Induced Modules for Affine Lie Algebras

We study induced modules of nonzero central charge with arbitrary multiplicities over affine Lie algebras. For a given pseudo parabolic subalgebra P of an affine Lie algebra G, our main result establishes the equivalence between a certain category of P-induced G-modules and the category of weight P-modules with injective action of the central element of G. In particular, the induction functor preserves irreducible modules. If P is a parabolic subalgebra with a finite-dimensional Levi factor then it defines a unique pseudo parabolic subalgebra P(ps), P subset of P(ps). The structure of P-induced modules in this case is fully determined by the structure of P(ps)-induced modules. These results generalize similar reductions in particular cases previously considered by V. Futorny, S. Konig, V. Mazorchuk [Forum Math. 13 (2001), 641-661], B. Cox [Pacific J. Math. 165 (1994), 269-294] and I. Dimitrov, V. Futorny, I. Penkov [Comm. Math. Phys. 250 (2004), 47-63].

On-site tests for the detection of potential induced degradation in modules

This paper presents different test alternatives which can be used on-site in a PV installation to detect potential induced degradation (PID) in modules. The testing procedures proposed are: thermal imaging; electroluminescence imaging; open circuit voltage measurements; operating voltage measurements; IV curve measurements; and dark IV curve measurements. Advantages and disadvantages of each test are reported.

Differential regulation of the Hippo pathway by adherens junctions and apical-basal cell polarity modules.

Adherens junctions (AJs) and cell polarity complexes are key players in the establishment and maintenance of apical-basal cell polarity. Loss of AJs or basolateral polarity components promotes tumor formation and metastasis. Recent studies in vertebrate models show that loss of AJs or loss of the basolateral component Scribble (Scrib) cause deregulation of the Hippo tumor suppressor pathway and hyperactivation of its downstream effectors Yes-associated protein (YAP) and Transcriptional coactivator with PDZ-binding motif (TAZ). However, whether AJs and Scrib act through the same or independent mechanisms to regulate Hippo pathway activity is not known. Here, we dissect how disruption of AJs or loss of basolateral components affect the activity of the Drosophila YAP homolog Yorkie (Yki) during imaginal disc development. Surprisingly, disruption of AJs and loss of basolateral proteins produced very different effects on Yki activity. Yki activity was cell-autonomously decreased but non-cell-autonomously elevated in tissues where the AJ components E-cadherin (E-cad) or α-catenin (α-cat) were knocked down. In contrast, scrib knockdown caused a predominantly cell-autonomous activation of Yki. Moreover, disruption of AJs or basolateral proteins had different effects on cell polarity and tissue size. Simultaneous knockdown of α-cat and scrib induced both cell-autonomous and non-cell-autonomous Yki activity. In mammalian cells, knockdown of E-cad or α-cat caused nuclear accumulation and activation of YAP without overt effects on Scrib localization and vice versa. Therefore, our results indicate the existence of multiple, genetically separable inputs from AJs and cell polarity complexes into Yki/YAP regulation.

Dihydroaeruginoic acid synthetase and pyochelin synthetase, products of the pchEF genes, are induced by extracellular pyochelin in Pseudomonas aeruginosa.

The siderophore pyochelin of Pseudomonas aeruginosa is derived from one molecule of salicylate and two molecules of cysteine. Two cotranscribed genes, pchEF, encoding peptide synthetases have been identified and characterized. pchE was required for the conversion of salicylate to dihydroaeruginoate (Dha), the condensation product of salicylate and one cysteine residue and pchF was essential for the synthesis of pyochelin from Dha. The deduced PchE (156 kDa) and PchF (197 kDa) proteins had adenylation, thiolation and condensation/cyclization motifs arranged as modules which are typical of those peptide synthetases forming thiazoline rings. The pchEF genes were coregulated with the pchDCBA operon, which provides enzymes for the synthesis (PchBA) and activation (PchD) of salicylate as well as a putative thioesterase (PchC). Expression of a translational pchE'-'lacZ fusion was strictly dependent on the PchR regulator and was induced by extracellular pyochelin, the end product of the pathway. Iron replete conditions led to Fur (ferric uptake regulator)-dependent repression of the pchE'-'lacZ fusion. A translational pchD'-'lacZ fusion was also positively regulated by PchR and pyochelin and repressed by Fur and iron. Thus, autoinduction by pyochelin (or ferric pyochelin) and repression by iron ensure a sensitive control of the pyochelin pathway in P. aeruginosa.

Modules d'endo-permutation

Dans la th´eorie des repr´esentations modulaires des groupes finis, les modules d?endo-permutation occupent une place importante. En e_et, c?est le r?ole jou´e par ces modules dans l?analyse de la structure de certains modules simples pour des groupes finis p-nilpotents, qui a amen´e E. Dade `a en introduire le concept, en 1978. Quelques ann´ees plus tard, L. Puig a d´emontr´e que la source de n?importe quel module simple pour un groupe fini p-r´esoluble quelconque est un module d?endo-permutation. Plus r´ecemment, on s?est rendu compte que ces modules interviennent aussi dans l?analyse locale des cat´egories d´eriv´ees et dans l?´etude des syst`emes de fusion. La situation que l?on consid`ere est la suivante. On se donne un nombre premier p, un p-groupe fini P, un corps alg´ebriquement clos k de caract´eristique p et on veut d´eterminer tous les kP-modules d?endo-permutation couverts ind´ecomposables de type fini, c?est-`a-dire tous les kP-modules ind´ecomposables de type fini, tels que leur alg`ebre d?endomorphismes est un kP-module de permutation ayant un facteur direct trivial. On d´efinit une relation d?´equivalence sur l?ensemble de ces kP-modules et le produit tensoriel des modules induit une structure de groupe ab´elien sur l?ensemble des classes d?´equivalence. On appelle ce groupe, le groupe de Dade de P. Ainsi, classifier les modules d?endo-permutation couverts revient `a d´eterminer le groupe de Dade de P. Le groupe de Dade d?un p-groupe fini arbitraire est encore inconnu, bien qu?E. Dade, en 1978, ´etait d´ej`a parvenu `a la classification dans le cas o`u P est ab´elien. La premi`ere partie de ce travail de th`ese est consacr´ee au probl`eme de la classification dans le cas g´en´eral et r´esoud la question dans le cas de deux familles de p-groupes finis, `a savoir celle des p-groupes m´etacycliques, pour un nombre premier p impair, et celle des 2-groupes extrasp´eciaux, de la forme D8 _ · · · _ D8. Ces deux choix ont ´et´e motiv´es par le fait que ces groupes sont "presque" ab´eliens. De plus, certains r´esultats sur la structure du groupe de Dade d?un p-groupe fini quelconque rendent le groupe de Dade des groupes de ces deux familles plus simple `a ´etudier. Dans un deuxi`eme temps, nous nous sommes int´eress´es `a deux occurrences de ces modules dans la th´eorie de la repr´esentation des groupes finis, c?est-`a-dire `a deux raisons qui motivent leur ´etude. Ainsi, nous avons r´ealis´e des modules d?endo-permutation comme sources de modules simples. En particulier, il s?av`ere que, dans le cas d?un nombre premier p impair, tout module d?endo-permutation ind´ecomposable dont la classe est un ´el´ement de torsion dans le groupe de Dade est la source d?un module simple. Finalement, nous avons d´etermin´e, parmi tous les modules d?endo-permutation connus actuellement, lesquels poss`edent une r´esolution de permutation endo-scind´ee. Nous sommes arriv´es `a la conclusion que les seuls modules d?endo-permutation qui n?ont pas de r´esolution de permutation endo-scind´ee sont les modules "exceptionnels" apparaissant pour un 2-groupe de quaternions g´en´eralis´es.<br/><br/>In modular representation theory, endo-permutation modules occupy an important position. Indeed, the role that these modules play, in the analysis of the structure of some particular simple modules for finite p-nilpotent groups, induced E. Dade, in 1978, to give them their current name. A few years later, L. Puig proved that the source of any simple module for any finite psolvable group is an endo-permutation module. More recently, the occurrence of endo-permutation modules has also been noticed in the local analysis of splendid equivalences between derived categories and in the study of fusion systems. We consider the following situation. Given a prime number p, a finite pgroup P and an algebraically closed field k of characteristic p, we are looking for all finitely generated indecomposable capped endo-permutation kP-modules. That is, all finitely generated indecomposable kP-modules such that their endomorphism algebra is a permutation kP-module having a trivial direct summand. Then, we define an equivalence relation on the set of all isomorphism classes of such modules, and it turns out that the tensor product (over k) induces a structure of abelian group on this set. We call this group the Dade group of P. Hence, classifying all indecomposable finitely generated capped endo-permutation kPmodules is equivalent to determining the Dade group of P. At present, the Dade group of an arbitrary finite p-group is still unknown. However, E. Dade computed the Dade group of all finite abelian p-groups, in 1978 already. The first part of this doctoral thesis is concerned with the problem of the classification in the general case and solve it in the case of two families of finite p-groups, namely the metacyclic p-groups, for an odd prime number p, and the extraspecial 2-groups of the shape D8 _· · ·_D8. These two choices have been motivated by the fact that these groups are not far from being abelian. Moreover, some general results concerning the Dade group of arbitrary finite p-groups suggest that the Dade group of the groups belonging to these two families is easier to study. In the second part of this thesis, we have been looking at two particular occurrences of these modules in representation theory of finite groups which motivate the interest of their classification. Thus, we realised endo-permutation modules as sources of simple modules. In particular, it turns out that, in case p is an odd prime, any indecomposable module whose class in the Dade group is a torsion element is the source of some simple module. Finally, we considered all the modules we know at present and determined which ones have an endo-split permutation resolution. We could then conclude that all but the "exceptionnal" modules occurring in the generalized quaternion case have an endo-split permutation resolution.<br/><br/>"Module d?endo-permutation" n?est pas le nom d?une maladie exotique contagieuse (du moins pas `a ma connaissance), comme vous pourriez peut-?etre l?imaginer si vous faites partie des personnes qui croient que le titre de docteur n?est destin´e qu?aux m´edecins. Dans ce cas, il se peut que le sujet dont il est question ici vous cause quelques naus´ees et r´eveille de douloureux souvenirs d?´ecole, car un module d?endo-permutation est un objet math´ematique, alg´ebrique, plus pr´ecis´ement. Ce concept a ´et´e introduit il y a un quart de si`ecle, de l?autre c?ot´e de l?Atlantique, et il s?est r´ev´el´e su_samment int´eressant pour qu?aujourd?hui il ait franchi bien des fronti`eres, celles de l?alg`ebre y compris. Mais de quoi s?agit-il ? Si vous entendez le terme "endo-permutation" probablement pour la premi`ere fois, ce n?est certainement pas le cas pour celui de "module". Cependant, sa d´efinition dans le pr´esent contexte ne co¨ýncide avec aucune de celles figurant dans les dictionnaires ordinaires. Les personnes qui ont d´ej`a entendu parler de Frobenius, Burnside, Schur, ou encore Brauer, pourront vous dire qu?un module est une repr´esentation. "De quoi ?" vous demanderezvous. "Un spectacle de marionnettes, peut-?etre ?" Bien s?ur que non ! Un module d?endo-permutation est une repr´esentation particuli`ere de certains groupes finis, o`u un groupe n?est pas un groupe de rock, comme vous pouvez vous en douter, mais d´esigne un objet math´ematique connu par tous les ´etudiants en sciences au terme de leur premi`ere ann´ee universitaire (en th´eorie, du moins). La "popularit´e" de la notion de groupe, fini ou non, est due au fait que les groupes sont fr´equemment utilis´es, aussi bien dans le domaine abstrait des math´ematiques, que dans le monde r´eel des physiciens, chimistes et autres biologistes (pour ne citer qu?eux). "Mais comment peut-on utiliser concr`etement ces objets invisibles ?" vous demanderez-vous alors. Et bien, justement, en les consid´erant par l?interm´ediaire de leurs repr´esentations, c?est-`a-dire en leur associant des matrices, de fa¸con plus ou moins naturelle. Or, comme il y a "beaucoup trop" de matrices pour un groupe donn´e, elles sont classifi´ees selon certaines de leurs propri´et´es, ce qui permet de les r´epertorier dans diverses familles (celle des modules d?endo-permutation, par exemple). Un groupe est ainsi rendu "concret", car les donn´ees matricielles sont manipulables par tous les scienti- fiques (et leurs ordinateurs), qui peuvent alors les utiliser dans leurs recherches, afin de contribuer au progr`es de la science. En toute franchise, c?est bien loin de ces soucis terre-`a-terre que ce travail de th`ese sur la classification des modules d?endo-permutation a ´et´e accompli. En fait, quitte `a choquer certaines ?ames sensibles, sa r´ealisation est surtout due au caract`ere ´epicure de son auteur, qui, avouons-le, en a ´et´e pleinement satisfait !

Modélisation d'arythmies auriculaires modulées par le système nerveux autonome

La fibrillation auriculaire (FA) est la forme d’arythmie la plus fréquente et représente environ un tiers des hospitalisations attribuables aux troubles du rythme cardiaque. Les mécanismes d’initiation et de maintenance de la FA sont complexes et multiples. Parmi ceux-ci, une contribution du système nerveux autonome a été identifiée mais son rôle exact demeure mal compris. Ce travail cible l’étude de la modulation induite par l’acétylcholine (ACh) sur l’initiation et le maintien de la FA, en utilisant un modèle de tissu bidimensionnel. La propagation de l’influx électrique sur ce tissu est décrite par une équation réaction-diffusion non-linéaire résolue sur un maillage rectangulaire avec une méthode de différences finies, et la cinétique d'ACh suit une évolution temporelle prédéfinie qui correspond à l’activation du système parasympathique. Plus de 4400 simulations ont été réalisées sur la base de 4 épisodes d’arythmies, 5 tailles différentes de région modulée par l’ACh, 10 concentrations d’ACh et 22 constantes de temps de libération et de dégradation d’ACh. La complexité de la dynamique des réentrées est décrite en fonction de la constante de temps qui représente le taux de variation d’ACh. Les résultats obtenus suggèrent que la stimulation vagale peut mener soit à une dynamique plus complexe des réentrées soit à l’arrêt de la FA en fonction des quatre paramètres étudiés. Ils démontrent qu’une décharge vagale rapide, représentée par des constantes de temps faibles combinées à une quantité suffisamment grande d’ACh, a une forte probabilité de briser la réentrée primaire provoquant une activité fibrillatoire. Cette activité est caractérisée par la création de plusieurs ondelettes à partir d’un rotor primaire sous l’effet de l’hétérogénéité du gradient de repolarisation causé par l’activité autonomique.

Torsion theories induced from commutative subalgebras

We begin a study of torsion theories for representations of finitely generated algebras U over a field containing a finitely generated commutative Harish-Chandra subalgebra Gamma. This is an important class of associative algebras, which includes all finite W-algebras of type A over an algebraically closed field of characteristic zero, in particular, the universal enveloping algebra of gl(n) (or sl(n)) for all n. We show that any Gamma-torsion theory defined by the coheight of the prime ideals of Gamma is liftable to U. Moreover, for any simple U-module M, all associated prime ideals of M in Spec Gamma have the same coheight. Hence, the coheight of these associated prime ideals is an invariant of a given simple U-module. This implies the stratification of the category of U-modules controlled by the coheight of the associated prime ideals of Gamma. Our approach can be viewed as a generalization of the classical paper by Block (1981) [4]; it allows, in particular, to study representations of gl(n) beyond the classical category of weight or generalized weight modules. (C) 2011 Elsevier B.V. All rights reserved.

Dentoskeletal changes induced by the Jasper jumper and the activator-headgear combination appliances followed by fixed orthodontic treatment

Introduction: The aim of this study was to compare the dentoskeletal changes of patients with Class II Division 1 malocclusion treated with either the Jasper jumper appliance or the activator-headgear combination, both associated with fixed appliances. Methods: The sample comprised 72 subjects with Class II Division 1 malocclusion divided into 3 groups: group 1 included 25 subjects treated with fixed appliances and the force modules of the Jasper jumper at an initial mean age of 12.72 years, group 2 included 25 subjects treated with the activator-headgear combination followed by fixed appliances at an initial mean age of 11.07 years, and group 3 included 22 untreated subjects at an initial mean age of 12.67 years. Initial cephalometric characteristics and dentoskeletal changes were compared with analysis of variance. Results: Both experimental groups had similar dentoskeletal changes: restrictive effect on the maxilla, clockwise mandibular rotation and a slight increase in anterior face height, retrusion of the maxillary incisors, distalization of the maxillary molars, protrusion of the mandibular incisors, extrusion of the mandibular molars, and significant improvements of the maxillomandibular relationship, overjet, overbite, and the molar relationship. Conclusions: The effects of the Jasper jumper and the activator-headgear combination followed by fixed orthodontic appliances were similar in Class II malocclusion treatment.

A growth factor-induced, spatially organizing cytoskeletal module enables rapid and persistent fibroblast migration

Directional migration requires robust front/back polarity. We find that fibroblasts treated with platelet-derived growth factor (PDGF) and prepolarized by plating on a fibronectin line substrate exhibit persistent migration for hours. This does not occur in the absence of PDGF or on uniformly coated fibronectin substrates. Persistent migration arises from establishment of two functional modules at cell front and back. At the front, formation of a zone containing podosome-like structures (PLS) dynamically correlates with low RhoA and myosin activity and absence of a contractile lamella. At the back, myosin contractility specifically controls tail retraction with minimal crosstalk to the front module. The PLS zone is maintained in a dynamic steady state that preserves size and position relative to the cell front, allowing for long-term coordination of front and back modules. We propose that front/back uncoupling achieved by the PLS zone is crucial for persistent migration in the absence of directional cues.

Low dimensionality of supraspinally induced force fields

Recent experiments using electrical and N-methyl-d-aspartate microstimulation of the spinal cord gray matter and cutaneous stimulation of the hindlimb of spinalized frogs have provided evidence for a modular organization of the frog’s spinal cord circuitry. A “module” is a functional unit in the spinal cord circuitry that generates a specific motor output by imposing a specific pattern of muscle activation. The output of a module can be characterized as a force field: the collection of the isometric forces generated at the ankle over different locations in the leg’s workspace. Different modules can be combined independently so that their force fields linearly sum. The goal of this study was to ascertain whether the force fields generated by the activation of supraspinal structures could result from combinations of a small number of modules. We recorded a set of force fields generated by the electrical stimulation of the vestibular nerve in seven frogs, and we performed a principal component analysis to study the dimensionality of this set. We found that 94% of the total variation of the data is explained by the first five principal components, a result that indicates that the dimensionality of the set of fields evoked by vestibular stimulation is low. This result is compatible with the hypothesis that vestibular fields are generated by combinations of a small number of spinal modules.

Comparison of the early stages of forced unfolding for fibronectin type III modules

The structural changes accompanying stretch-induced early unfolding events were investigated for the four type III fibronectin (FN-III) modules, FN-III7, FN-III8, FN-III9, and FN-III10 by using steered molecular dynamics. Simulations revealed that two main energy barriers, I and II, have to be overcome to initiate unraveling of FN-III's tertiary structure. In crossing the first barrier, the two opposing β-sheets of FN-III are rotated against each other such that the β-strands of both β-sheets align parallel to the force vector (aligned state). All further events in the unfolding pathway proceed from this intermediate state. A second energy barrier has to be overcome to break the first major cluster of hydrogen bonds between adjacent β-strands. Simulations revealed that the height of barrier I varied significantly among the four modules studied, being largest for FN-III7 and lowest for FN-III10, whereas the height of barrier II showed little variation. Key residues affecting the mechanical stability of FN-III modules were identified. These results suggest that FN-III modules can be prestretched into an intermediate state with only minor changes to their tertiary structures. FN-III10, for example, extends 12 Å from the native “twisted” to the intermediate aligned state, and an additional 10 Å from the aligned state to further unfolding where the first β-strand is peeled away. The implications of the existence of intermediate states regarding the elasticity of fibrillar fibers and the stretch-induced exposure of cryptic sites are discussed.

Short peptide alpha helices induced by multiple metal clips

Alpha helices are key structural components of proteins and important recognition motifs in biology. New techniques for stabilizing short peptide helices could be valuable for studying protein folding, modeling proteins, creating artificial proteins, and may aid the design of inhibitors or mimics of protein function. We previously reported* that 5-15 residue peptides, corresponding to the Zn-binding domain of thermolysin, react with [Pd(en)(ONO,),]in DMF-d’ and 90% H,O 10% DzO to form a 22-membered [Pd(en)(H*ELTH*)]2+ macrocycle that is helical in solution and acts as a template in nucleating helicity in both Cand N- terminal directions within the longer sequences in DMF. ~f~~&g7$$& d&qx~m ~. y AC&q& In water, however, there was less a-helicity observed, testifying to #..q,& &$--Lb &l-- &.$;,J~p?:~~q&~+~~ ’ w w the difficulty of fixing intramolecular amide NH...OC H-bonds in 6,“;;” ( k.$ U”C.a , p d$. competition with the H-bond donor solvent water. To expand the utility of [Pd(en)(H*XXXH*)]*+ as a helix- @r4”8 & oJ#:& &G& @-qd ,‘d@-gyp promoting module in solution, we now report the result that Ac- ‘$4: %$yyy + H*ELTH*H*VTDH*-NH,(l), AC-H*ELTH*AVTDYH*ELTH*- NH, (2) and AC-H*AAAH*H*ELTH*H*VTDH*-NH* (3) react with multiple equivalents of [Pd(en)(ONO,),] to produce exclusively 4-6 respectively in both DMF-d7 and water (90% Hz0 10% D,O). Mass spectrometry, 15N- and 2D ‘H- NMR spectroscopy, and CD spectra were used to characterise the structures 4-6, and their three dimensional structures were calculated from NOE restraints using simulated annealing protocols. Results demonstrate (a) selective coordination of metal ions at (i, i+4) histidine positions in water and DMF, (b) incorporation of 2 and 3 a turn-mimicking modules [Pd(en)(HELTH)]2+ in lo-15 residue peptides, and (c) facile conversion of unstructured peptides into 3- and 4- turn helices of macrocycles, with well defined a-helicity throughout and more structure in DMF than in water.

Multiobjective design optimization of IGBT power modules considering power cycling and thermal cycling

Insulated-gate bipolar transistor (IGBT) power modules find widespread use in numerous power conversion applications where their reliability is of significant concern. Standard IGBT modules are fabricated for general-purpose applications while little has been designed for bespoke applications. However, conventional design of IGBTs can be improved by the multiobjective optimization technique. This paper proposes a novel design method to consider die-attachment solder failures induced by short power cycling and baseplate solder fatigue induced by the thermal cycling which are among major failure mechanisms of IGBTs. Thermal resistance is calculated analytically and the plastic work design is obtained with a high-fidelity finite-element model, which has been validated experimentally. The objective of minimizing the plastic work and constrain functions is formulated by the surrogate model. The nondominated sorting genetic algorithm-II is used to search for the Pareto-optimal solutions and the best design. The result of this combination generates an effective approach to optimize the physical structure of power electronic modules, taking account of historical environmental and operational conditions in the field.

An Isoflavone From Dipteryx Alata Vogel Is Active Against The In Vitro Neuromuscular Paralysis Of Bothrops Jararacussu Snake Venom And Bothropstoxin I, And Prevents Venom-induced Myonecrosis.

Snakebite is a neglected disease and serious health problem in Brazil, with most bites being caused by snakes of the genus Bothrops. Although serum therapy is the primary treatment for systemic envenomation, it is generally ineffective in neutralizing the local effects of these venoms. In this work, we examined the ability of 7,8,3'-trihydroxy-4'-methoxyisoflavone (TM), an isoflavone from Dipteryx alata, to neutralize the neurotoxicity (in mouse phrenic nerve-diaphragm preparations) and myotoxicity (assessed by light microscopy) of Bothrops jararacussu snake venom in vitro. The toxicity of TM was assessed using the Salmonella microsome assay (Ames test). Incubation with TM alone (200 μg/mL) did not alter the muscle twitch tension whereas incubation with venom (40 μg/mL) caused irreversible paralysis. Preincubation of TM (200 μg/mL) with venom attenuated the venom-induced neuromuscular blockade by 84% ± 5% (mean ± SEM; n = 4). The neuromuscular blockade caused by bothropstoxin-I (BthTX-I), the major myotoxic PLA2 of this venom, was also attenuated by TM. Histological analysis of diaphragm muscle incubated with TM showed that most fibers were preserved (only 9.2% ± 1.7% were damaged; n = 4) compared to venom alone (50.3% ± 5.4% of fibers damaged; n = 3), and preincubation of TM with venom significantly attenuated the venom-induced damage (only 17% ± 3.4% of fibers damaged; n = 3; p < 0.05 compared to venom alone). TM showed no mutagenicity in the Ames test using Salmonella strains TA98 and TA97a with (+S9) and without (-S9) metabolic activation. These findings indicate that TM is a potentially useful compound for antagonizing the neuromuscular effects (neurotoxicity and myotoxicity) of B. jararacussu venom.

Changes In Chromatin Structure In Nih 3t3 Cells Induced By Valproic Acid And Trichostatin A.

Valproic acid (VPA) and trichostatin A (TSA) are known histone deacetylase inhibitors (HDACIs) with epigenetic activity that affect chromatin supra-organization, nuclear architecture, and cellular proliferation, particularly in tumor cells. In this study, chromatin remodeling with effects extending to heterochromatic areas was investigated by image analysis in non-transformed NIH 3T3 cells treated for different periods with different doses of VPA and TSA under conditions that indicated no loss of cell viability. Image analysis revealed chromatin decondensation that affected not only euchromatin but also heterochromatin, concomitant with a decreased activity of histone deacetylases and a general increase in histone H3 acetylation. Heterochromatin protein 1-α (HP1-α), identified immunocytochemically, was depleted from the pericentromeric heterochromatin following exposure to both HDACIs. Drastic changes affecting cell proliferation and micronucleation but not alteration in CCND2 expression and in ratios of Bcl-2/Bax expression and cell death occurred following a 48-h exposure of the NIH 3T3 cells particularly in response to higher doses of VPA. Our results demonstrated that even low doses of VPA (0.05 mM) and TSA (10 ng/ml) treatments for 1 h can affect chromatin structure, including that of the heterochromatin areas, in non-transformed cells. HP1-α depletion, probably related to histone demethylation at H3K9me3, in addition to the effect of VPA and TSA on histone H3 acetylation, is induced on NIH 3T3 cells. Despite these facts, alterations in cell proliferation and micronucleation, possibly depending on mitotic spindle defects, require a longer exposure to higher doses of VPA and TSA.