Advances in the treatment of malignant gliomas

Local control with surgery, radiation, and temozolomide chemotherapy remain the pillars of treatment for high-grade gliomas. Novel therapeutic strategies, including a variety of antiangiogenic agents, are under investigation. One of these agents, bevacizumab, was recently given accelerated approval by the US Food and Drug Administration as a single agent for recurrent glioblastoma. Recent trial results are generating important clinical questions regarding which patients to treat and when, and how best to monitor response. Encouraging results of recent studies are driving willingness to undertake aggressive treatment and to improve outcomes in this population. In this era, better understanding of biology, molecular aspects of cancer, and clinical trial methodology are crucial for clinicians. This review focuses on recent advances in the treatment malignant gliomas, especially antiangiogenic therapy.

Airway clearance of apoptotic cells in COPD

Apoptosis of bronchial epithelial cells and the phagocytic clearance of these cells by alveolar macrophages (a process termed efferocytosis) are integral processes leading to repair of airway epithelial injury. Efferocytosis allows for the removal of apoptotic material with minimal inflammation and prevents the development of secondary necrosis and ongoing inflammation. Defective efferocytosis and the increased presence of apoptotic cells have been identified in the airways of subjects with chronic obstructive pulmonary disease (COPD). There are three major potential causes for this accumulation of apoptotic cells: (i) increased apoptosis per se as a result of an increase in apoptotic mediators, (ii) defects in the recognition of apoptotic cells by AM and (iii) failure to clear the unwanted cells by the process of efferocytosis. The implications of these processes in COPD and novel treatment strategies aimed at improving clearance of apoptotic cells form the focus of the present review.

Shining the light on sunshine: a systematic review of the influence of sun exposure on type 2 diabetes mellitus-related outcomes

Prospective observational studies uniformly link vitamin D deficiency with the incidence of type 2 diabetes mellitus (T2DM), yet trials supplementing participants at risk of T2DM with vitamin D to reduce progression to T2DM have yielded inconsistent results. Inconsistencies between supplementation trials may be due to insufficient dosing or small sample sizes. Observational studies may also have reported spurious associations due to uncontrolled confounding by lifestyle or genetic factors. Alternatively, observational and intervention studies may not be entirely comparable. Observational studies show an association between higher vitamin D status, which is predominantly derived from sun exposure, and decreased incidence of T2DM. Trials intervene with vitamin D supplementation, and therefore may be missing alternate causes of the effect of sun exposure, as seen in observational studies. We propose that sun exposure may be the driving force behind the associations seen in observational studies; sun exposure may have additional benefits beyond increasing serum 25-hydroxyvitamin D (25OHD) levels. We performed an electronic literature search to identify articles that examined associations between sun exposure and T2DM and/or glucose metabolism. A best evidence synthesis was then conducted using outcomes from analyses deemed to have high methodological quality. Ten eligible full-text articles were identified, yielding 19 T2DM-related outcomes. The best evidence analysis considered 11 outcomes which were grouped into six outcome types: T2DM, fasting glucose, glucose tolerance, fasting insulin, insulin secretion and insulin sensitivity. There was moderate evidence to support a role of recreational sun exposure in reducing odds of T2DM incidence. High-level evidence was lacking; evidence presented for other outcomes was of low or insufficient level. This review highlights significant gaps in research pertaining to sun exposure and T2DM-related outcomes. Further research is encouraged as we aim to identify novel preventative strategies for T2DM.

A scalable and automatic mechanism for resource allocation in self-organizing cloud

Taking advantage of the huge potential of consumers’ untapped computing power, self-organizing cloud is a novel computing paradigm where the consumers are able to contribute/sell their computing resources. Meanwhile, host machines held by the consumers are connected by a peer-to-peer (P2P) overlay network on the Internet. In this new architecture, due to large and varying multitudes of resources and prices, it is inefficient and tedious for consumers to select the proper resource manually. Thus, there is a high demand for a scalable and automatic mechanism to accomplish resource allocation. In view of this challenge, this paper proposes two novel economic strategies based on mechanism design. Concretely, we apply the Modified Vickrey Auction (MVA) mechanism to the case where the resource is sufficient; and the Continuous Double Auction (CDA) mechanism is employed when the resource is insufficient. We also prove that aforementioned mechanisms have dominant strategy incentive compatibility. Finally, extensive experiment results are conducted to verify the performance of the proposed strategies in terms of procurement cost and execution efficiency.

Op Shop Series

This series of works by the Melbourne collaborative group, Bozo Ink, in undermines the art gallery’s system of exchange and representation. They make the observation that as a site that supposedly reflects and critiques contemporary cultures, histories and practices, the gallery is merely a space of exhibition. Like many contemporary artists, and the critics and academics who assess their work, they are aware of the inherent paradox of exhibiting a work critical of commodity culture since we enter into a process of consumption that actually magnifies commodity culture when we place work in a gallery context. Bozo Ink’s project, The Op-Shop Series, offers a critique of consumptive practices in the art gallery and looks to entwine art, everyday practices and resistance strategies. They do this to test the potential of the gallery as a site for resistance, and to reconsider its function in the age of “consumption and spectacular exhibition” (Agamben 2007, 82). In linking the counter-practices of profanation (Agamben 2007) with the Situationist strategy of détournement (Debord 1994; Wark 2013) they hope to recast the art object as one without currency in the gallery. They propose that it is possible for the art object to unsettle both the image and the system of exchange within which it operates.

Marcadores sociais da diferença nas experiências travestis de enfrentamento à aids

Os argumentos apresentados neste artigo partem de apontamentos etnográficos oriundos de pesquisa antropológica realizada entre travestis que se prostituem. A partir da análise dessas notas, apresentam-se as categorias classificatórias acionadas pelas travestis que se prostituem a fim de, por esses termos, demarcarem diferenças pouco consideradas pelos formuladores de políticas de saúde, mas que são significativas para elas, pois se referem a maneiras singularizadas de subjetividades nas quais gênero, geração, classe e raça estão implicadas. Assim, procura-se explorar como esses marcadores sociais da diferença operam contextual e relacionalmente nas respostas que esses sujeitos têm elaborado frente à sistemática associação entre travestis e aids, e como esses eixos se enfeixam compondo experiências específicas do adoecer e do sofrimento, ao mesmo tempo em que permitem que as travestis mobilizem diversas estratégias de resistência e enfrentamento a processos de estigmatização. A discussão a ser empreendida vale-se do escopo teórico pós-estruturalista, bem como das contribuições do feminismo como crítica epistemológica.

A máscara chinesa: Notas sobre uso das fontes produzidas pelo aparato repressivo da ditadura militar

The methodological aspects which the historians face when using documents produced by the Brazilian military dictatorship on the leftist movements which intended to trigger the revolutionary struggle are analyzed. Whereas the strategy of the repressive regime in producing and establishing the 'truth' is enhanced, the resistance strategies of the political forces targeted by the repressive apparatus are investigated. The documents on the political organization called Marxist-Leninist Popular Movement have been employed.

Contando estórias e inventando metodologias para discutir a violência contra as mulheres

In this article I write about the importance of creating alternative methodologies to work with violence against women in the field of psychology. Artistic productions like literature, theatre and storytelling, among others, make it possible to question fixed binary identities in gender regulation and may enable the reconstruction of identitary rules by means of original enunciations and gestures, which give occasion to new maps that can embrace differences and refute normalizations. I bring the possibility of thinking the insertion of the psychologist in this debate, supported by artistic devices as resistance strategies and construction of dissident subjectivities, and I illustrate this narrative bringing the story of Branca and José Pássaro Volante, characters of Lídia Jorge's work O dia dos prodígios (The day of the prodigies).

Dysregulation of Anti-Inflammatory Annexin A1 Expression in Progressive Crohns Disease

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

A structure-based proposal for a comprehensive myotoxic mechanism of phospholipase A(2)-like proteins from viperid snake venoms

Envenomation via snakebites is an important public health problem in many tropical and subtropical countries that, in addition to mortality, can result in permanent sequelae as a consequence of local tissue damage, which represents a major challenge to antivenom therapy. Venom phospholipases A(2) (PLA(2)s) and PLA(2)-like proteins play a leading role in the complex pathogenesis of skeletal muscle necrosis, nevertheless their precise mechanism of action is only partially understood. Recently, detailed structural information has been obtained for more than twenty different members of the PLA(2)-like myotoxin subfamily. In this review, we integrate the available structural, biochemical and functional data on these toxins and present a comprehensive hypothesis for their myotoxic mechanism. This process involves an allosteric transition and the participation of two independent interaction sites for docking and disruption of the target membrane, respectively, leading to a five-step mechanism of action. Furthermore, recent functional and structural studies of these toxins complexed with ligands reveal diverse neutralization mechanisms that can be classified into at least three different groups. Therefore, the data summarized here for the PLA(2)-like myotoxins could provide a useful molecular basis for the search for novel neutralizing strategies to improve the treatment of envenomation by viperid snakes. (C) 2014 Elsevier B.V. All rights reserved.

Extrinsic Purinergic Regulation of Neural Stem/Progenitor Cells: Implications for CNS Development and Repair

There has been tremendous progress in understanding neural stem cell (NSC) biology, with genetic and cell biological methods identifying sequential gene expression and molecular interactions guiding NSC specification into distinct neuronal and glial populations during development. Data has emerged on the possible exploitation of NSC-based strategies to repair adult diseased brain. However, despite increased information on lineage specific transcription factors, cell-cycle regulators and epigenetic factors involved in the fate and plasticity of NSCs, understanding of extracellular cues driving the behavior of embryonic and adult NSCs is still very limited. Knowledge of factors regulating brain development is crucial in understanding the pathogenetic mechanisms of brain dysfunction. Since injury-activated repair mechanisms in adult brain often recapitulate ontogenetic events, the identification of these players will also reveal novel regenerative strategies. Here, we highlight the purinergic system as a key emerging player in the endogenous control of NSCs. Purinergic signalling molecules (ATP, UTP and adenosine) act with growth factors in regulating the synchronized proliferation, migration, differentiation and death of NSCs during brain and spinal cord development. At early stages of development, transient and time-specific release of ATP is critical for initiating eye formation; once anatomical CNS structures are defined, purinergic molecules participate in calcium-dependent neuron-glia communication controlling NSC behaviour. When development is complete, some purinergic mechanisms are silenced, but can be re-activated in adult brain after injury, suggesting a role in regeneration and self-repair. Targeting the purinergic system to develop new strategies for neurodevelopmental disorders and neurodegenerative diseases will be also discussed.

Distribution of QPY and RAH haplotypes of granzyme B gene in distinct Brazilian populations

Introduction: The cytolysis mediated by granules is one of the most important effector functions of cytotoxic T lymphocytes and natural killer cells. Recently, three single nucleotide polymorphisms (SNPs) were identified at exons 2, 3, and 5 of the granzyme B gene, resulting in a haplotype in which three amino acids of mature protein Q48P88Y245 are changed to R48A88H245, which leads to loss of cytotoxic activity of the protein. In this study, we evaluated the frequency of these polymorphisms in Brazilian populations. Methods: We evaluated the frequency of these polymorphisms in Brazilian ethnic groups (white, Afro-Brazilian, and Asian) by sequencing these regions. Results: The allelic and genotypic frequencies of SNP 2364A/G at exon 2 in Afro-Brazilian individuals (42.3% and 17.3%) were significantly higher when compared with those in whites and Asians (p < 0.0001 and p = 0.0007, respectively). The polymorphisms 2933C/G and 4243C/T also were more frequent in Afro-Brazilians but without any significant difference regarding the other groups. The Afro-Brazilian group presented greater diversity of haplotypes, and the RAH haplotype seemed to be more frequent in this group (25%), followed by the whites (20.7%) and by the Asians (11.9%), similar to the frequency presented in the literature. Conclusions: There is a higher frequency of polymorphisms in Afro-Brazilians, and the RAH haplotype was more frequent in these individuals. We believe that further studies should aim to investigate the correlation of this haplotype with diseases related to immunity mediated by cytotoxic lymphocytes, and if this correlation is confirmed, novel treatment strategies might be elaborated.

La influencia de la estética oriental en la autotraducción: análisis de la novela bicultural The Good Earth de la autora P.S. Buck

[EN]This dissertation analyses the Eastern cultural influences present in the aesthetic of Buck’s best seller The Good Earth. The objective is to study the characteristics of Buck’s aesthetic as a product of a creative process of self-translation between Mandarin and English. The methodology of analysis has focused on the characters of the novel, the strategies used to refer to them, the characters’ idiolect and their social interaction (facework). Finally, these cultural aspects have been compared with one of the Spanish translations available of the novel. The results obtained show a novel highly influenced by the Eastern tradition, where the idiolect of the characters show an influence from both East and West possible thanks to the mechanism of self-translation.

Mapping the elastic response of epithelial apical cell membranes suspended across porous array

As the elastic response of cell membranes to mechanical stimuli plays a key role in various cellular processes, novel biophysical strategies to quantify the elasticity of native membranes under physiological conditions at a nanometer scale are gaining interest. In order to investigate the elastic response of apical membranes, elasticity maps of native membrane sheets, isolated from MDCK II (Madine Darby Canine kidney strain II) epithelial cells, were recorded by local indentation with an Atomic Force Microscope (AFM). To exclude the underlying substrate effect on membrane indentation, a highly ordered gold coated porous array with a pore diameter of 1.2 μm was used to support apical membranes. Overlays of fluorescence and AFM images show that intact apical membrane sheets are attached to poly-D-lysine coated porous substrate. Force indentation measurements reveal an extremely soft elastic membrane response if it is indented at the center of the pore in comparison to a hard repulsion on the adjacent rim used to define the exact contact point. A linear dependency of force versus indentation (-dF/dh) up to 100 nm penetration depth enabled us to define an apparent membrane spring constant (kapp) as the slope of a linear fit with a stiffness value of for native apical membrane in PBS. A correlation between fluorescence intensity and kapp is also reported. Time dependent hysteresis observed with native membranes is explained by a viscoelastic solid model of a spring connected to a Kelvin-Voight solid with a time constant of 0.04 s. No hysteresis was reported with chemically fixated membranes. A combined linear and non linear elastic response is suggested to relate the experimental data of force indentation curves to the elastic modulus and the membrane thickness. Membrane bending is the dominant contributor to linear elastic indentation at low loads, whereas stretching is the dominant contributor for non linear elastic response at higher loads. The membrane elastic response was controlled either by stiffening with chemical fixatives or by softening with F-actin disrupters. Overall, the presented setup is ideally suitable to study the interactions of the apical membrane with the underlying cytoskeleton by means of force indentation elasticity maps combined with fluorescence imaging.

Studio di caratteri correlati a stress idrico in una collezione di cultivar di frumento duro (Triticum durum Desf.)

L’agricoltura si trova ad affrontare una diminuzione della disponibilità d’acqua ed una crescente domanda della produzione di cereali per scopi alimentari. Sono perciò necessarie strategie di coltivazione innovative per migliorare la produttività e nuovi genotipi migliorati nell'efficienza dell’uso delle risorse in condizioni di siccità. Questi rappresentano gli obietti principali del progetto “DROPS” (Drought tolerant yielding Plants) all’interno del quale ha avuto luogo il mio progetto di Dottorato. La mia attività di ricerca è stata svolta come segue: 1. Caratterizzazione molecolare di un panel di188 accessioni di frumento duro con marcatori SSR e DaRT; 2. Esperimenti in serra su 100 accessioni del panel per valutare la Water-Use Efficiency (WUE) in sei repliche secondo un Alpha Lattice design; 3. Prove sul campo, effettuate secondo un Alpha Lattice design, in due stagioni di crescita: a. 2010/11, valutazione di 100 accessioni presso l’Azienda sperimentale dell'Università di Cadriano (BO); b. 2011/12, valutazione del panel completo in 3 ambienti, con due diversi regimi irrigui In entrambi gli anni, abbiamo valutato caratteri agronomici correlati con il ciclo di sviluppo, la resa di granella e sue componenti, nonché diversi fattori ambientali e del suolo. Per quanto riguarda WUE, abbiamo trovato differenze altamente significative tra accessioni; inoltre, cinque accessioni hanno mostrato elevati valori di WUE e cinque accessioni valori molto bassi di WUE in tutte e sei le repliche. Gli esperimenti di campo nelle stagioni 2011 e 2012 hanno evidenziato differenze altamente significative tra le accessioni del panel per la maggior parte dei caratteri analizzati, confermando inoltre che il panel di fiorisce entro una settimana. L'esperimento del secondo anno ci ha permesso osservare un significativa interazione Genotipo X Ambiente. Questi risultati saranno integrati con ulteriori analisi QTL, per identificare regioni cromosomiche coinvolte nel controllo genetico dei caratteri di interesse e verificare la stabilità dei QTL in diversi ambienti.