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https://www.readbyqxmd.com/read/28332719/rs7968606-polymorphism-of-anks1b-is-associated-with-improvement-in-the-panss-general-score-of-schizophrenia-caused-by-amisulpride
#1
Seung-Gul Kang, Ik-Seung Chee, Kwanghun Lee, Jonghun Lee
A recent genome-wide pharmacogenomics study showed that the rs7968606 single-nucleotide polymorphism (SNP) of the ankyrin repeat and sterile alpha motif domain-containing protein 1B (ANKS1B) gene approached the threshold of statistical significance. The aim of this study was to determine the association between the rs7968606 SNP of ANKS1B and the treatment response to amisulpride in schizophrenia patients. In total, 154 participants were enrolled from six university hospitals in Korea. All the subjects were interviewed before and after 6 weeks of amisulpride treatment with the aid of the positive and negative syndrome scale and the clinical global impression-severity scale...
March 23, 2017: Human Psychopharmacology
https://www.readbyqxmd.com/read/28323555/influence-of-dopamine-related-genes-on-neurobehavioral-recovery-after-traumatic-brain-injury-during-early-childhood
#2
Amery Treble-Barna, Shari L Wade, Lisa J Martin, Valentina Pilipenko, Keith Owen Yeates, H Gerry Taylor, Brad G Kurowski
The present study examined the association of dopamine-related genes with short- and long-term neurobehavioral recovery, as well as neurobehavioral recovery trajectories over time, in children who had sustained early childhood traumatic brain injuries (TBI) relative to children who had sustained orthopedic injuries (OI). Participants were recruited from a prospective, longitudinal study evaluating outcomes of children who sustained a TBI (n = 68) or OI (n = 72) between the ages of 3 and 7 years. Parents completed ratings of child executive function and behavior at the immediate post-acute period (0-3 months after injury); 6, 12, and 18 months after injury; and an average of 3...
March 21, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28321389/host-fih-mediated-asparaginyl-hydroxylation-of-translocated-legionella-pneumophila-effectors
#3
Christopher Price, Michael Merchant, Snake Jones, Ashley Best, Juanita Von Dwingelo, Matthew B Lawrenz, Nawsad Alam, Ora Schueler-Furman, Yousef A Kwaik
FIH-mediated post-translational modification through asparaginyl hydroxylation of eukaryotic proteins impacts regulation of protein-protein interaction. We have identified the FIH recognition motif in 11 Legionella pneumophila translocated effectors, YopM of Yersinia, IpaH4.5 of Shigella and an ankyrin protein of Rickettsia. Mass spectrometry analyses of the AnkB and AnkH effectors of L. pneumophila confirm their asparaginyl hydroxylation. Consistent with localization of the AnkB effector to the Legionella-containing vacuole (LCV) membrane and its modification by FIH, our data show that FIH and its two interacting proteins, Mint3 and MT1-MMP are acquired by the LCV in a Dot/Icm type IV secretion-dependent manner...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28320952/identification-of-a-putative-binding-site-critical-for-general-anesthetic-activation-of-trpa1
#4
Hoai T Ton, Thieu X Phan, Ara M Abramyan, Lei Shi, Gerard P Ahern
General anesthetics suppress CNS activity by modulating the function of membrane ion channels, in particular, by enhancing activity of GABAA receptors. In contrast, several volatile (isoflurane, desflurane) and i.v. (propofol) general anesthetics excite peripheral sensory nerves to cause pain and irritation upon administration. These noxious anesthetics activate transient receptor potential ankyrin repeat 1 (TRPA1), a major nociceptive ion channel, but the underlying mechanisms and site of action are unknown...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28319202/evolving-notch-polyq-tracts-reveal-possible-solenoid-interference-elements
#5
Albert J Erives
Polyglutamine (polyQ) tracts in regulatory proteins are extremely polymorphic. As functional elements under selection for length, triplet repeats are prone to DNA replication slippage and indel mutations. Many polyQ tracts are also embedded within intrinsically disordered domains, which are less constrained, fast evolving, and difficult to characterize. To identify structural principles underlying polyQ tracts in disordered regulatory domains, here I analyze deep evolution of metazoan Notch polyQ tracts, which can generate alleles causing developmental and neurogenic defects...
2017: PloS One
https://www.readbyqxmd.com/read/28319008/structure-of-yeast-osbp-related-protein-osh1-reveals-key-determinants-for-lipid-transport-and-protein-targeting-at-the-nucleus-vacuole-junction
#6
Mohammad Kawsar Manik, Huiseon Yang, Junsen Tong, Young Jun Im
Yeast Osh1 belongs to the oxysterol-binding protein (OSBP) family of proteins and contains multiple targeting modules optimized for lipid transport at the nucleus-vacuole junction (NVJ). The key determinants for NVJ targeting and the role of Osh1 at NVJs have remained elusive because of unknown lipid specificities. In this study, we determined the structures of the ankyrin repeat domain (ANK), and OSBP-related domain (ORD) of Osh1, in complex with Nvj1 and ergosterol, respectively. The Osh1 ANK forms a unique bi-lobed structure that recognizes a cytosolic helical segment of Nvj1...
March 10, 2017: Structure
https://www.readbyqxmd.com/read/28317937/identification-of-cancer-associated-missense-mutations-in-hace1-that-impair-cell-growth-control-and-rac1-ubiquitylation
#7
Emilie Andrio, Romain Lotte, Daniel Hamaoui, Jacqueline Cherfils, Anne Doye, Mads Daugaard, Poul H Sorensen, Frédéric Bost, Raymond Ruimy, Amel Mettouchi, Emmanuel Lemichez
The E3 ubiquitin ligase HACE1 is a potent tumor suppressor that controls cell proliferation and ubiquitylates the small GTPase Rac1 to target it to proteasomal degradation. Whether and how the activity of HACE1 is regulated by the N-terminal ankyrin (ANK) and the middle (MID) domains is ill defined. Here, we identified in the version 64 of the Catalogue of Somatic Mutations in Cancer (COSMIC) 13 missense mutations of hace1 located outside the HECT domain, and found that all lead to defective control of cell proliferation...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28303259/sensory-neuron-specific-deletion-of-trpa1-results-in-mechanical-cutaneous-sensory-deficits
#8
Katherine J Zappia, Crystal L O'Hara, Francie Moehring, Kelvin Y Kwan, Cheryl L Stucky
The nonselective cation channel transient receptor potential ankyrin 1 (TRPA1) is known to be a key contributor to both somatosensation and pain. Recent studies have implicated TRPA1 in additional physiologic functions and have also suggested that TRPA1 is expressed in nonneuronal tissues. Thus, it has become necessary to resolve the importance of TRPA1 expressed in primary sensory neurons, particularly since previous research has largely used global knock-out animals and chemical TRPA1 antagonists. We therefore sought to isolate the physiological relevance of TRPA1 specifically within sensory neurons...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28302725/ankyrin-repeat-and-zinc-finger-domain-containing-1-mutations-are-associated-with-infantile-onset-inflammatory-bowel-disease
#9
Désirée Y van Haaften-Visser, Magdalena Harakalova, Enric Mocholi, Joris M van Montfrans, Abdul Elkadri, Ester Rieter, Karoline Fiedler, Peter M van Hasselt, Emily M M Triffaux, Mieke M van Haelst, Isaac J Nijman, Wigard P Kloosterman, Edward E S Nieuwenhuis, Aleixo M Muise, Edwin Cuppen, Roderick H J Houwen, Paul J Coffer
Infantile-onset inflammatory bowel disease (IO IBD) is an invalidating illness with an onset before two years of age and has a complex pathophysiology in which genetic factors are important. Homozygosity mapping and whole exome sequencing in an IO IBD patient and subsequent sequencing of the candidate gene in twelve additional IO IBD patients revealed two patients with two mutated Ankyrin Repeat and Zinc Finger Domain containing 1 (ANKZF1) alleles (homozygous ANKZF1 R585Q mutation and compound heterozygous ANKZF1 E152K and V32_Q87del mutations respectively) and two patients with one mutated ANKZF1 allele...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28291541/evidence-for-a-novel-neurohumoral-antinociceptive-mechanism-mediated-by-peripheral-capsaicin-sensitive-nociceptors-in-conscious-rats
#10
Gábor Pethő, Kata Bölcskei, Réka Füredi, Bálint Botz, Teréz Bagoly, Erika Pintér, János Szolcsányi
Stimulation of capsaicin-sensitive peripheral sensory nerve terminals induces remote anti-inflammatory effects throughout the body of anesthetized rats and guinea-pigs mediated by somatostatin. As somatostatin has also antinociceptive effects, the study aimed at investigating whether similar remote antinociceptive effects can be demonstrated in awake animals. In conscious rats, nociceptive nerve endings of the right hind paw decentralized by cutting the sciatic and saphenous nerves 18h before were chemically stimulated, and drop of the noxious heat threshold (heat hyperalgesia) induced by prior (18h before) plantar incision was measured on the contralateral, left hind paw using an increasing-temperature water bath...
February 10, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28283581/mtcl1-plays-an-essential-role-in-maintaining-purkinje-neuron-axon-initial-segment
#11
Tomoko Satake, Kazunari Yamashita, Kenji Hayashi, Satoko Miyatake, Miwa Tamura-Nakano, Hiroshi Doi, Yasuhide Furuta, Go Shioi, Eriko Miura, Yukari H Takeo, Kunihiro Yoshida, Hiroyuki Yahikozawa, Naomichi Matsumoto, Michisuke Yuzaki, Atsushi Suzuki
The axon initial segment (AIS) is a specialized domain essential for neuronal function, the formation of which begins with localization of an ankyrin-G (AnkG) scaffold. However, the mechanism directing and maintaining AnkG localization is largely unknown. In this study, we demonstrate that in vivo knockdown of microtubule cross-linking factor 1 (MTCL1) in cerebellar Purkinje cells causes loss of axonal polarity coupled with AnkG mislocalization. MTCL1 lacking MT-stabilizing activity failed to restore these defects, and stable MT bundles spanning the AIS were disorganized in knockdown cells...
March 10, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28282454/identification-of-the-essential-protein-domains-for-mib2-function-during-the-development-of-the-drosophila-larval-musculature-and-adult-flight-muscles
#12
Katrin Domsch, Andreas Acs, Claudia Obermeier, Hanh T Nguyen, Ingolf Reim
The proper differentiation and maintenance of myofibers is fundamental to a functional musculature. Disruption of numerous mostly structural factors leads to perturbations of these processes. Among the limited number of known regulatory factors for these processes is Mind bomb2 (Mib2), a muscle-associated E3 ubiquitin ligase, which was previously established to be required for maintaining the integrity of larval muscles. In this study, we have examined the mechanistic aspects of Mib2 function by performing a detailed functional dissection of the Mib2 protein...
2017: PloS One
https://www.readbyqxmd.com/read/28282218/immunotoxins-in-cancer-therapy-review-and-update
#13
Bahman Akbari, Safar Farajnia, Shiva Ahdi Khosroshahi, Fatemeh Safari, Mohammadreza Yousefi, Hassan Dariushnejad, Leila Rahbarnia
Immunotoxins are a novel class of cancer therapeutics that contains a cytotoxic agent fused to a targeting moiety. Various toxic agents from different sources are used in immunotoxin development, including bacterial, plant and human origin cytotoxic elements. Although bacterial and plant-derived toxins are highly toxic and commonly used in immunotoxins, their immunogenicity for human restricted their application in cancer therapy. Here, we discuss the advantages and limitations of bacterial toxins such as Pseudomonas and Diphtheria toxins, plant toxins such as ricin and gelonin, and some endogenous protein of human origin such as RNases and Granzymes...
March 1, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28277613/activation-of-mutated-trpa1-ion-channel-by-resveratrol-in-human-prostate-cancer-associated-fibroblasts-caf
#14
Eric Vancauwenberghe, Lucile Noyer, Sandra Derouiche, Loïc Lemonnier, Pierre Gosset, Laura R Sadofsky, Pascal Mariot, Marine Warnier, Alexandre Bokhobza, Christian Slomianny, Brigitte Mauroy, Jean-Louis Bonnal, Etienne Dewailly, Philippe Delcourt, Laurent Allart, Natalia Prevarskaya, Morad Roudbaraki
Previous studies showed the effects of resveratrol (RES) on several cancer cells, including prostate cancer (PCa) cell apoptosis without taking into consideration the impact of the tumor microenvironment (TME). The TME is composed of cancer cells, endothelial cells, blood cells and cancer-associated fibroblasts (CAF), the main source of growth factors. The latter cells might modify in the TME the impact of RES on tumor cells via secreted factors. Recent data clearly show the impact of CAF on cancer cells apoptosis resistance via secreted factors...
March 9, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28271446/in-vitro-engineered-non-antibody-protein-therapeutics
#15
REVIEW
Rudo Simeon, Zhilei Chen
Antibodies have proved to be a valuable mode of therapy for numerous diseases, mainly owing to their high target binding affinity and specificity. Unfortunately, antibodies are also limited in several respects, chief amongst those being the extremely high cost of manufacture. Therefore, non-antibody binding proteins have long been sought after as alternative therapies. New binding protein scaffolds are constantly being designed or discovered with some already approved for human use by the FDA. This review focuses on protein scaffolds that are either already being used in humans or are currently being evaluated in clinical trials...
March 7, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28266632/specific-cpg-hyper-methylation-leads-to-ankrd26-gene-down-regulation-in-white-adipose-tissue-of-a-mouse-model-of-diet-induced-obesity
#16
Gregory A Raciti, Rosa Spinelli, Antonella Desiderio, Michele Longo, Luca Parrillo, Cecilia Nigro, Vittoria D'Esposito, Paola Mirra, Francesca Fiory, Vincenzo Pilone, Pietro Forestieri, Pietro Formisano, Ira Pastan, Claudia Miele, Francesco Beguinot
Epigenetic modifications alter transcriptional activity and contribute to the effects of environment on the individual risk of obesity and Type 2 Diabetes (T2D). Here, we have estimated the in vivo effect of a fat-enriched diet (HFD) on the expression and the epigenetic regulation of the Ankyrin repeat domain 26 (Ankrd26) gene, which is associated with the onset of these disorders. In visceral adipose tissue (VAT), HFD exposure determined a specific hyper-methylation of Ankrd26 promoter at the -436 and -431 bp CpG sites (CpGs) and impaired its expression...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28265104/mir-285-yki-mask-double-negative-feedback-loop-mediates-blood-brain-barrier-integrity-in-drosophila
#17
Dong Li, Yanling Liu, Chunli Pei, Peng Zhang, Linqing Pan, Jing Xiao, Songshu Meng, Zengqiang Yuan, Xiaolin Bi
The Hippo signaling pathway is highly conserved from Drosophila to mammals and plays a central role in maintaining organ size and tissue homeostasis. The blood-brain barrier (BBB) physiologically isolates the brain from circulating blood or the hemolymph system, and its integrity is strictly maintained to perform sophisticated neuronal functions. Until now, the underlying mechanisms of subperineurial glia (SPG) growth and BBB maintenance during development are not clear. Here, we report an miR-285-Yorkie (Yki)/Multiple Ankyrin repeats Single KH domain (Mask) double-negative feedback loop that regulates SPG growth and BBB integrity...
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28263875/molecular-architecture-of-an-n-formyltransferase-from-salmonella-enterica-o60
#18
Colin R Woodford, James B Thoden, Hazel M Holden
N-formylated sugars are found on the lipopolysaccharides of various pathogenic Gram negative bacteria including Campylobacter jejuni 81116, Francisella tularensis, Providencia alcalifaciens O30, and Providencia alcalifaciens O40. The last step in the biosynthetic pathways for these unusual sugars is catalyzed by N-formyltransferases that utilize N(10)-formyltetrahydrofolate as the carbon source. The substrates are dTDP-linked amino sugars with the functional groups installed at either the C-3' or C-4' positions of the pyranosyl rings...
March 2, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/28241082/modeling-of-the-axon-membrane-skeleton-structure-and-implications-for-its-mechanical-properties
#19
Yihao Zhang, Krithika Abiraman, He Li, David M Pierce, Anastasios V Tzingounis, George Lykotrafitis
Super-resolution microscopy recently revealed that, unlike the soma and dendrites, the axon membrane skeleton is structured as a series of actin rings connected by spectrin filaments that are held under tension. Currently, the structure-function relationship of the axonal structure is unclear. Here, we used atomic force microscopy (AFM) to show that the stiffness of the axon plasma membrane is significantly higher than the stiffnesses of dendrites and somata. To examine whether the structure of the axon plasma membrane determines its overall stiffness, we introduced a coarse-grain molecular dynamics model of the axon membrane skeleton that reproduces the structure identified by super-resolution microscopy...
February 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28239353/transient-receptor-potential-ankyrin-1-channel-expression-on-peripheral-blood-leukocytes-from-rheumatoid-arthritic-patients-and-correlation-with-pain-and-disability
#20
Ione Pereira, Saulo J F Mendes, Domingos M S Pereira, Thayanne F Muniz, Valderlane L P Colares, Cinara R A V Monteiro, Mahiba M R de S Martins, Marcos A G Grisotto, Valério Monteiro-Neto, Sílvio G Monteiro, João B Calixto, Susan D Brain, Elizabeth S Fernandes
Patients with rheumatoid arthritis (RA) suffer from pain and joint disability. The transient receptor potential ankyrin 1 (TRPA1) channel expressed on sensory neurones and non-neuronal cells mediates pain transduction and inflammation and it has been implicated in RA. However, there is little information on the contribution of TRPA1 for human disease. Here, we investigated the expression of TRPA1 on peripheral blood leukocytes and the circulating levels of its endogenous activators 4-hydroxynonenal (4-HNE) and hydrogen peroxide (H2O2) in RA patients treated or not with the anti-rheumatic leflunomide (LFN) or the anti-TNFα adalimumab (ADA)...
2017: Frontiers in Pharmacology
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