Activation of ERK1/2 MAP kinases in familial amyloidotic polyneuropathy

J Neurochem. 2006 Apr;97(1):151-61. Epub 2006 Mar 3. Activation of ERK1/2 MAP kinases in familial amyloidotic polyneuropathy. Monteiro FA, Sousa MM, Cardoso I, do Amaral JB, Guimarães A, Saraiva MJ. Molecular Neurobiology, Instituto de Biologia Celular e Molecular, ICBAS, University of Porto, and Estomatology, Maxillofacial Surgery, Hospital Geral de Santo António, Portugal. Abstract Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disorder characterized by the extracellular deposition of transthyretin (TTR), especially in the PNS. Given the invasiveness of nerve biopsy, salivary glands (SG) from FAP patients were used previously in microarray analysis; mitogen-activated protein (MAP) kinase phosphatase 1 (MKP-1) was down-regulated in FAP. Results were validated by RT-PCR and immunohistochemistry both in SG and in nerve biopsies of different stages of disease progression. MKP-3 was also down-regulated in FAP SG biopsies. Given the relationship between MKPs and MAPKs, the latter were investigated. Only extracellular signal-regulated kinases 1/2 (ERK1/2) displayed increased activation in FAP SG and nerves. ERK1/2 kinase (MEK1/2) activation was also up-regulated in FAP nerves. In addition, an FAP transgenic mouse model revealed increased ERK1/2 activation in peripheral nerve affected with TTR deposition when compared to control animals. Cultured rat Schwannoma cell line treatment with TTR aggregates stimulated ERK1/2 activation, which was partially mediated by the receptor for advanced glycation end-products (RAGE). Moreover, caspase-3 activation triggered by TTR aggregates was abrogated by U0126, a MEK1/2 inhibitor, indicating that ERK1/2 activation is essential for TTR aggregates-induced cytotoxicity. Taken together, these data suggest that abnormally sustained activation of ERK in FAP may represent an early signaling cascade leading to neurodegeneration. PMID: 16515552 [PubMed - indexed for MEDLINE

MoS2 flakes stabilized with DNA/RNA nucleotides: in vitro cell response

Two-dimensional transition metal dichalcogenides (TMDCs), such as MoS2 and WS2, have recently emerged as nanomaterials with potential use in biomedicine. An attractive means to favor their interaction with biological media is the use of proper biomolecules as exfoliating/dispersing agents. Here, MoS2 flakes were stabilized with different small functional biomolecules such as adenosine monophosphate (AMP), guanosine monophosphate (GMP) and flavin mononucleotide (FMN) through the strong nucleotide-MoS2 interaction of Lewis acid-base type, rather than just on the weak dispersive and hydrophobic forces commonly associated with the use of many surfactants. The impact of the nucleotide-stabilized MoS2 flakes on the viability and cell proliferation, on the production of intracellular reactive oxygen species (ROS), and on the preosteoblast differentiation process (early stage) has been also evaluated, as well as the incorporation and intracellular localization of the nanomaterials by MC3T3-E1 and Saos-2 cells. The nucleotide-stabilized MoS2 flakes were found to exhibit excellent biocompatibility. Furthermore, their incorporation did not affect the integrity of the cell plasma membrane, which makes them ideal candidates for delivering drug/gene directly into cells. The in vitro cell response of tumor cells to these nanomaterials differs from that of undifferentiated cells, which provides the basis for their potential use in cancer therapy.publishe

Relação entre características bioquímicas e agronômicas e o enfezamento pálido em milho.

Foram avaliadas, em plântulas de milho, características bioquímicas, como possíveis marcadores para seleção de genótipos resistentes ao enfezamento pálido, causado por Spiroplasma kunkelii, bem como o efeito dessa doença sobre o crescimento e a produção de genótipos de milho. Para isto, espiroplasma foi inoculado nas plântulas das linhagens parentais susceptíveis, P1, e resistente, P2, e nas gerações F1, F2 e F3. Essas linhagens parentais, utilizadas também em intercruzamentos para obtenção das demais gerações, são oriundas do programa de melhoramento da Embrapa Milho e Sorgo. A altura das plantas (AP), a altura de espiga (AE) e a produção de grãos (PG) foram as características afetadas pela infecção por espiroplasma, que causou reduções médias de, respectivamente, 9,60%, 12,83% e 42% nesses parâmetros. Elevados valores, acima de 0,80, foram obtidos em correlações fenotípica e genotípica entre nota da espiga (NE) e severidade da doença enfezamento pálido (SEV), entre SEV e PG e entre NE e PG, mostrando que essas características podem ser utilizadas como critério para seleção de genótipos resistentes ao enfezamento pálido. Dentre as características bioquímicas avaliadas, verificou-se tendência de as plantas resistentes apresentarem maiores valores de teor de proteínas solúveis e menores valores de atividade específica da peroxidase (PODesp). As correlações fenotípicas entre os teores de ácido ferúlico (FA) e 5,5`-di-ferúlico (DFA) e SEV não foram significativas e os zimogramas da peroxidase não apresentaram isoformas que estivessem associadas especificamente à resistência ou à susceptibilidade ao enfezamento pálido

Anti-de Sitter curvature radius constrained by quasars in brane-world scenarios

This paper is intended to investigate the luminosity due to accretion of gas in supermassive black holes (SMBHs) in the center of quasars, using a brane-world scenario naturally endowed with extra dimensions, whereon theories formulated introduce corrections in the field equations at high energies. SMBHs possess the necessary highly energetic environment for the introduction of these corrections, which are shown to produce small deviations in all SMBH properties and, consequentely, corrections in the accretion theory that supports quasars radiative processes. The radiative flux observed from quasars indicates these deviations, from which the magnitude of the AdS$_5$ bulk curvature radius, and consequently the extra dimension compactification radius is estimated.Comment: 11 pages, RevTeX, Eq.(2) and (3) expanded, and comments thereon update