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Background Obesity has become a significant public health problem within China. By observing dietary patterns, an individual’s actual dietary habit of nutrients or foods in combination can be identified. We aimed to examine dietary patterns in relation to the risk of obesity (body mass index (BMI) ≥ 25 kg/m2) and weight change (average weight change per five years) within a Chinese cohort. Methods We analyzed the data from 6,677 adults aged 18–65 years in the China Health and Nutrition Survey 1997–2015. Westernized, traditional Chinese, and high-starch plant-based dietary patterns were identified by principal components analysis. We estimated relative risks (RRs) and least-squares means (LS-means) with 95% confidence intervals (CIs) using the Cox proportional hazards models and the generalized linear models, respectively. Results High adherence to the Westernized dietary pattern was associated with increased risks of obesity and weight gain. Comparing top with bottom quintiles, RR (95% CI) for obesity (BMI ≥ 25 kg/m2) was 1.57 (1.26–1.95; P for trend < 0.001). LS-means of weight change (kg/5 years) were 1.73 (0.98–2.47) and 1.13 (0.39–1.87; P for trend = 0.036) in the top and bottom quintiles, respectively. Increased weight gain among those following the Westernized dietary pattern was stronger in the Southern region than the Northern region. There was a slight hint of an inverse association between the traditional Chinese dietary pattern and obesity. We did not find any significant association for the high-starch plant-based dietary pattern. Conclusions The Westernized dietary pattern increased the risk of obesity among Chinese adults. Weight gain associated with Western dietary pattern was more pronounced in the Southern region than in the Northern region. Our study will provide helpful data in developing dietary guidelines for the prevention of obesity specific to different regions in China.

Lobeglitazone (Lobe) is a novel thiazolidinedione antidiabetic drug that reduces insulin resistance by activating peroxisome proliferator-activated receptor-gamma (PPARγ). However, the exact mechanisms of antidiabetic effects of Lobe have not been established in an animal model. The aim of this study was to evaluate the hypoglycemic effects of Lobe and investigate possible factors involved in Lobe-enhanced hepatic steatosis in high-fat diet (HFD)-fed mice. Mice were fed an HFD for 15 weeks. Lobe was administrated orally during the last 9 weeks. Lobe treatment significantly reduced insulin resistance and increased expression of hepatic glucose transporter 4 (GLUT4) and PPARs in HFD-fed mice. However, increased body weight and hepatic steatosis were not reduced by Lobe in these mice. Metabolomics fingerprinting showed that several lipogenesis-related hepatic and serum metabolites in HFD-fed mice had positive or negative correlations with Lobe administration. In particular, increased leptin levels during HFD were further increased by Lobe. HFD-induced signaling transducer and activator of transcription 3 (STAT3) phosphorylation in the hypothalamus was increased by Lobe. In addition, immunohistochemical analysis showed more proopiomelanocortin (POMC)-positive neurons in the hypothalamus of HFD-fed mice (with or without Lobe) compared with normal diet-fed mice. Despite improving leptin signaling in the hypothalamus and enhancing insulin sensitivity in HFD-fed mice, Lobe increased body weight and steatosis. Further research is necessary regarding other factors affecting Lobe-enhanced hepatic steatosis and hyperphagia.

Background Dietary diversity—eating a more varied diet, may be one of the important components of a healthy diet. We aimed to examine whether dietary diversity score was associated with lower prevalence of obesity. Methods This is a cross-sectional study of 402 married immigrant participants enrolled in the Filipino Women’s diet and health study (FiLWHEL). Dietary information was obtained using the 24-hour recall method. Anthropometric measurements including height, weight, and waist circumference were directly measured. Dietary diversity score was calculated by summing up the reported number of food groups and additional scores for diversity within food groups were derived. We defined general obesity as body mass index (BMI) of ≥25 kg/m2 and abdominal obesity as waist circumference of ≥80 cm. We calculated odds ratios and 95% confidence intervals using the multivariable logistic regression accounting for several potential confounders. Results Dietary diversity score was inversely associated with abdominal and general obesity; odds ratios (95% confidence intervals) were 0.49 (0.30–0.82) (p for trend = 0.009) for abdominal obesity and 0.47 (0.28–0.81) (p for trend = 0.008) for general obesity when we compared the third tertile of diversity scores with the first tertile. In the analyses of diversity within food groups, greater diversity in other vegetables was associated with 49% or 50% lower prevalence of abdominal or general obesity, respectively. Furthermore, poultry diversity score was associated with 56% lower prevalence of general obesity. Conclusion Our study suggests the evidence that high dietary diversity appears to be related to low prevalence of obesity.

We identified two antimicrobial peptides (AMPs) with similarity to moronecidin in Antarctic fishes. The characteristics of both AMPs were determined using moronecidin as a control. Moronecidin, which was first isolated from hybrid striped bass, is highly salt-resistant, and possesses broad-spectrum activity against various microbes. The moronecidin-like peptide from Notothenia coriiceps exhibited a narrower spectrum of activity and a higher salt sensitivity than moronecidin. The AMP from Parachaenichthys charcoti exhibited similar antimicrobial activity to moronecidin, and similar salt sensitivity. In an experiment to identify toxic effects, both of the moronecidin-like peptides from the Antarctic fishes exhibited lower hemolytic activity than moronecidin. In spite of its low toxicity, the AMP from N. coriiceps is unlikely to be considered as a candidate for antibiotic development, owing to its narrow spectrum of activity and high salt sensitivity. In contrast, the high salt resistance and broad-spectrum activity of the AMP from P. charcoti could be more advantageous for clinical use than moronecidin, since it could kill bacteria under physiological conditions with low toxicity. A further comparison of these two AMPs from Antarctic fishes with other AMPs could help to reduce the toxicity of AMPs for clinical use.

Background No studies have reported the relationship between nonalcoholic fatty liver disease (NAFLD) and concurrent cerebral artery and coronary artery atherosclerosis simultaneously. We aimed at determining whether NAFLD, as assessed by ultrasound, is associated with subclinical cerebro-cardio vascular atherosclerosis (CCVA) by multidetector-row computed tomography (MDCT), and high resolution—magnetic resonance angiography (HR-MRA). This cross-sectional study included men in the general Korean population aged 20–70 years. Results A total of 1,652 men participated in the study (normal, n = 835; mild-to-moderate NAFLD, n = 512; severe NAFLD, n = 305). The risk of subclinical CCVA was positively associated with age (odds ratio [OR] 1.068; 1.054–1.081, p < 0.001), body mass index (OR 1.120; 1.08 0–1.162, p < 0.001), hepatic enzyme levels (OR 1.012; 1.001–1.023, p = 0.027; OR 1.006; 1.001–1.012, p = 0.036), fasting glucose (OR 1.021; 1.015–1.027, p < 0.001), triglycerides (OR 1.002; 1.000–1.003, p = 0.016), hypertension (OR 2.836; 2.268–3.546, p < 0.001), and diabetes (OR 2.911; 2.137–3.964, p < 0.001). Also, high-density lipoprotein cholesterol was inversely associated with subclinical CCVA (OR 0.974; 0.965–0.982, p < 0.001). Compared with normal controls, the OR for subclinical CCVA after full adjustment was 1.46 in the mild-to-moderate NAFLD group (95% confidence interval [CI]: 1.10 to 1.93) and 2.04 in the severe NAFLD group (95% CI: 1.44 to 2.89). Conclusions Our data show that NAFLD is common among Korean men, and NAFLD severity on ultrasonography is associated with subclinical CCVA, as assessed by MDCT, and HR-MRA.

Chalcone isomerase (CHI) is an important enzyme for flavonoid biosynthesis that catalyzes the intramolecular cyclization of chalcones into (S)-flavanones. CHIs have been classified into two types based on their substrate specificity. Type I CHIs use naringenin chalcone as a substrate and are found in most of plants besides legumes, whereas type II CHIs in leguminous plants can also utilize isoliquiritigenin. In this study, we found that the CHI from the Antarctic plant Deschampsia antarctica (DaCHI1) is of type I based on sequence homology but can use type II CHI substrates. To clarify the enzymatic mechanism of DaCHI1 at the molecular level, the crystal structures of unliganded DaCHI1 and isoliquiritigenin-bound DaCHI1 were determined at 2.7 and 2.1 Å resolutions, respectively. The structures revealed that isoliquiritigenin binds to the active site of DaCHI1 and induces conformational changes. Additionally, the activity assay showed that while DaCHI1 exhibits substrate preference for naringenin chalcone, it can also utilize isoliquiritigenin although the catalytic activity was relatively low. Based on these results, we propose that DaCHI1 uses various substrates to produce antioxidant flavonoids as an adaptation to oxidative stresses associated with harsh environmental conditions.

Background Little is known about the epidemiology on human papillomavirus (HPV) infection among HIV-infected men in Korea. The objective of this study was to determine the prevalence, genotype distribution and risk factors associated with anal HPV infection among HIV-infected men in Korea. Methods A single-center cross-sectional study was conducted with HIV-infected men in Korea. Participants completed a detailed sexual behavior risk factor questionnaire. Anal samples were collected for cytology and HPV genotyping. Factors associated with anal HPV infection were assessed using multivariable logistic regression, stratifying by sexual behaviour. Results A total of 201 HIV-infected men were included in the study: 133 were from men who have sex with men (MSM) and 68 from men who have sex with women (MSW). Any anal HPV infection was detected in 82.7% of HIV-infected MSM and in 51.5% of HIV- infected MSW (P < 0.001). High-risk HPV (HR-HPV) prevalence was higher among MSM (47.4%) than MSW (25.0%; P = 0.002). The HR-HPV types identified most frequently were HPV 16 (11%), HPV 18 (9.9%), and HPV 58 (5%) in MSM, and HPV 58(11%) and HPV 16 (8.9%) in MSW. Prevalence of any HPV types in 9-valent vaccine types was higher among MSM than MSW (47.4% vs 22.1%. P = 0.001). Abnormal anal cytology was more commonly detected in MSM than MSW (42.9% vs.19.1%, P < 0.001). In HIV-infected MSM, higher number of lifetime male sex partners was significantly associated with any anal HPV infection, but age was a significant risk factor associated with anal HR-HPV infection. Conclusion Anal HPV infection was highly prevalent in HIV-infected MSM in Korea, and also commonly found in HIV-infected MSW. In HIV-infected MSM, the significant risk factor for being infected with any HPV infection was lifetime number of male sexual partners, and with anal oncogenic HPV infection was age.

Background Due to the alarming increase in the incidence of thyroid cancer worldwide, more patients are receiving postoperative radioactive iodine (RAI) therapy and these patients are given a low-iodine diet along with levothyroxine withdrawal to induce a hypothyroid state to maximize the uptake of RAI by thyroid tissues. Recently, the reported cases of patients suffering from life-threatening severe hyponatremia following postoperative RAI therapy have increased. This study aimed to systematically assess risk factors for developing hyponatremia following RAI therapy in post-thyroidectomy patients. Methods We reviewed the medical records of all thyroid cancer patients who underwent thyroidectomy and postoperative RAI therapy from July 2009 to February 2012. Demographic and biochemical parameters including serum sodium and thyroid function tests were assessed along with medication history. Results A total of 2229 patients (47.0±11.0 years, female 76.3%) were enrolled in the analysis. Three hundred seven patients (13.8%) of all patients developed hyponatremia; 44 patients (2.0%) developed moderate to severe hyponatremia (serum Na+≤130 mEq/L) and another 263 (11.8%) patients showed mild hyponatremia (130 mEq/L

BACKGROUND: Prospective investigation of obesity and renal function decline in Asia is sparse. We examined the associations of body mass index (BMI) and waist circumference (WC) with renal function decline in a prospective study of Korean population. METHODS: A total of 454 participants who had baseline estimated glomerular filtration rate (eGFR) levels of more than 60 mL/min/1.73 m(2) in Hallym Aging Study (HAS) were included and followed for 6 years. Renal function decline was defined as follows: (1) an eGFR decline ≥3 mL/min/1.73 m(2)/year (n = 82 cases); (2) an eGFR decrease of 20% or greater (n = 87 cases) at follow-up; (3) an eGFR decrease of 20% greater at follow-up or eGFR decline ≥3 mL/min/1.73 m(2)/year (n = 91 cases); and (4) an eGFR 95 cm in men or >90 cm in women with ≤90 cm in men or ≤85 cm in women, ORs (95% CIs) ranged from 2.31 (1.14-4.69) to 2.78 (1.19-6.50) for the 4 definitions of renal function decline (all p-values for trend

Central nervous system (CNS) inflammatory demyelinating diseases (IDDs) are a group of disorders with different aetiologies, characterized by inflammatory lesions. These disorders include multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and idiopathic transverse myelitis (ITM). Differential diagnosis of the CNS IDDs still remains challenging due to frequent overlap of clinical and radiological manifestation, leading to increased demands for new biomarker discovery. Since cerebrospinal fluid (CSF) metabolites may reflect the status of CNS tissues and provide an interfacial linkage between blood and CNS tissues, we explored multi-component biomarker for different IDDs from CSF samples using gas chromatography mass spectrometry-based metabolite profiling coupled to multiplex bioinformatics approach. We successfully constructed the single model with multiple metabolite variables in coordinated regression with clinical characteristics, expanded disability status scale, oligoclonal bands, and protein levels. The multi-composite biomarker simultaneously discriminated four different immune statuses (a total of 145 samples; 54 MS, 49 NMOSD, 30 ITM, and 12 normal controls). Furthermore, systematic characterization of transitional metabolic modulation identified relapse-associated metabolites and proposed insights into the disease network underlying type-specific metabolic dysfunctionality. The comparative analysis revealed the lipids, 1-monopalmitin and 1-monostearin were common indicative for MS, NMOSD, and ITM whereas fatty acids were specific for the relapse identified in all types of IDDs.

Controlling bioaerosols has become more important with increasing participation in indoor activities. Treatments using natural-product nanomaterials are a promising technique because of their relatively low toxicity compared to inorganic nanomaterials such as silver nanoparticles or carbon nanotubes. In this study, antimicrobial filters were fabricated from natural Euscaphis japonica nanoparticles, which were produced by nebulizing E. japonica extract. The coated filters were assessed in terms of pressure drop, antimicrobial activity, filtration efficiency, major chemical components, and cytotoxicity. Pressure drop and antimicrobial activity increased as a function of nanoparticle deposition time (590, 855, and 1150 µg/cm2(filter) at 3-, 6-, and 9-min depositions, respectively). In filter tests, the antimicrobial efficacy was greater against Staphylococcus epidermidis than Micrococcus luteus; ~61, ~73, and ~82% of M. luteus cells were inactivated on filters that had been coated for 3, 6, and 9 min, respectively, while the corresponding values were ~78, ~88, and ~94% with S. epidermidis. Although statistically significant differences in filtration performance were not observed between samples as a function of deposition time, the average filtration efficacy was slightly higher for S. epidermidis aerosols (~97%) than for M. luteus aerosols (~95%). High-performance liquid chromatography (HPLC) and electrospray ionization-tandem mass spectrometry (ESI/MS) analyses confirmed that the major chemical compounds in the E. japonica extract were 1(ß)-O-galloyl pedunculagin, quercetin-3-O-glucuronide, and kaempferol-3-O-glucoside. In vitro cytotoxicity and disk diffusion tests showed that E. japonica nanoparticles were less toxic and exhibited stronger antimicrobial activity toward some bacterial strains than a reference soluble nickel compound, which is classified as a human carcinogen. This study provides valuable information for the development of a bioaerosol control system that is environmental friendly and suitable for use in indoor environments.

Wei Zheng and colleagues quantify the burden of tobacco-smoking-related deaths for adults in Asia. Please see later in the article for the Editors' Summary, Background Tobacco smoking is a major risk factor for many diseases. We sought to quantify the burden of tobacco-smoking-related deaths in Asia, in parts of which men's smoking prevalence is among the world's highest. Methods and Findings We performed pooled analyses of data from 1,049,929 participants in 21 cohorts in Asia to quantify the risks of total and cause-specific mortality associated with tobacco smoking using adjusted hazard ratios and their 95% confidence intervals. We then estimated smoking-related deaths among adults aged ≥45 y in 2004 in Bangladesh, India, mainland China, Japan, Republic of Korea, Singapore, and Taiwan—accounting for ∼71% of Asia's total population. An approximately 1.44-fold (95% CI = 1.37–1.51) and 1.48-fold (1.38–1.58) elevated risk of death from any cause was found in male and female ever-smokers, respectively. In 2004, active tobacco smoking accounted for approximately 15.8% (95% CI = 14.3%–17.2%) and 3.3% (2.6%–4.0%) of deaths, respectively, in men and women aged ≥45 y in the seven countries/regions combined, with a total number of estimated deaths of ∼1,575,500 (95% CI = 1,398,000–1,744,700). Among men, approximately 11.4%, 30.5%, and 19.8% of deaths due to cardiovascular diseases, cancer, and respiratory diseases, respectively, were attributable to tobacco smoking. Corresponding proportions for East Asian women were 3.7%, 4.6%, and 1.7%, respectively. The strongest association with tobacco smoking was found for lung cancer: a 3- to 4-fold elevated risk, accounting for 60.5% and 16.7% of lung cancer deaths, respectively, in Asian men and East Asian women aged ≥45 y. Conclusions Tobacco smoking is associated with a substantially elevated risk of mortality, accounting for approximately 2 million deaths in adults aged ≥45 y throughout Asia in 2004. It is likely that smoking-related deaths in Asia will continue to rise over the next few decades if no effective smoking control programs are implemented. Please see later in the article for the Editors' Summary, Editors' Summary Background Every year, more than 5 million smokers die from tobacco-related diseases. Tobacco smoking is a major risk factor for cardiovascular disease (conditions that affect the heart and the circulation), respiratory disease (conditions that affect breathing), lung cancer, and several other types of cancer. All told, tobacco smoking kills up to half its users. The ongoing global “epidemic” of tobacco smoking and tobacco-related diseases initially affected people living in the US and other Western countries, where the prevalence of smoking (the proportion of the population that smokes) in men began to rise in the early 1900s, peaking in the 1960s. A similar epidemic occurred in women about 40 years later. Smoking-related deaths began to increase in the second half of the 20th century, and by the 1990s, tobacco smoking accounted for a third of all deaths and about half of cancer deaths among men in the US and other Western countries. More recently, increased awareness of the risks of smoking and the introduction of various tobacco control measures has led to a steady decline in tobacco use and in smoking-related diseases in many developed countries. Why Was This Study Done? Unfortunately, less well-developed tobacco control programs, inadequate public awareness of smoking risks, and tobacco company marketing have recently led to sharp increases in the prevalence of smoking in many low- and middle-income countries, particularly in Asia. More than 50% of men in many Asian countries are now smokers, about twice the prevalence in many Western countries, and more women in some Asian countries are smoking than previously. More than half of the world's billion smokers now live in Asia. However, little is known about the burden of tobacco-related mortality (deaths) in this region. In this study, the researchers quantify the risk of total and cause-specific mortality associated with tobacco use among adults aged 45 years or older by undertaking a pooled statistical analysis of data collected from 21 Asian cohorts (groups) about their smoking history and health. What Did the Researchers Do and Find? For their study, the researchers used data from more than 1 million participants enrolled in studies undertaken in Bangladesh, India, mainland China, Japan, the Republic of Korea, Singapore, and Taiwan (which together account for 71% of Asia's total population). Smoking prevalences among male and female participants were 65.1% and 7.1%, respectively. Compared with never-smokers, ever-smokers had a higher risk of death from any cause in pooled analyses of all the cohorts (adjusted hazard ratios [HRs] of 1.44 and 1.48 for men and women, respectively; an adjusted HR indicates how often an event occurs in one group compared to another group after adjustment for other characteristics that affect an individual's risk of the event). Compared with never smoking, ever smoking was associated with a higher risk of death due to cardiovascular disease, cancer (particularly lung cancer), and respiratory disease among Asian men and among East Asian women. Moreover, the researchers estimate that, in the countries included in this study, tobacco smoking accounted for 15.8% of all deaths among men and 3.3% of deaths among women in 2004—a total of about 1.5 million deaths, which scales up to 2 million deaths for the population of the whole of Asia. Notably, in 2004, tobacco smoking accounted for 60.5% of lung-cancer deaths among Asian men and 16.7% of lung-cancer deaths among East Asian women. What Do These Findings Mean? These findings provide strong evidence that tobacco smoking is associated with a substantially raised risk of death among adults aged 45 years or older throughout Asia. The association between smoking and mortality risk in Asia reported here is weaker than that previously reported for Western countries, possibly because widespread tobacco smoking started several decades later in most Asian countries than in Europe and North America and the deleterious effects of smoking take some years to become evident. The researchers note that certain limitations of their analysis are likely to affect the accuracy of its findings. For example, because no data were available to estimate the impact of secondhand smoke, the estimate of deaths attributable to smoking is likely to be an underestimate. However, the finding that nearly 45% of the global deaths from active tobacco smoking occur in Asia highlights the urgent need to implement comprehensive tobacco control programs in Asia to reduce the burden of tobacco-related disease. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001631. The World Health Organization provides information about the dangers of tobacco (in several languages) and about the WHO Framework Convention on Tobacco Control, an international instrument for tobacco control that came into force in February 2005 and requires parties to implement a set of core tobacco control provisions including legislation to ban tobacco advertising and to increase tobacco taxes; its 2013 report on the global tobacco epidemic is available The US Centers for Disease Control and Prevention provides detailed information about all aspects of smoking and tobacco use The UK National Health Services Choices website provides information about the health risks associated with smoking MedlinePlus has links to further information about the dangers of smoking (in English and Spanish) SmokeFree, a website provided by the UK National Health Service, offers advice on quitting smoking and includes personal stories from people who have stopped smoking Smokefree.gov, from the US National Cancer Institute, offers online tools and resources to help people quit smoking

Introduction Recent studies demonstrated that circulating fibroblast growth factor (FGF)-23 was associated with risk of end stage renal disease (ESRD) and mortality. This study aims to examine whether the predictive effect of FGF-23 is independent from circulating levels of tumor necrosis factor receptor 1 (TNFR1), a strong predictor of ESRD in Type 2 diabetes (T2D). Methods We studied 380 patients with T2D who were followed for 8–12 years and were used previously to examine the effect of TNFR1. Baseline plasma FGF-23 was measured by immunoassay. Results During follow-up, 48 patients (13%) developed ESRD and 83 patients (22%) died without ESRD. In a univariate analysis, baseline circulating levels of FGF-23 and TNFR1 were significantly higher in subjects who subsequently developed ESRD or died without ESRD than in those who remained alive. In a Cox proportional hazard model, baseline concentration of FGF-23 was associated with increased risk of ESRD, however its effect was no longer significant after controlling for TNFR1 and other clinical characteristics (HR 1.3, p = 0.15). The strong effect of circulating level of TNFR1 on risk of ESRD was not changed by including circulating levels of FGF-23 (HR 8.7, p

EMBRYONIC FLOWER1 (EMF1) is a plant-specific gene crucial to Arabidopsis vegetative development. Loss of function mutants in the EMF1 gene mimic the phenotype caused by mutations in Polycomb Group protein (PcG) genes, which encode epigenetic repressors that regulate many aspects of eukaryotic development. In Arabidopsis, Polycomb Repressor Complex 2 (PRC2), made of PcG proteins, catalyzes trimethylation of lysine 27 on histone H3 (H3K27me3) and PRC1-like proteins catalyze H2AK119 ubiquitination. Despite functional similarity to PcG proteins, EMF1 lacks sequence homology with known PcG proteins; thus, its role in the PcG mechanism is unclear. To study the EMF1 functions and its mechanism of action, we performed genome-wide mapping of EMF1 binding and H3K27me3 modification sites in Arabidopsis seedlings. The EMF1 binding pattern is similar to that of H3K27me3 modification on the chromosomal and genic level. ChIPOTLe peak finding and clustering analyses both show that the highly trimethylated genes also have high enrichment levels of EMF1 binding, termed EMF1_K27 genes. EMF1 interacts with regulatory genes, which are silenced to allow vegetative growth, and with genes specifying cell fates during growth and differentiation. H3K27me3 marks not only these genes but also some genes that are involved in endosperm development and maternal effects. Transcriptome analysis, coupled with the H3K27me3 pattern, of EMF1_K27 genes in emf1 and PRC2 mutants showed that EMF1 represses gene activities via diverse mechanisms and plays a novel role in the PcG mechanism., Author Summary Polycomb group (PcG) proteins are epigenetic repressors maintaining developmental states in eukaryotic organisms. Plant PcG proteins are expected to be general epigenetic repressors; however, their overall impact on growth and differentiation and their mechanism of repression are still unclear. Here we identified several thousand target genes of the EMBRYONIC FLOWER 1 (EMF1) protein, which shares no sequence homology with known PcG proteins. EMF1 regulates developmental phase transitions as well as specifies cell fates during vegetative development. Trimethylation of histone 3 lysine 27 (H3K27me3) and ubiqutination of lysine 119 of histone H2A are carried out by different PcG protein complexes. EMF1 is required for both histone modifications on genes specifying stem cell fate in plants, thus revealing a novel role of EMF1 in linking the PcG protein complexes. Our results have important implications for the evolution of PcG regulatory mechanisms.

Lipopolysaccharide (LPS), the Gram-negative bacterial outer membrane glycolipid, induces sepsis through its interaction with myeloid differentiation protein-2 (MD-2) and Toll-like receptor 4 (TLR4). To block interaction between LPS/MD-2 complex and TLR4, we designed and generated soluble fusion proteins capable of binding MD-2, dubbed TLR4 decoy receptor (TOY) using 'the Hybrid leucine-rich repeats (LRR) technique'. TOY contains the MD-2 binding ectodomain of TLR4, the LRR motif of hagfish variable lymphocyte receptor (VLR), and the Fc domain of IgG1 to make it soluble, productive, and functional. TOY exhibited strong binding to MD-2, but not to the extracellular matrix (ECM), resulting in a favorable pharmacokinetic profile in vivo. TOY significantly extended the lifespan, when administered in either preventive or therapeutic manners, in both the LPS- and cecal ligation/puncture-induced sepsis models in mice. TOY markedly attenuated LPS-triggered NF-kappaB activation, secretion of proinflammatory cytokines, and thrombus formation in multiple organs. Taken together, the targeting strategy for sequestration of LPS/MD-2 complex using the decoy receptor TOY is effective in treating LPS- and bacteria-induced sepsis; furthermore, the strategy used in TOY development can be applied to the generation of other novel decoy receptor proteins.