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Novel Stimulant

Nicole Groh, Christian Seutter von Loetzen, Brinda Subbarayal, Christian Möbs, Lothar Vogel, Andreas Hoffmann, Kay Fötisch, Anna Koutsouridou, Stefanie Randow, Elke Völker, Andreas Reuter, Paul Rösch, Stefan Vieths, Wolfgang Pfützner, Barbara Bohle, Dirk Schiller
BACKGROUND: Allergen-specific immunotherapy (AIT) with birch pollen generates Bet v 1-specific immunoglobulin (Ig)G4 which blocks IgE-mediated hypersensitivity mechanisms. Whether IgG4 specific for Bet v1a competes with IgE for identical epitopes or whether novel epitope specificities of IgG4 antibodies are developed is under debate. OBJECTIVE: We sought to analyze the epitope specificities of IgE and IgG4 antibodies from sera of patients who received AIT. METHODS: 15 sera of patients (13/15 received AIT) with Bet v 1a-specific IgE and IgG4 were analyzed...
October 22, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
X-N Ma, C-X Ma, W-G Shi, J Zhou, H-P Ma, Y-H Gao, C J Xian, K-M Chen
OBJECTIVE: Icaritin, one effective metabolite of Herba Epimedii-derived flavonoid icariin, has a strong osteogenic activity. However, its action mechanism remains unclear. Since primary cilia have been shown to play a pivotal role in regulating the osteogenesis, we hypothesized primary cilia are indispensable in mediating icaritin osteogenic effect. MATERIALS AND METHODS: Primary rat calvarial osteoblasts were transfected with siRNA1 targeting intraflagellar transport protein 88 (IFT88), a protein required for ciliogenesis, to prevent formation of primary cilium and were treated with 10(-6) M icaritin...
October 21, 2016: Journal of Endocrinological Investigation
Fraser Henderson, Istvan Takacs
BACKGROUND: Troubleshooting of deep brain stimulators (Activa SC/PC/RC Medtronic PLC) sometimes results in a decision to replace a tunneled stretch-coil extension cable. We present a simple technique to accomplish this atraumatically without a tunneling tool. OBJECTIVES: In the treatment of patients with deep brain stimulators, complication avoidance and efficiency of operative time are paramount. We sought to find the most safe, effective, and rapid method for performing the conceptually-simple yet technically-nuanced act of replacing lead extension cables...
October 18, 2016: World Neurosurgery
Yufeng Li, Zheng Li, Dan Wang, Xiang Zhang, Jia Li, Sher Ali, Jingze Lu, Hao Zong, Xiaolan Xu
Insulin-stimulated GLUT4 translocation from GLUT4 storage vesicles (GSVs) to the plasma membrane (PM) constitutes a key process for blood glucose control. Therefore, compounds that could promote GLUT4 translocation into the PM represent potential drugs for the treatment of diabetes. In this research, we screened for agonists that induce GLUT4 translocation by using a novel pH-sensitive fluorescent probe, insulin-regulated aminopeptidase (IRAP)-mOrange2. We identified as well as validated one agonist, staurosporine, from a 64,000 compound library...
October 18, 2016: Biochemical and Biophysical Research Communications
Katharina Grundler, Raffaela Rotter, Sloane Tilley, Joachim Pircher, Thomas Czermak, Mustaf Yakac, Erik Gaitzsch, Steffen Massberg, Florian Krötz, Hae-Young Sohn, Ulrich Pohl, Hanna Mannell, Bjoern F Kraemer
INTRODUCTION: Platelets possess critical hemostatic functions in the system of thrombosis and hemostasis, which can be affected by a multitude of external factors. Previous research has shown that platelets have the capacity to synthesize proteins de novo and more recently a multicatalytic protein complex, the proteasome, has been discovered in platelets. Due to its vital function for cellular integrity, the proteasome has become a therapeutic target for anti-proliferative drug therapies in cancer...
October 13, 2016: Thrombosis Research
Lars Marstaller, Hana Burianová, David C Reutens
Safety learning describes the ability to learn that certain cues predict the absence of a dangerous or threatening event. Although incidental observations of activity within the default mode network (DMN) during the processing of safety cues have been reported previously, there is as yet no evidence demonstrating that the DMN plays a functional rather than a corollary role in safety learning. Using functional magnetic resonance imaging and a Pavlovian fear conditioning and extinction paradigm, we investigated the neural correlates of danger and safety learning...
October 21, 2016: Human Brain Mapping
Isabel Huang-Doran, Patsy Tomlinson, Felicity Payne, Alexandra Gast, Alison Sleigh, William Bottomley, Julie Harris, Allan Daly, Nuno Rocha, Simon Rudge, Jonathan Clark, Albert Kwok, Stefano Romeo, Emma McCann, Barbara Müksch, Mehul Dattani, Stefano Zucchini, Michael Wakelam, Lazaros C Foukas, David B Savage, Rinki Murphy, Stephen O'Rahilly, Inês Barroso, Robert K Semple
Obesity-related insulin resistance is associated with fatty liver, dyslipidemia, and low plasma adiponectin. Insulin resistance due to insulin receptor (INSR) dysfunction is associated with none of these, but when due to dysfunction of the downstream kinase AKT2 phenocopies obesity-related insulin resistance. We report 5 patients with SHORT syndrome and C-terminal mutations in PIK3R1, encoding the p85α/p55α/p50α subunits of PI3K, which act between INSR and AKT in insulin signaling. Four of 5 patients had extreme insulin resistance without dyslipidemia or hepatic steatosis...
October 20, 2016: JCI Insight
Angel Lareo, Caroline G Forlim, Reynaldo D Pinto, Pablo Varona, Francisco de Borja Rodriguez
Closed-loop activity-dependent stimulation is a powerful methodology to assess information processing in biological systems. In this context, the development of novel protocols, their implementation in bioinformatics toolboxes and their application to different description levels open up a wide range of possibilities in the study of biological systems. We developed a methodology for studying biological signals representing them as temporal sequences of binary events. A specific sequence of these events (code) is chosen to deliver a predefined stimulation in a closed-loop manner...
2016: Frontiers in Neuroinformatics
Peixin Dong, Ying Xiong, Hidemichi Watari, Sharon Jb Hanley, Yosuke Konno, Kei Ihira, Fumihiko Suzuki, Takahiro Yamada, Masataka Kudo, Junming Yue, Noriaki Sakuragi
Derepression of wild-type p53 by suppressing its negative inhibitor iASPP (Inhibitor of apoptosis-stimulating protein of p53) represents a potential therapeutic option for cervical cancer (CC). Here, we reported a novel functional significance of iASPP upregulation in cervical tumorigenesis: iASPP acts as a key promoter of CC cell proliferation, epithelial-mesenchymal transition, invasion and cancer stemness, by interacting with p53 to suppress p53-mediated transcription of target genes and reducing p53-responsive microRNA-34a levels...
October 21, 2016: Scientific Reports
Paul R Territo, Jill A Meyer, Jonathan S Peters, Amanda A Riley, Brian P McCarthy, Mingzhang Gao, Min Wang, Mark A Green, Qi-Huang Zheng, Gary D Hutchins
BACKGROUND: The P2X7 receptor represents a novel molecular target for imaging neuroinflammation via PET. GSK1482160, a potent P2X7 receptor antagonist, has high receptor affinity, blood-brain barrier penetration, and has been recently radiolabel ((11)C-GSK1482160). Therefore, we report the initial physical and biological characterization of this novel ligand. METHODS: (11)C-GSK1482160 synthesis was according to published methods. Cell density studies were performed in human embryonic kidney cell lines expressing human P2X7 receptors (HEK293-hP2X7R) and analyzed by western blot analysis, immuno-fluorescence assay (IFA), and radiologic-immunohistochemistry (RIHC) using P2X7R polyclonal antibodies...
October 20, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Justin D La Favor, Gabriel S Dubis, Huimin Yan, Joseph D White, Margaret A M Nelson, Ethan J Anderson, Robert C Hickner
OBJECTIVE: The objectives of this study were to determine the impact of in vivo reactive oxygen species (ROS) on microvascular endothelial function in obese human subjects and the efficacy of an aerobic exercise intervention on alleviating obesity-associated dysfunctionality. APPROACH AND RESULTS: Young, sedentary men and women were divided into lean (body mass index 18-25; n=14), intermediate (body mass index 28-32.5; n=13), and obese (body mass index 33-40; n=15) groups...
October 20, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Kotaro Horiguchi, Takashi Nakakura, Saishu Yoshida, Takehiro Tsukada, Naoko Kanno, Rumi Hasegawa, Shu Takigami, Shunji Ohsako, Takako Kato, Yukio Kato
Contact-dependent (juxtacrine) signaling is important for local cell-to-cell interaction and has received attention in recent years regarding its role in pituitary function, differentiation, and development. This study investigated one of the juxtacrine-related molecules, thymocyte differentiation antigen 1 (THY1), in the anterior lobe of the rat pituitary gland. Western blot analysis revealed expression of the THY1 protein in the adult rat anterior lobe. We also found that the THY1 ligand, integrin-β2 (ITGB2), is also expressed in the pituitary gland...
October 17, 2016: Biochemical and Biophysical Research Communications
Uday B Maachani, Uma Shankavaram, Tamalee Kramp, Philip J Tofilon, Kevin Camphausen, Anita T Tandle
Glioblastoma multiforme (GBM) continues to be the most frequently diagnosed and lethal primary brain tumor. Adjuvant chemo-radiotherapy remains the standard of care following surgical resection. In this study, using reverse phase protein arrays (RPPAs), we assessed the biological effects of radiation on signaling pathways to identify potential radiosensitizing molecular targets. We identified subsets of proteins with clearly concordant/discordant behavior between irradiated and non-irradiated GBM cells in vitro and in vivo...
October 14, 2016: Oncotarget
Yuan Ren, Nan Ji, Xixiong Kang, Renzhi Wang, Wenbin Ma, Zhenjun Hu, Xingfeng Liu, Yajie Wang
Glioblastoma is a highly vascularized brain tumor that causes high mortality. Kininogen-1 (KNG1) has demonstrated both tumor suppressor and antiangiogenesis properties in gliobastoma cells. We analyzed the microarray and proteomic profiles of tumor tissues from glioblastoma patients (N = 180), and identified potential RNA regulators of the KNG1. Validation experiments in U87 glioblastoma cells showed that the regulation of KNG1 by CTU1, KIAA1274, and RAX was mediated by miR-138. The siRNA-mediated knockdown of CTU1, KIAA1274, or RAX in U87 cells and immortalized human endothelial cells (iHECs) significantly reduced KNG1 expression (P < 0...
October 14, 2016: Oncotarget
Kenji Sugawara, Kohei Honda, Yoshie Reien, Norihide Yokoi, Chihiro Seki, Harumi Takahashi, Kohtaro Minami, Ichiro Mori, Akio Matsumoto, Haruaki Nakaya, Susumu Seino
Insulin secretagogues are used for treatment of type 2 diabetes. We attempted to discover novel small molecules to stimulate insulin secretion by using in silico similarity search using sulfonylureas as query, followed by measurement of insulin secretion. Among 38 compounds selected by in silico similarity search, we found three diphenylsemicarbazides and one quinolone that stimulate insulin secretion. We focused on compound 8 (C8), which had the strongest insulin-secreting effect. Based on the structure-activity relationship of C8-derivatives, we identified diphenylthiosemicarbazide (DSC) 108 as the most potent secretagogue...
2016: PloS One
Satsuki Nishigaki, Takashi Hamazaki, Keinosuke Fujita, Shuntaro Morikawa, Toshihiro Tajima, Haruo Shintaku
BACKGROUND: Hemizygous mutations in the<i> immunoglobulin superfamily member 1 (IGSF1) </i>gene have been demonstrated to cause congenital central hypothyroidism in males. We report one family with a novel mutation of the<i> IGSF1 </i>gene located on the long arm of the X chromosome. PATIENT FINDINGS: A two-month-old boy was diagnosed with central hypothyroidism because of prolonged jaundice. A thyrotropin releasing hormone (TRH) stimulation test indicated dysfunction in both the hypothalamus and the pituitary gland and prompted us to analyze the<i> IGSF1 </i>gene...
October 20, 2016: Thyroid: Official Journal of the American Thyroid Association
Megan Allen, Suhasini Ghosh, Gerard P Ahern, Sonia Villapol, Kathleen A Maguire-Zeiss, Katherine Conant
Matrix metalloproteinases (MMPs) are a family of secreted endopeptidases expressed by neurons and glia. Regulated MMP activity contributes to physiological synaptic plasticity, while dysregulated activity can stimulate injury. Disentangling the role individual MMPs play in synaptic plasticity is difficult due to overlapping structure and function as well as cell-type specific expression. Here, we develop a novel system to investigate the selective overexpression of a single MMP driven by GFAP expressing cells in vivo...
October 20, 2016: Scientific Reports
David S Freedman, Joseph B Schroeder, Gregory I Telian, Zhengyang Zhang, Smrithi Sunil, Jason T Ritt
OBJECTIVE: Behavioral neuroscience studies in freely moving rodents require small, light-weight implants to facilitate neural recording and stimulation. Our goal was to develop an integrated package of 3D printed parts and assembly aids for labs to rapidly fabricate, with minimal training, an implant that combines individually positionable microelectrodes, an optical fiber, zero insertion force (ZIF-clip) headstage connection, and secondary recording electrodes, e.g. for electromyography (EMG)...
October 20, 2016: Journal of Neural Engineering
Jungmin Seo, Jee Hye Wee, Jeong Hoan Park, Pona Park, Jeong-Whun Kim, Sung June Kim
OBJECTIVE: A novel nerve cuff electrode with embedded magnets was fabricated and developed. In this study, a pair of magnets was fully embedded and encapsulated in a liquid crystal polymer (LCP) substrate to utilize magnetic force in order to replace the conventional installing techniques of cuff electrodes. In vitro and in vivo experiments were conducted to evaluate the feasibility of the magnet-embedded nerve cuff electrode (MENCE). Lastly, several issues pertaining to the MENCE such as the cuff-to-nerve diameter ratio, the force of the magnets, and possible concerns were discussed in the discussion section...
October 20, 2016: Journal of Neural Engineering
Cyril G Eleftheriou, Jonas B Zimmermann, Henrik D Kjeldsen, Moshe David-Pur, Yael Hanein, Evelyne Sernagor
The choice of electrode material is of paramount importance in neural prosthetic devices. Electrodes must be biocompatible yet able to sustain repetitive current injections in a highly corrosive environment. We explored the suitability of carbon nanotube (CNT) electrodes to stimulate retinal ganglion cells (RGCs) in a mouse model of outer retinal degeneration. We investigated morphological changes at the bio-hybrid interface and changes in RGC responses to electrical stimulation following prolonged in vitro coupling to CNT electrodes...
October 11, 2016: Biomaterials
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