TLK1B promotes repair of UV-damaged DNA through chromatin remodeling by Asf1

BACKGROUND: The mammalian protein kinase TLK1 is a homologue of Tousled, a gene involved in flower development in Arabidopsis thaliana. The function of TLK1 is not well known, although knockout of the gene in Drosophila, or expression of a dominant negative mutant in mouse mammary cells causes loss of nuclear divisions and chromosome mis-segregation. TLK1B is a splice variant of TLK1 and it confers radioresistance in a normal mammary mouse cell line possibly due to increased chromatin remodeling capacity, but the mechanism of resistance remains to be fully elucidated. RESULTS: We now show that TLK1B also affords protection against UV radiation. We find that nuclear extracts isolated from TLK1B-containing mouse cells promote more efficient chromatin assembly than comparable extracts lacking TLK1B. TLK1B-containing extracts are also more efficient in repair of UV-damaged plasmid DNA assembled into nucleosomes. One of the two known substrates of TLK1 (or TLK1B) is the histone chaperone Asf1, and immuno-inactivation experiments suggest that TLK1B increases UV-repair through the action of Asf1 on chromatin assembly/disassembly. CONCLUSION: Our studies provide evidence for TLK1B-mediated phosphorylation of Asf1 triggering DNA repair. We suggest that this occurs via Asf1-mediated chromatin assembly at the sites of UV damage

Non-backtracking Walk Centrality for Directed Networks

The theory of zeta functions provides an expression for the generating function of nonbacktracking walk counts on a directed network. We show how this expression can be used to produce a centrality measure that eliminates backtracking walks at no cost. We also show that the radius of convergence of the generating function is related to the spectrum of a three-by-three block matrix involving the original adjacency matrix. This gives a means to choose appropriate values of the attenuation parameter. We find that three important additional benefits arise when we use this technique to eliminate traversals around the network that are unlikely to be of relevance. First, we obtain a larger range of choices for the attenuation parameter. Second, a natural approach for determining a suitable parameter range is invariant under the removal of certain types of nodes, we can gain computational efficiencies through reducing the dimension of the resulting eigenvalue problem. Third, the dimension of the linear system defining the centrality measures may be reduced in the same manner. We show that the new centrality measure may be interpreted as standard Katz on a modified network, where self loops are added, and where nonreciprocal edges are augmented with negative weights. We also give a multilayer interpretation, where negatively weighted walks between layers compensate for backtracking walks on the only non-empty layer. Studying the limit as the attenuation parameter approaches its upper bound also allows us to propose a generalization of eigenvector-based nonbacktracking centrality measure to this directed network setting. In this context, we find that the two-by-two block matrix arising in previous studies focused on undirected networks must be extended to a new three-by-three block structure to allow for directed edges. We illustrate the centrality measure on a synthetic network, where it is shown to eliminate a localization effect present in standard Katz centrality. Finally, we give results for real networks

Influence of Different Dry-Mixing Techniques on the Mechanical, Thermal and Electrical Behavior of Ultra High Molecular Weight Polyethylene/Exhausted Tire Carbon Composites

The mechanical, thermal and electrical behavior of ultra high molecular weight (UHMWPE) composites containing different amount of pyrolyzed exhausted tire carbon (ETC) is investigated. Composites were obtained by dry-mixing the powders with a homogenizer and an impact mill. The results clearly indicate that, by changing the mixing method, it is possible to tune the rheological and morphological characteristics of the composites and in turn their mechanical, thermal and electrical properties. Better performances were observed for the composites obtained with the impact mill, which showed improved Young modulus, reduced electrical and thermal resistance with respect to those of homogenized counterparts. All the composites exhibited a relevant decrease of electrical resistivity

Restorative Justice-Informed Moral Acquaintance: Resolving the Dual Role Problem in Correctional and Forensic Practice

The issue of dual roles within forensic and correctional fields has typically been conceptualized as dissonance—experienced by practitioners— when attempting to adhere to the conflicting ethical requirements associated with client well-being and community protection. In this paper, we argue that the dual role problem should be conceptualized more broadly; to incorporate the relationship between the offender and their victim. We also propose that Restorative Justice (RJ) is able to provide a preliminary ethical framework to deal with this common ethical oversight. Furthermore, we unite the RJ framework with that of Ward’s (2013) moral acquaintance model to provide a more powerful approach—RJ informed moral acquaintance—aimed at addressing the ethical challenges faced by practitioners within forensic and correctional roles

Efficacy of adalimumab as second-line therapy in a pediatric cohort of crohn’s disease patients who failed infliximab therapy: The Italian society of pediatric gastroenterology, hepatology, and nutrition experience

Background: Adalimumab (Ada) treatment is an available option for pediatric Crohn’s disease (CD) and the published experience as rescue therapy is limited. Objectives: We investigated Ada efficacy in a retrospective, pediatric CD cohort who had failed previous infliximab treatment, with a minimum follow-up of 6 months. Methods: In this multicenter study, data on demographics, clinical activity, growth, laboratory values (CRP) and adverse events were collected from CD patients during follow-up. Clinical remission (CR) and response were defined with Pediatric CD Activity Index (PCDAI) score ≤10 and a decrease in PCDAI score of ≥12.5 from baseline, respectively. Results: A total of 44 patients were consecutively recruited (mean age 14.8 years): 34 of 44 (77%) had active disease (mean PCDAI score 24.5) at the time of Ada administration, with a mean disease duration of 3.4 (range 0.3–11.2) years. At 6, 12, and 18 months, out of the total of the enrolled population, CR rates were 55%, 78%, and 52%, respectively, with a significant decrease in PCDAI scores (P<0.01) and mean CRP values (mean CRP 5.7 and 2.4 mL/dL, respectively; P<0.01) at the end of follow-up. Steroid-free remission rates, considered as the total number of patients in CR who were not using steroids at the end of this study, were 93%, 95%, and 96% in 44 patients at 6, 12, and 18 months, respectively. No significant differences in growth parameters were detected. In univariate analysis of variables related to Ada efficacy, we found that only a disease duration >2 years was negatively correlated with final PCDAI score (P<0.01). Two serious adverse events were recorded: 1 meningitis and 1 medulloblastoma. Conclusion: Our data confirm Ada efficacy in pediatric patients as second-line biological therapy after infliximab failure. Longer-term prospective data are warranted to define general effectiveness and safety in pediatric CD patients

Nitrogen functionalized carbon nanostructures supported Pd and Au-Pd NPs as catalyst for alcohols oxidation

Two different carbon nanotubes (CNTs) PR24-PS and Baytubes were functionalized by oxidation with nitric acid and further amination with gaseous NH3. Thus Au and Au-Pd nanoparticles were prepared by PVA/NaBH4 system and anchored on the surface of pristine CNTs and N-CNTs (Nitrogen functionalized carbon nanotubes). TEM analysis revealed that the introduction of nitrogen functionalities improves the dispersion of the metal nanoparticles on the surface of the support. This phenomena leads to an improved activity of N-CNTs based catalysts with the respect of pristine CNTs when tested in the liquid phase oxidation of alcohols

Altilix\uae Supplement Containing Chlorogenic Acid and Luteolin Improved Hepatic and Cardiometabolic Parameters in Subjects with Metabolic Syndrome: A 6 Month Randomized, Double-Blind, Placebo-Controlled Study

The objective was to evaluate the eects of 6 months of supplementation with Altilix\uae, containing chlorogenic acid and its derivatives, and luteolin and its derivatives, on cardiovascular risk and hepatic markers in subjects with metabolic syndrome (MetS). A randomized, double-blind, placebo-controlled study was performed in 100 subjects with MetS with a follow-up period of 6 months; 50 subjects were randomized to Altilix\uae (26 men and 24 women, mean age 63 8 years) and the other 50 to placebo (28 men and 22 women, mean age 63 11 years). Anthropometric, cardiometabolic, and hepatic parameters were assessed at baseline and at the end of follow-up. Carotid intima-media thickness and endothelial function were assessed by doppler ultrasound and by flow-mediated dilation of the brachial artery, respectively. The presence and degree of non-alcoholic fatty liver disease (NAFLD) was assessed by the fatty liver index (FLI), and subjects were divided into three subgroups: (1) without NAFLD; (2) with borderline NAFLD; and (3) with NAFLD. After 6 months of Altilix\uae supplementation, we found a significant improvement vs. placebo in most of the evaluated parameters, including body weight (2.40% (95% CI 3.79, 1.01); p < 0.001), waist circumference (2.76% (95% CI 4.55, 0.96); p = 0.003), HbA1c (0.95% (95% CI 1.22, 0.67); p < 0.001), plasma lipids, FLI (21.83% (95% CI 27.39, 16.27); p < 0.001), hepatic transaminases, flow-mediated dilation (10.56% (95% CI 5.00, 16.12); p < 0.001), and carotid intima-media thickness (39.48% (95% CI 47.98, 30.97); p < 0.001). Further, the improvement in cardiometabolic variables was independent of the degree of hepatic steatosis. Altilix\uae supplementation improved hepatic and cardio-metabolic parameters in MetS subjects. Altilix\uae supplementation was a beneficial approach in the management of hepatic and cardiometabolic alterations in MetS subjects

Weak Transversality and Partially Invariant Solutions

New exact solutions are obtained for several nonlinear physical equations, namely the Navier-Stokes and Euler systems, an isentropic compressible fluid system and a vector nonlinear Schroedinger equation. The solution methods make use of the symmetry group of the system in situations when the standard Lie method of symmetry reduction is not applicable.Comment: 23 pages, preprint CRM-284