Pilot GWAS of Caries in African-Americans Shows Genetic Heterogeneity

Background Dental caries is the most common chronic disease in the US and disproportionately affects racial/ethnic minorities. Caries is heritable, and though genetic heterogeneity exists between ancestries for a substantial portion of loci associated with complex disease, a genome-wide association study (GWAS) of caries specifically in African Americans has not been performed previously. Methods We performed exploratory GWAS of dental caries in 109 African American adults (age \u3e 18) and 96 children (age 3–12) from the Center for Oral Health Research in Appalachia (COHRA1 cohort). Caries phenotypes (DMFS, DMFT, dft, and dfs indices) assessed by dental exams were tested for association with 5 million genotyped or imputed single nucleotide polymorphisms (SNPs), separately in the two age groups. The GWAS was performed using linear regression with adjustment for age, sex, and two principal components of ancestry. A maximum of 1 million adaptive permutations were run to determine empirical significance. Results No loci met the threshold for genome-wide significance, though some of the strongest signals were near genes previously implicated in caries such as antimicrobial peptide DEFB1 (rs2515501; p = 4.54 × 10− 6) and TUFT1 (rs11805632; p = 5.15 × 10− 6). Effect estimates of lead SNPs at suggestive loci were compared between African Americans and Caucasians (adults N = 918; children N = 983). Significant (p \u3c 5 × 10− 8) genetic heterogeneity for caries risk was found between racial groups for 50% of the suggestive loci in children, and 12–18% of the suggestive loci in adults. Conclusions The genetic heterogeneity results suggest that there may be differences in the contributions of genetic variants to caries across racial groups, and highlight the critical need for the inclusion of minorities in subsequent and larger genetic studies of caries in order to meet the goals of precision medicine and to reduce oral health disparities

Strategic planning in the sphere of education in regions

The article is devoted to problems of strategic planning in education. Special attention is paid to the formation of regional education development programs. The article considers the main provisions of the strategic program for the development of the education system at the municipal level as a key position for the formation of a unified educational space. The authors’ analysis of such programs has shown that such programs are often devoid of consistency and are not consistent with the development programs of the leading branches of knowledge and the economy of the region. Based on the legal framework, scientific articles, and the experience of the regions the authors propose a model for the formation of regional strategic planning documents in the field of education, based on the principle of a triple helix of interaction between the state, educational organizations and business. The educational space planned according to this model will differ not only in a new organizational format designed to coordinate the path of education and training, but will also serve as a consolidation of resources from all three sources

VE-cadherin and claudin-5: it takes two to tango

Endothelial barrier function requires the adhesive activity of VE-cadherin and claudin-5, which are key components of adherens and tight endothelial junctions, respectively. Emerging evidence suggests that VE-cadherin controls claudin-5 expression by preventing the nuclear accumulation of FoxO1 and -catenin, which repress the claudin-5 promoter. This indicates that a crosstalk mechanism operates between these junctional structures

New interaction paradigm of ecological, social and economic structures of human activity

Realities of the XXI century demand searching and grounding measures on changing economic, political, and the main thing, ideological institutions that determine trends of evolution and managing vital human activity at national and over-national levels. Using synergetic approach, the authors made an attempt to synthesize conclusions and main theses of neo-institutionalism theory, onto-psychology, as well as results of biological evolution for determining the way to overcome global ecological crisis at nano-level and to form a model of the mankind's optimal evolution on the base of principle "priorities through parities", using DNAsymbol as a code of survival, through co-evolution of economy and ecology. The main problem, existing even in economically developed countries, is the realization of the fact that the paradigm of the stationary economy is the only condition for the mankind's survival. To solve this problem serious transformation of ideological institutions is necessary, at the expense of comprehensive and based on onto-psychological methods program of ecological literacy, that should harmonically blend with the presented by the authors triads of state strategic management and achieving the goal of development. It is the transformation of the national matrix, content and direction of which are set in order to ensure a balance of interests of all participants in ecological and economic development, will lay the necessary rules, both formal and informal, in the style of human behavior, social groups, the national economy. Realization of the program ecological literacy within the national policy on ecological development of the regions is one of the most important conditions for a natural, not imposed from the outside, prepare to use the paradigm of a sustainable economy as the basis of economic, political and ideological institutions of modern society, which is primarily the formation of a new paradigm of human device - devices nano-level decision-making, consumer behavior

Structure and transport properties of stephanite (Ag 5SbS 4) according to antimony nuclear quadrupole resonance

Silver sulfo-antimonide Ag 5SbS 4 (stephanite) has been studied by nuclear quadrupole resonance (NQR) spectroscopy on antimony nuclei. The temperature dependences of the spectroscopic and relaxation parameters have been examined in the range of 4. 2-395 K. A phase transition at 140 K and internal motions with an activation energy of 0. 29 eV have been experimentally detected. The nature of the phase transition and diffusion of silver ions has been discussed in view of the reported data. © 2012 Pleiades Publishing, Ltd

Effect of EMIC waves on relativistic and ultrarelativistic electron populations: Ground-based and Van Allen Probes observations

Abstract We study the effect of electromagnetic ion cyclotron (EMIC) waves on the loss and pitch angle scattering of relativistic and ultrarelativistic electrons during the recovery phase of a moderate geomagnetic storm on 11 October 2012. The EMIC wave activity was observed in situ on the Van Allen Probes and conjugately on the ground across the Canadian Array for Real-time Investigations of Magnetic Activity throughout an extended 18 h interval. However, neither enhanced precipitation of \u3e0.7 MeV electrons nor reductions in Van Allen Probe 90° pitch angle ultrarelativistic electron flux were observed. Computed radiation belt electron pitch angle diffusion rates demonstrate that rapid pitch angle diffusion is confined to low pitch angles and cannot reach 90°. For the first time, from both observational and modeling perspectives, we show evidence of EMIC waves triggering ultrarelativistic (~2-8 MeV) electron loss but which is confined to pitch angles below around 45° and not affecting the core distribution. Key Points EMIC wave activity is not associated with precipitation of MeV electrons EMIC waves do not deplete the ultra-relativistic belt down to 90° EMIC waves cause loss of low pitch angle electrons with energies ~2-8 MeV

Special features of the 9^9Be→\to2He fragmentation in emulsion at an energy of 1.2~A~GeV

The results of investigations of the relativistic $^9$Be nucleus fragmentation in emulsion which entails the production of two He fragments of an energy of 1.2~A~GeV are presented. The results of the angular measurements of the $^9$Be$\to$2He events are analyzed. The $^9$Be$\to^8$Be+n fragmentation channel involving the $^8$Be decay from the ground (0$^+$) and the first excited (2$^+$) states to two $\alpha$ particles is observed to be predominant.Comment: 10 pages, 6 figures, conference: Conference on Physics of Fundamental Interactions, Moscow, Russia, 5-9 Dec 2005 (Author's translation

Comparative analysis of IL-1β blood serum concentration, neutrophil-to-lymphocytes ratio in peripheral blood, and the levels of PD-L1 expression in malignant tissues of the patients with various solid tumors

The action of checkpoint inhibitors is based on activation of T cell antitumor immunity, and, therefore, the search for markers of lymphocyte functional activity before starting the therapy is highly relevant. Determination of the PD-L1 expression in tumor tissues reflects immunosuppressive activity of malignant cells, and it is used as a predictive marker in clinical practice. The ratio of neutrophils to lymphocytes in tumor tissue and in peripheral blood can also indicate the activity of adaptive immunity and correlates with the efficacy of therapy. It has been shown that a high level of interleukin 1 beta in the tumor microenvironment is associated with immunosuppression of lymphocytes and, possibly, reflects the activity of the tumor microenvironment. The aim of this work is to study the relationship between tumor expression of PD-L1, the concentration of serum interleukin-1 beta and the ratio of neutrophils and lymphocytes in peripheral blood.Before starting therapy with checkpoint inhibitors in patients with various solid tumors (n = 50), the serum level of interleukin-1 beta was determined by ELISA (ELISA-Best, Novosibirsk, Russia), expression of PD-L1 in the tumor by immunohistochemical method, complete blood count was performed using cytometry. Statistical analysis was performed in GraphPad Prism 6 (Graph Pad Software, USA) using the statistical methods of Fisher, Mann-Whitney, and Spearman.The average value of the index of the ratio of neutrophils and lymphocytes (NLR) in peripheral blood was 2.65± 0.21 (95% CI 2.22-3.07). The index value of more than 3.5 was found in 18% (9/50) of patients. The mean value of the PD-L1 expression level was 23.02±4.52% (95% CI 13.86-32.18). Expression of PD-L1 in tumor tissue was detected in 60.1% (25/40) of patients, among whom an increased expression of more than 50% was detected in 20.0% (5/25) of cases. A positive weak correlation was found between the concentration of interleukin 1 beta and the number of leukocytes (r = 0.34; p = 0.019) and index (r = 0.32; p = 0.029). The level of PD-L1 expression in tumor tissue also had a weak positive correlation with the serum interleukin 1 beta concentration (r = 0.33; p = 0.037) and the neutrophil-lymphocyte ratio (r = 0.33; p = 0.034). In the group of patients with PD-L1 expression > 5%, the mean value of the concentration of interleukin 1 beta was 1.65±0.62 pg/ml, and the mean value of the index was 4.26±0.94 х 10 9/l, which exceeds the values groups with undetectable PD-L1, but the differences were not statistically significant.The obtained result may indicate the influence of the immunosuppressive properties of the tumor on the state of the patient's immunity. Comprehensive determination of tumor PD-L1 expression, serum interleukin 1 beta concentration and the ratio of neutrophils and lymphocytes in peripheral blood can be used as an assessment of the patient's immune status before starting treatment with checkpoint inhibitors

Activation of Autophagy in a Rat Model of Retinal Ischemia following High Intraocular Pressure

Acute primary open angle glaucoma is an optic neuropathy characterized by the elevation of intraocular pressure, which causes retinal ischemia and neuronal death. Rat ischemia/reperfusion enhances endocytosis of both horseradish peroxidase (HRP) or fluorescent dextran into ganglion cell layer (GCL) neurons 24 h after the insult. We investigated the activation of autophagy in GCL-neurons following ischemia/reperfusion, using acid phosphatase (AP) histochemistry and immunofluorescence against LC3 and LAMP1. Retinal I/R lead to the appearance of AP-positive granules and LAMP1-positive vesicles 12 and 24 h after the insult, and LC3 labelling at 24 h, and induced a consistent retinal neuron death. At 48 h the retina was negative for autophagic markers. In addition, Western Blot analysis revealed an increase of LC3 levels after damage: the increase in the conjugated, LC3-II isoform is suggestive of autophagic activity. Inhibition of autophagy by 3-methyladenine partially prevented death of neurons and reduces apoptotic markers, 24 h post-lesion. The number of neurons in the GCL decreased significantly following I/R (I/R 12.21±1.13 vs controls 19.23±1.12 cells/500 µm); this decrease was partially prevented by 3-methyladenine (17.08±1.42 cells/500 µm), which potently inhibits maturation of autophagosomes. Treatment also prevented the increase in glial fibrillary acid protein immunoreactivity elicited by I/R. Therefore, targeting autophagy could represent a novel and promising treatment for glaucoma and retinal ischemia