Pathogens penetrating the central nervous system: Infection pathways and the cellular and molecular mechanisms of invasion

The brain is well protected against microbial invasion by cellular barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). In addition, cells within the central nervous system (CNS) are capable of producing an immune response against invading pathogens. Nonetheless, a range of pathogenic microbes make their way to the CNS, and the resulting infections can cause significant morbidity and mortality. Bacteria, amoebae, fungi, and viruses are capable of CNS invasion, with the latter using axonal transport as a common route of infection. In this review, we compare the mechanisms by which bacterial pathogens reach the CNS and infect the brain. In particular, we focus on recent data regarding mechanisms of bacterial translocation from the nasal mucosa to the brain, which represents a little explored pathway of bacterial invasion but has been proposed as being particularly important in explaining how infection with Burkholderia pseudomallei can result in melioidosis encephalomyelitis.

Mixture models of nucleotide sequence evolution that account for heterogeneity in the substitution process across sites and across lineages

Molecular phylogenetic studies of homologous sequences of nucleotides often assume that the underlying evolutionary process was globally stationary, reversible, and homogeneous (SRH), and that a model of evolution with one or more site-specific and time-reversible rate matrices (e.g., the GTR rate matrix) is enough to accurately model the evolution of data over the whole tree. However, an increasing body of data suggests that evolution under these conditions is an exception, rather than the norm. To address this issue, several non-SRH models of molecular evolution have been proposed, but they either ignore heterogeneity in the substitution process across sites (HAS) or assume it can be modeled accurately using the distribution. As an alternative to these models of evolution, we introduce a family of mixture models that approximate HAS without the assumption of an underlying predefined statistical distribution. This family of mixture models is combined with non-SRH models of evolution that account for heterogeneity in the substitution process across lineages (HAL). We also present two algorithms for searching model space and identifying an optimal model of evolution that is less likely to over- or underparameterize the data. The performance of the two new algorithms was evaluated using alignments of nucleotides with 10 000 sites simulated under complex non-SRH conditions on a 25-tipped tree. The algorithms were found to be very successful, identifying the correct HAL model with a 75% success rate (the average success rate for assigning rate matrices to the tree's 48 edges was 99.25%) and, for the correct HAL model, identifying the correct HAS model with a 98% success rate. Finally, parameter estimates obtained under the correct HAL-HAS model were found to be accurate and precise. The merits of our new algorithms were illustrated with an analysis of 42 337 second codon sites extracted from a concatenation of 106 alignments of orthologous genes encoded by the nuclear genomes of Saccharomyces cerevisiae, S. paradoxus, S. mikatae, S. kudriavzevii, S. castellii, S. kluyveri, S. bayanus, and Candida albicans. Our results show that second codon sites in the ancestral genome of these species contained 49.1% invariable sites, 39.6% variable sites belonging to one rate category (V1), and 11.3% variable sites belonging to a second rate category (V2). The ancestral nucleotide content was found to differ markedly across these three sets of sites, and the evolutionary processes operating at the variable sites were found to be non-SRH and best modeled by a combination of eight edge-specific rate matrices (four for V1 and four for V2). The number of substitutions per site at the variable sites also differed markedly, with sites belonging to V1 evolving slower than those belonging to V2 along the lineages separating the seven species of Saccharomyces. Finally, sites belonging to V1 appeared to have ceased evolving along the lineages separating S. cerevisiae, S. paradoxus, S. mikatae, S. kudriavzevii, and S. bayanus, implying that they might have become so selectively constrained that they could be considered invariable sites in these species.

Survey of dental clinic patients: Smoking and preferences for cessation support

Background: Smoking cessation interventions delivered by dental practitioners can be as effective as those delivered by general medical practitioners. However, concern that addressing smoking may cause offence to their patients is a reason cited by dental practitioners for not regularly addressing patient smoking behaviours, despite believing they should play a role in smoking cessation. This study aimed to elicit the smoking behaviour and smoking cessation preferences of dental patients to determine if these concerns accurately reflect patient attitudes. Methods: We surveyed 726 adult dental patients attending the University of Queensland’s School of Dentistry Dental Clinics, Brisbane Dental Hospital, and four private dental practices in South East Queensland. Results: Most (80%) current daily smokers had tried to quit smoking. Smokers and non-smokers both agreed that dentists should screen for smoking behaviour and are qualified to offer smoking cessation advice (99% and 96% respectively). Almost all participants (96%) said they would be comfortable with their dentist asking about their smoking and that if their smoking was affecting their oral health their dentist should advise them to quit. Conclusions: Patients are receptive to dental practitioners inquiring about smoking behaviour and offering advice on quitting. Smoking patients showed considerable motivation and interest in quitting smoking, particularly in the context of health problems related to smoking being identified. These results should encourage dentists to raise the issue with their patients.

Robust superhydrophobicity of hierarchical ZnO hollow microspheres fabricated by two-step self-assembly

Superhydrophobic and superhydrophilic surfaces have been extensively investigated due to their importance for industrial applications. It has been reported, however, that superhydrophobic surfaces are very sensitive to heat, ultraviolet (UV) light, and electric potential, which interfere with their long-term durability. In this study, we introduce a novel approach to achieve robust superhydrophobic thin films by designing architecture-defined complex nanostructures. A family of ZnO hollow microspheres with controlled constituent architectures in the morphologies of 1D nanowire networks, 2D nanosheet stacks, and 3D mesoporous nanoball blocks, respectively, was synthesized via a two-step self-assembly approach, where the oligomers or the constituent nanostructures with specially designed structures are first formed from surfactant templates, and then further assembled into complex morphologies by the addition of a second co-surfactant. The thin films composed of two-step synthesized ZnO hollow microspheres with different architectures presented superhydrophobicities with contact angles of 150°-155°, superior to the contact angle of 103° for one-step synthesized ZnO hollow microspheres with smooth and solid surfaces. Moreover, the robust superhydrophobicity was further improved by perfluorinated silane surface modification. The perfluorinated silane treated ZnO hollow microsphere thin films maintained excellent hydrophobicity even after 75 h of UV irradiation. The realization of environmentally durable superhydrophobic surfaces provides a promising solution for their long-term service under UV or strong solar light irradiations.