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Sahishna Phaniraj, Zhe Gao, Digamber Rane, Blake R Peterson
The endoplasmic reticulum (ER) of eukaryotic cells plays critical roles in the processing of secreted and transmembrane proteins. Defects in these functions are associated with a wide range of pathologies. To image this organelle, cells are often treated with fluorescent ER-Tracker dyes. Although these compounds are selective, existing red fluorescent probes of the ER are costly glibenclamide derivatives that inhibit ER-associated sulphonylurea receptors. To provide simpler and more cost-effective red fluorescent probes of the ER, we synthesized amino analogues of the fluorophore resorufin...
December 2016: Dyes and Pigments: An International Journal
Jonatan Enk, Assi Levi, Yiska Weisblum, Rachel Yamin, Yoav Charpak-Amikam, Dana G Wolf, Ofer Mandelboim
Herpes simplex virus 1 (HSV1) is a ubiquitous human pathogen that utilizes variable mechanisms to evade immune surveillance. The glycosylphosphatidylinositol (GPI) anchoring pathway is a multistep process in which a myriad of different proteins are covalently attached to a GPI moiety to be presented on the cell surface. Among the different GPI-anchored proteins there are many with immunological importance. We present evidence that the HSV1-encoded miR H8 directly targets PIGT, a member of the protein complex that covalently attaches proteins to GPI in the final step of GPI anchoring...
October 18, 2016: Cell Reports
Yang Cheng, Feng Lu, Bo Wang, Jian Li, Jin-Hee Han, Daisuke Ito, Deok-Hoon Kong, Lubin Jiang, Jian Wu, Kwon-Soo Ha, Eizo Takashima, Jetsumon Sattabongkot, Jun Cao, Myat Htut Nyunt, Myat Phone Kyaw, Sanjay A Desai, Louis H Miller, Takafumi Tsuboi, Eun-Taek Han
Plasmodium vivax, a major agent of malaria in both temperate and tropical climates, has been thought to be unable to infect humans lacking the Duffy (Fy) blood group antigen because this receptor is critical for erythrocyte invasion. Recent surveys in various endemic regions, however, have reported P. vivax infections in Duffy-negative individuals, suggesting that the parasite may utilize alternative receptor-ligand pairs to complete the erythrocyte invasion. Here, we identified and characterized a novel parasite ligand, Plasmodium vivax GPI-anchored micronemal antigen (PvGAMA), that bound human erythrocytes regardless of Duffy antigen status...
October 19, 2016: Scientific Reports
Mikkel M Schoos, Giuseppe De Luca, George D Dangas, Peter Clemmensen, Girma Minalu Ayele, Roxana Mehran, Gregg W Stone
AIMS: In the HORIZONS-AMI trial, bivalirudin compared to unfractionated heparin (UFH) plus a glycoprotein IIb/IIIa inhibitor (GPI) improved net clinical outcomes in patients undergoing primary percutaneous coronary intervention (PCI) at the cost of an increased rate of acute stent thrombosis. We sought to examine whether these effects are dependent on time to treatment. METHODS AND RESULTS: The interaction between anticoagulation regimen and symptom onset to first balloon inflation time (SBT) on the 30-day and three-year rates of major adverse cardiac events (MACE) was examined in 3,199 randomised patients according to SBT ≤3 hours versus >3 hours...
October 20, 2016: EuroIntervention
Isabelle Beaulieu-Boire, Camila C Aquino, Alfonso Fasano, Yu-Yan Poon, Melanie Fallis, Antony E Lang, Mojgan Hodaie, Suneil K Kalia, Andres Lozano, Elena Moro
BACKGROUND: Rare causes of inherited movement disorders often present with a debilitating phenotype of dystonia, sometimes combined with parkinsonism and other neurological signs. Since these disorders are often resistant to medications, DBS may be considered as a possible treatment. METHODS: Patients with identified genetic diseases (ataxia-telangiectasia, chorea-achantocytosis, dopa-responsive dystonia, congenital nemaline myopathy, methylmalonic aciduria, neuronal ceroid lipofuscinosis, spinocerebellar ataxia types 2 and 3, Wilson's disease, Woodhouse-Sakati syndrome, methylmalonic aciduria, and X trisomy) and disabling dystonia underwent bilateral GPi DBS (bilateral thalamic Vim nucleus in 1 case)...
October 4, 2016: Brain Stimulation
Leo Verhagen Metman, Gian Pal, Konstantin Slavin
Deep brain stimulation is now an established therapy for Parkinson's disease, and DBS continues to be refined. Well-established targets, such as the STN and GPi, have shown clear benefit in reducing motor complications in PD, and other more novel targets, such as PPN are being explored. Furthermore, there have been advances in imaging which allow for improved lead placement and also can reduce patient discomfort. The way electrical current is delivered through the DBS lead is also undergoing a transformation, allowing for more options regarding current shaping, steering, and new stimulation paradigms...
November 2016: Current Treatment Options in Neurology
Joohi Jimenez-Shahed, Ilknur Telkes, Ashwin Viswanathan, Nuri F Ince
Background: Deep brain stimulation (DBS) is an emerging treatment strategy for severe, medication-refractory Tourette syndrome (TS). Thalamic (Cm-Pf) and pallidal (including globus pallidus interna, GPi) targets have been the most investigated. While the neurophysiological correlates of Parkinson's disease (PD) in the GPi and subthalamic nucleus (STN) are increasingly recognized, these patterns are not well characterized in other disease states. Recent findings indicate that the cross-frequency coupling (CFC) between beta band and high frequency oscillations (HFOs) within the STN in PD patients is pathologic...
2016: Frontiers in Neuroscience
Ning Yu, Yaping Liang, Xinxiang Peng, Xuewen Hou
BACKGROUND: ROOT UV-B SENSITIVE (RUS) genes exist in most eukaryotic organisms, and encode proteins that contain a DUF647 (domain of unknown function 647). Although the RUS genes are known to play essential roles in Arabidopsis seedling development, their precise functions are not well understood in other plants, including rice. FINDINGS: In this study, six OsRUS genes were cloned from rice root and leaf cDNA libraries. Our analysis showed that the sequence and open reading frame of cloned OsRUS3 cDNA differs from the predictions reported in the RAP-DB and RGAP databases...
December 2016: Rice
Siamak Redhai, Josephine E E U Hellberg, Mark Wainwright, Sumeth W Perera, Felix Castellanos, Benjamin Kroeger, Carina Gandy, Aaron Leiblich, Laura Corrigan, Thomas Hilton, Benjamin Patel, Shih-Jung Fan, Freddie Hamdy, Deborah C I Goberdhan, Clive Wilson
Regulated secretion by glands and neurons involves release of signalling molecules and enzymes selectively concentrated in dense-core granules (DCGs). Although we understand how many secretagogues stimulate DCG release, how DCG biogenesis is then accelerated to replenish the DCG pool remains poorly characterised. Here we demonstrate that each prostate-like secondary cell (SC) in the paired adult Drosophila melanogaster male accessory glands contains approximately ten large DCGs, which are loaded with the Bone Morphogenetic Protein (BMP) ligand Decapentaplegic (Dpp)...
October 2016: PLoS Genetics
Omid Talakoub, Bogdan Neagu, Kaviraja Udupa, Eric Tsang, Robert Chen, Milos R Popovic, Willy Wong
We are interested in characterizing how brain networks interact and communicate with each other during voluntary movements. We recorded electrical activities from the globus pallidus pars interna (GPi), subthalamic nucleus (STN) and the motor cortex during voluntary wrist movements. Seven patients with dystonia and six patients with Parkinson's disease underwent bilateral deep brain stimulation (DBS) electrode placement. Local field potentials from the DBS electrodes and scalp EEG from the electrodes placed over the motor cortices were recorded while the patients performed externally triggered and self-initiated movements...
October 11, 2016: Scientific Reports
Yoshiko Murakami
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired GPI deficiency caused by somatic mutation of the PIGA gene in one or several hematopoietic stem cells. Recently, PNH caused by somatic mutation of one allele of the PIGT gene in combination with a germline mutation of the other allele was reported, showing that PIGA is not the only gene responsible for PNH, though other causes are rare. These mutant cells become GPI deficient, expand clonally and differentiate into all of the hematopoietic lineages. When GPI deficient erythrocytes increase in proportion, massive hemolysis occurs due to activated complement attack during infection...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Anna Castrioto, Odeya Marmor, Marc Deffains, Dafna Willner, Eduard Linetsky, Hagai Bergman, Zvi Israel, Renana Eitan, David Arkadir
Classical rate models of basal ganglia circuitry associate discharge rate of the globus pallidus external and internal segments (GPe, GPi respectively) solely with dopaminergic state and predict an inverse ratio between the discharge rates of the two pallidal segments. In contrast, the effects of other rate modulators such as general anesthesia (GA) on this ratio have been ignored. To respond to this need, we recorded the neuronal activity in the GPe and GPi in awake and anesthetized human patients with dystonia (57 and 53 trajectories respectively) and in awake patients with Parkinson's disease (PD, 16 trajectories) undergoing deep brain stimulation procedures...
September 26, 2016: European Journal of Neuroscience
Xiangyu Yao, Jian Wu, Meng Lin, Wenxiang Sun, Xiao He, Channe Gowda, Silvia Bolland, Carole A Long, Rongfu Wang, Xin-Zhuan Su
Both type I interferon (IFN-I) and CD40 play a significant role in various infectious diseases, including malaria and autoimmune disorders. CD40 is mostly known to function in adaptive immunity, but previous observations of elevated CD40 levels early after malaria infection of mice led us to investigate its roles in innate IFN-I responses and disease control. Using a Plasmodium yoelii nigeriensis N67 and C57BL/6 mouse model, we showed that infected CD40-/- mice had reduced STING and serum IFN-β levels day-2 post infection, higher day-4 parasitemia, and earlier deaths...
October 2016: PLoS Pathogens
Pengfei Wang, Dattatray A Devalankar, Qipu Dai, Ping Zhang, Suzanne M Michalek
Three QS-21-based vaccine adjuvant candidates with a terminal-functionalized side chain incorporated in the west wing trisaccharide have been synthesized. The terminal polar functional group serve to increase the solubility of these analogs in water. Two of the synthetic analogs have been shown to have adjuvant activity comparable to that of GPI-0100. The stand-alone adjuvant activity of the new synthetic analogs again confirmed that it is a feasible way to develop new saponin-based vaccine adjuvants through derivatizing at the west wing branched trisaccharide domain...
October 6, 2016: Journal of Organic Chemistry
David B Hood, Karin R Snyder, Tammy R Buckner, Beth L Hurley, Kelly R Pitts, Luis R Lopez
OBJECTIVE: The routine measurement of IgA anticardiolipin (aCL) and IgA anti-β2 glycoprotein I (anti-β2 GPI) antibodies remain controversial despite several studies demonstrating an association with thromboembolic disease in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). This controversy may be a contributing factor for the current under use of IgA antiphospholipid antibodies. We aimed to investigate the nature of discrepant IgA anti-β2 GPI reactivity to help define the diagnostic value of IgA antiphospholipid antibodies...
December 2015: Eur J Rheumatol
Erwin B Montgomery
Theories impact the movement disorders clinic, not only affecting the development of new therapies but determining how current therapies are used. Models are theories that are procedural rather than declarative. Theories and models are important because, as argued by Kant, one cannot know the thing-in-itself (das Ding an sich) and only a model is knowable. Further, biological variability forces higher level abstraction relevant for all variants. It is that abstraction that is raison d'être of theories and models...
2016: Frontiers in Human Neuroscience
Wei Liu, Zui Zou, Xin Huang, Hui Shen, Li Juan He, Si Min Chen, Li Ping Li, Lan Yan, Shi Qun Zhang, Jun Dong Zhang, Zheng Xu, Guo Tong Xu, Mao Mao An, Yuan Ying Jiang
Glycosylphosphatidyl inositol anchored proteins (GPI-APs) on fungal cell wall are essential for invasive infections. While the function of inositol deacylation of GPI-APs in mammalian cells has been previously characterized the impact of inositol deacylation in fungi and implications to host infection remains largely unexplored. Herein we describe our identification of BST1, an inositol deacylase of GPI-Aps in Candida albicans, was critical for GPI-APs cell wall attachment and host infection. BST1-deficient C...
October 6, 2016: Scientific Reports
Simon Edvardson, Yoshiko Murakami, Thi Tuyet Mai Nguyen, Maher Shahrour, Anik St-Denis, Avraham Shaag, Nadira Damseh, Françoise Le Deist, Yenan Bryceson, Bassam Abu-Libdeh, Philippe M Campeau, Taroh Kinoshita, Orly Elpeleg
BACKGROUND: Of our 1400 exome-studied patients, 67% originate from consanguineous families. ∼80% suffer from variable degree of intellectual disability (ID). The search for disease causing genes using homozygosity mapping was progressing slowly until 2010, then markedly accelerated by the introduction of exome analysis. OBJECTIVES: To identify the disease causing mutation(s) in three patients from two unrelated families who suffered from global developmental delay, severe ID and drug-responsive seizure disorder...
September 30, 2016: Journal of Medical Genetics
Emanuel Staudt, Pathmanaban Ramasamy, Helmut Plattner, Martin Simon
Phospholipase C (PLC) is an important enzyme of signal transduction pathways by generation of second messengers from membrane lipids. PLCs are also indicated to cleave glycosylphosphatidylinositol (GPI)-anchors of surface proteins thus releasing these into the environment. However, it remains unknown whether this enzymatic activity on the surface is due to distinct PLC isoforms in higher eukaryotes. Ciliates have, in contrast to other unicellular eukaryotes, multiple PLC isoforms as mammals do. Thus, Paramecium represents a perfect model to study subcellular distribution and potential surface activity of PLC isoforms...
September 29, 2016: Biochimica et Biophysica Acta
Laura Cif, Philippe Coubes
BACKGROUND: Heterogeneous by the underlying pathobiology and clinical presentation, childhood onset dystonia is most frequently progressive, with related disability and limitations in functions of daily living. Consequently, there is an obvious need for efficient symptomatic therapies. METHODS AND RESULTS: Following lesional surgery to basal ganglia (BG) and thalamus, deep brain stimulation (DBS) is a more conservative and adjustable intervention to and validated for internal segment of the globus pallidus (GPi), highly efficient in treating isolated "primary" dystonia and associated symptoms such as subcortical myoclonus...
September 7, 2016: European Journal of Paediatric Neurology: EJPN
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