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https://www.readbyqxmd.com/read/28938164/multifunctional-superparamagnetic-nanoparticles-conjugated-with-fluorescein-labeled-designed-ankyrin-repeat-protein-as-an-efficient-her2-targeted-probe-in-breast-cancer
#1
Dong-Li Li, Jian-Er Tan, Ying Tian, Shun Huang, Peng-Hui Sun, Meng Wang, Yan-Jiang Han, Hong-Sheng Li, Hu-Bing Wu, Xing-Mei Zhang, Yi-Kai Xu, Quan-Shi Wang
Based on the discordance of human epidermal growth factor receptor-2 (HER2) expression between primary and metastatic/recurrent breast cancer, HER2 molecular imaging, which had potential to systemically assess and dynamically monitor HER2 expression, might improve the selection of patients for anti-HER2 therapy. In this study, designed ankyrin repeat protein (DARPin) G3, a novel binding protein with picomolar affinity for HER2, was used and multifunctional superparamagnetic nanoparticles modified with fluorescein-5-maleimide-labeled DARPin G3 (SPIO-G3-5MF) were developed for HER2 imaging...
September 8, 2017: Biomaterials
https://www.readbyqxmd.com/read/28935134/sites-contributing-to-trpa1-activation-by-the-anesthetic-propofol-identified-by-photoaffinity-labeling
#2
Kellie A Woll, Kenneth A Skinner, Eleonora Gianti, Natarajan V Bhanu, Benjamin A Garcia, Vincenzo Carnevale, Roderic G Eckenhoff, Rachelle Gaudet
In addition to inducing anesthesia, propofol activates a key component of the pain pathway, the transient receptor potential ankyrin 1 ion channel (TRPA1). Recent mutagenesis studies suggested a potential activation site within the transmembrane domain, near the A-967079 cavity. However, mutagenesis cannot distinguish between protein-based and ligand-based mechanisms, nor can this site explain the complex modulation by propofol. Thus more direct approaches are required to reveal potentially druggable binding sites...
September 19, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28931666/trpa1-activation-in-a-human-sensory-neuronal-model-relevance-to-cough-hypersensitivity
#3
Rebecca Clarke, Kevin Monaghan, Imad About, Caoimhin S Griffin, Gerard P Sergeant, Ikhlas El Karim, J Graham McGeown, S Louise Cosby, Timothy M Curtis, Lorcan P McGarvey, Fionnuala T Lundy
The cough reflex becomes hyperresponsive in acute and chronic respiratory diseases, but understanding the underlying mechanism is hampered by difficulty accessing human tissue containing both nerve endings and neuronal cell bodies. We refined an adult stem cell sensory neuronal model to overcome the limited availability of human neurones and applied the model to study transient receptor potential ankyrin 1 (TRPA1) channel expression and activation.Human dental pulp stem cells (hDPSCs) were differentiated towards a neuronal phenotype, termed peripheral neuronal equivalents (PNEs)...
September 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28925718/interaction-analysis-between-blk-rs13277113-polymorphism-and-bank1-rs3733197-polymorphism-mmel1-tnfrsf14-rs3890745-polymorphism-in-determining-susceptibility-to-rheumatoid-arthritis
#4
Hua Huang, Si-Chao Huang, Dong-Jin Hua, Qing-Qing Sun, Han Cen, Xia-Fei Xin
Two pairwise genetic interactions (B cell lymphocyte kinase (BLK) rs13277113,B cell scaffold protein with ankyrin repeats 1 (BANK1) rs3733197and BLK rs13277113 membrane metalloendopeptidase like 1 (MMEL1)/ tumor necrosis factor receptor superfamily member 14 (TNFRSF14) rs3890745) have been demonstrated in determining susceptibility to rheumatoid arthritis (RA) without replication, thus this study was performed to examine whether abovementioned genetic polymorphisms were associated with RA and further tests were performed to see whether aforementioned genetic interactions existed in RA among Chinese population...
September 19, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28924205/the-multifunctional-polydnavirus-tnbvank1-protein-impact-on-host-apoptotic-pathway
#5
Rosanna Salvia, Gerarda Grossi, Angela Amoresano, Carmen Scieuzo, Marisa Nardiello, Chiara Giangrande, Ilaria Laurenzana, Vitalba Ruggieri, Sabino A Bufo, S Bradleigh Vinson, Monica Carmosino, David Neunemann, Heiko Vogel, Pietro Pucci, Patrizia Falabella
Toxoneuron nigriceps (Hymenoptera, Braconidae) is an endophagous parasitoid of the larval stages of the tobacco budworm, Heliothis virescens (Lepidoptera, Noctuidae). The bracovirus associated with this wasp (TnBV) is currently being studied. Several genes expressed in parasitised host larvae have been isolated and their possible roles partly elucidated. TnBVank1 encodes an ankyrin motif protein similar to insect and mammalian IκB, an inhibitor of the transcription nuclear factor κB (NF-κB). Here we show that, when TnBVank1 was stably expressed in polyclonal Drosophila S2 cells, apoptosis is induced...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28922860/structural-plasticity-of-synaptopodin-in-the-axon-initial-segment-during-visual-cortex-development
#6
Annabelle Schlüter, Domenico Del Turco, Thomas Deller, Annika Gutzmann, Christian Schultz, Maren Engelhardt
The axon initial segment (AIS) is essential for action potential generation. Recently, the AIS was identified as a site of neuronal plasticity. A subpopulation of AIS in cortical principal neurons contains stacks of endoplasmic reticulum (ER) forming the cisternal organelle (CO). The function of this organelle is poorly understood, but roles in local Ca2+-trafficking and AIS plasticity are discussed. To investigate whether the presence and/or the size of COs are linked to the development and maturation of AIS of cortical neurons, we analyzed the relationship between COs and the AIS during visual cortex development under control and visual deprivation conditions...
September 1, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28912869/association-of-ank1-variants-with-new-onset-type-2-diabetes-in-a-han-chinese-population-from-northeast-china
#7
Lulu Sun, Xuelong Zhang, Tongtong Wang, Meijun Chen, Hong Qiao
Previous studies have identified three loci (rs4737009, rs515071 and rs516946) in ankyrin 1 (ANK1) that are associated with type 2 diabetes mellitus (T2DM) in a number of ethnic groups. However, the impact of single nucleotide polymorphisms (SNPs) of ANK1 on T2DM in a Han Chinese population from northeast China has not yet been studied. The present study was undertaken to investigate the relationship between the ANK1 gene and new-onset T2DM in northeastern China. Three widely studied variants were genotyped and analyzed for T2DM susceptibility in 1,962 Chinese subjects (996 with T2DM and 966 healthy controls)...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28904196/vaccinia-virus-encodes-a-novel-inhibitor-of-apoptosis-that-associates-with-the-apoptosome
#8
Melissa R Ryerson, Monique M Richards, Marc Kvansakul, Christine J Hawkins, Joanna L Shisler
Apoptosis is an important anti-viral host defense mechanism. Here we report the identification of a novel apoptosis inhibitor encoded by the vaccinia virus (VACV) M1L gene. M1L is absent in the attenuated MVA strain of VACV, a strain that stimulates apoptosis in several types of immune cells. M1 expression increased the viability of MVA-infected THP-1 and Jurkat cells and reduced several biochemical hallmarks of apoptosis such as PARP-1 and procaspase-3 cleavage. Furthermore, ectopic M1L expression decreased staurosporine-induced (intrinsic) apoptosis in HeLa cells...
September 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28900390/genetically-driven-enhancement-of-dopaminergic-transmission-affects-moral-acceptability-in-females-but-not-in-males-a-pilot-study
#9
Silvia Pellegrini, Sara Palumbo, Caterina Iofrida, Erika Melissari, Giuseppina Rota, Veronica Mariotti, Teresa Anastasio, Andrea Manfrinati, Rino Rumiati, Lorella Lotto, Michela Sarlo, Pietro Pietrini
Moral behavior has been a key topic of debate for philosophy and psychology for a long time. In recent years, thanks to the development of novel methodologies in cognitive sciences, the question of how we make moral choices has expanded to the study of neurobiological correlates that subtend the mental processes involved in moral behavior. For instance, in vivo brain imaging studies have shown that distinct patterns of brain neural activity, associated with emotional response and cognitive processes, are involved in moral judgment...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28894181/rigidly-connected-multispecific-artificial-binders-with-adjustable-geometries
#10
Yufan Wu, Alexander Batyuk, Annemarie Honegger, Fabian Brandl, Peer R E Mittl, Andreas Plückthun
Multivalent binding proteins can gain biological activities beyond what is inherent in the individual binders, by bringing together different target molecules, restricting their conformational flexibility or changing their subcellular localization. In this study, we demonstrate a method to build up rigid multivalent and multispecific scaffolds by exploiting the modular nature of a repeat protein scaffold and avoiding flexible linkers. We use DARPins (Designed Ankyrin Repeat Proteins), synthetic binding proteins based on the Ankyrin-repeat protein scaffold, as binding units...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28894008/genetic-disruption-of-ankyrin-g-in-adult-mouse-forebrain-causes-cortical-synapse-alteration-and-behavior-reminiscent-of-bipolar-disorder
#11
Shanshan Zhu, Zachary A Cordner, Jiali Xiong, Chi-Tso Chiu, Arabiye Artola, Yanning Zuo, Andrew D Nelson, Tae-Yeon Kim, Natalya Zaika, Brian M Woolums, Evan J Hess, Xiaofang Wang, De-Maw Chuang, Mikhail M Pletnikov, Paul M Jenkins, Kellie L Tamashiro, Christopher A Ross
Genome-wide association studies have implicated the ANK3 locus in bipolar disorder, a major human psychotic illness. ANK3 encodes ankyrin-G, which organizes the neuronal axon initial segment (AIS). We generated a mouse model with conditional disruption of ANK3 in pyramidal neurons of the adult forebrain (Ank-G cKO). This resulted in the expected loss of pyramidal neuron AIS voltage-gated sodium and potassium channels. There was also dramatic loss of markers of afferent GABAergic cartridge synapses, resembling the cortical microcircuitry changes in brains from psychotic patients, and suggesting disinhibition...
September 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28884307/the-role-of-the-transient-receptor-potential-ankyrin-type-1-trpa1-channel-in-migraine-pain-evaluation-in-an-animal-model
#12
Chiara Demartini, Cristina Tassorelli, Anna Maria Zanaboni, Germana Tonsi, Oscar Francesconi, Cristina Nativi, Rosaria Greco
BACKGROUND: Clinical and experimental studies have pointed to the possible involvement of the transient receptor potential ankyrin type-1 (TRPA1) channels in migraine pain. In this study, we aimed to further investigate the role of these channels in an animal model of migraine using a novel TRPA1 antagonist, ADM_12, as a probe. METHODS: The effects of ADM_12 on nitroglycerin-induced hyperalgesia at the trigeminal level were investigated in male rats using the quantification of nocifensive behavior in the orofacial formalin test...
September 7, 2017: Journal of Headache and Pain
https://www.readbyqxmd.com/read/28882895/peptide-array-based-screening-reveals-a-large-number-of-proteins-interacting-with-the-ankyrin-repeat-domain-of-the-zdhhc17-s-acyltransferase
#13
Kimon Lemonidis, Ruth MacLeod, George S Baillie, Luke H Chamberlain
zDHHC S-acyl-transferases are enzymes catalyzing protein S-acylation, a common post-translational modification on proteins frequently affecting their membrane targeting and trafficking. The ankyrin-repeat (AR) domain of zDHHC17 (HIP14) and zDHHC13 (HIP14L) S-acyltransferases, which is involved in both substrate recruitment and S-acylation-independent functions, was recently shown to bind at least six proteins, by specific recognition of a consensus sequence in them. To further refine the rules governing binding to the AR of zDHHC17, we employed peptide arrays based on zDHHC AR-binding motif (zDABM) sequences of synaptosomal-associated protein 25 (SNAP25) and cysteine string protein alpha (CSPα)...
September 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28861035/molecular-disorganization-of-axons-adjacent-to-human-cortical-microinfarcts
#14
Hamza Coban, Spencer Tung, Bryan Yoo, Harry V Vinters, Jason D Hinman
Cortical microinfarcts (CMIs) are microscopically identified wedge-shaped ischemic lesions that occur at or near the cortical surface and result from occlusion of penetrating arterioles. These microscopic lesions can be observed with high-resolution magnetic resonance imaging in aging brains and in patients with cerebrovascular disease. Recent studies have suggested that strategically located microinfarcts strongly correlate with cognitive deficits, which can contribute to Alzheimer's disease as well as other forms of dementia...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28854834/drd2-and-ankk1-genes-associate-with-late-onset-heroin-dependence-in-men
#15
Chang-Chih Tsou, Han-Wei Chou, Pei-Shen Ho, Shin-Chang Kuo, Chun-Yen Chen, Chang-Chih Huang, Chih-Sung Liang, Ru-Band Lu, San-Yuan Huang
OBJECTIVES: Dopamine plays an important role in reward system of heroin dependence (HD), and dopaminergic D2 receptor (DRD2) gene is a candidate for the etiology of HD. Ankyrin repeat and kinase domain containing 1 (ANKK1) gene is proximal to DRD2 and may influence its expression. We explored whether DRD2 and ANKK1 associate with occurrence of HD, and whether the genetic variants influence personality traits in male patients with HD. METHODS: DRD2/ANKK1 polymorphisms were analyzed in 950 unrelated Han Chinese male participants (601 HD patients and 349 healthy controls)...
August 31, 2017: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/28851514/a-novel-calcium-independent-phospholipase-a2-and-its-physiological-roles-in-development-and-immunity-of-a-lepidopteran-insect-spodoptera-exigua
#16
Md Sadekuzzaman, Neelam Gautam, Yonggyun Kim
Phospholipase A2 (PLA2) catalyzes hydrolysis of ester linkage at sn-2 position of phospholipids. At least 15 groups (I-XV) of PLA2 gene superfamily are associated with various physiological processes such as digestion, secretion, immunity, and maintenance of membrane integrity. This study suggests that various insects encode putative Group VI PLA2s representing intracellular and calcium-independent PLA2s (iPLA2). These insect iPLA2s are separated into at least two subgroups: iPLA2A (Group VIA-like) and iPLA2B (non-Group VIA)...
August 26, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28845027/dibutyl-phthalate-rather-than-monobutyl-phthalate-facilitates-contact-hypersensitivity-to-fluorescein-isothiocyanate-in-a-mouse-model
#17
Kohta Kurohane, Kota Sekiguchi, Erina Ogawa, Masato Tsutsumi, Yasuyuki Imai
Dibutyl phthalate (DBP) is a plasticizer used for many consumer products including cosmetics. Potential health concerns regarding DBP include reproductive and developmental toxicity, endocrine disruption and neurotoxicity. DBP is a high priority chemical as to reduction of exposure of children to it. Through reproductive toxicity studies, monobutyl phthalate (MBP) has been proposed to be the active metabolite derived from DBP. We previously demonstrated that DBP activates transient receptor potential ankyrin 1 (TRPA1) cation channels expressed on sensory neurons...
August 26, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28841137/autoinhibition-of-ankyrin-b-g-membrane-target-bindings-by-intrinsically-disordered-segments-from-the-tail-regions
#18
Keyu Chen, Jianchao Li, Chao Wang, Zhiyi Wei, Mingjie Zhang
Ankyrins together with their spectrin partners are the master organizers of micron-scale membrane domains in diverse tissues. The 24 ankyrin (ANK) repeats of ankyrins bind to numerous membrane proteins, linking them to spectrin-based cytoskeletons at specific membrane microdomains. The accessibility of the target binding groove of ANK repeats must be regulated to achieve spatially defined functions of ankyrins/target complexes in different tissues, though little is known in this regard. Here we systemically investigated the autoinhibition mechanism of ankyrin-B/G by combined biochemical, biophysical and structural biology approaches...
August 25, 2017: ELife
https://www.readbyqxmd.com/read/28836328/the-mns-glycophorin-variant-gp-mur-affects-differential-erythroid-expression-of-rh-rhag-transcripts
#19
K Hsu, M-S Kuo, C-C Yao, H-C Cheng, H-J Lin, Y-S Chan, M Lin
BACKGROUND: The band 3 macrocomplex (also known as the ankyrin-associated complex) on the red cell membrane comprises two interacting subcomplexes: a band 3/glycophorin A subcomplex, and a Rh/RhAG subcomplex. Glycophorin B (GPB) is a component of the Rh/RhAG subcomplex that is also structurally associated with glycophorin A (GPA). Expression of glycophorin B-A-B hybrid GP.Mur enhances band 3 expression and is associated with lower levels of Rh-associated glycoprotein (RhAG) and Rh polypeptides...
August 24, 2017: Vox Sanguinis
https://www.readbyqxmd.com/read/28825979/covalent-coupling-of-high-affinity-ligands-to-the-surface-of-viral-vector-particles-by-protein-trans-splicing-mediates-cell-type-specific-gene-transfer
#20
Alexander Muik, Johanna Reul, Thorsten Friedel, Anke Muth, Karen Patricia Hartmann, Irene C Schneider, Robert C Münch, Christian J Buchholz
We have established a novel approach for the covalent coupling of large polypeptides to the surface of fully assembled adeno-associated viral gene transfer vector (AAV) particles via split-intein mediated protein-trans-splicing (PTS). This way, we achieved selective gene transfer to distinct cell types. Single-chain variable fragments (scFvs) or designed ankyrin repeat proteins (DARPins), exhibiting high-affinity binding to cell surface receptors selectively expressed on the surface of target cells, were coupled to AAV particles harboring mutations in the capsid proteins which ablate natural receptor usage...
July 25, 2017: Biomaterials
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