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Saima Zafar, Neelam Younas, Nadeem Sheikh, Waqas Tahir, Mohsin Shafiq, Matthias Schmitz, Isidre Ferrer, Olivier Andréoletti, Inga Zerr
A high priority in the prion field is to identify pre-symptomatic events and associated profile of molecular changes. In this study, we demonstrate the pre-symptomatic dysregulation of cytoskeleton assembly and its associated cofilin-1 pathway in strain and brain region-specific manners in MM1 and VV2 subtype-specific Creutzfeldt-Jakob disease at clinical and pre-clinical stage. At physiological level, PrP(C) interaction with cofilin-1 and phosphorylated form of cofilin (p-cofilin(Ser3)) was investigated in primary cultures of mouse cortex neurons (PCNs) of PrP(C) wild-type and knockout mice (PrP(-/-))...
June 1, 2017: Molecular Neurobiology
Shilpa M Kendre, Khushbu D Agrawal, Suresh K Kangane, Anand S Ambekar
Orthodontic alignment of ectopically placed incisors or canines can be challenging and time consuming. A variety of techniques are used to align such palatally or lingually placed teeth including indirect ties with ligature wires, E-chains, piggy-back methods. This article presents two case reports to describe an effective technique using 'slingshot' method. It is a relatively simple and rapid method which is operator friendly and easily tolerated by the patients.
April 2017: Journal of Clinical and Diagnostic Research: JCDR
Yifat Brill-Karniely, Fan Jin, Gerard C L Wong, Daan Frenkel, Jure Dobnikar
Pseudomonas aeruginosa move across surfaces by using multiple Type IV Pili (TFP), motorized appendages capable of force generation via linear extension/retraction cycles, to generate surface motions collectively known as twitching motility. Pseudomonas cells arrive at a surface with low levels of piliation and TFP activity, which both progressively increase as the cells sense the presence of a surface. At present, it is not clear how twitching motility emerges from these initial minimal conditions. Here, we build a simple model for TFP-driven surface motility without complications from viscous and solid friction on surfaces...
April 10, 2017: Scientific Reports
Piyali Majumder, Kasturi Roy, Brijesh Kumar Singh, Nihar Ranjan Jana, Debashis Mukhopadhyay
Alzheimer's disease (AD) manifests as neuronal loss. On the premise of Grb2 overexpression in AD mouse brain and brain tissues of AD patients, our study primarily focuses on the stability of cytoskeletal proteins in the context of degenerative AD-like conditions. Two predominant molecular features of AD, extracellular accumulation of β-amyloid oligomers and intracellular elevation of amyloid precursor protein intracellular domain levels, have been used to closely inspect the series of signalling events. In their presence, multiple signalling pathways involving ROCK and PAK1 proteins lead to disassembly of the cytoskeleton, and Grb2 partially counterbalances the cytoskeletal loss...
May 1, 2017: Disease Models & Mechanisms
Seon Young Lee, Wooil Kim, Young Geun Lee, Hyo Jin Kang, Sang-Hyun Lee, Sun Young Park, Jeong-Ki Min, Sang-Rae Lee, Sang J Chung
Phospho-cofilin (p-cofilin), which has a phosphate group on Ser-3, is involved in actin polymerization. Its dephosphorylated form promotes filopodia formation and cell migration by enhancing actin depolymerization. Protein phosphatase slingshot homologs (SSHs), known as dual-specificity phosphatases, catalyze hydrolytic removal of the Ser-3 phosphate group from phospho-cofilin. Aberrant SSH activity results in cancer metastasis, implicating SSHs as potential therapeutic targets for cancer metastasis. In this study, we screened 658 natural products purified from traditional oriental medicinal plants to identify three potent SSH inhibitors with submicromolar or single-digit micromolar Ki values: gossypol, hypericin, and sennoside A...
May 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Myung-Whan Suh, Jae Hong Park, Seong Il Kang, Jae Hyun Lim, Moo Kyun Park, Seong Keun Kwon
OBJECTIVES: The aim of this study was to quantitatively measure the tightness of the goggle strap during the video head impulse test (vHIT) and to identify slippage-induced artifacts according to tightness. We aimed to elucidate the mechanism of faulty gain caused by goggle slippage and explain the typical artifacts associated with it. SUBJECTS AND METHODS: An endotracheal tube cuff manometer was coupled to the EyeSeeCam vHIT system (Interacoustics, Assens, Denmark) to monitor strap tightness...
January 2017: Otology & Neurotology
Katsunori Takahashi, Haruka Okabe, Shin-Ichiro Kanno, Tomoaki Nagai, Kensaku Mizuno
Slingshot-1 (SSH1) is a protein phosphatase that specifically dephosphorylates and activates cofilin, an F-actin-severing protein. SSH1 binds to and co-localizes with F-actin, and the cofilin-phosphatase activity of SSH1 is markedly increased by binding to F-actin. In this study, we performed a secondary structure analysis of SSH1, which predicted the existence of a pleckstrin homology (PH)-like domain in the N-terminal region of SSH1. SSH1 also contains a DEK-C domain in the N-terminal region. The N-terminal fragment of SSH1 bound to and co-localized with F-actin, but mutation at Arg-96 or a Leu-His-Lys (LHK) motif in the PH-like domain reduced this activity...
January 22, 2017: Biochemical and Biophysical Research Communications
Per M Arvidsson, Johannes Töger, Marcus Carlsson, Katarina Steding-Ehrenborg, Gianni Pedrizzetti, Einar Heiberg, Håkan Arheden
Intracardiac blood flow is driven by hemodynamic forces that are exchanged between the blood and myocardium. Previous studies have been limited to 2D measurements or investigated only left ventricular (LV) forces. Right ventricular (RV) forces and their mechanistic contribution to asymmetric redirection of flow in the RV have not been measured. We therefore aimed to quantify 3D hemodynamic forces in both ventricles in a cohort of healthy subjects, using magnetic resonance imaging 4D flow measurements. Twenty five controls, 14 elite endurance athletes, and 2 patients with LV dyssynchrony were included...
February 1, 2017: American Journal of Physiology. Heart and Circulatory Physiology
Gleb Konotop, Elena Bausch, Tomoaki Nagai, Andrey Turchinovich, Natalia Becker, Axel Benner, Michael Boutros, Kensaku Mizuno, Alwin Krämer, Marc Steffen Raab
Centrosome amplification is a hallmark of virtually all types of cancers, including solid tumors and hematologic malignancies. Cancer cells with extra centrosomes use centrosome clustering (CC) to allow for successful division. Because normal cells do not rely on this mechanism, CC is regarded as a promising target to selectively eradicate cells harboring supernumerary centrosomes. To identify novel inhibitors of CC, we developed a cell-based high-throughput screen that reports differential drug cytotoxicity for isogenic cell populations with different centrosome contents...
September 13, 2016: Cancer Research
Nikolaj Hjort Schmidt, Poul Edling
Acute splenic rupture can be a life-threatening condition which needs immediate attention. We report a case where parenchymal splenic lesions and subcapsular haematoma were developed after a patient was being hit with a water balloon from a slingshot. The patient was treated conservatively but developed an arteriovenous fistula which was treated with central arterial coiling. We discuss the need for acute computed tomography after relevant trauma as well as the evidence for follow-up scans and management of splenic pseudoaneurysms with splenic arterial embolization...
July 25, 2016: Ugeskrift for Laeger
Kazuhiro Nakaya, Taketeru Tomita, Kenta Suda, Keiichi Sato, Keisuke Ogimoto, Anthony Chappell, Toshihiko Sato, Katsuhiko Takano, Yoshio Yuki
Five striking and prey capture events of two goblin sharks were videotaped at sea for the first time, showing their extraordinary biting process. The goblin sharks swung their lower jaw downward and backward to attain a huge gape and then rapidly protruded the jaws forward a considerable distance. The jaws were projected at a maximum velocity of 3.1 m/s to 8.6-9.4% of the total length of the shark, which is by far the fastest and greatest jaw protrusion among sharks. While the jaws were being retracted, the mouth opened and closed again, which was considered a novel feeding event for sharks...
2016: Scientific Reports
Jian Zhang, Pei Wang, Wen He, Fengjun Wang
OBJECTIVE: To study the effect of hypoxia on Slingshot protein expression in human intestinal epithelial cell and its relation with changes in barrier function of the cells. METHODS: The human intestinal epithelial cell line Caco-2 was used to reproduce monolayer-cells. One portion of the monolayer-cell specimens were divided into six parts according to the random number table, and they were respectively exposed to hypoxia for 0 (without hypoxia), 1, 2, 6, 12, and 24 h...
April 2016: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
Julie C Lauterborn, Enikö A Kramár, Jeffrey D Rice, Alex H Babayan, Conor D Cox, Carley A Karsten, Christine M Gall, Gary Lynch
Dendritic extension and synaptogenesis proceed at high rates in rat hippocampus during early postnatal life but markedly slow during the third week of development. The reasons for the latter, fundamental event are poorly understood. Here, we report that levels of phosphorylated (inactive) cofilin, an actin depolymerizing factor, decrease by 90% from postnatal days (pnds) 10 to 21. During the same period, levels of total and phosphorylated Arp2, which nucleates actin branches, increase. A search for elements that could explain the switch from inactive to active cofilin identified reductions in β1 integrin, TrkB, and LIM domain kinase 2b, upstream proteins that promote cofilin phosphorylation...
April 1, 2017: Cerebral Cortex
Rocio Ramirez-Munoz, Patricia Castro-Sánchez, Pedro Roda-Navarro
Ultrasensitivity allows filtering weak activating signals and responding emphatically to small changes in stronger stimuli. In the presence of positive feedback loops, ultrasensitivity enables the existence of bistability, which convert graded stimuli into switch-like, sometimes irreversible, responses. In this perspective, we discuss mechanisms that can potentially generate a bistable response in the phosphorylation/dephosphorylation monocycle that regulates the activity of cofilin in dynamic actin networks...
2016: Frontiers in Immunology
Kyle Caution, Mikhail A Gavrilin, Mia Tazi, Apurva Kanneganti, Daniel Layman, Sheshadri Hoque, Kathrin Krause, Amal O Amer
Inflammasomes are multiprotein complexes that include members of the NOD-like receptor family and caspase-1. Caspase-1 is required for the fusion of the Legionella vacuole with lysosomes. Caspase-11, independently of the inflammasome, also promotes phagolysosomal fusion. However, it is unclear how these proteases alter intracellular trafficking. Here, we show that caspase-11 and caspase-1 function in opposing manners to phosphorylate and dephosphorylate cofilin, respectively upon infection with Legionella. Caspase-11 targets cofilin via the RhoA GTPase, whereas caspase-1 engages the Slingshot phosphatase...
December 21, 2015: Scientific Reports
Kang-shuai Li, Peng Xiao, Dao-lai Zhang, Xu-Ben Hou, Lin Ge, Du-xiao Yang, Hong-da Liu, Dong-fang He, Xu Chen, Ke-rui Han, Xiao-yuan Song, Xiao Yu, Hao Fang, Jin-peng Sun
Slingshot proteins form a small group of dual-specific phosphatases that modulate cytoskeleton dynamics through dephosphorylation of cofilin and Lim kinases (LIMK). Small chemical compounds with Slingshot-inhibiting activities have therapeutic potential against cancers or infectious diseases. However, only a few Slingshot inhibitors have been investigated and reported, and their cellular activities have not been examined. In this study, we identified two rhodanine-scaffold-based para-substituted benzoic acid derivatives as competitive Slingshot inhibitors...
December 2015: ChemMedChem
Yuka Yamagishi, Hiroshi Abe
We examined the reorganization of actin filaments and microtubules during Xenopus oocyte maturation. Surrounding the germinal vesicle (GV) in immature oocytes, the cytoplasmic actin filaments reorganized to accumulate beneath the vegetal side of the GV, where the microtubule-organizing center and transient microtubule array (MTOC-TMA) assembled, just before GV breakdown (GVBD). Immediately after GVBD, both Xenopus ADF/cofilin (XAC) and its phosphatase Slingshot (XSSH) accumulated into the nuclei and intranuclear actin filaments disassembled from the vegetal side with the shrinkage of the GV...
December 1, 2015: Molecular Biology of the Cell
Zhiyao Bao, Xuelin Han, Fangyan Chen, Xiaodong Jia, Jingya Zhao, Changjian Zhang, Chen Yong, Shuguang Tian, Xin Zhou, Li Han
BACKGROUND: The internalization of Aspergillus fumigatus into alveolar epithelial cells (AECs) is tightly controlled by host cellular actin dynamics, which require close modulation of the ADF (actin depolymerizing factor)/cofilin family. However, the role of cofilin in A. fumigatus internalization into AECs remains unclear. RESULTS: Here, we demonstrated that germinated A. fumigatus conidia were able to induce phosphorylation of cofilin in A549 cells during the early stage of internalization...
2015: BMC Microbiology
Ramdas Balakrishna, Mahendra Reddy, Vinay M Kashyap, Joseph John
INTRODUCTION: Mandibular surgeries are the most common orthognathic procedures that are undertaken. The pharyngeal airway space (PAS) is influenced by the changes in the sagittal changes of the mandible. Mandibular advancement surgeries are used to an advantage in obstructive sleep apnea cases to improve the airway space. On the contrary, there can be a considerable decrease in the airway space during mandibular setback procedures. Numerous studies have been conducted to study the effect of changes in the PAS during mandibular procedures...
December 2014: Journal of Maxillofacial and Oral Surgery
Manuel Neiva-Sousa, João Almeida-Coelho, Inês Falcão-Pires, Adelino F Leite-Moreira
Titin (TTN), the largest protein in the human body, forms powerful elastic filaments along the sarcomere of cardiomyocytes. This multifunctional protein is involved in numerous cellular processes, including sarcomeric assembly, stabilization and mechanosensing. Along physiological sarcomere lengths, TTN is also the most important determinant of the passive tension of cardiac muscle. However, as the giant Goliath was brought down by David's slingshot, so single-base-pair mutations in the gene encoding TTN (TTN) can ultimately impair to some degree a normal cardiac function...
September 2015: Heart Failure Reviews
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