Structure and rational engineering of the PglX methyltransferase and specificity factor for BREX phage defence.

Bacteria have evolved a broad range of systems that provide defence against their viral predators, bacteriophages. Bacteriophage Exclusion (BREX) systems recognise and methylate 6 bp non-palindromic motifs within the host genome, and prevent replication of non-methylated phage DNA that encodes these same motifs. How BREX recognises cognate motifs has not been fully understood.

Diverse Durham collection phages demonstrate complex BREX defense responses.

Bacteriophages (phages) outnumber bacteria ten-to-one and cause infections at a rate of 10 per second. The ability of phages to reduce bacterial populations makes them attractive alternative antibacterials for use in combating the rise in antimicrobial resistance. This effort may be hindered due to bacterial defenses such as Bacteriophage Exclusion (BREX) that have arisen from the constant evolutionary battle between bacteria and phages.

Evasion of toll-like receptor recognition by is mediated via population level regulation of flagellin production.

Uropathogenic is a major cause of urinary tract infections. Analysis of the innate immune response in immortalized urothelial cells suggests that the bacterial flagellar subunit, flagellin, is key in inducing host defenses. A panel of 48 clinical uro-associated .

Crystal structure of the BREX phage defence protein BrxA.

Bacteria are constantly challenged by bacteriophage (phage) infection and have developed multitudinous and varied resistance mechanisms. Bacteriophage Exclusion (BREX) systems protect from phage infection by generating methylation patterns at non-palindromic 6 bp sites in host bacterial DNA, to distinguish and block replication of non-self DNA. Type 1 BREX systems are comprised of six conserved core genes.

A widespread family of WYL-domain transcriptional regulators co-localizes with diverse phage defence systems and islands.

Bacteria are under constant assault by bacteriophages and other mobile genetic elements. As a result, bacteria have evolved a multitude of systems that protect from attack. Genes encoding bacterial defence mechanisms can be clustered into 'defence islands', providing a potentially synergistic level of protection against a wider range of assailants.

Study protocol: Minimum effective low dose: anti-human thymocyte globulin (MELD-ATG): phase II, dose ranging, efficacy study of antithymocyte globulin (ATG) within 6 weeks of diagnosis of type 1 diabetes.

Introduction: Type 1 diabetes (T1D) is a chronic autoimmune disease, characterised by progressive destruction of the insulin-producing β cells of the pancreas. One immunosuppressive agent that has recently shown promise in the treatment of new-onset T1D subjects aged 12-45 years is antithymocyte globulin (ATG), Thymoglobuline, encouraging further exploration in lower age groups.

Methods And Analysis: Minimal effective low dose (MELD)-ATG is a phase 2, multicentre, randomised, double-blind, placebo-controlled, multiarm parallel-group trial in participants 5-25 years diagnosed with T1D within 3-9 weeks of planned treatment day 1.

The phage defence island of a multidrug resistant plasmid uses both BREX and type IV restriction for complementary protection from viruses.

Bacteria have evolved a multitude of systems to prevent invasion by bacteriophages and other mobile genetic elements. Comparative genomics suggests that genes encoding bacterial defence mechanisms are often clustered in 'defence islands', providing a concerted level of protection against a wider range of attackers. However, there is a comparative paucity of information on functional interplay between multiple defence systems.

Isolation and Characterisation of Bacteriophages with Activity against Invasive Non-Typhoidal Causing Bloodstream Infection in Malawi.

In recent years, novel lineages of invasive non-typhoidal (iNTS) serovars Typhimurium and Enteritidis have been identified in patients with bloodstream infection in Sub-Saharan Africa. Here, we isolated and characterised 32 phages capable of infecting . Typhimurium and .

Anticancer Ruthenium Complexes with HDAC Isoform Selectivity.

The histone deacetylase (HDAC) enzymes have emerged as an important class of molecular targets in cancer therapy, with five inhibitors in clinical use. Recently, it has been shown that a lack of selectivity between the 11 Zn-dependent HDAC isoforms may lead to unwanted side-effects. In this paper, we show that piano stool Ru complexes can act as HDAC inhibitors, and variation in the capping arene leads to differences in HDAC isoform selectivity.

Growth rate control of flagellar assembly in Escherichia coli strain RP437.

The flagellum is a rotary motor that enables bacteria to swim in liquids and swarm over surfaces. Numerous global regulators control flagellar assembly in response to cellular and environmental factors. Previous studies have also shown that flagellar assembly is affected by the growth-rate of the cell.

Detection of Citrus leprosis virus C using specific primers and TaqMan probe in one-step real-time reverse-transcription polymerase chain reaction assays.

Citrus leprosis virus C (CiLV-C), a causal agent of the leprosis disease in citrus, is mostly present in the South and Central America and spreading toward the North America. To enable better diagnosis and inhibit the further spread of this re-emerging virus a quantitative (q) real-time reverse transcription polymerase chain reaction (qRT-PCR) assay is needed for early detection of CiLV-C when the virus is present in low titer in citrus leprosis samples. Using the genomic sequence of CiLV-C, specific primers and probe were designed and synthesized to amplify a 73 nt amplicon from the movement protein (MP) gene.

Immunodiagnosis of Citrus leprosis virus C using a polyclonal antibody to an expressed putative coat protein.

Citrus leprosis virus C (CiLV-C), a causal agent for citrus leprosis disease, is present in South and Central America and is a threat for introduction into the U.S. citrus industry.

A novel virus of the genus Cilevirus causing symptoms similar to citrus leprosis.

Citrus leprosis in Colombia was previously shown to be caused by cytoplasmic Citrus leprosis virus (CiLV-C). In 2011, enzyme-linked immunosorbent assay and reverse-transcription polymerase chain reaction (RT-PCR)-based diagnostic methods failed to identify CiLV-C from citrus samples with symptoms similar to citrus leprosis; however, virions similar to CiLV-C were observed in the cytoplasm of the symptomatic leaves by transmission electron microscopy. Furthermore, the causal organism was transmitted by the false spider mite, Brevipalpus phoenicis, to healthy citrus seedlings.

First Report of Guignardia citricarpa Associated with Citrus Black Spot on Sweet Orange (Citrus sinensis) in North America.

In March 2010, citrus black spot symptoms were observed on sweet orange trees in a grove near Immokalee, FL. Symptoms observed on fruit included hard spot, cracked spot, and early virulent spot. Hard spot lesions were up to 5 mm, depressed with a chocolate margin and a necrotic, tan center, often with black pycnidia (140 to 200 μm) present.

Contamination skin doses and attenuation of radiation by clothing.

The potential operating environment following an attack using CBRN (chemical, biological, radiological, nuclear) materials has led to design work aiming to reduce the physiological burden of protective clothing, while maintaining satisfactory levels of chemical protection. In this paper, we review the radiological protection provided by these lighter, thinner clothing options. Monte Carlo modelling has been used to determine the contribution to skin dose from both beta and gamma radiation from four sources, each with different emission characteristics.

In-phantom characterisation studies at the Birmingham Accelerator-Generated epIthermal Neutron Source (BAGINS) BNCT facility.

A broad experimental campaign to validate the final epithermal neutron beam design for the BNCT facility constructed at the University of Birmingham concluded in November 2003. The final moderator and facility designs are overviewed briefly, followed by a summary of the dosimetric methods and presentation of a small subset of the results from this campaign. The dual ionisation chamber technique was used together with foil activation to quantify the fast neutron, photon, and thermal neutron beam dose components in a large rectangular phantom exposed to the beam with a 12 cm diameter beam delimiter in place.

An investigation into the effect of denture fixatives in increasing incisal biting forces with maxillary complete dentures.

The effect of denture fixatives on incisal biting forces was investigated in five subjects wearing maxillary complete dentures. Forces required to displace new and old dentures with and without fixatives were measured up to six hours post-insertion using a force transducer. The results showed that incisal forces were greater with new dentures than with old dentures when only saliva was present.

Some clinical investigations on retention forces of maxillary complete dentures with the use of denture fixatives.

The aim of this study was to evaluate objectively and clinically the relative improvement in retention forces of complete dentures with the use of three proprietary denture fixatives. Using the UCL Retentiometer, retention forces of ill-fitting maxillary complete dentures were measured with saliva alone as the interface medium and with the use of the three test denture fixatives in edentulous subjects over a period of 6 h. Results showed that forces with saliva alone were consistently and significantly lower when compared with the forces measured at any test period with the use of the test fixatives.

Some factors affecting retention forces with the use of denture fixatives in vivo.

Using the UCL retentiometer, the effect of three proprietary denture fixatives has been clinically investigated in 14 dentate subjects wearing mucosal-borne acrylic palatal plates over periods of 6 hours. The results showed that retention forces with saliva for the well-fitting plates were significantly better when compared with the forces for the ill-fitting plates. A substantial improvement in retention on all occasions was seen for both types of plate after the application of fixatives.

An investigation of the displacement of fixed bridges and their abutments under occlusal load in Monkeys (Macaca Fascicularis).

Previous investigations have established the displacement characteristics of the teeth under axial load in monkeys (Macaca Fascicularis). The methods employed in these investigations have been used to study the displacements under occlusal load of both conventional fixed bridges and cantilever bridges, having different numbers of abutments. Under axial load there was a reduction in displacement when two teeth were splinted together to act as abutments to a fixed bridge compared with the displacements of the individual teeth.

The effect on vertical tooth mobility of extraction and immediate replacement of incisors (Macaca fascicularis).

Intrusive displacement of 7 incisors was measured before and within 3 min of extraction. A substantial increase in intrusion with recovery from loads of 4 N followed replacement of the incisors. These changes are taken to indicate that tension is an important mechanism of support in the intact periodontal ligament.

Fissure sealants as a means of prolonging longevity of amalgam restorations--an in-vitro feasibility study.

The presence of an interface gap around the periphery of old amalgam restorations in extracted teeth was confirmed by scanning electron microscopy (SEM) and light microscopy. Two fissure sealant resins (Concise White Sealant and Delton Fissure Sealant) were placed over amalgam margins in vitro and were found to occlude this gap. SEM studies permitted assessment of the integrity of the resin in the interface defect and degree of sealant penetration toward the enamel/dentine junction.

The periodontal enigma: eruption versus tooth support.

The response of the periodontal ligament is reviewed when single or repeated loads are applied to the tooth, as in mastication. A more nearly elastic recovery is produced with simulated chewing than is indicated by single semi-static applications of force. The resting position of the tooth between loadings changes with the time of day and recent loading history.