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Per Martin Arvidsson, Johannes Töger, Marcus Carlsson, Katarina Steding-Ehrenborg, Gianni Pedrizzetti, Einar Heiberg, Hakan 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 LV forces. Right ventricular forces and their mechanistic contribution to asymmetric redirection of flow in the RV have not been measured. We therefore aimed to quantify three-dimensional hemodynamic forces in both ventricles in a cohort of healthy subjects, using magnetic resonance imaging 4D flow measurements. 25 controls,14 elite endurance athletes, and two patients with left ventricular dyssynchrony were included...
October 21, 2016: 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 S Raab
Centrosome amplification (CA) is a hallmark of virtually all types of cancers including solid tumors and hematological 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 12, 2016: 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
Marcelo F Montenegro, Alejandra Valdivia, Alexander Smolensky, Kiran Verma, W Robert Taylor, Alejandra San Martín
Vascular smooth muscle cells (VSMCs) are subjected to various types of mechanical forces within the vessel wall. Although it is known that VSMCs undergo cell body reorientation in response to mechanical stimulation, how this mechanical stretch is transduced within the cell into biochemical signals causing cytoskeleton reorganization remains unclear. Cofilin, a protein that controls actin dynamics, is activated by Slingshot phosphatase-dependent serine 3 dephosphorylation by redox-dependent mechanisms. Nox4 is a main source of reactive oxygen species (ROS) in the vessel wall that localizes in association with the cytoskeleton...
August 2015: Free Radical Biology & Medicine
J A Woo, X Zhao, H Khan, C Penn, X Wang, A Joly-Amado, E Weeber, D Morgan, D E Kang
Correction to: Cell Death and Differentiation (2015) 22, 921–934; doi:10.1038/cdd.2015.5; published online 20 February 2015. Since the publication of this paper, the authors have noticed the y-axis label of Figure 7e was incorrect. It should be % of the fESP slope. This has now been rectified and the corrected article appears in this issue together with this corrigendum.
June 2015: Cell Death and Differentiation
Kazumasa Ohashi
Reorganization of the actin cytoskeleton is essential for cellular processes during animal development. Cofilin and actin depolymerizing factor (ADF) are potent actin-binding proteins that sever and depolymerize actin filaments, acting to generate the dynamics of the actin cytoskeleton. The activity of cofilin is spatially and temporally regulated by a variety of intracellular molecular mechanisms. Cofilin is regulated by cofilin binding molecules, is phosphorylated at Ser-3 (inactivation) by LIM-kinases (LIMKs) and testicular protein kinases (TESKs), and is dephosphorylated (reactivation) by slingshot protein phosphatases (SSHs)...
May 2015: Development, Growth & Differentiation
Golfam Khoshkhouejad, Aman Ulhaq, Dirk Bister
Orthodontic alignment of palatally ectopic maxillary canines can be challenging. Treatment is usually prolonged and further complicated by the need for surgical exposure. Several methods are commonly used and have been described in the literature. This article presents two cases to describe a relatively unknown yet effective technique using the 'slingshot' method. This method is operator friendly and easily tolerated by patients.
June 2015: Journal of Orthodontics
Gonzalo Quassollo, Jose Wojnacki, Daniela A Salas, Laura Gastaldi, María Paz Marzolo, Cecilia Conde, Mariano Bisbal, Andrés Couve, Alfredo Cáceres
The neuronal Golgi apparatus (GA) localizes to the perinuclear region and dendrites as tubulo-vesicular structures designated Golgi outposts (GOPs). Current evidence suggests that GOPs shape dendrite morphology and serve as platforms for the local delivery of synaptic receptors. However, the mechanisms underlying GOP formation remain a mystery. Using live-cell imaging and confocal microscopy in cultured hippocampal neurons, we now show that GOPs destined to major "apical" dendrites are generated from the somatic GA by a sequence of events involving: (1) generation of a GA-derived tubule; (2) tubule elongation and deployment into the dendrite; (3) tubule fission; and (4) transport and condensation of the fissioned tubule...
April 20, 2015: Current Biology: CB
Michael Howell, Howard Brickner, Violaine D Delorme-Walker, Justin Choi, Jean-Michel Saffin, Daniel Miller, Andreas Panopoulos, Céline DerMardirossian, Arun Fotedar, Robert L Margolis, Rati Fotedar
We previously identified Waf1 Cip1 stabilizing protein 39 (WISp39) as a binding partner for heat shock protein 90 (Hsp90). We now report that WISp39 has an essential function in the control of directed cell migration, which requires WISp39 interaction with Hsp90. WISp39 knockdown (KD) resulted in the loss of directional motility of mammalian cells and profound changes in cell morphology, including the loss of a single leading edge. WISp39 binds Coronin 1B, known to regulate the Arp2/3 complex and Cofilin at the leading edge...
March 30, 2015: Journal of Cell Biology
J A Woo, T Boggess, C Uhlar, X Wang, H Khan, G Cappos, A Joly-Amado, E De Narvaez, S Majid, L S Minamide, J R Bamburg, D Morgan, E Weeber, D E Kang
Molecular pathways underlying the neurotoxicity and production of amyloid β protein (Aβ) represent potentially promising therapeutic targets for Alzheimer's disease (AD). We recently found that overexpression of the scaffolding protein RanBP9 increases Aβ production in cell lines and in transgenic mice while promoting cofilin activation and mitochondrial dysfunction. Translocation of cofilin to mitochondria and induction of cofilin-actin pathology require the activation/dephosphorylation of cofilin by Slingshot homolog 1 (SSH1) and cysteine oxidation of cofilin...
2015: Cell Death & Disease
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