Bril: A novel bone-specific modulator of mineralization

In the course of attempting to define the bone ""secretome"" using a signal-trap screening approach, we identified a gene encoding a small membrane protein novel to osteoblasts. Although previously identified in silico as ifitm5, no localization or functional studies had been undertaken on this gene. We characterized the expression patterns and localization of this gene in vitro and in vivo and assessed its role in matrix mineralization in vitro. The bone specificity and shown role in mineralization led us to rename the gene bone restricted ifitm-like protein (Bril). Bril encodes a 14.8-kDa 1.34 arnino acid protein with two transmembrane domains. Northern blot analysis showed bone-specific expression with no expression in other embryonic or adult tissues. In situ hybridization and immunohistochemistry in mouse embryos showed expression localized on the developing bone. Screening of cell lines showed Bril expression to be highest in osteoblasts, associated with the onset of matrix maturation/mineralization, suggesting a role in bone formation. Functional evidence of a role in mineralization was shown by adenovirus-mediated Brit overexpression and lentivirus-mediated Bril shRNA knockdown in vitro. Elevated Bril resulted in dose-dependent increases in mineralization in UMR106 and rat primary osteoblasts. Conversely, knockdown of Bril in MC3T3 osteoblasts resulted in reduced mineralization. Thus, we identified Bril as a novel osteoblast protein and showed a role in mineralization, possibly identifying a new regulatory pathway in bone formation.

INDEFINITE QUASILINEAR ELLIPTIC EQUATIONS IN EXTERIOR DOMAINS WITH EXPONENTIAL CRITICAL GROWTH

This paper is concerned with the existence of solutions for the quasilinear problem {-div(vertical bar del u vertical bar(N-2) del u) + vertical bar u vertical bar(N-2) u = a(x)g(u) in Omega u = 0 on partial derivative Omega, where Omega subset of R(N) (N >= 2) is an exterior domain; that is, Omega = R(N)\omega, where omega subset of R(N) is a bounded domain, the nonlinearity g(u) has an exponential critical growth at infinity and a(x) is a continuous function and changes sign in Omega. A variational method is applied to establish the existence of a nontrivial solution for the above problem.

Semilinear parabolic problems in thin domains with a highly oscillatory boundary

In this paper, we study the behavior of the solutions of nonlinear parabolic problems posed in a domain that degenerates into a line segment (thin domain) which has an oscillating boundary. We combine methods from linear homogenization theory for reticulated structures and from the theory on nonlinear dynamics of dissipative systems to obtain the limit problem for the elliptic and parabolic problems and analyze the convergence properties of the solutions and attractors of the evolutionary equations. (C) 2011 Elsevier Ltd. All rights reserved.

Dynamics in dumbbell domains II. The limiting problem

In this work we continue the analysis of the asymptotic dynamics of reaction-diffusion problems in a dumbbell domain started in [J.M. Arrieta, AN Carvalho, G. Lozada-Cruz, Dynamics in dumbbell domains I. Continuity of the set of equilibria, J. Differential Equations 231 (2) (2006) 551-597]. Here we study the limiting problem, that is, an evolution problem in a ""domain"" which consists of an open, bounded and smooth set Omega subset of R(N) with a curve R(0) attached to it. The evolution in both parts of the domain is governed by a parabolic equation. In Omega the evolution is independent of the evolution in R(0) whereas in R(0) the evolution depends on the evolution in Omega through the continuity condition of the solution at the junction points. We analyze in detail the linear elliptic and parabolic problem, the generation of linear and nonlinear semigroups, the existence and structure of attractors. (C) 2009 Elsevier Inc. All rights reserved.

Dynamics in dumbbell domains III. Continuity of attractors

In this paper we conclude the analysis started in [J.M. Arrieta, AN Carvalho, G. Lozada-Cruz, Dynamics in dumbbell domains I. Continuity of the set of equilibria, J. Differential Equations 231 (2006) 551-597] and continued in [J.M. Arrieta, AN Carvalho, G. Lozada-Cruz, Dynamics in dumbbell domains II. The limiting problem, J. Differential Equations 247 (1) (2009) 174-202 (this issue)] concerning the behavior of the asymptotic dynamics of a dissipative reaction-diffusion equation in a dumbbell domain as the channel shrinks to a line segment. In [J.M. Arrieta, AN Carvalho. G. Lozada-Cruz, Dynamics in dumbbell domains I. Continuity of the set of equilibria, J. Differential Equations 231 (2006) 551-597], we have established an appropriate functional analytic framework to address this problem and we have shown the continuity of the set of equilibria. In [J.M. Arrieta, AN Carvalho, G. Lozada-Cruz. Dynamics in dumbbell domains II. The limiting problem, J. Differential Equations 247 (1) (2009) 174-202 (this issue)], we have analyzed the behavior of the limiting problem. In this paper we show that the attractors are Upper semicontinuous and, moreover, if all equilibria of the limiting problem are hyperbolic, then they are lower semicontinuous and therefore, continuous. The continuity is obtained in L(p) and H(1) norms. (C) 2008 Elsevier Inc. All rights reserved.

A thermoelastic system of memory type in noncylindrical domains

In this paper, we consider a hyperbolic thermoelastic system of memory type in domains with moving boundary. The problem models vibrations of an elastic bar under thermal effects according to the heat conduction law of Gurtin and Pipkin. Global existence is proved by using the penalty method of Lions. (c) 2007 Elsevier Inc. All rights reserved.

Infeasibility handling in genetic algorithm using nested domains for production planning

In this paper we present a genetic algorithm with new components to tackle capacitated lot sizing and scheduling problems with sequence dependent setups that appear in a wide range of industries, from soft drink bottling to food manufacturing. Finding a feasible solution to highly constrained problems is often a very difficult task. Various strategies have been applied to deal with infeasible solutions throughout the search. We propose a new scheme of classifying individuals based on nested domains to determine the solutions according to the level of infeasibility, which in our case represents bands of additional production hours (overtime). Within each band, individuals are just differentiated by their fitness function. As iterations are conducted, the widths of the bands are dynamically adjusted to improve the convergence of the individuals into the feasible domain. The numerical experiments on highly capacitated instances show the effectiveness of this computational tractable approach to guide the search toward the feasible domain. Our approach outperforms other state-of-the-art approaches and commercial solvers. (C) 2009 Elsevier Ltd. All rights reserved.

Electrical transport in disordered and ordered magnetic domains under pressures and magnetic fields

Magnetic M( T, H, P) and electrical transport.( T, H, P) measurements in a strong spin-lattice-charge coupled La(0.7)Ca(0.3)MnO(3) system have been conducted. The application of H and P leads to the formation of different magnetic domain structures in the vicinity and below the polaronic-to-ferromagnetic transition temperature. The charge mobility is more sensitive to the variation of the spatial wave function overlap between Mn(3+) eg and O(2-) 2p orbitals due to the applied compacting pressure rather than the relative spin orientation between neighbouring Mn ions when the magnetic field is applied. In spite of the presence of different magnetic domain structures due to the sample history, the effect of magnetic field and pressure is less pronounced at lower temperatures on electrical transport properties.

Vesicles with charged domains

This work summarizes results obtained on membranes composed of the ternary mixture dioleoylphosphatidylglycerol (DOPG), egg sphingomyelin (eSM) and cholesterol (Chol). The membrane phase state as a function of composition is characterized from data collected with fluorescence microscopy on giant unilamellar vesicles. The results suggest that the presence of the charged DOPG significantly decreases the composition region of coexistence of liquid ordered and liquid disordered phases as compared to that in the ternary mixture of dioleoylphosphatidycholine, sphingomyelin and cholesterol. The addition of calcium chloride to DOPG:eSM:Chol vesicles, and to a lesser extent the addition of sodium chloride, leads to the stabilization of the two-phase coexistence region, which is expressed in an increase in the miscibility temperature. On the other hand, addition of the chelating agent EDTA has the opposite effect, suggesting that impurities of divalent cations in preparations of giant vesicles contribute to the stabilization of charged domains. We also explore the behavior of these membranes in the presence of extruded unilamellar vesicles made of the positively charged lipid dioleoyltrimethylammoniumpropane (DOTAP). The latter can induce domain formation in DOPG:eSM:Chol vesicles with initial composition in the one-phase region. (C) 2010 Elsevier B.V. All rights reserved.

The defensive functions of plant inhibitors are not restricted to insect enzyme inhibition

Three plant proteinase inhibitors BbKI (kallikrein inhibitor) and BbCI (cruzipain inhibitor) from Bauhinia bouhinioides, and a BrTI (trypsin inhibitor) from B. rufa, were examined for other effects in Callosobruchus maculatus development; of these only BrTI affected bruchid emergence. BrTI and BbKI share 81% identities in their primary sequences and the major differences between them are the regions comprising the RGD and RGE motifs in BrTI. These sequences were shown to be essential for BrTI insecticidal activity, since a modified BbKI [that is a recombinant form (BbKIm) with some amino acid residues replaced by those found in BrTI sequence] also strongly inhibited insect development. By using synthetic peptides related to the BrTI sequence, YLEAPVARGDGGLA-NH(2) (RGE) and IVYYPDRGETGL-NH(2) (RGE), it was found that the peptide with an RGE sequence was able to block normal development of C. maculatus larvae (ED(50) 0.16% and LD(50) 0.09%), this being even more effective than the native protein. (C) 2009 Elsevier Ltd. All rights reserved.

The Cariris Velhos tectonic event in Northeast Brazil

The Borborema Province in northeastern South America is a typical Brasiliano-Pan-African branching system of Neoproterozoic orogens that forms part of the Western Gondwana assembly. The province is positioned between the Sao Luis-West Africa craton to the north and the Sao Francisco (Congo-Kasai) craton to the south. For this province the main characteristics are (a) its subdivision into five major tectonic domains, bounded mostly by long shear zones, as follows: Medio Coreau, Ceara Central, Rio Grande do Norte, Transversal, and Southern; (b) the alternation of supracrustal belts with reworked basement inliers (Archean nuclei + Paleoproterozoic belts); and (c) the diversity of granitic plutonism, from Neoproterozoic to Early Cambrian ages, that affect supracrustal rocks as well as basement inliers. Recently, orogenic rock assemblages of early Tonian (1000-920 Ma) orogenic evolution have been recognized, which are restricted to the Transversal and Southern domains of the Province. Within the Transversal Zone, the Alto Pajeu terrane locally includes some remnants of oceanic crust along with island arc and continental arc rock assemblages, but the dominant supracrustal rocks are mature and immature pelitic metasedimentary and metavolcaniclastic rocks. Contiguous and parallel to the Alto Pajeu terrane, the Riacho Gravata subterrane consists mainly of low-grade metamorphic successions of metarhythmites, some of which are clearly turbiditic in origin, metaconglomerates, and sporadic marbles, along with interbedded metarhyolitic and metadacitic volcanic or metavolcaniclastic rocks. Both terrane and subterrane are cut by syn-contractional intrusive sheets of dominantly peraluminous high-K calc-alkaline, granititic to granodioritic metaplutonic rocks. The geochemical patterns of both supracrustal and intrusive rocks show similarities with associations of mature continental arc volcano-sedimentary sequences, but some subordinate intra-plate characteristics are also found. In both the Alto Pajeu and Riacho Gravata terranes, TIMS and SHRIMP U-Pb isotopic data from zircons from both metavolcanic and metaplutonic rocks yield ages between 1.0 and 0.92 Ga, which define the time span for an event of orogenic character, the Cariris Velhos event. Less extensive occurrences of rocks of Cariris Velhos age are recognized mainly in the southernmost domains of the Province, as for example in the Polo Redondo-Maranco terrane, where arc-affinity migmatite-granitic and meta-volcano-sedimentary rocks show U-Pb ages (SHRIMP data) around 0.98-0.97 Ga. For all these domains, Sm-Nd data exhibit Tom model ages between 1.9 and 1.1 Ga with corresponding slightly negative to slightly positive epsilon(Nd)(t) values. These domains, along with the Borborema Province as a whole, were significantly affected by tectonic and magmatic events of the Brasiliano Cycle (0.7-0.5 Ga), so that it is possible that there are some other early Tonian rock assemblages which were completely masked and hidden by these later Brasiliano events. Cariris Velhos processes are younger than the majority of orogenic systems at the end of Mesoproterozoic Era and beginning of Neoproterozoic throughout the world, e.g. Irumide belt, Kibaride belt and Namaqua-Natal belt, and considerably younger than those of the youngest orogenic process (Ottawan) in the Grenvillian System. Therefore, they were probably not associated with the proposed assembly of Rodinia. We suggest, instead, that Cariris Velhos magmatism and tectonism could have been related to a continental margin magmatic arc, with possible back-arc associations, and that this margin may have been a short-lived (<100 m.y.) leading edge of the newly assembled Rodinia supercontinent. (C) 2009 Elsevier Ltd. All rights reserved.

Reaction microtextures of monazite: Correlation between chemical and age domains in the Nazare Paulista migmatite, SE Brazil

Back-scattered imaging, X-ray element mapping and electron microprobe analyzer (EMPA) chemical dating reveal complex compositional and age zoning in monazite crystals from different layers and textural positions in a garnet-bearing migmatite in SE Brazil. Y-rich (variable Y(2)O(3), averaging 2.5 wt.%) relict cores are preserved in mesosome and melanosome monazite, and correspond to 793 +/- 6 Ma inherited crystals possibly generated in a previous metamorphic event. These cores are overgrown and widely replaced by two generations of monazite, which are present in all migmatite layers. The first, also Y-rich (average 2.5 wt.% Y(2)O(3)), was produced at similar to 635 Ma during prograde metamorphism under subsolidus conditions, while the second has an Y-poor (<1.5 wt.% Y(2)O(3)), low Th/U signature, and precipitated from low Y and HREE anatectic melts produced by reactions in which garnet was inert. Quartz-rich trondhjemitic leucosome represents lower temperature melt (bearing some subsolidus quartz and garnet with included monazite) formed at temperatures below muscovite breakdown; its Y-poor monazite indicates an age of 617 +/- 6 Ma. Granitic leucosomes formed close to peak metamorphic conditions (T>750 degrees C) above muscovite breakdown have their slightly younger character confirmed by a 609 +/- 7 Ma low-Y monazite age. A similar 606 +/- 5 Ma age was obtained for low-Y monazite rims and domains in mesosome and melanosome, and reflects the time of monazite saturation in interstitial granitic melt that was trapped in these layers. Our results confirm that inherited monazite crystals can be preserved during partial melting at temperatures above muscovite breakdown. Moreover, careful textural control aided by X-ray chemical mapping may allow monazite generated at different stages in a similar to 25 Myr prograde metamorphic path to be identified and dated using an electron microprobe. (C) 2008 Elsevier B.V. All rights reserved.

Filtered Multiplicative Bases of Restricted Enveloping Algebras

We study the problem of the existence of filtered multiplicative bases of a restricted enveloping algebra u(L), where L is a finite-dimensional and p-nilpotent restricted Lie algebra over a field of positive characteristic p.

Skipping of exon 30 in C5 gene results in complete human C5 deficiency and demonstrates the importance of C5d and CUB domains for stability

The deficiency of complement C5 is rare and frequently associated with severe and recurrent infections, especially caused by Neisseria spp. We observed the absence of component C5 in the serum of 3 siblings from a Brazilian family with history of consanguinity. The patients had suffered from recurrent episodes of meningitis and other less severe infections. Sera from these patients were unable to mediate hemolytic activity either by the classical or alternative pathways and presented extremely low levels of C5 protein (13, 0.9 and 1.0 mu g/ml-normal range: 45-190 mu g/ml). Hemolytic activity could be restored by the addition of purified C5 to deficient serum. Sequencing of sibling C5 cDNA revealed a homozygous 153 bp deletion that corresponds precisely to exon 30. The parents carried the same deletion but only in one allele. Sequencing of the corresponding region in the genomic DNA revealed a C to C substitution within intron 30 and, most significantly, the substitution of GAG(4028) for GAA(4028) at the 3` end of exon 30 which is most likely responsible for skipping of exon 30. The resulting in-frame deletion in the C5 mRNA codes for a mutant C5 protein lacking residues 1289-1339. These residues map to the CUB and C5d domains of the C5 alpha chain. This deletion is expected to produce a non-functional and unstable C5 protein which is more susceptible to degradation. (C) 2009 Published by Elsevier Ltd.