Regulation of Dendritic Branching by Cdc42 Gaps
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UNIX and Computer Science Spreading UNIX Around the World: by Ronda Hauben an Interview with John Lions
Winter/Spring 1994 Celebrating 25 Years of UNIX Volume 6 No 1 "I believe all significant software movements start at the grassroots level. UNIX, after all, was not developed by the President of AT&T." Kouichi Kishida, UNIX Review, Feb., 1987 UNIX and Computer Science Spreading UNIX Around the World: by Ronda Hauben An Interview with John Lions [Editor's Note: This year, 1994, is the 25th anniversary of the [Editor's Note: Looking through some magazines in a local invention of UNIX in 1969 at Bell Labs. The following is university library, I came upon back issues of UNIX Review from a "Work In Progress" introduced at the USENIX from the mid 1980's. In these issues were articles by or inter- Summer 1993 Conference in Cincinnati, Ohio. This article is views with several of the pioneers who developed UNIX. As intended as a contribution to a discussion about the sig- part of my research for a paper about the history and devel- nificance of the UNIX breakthrough and the lessons to be opment of the early days of UNIX, I felt it would be helpful learned from it for making the next step forward.] to be able to ask some of these pioneers additional questions The Multics collaboration (1964-1968) had been created to based on the events and developments described in the UNIX "show that general-purpose, multiuser, timesharing systems Review Interviews. were viable." Based on the results of research gained at MIT Following is an interview conducted via E-mail with John using the MIT Compatible Time-Sharing System (CTSS), Lions, who wrote A Commentary on the UNIX Operating AT&T and GE agreed to work with MIT to build a "new System describing Version 6 UNIX to accompany the "UNIX hardware, a new operating system, a new file system, and a Operating System Source Code Level 6" for the students in new user interface." Though the project proceeded slowly his operating systems class at the University of New South and it took years to develop Multics, Doug Comer, a Profes- Wales in Australia. -
Chr21 Protein-Protein Interactions: Enrichment in Products Involved in Intellectual Disabilities, Autism and Late Onset Alzheimer Disease
bioRxiv preprint doi: https://doi.org/10.1101/2019.12.11.872606; this version posted December 12, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Chr21 protein-protein interactions: enrichment in products involved in intellectual disabilities, autism and Late Onset Alzheimer Disease Julia Viard1,2*, Yann Loe-Mie1*, Rachel Daudin1, Malik Khelfaoui1, Christine Plancon2, Anne Boland2, Francisco Tejedor3, Richard L. Huganir4, Eunjoon Kim5, Makoto Kinoshita6, Guofa Liu7, Volker Haucke8, Thomas Moncion9, Eugene Yu10, Valérie Hindie9, Henri Bléhaut11, Clotilde Mircher12, Yann Herault13,14,15,16,17, Jean-François Deleuze2, Jean- Christophe Rain9, Michel Simonneau1, 18, 19, 20** and Aude-Marie Lepagnol- Bestel1** 1 Centre Psychiatrie & Neurosciences, INSERM U894, 75014 Paris, France 2 Laboratoire de génomique fonctionnelle, CNG, CEA, Evry 3 Instituto de Neurociencias CSIC-UMH, Universidad Miguel Hernandez-Campus de San Juan 03550 San Juan (Alicante), Spain 4 Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA 5 Center for Synaptic Brain Dysfunctions, Institute for Basic Science, Daejeon 34141, Republic of Korea 6 Department of Molecular Biology, Division of Biological Science, Nagoya University Graduate School of Science, Furo, Chikusa, Nagoya, Japan 7 Department of Biological Sciences, University of Toledo, Toledo, OH, 43606, USA 8 Leibniz Forschungsinstitut für Molekulare Pharmakologie -
Neural Stem Cell-Derived Exosomes Revert HFD-Dependent Memory Impairment Via CREB-BDNF Signalling
International Journal of Molecular Sciences Article Neural Stem Cell-Derived Exosomes Revert HFD-Dependent Memory Impairment via CREB-BDNF Signalling Matteo Spinelli 1, Francesca Natale 1,2, Marco Rinaudo 1, Lucia Leone 1,2, Daniele Mezzogori 1, Salvatore Fusco 1,2,* and Claudio Grassi 1,2 1 Department of Neuroscience, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; [email protected] (M.S.); [email protected] (F.N.); [email protected] (M.R.); [email protected] (L.L.); [email protected] (D.M.); [email protected] (C.G.) 2 Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy * Correspondence: [email protected] Received: 6 October 2020; Accepted: 25 November 2020; Published: 26 November 2020 Abstract: Overnutrition and metabolic disorders impair cognitive functions through molecular mechanisms still poorly understood. In mice fed with a high fat diet (HFD) we analysed the expression of synaptic plasticity-related genes and the activation of cAMP response element-binding protein (CREB)-brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signalling. We found that a HFD inhibited both CREB phosphorylation and the expression of a set of CREB target genes in the hippocampus. The intranasal administration of neural stem cell (NSC)-derived exosomes (exo-NSC) epigenetically restored the transcription of Bdnf, nNOS, Sirt1, Egr3, and RelA genes by inducing the recruitment of CREB on their regulatory sequences. Finally, exo-NSC administration rescued both BDNF signalling and memory in HFD mice. Collectively, our findings highlight novel mechanisms underlying HFD-related memory impairment and provide evidence of the potential therapeutic effect of exo-NSC against metabolic disease-related cognitive decline. -
PI3K Catalytic Isoform Alteration Promotes the LIMK1-Related
ANTICANCER RESEARCH 37 : 1805-1818 (2017) doi:10.21873/anticanres.11515 PI3K Catalytic Isoform Alteration Promotes the LIMK1-related Metastasis Through the PAK1 or ROCK1/2 Activation in Cigarette Smoke-exposed Ovarian Cancer Cells GA BIN PARK 1 and DAEJIN KIM 2 1Department of Biochemistry, Kosin University College of Medicine, Busan, Republic of Korea; 2Department of Anatomy, Inje University College of Medicine, Busan, Republic of Korea Abstract. Aim: To investigate the molecular mechanisms Several studies have shown a strong correlation between by which long-term exposure to cigarette smoke extract cigarette smoke (CS) and cancer metastasis through the (CSE) contributes to ovarian cancer metastasis. Materials induction of numerous factors involved in migration activity and Methods: Western blot analysis for diverse p110 (1-3). The exposure to CS induces the epithelial- isoforms of phosphoinositide 3-kinase (PI3K)-related mesenchymal transition (EMT) process and up-regulates the signaling pathway and epithelial-mesenchymal transition expression of EMT markers, including N-cadherin and (EMT) markers was performed to analyze the underlying vimentin (4, 5). Cigarette smoke extract (CSE) treatment mechanisms. Migratory activity of CSE-exposed ovarian significantly induces interleukin-8 (IL-8) and transforming cancer cells was determined by transendothelial migration growth factor-beta 1 (TGF- β1 ) production and profoundly and invasion assay. Results: After exposure to CSE for four suppresses the proliferation and growth of erythroid and weeks, CaOV3 (primary) and SKOV3 (metastatic) ovarian granulocyte-macrophage progenitors (6). Stimulation with cancer cells showed enhanced mesenchymal characteristics CSE in human lung fibroblast cells induces the expression and produced EMT-related cytokines [intwerleukin-8 (IL-8), of phosphorylated Smad3, a main downstream target of the vascular endothelial growth factor (VEGF) and TGF- β1 receptor, which results in the secretion of vascular transforming growth factor-beta 1 (TGF- β1 )]. -
Circular RNA Hsa Circ 0005114‑Mir‑142‑3P/Mir‑590‑5P‑ Adenomatous
ONCOLOGY LETTERS 21: 58, 2021 Circular RNA hsa_circ_0005114‑miR‑142‑3p/miR‑590‑5p‑ adenomatous polyposis coli protein axis as a potential target for treatment of glioma BO WEI1*, LE WANG2* and JINGWEI ZHAO1 1Department of Neurosurgery, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033; 2Department of Ophthalmology, The First Hospital of Jilin University, Jilin University, Changchun, Jilin 130021, P.R. China Received September 12, 2019; Accepted October 22, 2020 DOI: 10.3892/ol.2020.12320 Abstract. Glioma is the most common type of brain tumor APC expression with a good overall survival rate. UALCAN and is associated with a high mortality rate. Despite recent analysis using TCGA data of glioblastoma multiforme and the advances in treatment options, the overall prognosis in patients GSE25632 and GSE103229 microarray datasets showed that with glioma remains poor. Studies have suggested that circular hsa‑miR‑142‑3p/hsa‑miR‑590‑5p was upregulated and APC (circ)RNAs serve important roles in the development and was downregulated. Thus, hsa‑miR‑142‑3p/hsa‑miR‑590‑5p‑ progression of glioma and may have potential as therapeutic APC‑related circ/ceRNA axes may be important in glioma, targets. However, the expression profiles of circRNAs and their and hsa_circ_0005114 interacted with both of these miRNAs. functions in glioma have rarely been studied. The present study Functional analysis showed that hsa_circ_0005114 was aimed to screen differentially expressed circRNAs (DECs) involved in insulin secretion, while APC was associated with between glioma and normal brain tissues using sequencing the Wnt signaling pathway. In conclusion, hsa_circ_0005114‑ data collected from the Gene Expression Omnibus database miR‑142‑3p/miR‑590‑5p‑APC ceRNA axes may be potential (GSE86202 and GSE92322 datasets) and explain their mecha‑ targets for the treatment of glioma. -
Oncogenic Activation of Pak1-Dependent Pathway of Macropinocytosis Determines BCG Entry Into Bladder Cancer Cells
Cancer Molecular and Cellular Pathobiology Research Oncogenic Activation of Pak1-Dependent Pathway of Macropinocytosis Determines BCG Entry into Bladder Cancer Cells Gil Redelman-Sidi1,2, Gopa Iyer3,4, David B. Solit3,4, and Michael S. Glickman1,2 Abstract Bacille Calmette-Guerin (BCG) is an attenuated strain of Mycobacterium bovis that is used widely as a vaccine for tuberculosis and is used as an effective treatment for superficial bladder carcinoma. Despite being the most successful cancer biotherapy, its mechanism of action and response determinants remain obscure. Here, we establish a model system to analyze BCG interaction with bladder cancer cells, using it to show that these cells vary dramatically in their susceptibility to BCG infection. Unexpectedly, the uptake of BCG by bladder cancer cells occurs by macropinocytosis rather than phagocytosis. BCG entry into bladder cancer cells relied upon Rac1, Cdc42, and their effector kinase Pak1. The difference in susceptibility between BCG- permissive and -resistant bladder cancer cells was due to oncogenic activation of signaling pathways that activate macropinocytosis, with phosphoinositide 3-kinase inhibitor activation stimulating BCG uptake independently of Akt. Similarly, activated Ras strongly activated Pak1-dependent uptake of BCG. These results reveal that oncogenic activation of macropinocytosis determines BCG uptake by bladder cancer cells, implying that tumor responsiveness to BCG may be governed by the specific mutations present in the treated cancer cell. Cancer Res; 73(3); 1156–67. Ó2013 AACR. Introduction Despite more than 30 years of clinical experience with Bladder cancer is among the most common tumors diag- intravesical BCG for bladder cancer, its mechanism of antitu- nosed in the United States, with an estimated annual incidence mor effect remains unknown and no markers exist to predict of 70,530 new cases and 14,680 deaths in 2010 (1). -
Role of Rac1-Pak Pathway in Aggressive B-Cell Lymphoma
University of Nebraska Medical Center DigitalCommons@UNMC Theses & Dissertations Graduate Studies Spring 5-4-2019 Role of Rac1-Pak pathway in aggressive b-cell lymphoma Tian Tian University of Nebraska Medical Center Follow this and additional works at: https://digitalcommons.unmc.edu/etd Part of the Hemic and Lymphatic Diseases Commons, and the Neoplasms Commons Recommended Citation Tian, Tian, "Role of Rac1-Pak pathway in aggressive b-cell lymphoma" (2019). Theses & Dissertations. 344. https://digitalcommons.unmc.edu/etd/344 This Dissertation is brought to you for free and open access by the Graduate Studies at DigitalCommons@UNMC. It has been accepted for inclusion in Theses & Dissertations by an authorized administrator of DigitalCommons@UNMC. For more information, please contact [email protected]. i Role of Rac1-PAK Pathway in Aggressive B-cell Lymphomas By Tian Tian A DISSERTATION Presented to the Faculty of The University of Nebraska Graduate College in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Pathology & Microbiology Graduate program Under the Supervision of Professor Kai Fu University of Nebraska Medical Center, Omaha, Nebraska Dec, 2018 Supervisory Committee: Ying Yan, Ph.D. John S Davis, Ph.D. Timothy C Greiner, M.D. Javeed Iqbal, Ph.D. ii Role of Rac1-PAK pathway in Aggressive B-cell Lymphomas Tian Tian University of Nebraska Medical Center, 2018 Advisor: Kai Fu, M.D. Ph.D. Aggressive B-cell lymphomas are diverse group of neoplasms that arise at different stages of B-cell development and by various mechanisms of neoplastic transformation. Aggressive B-cell lymphomas include many types, subtypes and variants of diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), mantle cell lymphoma (MCL) and B lymphoblastic lymphoma. -
Evidence for Opposing Roles of Celsr3 and Vangl2 in Glutamatergic Synapse Formation
Evidence for opposing roles of Celsr3 and Vangl2 in glutamatergic synapse formation Sonal Thakara, Liqing Wanga, Ting Yua, Mao Yea, Keisuke Onishia, John Scotta, Jiaxuan Qia, Catarina Fernandesa, Xuemei Hanb, John R. Yates IIIb, Darwin K. Berga, and Yimin Zoua,1 aNeurobiology Section, Biological Sciences Division, University of California, San Diego, La Jolla, CA 92093; and bDepartment of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037 Edited by Liqun Luo, Stanford University, Stanford, CA, and approved December 5, 2016 (received for review July 22, 2016) The signaling mechanisms that choreograph the assembly of the conditionally knocking out these components in defined synapses highly asymmetric pre- and postsynaptic structures are still poorly after the development of axons and dendrites. defined. Using synaptosome fractionation, immunostaining, and In this study, we directly address the role of Celsr3 and Vangl2 coimmunoprecipitation, we found that Celsr3 and Vangl2, core in glutamatergic synapse formation by deleting Celsr3 and Vangl2 components of the planar cell polarity (PCP) pathway, are localized in hippocampal pyramidal neurons after the first postnatal week at developing glutamatergic synapses and interact with key synap- (postnatal day 7; P7). We found that at the peak of synapse for- tic proteins. Pyramidal neurons from the hippocampus of Celsr3 mation (P14), Celsr3 and Vangl2 are specifically localized in de- knockout mice exhibit loss of ∼50% of glutamatergic synapses, veloping glutamatergic synapses and colocalized with pre- and but not inhibitory synapses, in culture. Wnts are known regulators postsynaptic proteins. In the absence of Celsr3,hippocampal of synapse formation, and our data reveal that Wnt5a inhibits glu- neurons showed ∼50% reduction in the number of glutamatergic tamatergic synapses formed via Celsr3. -
BDNF Integrity in Ageing and Stress
MOJ Gerontology & Geriatrics Editorial Open Access BDNF integrity in ageing and stress Editorial Volume 1 Issue 6 - 2017 Alzheimer’s disease (AD) presents a progressive, stage-dependent Trevor Archer age-related neurodegenerative disorder that is characterized by Department of Psychology, University of Gothenburg, Sweden aggregation of toxic forms of amyloid β peptide (Aβ). There is much support for the notion that that brain-derived neurotrophic factor Correspondence: Trevor Archer, Department of Psychology, (BDNF) mediates beneficial effects of exercise on neuroplasticity and University of Gothenburg, Sweden, cellular stress resistance.1‒3 BDNF is associated with neuroplasticity Email [email protected] changes promoting health and well-being whereas these influences Received: July 16, 2017 | Published: August 01, 2017 may be opposed by pro-inflammatory cytokines, key factors in neurodegenerative processes.4 Lower serum levels are linked to greater symptom, cognitive, impairment.5 Thus, interventions, as for example physical exercise, whether acute or chronic, endurance or resistance, promote the mobilization of BDNF and other neurotrophic factors6,7 increase hippocampal and other brain regional resilience8 and therewith progression under conditions of stress when confronted critical life protect against cell death by inducing cell proliferation and maturation episodes or periods, appears to be modulated by the availability and with enhanced neuronal reparation, neurogenesis and the growth and accessibility of BDNF.20‒22 Over a wide range of neurologic and functioning of neurons in neurodegenerative disorders.9,10 Sampaio et psychiatric disease states it is found that the integrity and concentrations al.11 in a review of the therapeutic applications of neurotrophic factors, of brain, serum and plasma BDNF is compromised, particularly under particularly BDNF, postulate that they are essential for survival, stressful conditions. -
Epithelial-To-Mesenchymal Transition Enhances Cancer Cell Sensitivity to Cytotoxic Effects of Cold Atmospheric Plasmas in Breast and Bladder Cancer Systems
cancers Article Epithelial-to-Mesenchymal Transition Enhances Cancer Cell Sensitivity to Cytotoxic Effects of Cold Atmospheric Plasmas in Breast and Bladder Cancer Systems Peiyu Wang 2,3 , Renwu Zhou 4 , Patrick Thomas 2,3,5 , Liqian Zhao 6, Rusen Zhou 4, Susmita Mandal 7, Mohit Kumar Jolly 7, Derek J. Richard 2,3, Bernd H. A. Rehm 8, Kostya (Ken) Ostrikov 9, Xiaofeng Dai 1,*, Elizabeth D. Williams 2,3,4 and Erik W. Thompson 2,3 1 Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China 2 Queensland University of Technology (QUT), School of Biomedical Sciences, Brisbane 4059, Australia 3 Translational Research Institute, Woolloongabba 4102, Australia 4 School of Chemical and Biomolecular Engineering, The University of Sydney, Sydney 2006, Australia 5 Queensland Bladder Cancer Initiative (QBCI), Woolloongabba 4102, Australia 6 The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China 7 Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore 560012, India 8 Centre for Cell Factories and Biopolymers, Griffith Institute for Drug Discovery, Griffith University, Nathan 4111, Australia 9 School of Chemistry and Physics, Queensland University of Technology, Brisbane 4000, Australia; Citation: Wang, P.; Zhou, R.; * Correspondence: [email protected] Thomas, P.; Zhao, L.; Zhou, R.; Mandal, S.; Jolly, M.K.; Richard, D.J.; Simple Summary: Cold atmospheric plasma (CAP) and plasma-activated medium (PAM) are known Rehm, B.H.A.; Ostrikov, K.; et al. to selectively kill cancer cells, however the efficacy of CAP in cancer cells following epithelial- Epithelial-to-Mesenchymal Transition mesenchymal transition (EMT), a process which endows cancer cells with increased stemness, Enhances Cancer Cell Sensitivity to metastatic potential, and resistance to conventional therapies, has not been previously examined. -
Supplementary Table 8. Cpcp PPI Network Details for Significantly Changed Proteins, As Identified in 3.2, Underlying Each of the Five Functional Domains
Supplementary Table 8. cPCP PPI network details for significantly changed proteins, as identified in 3.2, underlying each of the five functional domains. The network nodes represent each significant protein, followed by the list of interactors. Note that identifiers were converted to gene names to facilitate PPI database queries. Functional Domain Node Interactors Development and Park7 Rack1 differentiation Kcnma1 Atp6v1a Ywhae Ywhaz Pgls Hsd3b7 Development and Prdx6 Ncoa3 differentiation Pla2g4a Sufu Ncf2 Gstp1 Grin2b Ywhae Pgls Hsd3b7 Development and Atp1a2 Kcnma1 differentiation Vamp2 Development and Cntn1 Prnp differentiation Ywhaz Clstn1 Dlg4 App Ywhae Ywhab Development and Rac1 Pak1 differentiation Cdc42 Rhoa Dlg4 Ctnnb1 Mapk9 Mapk8 Pik3cb Sod1 Rrad Epb41l2 Nono Ltbp1 Evi5 Rbm39 Aplp2 Smurf2 Grin1 Grin2b Xiap Chn2 Cav1 Cybb Pgls Ywhae Development and Hbb-b1 Atp5b differentiation Hba Kcnma1 Got1 Aldoa Ywhaz Pgls Hsd3b4 Hsd3b7 Ywhae Development and Myh6 Mybpc3 differentiation Prkce Ywhae Development and Amph Capn2 differentiation Ap2a2 Dnm1 Dnm3 Dnm2 Atp6v1a Ywhab Development and Dnm3 Bin1 differentiation Amph Pacsin1 Grb2 Ywhae Bsn Development and Eef2 Ywhaz differentiation Rpgrip1l Atp6v1a Nphp1 Iqcb1 Ezh2 Ywhae Ywhab Pgls Hsd3b7 Hsd3b4 Development and Gnai1 Dlg4 differentiation Development and Gnao1 Dlg4 differentiation Vamp2 App Ywhae Ywhab Development and Psmd3 Rpgrip1l differentiation Psmd4 Hmga2 Development and Thy1 Syp differentiation Atp6v1a App Ywhae Ywhaz Ywhab Hsd3b7 Hsd3b4 Development and Tubb2a Ywhaz differentiation Nphp4 -
A Brief History of Unix
A Brief History of Unix Tom Ryder [email protected] https://sanctum.geek.nz/ I Love Unix ∴ I Love Linux ● When I started using Linux, I was impressed because of the ethics behind it. ● I loved the idea that an operating system could be both free to customise, and free of charge. – Being a cash-strapped student helped a lot, too. ● As my experience grew, I came to appreciate the design behind it. ● And the design is UNIX. ● Linux isn’t a perfect Unix, but it has all the really important bits. What do we actually mean? ● We’re referring to the Unix family of operating systems. – Unix from Bell Labs (Research Unix) – GNU/Linux – Berkeley Software Distribution (BSD) Unix – Mac OS X – Minix (Intel loves it) – ...and many more Warning signs: 1/2 If your operating system shows many of the following symptoms, it may be a Unix: – Multi-user, multi-tasking – Hierarchical filesystem, with a single root – Devices represented as files – Streams of text everywhere as a user interface – “Formatless” files ● Data is just data: streams of bytes saved in sequence ● There isn’t a “text file” attribute, for example Warning signs: 2/2 – Bourne-style shell with a “pipe”: ● $ program1 | program2 – “Shebangs” specifying file interpreters: ● #!/bin/sh – C programming language baked in everywhere – Classic programs: sh(1), awk(1), grep(1), sed(1) – Users with beards, long hair, glasses, and very strong opinions... Nobody saw it coming! “The number of Unix installations has grown to 10, with more expected.” — Ken Thompson and Dennis Ritchie (1972) ● Unix in some flavour is in servers, desktops, embedded software (including Intel’s management engine), mobile phones, network equipment, single-board computers..