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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
Olena Odnokoz, Kyle Nakatsuka, Vladimir I Klichko, Jacqueline Nguyen, Liz Calderon Solis, Kaitlin Ostling, Marziyeh Badinloo, William C Orr, Svetlana N Radyuk
Previously, we have shown that flies under-expressing the two mitochondrial peroxiredoxins (Prxs), dPrx3 and dPrx5, display increases in tissue-specific apoptosis and dramatically shortened life span, associated with a redox crisis, manifested as changes in GSH:GSSG and accumulation of protein mixed disulfides. To identify specific pathways responsible for the observed biological effects, we performed a transcriptome analysis. Functional clustering revealed a prominent group enriched for immunity-related genes, including a considerable number of NF-kB-dependent antimicrobial peptides (AMP) that are up-regulated in the Prx double mutant...
October 19, 2016: Biochimica et Biophysica Acta
Yakun Wang, Xiaoqiong Hao, Jing Yang, Jia Li, Meijia Zhang
A surge of luteinizing hormone (LH) from the pituitary gland induces the expression of the epidermal growth factor (EGF)-like factors, which triggers oocyte maturation, cumulus expansion, and ovulation. How LH induces EGF-like factor expression is unclear. In the present study, a rapid increase of phosphorylated cAMP response element binding protein (CREB) was observed after the activation of LH receptor by human chorionic gonadotropin. Large antral follicles from equine chorionic gonadotropin-primed mice were cultured in medium with LH to stimulate the expression of EGF-like factors...
October 22, 2016: Molecular Reproduction and Development
Ying Zhang, Qinqin Yu, Nan Jiang, Xu Yan, Chao Wang, Qingmei Wang, Jianzhong Liu, Muyuan Zhu, Sebastian Y Bednarek, Jian Xu, Jianwei Pan
Phototropism is the process by which plants grow towards light in order to maximize the capture of light for photosynthesis, which is particularly important for germinating seedlings. In Arabidopsis, hypocotyl phototropism is predominantly triggered by blue light (BL), which has a profound effect on the establishment of asymmetric auxin distribution, essential for hypocotyl phototropism. Two auxin efflux transporters ATP-BINDING CASSETTE B19 (ABCB19) and PIN-FORMED 3 (PIN3), are known to mediate the effect of BL on auxin distribution in the hypocotyl, but the details for how BL triggers PIN3 lateralization remain poorly understood...
October 22, 2016: Plant, Cell & Environment
Lin Fu, Jinlong Shi, Anqi Liu, Lei Zhou, Mengmeng Jiang, Huaping Fu, Keman Xu, Dandan Li, Ailing Deng, Qingyi Zhang, Yifan Pang, Yujie Guo, Kai Hu, Jiansuo Zhou, Yapeng Wang, Wenrong Huang, Yu Jing, Liping Dou, Lili Wang, Kailin Xu, Xiaoyan Ke, Clara Nervi, Yonghui Li, Li Yu
MicroRNA-9-1(miR-9-1) plays an important role in the mechanism that regulates the lineage fate of differentiating hematopoietic cells. Recent studies have shown that miR-9-1 is downregulated in t (8; 21) AML. However, the pathogenic mechanisms underlying miR-9-1 down-regulation and the RUNX1-RUNX1T1 fusion protein, generated from the translocation of t (8; 21) in AML, remain unclear. RUNX1-RUNX1T1 can induce leukemogenesis through resides in and functions as a stable RUNX1-RUNX1T1-containing transcription factor complex...
October 22, 2016: International Journal of Cancer. Journal International du Cancer
S Tatishvili, M Sinitsa, R Jorbendaze, G Kavtaradze
Severe infarction or its consequences are considered as triggering factors of incidental depression. The aim of our study was to reveal factors associated with depressive episode in patients hospitalized with acute coronary syndrome (acute myocardial infarction, unstable angina). The Beck Depression inventory (BDI) was used for assessment of depressive symptoms in patients with coronary disease in Emergency Cardiology Clinic Tbilisi, Georgia. The study sample included 84 patients. The clinical Information was collected from hospital recordings...
September 2016: Georgian Medical News
E Saralidze, L Khuchua, I Kobaidze
The interaction between different brain structures could be crucial to predicting seizure occurrence, threshold and spread. Moreover, the sleep-wake cycle and electrical activity of brain structures in different phases of sleep could significantly affect the pattern and extent of seizure spread, and therefore the characteristics of epileptic activity. In this animal model using 15 Wistar rats, we show that the duration of hippocampal seizures, induced by electrical stimulation of the hippocampus, is significantly increased during slow sleep...
September 2016: Georgian Medical News
M G Jones, A P Andreou, S B McMahon, D Spanswick
BACKGROUND: Migraineurs are highly sensitive to the nitric oxide donor glyceryl trinitrate which triggers attacks in many sufferers. In animal studies, glyceryl trinitrate increases neuronal activity in the trigeminovascular pathway and elevates neurotransmitter levels in the brainstem. Many migraineurs also display alterations in blink reflexes, known to involve brainstem circuits. We investigated the effect of GTN on evoked blinks in the anaesthetised rat to determine whether such reflexes may prove useful as the basis for a novel animal model to evaluate potential anti-migraine therapeutic agents...
December 2016: Journal of Headache and Pain
Akhi Akhter, Emanuel Rosonina
The Saccharomyces cerevisiae transcription factor Gcn4 is expressed during amino acid starvation and its abundance is controlled by ubiquitin-mediated proteolysis. Cdk8, a kinase component of the RNA polymerase II Mediator complex, phosphorylates Gcn4 which triggers its ubiquitination/proteolysis and is thought to link Gcn4 degradation with transcription of target genes. In addition to phosphorylation and ubiquitination, we previously showed that Gcn4 becomes sumoylated in a DNA-binding dependent manner, while a non-sumoylatable form of Gcn4 showed increased chromatin occupancy, but only if Cdk8 was present...
October 21, 2016: Genetics
Adrian Fischer, Wilfried Weber, Bettina Warscheid, Gerald Radziwill
Scaffold proteins are hubs for the coordination of intracellular signaling networks. The scaffold protein CNK1 promotes several signal transduction pathway. Here we demonstrate that sterile motif alpha (SAM) domain-dependent oligomerization of CNK1 stimulates CNK1-mediated signaling in growth factor-stimulated cells. We identified Ser22 located within the SAM domain as AKT-dependent phosphorylation site triggering CNK1 oligomerization. Oligomeric CNK1 increased the affinity for active AKT indicating a positive AKT feedback mechanism...
October 19, 2016: Biochimica et Biophysica Acta
Jia Cheng, XiaoFeng Guo, Tian Zhang, Li Zhong, GuoJun Bu, XiaoFen Chen
Triggering receptor expressed on myeloid cells (TREMs) receptors constitute a family modulators in human innate immunity system that encode by a gene cluster. Rare variants in TREM2 were reported to be associated with significant Alzheimer's disease (AD) risk. However, inconsistent results were also reported in some studies of Non-European descents. Recently, the other TREM family members are also considered to involve in AD and cerebrospinal fluid (CSF) soluble form of TREM2 (sTREM2) levels has also been associated with respond to progression of disease...
October 18, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
Kristine Moltu, Karen Henjum, Nikolaus G Oberprieler, Bjørn A Bjørnbeth, Kjetil Taskén
Patients with colorectal cancer (CRC) have been shown to have elevated levels of circulating prostaglandin E2(PGE2) which promotes cancer progression and suppresses T-cell immune responses. In this study we evaluated whether signaling responses in T lymphocytes obtained from peripheral blood of CRC patients were affected by the sustained exposure to increased levels of PGE2. The phosphorylation status of an extended panel of proteins involved in downstream signaling cascades in T cells was profiled at a single cell level both in naïve and antigen-experienced cells after triggering T cell-, prostaglandin- and interleukin-2 receptors...
October 18, 2016: Human Immunology
Franziska Richter, Julia Gerstenberger, Anne Bauer, Chun-Chi Liang, Angelika Richter
Hereditary generalized dystonia is often caused by a GAG deletion in TOR1A (DYT1) that encodes for the protein torsinA. Although mutation carriers show alterations in neuronal connectivity and sensorimotor deficits, only 30% develop dystonia. Uncovering the factors triggering the dystonic symptoms and underlying pathophysiology would greatly benefit the development of more effective therapies. In DYT1 knock-in (KI) mice, the expression of torsinA mutant alters the connectivity of neurons and the function of striatal cholinergic interneurons...
October 18, 2016: Behavioural Brain Research
Benjamin Albright, Roni Dhaher, Helen Wang, Roa Harb, Tih-Shih W Lee, Hitten Zaveri, Tore Eid
Loss of glutamine synthetase (GS) in hippocampal astrocytes has been implicated in the causation of human mesial temporal lobe epilepsy (MTLE).However, the mechanism by which the deficiency in GS leads to epilepsy is incompletely understood. Here we ask how hippocampal GS inhibition affects seizure phenotype and neuronal activation during epilepsy development (epileptogenesis). Epileptogenesis was induced by infusing the irreversible GS blocker methionine sulfoximine (MSO) unilaterally into the hippocampal formation of rats...
October 18, 2016: Experimental Neurology
Carla Elena Sartori Oliveira, Marcel Henrique Marcondes Sari, Vanessa A Zborowski, Vinicius Costa Prado, Cristina Wayne Nogueira, Gilson Zeni
Depression and pain comorbidity represent a neuropsychiatric condition with substantial socioeconomic impact to society. The commonly used antidepressants and analgesics to treat this comorbidity have shown restricted clinical efficacy. In this way, the aim of this study was to investigate the behavioral, biochemical and neurochemical effects of a p,p'-methoxyl-diphenyl diselenide (OMePhSe)2 supplemented diet on pain-depression dyad induced by reserpine in rats. Adult Wistar rats were fed with 10mg (MeOPhSe)2 per kg of rat chow supplemented diet for 30 days...
October 18, 2016: European Journal of Pharmacology
C Romano, E Fanelli, G D'Anna, C Pipitone, S Vizzini, A Mazzola, F Badalamenti
This study examines the impact of bottom trawl fishing on the macrobenthic communities inhabiting the coastal terrigenous mud off the northern coast of Sicily (Western Mediterranean). Two intensely trawled gulfs were compared with two gulfs from which trawling has been excluded for 15 years. The results show a significant effect of trawling on the faunal assemblage and when comparing the mean biomass and the whole isotopic composition of the benthic communities. A similar pattern, although not significant, was found for total abundance, biomass, production/biomass ratio and diversity...
October 11, 2016: Marine Environmental Research
A D Surowka, M Töpperwien, M Bernhardt, J D Nicolas, M Osterhoff, T Salditt, D Adamek, M Szczerbowska-Boruchowska
Human dopaminergic system in general, and substantia nigra (SN) neurons, in particular, are implicated in the pathologies underlying the human brain aging. The interplay between aberrations in the structural organization and elemental composition of SN neuron bodies has recently gained in importance as selected metals: Fe, Cu, Zn, Ca were found to trigger oxidative-stress-mediated aberration in their molecular assembly due to concomitant protein (alpha-synuclein, tau-protein) aggregation, gliosis and finally oxidative stress...
December 1, 2016: Talanta
Yan Zhou, Shuchen Lin, Kuo-Fu Tseng, Kun Han, Yaling Wang, Zhi-Hua Gan, Da-Liu Min, Hai-Yan Hu
BACKGROUND: Triple-negative breast cancer (TNBC) has aggressive progression with poor prognosis and ineffective treatments. Selumetinib is an allosteric, ATP-noncompetitive inhibitor of MEK1/2, which has benn known as effective antineoplastic drugs for several malignant tumors. We hypothesized that Selumetinib might be potential drug for TNBC and explore the mechanism. METHODS: After treated with Selumetinib, the viability and mobility of HCC1937 and MDA-MB-231 were detected by MTT, tunnel, wound-healing assay, transwell assay and FCM methods...
October 21, 2016: BMC Cancer
Chilala Cheelo, Selestine Nzala, Joseph M Zulu
BACKGROUND: In 2010 the government of the republic of Zambia stopped training traditional birth attendants and forbade them from conducting home deliveries as they were viewed as contributing to maternal mortality. This study explored positive and negative maternal health related experiences and effects of the ban in a rural district of Kazungula. METHODS: This was a phenomenological study and data were collected through focus group discussions as well as in-depth interviews with trained traditional birth attendants (tTBAs) and key informant interviews with six female traditional leaders that were selected one from each of the six zones...
October 21, 2016: BMC Pregnancy and Childbirth
Toshifumi Mori, Shinji Saito
Proteins involve motions over a wide range of spatial and temporal scales. While the large conformational changes such as folding and functioning are slow and appear to occur in a highly cooperative manner, how the hierarchical dynamics over different timescales play a role during these slow transitions has been of great interest over the decades. Here we study the folding mechanism of the villin headpiece subdomain (HP35) to understand the molecular mechanism behind this prototypical fast-folding protein. The ~ 400 µs molecular dynamics (MD) trajectories obtained by Piana et al...
October 21, 2016: Journal of Physical Chemistry. B
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