Identification of the novel recessive gene pi55(t) conferring resistance to Magnaporthe oryzae

The elite rice cultivar Yuejingsimiao 2 (YJ2) is characterized by a high level of grain quality and yield, and resistance against Magnaporthe oryzae. YJ2 showed 100% resistance to four fungal populations collected from Guangdong, Sichuan, Liaoning, and Heilongjiang Provinces, which is a higher frequency than that shown by the well-known resistance (R) gene donor cultivars such as Sanhuangzhan 2 and 28zhan. Segregation analysis for resistance with F₂ and F₄ populations indicated the resistance of YJ2 was controlled by multiple genes that are dominant or recessive. The putative R genes of YJ2 were roughly tagged by SSR markers, located on chromosomes 2, 6, 8, and 12, in a bulked-segregant analysis using genome-wide selected SSR markers with F₄ lines that segregated into 3 resistant (R):1 susceptible (S) or 1R:3S. The recessive R gene on chromosome 8 was further mapped to an interval ≈1.9 cM/152 kb in length by linkage analysis with genomic position-ready markers in the mapping population derived from an F₄ line that segregated into 1R:3S. Given that no major R gene was mapped to this interval, the novel R gene was designated as pi55(t). Out of 26 candidate genes predicted in the region based on the reference genomic sequence of the cultivar Nipponbare, two genes that encode a leucine-rich repeat-containing protein and heavy-metal-associated domain-containing protein, respectively, were suggested as the most likely candidates for pi55(t).     

Genome-wide DNA methylation indicates silencing of tumor suppressor genes in uterine leiomyoma

Background

Uterine leiomyomas, or fibroids, represent the most common benign tumor of the female reproductive tract. Fibroids become symptomatic in 30% of all women and up to 70% of African American women of reproductive age. Epigenetic dysregulation of individual genes has been demonstrated in leiomyoma cells; however, the in vivo genome-wide distribution of such epigenetic abnormalities remains unknown.

Principal Findings

We characterized and compared genome-wide DNA methylation and mRNA expression profiles in uterine leiomyoma and matched adjacent normal myometrial tissues from 18 African American women. We found 55 genes with differential promoter methylation and concominant differences in mRNA expression in uterine leiomyoma versus normal myometrium. Eighty percent of the identified genes showed an inverse relationship between DNA methylation status and mRNA expression in uterine leiomyoma tissues, and the majority of genes (62%) displayed hypermethylation associated with gene silencing. We selected three genes, the known tumor suppressors KLF11, DLEC1, and KRT19 and verified promoter hypermethylation, mRNA repression and protein expression using bisulfite sequencing, real-time PCR and western blot. Incubation of primary leiomyoma smooth muscle cells with a DNA methyltransferase inhibitor restored KLF11, DLEC1 and KRT19 mRNA levels.

Conclusions

These results suggest a possible functional role of promoter DNA methylation-mediated gene silencing in the pathogenesis of uterine leiomyoma in African American women.     

Structural and functional diversity of acidic scorpion potassium channel toxins

Background

Although the basic scorpion K⁺ channel toxins (KTxs) are well-known pharmacological tools and potential drug candidates, characterization the acidic KTxs still has the great significance for their potential selectivity towards different K⁺ channel subtypes. Unfortunately, research on the acidic KTxs has been ignored for several years and progressed slowly.

Principal Findings

Here, we describe the identification of nine new acidic KTxs by cDNA cloning and bioinformatic analyses. Seven of these toxins belong to three new α-KTx subfamilies (α-KTx28, α-KTx29, and α-KTx30), and two are new members of the known κ-KTx2 subfamily. ImKTx104 containing three disulfide bridges, the first member of the α-KTx28 subfamily, has a low sequence homology with other known KTxs, and its NMR structure suggests ImKTx104 adopts a modified cystine-stabilized α-helix-loop-β-sheet (CS-α/β) fold motif that has no apparent α-helixs and β-sheets, but still stabilized by three disulfide bridges. These newly described acidic KTxs exhibit differential pharmacological effects on potassium channels. Acidic scorpion toxin ImKTx104 was the first peptide inhibitor found to affect KCNQ1 channel, which is insensitive to the basic KTxs and is strongly associated with human cardiac abnormalities. ImKTx104 selectively inhibited KCNQ1 channel with a K_d of 11.69 µM, but was less effective against the basic KTxs-sensitive potassium channels. In addition to the ImKTx104 toxin, HeTx204 peptide, containing a cystine-stabilized α-helix-loop-helix (CS-α/α) fold scaffold motif, blocked both Kv1.3 and KCNQ1 channels. StKTx23 toxin, with a cystine-stabilized α-helix-loop-β-sheet (CS-α/β) fold motif, could inhibit Kv1.3 channel, but not the KCNQ1 channel.

Conclusions/Significance

These findings characterize the structural and functional diversity of acidic KTxs, and could accelerate the development and clinical use of acidic KTxs as pharmacological tools and potential drugs.     

Cathepsin S deficiency results in abnormal accumulation of autophagosomes in macrophages and enhances Ang II-induced cardiac inflammation

Background

Cathepsin S (Cat S) is overexpressed in human atherosclerotic and aneurysmal tissues and may contributes to degradation of extracellular matrix, especially elastin, in inflammatory diseases. We aimed to define the role of Cat S in cardiac inflammation and fibrosis induced by angiotensin II (Ang II) in mice.

Methods and Results

Cat S-knockout (Cat S^−/−) and littermate wild-type (WT) C57BL/6J mice were infused continuously with Ang II (750 ng/kg/min) or saline for 7 days. Cat S^−/− mice showed severe cardiac fibrosis, including elevated expression of collagen I and α-smooth muscle actin (α-SMA), as compared with WT mice. Moreover, macrophage infiltration and expression of inflammatory cytokines (tumor necrosis factor α, transforming growth factor β and interleukin 1β) were significantly greater in Cat S^−/− than WT hearts. These Ang II-induced effects in Cat S^−/− mouse hearts was associated with abnormal accumulation of autophagosomes and reduced clearance of damaged mitochondria, which led to increased levels of reactive oxygen species (ROS) and activation of nuclear factor-kappa B (NF-κB) in macrophages.

Conclusion

Cat S in lysosomes is essential for mitophagy processing in macrophages, deficiency in Cat S can increase damaged mitochondria and elevate ROS levels and NF-κB activity in hypertensive mice, so it regulates cardiac inflammation and fibrosis.     

Levels of Hexachlorocyclohexanes and Dichloro-Dipheny-Trichloroethanes in Penguin Droppings Collected from Ardley Island,Maritime Antarctic

This article reports the concentrations of hexachlorocyclohexanes (HCHs) and dichloro-diphenyl-trichloroethanes (DDTs) in fresh Gentoo penguin (Pygoscelis Papua) droppings deposited on the Ardley Island (62°13′S, 58°56′W), West Antarctica, and those in the island's two lake cores. In the fresh penguin droppings, metabolites were the predominant constituents of the DDT group, most likely due to the ban on DDT use in agriculture and the higher stability of the metabolites in the environment. In contrast, γ-HCH comprised 66% of the total HCHs, apparently due to the continuous use of Lindane in the Southern Hemisphere. The concentrations of HCHs and DDTs in the fresh droppings are many times higher than those in penguin plume, the latter currently being used as biomaterial for monitoring coastal contaminations in Antarctica. Results of this study indicate that penguin droppings have a good potential for use as another biomonitoring material in detecting the organochlorine pesticides and other contaminants in the maritime Antarctic. Because penguin droppings can be well preserved in lake sediments, they also provide a good and continuous historical record of these contaminants. The slight increase of DDTs since the 1990s, as observed in the aged penguin droppings in the sediment cores, suggests there have been new inputs of DDT into the Antarctic coastal ecosystem, probably from the illegal use of DDT in the Southern Hemisphere.     

Clinical,Virological and Immunological Features from Patients Infected with Re-Emergent Avian-Origin Human H7N9 Influenza Disease of Varying Severity in Guangdong Province

BackgroundThe second wave of avian influenza H7N9 virus outbreak in humans spread to the Guangdong province of China by August of 2013 and this virus is now endemic in poultry in this region.MethodsFive patients with H7N9 virus infection admitted to our hospital during August 2013 to February 2014 were intensively investigated. Viral load in the respiratory tract was determined by quantitative polymerase chain reaction (Q-PCR) and cytokine levels were measured by bead-based flow cytometery.ResultsFour patients survived and one died. Viral load in different clinical specimens was correlated with cytokine levels in plasma and broncho-alveolar fluid (BALF), therapeutic modalities used and clinical outcome. Intravenous zanamivir appeared to be better than peramivir as salvage therapy in patients who failed to respond to oseltamivir. Higher and more prolonged viral load was found in the sputum or endotracheal aspirates compared to throat swabs. Upregulation of proinflammatory cytokines IP-10, MCP-1, MIG, MIP-1α/β, IL-1β and IL-8 was found in the plasma and BALF samples. The levels of cytokines in the plasma and viral load were correlated with disease severity. Reactivation of herpes simplex virus type 1(HSV-1) was found in three out of five patients (60%).ConclusionExpectorated sputum or endotracheal aspirate specimens are preferable to throat swabs for detecting and monitoring H7N9 virus. Severity of the disease was correlated to the viral load in the respiratory tract as well as the extents of cytokinemia. Reactivation of HSV-1 may contribute to clinical outcome.     

应用生物法合成内酯化合物

内酯是广泛存在于自然界中具有生物活性的一类化合物。由于大多数内酯化合物具有手性,用化学方法合成不仅过程复杂,而且产率也不高。利用酶反应的特异性,应用生物法合成内酯化合物具有很好的应用前景,其中包括微生物次生代谢合成内酯,脂肪酸生物转化合成内酯和脂肪酶在有机相中催化羟基脂肪酸形成内酯。本文报道这些领域的进展。     

The myocardial response to adrenomedullin involves increased cAMP generation as well as augmented Akt phosphorylation

In this work we aimed to observe (1) the changes in adrenomedullin (AM) and its receptor system - calcitonin receptor-like receptor (CRLR) and receptor activity modifying proteins (RAMPs) - in myocardial ischemic injury and (2) the response of injuried myocardia to AM and the phosphorylation of Akt to illustrate the protective mechanism of AM in ischemic myocardia. Male SD rats were subcutaneously injected with isoproterenol (ISO) to induce myocardial ischemia. The mRNA levels of AM, CRLR, RAMP1, RAMP2 and RAMP3 were determined by RT-PCR. Protein levels of Akt, phosphor-Akt, CRLR, RAMP1, RAMP2 and RAMP3 were assayed by Western blot. Results showed that, compared with that of the controls, ISO-treated rats showed lower cardiac function and myocardial injury. The mRNA relative amount of AM, CRLR, RAMP1, RAMP2 and RAMP3 in the myocardia of ISO-treated rats was increased. The elevated mRNA levels of CRLR, RAMP1, RAMP2 and RAMP3 were positively correlated with AM content in injured myocardia. The protein levels of CRLR, RAMP1, RAMP2 and RAMP3 in injured myocardia were increased compared with that of control myocardia. AM-stimulated cAMP generation in myocardia was elevated in the ISO group, and was antagonized by AM(22-52) and CGRP(8-37). Western blot analyses revealed that AM significantly enhanced Akt phosphorylation in injured myocardia, which was blocked by pretreatment with AM(22-52) or CGRP(8-37). Ischemia-injured myocardia hyper-expressed AM and its receptors - CRLR, RAMP1, RAMP2 and RAMP3 - and the response of ischemic myocardia to AM was potentiated, and the level of Akt phosphorylation was also increased, which suggests that changes in cardiac AM/AM receptor might play an important role in the pathogenesis of myocardial ischemic injury.     

棉铃虫幼虫自相残杀习性与其龄期和食物营养的相关性（英文）

【目的】 昆虫自相残杀行为可以促进特定病原体的传播,这在利用昆虫病原体防治害虫方面有潜在的应用价值。本研究旨在探究棉铃虫 Helicoverpa armigera 幼虫自相残杀习性与其龄期及食物营养之间的相关性。【方法】 分别饲喂室内品系和野外品系的棉铃虫幼虫含不同Na⁺浓度的人工饲料,并在饲养至3龄、4龄、5龄和6龄时,将取食相同饲料的10头幼虫为一群组移入同一培养皿中,通过测定各处理幼虫存活率,评估幼虫龄期和饲料中的Na⁺含量对自相残杀行为的影响。【结果】 当以3龄和4龄为群组的起始龄期时,棉铃虫幼虫存活率显著低于起始龄期为5龄和6龄的群组。此外,取食正常人工饲料的幼虫存活率最高,取食缺钠饲料时,幼虫存活率明显下降。最后,幼虫群组起始龄期和食物Na⁺含量对幼虫化蛹率无明显影响。【结论】结果说明,棉铃虫4和5龄幼虫与3和6龄幼虫相比,自相残杀行为发生的概率更大,而Na⁺含量较低的食物在一定程度上促进自相残杀行为发生的可能性。本研究为在这一领域的进一步工作提供了基础。