螺旋藻基因组结构分析和藻胆蛋白的适应性进化

螺旋藻 (Spirulina，或称节旋藻 Arthrospira) 是一类丝状不形成异型胞的蓝藻，常分布于湖泊、池塘和半咸水中。作为目前利用最广泛的经济微藻，螺旋藻的规模培养、生理生化以及分子遗传等都受到了广泛的关注。但由于缺乏足够的基因组信息，影响了螺旋藻的品种改良以及进一步的基因功能产品的开发。 本研究从挑取单藻丝开始，建立了钝顶螺旋藻 (Spirulina platensis) 的纯培养体系，并构建插入片段分别为1-2Kb和4-6Kb的基因组文库，利用鸟枪法进行全基因组测序，共得到具有8倍覆盖度的7.4Mb拼接后的基因组数据。在该草图中，预测有7795个开放读码框 (ORFs)，其中包括长度小于120个氨基酸的ORFs和非全长ORFs。在所有蛋白编码序列中，约有39%的基因是螺旋藻特有的，此外，还有389个基因相对于其他蓝藻，与非蓝藻基因有着更高的相似性。通过Pfam结构域聚类分析发现，螺旋藻含有特有的结构域，如Peptidase_MA、DMT、OB、ATP-grasp、Flavokinase 等。 由于目前尚未有成熟的螺旋藻遗传转化系统，而其体内复杂的限制性内切酶系可能是妨碍外源基因顺利导入和整合的关键因素。在此草图的基础上，我们利用比较基因组学和分子进化的手段，深入分析了螺旋藻及其他蓝藻的限制修饰系统 (Restriction-modification system)，为建立螺旋藻的遗传转化技术，并实现后续的螺旋藻基因功能验证模式奠定了基础。 螺旋藻及其他蓝藻的基因组计划提供了大量基因组序列和结构信息，有助于我们深入了解光合微生物基因的结构、功能和进化，以及环境因子或特定突变是如何塑造其基因组的。本文以藻胆蛋白为例，利用分子进化和群体遗传学理论，描绘出一幅藻胆蛋白进化的动态图景，并分析了环境 - 结构 - 功能之间的相互联系，为藻类捕光色素进化机制理论提供了科学依据。 本研究结果发现低光适应型原绿球藻和海洋聚球藻的藻红蛋白中正选择位点分布有着显著差异，提示二者的藻红蛋白基因有不同的进化模式；正选择作用位点多集中在藻胆蛋白的色基结合区域及XY发卡结构处，这些结构域主要与藻胆蛋白的光能捕获、能量传递和结构组装有关。该研究结果不仅揭示了正选择作用的重要性，而且提示光质、光强和能量传递压等可能是潜在的正选择压力。此外，又深入研究了高光和低光适应型两个生态群体的原绿球藻藻红蛋白基因系统发育、种内多态性和种间变异度，以此揭示环境因子对藻胆蛋白进化的影响。 本研究首次对螺旋藻全基因组进行测序，并以藻胆蛋白为例，从分子进化角度揭示其结构和功能的关系，并首次提出正选择压力可能是促使藻胆蛋白功能分化的主要原因，并认为原绿球藻中藻红蛋白的进化呈现出不同的模式，新的捕光色素的出现以及其所处的海洋环境可能使藻红蛋白获得了新的功能。

土壤中游离重金属离子的测定——唐南膜平衡法

对比了最近几十年来国内外土壤溶液中游离重金属离子浓度的测定方法,在此基础上建立了一种新的测量方法———唐南膜平衡法(DMT) 。研究表明,该实验方法可以在不影响反应体系平衡的基础上同时测定多金属元素,而且彼此之间不会发生干扰。

Multi-touch accceptance: perceived disorientation and consequences on task engagement

The research project takes place within the technology acceptability framework which tries to understand the use made of new technologies, and concentrates more specifically on the factors that influence multi-touch devices’ (MTD) acceptance and intention to use. Why be interested in MTD? Nowadays, this technology is used in all kinds of human activities, e.g. leisure, study or work activities (Rogowski and Saeed, 2012). However, the handling or the data entry by means of gestures on multi-touch-sensitive screen imposes a number of constraints and consequences which remain mostly unknown (Park and Han, 2013). Currently, few researches in ergonomic psychology wonder about the implications of these new human-computer interactions on task fulfillment.This research project aims to investigate the cognitive, sensori-motor and motivational processes taking place during the use of those devices. The project will analyze the influences of the use of gestures and the type of gesture used: simple or complex gestures (Lao, Heng, Zhang, Ling, and Wang, 2009), as well as the personal self-efficacy feeling in the use of MTD on task engagement, attention mechanisms and perceived disorientation (Chen, Linen, Yen, and Linn, 2011) when confronted to the use of MTD. For that purpose, the various above-mentioned concepts will be measured within a usability laboratory (U-Lab) with self-reported methods (questionnaires) and objective indicators (physiological indicators, eye tracking). Globally, the whole research aims to understand the processes at stakes, as well as advantages and inconveniences of this new technology, to favor a better compatibility and adequacy between gestures, executed tasks and MTD. The conclusions will allow some recommendations for the use of the DMT in specific contexts (e.g. learning context).

A mixed cost-function adaptive algorithm for ADSL time-domain equalization

We propose a mixed cost-function adaptive initialization algorithm for the time domain equalizer in a discrete multitone (DMT)-based asymmetric digital subscriber line. Using our approach, a higher convergence rate than that of the commonly used least-mean square algorithm is obtained, whilst attaining bit rates close to the optimum maximum shortening SNR and the upper bound SNR. Furthermore, our proposed method outperforms the minimum mean-squared error design for a range of time domain equalizer (TEQ) filter lengths. The improved performance outweighs the small increase in computational complexity required. A block variant of our proposed algorithm is also presented to overcome the increased latency imposed on the feedback path of the adaptive system.

Dual-Hop Cognitive Amplify-and-Forward Relaying Networks over η− μ Fading Channels

This paper presents a thorough performance analysis of dual-hop cognitive amplify-and-forward (AF) relaying networks under spectrum-sharing mechanism over independent non-identically distributed (i.n.i.d.) 􀀀 fading channels. In order to guarantee the quality-of-service (QoS) of primary networks, both maximum tolerable peak interference power Q at the primary users (PUs) and maximum allowable transmit power P at secondary users (SUs) are considered to constrain transmit power at the cognitive transmitters. For integer-valued fading parameters, a closed-form lower bound for the outage probability (OP) of the considered networks is obtained. Moreover, assuming arbitrary-valued fading parameters, the lower bound in integral form for the OP is derived. In order to obtain further insights on the OP performance, asymptotic expressions for the OP at high SNRs are derived, from which the diversity/coding gains and the diversity-multiplexing gain tradeoff (DMT) of the secondary network can be readily deduced. It is shown that the diversity gain and also the DMT are solely determined by the fading parameters of the secondary network whereas the primary network only affects the coding gain. The derived results include several others available in previously published works as special cases, such as those for Nakagami-m fading channels. In addition, performance evaluation results have been obtained by Monte Carlo computer simulations which have verified the accuracy of the theoretical analysis.

A hybrid mixed cost-function TEQ initialization algorithm for ADSL modems

In this paper, we present a hybrid mixed cost-function adaptive initialization algorithm for the time domain equalizer in a discrete multitone (DMT)-based asymmetric digital subscriber loop. Using our approach, a higher convergence rate than that of the commonly used least-mean square algorithm is obtained, whilst attaining bit rates close to the optimum maximum shortening SNR and the upper bound SNR. Moreover, our proposed method outperforms the minimum mean-squared error design for a range of TEQ filter lengths.

Avaliação e correlação de parâmetros físicos e mecânicos de um solo residual granítico

Os solos residuais mostram divergências em relação aos solos transportados modelados pelas teorias da Mecânica dos Solos. Estas divergências são em grande parte devido a uma estrutura de cimentação herdada da rocha mãe. Este estudo foi baseado nos resultados obtidos em sondagens mecânicas e ensaios de penetração dinâmica, estática e laboratoriais e consistiu na avaliação e correlação dos parâmetros que determinam o comportamento geomecânico do terreno, como a resistência e a deformabilidade.

Conception and first results of a cross-sectional national study on the demography, disease characteristics and socioeconomics status of the Portuguese patients with multiple sclerosis : the PORT-MS study

RESUMO: Introdução e objetivos: Não existia um estudo multicêntrico que descrevesse as características dos doentes com EM, da doença em si, ou do seu tratamento, em Portugal.Métodos: Doentes McDonald 2010 positivos foram sequencialmente recrutados em 7 centros entre Maio e Novembro 2014. Aplicou-se um Caderno de Recolha de Dados incidindo na demografia, doença, educação e emprego (estudo PORT-MS). Resultados: 561 doentes incluídos. Primeiros sintomas aos 30,2±10,5 anos (RRMS 29,2±10, PPMS 39,4±11,7, p<0,001); diagnóstico 3,2±5,3 anos depois (RRMS 3,0±5,1, PPMS 4,9±2,5, p=0,002); tempo de doença após diagnóstico 9,4±7,2 anos (semelhante RRMS no diagnóstico e PPMS); idade atual 42,9±12,4 anos (grupo RRMS no diagnóstico 42,0±12,1, PPMS 52,5±11,3, p<0,001); EDSS atual 2,5 (RRMS 2.0, PPMS 6.0); proporção feminino:masculino é 2,5:1 (RRMS semelhante, PPMS 1,1:1, p<0,05); no diagnóstico RRMS 90,6%, SPMS 0,9%, PPMS 8,6%; 9,5% dos RRMS encontravam-se em SP na inclusão (nomeadamente os com mais idade no diagnóstico e/ou atualidade ou tempo de doença mais prolongado). PPMS mais frequente em doentes diagnosticados mais tardiamente (p<0,001), onde aumenta também ligeiramente a proporção de mulheres na PPMS. Nas últimas décadas: novos casos mostram estabilidade na proporção de géneros e tipos de doença; idade nos primeiros sintomas e no diagnóstico aumentou ligeiramente, tempo entre eles diminuiu ligeiramente. Proporção sob DMT (Maio 2014): global 84,5%; atualmente RRMS 90,4%; SPMS 70,8%; PPMS 36,8%; progressivas agregadas 48%. Tipo de DMT, amostra global: interferões 56,5%, GA 18,4%, Natalizumab 11,6%, Fingolimod 9,7%. Global: economicamente ativos 61,5%, desemprego 13,5%, 74,1% dos não activos estão reformados por doença. Gravidezes após diagnóstico em 15% mulheres. Casos com história familiar positiva 7,8%. Discussão e conclusões: Incluída cerca de 10% da população portuguesa. Resultados congruentes com dados internacionais. Elevada proporção sob DMT, mesmo EDSS alto e formas progressivas. Terapêuticas de segunda linha sub representadas. Doentes jovens e com doença ligeira com vida económica ativa; restantes essencialmente reformados por doença.---------------- ABSTRACT : Background/aims: In Portugal, there wasn’t a multicentric study on the general characteristics (demography, disease milestones, DMT, socioeconomic status) of Multiple Sclerosis patients. Methods: Patients fulfilling McDonald 2010 criteria were sequentially recruited from May to November 2014 in 7 centers and data was systematically collected. Results: 561 patients included. First symptoms occurred at 30,2±10,5 years-old (RRMS 29,2±10, PPMS 39,4±11,7, p<0,001); diagnosis 3,2±5,3 years later (RRMS 3,0±5,1, PPMS 4,9±2,5, p=0,002); 9,4±7,2 years elapsed since diagnosis (similar for those is RRMS at diagnosis and PPMS); current age 42,9±12,4 years-old (group RRMS at diagnosis 42,0±12,1, PPMS 52,5±11,3, p<0,001); current EDSS 2,5 (RRMS 2.0, PPMS 6.0); females to males 2,5:1 (RRMS similar, PPMS 1,1:1, p<0,05); at diagnosis RRMS 90,6%, SPMS 0,9%, PPMS 8,6%; 9,5% of RRMS reached SP at inclusion (those older at diagnosis, in actuality, or with longer follow-up). PPMS more frequente in patients diagnosed at older ages (p<0,001), also slight increase in females. Along the last decades: new cases have showed stable proportions of gender and disease types; age at first symptoms and diagnosis slightly increased, time between them slightly decreased. Proportion on DMT (May 2014): 84,5% of all; 90,4% of currently in RRMS; 70,8% of SPMS; 36,8% of PPMS; 48% of progressive forms together. Type of DMT, all patients: interferons 56,5%, Glatiramer Acetate 18,4%, Natalizumab 11,6%, Fingolimod 9,7%. Economically active 61,5% of all, unemployment 13,5%, 74,1% of non-active are retired due to disease. Females pregnant after diagnosis 15%. Positive family cases in 7,8%. Discussion/Conclusions: 10% of the national MS population collected. Data generally consistente with international reports. Proportion under DMT relatively high in all disease types, but second line therapies underrepresented. Young patients with mild disease have an active economic life. Those not active are essentially retired due to disease.

SYNTHESIS OF CYCLIC AZOBENZENE ANALOGUES FOR INCORPORATION INTO OLIGONUCLEOTIDES, PEPTIDES AND POLYMERS

(A) In recent years, considerable amount of effort has contributed towards enhancing our understanding of the new photoswitch, cyclic azobenzene, particularly from the theoretical point of view. However, the challenging part with this system was poor efficiency of its synthesis from 2,2’- dinitrodibenzyl and lack of effective methods for further modification which would be useful to incorporate this system into biomolecules as a photoswitch. We report the synthesis of cyclic azobenzene and analogues from 2,2’-dinitrodibenzyl, which would allow for further incorporation of this cyclic azobenzene into biomolecules. Reaction of 2,2’-dinitrodibenzyl with zinc metal powder in the presence of triethylammonium formate buffer (pH-9.5) gave a cyclic azoxybenzene, 11,12-dihydrodibenzo[c,g][1,2]diazocine-5-oxide. The latter compound was converted into cyclic azobenzene analogues (bromo-, chloro-, cyano-, and carboxyl) through subsequent transformations. The carboxylic acid analogue was reacted with D-threoninol to give the corresponding amide, which readily undergoes photo-isomerization upon illumination with light. Upon illumination with light at 400 nm, approximately 70% of cis- isomer of amide was isomerized to trans- isomer. It was observed that cis- to trans- isomerization reached the maximum steady state of light transmission after approximately 40 min, whereas the trans- to cis- isomerization approximately acquired in 2 h to regain full recovery of light transmission. Cyclic azobenzene phosphoramidite was synthesized from DMT-protected D-threoninol linked cyclic azobenzene. (B) In recent years, there has been considerable interest invested towards the synthesis of azobenzene analogues for incorporation into proteins. Among the many azobenzene analogues, the synthesis of bi-functional cyclic azobenzene analogues for the incorporation into proteins is relatively new. In this thesis, we report the synthesis of a cyclic azobenzene biscarboxylic acid from 4-(bromomethyl)benzonitrile. (C) Azobenzene has been widely used in the field of polymer science to study the surface morphology and surface properties of polymers. In this thesis, we report the incorporation of cyclic azobenzene into a commercial polymer 2- (hydroxyethyl)methacrylate. Samples collected after 24 h from the reaction solution showed approximately 9% of incorporation of cyclic azobenzene into polymer compared to samples collected after 10 h, which showed approximately 6% incorporation.

(A) Photoregulation of DNA Functions by Cyclic Azobenzene-tethered Oligonucleotides (B) Site-specific Fluorescent Labeling of DNA using Inverse Electron Demand Diels-Alder Reaction between trans-Cyclooctene Derivatives and BODIPY-Tetrazine Adducts

(A) Most azobenzene-based photoswitches require UV light for photoisomerization, which limit their applications in biological systems due to possible photodamage. Cyclic azobenzene derivatives, on the other hand, can undergo cis-trans isomerization when exposed to visible light. A shortened synthetic scheme was developed for the preparation of a building block containing cyclic azobenzene and D-threoninol (cAB-Thr). trans-Cyclic azobenzene was found to thermally isomerize back to the cis-form in a temperature-dependent manner. cAB-Thr was transformed into the corresponding phosphoramidite and subsequently incorporated into oligonucleotides by solid phase synthesis. Melting temperature measurement suggested that incorporation of cis-cAB into oligonucleotides destabilizes DNA duplexes, these findings corroborate with circular dichroism measurement. Finally, Fluorescent Energy Resonance Transfer experiments indicated that trans-cAB can be accommodated in DNA duplexes. (B) Inverse Electron Demand Diels-Alder reactions (IEDDA) between trans-olefins and tetrazines provide a powerful alternative to existing ligation chemistries due to its fast reaction rate, bioorthogonality and mutual orthogonality with other click reactions. In this project, an attempt was pursued to synthesize trans-cyclooctene building blocks for oligonucleotide labeling by reacting with BODIPY-tetrazine. Rel-(1R-4E-pR)-cyclooct-4-enol and rel-(1R,8S,9S,4E)-Bicyclo[6.1.0]non-4-ene-9-ylmethanol were synthesized and then transformed into the corresponding propargyl ether. Subsequent Sonogashira reactions between these propargylated compounds with DMT-protected 5-iododeoxyuridine failed to give the desired products. Finally a methodology was pursued for the synthesis of BODIPY-tetrazine conjugates that will be used in future IEDDA reactions with trans-cyclooctene modified oligonucleotides.

Ethnographie de l'usage rituel d'ayahuasca au Québec

L’ayahuasca est une décoction de plantes originaires de la forêt amazonienne. Elle contient la vigne nommée ayahuasca (Banistereopsis caapi) et un arbuste (Psychotria viridis). Ces plantes contiennent des substances psychoactives. Respectivement il s’agit de l’harmine et de la diméthyle-tryptamine (DMT). Ce mélange est utilisé par plusieurs peuples autochtones du bassin amazonien depuis une époque qui précède la Conquête. L’ayahuasca est utilisée par ces peuples à des fins chamaniques. Au début du 20e siècle, la demande en caoutchouc a engendrée une migration de travailleurs dans ces régions. Un de ces travailleurs d’origine africaine est entré en contact avec cette substance. De croyance chrétienne, il a interprété son expérience comme une rencontre avec le divin. Ceci l’a amené à fonder dans les années 30 une église syncrétique nommée Santo Daime. Depuis, l’utilisation rituelle d’ayahuasca est répandue dans le monde. Aujourd’hui, On retrouve au Québec des groupes faisant un usage rituel d’ayahuasca. Ce mémoire est une ethnographie d’un groupe actif au Québec. Ce groupe a fait l’objet d’observations participantes durant l’été 2010. L’étude a démontré que la participation aux cérémonies d’ayahuasca engendre des prises de conscience et le travail de groupe en permet l’intégration dans le quotidien des participants. De plus, la structure rituelle garanti un usage non abusif.

Analisis de un tratamiento individual de danza movimiento terapia en un caso crónico de esquizofrenia residual

En el siguiente estudio presento1 el análisis retrospectivo de un tratamiento individual de 17 sesiones de danza movimiento terapia en un caso crónico de una mujer de 59 años, institucionalizada, con un diagnóstico de esquizofrenia residual. Mi objetivo es evaluar la evolución y conclusión del tratamiento, con el fin de encontrar puntualizaciones de interés en la técnica de la DMT para pacientes con diagnósticos de psicosis y seguir construyendo y fortaleciendo la teoría y técnica de la DMT en esta población. Mis influencias teórico-técnicas provienen principalmente de los modelos de trabajo con pacientes psiquiátricos de Chaiklin y Schmais, S. (1979), Chaiklin, S. (1981), Jones (1992) y Liebowitz (1992). Utilicé las técnicas de la improvisación, el reflejo empático (Sandel, S. 1995), la verbalización (Stark & Lohn, 1995), la imagen, la metáfora y el símbolo (Sandel, S. 1995) y las enseñanzas del sistema de análisis del movimiento de Kestenberg (1999). Las aportaciones sobre creatividad de Brainsky (1988) y Pinchas Noy (1968-1969) me fueron de gran ayuda. Para el análisis triangulo información de varias fuentes: diarios de campo realizados durante el tratamiento junto con sus señalamientos producto de supervisiones y tutorías, la entrevista inicial y final a la paciente y un video analizado con la paciente y posteriormente estudiado bajo la óptica del sistema de análisis del movimiento de Kestenberg (Kestenberg y otros, 1999). Vivencio a través de mi paciente la utilidad y éxito de la DMT en la psicosis y las técnicas que nos permiten acercarnos a esta población. La DMT trabaja la estructura, no exclusivamente el fenómeno psicótico; aunque no se transforme la personalidad se fortalece, permitiéndole al sujeto vivir mejor en su condición, ser más autónomo, eficaz, feliz y móvil. La condición perse del proceso terapéutico con un psicótico es establecer una relación terapéutica para la cual es necesario entender en el cuerpo y en la mente que el funcionamiento de un psicótico no es el mismo que el de un neurótico; la barrera neurótica del terapeuta ha de sobrepasarse para lograr la fusión simbiótica que permitirá el bottom-up del psicótico. Los objetivos de trabajo en el caso individual son: integrar y desarrollar la unidad psiquesoma, contactar y expresar emociones, desarrollar las habilidades interpersonales y sociales, expandir el universo simbólico y desarrollar el movimiento espontáneo y la creatividad. Las fases del tratamiento son: los acercamientos y observaciones preliminares; la exploración del cuerpo, identificación de los focos de trabajo y comienzo de la ampliación del movimiento; la profundización y nacimiento del símbolo en la terapia y la consolidación de los avances y cierre del tratamiento. La técnica principal, es el reflejo empático del movimiento y la emoción en la improvisación y otras útiles, el masaje, automasaje, relajación, el dibujo, entre otras.

Gesti?? de la competici?? durant el triatl?? de dist??ncia ol??mpica : an??lisi dels resultats de les temporades 1998, 1999 i 2000

Se muestran tablas y gr??ficas de resultado. Resumen tomado del autor

Estudo de fase I e farmacocinética com etoposide oral em crianças e adolescentes com tumores sólidos refratários

Introdução. Embora muitas crianças com câncer possam ser curadas, um número significativo têm resposta insatisfatória por ineficácia da terapêutica tornando necessário identificar agentes anticâncer mais efetivos contra tumores refratários ou recaídos. Estudos com Etoposide revelaram uma clara relação entre o tempo de exposição e os seus efeitos citotóxicos, mostrando resultados superiores com o uso de doses fracionadas quando comparado ao uso de uma dose única. Estudos de farmacocinética sugerem que as concentrações plasmáticas ativas de Etoposide se situa entre 1 e 5 μg/ml e que níveis acima de 5 μg/ml determinam uma mielotoxicidade importante. O Etoposide apresenta um bom espectro antitumoral mesmo em pacientes que já foram tratados por via parenteral e uma adequada biodisponibilidade pela via oral, podendo ser administrado com segurança em regime ambulatorial. Portanto, torna-se atraente a busca de esquemas de administração deste agente, os quais produzem níveis de concentração plasmática seguras pelo maior tempo possível. Objetivos. Os objetivos deste estudo de fase I é avaliar o perfil de toxicidade, a toxicidade dose-limitante, a dose máxima tolerada, a farmacocinética plasmática e a dose segura do Etoposide oral recomendada para estudos de fase II em pacientes pediátricos portadores de tumor sólido refratário. Materiais e Métodos. Todos os pacientes eram portadores de tumor sólido não responsivo aos tratamentos estabelecidos. A dose inicial do Etoposide foi de 20mg/m2/dose, a cada 8 horas durante 14 dias seguido de um intervalo de 7 dias antes de iniciar o próximo ciclo. A farmacocinética plasmática do Etoposide foi estudada durante o primeiro dia de tratamento e os níveis de Etoposide determinados pelo método de HPLC. Resultados. Dezessete pacientes foram incluídos no estudo, sendo que em 13 foram realizados o estudo de farmacocinética. O número total de cursos de quimioterapia foi de 64. Nove pacientes foram incluídos no Nível de dose I, sendo que leucopenia grau 2-3 foi observada em 5. A dose foi então escalonada para 25 mg/m2 (Nível de dose II) e fornecida a 8 pacientes subsequentes o que determinou leucopenia grau 3-4 em 4 deles. Este Nível de dose foi então considerado como DMT (Dose Máxima Tolerada). A TDL foi neutropenia. As concentrações plasmáticas máximas de Etoposide nos pacientes incluídos no Nível de dose I e II foram de 2,97 e 8,59 μg/ml, respectivamente, e os níveis da droga >1 μg/ml foi mantido durante cerca de 6,3 horas após a administração da droga em ambos os níveis de dose. Resposta parcial foi observada em 1 paciente e 4 apresentaram doença estável. Conclusões. A administração prolongada de Etoposide oral nas doses de 20 mg/m2 a cada 8 horas durante 14 dias consecutivos, seguidos de 7 dias de repouso, foi bem tolerada e determinou uma toxicidade manejável em crianças e adolescentes portadores de doenças malignas refratárias. A dose de 20 mg/m2 aparentemente preencheu os requisitos farmacocinéticos que objetivam melhorar o índice terapêutico do Etoposide, ou seja, a obtenção de níveis plasmáticos citotóxicos sustentados e abaixo do limite de toxicidade clínica da droga.

Alterações da default mode network provocadas pela ingestão de Ayahuasca investigadas por Ressonância Magnética Funcional

Ayahuasca is psychotropic beverage that has been used for ages by indigenous populations in South America, notably in the Amazon region, for religious and medicinal purposes. The tea is obtained by the decoction of leaves from the Psychotria viridis with the bark and stalk of a shrub, the Banisteriopsis caapi. The first is rich in N-N-dimethyltryptamine (DMT), which has an important and well-known hallucinogenic effect due to its agonistic action in serotonin receptors, specifically 5-HT2A. On the other hand, β-carbolines present in B. caapi, particularly harmine and harmaline, are potent monoamine oxidase inhibitors (MAOi). In addition, the tetrahydroharmine (THH), also present in B. caapi, acts as mild selective serotonin reuptake inhibitor and a weak MAOi. This unique composition induces a number of affective, sensitive, perceptual and cognitive changes in individuals under the effect of Ayahuasca. On the other hand, there is growing interest in the Default Mode Network (DMN), which has been consistently observed in functional neuroimaging studies. The key components of this network include structures in the brain midline, as the anterior medial frontal cortex, ventral medial frontal cortex, posterior cingulate cortex, precuneus, and some regions within the inferior parietal lobe and middle temporal gyrus. It has been argued that DMN participate in tasks involving self-judgments, autobiographical memory retrieval, mental simulations, thinking in perspective, meditative states, and others. In general, these tasks require an internal focus of attention, hence the conclusion that the DMN is associated with introspective mental activity. Therefore, this study aimed to evaluate by functional magnetic resonance imaging (fMRI) changes in DMN caused via the ingestion of Ayahuasca by 10 healthy subjects while submitted to two fMRI protocols: a verbal fluency task and a resting state acquisition. In general, it was observed that Ayahuasca causes a reduction in the fMRI signal in central nodes of DMN, such as the anterior cingulate cortex, the medial prefrontal cortex, the posterior cingulate cortex, precuneus and inferior parietal lobe. Furthermore, changes in connectivity patterns of the DMN were observed, especially a decrease in the functional connectivity of the precuneus. Together, these findings indicate an association between the altered state of consciousness experienced by individuals under the effect of Ayahuasca, and changes in the stream of spontaneous thoughts leading to an increased introspective mental activity