738 research outputs found

    Paisajes distópicos en la trilogía Bruna Husky de Rosa Montero

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    Nei romanzi della detective Bruna Husky, Rosa Montero si avvale di un paesaggio urbano degradato, inspirato al noto film Blade Runner. La coesistenza di elementi attuali e futuristici, permettono all’autrice di proiettare le preoccupazioni del suo presente in un Madrid distopico, a partire dal ricorso a elementi sia del romanzo poliziesco che della fantascienza.In the novels of the detective Bruna Husky, Rosa Montero uses a degraded urban landscape, inspired by the well-known film Blade Runner. The coexistence of current and futuristic elements allows the author to project the concerns of her present into a dystopian Madrid, starting from the use of elements of both hard-boiled and science fiction

    Bruna.Mundim.ASN.2015

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    <p>R Code to map data on author home country presented in Bruna and Mundim's 2015 talk at the ASN/SSB/SSE meeting in Guaruja, Brazil</p

    In vitro functional characterization of PCSK9 variants identified in patients with Familial Hypercholesterolemia

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    A Hipercolesterolemia Familial (HF) é uma doença genética do metabolismo das lipoproteínas, caracterizada pelo aumento do colesterol plasmático, transportado principalmente pela lipoproteína de baixa densidade (LDL). A HF é causada principalmente por mutações nos genes LDLR, APOB e PCSK9. As mutações conhecidas na PCSK9 podem levar ao aumento ou diminuição da função proteolítica da proteína, as quais são associadas ao aumento ou diminuição da LDL-c plasmática, respectivamente. Com o projeto genoma humano surgiram novos métodos de sequenciamento, o que resultou em um grande número de novas variantes genéticas relacionadas à HF. Entretanto, os mecanismos pelos quais essas variantes influenciam na concentração do colesterol e sua interferência na resposta terapêutica não estão totalmente elucidados. O objetivo do presente trabalho foi avaliar in vitro o efeito de variantes na região codificadora e reguladora do gene PCSK9 identificadas em pacientes HF utilizando sequenciamento de nova geração. Para a caracterização funcional das variantes na região codificadora da PCSK9, primeiramente foi avaliado o impacto dessas variantes na interação PCSK9-LDLR via Docking molecular. Células HEK293FT foram transfectadas com as diferentes construções da PCSK9, e posteriormente, foram utilizadas em ensaios para avaliar a atividade do LDLR e a internalização de LDL por citometria de fluxo. Para as variantes na região reguladora da PCSK9, foi realizado uma predição in silico do possível efeito de variantes na região 3UTR na ligação de miRNAs. A avalição da interação entre os miRNAs preditos, e a região 3UTR da PCSK9, e o possível impacto nessa interação na presença de variantes na região 3UTR, foi realizada em células HEK293FT transfectadas com um plasmídeo contendo a 3UTR da PCSK9 e um gene repórter da Gaussia luciferase, juntamente com um plasmídeo de expressão contendo os miRNAs de interesse. Foi também estudado o efeito dos miRNAs preditos sobre a expressão, RNAm e proteína, da PCSK9 via RT-qPCR e Western blot, em células HepG2. Foram identificadas 9 variantes na região codificadora da PCSK9, e duas, E32K e R469W, foram selecionadas para os ensaios posteriores. Para a R469W foi observada uma possível alteração conformacional a qual poderia aumentar a afinidade da PCSK9 pelo LDLR. Para a E32K, uma possível associação com HF foi observada em uma família brasileira com ascendência japonesa. As variantes E32K e R469W apresentaram uma redução na atividade do LDLR de 5 e 11%, respectivamente em comparação a PCSK9-WT. Entretanto, não foram observadas reduções estaticamente significativas na atividade do LDLR e na internalização da LDL em células transfectadas com ambas as variantes. Dez variantes foram encontradas na região 3UTR da PCSK9, entre elas três foram selecionadas por impactar a ligação de quatro miRNAs. Nossos dados demonstraram uma redução significativa na expressão da PCSK9 em células HepG2 transfectadas com os miR-4721 e miR-564 (p=0,036 e p=0,010, respectivamente). Porém, não foi observada diferenças na expressão da luciferase em células transfectadas com esses miRNAs, não sendo possível validar a interação miRNA-RNAm. As variantes no gene PCSK9 identificadas no nosso estudo podem não explicar individualmente o fenótipo HF, mas podem contribuir para a severidade da doença juntamente com outras variantes em outros genes.Familial Hypercholesterolemia (FH) is a genetic disorder of lipoprotein metabolism, characterized by elevated plasma cholesterol levels, mostly carried by low-density lipoprotein (LDL). FH is mainly caused by mutations in three genes, LDLR, APOB, and PCSK9. Gain-of-function mutations in PCSK9 reduce LDL receptor levels, resulting in high levels of LDL cholesterol in the plasma. Loss-of-function mutations lead to higher levels of the LDL receptor, resulting in lower LDL cholesterol levels. The Human Genome Project led to a faster technological development related to sequencing methods, which allowed identifying many novel variants associated with FH. However, the mechanisms by which these variants influence cholesterol levels and their interference in therapeutic response are not fully understood. The aim of the present study was to perform an in vitro characterization of the effect of PCSK9 variants identified in FH patients using Next-Generation Sequencing. For the functional characterization of variants in the coding region of PCSK9, the impact of these variants on PCSK9-LDLR interaction was evaluated by molecular docking. HEK293FT cells were transiently transfected with different PCSK9 constructs, and the amount of cell surface LDLR and LDL internalization were determined by flow cytometry. For the variants in PCSK9 3UTR region, an in silico prediction of PCSK9 3UTR variants in miRNA seed regions and target sites was performed. To determine whether the predicted miRNAs directly interact with PCSK9 3UTR region, HEK293FT cells were co-transfected with a vector containing a PCSK9 3\'UTR region and a Gaussia luciferase reporter gene, together with an expression plasmid containing the miRNAs of interest. The effect of the predicted miRNAs on the expression of PCSK9 was evaluated using RT-qPCR and Western blot in HepG2 cells transiently transfected with miRNA mimics. Nine missense variants were identified in PCSK9 gene. E32K e R469W were chosen for further analysis. For R469W, a possible conformational change was observed that could increase the affinity of PCSK9 for LDLR, when compared to the wild-type. For E32K, a possible association with FH in a Brazilian family with Japanese ancestry was observed. E32K and R469W had a 5% and 11% decreased level of cell surface LDLR, respectively, as compared with WT-PCSK9. However, no significant reduction in the number of cell surface LDLR and LDL internalization was observed in transfected cells for both variants. Ten variants were found in PCSK9 3\'UTR region, of which three were selected for affecting the binding of four miRNAs. Our data demonstrated a significant downregulation of PCSK9 in cells transfected with miR-4721 and miR-564 miRNA mimics, compared to cells transfected with a scramble control (p=0,036 and p=0,010, respectively). However, no differences in luciferase expression were observed in cells transfected with these miRNAs, therefore, it was not possible to experimentally validate miRNA-mRNA interaction. PCSK9 variants found in our study may not fully explain FH phenotype but may contribute to the severity of the disease together with other variants in other genes

    Un dépotoir du bas Moyen Âge dans le quartier Saint-Jean à Lyon

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    Bruna Maccari-Poisson, Ein Schuttabladeplatz des Spätmittelalters im Stadtviertel Saint-Jean in Lyon. Der Verfasser untersucht Keramikscherben, die sich in einem ehemaligen Brunnen fanden, der gegen Ende des Mittelalters zugeschiittet und als Schuttabladeplatz verwendet wurde ; acht stratigraphische Einheiten konnten ermittelt werden. Der Autor schlägt unter Anwendung von typologischen Kriterien vor, einerseits das XV. Jh., andererseits das beginnende XVI. Jh. als Entstehungszeit dieser Keramikscherben zu bestimmen. Eine zusammenfassende Übersicht der Formen läßt ihre Entwicklung während der Auffüllphasen erkennen.Bruna Maccari-Poisson : A rubbish pit from the Late Middle Ages in the Saint-Jean quarter of Lyon. The author examines pottery found in an ancient well, filled in towards the end of the Middle Ages and then converted into a rubbish pit, in which eight stratigraphie units have been identified. Using typological criteria, the author proposes to date some of the pottery to the fifteenth century, and the rest to the early sixteenth century. A table recapitulating their forms, makes their evolution through the in filling of the pit very clear.L'auteur étudie un lot de céramiques trouvées dans un ancien puits comblé vers la fin du Moyen Age et converti en dépotoir, dans lequel huit unités stratigraphiques ont été reconnues. L'auteur, utilisant des critères typologiques, propose de dater ces céramiques, d'une part du XVe siècle, d'autre part du début du XVIe. Un tableau récapitulatif des formes fait apparaître leur évolution au cours du remplissage du dépotoir.Maccari-Poisson Bruna. Un dépotoir du bas Moyen Âge dans le quartier Saint-Jean à Lyon. In: Archéologie médiévale, tome 18, 1988. pp. 215-237

    Leonardo Manrique Castañeda: una visión interdisciplinaria. 1 Año 1 (2014) enero-marzo. Rutas de Campo. Estudiosos de Guerrero: Semblanzas

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    Grosser Lerner, Eva y Benjamín Pérez González, “Leonardo Manrique Castañeda (entrevista)”, en Martha C. Muntzel y Bruna Radelli (coords.), Homenaje a Leonardo Manrique, México, INAH, 1993, pp. 9-45.Guzmán Betancourt, Ignacio, “Bibliografía de Leonardo Manrique Castañeda”, en Martha C. Muntzel y Bruna Radelli (coords.), Homenaje a Leonardo Manrique, México, INAH, 1993, pp. 141-152.Manrique Castañeda, Leonardo, “Historia de las lenguas indígenas de México”, en Beatriz Garza Cuarón y George Baudot, Historia de la literatura mexicana. Las literaturas amerindias de México y la literatura en español del siglo XVI, México, Siglo XXI, vol. 1, 1996, pp. 51-83.Manrique, Leonardo, “El panorama de los estudios lingüísticos de Guerrero”, en Gloria Artís, Miguel Ángel Rubio y Mette Marie Wacher, Guerrero: una mirada antropológica e histórica, México, INAH, 2007, pp. 493-498.Zúñiga, Rosa María, “Reconstrucciones lingüísticas efectuadas por Leonardo Manrique”, en Martha C. Muntzel y Bruna Radelli (coords.), Homenaje a Leonardo Manrique, México, INAH, 1993, pp. 135-140

    Electroendephalography data from study on neurorehabilitation after stroke

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    Electroencephalography data collected from a study investigating the neurophysiological aspects of a neurorehabilitation protocol combining neuromodulation with transcranial direct current stimulation (tDCS) and extreme reality for people with stroke. The generated data associated with the study are not publicly available due to ethical requirements, but are available from the corresponding author on reasonable request

    Geological and structural map of the southeastern Pag Island, Croatia: field constraints on the Cretaceous - Eocene evolution of the Dinarides foreland

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    The sedimentary succession exposed in the Northern Dalmatia Islands mainly consists of Cretaceous to Neogene shallow water carbonates, folded and imbricated within the External Dinarides thrust belt. During Cretaceous times, carbonate sediments were deposed on a heterogeneous, tectonically-influenced carbonate platform, which was then uplifted and eroded, as evidenced by a regional unconformity embracing the Late Cretaceous and Paleocene. Sedimentation resumed during the Eocene, when the area was part of the foreland basin of the Dinaric belt. With our geological and structural map of the southeastern Pag Island at the 1:25,000 scale, we refined the stratigraphic and structural setting and the tectono- sedimentary evolution of the area.Applied Geolog

    Pressure transient analysis to investigate a coupled fracture corridor and a fault damage zone causing an early thermal breakthrough in the North Alpine Foreland Basin

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    The heterogeneity of the Upper Jurassic carbonate reservoir (Malm reservoir) beneath the North Alpine Foreland Basin has a significant influence on the mass and heat flow processes during geothermal exploitation. Geophysical borehole data revealed that sub-seismic scale fractures and karstified fractures occur at the inflow zones of deep geothermal wells. However, pressure transient analysis (PTA) in some previous studies concluded that it is difficult to detect the influence of sub-seismic scale features, suggesting that radial flow regime is dominant. Accordingly, a regional thermal-hydraulic model adopted the equivalent porous medium (EPM) approach, homogenizing the sub-seismic scale reservoir heterogeneities; however, unable to detect an early thermal breakthrough (ETB) in a geothermal doublet located SE of Munich. We apply PTA on three buildup tests belonging to that doublet following a deterministic approach to constrain the reservoir type by interpreting the pressure derivative (PD) plots constrained by geophysical and geological data. We derive the magnitudes of the reservoir hydraulic parameters by matching the PD plots with the selected interpretation models. We find that clustered fractures have a significant influence on the reservoir hydraulics, evidenced by trough-shaped curves in the PD plots. Linear flow regime interpreted from the interference test between the two wells indicates permeability anisotropy, which may have caused the ETB. Geophysical data interpretations indicate that these fractures correspond to a coupled fault damage zone and a fracture corridor. Finally, we present a fit-for-purpose 2D discrete fracture network model utilizing the PTA results to match our analytically calibrated model. Our study offers a potential hydraulic explanation to the cause of the ETB highlighting the importance of integrating multi-scale/disciplinary data sets to improve the reliability of dynamic reservoir models, based on which, economic-related decisions are made.Applied Geolog

    Dermoscopy on black skin- a comparative study of melanocytic lesions and features of dermoscopic findings in individuals with skin type V and VI to those with skin type I and II

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    BLACKGROUND: The identification of "normal" dermoscopic pattern of acquired melanocytic nevi (AMN) provides a better diagnostic accuracy of melanoma in people with black skin. OBJECTIVE: Describe melanocytic lesions (number and anatomical distribution) in skin types V and VI (ST V/VI) compared to skin types I and II (ST I/II) according to Fitzpatrick's classification. Identify differences in dermoscopic findings of acquired melanocytic nevi (global pattern, pigment and color distribution) between the groups. METHODS: Cross-sectional, prospective and consecutive data collection in two dermatological outpatient clinic, between October 8, 2010, and March 20, 2013. From the 501 volunteers, 480 participants fullfilled the eligibility criteria. A total of 460 acquired melanocytic nevi were selected for dermoscopy analysis. RESULTS: The individuals with ST V/VI had less melanocytic lesions than those with ST I/II (15,08 vs 7,90, p=0,032), and the anatomical distribution in the first group was predominantly in the face and acral sites (p<0,001). The AMN in the group ST V/VI were associated with reticular pattern (p<0.0001), tendency to central hyperpigmentation (p=0.0025). LIMITATIONS: Choice of a single representative nevus per patient. CONCLUSION: The AMN in the individuals with ST V/VI has a distinct dermoscopic pattern from those with ST I/II.Objetivo: Descrever as lesões melanocíticas (número e distribuição por região anatômica) nos portadores de fototipos V e VI comparados aos fototipos I e II. Identificar as diferenças dos padrões dermatoscópicos dos nevos melanocíticos adquiridos entre os dois grupos (F V/ VI versus F I/ II). Método: Estudo transversal, realizada em duas instituições, a Universidade Federal de São Paulo e a Universidade Estadual de Londrina, com coleta consecutiva e prospectiva. Dos 501 voluntários, 480 preenchiam os critérios de inclusão. No total foram selecionados 460 nevos melanocíticos adquiridos para análise dermatoscópica. Resultados: Os portadores de fototipos V e VI apresentaram menor número de nevos comparados aos portadores de fototipos I e II (15,08 vs 7,90, p=0,032), essas lesões estavam distribuídas principalmente na face e região acral (p<0,001) enquanto os portadores de fototipos I e II apresentaram distribuição predominantemente em tronco. O grupo dos portadores dos fototipos I e II apresentou nevos com padrão reticular, de coloração marrom e distribuição uniforme com tendência à distribuição em múltiplos focos de hipo e hiperpigmentação. No grupo dos fototipos FV e VI, as características dermatoscópicas predominantes foram: padrão reticular (p<0,0001), distribuição uniforme com tendência à hiperpigmentação central (p=0,0025), de coloração marrom, com presença marcante das cores preta e cinza-azulado. Limitação: A escolha de um nevo representativo por paciente. Conclusão: Existem diferenças clínicas e dermatoscópicas na apresentação das lesões melanocíticas adquiridas nos pacientes com fototipos I e II e os com fototipos V e VI. As diferenças de distribuição por região anatômica são importante pois sinalizam a importância do exame da face, mãos e pés nos portadores de fototipos altos. A diferença dos achados dermatoscópicos entre os fototipos demonstra que os indíviduos portadores de fototipos V e VI apresentam particularidades no exame dermatoscópico, e o conhecimento do padrão de "normalidade" propiciará a identificação das lesões suspeitas de melanoma nessa população.Dados abertos - Sucupira - Teses e dissertações (2013 a 2016
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