Hepatic adenoma in a 7-year-old girl: a case report and literature review.

BACKGROUND: Hepatocellular adenomas (HCAs) are rare benign tumors of the liver that occur predominantly in women taking oral contraceptives. In children, HCAs comprise < 5% of hepatic tumors. We report a case of HCAs in a 7-year-old girl with estrogen and glucose imbalance. CASE PRESENTATION: A 7-year-old girl was presented to our hospital with bilateral breast enlargement for 2 months, polydipsia, polyuria, polyphagia, hyperglycemia, and significant weight gain. Computed tomography (CT) showed a 7.2 cm×6.9 cm×5.3 cm round-shaped mass in the left inner lobe of the liver, ovarian ultrasound showed multiple follicles in the ovaries bilaterally, and cranial magnetic resonance imaging (MRI) showed an enlarged superior pituitary. Hematological and biochemical results were as follows: fasting glucose was 19.7 mmol/L, estradiol was 122.9 pmol/L, follicle-stimulating hormone 10.81 IU/L, luteinizing hormone 10.99 IU/L, insulin-like growth factor 1,513 ng/mL, glutamine aminotransferase 86 U/L, and alkaline phosphatase 362 U/L. Thyroid functions, methemoglobin, fetal protein, carcinoembryonic antigen, and chorionic gonadotropin were normal. The patient had a complete surgical resection of the liver tumor, and the postoperative histopathological diagnosis was HCAs. After the surgery, insulin was injected and the glucose levels were stable. During the 36-month follow-up period, neither tumor recurrence nor significant abnormalities were detected using color Doppler ultrasound of the liver. The child's precocious puberty is currently under control. CONCLUSIONS: HCAs are particularly rare in children with liver tumors, and risk factors for the development of HCAs in children include sex hormone imbalance, obesity, Fanconi anemia (FA), glycogen storage diseases (GSDs) type I, III, and IV, galactosemia, immunodeficiency, congenital portosystemic shunts (CPSS), cardiac hepatopathy status-post Fontan procedure, Hurler syndrome, familial adenomatous polyposis, germline HNF1A mutations, and maturity-onset diabetes of the young type 3. Most HCAs are detected during a physical examination without clinical symptoms, and some patients may present with symptoms such as abdominal pain, abdominal distension, and abdominal masse. Serum liver function tests can show increased alkaline phosphatase (ALP) and γ- glutamyl transferase (GT), whereas α-Fetoprofein (AFP) levels are normal. The definitive diagnosis relies mainly on histopathological examination. Because HCAs can rupture and bleed and become malignant. Early surgical treatment is recommended after detection.

A point mutation in the gene encoding magnesium chelatase I subunit influences strawberry leaf color and metabolism.

Magnesium chelatase (MgCh) catalyzes the insertion of magnesium into protoporphyrin IX, a vital step in chlorophyll (Chl) biogenesis. The enzyme consists of 3 subunits, MgCh I subunit (CHLI), MgCh D subunit (CHLD), and MgCh H subunit (CHLH). The CHLI subunit is an ATPase that mediates catalysis. Previous studies on CHLI have mainly focused on model plant species, and its functions in other species have not been well described, especially with regard to leaf coloration and metabolism. In this study, we identified and characterized a CHLI mutant in strawberry species Fragaria pentaphylla. The mutant, noted as p240, exhibits yellow-green leaves and a low Chl level. RNA-Seq identified a mutation in the 186th amino acid of the CHLI subunit, a base conserved in most photosynthetic organisms. Transient transformation of wild-type CHLI into p240 leaves complemented the mutant phenotype. Further mutants generated from RNA-interference (RNAi) and CRISPR/Cas9 gene editing recapitulated the mutant phenotype. Notably, heterozygous chli mutants accumulated more Chl under low light conditions compared with high light conditions. Metabolite analysis of null mutants under high light conditions revealed substantial changes in both nitrogen and carbon metabolism. Further analysis indicated that mutation in Glu186 of CHLI does not affect its subcellular localization nor the interaction between CHLI and CHLD. However, intramolecular interactions were impaired, leading to reduced ATPase and MgCh activity. These findings demonstrate that Glu186 plays a key role in enzyme function, affecting leaf coloration via the formation of the hexameric ring itself, and that manipulation of CHLI may be a means to improve strawberry plant fitness and photosynthetic efficiency under low light conditions.

Deciphering the genetic basis of resistance to soybean cyst nematode combining IBD and association mapping.

KEY MESSAGE: IBD analysis clarified the dynamics of chromosomal recombination during the ZP pedigree breeding process and identified ten genomic regions resistant to SCN race3 combining association mapping. Soybean cyst nematode (SCN, Heterodera glycines Ichinohe) is one of the most devastating pathogens for soybean production worldwide. The cultivar Zhongpin03-5373 (ZP), derived from SCN-resistant progenitor parents, Peking, PI 437654 and Huipizhi Heidou, is an elite line with high resistance to SCN race3. In the current study, a pedigree variation map was generated for ZP and its ten progenitors using 3,025,264 high-quality SNPs identified from an average of 16.2 × re-sequencing for each genome. Through identity by decent (IBD) tracking, we showed the dynamic change of genome and detected important IBD fragments, which revealed the comprehensively artificial selection of important traits during ZP breeding process. A total of 2,353 IBD fragments related to SCN resistance including SCN-resistant genes rhg1, rhg4 and NSFRAN07 were identified based on the resistant-related genetic paths. Moreover, 23 genomic regions underlying resistance to SCN race3 were identified by genome-wide association study (GWAS) in 481 re-sequenced cultivated soybeans. Ten common loci were found by both IBD tracking and GWAS analysis. Haplotype analysis of 16 potential candidate genes suggested a causative SNP (C/T, - 1065) located in the promoter of Glyma.08G096500 and encoding a predicted TIFY5b-related protein on chr8 was highly correlated with SCN race3 resistance. Our results more thoroughly elucidated the dynamics of genomic fragments during ZP pedigree breeding and the genetic basis of SCN resistance, which will provide useful information for gene cloning and the development of resistant soybean cultivars using a marker-assisted selection approach.

Genic C-Methylation in Soybean Is Associated with Gene Paralogs Relocated to Transposable Element-Rich Pericentromeres.

Most plants are polyploid due to whole-genome duplications (WGD) and can thus have duplicated genes. Following a WGD, paralogs are often fractionated (lost) and few duplicate pairs remain. Little attention has been paid to the role of DNA methylation in the functional divergence of paralogous genes. Using high-resolution methylation maps of accessions of domesticated and wild soybean, we show that in soybean, a recent paleopolyploid with many paralogs, DNA methylation likely contributed to the elimination of genetic redundancy of polyploidy-derived gene paralogs. Transcriptionally silenced paralogs exhibit particular genomic features as they are often associated with proximal transposable elements (TEs) and are preferentially located in pericentromeres, likely due to gene movement during evolution. Additionally, we provide evidence that gene methylation associated with proximal TEs is implicated in the divergence of expression profiles between orthologous genes of wild and domesticated soybean, and within populations.

Genome-wide association mapping of QTL underlying seed oil and protein contents of a diverse panel of soybean accessions.

To investigate the genetic basis of variation in oil and protein contents in soybean seeds, a diverse collection of 421 mainly Chinese soybean cultivars was genotyped using 1536 SNPs, mostly from candidate genes related to acyl-lipid metabolism and from regions harboring known QTL. Six significant associations were identified for each of seed oil and protein contents which individually explained 2.7-5.9% of the phenotypic variance. Six associations occurred in or near known QTL and the remaining are putative novel QTL. Ten significant associations influenced the oil content without decreasing protein content, and vice versa. One SNP was pleiotropic, with opposite effects on oil and protein contents. The genetic region covering Map-6076 and-6077 was shown to be involved in controlling oil content in soybean by integrating the results of association mapping with information on known QTL and tissue-specific expression data. This region was subject to strong selection during the genetic improvement of soybean. Our results not only confirm and refine the map positions of known QTL but also contribute to a further elucidation of the genetic architecture of protein and oil contents in soybean seeds by identifying new associations exhibiting pleiotropic effects on seed protein and oil contents.

Dissecting the Genetic Basis of Resistance to Soybean Cyst Nematode Combining Linkage and Association Mapping.

A set of 585 informative single-nucleotide polymorphism (SNP) loci was used to genotype both a panel of diverse accessions and a set of recombinant inbred lines (RILs) bred from the cross Zhongpin03-5373 (ZP; resistant to SCN) × Zhonghuang13 (ZH; susceptible). The SNP loci are mostly sited within genic sequence in regions of the soybean [ (L.) Merr.] genome thought to harbor genes determining resistance to the soybean cyst nematode (SCN, Ichinohe). The three strongest quantitative trait nucleotides (QTNs) identified by association mapping (AM) involved the genes (a component of the multigene locus ), and (an paralog), as well as some other loci with smaller effects. The linkage mapping (LM) analysis performed using the RILs revealed two putative quantitative trait loci (QTL): one mapping to and the other to an paralog; both of these loci were also identified by AM. The former locus explained 25.5% of the phenotypic variance for SCN resistance and the latter 5.8%. In combination, the two major loci acted nonadditively, providing a high level of SCN resistance.

Crystal structures of (1,4,7,10-tetra-aza-cyclo-dodecane-κ(4) N)bis-(tri-cyano-methanido-κN)nickel and (1,4,7,10-tetra-aza-cyclo-dodecane-κ(4) N)(tri-cyano-methanido-κN)copper tri-cyano-methanide.

The structures of two mononuclear transition-metal complexes with tri-cyano-methanide (tcm(-)) and 1,4,7,10-tetra-aza-cyclo-dodecane (cyclen) ligands, [Ni(C4N3)2(C8H20N4)], (I), and [Cu(C4N3)(C8H20N4)](C4N3), (II), are reported. In the neutral complex (I), the nickel cation is coordinated by one cyclen ligand and two monodentate N-bound tcm(-) anions in a distorted octa-hedral geometry. The tcm(-) ligands are mutually cis. The Cu(II) atom in (II) displays a distorted tetra-gonal-pyramidal geometry, with the four N-donor atoms of the cyclen ligand in the equatorial plane, and one tcm(-) anion bound through a single N atom in an axial site, forming a monocation. The second tcm(-) molecule acts as a counter-ion not directly coordinating to the copper cation. In both (I) and (II), extensive series of N-H⋯N and C-H⋯N hydrogen bonds generate three-dimensional network structures.

Functional marker development of miR1511-InDel and allelic diversity within the genus Glycine.

BACKGROUND: Single-stranded non-protein coding small RNAs, 18-25 nucleotides in length, are ubiquitous throughout plants genomes and are involved in post-transcriptional gene regulation. Several types of DNA markers have been reported for the detection of genetic diversity or sequence variation in soybean, one of the most important legume crops in worldwide for seed protein and oil content. Recently, with the available of public genomic databases, there has been a shift from the labor-intensive development of PCR-based markers to sequence-based genotyping and the development of functional markers within genes, often coupled with the use of RNA information. But thus far miRNA-based markers have been only developed in rice and tobacco. Here we report the first functional molecular miRNA marker, miR1511-InDel, in soybean for a specific single copy locus used to assess genetic variation in domesticated soybean (Glycine max [L.] Merr) and its wild progenitor (Glycine soja Sieb. & Zucc.). RESULTS: We genotyped a total of 1,669 accessions of domesticated soybean (G. max) and its wild progenitor G. soja which are native throughout the China and parts of Korea, Japan and Russia. The results indicate that the miR1511 locus is distributed in cultivated soybean and has three alleles in annual wild soybean. Based on this result, we proposed that miR-InDel marker technology can be used to assess genetic variation. The inclusion of geo-reference data with miR1511-InDel marker data corroborated that accessions from the Yellow River basin (Huanghuai) exhibited high genetic diversity which provides more molecular evidence for gene diversity in annual wild soybean and domestication of soybean. CONCLUSIONS: These results provide evidence for the use of RNA marker, miRNA1511-InDel, as a soybean-specific functional maker for the study of genetic diversity, genotyping of germplasm and evolution studies. This is also the first report of functional marker developed from soybean miRNA located within the functional region of pre-miRNA1511.

Meta-analysis of association between cytokine gene polymorphisms and Behcet's disease risk.

The aim of this study was to perform a meta-analysis of eligible studies to derive precise estimation of the association of interleukin-1 (IL-1), IL-10 and tumor necrosis factor (TNF)-α polymorphisms with Behcet's disease (BD). Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. A total of 4003 cases and 4748 controls in 19 eligible studies were included in the meta-analysis. We examined the relationship between seven single nucleotide polymorphisms (SNPs) in the above-mentioned three cytokine genes and susceptibility to BD. Meta-analysis indicated the association between the cytokine gene polymorphisms in all study subjects in the allelic model (TNF-α -308A/G: OR = 0.73, 95% CI: 0.61-0.88, P = 0.001; IL-10 -819C/T: OR = 0.72, 95% CI: 0.66-0.78, P < 0.001; IL-10 -592C/A: OR = 0.74, 95% CI: 0.64-0.86, P < 0.001); the dominant model (TNF-α -308A/G: OR = 0.77, 95% CI: 0.64-0.92, P = 0.004; IL-10 -1082G/A: OR = 1.64, 95% CI: 1.10-2.44, P = 0.014); the recessive model (TNF-α -308A/G: OR = 0.27, 95% CI: 0.12-0.65, P = 0.003; IL-10 -819C/T: OR = 0.71, 95% CI: 0.57-0.90, P = 0.004). However, no significant evidence for the associations of IL-1α -889C/T, IL-1ß -551C/T, IL-1ß -3962C/T polymorphisms with BD susceptibility was detected. The present study might suggest that TNF-α -308A/G, IL-10 -1082G/A, -819C/T, -592C/A polymorphisms are associated with BD susceptibility.

Bis(dicyanamido-κN)[tris-(3-amino-propyl)amine-κ(4) N]nickel(II).

In the title complex, [Ni(C2N3)2(C9H24N4)], the Ni(II) atom is coordinated in a distorted octa-hedral geometry by one tris-(3-amino-prop-yl)amine (tris-apa) ligand and two dicyanamide (dca) ligands [one of them disordered in a 0.681 (19):0319 (19) ratio]. Inter-molecular N-H⋯N hydrogen bonds involving the N atoms of the dca anions and the tris-apa amine H atoms result in the formation of a three-dimensional network.

DNA sequence polymorphism of the Rhg4 candidate gene conferring resistance to soybean cyst nematode in Chinese domesticated and wild soybeans.

Rhg4 is one of the major resistant genes conferring resistance to soybean cyst nematode races 1, 3 and 4. In order to better understand its sequence diversity among different Chinese soybean populations and the impact of human activities on it, we designed 5 primer sets based on its sequence deposited in Genbank (Genbank accession No. AF506518) to obtain the Rhg4 sequence from 104 Chinese cultivated and wild soybean genotypes, and then analyzed the DNA sequence polymorphism in different Chinese soybean populations. The alignment of Rhg4 sequence included 5,216 nucleotide base pairs. A total of 67 single nucleotide polymorphisms (SNPs) including 59 single base changes and 8 DNA insertion-deletions (InDels) were identified with a SNP frequency of 1/78. Except for a 14-base InDel, there were 29 SNPs in coding regions, and among them, 13 were non-synonymous (9 in functional domains with 1 in a leucine-rich repeats region, 2 in a transmembrane region and 6 in a Ser/Thr kinase domain). The probability of substitution at each site was not the same, there were two hot spots, one was in the 5'-untranslated region between positions 124 and 804, and the other was in the region between positions 2520 and 3733. Sequence diversity analysis among 104 soybean genotypes showed π = 0.00102 and θ = 0.00218 for Rhg4. A domestication bottleneck was found because of lower sequence diversity and 58% unique SNPs loss in landraces compared with Glycine soja. Intensive selection increased the sequence diversity of cultivars, which had higher diversity and more unique SNPs than landraces. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11032-012-9703-1) contains supplementary material, which is available to authorized users.

[Genetic variation of SNP loci based on candidate gene for resistance to soybean cyst nematode].

For clarifying the difference of genetic diversity and linkage disequilibrium (LD) level between cultivated (Glycine max (L.) Merr.) and annual wild soybean (Glycine soja Sieb. & Zucc.), genetic variation pattern of 8 SNP loci developed from soybean cyst nematode resistance candidate genes rhg1 and Rhg4 in soybean germplasm were analyzed. The results indicated that G. max population, consisted of cultivated soybean mini-core collection and modern cultivars, had a higher LD levels (R2 value is 0.216) than G. soja population. Since 100% of pairwise loci within a gene and 16.6% of pairwise loci between genes were significant in G. max population, two specific LD regions were formed for each gene. A total of 46 haplotypes were detected in 363 soybean germplasm. The population of G. soja had less number of haplotypes and higher haplotype diversity than the population of G. max. Among the 31 population-specific haplotypes, 15 haplotypes were specific for G. soja population. In addition, the frequency of two major predominant haplotypes (Hap_10 and Hap_11) in G. soja population was obviously decreased in G. max population, which might indicate that some new haplotypes were formed and some old haplotypes were lost during the G. max domesticated from G. soja.