Molecular Typing of Pathogenic Leptospira Serogroup Icterohaemorrhagiae Strains Circulating in China during the Past 50 Years

Background

Leptospirosis is one of the most important neglected tropical infectious diseases worldwide. Icterohaemorrhagiae has been throughout recent history, and still is, the predominant serogroup of this pathogen in China. However, very little in detail is known about the serovars or genotypes of this serogroup.

Methodology/Principal Findings

In this study, 120 epidemic strains from five geographically diverse regions in China collected over a 50 year period (1958~2008), and 8 international reference strains characterized by 16S rRNA sequencing and MLST analysis. 115, 11 and 2 strains were identified as L. interrogans, L. borgpetersenii, and L. kirschneri, respectively. 17 different STs were identified including 69 ST1 strains, 18 ST17, 18 ST128, 9 ST143 and 2 ST209. The remaining 12 strains belonged to 12 different STs. eBURST analysis demonstrated that, among the clonal complexes isolated (CCs), CC1 accounted for 73.3% (88/120) strains representing three STs: ST1, ST128 and ST98. ST1 was the most likely ancestral strain of this CC, followed by singleton CC17 (17/120) and CC143 (11/120). Further analysis of adding 116 serogroup Icterohaemorrhagiae strains in the MLST database and studies previously described using global eBURST analysis and MST dendrogram revealed relatively similar ST clustering patterns with five main CCs and 8 singletons among these 244 strains. CC17 was found to be the most prevalent clone of pathogenic Leptospira circulating worldwide. This is the first time, to our knowledge, that ST1 and ST17 strains were distributed among 4 distinct serovars, indicating a highly complicated relationship between serovars and STs.

Conclusions/Significance

Our studies demonstrated a high level of genetic diversity in the serogroup Icterohaemorrhagiae strains. Distinct from ST17 or ST37 circulating elsewhere, ST1 included in CC1, has over the past 50 years or so, proven to be the most prevalent ST of pathogenic leptospires isolated in China. Moreover, the complicated relationship between STs and serovars indicates an urgent need to develop an improved scheme for Leptospira serotyping.     

Tandem action of glycosyltransferases in the maturation of vancomycin and teicoplanin aglycones: novel glycopeptides

The glycopeptides vancomycin and teicoplanin are clinically important antibiotics. The carbohydrate portions of these molecules affect biological activity, and there is great interest in developing efficient strategies to make carbohydrate derivatives. To this end, genes encoding four glycosyltransferases, GtfB, C, D, E, were subcloned from Amycolatopsis orientalis strains that produce chloroeremomycin (GtfB, C) or vancomycin (GtfD, E) into Escherichia coli. After expression and purification, each glycosyltransferase (Gtf) was characterized for activity either with the aglycones (GtfB, E) or the glucosylated derivatives (GtfC, D) of vancomycin and teicoplanin. GtfB efficiently glucosylates vancomycin aglycone using UDP-glucose as the glycosyl donor to form desvancosaminyl-vancomycin (vancomycin pseudoaglycone), with k(cat) of 17 min(-1), but has very low glucosylation activity, < or = 0.3 min(-1), for an alternate substrate, teicoplanin aglycone. In contrast, GtfE is much more efficient at glucosylating both its natural substrate, vancomycin aglycone (k(cat) = 60 min(-1)), and an unnatural substrate, teicoplanin aglycone (k(cat) = 20 min(-1)). To test the addition of the 4-epi-vancosamine moiety by GtfC and GtfD, synthesis of UDP-beta-L-4-epi-vancosamine was undertaken. This NDP-sugar served as a substrate for both GtfC and GtfD in the presence of vancomycin pseudoaglycone (GtfC and GtfD) or the glucosylated teicoplanin scaffold, 7 (GtfD). The GtfC product was the 4-epi-vancosaminyl form of vancomycin. Remarkably, GtfD was able to utilize both an unnatural acceptor, 7, and an unnatural nucleotide sugar donor, UDP-4-epi-vancosamine, to synthesize a novel hybrid teicoplanin/vancomycin glycopeptide. These results establish the enzymatic activity of these four Gtfs, begin to probe substrate specificity, and illustrate how they can be utilized to make variant sugar forms of both the vancomycin and the teicoplanin class of glycopeptide antibiotics.     

An Invisibility Cloak Using Silver Nanowires

In this paper, we use the parameter retrieval method together with an analytical effective medium approach to design a well-performed invisible cloak, which is based on an empirical revised version of the reduced cloak. The designed cloak can be implemented by silver nanowires with elliptical cross sections embedded in a polymethyl methacrylate host. This cloak is numerically proved to be robust for both the inner hidden object as well as incoming detecting waves and is much simpler, thus easier to manufacture when compared with the earlier one proposed by Cai et al. (Nat Photon 1: 224, 2007).     

‘Green tides’ are overwhelming the coastline of our blue planet: taking the world’s largest example

A broad spectrum of events that come under the category of green tide are recognized world-wide as a response to elevated levels of seawater nutrients in coastal areas. Green tides involve a wide diversity of sites, macroalgal species, consequences, and possible causes. Here we review the effect of natural and man-induced environmental fluctuations on the frequency and apparent spread of green tides. This article highlights the need for interdisciplinary research aimed at shedding light on the basic mechanisms governing the occurrence and succession of green algae in coastal seas. This will result in more effective management and mitigation of the effects of green tides, thus safeguarding the intrinsic and commercial value of coastal marine ecosystems.     

白蜡虫碱性磷酸酶功能基团的研究

白蜡ricerus pela雌成虫经匀浆,正丁醇抽提,硫酸铵分段盐析,SephadexG-150凝胶过滤等步骤,得到比活力为136.65U/mg蛋白酶制品,用苯甲基磺酰氟、N-溴代琥珀酰亚胺、三硝基苯磺酸、二巯基苏糖醇、对氯汞苯甲酸、琥珀酸酐、溴乙酸、碘乙酸等化学修饰剂在一定条件下选择修饰白蜡虫碱性磷酸酶的几种氨基酸残基,并测定酶活力变化。结果表明：苯甲基磺酰氟、N-溴代琥珀酰亚胺、三硝基苯磺酸、琥珀酸酐、二巯基苏糖醇的修饰能显著抑制酶的活力,活力的降低与修饰剂的浓度有关,氯汞苯甲酸、溴乙酸、碘乙酸的修饰对酶的抑制作用影响较小。初步认为：丝氨酸、赖氨酸和色氨酸残基是白蜡虫碱性磷酸酶的必需功能基团,部分二硫键也是酶的催化功能所必需的。     

白蜡虫及其寄主植物游离氨基酸的研究

作者研究了白蜡虫越冬前后体内游离氨基酸的组成及变化 ,并通过对虫体、蜜露及被寄生植物游离氨基酸含量及百分率组成进行对比分析 ,探讨了白蜡虫对游离氨基酸的利用问题。虫体含量较高的氨基酸有丙氨酸、谷氨酸、苏氨酸、丝氨酸、缬氨酸。大部分氨基酸及其总量在越冬期下降 ,越冬以后升高 ,逐渐超过越冬前水平。虫体大量吸收的氨基酸是丙氨酸 ,利用较少的氨基酸是天门冬氨酸 ,其它氨基酸或多或少地为白蜡虫所利用。     

Different Survival of Barcelona Clinic Liver Cancer Stage C Hepatocellular Carcinoma Patients by the Extent of Portal Vein Invasion and the Type of Extrahepatic Spread

Portal vein invasion (PVI) and extrahepatic spread (ES) are two tumor-related factors that define advanced stage in the Barcelona Clinic Liver Cancer (BCLC) staging system (BCLC stage C), and the recommended first line therapy in this stage is sorafenib. However, the extent of PVI and the type of ES may affect patient prognosis as well as treatment outcome. This study analyzed survival of BCLC stage C HCC patients in order to see whether sub-classification of BCLC stage C is necessary. A total of 582 treatment naïve, BCLC stage C HCC patients [age: 54.3 ± 10.8 years, males = 494 (84.9%), hepatitis B virus (458, 78.7%)], defined by PVI and/or ES, were analyzed. Extent of PVI was divided into none, type I-segmental/sectoral branches, type II-left and/or right portal vein, and type III-main portal vein trunk. Type of ES was divided into nodal and distant metastasis. The extent of PVI and type of ES were independent factors for survival. When patients were sub-classified according to the extent of PVI and type of ES, the median survival was significantly different [11.7 months, 5.7 months, 4.9 months and 2.3 months for C1 (PVI-O/I without distant ES), C2 (PVI-II/III without distant ES), C3 (PVI-0/I with distant ES), and C4 (PVI-II/III with distant ES), respectively, P = 0.01]. Patients’ survival was different according to the treatment modality in each sub-stage. Sub-classification of BCLC stage C according to the extent of PVI and type of ES resulted in a better prediction of survival. Also, different outcome was observed by treatment modalities in each sub-stage. Sub-classification of BCLC stage C is required to minimize heterogeneity within the same tumor stage, that will help better predict survival and to select optimal treatment strategies.     

Neurexin-1, a presynaptic adhesion molecule, localizes at the slit diaphragm of the glomerular podocytes in kidneys

The slit diaphragm connecting the adjacent foot processes of glomerular epithelial cells (podocytes) is the final barrier of the glomerular capillary wall and serves to prevent proteinuria. Podocytes are understood to be terminally differentiated cells and share some common features with neurons. Neurexin is a presynaptic adhesion molecule that plays a role in synaptic differentiation. Although neurexin has been understood to be specifically expressed in neuronal tissues, we found that neurexin was expressed in several organs. Several forms of splice variants of neurexin-1α were detected in the cerebrum, but only one form of neurexin-1α was detected in glomeruli. Immunohistochemical study showed that neurexin restrictedly expressed in the podocytes in kidneys. Dual-labeling analyses showed that neurexin was colocalized with CD2AP, an intracellular component of the slit diaphragm. Immunoprecipitation assay using glomerular lysate showed that neurexin interacted with CD2AP and CASK. These observations indicated that neurexin localized at the slit diaphragm area. The staining intensity of neurexin in podocytes was clearly lowered, and their staining pattern shifted to a more discontinuous patchy pattern in the disease models showing severe proteinuria. The expression and localization of neurexin in these models altered more clearly and rapidly than that of other slit diaphragm components. We propose that neurexin is available as an early diagnostic marker to detect podocyte injury. Neurexin coincided with nephrin, a key molecule of the slit diaphragm detected in a presumptive podocyte of the developing glomeruli and in the glomeruli for which the slit diaphragm is repairing injury. These observations suggest that neurexin is involved in the formation of the slit diaphragm and the maintenance of its function.     

Further spread of and domination by Bemisia tabaci (Hemiptera: Aleyrodidae) biotype Q on field crops in China

The sweetpotato whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae), causes severe crop losses to many crops. The worst of these losses are often associated with the invasion and establishment of biotypes B and Q of this pest. Previous research in 2007 showed that biotype Q occurred with other biotypes in most field populations in China. To determine the current status of the biotype composition in the field, an extensive survey covering mainly eastern parts of China was conducted in 2009. Using polymerase chain reaction primers specific for the mitochondrial cytochrome oxidase I of biotypes B and Q and gene sequencing, we determined the biotypes composition in 61 whitefly populations and their distribution across 19 provinces in China. Our research revealed that only biotypes B and Q have been found in the field in 2009 in China. Among them, biotype Q was dominant in 44 locations (100.0%) and biotype B was dominant in 17 locations (100.0%). The current survey indicates that biotype Q has rapidly displaced biotype B in most locations in China.