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On-surface synthesis has proven to be a powerful approach for fabricating various low-dimensional covalent nanostructures with atomic precision that could be challenging for conventional solution chemistry. Dehydrogenative Caryl-Caryl coupling is one of the most popular on-surface reactions, of which the mechanisms, however, have not been well understood due to the lack of microscopic insights into the intermediates that are fleetingly existing under harsh reaction conditions. Here, we bypass the most energy-demanding initiation step to generate and capture some of the intermediates at room temperature (RT) via the cyclodehydrobromination of 1-bromo-8-phenylnaphthalene on a Cu(111) surface. Bond-level scanning probe imaging and manipulation in combination with DFT calculations allow for the identification of chemisorbed radicals, cyclized intermediates, and dehydrogenated products. These intermediates correspond to three main reaction steps, namely, debromination, cyclization (radical addition), and H elimination. H elimination is the rate-determining step as evidenced by the predominant cyclized intermediates. Furthermore, we reveal a long-overlooked pathway of dehydrogenation, namely, atomic hydrogen-catalyzed H shift and elimination, based on the observation of intermediates for H shift and superhydrogenation and the proof of a self-amplifying effect of the reaction. This pathway is further corroborated by comprehensive theoretical analysis on the reaction thermodynamics and kinetics.
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Amyloid-like fibrils are a special class of self-assembling peptides that emerge as a promising nanomaterial with rich bioactivity for applications such as cell adhesion and growth. Unlike the extracellular matrix, the intrinsically stable amyloid-like fibrils do not respond nor adapt to stimuli of their natural environment. Here, a self-assembling motif (CKFKFQF), in which a photosensitive o-nitrobenzyl linker (PCL) is inserted, is designed. This peptide (CKFK-PCL-FQF) assembles into amyloid-like fibrils comparable to the unsubstituted CKFKFQF and reveals a strong response to UV-light. After UV irradiation, the secondary structure of the fibrils, fibril morphology, and bioactivity are lost. Thus, coating surfaces with the pre-formed fibrils and exposing them to UV-light through a photomask generate well-defined areas with patterns of intact and destroyed fibrillar morphology. The unexposed, fibril-coated surface areas retain their ability to support cell adhesion in culture, in contrast to the light-exposed regions, where the cell-supportive fibril morphology is destroyed. Consequently, the photoresponsive peptide nanofibrils provide a facile and efficient way of cell patterning, exemplarily demonstrated for A549, Chinese Hamster Ovary, and Raw Dual type cells. This study introduces photoresponsive amyloid-like fibrils as adaptive functional materials to precisely arrange cells on surfaces.
Assuntos
Amiloide , Peptídeos , Cricetinae , Animais , Amiloide/química , Amiloide/metabolismo , Células CHO , Cricetulus , Estrutura Secundária de ProteínaRESUMO
Breaking an impasse in finding mechanism-based therapies of neuropsychiatric disorders requires a strategic shift towards alleviating individual symptoms. Here we present a symptom and circuit-specific approach to rescue deficits of reward learning in Fmr1 knockout mice, a model of Fragile X syndrome (FXS), the most common monogenetic cause of inherited mental disability and autism. We use high-throughput, ecologically-relevant automated tests of cognition and social behavior to assess effectiveness of the circuit-targeted injections of designer nanoparticles, loaded with TIMP metalloproteinase inhibitor 1 protein (TIMP-1). Further, to investigate the impact of our therapeutic strategy on neuronal plasticity we perform long-term potentiation recordings and high-resolution electron microscopy. We show that central amygdala-targeted delivery of TIMP-1 designer nanoparticles reverses impaired cognition in Fmr1 knockouts, while having no impact on deficits of social behavior, hence corroborating symptom-specificity of the proposed approach. Moreover, we elucidate the neural correlates of the highly specific behavioral rescue by showing that the applied therapeutic intervention restores functional synaptic plasticity and ultrastructure of neurons in the central amygdala. Thus, we present a targeted, symptom-specific and mechanism-based strategy to remedy cognitive deficits in Fragile X syndrome.
Assuntos
Síndrome do Cromossomo X Frágil , Animais , Cognição , Modelos Animais de Doenças , Proteína do X Frágil da Deficiência Intelectual/genética , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Síndrome do Cromossomo X Frágil/metabolismo , Camundongos , Camundongos Knockout , Inibidor Tecidual de Metaloproteinase-1/metabolismoRESUMO
Coal combustion, which is one of the most important energy sources of electricity generation, produces airborne pollutants: NOx, CO2, SO2, particulates and Hg°. A range of technologies is being developed to reduce the environmental impact of coal-fired power stations. No optimal technology that can be broadly applied exists as yet, but sorption of mercury is considered a promising approach. We report a novel adsorbent, which shows an extraordinary mechanical resistance and high adsorption capacity of mercury vapour. These adsorbent samples were synthesized in the gas sulphonitriding process using steel sheets. The chemisorption capacity of the sorbent materials, the process of the thermal desorption of mercury and the effect of the hydrogen activation treatment have been investigated in the work. It has been established that the capacity of mercury chemisorption increased more than twice after the heating treatment of the adsorbent in H2 atmosphere at 500 °C in comparison with the non-activated one. The mechanism of activation has been elucidated in the paper. For the purpose of comparison, activated carbon was also investigated.
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The recent re-description of Paramacrobiotus Guidetti, Schill, Bertolani, Dandekar and Wolf, 2009 has inadvertently led to the description of an objective synonym within its subgenera nominal taxa. To resolve this issue, we have re-described both subgenera, and proposed a new substitute name for one subgenus, in line with the International Code of Zoological Nomenclature. Additionally we have confirmed the placement of two recently published Paramacrobiotus species, not included in the last revision, within the respective subgenera established herein.
Assuntos
Tardígrados , AnimaisRESUMO
Imaging of the surface of materials by atomic force microscopy under tapping and phase imaging mode, with use of modified probes is addressed. In this study, the circularly shaped holes located in varying distance from the probe base, were cut out by focused ion beam. Such modification was a consequence of the results of the previous experiments (probe tip sharpening and cantilever thinning) where significant improvement of image quality in tapping and phase imaging mode has been revealed. The solution proposed herein gives similar results, but is much simpler from the technological point of view. Shorter exposition time of the tip onto gallium ions during FIB processing allows to reduce material degradation. The aim of this modification was to change harmonic oscillators' properties in the simplest and fastest way, to obtain stronger signal for higher resonant frequencies, which can be advantageous for improving the quality of imaging in PI mode. Probes shaped in that way were used for AFM investigations with Bruker AFM nanoscope 8. As a testing material, titanium roughness standard sample, supplied by Bruker, was used. The results have shown that the modifications performed within these studies influence the oscillation of the probes, which in some cases may result in deterioration of the imaging quality under tapping mode for one or both self-resonant frequencies. However, phase imaging results obtained using modified probes are of higher quality. The numerical simulations performed by application of finite element method were used to explain the results obtained experimentally. Phenomenon described within this study allows to apply developed modelling methodology for prediction of effects of various modifications on the probes' tip, and as a result, to predict how proposed modifications will affect AFM imaging quality.
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OBJECTIVE: Chronic disease is a critical life event which demands significant psychological adjustment. Coping strategies and resources such as sense of coherence, self-efficacy, etc. remain factors affecting stress response. PATIENTS AND METHODS: The examined group included patients with ischemic heart disease (n = 134), type 1 diabetes mellitus (n = 109) or rheumatoid arthritis (n = 92). 159 patients came from urban area whereas 176 came from rural setting. All patients filled up inventories of life satisfaction, severity of depression, coping strategies, self-efficacy, social support and sense of coherence. RESULTS: The analysis showed that patients from rural areas had higher levels of well-being, i.e., were characterized by lower severity of depression. The predictors of satisfaction with life included two types of resources i.e. self-efficacy, social support and two coping strategies i.e. turning to religion and self-distraction (R2 = 0.39; F = 26.87**). Life satisfaction was determined by social support, sense of coherence and positive reappraisal (R2 = 0.36; F = 29.11**). CONCLUSIONS: Rural/urban differences in the use of coping strategies may be associated with environmental or lifestyle differences. Patients with IHD, T1D or RA in Polish rural areas are high risk for depression so they may need help in finding systematic contact with specialists of healthcare.
Assuntos
Adaptação Psicológica , Artrite Reumatoide/psicologia , Diabetes Mellitus Tipo 1/psicologia , Isquemia Miocárdica/psicologia , População Rural , População Urbana , Adulto , Idoso , Artrite Reumatoide/epidemiologia , Doença Crônica , Depressão/psicologia , Diabetes Mellitus Tipo 1/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/epidemiologia , Polônia/epidemiologia , Qualidade de Vida/psicologia , Apoio Social , Adulto JovemRESUMO
Studies using the Morris water maze to assess hippocampal function in animals, in which adult hippocampal neurogenesis had been suppressed, have yielded seemingly contradictory results. Cyclin D2 knockout (Ccnd2(-/-)) mice, for example, have constitutively suppressed adult hippocampal neurogenesis but had no overt phenotype in the water maze. In other paradigms, however, ablation of adult neurogenesis was associated with specific deficits in the water maze. Therefore, we hypothesized that the neurogenesis-related phenotype might also become detectable in Ccnd2(-/-) mice, if we used the exact setup and protocol that in our previous study had revealed deficits in mice with suppressed adult neurogenesis. Ccnd2(-/-) mice indeed learned the task and developed a normal preference for the goal quadrant, but were significantly less precise for the exact goal position and were slower in acquiring efficient and spatially more precise search strategies. Upon goal reversal (when the hidden platform was moved to a new position) Ccnd2(-/-) mice showed increased perseverance at the former platform location, implying that they were less flexible in updating the previously learned information. Both with respect to adult neurogenesis and behavioral performance, Ccnd2(+/-) mice ranged between wild types and knockouts. Importantly, hippocampus-dependent learning was not generally impaired by the mutation, but specifically functional aspects relying on precise and flexible encoding were affected. Whether ablation of adult neurogenesis causes a specific behavioral phenotype thus also depends on the actual task demands. The test parameters appear to be important variables influencing whether a task can pick up a contribution of adult neurogenesis to test performance.
Assuntos
Ciclina D2/metabolismo , Deleção de Genes , Hipocampo/fisiologia , Aprendizagem em Labirinto , Neurogênese , Neurônios/citologia , Animais , Proliferação de Células , Ciclina D2/genética , Feminino , Hipocampo/citologia , Hipocampo/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios/metabolismo , Neurônios/fisiologiaRESUMO
The complete NMR signal assignment of title compounds were carried out by extensive use of 1D and 2D NMR techniques (1H, 13C, COSY, HSQC and HMBC).
Assuntos
Antineoplásicos/química , Antineoplásicos/classificação , Indóis/química , Quinolinas/química , Isótopos de Carbono , Espectroscopia de Ressonância Magnética/normas , Estrutura Molecular , Isótopos de Nitrogênio , Prótons , Padrões de ReferênciaRESUMO
A significant improvement of the patent route for exemestane synthesis has been achieved. The key intermediate 1alpha,3-dipyrrolidino-androsta-3,5-diene-17-one (7) was obtained in a good yield and effectively used without further isolation in the next reaction step. The original analytical method for the identification and quantification of the substrate androsta-1,4-diene-3,17-dione (ADD, 6), intermediate 7 and 1-pyrrolidinoandrosta-1,3,5-triene-17-one (9) impurity in the reaction mixture was applied. Due to the newly developed process, the economical synthesis of the final pharmaceutical product in a large scale was possible. In addition, the complete NMR characteristics of 7 was described for the first time. The experiments were also analyzed with the theoretical quantum mechanical density functional B3LYP calculations for the energy outputs in model reactions. Based on these studies hypothetical routes of key intermediate (7) formation have been suggested. These predictions were consistent with the solutions of kinetic equations fitted to the experimental curves for time-dependence of three components of the reaction mixture.
Assuntos
Androstadienos/síntese química , Antineoplásicos/síntese química , Pirrolidinonas/síntese química , Catálise , Indicadores e Reagentes , Cinética , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Teoria QuânticaRESUMO
Inhibitory effects of passive ethanol exposure on brain neurogenesis have been extensively documented in animal models. In contrast, a role of brain neurogenesis in ethanol self-administration has not been addressed, as yet. The aim of this study was to assess intake of, and preference for, ethanol solutions [2-16% (v/v)] in a mouse model of adult neurogenesis deficiency based on permanent knockout (KO) of cyclin D2 (Ccnd2). Wild type (WT) and Ccnd2 KO mice did not differ in 2% and 4% ethanol intake. The KO group consumed significantly more ethanol in g/kg when offered with 8% or 16% ethanol as compared with the WT controls. The WT and KO mice did not differ in 2% ethanol preference, but the KO group showed a significantly higher preference for 4-16% ethanol. Animal and human studies have suggested that the low level of response to the sedative/hypnotic effects of alcohol is genetically associated with enhanced alcohol consumption. However, in this study, there were no between-genotype differences in ethanol-induced loss of righting reflex. Previous reports have also suggested that high ethanol intake is genetically associated with the avidity for sweets and better acceptance of bitter solutions. However, the KO and WT mice consumed similar amounts of saccharin solutions and the KOs consumed less quinine (i.e. bitter) solutions as compared with the WTs. In conclusion, these results may indicate that Ccnd2 and, possibly, brain neurogenesis are involved in central regulation of ethanol intake in mice.
Assuntos
Consumo de Bebidas Alcoólicas/genética , Comportamento de Escolha/fisiologia , Ciclina D2/genética , Etanol/administração & dosagem , Neurogênese/genética , Animais , Ciclina D2/metabolismo , Genótipo , Camundongos , Camundongos Knockout , AutoadministraçãoRESUMO
Understanding of the molecular basis of long-term fear memory (fear LTM) formation provides targets in the treatment of emotional disorders. Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is one of the key synaptic molecules involved in fear LTM formation. There are two endogenous inhibitor proteins of CaMKII, CaMKII N alpha and N beta, which can regulate CaMKII activity in vitro. However, the physiological role of these endogenous inhibitors is not known. Here, we have investigated whether CaMKII N beta protein expression is regulated after contextual fear conditioning or exposure to a novel context. Using a novel CaMKII N beta-specific antibody, CaMKII N beta expression was analysed in the naïve mouse brain as well as in the amygdala and hippocampus after conditioning and context exposure. We show that in naïve mouse forebrain CaMKII N beta protein is expressed at its highest levels in olfactory bulb, prefrontal and piriform cortices, amygdala and thalamus. The protein is expressed both in dendrites and cell bodies. CaMKII N beta expression is rapidly and transiently up-regulated in the hippocampus after context exposure. In the amygdala, its expression is regulated only by contextual fear conditioning and not by exposure to a novel context. In conclusion, we show that CaMKII N beta expression is differentially regulated by novelty and contextual fear conditioning, providing further insight into molecular basis of fear LTM.
Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/antagonistas & inibidores , Condicionamento Clássico/fisiologia , Medo/fisiologia , Memória/fisiologia , Tonsila do Cerebelo/metabolismo , Animais , Comportamento Animal , Western Blotting , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Inibidores Enzimáticos/metabolismo , Expressão Gênica , Hipocampo/metabolismo , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Bulbo Olfatório/metabolismo , Prosencéfalo/metabolismo , Regulação para CimaRESUMO
Recent studies have demonstrated that total cellular levels of voltage-gated potassium channel subunits can change on a time scale of minutes in acute slices and cultured neurons, raising the possibility that rapid changes in the abundance of channel proteins contribute to experience-dependent plasticity in vivo. In order to investigate this possibility, we took advantage of the medial nucleus of the trapezoid body (MNTB) sound localization circuit, which contains neurons that precisely phase-lock their action potentials to rapid temporal fluctuations in the acoustic waveform. Previous work has demonstrated that the ability of these neurons to follow high-frequency stimuli depends critically upon whether they express adequate amounts of the potassium channel subunit Kv3.1. To test the hypothesis that net amounts of Kv3.1 protein would be rapidly upregulated when animals are exposed to sounds that require high frequency firing for accurate encoding, we briefly exposed adult rats to acoustic environments that varied according to carrier frequency and amplitude modulation (AM) rate. Using an antibody directed at the cytoplasmic C-terminus of Kv3.1b (the adult splice isoform of Kv3.1), we found that total cellular levels of Kv3.1b protein-as well as the tonotopic distribution of Kv3.1b-labeled cells-was significantly altered following 30 min of exposure to rapidly modulated (400 Hz) sounds relative to slowly modulated (0-40 Hz, 60 Hz) sounds. These results provide direct evidence that net amounts of Kv3.1b protein can change on a time scale of minutes in response to stimulus-driven synaptic activity, permitting auditory neurons to actively adapt their complement of ion channels to changes in the acoustic environment.
Assuntos
Vias Auditivas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Plasticidade Neuronal/fisiologia , Rombencéfalo/metabolismo , Canais de Potássio Shaw/metabolismo , Localização de Som/fisiologia , Estimulação Acústica , Adaptação Fisiológica/fisiologia , Animais , Especificidade de Anticorpos , Vias Auditivas/citologia , Limiar Auditivo/fisiologia , Imuno-Histoquímica/métodos , Ativação do Canal Iônico/fisiologia , Ratos , Ratos Sprague-Dawley , Tempo de Reação/fisiologia , Rombencéfalo/citologia , Transmissão Sináptica/fisiologia , Fatores de Tempo , Regulação para Cima/fisiologiaRESUMO
Evidence is accumulating for a role for amyloid peptides in impaired synaptic plasticity and cognition, while the underlying mechanisms remain unclear. We here analyzed the effects of amyloid peptides on NMDA-receptor function in vitro and in vivo. A synthetic amyloid peptide preparation containing monomeric and oligomeric A beta (1-42) peptides was used and demonstrated to bind to synapses expressing NMDA-receptors in cultured hippocampal and cortical neurons. Pre-incubation of primary neuronal cultures with A beta peptides significantly inhibited NMDA-receptor function, albeit not by a direct pharmacological inhibition of NMDA-receptors, since acute application of A beta peptides did not change NMDA-receptor currents in autaptic hippocampal cultures nor in xenopus oocytes expressing recombinant NMDA-receptors. Pre-incubation of primary neuronal cultures with A beta peptides however decreased NR2B-immunoreactive synaptic spines and surface expression of NR2B containing NMDA-receptors. Furthermore, we extended these findings for the first time in vivo, demonstrating decreased concentrations of NMDA-receptor subunit NR2B and PSD-95 as well as activated alpha-CaMKII in postsynaptic density preparations of APP[V717I] transgenic mice. This was associated with impaired NMDA-dependent LTP and decreased NMDA- and AMPA-receptor currents in hippocampal CA1 region in APP[V717I] transgenic mice. In addition, induction of c-Fos following cued and contextual fear conditioning was significantly impaired in the basolateral amygdala and hippocampus of APP[V717I] transgenic mice. Our data demonstrate defects in NMDA-receptor function and learning dependent signaling cascades in vivo in APP[V717I] transgenic mice and point to decreased surface expression of NMDA-receptors as a mechanism involved in early synaptic defects in APP[V717I] transgenic mice in vivo.
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Peptídeos beta-Amiloides/administração & dosagem , Precursor de Proteína beta-Amiloide/genética , Neurônios/metabolismo , Fragmentos de Peptídeos/administração & dosagem , Receptores de Superfície Celular/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Transdução de Sinais/fisiologia , Animais , Células Cultivadas , Camundongos , Camundongos Transgênicos , Neurônios/efeitos dos fármacos , Nexinas de Proteases , Transdução de Sinais/efeitos dos fármacosRESUMO
Synaptic plasticity involves remodeling of extracellular matrix. This is mediated, in part, by enzymes of the matrix metalloproteinase (MMP) family, in particular by gelatinase MMP-9. Accordingly, there is a need of developing methods to visualize gelatinolytic activity at the level of individual synapses, especially in the context of neurotransmitters receptors. Here we present a high-resolution fluorescent in situ zymography (ISZ), performed in thin sections of the alcohol-fixed and polyester wax-embedded brain tissue of the rat (Rattus norvegicus), which is superior to the current ISZ protocols. The method allows visualization of structural details up to the resolution-limit of light microscopy, in conjunction with immunofluorescent labeling. We used this technique to visualize and quantify gelatinolytic activity at the synapses in control and seizure-affected rat brain. In particular, we demonstrated, for the first time, frequent colocalization of gelatinase(s) with synaptic N-methyl-D-aspartic acid (NMDA)- and AMPA-type glutamate receptors. We believe that our method represents a valuable tool to study extracellular proteolytic processes at the synapses, it could be used, as well, to investigate proteinase involvement in a range of physiological and pathological phenomena in the nervous system.
Assuntos
Encéfalo/enzimologia , Ácido Glutâmico/metabolismo , Metaloproteinases da Matriz/metabolismo , Sinapses/enzimologia , Animais , Bioensaio/métodos , Encéfalo/ultraestrutura , Epilepsia/enzimologia , Epilepsia/fisiopatologia , Matriz Extracelular/metabolismo , Imunofluorescência/métodos , Masculino , Metaloproteinases da Matriz/análise , Microscopia de Fluorescência/métodos , Neuroquímica/métodos , Proteômica/métodos , Ratos , Ratos Wistar , Receptores de AMPA/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Sinapses/ultraestrutura , Inclusão do Tecido/métodos , Fixação de Tecidos/métodosRESUMO
OBJECTIVES: Angiogenesis, the process of formation of blood vessels, is essential for many physiological as well as pathological processes. It has been shown that human adipose tissue contains a population of non-characterized cells, called stromal-vascular fraction (SVF) cells, which are able to differentiate into several lineages. The aim of this study was to determine conditions for promoting differentiation of human adipose tissue progenitors towards endothelial cells, as well as to show that SVF cells cooperate with differentiated endothelium in capillary network formation. MATERIALS AND METHODS: Stromal vascular fraction cells were isolated according to modified Hauner's method and after adaptation they were cultured in pro-angiogenic or pro-adipogenic medium. Cells were characterized by presence of surface antigens by flow cytometry, and by expression of genes characteristic for endothelial cells or for adipocytes, quantitative real-time polymerase chain reaction. A number of tests were performed to verify their differentiation. RESULTS: Differentiation of human SVF cells towards endothelium was stimulated by the presence of serum and absence of adipogenic factors, documented by the pattern of gene expression as well as different functional in vitro assays. SVF cells were found to work together with human umbilical vein endothelial cells to form capillary networks. CONCLUSIONS: Here, we show that differentiation of SVF cells to endothelial cells or adipocyte-like cells depended on the medium used. Our work provides a clear model for analysing the differentiation capacity of SVF cells.
Assuntos
Tecido Adiposo/citologia , Vasos Sanguíneos/citologia , Diferenciação Celular , Meios de Cultura/metabolismo , Células Estromais/citologia , Adipócitos/citologia , Adulto , Capilares/citologia , Movimento Celular , Proliferação de Células , Separação Celular , Células Cultivadas , Colágeno/metabolismo , Meios de Cultura Livres de Soro , Combinação de Medicamentos , Feminino , Regulação da Expressão Gênica , Humanos , Laminina/metabolismo , Pessoa de Meia-Idade , Neovascularização Fisiológica , Proteoglicanas/metabolismo , Fatores de TempoRESUMO
The phenomenon of dendritic transport and local translation of mRNA is considered to be one of the most fundamental mechanisms underlying long-term synaptic plasticity. Matrix metalloproteinase 9 (gelatinase B) (MMP-9) is a matrix metalloproteinase implicated in synaptic long-term potentiation and hippocampus-dependent memory. It was recently shown to be prominently up-regulated in the hippocampal dentate gyrus (DG) upon kainate-mediated seizures. Here, using a high resolution nonradioactive in situ hybridization at the light- and electron-microscopic levels, as well as subcellular fractionation, we provide evidence that in the rat hippocampus, MMP-9 mRNA is associated with dendrites and dendritic spines bearing asymmetric (excitatory) synapses. Moreover we observe that after kainate treatment the number of dendrites and synapses containing MMP-9 mRNA increases markedly. Our results indicate that we are observing the phenomenon of dendritic transport of seizure-induced MMP-9 mRNA.
Assuntos
Hipocampo/citologia , Metaloproteinase 9 da Matriz/genética , RNA Mensageiro/genética , Estado Epiléptico/metabolismo , Estado Epiléptico/patologia , Sinapses/metabolismo , Animais , Dendritos/metabolismo , Dendritos/ultraestrutura , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Ácido Caínico , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Microscopia Imunoeletrônica/métodos , Proteínas Oncogênicas v-fos/metabolismo , Ratos , Ratos Wistar , Proteínas S100/metabolismo , Estado Epiléptico/induzido quimicamente , Sinapses/ultraestrutura , Sinaptossomos/metabolismo , Sinaptossomos/ultraestrutura , Fatores de TempoAssuntos
Encéfalo/enzimologia , Ácido Glutâmico/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Degeneração Neural/enzimologia , Plasticidade Neuronal/fisiologia , Animais , Infarto Encefálico/embriologia , Infarto Encefálico/fisiopatologia , Membrana Celular/enzimologia , Humanos , Metaloproteinase 9 da Matriz/genética , Degeneração Neural/fisiopatologia , Neurotoxinas , Transporte Proteico/fisiologiaRESUMO
At least in mammals, we have some understanding of how caspases facilitate mitochondria-mediated cell death, but the biochemical mechanisms by which other factors promote or inhibit programmed cell death are not understood. Moreover, most of these factors are only studied after treating cells with a death stimulus. A growing body of new evidence suggests that cell death regulators also have 'day jobs' in healthy cells. Even caspases, mitochondrial fission proteins and pro-death Bcl-2 family proteins appear to have normal cellular functions that promote cell survival. Here, we review some of the supporting evidence and stretch beyond the evidence to seek an understanding of the remaining questions.
Assuntos
Apoptose/fisiologia , Sobrevivência Celular/fisiologia , Mitocôndrias/fisiologia , Animais , Bactérias/citologia , Humanos , Saccharomyces cerevisiae/citologiaRESUMO
The complete NMR signal assignment of title compounds were carried out by extensive use of 1D and 2D NMR techniques (1H, 13C, GCOSY, GHSQC and GHMBC).