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Danielle Oliveira Dos Anjos, Eliomara Sousa Sobral Alves, Vinicius Tomaz Gonçalves, Sheila Suarez Fontes, Mateus Lima Nogueira, Ana Márcia Suarez-Fontes, João Batista Neves da Costa, Fabricio Rios-Santos, Marcos André Vannier-Santos
Natural products comprise valuable sources for new antiparasitic drugs. Here we tested the effects of a novel β-lapachone derivative on Trypanosoma cruzi parasite survival and proliferation and used microscopy and cytometry techniques to approach the mechanism(s) underlying parasite death. The selectivity index determination indicate that the compound trypanocidal activity was over ten-fold more cytotoxic to epimastigotes than to macrophages or splenocytes. Scanning electron microscopy analysis revealed that the R72 β-lapachone derivative affected the T...
October 12, 2016: International Journal for Parasitology, Drugs and Drug Resistance
Vasanthanathan Poongavanam, Jacob Kongsted
The high rate of drug resistance as well as the complex biochemical process of the parasite reproduction cycle makes development of new drugs for malaria a very important but challenging task. Falcipain 2 (FL2) and Falcipain 3 (FL3) are the major cysteine protease enzymes that play a central role in providing essential amino acids for the parasite's protein biosynthesis through the hemoglobin hydrolysis process. Selective inhibition of these enzymes is considered as a promising chemotherapeutic target. In the present investigation, the highly efficient linear interaction energy (LIE) method has been parameterized for binding affinity predictions and assessed with a set of 244 compounds for FL2 and FL3 inhibition...
June 26, 2016: Journal of Molecular Graphics & Modelling
Andrew F Leuchter, Aimee M Hunter, Felipe A Jain, Molly Tartter, Caroline Crump, Ian A Cook
Serotonin modulates brain oscillatory activity, and serotonergic projections to the thalamus and cortex modulate the frequency of prefrontal rhythmic oscillations. Changes in serotonergic tone have been reported to shift oscillations between the combined delta-theta (2.5-8 Hz) and the alpha (8-12 Hz) frequency ranges. Such frequency shifts may constitute a useful biomarker for the effects of selective serotonin reuptake inhibitor (SSRI) medications in Major Depressive Disorder (MDD). We utilized quantitative electroencephalography (qEEG) to measure shifts in prefrontal rhythmic oscillations early in treatment with either the SSRI escitalopram or placebo, and examined the relationship between these changes and remission of depressive symptoms...
October 7, 2016: Journal of Psychiatric Research
Mostafa M Ghorab, Mansour S Alsaid, Ghada H Al-Ansary, Ghada A Abdel-Latif, Dalal A Abou El Ella
Twenty novel chromene derivatives carrying different sulfonamide moieties (3-22) were designed and synthesized. All the newly prepared compounds were evaluated for their in vitro anticancer activity against breast cancer cell line (T47D). Most of the synthesized compounds showed good to moderate activity (IC50 = 8.8-108.9 μM), where compound 16 (IC50 = 8.8 μM) exhibited higher activity compared to doxorubicin (IC50 = 9.8 μM). In order to determine the mechanism of the anticancer activity in T47D cells, the effect of the most potent compounds (5-8, 11-14, and 16-18) on the aromatase activity was tested...
October 13, 2016: European Journal of Medicinal Chemistry
Yan Li, Mourad Harir, Marianna Lucio, Michael Gonsior, Boris P Koch, Philippe Schmitt-Kopplin, Norbert Hertkorn
Deciphering the molecular codes of dissolved organic matter (DOM) improves our understanding of its role in the global element cycles and its active involvement in ecosystem services. This study demonstrates comprehensive characterization of DOM by an initial polarity-based stepwise solid phase extraction (SPE) with single methanol elution of the cartridges, but separate collection of equal aliquots of eluate. The reduction of molecular complexity in the individual DOM fractions attenuates intermolecular interactions and substantially increases the disposable resolution of any structure selective characterization...
October 14, 2016: Water Research
Devis Peressutti, Matthew Sinclair, Wenjia Bai, Thomas Jackson, Jacobus Ruijsink, David Nordsletten, Liya Asner, Myrianthi Hadjicharalambous, Christopher A Rinaldi, Daniel Rueckert, Andrew P King
We present a framework for combining a cardiac motion atlas with non-motion data. The atlas represents cardiac cycle motion across a number of subjects in a common space based on rich motion descriptors capturing 3D displacement, velocity, strain and strain rate. The non-motion data are derived from a variety of sources such as imaging, electrocardiogram (ECG) and clinical reports. Once in the atlas space, we apply a novel supervised learning approach based on random projections and ensemble learning to learn the relationship between the atlas data and some desired clinical output...
October 11, 2016: Medical Image Analysis
Mehmet Cemal Kahya, Oğuz Sebik, Kemal S Türker
Painful stimulation of the hand results in an inhibitory response in the hand muscles known as the cutaneous silent period (CSP). In this study, we employed probability- and frequency-based analysis methods to examine the CSP induced by laser stimuli. Subjects were asked to contract their first dorsal interosseous muscle so that selected motor units discharged at a rate of about 8Hz. Laser pulses were delivered to the palm of the hand, and reflex responses were recorded. The stimuli generated CSP in all test subjects...
October 14, 2016: Journal of Electromyography and Kinesiology
Tahereh Zargar, Taghi Khayamian, Mohammad T Jafari
A selective thin-film microextraction based on aptamer immobilized on cellulose paper was used as a paper spray ionization source for ion mobility spectrometry (PSI-IMS), for the first time. In this method, the paper is not only used as an ionization source but also it is utilized for the selective extraction of analyte, based on immobilized aptamer. This combination integrates both sample preparation and analyte ionization in a Whatman paper. To that end, an appropriate sample introduction system with a novel design was constructed for the paper spray ionization source...
October 17, 2016: Journal of Pharmaceutical and Biomedical Analysis
Påvel G Lindberg, Maxime Térémetz, Sylvain Charron, Oussama Kebir, Agathe Saby, Narjes Bendjemaa, Stéphanie Lion, Benoît Crépon, Raphaël Gaillard, Catherine Oppenheim, Marie-Odile Krebs, Isabelle Amado
Inhibition is considered a key mechanism in schizophrenia. Short-latency intracortical inhibition (SICI) in the motor cortex is reduced in schizophrenia and is considered to reflect locally deficient γ-aminobutyric acid (GABA)-ergic modulation. However, it remains unclear how SICI is modulated during motor inhibition and how it relates to neural processing in other cortical areas. Here we studied motor inhibition Stop signal task (SST) in stabilized patients with schizophrenia (N = 28), healthy siblings (N = 21) and healthy controls (n = 31) matched in general cognitive status and educational level...
September 30, 2016: Cortex; a Journal Devoted to the Study of the Nervous System and Behavior
Ki Mo Kim, Deok Rim Heo, Young-A Kim, Jun Lee, No Soo Kim, Ok-Sun Bang
Coniferaldehyde (CA) exerts anti-inflammatory properties by inducing heme oxygenase-1 (HO-1). To define the regulation mechanism by which CA induces a cytoprotective function and HO-1 expression, the up-stream regulations involved in the activation of nuclear transcription factor-erythroid 2-related factor (Nrf)-2/HO-1 pathway were investigated. CA dramatically increased the Nrf-2 nuclear translocation and HO-1 expression. Lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and cell death were down-regulated by CA, which were reversed by inhibition of HO-1 activity...
October 17, 2016: Environmental Toxicology and Pharmacology
Cristiane Ávila Santana, Dinorah Machado Vaz Lima, Luis Humberto da Cunha Andrade, Yzel Rondon Súarez, Sandro Marcio Lima
The aim of this study was to evaluate the fluorescence of Astyanax lacustris fish scales when excited in the UV-A and blue regions for use as a bioindicator of aquatic ecosystems. This species was firstly defined as Astyanax altiparanae, popularly known as "lambari-do-rabo-amarelo". Currently, abiotic/biotic environmental integrity is generally assessed using limnological and physicochemical parameters related to biological indicators in streams or rivers, which are not sufficient to evaluate the real environmental conditions: in some cases, these parameters can be strongly dependent on local weather conditions...
October 8, 2016: Journal of Photochemistry and Photobiology. B, Biology
Teresa V Mitchell
Deafness is known to affect processing of visual motion and information in the visual periphery, as well as the neural substrates for these domains. This study was designed to characterize the effects of early deafness and lifelong sign language use on visual category sensitivity of the N170 event-related potential. Images from nine categories of visual forms including upright faces, inverted faces, and hands were presented to twelve typically hearing adults and twelve adult congenitally deaf signers. Classic N170 category sensitivity was observed in both participant groups, whereby faces elicited larger amplitudes than all other visual categories, and inverted faces elicited larger amplitudes and slower latencies than upright faces...
October 19, 2016: Hearing Research
Moushira E Zaki, Hala T El-Bassyouni, Angie M S Tosson, Eman Youness, Jihan Hussein
OBJECTIVE: Evidence of oxidative stress was reported in individuals with Down syndrome. There is a growing interest in the contribution of the immune system in Down syndrome. The aim of this study is to evaluate the coenzyme Q10 (CoQ10) and selected pro-inflammatory markers such as interleukin 6 (IL-6) and tumor necrosis factor α (TNFα) in children with Down syndrome. METHODS: Eighty-six children (5-8 years of age) were enrolled in this case-control study from two public institutions...
October 19, 2016: Jornal de Pediatria
Fausto Castagnetti, Francesco Di Raimondo, Antonio De Vivo, Antonio Spitaleri, Gabriele Gugliotta, Francesco Fabbiano, Isabella Capodanno, Donato Mannina, Marzia Salvucci, Agostino Antolino, Roberto Marasca, Maurizio Musso, Monica Crugnola, Stefana Impera, Elena Trabacchi, Caterina Musolino, Francesco Cavazzini, Giuseppe Mineo, Patrizia Tosi, Carmela Tomaselli, Michele Rizzo, Sergio Siragusa, Miriam Fogli, Riccardo Ragionieri, Alessandro Zironi, Simona Soverini, Giovanni Martinelli, Michele Cavo, Paolo Vigneri, Fabio Stagno, Gianantonio Rosti, Michele Baccarani
Chronic myeloid leukemia (CML) treatment is based on company-sponsored and academic trials testing different tyrosine kinase inhibitors (TKIs) as first-line therapy. These studies included patients selected according to many inclusion-exclusion criteria, particularly age and comorbidities, with specific treatment obligations. In daily clinical practice (real-life), inclusion-exclusion criteria do not exist and the treatment outcome does not only depend on the choice of first-line TKI, but also on second- and third-line TKIs...
October 22, 2016: American Journal of Hematology
Arash Momeni, Suhail K Kanchwala
BACKGROUND: Autologous breast reconstruction is associated with long-term patient satisfaction that is superior to implant-based approaches. Occasionally, however, patients who desire autologous reconstruction present with inadequate donor-site volume. A hybrid approach, combining free flap reconstruction with simultaneous implant placement, is a solution. We present our experience with the use of mesh for improved pocket control using this reconstructive modality. METHODS: A retrospective analysis of a prospectively maintained database of patients undergoing autologous breast reconstruction was performed...
October 22, 2016: Microsurgery
Agnieszka Fiszer, Marianna E Ellison-Klimontowicz, Wlodzimierz J Krzyzosiak
Polyglutamine (polyQ) diseases comprise a group of nine genetic disorders that are caused by the expansion of the CAG triplet repeat, which encodes glutamine, in unrelated single genes. Various oligonucleotide (ON)-based therapeutic approaches have been considered for polyQ diseases. The very attractive CAG repeat-targeting strategy offers selective silencing of the mutant allele by directly targeting the mutation site. CAG repeat-targeting miRNA-like siRNAs have been shown to specifically inhibit the mutant gene expression, and their characteristic feature is the formation of mismatches in their interactions with the target site...
October 21, 2016: Acta Biochimica Polonica
Verónica María Corrales-Carvajal, Aldo A Faisal, Carlos Ribeiro
Internal states can profoundly alter the behavior of animals. A quantitative understanding of the behavioral changes upon metabolic challenges is key to a mechanistic dissection of how animals maintain nutritional homeostasis. We used an automated video tracking setup to characterize how amino acid and reproductive states interact to shape exploitation and exploration decisions taken by adult Drosophila melanogaster. We find that these two states have specific effects on the decisions to stop at and leave proteinaceous food patches...
October 22, 2016: ELife
Alexander Jarasch, Arne Skerra
The analysis and comparison of large numbers of immunoglobulin (Ig) sequences that arise during an antibody selection campaign can be time-consuming and tedious. Typically, the identification and annotation of framework as well as complementarity-determining regions (CDRs) is based on multiple sequence alignments using standardized numbering schemes, which allow identification of equivalent residues among different family members but often necessitate expert knowledge and manual intervention. Moreover, due to the enormous length variability of some CDRs the benefit of conventional Ig numbering schemes is limited and the calculation of correct sequence alignments can become challenging...
October 22, 2016: Proteins
Patrick R Arsenault, Daisheng Song, Marian Bergkamp, Andrew M Ravaschiere, Bradleigh E Navalsky, Paul M Lieberman, Frank S Lee
The Prolyl Hydroxylase Domain protein (PHD):Hypoxia Inducible Factor (HIF) pathway is the main pathway by which changes in oxygen concentration are transduced to changes in gene expression. In mammals, there are three PHD paralogues, and PHD2 has emerged as a particularly critical one for regulating HIF target genes such as ERYTHROPOIETIN (EPO), which controls red cell mass and hematocrit. PHD2 is distinctive among the three PHDs in that it contains an N-terminal MYND type zinc finger. We have proposed that this zinc finger binds a Pro-Xaa-Leu-Glu (PXLE) motif found in proteins of the HSP90 pathway to facilitate HIF-α hydroxylation...
October 22, 2016: Chembiochem: a European Journal of Chemical Biology
Jingzhao Xia, Guoqiang Yang, Ruijing Zhuge, Yangang Liu, Wanbin Zhang
An iridium-catalyzed asymmetric hydrogenation of unfunctionalized exocyclic C=C bonds was achieved using an axially flexible chiral phosphine-oxazoline ligand, providing the desired (S)-1-benzyl-2,3-dihydro-1H-indene products with up to 98% ee. This represents the first general hydrogenation of unfunctionalized exocyclic olefins with the highest selectivity reported thus far. The additive acetate ion plays an important role in the reaction's high enantioselectivity. The chiral product can be further transformed to key intermediates required for the synthesis of an important insecticide and a drug compound...
October 22, 2016: Chemistry: a European Journal
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