Tree mycorrhizal associations determine how biodiversity,large trees,and environmental factors drive aboveground carbon stock in temperate forests

Biodiversity,large trees,and environmental conditions such as climate and soil have important effects on forest carbon stocks.However,recent studies in temperate forests suggest that the relative importance of these factors depends on tree mycorrhizal associations,whereby large-tree effects may be driven by ectomycorrhizal(EM)trees,diversity effects may be driven by arbuscular mycorrhizal(AM)trees,and environment effects may depend on differential climate and soil preferences of AM and EM trees.To test this hypothesis,we used forest-inventory data consisting of over 80,000 trees from 631 temperate-forest plots(30 m×30 m)across Northeast China to examine how biodiversity(species diversity and ecological uniqueness),large trees(top 1%of tree diameters),and environmental factors(climate and soil nutrients)differently regulate aboveground carbon stocks of AM trees,EM trees,and AM and EM trees combined(i.e.total aboveground carbon stock).We found that large trees had a positive effect on both AM and EM tree carbon stocks.However,biodiversity and environmental factors had opposite effects on AM vs.EM tree carbon stocks.Specifically,the two components of biodiversity had positive effects on AM tree carbon stocks,but negative effects on EM tree carbon stocks.Environmental heterogeneity(mean annual temperature and soil nutrients)also exhibited contrasting effects on AM and EM tree carbon stocks.Consequently,for the total carbon stock,the positive large-tree effect far surpasses the diversity and environment effect.This is mainly because when integrating AM and EM tree carbon stock into total carbon stock,the opposite diversity-effect(also environment-effect)on AM vs.EM tree carbon stock counteracts each other while the consistent positive large-tree effect on AM and EM tree carbon stock is amplified.In summary,this study emphasized a mycorrhizal viewpoint to better understand the determinants of overarching aboveground carbon profile across regional forests.

Casual associations between blood metabolites and colon cancer

BACKGROUND Limited knowledge exists regarding the casual associations linking blood metabolites and the risk of developing colorectal cancer.AIM To investigate causal associations between blood metabolites and colon cancer.METHODS The study utilized a two-sample Mendelian randomization(MR)analysis to investigate the causal impact of 486 blood metabolites on colorectal cancer.The primary method of analysis used was the inverse variance weighted model.To further validate the results several sensitivity analyses were performed,including Cochran's Q test,MR-Egger intercept test,and MR robust adjusted profile score.These additional analyses were conducted to ensure the reliability and robustness of the findings.RESULTS After rigorous selection for genetic variation,486 blood metabolites were included in the MR analysis.We found Mannose[odds ratio(OR)=2.09(1.10-3.97),P=0.024],N-acetylglycine[OR=3.14(1.78-5.53),P=7.54×10^(-8)],X-11593-O-methylascorbate[OR=1.68(1.04-2.72),P=0.034],1-arachidonoylglycerophosphocholine[OR=4.23(2.51-7.12),P=6.35×10^(-8)]and 1-arachidonoylglycerophosphoethanolamine 4[OR=3.99(1.17-13.54),P=0.027]were positively causally associated with colorectal cancer,and we also found a negative causal relationship between Tyrosine[OR=0.08(0.01-0.63),P=0.014],Urate[OR=0.25(0.10-0.62),P=0.003],N-acetylglycine[0.73(0.54-0.98),P=0.033],X-12092[OR=0.89(0.81-0.99),P=0.028],Succinylcarnitine[OR=0.48(0.27-0.84),P=0.09]with colorectal cancer.A series of sensitivity analyses were performed to confirm the rigidity of the results.CONCLUSION This study showed a causal relationship between 10 blood metabolites and colorectal cancer,of which 5 blood metabolites were found to be causal for the development of colorectal cancer and were confirmed as risk factors.The other five blood metabolites are protective factors.

Reform of the Irrigation Sector and Creation of Functional and Sustainable Irrigation Water Users Associations (AUEI) in Niger: Capitalization of the Experience of the Konni AHA

During the 1980s, as part of a policy of liberalization, following budgetary cuts linked to the implementation of structural adjustment programs, management responsibilities for AHAs were transferred from ONAHA to cooperatives concerned. Due to lack of financial resources, but also because of poor management, everywhere in Niger we are witnessing an accelerated deterioration of the irrigation infrastructure of hydro-agricultural developments. Institutional studies carried out on this situation led the State of Niger to initiate a reform of the governance of hydro-agricultural developments, by streng-thening the status of ONAHA, by creating an Association of Irrigation Water Users (AUEI) and by restructuring the old cooperatives. Indeed, this research aims to analyze the creation of functional and sustainable Irrigation Water User Associations (AUEI) in Niger in a context of reform of the irrigation sector, and based on the experience of the Konni AHA. It is based on a methodological approach which takes into account documentary research and the collection of data from 115 farmers, selected by reasoned choice and directly concerned by the management of the irrigated area. The data collected was analyzed and the results were analyzed using the systemic approach and the diagnostic process. The results show that the main mission of the AUEI is to ensure better management of water, hydraulic equipment and infrastructure on the hydro-agricultural developments of Konni. The creation of the Konni AUEI was possible thanks to massive support from the populations and authorities in the implementation process. After its establishment, the AUEI experienced a certain lethargy for some time due to the rehabilitation work of the AHA but currently it is functional and operational in terms of associative life and governance. Thus, the constraints linked to the legal system, the delay in the completion of the work, the uncertainties of access to irrigation water but also the problems linked to the change in mentality of certain ONAHA agents constitute the challenges that must be resolved in the short term for the operationalization of the Konni AUEI.

The Development and Experience of American Pharmaceutical Industry Associations and Its Enlightenment to China

Objective To study the development history and current situation of pharmaceutical industry associations in the United State and to provide reference for China’s pharmaceutical industry associations.Methods Literature research and comparative study were used to investigate the development history and current situation of pharmaceutical associations in the United States.Then,their characteristics and experiences were summarized.Some countermeasures and suggestions were put forward for the existing problems of pharmaceutical associations in China.Results and Conclusion The institutional environment of pharmaceutical associations in the United States is relatively good,reflecting the characteristics of emphasizing process management and neglecting entrance management with and the help of public supervision.At the same time,the government advocates market competition by adhering to the market-oriented services for the public.American pharmaceutical industry associations have strong innovation capacity and perfect credit system.Drawing on the experience of pharmaceutical industry associations in the United States,China should strengthen the construction of pharmaceutical industry associations.Firstly,the supervision mechanism should be improved.Secondly,these associations should have good partnerships with the government and offer the public the best services.Finally,the fund-raising mechanism of pharmaceutical industry associations should be optimized to ensure the innovative development of the pharmaceutical industry.

Diabetes and cancer: Associations, mechanisms, and implications for medical practice

Both diabetes mellitus and cancer are prevalent diseases worldwide. It is evident that there is a substantial increase in cancer incidence in diabetic patients. Epidemiologic studies have indicated that diabetic patients are at significantly higher risk of common cancers including pancreatic, liver, breast, colorectal, urinary tract, gastric and female reproductive cancers. Mortality due to cancer is moderately increased among patients with diabetes compared with those without. There is increasing evidence that some cancers are associated with diabetes, but the underlying mechanisms of this potential association have not been fully elucidated. Insulin is a potent growth factor that promotes cell proliferation and carcinogenesis directly and/or through insulin-like growth factor 1(IGF-1). Hyperinsulinemia leads to an increase in the bioactivity of IGF-1 by inhibiting IGF binding protein-1. Hyperglycemia serves as a subordinate plausible explanation of carcinogenesis. High glucose may exert direct and indirect effects upon cancer cells to promote proliferation. Also chronic inflammation is considered as a hallmark of carcinogenesis. The multiple drugs involved in the treatment of diabetes seem to modify the risk of cancer. Screening to detect cancer at an early stage and appropriate treatment of diabetic patients with cancer are important to improve their prognosis. This paper summarizes the associations between diabetes and common cancers, interprets possible mechanisms involved, and addresses implications for medical practice.

Dairy Consumption and Associations with Nutritional Status of Chinese Children and Adolescents

Objective This study aimed to describe frequency and quantity of total dairy consumption of Chinese children and adolescents and explore the associations between dairy consumption and nutrition status, including stunting, wasting, overweight, and obesity. Methods Participants included 28,250 children and adolescents aged 6-17 years old. A food frequency questionnaire(FFQ) including 100 kinds of food was used to collect information about frequency and quantity of dairy consumption. Determination of stunting was with a height cutoff value for age and gender, and determination for wasting, overweight, and obesity was with BMI for age and gender. Results Of the total sample, 36.1% of children aged 6-17 reported consuming dairy food more than once per day(≥ 1/day). The average total dairy intake of all the participants was 126.7 g/day. For boys, dairy consumption had an inverse correlation with stunting and wasting after controlling for confounders. For girls, dairy consumption was negatively associated with stunting and obesity after controlling for confounders as above. Conclusion Dairy consumption in Chinese children and adolescents was relatively lower than that in developed countries, and was negatively associated with stunting and wasting for boys and with stunting and obesity for girls.

Modeling the dose-response rate/associations between VO2max and self-reported Physical Activity Questionnaire in children and adolescents

Background'. This study sought to explore the dose—response rate/association between aerobic fitness (VC)2max) and self-reported physical activity(PA) and to assess whether this association varies by sex, age, and weight status.Methods. VO2max was assessed using the 20・m shuttle・run test. PA was assessed using the Physical Activity Questionnaire (PAQ) for Adolescents(aged > 11 years, PAQ-A) or for Children (aged <11 years, PAQ-C). The associations between V02raax and PAQ were analyzed using analysisof covariance (ANCOVA), adopting PAQ and PAQ2 as covariates but allowing the intercepts and slope parameters of PAQ and PAQ2 tovary with the categorical variables sex, age group, and weight status.Results: ANCOVA identified a curvilinear association between VO2max and PAQ, with positive linear PAQ terms that varied for both sex andweight status but with a negative PAQ2 term of —0.39 (95% confidence interval (CI): —0.57 to —0.21) that was common for all groups in regardto age, sex, and weight status. These curvilinear (inverted U) associations suggest that the benefits of increasing PA (same dose) on VO2max isgreater when children report lower levels of PA compared to children who report higher levels of PA. These dose-response rates were alsosteeper for boys and were steeper for lean children compared to overweight/obese children.Conclusion'. Health practitioners should be aware that encouraging greater PA (same dose) in inactive and underweight children will result ingreater gains in V02max (response) compared with their active and overweight/obese counterparts.

Single-Nucleotide Polymorphism Associations for Colorectal Cancer in Southern Chinese Population

Objective： Genome-wide association studies （GWAS） have identified 11 loci that influence the risk of developing colorectal cancer （CRC）. Given that these studies were conducted in European Caucasian populations, it is not clear whether the results are relevant for populations with different ethnicities. The aim of this study was to examine these associations in a southern Chinese population. Methods： Eleven single-nucleotide polymorphisms （SNPs）, rs12701937, rs16892766, rs7014346, rs6983267, rs719725, rs10795668, rs3802842, rs4444235, rs9929218, rs10411210, and rs961253, were genotyped in 229 CRC patients and 267 controls using the MassArray SNP genotyping system. Results： Evidence of an association with CRC was found for four of the 11 loci. The strongest associations were with rs4444235 and rs961253, with significant odds ratios close to those reported in previous GWAS. Among these four loci, rs719725 and rs4444235 were significantly associated with female gender, rs3802842, rs961253, and rs4444235 with early disease onset, and rs3802842 with later disease onset. However, no associations with CRC risk were detected for six other loci （rs9929218, rs10411210, rs12701937, rs7014346, rs6983267, and rs10795668）, and one SNP, rs16892766, was not polymorphic in any of the study participants. Conclusion： The rs4444235 and rs961253 loci are strongly associated with the risk of CRC in southern Chinese.

Habitat associations of saplings and adults in an old-growth temperate forest in the Changbai mountains, northeastern China

Species-habitat association analysis is useful to detect spatial arrangement of individual plants, to discover rules about the distribution of species and to generate hypotheses about the possible underlying process controlling observed structures. Quantifying methods were used to classify habitats in terms of topographical variables in a mixed temperate broad-leaved Korean pine forest of the Changbai mountains in northeastern China. All of the 625 20 m × 20 m quadrats of the plot could be unambiguously assigned to one of three habitat categories （low-plateau, high-plateau and slope）. Torus-translation tests were used to estimate species-habitat associations. Many species are clearly distributed in a biased fashion with respect to habitats. Fifteen （55.6%） out of 27 species showed strong positive or negative association with specific habitats. We compared species-habitat associations at the sapling and adult stages. Adjusted density values indicated few species exhibit extremely strong habitat associations. Only 9 out of 26 species had adjusted densities 〉 3 in the habitat for which they had strong positive affinity. Few species show the same associations at the small tree and large tree stages. Only 3 out of 22 occurring associations with a specific habitat appeared to have a consistent habitat association at the two stages. These results suggest that species-habitat associations exist in the 25-ha plot of the temperate forest of the Chang- bai mountains. Owing to limitations in our statistical methodology, we partly underestimated associations by ignoring rare species. Regeneration niches can contribute to co-existence, but regeneration niches due to habitat associations play a limited role in species co-existence, since most species show a similar trend in habitat associations at the sapling and adult stages. We should pay more attention to shifts in habitat associations, i.e. niche shifts at different stages of existence.

Genetic associations with adverse events from anti-tumor necrosis factor therapy in inflammatory bowel disease patients

AIM To study the type and frequency of adverse events associated with anti-tumor necrosis factor(TNF)therapy and evaluate for any serologic and genetic associations.METHODS This study was a retrospective review of patients attending the inflammatory bowel disease(IBD) centers at Cedars-Sinai IBD Center from 2005-2016. Adverse events were identified via chart review. IBD serologies were measured by ELISA. DNA samples were genotyped at Cedars-Sinai using Illumina Infinium Immunochipv1 array per manufacturer's protocol. SNPs underwent methodological review and were evaluated using several SNP statistic parameters to ensure optimal allele-calling. Standard and rigorous QC criteria were applied to the genetic data, which was generated using immunochip. Genetic association was assessed by logistic regression after correcting for population structure.RESULTS Altogether we identified 1258 IBD subjects exposed to anti-TNF agents in whom Immunochip data were available. 269/1258 patients(21%) were found to have adverse events to an anti-TNF-α agent that required the therapy to be discontinued. 25% of women compared to 17% of men experienced an adverse event. All adverse events resolved after discontinuing the antiTNF agent. In total: n = 66(5%) infusion reactions; n = 49(4%) allergic/serum sickness reactions; n = 19(1.5%) lupus-like reactions, n = 52(4%) rash, n = 18(1.4%) infections. In Crohn's disease, Ig A ASCA(P = 0.04) and Ig G-ASCA(P = 0.02) levels were also lower in patients with any adverse events, and anti-I2 level in ulcerative colitis was significantly associated with infusion reactions(P = 0.008). The logistic regression/human annotation and network analyses performed on the Immunochip data implicated the following five signaling pathways: JAK-STAT(Janus Kinase-signal transducer and activator of transcription), measles, IBD, cytokine-cytokine receptor interaction, and toxoplasmosis for any adverse event. CONCLUSION Our study shows 1 in 5 IBD patients experience an adverse event to anti-TNF therapy with novel serologic, genetic, and pathways associations.

Determination of Residual Feed Intake and Its Associations with Single Nucleotide Polymorphism in Chickens

Marker assisted selection （MAS） for residual feed intake （RFI） is considered to be one of the powerful means to improve feed conversion efficiency, and therefore reduce production costs. To test the inner relationship among body compositions, growth traits and RFI, four models were proposed to assess the extensively explanatory variables accounting for partial variables in feed intake besides metabolic body weight and growth rate. As a result, the original model （Koch＇s model） had the lowest R2 （80.78%） and the highest Bayesian information criterion （1 323.3） value among the four models. Moreover, the effects on RFI caused by single nucleotide polymorphisms （SNPs） were assessed in this study. Twelve SNPs from 7 candidate genes were genotyped in 2 Chinese native strains, rs14743490 of RPLP2 gene showed suggestively significant association with initial body weight in both strains （P〈0.10）. rs15047274 of TAF15 was significantly associated with growth weight, final weight, and feed intake （P〈0.05） in N301 strain, in contrast, it was only suggestively significant associated with feed intake （P〈0.10） in N414 strain, rs15869967 was significantly associated with RFI in N414 strain but not in N301 strain. This study has identified potential genetic markers suitable for MAS in improving the above mentioned traits, but these associations need to be rectified in other larger populations in future.

Isotope Geochronologic and Geochemical Constraints on the Magmatic Associations of the Collisional Orogenic Zone in the West Kunlun Orogen, China

The Jiajiwaxi pluton in the southern portion of the West Kunlun Range can be divided into two collision-related intrusive rock series, i.e., a gabbro-quartz diorite-granodiorite series that formed at 224±2.0 Ma and a monzonitic granite-syenogranite series that formed at 222±2.0 Ma. The systematic analysis of zircon U-Pb geochronology and bulk geochemistry is used to discuss the magmatic origin （material source and thermal source）, tectonic setting, genesis and geotectonic implications of these rocks. The results of this analysis indicate that the parent magma of the first series, representing a transition from I-type to S-type granites, formed from thermally triggered partial melting of deep crustal components in an early island-arc-type igneous complex, similar to an I-type granite, during the continental collision orogenic stage. The parent magma of the second series, corresponding to an S-type granite, formed from the partial melting of forearc accretionary wedge sediments in a subduction zone in the late Palaeozoic-Triassic. During continued collision, the second series magma was emplaced into the first series pluton along a central fault zone in the original island arc region, forming an immiscible puncture-type complex. The deep tectonothermal events associated with the continent-continent collision during the orogenic cycle are constrained by the compositions and origins of the two series. The new information provided by this paper will aid in future research into the dynamic mechanisms affecting magmatic evolution in the West Kunlun orogenic belt.

ROBUST DEPENDENCE MEASURE FOR DETECTING ASSOCIATIONS IN LARGE DATA SET

In this paper, we proposed a new statistical dependency measure for two random vectors based on copula, called copula dependency coefficient （CDC）. The CDC is proved to be robust to outliers and easy to be implemented. Especially, it is powerful and applicable to high-dimensional problems. All these properties make CDC practically important in related applications. Both experimental and application results show that CDC is a good robust dependence measure for association detecting.

Management of Associations in the IRBAC 2000 Model

Secure interaction and interoperability between two or more administrative domains is a major concern. The IRBAC 2000 model accomplishes secure interaction and interoperability by flexibly dynamic inter-domain role translations. Associations are the key element of the IRBAC 2000 model, which have a great impact on security and efficiency of dynamic role translations. Therefore, it is a crucial problem how to manage the associations in the IRBAC 2000 model. There are two cases under which some matters will emerge. One is where conflicting associations may result in a security hazard. Another is where redundant associations may reduce the efficiency of dynamic role translations and increase the difficulty of management of associations. The formal definitions on conflicting associations and redundant associations are given, and the methods are discusses to judge whether there are conflicting associations or redundant associations in IRBAC 2000 model. The protective mechanism is presented, which utilizes prerequisite conditions to prevent conflicting or redundant associations from appearing in IRBAC 2000 model.

New insights into the associations among feed efficiency, metabolizable efficiency traits and related QTL regions in broiler chickens

Background: Improving the feed efficiency would increase profitability for producers while also reducing the environmental footprint of livestock production. This study was conducted to investigate the relationships among feed efficiency traits and metabolizable efficiency traits in 180 male broilers. Significant loci and genes affecting the metabolizable efficiency traits were explored with an imputation-based genome-wide association study. The traits measured or calculated comprised three growth traits, five feed efficiency related traits, and nine metabolizable efficiency traits.Results: The residual feed intake(RFI) showed moderate to high and positive phenotypic correlations with eight other traits measured, including average daily feed intake(ADFI), dry excreta weight(DEW), gross energy excretion(GEE), crude protein excretion(CPE), metabolizable dry matter(MDM), nitrogen corrected apparent metabolizable energy(AMEn), abdominal fat weight(Ab F), and percentage of abdominal fat(Ab P). Greater correlations were observed between growth traits and the feed conversion ratio(FCR) than RFI. In addition, the RFI, FCR, ADFI, DEW,GEE, CPE, MDM, AMEn, Ab F, and Ab P were lower in low-RFI birds than high-RFI birds(P < 0.01 or P < 0.05), whereas the coefficients of MDM and MCP of low-RFI birds were greater than those of high-RFI birds(P < 0.01). Five narrow QTLs for metabolizable efficiency traits were detected, including one 82.46-kb region for DEW and GEE on Gallus gallus chromosome(GGA) 26, one 120.13-kb region for MDM and AMEn on GGA1, one 691.25-kb region for the coefficients of MDM and AMEn on GGA5, one region for the coefficients of MDM and MCP on GGA2(103.45–103.53 Mb), and one 690.50-kb region for the coefficient of MCP on GGA14. Linkage disequilibrium(LD) analysis indicated that the five regions contained high LD blocks, as well as the genes chromosome 26 C6 orf106 homolog(C26 H6 orf106), LOC396098, SH3 and multiple ankyrin repeat domains 2(SHANK2), ETS homologous factor(EHF), and histamine receptor H3-like(HRH3 L), which are known to be involved in the regulation of neurodevelopment, cell proliferation and differentiation, and food intake.Conclusions: Selection for low RFI significantly decreased chicken feed intake, excreta output, and abdominal fat deposition, and increased nutrient digestibility without changing the weight gain. Five novel QTL regions involved in the control of metabolizable efficiency in chickens were identified. These results, combined through nutritional and genetic approaches, should facilitate novel insights into improving feed efficiency in poultry and other species.

Effect of Body Mass Index on the Associations between Parity and Metabolic Syndrome and its Components among Northern Chinese Women

Objectives The aims of this study were to assess the associations between parity and metabolic syndrome(Met S)and its components and to evaluate the effects of body mass index(BMI)on these associations.Methods A total of 5,674 women were enrolled from Jidong and Kailuan communities(Tangshan,Hebei)in Northern China.All participants completed standardized questionnaires,physical examination,and biochemical measurements.Logistic regression analysis was used to test the associations.Results Compared with women with parity of one,nulliparous women had decreased odds ratios(ORs);those with parity of two had odds of abdominal obesity[OR=1.45,95%confidence interval(CI)1.17–1.81,P<0.001],high blood pressure(OR=1.26,95%CI:1.03–1.54,P=0.025),elevated fasting glucose levels(OR=1.36,95%CI:1.03–1.79,P=0.029),and Met S(OR=1.39,95%CI:1.13–1.73,P=0.002);and those with parity of three or more had increased odds of elevated triglyceride levels(OR=1.42,95%CI:1.04–1.94,P=0.027)and Met S(OR=1.50,95%CI:1.10–2.05,P=0.011)after complete adjustment for confounders.Furthermore,BMI and age subgroups partially modified the associations between parity and Met S and its components.Conclusions Parity is positively associated with Met S and select components in women.BMI is an important modifier involved in the associations between parity and MetS.

Distribution Patterns and Associations of Dominant Tree Species in a Mixed Coniferous-Broadleaf Forest in the Changbai Mountains

In 2012 a plot was established with 1-ha area in a mixed coniferous-broadleaf forest in the Changbai Mountains, northeastern China for examining local forest processes, structure and succession. A method of O-ring statistics （pair- correlation function） was applied to analyze the spatial patterns and associations of the dominant species within different vertical layers. After the evaluation by their importance values, six tree species （or group） （i.e. Abies nephrolepis, Picea jezoensis, Pinus koraiensis, Tilia amurensis, and species group of Betula ssp. and species group of Acer ssp.） were determined as dominant trees species. It was found that some of these species exhibited closely clustered distributions at fine distances. As spatial distance increased, a random or even regular distribution gradually appeared with the exception of the upper layers of A. nephrolepis and P. koraiensis, and the lower layers of P. jezoensis, P. koraiensis and Betula ssp., which were substantially randomly distributed. Intra- and inter-species spatial associations varied in accordance with species, tree height and reciprocal distances. Positive associations were observed between the lower and upper height classes of trees of the same species （except for that of P. jezoensis） at fine distances. This may be owing to limited seed dispersal and geological heterogeneity. The aggregation intensity declines with increasing distances and this consistent with the predictions of self-thinning. Some coniferous trees （e.g. Pinus koraiensis） in the lower height class were positively associated with T. amurensis and group of Betula ssp. of the upper height class at some distances, suggesting that saplings of coniferous trees occupy a broader niche and can grow well under the canopy of the adult of broad-leaved trees. Negative associations were observed between upper coniferous trees and lower broad-leaved trees and between upper P. jezoensis and lower P. koraiensis, suggesting that a canopy of these trees might not provide suitable environment for the survival, establishment, and growth of o lower individuals, corresponding well to Janzen-Connell hypothesis.

Identification of single nucleotide polymorphisms of PIK3R1 and DUSP1 genes and their genetic associations with milk production traits in dairy cows

Background:Previously,phosphoinositide-3-kinase regulatory subunit 1(PIK3R1)and dual specificity phosphatase 1(DUSP1)were identified as promising candidate genes for milk production traits due to their being differentially expressed between the dry period and the peak of lactation in livers of dairy cows.Hence,in this study,the single nucleotide polymorphisms(SNPs)of PIK3R1 and DUSP1 genes were identified and their genetic associations with milk yield,fat yield,fat percentage,protein yield,and protein percentage,were investigated using 1067 Chinese Holstein cows from 40 sire families.Results:By re-sequencing the entire coding region and 2000 bp of the 5′and 3′flanking regions of the two genes,one SNP in the 5′untranslated region(UTR),three in the 3′UTR,and two in the 3′flanking region of PIK3R1 were identified,and one in the 5′flanking region,one in the 3′UTR,and two in the 3′flanking region of DUSP1 were found.Subsequent single-locus association analyses showed that five SNPs in PIK3 R1,rs42590258,rs210389799,rs208819656,rs41255622,rs133655926,and rs211408208,and four SNPs in DUSP1,rs207593520,rs208460068,rs209154772,and rs210000760,were significantly associated with milk,fat and protein yields in the first or second lactation(P values≤0.0001 and 0.0461).In addition,by the Haploview 4.2 software,the six and four SNPs in PIK3R1 and DUSP1 respectively formed one haplotype block,and the haplotype-based association analyses showed significant associations between their haplotype combinations and the milk traits in both two lactations(P values≤0.0001 and 0.0364).One SNP,rs207593520(T/G),was predicted to alter the transcription factor binding sites(TFBSs)in the 5′flanking region of DUSP1.Further,the dual-luciferase assay showed that the transcription activity of allele T in rs207593520 was significantly higher than that of allele G,suggesting the activation of transcriptional activity of DUSP1 gene by allele T of rs207593520.Thus,the rs207593520 SNP was highlighted as a potential causal mutation that should be further verified.Conclusions:We demonstrated novel and significant genetic effects of the PIK3R1 and DUSP1 genes on milk production traits in dairy cows,and our findings provide information for use in dairy cattle breeding.

Primary sclerosing cholangitis associated colitis: Characterization of clinical, histologic features, and their associations with liver transplantation

BACKGROUND Primary sclerosing cholangitis(PSC)associated inflammatory bowel disease(IBD)is a unique form of IBD(PSC-IBD)with distinct clinical and histologic features from ulcerative colitis(UC)and Crohn disease(CD).In patients with PSC and IBD,the severity of the two disease processes may depend on each other.AIM To study the histologic and clinical features of PSC patients with and without IBD.METHODS We assessed specimens from patients with UC(n=28),CD(n=10),PSC and UC(PSC-UC;n=26);PSC and CD(PSC-CD;n=6);and PSC and no IBD(PSC-no IBD;n=4)between years 1999-2013.PSC-IBD patients were matched to IBD patients without PSC by age and colitis duration.Clinical data including age,gender,age at IBD and PSC diagnoses,IBD duration,treatment,follow-up,orthotopic liver transplantation(OLT)were noted.RESULTS PSC-UC patients had more isolated right-sided disease(P=0.03),and less active inflammation in left colon,rectum(P=0.03 and P=0.0006),and overall(P=0.0005)compared to UC.They required less steroids(P=0.01)and fewer colectomies(P=0.03)than UC patients.The PSC-CD patients had more ileitis and less rectal involvement compared to PSC-UC and CD.No PSC-CD patients required OLT compared to 38%of PSC-UC(P=0.1).PSC-IBD(PSC-UC and PSCCD)patients with OLT had severe disease in the left colon and rectum(P=0.04).CONCLUSION PSC-UC represents a distinct form of IBD.The different disease phenotype in PSC-IBD patients with OLT may support liver-gut axis interaction,however warrants clinical attention and further research.

Causal associations between inflammatory bowel disease and anxiety:A bidirectional Mendelian randomization study

BACKGROUND Anxiety is common in patients with inflammatory bowel disease(IBD),including those with ulcerative colitis(UC)and Crohn’s disease(CD);however,the causal relationship between IBD and anxiety remains unknown.AIM To investigate the causal relationship between IBD and anxiety by using bidirectional Mendelian randomization analysis.METHODS Single nucleotide polymorphisms retrieved from genome-wide association studies(GWAS)of the European population were identified as genetic instrument variants.GWAS statistics for individuals with UC(6968 patients and 20464 controls;adults)and CD(5956 patients and 14927 controls;adults)were obtained from the International IBD Genetics Consortium.GWAS statistics for individuals with anxiety were obtained from the Psychiatric Genomics Consortium(2565 patients and 14745 controls;adults)and FinnGen project(20992 patients and 197800 controls;adults),respectively.Inverse-variance weighted was applied to assess the causal relationship,and the results were strengthened by heterogeneity,pleiotropy and leave-one-out analyses.RESULTS Genetic susceptibility to UC was associated with an increased risk of anxiety[odds ratio:1.071(95%confidence interval:1.009-1.135),P=0.023],while genetic susceptibility to CD was not associated with anxiety.Genetic susceptibility to anxiety was not associated with UC or CD.No heterogeneity or pleiotropy was observed,and the leave-one-out analysis excluded the potential influence of a particular variant.CONCLUSION This study revealed that genetic susceptibility to UC was significantly associated with anxiety and highlighted the importance of early screening for anxiety in patients with UC.