Ligation of Signal Inhibitory Receptor on Leukocytes-1 Suppresses the Release of Neutrophil Extracellular Traps in Systemic Lupus Erythematosus

Neutrophil extracellular traps (NETs) have been implicated in the pathogenesis of systemic Lupus erythematosus (SLE), since netting neutrophils release potentially immunogenic autoantigens including histones, LL37, human neutrophil peptide (HNP), and self-DNA. In turn, these NETs activate plasmacytoid dendritic cells resulting in aggravation of inflammation and disease. How suppression of NET formation can be targeted for treatment has not been reported yet. Signal Inhibitory Receptor on Leukocytes-1 (SIRL-1) is a surface molecule exclusively expressed on phagocytes. We recently identified SIRL-1 as a negative regulator of human neutrophil function. Here, we determine whether ligation of SIRL-1 prevents the pathogenic release of NETs in SLE. Peripheral blood neutrophils from SLE patients with mild to moderate disease activity and healthy donors were freshly isolated. NET release was assessed spontaneously or after exposure to anti-neutrophil antibodies or plasma obtained from SLE patients. The formation of NETs was determined by microscopic evaluation using DNA dyes and immunostaining of NET components, as well as by live cell imaging. We show that SLE neutrophils spontaneously release NETs. NET formation is enhanced by stimulation with antibodies against LL37. Inhibition of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and MEK-ERK signaling prevents NET release in response to these antibodies. Signaling via the inhibitory receptor SIRL-1 was induced by ligation with anti-SIRL-1 specific antibodies. Both spontaneous and anti-neutrophil antibody-induced NET formation is suppressed by engagement of SIRL-1. Furthermore, NET release by healthy neutrophils exposed to SLE plasma is inhibited by SIRL-1 ligation. Thus, SIRL-1 engagement can dampen spontaneous and anti-neutrophil antibody-induced NET formation in SLE, likely by suppressing NAPDH oxidase and MEK-ERK activity. Together, these findings reveal a regulatory role for SIRL-1 in NET formation, potentially providing a novel therapeutic target to break the pathogenic loop in SLE.     

Lack of structure in the gene pool of the highly polyploid ornamental chrysanthemum

Selection of clonally propagated chrysanthemums is mostly performed on F1 hybrids using phenotypic characteristics without the use of molecular information. We applied 448 amplified fragment length polymorphism markers to a set of 81 accessions, mainly from the European gene pool, covering the different horticultural types (cut, pot and garden varieties) and originating from the most important European chrysanthemum breeders. The average pairwise genetic similarity of 0.69 was moderate to rather high. Neighbour-joining clustering resulted in no grouping of the accessions, either by their common origin or their horticultural type, or by similarities in important phenotypic characteristics. The structure of the dendrogram could not be supported by bootstrap analysis. Furthermore, network analysis using SplitsTree, principal coordinate analysis via DARwin or analysis of the population with structure did not differentiate reliable and invariable clusters. Therefore, we tested the marker saturation by plotting the mean coefficient of variation for every pairwise similarity of the bootstrap analysis against the different numbers of markers. We showed that the number of markers is sufficient for a precise estimate of genetic similarity and that the lack of bootstrap support is not due to a low genetic diversity or a lack of marker information, but most likely resulted from the breeding history of the cultivars, involving repeated backcrosses and the exchange of genotypes between breeders.     

Über ein symbiotisches Phänomen zwischen ammonverarbeitenden Darmbakterien und einem apathogenen gramnegativen Bakterium in synthetischer Nährlösung

Zusammenfassung Es wird ein gemeinsames Wachstum von ammonstarken monosaccharidspaltenden Darmbakterien mit einem nicht näher definierten gramnegativen Verunreinigungskeim in synthetischer 1%iger Koser-Saccharose-Lösung beschrieben. Da die fortlaufende Kultivierung unbegrenzt gelang, handelte es sich um eine echte Vermehrung, die keinem der beiden Keime in dieser Form als Reinkultur möglich war. Es werden Angaben über verschiedene Stoffwechselleistungen der Reinkulturen bzw. im symbiotischen System gegeben.     

The effect of body temperature on the hunting response of the middle finger skin temperature

The relationship between body temperature and the hunting response (intermittent supply of warm blood to cold exposed extremities) was quantified for nine subjects by immersing one hand in 8°C water while their body was either warm, cool or comfortable. Core and skin temperatures were manipulated by exposing the subjects to different ambient temperatures (30, 22, or 15°C), by adjusting their clothing insulation (moderate, light, or none), and by drinking beverages at different temperatures (43, 37 and 0°C). The middle finger temperature (T _fi) response was recorded, together with ear canal (T _ear), rectal (T _re), and mean skin temperature (Tˉ _sk). The induced mean T _ear changes were −0.34 (0.08) and +0.29 (0.03)°C following consumption of the cold and hot beverage, respectively. Tˉ _sk ranged from 26.7 to 34.5°C during the tests. In the warm environment after a hot drink, the initial finger temperature (T _fi,base) was 35.3 (0.4)°C, the minimum finger temperature during immersion (T _fi,min) was 11.3 (0.5)°C, and 2.6 (0.4) hunting waves occurred in the 30-min immersion period. In the neutral condition (thermoneutral room and beverage) T _fi,base was 32.1 (1.0)°C, T _fi,min was 9.6 (0.3)°C, and 1.6 (0.2) waves occurred. In the cold environment after a cold drink, these values were 19.3 (0.9)°C, 8.7 (0.2)°C, and 0.8 (0.2) waves, respectively. A colder body induced a decrease in the magnitude and frequency of the hunting response. The total heat transferred from the hand to the water, as estimated by the area under the middle finger temperature curve, was also dependent upon the induced increase or decrease in T _ear and Tˉ _sk. We conclude that the characteristics of the hunting temperature response curve of the finger are in part determined by core temperature and Tˉ _sk. Both T _fi,min and the maximal finger temperature during immersion were higher when the core temperature was elevated; Tˉ _sk seemed to be an important determinant of the onset time of the cold-induced vasodilation response. Accepted: 29 April 1997     

短柄五加开花及传粉生物学研究

本文对短柄五加（Ｅｌｅｕｔｈｅｒｏｃｏｃｃｕｓｂｒａｃｈｙｐｕｓ）的花期物候、开花式样、访花昆虫种类、访花行为及访花频率进行了观察,对花粉活力、柱头可授性、花粉胚珠比以及传粉效果和繁育系统做了检测。初步结果表明,短柄五加以根茎进行无性繁殖,１个居群为１个无性系。虽自交亲和,但昆虫的访花活动可显著提高座果率。昆虫传粉主要在无性系内异花间进行,属于广义的自花传粉。传粉者为多种不同的昆虫,包括马蜂和胡蜂在内的蜂类、蝇类和甲虫。其花期物候、花粉活力、柱头可授期和蜜汁分泌期等特征使其能够适应环境,从而获得较高的座果率。平均座果率为６５％,饱满种子率为４５．５％。自然条件下未发现实生苗,广义的自花传粉导致的种子质量低下可能是其原因,也是限制短柄五加分布范围的重要因素。     

Genetic Control of Capsid Length in Bacteriophage T4 I. Isolation and Preliminary Description of Four New Mutants

Four new mutants are described whose phenotypic expression affects the length of the head of bacteriophage T4D. All mutants produce some phenotypically normal phage particles. Mutant pt21-34 also produces at least two size classes of phage particle which have heads that are shorter than normal. The other three mutants, ptg19-2, ptg19-80, and ptg191, produce, in addition to phages with normal and with shorter-than-normal heads, giant phages with heads from 1.5 to at least 10 times the normal length. All mutations are clustered near gene 23. Giant phage particles have the following properties: they are infectious and contain and inject multiple genomes as a single continuous bihelical DNA molecule of greater-than-unit length. Their frequency, relative to the total plaque-former population, increases late in the infectious cycle. They have a normal diameter, variable length, and a buoyant density range in CsCl from equal to slightly greater than that of normal phage. The arrangement of capsomers is visible in the capsids, which are composed of cleaved gene 23 protein.