A functional variant in SLC1A3 influences ADHD risk by disrupting a hsa‐miR‐3171 binding site: A two‐stage association study

Attention‐deficit hyperactivity disorder (ADHD) is one of the most common neuropsychiatric disorders in children and adolescents with high heritability. Evidence is accumulating that SLC1A3 may play a role in ADHD etiology. Therefore, a two‐stage case‐control study was conducted on 752 cases and 774 controls to explore the role of SLC1A3 in ADHD. Bioinformatic annotations and functional experiments were applied to reveal the potential biological mechanisms. Finally, SLC1A3 rs1049522 showed significant association with ADHD risk in two stages with CA genotype vs AA genotype, odds ratio (OR) = 0.694 (95% confidence interval, CI = 0.570‐0.844) and dominant model, OR = 0.749 (95% CI = 0.621‐0.904) in the combined stage. Besides, rs1049522 was found to be related to ADHD hyperactive/impulsive symptom, and rs1049522‐C showed increased SLC1A3 mRNA expression in the cerebellar cortex. Dual‐luciferase reporter assay further indicated that rs1049522‐C allele enhanced SLC1A3 expression by disrupting the hsa‐miR‐3171 binding site. In conclusion, SLC1A3 variant rs1049522 was implicated in ADHD susceptibility in a Chinese Han population probably by enhancing the SLC1A3 expression in a miRNA‐mediated manner.     

Atomic Sn4+ Decorated into Vanadium Carbide MXene Interlayers for Superior Lithium Storage

Ion intercalation is an important way to improve the energy storage performance of 2D materials. The dynamic energy storage process in such layered intercalations is important but still a challenge mainly due to the lack of effective operando methods. Herein, a unique atomic Sn⁴⁺–decorated vanadium carbide (V₂C) MXene not only exhibiting highly enhanced lithium‐ion battery (LIB) performance, but also possessing outstanding rate and cyclic stability because of the expanded interlayer space and the formation of V? O? Sn bonding is demonstrated. In combination with ex situ tests, an operando X‐ray absorption fine structure measurement is developed to explore the dynamic mechanism of V₂C@Sn MXene electrodes in LIBs. The results clearly reveal the valence changes of vanadium (V), tin (Sn), and positive contribution of oxygen (O) atoms during the charging/discharging process, confirming their contribution for lithium storage capacity. The stability of intercalated MXene electrode is further in situ studied to prove the key role of V? O? Sn bonding.     

Possible risk factors for keel bone damage in organic laying hens

Keel bone damage (KBD) in laying hens is an important welfare problem in both conventional and organic egg production systems. We aimed to identify possible risk factors for KBD in organic hens by analysing cross-sectional data of 107 flocks assessed in eight European countries. Due to partly missing data, the final multiple regression model was based on data from 50 flocks. Keel bone damage included fractures and/or deviations, and was recorded, alongside with other animal based measures, by palpation and visual inspection of at least 50 randomly collected hens per flock between 52 and 73 weeks of age. Management and housing data were obtained by interviews, inspection and by feed analysis. Keel bone damage flock prevalences ranged from 3% to 88%. Compiled on the basis of literature and practical experience, 26 potential associative factors of KBD went into an univariable selection by Spearman correlation analysis or Mann–Whitney U test (with P<0.1 level). The resulting nine factors were presented to stepwise forward linear regression modelling. Aviary v. floor systems, absence of natural daylight in the hen house, a higher proportion of underweight birds, as well as a higher laying performance were found to be significantly associated with a higher percentage of hens with KBD. The final model explained 32% of the variation in KBD between farms. The moderate explanatory value of the model underlines the multifactorial nature of KBD. Based on the results increased attention should be paid to an adequate housing design and lighting that allows the birds easy orientation and safe manoeuvring in the system. Furthermore, feeding management should aim at sufficient bird live weights that fulfil breeder weight standards. In order to achieve a better understanding of the relationships between laying performance, feed management and KBD further investigations are needed.     

Highly tunable thiosulfonates as a novel class of cysteine protease inhibitors with anti-parasitic activity against Schistosoma mansoni

The development of a new class of cysteine protease inhibitors utilising the thiosulfonate moiety as an SH specific electrophile is described. This moiety has been introduced into suitable amino acid derived building blocks, which were incorporated into peptidic sequences leading to very potent i.e. sub micromolar inhibitors of the cysteine protease papain in the same range as the vinyl sulfone based inhibitor K11777. Therefore, their inhibitory effect on Schistosoma mansoni, a human blood parasite, that expresses several cysteine proteases, was evaluated. The homophenylalanine side chain containing compounds 27–30 and especially 36 showed promising activities compared with K11777 and warrant further investigations of these peptidic thiosulfonate inhibitors as new potential anti-parasitic compounds.     

Leveraging GWAS data to identify metabolic pathways and networks involved in maize lipid biosynthesis

Maize (Zea mays mays) oil is a rich source of polyunsaturated fatty acids (FAs) and energy, making it a valuable resource for human food, animal feed, and bio‐energy. Although this trait has been studied via conventional genome‐wide association study (GWAS), the single nucleotide polymorphism (SNP)‐trait associations generated by GWAS may miss the underlying associations when traits are based on many genes, each with small effects that can be overshadowed by genetic background and environmental variation. Detecting these SNPs statistically is also limited by the levels set for false discovery rate. A complementary pathways analysis that emphasizes the cumulative aspects of SNP‐trait associations, rather than just the significance of single SNPs, was performed to understand the balance of lipid metabolism, conversion, and catabolism in this study. This pathway analysis indicated that acyl‐lipid pathways, including biosynthesis of wax esters, sphingolipids, phospholipids and flavonoids, along with FA and triacylglycerol (TAG) biosynthesis, were important for increasing oil and FA content. The allelic variation found among the genes involved in many degradation pathways, and many biosynthesis pathways leading from FAs and carbon partitioning pathways, was critical for determining final FA content, changing FA ratios and, ultimately, to final oil content. The pathways and pathway networks identified in this study, and especially the acyl‐lipid associated pathways identified beyond what had been found with GWAS alone, provide a real opportunity to precisely and efficiently manipulate high‐oil maize genetic improvement.     

Serum immunoglobulin levels and the risk of bladder cancer in the AMORIS Cohort

BackgroundThe anti-tumour T-cell response in bladder cancer has been shown to correlate with response to treatment and prognosis. However, little is known about the role of humoral immunity in this highly immunogenic human cancer, which is characterised by a high mutation-associated neoantigen load and a strong response to immunotherapy. In the present study, we interrogated the Swedish Apolipoprotein Mortality Risk Study (AMORIS) to explore the relationship between pre-diagnostic serum immunoglobulin levels and the risk of developing bladder cancer.MethodsOur analysis included all AMORIS participants aged 20 years or older, who had all three major serum immunoglobulins (IgA, IgM, IgG) recorded at the same baseline measurement (n = 29,876). All participants were free from bladder cancer at the time of measurement. Samples were obtained between 1985–1996, with follow-up information until 2011. Multivariate Cox proportional hazards regression was used to investigate the association between bladder cancer risk and different levels of pre-diagnostic serum immunoglobulins.ResultsDuring a mean follow-up period of 15.31 years, 163 (0.5%) individuals were diagnosed with bladder cancer. Multivariate Cox regression showed an inverse association between pre-diagnostic serum IgM levels ≥ 1.4 g/L and bladder cancer risk compared to serum IgM levels < 1.4 g/L [HR: 0.68 (95% CI 0.45–1.03)]. Corresponding associations could not be established for serum IgA or IgG.ConclusionOur findings implicate serum IgM in the pathogenesis of bladder cancer and suggest that the concept of humoral immune surveillance against cancer warrants further mechanistic investigation.     

Colorectal cancer among farmers in the AGRICAN cohort study

ObjectivesSpecific farming types and tasks have rarely been studied in relation to colorectal cancer (CRC). We evaluated associations between 5 types of livestock and 13 types of crops in relation to CRC and its subsites within the Agriculture and Cancer (AGRICAN) study.MethodsAGRICAN cohort includes 181,842 agricultural workers living in 11 French geographical areas. Data on farming types and tasks was collected by self-administered questionnaires. We identified 2 609 CRC, 972 right colon, 689 left colon and 898 rectal incident cancer cases during follow-up from 2005 to 2015. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI).ResultsSignificantly increased CRC risk was observed for farmers producing horses (HR=1.18, 95% CI 1.06–1.31), sunflower (HR=1.23, 95% CI 1.03–1.45) and field vegetables (HR=1.18, 95% CI 1.02–1.36). Positive associations were also observed for pig, poultry and wheat/barley. Some associations were observed only for specific subsites: left colon cancer was associated with fruit growing (HR=1.36, 95% CI 1.09–1.70) and potato (HR=1.28, 95% CI 1.05–1.57). Tasks related to livestock (animal care, insecticide treatment, disinfection of milking equipment and building) or to crop (haymaking, sowing, pesticide treatment, seed treatment, harvesting) were also associated with CRC. Duration and size of farming types/task increased the risk for some of the associations. Analysis stratified by sex suggested an interaction with several farming types/task.ConclusionsThe current study showed original and positive findings for several farming types and tasks and CRC risk, overall and by subsites.     

Long-term feeding a high-fat diet causes histological and parasitological effects on murine schistosomiasis mansoni outcome

This study investigated whether long-term feeding a high-fat diet (HFC) has an effect on schistosomiasis mansoni outcome compared to standard chow diet (SC). Swiss Webster female mice (3 wk old) fed each diet over 5 months, and then were infected with 50 Schistosoma mansoni cercariae. Their nutritional status was assessed by monitoring growth rates twice a week and measuring serum levels of lipoproteins. Mice were euthanised 63 days after infection. Parasitological and liver histological analyses were performed. The levels of TC, HDL-C and LDL-C, fecal and tissue schistosome eggs were statistically different (p<0.05) between groups. Livers from HFC mice showed exudative, exudative/exudative-productive, exudative-productive and productive granulomas, some degree of hepatic steatosis and focal necrosis. Mice fed normal-chow did not present productive granulomas and hepatic steatosis. The morphometric evaluation of hepatic granulomas did not reach statistical significance (p>0.05) between diets assayed. The high-fat diet for long-term produces effects on schistosomiasis mansoni outcome.