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https://www.readbyqxmd.com/read/27911898/bilaterian-giant-ankyrins-have-a-common-evolutionary-origin-and-play-a-conserved-role-in-patterning-the-axon-initial-segment
#1
Timothy Jegla, Michelle M Nguyen, Chengye Feng, Daniel J Goetschius, Esteban Luna, Damian B van Rossum, Bishoy Kamel, Aditya Pisupati, Elliott S Milner, Melissa M Rolls
In vertebrate neurons, the axon initial segment (AIS) is specialized for action potential initiation. It is organized by a giant 480 Kd variant of ankyrin G (AnkG) that serves as an anchor for ion channels and is required for a plasma membrane diffusion barrier that excludes somatodendritic proteins from the axon. An unusually long exon required to encode this 480Kd variant is thought to have been inserted only recently during vertebrate evolution, so the giant ankyrin-based AIS scaffold has been viewed as a vertebrate adaptation for fast, precise signaling...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27908969/synthesis-and-evaluation-of-the-new-estrogen-receptor-%C3%AE-selective-radioligand-18f-fhnp-comparison-with-18f-fes
#2
Inês F Antunes, Aren van Waarde, Rudi A Dierckx, Elisabeth G E de Vries, Geke A P Hospers, Erik F de Vries
: Estrogen receptors (ER) are targets for endocrine treatment of estrogen-dependent cancers. The ER consists of 2 isoforms, ERα and ERβ, which have distinct biological functions. While activation of ERα stimulates cell proliferation and cell survival, ERβ promotes apoptosis. Positron emission tomography (PET) of ERα and ERβ levels could provide more insight in response to hormonal treatment. 16α-(18)F-Fluoro-17β-estradiol ((18)F-FES) is a PET tracer for ER with relative selectivity for ERα...
December 1, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27903899/human-mitochondrial-transcription-factors-tfam-and-tfb2m-work-synergistically-in-promoter-melting-during-transcription-initiation
#3
Aparna Ramachandran, Urmimala Basu, Shemaila Sultana, Divya Nandakumar, Smita S Patel
Human mitochondrial DNA is transcribed by POLRMT with the help of two initiation factors, TFAM and TFB2M. The current model postulates that the role of TFAM is to recruit POLRMT and TFB2M to melt the promoter. However, we show that TFAM has 'post-recruitment' roles in promoter melting and RNA synthesis, which were revealed by studying the pre-initiation steps of promoter binding, bending and melting, and abortive RNA synthesis. Our 2-aminopurine mapping studies show that the LSP (Light Strand Promoter) is melted from -4 to +1 in the open complex with all three proteins and from -4 to +3 with addition of ATP...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27902373/feline-coronavirus-replication-is-affected-by-both-cyclophilin-a-and-cyclophilin-b
#4
Yoshikazu Tanaka, Yuka Sato, Takashi Sasaki
Feline coronavirus (FCoV) causes the fatal disease feline infectious peritonitis (FIP), which is currently incurable by drug treatment, and no effective vaccines are available. Cyclosporin A (CsA), a cyclophilin (Cyp) inhibitor, inhibits the replication of FCoV in vitro and in vivo as well as the replication of human and animal coronaviruses (CoVs). However, the mechanism underlying the regulation of CoV replication by CsA is unknown. In this study, we analyzed the role of Cyps in FCoV replication using knockdown (KD) and knockout (KO) cells specific to Cyps...
November 21, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27902325/targeting-naturally-occurring-epitope-variants-of-hepatitis-c-virus-with-high-affinity-t-cell-receptors
#5
Huajun Zhang, Jianbing Zhang, Lei Chen, Zhiming Weng, Ye Tian, Haifeng Zhao, Youjia Li, Lin Chen, Zhaoduan Liang, Hongjun Zheng, Wenzhuo Zhao, Shi Zhong, Yi Li
Hepatitis C virus (HCV) readily establishes chronic infection, which is characterized by failure of virus-specific CD8+ T cells. HCV uses epitope mutation and T-cell exhaustion to escape from the host immune response. Previously, we engineered high-affinity T-cell receptors (HATs) targeting HIV escape mutants. In this study, the affinity of a T-cell receptor specific for the human leukocyte antigen (HLA)-A2-restricted HCV immunodominant epitope NS3 1406-1415 (KLVALGINAV) was improved from a KD of 6.6 µM to 40 pM...
November 11, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27899882/tumor-metabolism-the-ketogenic-diet-and-%C3%AE-hydroxybutyrate-novel-approaches-to-adjuvant-brain-tumor-therapy
#6
REVIEW
Eric C Woolf, Nelofer Syed, Adrienne C Scheck
Malignant brain tumors are devastating despite aggressive treatments such as surgical resection, chemotherapy and radiation therapy. The average life expectancy of patients with newly diagnosed glioblastoma is approximately ~18 months. It is clear that increased survival of brain tumor patients requires the design of new therapeutic modalities, especially those that enhance currently available treatments and/or limit tumor growth. One novel therapeutic arena is the metabolic dysregulation that results in an increased need for glucose in tumor cells...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27899593/the-kdm5-family-is-required-for-activation-of-pro-proliferative-cell-cycle-genes-during-adipocyte-differentiation
#7
Ann-Sofie B Brier, Anne Loft, Jesper G S Madsen, Thomas Rosengren, Ronni Nielsen, Søren F Schmidt, Zongzhi Liu, Qin Yan, Hinrich Gronemeyer, Susanne Mandrup
The KDM5 family of histone demethylases removes the H3K4 tri-methylation (H3K4me3) mark frequently found at promoter regions of actively transcribed genes and is therefore generally considered to contribute to corepression. In this study, we show that knockdown (KD) of all expressed members of the KDM5 family in white and brown preadipocytes leads to deregulated gene expression and blocks differentiation to mature adipocytes. KDM5 KD leads to a considerable increase in H3K4me3 at promoter regions; however, these changes in H3K4me3 have a limited effect on gene expression per se...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899299/catalytic-kinetic-and-thermodynamic-properties-of-stabilized-bacillus-stearothermophilus-alkaline-protease
#8
Mohamed A Abdel-Naby, Samia A Ahmed, Hala R Wehaidy, Said A El-Mahdy
Bacillus stearothermophilus alkaline protease was conjugated to several oxidized polysaccharides of different chemical structure. The conjugates were evaluated for the kinetic and thermodynamic stability. The conjugated enzyme with oxidized pectin had the highest retained activity (79.5%) and the highest half-life (T1/2) at 50°C and pH 9.0. Compared to the native protease, the conjugated preparation exhibited lower activation energy (Ea), lower deactivation constant rate (kd), higher T1/2, and higher D values (decimal reduction time) within the temperature range of 50-60 °C...
November 26, 2016: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27899266/dna-aptamers-against-foki-nuclease-domain-for-genome-editing-applications
#9
Maui Nishio, Daisuke Matsumoto, Yoshio Kato, Koichi Abe, Jinhee Lee, Kaori Tsukakoshi, Ayana Yamagishi, Chikashi Nakamura, Kazunori Ikebukuro
Genome editing with site-specific nucleases (SSNs) can modify only the target gene and may be effective for gene therapy. The main limitation of genome editing for clinical use is off-target effects; excess SSNs in the cells and their longevity can contribute to off-target effects. Therefore, a controlled delivery system for SSNs is necessary. FokI nuclease domain (FokI) is a common DNA cleavage domain in zinc finger nuclease (ZFN) and transcription activator-like effector nuclease. Previously, we reported a zinc finger protein delivery system that combined aptamer-fused, double-strand oligonucleotides and nanoneedles...
November 22, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27897272/analysis-of-the-interaction-of-calcitriol-with-the-disulfide-isomerase-erp57
#10
Elisa Gaucci, Domenico Raimondo, Caterina Grillo, Laura Cervoni, Fabio Altieri, Giulio Nittari, Margherita Eufemi, Silvia Chichiarelli
Calcitriol, the active form of vitamin D3, can regulate the gene expression through the binding to the nuclear receptor VDR, but it can also display nongenomic actions, acting through a membrane-associated receptor, which has been discovered as the disulfide isomerase ERp57. The aim of our research is to identify the binding sites for calcitriol in ERp57 and to analyze their interaction. We first studied the interaction through bioinformatics and fluorimetric analyses. Subsequently, we focused on two protein mutants containing the predicted interaction domains with calcitriol: abb'-ERp57, containing the first three domains, and a'-ERp57, the fourth domain only...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27893416/the-effect-of-fc%C3%AE-riia-and-fc%C3%AE-riib-on-coronary-artery-lesion-formation-and-intravenous-immunoglobulin-treatment-responses-in-children-with-kawasaki-disease
#11
Ling-Sai Chang, Mao-Hung Lo, Sung-Chou Li, Ming-Yu Yang, Kai-Sheng Hsieh, Ho-Chang Kuo
Previous research has found patients with the FcγRIIIB NA1 variant having increased risk of intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD). Our previous studies revealed that elevated FcγRIIA expression correlated with the susceptibility of KD patients. We conducted this research to determine whether and how Fcγ receptors affect the susceptibility, IVIG treatment response, and coronary artery lesions (CAL) of KD patients. The activating FcγRIIA and inhibitory FcγRIIB methylation levels of seven patients with KD and four control subjects were examined using HumanMethylation27 BeadChip...
November 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27893356/single-stranded-dna-aptamer-targeting-and-neutralization-of-anti-d-alloantibody-a-potential-therapeutic-strategy-for-haemolytic-diseases-caused-by-rhesus-alloantibody
#12
Yinze Zhang, Fan Wu, Manni Wang, Naibao Zhuang, Huayou Zhou, Hua Xu
BACKGROUND: Rhesus (Rh) D antigen is the most important antigen in the Rh blood group system because of its strong immunogenicity. When RhD-negative individuals are exposed to RhD-positive blood, they may produce anti-D alloantibody, potentially resulting in delayed haemolytic transfusion reactions and Rh haemolytic disease of the foetus and newborn, which are difficult to treat. Inhibition of the binding of anti-D antibody with RhD antigens on the surface of red blood cells may effectively prevent immune haemolytic diseases...
November 11, 2016: Blood Transfusion, Trasfusione del Sangue
https://www.readbyqxmd.com/read/27891685/the-dna-aptamer-binds-stemness-enriched-cancer-cells-in-pancreatic-cancer
#13
Yoon-Jin Kim, Hee Seung Lee, Dawoon E Jung, Jeong Mi Kim, Si Young Song
Pancreatic cancer remains one of the most common and lethal cancers. Most patients (80%) present with inoperable advanced pancreatic cancer at initial diagnosis, and their early diagnosis is a significant unmet challenge. Recent studies indicate that cancer, including pancreatic cancer, is initiated and propagated by cancer stem cells (CSCs). CSCs are responsible not only for the pathogenesis of cancer but also for the heterogeneity, malignant degree, anticancer therapy resistance, and recurrence of tumors...
November 28, 2016: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/27890614/structural-insights-into-the-binding-of-lauric-acid-to-cyp107l2-from-streptomyces-avermitilis
#14
Songhee Han, Tan-Viet Pham, Joo-Hwan Kim, Young-Ran Lim, Hyoung-Goo Park, Dabin Jeong, Chul-Ho Yun, Young-Jin Chun, Lin-Woo Kang, Donghak Kim
Streptomyces avermitilis is an actinobacterium known to produce clinically useful macrolides including avermectins. CYP107L2 from S. avermitilis shares a high sequence similarity with the PikC (CYP107L1) from S. venezuelae. To elucidate the structural features of CYP107L2, we conducted biochemical and structural characterization of CYP107L2 from S. avermitilis. The CYP107L2 gene was cloned, and its recombinant protein was expressed and purified. The CYP107L2 showed a low-spin state of heme, and the reduced form yielded the CO difference spectra with a maximal absorption at 449 nm...
November 25, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27888841/nmr-in-drug-discovery-a-practical-guide-to-identification-and-validation-of-ligands-interacting-with-biological-macromolecules
#15
REVIEW
Alvar D Gossert, Wolfgang Jahnke
Protein-ligand interactions are at the heart of drug discovery research. NMR spectroscopy is an excellent technology to identify and validate protein-ligand interactions. A plethora of NMR methods are available which are powerful, robust and information-rich, but also have pitfalls and limitations. In this review, we will focus on how to choose between different experiments, and assess their strengths and liabilities. We introduce the concept of the validation cross, which helps to categorize experiments according to their information content and to simplify the choice of the right experiment in order to address a specific question...
November 2016: Progress in Nuclear Magnetic Resonance Spectroscopy
https://www.readbyqxmd.com/read/27886148/extraction-of-opuntia-dillenii-haw-polysaccharides-and-their-antioxidant-activities
#16
Heng Li, Qingxia Yuan, Xianjiao Zhou, Fuhua Zeng, Xiangyang Lu
Use of natural polysaccharides in medicine and food has wide interest in research. In this study, we extracted and purified some polysaccharides from cactus Opuntia dillenii Haw. (ODP). Some preliminary functions of these products were characterized. Under the optimal purification conditions, the yield of ODP extracted from the 2-4 month-old Opuntia dillenii Haw. (T-ODP) was 30.60% ± 0.40%, higher than that of ODP from the 5-10 month-old materials (O-ODP) (18.97% ± 0.58%). The extracted ODP was purified by DEAE sepharose fast flow anion exchange and Sephacryl S-400 chromatography with four fractions obtained (ODP-Ia, ODP-Ib, ODP-IIa and ODP-IIb)...
November 24, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27883257/determining-the-binding-affinities-of-prostate-specific-antigen-to-lectins-spr-and-microarray-approaches
#17
Pavel Damborský, Martina Zámorová, Jaroslav Katrlík
Prostate cancer (PCa) is one of the most common newly diagnosed cancer among men and we focused on its traditional biomarker, prostate-specific antigen (PSA), using targeted glycomics-based strategies. The aberrant glycosylation pattern of PSA may serve as valuable tool for improving PCa diagnosis including its early-stage. In the present work we evaluated the usability of two techniques, surface plasmon resonance and protein microarray assay, for the study and characterization of interactions of PSA (both free and complexed) with 6 lectins (SNA, ConA, RCA, AAL, WGA and MAA II)...
November 24, 2016: Proteomics
https://www.readbyqxmd.com/read/27883077/tgf-beta-receptor-ii-interacting-protein-1-an-intracellular-protein-has-an-extracellular-role-as-a-modulator-of-matrix-mineralization
#18
Amsaveni Ramachandran, Sriram Ravindran, Chun-Chieh Huang, Anne George
Transforming growth factor beta receptor II interacting protein 1 (TRIP-1), a predominantly intracellular protein is localized in the ECM of bone. TRIP-1 lacks a signal peptide, therefore, in this study, we provide evidence that intracellular TRIP-1 can be packaged and exported to the ECM via exosomes. Overexpression of TRIP-1 in MC3T3-E1 cells resulted in increased matrix mineralization during differentiation and knockdown resulted in reduced effects. In vivo function of TRIP-1 was studied by an implantation assay performed using TRIP-1 overexpressing and knockdown cells cultured in a 3-dimmensional scaffold...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27881680/structures-and-short-linear-motif-of-disordered-transcription-factor-regions-provide-clues-to-the-interactome-of-the-cellular-hub-radical-induced-cell-death1
#19
Charlotte O'Shea, Lasse Staby, Sidsel Krogh Bendsen, Frederik Grønbæk Tidemand, Andreas Redsted, Martin Willemoës, Birthe B Kragelund, Karen Skriver
Intrinsically disordered protein regions (IDRs) lack a well-defined three-dimensional structure, but often facilitate key protein functions. Some interactions between IDRs and folded protein domains rely on short linear motifs (SLiMs). These motifs are challenging to identify, but once found can point to larger networks of interactions, such as with proteins that serve as hubs for essential cellular functions. The stress-associated plant protein Radical-Induced Cell Death1 (RCD1) is one such hub, interacting with many transcription factors via their flexible IDRs...
November 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27881485/visualization-of-ligand-induced-gi-protein-activation-in-chemotaxing-cells
#20
Kazuyuki Masuda, Jun-Ichi Kitakami, Tohru Kozasa, Tatsuhiko Kodama, Sigeo Ihara, Takao Hamakubo
Cell migration to chemoattractants is critically important in both normal physiology and the pathogenesis of many diseases. In GPCR-mediated chemotaxis, GPCRs transduce the gradient of an extracellular chemotactic ligand into intracellular responses via the activation of heterotrimeric G proteins. However, ligand-induced G protein activation has not been directly imaged as yet in mammalian chemotaxing cells. We developed a Förster resonance energy transfer (FRET) probe (R10-Gi) by linking the Gi protein α subunit to the regulator of G protein signaling domain...
November 23, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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