Targeted antimicrobial therapy against Streptococcus mutans establishes protective non-cariogenic oral biofilms and reduces subsequent infection.

AimDental biofilms are complex communities composed largely of harmless bacteria. Certain pathogenic species including Streptococcus mutans (S. mutans) can become predominant when host factors such as dietary sucrose intake imbalance the biofilm ecology. Current approaches to control S. mutans infection are not pathogen-specific and eliminate the entire oral community along with any protective benefits provided. Here, we tested the hypothesis that removal of S. mutans from the oral community through targeted antimicrobial therapy achieves protection against subsequent S. mutans colonization.MethodologyControlled amounts of S. mutans were mixed with S. mutans-free saliva, grown into biofilms and visualized by antibody staining and cfu quantization. Two specifically-targeted antimicrobial peptides (STAMPs) against S. mutans were tested for their ability to reduce S. mutans biofilm incorporation upon treatment of the inocula. The resulting biofilms were also evaluated for their ability to resist subsequent exogenous S. mutans colonization.ResultsS. mutans colonization was considerably reduced ( +/- 0.4 fold reduction, P=0.01) when the surface was preoccupied with saliva-derived biofilms. Furthermore, treatment with S. mutans-specific STAMPs yielded S. mutans-deficient biofilms with significant protection against further S. mutans colonization (5 minutes treatment: 38 +/- 13 fold reduction P=0.01; 16 hours treatment: 96 +/- 28 fold reduction P=0.07).ConclusionS. mutans infection is reduced by the presence of existing biofilms. Thus maintaining a healthy or "normal" biofilm through targeted antimicrobial therapy (such as the STAMPs) could represent an effective strategy for the treatment and prevention of S. mutans colonization in the oral cavity and caries progression

The initial temporal evolution of a feedback dynamo for Mercury

Various possibilities are currently under discussion to explain the observed weakness of the intrinsic magnetic field of planet Mercury. One of the possible dynamo scenarios is a dynamo with feedback from the magnetosphere. Due to its weak magnetic field Mercury exhibits a small magnetosphere whose subsolar magnetopause distance is only about 1.7 Hermean radii. We consider the magnetic field due to magnetopause currents in the dynamo region. Since the external field of magnetospheric origin is antiparallel to the dipole component of the dynamo field, a negative feedback results. For an alpha-omega-dynamo two stationary solutions of such a feedback dynamo emerge, one with a weak and the other with a strong magnetic field. The question, however, is how these solutions can be realized. To address this problem, we discuss various scenarios for a simple dynamo model and the conditions under which a steady weak magnetic field can be reached. We find that the feedback mechanism quenches the overall field to a low value of about 100 to 150 nT if the dynamo is not driven too strongly

Cognitive architectures as Lakatosian research programmes: two case studies

Cognitive architectures - task-general theories of the structure and function of the complete cognitive system - are sometimes argued to be more akin to frameworks or belief systems than scientific theories. The argument stems from the apparent non-falsifiability of existing cognitive architectures. Newell was aware of this criticism and argued that architectures should be viewed not as theories subject to Popperian falsification, but rather as Lakatosian research programs based on cumulative growth. Newell's argument is undermined because he failed to demonstrate that the development of Soar, his own candidate architecture, adhered to Lakatosian principles. This paper presents detailed case studies of the development of two cognitive architectures, Soar and ACT-R, from a Lakatosian perspective. It is demonstrated that both are broadly Lakatosian, but that in both cases there have been theoretical progressions that, according to Lakatosian criteria, are pseudo-scientific. Thus, Newell's defense of Soar as a scientific rather than pseudo-scientific theory is not supported in practice. The ACT series of architectures has fewer pseudo-scientific progressions than Soar, but it too is vulnerable to accusations of pseudo-science. From this analysis, it is argued that successive versions of theories of the human cognitive architecture must explicitly address five questions to maintain scientific credibility

Development and Morphology of the Ventricular Outflow Tracts.

It is customary, at the current time, to consider many, if not most, of the lesions involving the ventricular outflow tract in terms of conotruncal malformations. This reflects the introduction, in the early 1940s, of the terms conus and truncus to describe the components of the developing outflow tract. The definitive outflow tracts in the postnatal heart, however, possess three, rather than two, components. These are the intrapericardial arterial trunks, the arterial roots, and the subvalvar ventricular outflow tracts. Congenital lesions afflicting the arterial roots, however, are not currently considered to be conotruncal malformations. This suggests a lack of logic in the description of cardiac development and its use as a means of categorizing congenital malformations. It is our belief that the developing outflow tract, like the postnatal outflow tracts, can readily be described in tripartite fashion, with its distal, intermediate, and proximal components forming the primordiums of the postnatal parts. In this review, we present evidence obtained from developing mice and human hearts to substantiate this notion. We show that the outflow tract, initially with a common lumen, is divided into its aortic and pulmonary components by a combination of an aortopulmonary septum derived from the dorsal wall of the aortic sac and outflow tract cushions that spiral through its intermediate and proximal components. These embryonic septal structures, however, subsequently lose their septal functions as the outflow tracts develop their own discrete walls. We then compare the developmental findings with the anatomic arrangements seen postnatally in the normal human heart. We show how correlations with the embryologic findings permit logical analysis of the congenital lesions involving the outflow tracts

Traffic-related pollution and asthma prevalence in children. Quantification of associations with nitrogen dioxide.

Ambient nitrogen dioxide is a widely available measure of traffic-related air pollution and is inconsistently associated with the prevalence of asthma symptoms in children. The use of this relationship to evaluate the health impact of policies affecting traffic management and traffic emissions is limited by the lack of a concentration-response function based on systematic review and meta-analysis of relevant studies. Using systematic methods, we identified papers containing quantitative estimates for nitrogen dioxide and the 12 month period prevalence of asthma symptoms in children in which the exposure contrast was within-community and dominated by traffic pollution. One estimate was selected from each study according to an a priori algorithm. Odds ratios were standardised to 10 μg/m(3) and summary estimates were obtained using random- and fixed-effects estimates. Eighteen studies were identified. Concentrations of nitrogen dioxide were estimated for the home address (12) and/or school (8) using a range of methods; land use regression (6), study monitors (6), dispersion modelling (4) and interpolation (2). Fourteen studies showed positive associations but only two associations were statistically significant at the 5 % level. There was moderate heterogeneity (I(2) = 32.8 %) and the random-effects estimate for the odds ratio was 1.06 (95 % CI 1.00 to 1.11). There was no evidence of small study bias. Individual studies tended to have only weak positive associations between nitrogen dioxide and asthma prevalence but the summary estimate bordered on statistical significance at the 5 % level. Although small, the potential impact on asthma prevalence could be considerable because of the high level of baseline prevalence in many cities. Whether the association is causal or indicates the effects of a correlated pollutant or other confounders, the estimate obtained by the meta-analysis would be appropriate for estimating impacts of traffic pollution on asthma prevalence

Visualizing the emergence of the pseudogap state and the evolution to superconductivity in a lightly hole-doped Mott insulator

Superconductivity emerges from the cuprate antiferromagnetic Mott state with hole doping. The resulting electronic structure is not understood, although changes in the state of oxygen atoms appear paramount. Hole doping first destroys the Mott state yielding a weak insulator where electrons localize only at low temperatures without a full energy gap. At higher doping, the 'pseudogap', a weakly conducting state with an anisotropic energy gap and intra-unit-cell breaking of 90\degree-rotational (C4v) symmetry appears. However, a direct visualization of the emergence of these phenomena with increasing hole density has never been achieved. Here we report atomic-scale imaging of electronic structure evolution from the weak-insulator through the emergence of the pseudogap to the superconducting state in Ca2-xNaxCuO2Cl2. The spectral signature of the pseudogap emerges at lowest doping from a weakly insulating but C4v-symmetric matrix exhibiting a distinct spectral shape. At slightly higher hole-density, nanoscale regions exhibiting pseudogap spectra and 180\degree-rotational (C2v) symmetry form unidirectional clusters within the C4v-symmetric matrix. Thus, hole-doping proceeds by the appearance of nanoscale clusters of localized holes within which the broken-symmetry pseudogap state is stabilized. A fundamentally two-component electronic structure11 then exists in Ca2-xNaxCuO2Cl2 until the C2v-symmetric clusters touch at higher doping, and the long-range superconductivity appears.Comment: See the Nature Physics website for the published version available at http://dx.doi.org/10.1038/Nphys232

Translational outcomes in a full gene deletion of ubiquitin protein ligase E3A rat model of Angelman syndrome.

Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by developmental delay, impaired communication, motor deficits and ataxia, intellectual disabilities, microcephaly, and seizures. The genetic cause of AS is the loss of expression of UBE3A (ubiquitin protein ligase E6-AP) in the brain, typically due to a deletion of the maternal 15q11-q13 region. Previous studies have been performed using a mouse model with a deletion of a single exon of Ube3a. Since three splice variants of Ube3a exist, this has led to a lack of consistent reports and the theory that perhaps not all mouse studies were assessing the effects of an absence of all functional UBE3A. Herein, we report the generation and functional characterization of a novel model of Angelman syndrome by deleting the entire Ube3a gene in the rat. We validated that this resulted in the first comprehensive gene deletion rodent model. Ultrasonic vocalizations from newborn Ube3am-/p+ were reduced in the maternal inherited deletion group with no observable change in the Ube3am+/p- paternal transmission cohort. We also discovered Ube3am-/p+ exhibited delayed reflex development, motor deficits in rearing and fine motor skills, aberrant social communication, and impaired touchscreen learning and memory in young adults. These behavioral deficits were large in effect size and easily apparent in the larger rodent species. Low social communication was detected using a playback task that is unique to rats. Structural imaging illustrated decreased brain volume in Ube3am-/p+ and a variety of intriguing neuroanatomical phenotypes while Ube3am+/p- did not exhibit altered neuroanatomy. Our report identifies, for the first time, unique AS relevant functional phenotypes and anatomical markers as preclinical outcomes to test various strategies for gene and molecular therapies in AS

Ferroelectricity induced by interatomic magnetic exchange interaction

Multiferroics, where two or more ferroic order parameters coexist, is one of the hottest fields in condensed matter physics and materials science[1-9]. However, the coexistence of magnetism and conventional ferroelectricity is physically unfavoured[10]. Recently several remedies have been proposed, e.g., improper ferroelectricity induced by specific magnetic[6] or charge orders[2]. Guiding by these theories, currently most research is focused on frustrated magnets, which usually have complicated magnetic structure and low magnetic ordering temperature, consequently far from the practical application. Simple collinear magnets, which can have high magnetic transition temperature, have never been considered seriously as the candidates for multiferroics. Here, we argue that actually simple interatomic magnetic exchange interaction already contains a driving force for ferroelectricity, thus providing a new microscopic mechanism for the coexistence and strong coupling between ferroelectricity and magnetism. We demonstrate this mechanism by showing that even the simplest antiferromagnetic (AFM) insulator MnO, can display a magnetically induced ferroelectricity under a biaxial strain