The neurotoxicity of 5-S-cysteinyldopamine is mediated by the early activation of ERK1/2 followed by the subsequent activation of ASK1/JNK1/2 pro-apoptotic signalling

Parkinson's disease is characterized by the progressive and selective loss of dopaminergic neurons in the substantia nigra. It has been postulated that endogenously formed CysDA (5-S-cysteinyldopamine) and its metabolites may be, in part, responsible for this selective neuronal loss, although the mechanisms by which they contribute to such neurotoxicity are not understood. Exposure of neurons in culture to CysDA caused cell injury, apparent 12-48 h post-exposure. A portion of the neuronal death induced by CysDA was preceded by a rapid uptake and intracellular oxidation of CysDA, leading to an acute and transient activation of ERK2 (extracellular-signal-regulated kinase 2) and caspase 8. The oxidation of CysDA also induced the activation of apoptosis signal-regulating kinase 1 via its de-phosphorylation at Ser967, the phosphorylation of JNK (c-Jun N-terminal kinase) and c-Jun (Ser73) as well as the activation of p38, caspase 3, caspase 8, caspase 7 and caspase 9. Concurrently, the inhibition of complex I by the dihydrobenzothiazine DHBT-1 [7-(2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4-benzothiazine-3-carboxylic acid], formed from the intracellular oxidation of CysDA, induces complex I inhibition and the subsequent release of cytochrome c which further potentiates pro-apoptotic mechanisms. Our data suggest a novel comprehensive mechanism for CysDA that may hold relevance for the selective neuronal loss observed in Parkinson's disease.

Making sense of the early-2000s warming slowdown

It has been claimed that the early-2000s global warming slowdown or hiatus, characterized by a reduced rate of global surface warming, has been overstated, lacks sound scientific basis, or is unsupported by observations. The evidence presented here contradicts these claims.

Differential expression of connexins during histogenesis of the chick retina

Gap junction (GJ) channels couple adjacent cells, allowing transfer of second messengers, ions, and molecules up to 1 kDa. These channels are composed by a multigene family of integral membrane proteins called connexins (Cx). In the retina, besides being essential circuit element in the visual processing, GJ channels also play important roles during its development. Herein, we analyzed Cx43, Cx45, Cx50, and Cx56 expression during chick retinal histogenesis. Cx exhibited distinct expression profiles during retinal development, except for Cx56, whose expression was not detected. Cx43 immunolabeling was observed at early development, in the transition of ventricular zone and pigmented epithelium. Later, Cx43 was seen in the outer plexiform and ganglion cell layers, and afterwards also in the inner plexiform layer. We observed remarkable changes in the phosphorylation status of this protein, which indicated modifications in functional properties of this Cx during retinal histogenesis. By contrast, Cx45 showed stable gene expression levels throughout development and ubiquitous immunoreactivity in progenitor cells. From later embryonic development, Cx45 was mainly observed in the inner retina, and it was expressed by glial cells and neurons. In turn, Cx50 was virtually absent in the chick retina at initial embryonic phases. Combination of PCR, immunohistochemistry and Western blot indicated that this Cx was present in differentiated cells, arising in parallel with the formation of the visual circuitry. Characterization of Cx expression in the developing chick retina indicated particular roles for these proteins and revealed similarities and differences when compared to other species. (C) 2008 Wiley Periodicals, Inc.

Acanthoscurrin Fragment 101-132: Total Synthesis at 60 degrees C of a Novel Difficult Sequence

Glycine-rich proteins (GRP), serve a variety of biological functions. Acanthoscurrin is an antimicrobial GRP isolated front hemocytes-of the Brazilian spider Acanthoscurria gomesiana. Aiming to contribute to the knowledge of the secondary structure and stepwise solid-phase synthesis of GRPs` glycine-rich domains, we attempted to prepare G(101)GGLGGGRGGGYG(113) GGGGYGGGYG(123)GGy(126)GGGKYK(132)-NH(2), acanthoscurrin C-terminal amidated fragment. Although a theoretical prediction did not indicate high aggregation potential for this peptide, repetitive incomplete aminoacylations were observed after incorporating Tyr(126) to the growing peptide-MBHA resin (Boc chemistry) at 60 degrees C. The problem was not solved by varying the coupling reagents or solvents, adding chaotropic salts to the reaction media or changing the resin/chemistry (Rink amide resin/Fmoc chemistry). Some improvement was mode when CLEAR amide resin (Fmoc chemistry) was 32 used, as it allowed for obtaining fragment (G(113)-K(132) NIR-FT-Raman spectra collected for samples of the growing peptide-MBHA, -Rink amide resin and -CLEAR amide resin revealed the presence of beta-sheet structures. Only the combination of CLEAR-amide resin, 60 degrees C, Fmoc-(Fmoc-Hmb)Gly-OH and LiCl (the last two used alternately) was able to inhibit the phenomenon, as proven by NIR-FT-Raman analysis of the growing peptide-resin, allowing the total synthesis of desired 132 fragment Gly(101)-K(132). In summary, this work describes a new difficult sequence, contributes to understanding stepwise solid-phase synthesis of this type of peptide and shows that, at least while protected and linked to a resin, this GRPs glycine-rich motif presents all early tendency to assume beta-sheet structures. (c) 2008 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 92: 65-75, 2009.

Models of complexity in Robert Coover's John's wife and the adventures of Lucky Pierre

This doctoral dissertation analyzes two novels by the American novelist Robert Coover as examples of hypertextual writing on the book bound page, as tokens of hyperfiction. The complexity displayed in the novels, John's Wife and The Adventures of Lucky Pierre, integrates the cultural elements that characterize the contemporary condition of capitalism and technologized practices that have fostered a different subjectivity evidenced in hypertextual writing and reading, the posthuman subjectivity. The models that account for the complexity of each novel are drawn from the concept of strange attractors in Chaos Theory and from the concept of rhizome in Nomadology. The transformations the characters undergo in the degree of their corporeality sets the plane on which to discuss turbulence and posthumanity. The notions of dynamic patterns and strange attractors, along with the concept of the Body without Organs and Rhizome are interpreted, leading to the revision of narratology and to analytical categories appropriate to the study of the novels. The reading exercised throughout this dissertation enacts Daniel Punday's corporeal reading. The changes in the characters' degree of materiality are associated with the stages of order, turbulence and chaos in the story, bearing on the constitution of subjectivity within and along the reading process. Coover's inscription of planes of consistency to counter linearity and accommodate hypertextual features to the paper supported narratives describes the characters' trajectory as rhizomatic. The study led to the conclusion that narrative today stands more as a regime in a rhizomatic relation with other regimes in cultural practice than as an exclusively literary form and genre. Besides this, posthuman subjectivity emerges as class identity, holding hypertextual novels as their literary form of choice.

CMS tracking performance results from early LHC operation

The first LHC pp collisions at centre-of-mass energies of 0.9 and 2.36 TeV were recorded by the CMS detector in December 2009. The trajectories of charged particles produced in the collisions were reconstructed using the all-silicon Tracker and their momenta were measured in the 3.8 T axial magnetic field. Results from the Tracker commissioning are presented including studies of timing, efficiency, signal-to-noise, resolution, and ionization energy. Reconstructed tracks are used to benchmark the performance in terms of track and vertex resolutions, reconstruction of decays, estimation of ionization energy loss, as well as identification of photon conversions, nuclear interactions, and heavy-flavour decays.

Cephalosporin C production by immobilized Cephalosporium acremonium cells in a repeated batch tower bioreactor

The industrial production of antibiotics with filamentous fungi is usually carried out in conventional aerated and agitated tank fermentors. Highly viscous non-Newtonian broths are produced and a compromise must be found between convenient shear stress and adequate oxygen transfer. In this work, cephalosporin C production by bioparticles of immobilized cells of Cephalosporium acremonium ATCC 48272 was studied in a repeated batch tower bioreactor as an alternative to the conventional process. Also, gas-liquid oxygen transfer volumetric coefficients, k(L)a, were determined at various air flow-rates and alumina contents in the bioparticle. The bioparticles were composed of calcium alginate (2.0% w/w), alumina (<44 micra), cells, and water. A model describing the cell growth, cephalosporin C production, oxygen, glucose, and sucrose consumption was proposed. To describe the radial variation of oxygen concentration within the pellet, the reaction-diffusion model forecasting a dead core bioparticle was adopted. The k(L)a measurements with gel beads prepared with 0.0, 1.0, 1.5, and 2.0% alumina showed that a higher k(L)a value is attained with 1.5 and 2.0%. An expression relating this coefficient to particle density, liquid density, and air velocity was obtained and further utilized in the simulation of the proposed model. Batch, followed by repeated batch experiments, were accomplished by draining the spent medium, washing with saline solution, and pouring fresh medium into the bioreactor. Results showed that glucose is consumed very quickly, within 24 h, followed by sucrose consumption and cephalosporin C production. Higher productivities were attained during the second batch, as cell concentration was already high, resulting in rapid glucose consumption and an early derepression of cephalosporin C synthesizing enzymes. The model incorporated this improvement predicting higher cephalosporin C productivity. (C) 2004 Wiley Periodicals, Inc.

Study of spore germination in Thelypteris-dentata (forssk) e-st-john

The spore germination in Thelypteris dentata was studied and the optimum temperature of 25 C was determined by the maximum percentage germination and the highest germination index. The necessity of continuous white light irradiation and reversion of spore germination by subsequent far-red light irradiation indicate the involvement of phytochrome in the control of the process. The dependence of induction of spore germination to the continuous white light low irradiance confirms the phytochrome control through the low fluence response.

O estatuto ontológico do inconsciente em Freud: uma discussão a partir da crítica de John Searle

Pós-graduação em Filosofia - FFC

Uma investigação sobre o problema mente-corpo segundo o ponto de vista de John Searle

Pós-graduação em Filosofia - FFC

Early hunter-gatheres in the Terra Firme Rainforest: stemmed projectile points from the Curuá goldmines

Achados acidentais de instrumentos líticos em região de terra firme junto ao rio Curuá, no médio curso da Bacia do Xingu, sugere uma ocupação disseminada por caçador-coletores pré-cerâmicos na região, contrariamente a expectativas de que a floresta tropical teria recursos alimentares insuficientes para a ocupação humana longe da várzea. Os artefatos líticos incluem pontas de projétil de lascamento cuidadoso, possivelmente relacionados a alguns artefatos do Pleistoceno final encontrados na Caverna da Pedra Pintada, em Monte Alegre. Os resíduos alimentares encontrados com os artefatos de Monte Alegre eram de uma economia de coleta de ambientes rupestres e ribeirinhos. As pontas do Xingu foram recolhidas por garimpeiros nas reias e cascalhos no leito do rio Curuá. Os garimpeiros encontraram os artefatos enquanto escavavam e peneiravam sedimentos auríferos. Tais depósitos algumas vezes também contêm remanescentes de plantas e artefatos de madeira pré-históricos, fontes de informação potencial sobre antigos habitats, subsistência e tecnologia. O grupo de pesquisa do Projeto Baixo Amazonas viajou a diversos dos sítios submersos com os garimpeiros para preparar escavações para o futuro. Em um sítio, Curupité, onde os garimpeiros encontraram uma grande ponta com pedúnculo e um arpão de madeira inteiro em 1986, a equipe utilizou equipamento de mergulho para prospectar o leito do rio e os barrancos, e mapearam a topografa com um teodolito a laser.

A metáfora fundamental do discurso de John Dewey

This work aims to identify the rootmetaphor of John Dewey’s philosophical and educational discourse, by means of rhetorical analyses parameters. This methodology is founded in Aristotle and in the works of Chaïm Perelman and other contemporary authors involved in the revision of Aristotelian philosophy. The article examines the essays “The philosophical work of Herbert Spencer” and “The influence of darwinism on philosophy”, published by John Dewey respectively in 1904 e 1909. They were written in the early years of Dewey in Columbia University, which intellectual environment was not dominated by Pragmatism, and for this reason they can be considered seminal in the structuring of the author’s arguments. The analysis reveals that Dewey is favorable to Darwinian evolutionism thesis and opposite to Spencer’s one. This positioning suggests that Dewey’s discourse is bound to the metaphor “undetermined route” because it situates evolution as a process devoid of previously listed purposes at a pre-determined plan, subject only to the relations that are established, so unpredictable, between organisms and the environmental conditions that surround. Analyzing Dewey’s ideas about education, the article concludes that “undetermined route” is the rootmetaphor of Dewey’s discourse, hypothesis that can contribute to discuss Dewey in the context of contemporary philosophy.

O fluxo da consciência em Ask the dust, de John Fante

The purpose of this research is to present de narrative techniques of the Stream of Consciousness in the novel Ask the dust, by American writer John Fante, as well as analyzing the technique applying it to the character/narrator Arturo Bandini. Among others, the emphasys was given to the interior monologue technique, for its large and intense use throughout the analyzed novel. This research was based specially on O Fluxo da consciência (1976), by Robert Humphrey, and Foco narrativo e fluxo da consciência (2012), de Alfredo Leme Coelho de Carvalho, both important researchers in the studied theme. This research, therefore, intends to demonstrate the geniality of the still little-known John Fante and point out the peculiarities of the so-called 'psychological fiction', that in the early 20th century united literature and psychology studies, becoming very popular in modern literature, with exponents like Virginia Woolf and James Joyce

Consequences of Early Late-Pleistocene Megadroughts in Tropical Africa

Extremely arid conditions in tropical Africa occurred in several discrete episodes between 135 and 90 ka, as demonstrated by lake core and seismic records from multiple basins [Scholz CA, Johnson TC, Cohen AS, King JW, Peck J, Overpeck JT, Talbot MR, Brown ET, Kalindekafe L,Amoako PYO, et al. (2007) Proc Natl Acad SciUSA104:16416–16421]. This resulted in extraordinarily low lake levels, even in Africa’s deepest lakes.On the basis of well dated paleoecological records from Lake Malawi, which reflect both local and regional conditions, we show that this aridity had severe consequences for terrestrial and aquatic ecosystems. During the most arid phase, there was extremely low pollen production and limited charred-particle deposition, indicating insufficient vegetation to maintain substantial fires, and the Lake Malawi watershed experienced cool, semidesert conditions (<400 mm>/yr precipitation). Fossil and sedimentological data show that Lake Malawi itself, currently 706mdeep, was reduced to an ~125 m deep saline, alkaline, well mixed lake. This episode of aridity was far more extreme than any experienced in the Afrotropics during the Last Glacial Maximum (~35–15 ka). Aridity diminished after 95 ka, lake levels rose erratically, and salinity/alkalinity declined, reaching near-modern conditions after 60 ka. This record of lake levels and changing limnological conditions provides a framework for interpreting the evolution of the Lake Malawi fish and invertebrate species flocks. Moreover, this record, coupled with other regional records of early Late Pleistocene aridity, places new constraints on models of Afrotropical biogeographic refugia and early modern human population expansion into and out of tropical Africa.

O fluxo da consciência em Ask the dust, de John Fante

The purpose of this research is to present de narrative techniques of the Stream of Consciousness in the novel Ask the dust, by American writer John Fante, as well as analyzing the technique applying it to the character/narrator Arturo Bandini. Among others, the emphasys was given to the interior monologue technique, for its large and intense use throughout the analyzed novel. This research was based specially on O Fluxo da consciência (1976), by Robert Humphrey, and Foco narrativo e fluxo da consciência (2012), de Alfredo Leme Coelho de Carvalho, both important researchers in the studied theme. This research, therefore, intends to demonstrate the geniality of the still little-known John Fante and point out the peculiarities of the so-called 'psychological fiction', that in the early 20th century united literature and psychology studies, becoming very popular in modern literature, with exponents like Virginia Woolf and James Joyce