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https://www.readbyqxmd.com/read/29153032/evaluation-of-the-carcinogenic-potential-of-roxadustat-fg-4592-a-small-molecule-inhibitor-of-hypoxia-inducible-factor-prolyl-hydroxylase-in-cd-1-mice-and-sprague-dawley-rats
#1
James Beck, Carroll Henschel, James Chou, Al Lin, Ughetta Del Balzo
The carcinogenic potential of roxadustat (FG-4592), a novel orally active, heterocyclic small molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PH) enzymes in clinical development for treatment of anemia, was evaluated in CD-1 mice and Sprague Dawley rats. Inhibition of HIF-PH by roxadustat leads to a rapid increase in cytoplasmic HIF-α concentrations, followed by translocation of HIF-α to the nucleus and upregulation of HIF-responsive genes, including erythropoietin. Roxadustat was dosed by oral gavage 3 times weekly (TIW) for up to 104 weeks in mice at 0, 15, 30, and 60 mg/kg and in rats at 0, 2...
January 1, 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/29151891/the-exon-junction-complex-factor-y14-is-dynamic-in-the-nucleus-of-the-beetle-tribolium-castaneum-during-late-oogenesis
#2
Artem M Kiselev, Irina S Stepanova, Leonid S Adonin, Florina M Batalova, Vladimir N Parfenov, Dmitry S Bogolyubov, Olga I Podgornaya
Background: The oocyte chromosomes of the red flour beetle, Tribolium castaneum, are gathered into a knot, forming a karyosphere at the diplotene stage of meiotic prophase. Chromatin rearrangement, which is a characteristic feature of oocyte maturation, is well documented. The T. castaneum karyosphere is surrounded by a complex extrachromosomal structure termed the karyosphere capsule. The capsule contains the vast majority of oocyte RNA. We have previously shown using a BrUTP assay that oocyte chromosomes in T...
2017: Molecular Cytogenetics
https://www.readbyqxmd.com/read/29133374/the-rin-mc-fusion-of-mads-box-transcription-factors-has-transcriptional-activity
#3
Shan Li, Huijinlan Xu, Zheng Ju, Dongyan Cao, Hongliang Zhu, Daqi Fu, Donald Grierson, Guozheng Qin, Yunbo Luo, Benzhong Zhu
Fruit development and ripening is regulated by genetic and environmental factors and is of critical importance for seed dispersal, reproduction and fruit quality. Tomato rin mutant fruit have a classic ripening-inhibited phenotype, which is attributed to a genomic DNA deletion resulting in the fusion of two truncated transcription factors, RIN and MC. In wild-type fruit, RIN, a MADS-box transcription factor, is a key regulator of the ripening gene expression network with hundreds of gene targets controlling changes in color, flavor, texture and taste during tomato fruit ripening; MC, on the other hand, has low expression in fruit, and the potential functions of the RIN-MC fusion gene in ripening remain unclear...
November 13, 2017: Plant Physiology
https://www.readbyqxmd.com/read/29128706/consumption-of-ellagic-acid-and-dihydromyricetin-synergistically-protects-against-uv-b-induced-photoaging-possibly-by-activating-both-tgf-%C3%AE-1-and-wnt-signaling-pathways
#4
Na Rang Moon, Suna Kang, Sunmin Park
Ellagic acid (EGA) and dihydromyricetin (DHM) are both found in fruits and vegetables are used for anti-aging treatment for the skin. The anti-photoaging efficacy of EGA and DHM was investigated in UV-B irradiated skin in vivo and the involvement of transforming growth factor (TGF)-β1 and wnt signaling pathways were examined in vitro. HaCaT cells were treated with either 50μM EGA, 50μM DHM or 25μM EGA+25μM DHM before 100mJ/cm(2) UV-B exposure, and then oxidative stress and inflammation was measured. The involvement of TGF-β1 and wnt signaling was measured using their inhibitors, respectively, in HaCaT cells...
November 7, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29111022/association-of-freezing-of-gait-with-nigral-iron-accumulation-in-patients-with-parkinson-s-disease
#5
Rajini M Naduthota, Arush Arun Honnedevasthana, Abhishek Lenka, Jitender Saini, Sairam Geethanath, Rose Dawn Bharath, Rita Christopher, Ravi Yadav, Arun Kumar Gupta, Pramod Kumar Pal
BACKGROUND AND PURPOSE: The objective of this work was to investigate whether patients with and without freezing of gait (FOG) in Parkinson's disease (PD) have differences in iron accumulation in substantia nigra using R2* relaxometry. MATERIALS AND METHODS: This study included seventeen PD patients with FOG [FOG (+)], equal number of age and gender matched patients without FOG [FOG (-)] and 34 healthy controls (HC). T2* images were obtained from a 3-Tesla MRI system using multi-echo sequence...
November 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29101813/cytotoxic-and-cytostatic-effects-of-digitoxigenin-monodigitoxoside-dgx-in-human-lung-cancer-cells-and-its-link-to-na-k-atpase
#6
Naira Fernanda Zanchett Schneider, Lara Persich, Sayonarah C Rocha, Ana Carolina Pacheco Ramos, Vanessa Faria Cortes, Izabella Thaís Silva, Jennifer Munkert, Rodrigo M Pádua, Wolfgang Kreis, Alex G Taranto, Leandro A Barbosa, Fernão C Braga, Cláudia M O Simões
Cardiac glycosides (CGs) are natural compounds widely used to treat several cardiac conditions and more recently have been recognized as potential antitumor agents. They are known as Na,K-ATPases ligands, which is a promising drug target in cancer. In this study, the short and long-lasting cytotoxic effects of the natural cardenolide digitoxigenin monodigitoxoside (DGX) were evaluated against two non-small cell lung cancer lines (A549 and H460 cells). It was found that DGX induced cytotoxic effects in both cells and the apoptotic effects were more pronounced on H460 cells...
November 1, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29082495/high-content-positional-biosensor-assay-to-screen-for-compounds-that-prevent-or-disrupt-androgen-receptor-and-transcription-intermediary-factor-2-protein-protein-interactions
#7
Yun Hua, Daniel P Camarco, Christopher J Strock, Paul A Johnston
Transcriptional Intermediary Factor 2 (TIF2) is a key Androgen receptor (AR) coactivator that has been implicated in the development and progression of castration resistant prostate cancer (CRPC). This chapter describes the implementation of an AR-TIF2 protein-protein interaction (PPI) biosensor assay to screen for small molecules that can induce AR-TIF2 PPIs, inhibit the DHT-induced formation of AR-TIF2 PPIs, or disrupt pre-existing AR-TIF2 PPIs. The biosensor assay employs high content imaging and analysis to quantify AR-TIF2 PPIs and integrates physiologically relevant cell-based assays with the specificity of binding assays by incorporating structural information from AR and TIF2 functional domains along with intracellular targeting sequences using fluorescent protein reporters...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29070474/-histological-structure-of-the-trabecular-meshwork-in-the-eyeball-challenging-the-traditional-concept-and-preliminary-findings-in-rabbits-rats-and-mice
#8
Yun Shi, Fan-Qi Zhou, Zhou-Cai Luo, Ying-Hua Chen, Yu Chen, Wei-Ren Dong
OBJECTIVE: To verify that the trabecular meshwork (TM) in the wall of the eyeball consists of smooth muscle fibers instead of collagen fibers or endothelial cells. METHODS: Eighteen fresh eyeballs from 3 rabbits, 3 SD rats and 3 mice were sectioned along the sagittal plane and sliced after paraffin embedding for HE staining, VG staining, Masson staining, α-SMA immunohistochemistry or CD31 immunohistochemistry. These slices were observed under microscope and the structure of the TM was compared with those of scleral collagen fibers, ciliary muscles and endothelial cells...
October 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/29066252/abca1-affects-placental-function-via-trophoblast-and-macrophage
#9
Xie Chengmao, Lin Li, Long Yan, Yang Jie, Wang Xiaoju, Cai Xiaohui, Guan Huimin
AIMS: To study the potential impact of ABCA1 on the function of the placenta. MAIN METHODS: Trophoblasts and macrophages were isolated from the placenta with enzymatic digestion; Immunofluorescence assay was used to detect the location of ABCA1 in cells; RT-PCR and Western-blot were used to detect the expression of ABCA1; The cholesterol efflux assays of primary trophoblasts was detected by Amplex Red cholesterol assay kit (Invitrogen);Inflammatory factor secretion from primary macrophages was detected by Elisa...
October 21, 2017: Life Sciences
https://www.readbyqxmd.com/read/29056105/colonic-and-systemic-effects-of-extruded-whole-grain-sorghum-consumption-in-growing-wistar-rats
#10
Emilce E Llopart, Raúl E Cian, Muñoz María Elvira López-Oliva, Ángela Zuleta, Adriana Weisstaub, Silvina R Drago
Colonic effects of extruded whole-grain sorghum diets were evaluated using a model of growing rats. In all, twenty-four male Wistar rats were fed control (C), extruded white sorghum (EWS) or red sorghum (ERS). Consumption of sorghum diets showed satiety properties, with reduction of caecal pH, and lower activity of β-glucosidase and β-glucuronidase enzymes. Decreased copper zinc superoxide dismutase and manganese superoxide dismutase and increased catalase and glutathione peroxidase levels were observed in colonic mucosa...
October 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/29055240/automatic-processing-of-emotional-facial-expressions-as-a-function-of-social-anhedonia
#11
Vivien Günther, Juliane Zimmer, Anette Kersting, Karl-Titus Hoffmann, Donald Lobsien, Thomas Suslow
Anhedonia is an important feature of major depression and schizophrenia-spectrum disorders. Few neuroimaging studies have investigated neural alterations in high anhedonia, isolated from other psychopathological variables, by including only participants without clinical diagnoses. The present study examined healthy individuals scoring high (N = 18) vs. low (N = 19) in social anhedonia, who were carefully selected from a sample of N = 282 participants. To examine differences in automatic brain responses to social-affective stimuli between high vs...
December 30, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/29035999/effects-on-18f-fdg-pet-ct-brain-glucose-metabolism-in-rectal-cancer-patients-undergoing-neoadjuvant-chemotherapy
#12
Alexei M C Machado, Theara C Fagundes, Arnoldo Mafra, Rodrigo G Silva, Ana Carolina G Castro, Marcelo Mamede
PURPOSE: Retrospective study of the effects of anticancer treatment on the brain metabolism of patients diagnosed with rectal cancer based on a large and homogeneous sample of 40 paired F-FDG PET/CT volumes taken from 20 patients. The results are compared to the ones presented by related works to help elucidating the mechanisms of neurotoxicity associated to a decrease in memory, learning and motor skills. PATIENTS AND METHODS: Twenty patients with rectal adenocarcinoma were scanned before and after neoadjuvant chemoradiation based exclusively on 5-fluorouracil and leucovorin...
October 13, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/29016618/nigrosome-1-visibility-at-susceptibility-weighted-7t-mri-a-dependable-diagnostic-marker-for-parkinson-s-disease-or-merely-an-inconsistent-age-dependent-imaging-finding
#13
Carolin Gramsch, Iris Reuter, Oliver Kraff, Harald H Quick, Christian Tanislav, Florian Roessler, Cornelius Deuschl, Michael Forsting, Marc Schlamann
BACKGROUND: Visualisation of nigrosome 1, a substructure of the healthy substantia nigra, was restricted in susceptibility weighted MR imaging in almost all patients with Parkinson's disease studied so far. The purpose of this study was to determine the degree of visibility of this substructure in subjects without Parkinson's disease and to examine the potential link between increasing brain iron accumulation with age and its detectability. METHODS: In 46 subjects (21 women, 25 men; 19 to 75 y; mean age: 44...
2017: PloS One
https://www.readbyqxmd.com/read/28992226/arginine-vasotocin-and-neuropeptide-y-vary-with-seasonal-life-history-transitions-in-garter-snakes
#14
Ashley R Lucas, Daelyn Y Richards, Lucy M Ramirez, Deborah I Lutterschmidt
Transitions between life-history stages are often accompanied by dramatic behavioral switches that result from a shift in motivation to pursue one resource over another. While the neuroendocrine mechanisms that regulate such behavioral transitions are poorly understood, arginine vasotocin (AVT) and neuropeptide Y (NPY) are excellent candidates because they modulate reproductive and feeding behavior, respectively. We asked if seasonal changes in AVT and NPY are concomitant with the seasonal migration to and from the feeding grounds in red-sided garter snakes (Thamnophis sirtalis parietalis)...
August 1, 2017: Integrative and Comparative Biology
https://www.readbyqxmd.com/read/28990041/brain-iron-deposition-analysis-using-susceptibility-weighted-imaging-and-its-association-with-body-iron-level-in-patients-with-mild-cognitive-impairment
#15
Lili Gao, Zhihong Jiang, Zhaocheng Cai, Ming Cai, Qing Zhang, Yingying Ma, Guoliang Li, Fengzhu Zhao, Qiang Ma
The aim of the present study was to analyze brain and body iron levels among patients with mild cognitive impairment (MCI), Alzheimer's disease (AD), and normal controls (NCs). A total of 90 participants (30 MCI, 30 AD, 30 NC) were enrolled. Brain iron content was quantified using susceptibility weighted imaging (SWI). Phase values were used to calculate bilateral iron content in the hippocampus (HP), substantia nigra, red nucleus (RN), dentate nucleus (DN), caudate nucleus (CN), globus pallidus (GP), putamen (PUT), frontal white matter, temporal cortex (TC), and parietal cortex...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28986653/pool-size-ratio-of-the-substantia-nigra-in-parkinson-s-disease-derived-from-two-different-quantitative-magnetization-transfer-approaches
#16
Paula Trujillo, Paul E Summers, Alex K Smith, Seth A Smith, Luca T Mainardi, Sergio Cerutti, Daniel O Claassen, Antonella Costa
PURPOSE: We sought to measure quantitative magnetization transfer (qMT) properties of the substantia nigra pars compacta (SNc) in patients with Parkinson's disease (PD) and healthy controls (HCs) using a full qMT analysis and determine whether a rapid single-point measurement yields equivalent results for pool size ratio (PSR). METHODS: Sixteen different MT-prepared MRI scans were obtained at 3 T from 16 PD patients and eight HCs, along with B1, B0, and relaxation time maps...
December 2017: Neuroradiology
https://www.readbyqxmd.com/read/28985148/phytochrome-interacting-factors-from-physcomitrella-patens-are-active-in-arabidopsis-and-complement-the-pif-quadruple-mutant
#17
Tengfei Xu, Andreas Hiltbrunner
Phytochromes are red/far-red light receptors in plants involved in the regulation of growth and development in response to changes in the ambient environment. An important mode of action of plant phytochromes depends on their light-regulated relocation from the cytosol into the nucleus and control of gene expression; in addition, there is also evidence for a cytosolic or plasma membrane associated function of phytochromes in different species. The PHYTOCHROME INTERACTING FACTORs (PIFs) form a subgroup of the bHLH transcription factors and it is well established that PIFs are key components of phytochrome downstream signalling in the nucleus of seed plants...
October 6, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28982949/the-existence-of-dead-cells-in-donor-corneal-endothelium-preserved-with-storage-media
#18
Koji Kitazawa, Tsutomu Inatomi, Hidetoshi Tanioka, Satoshi Kawasaki, Hiroko Nakagawa, Osamu Hieda, Hideki Fukuoka, Naoki Okumura, Noriko Koizumi, Bernie Iliakis, Chie Sotozono, Shigeru Kinoshita
AIM: To investigate the viability of donor corneal endothelial cells (CECs) preserved in storage media by histological examination. METHODS: Twenty-eight donor corneas were obtained from SightLife Eye Bank (Seattle, Washington), and redundant peripheral portions of those corneas were used for histological examination after removal of the centre corneal graft for transplantation. To assess cell viability in the corneal endothelium, biostaining experiments were performed using propidium iodide, calcein-AM, Hoechst 33 342, annexin V, anti-vimentin antibody and toluidine blue...
October 5, 2017: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/28980355/cortical-disconnection-of-the-ipsilesional-primary-motor-cortex-is-associated-with-gait-speed-and-upper-extremity-motor-impairment-in-chronic-left-hemispheric-stroke
#19
Denise M Peters, Julius Fridriksson, Jill C Stewart, Jessica D Richardson, Chris Rorden, Leonardo Bonilha, Addie Middleton, Ezequiel Gleichgerrcht, Stacy L Fritz
Advances in neuroimaging have enabled the mapping of white matter connections across the entire brain, allowing for a more thorough examination of the extent of white matter disconnection after stroke. To assess how cortical disconnection contributes to motor impairments, we examined the relationship between structural brain connectivity and upper and lower extremity motor function in individuals with chronic stroke. Forty-three participants [mean age: 59.7 (±11.2) years; time poststroke: 64.4 (±58.8) months] underwent clinical motor assessments and MRI scanning...
October 5, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/28947499/a-circuit-for-detection-of-interaural-time-differences-in-the-nucleus-laminaris-of-turtles
#20
Katie L Willis, Catherine E Carr
The physiological hearing range of turtles is approximately 50-1000 Hz, as determined by cochlear microphonics ( Wever and Vernon, 1956a). These low frequencies can constrain sound localization, particularly in red-eared slider turtles, which are freshwater turtles with small heads and isolated middle ears. To determine if these turtles were sensitive to interaural time differences (ITDs), we investigated the connections and physiology of their auditory brainstem nuclei. Tract tracing experiments showed that cranial nerve VIII bifurcated to terminate in the first-order nucleus magnocellularis (NM) and nucleus angularis (NA), and the NM projected bilaterally to the nucleus laminaris (NL)...
November 15, 2017: Journal of Experimental Biology
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