Insights into the structure and dynamics of lysyl oxidase propeptide, a flexible protein with numerous partners

Lysyl oxidase (LOX) catalyzes the oxidative deamination of lysine and hydroxylysine residues in collagens and elastin, which is the first step of the cross-linking of these extracellular matrix proteins. It is secreted as a proenzyme activated by bone morphogenetic protein-1, which releases the LOX catalytic domain and its bioactive N-terminal propeptide. We characterized the recombinant human propeptide by circular dichroism, dynamic light scattering, and small-angle X-ray scattering (SAXS), and showed that it is elongated, monomeric, disordered and flexible (Dmax: 11.7 nm, Rg: 3.7 nm). We generated 3D models of the propeptide by coarse-grained molecular dynamics simulations restrained by SAXS data, which were used for docking experiments. Furthermore, we have identified 17 new binding partners of the propeptide by label-free assays. They include four glycosaminoglycans (hyaluronan, chondroitin, dermatan and heparan sulfate), collagen I, cross-linking and proteolytic enzymes (lysyl oxidase-like 2, transglutaminase-2, matrix metalloproteinase-2), a proteoglycan (fibromodulin), one growth factor (Epidermal Growth Factor, EGF), and one membrane protein (tumor endothelial marker-8). This suggests new roles for the propeptide in EGF signaling pathway

Visual and auditory perceptual strength norms for 3,596 French nouns and their relationship with other psycholinguistic variables

Perceptual experience plays a critical role in the conceptual representation of words. Higher levels of semantic variables such as imageability, concreteness, and sensory experience are generally associated with faster and more accurate word processing. Nevertheless, these variables tend to be assessed mostly on the basis of visual experience. This underestimates the potential contributions of other perceptual modalities. Accordingly, recent evidence has stressed the importance of providing modality-specific perceptual strength norms. In the present study, we developed French Canadian norms of visual and auditory perceptual strength (i.e., the modalities that have major impact on word processing) for 3,596 nouns. We then explored the relationship between these newly developed variables and other lexical, orthographic, and semantic variables. Finally, we demonstrated the contributions of visual and auditory perceptual strength ratings to visual word processing beyond those of other semantic variables related to perceptual experience (e.g., concreteness, imageability, and sensory experience ratings). The ratings developed in this study are a meaningful contribution toward the implementation of new studies that will shed further light on the interaction between linguistic, semantic, and perceptual systems

External and internal noise surveys of London primary schools

Internal and external noise surveys have been carried out around schools in London, UK, to provide information on typical levels and sources to which children are exposed while at school. Noise levels were measured outside 142 schools, in areas away from flightpaths into major airports. 86% of the schools surveyed were exposed to noise from road traffic, the average external noise level outside a school being 57 dB LAeq. Detailed internal noise surveys have been carried out in 140 classrooms in 16 schools, together with classroom observations. It was found that noise levels inside classrooms depend upon the activities in which the children are engaged, with a difference of 20 dB LAeq between the 'quietest' and 'noisiest' activities. The average background noise level in classrooms exceeds the level recommended in current standards. The number of children in the classroom was found to affect noise levels. External noise influenced internal noise levels only when children were engaged in the quietest classroom activities. The effects of the age of the school buildings and types of window upon internal noise were examined but results were inconclusive

Optimal dietary energy and amino acids for gilt development: Growth, body composition, feed intake, and carcass composition traits

The objective of this study was to determine if body composition of developing gilts could be altered at the onset of estrus by ad libitum feeding diets differing in standard ileal digestible (SID) lysine and ME using levels that are within those used in practice by pig producers in the United States. Crossbred Large White × Landrace gilts (n = 1,221), housed in groups, were randomly allotted to 6 corn–soybean diets in a 2 × 3 factorial arrangement formulated to provide 2 SID lysine and 3 ME levels. Gilts received grower diets formulated to provide 0.86 (low) or 1.02% (high) SID lysine and 2.94 (low), 3.25 (medium), or 3.57 (high) Mcal of ME/kg from 100 d of age until approximately 90 kg BW. Then, gilts were fed finisher diets containing 0.73 (low) or 0.85% (high) SID lysine and 2.94 (low), 3.26 (medium) or 3.59 (high) Mcal of ME/kg until 260 d of age. The medium SID lysine and medium-ME diets were based on an informal survey from the U.S. commercial swine industry to obtain average levels that are currently being formulated for developing gilts. Gilts were weighed and backfat thickness and loin area were recorded at the beginning of the trial and then every 28 d. Feed intake (FI) was recorded as feed disappearance within the pen at 2-wk intervals. Lysine (g) and ME (Mcal) consumed were calculated based on diet formulations. At approximately 260 d of age, gilts were slaughtered and warm carcass weight and fat thickness were recorded. There were no differences between lysine or ME levels for growth and body composition, except for backfat, which was slightly greater for gilts fed a high-ME diet. Gilts fed high-ME diets had a lower FI but a greater ME intake compared with gilts fed low ME (P \u3c 0.05). Additionally, gilts fed the high-ME diet had lower FI and lysine intake per kilogram of BW gain when compared with gilts fed low- or medium-ME diets (P \u3c 0.05). However, there was no difference in the megacalories consumed per kilogram of BW gain among treatments (P \u3e 0.05). Carcasses from gilts fed the high-ME diet were 3.3 and 2.5 kg heavier than those from gilts fed the low- or medium-ME diets (P \u3c 0.05). Despite significant differences in the lysine:ME ratio in the diets, no changes in growth or body composition occurred, likely due to compensatory changes in FI in response to dietary ME content. Caloric efficiency (Mcal to deposit 1 kg of BW) was similar among treatments

Silica Materials for Medical Applications

The two main applications of silica-based materials in medicine and biotechnology, i.e. for bone-repairing devices and for drug delivery systems, are presented and discussed. The influence of the structure and chemical composition in the final characteristics and properties of every silica-based material is also shown as a function of the both applications presented. The adequate combination of the synthesis techniques, template systems and additives leads to the development of materials that merge the bioactive behavior with the drug carrier ability. These systems could be excellent candidates as materials for the development of devices for tissue engineering

Training a perceptron in a discrete weight space

On-line and batch learning of a perceptron in a discrete weight space, where each weight can take $2 L+1$ different values, are examined analytically and numerically. The learning algorithm is based on the training of the continuous perceptron and prediction following the clipped weights. The learning is described by a new set of order parameters, composed of the overlaps between the teacher and the continuous/clipped students. Different scenarios are examined among them on-line learning with discrete/continuous transfer functions and off-line Hebb learning. The generalization error of the clipped weights decays asymptotically as $exp(-K \alpha^2)$/$exp(-e^{|\lambda| \alpha})$ in the case of on-line learning with binary/continuous activation functions, respectively, where $\alpha$ is the number of examples divided by N, the size of the input vector and $K$ is a positive constant that decays linearly with 1/L. For finite $N$ and $L$, a perfect agreement between the discrete student and the teacher is obtained for $\alpha \propto \sqrt{L \ln(NL)}$. A crossover to the generalization error $\propto 1/\alpha$, characterized continuous weights with binary output, is obtained for synaptic depth $L > O(\sqrt{N})$.Comment: 10 pages, 5 figs., submitted to PR

The relevance of biomaterials to the prevention and treatment of osteoporosis

Osteoporosis is a worldwide disease with a very high prevalence in humans older than 50. The main clinical consequences are bone fractures, which often lead to patient disability or even death. A number of commercial biomaterials are currently used to treat osteoporotic bone fractures, but most of these have not been specifically designed for that purpose. Many drug- or cell-loaded biomaterials have been proposed in research laboratories, but very few have received approval for commercial use. In order to analyze this scenario and propose alternatives to overcome it, the Spanish and European Network of Excellence for the Prevention and Treatment of Osteoporotic Fractures, ‘‘Ageing’’, was created. This network integrates three communities, e.g. clinicians, materials scientists and industrial advisors, tackling the same problem from three different points of view. Keeping in mind the premise ‘‘living longer, living better’’, this commentary is the result of the thoughts, proposals and conclusions obtained after one year working in the framework of this network

Magnetic and structural-properties of electrodeposited Co1-xPx amorphous ribbons

The specific magnetic moment, coercive force, anisotropy field, and saturation magnetostriction constant have been measured in Co(1-x)P(x) amorphous ribbons with 0.04 less-than-or-equal-to x less-than-or-equal-to 0.27. Differential scanning calorimetry, x-ray diffraction, and transmission electron microscopy analysis have been made in order to study the transition from the amorphous state to the crystalline one. Results suggest that transition takes place when x decreases from 0.19

Fractal Spin Glass Properties of Low Energy Configurations in the Frenkel-Kontorova chain

We study numerically and analytically the classical one-dimensional Frenkel-Kontorova chain in the regime of pinned phase characterized by phonon gap. Our results show the existence of exponentially many static equilibrium configurations which are exponentially close to the energy of the ground state. The energies of these configurations form a fractal quasi-degenerate band structure which is described on the basis of elementary excitations. Contrary to the ground state, the configurations inside these bands are disordered.Comment: revtex, 9 pages, 9 figure

On Nonlinear Stochastic Balance Laws

We are concerned with multidimensional stochastic balance laws. We identify a class of nonlinear balance laws for which uniform spatial $BV$ bounds for vanishing viscosity approximations can be achieved. Moreover, we establish temporal equicontinuity in $L^1$ of the approximations, uniformly in the viscosity coefficient. Using these estimates, we supply a multidimensional existence theory of stochastic entropy solutions. In addition, we establish an error estimate for the stochastic viscosity method, as well as an explicit estimate for the continuous dependence of stochastic entropy solutions on the flux and random source functions. Various further generalizations of the results are discussed