Epidemiology of and prenatal molecular distinction between invasive and colonizing group B streptococci in The Netherlands and Taiwan

The identification of markers for virulent group B streptococci (GBS) could guide prenatal prevention and intervention strategies. We compared the distribution of serotypes and potential pathogenicity islands (PPIs) between invasive and colonizing GBS. Colonizing and invasive strains from The Netherlands and Taiwan were serotyped. We used polymerase chain reaction (PCR) for the amplification of several new PPI markers. Several combinations of PPI-specific markers and serotypes were associated with invasiveness. For Dutch neonatal strains, a receiver operating characteristic (ROC) curve with serotype and five PPI markers showed an area under the curve (AUC) of 0.963 (95% confidence interval [CI] 0.935–0.99). For Taiwanese neonatal strains, serotype and four different PPI markers resulted in an ROC curve with an AUC of 0.894 (95% CI 0.826–0.963). PPI-specific and serological markers can distinguish local neonatal invasive GBS strains from colonizing ones. Apparently, there are clear regional differences in the GBS epidemiology and infection potential of clones

The proangiogenic capacity of polymorphonuclear neutrophils delineated by microarray technique and by measurement of neovascularization in wounded skin of CD18-deficient mice

Growing evidence supports the concept that polymorphonuclear neutrophils (PMN) are critically involved in inflammation-mediated angiogenesis which is important for wound healing and repair. We employed an oligonucleotide microarray technique to gain further insight into the molecular mechanisms underlying the proangiogenic potential of human PMN. In addition to 18 known angiogenesis-relevant genes, we detected the expression of 10 novel genes, namely midkine, erb-B2, ets-1, transforming growth factor receptor-beta(2) and -beta(3), thrombospondin, tissue inhibitor of metalloproteinase 2, ephrin A2, ephrin B2 and restin in human PMN freshly isolated from the circulation. Gene expression was confi rmed by the RT-PCR technique. In vivo evidence for the role of PMN in neovascularization was provided by studying neovascularization in a skin model of wound healing using CD18-deficient mice which lack PMN infi ltration to sites of lesion. In CD18-deficient animals, neo- vascularization was found to be signifi cantly compromised when compared with wild- type control animals which showed profound neovascularization within the granulation tissue during the wound healing process. Thus, PMN infiltration seems to facilitate inflammation mediated angiogenesis which may be a consequence of the broad spectrum of proangiogenic factors expressed by these cells. Copyright (c) 2006 S. Karger AG, Basel

Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: clinical and therapeutic implications

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of conditions unified by the presence of chronic childhood arthritis without an identifiable cause. Systemic JIA (sJIA) is a rare form of JIA characterised by systemic inflammation. sJIA is distinguished from other forms of JIA by unique clinical features and treatment responses that are similar to autoinflammatory diseases. However, approximately half of children with sJIA develop destructive, long-standing arthritis that appears similar to other forms of JIA. Using genomic approaches, we sought to gain novel insights into the pathophysiology of sJIA and its relationship with other forms of JIA. METHODS: We performed a genome-wide association study of 770 children with sJIA collected in nine countries by the International Childhood Arthritis Genetics Consortium. Single nucleotide polymorphisms were tested for association with sJIA. Weighted genetic risk scores were used to compare the genetic architecture of sJIA with other JIA subtypes. RESULTS: The major histocompatibility complex locus and a locus on chromosome 1 each showed association with sJIA exceeding the threshold for genome-wide significance, while 23 other novel loci were suggestive of association with sJIA. Using a combination of genetic and statistical approaches, we found no evidence of shared genetic architecture between sJIA and other common JIA subtypes. CONCLUSIONS: The lack of shared genetic risk factors between sJIA and other JIA subtypes supports the hypothesis that sJIA is a unique disease process and argues for a different classification framework. Research to improve sJIA therapy should target its unique genetics and specific pathophysiological pathways

The C-Type Lectin of the Aggrecan G3 Domain Activates Complement

Excessive complement activation contributes to joint diseases such as rheumatoid arthritis and osteoarthritis during which cartilage proteins are fragmented and released into the synovial fluid. Some of these proteins and fragments activate complement, which may sustain inflammation. The G3 domain of large cartilage proteoglycan aggrecan interacts with other extracellular matrix proteins, fibulins and tenascins, via its C-type lectin domain (CLD) and has important functions in matrix organization. Fragments containing G3 domain are released during normal aggrecan turnover, but increasingly so in disease. We now show that the aggrecan CLD part of the G3 domain activates the classical and to a lesser extent the alternative pathway of complement, via binding of C1q and C3, respectively. The complement control protein (CCP) domain adjacent to the CLD showed no effect on complement initiation. The binding of C1q to G3 depended on ionic interactions and was decreased in D2267N mutant G3. However, the observed complement activation was attenuated due to binding of complement inhibitor factor H to CLD and CCP domains. This was most apparent at the level of deposition of terminal complement components. Taken together our observations indicate aggrecan CLD as one factor involved in the sustained inflammation of the joint

DGCR8 HITS-CLIP reveals novel functions for the Microprocessor

The Drosha-DGCR8 complex (Microprocessor) is required for microRNA (miRNA) biogenesis. DGCR8 recognizes the RNA substrate, whereas Drosha functions as the endonuclease. High-throughput sequencing and crosslinking immunoprecipitation (HITS-CLIP) was used to identify RNA targets of DGCR8 in human cells. Unexpectedly, miRNAs were not the most abundant targets. DGCR8-bound RNAs also comprised several hundred mRNAs as well as snoRNAs and long non-coding RNAs. We found that the Microprocessor controls the abundance of several mRNAs as well as of MALAT-1. By contrast, DGCR8-mediated cleavage of snoRNAs is independent of Drosha, suggesting the involvement of DGCR8 in cellular complexes with other endonucleases. Interestingly, binding of DGCR8 to cassette exons, acts as a novel mechanism to regulate the relative abundance of alternatively spliced isoforms. Collectively, these data provide new insights in the complex role of DGCR8 in controlling the fate of several classes of RNAs

Genotyping of Streptococcus agalactiae (group B streptococci) isolated from vaginal and rectal swabs of women at 35-37 weeks of pregnancy

<p>Abstract</p> <p>Background</p> <p>Group B streptococci (GBS), or <it>Streptococcus agalactiae</it>, are the leading bacterial cause of meningitis and bacterial sepsis in newborns. Here we compared different culture media for GBS detection and we compared the occurrence of different genotypes and serotypes of GBS isolates from the vagina and rectum.</p> <p>Methods</p> <p><it>Streptococcus agalactiae </it>was cultured separately from both rectum and vagina, for a total of 150 pregnant women, i) directly onto Columbia CNA agar, or indirectly onto ii) Granada agar resp. iii) Columbia CNA agar, after overnight incubation in Lim broth.</p> <p>Results</p> <p>Thirty six women (24%) were colonized by GBS. Of these, 19 harbored GBS in both rectum and vagina, 9 only in the vagina and 8 exclusively in the rectum. The combination of Lim broth and subculture on Granada agar was the only culture method that detected all GBS positive women. Using RAPD-analysis, a total of 66 genotypes could be established among the 118 isolates from 32 women for which fingerprinting was carried out. Up to 4 different genotypes in total (rectal + vaginal) were found for 4 women, one woman carried 3 different genotypes vaginally and 14 women carried two 2 different genotypes vaginally. Only two subjects were found to carry strains with the same genotype, although the serotype of both of these strains was different.</p> <p>Eighteen of the 19 subjects with GBS at both sites had at least one vaginal and one rectal isolate with the same genotype.</p> <p>We report the presence of two to four different genotypes in 22 (61%) of the 36 GBS positive women and the presence of identical genotypes in both sites for all women but one.</p> <p>Conclusion</p> <p>The combination of Lim broth and subculture on Granada medium provide high sensitivity for GBS detection from vaginal and rectal swabs from pregnant women. We established a higher genotypic diversity per individual than other studies, with up to four different genotypes among a maximum of 6 isolates per individual picked. Still, 18 of the 19 women with GBS from both rectum and vagina had at least one isolate from each sampling site with the same genotype.</p

Water Quality and Herbivory Interactively Drive Coral-Reef Recovery Patterns in American Samoa

BACKGROUND: Compared with a wealth of information regarding coral-reef recovery patterns following major disturbances, less insight exists to explain the cause(s) of spatial variation in the recovery process. METHODOLOGY/PRINCIPAL FINDINGS: This study quantifies the influence of herbivory and water quality upon coral reef assemblages through space and time in Tutuila, American Samoa, a Pacific high island. Widespread declines in dominant corals (Acropora and Montipora) resulted from cyclone Heta at the end of 2003, shortly after the study began. Four sites that initially had similar coral reef assemblages but differential temporal dynamics four years following the disturbance event were classified by standardized measures of 'recovery status', defined by rates of change in ecological measures that are known to be sensitive to localized stressors. Status was best predicted, interactively, by water quality and herbivory. Expanding upon temporal trends, this study examined if similar dependencies existed through space; building multiple regression models to identify linkages between similar status measures and local stressors for 17 localities around Tutuila. The results highlighted consistent, interactive interdependencies for coral reef assemblages residing upon two unique geological reef types. Finally, the predictive regression models produced at the island scale were graphically interpreted with respect to hypothesized site-specific recovery thresholds. CONCLUSIONS/SIGNIFICANCE: Cumulatively, our study purports that moving away from describing relatively well-known patterns behind recovery, and focusing upon understanding causes, improves our foundation to predict future ecological dynamics, and thus improves coral reef management

The genetic profile of RF-positive polyarticular juvenile idiopathic arthritis (JIA) resembles adult rheumatoid arthritis (RA)

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is comprised of seven heterogeneous categories of chronic childhood arthritides. About 5% of children with JIA have rheumatoid factor (RF) positive arthritis, which phenotypically resembles adult rheumatoid arthritis (RA). Our objective was to compare and contrast the genetics of RF-positive polyarticular JIA with RA, and selected other JIA categories, to more fully understand the pathophysiological relationships of inflammatory arthropathies. METHODS: RF-positive polyarticular JIA cases (n=340) and controls (n=14,412) were genotyped using the Immunochip array. Single nucleotide polymorphisms (SNPs) were tested for association using a logistic regression model adjusting for admixture proportions. Weighted genetic risk scores (wGRS) of published RA and JIA risk loci were calculated and their ability to predict RF-positive polyarticular JIA were compared. RESULTS: As expected, the HLA region was strongly associated with RF-positive polyarticular JIA (p=5.51x10-31). Nineteen of 44 RA risk loci and 6 of 27 oligoarticular/RF-negative polyarticular JIA risk loci were associated (p70 years. CONCLUSIONS: RF-positive polyarticular JIA is genetically more similar to adult RA than to the most common JIA categories and thus appears to be a childhood-onset presentation of autoantibody positive RA. These findings suggest common disease mechanisms, which could lead to novel therapeutic targets and shared treatment strategies. This article is protected by copyright. All rights reserved