Comparison of different therapies in high-risk patients with idiopathic membranous nephropathy.

BACKGROUND/PURPOSE: Immunosuppressive therapy plays an important role in patients with high-risk idiopathic membranous nephropathy (IMN), but the therapeutic modality is still controversial. METHODS: Corticosteroid combined with oral tacrolimus (TAC, target trough blood concentration of 4-8 ng/mL), intravenous cyclophosphamide (CYC, 750 mg/m(2)/mo, or oral mycophenolate mofetil (MMF, 1.5-2.0 g/d) were randomly administered for 9 months to 90 patients with IMN proved with renal biopsy with severe proteinuria (>8 g/d). RESULTS: Eighty-six of the 90 patients completed the study. The total remission (TR) rates in the TAC group were significantly higher than those in the CYC group at 1 and 2 months (p < 0.01) and the MMF group at 1-4 months (p < 0.01). The TR rates were 83.3%, 73.3%, and 70.0% in the TAC, CYC, and MMF groups at 9 months (p = 0.457), and there were no significant differences between the three groups from 5 to 9 months. Furthermore, TAC reduced proteinuria and ameliorated hypoalbuminemia more quickly and effectively than CYC and MMF. We observed no severe adverse events in the three groups. CONCLUSION: Tacrolimus combined with corticosteroid had tolerable adverse effects and induced the remission of IMN more effectively and more rapidly. This is the first prospective randomized cohort study to compare three different therapies in patients at high risk for IMN. It provides strong evidence for choosing optimal treatment for patients with IMN. The long-term efficacy of this treatment strategy should be investigated further in future studies.

Genome-Wide Function, Evolutionary Characterization and Expression Analysis of Sugar Transporter Family Genes in Pear (Pyrus bretschneideri Rehd).

The sugar transporter (ST) plays an important role in plant growth, development and fruit quality. In this study, a total of 75 ST genes were identified in the pear (Pyrus bretschneideri Rehd) genome based on systematic analysis. Furthermore, all ST genes identified were grouped into eight subfamilies according to conserved domains and phylogenetic analysis. Analysis of cis-regulatory element sequences of all ST genes identified the MYBCOREATCYCB1 promoter in sucrose transporter (SUT) and monosaccharide transporter (MST) genes of pear, while in grape it is exclusively found in SUT subfamily members, indicating divergent transcriptional regulation in different species. Gene duplication event analysis indicated that whole-genome duplication (WGD) and segmental duplication play key roles in ST gene amplification, followed by tandem duplication. Estimation of positive selection at codon sites of ST paralog pairs indicated that all plastidic glucose translocator (pGlcT) subfamily members have evolved under positive selection. In addition, the evolutionary history of ST gene duplications indicated that the ST genes have experienced significant expansion in the whole ST gene family after the second WGD, especially after apple and pear divergence. According to the global RNA sequencing results of pear fruit development, gene expression profiling showed the expression of 53 STs. Combined with quantitative real-time PCR (qRT-PCR) analysis, two polyol/monosaccharide transporter (PLT) and three tonoplast monosaccharide transporter (tMT) members were identified as candidate genes, which may play important roles in sugar accumulation during pear fruit development and ripening. Identification of highly expressed STs in fruit is important for finding novel genes contributing to enhanced levels of sugar content in pear fruit.

High-density genetic linkage map construction and identification of fruit-related QTLs in pear using SNP and SSR markers.

Pear (Pyrus spp) is an important fruit crop, grown in all temperate regions of the world, with global production ranked after grape and apples among deciduous tree crops. A high-density linkage map is a valuable tool for fine mapping quantitative trait loci (QTL) and map-based gene cloning. In this study, we firstly constructed a high-density linkage map of pear using SNPs integrated with SSRs, developed by the rapid and robust technology of restriction-associated DNA sequencing (RADseq). The linkage map consists of 3143 SNP markers and 98 SSRs, 3241 markers in total, spanning 2243.4 cM, with an average marker distance of 0.70 cM. Anchoring SSRs were able to anchor seventeen linkage groups to their corresponding chromosomes. Based on this high-density integrated pear linkage map and two years of fruit phenotyping, a total of 32 potential QTLs for 11 traits, including length of pedicel (LFP), single fruit weight (SFW), soluble solid content (SSC), transverse diameter (TD), vertical diameter (VD), calyx status (CS), flesh colour (FC), juice content (JC), number of seeds (NS), skin colour (SC), and skin smooth (SS), were identified and positioned on the genetic map. Among them, some important fruit-related traits have for the first time been identified, such as calyx status, length of pedicel, and flesh colour, and reliable localization of QTLs were verified repeatable. This high-density linkage map of pear is a worthy reference for mapping important fruit traits, QTL identification, and comparison and combination of different genetic maps.

Huai Qi Huang ameliorates proteinuria and hematuria in mild IgA nephropathy patients: a prospective randomized controlled study.

BACKGROUND/PURPOSE: Huai Qi Huang (HQH) is a compound Chinese herbal medicine that contains Trametes robiniophila murr, wolfberry fruit, and Polygonatum. In the present study, we investigated the effects of HQH on patients with mild immunoglobulin A nephropathy (IgAN) through a prospective randomized controlled study. METHODS: Forty-five adults diagnosed with IgAN according to renal pathology, who had hematuria or/and proteinuria (≤ 2 g/day), were randomly assigned to receive HQH or no treatment for 12 weeks. Twenty-four hour urinary protein excretion and hematuria were measured at Weeks 0, 4, 8, and 12. The rate of complete remission of proteinuria and hematuria was evaluated. Any adverse events induced by HQH were also observed during the treatment period. RESULTS: Twenty-four hour urinary protein excretion was significantly reduced by HQH treatment compared with that in the control group at Weeks 8 and 12. A much higher rate of complete remission of proteinuria was observed in the HQH group than in control group at Week 12. HQH administration also obviously reduced the extent of hematuria compared with that in the control group at Week 12. HQH treatment dramatically increased the rate of complete remission of hematuria compared with that in control group at Weeks 8 and 12. No obvious adverse events caused by HQH were observed. CONCLUSION: HQH could be a new conservative therapy for IgAN patients who cannot tolerate steroids and immunosuppressive agents. The relapse rate after discontinuing treatment still needs further investigation.

Construction of a high-density bin-map and identification of fruit quality-related quantitative trait loci and functional genes in pear.

Pear (Pyrus spp.) is one of the most common fruit crops grown in temperate regions worldwide. Genetic enhancement of fruit quality is a fundamental goal of pear breeding programs. The genetic control of pear fruit quality traits is highly quantitative, and development of high-density genetic maps can facilitate fine-mapping of quantitative trait loci (QTLs) and gene identification. Bin-mapping is a powerful method of constructing high-resolution genetic maps from large-scale genotyping datasets. We performed whole-genome sequencing of pear cultivars 'Niitaka' and 'Hongxiangsu' and their 176 F 1 progeny to identify genome-wide single-nucleotide polymorphism (SNP) markers for constructing a high-density bin-map of pear. This analysis yielded a total of 1.93 million SNPs and a genetic bin-map of 3190 markers spanning 1358.5 cM, with an average adjacent interval of 0.43 cM. This bin-map, along with other high-density genetic maps in pear, improved the reference genome assembly from 75.5 to 83.7% by re-anchoring the scaffolds. A quantitative genetic analysis identified 148 QTLs for 18 fruit-related traits; among them, QTLs for stone cell content, several key monosaccharides, and fruit pulp acids were identified for the first time in pear. A gene expression analysis of six pear cultivars identified 399 candidates in the identified QTL regions, which showed expression specific to fruit developmental stages in pear. Finally, we confirmed the function of PbrtMT1, a tonoplast monosaccharide transporter-related gene responsible for the enhancement of fructose accumulation in pear fruit on linkage group 16, in a transient transformation experiment. This study provides genomic and genetic resources as well as potential candidate genes for fruit quality improvement in pear.

Overexpression of a bHLH1 Transcription Factor of Pyrus ussuriensis Confers Enhanced Cold Tolerance and Increases Expression of Stress-Responsive Genes.

The basic helix-loop-helix (bHLH) transcription factors are involved in arrays of physiological and biochemical processes. However, knowledge concerning the functions of bHLHs in cold tolerance remains poorly understood. In this study, a PubHLH1 gene isolated from Pyrus ussuriensis was characterized for its function in cold tolerance. PubHLH1 was upregulated by cold, salt, and dehydration, with the greatest induction under cold conditions. PubHLH1 had the transactivational activity and localized in the nucleus. Ectopic expression of PubHLH1 in transgenic tobacco conferred enhanced tolerance to cold stress. The transgenic lines had higher survival rates, higher chlorophyll, higher proline contents, lower electrolyte leakages and MDA when compared with wild type (WT). In addition, transcript levels of eight genes associated with ROS scavenging, regulation, and stress defense were higher in the transgenic plants relative to the WT under the chilling stress. Taken together, these results demonstrated that PubHLH1 played a key role in cold tolerance and, at least in part, contributed to activation of stress-responsive genes.

The coffee genome provides insight into the convergent evolution of caffeine biosynthesis.

Coffee is a valuable beverage crop due to its characteristic flavor, aroma, and the stimulating effects of caffeine. We generated a high-quality draft genome of the species Coffea canephora, which displays a conserved chromosomal gene order among asterid angiosperms. Although it shows no sign of the whole-genome triplication identified in Solanaceae species such as tomato, the genome includes several species-specific gene family expansions, among them N-methyltransferases (NMTs) involved in caffeine production, defense-related genes, and alkaloid and flavonoid enzymes involved in secondary compound synthesis. Comparative analyses of caffeine NMTs demonstrate that these genes expanded through sequential tandem duplications independently of genes from cacao and tea, suggesting that caffeine in eudicots is of polyphyletic origin.

Genome of the long-living sacred lotus (Nelumbo nucifera Gaertn.).

BACKGROUND: Sacred lotus is a basal eudicot with agricultural, medicinal, cultural and religious importance. It was domesticated in Asia about 7,000 years ago, and cultivated for its rhizomes and seeds as a food crop. It is particularly noted for its 1,300-year seed longevity and exceptional water repellency, known as the lotus effect. The latter property is due to the nanoscopic closely packed protuberances of its self-cleaning leaf surface, which have been adapted for the manufacture of a self-cleaning industrial paint, Lotusan. RESULTS: The genome of the China Antique variety of the sacred lotus was sequenced with Illumina and 454 technologies, at respective depths of 101× and 5.2×. The final assembly has a contig N50 of 38.8 kbp and a scaffold N50 of 3.4 Mbp, and covers 86.5% of the estimated 929 Mbp total genome size. The genome notably lacks the paleo-triplication observed in other eudicots, but reveals a lineage-specific duplication. The genome has evidence of slow evolution, with a 30% slower nucleotide mutation rate than observed in grape. Comparisons of the available sequenced genomes suggest a minimum gene set for vascular plants of 4,223 genes. Strikingly, the sacred lotus has 16 COG2132 multi-copper oxidase family proteins with root-specific expression; these are involved in root meristem phosphate starvation, reflecting adaptation to limited nutrient availability in an aquatic environment. CONCLUSIONS: The slow nucleotide substitution rate makes the sacred lotus a better resource than the current standard, grape, for reconstructing the pan-eudicot genome, and should therefore accelerate comparative analysis between eudicots and monocots.