JNK regulates dendrite and spine architecture in the central nervous system influencing spatial learning and motor tasks

JNK1 is a MAP-kinase that has proven a significant player in the central nervous system. It regulates brain development and the maintenance of dendrites and axons. Several novel phosphorylation targets of JNK1 were identified in a screen performed in the Coffey lab. These proteins were mainly involved in the regulation of neuronal cytoskeleton, influencing the dynamics and stability of microtubules and actin. These structural proteins form the dynamic backbone for the elaborate architecture of the dendritic tree of a neuron. The initiation and branching of the dendrites requires a dynamic interplay between the cytoskeletal building blocks. Both microtubules and actin are decorated by associated proteins which regulate their dynamics. The dendrite-specific, high molecular weight microtubule associated protein 2 (MAP2) is an abundant protein in the brain, the binding of which stabilizes microtubules and influences their bundling. Its expression in non-neuronal cells induces the formation of neurite-like processes from the cell body, and its function is highly regulated by phosphorylation. JNK1 was shown to phosphorylate the proline-rich domain of MAP2 in vivo in a previous study performed in the group. Here we verify three threonine residues (T1619, T1622 and T1625) as JNK1 targets, the phosphorylation of which increases the binding of MAP2 to microtubules. This binding stabilizes the microtubules and increases process formation in non-neuronal cells. Phosphorylation-site mutants were engineered in the lab. The non-phosphorylatable mutant of MAP2 (MAP2- T1619A, T1622A, T1625A) in these residues fails to bind microtubules, while the pseudo-phosphorylated form, MAP2- T1619D, T1622D, Thr1625D, efficiently binds and induces process formation even without the presence of active JNK1. Ectopic expression of the MAP2- T1619D, T1622D, Thr1625D in vivo in mouse brain led to a striking increase in the branching of cortical layer 2/3 (L2/3) pyramidal neurons, compared to MAP2-WT. The dendritic complexity defines the receptive field of a neuron and dictates the output to the postsynaptic cells. Previous studies in the group indicated altered dendrite architecture of the pyramidal neurons in the Jnk1-/- mouse motor cortex. Here, we used Lucifer Yellow loading and Sholl analysis of neurons in order to study the dendritic branching in more detail. We report a striking, opposing effect in the absence of Jnk1 in the cortical layers 2/3 and 5 of the primary motor cortex. The basal dendrites of pyramidal neurons close to the pial surface at L2/3 show a reduced complexity. In contrast, the L5 neurons, which receive massive input from the L2/3 neurons, show greatly increased branching. Another novel substrate identified for JNK1 was MARCKSL1, a protein that regulates actin dynamics. It is highly expressed in neurons, but also in various cancer tissues. Three phosphorylation target residues for JNK1 were identified, and it was demonstrated that their phosphorylation reduces actin turnover and retards migration of these cells. Actin is the main cytoskeletal component in dendritic spines, the site of most excitatory synapses in pyramidal neurons. The density and gross morphology of the Lucifer Yellow filled dendrites were characterized and we show reduced density and altered morphology of spines in the motor cortex and in the hippocampal area CA3. The dynamic dendritic spines are widely considered to function as the cellular correlate during learning. We used a Morris water maze to test spatial memory. Here, the wild-type mice outperformed the knock-out mice during the acquisition phase of the experiment indicating impaired special memory. The L5 pyramidal neurons of the motor cortex project to the spinal cord and regulate the movement of distinct muscle groups. Thus the altered dendrite morphology in the motor cortex was expected to have an effect on the input-output balance in the signaling from the cortex to the lower motor circuits. A battery of behavioral tests were conducted for the wild-type and Jnk1-/- mice, and the knock-outs performed poorly compared to wild-type mice in tests assessing balance and fine motor movements. This study expands our knowledge of JNK1 as an important regulator of the dendritic fields of neurons and their manifestations in behavior.

An EDTA-β-cyclodextrin adsorbent for the adsorption of rare earth elements and its application in preconcentration of ultratrace rare earth elements from seawater

The objectives of this work were synthesizing an EDTA-β-CD adsorbent and investigating its adsorption potential and applications in preconcentration of REEs from aqueous phase. The adsorption capacity of EDTA-β-CD was investigated. The adsorption studies were performed by batch techniques both in one- and multi-component systems. The effects of pH, contact time and initial concentration were evaluated. The analytical detection methods and characterization methods were presented. EDTA-β-CD adsorbent was synthesized successfully with high EDTA coverage. The maximum REEs uptake was 0.310 mmol g-1 for La(III), 0.337 mmol g-1 for Ce(III) and 0.353 mmol g-1 for Eu(III), respectively. The kinetics of REEs onto EDTA-β-CD fitted well to pseudo-second-order model and the adsorption rate was affected by intra-particle diffusion. The experimental data of one component studies fitted to Langmuir isotherm model indicating the homogeneous surface of the adsorbent. The extended Sips model was applicable for the isotherm studies in three-component system. The electrostatic interaction, chelation and complexation were all involved in the adsorption mechanism. The preconcentration of RE ions and regeneration of EDTA-β-CD were successful. Overall, EDTA-β-CD is an effective adsorbent in adsorption and preconcentration of REEs.

Diversity among satellite glial cells in dorsal root ganglia of the rat

Peripheral glial cells consist of satellite, enteric glial, and Schwann cells. In dorsal root ganglia, besides pseudo-unipolar neurons, myelinated and nonmyelinated fibers, macrophages, and fibroblasts, satellite cells also constitute the resident components. Information on satellite cells is not abundant; however, they appear to provide mechanical and metabolic support for neurons by forming an envelope surrounding their cell bodies. Although there is a heterogeneous population of neurons in the dorsal root ganglia, satellite cells have been described to be a homogeneous group of perineuronal cells. Our objective was to characterize the ultrastructure, immunohistochemistry, and histochemistry of the satellite cells of the dorsal root ganglia of 17 adult 3-4-month-old Wistar rats of both genders. Ultrastructurally, the nuclei of some satellite cells are heterochromatic, whereas others are euchromatic, which may result from different amounts of nuclear activity. We observed positive immunoreactivity for S-100 and vimentin in the cytoplasm of satellite cells. The intensity of S-100 protein varied according to the size of the enveloped neuron. We also noted that vimentin expression assumed a ring-like pattern and was preferentially located in the cytoplasm around the areas stained for S-100. In addition, we observed nitric oxide synthase-positive small-sized neurons and negative large-sized neurons equal to that described in the literature. Satellite cells were also positive for NADPH-diaphorase, particularly those associated with small-sized neurons. We conclude that all satellite cells are not identical as previously thought because they have different patterns of glial marker expression and these differences may be correlated with the size and function of the neuron they envelope.

Fracionamento do grão de Amaranthus cruentus brasileiro por moagem e suas características composicionais

O grão de amaranto é geralmente consumido na sua forma integral. Este estudo teve como objetivo avaliar o efeito da moagem do grão de amaranto (Amaranthus cruentus) brasileiro na composição química, nutricional, a estabilidade à oxidação e cor da farinha. Os grãos foram pré-condicionados para umidades entre 9,2 e 13,7% e fracionados em moinho para cereais. O aumento da umidade de 9,2 para 13,7% resultou na diminuição progressiva do rendimento da farinha, de 39 para 14%. A farinha refinada (quebra + redução), com 9,2% de umidade, mostrou teores de proteína total de 13,9%, contra 16,2% da farinha integral. O teor de lipídeos totais no amaranto integral (9,2% de umidade) variou de 6,78, para 6,11% na farinha refinada e o teor de fibra nos farelos diminuiu de 3,6 para 3,1%, ao passo que a cor da farinha se tornou mais atraente. Conclui-se que o fracionamento da farinha do grão de amaranto, apesar de produzir uma farinha com melhor aparência e alto teor protéico, apresenta rendimento baixo e não mostra diminuição substancial no teor de óleo da farinha refinada como para garantir uma maior estabilidade à autooxidação.

Estimativa das propriedades térmicas efetivas de grãos em um secador de leito fixo

A secagem de grãos em leito fixo é um processo complexo, ocorrendo simultaneamente a transferência de calor e de massa, dificultando a estimativa dos parâmetros térmicos efetivos, pois estes podem sofrer variações significativas no decorrer da secagem em função de alterações no teor de umidade. Neste trabalho, este problema foi contornado estimando-se os parâmetros térmicos efetivos no final da secagem, quando o teor de umidade dos grãos que compõem o leito alcança valores de equilíbrio, deixando de existir a transferência de massa, persistindo apenas a transferência de calor em regime permanente. Nestas condições, o leito possui um teor de umidade constante e a estimativa dos parâmetros térmicos efetivos pode ser efetuada a partir do ajuste de um modelo pseudo-homogêneo bidimensional estático à várias medidas de temperatura no leito de grãos no final da secagem. Os resultados indicam que a estratégia utilizada para estimativa da condutividade térmica efetiva radial e do coeficiente efetivo de transferência de calor parede-leito foi adequada. Além do que, constatou-se que dentre os grãos estudados - soja, feijão, milho e trigo - a soja apresenta os menores valores de condutividade efetiva radial, enquanto o trigo apresenta o maior valor do coeficiente de transferência de calor parede-leito.

Changes in physical properties of extruded sour cassava starch and quinoa flour blend snacks

Given the broad acceptance of sour cassava starch biscuits in Brazil and the nutritional quality of quinoa flour, this study aimed to evaluate the effect of extrusion temperature, screw speed, moisture, and amount of quinoa flour on the physical properties of puffed snacks. Extrusion process was carried out using a single-screw extruder in a factorial central composite design with four factors. Effects of moisture and amount of quinoa flour on the expansion index and specific volume of snacks were observed. There was a pronounced increase in water solubility index of blends with the extrusion process with significant effects of all process parameters on the WSI. Higher water absorption index (WAI) was observed under high temperature, low moisture, and lower quinoa flour amount. Temperature and amount of quinoa flour influenced the color of the snacks. A positive quadratic effect of quinoa flour on hardness of products was observed. Blends of sour cassava starch and quinoa flour have good potential for use as raw material in production of extruded snacks with good physical properties.

Alterations of palm oil (Elaeis guineensis) in the continuous industrial par frying of breaded chicken snacks

The physical and chemical alterations in palm oil during continuous industrial par frying of breaded chicken snacks were evaluated using a pseudo first-order kinetic model. The acidity index, refractive index, concentration of polar compounds, viscosity, color, and absorbance (232 and 268 nm) of 238 samples of the frying oil collected during 26 days of production were analyzed. For all of the analyses, the results of the oil were below the limits recommended for oil disposal, indicating that the processing conditions were safe and that under these experimental conditions the oil remained suitable for frying. The linear regressions were significant for refractive index, content of polar compounds, and lightness (L*). The content of polar compounds was determined using a cooking oil tester, and it had the best fit to the proposed model and can be used as an effective index for monitoring palm oil during the continuous par frying of breaded chicken snacks. The high turnover rate of the oil was important for maintaining the oil in good running conditions.

Multivariate study and regression analysis of gluten-free granola

This study developed a gluten-free granola and evaluated it during storage with the application of multivariate and regression analysis of the sensory and instrumental parameters. The physicochemical, sensory, and nutritional characteristics of a product containing quinoa, amaranth and linseed were evaluated. The crude protein and lipid contents ranged from 97.49 and 122.72 g kg-1 of food, respectively. The polyunsaturated/saturated, and n-6:n-3 fatty acid ratios ranged from 2.82 and 2.59:1, respectively. Granola had the best alpha-linolenic acid content, nutritional indices in the lipid fraction, and mineral content. There were good hygienic and sanitary conditions during storage; probably due to the low water activity of the formulation, which contributed to inhibit microbial growth. The sensory attributes ranged from 'like very much' to 'like slightly', and the regression models were highly fitted and correlated during the storage period. A reduction in the sensory attribute levels and in the product physical stabilisation was verified by principal component analysis. The use of the affective test acceptance and instrumental analysis combined with statistical methods allowed us to obtain promising results about the characteristics of gluten-free granola.

O uno e o ser no pensamento de Meister Eckhart

O problema de fundo da especulação eckhartiana é a verdade do ser uno enquanto Deus e divino ligada à questão do seu conhecimento. Operando uma síntese da tradição neoplatônico-agostiniana e do pensamento do Pseudo-Dionísio Areopagita, o mestre dominicano funda os alicerces da sua teologia unitiva na teoria do ser.

Kant and zeno of elea: historical precedents of the "sceptical method"

For Kant's interpretation of Zeno in KrV A502-507/B530-535, scholars have usually referred to Plato's Phaedrus (261d); in reality the sources Kant uses are, on one hand, Brucker (who depends in turn on the pseudo-Aristotelian De Melisso, Xenophane, et Gorgia, 977 b 2-21), and, on the other, Plato's Parmenides (135e6-136b1) and Proclus' commentary on it, as quoted by Gassendi in a popular textbook he wrote on the history of logic.

A “MÍSTICA DO LOGOS” E O FUNDAMENTO DA FILOSOFIA DA LINGUAGEM DE NICOLAU DE CUSA

Partimos da afirmação de K.-O. Apel, repetida por João Maria André (1986, p. 400), de que "[...] é na ‘mística' do ‘logos' e na teologia negativa do Pseudo-Dionísio que, de modo determinante, Nicolau de Cusa irá beber os traços fundamentais da sua filosofia da linguagem". Com base no De filiatione Dei (1450) propomo-nos refletir sobre a relação fundamental e constitutiva entre o verbo mental humano e o Verbo ou Logos eterno. A importância desse texto, no âmbito do problema da linguagem em Nicolau de Cusa, é reconhecida por Casarella (1992) justamente por sua inflexão cristológica em relação aos primeiros sermões, pois, em oposição à reflexão intratrinitária dos sermões, a imagem humanamente visível de Cristo torna-se o espelho da linguagem, ou seja, em Cristo, vemos de modo perfeito o que pode ser expresso por meio da linguagem. O texto cusano é uma meditação sobre Jo, I, 12: "Mas a todos que o receberam deu o poder de se tornarem filhos de Deus: aos que creem em seu nome". Interessa-nos principalmente a meditação sobre os exemplos aduzidos por Nicolau de Cusa para explicitar de que modo colhemos a unidade divina intelectualmente, pois serão nesses exemplos ou enigmas que o autor pensará a relação constitutiva entre o verbo mental humano e o verbo mental inefável.

[Recueil]

S. Augustinus, De baptismo parvulorum (1-30). - S. Anselmus Cantuariensis, Epistola ad monasterium Sancti Albani super Trinitatem (30-30v). - S. Gregorius, Epistolae (30v-31). - Remigius Autissiodorensis, Tractatus in Cantica canticorum (32-58). - Alcuinus, Expositio super Ecclesiastem (58-79v). - S. Augustinus, Altercatio contra Felicianum Arriomantem de unitate Trinitatis (79v-87). - Pseudo-Augustinus, De quattuor virtutibus caritatis (87-87v). - Alcuinus, De virtutibus et vitiis (88-94).- Liber Scintillarum (94-116v). - Isidorus Hispalensis, Sententiae de exemplis sanctorum (116v-121v). - De sacramentis ecclesiae (121v-124). - Teobaldus Stapensis, Epistola ad abbatem Saloberiensem (124-124v). - S. Bernardus Claraevallensis, Parabola de conflictu civitatis Babilonie et Jerusalem (124v-132v). - S. Augustinus, De incarnatione Domini contra Judeos (132v-133), Liber de predestinatione (133-136). - Hugo de Sancto Victore, Quaestio ("De eo quod dicitur: funes ceciderunt mihi in praeclaris") (136-136v). - S. Gregorius, Regula pastoralis (136v-137v). - S. Anselmus Cantuariensis, Cur Deus homo (138-155). - Robertus Pullus, Sermo (155-156). - Elucidarium (156-173v). - Adso Dermensis, D761De Antichristo ejusque signis (173v-174). - S. Augustinus, De libero arbitrio (174v). - Anselmus Lauduniensis, Sententiae de matrimonio (174v-177). - Sententiae variae (177-181).

[Recueil]

Julianus Pomerius, De vita activa et contemplativa (1-45). - Prosperus Aquitanus, De vocatione gentium (45v-74v), Epistola ad Rufinum de gratia et libero arbitrio (74v-80), De gratia Dei et libero arbitrio contra collatorem (80-101v), Responsiones ad excerpta Genuensium (101v-107), Responsiones ad capitula objectionum Gallorum (107-113), Responsiones ad capitula objectionum Vincentianarum (113-117), Sententiae ex operibus sancti Augustini (117-137), Epigrammata (137v-147v). - Pseudo Paulanus Nolensis, Poema conjugis ad uxorem (147v-148). - Pseudo Prosperus, Confessio (148-148v). - S. Leo, Sermones XVI et XVII [fragments] (149-149v).

[Recueil].

Pseudo-Augustinus, De spiritu et anima (1-8). - Ricardus de Sancto Victore, De gradibus caritatis (8v-17v). - Hugo de Sancto Caro, Speculum ecclesiae (17v-22). - De canone missae (22-34v). - Instructio confessorum (34v-36). - Sermones [Nicolaus de Byard et alii] (37-193v). - Adelardus Bathoniensis, Quaestiones naturales perdifficiles (195-210v). - Alanus de Insulis, Quaestiones naturales (210v-227). - Marbodus Redonensis, Liber lapidum (227-231v). - Zacharias de Salerno, Liber de passionibus oculorum (231v-238v). - Versus de signis tempestatum (238v-239v).

[Recueil].

Collectio decretorum et epistolarum decretalium (1-51v). - Ivo Carnotensis, Decretum et epistolae (52-62v). - Hugo de Sancto Victore, Miscellanea; S. Bernardus, Sermones de diversis (excerpta) (63-70v) - Sermones varii (71-101v). - Commentarii diversi excerptorum Bibliae (compilatio) (102-126v). D'après les ex-libris contemporains, le recueil a peut-être été copié dans l'abbaye du Mont-Saint-Quentin (Somme). La première partie de ce ms. contient des extraits des Décrétales du Pseudo-Isidorus Mercator (cf. L. Kéry). Parmi les commentaires sur la Bible (102-126v) figurent des écrits de st Bernard, découverts par H.M. Rochais (cf. H.M. Rochais). Les feuillets 24-25, 46-51 se trouvent dans le ms. lat. 18248."