On the transferability of three water models developed by adaptive force matching

Water is perhaps the most simulated liquid. Recently three water models have been developed following the adaptive force matching (AFM) method that provides excellent predictions of water properties with only electronic structure information as a reference. Compared to many other electronic structure based force fields that rely on fairly sophisticated energy expressions, the AFM water models use point-charge based energy expressions that are supported by most popular molecular dynamics packages. An outstanding question regarding simple force fields is whether such force fields provide reasonable transferability outside of their conditions of parameterization. A survey of three AFM water models, B3LYPD-4F, BLYPSP-4F, and WAIL are provided for simulations under conditions ranging from the melting point up to the critical point. By including ice-Ih configurations in the training set, the WAIL potential predicts the melting temperate, TM, of ice-Ih correctly. Without training for ice, BLYPSP-4F underestimates TM by about 15 K. Interestingly, the B3LYPD-4F model gives a TM 14 K too high. The overestimation of TM by B3LYPD-4F mostly likely reflects a deficiency of the B3LYP reference. The BLYPSP-4F model gives the best estimate of the boiling temperature TB and is arguably the best potential for simulating water in the temperature range from TM to TB. None of the three AFM potentials provides a good description of the critical point. Although the B3LYPD-4F model gives the correct critical temperature TC and critical density, there are good reasons to believe the agreement is reached fortuitously. Links to Gromacs input files for the three water models are provided at the end of the paper.Comment: 25 pages, 2 figure

Differential adherence and expression of virulence traits by Candida albicans and Candida parapsilosis in mono- and dual-species cultures in artificial saliva

AIMS: To evaluate specific virulence factors of Candida albicans and Candida parapsilosis clinical oral isolates in mono- and dual-species culture in the presence of artificial saliva. METHODS AND RESULTS: Two of the strains used in this study were isolated from co-infection (C. albicans AM and C. parapsilosis AM2), and the other two were isolated from single infection (C. albicans AC and C. parapsilosis AD). The number of adhered yeast cells was measured and their enzymatic activity was determined simultaneously. In mono-species culture, C. parapsilosis strains adhered to a higher extent to the surface in comparison with the C. albicans strains. In dual-species culture, the C. parapsilosis strains adhered more in the presence of C. albicans AM. Interestingly, C. albicans AM and C. parapsilosis AD adhered to a higher extent when compared with all other co-cultures. In dual-species culture, the enzymatic activity of C. parapsilosis strains in the presence of C. albicans AC was higher than in the presence of C. albicans AM. CONCLUSIONS: The virulence factors of C. albicans and C. parapsilosis differ from strain to strain and are influenced by the presence of other species in culture. SIGNIFICANCE AND IMPACT OF THE STUDY: To understand the expression of virulence factors in Candida dual-species systems.This work was supported by Portuguese Foundation for Science and Technology (FCT) through the grant SFRH/BPD/20987/2004 attributed to Claudia Botelho

Ninth and Tenth Order Virial Coefficients for Hard Spheres in D Dimensions

We evaluate the virial coefficients B_k for k<=10 for hard spheres in dimensions D=2,...,8. Virial coefficients with k even are found to be negative when D>=5. This provides strong evidence that the leading singularity for the virial series lies away from the positive real axis when D>=5. Further analysis provides evidence that negative virial coefficients will be seen for some k>10 for D=4, and there is a distinct possibility that negative virial coefficients will also eventually occur for D=3.Comment: 33 pages, 12 figure

Blindness in Childhood in Developing Countries: Time for a Reassessment?

Paul Courtright and colleagues argue that the changing patterns of global childhood blindness suggest a need to reassess research, training, and programmatic requirements

Ultrasensitive plano-concave optical microresonators for ultrasound sensing

Highly sensitive broadband ultrasound detectors are needed to expand the capabilities of biomedical ultrasound, photoacoustic imaging and industrial ultrasonic non-destructive testing techniques. Here, a generic optical ultrasound sensing concept based on a novel plano-concave polymer microresonator is described. This achieves strong optical confinement (Q-factors > 105) resulting in very high sensitivity with excellent broadband acoustic frequency response and wide directivity. The concept is highly scalable in terms of bandwidth and sensitivity. To illustrate this, a family of microresonator sensors with broadband acoustic responses up to 40 MHz and noise-equivalent pressures as low as 1.6 mPa per √Hz have been fabricated and comprehensively characterized in terms of their acoustic performance. In addition, their practical application to high-resolution photoacoustic and ultrasound imaging is demonstrated. The favourable acoustic performance and design flexibility of the technology offers new opportunities to advance biomedical and industrial ultrasound-based techniques

The Exopolysaccharide Matrix Modulates the Interaction between 3D Architecture and Virulence of a Mixed-Species Oral Biofilm

Virulent biofilms are responsible for a range of infections, including oral diseases. All biofilms harbor a microbial-derived extracellular-matrix. The exopolysaccharides (EPS) formed on tooth-pellicle and bacterial surfaces provide binding sites for microorganisms; eventually the accumulated EPS enmeshes microbial cells. The metabolic activity of the bacteria within this matrix leads to acidification of the milieu. We explored the mechanisms through which the Streptococcus mutans-produced EPS-matrix modulates the three-dimensional (3D) architecture and the population shifts during morphogenesis of biofilms on a saliva-coated-apatitic surface using a mixed-bacterial species system. Concomitantly, we examined whether the matrix influences the development of pH-microenvironments within intact-biofilms using a novel 3D in situ pH-mapping technique. Data reveal that the production of the EPS-matrix helps to create spatial heterogeneities by forming an intricate network of exopolysaccharide-enmeshed bacterial-islets (microcolonies) through localized cell-to-matrix interactions. This complex 3D architecture creates compartmentalized acidic and EPS-rich microenvironments throughout the biofilm, which triggers the dominance of pathogenic S. mutans within a mixed-species system. The establishment of a 3D-matrix and EPS-enmeshed microcolonies were largely mediated by the S. mutans gtfB/gtfC genes, expression of which was enhanced in the presence of Actinomyces naeslundii and Streptococcus oralis. Acidic pockets were found only in the interiors of bacterial-islets that are protected by EPS, which impedes rapid neutralization by buffer (pH 7.0). As a result, regions of low pH (<5.5) were detected at specific locations along the surface of attachment. Resistance to chlorhexidine was enhanced in cells within EPS-microcolony complexes compared to those outside such structures within the biofilm. Our results illustrate the critical interaction between matrix architecture and pH heterogeneity in the 3D environment. The formation of structured acidic-microenvironments in close proximity to the apatite-surface is an essential factor associated with virulence in cariogenic-biofilms. These observations may have relevance beyond the mouth, as matrix is inherent to all biofilms

Oral Biofilm Architecture on Natural Teeth

Periodontitis and caries are infectious diseases of the oral cavity in which oral biofilms play a causative role. Moreover, oral biofilms are widely studied as model systems for bacterial adhesion, biofilm development, and biofilm resistance to antibiotics, due to their widespread presence and accessibility. Despite descriptions of initial plaque formation on the tooth surface, studies on mature plaque and plaque structure below the gum are limited to landmark studies from the 1970s, without appreciating the breadth of microbial diversity in the plaque. We used fluorescent in situ hybridization to localize in vivo the most abundant species from different phyla and species associated with periodontitis on seven embedded teeth obtained from four different subjects. The data showed convincingly the dominance of Actinomyces sp., Tannerella forsythia, Fusobacterium nucleatum, Spirochaetes, and Synergistetes in subgingival plaque. The latter proved to be new with a possibly important role in host-pathogen interaction due to its localization in close proximity to immune cells. The present study identified for the first time in vivo that Lactobacillus sp. are the central cells of bacterial aggregates in subgingival plaque, and that Streptococcus sp. and the yeast Candida albicans form corncob structures in supragingival plaque. Finally, periodontal pathogens colonize already formed biofilms and form microcolonies therein. These in vivo observations on oral biofilms provide a clear vision on biofilm architecture and the spatial distribution of predominant species

Elevated Incidence of Dental Caries in a Mouse Model of Cystic Fibrosis

Saliva bicarbonate constitutes the main buffering system which neutralizes the pH fall generated by the plaque bacteria during sugar metabolism. We found that the saliva pH is severely decreased in a mouse model of cystic fibrosis disease (CF). Given the close relationship between pH and caries development, we hypothesized that caries incidence might be elevated in the mouse CF model.). are enhanced at low pH values, we speculate that the decrease in the bicarbonate content and pH buffering of the saliva is at least partially responsible for the increased severity of lesions observed in the CF mouse

Role of Porphyromonas gingivalis gingipains in multi-species biofilm formation

BackgroundPeriodontal diseases are polymicrobial diseases that cause the inflammatory destruction of the tooth-supporting (periodontal) tissues. Their initiation is attributed to the formation of subgingival biofilms that stimulate a cascade of chronic inflammatory reactions by the affected tissue. The Gram-negative anaerobes Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola are commonly found as part of the microbiota of subgingival biofilms, and they are associated with the occurrence and severity of the disease. P. gingivalis expresses several virulence factors that may support its survival, regulate its communication with other species in the biofilm, or modulate the inflammatory response of the colonized host tissue. The most prominent of these virulence factors are the gingipains, which are a set of cysteine proteinases (either Arg-specific or Lys-specific). The role of gingipains in the biofilm-forming capacity of P. gingivalis is barely investigated. Hence, this in vitro study employed a biofilm model consisting of 10 ¿subgingival¿ bacterial species, incorporating either a wild-type P. gingivalis strain or its derivative Lys-gingipain and Arg-gingipan isogenic mutants, in order to evaluate quantitative and qualitative changes in biofilm composition.ResultsFollowing 64 h of biofilm growth, the levels of all 10 species were quantified by fluorescence in situ hybridization or immunofluorescence. The wild-type and the two gingipain-deficient P. gingivalis strains exhibited similar growth in their corresponding biofilms. Among the remaining nine species, only the numbers of T. forsythia were significantly reduced, and only when the Lys-gingipain mutant was present in the biofilm. When evaluating the structure of the biofilm by confocal laser scanning microscopy, the most prominent observation was a shift in the spatial arrangement of T. denticola, in the presence of P. gingivalis Arg-gingipain mutant.ConclusionsThe gingipains of P. gingivalis may qualitatively and quantitatively affect composition of polymicrobial biofilms. The present experimental model reveals interdependency between the gingipains of P. gingivalis and T. forsythia or T. denticola