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Minhan Ka, Jeffrey J Moffat, Woo-Yang Kim
GABAergic interneurons develop in the ganglionic eminence in the ventral telencephalon and tangentially migrate into the cortical plate during development. However, key molecules controlling interneuron migration remain poorly identified. Here, we show that microtubule-actin cross-linking factor 1 (MACF1) regulates GABAergic interneuron migration and positioning in the developing mouse brain. To investigate the role of MACF1 in developing interneurons, we conditionally deleted the MACF1 gene in mouse interneuron progenitors and their progeny using Dlx5/6-Cre-IRES-EGFP and Nkx2...
October 18, 2016: Cerebral Cortex
N Gerdes, E Farin
Objective: Taking Fibromyalgia syndrome (FMS) as an example, the article illustrates a problem that to our knowledge has not been addressed in rehabilitation research so far: According to our large dataset, a sizeable proportion of patients had to be sent home with extremely severe burdens (<2(nd) percentile in the normal population) at discharge - in spite of good improvements during their stay. Data and methods: Since 2009, patients in the RehaKlinikum Bad Säckingen, an in-patient rehab center for orthopedic-rheumatic diseases, answer the questionnaire "Indicators of Rehabilitation Status" (IRES) at the beginning and the end of their stay...
October 2016: Die Rehabilitation
L Bond, B Schulz, T VanMeter, R C G Martin
INTRODUCTION: Irreversible electroporation (IRE) uses multiple needles and a series of electrical pulses to create pores in cell membranes and cause cell apoptosis. One of the demands of IRE is the precise needle spacing required. Two-dimensional intraoperative ultrasound (2-D iUS) is currently used to measure inter-needle distances but requires significant expertise. This study evaluates the potential of three-dimensional (3-D) image guidance for placing IRE needles and calculating needle spacing...
September 29, 2016: European Journal of Surgical Oncology
Xiaoping Chen, Ping Han, Tao Zhou, Xuejiang Guo, Xiaofeng Song, Yan Li
It has been known that circular RNAs are widely expressed in human tissues and cells, and play important regulatory roles in physiological or pathological processes. However, there is lack of comprehensively annotated human circular RNAs database. In this study we established a circRNA database, named as circRNADb, containing 32,914 human exonic circRNAs carefully selected from diversified sources. The detailed information of the circRNA, including genomic information, exon splicing, genome sequence, internal ribosome entry site (IRES), open reading frame (ORF) and references were provided in circRNADb...
October 11, 2016: Scientific Reports
Satoshi Sugita, Leland L Fleming, Caleb Wood, Sydney K Vaughan, Matheus P S M Gomes, Wallace Camargo, Ligia A Naves, Vania F Prado, Marco A M Prado, Cristina Guatimosim, Gregorio Valdez
BACKGROUND: Cholinergic dysfunction occurs during aging and in a variety of diseases, including amyotrophic lateral sclerosis (ALS). However, it remains unknown whether changes in cholinergic transmission contributes to age- and disease-related degeneration of the motor system. Here we investigated the effect of moderately increasing levels of synaptic acetylcholine (ACh) on the neuromuscular junction (NMJ), muscle fibers, and motor neurons during development and aging and in a mouse model for amyotrophic lateral sclerosis (ALS)...
2016: Skeletal Muscle
Thomas K Smylla, Anette Preiss, Dieter Maier
Cell communication in metazoans requires the highly conserved Notch signaling pathway, which is subjected to strict regulation of both activation and silencing. In Drosophila melanogaster, silencing involves the assembly of a repressor complex by Hairless (H) on Notch target gene promoters. We previously found an in-frame internal ribosome entry site in the full length H transcript resulting in two H protein isoforms (H(p120) and H(p150)). Hence, H may repress Notch signalling activity in situations where cap-dependent translation is inhibited...
October 7, 2016: Scientific Reports
Xianfeng Zha, Ling Xu, Shaohua Chen, Lijian Yang, Yikai Zhang, Yuhong Lu, Zhi Yu, Bo Li, Xiuli Wu, Wenjie Zheng, Yangqiu Li
Adoptive immunotherapy with antigen-specific T cells can be effective for treating melanoma and chronic myeloid leukemia (CML). However, to obtain sufficient antigen-specific T cells for treatment, the T cells have to be cultured for several weeks in vitro, but in vitro T cell expansion is difficult to control. Alternatively, the transfer of T cell receptors (TCRs) with defined antigen specificity into recipient T cells may be a simple solution for generating antigen-specific T cells. The objective of this study was to identify CML-associated, antigen-specific TCR genes and generate CML-associated, antigen-specific T cells with T cell receptor (TCR) gene transfer...
October 4, 2016: Oncotarget
Jacey H Ma, Joshua J Wang, Junhua Li, Bruce A Pfeffer, Yiming Zhong, Sarah X Zhang
Purpose: The retinal pigment epithelium (RPE) tight junctions play a pivotal role in maintaining the homeostatic environment of the neural retina. Herein, we investigated the role of X-box binding protein 1 (XBP1), an endoplasmic reticulum (ER) stress-responsive transcription factor, in regulation of RPE tight junctions. Methods: Human RPE cell line (ARPE-19) and primary primate RPE cells were used for in vitro experiments and RPE-specific XBP1 knockout (KO) mice were used for in vivo study...
October 1, 2016: Investigative Ophthalmology & Visual Science
Matthew Torres, Henry Dewhurst, Niveda Sundararaman
Post-translational modifications (PTMs) regulate protein behavior through modulation of protein-protein interactions, enzymatic activity, and protein stability essential in the translation of genotype to phenotype in eukaryotes. Currently, less than 4% of all eukaryotic PTMs are reported to have biological function &- a statistic that continues to decrease with an increasing rate of PTM detection. Previously, we developed SAPH-ire (Structural Analysis of PTM Hotspots) &- a method for the prioritization of PTM function potential that has been used effectively to reveal novel PTM regulatory elements in discrete protein families (Dewhurst et al...
October 3, 2016: Molecular & Cellular Proteomics: MCP
Massimo Valerio, Louise Dickinson, Afia Ali, Navin Ramachadran, Ian Donaldson, Neil Mccartan, Alex Freeman, Hashim U Ahmed, Mark Emberton
PURPOSE: Irreversible electroporation (IRE) has attractive attributes for focal ablation, namely non-thermal effect, precise demarcation of treatment, and tissue-selectivity. We report on a prospective development study investigating focal IRE. MATERIALS AND METHODS: 20 men with the following characteristics were recruited: anterior MR-visible index lesion concordant with transperineal targeted and template prostate mapping biopsy, absence of clinically significant disease elsewhere (UCL definition 2), and PSA </= 15 ng/ml...
September 30, 2016: Journal of Urology
Ishan Goswami, Sheryl Coutermarsh-Ott, Ryan G Morrison, Irving C Allen, Rafael V Davalos, Scott S Verbridge, Lissett R Bickford
Low-level electric fields have been demonstrated to induce spatial re-distribution of cell membrane receptors when applied for minutes or hours. However, there is limited literature on the influence on cell signaling with short transient high-amplitude pulses typically used in irreversible electroporation (IRE) for cancer treatment. Moreover, literature on signaling pertaining to immune cell trafficking after IRE is conflicting. We hypothesized that pulse parameters (field strength and exposure time) influence cell signaling and subsequently impact immune-cell trafficking...
September 25, 2016: Bioelectrochemistry
Donald B Smith, Paul Becher, Jens Bukh, Ernest A Gould, Gregor Meyers, Thomas Monath, A Scott Muerhoff, Alexander Pletnev, Rebecca Rico-Hesse, Jack T Stapleton, Peter Simmonds
Proposals are described for the assignment of recently reported viruses, infecting rodents, bats and other mammalian species, to new species within the Hepacivirus and Pegivirus genera (Family Flaviviridae). Assignments into 14 Hepacivirus species (Hepacivirus A to N) and 11 Pegivirus species (Pegivirus A to K) are based on phylogenetic relationships and sequence distances between conserved regions extracted from complete coding sequences of each proposed taxon. We propose that the species hepatitis C virus is renamed Hepacivirus C in order to acknowledge its unique historical position and so as to minimise confusion...
September 28, 2016: Journal of General Virology
Douglas J Cattie, Claire E Richardson, Kirthi C Reddy, Elan M Ness-Cohn, Rita Droste, Mary K Thompson, Wendy V Gilbert, Dennis H Kim
The translation initiation factor eIF3 is a multi-subunit protein complex that coordinates the assembly of the 43S pre-initiation complex in eukaryotes. Prior studies have demonstrated that not all subunits of eIF3 are essential for the initiation of translation, suggesting that some subunits may serve regulatory roles. Here, we show that loss-of-function mutations in the genes encoding the conserved eIF3k and eIF3l subunits of the translation initiation complex eIF3 result in a 40% extension in lifespan and enhanced resistance to endoplasmic reticulum (ER) stress in Caenorhabditis elegans...
September 2016: PLoS Genetics
Juan Wang, Lian-Guo Zhang, Ning Li, Ming Lei, Yun Ma, Yuan-Hong Peng, Wei-Hua Bian
OBJECTIVE: To construct a lentivirus vector carrying wheat germ agglutinin (WGA) and evaluate its ability of tracing WGA in the brain of mice with ischemic brain injury. METHODS: WGA gene was inserted into the lentiviral vector Plvx IRES-ZsGreen1 using genetic engineering methods. 293T cells were transfected with the vector and 3 packaging plasmids (RPEV, PRRE, and VSVG) to obtain the recombinant lentivirus for infection of human adipose-derived stem cells (hADSCs)...
August 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Andrei Golovko, Artyom Kojukhov, Bo-Jhih Guan, Benjamin Morpurgo, William C Merrick, Barsanjit Mazumder, Maria Hatzoglou, Anton A Komar
Eukaryotic initiation factor 2A (eIF2A) is a 65-kDa protein that was first identified in the early 1970s as a factor capable of stimulating initiator methionyl-tRNAi (Met-tRNA(Met)i) binding to 40S ribosomal subunits in vitro. However, in contrast to the eIF2, which stimulates Met-tRNA(Met)i binding to 40S ribosomal subunits in a GTP-dependent manner, eIF2A didn't reveal any GTP-dependence, but instead was found to direct binding of the Met-tRNA(Met)i to 40S ribosomal subunits in a codon-dependent manner. eIF2A appears to be highly conserved across eukaryotic species, suggesting conservation of function in evolution...
September 29, 2016: Cell Cycle
Zi Xu, Weijia Sun, Yuheng Li, Shukuan Ling, Chenyang Zhao, Guohui Zhong, Dingsheng Zhao, Jinping Song, Hailin Song, Jinqiao Li, Linhao You, Guangjun Nie, Yanzhong Chang, Yingxian Li
Iron overload inhibits osteoblast function and promotes osteoclastogenesis. Hepcidin plays an important role in this process. The changes in iron content and the regulation of hepcidin under unloading-induced bone loss remain unknown. A hindlimb suspension model was adopted to simulate unloading-induced bone loss in mice. The results showed that iron deposition in both liver and bone was markedly increased in hindlimb unloaded mice, and was accompanied by the upregulation of osteoclast activity and downregulation of osteoblast activity...
September 26, 2016: Bone
Gui-Fang Wang, Bing Qi, Lei-Lei Tu, Lian Liu, Guo-Cheng Yu, Jing-Xiang Zhong
AIM: To construct adenovirus vectors of lumican gene by gateway recombinant cloning technology to further understand the role of lumican gene in myopia. METHODS: Gateway recombinant cloning technology was used to construct adenovirus vectors. The wild-type (wt) and mutant (mut) forms of the lumican gene were synthesized and amplified by polymerase chain reaction (PCR). The lumican cDNA fragments were purified and ligated into the adenovirus shuttle vector pDown-multiple cloning site (MCS)-/internal ribozyme entry site (IRES)/enhanced green fluorescent protein (EGFP)...
2016: International Journal of Ophthalmology
Lubing Gu, Hailong Zhang, Tao Liu, Sheng Zhou, Yuhong Du, Jing Xiong, Sha Yi, Cheng-Kui Qu, Haian Fu, Muxiang Zhou
MDM2 and XIAP are mutually regulated. Binding of MDM2 RING protein to the IRES region on XIAP mRNA results in MDM2 protein stabilization and enhanced XIAP translation. In this study, we developed a protein-RNA fluorescence polarization (FP) assay for high-throughput screening (HTS) of chemical libraries. Our FP-HTS identified eight inhibitors that blocked the MDM2 protein-XIAP RNA interaction, leading to MDM2 degradation. The compound-induced MDM2 downregulation resulted not only in inhibition of XIAP expression, but also in activation of p53, which contributed to cancer cell apoptosis in vitro and inhibition of cancer cell proliferation in vivo...
October 10, 2016: Cancer Cell
Yael Yoffe, Maya David, Rinat Kalaora, Lital Povodovski, Gilgi Friedlander, Ester Feldmesser, Elena Ainbinder, Ann Saada, Shani Bialik, Adi Kimchi
Multiple transcriptional and epigenetic changes drive differentiation of embryonic stem cells (ESCs). This study unveils an additional level of gene expression regulation involving noncanonical, cap-independent translation of a select group of mRNAs. This is driven by death-associated protein 5 (DAP5/eIF4G2/NAT1), a translation initiation factor mediating IRES-dependent translation. We found that the DAP5 knockdown from human ESCs (hESCs) resulted in persistence of pluripotent gene expression, delayed induction of differentiation-associated genes in different cell lineages, and defective embryoid body formation...
September 1, 2016: Genes & Development
Suyashree Bhonsle, Mohammad Bonakdar, Robert E Neal, Charles Aardema, John L Robertson, Jonathon Howarth, Helen Kavnoudias, Kenneth R Thomson, S Nahum Goldberg, Rafael V Davalos
PURPOSE: To develop and validate a perfused organ model for characterizing ablations for irreversible electroporation (IRE)-based therapies. MATERIALS AND METHODS: Eight excised porcine livers were mechanically perfused with a modified phosphate-buffered saline solution to maintain viability during IRE ablation. IRE pulses were delivered using 2 monopolar electrodes over a range of parameters, including voltage (1,875-3,000 V), pulse length (70-100 µsec), number of pulses (50-600), electrode exposure (1...
September 20, 2016: Journal of Vascular and Interventional Radiology: JVIR
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