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A resistência microbiana é um problema de saúde pública, que vem crescendo mundialmente, podendo chegar a um total de 10 milhões em 2050, em decorrência de infecções causadas por microrganismos multirresistentes. Neste sentido a busca de novas alternativas no combate a essa resistência microbiana é dos problemas que necessitam de soluções urgente. Nesse contexto as tiossemicarbazonas se apresentam como fragmentos multifuncionais que podem conduzir a novas moléculas potencialmente bioativas como agentes antimicrobianos. Este trabalho apresenta uma mini revisão da literatura sobre a aplicação de moléculas tiossemicarbazonas como antimicrobianos.

This research was funded by Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq) (Grant Number: 455078/2014-9) and Evandro Chagas Institute. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Cultura de Tecidos e Citogen?tica. Ananindeua, PA, Brasil Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Cultura de Tecidos e Citogen?tica. Ananindeua, PA, Brasil Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laborat?rio de Citogen?tica Humana. Bel?m, PA, Brasil / Hospital Universit?rio Jo?o de Barros Barreto. N?cleo de Pesquisas em Oncologia. Bel?m, PA, Brasil / Hospital Ophir Loyola. Laborat?rio de Biologia Molecular. Bel?m, PA, Brasil. Universidade de Bras?lia. Instituto de Ci?ncias Biol?gicas. Departamento de Gen?tica e Morfologia. Bras?lia, DF, Brasil. A.C. Camargo Cancer Center. Centro Internacional de Pesquisa. S?o Paulo, SP, Brasil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Faculdade de Biomedicina. Bel?m, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Cultura de Tecidos e Citogen?tica. Ananindeua, PA, Brasil / Universidade Federal do Par?. Instituto de Ci?ncias Exatas e Naturais. Faculdade de Ci?ncias Naturais. Bel?m, PA, Brasil. Cancer cell lines are widely used as in vitro models of tumorigenesis, facilitating fundamental discoveries in cancer biology and translational medicine. Currently, there are few options for glioblastoma (GBM) treatment and limited in vitro models with accurate genomic and transcriptomic characterization. Here, a detailed characterization of a new GBM cell line, namely AHOL1, was conducted in order to fully characterize its molecular composition based on its karyotype, copy number alteration (CNA), and transcriptome profiling, followed by the validation of key elements associated with GBM tumorigenesis. Large numbers of CNAs and differentially expressed genes (DEGs) were identified. CNAs were distributed throughout the genome, including gains at Xq11.1-q28, Xp22.33-p11.1, Xq21.1-q21.33, 4p15.1-p14, 8q23.2-q23.3 and losses at Yq11.21-q12, Yp11.31-p11.2, and 15q11.1-q11.2 positions. Nine druggable genes were identified, including HCRTR2, ETV1, PTPRD, PRKX, STS, RPS6KA6, ZFY, USP9Y, and KDM5D. By integrating DEGs and CNAs, we identified 57 overlapping genes enriched in fourteen pathways. Altered expression of several cancer-related candidates found in the DEGs-CNA dataset was confirmed by RT-qPCR. Taken together, this first comprehensive genomic and transcriptomic landscape of AHOL1 provides unique resources for further studies and identifies several druggable targets that may be useful for therapeutics and biologic and molecular investigation of GBM.

From dye-sensitized solar cells to photodynamic therapy, the design of new photosensitizers involves different computational strategies. In this work, we present selected examples aiming at illustrating the limitations and advantages of each selected strategy, as well as listing useful descriptors. Hybrid functionals are reasonable approaches to determine properties related to the electronic absorption spectrum; however, for metallic complexes such as metalloporphyrins, one may be careful in selecting the DFT approach. Self-aggregation of dyes is a phenomenon the experimentalists try to avoid, and it is essential to include dispersion corrections and solvation effects to understand the energetics of this process. Aggregation may be driven by π-stacking or hydrophobic effects, depending on the dye composition. Besides all those characteristics, the design of a new photosensitizer may involve evaluating substitution and anchoring groups, push-pull effects, photostability, and reaction mechanisms in the excited states.

Inovações têm surgido no contexto dos métodos de ensino-aprendizagem, sob influência de pesquisas e modelos comportamentais provenientes da educação, da neurociência e da psicologia. Destaca-se neste cenário, os métodos de aprendizagem ativa, em que o papel do professor passa a ser de um mediador do aprendizado, enquanto o aluno assume o papel de protagonista do processo de aquisição de seu próprio conhecimento.

Apresentamos e comentamos o artigo homônimo de William Thomson, originalmente publicado em 1847, no qual o autor explora a analogia entre os estados de deformação em um sólido elástico e as configurações das linhas de força de Faraday. Nele Thomson introduz pela primeira vez o potencial vetorial magnético, associando-o à deformação rotacional de um sólido. Apresentamos também um apanhado histórico do contexto dentro do qual o original de Thomson foi concebido. We present and comment the homonimous article originally published by William Thomson, in 1847, in which the author explores the analogy between the estates of deformation in an elastic solid and the configurations of Faraday's lines of force. In this article Thomson has introduced for the first time the magnetic potential vector, associated in this context with rotational deformations in the solid. We present as well, the historical context in which Thomson's original paper has been conceived.

Zika virus (ZIKV) transmission in the Americas was first confirmed in May 2015 in Northeast Brazil1. Brazil has the highest number of reported ZIKV cases worldwide (>200,000 by 24 Dec 20162) as well as the greatest number of cases associated with microcephaly and other birth defects (2,366 confirmed cases by 31 Dec 20162). Following the initial detection of ZIKV in Brazil, 47 countries and territories in the Americas have reported local ZIKV transmission, with 24 of these reporting ZIKV-associated severe disease3. Yet the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of such information for interpreting past and future trends in reported microcephaly. To address this we generated 54 complete or partial ZIKV genomes, mostly from Brazil, and report data generated by the ZiBRA project – a mobile genomics lab that travelled across Northeast (NE) Brazil in 2016. One sequence represents the earliest confirmed ZIKV infection in Brazil. Joint analyses of viral genomes with ecological and epidemiological data estimate that ZIKV epidemic was present in NE Brazil by March 2014 and likely disseminated from there, both nationally and internationally, before the first detection of ZIKV in the Americas. Estimated dates of the international spread of ZIKV from Brazil indicate the duration of pre-detection cryptic transmission in recipient regions. NE Brazil’s role in the establishment of ZIKV in the Americas is further supported by geographic analysis of ZIKV transmission potential and by estimates of the virus’ basic reproduction number.One Sentence SummaryVirus genomes reveal the establishment of Zika virus in Brazil and the Americas, and provide an appropriate timeframe for baseline (pre-Zika) microcephaly in different regions.

During the last 4 decades, intensive research has focussed on the effect of small organic molecules with antitumour activity that are able to intercalate into DNA and inhibit topoisomerase and telomerase enzymes. In this review, we describe some of the chemical and biological properties of acridine, which is a chemotherapeutic agent that has been used for cancer treatment since 1970. In addition, we summarise the progress that has been made in the development of anticancer agents based on the clinical in vivo/in vitro studies that have been conducted for 13 classes of natural and synthetic acridines.

The overall production costs of precast concrete elements are important to quantify. Analyses of the constructive stages of these elements, however, may more realistically lead to a function representing production, transport, assembly and casting costs. This article investigates the cost minimisation problems of joists in beam-block floors using a heuristic method known as genetic algorithm (GA) and a conventional method known as generalised reduced gradient (GRG2). The continuous variables considered in the problem were prestressed reinforcements in the three levels, distance between reinforcements, concrete layer strength, distance between joists, concrete layer thickness and degree of redistribution of the continuous slabs’ negative moments. Based on the results, the heuristic method was found to be effective in identifying the solution for precast element cost minimisation problems. The performance of the cost function vis-a-vis market alterations was evaluated considering the influence of concrete, ...

Summary Background: The large majority of depressed patients fail to remit on the first antidepressant prescribed. These patients with residual symptoms have higher relapse rates and poorer outcomes than those who remit. Treatment-resistant depression (TRD) is a therapeutic challenge for the clinician. Augmentation pharmacotherapy refers to the addition of drugs that are not standard antidepressants in order to enhance the effect of a classical antidepressant drug. The aim of this paper was to review the available evidence on the various augmenting agents that have been tested for efficacy in TRD. Methods: Electronic databases and relevant textbooks were searched and the information retrieved was integrated in this review. Results : Although augmentation strategies have been tested with various pharmacological agents, there are few controlled studies published. Lithium, triiodothyronine (T3), buspirone and pindolol have been most widely studied. Other agents include dopaminergic agents, atypical antipsychotics, psychostimulants, benzodiazepines/hypnotics, hormones and anticonvulsants. Conclusion : The augmentation therapy with the best evidence was the lithium-antidepressant combination, especially in patients not responding to tricyclic agents. However, good results have also been reported with augmentation strategies involving T3 and buspirone.

Due to the presence of the blood-brain barrier, the central nervous system (CNS) is not easily accessible to systemically delivered macromolecules with therapeutic activity such as growth factors, cytokines or enzymes. Therefore, the expression of exogenously administered genes in the brain has been proposed for a wide variety of inherited and acquired diseases of the CNS, for which classical pharmacotherapy is unavailable or not easily applicable. Gene therapy to the CNS has been the target of a great number of studies aiming at finding a viable therapeutic strategy for the treatment of neurological disorders. This approach has already been used as a promising tool for brain protection and repair from neuronal insults and degeneration in several animal models, and is currently being applied in clinical trials. The choice of an appropriate vector system for transferring the desired gene into the affected brain area is an important issue for developing a safe and efficient gene therapy approach for the CNS. In this review, we focus on the various types of vectors that have been used for gene delivery into the CNS. Particular emphasis is given to their mode of preparation, biological activity, safety and in vivo behavior. Examples illustrating the potential of both viral and non-viral vectors in therapeutic applications to brain disorders are provided. In addition, the use of lentiviral vectors for in vivo modeling of genetic disorders of the CNS is discussed.

En este trabajo presentamos el análisis de la discusión de un grupo de estudiantes de segundo año de enseñanza básica sobre la resolución de un ejercicio de razonamiento sobre la máquina simple «sarilho». Ese ejercicio está basado en la historia «Tao Simples e Tao Úteis» (Barbosa Lima, 1997) leída por todo el grupo bajo la orientación de la profesora. Nuestro análisis tiene como base el estudio de la transcripción de las intervenciones de los estudiantes en el momento de socializar sus hipótesis con sus compañeros.

This paper reports the results of a comparative study of the electron impact mass spectrometry data for a series of previously synthetized 5-arylidene-3-(4-chloro-benzyl)-4-thioxo-thiazolidin-2-one, and 5-arylidene-3-(2-biphenyl-4-yl-2-oxo-ethyl)-4-thioxo-thiazolidin-2-one derivatives. Theoretical calculations of molecular mechanics, MOPAC‒AM1, were used to explain the fragmentations observed.

Little information is available on hyperiidean amphipods from the tropical and subtropical areas of the south-western Atlantic Ocean. Forty-nine samples were collected during the FINEP XI Cruise (23-27°S/41-48°W). from Cabo Frio to Santa Catarina Island in January 1980. Zooplankton was collected with a 333 μm mesh size net on the continental shelf. The material comprised mainly specimens from the Infraorder Physocephalata, members of which usually inhabit the surface and middle depths of the ocean. Forty species belonging to 27 genera and 14 families were identified, resulting in 12 new records for the Brazilian coast. Laxohyperia vespuliformis Vinogradov and Volkov, 1982 and Amphithyrus muratus Volkov, 1982 are recorded from the Atlantic Ocean for the first time. Twelve instances of association were observed between hyperiids and gelatinous zooplankton (salps and siphonophores). Qualitative and quantitative variations in the species composition are analysed in accordance with the bathymetric and hydrological local conditions. The present study is a step towards a better understanding of the taxonomy and distribution of the Amphipoda Hyperiidea in Brazillian waters.

This paper reports the authors' experience in the application of decomposition techniques to VAr planning. Numerical examples to illustrate the application of the methodology to large scale networks in different planning options, with different combinations of new reactive equipment types and alternative investment cost functions are presented and discussed. >

Summary Background Visceral tone supposedly affects gut sensitivity in irritable bowel syndrome (IBS). Sildenafil increases nitric oxide and influences visceral compliance. Aim To evaluate the effects of sildenafil tone inhibition on rectal sensitivity. Methods Eight controls and 21 IBS patients (Rome II) were enrolled in a double-blind study, after dosing with placebo or sildenafil (50 mg p.o.). Thresholds for first sensation, first desire to defecate, pain and supraliminar pain were the sensory endpoints, measured with a barostat and 600-mL rectal bag. Pain (100-mm VAS) and depression-anxiety (Hamilton questionnaire) were scored. Results Irritable bowel syndrome rectal compliance and sensory-endpoint thresholds were similar to controls. Five IBS patients had pain threshold lower than controls 95% confidence interval (hypersensitive). Depression score was greater in IBS than controls (11.9 ± 1.3 vs. 6.3 ± 2.5, P = 0.036). In IBS, pain intensity was nonsignificantly higher (37.6 ± 5.3 mm vs. 23.4 ± 8.5 mm, P = 0.064) and supraliminar pain intensity was greater (45.6 ± 5.4 mm vs. 25.9 ± 5.1 mm, P = 0.044) than controls. IBS rectal relaxation increased volume (155.4 ± 41.3 mL vs. 118.8 ± 47.7 mL, P = 0.004) and tension (193.1 ± 118.6 mmHg mL−1 vs. 133.2 ± 98.1 mmHg mL−1, P = 0.019) for triggering first desire to defecate but not for other perceptions. Sildenafil increased volume for both first desire to defecate and pain in the hypersensitive IBS patients. Sildenafil increased rectal compliance only in diarrhoea-IBS. Mixed-IBS obtained higher anxiety (12.9 ± 1.3 vs. 5.9 ± 3.1, P

The large majority of depressed patients fail to remit on the first antidepressant prescribed. These patients with residual symptoms have higher relapse rates and poorer outcomes than those who remit. Treatment-resistant depression (TRD) is a therapeutic challenge for the clinician. Augmentation pharmacotherapy refers to the addition of drugs that are not standard antidepressants in order to enhance the effect of a classical antidepressant drug. The aim of this paper was to review the available evidence on the various augmenting agents that have been tested for efficacy in TRD.Electronic databases and relevant textbooks were searched and the information retrieved was integrated in this review.Although augmentation strategies have been tested with various pharmacological agents, there are few controlled studies published. Lithium, triiodothyronine (T3), buspirone and pindolol have been most widely studied. Other agents include dopaminergic agents, atypical antipsychotics, psychostimulants, benzodiazepines/hypnotics, hormones and anticonvulsants.The augmentation therapy with the best evidence was the lithium-antidepressant combination, especially in patients not responding to tricyclic agents. However, good results have also been reported with augmentation strategies involving T3 and buspirone.

This case report describes a 35-year-old woman with a first depressive episode. She was treated with the serotonergic antidepressant citalopram for 12 weeks without therapeutic response. Low-dose amisulpride augmentation resulted in a significant clinical improvement. We hypothesize that the dopaminergic properties of amisulpride might augment the effects of serotonergic antidepressants in refractory patients.

Synthesis and physico-chemical properties of 3-benzyl-5-(4-fluoro-benzylidene)-1-methyl-2-thioxo-imidazolidin-4-ones, 5-benzylidene-3-(4-nitro-benzyl)-2-thioxo-imidazolidin-4-ones and 4-acridin-9-ylmethylene-1-benzyl-5-thioxo-imidazolidin-2-ones compounds are described. These thioxo-imidazolidine derivatives were prepared by alkylation and condensation with 4-fluoro-benzaldehyde or nucleophilic Michael addition with cyanoacrylates. The schistosomicidal activity of 3-benzyl-5-(4-fluoro-benzylidene)-1-methyl-2-thioxo-imidazolidin-4-one compounds was evaluated.

A new set of derivative thioxothiazolidinones and thioxoimidazolidinones 3,5-dissubstituted has been synthesized with satisfactory yield from the condensation Knoevenagel type between benzaldéhydes and 4-thioxothiazolidin-2-one, 2-thioxothiazolidin-4-one and 1-méthyl-2-thioxoimidazolidin-4-one compounds following by N-alkylation with aryl or acyl halides. The physico-chemical properties of the 5-benzylidene-3-[2-(4-chlorophenyl)-2-oxoethyl]-2 (or 4)-thioxothiazolidin-4 (or 2)-ones and 5-benzylidene-1-methyl-2-thioxoimidazolidin-4-ones synthesized have been described.

Synthesis and physico-chemical properties of some 3-benzyl- and 3-phenacyl-4-thioxo-5-benzylidenethiazolidin-2-one derivatives are described. Fifteen new compounds were synthesized from thiazolidin-2-one by thionation of the 4-carbonyle, alkylation of the 3-N and aldolisation-crotonisation of 5-CH(2) with aromatic aldehydes. Soon, these new compounds will be tested for their bacteriostatic activity.

Fusion of African swine fever virus (ASFV) with model membranes was monitored by a fluorescence dequenching assay. ASFV was able to fuse with liposomes of various compositions. Fusion was more extensive with liposomes made of negatively charged phospholipids, and reduced in the presence of the neutral phospholipid phosphatidylcholine (PC). Fusion activity of ASFV was pH-dependent, the extent of fusion increasing with decreasing pH for all target membranes. These results are consistent with the in vivo characteristics of fusion of ASFV with the endosome membrane. An increase in fusion activity was obtained with dehydrating agents, similarly to what occurs with other lipid-enveloped viruses. Dehydrating agents such as dimethylsulfoxide and dimethylsulfone greatly enhanced fusion, the effect of dimethylsulfone being more pronounced than that of dimethylsulfoxide. Poly(ethylene glycol) also potentiated ASFV fusion activity, and the effect of this polymer was found to be dependent on its molecular weight. These results stress the importance of dehydration and hydrophobic interactions on the early events of viral penetration into target cells.

We have studied the importance of hydrophobic interactions in the fusion activity of Sendai virus. Viral fusion activity towards model lipid membranes was monitored using a fluorescence dequenching assay. Fusion was dependent on the composition of the target membrane and was more rapid and extensive at low pH. Dehydrating agents such as dimethylsulfoxide and dimethylsulfone greatly enhanced the initial rate and extent of the fusion process, the effect of dimethylsulfone doubling that of dimethylsulfoxide. However, dehydrating agents had a less pronounced stimulatory effect at low pH. Using the fluorescent probe ANS (1-aminonaphthalene-8-sulfonate) we have shown that low pH by itself involves a marked increase in the viral envelope hydrophobicity, probably resulting in the observed lower stimulation of viral fusion activity by dehydrating agents. Therefore, there seems to be a strong correlation between viral envelope hydrophobicity and viral fusion activity.

The interaction of clathrin with large unilamellar vesicles of various lipid compositions has been examined at neutral pH. Clathrin induces leakage of contents of vesicles that contain the acidic phospholipid phosphatidylserine. Leakage is greatly enhanced by the presence of a relatively minor amount of cholesterol, but is inhibited by phosphatidylcholine. Resonance energy transfer measurements between tryptophan residues of the protein and a fluorescent lipid analog, N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)phosphatidylethanolamine incorporated into the liposomal bilayer, suggests a dynamic interaction of clathrin with the bilayer at neutral pH. This interaction includes a (partial) penetration of the protein into the lipid bilayer, as revealed by hydrophobic photoaffinity labeling with 3-(trifluoromethyl)-3-(m-[125I]iodophenyl)-diazirine. The interaction of clathrin with lipid vesicles at neutral pH is inhibited when the protein is pretreated with trypsin or with the reducing agent dithiothreitol, suggesting that structural requirements govern clathrin-membrane interaction at these conditions. The physiological relevance of the present observations in light of vesiculation and endosomal maturation is discussed.

The synthesis of six benzylidene thiazolidine-diones and three benzylidene imidazolidine-diones is described. In order to investigate their antimicrobial activity, they are evaluated against micro-organism such as Staphylococcus aureus, Streptococcus feacalis, Mycobacterium smegmatis and Neurospora crassa.

The synthesis of six benzylidene thiazolidinediones and four benzylidene imidazolidinediones is described. In order to investigate their antifungal activity, they are evaluated against microorganism such as Candida albicans, Neurospora crassa, Staphylococcus aureus and Escherichia coli.