Origin of the Diversity in DNA Recognition Domains in Phasevarion Associated modA Genes of Pathogenic Neisseria and Haemophilus influenzae

Phase variable restriction-modification (R-M) systems have been identified in a range of pathogenic bacteria. In some it has been demonstrated that the random switching of the mod (DNA methyltransferase) gene mediates the coordinated expression of multiple genes and constitutes a phasevarion (phase variable regulon). ModA of Neisseria and Haemophilus influenzae contain a highly variable, DNA recognition domain (DRD) that defines the target sequence that is modified by methylation and is used to define modA alleles. 18 distinct modA alleles have been identified in H. influenzae and the pathogenic Neisseria. To determine the origin of DRD variability, the 18 modA DRDs were used to search the available databases for similar sequences. Significant matches were identified between several modA alleles and mod gene from distinct bacterial species, indicating one source of the DRD variability was via horizontal gene transfer. Comparison of DRD sequences revealed significant mosaicism, indicating exchange between the Neisseria and H. influenzae modA alleles. Regions of high inter- and intra-allele similarity indicate that some modA alleles had undergone recombination more frequently than others, generating further diversity. Furthermore, the DRD from some modA alleles, such as modA12, have been transferred en bloc to replace the DRD from different modA alleles

Chronic Viral Infection and Primary Central Nervous System Malignancy

Primary central nervous system (CNS) tumors cause significant morbidity and mortality in both adults and children. While some of the genetic and molecular mechanisms of neuro-oncogenesis are known, much less is known about possible epigenetic contributions to disease pathophysiology. Over the last several decades, chronic viral infections have been associated with a number of human malignancies. In primary CNS malignancies, two families of viruses, namely polyomavirus and herpesvirus, have been detected with varied frequencies in a number of pediatric and adult histological tumor subtypes. However, establishing a link between chronic viral infection and primary CNS malignancy has been an area of considerable controversy, due in part to variations in detection frequencies and methodologies used among researchers. Since a latent viral neurotropism can be seen with a variety of viruses and a widespread seropositivity exists among the population, it has been difficult to establish an association between viral infection and CNS malignancy based on epidemiology alone. While direct evidence of a role of viruses in neuro-oncogenesis in humans is lacking, a more plausible hypothesis of neuro-oncomodulation has been proposed. The overall goals of this review are to summarize the many human investigations that have studied viral infection in primary CNS tumors, discuss potential neuro-oncomodulatory mechanisms of viral-associated CNS disease and propose future research directions to establish a more firm association between chronic viral infections and primary CNS malignancies

Privacy and information security risks in a technology platform for home-based chronic disease rehabilitation and education

BACKGROUND: Privacy and information security are important for all healthcare services, including home-based services. We have designed and implemented a prototype technology platform for providing home-based healthcare services. It supports a personal electronic health diary and enables secure and reliable communication and interaction with peers and healthcare personnel. The platform runs on a small computer with a dedicated remote control. It is connected to the patient’s TV and to a broadband Internet. The platform has been tested with home-based rehabilitation and education programs for chronic obstructive pulmonary disease and diabetes. As part of our work, a risk assessment of privacy and security aspects has been performed, to reveal actual risks and to ensure adequate information security in this technical platform. METHODS: Risk assessment was performed in an iterative manner during the development process. Thus, security solutions have been incorporated into the design from an early stage instead of being included as an add-on to a nearly completed system. We have adapted existing risk management methods to our own environment, thus creating our own method. Our method conforms to ISO’s standard for information security risk management. RESULTS: A total of approximately 50 threats and possible unwanted incidents were identified and analysed. Among the threats to the four information security aspects: confidentiality, integrity, availability, and quality; confidentiality threats were identified as most serious, with one threat given an unacceptable level of High risk. This is because health-related personal information is regarded as sensitive. Availability threats were analysed as low risk, as the aim of the home programmes is to provide education and rehabilitation services; not for use in acute situations or for continuous health monitoring. CONCLUSIONS: Most of the identified threats are applicable for healthcare services intended for patients or citizens in their own homes. Confidentiality risks in home are different from in a more controlled environment such as a hospital; and electronic equipment located in private homes and communicating via Internet, is more exposed to unauthorised access. By implementing the proposed measures, it has been possible to design a home-based service which ensures the necessary level of information security and privacy

Phase variation of Opa proteins of Neisseria meningitidis and the effects of bacterial transformation

Opa proteins are major proteins involved in meningococcal colonization of the nasopharynx and immune interactions. Opa proteins undergo phase variation (PV) due to the presence of the 5′-CTCTT-3′ coding repeat (CR) sequence. The dynamics of PV of meningococcal Opa proteins is unknown. Opa PV, including the effect of transformation on PV, was assessed using a panel of Opa-deficient strains of Neisseria meningitidis. Analysis of Opa expression from UK disease-causing isolates was undertaken. Different opa genes demonstrated variable rates of PV, between 6.4 ×10–4 and 6.9 ×10–3 per cell per generation. opa genes with a longer CR tract had a higher rate of PV (r 2=0.77, p=0.1212). Bacterial transformation resulted in a 180-fold increase in PV rate. The majority of opa genes in UK disease isolates (315/463, 68.0%) were in the ‘on’ phase, suggesting the importance of Opa proteins during invasive disease. These data provide valuable information for the first time regarding meningococcal Opa PV. The presence of Opa PV in meningococcal populations and high expression of Opa among invasive strains likely indicates the importance of this protein in bacterial colonization in the human nasopharynx. These findings have potential implications for development of vaccines derived from meningococcal outer membranes

Influences of Channel Deepening and Widening on the Tidal and Nontidal Circulations of Tampa Bay

A high-resolution, three-dimensional coastal ocean circulation model is applied to Tampa Bay to determine the effects that channel deepening and widening may have on the estuary’s tidal and nontidal circulations. The model domain includes all of Tampa Bay, Sarasota Bay, the Intra-coastal Waterway, and the adjoining rivers. With resolution as high as 20 m, the model resolves the main shipping channels, the bridge causeways, and all important inlet mass conveyances. Model evaluations are made against in situ data and a previously published, relatively lower-resolution version. By deepening and widening the shipping channels for the purpose of accommodating larger vessels, our results suggest an increase in tidal range and a decrease in tidal phase from the mouth to the head of the bay. Along with these tidal effects, our results also suggest an increase in the nontidal circulation, resulting in an increase in salinity and attendant consequences to the estuary’s ecology