Substructure of the Nucleus

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Substructure of the Nucleus Substructure of the Nucleus Bởi: OpenStaxCollege What is inside the nucleus? Why are some nuclei stable while others decay? (See [link].) Why are there different types of decay (α, β and γ)? Why are nuclear decay energies so large? Pursuing natural questions like these has led to far more fundamental discoveries than you might imagine Why is most of the carbon in this coal stable (a), while the uranium in the disk (b) slowly decays over billions of years? Why is cesium in this ampule (c) even less stable than the uranium, decaying in far less than 1/1,000,000 the time? What is the reason uranium and cesium undergo different types of decay (α and β, respectively)? (credits: (a) Bresson Thomas, Wikimedia Commons; (b) U.S Department of Energy; (c) Tomihahndorf, Wikimedia Commons) We have already identified protons as the particles that carry positive charge in the nuclei However, there are actually two types of particles in the nuclei—the proton and the neutron, referred to collectively as nucleons, the constituents of nuclei As its name implies, the neutron is a neutral particle (q = 0) that has nearly the same mass and intrinsic spin as the proton [link] compares the masses of protons, neutrons, and electrons Note how close the proton and neutron masses are, but the neutron is slightly more massive once you look past the third digit Both nucleons are much more massive than an electron In fact, mp = 1836me (as noted in Medical Applications of Nuclear Physics and mn = 1839me [link] also gives masses in terms of mass units that are more convenient than kilograms on the atomic and nuclear scale The first of these is the unified atomic mass unit (u), defined as u = 1.6605 × 10 −27 kg This unit is defined so that a neutral carbon 12C atom has a mass of exactly 12 u Masses are also expressed in units of MeV/c2 These units are very convenient when 1/10 Substructure of the Nucleus considering the conversion of mass into energy (and vice versa), as is so prominent in nuclear processes Using E = mc2 and units of m in MeV/c2, we find that c2 cancels and E comes out conveniently in MeV For example, if the rest mass of a proton is converted entirely into energy, then E = mc2 = (938.27 MeV/c2)c2 = 938.27 MeV It is useful to note that u of mass converted to energy produces 931.5 MeV, or u=931.5 MeV/ c2 All properties of a nucleus are determined by the number of protons and neutrons it has A specific combination of protons and neutrons is called a nuclide and is a unique nucleus The following notation is used to represent a particular nuclide: A XN , Z where the symbols A, X, Z , and N are defined as follows: The number of protons in a nucleus is the atomic number Z, as defined in Medical Applications of Nuclear Physics X is the symbol for the element, such as Ca for calcium However, once Z is known, the element is known; hence, Z and X are redundant For example, Z = 20 is always calcium, and calcium always has Z = 20 N is the number of neutrons in a nucleus In the notation for a nuclide, the subscript N is usually omitted The symbol A is defined as the number of nucleons or the total number of protons and neutrons, A = N + Z, where A is also called the mass number This name for A is logical; the mass of an atom is nearly equal to the mass of its nucleus, since electrons have so little mass The mass of the nucleus turns out to be nearly equal to the sum of the masses of the protons and neutrons in it, which is proportional to A In this context, it is particularly convenient to express masses in units of u Both protons and neutrons have masses close to u, and so the mass of an atom is close to A u For example, in an oxygen nucleus with eight protons and eight neutrons, A = 16, and its mass is 16 u As noticed, the unified atomic mass unit is defined so that a neutral carbon atom (actually a 12C atom) has a mass of exactly 12 u Carbon was chosen as the standard, partly because of its importance in organic chemistry (see Appendix A) Masses of the Proton, Neutron, and Electron Particle Symbol kg Proton p u 1.67262 × 10 −27 1.007276 MeVc2 938.27 2/10 Substructure of the Nucleus Particle Symbol kg u MeVc2 939.57 Neutron n 1.67493×10 −27 1.008665 Electron e 9.1094×10 −31 0.00054858 0.511 Let us look at a few examples of nuclides expressed in the AXN notation The nucleus Z of the simplest atom, hydrogen, is a single proton, or 1H (the zero for no neutrons is often omitted) To check this symbol, refer to the periodic table—you see that the atomic number Z of hydrogen is Since you are given that there are no neutrons, the mass number A is also Suppose you are told that the helium nucleus or α particle has two protons and two neutrons You can then see that it is written 4He2 There is a scarce form of hydrogen found in nature called deuterium; its nucleus has one proton and one neutron and, hence, twice the mass of common hydrogen The symbol for deuterium is, thus, 2H1 (sometimes D is used, as for deuterated ...RESEARC H Open Access Protein kinase A-dependent Neuronal Nitric Oxide Synthase Activation Mediates the Enhancement of Baroreflex Response by Adrenomedullin in the Nucleus Tractus Solitarii of Rats David HT Yen 1,2† , Lih-Chi Chen 3† , Yuh-Chiang Shen 4 , Ying-Chen Chiu 5 , I-Chun Ho 5 , Ya-Jou Lou 3 , I-Chin Chen 3 and Jiin-Cherng Yen 3,5* Abstract Background: Adrenomedullin (ADM) exerts its biological functions through the receptor-mediated enzymatic mechanisms that involve protein kinase A (PKA), or neuronal nitric oxide synthase (nNOS). We previously demonstrated that the receptor-mediated cAMP/PKA pathway involves in ADM-enhanced baroreceptor reflex (BRR) response. It remains unclear whe ther ADM may enhance BRR response via activation of nNOS-dependent mechanism in the nucleus tractus solitarii (NTS). Methods: Intravenous injection of phenylephrine was administered to evoke the BRR before and at 10, 30, and 60 min after microinjection of the test agents into NTS of Sprague-Dawley rats. Western blotting analysis was used to measure the level and phosphorylation of proteins that involved in BRR-enhancing effects of ADM (0.2 pmol) in NTS. The colocalization of PKA and nNOS was examined by immunohistochemical staining and observed with a laser confocal microscope. Results: We found that ADM-induced enhancement of BRR response was blunted by microinjection of NPLA or Rp-8-Br-cGMP, a selective inhibitor of nNOS or protein kinase G (PKG) respectively, into NTS. Western blot analysis further revealed that ADM induced an increase in the protein level of PKG-I which could be attenuated by co-microinjection with the ADM receptor antagonist ADM 22-52 or NPLA. Moreover, we observed an increase in phosphorylation at Ser1416 of nNOS at 10, 30, and 60 min after in tra-NTS administration of ADM. As such, nNOS/PKG signaling may also account for the enhancing effect of ADM on BRR response. Interestingly, biochemical evidence further showed that ADM-induced increase of nNOS phos phorylation was prevented by co-microinjection with Rp-8-Br-cAMP, a PKA inhibitor. The possibility of PKA-dependent nNOS activation was substantiated by immunohistochemical demonstration of co-localization of PKA and nNOS in putative NTS neurons. Conclusions: The novel finding of this study is that the signal transduction cascade that underli es the enhancement of BRR response by ADM in NTS is composed sequentially of cAMP/PKA and nNOS/PKG pathways. * Correspondence: jcyen@ym.edu.tw † Contributed equally 3 Department of Pharmacy, Taipei City Hospital, Taipei, Taiwan Full list of author information is available at the end of the article Yen et al. Journal of Biomedical Science 2011, 18:32 http://www.jbiomedsci.com/content/18/1/32 © 2011 Yen et al; licensee BioMed Centr al Ltd. This is an Open Access article distributed und er the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reprod uction in any medium, provide d the original work is properly cited. Background Adrenomedullin (ADM), a 52-amino acid peptide, was originally isolated from human pheochromocytoma and initially shown to have potent vasodilatory activity [1]. The physiologic and pharmacologic functions of ADM have been intensively investiga ted after its discovery (for review see [2]). ADM exerts multiple biological activities by acting on its specific receptors, composed of calcito- nin receptor-like r eceptor (CRLR) and receptor activity modifying protein (RAMP)-2 or -3 [3]. The hypotensive effect of intravenously administered ADM has been attributed to activation of ADM receptors (ADMRs) located on blood vessels [1]. In addition to distribution in the cardiovascular system, ADM and ADMRs are also expressed in the central nervous system (CNS) and are particularly localized to the autonomic nuclei, including nucleus tractus solitarii (NTS), lateral parabrachial nucleus (LPBN), and rostral ventrolateral Despite many concerns, profi ling has been used success- fully to identify or predict possible antisocial behaviors. Profi ling relies on highlighting unique traits against a background of confounding signals. Similarly, transcrip- tional profi ling is a powerful technique to determine marker genes that characterize and distinguish a particu- lar cell type. In a recent issue of Arthritis Research &  erapy, Minogue and colleagues [1] used transcriptional profi ling to examine the phenotypic characteristics of bovine intervertebral disc cells and provided some novel insights into the current debate concerning the origin of cells of the adult nucleus pulposus. One aspect of this ongoing controversy is whether the onset of degenerative disc disease is due to the loss of the original notochordal cells or to the replacement of them by unrelated cell types or to both [2].  is dispute aff ects investigational strategies in which the choice of animal model for a study is governed by the consideration of whether notochordal cells are present in the disc or have been replaced by cells that are non-notochordal in origin [3].  e focus of this editorial is to address these long-standing arguments in the light of the profi ling studies and work of other investigators. Minogue and colleagues [1] report the identifi cation of a number of marker genes that distinguish nucleus pulposus cells from those of the annulus fi brosus cells and cartilage (chondrocytes).  e authors document diff erential expression of 49 disc-specifi c and 34 nucleus pulposus-specifi c genes.  e presence of a number of these genes provides a new understanding of the origin of the nucleus pulposus in relationship to the notochord. Notochordal cells have been reported to be present in the nucleus pulposus in young animals, including humans [2,4]. It has also been proposed that most of these cells gradually disappear during aging [2,4] and are replaced by endplate chondrocytes or inner annulus fi brosus cells [5]. In humans, notochordal cells are rarely observed after the age of puberty [4], although a few studies allude to their existence well into maturity [6,7].  ese obser- vations raise the question, is there cellular heterogeneity in the nucleus pulposus? To address this question, Choi and colleagues [8] generated fate maps of notochordal cells using tamoxifen-inducible ShhCreERT2 mice.  ese studies showed unequivocally that the entire cell population of the nucleus pulposus, even in the adult, was descended from the notochord. Another invaluable marker of the ontology of the cells of the nucleus pulposus is the T-box gene brachyury, which is required for diff erentiation and survival of the notochord [9]. Similarly to profi ling studies of rodents and canines, the study by Minogue and colleagues [1] indicated that cells present in the nucleus pulposus of adult bovine as well as human discs express brachyury and cytokeratins 8, 18, and 19, genes that are present in the notochord [10,11]. If it is assumed that the notochordal cells are lost from the disc early in life in these species, then these results are unexpected. A more acceptable explanation is that the nucleus pulposus is populated by notochordal cells. Minogue and colleagues [1] showed, in direct relevance to this fi nding, that the large notochordal and small chondrocyte-like nucleus pulposus cells in bovine disc have substantially over lapping gene expression profi les, Abstract This editorial addresses the debate concerning the origin of adult nucleus pulposus cells in the light of pro ling studies by Minogue and colleagues. In their report of several marker genes that distinguish nucleus pulposus cells from other related cell types, the authors provide novel insights into the notochordal nature of the former. Together with recently published work, their work lends support to the view that all cells present within the nucleus pulposus are derived RESEARCH Open Access Trafficking of some old world primate TRIM5a proteins through the nucleus Felipe Diaz-Griffero 1 , Daniel E Gallo 4 , Thomas J Hope 4 and Joseph Sodroski 2,3* Abstract Background: TRIM5a and TRIMCyp are cytoplasmic proteins that bind incoming retroviral capsids and mediate early blocks to viral infection. TRIM5 proteins form cytoplasmic bodies, which are highly dynamic structures. So far, TRIM5 proteins have been found only in the cytoplasm of cells. Interestingly, oth er proteins from the TRIM family localize to the nucleus. Therefore, we tested the possibility that TRIM5 proteins traffic to the nucleus and the impact of this trafficking on retroviral restriction. Results: Here we report that the TRIM5a proteins of two Old World primates, humans and rhesus monkeys, are transported into the nucleus and are shuttled back to the cytoplasm by a leptomycin B-sensitive mechanism. In leptomycin B-treated cells, these TRIM5a proteins formed nuclear bodies that also contained TRIM19 (PML). Deletion of the amino terminus, including the linker 1 (L1) region, resulted in TRIM5a proteins that accumulated in nuclear bodies. Leptomycin B treatment of TRIM5a-expressing target cells only minimally affected the restriction of retrovirus infection. Conclusions: We discovered the ability of human and rhesus TRIM5a to shuttle into and out of the nucleus. This novel trafficking ability of TRIM5a proteins could be important for an as-yet-unknown function of TRIM5a. Keywords: Restriction factor intracellular localization, retrovirus, leptomycin B Background Proteins of the tripartite motif (TRIM) family contain RING, B-Box and coiled-coil domains, and thus have bee n referred to as RBCC protei ns [1] . Members of this family have been implicated in diverse processes such as cell proliferat ion, differentiation, development, oncogen- esis and apoptosis [1,2]. TRIM proteins often self-associ- ate and, when overexpressed, aggregate to form nuclear or cytoplasmic bodies [1]. TRIM5a is a cytoplasmic protein that is capable of restricting retrovirus infection in a species-dependent manner [3]. Variation among TRIM5a proteins in dif- ferent primates accounts for the early, post-entry blocks to infection by particular retroviruses [3-7]. For exam- ple, TRIM5a proteins of Old World monkeys block human immunodeficiency virus (HIV-1) infection [3-5,7], whereas TRIM5a proteins of New W orld monkeys block infection by simian immunodeficiency virus (SIV mac )[8].TRIM5a from humans (TRIM5a hu ) is not as potent in restricting HIV-1 infection as Old World monkey TRIM5a,butTRIM5a hu potently restricts other retroviruses, e.g., N-tropic murine leuke- mia virus (N-MLV) and equine infectious anemia virus (EIAV) [3,4,6-8]. Owl monkeys, a New World monkey species, are unusual in not expressing a TRIM5a pro- tein, but instead express TRIMCyp, in whi ch the RBCC domains of TRIM5 are fused to a cyclophilin A moiety [9,10]. Variation in splicing of the TRIM5 primary transcript leads to the expression of TRIM5 isoforms, designated a, g and δ [1]. The TRIM5a isoform contains, in add i- tion to the RING, B-box 2 and coiled-coil domains, a carboxy-terminal B30.2(SPRY) domain. The B30.2 (SPRY) domain is essential for the antiretroviral activity of TRIM5a [3]. In some cases, the differences in the ability of TRIM5a proteins from various primate species to restrict particular retroviruses are determined by sequences in the B30.2(SPRY) domain [11-19]. The B30.2(SPRY) domain in TRIM5a and the cyclophilin A * Correspondence: joseph_sodroski@dfci.harvard.edu 2 Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Pathology, Division of AIDS, Harvard Medical School, Boston, MA 02115, USA Full list of author information is available at the end of the article Diaz-Griffero et al. Retrovirology 2011, 8:38 http://www.retrovirology.com/content/8/1/38 © 2011 Diaz-Griffero et al; licensee BioMed Cent ral Ltd. This is an Open Access article ROLE OF THE NUCLEUS INCERTUS IN COGNITION WU YOU (B.Sc) A THESIS SUBMITTED FOR THE DEGREE OF MASTER OF SCIENCE DEPARTMENT OF PHARMACOLOGY NATIONAL UNIVERSITY OF SINGAPORE 2014 DECLARATION I here by declare that the thesis is my original work and it has been written by me in its entirety. I have duly acknowledged all the sources of information which have been used in the thesis. This thesis has also no been submitted for any degree in any university previously. Wu You 01 June 2014   i   ACKNOWLEDGEMENTS I would like to express my highest appreciation to my supervisor, Prof. Gavin Dawe for his mentor and fully support in this project and my postgraduate study. His enlightening supervision have triggered my motivation in exploring this research field and step by step solving the interesting research problems. His considerate care and encouragement have allowed me to pass throw the hardships and rebuild a more optimal and positive self. It is the most grateful and fortunate decision in my life ever to choose him to be my supervisor. I would also like to thank my lab mates, especially Dr. Rajkumar for his guidance on the project. He tutored me all the delicate techniques from zero to all. His suggestions were invaluable to me in the progression of the project. He is so patient and kind that always ready there to help me. Moreover, I would like to thank other lab mates, Jiamei, Jigna, Usman, etc. for their suggestions and accompany. Last but not least, I would like to show my sincere gratitude to my parents and my dearest friend Zhao Wei. Your infinite love and support continuously decorate my life with sunshine, make my postgraduate study bright and happy. Thanks to all the people I meet in the past two years. Every person has their unique merit that exerts effects on my attitude towards life.   ii   TABLE OF CONTENTS Summary ........................................................................................................ vi Abbreviations .............................................................................................. viii List of Figures ................................................................................................. x Chapter 1 Introduction ......................................................................................................................... 1 1. Stress and cognition ........................................................................................... 1 1.1 Stress ........................................................................................... 1 1.2 Effects of stress on cognition ...................................................... 1 2. Nucleus Incertus ............................................................................... 2 2.1 NI anatomy ................................................................................. 2 2.2 NI chemoarchitecture ................................................................. 3 2.3 NI connections ............................................................................ 3 2.4 NI and stress response ................................................................ 4 3. Stress and PFC ................................................................................... 5 3.1 Stress and mPFC ......................................................................... 5 3.2 Stress and ACC ........................................................................... 6 3.3 NI and mPFC/ACC ..................................................................... 7 Chapter 2 Hypothesis, Aims and Significance of the study .......................................... 8 Chapter 3 Chemoarchitecture of NI projections to PFC ............................................ 10 1. 2. 3.   Introduction ...................................................................................... 10 1.1 Retrograde tracing .................................................................... 10 1.2 NI projection ... logical; the mass of an atom is nearly equal to the mass of its nucleus, since electrons have so little mass The mass of the nucleus turns out to be nearly equal to the sum of the masses of the protons... (b) What is the ratio of the radius of 58Ni to that of 258Ha, one of the largest nuclei ever made? Note that the radius of the largest nucleus is still much smaller than the size of an atom (a)... combination of protons and neutrons, denoted by 7/10 Substructure of the Nucleus A XN Z or simplyAX, Z is the number of protons or atomic number, X is the symbol for the element, N is the number of neutrons,