Activation of c-Jun N-terminal kinases and p38-mitogen-activated protein kinases in human heart failure secondary to ischaemic heart disease.

Three well-characterized mitogen-activated protein kinase (MAPK) subfamilies are expressed in rodent and rabbit hearts, and are activated by pathophysiological stimuli. We have determined and compared the expression and activation of these MAPKs in donor and failing human hearts. The amount and activation of MAPKs was assessed in samples from the left ventricles of 4 unused donor hearts and 12 explanted hearts from patients with heart failure secondary to ischaemic heart disease. Total MAPKs or dually phosphorylated (activated) MAPKs were detected by Western blotting and MAPK activities were measured by in gel kinase assays. As in rat heart, c-Jun N-terminal kinases (JNKs) were detected in human hearts as bands corresponding to 46 and 54 kDa; p38-MAPK(s) was detected as a band corresponding to approximately 40 kDa, and extracellularly regulated kinases, ERK1 and ERK2, were detected as 44- and 42-kDa bands respectively. The total amounts of 54 kDa JNK, p38-MAPK and ERK2 were similar in all samples, although 46-kDa JNK was reduced in the failing hearts. However, the mean activities of JNKs and p38-MAPK(s) were significantly higher in failing heart samples than in those from donor hearts (P<0.05). There was no significant difference in phosphorylated (activated) ERKs between the two groups. In conclusion, JNKs, p38-MAPK(s) and ERKs are expressed in the human heart and the activities of JNKs and p38-MAPK(s) were increased in heart failure secondary to ischaemic heart disease. These data indicate that JNKs and p38-MAPKs may be important in human cardiac pathology.

Up-regulation of c-jun mRNA in cardiac myocytes requires the extracellular signal-regulated kinase cascade, but c-Jun N-terminal kinases are required for efficient up-regulation of c-Jun protein.

Cardiac hypertrophy, an important adaptational response, is associated with up-regulation of the immediate early gene, c- jun, which encodes the c-Jun transcription factor. c-Jun may feed back to up-regulate its own transcription and, since the c-Jun N-terminal kinase (JNK) family of mitogen-activated protein kinases (MAPKs) phosphorylate c-Jun(Ser-63/73) to increase its transactivating activity, JNKs are thought to be the principal factors involved in c- jun up-regulation. Hypertrophy in primary cultures of cardiac myocytes is induced by endothelin-1, phenylephrine or PMA, probably through activation of one or more of the MAPK family. These three agonists increased c- jun mRNA with the rank order of potency of PMA approximately endothelin-1>phenylephrine. Up-regulation of c- jun mRNA by endothelin-1 was attenuated by inhibitors of protein kinase C (GF109203X) and the extracellular signal-regulated kinase (ERK) cascade (PD98059 or U0126), but not by inhibitors of the JNK (SP600125) or p38-MAPK (SB203580) cascades. Hyperosmotic shock (0.5 M sorbitol) powerfully activates JNKs, but did not increase c- jun mRNA. These data suggest that ERKs, rather than JNKs, are required for c- jun up-regulation. However, endothelin-1 and phenylephrine induced greater up-regulation of c-Jun protein than PMA and phosphorylation of c-Jun(Ser-63/73) correlated with the level of c-Jun protein. Up-regulation of c-Jun protein by endothelin-1 was attenuated by inhibitors of protein kinase C and the ERK cascade, probably correlating with a primary input of ERKs into transcription. In addition, SP600125 inhibited the phosphorylation of c-Jun(Ser-63/73), attenuated the increase in c-Jun protein induced by endothelin-1 and increased the rate of c-Jun degradation. Thus whereas ERKs are the principal MAPKs required for c- jun transcription, JNKs are necessary to stabilize c-Jun for efficient up-regulation of the protein.

Bayesian coalescent analysis reveals a high rate of molecular evolution in GB virus C

GB virus C/hepatitis G (GBV-C) is an RNA virus of the family Flaviviridae. Despite replicating with an RNA-dependent RNA polymerase, some previous estimates of rates of evolutionary change in GBV-C suggest that it fixes mutations at the anomalously low rate of similar to 100(-7) nucleotide substitution per site, per year. However, these estimates were largely based on the assumption that GBV-C and its close relative GBV-A (New World monkey GB viruses) codiverged with their primate hosts over millions of years. Herein, we estimated the substitution rate of GBV-C using the largest set of dated GBV-C isolates compiled to date and a Bayesian coalescent approach that utilizes the year of sampling and so is independent of the assumption of codivergence. This revealed a rate of evolutionary change approximately four orders of magnitude higher than that estimated previously, in the range of 10(-2) to 10(-3) sub/site/year, and hence in line with those previously determined for RNA viruses in general and the Flaviviridae in particular. In addition, we tested the assumption of host-virus codivergence in GBV-A by performing a reconciliation analysis of host and virus phylogenies. Strikingly, we found no statistical evidence for host-virus codivergence in GBV-A, indicating that substitution rates in the GB viruses should not be estimated from host divergence times.

Study of the mechanism of action of anoplin, a helical antimicrobial decapeptide with ion channel-like activity, and the role of the amidated C-terminus

Anoplin, an antimicrobial, helical decapeptide from wasp venom, looses its biological activities by mere deamidation of its C-terminus. Secondary structure determination, by circular dichroism spectroscopy in amphipathic environments, and lytic activity in zwitterionic and anionic vesicles showed quite similar results for the amidated and the carboxylated forms of the peptide. The deamidation of the C-terminus introduced a negative charge at an all-positive charged peptide, causing a loss of amphipathicity, as indicated by molecular dynamics simulations in TFE/water mixtures and this subtle modification in a peptide`s primary structure disturbed the interaction with bilayers and biological membranes. Although being poorly lytic, the amidated form, but not the carboxylated, presented ion channel-like activity on anionic bilayers with a well-defined conductance step; at approximately the same concentration it showed antimicrobial activity. The pores remain open at trans-negative potentials, preferentially conducting cations, and this situation is equivalent to the interaction of the peptide with bacterial membranes that also maintain a high negative potential inside. Copyright (C) 2007 European Peptide Society and John Wiley & Sons, Ltd.

Indecomposable and noncrossed product division algebras over function fields of smooth p-adic curves

We construct indecomposable and noncrossed product division algebras over function fields of connected smooth curves X over Z(p). This is done by defining an index preserving morphism s: Br(<(K(X))over cap>)` --> Br(K(X))` which splits res : Br(K (X)) --> Br(<(K(X))over cap>), where <(K(X))over cap> is the completion of K (X) at the special fiber, and using it to lift indecomposable and noncrossed product division algebras over <(K(X))over cap>. (C) 2010 Elsevier Inc. All rights reserved.

Hyperbolic unit groups and quaternion algebras

We classify the quadratic extensions K = Q[root d] and the finite groups G for which the group ring o(K)[G] of G over the ring o(K) of integers of K has the property that the group U(1)(o(K)[G]) of units of augmentation 1 is hyperbolic. We also construct units in the Z-order H(o(K)) of the quaternion algebra H(K) = (-1, -1/K), when it is a division algebra.

COMMUTATIVE FINITE-DIMENSIONAL ALGEBRAS SATISFYING x(x(xy))=0 ARE NILPOTENT

We investigate the structure of commutative non-associative algebras satisfying the identity x(x(xy)) = 0. Recently, Correa and Hentzel proved that every commutative algebra satisfying above identity over a field of characteristic not equal 2 is solvable. We prove that every commutative finite-dimensional algebra u over a field F of characteristic not equal 2, 3 which satisfies the identity x(x(xy)) = 0 is nilpotent. Furthermore, we obtain new identities and properties for this class of algebras.

Examples of Self-Iterating Lie Algebras, 2

We study properties of self-iterating Lie algebras in positive characteristic. Let R = K[t(i)vertical bar i is an element of N]/(t(i)(p)vertical bar i is an element of N) be the truncated polynomial ring. Let partial derivative(i) = partial derivative/partial derivative t(i), i is an element of N, denote the respective derivations. Consider the operators v(1) = partial derivative(1) + t(0)(partial derivative(2) + t(1)(partial derivative(3) + t(2)(partial derivative(4) + t(3)(partial derivative(5) + t(4)(partial derivative(6) + ...))))); v(2) = partial derivative(2) + t(1)(partial derivative(3) + t(2)(partial derivative(4) + t(3)(partial derivative(5) + t(4)(partial derivative(6) + ...)))). Let L = Lie(p)(v(1), v(2)) subset of Der R be the restricted Lie algebra generated by these derivations. We establish the following properties of this algebra in case p = 2, 3. a) L has a polynomial growth with Gelfand-Kirillov dimension lnp/ln((1+root 5)/2). b) the associative envelope A = Alg(v(1), v(2)) of L has Gelfand-Kirillov dimension 2 lnp/ln((1+root 5)/2). c) L has a nil-p-mapping. d) L, A and the augmentation ideal of the restricted enveloping algebra u = u(0)(L) are direct sums of two locally nilpotent subalgebras. The question whether u is a nil-algebra remains open. e) the restricted enveloping algebra u(L) is of intermediate growth. These properties resemble those of Grigorchuk and Gupta-Sidki groups.

Crossed products by twisted partial actions and graded algebras

For a twisted partial action e of a group G on an (associative non-necessarily unital) algebra A over a commutative unital ring k, the crossed product A x(Theta) G is proved to be associative. Given a G-graded k-algebra B = circle plus(g is an element of G) B-g with the mild restriction of homogeneous non-degeneracy, a criteria is established for B to be isomorphic to the crossed product B-1 x(Theta) G for some twisted partial action of G on B-1. The equality BgBg-1 B-g = B-g (for all g is an element of G) is one of the ingredients of the criteria, and if it holds and, moreover, B has enough local units, then it is shown that B is stably isomorphic to a crossed product by a twisted partial action of G. (c) 2008 Elsevier Inc. All rights reserved.

Hyperbolicity of semigroup algebras

Let A be a finite-dimensional Q-algebra and Gamma subset of A a Z-order. We classify those A with the property that Z(2) negated right arrow U(Gamma) and refer to this as the hyperbolic property. We apply this in case A = K S is a semigroup algebra, with K = Q or K = Q(root-d). A complete classification is given when KS is semi-simple and also when S is a non-semi-simple semigroup. (c) 2008 Elsevier Inc. All rights reserved.

The bar-radical of a class of almost alternative baric algebras

In this article we prove that, if (U, ) is a finite dimensional baric algebra of (gamma, delta) type over a field F of characteristic not equal 2,3,5 such that gamma(2) - delta(2) + delta = 1 and 0,1, then rad(U) = R(U)boolean AND(bar(U))(2), where R(U) is the nilradical (maximal nil ideal) of U.

Finite-dimensional non-associative algebras and codimension growth

Let A be a (non-necessarily associative) finite-dimensional algebra over a field of characteristic zero. A quantitative estimate of the polynomial identities satisfied by A is achieved through the study of the asymptotics of the sequence of codimensions of A. It is well known that for such an algebra this sequence is exponentially bounded. Here we capture the exponential rate of growth of the sequence of codimensions for several classes of algebras including simple algebras with a special non-degenerate form, finite-dimensional Jordan or alternative algebras and many more. In all cases such rate of growth is integer and is explicitly related to the dimension of a subalgebra of A. One of the main tools of independent interest is the construction in the free non-associative algebra of multialternating polynomials satisfying special properties. (C) 2010 Elsevier Inc. All rights reserved.

Commutative Moufang loops and alternative algebras

We describe bases of free commutative Moufang loop with seven generators and calculate the order of this loop. (c) 2011 Published by Elsevier Inc.

d-Koszul algebras, 2-d-determined algebras and 2-d-Koszul algebras

The relationship between an algebra and its associated monomial algebra is investigated when at least one of the algebras is d-Koszul It is shown that an algebra which has a reduced Grobnerbasis that is composed of homogeneous elements of degree d is d-Koszul if and only if its associated monomial algebra is d-Koszul The class of 2-d-determined algebras and the class 2-d-Koszul algebras are introduced In particular it is shown that 2-d-determined monomial algebras are 2-d-Koszul algebras and the structure of the ideal of relations of such an algebra is completely determined (C) 2010 Elsevier B V All rights reserved

Representation type of Jordan algebras

The problem of classification of Jordan bit-nodules over (non-semisimple) finite dimensional Jordan algebras with respect to their representation type is considered. The notions of diagram of a Jordan algebra and of Jordan tensor algebra of a bimodule are introduced and a mapping Qui is constructed which associates to the diagram of a Jordan algebra J the quiver of its universal associative enveloping algebra S(J). The main results are concerned with Jordan algebras of semi-matrix type, that is, algebras whose semi-simple component is a direct sum of Jordan matrix algebras. In this case, criterion of finiteness and tameness for one-sided representations are obtained, in terms of diagram and mapping Qui, for Jordan tensor algebras and for algebras with radical square equals to 0. (c) 2010 Elsevier Inc. All rights reserved.