Clinical concentrations of peroxidases cause dysbiosis in invitro oral biofilms

Background and Objective: Little is known about the initiation of dysbiosis in oral biofilms, a topic of prime importance for understanding the etiology of, and preventing, periodontitis. The aim of this study was to evaluate the effect of different concentrations of crevicular and salivary peroxidase and catalase on dysbiosis in multispecies biofilms in vitro. Material and Methods: The spotting technique was used to identify the effect of different concentrations of myeloperoxidase, lactoperoxidase, erythrocyte catalase, and horseradish peroxidase in salivary and crevicular fluid on the inhibitory effect of commensals on pathobiont growth. Vitality-quantitative real-time PCR was performed to quantify the dysbiotic effect of the peroxidases (adjusted to concentrations found in periodontal health, gingivitis, and periodontitis) on multispecies microbial communities. Results: Agar plate and multispecies ecology experiments showed that production of hydrogen peroxide (H2O2) by commensal bacteria decreases pathobiont growth and colonization. Peroxidases at concentrations found in crevicular fluid and saliva neutralized this inhibitory effect. In multispecies communities, myeloperoxidase, at the crevicular fluid concentrations found in periodontitis, resulted in a 1-3 Log increase in pathobionts when compared with the crevicular fluid concentrations found in periodontal health. The effect of salivary lactoperoxidase and salivary myeloperoxidase concentrations was, in general, similar to the effect of crevicular myeloperoxidase concentrations. Conclusions: Commensal species suppress pathobionts by producing H2O2. Catalase and peroxidases, at clinically relevant concentrations, can neutralize this effect and thereby can contribute to dysbiosis by allowing the outgrowth of pathobionts

Geology and rural landscapes in central Spain (Guadalajara, Castilla—La Mancha)

Methods commonly used in regional geological analysis were employed to study the visual landscapes of the Sigüenza–Molina de Aragón area (Spain). Landscape data were compiled to produce a landscape map and a photograph catalogue. Lithological composition, tectonic structure and recent erosive processes are the main factors controlling the visual landscapes. Territorial properties, such as colours and agricultural capacities, are controlled by these geological characteristics. The landscape map and the photographic catalogue is the main contribution of this paper. The first level of landscape classification distinguishes zones with dominance of either flat, concave or convex areas. Other parts of the territory are, however, composed of concave and convex combinations that originate hybrid orographic structures. In a second level of classification, several subdivisions for each of these types are established

Search for the neutral Higgs bosons of the minimal supersymmetric standard model in pp collisions at root s=7 TeV with the ATLAS detector

A search for neutral Higgs bosons of the Minimal Supersymmetric Standard Model (MSSM) is reported. The analysis is based on a sample of proton-proton collisions at a centre-of-mass energy of 7TeV recorded with the ATLAS detector at the Large Hadron Collider. The data were recorded in 2011 and correspond to an integrated luminosity of 4.7 fb-1 to 4.8 fb-1. Higgs boson decays into oppositely-charged muon or τ lepton pairs are considered for final states requiring either the presence or absence of b-jets. No statistically significant excess over the expected background is observed and exclusion limits at the 95% confidence level are derived. The exclusion limits are for the production cross-section of a generic neutral Higgs boson, φ, as a function of the Higgs boson mass and for h/A/H production in the MSSM as a function of the parameters mA and tan β in the mhmax scenario for mA in the range of 90GeV to 500 GeV. Copyright CERN

How many human proteoforms are there?

Despite decades of accumulated knowledge about proteins and their post-translational modifications (PTMs), numerous questions remain regarding their molecular composition and biological function. One of the most fundamental queries is the extent to which the combinations of DNA-, RNA- and PTM-level variations explode the complexity of the human proteome. Here, we outline what we know from current databases and measurement strategies including mass spectrometry-based proteomics. In doing so, we examine prevailing notions about the number of modifications displayed on human proteins and how they combine to generate the protein diversity underlying health and disease. We frame central issues regarding determination of protein-level variation and PTMs, including some paradoxes present in the field today. We use this framework to assess existing data and to ask the question, "How many distinct primary structures of proteins (proteoforms) are created from the 20,300 human genes?" We also explore prospects for improving measurements to better regularize protein-level biology and efficiently associate PTMs to function and phenotype

Biophysical Basis for Three Distinct Dynamical Mechanisms of Action Potential Initiation

Transduction of graded synaptic input into trains of all-or-none action potentials (spikes) is a crucial step in neural coding. Hodgkin identified three classes of neurons with qualitatively different analog-to-digital transduction properties. Despite widespread use of this classification scheme, a generalizable explanation of its biophysical basis has not been described. We recorded from spinal sensory neurons representing each class and reproduced their transduction properties in a minimal model. With phase plane and bifurcation analysis, each class of excitability was shown to derive from distinct spike initiating dynamics. Excitability could be converted between all three classes by varying single parameters; moreover, several parameters, when varied one at a time, had functionally equivalent effects on excitability. From this, we conclude that the spike-initiating dynamics associated with each of Hodgkin's classes represent different outcomes in a nonlinear competition between oppositely directed, kinetically mismatched currents. Class 1 excitability occurs through a saddle node on invariant circle bifurcation when net current at perithreshold potentials is inward (depolarizing) at steady state. Class 2 excitability occurs through a Hopf bifurcation when, despite net current being outward (hyperpolarizing) at steady state, spike initiation occurs because inward current activates faster than outward current. Class 3 excitability occurs through a quasi-separatrix crossing when fast-activating inward current overpowers slow-activating outward current during a stimulus transient, although slow-activating outward current dominates during constant stimulation. Experiments confirmed that different classes of spinal lamina I neurons express the subthreshold currents predicted by our simulations and, further, that those currents are necessary for the excitability in each cell class. Thus, our results demonstrate that all three classes of excitability arise from a continuum in the direction and magnitude of subthreshold currents. Through detailed analysis of the spike-initiating process, we have explained a fundamental link between biophysical properties and qualitative differences in how neurons encode sensory input

Smoking in public places in six European countries: Findings from the EUREST-PLUS ITC Europe Survey

Introduction: Surveillance of tobacco consumption in public places is an important measure to evaluate the impact of tobacco control interventions over time. The objective of this study was to estimate the prevalence of smoking as seen by smokers and their smoking behaviour in public places, in six European countries. Methods: We used baseline data of the International Tobacco Control Six European countries (ITC 6E) Survey, part of the EUREST-PLUS Project, conducted in 2016 in national representative samples of about 1000 adult smokers aged 18 years and older in Germany, Greece, Hungary, Poland, Romania and Spain. For each setting (workplaces, restaurants, bars/pubs and discos) participants were asked whether they had seen someone smoking during their last visit there and whether they too had smoked there. We report the overall and by-country weighted prevalence of seeing someone smoking and the smokers’ own smoking behaviour at each setting. We also assess the relationship between seeing someone smoking and smoking themselves at these settings. Results: The prevalence of smoking as seen by smokers was 18.8% at workplaces, with high variability among countries (from 4.7% in Hungary to 40.8% in Greece). Among smokers visiting leisure facilities in the last year, during their last visit 22.7% had seen someone smoking inside restaurants and 12.2% had smoked themselves there, while for bars/pubs the corresponding prevalences were 33.9% and 20.4%, and inside discos 44.8% and 34.8%. Conclusions: Smoking is still prevalent at leisure facilities, particularly at discos in Europe, with high variability among countries. More extensive awareness campaigns and stricter enforcement are needed to increase the compliance of smokefree regulations, especially in leisure facilities

The histology of ovarian cancer: worldwide distribution and implications for international survival comparisons (CONCORD-2)

Objective Ovarian cancers comprise several histologically distinct tumour groups with widely different prognosis. We aimed to describe the worldwide distribution of ovarian cancer histology and to understand what role this may play in international variation in survival. Methods The CONCORD programme is the largest population-based study of global trends in cancer survival. Data on 681,759 women diagnosed during 1995â\u80\u932009 with cancer of the ovary, fallopian tube, peritoneum and retroperitonum in 51 countries were included. We categorised ovarian tumours into six histological groups, and explored the worldwide distribution of histology. Results During 2005â\u80\u932009, type II epithelial tumours were the most common. The proportion was much higher in Oceania (73.1%), North America (73.0%) and Europe (72.6%) than in Central and South America (65.7%) and Asia (56.1%). By contrast, type I epithelial tumours were more common in Asia (32.5%), compared with only 19.4% in North America. From 1995 to 2009, the proportion of type II epithelial tumours increased from 68.6% to 71.1%, while the proportion of type I epithelial tumours fell from 23.8% to 21.2%. The proportions of germ cell tumours, sex cord-stromal tumours, other specific non-epithelial tumours and tumours of non-specific morphology all remained stable over time. Conclusions The distribution of ovarian cancer histology varies widely worldwide. Type I epithelial, germ cell and sex cord-stromal tumours are generally associated with higher survival than type II tumours, so the proportion of these tumours may influence survival estimates for all ovarian cancers combined. The distribution of histological groups should be considered when comparing survival between countries and regions

Patterns of tobacco use, quit attempts, readiness to quit and self-efficacy among smokers with anxiety or depression: Findings among six countries of the EUREST-PLUS ITC Europe Surveys

Introduction: We compared smoking behaviors, past quit attempts, readiness to quit and beliefs about quitting among current cigarette smokers with probable anxiety or depression (PAD) to those without PAD, from six European Union (EU) Member States (MS). Methods: A nationally representative cross-sectional sample of 6011 adult cigarette smokers from six EU MS (Germany, Greece, Hungary, Poland, Romania, Spain) was randomly selected through a multistage cluster sampling design in 2016. Respondents were classified as having PAD based on self-reported current diagnosis or treatment for anxiety or depression, or a positive screen for major depression, according to a validated two-item instrument. Sociodemographic characteristics, patterns of tobacco use, past quitting, readiness to quit, self-efficacy and beliefs about quitting were assessed for patients with and without PAD. Logistic regression was used to examine predictors of PAD. All analyses were conducted using the complex samples package of SPSS. Results: Among smokers sampled, 21.0% (95% CI: 19.3–22.9) were identified as having PAD. Logistic regression analyses controlling for socioeconomic variables and cigarettes smoked per day found smokers with PAD were more likely to have made an attempt to quit smoking in the past (AOR=1.48; 95% CI: 1.25–1.74), made a quit attempt in the last 12 months (AOR=1.75; 95% CI: 1.45–2.11), and report lower self-efficacy with quitting (AOR=1.83; 95% CI: 1.44–2.32) compared to smokers without PAD. Additionally, it was found that individuals with PAD were more likely to report having received advice to quit from a doctor or health professional and having used quitline support as part of their last quit attempt. Conclusions: Smokers with PAD report a greater interest in quitting in the future and more frequent failed quit attempts than smokers without PAD; however, the high rates of untreated anxiety or depression, nicotine dependence, low confidence in the ability to quit, infrequent use of cessation methods, as well as socioeconomic factors may make quitting difficult