield than all pathogens combined. To adapt to moisture gradients in soil, plants alter their physiology, modify root growth and architecture, and close stomata on their aboveground segments. These tissue-specific responses modify the flux of cellular signals, resulting in early flowering or stunted growth and, often, reduced yield. Physiological and molecular analyses of the model plant Arabidopsis thaliana have identified phytohormone signaling as key for regulating the response to drought or water insufficiency. Here we discuss how engineering hormone signaling in specific cells and cellular domains can facilitate improved plant responses to drought. We explore current knowledge and future questions central to the quest to produce high-yield, drought-resistant crops.

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The physiology of plant responses to drought

To gain further insight into the genetic architecture of psoriasis, we conducted a meta-analysis of 3 genome-wide association studies (GWAS) and 2 independent data sets genotyped on the Immunochip, including 10,588 cases and 22,806 controls. We identified 15 new susceptibility loci, increasing to 36 the number associated with psoriasis in European individuals. We also identified, using conditional analyses, five independent signals within previously known loci. The newly identified loci shared with other autoimmune diseases include candidate genes with roles in regulating T-cell function (such as RUNX3, TAGAP and STAT3). Notably, they included candidate genes whose products are involved in innate host defense, including interferon-mediated antiviral responses (DDX58), macrophage activation (ZC3H12C) and nuclear factor (NF)-κB signaling (CARD14 and CARM1). These results portend a better understanding of shared and distinctive genetic determinants of immune-mediated inflammatory disorders and emphasize the importance of the skin in innate and acquired host defense. © 2012 Nature America, Inc. All rights reserved.

Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity

Brassinosteroids (BRs) are a group of polyhydroxylated plant steroid hormones crucial for many aspects of plant life. BRs were originally characterized for their function in cell elongation, but it is becoming clear that they play major roles in plant growth, development and responses to several stresses such as temperature and drought. A BR signaling pathway from cell surface receptors to central transcription factors has been well characterized. Here we summarize recent progress towards understanding the BR pathway including BR perception and the molecular mechanisms of BR signaling. Next, we discuss the roles of BRs in development and stress responses. Finally, we show how knowledge of the BR pathway is being applied to manipulate the growth and stress responses in crops. These studies highlight the complex regulation of BR signaling, multiple points of crosstalk between BRs and other hormones or stress responses, and finely tuned spatiotemporal regulation of BR signaling.

/pdf/brassinosteroids-multidimensional-regulators-of-plant-growth-4n5b10kmz9.pdf

Brassinosteroids: Multidimensional Regulators of Plant Growth, Development, and Stress Responses.

Plants cannot move, so they must endure abiotic stresses such as drought, salinity and extreme temperatures. These stressors greatly limit the distribution of plants, alter their growth and development, and reduce crop productivity. Recent progress in our understanding of the molecular mechanisms underlying the responses of plants to abiotic stresses emphasizes their multilevel nature; multiple processes are involved, including sensing, signalling, transcription, transcript processing, translation and post-translational protein modifications. This improved knowledge can be used to boost crop productivity and agricultural sustainability through genetic, chemical and microbial approaches.

Abiotic stress responses in plants.

Brassinosteroids (BRs) are steroid hormones that are essential for plant growth and development. These hormones control the division, elongation and differentiation of various cell types throughout the entire plant life cycle. Our current understanding of the BR signaling pathway has mostly been obtained from studies using Arabidopsis thaliana as a model. In this context, the membrane steroid receptor BRI1 (BRASSINOSTEROID INSENSITIVE 1) binds directly to the BR ligand, triggering a signal cascade in the cytoplasm that leads to the transcription of BR-responsive genes that drive cellular growth. However, recent studies of the primary root have revealed distinct BR signaling pathways in different cell types and have highlighted cell-specific roles for BR signaling in controlling adaptation to stress. In this Review, we summarize our current knowledge of the spatiotemporal control of BR action in plant growth and development, focusing on BR functions in primary root development and growth, in stem cell self-renewal and death, and in plant adaption to environmental stress.

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Brassinosteroid signaling in plant development and adaptation to stress.

Glucose (Glc) plays a fundamental role in regulating lateral root (LR) development as well as LR emergence In this study, we show that brassinosteroid (BR) signaling works downstream of Glc in controlling LR production/emergence in Arabidopsis (Arabidopsis thaliana) seedlings Glc and BR can promote LR emergence at lower concentrations, while at higher concentrations, both have an inhibitory effect The BR biosynthesis and perception mutants showed highly reduced numbers of emerged LRs at all the Glc concentrations tested BR signaling works downstream of Glc signaling in regulating LR production, as in the glucose insensitive2-1brassinosteroid insensitive1 double mutant, Glc-induced LR production/emergence was severely reduced Differential auxin distribution via the influx carriers AUXIN RESISTANT1/LIKE AUXIN RESISTANT1-3 and the efflux carrier PIN-FORMED2 plays a central role in controlling LR production in response to Glc and BR Auxin signaling components AUXIN RESISTANT2,3 and SOLITARY ROOT act downstream of Glc and BR AUXIN RESPONSE FACTOR7/19 work farther downstream and control LR production by regulating the expression of LATERAL ORGAN BOUNDARIES-DOMAIN29 and EXPANSIN17 genes Increasing light flux could also mimic the Glc effect on LR production/emergence However, increased light flux could not affect LR production in those BR and auxin signaling mutants that were defective for Glc-induced LR production Altogether, our study suggests that, under natural environmental conditions, modulation of endogenous sugar levels can manipulate root architecture for optimized development by altering its nutrient/water uptake as well as its anchorage capacity

/pdf/interaction-between-glucose-and-brassinosteroid-during-the-i7ilsl29cn.pdf

Interaction between Glucose and Brassinosteroid during the Regulation of Lateral Root Development in Arabidopsis

Objective Over 100 ulcerative colitis (UC) loci have been identified by genome-wide association studies (GWASs) primarily in Caucasians (CEUs). Many of them have weak effects on disease susceptibility, and the bulk of the heritability cannot be ascribed to these loci. Very little is known about the genetic background of UC in non-CEU groups. Here we report the first GWAS on UC in a genetically distinct north Indian (NI) population.

https://gut.bmj.com/content/gutjnl/early/2014/05/16/gutjnl-2013-306625.full.pdf

Genome-wide association scan in north Indians reveals three novel HLA-independent risk loci for ulcerative colitis

Directional growth of roots is a complex process that is modulated by various environmental signals. This work shows that presence of glucose (Glc) in the medium also extensively modulated seedling root growth direction. Glc modulation of root growth direction was dramatically enhanced by simultaneous brassinosteroid (BR) application. Glc enhanced BR receptor BRASSINOSTEROID INSENSITIVE1 (BRI1) endocytosis from plasma membrane to early endosomes. Glc-induced root deviation was highly enhanced in a PP2A-defective mutant, roots curl in naphthyl phthalamic acid 1-1 (rcn1-1) suggesting that there is a role of phosphatase in Glc-induced root-growth deviation. RCN1, therefore, acted as a link between Glc and the BR-signalling pathway. Polar auxin transport worked further downstream to BR in controlling Glc-induced root deviation response. Glc also affected other root directional responses such as root waving and coiling leading to altered root architecture. High light intensity mimicked the Glc-induced changes in root architecture that were highly reduced in Glc-signalling mutants. Thus, under natural environmental conditions, changing light flux in the environment may lead to enhanced Glc production/response and is a way to manipulate root architecture for optimized development via integrating several extrinsic and intrinsic signalling cues.

/pdf/glucose-control-of-root-growth-direction-in-arabidopsis-1p6ur1els6.pdf

Aditi Gupta

Papers

The physiology of plant responses to drought

Brassinosteroid signaling in plant development and adaptation to stress.

Interaction between Glucose and Brassinosteroid during the Regulation of Lateral Root Development in Arabidopsis

Genome-wide association scan in north Indians reveals three novel HLA-independent risk loci for ulcerative colitis

Glucose control of root growth direction in Arabidopsis thaliana