Ribonucleotides and manganese ions improve non-homologous end joining by human Polμ

Human DNA polymerase mu (Polμ), a family X member involved in DNA repair, has both template-directed and terminal transferase (template-independent) activities. In addition to their ability to incorporate untemplated nucleotides, another similarity between Polµ and terminal deoxynucleotidyl transferase (TdT) is their promiscuity in using ribonucleotides (NTPs), whose physiological significance is presently unknown. As shown here, Polµ can use NTPs instead of deoxynucleotides (dNTPs) during non-homologous end joining (NHEJ) of non-complementary ends, a Polµ-specific task. Moreover, a physiological concentration of Mn 2+ ions did benefit Polµ-mediated NHEJ by improving the efficiency and accuracy of nucleotide insertion. Analysis of different mutations in the ‘steric gate’ of the active site indicated that Polµ is taking advantage of an open active site, valid for selecting alternative activating metal ions and nucleotides as substrates. This versatility would allow ad hoc selection of the most appropriate nucleotide/metal ion combination for individual NHEJ events to gain efficiency without a cost in terms of fidelity, thus widening the spectrum of available solutions to position a discontinuous template strand in proper register for connection

Study of the Molecular Weight Influence on the Formation of the ß-polymorph in Metallocenic Isotactic Polypropylene

Isotactic polypropylene, iPP, is one of the most important thermoplastic polymers due to its low manufacturing cost and rather versatile properties. iPP exhibits a very interesting polymorphic behavior depending on the polymerization procedure, thermal history and use of different nucleating agents. Recently, studies on different aspects of the iPP β-polymorph have been published [1, 2]. This paper completes these previous works by analyzing the formation of the β-polymorph starting from samples of metallocenic iPP of different molecular weight. We also consider the effect of the cooling rate in the appearance of β-polymorph in the iPP samples that were studied

Diffantom: Whole-Brain Diffusion MRI Phantoms Derived from Real Datasets of the Human Connectome Project.

Food allergies are believed to be on the rise and currently management relies on the avoidance of the food. Hen's egg allergy is after cow's milk allergy the most common food allergy; eggs are used in many food products and thus difficult to avoid. A technological process using a combination of enzymatic hydrolysis and heat treatment was designed to produce modified hen's egg with reduced allergenic potential. Biochemical (SDS-PAGE, Size exclusion chromatography and LC-MS/MS) and immunological (ELISA, immunoblot, RBL-assays, animal model) analysis showed a clear decrease in intact proteins as well as a strong decrease of allergenicity. In a clinical study, 22 of the 24 patients with a confirmed egg allergy who underwent a double blind food challenge with the hydrolysed egg remained completely free of symptoms. Hydrolysed egg products may be beneficial as low allergenic foods for egg allergic patients to extent their diet. This article is protected by copyright. All rights reserved

A specific N-terminal extension of the 8 kDa domain is required for DNA end-bridging by human Polµ and Polλ

Human DNA polymerases mu (Polµ) and lambda (Polλ) are X family members involved in the repair of double-strand breaks in DNA during non-homologous end joining. Crucial abilities of these enzymes include bridging of the two 3′ single-stranded overhangs and trans-polymerization using one 3′ end as primer and the other as template, to minimize sequence loss. In this context, we have studied the importance of a previously uncharacterised sequence (‘brooch’), located at the N-terminal boundary of the Polß-like polymerase core, and formed by Tyr141, Ala142, Cys143, Gln144 and Arg145 in Polµ, and by Trp239, Val240, Cys241, Ala242 and Gln243 in Polλ. The brooch is potentially implicated in the maintenance of a closed conformation throughout the catalytic cycle, and our studies indicate that it could be a target of Cdk phosphorylation in Polµ. The brooch is irrelevant for 1 nt gap filling, but of specific importance during end joining: single mutations in the conserved residues reduced the formation of two ended synapses and strongly diminished the ability of Polµ and polymerase lambda to perform non-homologous end joining reactions in vitro

Data on the verification and validation of segmentation and registration methods for diffusion MRI.

The verification and validation of segmentation and registration methods is a necessary assessment in the development of new processing methods. However, verification and validation of diffusion MRI (dMRI) processing methods is challenging for the lack of gold-standard data. The data described here are related to the research article entitled "Surface-driven registration method for the structure-informed segmentation of diffusion MR images" [1], in which publicly available data are used to derive golden-standard reference-data to validate and evaluate segmentation and registration methods in dMRI

Global attractor for a nonlinear oscillator coupled to the Klein-Gordon field

The long-time asymptotics is analyzed for all finite energy solutions to a model U(1)-invariant nonlinear Klein-Gordon equation in one dimension, with the nonlinearity concentrated at a single point: each finite energy solution converges as time goes to plus or minus infinity to the set of all ``nonlinear eigenfunctions'' of the form \psi(x)e\sp{-i\omega t}. The global attraction is caused by the nonlinear energy transfer from lower harmonics to the continuous spectrum and subsequent dispersive radiation. We justify this mechanism by the following novel strategy based on inflation of spectrum by the nonlinearity. We show that any omega-limit trajectory has the time-spectrum in the spectral gap [-m,m] and satisfies the original equation. This equation implies the key spectral inclusion for spectrum of the nonlinear term. Then the application of the Titchmarsh Convolution Theorem reduces the spectrum of each omega-limit trajectory to a single harmonic in [-m,m]. The research is inspired by Bohr's postulate on quantum transitions and Schroedinger's identification of the quantum stationary states to the nonlinear eigenfunctions of the coupled U(1)-invariant Maxwell-Schroedinger and Maxwell-Dirac equations.Comment: 29 pages, 1 figur

Inducible nitric oxide synthase in human lymphomononuclear cells activated by synthetic peptides derived from extracellular matrix proteins.

Synthetic peptides with sequences present in extracellular matrix proteins are capable of causing the expression of the inducible form of nitric oxide synthase (iNOS), detected by immunocytochemistry, and the release of NO by human lymphomononuclear cells incubated in their presence. Active peptides are 15-mers containing a characteristic 2-6-11 motif in which the amino acid residue at position 2 is Leu, Ile, Val, Gly, Ala or Lys; the residue at position 6 is always Pro; and residue 11 is Glu or Asp. The induction of iNOS in human monocytes and macrophages could be involved in the cytotoxicity against tumor cell lines also elicited by these peptides

Immunomodulation induced by synthetic peptides derived from Staphylococcus aureus protein A

Peptides from 10 to 22 amino acids containing sequences encompassed by Staphylococcus aureus protein A were synthesized. Some of these peptides, when present in cultures of lymphomononuclear cells from healthy donors or from cancer patients (melanoma, breast carcinoma, non-Hodgkin lymphoma and renal cell carcinoma) promoted: (i) changes in the phenotype of the lymphomononuclear population, (ii) stimulation of monocytes (release of IL-1 and TNF-alpha), and (iii) an increase in cytotoxicity against K562, Daudi and HT-29 cells. Isolated monocytes responded also to those peptides with a release of IL-1 and TNF alpha and an increase of cytotoxicity against HT-29 cells. It was found that the active peptides had the following structural pattern: a length of at least 15 amino-acid residues with a proline at position 6, valine, leucine, isoleucine, glycine, alanine or lysine at position 2, and glutamic or aspartic acid at position 11. Replacement of Pro at position 6 with any other residue turned the peptide inactive. Replacement of residues at positions 2 and 11 with amino-acid residues other than those required for activity resulted in compounds with a marked decrease in the immunomodulating properties described, or lacking these properties altogether

Multiple solutions to a magnetic nonlinear Choquard equation

We consider the stationary nonlinear magnetic Choquard equation [(-\mathrm{i}\nabla+A(x))^{2}u+V(x)u=(\frac{1}{|x|^{\alpha}}\ast |u|^{p}) |u|^{p-2}u,\quad x\in\mathbb{R}^{N}%] where $A\$is a real valued vector potential, $V$ is a real valued scalar potential$,$ $N\geq3$, $\alpha\in(0,N)$ and $2-(\alpha/N) <p<(2N-\alpha)/(N-2)$. \ We assume that both $A$ and $V$ are compatible with the action of some group $G$ of linear isometries of $\mathbb{R}^{N}$. We establish the existence of multiple complex valued solutions to this equation which satisfy the symmetry condition $$u(gx)=\tau(g)u(x)\text{\ \ \ for all}g\in G,\text{}x\in\mathbb{R}^{N},$$ where $\tau:G\rightarrow\mathbb{S}^{1}$ is a given group homomorphism into the unit complex numbers.Comment: To appear on ZAM

Influence of moisture content on the wave velocity to estimate the mechanical properties of large cross-section pieces for structural use of scots pine from spain

The aim of this research is to evaluate the influence of the moisture content of wood on stress wave velocity, as a nondestructive technique for estimating the mechanical properties of gross cross-section Spanish Scots pine (Pinus sylvestris) lumber for structural use. 26 100 x 150 x 3000 mm pieces from Segovia, Spain, were tested with different moisture content values, from 35,5 to 9%. Measurements of longitudinal stress wave velocity were carried out during the natural drying process by using three commercial portable devices based on ultrasonic, acoustic and vibrational techniques. The results can be summarized as three percentage points of decreasing velocity per percentage point of increased wood moisture content in the range from 11,8 to 21,4%: 0,48% for ultrasonic, 0,50% for acoustic wave and 0,65% for longitudinal vibration