Metabolic signature associated with parameters of the complete blood count in apparently healthy individuals

Metabolomics studies now approach large sample sizes and the health characterization of the study population often include complete blood count (CBC) results. Upon careful interpretation the CBC aids diagnosis and provides insight into the health status of the patient within a clinical setting. Uncovering metabolic signatures associated with parameters of the CBC in apparently healthy individuals may facilitate interpretation of metabolomics studies in general and related to diseases. For this purpose 879 subjects from the population‐based Study of Health in Pomerania (SHIP)‐TREND were included. Using metabolomics data resulting from mass‐spectrometry based measurements in plasma samples associations of specific CBC parameters with metabolites were determined by linear regression models. In total, 118 metabolites significantly associated with at least one of the CBC parameters. Strongest associations were observed with metabolites of heme degradation and energy production/consumption. Inverse association seen with mean corpuscular volume and mean corpuscular haemoglobin comprised metabolites potentially related to kidney function. The presently identified metabolic signatures are likely derived from the general function and formation/elimination of blood cells. The wealth of associated metabolites strongly argues to consider CBC in the interpretation of metabolomics studies, in particular if mutual effects on those parameters by the disease of interest are known.     

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.     

高尿酸血症人群血清钙与代谢综合征的相关性研究

目的:探讨血清钙(Calcium,Ca)水平与高尿酸血症(Hyperuricemia,HU)人群发生代谢综合征(Metabolic syndrome,MetS)的相关性。方法:纳入在中南大学湘雅医院健康管理中心进行健康体检的HU患者作为研究对象。通过Beckman Coulter AU 5800全自动生化分析仪检测纳入研究对象的血清Ca水平,根据中国糖尿病学会标准诊断MetS。根据血清Ca水平将研究人群进行四分类,采用Logistic回归模型探讨不同血清Ca水平与MetS患病的相关性。结果:共纳入711例HU患者作为研究对象,Logistic回归模型结果显示:未校正混杂因素时,与第1分类(最低)血清Ca组相比,总人群中第2-4分类血清Ca组MetS患病率比值比和95%可信区间(95%confidence interval,95%CI)分别为1.45 (95%CI:0.92, 2.29)、1.87 (95%CI:1.21, 2.89)和1.88 (95%CI:1.19,2.95)(趋势检验P=0.003),校正年龄和性别以及多因素校正后结果无明显变化。性别亚组分析结果显示该相关性只存在于男性亚组,女性亚组中无显著相关性。结论:男性HU人群血清Ca水平与MetS患病呈正相关,可能为MetS患病的危险因素,适当降低Ca的摄入可能有助于男性HU人群MetS的防治,而女性HU人群中血清Ca水平与MetS患病不相关。     

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.     

Putting the genes into community genetics

As part of the long‐term fusion of evolutionary biology and ecology (Ford, 1964), the field of community genetics has made tremendous progress in describing the impacts of plant genetic variation on community and ecosystem processes. In the “genes‐to‐ecosystems” framework (Whitham et al., 2003), genetically based traits of plant species have ecological consequences, but previous studies have not identified specific plant genes responsible for community phenotypes. The study by Barker et al. (2019) in this issue of Molecular Ecology uses an impressive common garden experiment of trembling aspen (Figure 1) to test for the genetic basis of tree traits that shape the insect community composition. Using a Genome‐Wide Association Study (GWAS), they found that genomic regions associated with phytochemical traits best explain variation in herbivore community composition, and identified specific genes associated with different types of leaf‐modifying herbivores and ants. This is one of the first studies to identify candidate genes underlying the heritable plant traits that explain patterns of insect biodiversity.     

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.