Active role of small peptides in Arabidopsis reproduction: Expression evidence

<正>Dear Editor,Successful sexual reproduction in plants requires extensive communication between male and female gametophytes,their gametes,and with the surrounding sporophytic tissues(Dresselhaus and Franklin-Tong 2013).Over the past two decades,many peptides including small cysteine-rich peptides(CRPs)and non-CRPs were found to play key roles in plant reproduction,mainly acting as signaling cues in this male–the Editor     

Identification of differentially methylated markers among cytogenetic risk groups of acute myeloid leukemia

Aberrant DNA methylation is known to occur in cancer, including hematological malignancies such as acute myeloid leukemia (AML). However, less is known about whether specific methylation profiles characterize specific subcategories of AML. We examined this issue by using comprehensive high-throughput array-based relative methylation analysis (CHARM) to compare methylation profiles among patients in different AML cytogenetic risk groups. We found distinct profiles in each group, with the high-risk group showing overall increased methylation compared with low- and mid-risk groups. The differentially methylated regions (DMRs) distinguishing cytogenetic risk groups of AML were enriched in the CpG island shores. Specific risk-group associated DMRs were located near genes previously known to play a role in AML or other malignancies, such as MN1, UHRF1, HOXB3, and HOXB4, as well as TRIM71, the function of which in cancer is not well characterized. These findings were verified by quantitative bisulfite pyrosequencing and by comparison with results available at the TCGA cancer genome browser. To explore the potential biological significance of the observed methylation changes, we correlated our findings with gene expression data available through the TCGA database. The results showed that decreased methylation at HOXB3 and HOXB4 was associated with increased gene expression of both HOXB genes specific to the mid-risk AML, while increased DNA methylation at DCC distinctive to the high-risk AML was associated with increased gene expression. Our results suggest that the differential impact of cytogenetic changes on AML prognosis may, in part, be mediated by changes in methylation.     

Urinary Levels of N-Nitroso Compounds in Relation to Risk of Gastric Cancer: Findings from the Shanghai Cohort Study

BackgroundN-Nitroso compounds are thought to play a significant role in the development of gastric cancer. Epidemiological data, however, are sparse in examining the associations between biomarkers of exposure to N-nitroso compounds and the risk of gastric cancer.MethodsA nested case-control study within a prospective cohort of 18,244 middle-aged and older men in Shanghai, China, was conducted to examine the association between urinary level of N-nitroso compounds and risk of gastric cancer. Information on demographics, usual dietary intake, and use of alcohol and tobacco was collected through in-person interviews at enrollment. Urinary levels of nitrate, nitrite, N-nitroso-2-methylthiazolidine-4-carboxylic acid (NMTCA), N-nitrosoproline (NPRO), N-nitrososarcosine (NSAR), N-nitrosothiazolidine-4-carboxylic acid (NTCA), as well as serum H. pylori antibodies were quantified in 191 gastric cancer cases and 569 individually matched controls. Logistic regression method was used to assess the association between urinary levels of N-nitroso compounds and risk of gastric cancer.ResultsCompared with controls, gastric cancer patients had overall comparable levels of urinary nitrate, nitrite, and N-nitroso compounds. Among individuals seronegative for antibodies to H. pylori, elevated levels of urinary nitrate were associated with increased risk of gastric cancer. The multivariate-adjusted odds ratios for the second and third tertiles of nitrate were 3.27 (95% confidence interval = 0.76–14.04) and 4.82 (95% confidence interval = 1.05–22.17), respectively, compared with the lowest tertile (P for trend = 0.042). There was no statistically significant association between urinary levels of nitrite or N-nitroso compounds and risk of gastric cancer. Urinary NMTCA level was significantly associated with consumption of alcohol and preserved meat and fish food items.ConclusionThe present study demonstrates that exposure to nitrate, a precursor of N-nitroso compounds, may increase the risk of gastric cancer among individuals without a history of H. pylori infection.     

Promising Loci and Genes for Yolk and Ovary Weight in Chickens Revealed by a Genome-Wide Association Study

Because it serves as the cytoplasm of the oocyte and provides a large amount of reserves, the egg yolk has biological significance for developing embryos. The ovary and its hierarchy of follicles are the main reproductive organs responsible for yolk deposition in chickens. However, the genetic architecture underlying the yolk and ovarian follicle weights remains elusive. Here, we measured the yolk weight (YW) at 11 age points from onset of egg laying to 72 weeks of age and measured the follicle weight (FW) and ovary weight (OW) at 73 weeks as part of a comprehensive genome-wide association study (GWAS) in 1,534 F₂ hens derived from reciprocal crosses between White Leghorn (WL) and Dongxiang chickens (DX). For all ages, YWs exhibited moderate single nucleotide polymorphism (SNP)-based heritability estimates (0.25–0.38), while the estimates for FW (0.16) and OW (0.20) were relatively low. Independent univariate genome-wide screens for each trait identified 12, 3, and 31 novel significant associations with YW, FW, and OW, respectively. A list of candidate genes such as ZAR1, STARD13, ACER1b, ACSBG2, and DHRS12 were identified for having a plausible function in yolk and follicle development. These genes are important to the initiation of embryogenesis, lipid transport, lipoprotein synthesis, lipid droplet promotion, and steroid hormone metabolism, respectively. Our study provides for the first time a genome-wide association (GWA) analysis for follicle and ovary weight. Identification of the promising loci as well as potential candidate genes will greatly advance our understanding of the genetic basis underlying dynamic yolk weight and ovarian follicle development and has practical significance in breeding programs for the alteration of yolk weight at different age points.     

Chronic Compression of the Dorsal Root Ganglion Enhances Mechanically Evoked Pain Behavior and the Activity of Cutaneous Nociceptors in Mice

Radicular pain in humans is usually caused by intraforaminal stenosis and other diseases affecting the spinal nerve, root, or dorsal root ganglion (DRG). Previous studies discovered that a chronic compression of the DRG (CCD) induced mechanical allodynia in rats and mice, with enhanced excitability of DRG neurons. We investigated whether CCD altered the pain-like behavior and also the responses of cutaneous nociceptors with unmyelinated axons (C-fibers) to a normally aversive punctate mechanical stimulus delivered to the hairy skin of the hind limb of the mouse. The incidence of a foot shaking evoked by indentation of the dorsum of foot with an aversive von Frey filament (tip diameter 200 μm, bending force 20 mN) was significantly higher in the foot ipsilateral to the CCD surgery as compared to the contralateral side on post-operative days 2 to 8. Mechanically-evoked action potentials were electrophysiologically recorded from the L3 DRG, in vivo, from cell bodies visually identified as expressing a transgenically labeled fluorescent marker (neurons expressing either the receptor MrgprA3 or MrgprD). After CCD, 26.7% of MrgprA3⁺ and 32.1% MrgprD⁺ neurons exhibited spontaneous activity (SA), while none of the unoperated control neurons had SA. MrgprA3⁺ and MrgprD⁺ neurons in the compressed DRG exhibited, in comparison with neurons from unoperated control mice, an increased response to the punctate mechanical stimuli for each force applied (6, 20, 40, and 80 mN). We conclude that CCD produced both a behavioral hyperalgesia and an enhanced response of cutaneous C-nociceptors to aversive punctate mechanical stimuli.     

Urinary tract abnormalities in Chinese rural children who consumed melamine-contaminated dairy products: a population-based screening and follow-up study

Background

Kidney damage related to consumption of melamine-contaminated dairy products by young children in China has been described. However, no studies have reported on the population-based prevalence of kidney damage among exposed children or on the condition of affected children after follow-up.

Methods

We conducted an ultrasound-based screening in September 2008 of 7933 children younger than 36 months of age who lived in a rural area in China where the dairy products most highly contaminated with melamine were sold. We monitored children who had evidence of nephrolithiasis or hydronephrosis at screening using renal ultrasonography after one, three and six months. We also collected information from the mothers of affected children about consumption of melamine-contaminated products between June and August 2008.

Results

The overall prevalence of urinary tract abnormalities among screened children was 0.61% (95% confidence interval [CI] 0.45%–0.80%). The mean exposure dose of melamine was estimated to be 116 (range 36–220) mg per day. Of the 48 affected children, 43 (89.6%) were asymptomatic, 2 had symptoms and were hospitalized, and 3 had symptoms but treatment had been not sought for them. Of the 46 children for whom six-month follow-up information was available, renal abnormalities persisted in 5 children and resolved in the remaining 41.

Interpretation

Among children who underwent screening, 0.61% showed ultrasonographic evidence of nephrolithiasis or hydronephrosis. Most of the affected children were asymptomatic. The majority of the affected children recovered from the toxic effects of melamine over time without specific treatment. Renal abnormalities remained in 12% of the affected children.Contamination of dairy products with melamine in China has resulted in a widespread outbreak of serious kidney damage in children.^1–4 On Sept. 12, 2008, the Chinese government announced to the public that the outbreak had occurred and initiated various emergency responses, including the set-up of a high-level national coordinating group, free screening and treatment of affected children, thorough inspection of all dairy products and producers, timely release of information to the public, recalls of contaminated products, suspension of production of the contaminated milk and compensation to the families of affected children. More than 50 000 children have been hospitalized and six have died because of kidney damage.⁵Melamine is a nitrogen-containing compound commonly used in chemical industry. Because its addition to milk elevates apparent protein content, raw milk was intentionally adulterated with melamine in the production-chain, leading to contamination of dairy products and high-level exposure of thousands of children.⁶Melamine is known to cause formation of calculi in weanling rats and has led to acute renal failure in cats and dogs consuming melamine-contaminated pet foods.^7,8 In humans, melamine-related disease has been recognized only recently, and the full adverse effects of exposure remain unknown.^4,9 A clinicopathologic study suggests that the size of urinary stones is related to melamine concentration.⁹ A recent hospital-based study in Beijing reported the prevalence of nephrolithiasis was 8.5% among children who were exposed and referred by other hospitals.¹⁰However, no studies have reported on the population-based prevalence of kidney disease among exposed children, nor have follow-up reports been released about affected children. We performed a population-based screening and follow-up study involving residents of a rural area situated close to the manufacturer of Sanlu dairy products, which was the source of the most severely melamine-contaminated products in the mainland of China.¹¹ The study was approved by the Institutional Review Board of Peking University.     

Proteomic analysis of primary porcine endothelial cells after infection by classical swine fever virus

Endothelial cells are the main target of classical swine fever virus during infection, and extensive hemorrhage is the most typical clinical sign of classical swine fever. To investigate the molecular mechanism of hemorrhagic pathogenesis, two-dimensional difference gel electrophoresis with fluorescent dyes (2D-DIGE) was used to analyze the proteomic profile of primary porcine umbilical vein endothelial cells (PUVECs) following CSFV infection. Of 15 protein spots with differential expression, 8 were characterized by MALDI-TOF-MS/MS in infected PUVECs at 48 h p.i.: moesin, peroxiredoxin 6, stathmin-1, a protein similar to nascent polypeptide-associated complex alpha subunit isoform 2, phosphoglycerate kinase 1, glucosidase II, transketolase and α-tubulin. These could be sorted into 5 functional groups: glycometabolism, cell proliferation, anti-oxidative stress, inflammatory response and cytoskeleton. Western blot and real-time RT-PCR analysis confirmed the down-regulation of phosphoglycerate kinase 1 (PGK1) and up-regulation of moesin identified by 2D-DIGE. Pathway analysis of these 15 differentially expressed proteins showed that CSFV infection altered the metabolism, cytoskeleton and cell proliferation of PUVECs, and that consequently an inflammatory response was induced.     

A study on the interaction between 5-Methyluridine and human serum albumin using fluorescence quenching method and molecular modeling

This work was designed to study the interaction between 5-Methyluridine and human serum albumin (HSA) under simulative physiological conditions using fluorescence spectroscopy in combination with molecular modeling technique for the first time. Static quenching was suggested by the fluorescence measurement. The binding constants (K) were calculated according to the relevant fluorescence data at different conditions including temperature. Thermodynamic parameter, different conditions including temperature to determine enthalpy change and entropy change, indicating the hydrophobic force played a major role in the binding interaction between 5-Methyluridine and HSA. The experimental result was in correspondence with molecular modeling theory.