Genetics of ankylosing spondylitis

Ankylosing spondylitis is a common inflammatory rheumatic disease. Both susceptibility to and clinical manifestations of the disease are highly heritable. Although some genes, notably HLA-B27, have been implicated in susceptibility to the disease, the genetics of the condition are complex and many more genes involved in the condition await discovery.

Genetics of ankylosing spondylitis and rheumatoid arthritis: Where are we at currently, and how do they compare?

Both ankylosing spondylitis (AS) and rheumatoid arthritis (RA) are common, highly heritable conditions, the pathogenesis of which are incompletely understood. Gene-mapping studies in both conditions have over the last couple of years made major breakthroughs in identifying the mechanisms by which these diseases occur. Considering RA, there is an over-representation of genes involved in TNF signalling and the NFκB pathway that have been shown to influence the disease risk. There is also considerable sharing of susceptibility genes between RA and other autoimmune diseases such as systemic lupus erythematosus, type 1 diabetes, autoimmune thyroid disease and celiac disease, with thus far little overlap with AS. In AS, genes involved in response to IL12/IL23, and in endoplasmic reticulum peptide presentation, have been identified, but a full genomewide association study has not yet been reported.

The genetics of osteoporosis: Future diagnostic possibilities

The risk of developing osteoporosis is determined by the interaction of several mostly unknown genes and environmental factors. Genetic studies in osteoporosis have largely focussed on association studies of a small number of candidate genes, with few linkage studies performed, and large areas of the genome remaining unexplored. Identifying the genes involved in osteoporosis would be a major advance in our understanding of the causation of the disease, and lead to advances in diagnosis, risk prediction, and potentially preventive and therapeutic measures.

Genetics and the pathogenesis of ankylosing spondylitis

Purpose of review The field of genetic research in ankylosing spondylitis (AS) is advancing rapidly. The purpose of this review is to outline recent findings, particularly, in regard to genetic studies of the major histocompatibility complex (MHC) and the non-MHC genes IL23R, ERAP1, and killer cell immunologlobulin-like receptor (KIR) complex, in AS. Recent findings: Convincing evidence has been reported for the existence of further non-B27 MHC genes involved in AS. Strong, replicated association has been reported with IL23R and ERAP1 and AS. The IL23R finding strongly implicates the TH17 lymphocyte system in AS aetiopathogenesis. Suggestive evidence of a role for KIR gene polymorphism in AS exists, but definitive findings are awaited. Summary: The findings suggest that further genome-wide studies in large case-control cohorts are likely to be very productive in this disease. The IL23R findings and subsequent immunological investigations suggest that targeted intervention in the TH17 system is likely to have major therapeutic benefit, as it does in the genetically related diseases, inflammatory bowel disease and psoriasis.

Genetics of ankylosing spondylitis

Purpose of Review Over the past 3 years, several new genes and gene deserts have been identified that are associated with ankylosing spondylitis (AS). The purpose of this review is to discuss the major findings of these studies, and the answers they provide and questions they raise about the pathogenesis of this common condition. Recent Findings: Five genes/genetic regions have now definitively been associated with AS [the major histocompatibility complex (MHC), IL23R, ERAP1, 2p15 and 21q22]. Strong evidence to support association with the disease has been demonstrated for the genes IL1R2, ANTXR2, TNFSF15, TNFR1 and a region on chromosome 16q including the gene TRADD. There is an overrepresentation of genes involved in Th17 lymphocyte differentiation/activation among genes associated with AS and the related diseases inflammatory bowel disease and psoriasis, pointing strongly to this pathway as playing a major causative role in the disease. Increasing information about differential association of HLA-B27 subtypes with disease suggests a hierarchy of strength of association of those alleles with AS, providing a useful test as to the validity of different potential mechanisms of association of HLA-B27 with AS. The mechanism underlying the association of the gene deserts, 2p15 and 21q22, suggests the involvement of noncoding RNA in AS etiopathogenesis. Summary: The increasing list of genes identified as being definitely involved in AS provides a useful platform for hypothesis-driven research in the field, providing a potential alternative route to determining the underlying mechanisms involved in the disease to research focusing on HLA-B27 alone.

Behavior of simetryn and thiobencarb in the plough zone of rice fields

The behavior of simetryn and thiobencarb in flooded rice soil was investigated in a 2-year study. The concentrations of simetryn and thiobencarb were in the hundreds of μg kg^-1 in the top soil layer (0-5 cm) and became significantly lower in tens of μg kg^-1 in the deeper soil layers (5-10 and 10-15 cm). The half-lives of the two herbicides were also shorter (36 and 17 days for simetryn and thiobencarb, respectively) in the top soil layer, as they were most affected by environmental conditions, compared with corresponding values of 82 and 69 days in the 5-10 cm soil layer. Simetryn concentration was stable, while thiobencarb's half-life was 165 days in the 10-15 cm layer. About 35% of the applied mass of simetryn and thiobencarb were found in the rice soil compartment.

Simulated rainfall removal of tricyclazole sprayed on rice foliage

Two rainfall simulations of 30 mm h^-1, with 48-h interval between two simulations, were performed on rice lysimeters at 24, 48, and 72 h after being sprayed with tricyclazole. In the first simulated rainfall, wash-off concentration of tricyclazole was significant irrespective of the interval between the spray time and the rainfall simulation. And from 20.5% to 24.2% of tricyclazole deposited on leaves was removed from the rice foliage. In the second simulated rainfall, concentration of tricyclazole in wash-off water was significantly lower and less than 3.6% of the deposited tricyclazole was lost. © 2008 Springer Science+Business Media, LLC.

Behavior of sprayed tricyclazole in rice paddy lysimeters

The behavior of sprayed tricyclazole in rice paddy lysimeters was studied. Tricyclazole residues were measured from rice leaves and paddy water after tricyclazole spraying in paddy lysimeters. The rate of photolysis and hydrolysis of tricyclazole on the surface of rice leaves was also determined in a laboratory experiment. Tricyclazole was extracted from leaf and water samples and determined by liquid chromatography with UV or mass spectrometry. The hydrolysis half-lives of tricyclazole on rice leaves were 11.9 and 5.1 d for the formulated product and standard, respectively. The photolysis half-lives were longer, 16.4 d for the formulated product and 20.9 d for the standard. In the paddy lysimeter, tricyclazole dissipation on leaves involved either biphasic first-order kinetics or single-phase first-order kinetics, depending on the rainfall pattern. Half-lives of tricyclazole on lysimeter rice leaves were from 3.0 to 5.7 d. The dissipation of tricyclazole in paddy water followed single-phase first-order kinetics with half-lives ranging from 2.1 to 5.0 d.

Analysis of parameter uncertainty and sensitivity in PCPF-1 modeling for predicting concentrations of rice herbicides

This paper demonstrates the procedures for probabilistic assessment of a pesticide fate and transport model, PCPF-1, to elucidate the modeling uncertainty using the Monte Carlo technique. Sensitivity analyses are performed to investigate the influence of herbicide characteristics and related soil properties on model outputs using four popular rice herbicides: mefenacet, pretilachlor, bensulfuron-methyl and imazosulfuron. Uncertainty quantification showed that the simulated concentrations in paddy water varied more than those of paddy soil. This tendency decreased as the simulation proceeded to a later period but remained important for herbicides having either high solubility or a high 1st-order dissolution rate. The sensitivity analysis indicated that PCPF-1 parameters requiring careful determination are primarily those involve with herbicide adsorption (the organic carbon content, the bulk density and the volumetric saturated water content), secondary parameters related with herbicide mass distribution between paddy water and soil (1st-order desorption and dissolution rates) and lastly, those involving herbicide degradations. © Pesticide Science Society of Japan.

Probabilistic assessment of herbicide runoff from Japanese rice paddies: The effects of local meteorological conditions and site-specific water management

Uncertainty assessments of herbicide losses from rice paddies in Japan associated with local meteorological conditions and water management practices were performed using a pesticide fate and transport model, PCPF-1, under the Monte Carlo (MC) simulation scheme. First, MC simulations were conducted for five different cities with a prescribed water management scenario and a 10-year meteorological dataset of each city. The effectiveness of water management was observed regarding the reduction of pesticide runoff. However, a greater potential of pesticide runoff remained in Western Japan. Secondly, an extended analysis was attempted to evaluate the effects of local water management and meteorological conditions between the Chikugo River basin and the Sakura River basin using uncertainty inputs processed from observed water management data. The results showed that because of more severe rainfall events, significant pesticide runoff occurred in the Chikugo River basin even when appropriate irrigation practices were implemented. © Pesticide Science Society of Japan.

Behavior of pretilachlor and dimethametryn in water of flooded rice fields

In order to understand the behavior of pretilachlor, a popular rice herbicide in the world, and a synergetic active ingredient, dimethametryn, a monitoring study was conducted in 3 paddy plots in Kyushu region, Japan. The monitoring indicated different behaviors for both pesticides from those reported in the literature. Maximum concentrations of pretilachlor and dimethametryn were 1 order of magnitude lower than the values observed in previous studies. However, the dissipation rates estimated from monitoring data were in agreement with other studies in Japan. The pesticide product was tested and showed good dissolution of pretilachlor and dimethametryn in water, suggesting that another study is needed to explain the low concentrations of the two pesticides in the fields. Besides pesticide behaviors, it was observed from the monitoring that water management in paddy rice cultivation still requires more attention to reduce the environmental risk of rice pesticides.

Pesticide exposure assessment in rice paddy areas: A Japanese perspective

This chapter provides an overview of the Japanese regulatory issues regarding pesticide use in rice paddies and an introduction of the new pesticide registration program. In addition, the experience of the environmental monitoring of pesticides and the modeling approaches used for the calculation of predicted environmental concentrations (PECs) in surface water and ground water systems adjacent to rice paddies in Japan are also discussed. Japan has been one of the major pesticide users in the world. Although having a long history in rice cultivation, the pesticide exposure assessment for paddy rice production received less attention compared with EU and US. Applications of up-to-date techniques and the development of realistic assessment procedures under specific climatic conditions as well as mitigation management practices for controlling pesticide contamination are important for an environmental-friendly rice production. Through the international cooperation and research exchanges, advances in pesticide risk assessment for rice paddies in Asian region and other rice-growing areas in the world would contribute to sustainable rice production. Transplanting of rice seedlings grows almost all rice paddies in Japan. The land preparation starts around April and June, and the harvest season lasts from August to October depending on the region and the rice varieties. Most of the rice paddies are treated with herbicides and other crop protection products, such as fungicides and insecticides that are applied during the crop season accordingly. Newly developed insecticides and fungicides are also applied during seedbed preparation.

Behavior of simetryn and thiobencarb in rice paddy lysimeters and the effect of excess water storage depth in controlling herbicide run-off

Eight small-scale lysimeters with different excess water storage depths (EWSDs) were used to investigate the behavior of two herbicides, simetryn and thiobencarb, under paddy conditions. The concentration of simetryn dissipated similarly in all the lysimeters, while the thiobencarb concentration varied significantly because thiobencarb can adsorb onto the dissolved organic matter in a manure slurry, which was applied to six of the lysimeters. The herbicide losses (the percentage of the applied mass) from the lysimeters were reversely proportional with the EWSD. The correlation was stronger for simetryn than for thiobencarb. An appropriate EWSD is required to effectively prevent herbicide run-off from the paddy field, especially when a rainfall event occurs soon after herbicide application.

Modeling approaches for pesticide exposure assessment in rice paddies

Pesticide use in paddy rice production may contribute to adverse ecological effects in surface waters. Risk assessments conducted for regulatory purposes depend on the use of simulation models to determine predicted environment concentrations (PEC) of pesticides. Often tiered approaches are used, in which assessments at lower tiers are based on relatively simple models with conservative scenarios, while those at higher tiers have more realistic representations of physical and biochemical processes. This chapter reviews models commonly used for predicting the environmental fate of pesticides in rice paddies. Theoretical considerations, unique features, and applications are discussed. This review is expected to provide information to guide model selection for pesticide registration, regulation, and mitigation in rice production areas.

Genetics of ankylosing spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory arthritis that affects the spine and sacroiliac joints. It causes significant disability and is associated with a number of other features including peripheral arthritis, anterior uveitis, psoriasis and inflammatory bowel disease (IBD). Significant progress has been made in the genetics of AS have in the last five years, leading to new treatments in trial, and major leaps in understanding of the aetiopathogenesis of the disease.