Zoonotic and other veterinary chlamydiae - an update, the role of the plasmid and plasmid-mediated transformation.

The obligate intracellular bacterial genus Chlamydia harbours species with zoonotic potential, particularly C. psittaci, causative agent of psittacosis, and C. abortus, which may lead to miscarriage in pregnant women.

Patient and public involvement in the design of an international clinical trial: real world experience.

Background: The value of patient and public involvement (PPI) during the earliest stages of clinical trial development, and prior to the award of substantive funding, is widely recognised. However, it is often under-resourced and PPI processes during this phase are rarely reported in detail. Having benefitted from seed funding to develop an international clinical trial proposal, we sought to describe and appraise PPI activities and processes that support pre-award co-development.

The Structure of : Exploring the Capsid Diversity of the .

(SpV4) is a bacteriophage of the , which packages circular ssDNA within non-enveloped T = 1 icosahedral capsids. It infects spiroplasmas, which are known pathogens of honeybees. Here, the structure of the SpV4 virion is determined using cryo-electron microscopy to a resolution of 2.

An inducible transposon mutagenesis approach for the intracellular human pathogen .

is a prolific human pathogen that can cause serious long-term conditions if left untreated. Recent developments in genetics have opened the door to conducting targeted and random mutagenesis experiments to identify gene function. In the present study, an inducible transposon mutagenesis approach was developed for using a self-replicating vector to deliver the transposon-transposase cassette - a significant step towards our ultimate aim of achieving saturation mutagenesis of the genome.

Stability of pemetrexed disodium in sodium chloride 0.9% w/v intravenous Viaflo infusion bags.

Objectives: The aim of this study was to assess the stability of pemetrexed disodium (Alimta), reconstituted in 100 mL sodium chloride 0.9% w/v intravenous infusion bags (Baxter Viaflo) at two target bag concentrations (2.0 and 13.

Progress towards an inducible, replication-proficient transposon delivery vector for .

Genetic systems have been developed for but the extremely low transformation frequency remains a significant bottleneck.  Our goal is to develop a self-replicating transposon delivery vector for which can be expanded prior to transposase induction. We made / shuttle vectors bearing the C9  transposase under control of the promoter and a novel rearrangement of the transposon with the β-lactamase gene.

Diversity in Chlamydial plasmids.

Background: Evolutionary studies have been conducted that have investigated the chromosomal variance in the genus of Chlamydia. However, no all-encompassing genus-wide comparison has been performed on the plasmid. Therefore, there is a gap in the current knowledge on Chlamydia plasmid diversity.

The Nature and Extent of Plasmid Variation in .

is an obligate intracellular pathogen of humans, causing both the sexually transmitted infection, chlamydia, and the most common cause of infectious blindness, trachoma. The majority of sequenced clinical isolates carry a 7.5-Kb plasmid, and it is becoming increasingly evident that this is a key determinant of pathogenicity.

Growth kinetics of Chlamydia trachomatis in primary human Sertoli cells.

Chlamydia trachomatis (Ct) is the leading cause of bacterial sexually transmitted infections worldwide and has been associated with male infertility. Recently, it was hypothesized that Ct may infect the epithelium of the seminiferous tubule, formed by Sertoli cells, thus leading to impaired spermatogenesis. To date, there is a lack of data on Ct infection of the seminiferous epithelium; therefore, we aimed to characterize, for the first time, an in vitro infection model of primary human Sertoli cells.

Wnt and Notch signaling govern self-renewal and differentiation in a subset of human glioblastoma stem cells.

Developmental signal transduction pathways act diversely, with context-dependent roles across systems and disease types. Glioblastomas (GBMs), which are the poorest prognosis primary brain cancers, strongly resemble developmental systems, but these growth processes have not been exploited therapeutically, likely in part due to the extreme cellular and genetic heterogeneity observed in these tumors. The role of Wnt/βcatenin signaling in GBM stem cell (GSC) renewal and fate decisions remains controversial.

Genetic Transformation of a Ocular Isolate With the Functional Tryptophan Synthase Operon Confers an Indole-Rescuable Phenotype.

is the leading cause of preventable blindness and the most common bacterial sexually transmitted infection. Different strains are associated with ocular or urogenital infections, and a proposed mechanism that may explain this tissue tropism is the active tryptophan biosynthesis pathway encoded by the genomic operon in urogenital strains. Here we describe genetic complementation studies that are essential to confirm the role of tryptophan synthase in the context of an ocular genomic background.

The Genetic Transformation of Chlamydia pneumoniae.

We demonstrate the genetic transformation of using a plasmid shuttle vector system which generates stable transformants. The equine N16 isolate harbors the 7.5-kb plasmid pCpnE1.

The plasmid revisited : new insights into growth kinetics.

Research in chlamydial genetics is challenging because of its obligate intracellular developmental cycle. systems exist that allow studies of different aspects of basic biology of chlamydiae, the murine model is one of great importance and thus an essential research tool. carries a plasmid that has a role in virulence.

Detailed molecular epidemiology of Chlamydia trachomatis in the population of Southampton attending the genitourinary medicine clinic in 2012-13 reveals the presence of long established genotypes and transitory sexual networks.

Chlamydia trachomatis is the most common sexually transmitted infection (STI) in England. Our objective was to perform a detailed survey of the molecular epidemiology of C. trachomatis in the population of Southampton UK attending the genitourinary medicine clinic (GUM) to seek evidence of sexual network activity.

ASCL1 Reorganizes Chromatin to Direct Neuronal Fate and Suppress Tumorigenicity of Glioblastoma Stem Cells.

Glioblastomas exhibit a hierarchical cellular organization, suggesting that they are driven by neoplastic stem cells that retain partial yet abnormal differentiation potential. Here, we show that a large subset of patient-derived glioblastoma stem cells (GSCs) express high levels of Achaete-scute homolog 1 (ASCL1), a proneural transcription factor involved in normal neurogenesis. ASCL1 GSCs exhibit a latent capacity for terminal neuronal differentiation in response to inhibition of Notch signaling, whereas ASCL1 GSCs do not.

Comprehensive global genome dynamics of show ancient diversification followed by contemporary mixing and recent lineage expansion.

is the world's most prevalent bacterial sexually transmitted infection and leading infectious cause of blindness, yet it is one of the least understood human pathogens, in part due to the difficulties of in vitro culturing and the lack of available tools for genetic manipulation. Genome sequencing has reinvigorated this field, shedding light on the contemporary history of this pathogen. Here, we analyze 563 full genomes, 455 of which are novel, to show that the history of the species comprises two phases, and conclude that the currently circulating lineages are the result of evolution in different genomic ecotypes.

Development and evaluation of an enzyme-linked immunosorbent assay for the detection of antibodies to a common urogenital derivative of Chlamydia trachomatis plasmid-encoded PGP3.

Background: Urogenital infection with Chlamydia trachomatis is the most commonly diagnosed sexually transmitted infection in the developed world. Accurate measurement and therefore understanding the seroprevalence of urogenital C. trachomatis infections requires a rigorously optimised and validated ELISA.

Mid-term results of ReCap/Magnum/Taperloc metal-on-metal total hip arthroplasty with mean follow-up of 7.1 years.

Introduction: Despite enthusiasm for metal-on-metal bearings, disappointing short- to mid-term outcomes has all but halted the use of this bearing articulation. This review presents mid-term results for the ReCap Magnum total hip replacement.

Patients And Methods: This prospective study evaluated 79 ReCap/Magnum/Taperloc total hip replacements with mean follow-up of 7.

Clinical Characteristics and Short-Term Outcomes of HIV Patients Admitted to an African Intensive Care Unit.

. In high-income countries, improved survival has been documented among intensive care unit (ICU) patients infected with human immune deficiency virus (HIV). There are no data from low-income country ICUs.

Inhibition of Dopamine Receptor D4 Impedes Autophagic Flux, Proliferation, and Survival of Glioblastoma Stem Cells.

Glioblastomas (GBM) grow in a rich neurochemical milieu, but the impact of neurochemicals on GBM growth is largely unexplored. We interrogated 680 neurochemical compounds in patient-derived GBM neural stem cells (GNS) to determine the effects on proliferation and survival. Compounds that modulate dopaminergic, serotonergic, and cholinergic signaling pathways selectively affected GNS growth.

Chlamydia trachomatis from Australian Aboriginal people with trachoma are polyphyletic composed of multiple distinctive lineages.

Chlamydia trachomatis causes sexually transmitted infections and the blinding disease trachoma. Current data on C. trachomatis phylogeny show that there is only a single trachoma-causing clade, which is distinct from the lineages causing urogenital tract (UGT) and lymphogranuloma venerum diseases.

Quantitative Proteomics of the Infectious and Replicative Forms of Chlamydia trachomatis.

The obligate intracellular developmental cycle of Chlamydia trachomatis presents significant challenges in defining its proteome. In this study we have applied quantitative proteomics to both the intracellular reticulate body (RB) and the extracellular elementary body (EB) from C. trachomatis.

MLL5 Orchestrates a Cancer Self-Renewal State by Repressing the Histone Variant H3.3 and Globally Reorganizing Chromatin.

Mutations in the histone 3 variant H3.3 have been identified in one-third of pediatric glioblastomas (GBMs), but not in adult tumors. Here we show that H3.