Publications by authors named "Holden M"

Intrinsically disordered proteins, such as tau protein, adopt a variety of conformations in solution, complicating solution-phase structural studies. We employed an anti-Brownian electrokinetic (ABEL) trap to prolong measurements of single tau proteins in solution. Once trapped, we recorded the fluorescence anisotropy to investigate the diversity of conformations sampled by the single molecules.

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Pep-1 is a cell-penetrating peptide that represents a powerful strategy for delivering large, hydrophilic therapeutic molecules into cells. Model membranes, such as lipid vesicles and planar bilayers, have been useful for investigating the direct translocation of cell-penetrating peptides. Here, we present a droplet interface bilayer-based approach to quantify pep-1-mediated β-galactosidase translocation.

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Melioidosis is a tropical disease caused by the bacterium . Outbreaks are uncommon and can generally be attributed to a single point source and strain. We used whole-genome sequencing to analyse isolates collected from an historical 2-year long case cluster that occurred in a remote northern Australian indigenous island community, where infections were previously linked to a contaminated communal water supply.

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Antibiotic resistance forms a serious threat to the health of hospitalised patients, rendering otherwise treatable bacterial infections potentially life-threatening. A thorough understanding of the mechanisms by which resistance spreads between patients in different hospitals is required in order to design effective control strategies. We measured the differences between bacterial populations of 52 hospitals in the United Kingdom and Ireland, using whole-genome sequences from 1085 MRSA clonal complex 22 isolates collected between 1998 and 2012.

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Staphylococcus aureus is an opportunistic pathogen and variable component of the human microbiota. A characteristic of atopic eczema (AE) is colonization by S. aureus, with exacerbations associated with an increased bacterial burden of the organism.

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Iceland is free of the major infectious diseases of horses. However, in 2010 an epidemic of respiratory disease of unknown cause spread through the country's native horse population of 77,000. Microbiological investigations ruled out known viral agents but identified the opportunistic pathogen subsp.

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The fabrication of DNA arrays directly on aminolyzed sheets of poly(ethylene terephthalate) (PET) is described. Array surfaces typically employ bifunctional linkers or layers of covalently attached polymers to provide substrate hydroxy groups as synthesis attachment points. An amine treatment is used here to expose hydroxy groups on films of PET.

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Background: The spread of drug-resistant bacterial pathogens poses a major threat to global health. It is widely recognised that the widespread use of antibiotics has generated selective pressures that have driven the emergence of resistant strains. Methicillin-resistant Staphylococcus aureus (MRSA) was first observed in 1960, less than one year after the introduction of this second generation beta-lactam antibiotic into clinical practice.

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Therapeutic Residential Care for Children and Youth: A Consensus Statement of the International Work Group on Therapeutic Residential Care. In many developed countries around the world residential care interventions for children and adolescents have come under increasing scrutiny. Against this background an international summit was organised in England (spring 2016) with experts from 13 countries to reflect on therapeutic residential care (TRC).

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Consumer demand for plant and animal products threatens many populations with extinction. The anthropogenic Allee effect (AAE) proposes that such extinctions can be caused by prices for wildlife products increasing with species rarity. This price-rarity relationship creates financial incentives to extract the last remaining individuals of a population, despite higher search and harvest costs.

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Background: Methicillin-resistant Staphylococcus aureus (MRSA) is the most common healthcare-associated multidrug-resistant organism. Despite the interconnectedness between acute care hospitals (ACHs) and intermediate- and long-term care facilities (ILTCFs), the transmission dynamics of MRSA between healthcare settings is not well understood.

Methods: We conducted a cross-sectional study in a network comprising an ACH and 5 closely affiliated ILTCFs in Singapore.

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Background: Streptococcus agalactiae (group B Streptococcus [GBS]) has not been described as a foodborne pathogen. However, in 2015, a large outbreak of severe invasive sequence type (ST) 283 GBS infections in adults epidemiologically linked to the consumption of raw freshwater fish occurred in Singapore. We attempted to determine the scale of the outbreak, define the clinical spectrum of disease, and link the outbreak to contaminated fish.

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Background: Recent large-scale undertakings such as ENCODE and Roadmap Epigenomics have generated experimental data mapped to the human reference genome (as genomic tracks) representing a variety of functional elements across a large number of cell types. Despite the high potential value of these publicly available data for a broad variety of investigations, little attention has been given to the analytical methodology necessary for their widespread utilisation.

Findings: We here present a first principled treatment of the analysis of collections of genomic tracks.

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Background: A group A Streptococcus (GAS) lineage of genotype emm3, sequence type 15 (ST15) was associated with a 6 month upsurge in invasive GAS disease in the UK. The epidemic lineage (Lineage C) had lost 2 typical emm3 prophages, Φ315.1 and Φ315.

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Article Synopsis
  • The study investigates the role of the cortical actin cytoskeleton in the organization and dynamics of the plasma membrane in T cells, using advanced imaging techniques.
  • Researchers found that both the actin cortex and the plasma membrane flow retrograde toward the synapse center in a coordinated manner.
  • The flow of actin is linked to the protein α-actinin, with the loss of this protein affecting the direction of plasma membrane flow, suggesting a mechanism for the movement of signaling molecules within T cells.
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Background: Recruitment to randomised prevention trials is challenging, not least for intracerebral haemorrhage (ICH) associated with antithrombotic drug use. We investigated reasons for not recruiting apparently eligible patients at hospital sites that keep screening logs in the ongoing REstart or STop Antithrombotics Randomised Trial (RESTART), which seeks to determine whether to start antiplatelet drugs after ICH.

Method: By the end of May 2015, 158 participants had been recruited at 108 active sites in RESTART.

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Melioidosis, caused by the highly recombinogenic bacterium , is a disease with high mortality. Tracing the origin of melioidosis outbreaks and understanding how the bacterium spreads and persists in the environment are essential to protecting public and veterinary health and reducing mortality associated with outbreaks. We used whole-genome sequencing to compare isolates from a historical quarter-century outbreak that occurred between 1966 and 1991 in the Avon Valley, Western Australia, a region far outside the known range of endemicity.

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Article Synopsis
  • USA300 is a type of bacteria that often causes skin infections in the USA and has developed resistance to certain antibiotics.
  • Researchers studied 191 samples of this bacteria from different places and times between 2004 and 2010 to see how it changed over the years.
  • They found that the bacteria became more diverse and that some newer samples had different characteristics compared to older ones, indicating that it is evolving.
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Visualization is frequently used to aid our interpretation of complex datasets. Within microbial genomics, visualizing the relationships between multiple genomes as a tree provides a framework onto which associated data (geographical, temporal, phenotypic and epidemiological) are added to generate hypotheses and to explore the dynamics of the system under investigation. Selected static images are then used within publications to highlight the key findings to a wider audience.

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The aim of this study was to evaluate the correlation between antimicrobial resistance (AMR) profiles of 96 clinical isolates of , an important porcine respiratory pathogen, and the identification of AMR genes in whole genome sequence (wgs) data. Susceptibility of the isolates to nine antimicrobial agents (ampicillin, enrofloxacin, erythromycin, florfenicol, sulfisoxazole, tetracycline, tilmicosin, trimethoprim, and tylosin) was determined by agar dilution susceptibility test. Except for the macrolides tested, elevated MICs were highly correlated to the presence of AMR genes identified in wgs data using ResFinder or BLASTn.

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