bluuebunny/crossref_metadata_2025 huggingface dataset:
A Hölder continuous ODE related to traffic flow
Authors: Colombo Rinaldo M. , Marson Andrea
Published: July 2007

This paper is devoted to the proof of the well posedness of a class of ordinary differential equations (ODEs). The vector field depends on the solution to a scalar conservation law. Forward uniqueness of Filippov solutions is obtained, as well as their Hölder continuous dependence on the initial data of the ODE. Furthermore, we prove the continuous dependence in C0 of the solution to the ODE from the initial data of the conservation law in L1.

This problem is motivated by a model of traffic flow.
Homogenization of a Hamilton–Jacobi equation associated with the geometric motion of an interface
Authors: Craciun Bogdan , Bhattacharya Kaushik
Published: July 2007

This paper studies the overall evolution of fronts propagating with a normal velocity that depends on position, υn = f(x), where f is rapidly oscillating and periodic. A level-set formulation is used to rewrite this problem as the periodic homogenization of a Hamilton–Jacobi equation. The paper presents a series of variational characterization (formulae) of the effective Hamiltonian or effective normal velocity. It also examines the situation when f changes sign.
Some limiting properties of randomly forced two-dimensional Navier–Stokes equations
Authors: Kuksin Sergei , Shirikyan Armen
Published: July 2007

We consider random perturbations of two-dimensional Navier–Stokes equations. Under some natural conditions on random forces, we study asymptotic properties of solutions and stationary measures.
Singularities of line congruences
Authors: Izumiya Shyuichi , Saji Kentaro , Takeuchi Nobuko
Published: July 2007

A line congruence is a two-parameter family of lines in R3. In this paper we study singularities of line congruences. We show that generic singularities of general line congruences are the same as those of stable mappings between three-dimensional manifolds. Moreover, we also study singularities of normal congruences and equiaffine normal congruences from the viewpoint of the theory of Lagrangian singularities.
On new geometric conditions for some weakly lower semicontinuous functionals with applications to the rank-one conjecture of Morrey
Authors: Kałamajska Agnieszka
Published: July 2007

We obtain new geometric necessary conditions for a function f to define a lower semicontinuous functional of the form If(u) = ∫Ωf(u)dx, where u satisfies a given conservation law, Pu = 0, defined by a differential operator P of degree one with constant coefficients. Those conditions imply the so-called Λ-convexity condition known as the rank-one condition when we deal with a functional of the calculus of variations. In particular, we derive some new geometric properties of quasi-convex functions and state some new questions related to the rank-one conjecture of Morrey.
Bouncing solutions of an equation with attractive singularity
Authors: Qian Dingbian , Torres Pedro J.
Published: July 2007

For any n, m ∈ N, we prove the existence of 2mπ-periodic solutions, with n bouncings in each period, for a second-order forced equation with attractive singularity by using the approach of successor map and Poincaré-Birkhoff twist theorem.
Ordinary differential equations and systems with time-dependent discontinuity sets
Authors: Cid J. Ángel , Pouso Rodrigo L.
Published: July 2007

In this paper we prove new existence results for non-autonomous systems of first order ordinary differential equations under weak conditions on the nonlinear part. Discontinuities with respect to the unknown are allowed to occur over general classes of time-dependent sets which are assumed to satisfy a kind of inverse viability condition.
The electromagnetic inverse-scattering problem for partly coated Lipschitz domains
Authors: Cakoni Fioralba , Colton David , Monk Peter
Published: July 2007

We consider the inverse-scattering problem of determining the shape of a partly coated obstacle in R3 from a knowledge of the incident time-harmonic electromagnetic plane wave and the electric far-field pattern of the scattered wave. A justification is given of the linear sampling method in this case and numerical examples are provided showing the practicality of our method.
Multi-parameter homogenization by localization and blow-up
Authors: Alvarez Felipe , Mandallena Jean-Philippe
Published: July 2007

We give an alternative self-contained proof of the homogenization theorem for periodic multi-parameter integrals that was established by the authors. The proof in that paper relies on the so-called compactness method for Γ-convergence, while the one presented here is by direct verification: the candidate to be the limit homogenized functional is first exhibited and the definition of Γ-convergence is then verified. This is done by an extension of bounded gradient sequences using the Acerbi et al. extension theorem from connected sets, and by the adaptation of some localization and blow-up techniques developed by Fonseca and Müller, together with De Giorgi's slicing method.
Diffusive–dispersive travelling waves and kinetic relations V. Singular diffusion and nonlinear dispersion
Authors: Bedjaoui Nabil , LeFloch Philippe G.
Published: July 2007

We consider scalar hyperbolic conservation laws with non-convex flux and vanishing, nonlinear and possibly singular, diffusion and dispersion terms. The diffusion has the form R(u, ux)x and we cover, for instance, the singular diffusion (|ux|pux)x, where p ≥ 0 is arbitrary. We investigate the existence, uniqueness and various properties of classical and non-classical travelling waves and of the kinetic function. The latter serves to characterize non-classical shock waves, via an additional algebraic constrain called a kinetic relation. We discover that p = ⅓ is a somewhat unexpected critical value. For p ≤ ⅓, we obtain properties that are qualitatively similar to those we established earlier for regular and linear diffusion. However, for p > ⅓, the behaviour of the kinetic function is very different, as, for instance, non-classical shocks can have arbitrary small strength. The behaviour of the kinetic function near the origin is carefully investigated and depends on whether p < ½, p = ½ or p > ½. In particular, in the special case of the cubic flux-function and for the regularization (|ux|pux)x with p = 0, ½ or 1, the kinetic function can be computed explicitly. When p = ½, the kinetic function is simply a linear function of its argument.
Uniqueness of the algebraic multiplicity
Authors: Mora-Corral Carlos
Published: July 2007

Given a smooth function 𝔏 of a real or complex variable and taking its values in the class of Fredholm operators of index zero in a Banach space, there are some available definitions in the literature of algebraic multiplicity of the family 𝔏 at a point x0 of the parameter at which the operator 𝔏(x0) becomes non-invertible. The purpose of this paper is to suggest an axiomatic for the multiplicity and to prove that the algebraic multiplicity is uniquely determined by a few of its properties, independently of its construction.
Strict convergence and minimal liftings in BV
Authors: Jerrard R. L. , Jung N.
Published: July 2007

Given a function υ ∈ BV (Ω; Rm), we introduce the notion of a minimal lifting of Dυ. We prove that every υ ∈ BV (Ω; Rm) has a unique minimal lifting, and we show that if υk → υ strictly in BV, then the minimal liftings of υk converge weakly as measures to the minimal lifting of υ. As an application, we deduce a result about weak continuity of the distributional determinant Det D2u with respect to strict convergence.
A-quasi-convexity with variable coefficients
Authors: Santos Pedro M.
Published: July 2007

It is shown that, for integrals of the type

with Ω RN open, bounded and f: Ω × Rm × Rd → [0, + ∞) Carathéodory satisfying a growth condition 0 ≤ f(x, u, υ) ≤ C(1 + |υ|p), for some p ∈ (1, + ∞), a sufficient condition for lower semi-continuity along sequences un → u in measure, υn → υ in Lp, Aυn → 0 in W−1, p is the Ax-quasi-convexity of f(x, u, ·). Here, A is a variable coefficients operator of the form

with A(i) ∈ C∞ (Ω; Ml × d) ∩ W1, ∞, i = 1, …, N, satisfying the condition

and Ax denotes the constant coefficients operator one obtains by freezing x. Under additional regularity conditions on f, it is proved that the condition above is also necessary. A characterization of the Young measures generated by bounded sequences {υn} in Lp satisfying the condition Aυn → 0 in W−1,p, is obtained.
Multi-parameter bifurcation and asymptotics for the singular Lane–Emden–Fowler equation with a convection term
Authors: Ghergu Marius , Rădulescu Vicenţiu
Published: July 2007

We establish some bifurcation results for the boundary-value problem −Δu = g (u) + λ|∇u|p + μf (x, u) in Ω, u > 0 in Ω, u = 0 on δΩ, where Ω is a smooth bounded domain in RN, λ, μ ≥ 0, 0 < p ≤ 2, f is non-decreasing with respect to the second variable and g is unbounded around the origin. The asymptotic behaviour of the solution around the bifurcation point is also established, provided g(u) behaves like u−α around the origin, for some 0 < α < 1. Our approach relies on finding explicit sub- and supersolutions combined with various techniques related to the maximum principle for elliptic equations. The analysis we develop in this paper shows the key role played by the convection term |∇u|p.
Optimal bounds for bifurcation values of a superlinear periodic problem
Authors: Ortega Rafael , Zhang Meirong
Published: July 2007

In this paper we will show that the optimal bounds for certain static and dynamic bifurcation values of periodic solutions of some superlinear differential equations can be expressed explicitly using Sobolev constants.
Positive steady states of the Holling–Tanner prey–predator model with diffusion
Authors: Peng Rui , Wang Mingxin
Published: July 2007

This paper is concerned with the Holling–Tanner prey–predator model with diffusion subject to the homogeneous Neumann boundary condition. We obtain the existence and non-existence of positive non-constant steady states.
Canonical systems of differential equations with self-adjoint interface conditions on graphs
Authors: de Snoo Henk , Winkler Henrik
Published: July 2007

For n canonical systems of differential equations, the corresponding n copies of their domain (0, ∞) are thought of as a graph with vertex 0. An interface condition at 0 is given by a so-called Nevanlinna pair. Explicit formulae are deduced for the spectral representation of the corresponding underlying self-adjoint relation and the generalized Fourier transformation. Furthermore, results on compressions of the Fourier transformation to closed linear subspaces and the multiplicity of the eigenvalues if the spectrum is discrete are presented
A note on the monotonicity of the Maslov-type index of linear Hamiltonian systems with applications
Authors: Liu Chun-Gen
Published: July 2007

In this note, we first consider the monotonicity of the Maslov-type index theory. More precisely, for any two 1-periodic symmetric continuous matrix functions B0(t) and B1(t) with B0(t) < B1(t), we consider the relations between the Maslov-type indices (i(B0), ν (B0)) and (i(B1), ν (B1)). We then apply this theory to study the existence and multiplicity of some kinds of asymptotically linear Hamiltonian systems
Boundedness of pseudodifferential operators of a C*-algebra-valued symbol
Authors: Merklen Marcela I.
Published: July 2007

Let us consider the set SA(Rn) of rapidly decreasing functions G: Rn → A, where A is a separable C*-algebra. We prove a version of the Calderón–Vaillancourt theorem for pseudodifferential operators acting on SA(Rn) whose symbol is A-valued. Given a skew-symmetric matrix, J, we prove that a pseudodifferential operator that commutes with G(x + JD), G ∈ SA(Rn), is of the form F(x − JD), for F a C∞-function with bounded derivatives of all orders.
Stability, fixed points and inverses of delays
Authors: Becker Leigh C. , Burton T. A.
Published: July 2007

The scalar equation

with variable delay r(t) ≥ 0 is investigated, where t−r(t) is increasing and xg(x) > 0 (x ≠ 0) in a neighbourhood of x = 0. We find conditions for r, a and g so that for a given continuous initial function ψ a mapping P for (1) can be defined on a complete metric space Cψ and in which P has a unique fixed point. The end result is not only conditions for the existence and uniqueness of solutions of (1) but also for the stability of the zero solution. We also find conditions ensuring that the zero solution is asymptotically stable by changing to an exponentially weighted metric on a closed subset of Cψ. Finally, we parlay the methods for (1) into results for
On the asymptotic behaviour of solutions of nonlinear parabolic equations
Authors: Kon'kov A.
Published: July 2007

For a class of nonlinear parabolic equations and inequalities, we establish conditions guaranteeing that any solution tends to 0 as t → ∞.
On composition and absolute-valued algebras
Authors: Mira José Antonio Cuenca
Published: July 2007

In this note we give a complete description of the composition algebras A over fields of characteristic ≠ 2, 3 in the following cases: if A has an anisotropic norm and x2x = xxx2 for every element; when A has a unitary central idempotent, it satisfies the identity (x2x2)x2 = x2(x2x2), and A is of finite dimension or has anisotropic norm. As a consequence, we obtain the existence, up to an isomorphism, of only seven absolute-valued algebras with a non-zero central idempotent where the last identity holds. This result completes the study of the absolute-valued algebras of this kind that was initiated by El-Mallah and Agawany.

We also introduce the class of e-quadratic algebra, which contains the quadratic algebras, but also includes large classes of composition and absolute-valued algebras. Many results on composition, absolute-valued and e-quadratic algebras are shown, and new proofs of some well-known theorems are given.
On uniqueness for a class of nonlinear boundary-value problems
Authors: Hai D. D. , Smith R. C.
Published: July 2007

We prove the uniqueness of positive solutions for a class of second-order nonlinear elliptic boundary-value problems with sublinear nonlinearities.
Convergence of a heat flow on a Hilbert manifold
Authors: Rybka Piotr
Published: July 2007

We study the heat flow projected on a manifold M ⊂ L2(Ω). This manifold is defined by the condition that the integrals ∫Ωuk (t,x) dx, k = 1,…,N, are constants of motion. We show that solutions to this problem converge to a steady state as time tends to +∞. We use in an essential way a variant of the Łojasiewicz inequality.
An operator is a product of two quasi-nilpotent operators if and only if it is not semi-Fredholm
Authors: Drnovšek Roman , Novak Nika , Müller Vladimir
Published: July 2007

We prove that a (bounded, linear) operator acting on an infinite-dimensional, separable, complex Hilbert space can be written as a product of two quasi-nilpotent operators if and only if it is not a semi-Fredholm operator. This solves the problem posed by Fong and Sourour in 1984. We also consider some closely related questions. In particular, we show that an operator can be expressed as a product of two nilpotent operators if and only if its kernel and co-kernel are both infinite dimensional. This answers the question implicitly posed by Wu in 1989.
Continuity of the derivatives of solutions related to elliptic systems
Authors: Ragusa Maria Alessandra
Published: July 2007

We consider elliptic systems with discontinuous coefficients and prove that if the known term belongs to the Morrey space Lp,λ, then the highest-order derivatives of the local solution belong to the same space. We also obtain local Hölder continuity for lower-order derivatives.
On a coagulation and fragmentation equation with mass loss
Authors: Banasiak Jacek , Lamb Wilson
Published: July 2007

A nonlinear integro-differential equation that models a coagulation and multiple fragmentation process in which continuous and discrete fragmentation mass loss can occur is examined using the theory of strongly continuous semigroups of operators. Under the assumptions that the coagulation kernel is constant, the fragmentation-rate function is linearly bounded, and the continuous mass-loss-rate function is locally Lipschitz, global existence and uniqueness of solutions that lose mass in accordance with the model are established. In the case when no coagulation is present and the fragmentation process is binary with constant fragmentation kernel and constant continuous mass loss, an explicit formula is given for the associated substochastic semigroup.
Generic affine differential geometry of curves in Rn
Authors: Davis Declan
Published: July 2007

This paper considers curves in Rn. It defines affine arc length and affine curvatures. The family of affine distance functions is generalized, along with the family of affine height functions. A new basis is constructed that makes the conditions for Ak singularity types easier to calculate, and applications are given to geometrical problems.
Ultrastructural changes in the follicular epithelium ofCeratophrys cranwelliprevitellogenic oocytes
Authors: Villecco E.I. , Mónaco M.E. , Sánchez S.S.
Published: July 2007

In this work we carried out ultrastructural, autoradiographic and biochemical analyses of the follicular epithelium duringC. cranwelliprevitellogenesis. This study revealed that the follicular epithelium in early previtellogenesis is constituted of a single layer of squamous homogeneous cells. During mid-previtellogenesis two types of cells develop: dark cells and clear cells. The follicular dark cells are actively involved in the synthesis of RNA, which is transferred to the oocyte through the interface. In late previtellogenesis the dark cells show apoptotic characteristics such as chromatin condensation, DNA fragmentation and cytoplasm shrinkage. This process forms apoptotic bodies that seem to be engulfed by the oocyte. Our results show evidence that, during mid- and lateC. cranwelliprevitellogenesis, the follicular epithelium undergoes remodelling processes interacting with the oocyte.
INTRODUCTION: WHY VICTORIAN NATURAL HISTORY?
Authors: Gates Barbara T.
Published: July 2007

VICTORIANS WERE IN LOVE WITHnatural history. David Allen describes their passion as a series of crazes – over geology, over shells, and over ferns, as in pteridomania (mania over ferns) – to cite just a very few examples. Lynn Merrill, on the other hand, delineates a more comprehensive, cultural romance, one extending over many years. Whatever we choose to call this love, we are still in the process of discovering just how deep and lasting it was. Like many love affairs, it was marked at first by a blush enthusiasm and fascination with otherness. This was followed by curiosity and a rage to risk self in the quest to know more about the other – and sometimes, as a result, by ridiculous missteps. Think of George Eliot and George Henry Lewes sloshing around at the seashore, ill-equipped but determined to find out enough to write about what they were trying to capture and study. Or recall Mary Kingsley out in Africa in a canoe propelled by several Congolese, tumbling out of the boat but saving her trusted copy of Albert Günther's 1880Introduction to the Study of Fishes, tenacious in her desire to bring back labeled specimens to the British Museum of Natural history. Earlier, in a similarly resolute quest to record birdlife, John and Elizabeth Gould globe-trotted to the extent that they put Elizabeth's life and their growing family at risk. And people like explorer/naturalist Thomas Bowdich died of fever for their fervor over natural history, in Bowdich's case as he worked to detail facts about specimens in Porto Santo, off the coast of West Africa. Bowdich left a wife to fend for herself and their family via her own study of natural history, and one result was Sara Bowdich Lee's beautifully illustratedFresh-Water Fishes of Great Britain(1828). The romance with nature certainly cut across class and gender barriers. Stonecutter Hugh Miller could lose himself as easily in geological pursuits as could Charles Darwin or Sir Charles Lyell and Marianne North's passion for plants may well have matched or exceeded that of Kew's famous botanist, Sir Joseph Hooker.
INTRODUCING GILBERT WHITE: AN EXEMPLARY NATURAL HISTORIAN AND HIS EDITORS
Authors: Lipscomb Susan Bruxvoort
Published: July 2007

IN 1887,RICHARD JEFFERIES, a popular nature essayist, added his name to the list of several dozen individuals who had written either introductions or notes to Gilbert White'sThe Natural History of Selborne(1789). Jefferies, like many who chose to edit and introduce this text throughout the Victorian period, represents White as a model figure – but a model for two quite different things. On the one hand, Jefferies commends White and hisNatural Historyas examples of simple, reflective engagement with a local, natural economy – an approach to nature that any inquisitive and observant person could emulate. White is thus allied to fictional working-class naturalists like Job Legh in Elizabeth Gaskell'sMary Bartonand leisured clergyman like Mr. Farebrother in George Eliot'sMiddlemarch. All that is needed to become a student of natural history, Jefferies suggests, is curiosity and intelligence. He informs his reader that, “In the same manner [as White] any one who has a taste for out-of-door observations may study natural history without any previous scientific learning. There is not the smallest need to know the Latin names of the birds in order to watch them, or of the flowers in order to gather them” (viii). White is thus put forward as an exemplar of what anyone may aspire to be. White, Jefferies tells his readers, Was not full of evolution when he walked out, or variation, or devolution, or degeneration. He did not look for microbes everywhere. His mind was free and his eye open. To many it would do much good to read this work if only with the object of getting rid of some of the spiders’ webs that have been so industriously spun over the eyesight of those who would like to think for themselves. (ix)
ANTHROPOMORPHIC TAXIDERMY AND THE DEATH OF NATURE: THE CURIOUS ART OF HERMANN PLOUCQUET, WALTER POTTER, AND CHARLES WATERTON
Authors: Henning Michelle
Published: July 2007

MR. POTTER'S MUSEUM OF CURIOSITIESwas a small Victorian museum that contained unique anthropomorphic tableaux made by the taxidermist Walter Potter (1835–1918). Its glass cases were crammed with small “stuffed” or “mounted” animals, such as birds, squirrels, rats, weasels, and rabbits, wearing miniature clothes and placed in models of the human settings of Potter's time. They play sports, get married, fill schoolrooms and clubs, but they also illustrate well known sayings, rhymes, and rural myths. From the 1860s the tableaux were displayed in Bramber, Sussex, in the southeast of England. In 1972 the Museum was sold and relocated to Brighton and two years later to Arundel, in Sussex. In 1985 it was sold again and moved to the Jamaica Inn – a Daphne du Maurier inspired tourist attraction on the edge of the bleak Bodmin Moor in Cornwall. The collection was finally dispersed in an auction sale in 2003. This sale attracted some media attention and several campaigns attempted to preserve the museum intact. The artist Damien Hirst claimed he had offered to buy the entire collection, but the auction went ahead (Hirst). Hirst was perhaps only the most high profile of those campaigning to keep Potter's collection together. Nevertheless, at the time it seemed hardly surprising that this unusual museum stood more chance of being rescued by an artist whose work often uses animal corpses to speak of mortality and the processes of preservation and decay, than it did of being bought by any public museum.
PTEN is destabilized by phosphorylation on Thr366
Authors: Maccario Helene , Perera Nevin M. , Davidson Lindsay , Downes C. Peter , Leslie Nick R.
Published: July 2007

Although PTEN (phosphatase and tensin homologue deleted on chromosome 10) is one of the most commonly mutated tumour suppressors in human cancers, loss of PTEN expression in the absence of mutation appears to occur in an even greater number of tumours. PTEN is phosphorylated in vitro on Thr366 and Ser370 by GSK3 (glycogen synthase kinase 3) and CK2 (casein kinase 2) respectively, and specific inhibitors of these kinases block these phosphorylation events in cultured cells. Although mutation of these phosphorylation sites did not alter the phosphatase activity of PTEN in vitro or in cells, blocking phosphorylation of Thr366 by either mutation or GSK3 inhibition in glioblastoma cell lines led to a stabilization of the PTEN protein. Our data support a model in which the phosphorylation of Thr366 plays a role in destabilizing the PTEN protein.
Molecular characterization of centerin, a germinal centre cell serpin
Authors: Paterson Melinda A. , Horvath Anita J. , Pike Robert N. , Coughlin Paul B.
Published: July 2007

Centerin [SERPINA9/GCET1 (germinal centre B-cell-expressed transcript 1)] is a serpin (serine protease inhibitor) whose expression is restricted to germinal centre B-cells and lymphoid malignancies with germinal centre B-cell maturation. Expression of centerin, together with bcl-6 and GCET2, constitutes a germinal centre B-cell signature, which is associated with a good prognosis in diffuse large B-cell lymphomas, but the molecular basis for this remains to be elucidated. We report here the cloning, expression and molecular characterization of bacterial recombinant centerin. Biophysical studies demonstrated that centerin was able to undergo the ‘stressed to relaxed’ conformational change which is an absolute requirement for protease inhibitory activity. Kinetic analysis showed that centerin rapidly inhibited the serine protease trypsin (ka=1.9×105 M−1·s−1) and also demonstrated measurable inhibition of thrombin (ka=1.17×103 M−1·s−1) and plasmin (ka=1.92×103 M−1·s−1). Centerin also bound DNA and unfractionated heparin, although there was no functionally significant impact on the rate of inhibition. These results suggest that centerin is likely to function in vivo in the germinal centre as an efficient inhibitor of a trypsin-like protease.
Identification of a novel 82 kDa proMMP-9 species associated with the surface of leukaemic cells: (auto-)catalytic activation and resistance to inhibition by TIMP-1
Authors: Ries Christian , Pitsch Thomas , Mentele Reinhard , Zahler Stefan , Egea Virginia , Nagase Hideaki , Jochum Marianne
Published: July 2007

MMP-9 (matrix metalloproteinase 9) plays a critical role in tumour progression. Although the biochemical properties of the secreted form of proMMP-9 are well characterized, little is known about the function and activity of cell surface-associated proMMP-9. We purified a novel 82 kDa species of proMMP-9 from the plasma membrane of THP-1 leukaemic cells, which has substantial differences from the secreted 94 kDa proMMP-9. The 82 kDa form was not detected in the medium even upon stimulation with a phorbol ester. It is truncated by nine amino acid residues at its N-terminus, lacks O-linked oligosaccharides present in the 94 kDa proMMP-9, but retains N-linked carbohydrates. Incubation of 94 kDa proMMP-9 with MMP-3 generated the well-known 82 kDa active form, but the 82 kDa proMMP-9 was converted into an active species of 35 kDa, which was also produced by autocatalytic processing in the absence of activating enzymes. The activated 35 kDa MMP-9 efficiently degraded gelatins, native collagen type IV and fibronectin. The enzyme was less sensitive to TIMP-1 (tissue inhibitor of metalloproteinase 1) inhibition with IC50 values of 82 nM compared with 1 nM for the 82 kDa active MMP-9. The synthetic MMP inhibitor GM6001 blocked the activity of both enzymes, with similar IC50 values below 1 nM. The 82 kDa proMMP-9 is also produced in HL-60 and NB4 leukaemic cell lines as well as ex vivo leukaemic blast cells. It is, however, absent from neutrophils and mononuclear cells isolated from peripheral blood of healthy individuals. Thus, the 82 kDa proMMP-9 expressed on the surface of malignant cells may escape inhibition by natural TIMP-1, thereby facilitating cellular invasion in vivo.
Bnip3 mediates mitochondrial dysfunction and cell death through Bax and Bak
Authors: Kubli Dieter A. , Ycaza John E. , Gustafsson Åsa B.
Published: July 2007

Bnip3 is a pro-apoptotic member of the Bcl-2 family that is down-regulated in pancreatic cancers, which correlates with resistance to chemotherapy and a worsened prognosis. In contrast, Bnip3 is up-regulated in heart failure and contributes to loss of myocardial cells during I/R (ischaemia/reperfusion). Bnip3 exerts its action at the mitochondria, but the mechanism by which Bnip3 mediates mitochondrial dysfunction is not clear. In the present study, we have identified Bax and Bak as downstream effectors of Bnip3-mediated mitochondrial dysfunction. Bnip3 plays a role in hypoxia-mediated cell death, but MEFs (mouse embryonic fibroblasts) derived from mice deficient in Bax and Bak were completely resistant to hypoxia even with substantial up-regulation of Bnip3. These cells were also resistant to Bnip3 overexpression, but re-expression of Bax or Bak restored susceptibility to Bnip3, suggesting that Bnip3 can act via either Bax or Bak. In contrast, Bnip3 overexpression in wild-type MEFs induced mitochondrial dysfunction with loss of membrane potential and release of cytochrome c. Cell death by Bnip3 was reduced in the presence of mPTP (mitochondrial permeability transition pore) inhibitors, but did not prevent Bnip3-mediated activation of Bax or Bak. Moreover, overexpression of Bnip3ΔTM, a dominant-negative form of Bnip3, reduced translocation of GFP (green fluorescent protein)–Bax to mitochondria during sI/R (simulated I/R) in HL-1 myocytes. Similarly, down-regulation of Bnip3 using RNA interference decreased activation of Bax in response to sI/R in HL-1 myocytes. These results suggest that Bnip3 mediates mitochondrial dysfunction through activation of Bax or Bak which is independent of mPTP opening.
MAPK activation by radio waves
Authors: Arthur J. Simon C.
Published: July 2007

In this issue of the Biochemical Journal, Freidman et al. report the findings of a study to look at the potential of mobile phones to activate intracellular signalling cascades. They found that radio waves corresponding to the frequency commonly used by mobile phones are able to activate ERK1/2 (extracellular-signal-regulated kinases 1 and 2). This effect was observed even at intensities lower than those emitted by mobile phones that are unable to cause any measurable heating effects. This study provides evidence that radio waves induce ERK1/2 activation downstream of the EGF (epidermal growth factor) receptor, which is in turn activated by the release of reactive oxygen species.
Influence of potassium and nitrogen fertiliser on yield, oil and protein concentration of canola (Brassica napus L.) grain harvested in south-western Australia
Authors: Brennan R. F. , Bolland M. D. A.
Published: July 2007

Most soils used for agriculture in south-western Australia are sandy and are now deficient in both potassium (K) and nitrogen (N) for cereal and canola (oilseed rape; Brassica napus L.) grain production. However, the effect of applying different levels of both fertiliser K and N on grain yields of these crops is not known. We report results of 10 field experiments, conducted on sandy soils in the region, to measure the effects of applying both K and N on canola grain yields and concentration of oil and protein in grain. Four levels of K (0–60 kg K/ha as potassium chloride) and four levels of N (0–138 kg N/ha as urea) were applied. Significant grain yield responses to applied N occurred in all experiments for the nil-K treatment and each level of K applied, with responses increasing as more N was applied. For all levels of N applied, significant grain yield responses occurred when up to 30 kg K/ha was applied, with no further significant grain yield responses occurring when 60 kg K/ha was applied. The K × N interaction was always significant for grain production. Application of K had no effect on the concentration of oil and protein in grain. Application of N consistently decreased concentration of oil and increased concentration of protein in grain. The K × N interaction was not significant for concentration of oil or protein in grain, but application of up to 30 kg K/ha significantly increased canola grain and so oil yields (concentration of oil in grain multiplied by grain yield). Our results are likely to be relevant for all acidic to neutral sandy soils worldwide used for growing canola crops.
Effect of fertiliser phosphorus and nitrogen on the concentrations of oil and protein in grain and the grain yield of canola (Brassica napus L.) grown in south-western Australia
Authors: Brennan R. F. , Bolland M. D. A.
Published: July 2007

The effect of fertiliser phosphorus (P) and nitrogen (N) on seed (grain) yield and concentration of oil and protein in grain of canola (oil-seed rape; Brassica napus L.) was measured in two field experiments undertaken at eight sites from 1993–2005 in south-western Australia, on soils deficient in P and N. Six rates of P (0–40 kg P/ha as single superphosphate) and four rates of N (0–138 kg N/ha as urea) were applied. Significant grain yield increases (responses) to applied P occurred in both experiments and these responses increased as rates of applied N increased. For grain production, the P × N interaction was significant in all eight years and locations of the two experiments. Application of P had no effect on concentration of oil and protein in grain. Application of N always decreased the concentration of oil and increased the concentration of protein in grain. For canola grain production in the region, responses to applied N always occur whereas responses to applied P are rare, but if soil P testing indicates likely P deficiency, both P and N fertiliser need to be applied.
Localization of Giα proteins in the centrosomes and at the midbody: implication for their role in cell division
Authors: Cho Hyeseon , Kehrl John H.
Published: July 2007

At the plasma membrane, heterotrimeric G proteins act as molecular switches to relay signals from G protein–coupled receptors; however, Gα subunits also have receptor-independent functions at intracellular sites. Regulator of G protein signaling (RGS) 14, which enhances the intrinsic GTPase activity of Giα proteins, localizes in centrosomes, which suggests the coexpression of Giα. We show expression of Giα1, Giα2, and Giα3 in the centrosomes and at the midbody. Fluorescence resonance energy transfer analysis confirms a direct interaction between RGS14 and Giα1 in centrosomes. Expression of GTPase-deficient Giα1 results in defective cytokinesis, whereas that of wild-type or GTPase-deficient Giα3 causes prolonged mitosis. Cells treated with pertussis toxin, with reduced expression of Giα1, Giα2, and Giα3 or with decreased expression of RGS14 also exhibit cytokinesis defects. These results suggest that Giα proteins and their regulators at these sites may play essential roles during mammalian cell division.
Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis
Authors: Ancrile Brooke , Lim Kian-Huat , Counter Christopher M.
Published: July 2007

Ras is mutated to remain in the active oncogenic state in many cancers. As Ras has proven difficult to target therapeutically, we searched for secreted, druggable proteins induced by Ras that are required for tumorigenesis. We found that Ras induces the secretion of cytokine IL6 in different cell types, and that knockdown of IL6, genetic ablation of theIL6gene, or treatment with a neutralizing IL6 antibody retard Ras-driven tumorigenesis. IL6 appears to act in a paracrine fashion to promote angiogenesis and tumor growth. Inhibiting IL6 may therefore have therapeutic utility for treatment of cancers characterized by oncogenic Ras mutations.
Hop2/Mnd1 acts on two critical steps in Dmc1-promoted homologous pairing
Authors: Pezza Roberto J. , Voloshin Oleg N. , Vanevski Filip , Camerini-Otero R. Daniel
Published: July 2007

Meiotic recombination between homologous chromosomes ensures their proper segregation at the first division of meiosis and is the main force shaping genetic variation of genomes. The HOP2 and MND1 genes are essential for this recombination: Their disruption results in severe defects in homologous chromosome synapsis and an early-stage failure in meiotic recombination. The mouse Hop2 and Mnd1 proteins form a stable heterodimer (Hop2/Mnd1) that greatly enhances Dmc1-mediated strand invasion. In order to elucidate the mechanism by which Hop2/Mnd1 stimulates Dmc1, we identify several intermediate steps in the homologous pairing reaction promoted by Dmc1. We show that Hop2/Mnd1 greatly stimulates Dmc1 to promote synaptic complex formation on long duplex DNAs, a step previously revealed only for bacterial homologous recombinases. This synaptic alignment is a consequence of the ability of Hop2/Mnd1 to (1) stabilize Dmc1–single-stranded DNA (ssDNA) nucleoprotein complexes, and (2) facilitate the conjoining of DNA molecules through the capture of double-stranded DNA by the Dmc1–ssDNA nucleoprotein filament. To our knowledge, Hop2/Mnd1 is the first homologous recombinase accessory protein that acts on these two separate and critical steps in mammalian meiotic recombination.
Bipartite stimulatory action of the Hop2–Mnd1 complex on the Rad51 recombinase
Authors: Chi Peter , San Filippo Joseph , Sehorn Michael G. , Petukhova Galina V. , Sung Patrick
Published: July 2007

The HOP2 and MND1 genes are indispensable for meiotic recombination. The products of these genes associate to form a stable heterodimeric complex that binds DNA and stimulates the recombinase activity of Rad51 and Dmc1. Here we conduct molecular studies to delineate the action mechanism of the Hop2–Mnd1 complex. We present evidence to implicate Hop2 as the major DNA-binding subunit and Mnd1 as the prominent Rad51 interaction entity. Hop2–Mnd1 stabilizes the Rad51–single-stranded DNA (ssDNA) nucleoprotein filament, the catalytic intermediate in recombination reactions. We also show that Hop2–Mnd1 enhances the ability of the Rad51–ssDNA nucleoprotein filament to capture duplex DNA, an obligatory step in the formation of the synaptic complex critical for DNA joint formation. Thus, our results unveil a bipartite mechanism of Hop2–Mnd1 in homologous DNA pairing: stabilization of the Rad51 presynaptic filament and duplex DNA capture to enhance synaptic complex formation.
Mucosal challenge with cell‐associated or cell‐free feline immunodeficiency virus induces rapid and distinctly different patterns of phenotypic change in the mucosal and systemic immune systems
Authors: Howard Kristina E. , Burkhard Mary Jo
Published: July 2007

The majority of human immunodeficiency virus type 1 (HIV‐1) infections occur via mucosal transmission through contact with genital secretions containing cell‐associated and cell‐free virus. However, few studies have assessed whether exposure to cells, HIV‐1 infected or uninfected, plays a role in the sexual transmission of HIV‐1. This study examined phenotypic changes in mucosal and systemic lymphoid tissue 24 hr after vaginal exposure toin vitroequilibrated infectious doses of cell‐associated or cell‐free feline immunodeficiency virus, uninfected heterologous cells, or medium alone. We found that even at this early time‐point, mucosal exposure to virus induced substantial alterations in the phenotype and distribution of leucocytes, particularly in the tissues of the mucosal immune system. Second, we found that the type of virus inoculum directly influenced the phenotypic changes seen. Vaginal exposure to cell‐free virus tended to induce more generalized phenotypic changes, typically in the peripheral immune system (blood and systemic lymph nodes). In contrast, exposure to cell‐associated virus was primarily associated with phenotypic shifts in the mucosal immune system (gut and mucosal/draining lymph nodes). In addition, we found that exposure to uninfected heterologous cells also induced alterations in the mucosal immune system. These data suggest that significant immune changes occur within the first 24 hr of virus exposure, well before substantial replication would be anticipated. As the mucosal immune system, and particularly the gut, is an early and persistent target for lentiviral replication, these findings have substantial implications for HIV‐1 pathogenesis and vaccine development.
Histone deacetylase inhibitors decrease Toll‐like receptor‐mediated activation of proinflammatory gene expression by impairing transcription factor recruitment
Authors: Bode Konrad A. , Schroder Kate , Hume David A. , Ravasi Timothy , Heeg Klaus , Sweet Matthew J. , Dalpke Alexander H.
Published: July 2007

Post‐translational modifications of histone proteins are major mechanisms that modify chromatin structure and regulate gene expression in eukaryotes. Activation of histone acetyltransferases or inhibition of histone deacetylases (HDACs) is generally believed to allow chromatin to assume a more open state, permitting transcriptional activity. We report here the surprising observation that treatment of murine dendritic cells with the HDAC inhibitors trichostatin A (TSA) or suberoylanilide hydroxamic acid (SAHA) in non‐apoptotic concentrations strongly inhibited induction of both interleukin‐12 protein p40 (IL‐12p40) mRNA and protein upon stimulation of Toll‐like receptors (TLRs). Moreover, TLR‐mediated up‐regulation of costimulatory molecules was also inhibited. Up‐regulation of tumour necrosis factor‐α mRNA and protein in response to TLR agonists was only affected upon prolonged exposure to HDAC inhibitors and regulation of IL‐1β was not affected. Similar effects were apparent in murine and human macrophages. Regarding the mode of action, HDAC inhibition increased the acetylation status at the IL‐12p40 locus. Nevertheless, IL‐12p40 chromatin remodelling, binding of Rel‐A and IRF1 to the IL‐12p40 promoter and transcriptional activation were abrogated. In contrast, HDAC inhibitors had no effects on upstream nuclear factor‐κB and mitogen‐activated protein kinase activation. Thus HDACs positively regulate the expression of a subset of cytokine genes by enabling transcription factor recruitment.
Recruitment of mRNAs to cytoplasmic ribonucleoprotein granules in trypanosomes
Authors: Cassola Alejandro , De Gaudenzi Javier G. , Frasch Alberto C.
Published: July 2007

Trypanosomes are outstanding examples of the importance of mRNA metabolism in the regulation of gene expression, as these unicellular eukaryotes mostly control protein synthesis by post‐transcriptional mechanisms. Here, we show that mRNA metabolism in these organisms involves recruitment of mRNAs and proteins to microscopically visible ribonucleoprotein granules in the cytoplasm. These structures engage transcripts that are being translated and protect mRNAs from degradation. Analysis of the protein composition of trypanosomal mRNA granules indicated that they contain orthologous proteins to those present in P bodies and stress granules from metazoan organisms. Formation of mRNA granules was observed after carbon‐source deprivation of parasites in axenic culture. More important, mRNA granules are formed naturally in trypanosomes present in the intestinal tract of the insect vector. We suggest that trypanosomes make use of mRNA granules for transient transcript protection as a strategy to cope with periods of starvation that they have to face during their complex life cycles.
CD59 Efficiently Protects Human NT2‐N Neurons Against Complement‐mediated Damage
Authors: Pedersen E. D. , Aass H. C. D. , Rootwelt T. , Fung M. , Lambris J. D. , Mollnes T. E.
Published: July 2007

The complement regulatory protein CD59 controls cell survival by the inhibition of C5b–9 formation on the cell membrane. Loss of CD59 increases the susceptibility of cells to complement‐mediated damage and lysis. Deposition of IgM can induce complement activation with subsequent cell death. We have previously demonstrated the presence of CD59 on human NT2‐N neurons. In this study, we investigated the functional role of CD59 for NT2‐N cell survival after IgM‐mediated complement activation. Complement activation was induced on NT2‐N neurons with human serum following incubation with the IgM monoclonal antibody A2B5 reacting with a neuronal cell membrane epitope. Deposition of C1q and C5b–9 was detected on the cell membrane and sC5b–9 in the culture supernatant. Specific inhibition of complement was obtained by the C3 inhibitor compstatin, and by anti‐C5/C5a MoAb. CD59 was blocked by the MoAb BRIC 229. Membrane damage of propidium iodide‐stained NT2‐N cells was confirmed by immunofluorescence microscopy and degeneration of neuronal processes was shown with crystal violet staining. A2B5, but not the irrelevant control IgM antibody, induced complement activation on NT2‐N neurons after incubation with a human serum, as detected by the deposition of C1q. A marked membrane deposition of C5b–9 on NT2‐N neurons with accompanying cell death and axonal degeneration was found after the blocking of CD59 with MoAb BRIC 229 but not with an isotype‐matched control antibody. Compstatin and anti‐C5 monoclonal antibodies which blocked C5 activation efficiently inhibited complement activation. In conclusion, CD59 is essential for protecting human NT2‐N neurons against complement‐mediated damage, which is known to occur in a number of clinical conditions including stroke.
CD4+CD25+Foxp3+ Indirect Alloreactive T cells from Renal Transplant Patients Suppress Both the Direct and Indirect Pathways of Allorecognition
Authors: Spadafora‐Ferreira M. , Caldas C. , Faé K. C. , Marrero I. , Monteiro S. M. , Lin‐Wang H. T. , Socorro‐Silva A. , Fonseca S. G. , Fonseca J. A. , Kalil J. , Coelho V.
Published: July 2007

Alloreactive T cells recognize donor antigens by two routes: direct and indirect pathways of allorecognition. Although the direct pathway is reported to be dominant in allograft rejection, indirect allorecognition also plays an important role. Indirect alloreactivity is also observed in renal transplant patients irrespective of rejection. Previously we showed a predominance of interleukin (IL)‐10 induced by indirect allorecognition of donor human leucocyte antigen (HLA)‐DR peptides, suggesting the existence of indirect alloreactive T cells displaying regulatory activity. In the present work, our objective was to characterize these regulatory T cells. We detected indirect alloproliferation of peripheral blood mononuclear cells (PBMC) from renal transplant patients, induced by donor HLA‐DR peptides, dependent on IL‐4 or IL‐10, suggesting regulatory activity as part of the alloreactive T‐cell repertoire. PBMC‐derived indirect alloreactive T‐cell lines were established and produced both inflammatory and regulatory cytokines. We showed that two of these T‐cell lines which were able to inhibit both direct and indirect alloproliferation of another T‐cell line from the same patient presented a CD4+CD25+Foxp3+ T‐cell population. These data support the idea that indirect alloreactive T cells may also have regulatory activity and may contribute to the maintenance of the human renal allograft.