Sensitive and quantitative method to evaluate DNA methylation of the positive regulatory domains (PRDI, PRDII) and cAMP response element (CRE) in human endothelial nitric oxide synthase promote

Nitric oxide plays a prominent role in the cardiovascular system and much attention has been devoted in the last years on deciphering the regulation of human endothelial nitric oxide synthase (eNOS) expression. Epigenetic-based mechanisms have a key role in the eNOS expression and their pathologic perturbations may have profound effects on the steady state RNA levels in the endothelium. The human eNOS promoter lacks a canonical TATA box and it does not contain a proximal CpG island. A differentially DNA methylated region (DMR) in the native eNOS proximal promoter is involved in gene expression regulation. Here we describe a quantitative, sensitive and cost-effective method that, relying on a novel normalization strategy, allows the quantification of DNA methylation status of the positive regulatory domains (PRDI, PRDII) and cAMP response element (CRE) in human eNOS promoter. This technique will enable to explore the functional relevance of DNA methylation perturbations of eNOS promoter both under pathological and physiological conditions

Cognitive Impairment and Age-Related Vision Disorders: Their Possible Relationship and the Evaluation of the Use of Aspirin and Statins in a 65 Years-and-Over Sardinian Population

Neurological disorders (Alzheimer’s disease, vascular and mixed dementia) and visual loss (cataract, age-related macular degeneration, glaucoma, and diabetic retinopathy) are among the most common conditions that afflict people of at least 65 years of age. An increasing body of evidence is emerging, which demonstrates that memory and vision impairment are closely, significantly, and positively linked and that statins and aspirin may lessen the risk of developing age-related visual and neurological problems. However, clinical studies have produced contradictory results. Thus, the intent of the present study was to reliably establish whether a relationship exist between various types of dementia and age-related vision disorders, and to establish whether statins and aspirin may or may not have beneficial effects on these two types of disorders. We found that participants with dementia and/or vision problems were more likely to be depressed and displayed worse functional ability in basic and instrumental activities of daily living than controls. Mini mental state examination scores were significantly lower in patients with vision disorders compared to subjects without vision disorders. A closer association with macular degeneration was found in subjects with Alzheimer’s disease than in subjects without dementia or with vascular dementia, mixed dementia, or other types of age-related vision disorders. When we considered the associations between different types of dementia and vision disorders and the use of statins and aspirin, we found a significant positive association between Alzheimer’s disease and statins on their own or in combination with aspirin, indicating that these two drugs do not appear to reduce the risk of Alzheimer’s disease or improve its clinical evolution and may, on the contrary, favor its development. No significant association in statin use alone, aspirin use alone, or the combination of these was found in subjects without vision disorders but with dementia, and, similarly, none in subjects with vision disorders but without dementia. Overall, these results confirm the general impression so far; namely, that macular degeneration may contribute to cognitive disorders (Alzheimer’s disease in particular). In addition, they also suggest that, while statin and aspirin use may undoubtedly have some protective effects, they do not appear to be magic pills against the development of cognitive impairment or vision disorders in the elderly

Type I Non-Abelian Superconductors in Supersymmetric Gauge Theories

Non-BPS non-Abelian vortices with CP^1 internal moduli space are studied in an N=2 supersymmetric U(1) x SU(2) gauge theory with softly breaking adjoint mass terms. For generic internal orientations the classical force between two vortices can be attractive or repulsive. On the other hand, the mass of the scalars in the theory is always less than that of the vector bosons; also, the force between two vortices with the same CP^1 orientation is always attractive: for these reasons we interpret our model as a non-Abelian generalization of type I superconductors. We compute the effective potential in the limit of two well separated vortices. It is a function of the distance and of the relative colour-flavour orientation of the two vortices; in this limit we find an effective description in terms of two interacting CP^1 sigma models. In the limit of two coincident vortices we find two different solutions with the same topological winding and, for generic values of the parameters, different tensions. One of the two solutions is described by a CP^1 effective sigma model, while the other is just an Abelian vortex without internal degrees of freedom. For generic values of the parameters, one of the two solutions is metastable, while there are evidences that the other one is truly stable.Comment: 35 pages, 8 figures. v2: fixed typos and added small comments, v3 removed an unecessary figur

Phosphorus species in sequentially extracted soil organic matter fractions

The majority of organic P (Porg) in soil is considered to be part of soil organic matter (SOM) associations, but its chemical nature is largely ‘unresolved’. In this study, we investigated the Porg composition in different SOM fractions of a Gleysol soil using the Humeomics sequential chemical fractionation (SCF) procedure combined with nuclear magnetic resonance (NMR) spectroscopy. In summary, SCF procedure with subsequent NaOH-EDTA extraction of the soil residue extracted a total of 1769 mg P/kgsoil compared to 1682 mg P/kgsoil of a single-step NaOH-EDTA extraction. Approximately 38 % of the extracted Porg was present in the form of the unresolved Porg pool, which was represented by one or two underlying broad signals in the phosphomonoester region of solution 31P NMR spectra. The SCF revealed that phosphomonoesters were recovered in each fraction: 47 % of the unresolved phosphomonoesters were associated with the SOM fraction released by breaking ester bonds (40 %) and ether bonds (7 %), whereas about 30 % of this unresolved Porg pool appeared in the SOM fraction closely associated with the soil mineral phase. Furthermore, the extractability of inositol phosphates (IP) was increased from 312 mg P/kgsoil to 534 mg P/kgsoil (factor 1.7) using the SCF procedure compared to a single-step NaOH-EDTA extraction. Previous studies have reported the presence of IP in molecular size fractions greater than 10 kDa. Our findings on the removal of IP with the fractionation of the SOM could explain the presence of IP in these large associations. We demonstrate that major pools of Porg are closely associated with SOM structures, comprising a diverse array of chemical species and bonding types. These results forward our understanding of Porg stabilisation, P transformation, and P cycling in terrestrial ecosystems towards an association point of view

Infantile/congenital high-grade gliomas: molecular features and therapeutic perspectives

Brain tumors in infants account for less than 10% of all pediatric nervous system tumors. They include tumors diagnosed in fetal age, neonatal age and in the first years of life. Among these, high-grade gliomas (HGGs) are a specific entity with a paradoxical clinical course that sets them apart from their pediatric and adult counterparts. Currently, surgery represents the main therapeutic strategy in the management of these tumors. Chemotherapy does not have a well-defined role whilst radiotherapy is rarely performed, considering its late effects. Information about molecular characterization is still limited, but it could represent a new fundamental tool in the therapeutic perspective of these tumors. Chimeric proteins derived from the fusion of several genes with neurotrophic tyrosine receptor kinase mutations have been described in high-grade gliomas in infants as well as in neonatal age and the recent discovery of targeted drugs may change the long-term prognosis of these tumors, along with other target-driven therapies. The aim of this mini review is to highlight the recent advances in the diagnosis and treatment of high-grade gliomas in infants with a particular focus on the molecular landscape of these neoplasms and future clinical applications

MRI Tractography of Corticospinal Tract and Arcuate Fasciculus in High-Grade Gliomas Performed by Constrained Spherical Deconvolution: Qualitative and Quantitative Analysis

BACKGROUND AND PURPOSE: MR imaging tractography is increasingly used to perform noninvasive presurgical planning for brain gliomas. Recently, constrained spherical deconvolution tractography was shown to overcome several limitations of commonly used DTI tractography. The purpose of our study was to evaluate WM tract alterations of both the corticospinal tract and arcuate fasciculus in patients with high-grade gliomas, through qualitative and quantitative analysis of probabilistic constrained spherical deconvolution tractography, to perform reliable presurgical planning. MATERIALS AND METHODS: Twenty patients with frontoparietal high-grade gliomas were recruited and evaluated by using a 3T MR imaging scanner with both morphologic and diffusion sequences (60 diffusion directions). We performed probabilistic constrained spherical deconvolution tractography and tract quantification following diffusion tensor parameters: fractional anisotropy; mean diffusivity; linear, planar, and spherical coefficients. RESULTS: In all patients, we obtained tractographic reconstructions of the medial and lateral portions of the corticospinal tract and arcuate fasciculus, both on the glioma-affected and nonaffected sides of the brain. The affected lateral corticospinal tract and the arcuate fasciculus showed decreased fractional anisotropy ( z = 2.51, n = 20, P = .006; z = 2.52, n = 20, P = .006) and linear coefficient ( z = 2.51, n = 20, P = .006; z = 2.52, n = 20, P = .006) along with increased spherical coefficient ( z = −2.51, n = 20, P = .006; z = −2.52, n = 20, P = .006). Mean diffusivity values were increased only in the lateral corticospinal tract ( z = −2.53, n = 20, P = .006). CONCLUSIONS: In this study, we demonstrated that probabilistic constrained spherical deconvolution can provide essential qualitative and quantitative information in presurgical planning, which was not otherwise achievable with DTI. These findings can have important implications for the surgical approach and postoperative outcome in patients with glioma

Spatial planning, urban governance and the economic context: The case of 'Mehr' housing plan, Iran

With the increasing concentration of population and economic activities in metropolitan regions, dwelling shortages and housing quality have become critical issues in urban management. Town plans considering social, economic, political, and cultural features of local communities have been developed with the aim of supporting housing, especially in emerging economies. In Iran, the 'Mehr Housing' Plan has been considered as one of the most relevant strategies for social housing since the 2000s. However, the acceptance of 'Mehr Housing' plans at the community scale has been rather low, reflecting the fact that it is a top-down, non-participatory policy. The present study investigates the most important factors affecting social acceptance of 'Mehr Housing' plans by interviewing 45 experts through a structured questionnaire that evaluated multiple analyses' dimensions of housing and urban planning in Iran. Results showed that six dimensions (physical, institutional-managerial, economic, socio-cultural, legal, and locational) had contributed to social dissatisfaction with 'Mehr Housing' local initiatives. In particular, socio-cultural and legal dimensions were demonstrated to have a large impact on local communities' dissatisfaction

Link between laboratory and astrophysical radiative shocks

This work provides analytical solutions describing the post-shock structure of radiative shocks growing in astrophysics and in laboratory. The equations including a cooling function $\Lambda \propto \rho^{\epsilon} P^{\zeta} x^{\theta}$ are solved for any values of the exponents $\epsilon$, $\zeta$ and $\theta$. This modeling is appropriate to astrophysics as the observed radiative shocks arise in optically thin media. In contrast, in laboratory, radiative shocks performed using high-power lasers present a radiative precursor because the plasma is more or less optically thick. We study the post-shock region in the laboratory case and compare with astrophysical shock structure. In addition, we attempt to use the same equations to describe the radiative precursor, but the cooling function is slightly modified. In future experiments we will probe the PSR using X-ray diagnostics. These new experimental results will allow to validate our astrophysical numerical codes

Static Interactions of non-Abelian Vortices

Interactions between non-BPS non-Abelian vortices are studied in non-Abelian U(1) x SU(N) extensions of the Abelian-Higgs model in four dimensions. The distinctive feature of a non-Abelian vortex is the presence of an internal CP^{N-1} space of orientational degrees of freedom. For fine-tuned values of the couplings, the vortices are BPS and there is no net force between two static parallel vortices at arbitrary distance. On the other hand, for generic values of the couplings the interactions between two vortices depend non-trivially on their relative internal orientations. We discuss the problem both with a numerical approach (valid for small deviations from the BPS limit) and in a semi-analytical way (valid at large vortex separations). The interactions can be classified with respect to their asymptotic property at large vortex separation. In a simpler fine-tuned model, we find two regimes which are quite similar to the usual type I/II Abelian superconductors. In the generic model we find other two new regimes: type I*/II*. Unlike the type I (type II) case, where the interaction is always attractive (repulsive), the type I* and II* have both attractive and repulsive interactions depending on the relative orientation. We have found a rich variety of interactions at small vortex separations. For some values of the couplings, a bound state of two static vortices at a non-zero distance exists.Comment: 36 pages, 13 figures; v2 a small comment and a reference adde