Knowledge-Based Design of Long-Chain Arylpiperazine Derivatives Targeting Multiple Serotonin Receptors as Potential Candidates for Treatment of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) includes a group of neurodevelopmental disorders characterized by core symptoms such as impaired social interaction and communication, repetitive and stereotyped behaviors, and restricted interests. To date, there are no effective treatments for these core symptoms. Several studies have shown that the brain serotonin (5-HT) neurotransmission system is altered in both ASD patients and animal models of the disease. Multiple pieces of evidence suggest that targeting 5-HT receptors may treat the core symptoms of ASD and associated intellectual disabilities. In fact, stimulation of the 5-HT1A receptor reduces repetitive and restricted behaviors; blockade of the 5-HT2A receptor reduces both learning deficits and repetitive behavior, and activation of the 5-HT7 receptor improves cognitive performances and reduces repetitive behavior. On such a basis, we have designed novel arylpiperazine derivatives pursuing unprecedently reported activity profiles: dual 5-HT7/5-HT1A receptor agonist properties and mixed 5-HT7 agonist/5-HT1A agonist/5-HT2A antagonist properties. Seventeen new compounds were synthesized and tested in radioligand binding assay at the target receptors. We have identified the dual 5-HT1AR/5-HT7R agonists 8c and 29 and the mixed 5-HT1AR agonist/5-HT7R agonist/5-HT2AR antagonist 20b. These compounds are metabolically stable in vitro and have suitable central nervous system druglike properties

CYTOTOXICITY, ANTI-POLIOVIRUS ACTIVITY AND IN SILICO BIOLOGICAL EVALUATION OF CONSTITUENTS FROM MAYTENUS GONOCLADA (CELASTRACEAE)

Objective: The in silico free access web tools PASS online and ChemMapper were used to predict potential biological activities of compounds 1 to 8 isolated from Maytenus gonoclada (Celastraceae). The constituents 4'-O-methylepigalocatequin (6), tingenone (7) and proanthocyanidin A (8), and ethanolic extracts were subjected to in vitro cytotoxicity using VERO cells and anti-Poliovirus assays. Methods: QSAR and molecular superposition, correlating the average number of pharmacophores were used in the prediction studies. Cellular line VERO ATCC CCL-81 was used to determine anti-Poliovirus effect, observed by colorimetric (MTT) method. The annexing V/propidium iodide assay was used to determine the occurrence of apoptosis in the cytotoxicity assays. Results: The experimental results found for constituents 6-8 were in accordance with observed data obtained through PASS online and ChemMapper simulation. Conclusion: Compound 7 showed higher cytotoxic and apoptosis induction properties, and 6 and 8 presented anti-Poliovirus activity

Indicação de eucaliptos para plantios em faixas de quebra-ventos em propriedades rurais de Mato Grosso do Sul.

Segundo o IBGE (2005), o Estado de Mato Grosso do Sul possui uma área de 357.145,531 km2, composto por três biomas sendo que a área de Cerrado corresponde a 61%; o Pantanal a 25% e a Mata Atlântica 14%. A economia do estado se baseia predominantemente na pecuária em suas diversas formas. Na ocupação do território houve o uso generalizado da técnica do correntão, na qual são utilizados dois tratores em cada ponto extremo de uma corrente pesada e com seu arraste suprime a vegetação. Essa técnica é indicada para a formação de extensas áreas de pastagens cultivadas e agricultura. Atualmente essas áreas carecem de barreiras físicas para o vento quase que constante principalmente nos meses secos do ano.bitstream/item/206426/1/Indicacao-de-eucaliptos-para-plantios.pd

Elemental composition of algae-based supplements by energy dispersive X-ray fluorescence

The aim of this study is to evaluate the elemental composition of fifteen algae-based supplements commonly sold in the Portuguese market, by energy dispersive X-ray fluorescence. Despite the fact that the majority of Kelp samples were a good source of iodine, the levels observed might well contribute to an excess in the human body, which can cause dysfunction of the thyroid gland. Furthermore, the presence of lead in Sea spaghetti, Arame, Hijiki and Wakame caused a considerable risk to public health vis a vis possible ingestion of a high daily dose. Regarding arsenic, great variability was observed in all the samples with concentrations equal to or above 60 μg/g in the case of Arame, KelpJ and Hijiki. Although algae mainly accumulate organic arsenic, some also contain high levels of its inorganic form, as is commonly pointed out for Hijiki. Thus, regular ingestion of these supplements must also take into account the mentioned facts. There is no doubt that these supplements are also good sources of other nutrients, but the lack of accurate regulations and control should alert consumers to avoid indiscriminate use of these types of productsinfo:eu-repo/semantics/publishedVersio

Non-Anticoagulant Heparan Sulfate from the Ascidian Phallusia nigra Prevents Colon Carcinoma Metastasis in Mice by Disrupting Platelet-Tumor Cell Interaction

Although metastasis is the primary cause of death in patients with malignant solid tumors, efficient anti-metastatic therapies are not clinically available currently. Sulfated glycosaminoglycans from marine sources have shown promising pharmacological effects, acting on different steps of the metastatic process. Oversulfated dermatan sulfates from ascidians are effective in preventing metastasis by inhibition of P-selectin, a platelet surface protein involved in the platelet-tumor cell emboli formation. We report in this work that the heparan sulfate isolated from the viscera of the ascidian Phallusia nigra drastically attenuates metastases of colon carcinoma cells in mice. Our in vitro and in vivo assessments demonstrate that the P. nigra glycan has very low anticoagulant and antithrombotic activities and a reduced hypotension potential, although it efficiently prevented metastasis. Therefore, it may be a promising candidate for the development of a novel anti-metastatic drug

SEXUALITY AND GENDER DIFFERENCES AMONG UNIVERSITY YOUTHS

The purpose of the present study was to examine aspects related to the initiation of sexual activity among young people. Forty-two men and thirty-six women (M = 22 years old) answered a questionnaire. Main results showed that: a) the first sexual intercourse, in general, occurred earlier to men than to women; b) only 14.3 % of women assessed positively the experience in relation to orgasm during the first sexual intercourse, while among men this value wasconsiderably higher (about 85 %); c) the majority of women (63 %) reported to have had only one partner during their sexual life; 85 % of men reported to have had sexual involvement with two or more women until that moment. In conclusion, it appears that among the young people who participated in the research, there are gender differences in the perception they have of the role that their parents had throughout their childhood, the characteristics of the initiation of their sexual activity and other aspects of sexuality.O objetivo da presente pesquisa foi investigar aspectos relacionados com a ini-ciação sexual entre jovens. Foi aplicado um questionário a 42 homens e 36 mulheres com idade média de 22 anos. Os principais resultados foram: a) a iniciação sexual, em média, ocorreu mais cedo para os homens do que para as mulheres; b) apenas 14,3% da amostra feminina avaliou positivamente a experiência em relação ao orgasmo durante o pnmeiro ato sexual, enquanto no caso dos homens esse valor foi consideravelmente maior (em torno de 85%); c) a maioria das mulheres (63%) relatou ter apenas um parceiro durante a vida sexual; entre os homens, 85% afirmou ter envolvimento sexual com duas ou mais parceiras até hoje. Conclui-se que entre os jovens pesquisados parecem existir acentuadas diferenças de género desde a percepção que esses jovens tem a respeito do papel que os pais tiveram durante a infancia, até características da iniciação sexual e outras aspectos relacionados à sexualidade

Reduced graphene oxide multilayers for gas and liquid phases chemical sensing

Graphene oxide (GO) multilayers were produced by the layer-by-layer technique after successive immersions of quartz slides into aqueous suspensions of cationic poly(diallyldimethyl ammonium chloride) (PDAC) and anionic GO. The adsorbed amount of GO within the multilayers measured ex situ by UV-vis spectroscopy was found to increase linearly with the number of PDAC-GO bilayers. UV-vis and Raman spectra confirmed the conversion of GO to its reduced form, namely reduced graphene oxide (RGO), when the multilayers were subjected to hot hydrazine. According to AFM images, multilayers are flat with GO sheets forming edge structures. Additionally, impedance spectroscopy provided information regarding the multilayer growth mechanism, which starts with isolated GO sheets that bridge each other after deposition of five PDAC-GO bilayers. As a proof of principle, it was demonstrated that a sensor array composed by reduced multilayers deposited onto interdigitated microelectrodes and interrogated by impedance spectroscopy is capable of discriminating vapours of volatile solvents, including toluene, gasoline, ethanol, chloroform, and acetone, as well as chemicals in aqueous solutions, such as hydrochloric acid, sodium chloride, ammonium hydroxide, and sucrose. This capability was made possible only because the LbL assembly permitted one to tune the sensors' sensitivity with the number of PDAC-GO bilayers. The results presented herein suggest that the reduced PDAC-GO multilayers are promising elements for non-specific chemical sensors.CNPq (308038/2012-6)CAPE

A precise asteroseismic age and radius for the evolved Sun-like star KIC 11026764

The primary science goal of the Kepler Mission is to provide a census of exoplanets in the solar neighborhood, including the identification and characterization of habitable Earth-like planets. The asteroseismic capabilities of the mission are being used to determine precise radii and ages for the target stars from their solar-like oscillations. Chaplin et al. (2010) published observations of three bright G-type stars, which were monitored during the first 33.5 days of science operations. One of these stars, the subgiant KIC 11026764, exhibits a characteristic pattern of oscillation frequencies suggesting that it has evolved significantly. We have derived asteroseismic estimates of the properties of KIC 11026764 from Kepler photometry combined with ground-based spectroscopic data. We present the results of detailed modeling for this star, employing a variety of independent codes and analyses that attempt to match the asteroseismic and spectroscopic constraints simultaneously. We determine both the radius and the age of KIC 11026764 with a precision near 1%, and an accuracy near 2% for the radius and 15% for the age. Continued observations of this star promise to reveal additional oscillation frequencies that will further improve the determination of its fundamental properties.Comment: 16 pages, 6 figures, 4 tables, ApJ in pres

From traditionally extensive to sustainably intensive: a review on the path to a sustainable and inclusive beef farming in Brazil

Brazil is the second largest beef producer and a leading exporter, contributing to some 3000 t CWE in global markets (27.7% of market share). The sector has experienced substantial development, but yields remain far below potential, and there are growing concerns regarding land use change and greenhouse gas emissions. The need for sustainable technologies, such as sound pasture management and integrated farming systems, is evident, but adoption may be low amongst farmers unable to keep up with technological advances. This article describes the historical developments of Brazilian beef farming towards sustainability and discusses possible socioenvironmental outcomes. We combined an extensive literature review, public data, and our own insights as senior researchers to achieve that. The trajectory shown here evidenced the technological intensification of Brazilian beef farming, with strong support of public policies for decarbonizing agriculture. Nonetheless, the pace of this transition may affect small to medium farmers with limited access to information, technologies, and credit. Our recommendations involve a broad program of technical assistance and training on sustainable technologies, including financial and digital literacy. A novel approach to financing farmers is suggested to support a sustainable and inclusive transition in beef farming in Brazil