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The aetiology and cell biology of inflammation in sexually transmitted bacterial infections
No full textIn the presented study, clinical samples were obtained in order to investigate host responses (such as cytokine production) and pathogen factors (strain genotype, infectious load) that may determine the clinical manifestations of gonococcal infection. However, the prevalence of N, gonorrhoeae - as determined by polymerase chain reaction (PCR) assays - was 0% in two Thai study populations [480 asymptomatic male students and 90 mucopurulent crevices (MPC) patients], and 5.5% (all porin genotype porB1b) in 348 Sir Lankan female sexually transmitted disease (STD) clinic attendees. This precluded a patient based study of the immunopathology of gonorrhoea. In contrast, Chlamydia trachomatis infection was present in 4.2% of the Thai students, 25.6% of the Sri Lankan women, and 26.7% of the Thai MPC patients.Neither gonococcal nor chlamydial infection was significantly associated with cervical abnormalities in the Sri Lankan population, nor was the presence or infectious load of chlamydiae linked to the severity of MPC in Thai women. However, quantitative TaqMan® PCR assays revealed that in the latter group, women who shed large numbers of chlamydiae from the endocervix were more likely to have chlamydial urethritis or endometritis than were women who shed few or no organisms. Endocervical cytokine levels (measured by time-resolved fluorescence immunoassays) were not associated with the presence or load of chlamydiae; but secretion of interleukin (IL)-1β, IL-6 and IL-8 was increased in patients with overt cervical mucopus.The inflammatory cytokine response to an STD pathogen was further explored in vitro, using N. gonorrhoeae strain P9 and human mononuclear phagocytes resembling 'tissue-resident' macrophages.</p
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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Hyperendemic <i>Chlamydia trachomatis</i> sexually transmitted infections among females represent a high burden of asymptomatic disease and health disparity among Pacific Islanders in Fiji
Get PDFBackgroundChlamydia trachomatis is the most common bacterial sexually transmitted infection worldwide with some of the highest prevalence rates among Pacific Island Countries where syndromic management is practiced. However, little is known about the true prevalence and risk indicators for infection among neglected populations in these countries that suffer from health disparities.Methodology/Principal findingsConsecutive sampling was used to enroll sexually active females, aged 18–40 years, attending 12 Fijian Ministry of Health and Medical Services Health Centers and outreach locations from February to December, 2018. A Behavioral Surveillance Survey was administered to assess risk indicators for infection. Signs and symptoms were recorded, and vaginal swabs were tested for C. trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Candida and bacterial vaginosis. Bivariate and multivariate logistic regression analyses were performed using R-Studio. Of 577 participants, 103 (17.85%) were infected with C. trachomatis of whom 80% were asymptomatic and only 11 met criteria for syndromic management; 38.8% of infected women were 18–24 years old with a prevalence of 30.5%. 91.7% of participants intermittently or did not use condoms. C. trachomatis infection was associated with iTaukei ethnicity (OR 21.41 [95% CI: 6.38–133.53]); two lifetime partners (OR 2.12 [95% CI: 1.08–4.18]); and N. gonorrhoeae co-infection (OR 9.56 [95% CI: 3.67–28.15]) in multivariate analyses.ConclusionsA disproportionately high burden of C. trachomatis is present among young asymptomatic women in Fiji of iTaukei ethnicity despite the low number of lifetime partners. Syndromic management and lack of barrier contraceptives contribute to hyperendemic levels. Strategic STI education and screening of at-risk adolescents, young women, and their partner(s) with appropriate treatment are urgently needed to control the epidemic.</div
A mouse infection model and long-term lymphatic endothelium co-culture system to evaluate drugs against adult Brugia malayi
Get PDFThe development of new drugs targeting adult-stage lymphatic filarial nematodes is hindered by the lack of a robust long-term in vitro culture model. Testing potential direct-acting and anti-Wolbachia therapeutic candidates against adult lymphatic filariae in vitro requires their propagation via chronic infection of gerbils. We evaluated Brugia malayi parasite burden data from male Mongolian gerbils compared with two immune-deficient mouse strains highly susceptible to B. malayi: CB.17 Severe-Combined Immmuno-Deficient (SCID) and interleukin-4 receptor alpha, interleukin-5 double knockout (IL-4Rα-/-IL-5-/-) mice. Adult worms generated in IL-4Rα-/-IL-5-/- mice were tested with different feeder cells (human embryonic kidney cells, human adult dermal lymphatic endothelial cells and human THP-1 monocyte differentiated macrophages) and comparative cell-free conditions to optimise and validate a long-term in vitro culture system. Cultured parasites were compared against those isolated from mice using motility scoring, metabolic viability assay (MTT), ex vivo microfilariae release assay and Wolbachia content by qPCR. A selected culture system was validated as a drug screen using reference anti-Wolbachia (doxycycline, ABBV-4083 / flubentylosin) or direct-acting compounds (flubendazole, suramin). BALB/c IL-4Rα-/-IL-5-/- or CB.17 SCID mice were superior to Mongolian gerbils in generating adult worms and supporting in vivo persistence for periods of up to 52 weeks. Adult females retrieved from BALB/c IL-4Rα-/-IL-5-/- mice could be cultured for up to 21 days in the presence of a lymphatic endothelial cell co-culture system with comparable motility, metabolic activity and Wolbachia titres to those maintained in vivo. Drug studies confirmed significant Wolbachia depletions or direct macrofilaricidal activities could be discerned when female B. malayi were cultured for 14 days. We therefore demonstrate a novel methodology to generate adult B. malayi in vivo and accurately evaluate drug efficacy ex vivo which may be adopted for drug screening with the dual benefit of reducing overall animal use and improving anti-filarial drug development
Interactions of Neisseria gonorrhoeae with mature human macrophage opacity proteins influence production of proinflammatory cytokines
No full textThe pathological features of ascending gonococcal infection suggest that proinflammatory mediators secreted by tissue-resident macrophages are important components of the host response. Challenge of fully differentiated, mature macrophages with variants of Neisseria gonorrhoeae strain P9 or purified bacterial surface components (pili, lipooligosaccharide, and outer membrane vesicles) induced the secretion of interleukin 6 (IL-6), tumor necrosis factor alpha, growth-related protein alpha, macrophage inflammatory protein 1alpha (MIP-1alpha), and RANTES cytokines but had no effect on IL-8 production. No secretion of IL-1beta, epithelial-derived neutrophil attractant 78, granulocyte-macrophage colony-stimulating factor, IL-10, or IL-12 cytokines was observed. Notably, the P9-Opa(b) protein, in comparison to P9-Opa(a), increased the association of gonococci with macrophages and elevated the secretion of cytokines. Thus, variation in Opa protein expression by the gonococcus may be a determining factor in the severity of pelvic inflammatory disease
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Brugia malayi microfilariae adhere to human vascular endothelial cells in a C3-dependent manner
Get PDFBrugia malayi causes the human tropical disease, lymphatic filariasis. Microfilariae (Mf) of this nematode live in the bloodstream and are ingested by a feeding mosquito vector. Interestingly, in a remarkable co-evolutionary adaptation, Mf appearance in the peripheral blood follows a circadian periodicity and reaches a peak when the mosquito is most likely to feed. For the remaining hours, the majority of Mf sequester in the lung capillaries. This circadian phenomenon has been widely reported and is likely to maximise parasite fitness and optimise transmission potential. However, the mechanism of Mf sequestration in the lungs remains largely unresolved. In this study, we demonstrate that B. malayi Mf can, directly adhere to vascular endothelial cells under static conditions and under flow conditions, they can bind at high (but not low) flow rates. High flow rates are more likely to be experienced diurnally. Furthermore, a non-periodic nematode adheres less efficiently to endothelial cells. Strikingly C3, the central component of complement, plays a crucial role in the adherence interaction. These novel results show that microfilariae have the ability to bind to endothelial cells, which may explain their sequestration in the lungs, and this binding is increased in the presence of inflammatory mediators
Characterisation of prophages from Wolbachia symbionts maintained in insect cell culture systems.
Get PDFWolbachia is a bacterial endosymbiont with a profound impact on the ecology of many medically or economically significant insect species. As invasive arthropods and their associated epidemiology become increasingly important, the genetic manipulation of Wolbachia could have huge implications for pest and disease control. To date, conventional approaches such as CRISPR-based techniques have not proven successful, chiefly due to Wolbachia’s obligate endosymbiosis. Additionally, Wolbachia’s abundance of mobile and repetitive elements complicate sequencing and whole-genome assembly.
This study investigates the associated bacteriophage WO as an alternate route for transformation. Long-read metagenomic sequencing by Oxford Nanopore Technologies’ MinION, corrected by short-read high-accuracy Illumina sequencing, was used to generate circularised single-contig genome assemblies for the supergroup B Wolbachia strains wStri (1.75 Mb) and wBol-1b (1.47 Mb), cultured in transinfected SF9 and C6/36 host cells. Both represent the most complete genome of each strain to date. Prophage regions were identified and characterised with a variety of homology-based approaches. Transcription from within these elements was confirmed by RNA-Seq performed with reference to the new assemblies, and differential expression from prophage regions analysed between hosts. Prophage regions were found to be less transcriptionally active overall than the rest of the genome, but more likely to be differentially expressed, suggesting context-dependent regulation. Phage structural proteins were highly expressed in wStri, absent critical tail components. This may indicate production of non-infectious virions that nonetheless may have effector roles.
A variety of gene editing and transgenic methodologies were investigated, with a focus on wStri as the strain with the most diverse and complete prophage. The most ambitious approach was Transformation Associated Recombination (TAR) cloning of sections of the Wolbachia genome. While unsuccessful, the attempt established a methodology and identified quality of genomic DNA extraction as a limiting factor. An alternative strategy for transformation was also investigated, inoculating Wolbachia cultures with Escherichia coli carrying conjugative plasmids, but without success. Additionally, wStri prophage genes encoding RuvC resolvases were transformed into E. coli for functional characterisation, identifying a discriminating cleavage action unlike typical viral resolvases.
This study resulted in the improved genomic assembly and characterisation of the wStri and wBol1-b strains of Wolbachia, and the first transcriptomic analysis of supergroup B Wolbachia. It will support future exploration of phage and prophage in parasitic strains and lays groundwork for gene editing in Wolbachia
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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